@article {pmid42246405, year = {2026}, author = {Zheng, Z and Yousefi, M and Marks, M and Dixit, A and Wahid, R and Viscidi, E and Anderson, EJ}, title = {A narrative review of COVID-19 epidemiology and mRNA vaccine impact in children &lt; 12 years during the omicron era (November 2021 - December 2025).}, journal = {Expert review of vaccines}, volume = {}, number = {}, pages = {2684961}, doi = {10.1080/14760584.2026.2684961}, pmid = {42246405}, issn = {1744-8395}, abstract = {INTRODUCTION: COVID-19 continues to pose a burden in children under 12 years of age during the Omicron era (November 2021 - December 2025). Following Omicron's emergence, SARS-CoV-2 seroprevalence increased rapidly, with most children infected by ages 2-4 years. Pediatric hospitalization rates declined after the initial Omicron wave but remained elevated in children under 2 years and in those with underlying conditions. While healthy children typically experience mild illnesses, severe outcomes - including hospitalization, admission to intensive care unit, death, and multisystem inflammatory syndrome - can occur, particularly in unvaccinated children.<br><br>AREAS COVERED: This narrative review summarizes current evidence on pediatric COVID-19 epidemiology and vaccine impact, including infection rates, severe outcomes, post-acute COVID-19 syndrome (Long COVID), and mRNA vaccine effectiveness and uptake in high-income regions. A literature search included peer-reviewed publications, surveillance data, and reports from health agencies during the Omicron era.<br><br>EXPERT OPINION: mRNA vaccines are effective in reducing pediatric COVID-19-related morbidity, but uptake remains low globally. Addressing parental concerns, improving vaccine accessibility, and promoting evidence-based communication are critical to increasing uptake. Given the continued disease burden and the potential for severe outcomes, ensuring access to mRNA COVID-19 vaccines for children at higher risk and for families who wish to vaccinate their children is beneficial.}, }
@article {pmid37816180, year = {2023}, author = {Riepl, M and Kaiser, J}, title = {Compounding for the Treatment of COVID-19 and Long COVID, Part 5: Associated Conditions, Prophylaxis, and Effective Treatment.}, journal = {International journal of pharmaceutical compounding}, volume = {27}, number = {5}, pages = {368-380}, pmid = {37816180}, issn = {1092-4221}, mesh = {Humans ; *COVID-19/prevention &amp; control ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Treatment Outcome ; }, abstract = {The effects of infection with the highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the coronavirus- disease-2019 (COVID-19) it engenders continue to demonstrate that worldwide, the detection, prediction, and control of novel-pathogen pandemics remain largely unattained achievements. Key to successfully meeting those goals is a thorough understanding of the mechanisms of evolving causative agents and effective prophylaxis against them. In this article, we review common conditions that afflict people with COVID-19 or long COVID, examine the effectiveness of vaccines designed to prevent infection with SARS-CoV-2 and mitigate its sequelae, and provide formulations for 2 compounded preparations that can assist recovery from acute and chronic conditions caused by that virus when manufactured drugs are unavailable in required dosages or dosage forms or cannot be tolerated by the patient.}, }
@article {pmid37817031, year = {2024}, author = {Megha, KB and Reshma, S and Amir, S and Krishnan, MJA and Shimona, A and Alka, R and Mohanan, PV}, title = {Comprehensive Risk Assessment of Infection Induced by SARS-CoV-2.}, journal = {Molecular neurobiology}, volume = {61}, number = {12}, pages = {9851-9872}, pmid = {37817031}, issn = {1559-1182}, mesh = {Humans ; *COVID-19/complications/epidemiology ; *SARS-CoV-2 ; Risk Assessment ; Host-Pathogen Interactions ; Pandemics ; }, abstract = {The pandemic COVID-19 (coronavirus disease 2019) is caused by the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), which devastated the global economy and healthcare system. The infection caused an unforeseen rise in COVID-19 patients and increased the mortality rate globally. This study gives an overall idea about host-pathogen interaction, immune responses to COVID-19, recovery status of infection, targeted organs and complications associated, and comparison of post-infection immunity in convalescent subjects and non-infected individuals. The emergence of the variants and episodes of COVID-19 infections made the situation worsen. The timely introduction of vaccines and precautionary measures helped control the infection's severity. Later, the population that recovered from COVID-19 grew significantly. However, understanding the impact of healthcare issues resulting after infection is paramount for improving an individual's health status. It is now recognised that COVID-19 infection affects multiple organs and exhibits a broad range of clinical manifestations. So, post COVID-19 infection creates a high risk in individuals with already prevailing health complications. The identification of post-COVID-19-related health issues and their appropriate management is of greater importance to improving patient's quality of life. The persistence, sequelae and other medical complications that normally last from weeks to months after the recovery of the initial infection are involved with COVID-19. A multi-disciplinary approach is necessary for the development of preventive measures, techniques for rehabilitation and strategies for clinical management when it comes to long-term care.}, }
@article {pmid37828990, year = {2023}, author = {Shafqat, A and Omer, MH and Albalkhi, I and Alabdul Razzak, G and Abdulkader, H and Abdul Rab, S and Sabbah, BN and Alkattan, K and Yaqinuddin, A}, title = {Neutrophil extracellular traps and long COVID.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1254310}, pmid = {37828990}, issn = {1664-3224}, mesh = {Humans ; *Extracellular Traps ; *COVID-19/metabolism ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Pulmonary Fibrosis/etiology/metabolism ; Inflammation/metabolism ; }, abstract = {Post-acute COVID-19 sequelae, commonly known as long COVID, encompasses a range of systemic symptoms experienced by a significant number of COVID-19 survivors. The underlying pathophysiology of long COVID has become a topic of intense research discussion. While chronic inflammation in long COVID has received considerable attention, the role of neutrophils, which are the most abundant of all immune cells and primary responders to inflammation, has been unfortunately overlooked, perhaps due to their short lifespan. In this review, we discuss the emerging role of neutrophil extracellular traps (NETs) in the persistent inflammatory response observed in long COVID patients. We present early evidence linking the persistence of NETs to pulmonary fibrosis, cardiovascular abnormalities, and neurological dysfunction in long COVID. Several uncertainties require investigation in future studies. These include the mechanisms by which SARS-CoV-2 brings about sustained neutrophil activation phenotypes after infection resolution; whether the heterogeneity of neutrophils seen in acute SARS-CoV-2 infection persists into the chronic phase; whether the presence of autoantibodies in long COVID can induce NETs and protect them from degradation; whether NETs exert differential, organ-specific effects; specifically which NET components contribute to organ-specific pathologies, such as pulmonary fibrosis; and whether senescent cells can drive NET formation through their pro-inflammatory secretome in long COVID. Answering these questions may pave the way for the development of clinically applicable strategies targeting NETs, providing relief for this emerging health crisis.}, }
@article {pmid37832998, year = {2023}, author = {Voss, JG and Pinto, MD and Burton, CW}, title = {How do the Social Determinants of Health Impact the Post-Acute Sequelae of COVID-19: A Critical Review.}, journal = {The Nursing clinics of North America}, volume = {58}, number = {4}, pages = {541-568}, doi = {10.1016/j.cnur.2023.07.004}, pmid = {37832998}, issn = {1558-1357}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; Social Determinants of Health ; Disease Progression ; }, abstract = {The review critically analyzes the social determinants of health (SDOH) variables in the current literature of patients with post-acute sequelae (PASC) of COVID-19 in the United States. Race, gender, and age were discussed as well as health outcomes, severity of illness, and phenotypes of long-COVID. Most research was retrospectively with samples that had access to health insurance, which did not capture populations with poor or no access to health care. More research is needed that directly addresses the impact on SDOH on PASC. The current literature is sparse and provides little actionable information.}, }
@article {pmid37834270, year = {2023}, author = {Moreno-Corona, NC and López-Ortega, O and Pérez-Martínez, CA and Martínez-Castillo, M and De Jesús-González, LA and León-Reyes, G and León-Juárez, M}, title = {Dynamics of the Microbiota and Its Relationship with Post-COVID-19 Syndrome.}, journal = {International journal of molecular sciences}, volume = {24}, number = {19}, pages = {}, pmid = {37834270}, issn = {1422-0067}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; Dysbiosis/complications ; *COVID-19/complications ; SARS-CoV-2 ; *Microbiota ; }, abstract = {Coronavirus disease (COVID-19) is an infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can be asymptomatic or present with multiple organ dysfunction. Many infected individuals have chronic alterations associated with neuropsychiatric, endocrine, gastrointestinal, and musculoskeletal symptoms, even several months after disease onset, developing long-COVID or post-acute COVID-19 syndrome (PACS). Microbiota dysbiosis contributes to the onset and progression of many viral diseases, including COVID-19 and post-COVID-19 manifestations, which could serve as potential diagnostic and prognostic biomarkers. This review aimed to discuss the most recent findings on gut microbiota dysbiosis and its relationship with the sequelae of PACS. Elucidating these mechanisms could help develop personalized and non-invasive clinical strategies to identify individuals at a higher risk of experiencing severe disease progression or complications associated with PACS. Moreover, the review highlights the importance of targeting the gut microbiota composition to avoid dysbiosis and to develop possible prophylactic and therapeutic measures against COVID-19 and PACS in future studies.}, }
@article {pmid37834324, year = {2023}, author = {Georgieva, E and Ananiev, J and Yovchev, Y and Arabadzhiev, G and Abrashev, H and Abrasheva, D and Atanasov, V and Kostandieva, R and Mitev, M and Petkova-Parlapanska, K and Karamalakova, Y and Koleva-Korkelia, I and Tsoneva, V and Nikolova, G}, title = {COVID-19 Complications: Oxidative Stress, Inflammation, and Mitochondrial and Endothelial Dysfunction.}, journal = {International journal of molecular sciences}, volume = {24}, number = {19}, pages = {}, pmid = {37834324}, issn = {1422-0067}, support = {Project &#x2116; BG-RRP-2.004-0006-C02//Bulgarian Ministry of Education and Science (MES) in the frames of Bulgarian National Recovery and Resilience Plan, Component "Innovative Bulgaria" the Project &#x2116; BG-RRP-2.004-0006-C02 "Development of research and innovation at Trakia University in service/ ; Young Scientists and Postdoctoral Students-2//Bulgarian Ministry of Education and Science under the National Program/ ; }, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Inflammation ; Oxidative Stress ; Free Radicals ; }, abstract = {SARS-CoV-2 infection, discovered and isolated in Wuhan City, Hubei Province, China, causes acute atypical respiratory symptoms and has led to profound changes in our lives. COVID-19 is characterized by a wide range of complications, which include pulmonary embolism, thromboembolism and arterial clot formation, arrhythmias, cardiomyopathy, multiorgan failure, and more. The disease has caused a worldwide pandemic, and despite various measures such as social distancing, various preventive strategies, and therapeutic approaches, and the creation of vaccines, the novel coronavirus infection (COVID-19) still hides many mysteries for the scientific community. Oxidative stress has been suggested to play an essential role in the pathogenesis of COVID-19, and determining free radical levels in patients with coronavirus infection may provide an insight into disease severity. The generation of abnormal levels of oxidants under a COVID-19-induced cytokine storm causes the irreversible oxidation of a wide range of macromolecules and subsequent damage to cells, tissues, and organs. Clinical studies have shown that oxidative stress initiates endothelial damage, which increases the risk of complications in COVID-19 and post-COVID-19 or long-COVID-19 cases. This review describes the role of oxidative stress and free radicals in the mediation of COVID-19-induced mitochondrial and endothelial dysfunction.}, }
@article {pmid37835106, year = {2023}, author = {Ambalavanan, R and Snead, RS and Marczika, J and Kozinsky, K and Aman, E}, title = {Advancing the Management of Long COVID by Integrating into Health Informatics Domain: Current and Future Perspectives.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {19}, pages = {}, pmid = {37835106}, issn = {1660-4601}, mesh = {Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Artificial Intelligence ; Pandemics/prevention &amp; control ; *Medical Informatics ; }, abstract = {The ongoing COVID-19 pandemic has profoundly affected millions of lives globally, with some individuals experiencing persistent symptoms even after recovering. Understanding and managing the long-term sequelae of COVID-19 is crucial for research, prevention, and control. To effectively monitor the health of those affected, maintaining up-to-date health records is essential, and digital health informatics apps for surveillance play a pivotal role. In this review, we overview the existing literature on identifying and characterizing long COVID manifestations through hierarchical classification based on Human Phenotype Ontology (HPO). We outline the aspects of the National COVID Cohort Collaborative (N3C) and Researching COVID to Enhance Recovery (RECOVER) initiative in artificial intelligence (AI) to identify long COVID. Through knowledge exploration, we present a concept map of clinical pathways for long COVID, which offers insights into the data required and explores innovative frameworks for health informatics apps for tackling the long-term effects of COVID-19. This study achieves two main objectives by comprehensively reviewing long COVID identification and characterization techniques, making it the first paper to explore incorporating long COVID as a variable risk factor within a digital health informatics application. By achieving these objectives, it provides valuable insights on long COVID's challenges and impact on public health.}, }
@article {pmid37838675, year = {2023}, author = {Sanal-Hayes, NEM and Mclaughlin, M and Hayes, LD and Mair, JL and Ormerod, J and Carless, D and Hilliard, N and Meach, R and Ingram, J and Sculthorpe, NF}, title = {A scoping review of 'Pacing' for management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): lessons learned for the long COVID pandemic.}, journal = {Journal of translational medicine}, volume = {21}, number = {1}, pages = {720}, pmid = {37838675}, issn = {1479-5876}, support = {COV/LTE/20/08/DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; *Fatigue Syndrome, Chronic/diagnosis ; Pandemics ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Exercise Therapy/methods ; Observational Studies as Topic ; }, abstract = {BACKGROUND: Controversy over treatment for people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a barrier to appropriate treatment. Energy management or pacing is a prominent coping strategy for people with ME/CFS. Whilst a definitive definition of pacing is not unanimous within the literature or healthcare providers, it typically comprises regulating activity to avoid post exertional malaise (PEM), the worsening of symptoms after an activity. Until now, characteristics of pacing, and the effects on patients' symptoms had not been systematically reviewed. This is problematic as the most common approach to pacing, pacing prescription, and the pooled efficacy of pacing was unknown. Collating evidence may help advise those suffering with similar symptoms, including long COVID, as practitioners would be better informed on methodological approaches to adopt, pacing implementation, and expected outcomes.<br><br>OBJECTIVES: In this scoping review of the literature, we aggregated type of, and outcomes of, pacing in people with ME/CFS.<br><br>ELIGIBILITY CRITERIA: Original investigations concerning pacing were considered in participants with ME/CFS.<br><br>SOURCES OF EVIDENCE: Six electronic databases (PubMed, Scholar, ScienceDirect, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials [CENTRAL]) were searched; and websites MEPedia, Action for ME, and ME Action were also searched for grey literature, to fully capture patient surveys not published in academic journals.<br><br>METHODS: A scoping review was conducted. Review selection and characterisation was performed by two independent reviewers using pretested forms.<br><br>RESULTS: Authors reviewed 177 titles and abstracts, resulting in 17 included studies: three randomised control trials (RCTs); one uncontrolled trial; one interventional case series; one retrospective observational study; two prospective observational studies; four cross-sectional observational studies; and five cross-sectional analytical studies. Studies included variable designs, durations, and outcome measures. In terms of pacing administration, studies used educational sessions and diaries for activity monitoring. Eleven studies reported benefits of pacing, four studies reported no effect, and two studies reported a detrimental effect in comparison to the control group.<br><br>CONCLUSIONS: Highly variable study designs and outcome measures, allied to poor to fair methodological quality resulted in heterogenous findings and highlights the requirement for more research examining pacing. Looking to the long COVID pandemic, our results suggest future studies should be RCTs utilising objectively quantified digitised pacing, over a longer duration of examination (i.e. longitudinal studies), using the core outcome set for patient reported outcome measures. Until these are completed, the literature base is insufficient to inform treatment practises for people with ME/CFS and long COVID.}, }
@article {pmid37841213, year = {2023}, author = {Yang, J and Lim, KH and Lim, KT and Woods, JT and Mohabbat, AB and Wahner-Roedler, DL and Ganesh, R and Bauer, BA}, title = {Complementary and alternative medicine for long COVID: a systematic review of randomized controlled trials.}, journal = {Therapeutic advances in chronic disease}, volume = {14}, number = {}, pages = {20406223231204727}, pmid = {37841213}, issn = {2040-6223}, support = {R21 AT001218/AT/NCCIH NIH HHS/United States ; }, abstract = {BACKGROUND: Complementary and alternative medicine (CAM) interventions are growing in popularity as possible treatments for long COVID symptoms. However, comprehensive analysis of current evidence in this setting is still lacking.<br><br>OBJECTIVE: This study aims to review existing published studies on the use of CAM interventions for patients experiencing long COVID through a systematic review.<br><br>DESIGN: Systematic review of randomized controlled trials (RCTs).<br><br>METHODS: A comprehensive electronic literature search was performed in multiple databases and clinical trial registries from September 2019 to January 2023. RCTs evaluating efficacy and safety of CAM for long COVID were included. Methodological quality of each included trial was appraised with the Cochrane 'risk of bias' tool. A qualitative analysis was conducted due to heterogeneity of included studies.<br><br>RESULTS: A total of 14 RCTs with 1195 participants were included in this review. Study findings demonstrated that CAM interventions could benefit patients with long COVID, especially those suffering from neuropsychiatric disorders, olfactory dysfunction, cognitive impairment, fatigue, breathlessness, and mild-to-moderate lung fibrosis. The main interventions reported were self-administered transcutaneous auricular vagus nerve stimulation, neuro-meditation, dietary supplements, olfactory training, aromatherapy, inspiratory muscle training, concurrent training, and an online breathing and well-being program.<br><br>CONCLUSION: CAM interventions may be effective, safe, and acceptable to patients with symptoms of long COVID. However, the findings from this systematic review should be interpreted with caution due to various methodological limitations. More rigorous trials focused on CAM for long COVID are warranted in the future.}, }
@article {pmid37842301, year = {2023}, author = {Meng, QT and Song, WQ and Churilov, LP and Zhang, FM and Wang, YF}, title = {Psychophysical therapy and underlying neuroendocrine mechanisms for the rehabilitation of long COVID-19.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1120475}, pmid = {37842301}, issn = {1664-2392}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/therapy ; SARS-CoV-2 ; Neurosecretory Systems ; Disease Progression ; }, abstract = {With the global epidemic and prevention of the COVID-19, long COVID-19 sequelae and its comprehensive prevention have attracted widespread attention. Long COVID-19 sequelae refer to that three months after acute COVID-19, the test of SARS-CoV-2 is negative, but some symptoms still exist, such as cough, prolonged dyspnea and fatigue, shortness of breath, palpitations and insomnia. Its pathological mechanism is related to direct viral damage, immunopathological response, endocrine and metabolism disorders. Although there are more effective methods for treating COVID-19, the treatment options available for patients with long COVID-19 remain quite limited. Psychophysical therapies, such as exercise, oxygen therapy, photobiomodulation, and meditation, have been attempted as treatment modalities for long COVID-19, which have the potential to promote recovery through immune regulation, antioxidant effects, and neuroendocrine regulation. Neuroendocrine regulation plays a significant role in repairing damage after viral infection, regulating immune homeostasis, and improving metabolic activity in patients with long COVID-19. This review uses oxytocin as an example to examine the neuroendocrine mechanisms involved in the psychophysical therapies of long COVID-19 syndrome and proposes a psychophysical strategy for the treatment of long COVID-19.}, }
@article {pmid37844017, year = {2023}, author = {Martino, L and Morello, R and De Rose, C and Buonsenso, D}, title = {Persistent respiratory symptoms associated with post-Covid condition (Long Covid) in children: a systematic review and analysis of current gaps and future perspectives.}, journal = {Expert review of respiratory medicine}, volume = {17}, number = {10}, pages = {837-852}, doi = {10.1080/17476348.2023.2271836}, pmid = {37844017}, issn = {1747-6356}, mesh = {Child ; Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; SARS-CoV-2 ; }, abstract = {INTRODUCTION: There is increasing evidence that also children can develop Long Covid. However, there are no specific reviews providing a clear description of reported respiratory symptoms and potential diagnostics.<br><br>AREAS COVERED: We performed on PubMed a systematic search of studies conducted on children aged less than 18 years with previous SARS-CoV-2 infection complaining about persistent respiratory symptoms; the aim of our review is to characterize the incidence, pattern and duration of respiratory symptoms after the acute infection in pediatric population.<br><br>EXPERT OPINION: Children can develop persisting respiratory symptoms, as documented by several follow-up studies both including or not control groups of non-infected children. However, the methodological variabilities of the analyzed studies does not allow to provide firm conclusions about the rate, type and best diagnostics for children with persistent respiratory symptoms. Future studies should investigate on larger pediatric cohorts the role of noninvasive diagnostics and new biomarkers as well as investigating therapeutic options both during acute infection or when Long Covid has been diagnosed.}, }
@article {pmid37844358, year = {2023}, author = {Yang, L and Wu, Y and Jin, W and Mo, N and Ye, G and Su, Z and Tang, L and Wang, Y and Li, Y and Du, J}, title = {The potential role of ferroptosis in COVID-19-related cardiovascular injury.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {168}, number = {}, pages = {115637}, doi = {10.1016/j.biopha.2023.115637}, pmid = {37844358}, issn = {1950-6007}, mesh = {Humans ; Aged ; *Ferroptosis/physiology ; Reactive Oxygen Species/metabolism ; *COVID-19/complications ; *Cardiovascular Diseases/etiology ; SARS-CoV-2/metabolism ; Iron/metabolism ; *Reperfusion Injury ; }, abstract = {COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged as a global health threat in 2019. An important feature of the disease is that multiorgan symptoms of SARS-CoV-2 infection persist after recovery. Evidence indicates that people who recovered from COVID-19, even those under the age of 65 years without cardiovascular risk factors such as smoking, obesity, hypertension, and diabetes, had a significantly increased risk of cardiovascular disease for up to one year after diagnosis. Therefore, it is important to closely monitor individuals who have recovered from COVID-19 for potential cardiovascular damage that may manifest at a later stage. Ferroptosis is an iron-dependent form of non-apoptotic cell death characterized by the production of reactive oxygen species (ROS) and increased lipid peroxide levels. Several studies have demonstrated that ferroptosis plays an important role in cancer, ischemia/reperfusion injury (I/RI), and other cardiovascular diseases. Altered iron metabolism, upregulation of reactive oxygen species, and glutathione peroxidase 4 inactivation are striking features of COVID-19-related cardiovascular injury. SARS-CoV-2 can cause cardiovascular ferroptosis, leading to cardiovascular damage. Understanding the mechanism of ferroptosis in COVID-19-related cardiovascular injuries will contribute to the development of treatment regimens for preventing or reducing COVID-19-related cardiovascular complications. In this article, we go over the pathophysiological underpinnings of SARS-CoV-2-induced acute and chronic cardiovascular injury, the function of ferroptosis, and prospective treatment approaches.}, }
@article {pmid37852458, year = {2024}, author = {Houweling, L and Maitland-Van der Zee, AH and Holtjer, JCS and Bazdar, S and Vermeulen, RCH and Downward, GS and Bloemsma, LD}, title = {The effect of the urban exposome on COVID-19 health outcomes: A systematic review and meta-analysis.}, journal = {Environmental research}, volume = {240}, number = {Pt 2}, pages = {117351}, doi = {10.1016/j.envres.2023.117351}, pmid = {37852458}, issn = {1096-0953}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; *Exposome ; Pandemics ; *Air Pollutants/toxicity ; *Environmental Pollutants ; Particulate Matter/toxicity ; }, abstract = {BACKGROUND: The global severity of SARS-CoV-2 illness has been associated with various urban characteristics, including exposure to ambient air pollutants. This systematic review and meta-analysis aims to synthesize findings from ecological and non-ecological studies to investigate the impact of multiple urban-related features on a variety of COVID-19 health outcomes.<br><br>METHODS: On December 5, 2022, PubMed was searched to identify all types of observational studies that examined one or more urban exposome characteristics in relation to various COVID-19 health outcomes such as infection severity, the need for hospitalization, ICU admission, COVID pneumonia, and mortality.<br><br>RESULTS: A total of 38 non-ecological and 241 ecological studies were included in this review. Non-ecological studies highlighted the significant effects of population density, urbanization, and exposure to ambient air pollutants, particularly PM2.5. The meta-analyses revealed that a 1&#xa0;&#x3bc;g/m[3] increase in PM2.5 was associated with a higher likelihood of COVID-19 hospitalization (pooled OR 1.08 (95% CI:1.02-1.14)) and death (pooled OR 1.06 (95% CI:1.03-1.09)). Ecological studies, in addition to confirming the findings of non-ecological studies, also indicated that higher exposure to nitrogen dioxide (NO2), ozone (O3), sulphur dioxide (SO2), and carbon monoxide (CO), as well as lower ambient temperature, humidity, ultraviolet (UV) radiation, and less green and blue space exposure, were associated with increased COVID-19 morbidity and mortality.<br><br>CONCLUSION: This systematic review has identified several key vulnerability features related to urban areas in the context of the recent COVID-19 pandemic. The findings underscore the importance of improving policies related to urban exposures and implementing measures to protect individuals from these harmful environmental stressors.}, }
@article {pmid37858583, year = {2023}, author = {Müller, SA and Isaaka, L and Mumm, R and Scheidt-Nave, C and Heldt, K and Schuster, A and Abdulaziz, M and El Bcheraoui, C and Hanefeld, J and Agweyu, A}, title = {Prevalence and risk factors for long COVID and post-COVID-19 condition in Africa: a systematic review.}, journal = {The Lancet. Global health}, volume = {11}, number = {11}, pages = {e1713-e1724}, doi = {10.1016/S2214-109X(23)00384-4}, pmid = {37858583}, issn = {2214-109X}, mesh = {Child ; Humans ; Female ; Infant, Newborn ; *COVID-19/epidemiology/prevention &amp; control ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Prevalence ; Risk Factors ; Ghana ; }, abstract = {BACKGROUND: An improved estimation of the clinical sequelae of SARS-CoV-2 infection is crucial in African countries, where the subject has received little attention despite more than 12 million reported cases and evidence that many more people were infected. We reviewed the evidence on prevalence, associated risk factors for long COVID, and systemic or sociocultural determinants of reporting long COVID.<br><br>METHODS: We conducted a systematic review, searching PubMed, the Living OVerview of Evidence platform, and grey literature sources for publications from Dec 1, 2019, to Nov 23, 2022. We included articles published in English, French, Spanish, or Portuguese that reported on any study type in Africa with participants of any age who had symptoms for 4 weeks or more after an acute SARS-CoV-2 infection. We excluded secondary research, comments, and correspondence. Screening and data extraction were performed by two reviewers. Summary estimates were extracted, including sociodemographic factors, medical history, prevalence of persistent symptoms, and symptoms and associated factors. Results were analysed descriptively. The study was registered on the Open Science Framework platform.<br><br>FINDINGS: Our search yielded 294 articles, of which 24 peer-reviewed manuscripts were included, reporting on 9712 patients from eight African countries. Only one study exclusively recruited children, and one other study included children as part of their study population. Studies indicated moderate to low risk of bias. Prevalence of long COVID varied widely, from 2% in Ghana to 86% in Egypt. Long COVID was positively associated with female sex, older age, non-Black ethnicity, low level of education, and the severity of acute infection and underlying comorbidity. HIV and tuberculosis were not identified as risk factors. Factors influencing reporting included absence of awareness, inadequate clinical data and diagnostics, and little access to health-care services.<br><br>INTERPRETATION: In Africa, research on long COVID is scarce, particularly among children, who represent the majority of the population. However, existing studies show a substantial prevalence across settings, emphasising the importance of vaccination and other prevention strategies to avert the effects of long COVID on individual wellbeing, the increased strain on health systems, and the potential negative effects on economically vulnerable populations. At a global level, including African countries, tools for research on long COVID need to be harmonised to maximise the usefulness of the data collected.<br><br>FUNDING: None.}, }
@article {pmid37859501, year = {2023}, author = {Molero, P and Reina, G and Blom, JD and Martínez-González, M&#xc1; and Reinken, A and de Kloet, ER and Molendijk, ML}, title = {COVID-19 risk, course and outcome in people with mental disorders: a systematic review and meta-analyses.}, journal = {Epidemiology and psychiatric sciences}, volume = {32}, number = {}, pages = {e61}, pmid = {37859501}, issn = {2045-7979}, mesh = {Humans ; *COVID-19/epidemiology ; Prospective Studies ; Post-Acute COVID-19 Syndrome ; Bayes Theorem ; Cross-Sectional Studies ; *Mental Disorders/epidemiology ; }, abstract = {AIMS: It has been suggested that people with mental disorders have an elevated risk to acquire severe acute respiratory syndrome coronavirus 2 and to be disproportionally affected by coronavirus disease 19 (COVID-19) once infected. We aimed to analyse the COVID-19 infection rate, course and outcome, including mortality and long COVID, in people with anxiety, depressive, neurodevelopmental, schizophrenia spectrum and substance use disorders relative to control subjects without these disorders.<br><br>METHODS: This study constitutes a preregistered systematic review and random-effects frequentist and Bayesian meta-analyses. Major databases were searched up until 27 June 2023.<br><br>RESULTS: Eighty-one original articles were included reporting 304 cross-sectional and prospective effect size estimates (median n per effect-size = 114837) regarding associations of interest. Infection risk was not significantly increased for any mental disorder that we investigated relative to samples of people without these disorders. The course of COVID-19, however, is relatively severe, and long COVID and COVID-19-related hospitalization are more likely in all patient samples that we investigated. The odds of dying from COVID-19 were high in people with most types of mental disorders, except for those with anxiety and neurodevelopmental disorders relative to non-patient samples (pooled ORs range, 1.26-2.57). Bayesian analyses confirmed the findings from the frequentist approach and complemented them with estimates of the strength of evidence.<br><br>CONCLUSIONS: Once infected, people with pre-existing mental disorders are at an elevated risk for a severe COVID-19 course and outcome, including long COVID and mortality, relative to people without pre-existing mental disorders, despite an infection risk not significantly increased.}, }
@article {pmid37864020, year = {2024}, author = {Luchting, B and Behrends, U and Eigner, B and Stojanov, S and Warlitz, C and Haegele, M and Neuwirth, E and Mihatsch, L and Richter, HP}, title = {[Interdisciplinary multimodal pain therapy in postviral syndromes and ME/CFS : Features, pitfalls and model concept].}, journal = {Schmerz (Berlin, Germany)}, volume = {38}, number = {3}, pages = {183-189}, pmid = {37864020}, issn = {1432-2129}, mesh = {Humans ; Combined Modality Therapy ; *Intersectoral Collaboration ; *Interdisciplinary Communication ; *Pain Management/methods ; Patient Care Team ; Postpoliomyelitis Syndrome/therapy ; Psychotherapy, Group ; Cooperative Behavior ; Conversion Disorder/therapy/psychology ; }, abstract = {BACKGROUND: Multimodal pain therapy usually take place in the context of group therapy lasting several weeks and is based on a generally activating approach. Due to the specificity of stress intolerance with postexertional malaise (PEM) in patients with postviral syndromes, physical as well as psychological overload must be urgently avoided in these cases; however, these aspects can only be insufficiently considered in current medical pain therapy concepts.<br><br>METHODS: Summary of the current literature and presentation of clinical characteristics as well as presentation of a&#xa0;model project for a&#xa0;multimodal pain therapy in postviral syndromes with PEM.<br><br>MODEL CONCEPT: The presented model project describes a&#xa0;day clinic treatment setting for interdisciplinary multimodal pain therapy adapted to the individual resilience with minimization of the risk of strain-induced deterioration of the condition.}, }
@article {pmid37865841, year = {2023}, author = {Aiyegbusi, OL}, title = {COVID-19 related headaches: epidemiology, pathophysiology, impacts, and management.}, journal = {Current opinion in neurology}, volume = {36}, number = {6}, pages = {609-614}, doi = {10.1097/WCO.0000000000001219}, pmid = {37865841}, issn = {1473-6551}, mesh = {Humans ; Female ; *COVID-19/complications/epidemiology ; Post-Acute COVID-19 Syndrome ; Quality of Life ; SARS-CoV-2 ; Headache/epidemiology/therapy/diagnosis ; }, abstract = {PURPOSE OF REVIEW: This is an expert overview of the recent literature on the nature, epidemiology, pathophysiology, impact, and management of COVID-19 related headache, in the acute phase of infection and in post-COVID-19 syndrome.<br><br>RECENT FINDINGS: Headache is one of the commonest symptoms of COVID-19 during acute infection and it is often experienced by individuals who go on to develop long COVID. There is a higher prevalence of headache in individuals with long COVID who contracted the Delta variant than in those who were infected with the Wuhan or Alpha variants. Headaches related to COVID-19 infection are commoner and may be more intense in women.There are indications that presence of headache might indicate a more benign COVID-19 infection and a better chance of survival. However, the impact of COVID-19 related headache could be substantial leading to poor quality of life in individuals affected. Headache that changes in its nature in terms of frequency and severity should be investigated to exclude cerebrovascular complications. There are promising new therapies for its treatment, but further research is needed.<br><br>SUMMARY: The findings of this review can promote a better understanding of COVID-19 related headache and guide clinicians in the management of patients.}, }
@article {pmid37866679, year = {2024}, author = {Luo, D and Mei, B and Wang, P and Li, X and Chen, X and Wei, G and Kuang, F and Li, B and Su, S}, title = {Prevalence and risk factors for persistent symptoms after COVID-19: a systematic review and meta-analysis.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {30}, number = {3}, pages = {328-335}, doi = {10.1016/j.cmi.2023.10.016}, pmid = {37866679}, issn = {1469-0691}, mesh = {Female ; Humans ; Male ; Anxiety/epidemiology/etiology ; *COVID-19/epidemiology/complications ; Depression/epidemiology/etiology ; Fatigue/epidemiology/etiology ; *Post-Acute COVID-19 Syndrome/complications/epidemiology ; Prevalence ; Risk Factors ; SARS-CoV-2 ; Stress Disorders, Post-Traumatic/epidemiology/etiology ; }, abstract = {BACKGROUND: Long-term physical and mental persistent symptoms after COVID-19 represent a growing global public health concern. However, there remains a substantial knowledge gap regarding their prevalence and risk factors.<br><br>OBJECTIVES: To estimate the prevalence and risk factors for persistent symptoms after COVID-19.<br><br>METHODS OF DATA SYNTHESIS: We used a random-effects model to pool persistent symptom prevalence and risk ratios comparing COVID-19 patients with non-COVID-19 individuals.<br><br>DATA SOURCES: Electronic databases were searched for studies published from December 2019 to January 2023.<br><br>STUDY ELIGIBILITY CRITERIA: Eligible studies that reported the prevalence and risk factors for persistent symptoms after COVID-19 were included.<br><br>PARTICIPANTS: Patients who recovered from COVID-19.<br><br>ASSESSMENT OF RISK OF BIAS: The Joanna Briggs Institute critical appraisal tool was used to assess the risk of bias in prevalence studies, whereas the risk of bias in cohort studies was evaluated with the Newcastle-Ottawa Scale.<br><br>RESULTS: After screening 4359 studies, a total of 211 eligible studies were included, covering a population of 13 368 074 individuals. Fatigue, dyspnoea, post-traumatic stress disorder, anxiety, and depression were the most frequently reported persistent symptoms after COVID-19. Subgroup analyses revealed that individuals with more severe illness in the acute phase or from Europe exhibited a higher prevalence of certain symptoms, whereas children demonstrated a lower prevalence. Furthermore, COVID-19 patients had a significantly higher prevalence of most persistent symptoms compared with non-COVID-19 individuals. Factors frequently associated with a higher prevalence of persistent symptoms included female gender, advanced age, severe illness during the acute phase of COVID-19, multiple comorbidities, an extended duration of hospital stay, and a high body mass index.<br><br>CONCLUSION: This meta-analysis provides a thorough review of the prevalence and risk factors for persistent symptoms following COVID-19. The findings underscore the importance of long-term monitoring and support for individuals recovering from COVID-19.}, }
@article {pmid37868668, year = {2023}, author = {Shah, B and Ahmad, MN and Khalid, M and Minhas, A and Ali, R and Sarfraz, Z and Sarfraz, A}, title = {Long COVID and Wavering Incidence of Pulmonary Embolism: A Systematic Review.}, journal = {Journal of community hospital internal medicine perspectives}, volume = {13}, number = {5}, pages = {23-31}, pmid = {37868668}, issn = {2000-9666}, abstract = {Pulmonary embolism (PE) is a serious medical condition that can occur as a result of venous thromboembolism (VTE). COVID-19, also known as Post-Acute Sequelae of SARS-CoV-2 infection (PASC), can potentially lead to PE due to the formation of blood clots in the lungs. This study aims to collate and report trends of PE in patients with long COVID (4-12 weeks since infection) and post-COVID-19 syndrome (>12 weeks since infection). The study adhered to PRISMA Statement 2020 guidelines, and a systematic search was conducted in four databases. In total, nine observational studies were included with a total patient count of 45,825,187. The incidence of PE with long COVID/post-COVID-19 syndrome was seen among 31,885 individuals out of 44,967,887 participants. The incidence rate of PE was observed as 0.07%, given that the studies included matched controls. While we cannot state with certainty that COVID-19 infection in itself leads to higher risks of PE at a later time, this study emphasizes the need for optimized care and longitudinal studies during the COVID-19 era to account for deviations from the norm.}, }
@article {pmid37880142, year = {2023}, author = {Zhang, Y and Li, Y}, title = {Clinical Translation of Aptamers for COVID-19.}, journal = {Journal of medicinal chemistry}, volume = {66}, number = {24}, pages = {16568-16578}, doi = {10.1021/acs.jmedchem.3c01607}, pmid = {37880142}, issn = {1520-4804}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Oligonucleotides ; }, abstract = {The COVID-19 etiologic agent, SARS-CoV-2, continues to be one of the leading causes of death on a global scale. Although efficient methods for diagnosis and treatment of COVID-19 have been developed, new methods of battling SARS-CoV-2 variants and long COVID are still urgently needed. A number of aptamers have demonstrated tremendous potential to be developed into diagnostic and therapeutic agents for COVID-19. The translation of the aptamers for clinical uses, however, has been extremely slow. Overcoming the difficulties faced by aptamers would advance this technology toward clinical use for COVID-19 and other serious disorders.}, }
@article {pmid37890221, year = {2023}, author = {Moyo, E and Chimene, M and Moyo, P and Musuka, G and Mangoya, D and Murewanhema, G and Dzinamarira, T}, title = {Risk factors and clinical presentations of long COVID in Africa: A scoping review.}, journal = {Journal of infection and public health}, volume = {16}, number = {12}, pages = {1982-1988}, doi = {10.1016/j.jiph.2023.09.021}, pmid = {37890221}, issn = {1876-035X}, mesh = {Humans ; Female ; Male ; *COVID-19/epidemiology/therapy ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; Case-Control Studies ; Cross-Sectional Studies ; Prospective Studies ; Risk Factors ; }, abstract = {COVID-19-related complications can last for years, even in patients who are asymptomatic during the acute phase, a phenomenon referred to as long COVID. This scoping review aimed to summarize the risk factors and clinical symptoms of long COVID in Africa between 2020 and 2022. Five studies were included. Three of the studies used in this review were retrospective cross-sectional studies, one was a prospective cohort study while another one was a case-control study. The review identified several risk factors for long COVID, including being female, being older than 40 years, having more than four acute COVID-19 symptoms, and having concomitant conditions such as asthma, hypertension, and depression. General, respiratory, cardiovascular, otolaryngological, gastrointestinal, and neurological symptoms were among the reported long COVID symptoms. To ensure that patients with long COVID are diagnosed and treated early, the risk factors and clinical symptoms of long COVID need to be identified for different population groups.}, }
@article {pmid37894116, year = {2023}, author = {Tziolos, NR and Ioannou, P and Baliou, S and Kofteridis, DP}, title = {Long COVID-19 Pathophysiology: What Do We Know So Far?.}, journal = {Microorganisms}, volume = {11}, number = {10}, pages = {}, pmid = {37894116}, issn = {2076-2607}, abstract = {Long COVID-19 is a recognized entity that affects millions of people worldwide. Its broad clinical symptoms include thrombotic events, brain fog, myocarditis, shortness of breath, fatigue, muscle pains, and others. Due to the binding of the virus with ACE-2 receptors, expressed in many organs, it can potentially affect any system; however, it most often affects the cardiovascular, central nervous, respiratory, and immune systems. Age, high body mass index, female sex, previous hospitalization, and smoking are some of its risk factors. Despite great efforts to define its pathophysiology, gaps remain to be explained. The main mechanisms described in the literature involve viral persistence, hypercoagulopathy, immune dysregulation, autoimmunity, hyperinflammation, or a combination of these. The exact mechanisms may differ from system to system, but some share the same pathways. This review aims to describe the most prevalent pathophysiological pathways explaining this syndrome.}, }
@article {pmid37897034, year = {2023}, author = {Koleničová, V and Vňuková, MS and Anders, M and Fišerová, M and Raboch, J and Ptáček, R}, title = {A Review Article on Exercise Intolerance in Long COVID: Unmasking the Causes and Optimizing Treatment Strategies.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {29}, number = {}, pages = {e941079}, pmid = {37897034}, issn = {1643-3750}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Quality of Life ; SARS-CoV-2 ; Cognitive Training ; Fatigue/etiology/therapy ; }, abstract = {There is a growing body of research on SARS-CoV-2 (PASC), previously known as the post-COVID syndrome, a chronic condition characterized by symptoms that persist after SARS-CoV-2 infection. Among these symptoms, feelings of physical exhaustion and prolonged fatigue are particularly prevalent and can significantly impact patients' quality of life. These symptoms are associated with reduced overall physical capacity, decreased daily physical activity, malaise after intense training, and intolerance to physical activity (IFA). IFA, described as a reduced ability to perform physical activities typical for the patient's age, can often lead to a sedentary lifestyle. Prolonged physical inactivity can cause deterioration in the overall physical condition and disrupt mitochondrial function, triggering a vicious cycle of gradual symptom worsening. The underlying causes of PASC remain unclear; however, several biochemical mechanisms have been discussed to explain the body's energy depletion, and a multidisciplinary approach that combines physical and cognitive rehabilitation and lifestyle interventions such as exercise and diet modifications has been suggested to improve the overall health and well-being of PASC patients. This critical review aims to review the existing research on the possible causes and links among chronic fatigue, reduced physical activity, and exercise intolerance in patients with PASC. Further research into the underlying causes and treatment of PASC and the importance of developing individualized treatment is needed to address each patient's unique health requirements.}, }
@article {pmid37898059, year = {2023}, author = {Chinvararak, C and Chalder, T}, title = {Prevalence of sleep disturbances in patients with long COVID assessed by standardised questionnaires and diagnostic criteria: A systematic review and meta-analysis.}, journal = {Journal of psychosomatic research}, volume = {175}, number = {}, pages = {111535}, doi = {10.1016/j.jpsychores.2023.111535}, pmid = {37898059}, issn = {1879-1360}, mesh = {Humans ; Male ; Female ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Prevalence ; *Sleep Wake Disorders/diagnosis/epidemiology/etiology ; Sleep ; COVID-19 Testing ; }, abstract = {OBJECTIVE: We aimed to study the prevalence of sleep disturbances in patients with long COVID-19.<br><br>METHODS: We conducted a systematic review and meta-analysis of the pooled prevalence of sleep disturbances in patients post COVID-19. We systematically searched relevant studies from three databases, including Medline, Embase and Scopus. Original articles were included based on specific criteria: peer-reviewed, observational studies involving adults (18 or older) with confirmed post COVID-19 status through PCR testing and focused on sleep in the context of post COVID-19. Exclusion criteria included non-English articles, studies with insufficient data, and narrative/systematic reviews. The search was performed from 31st July 2023 to 15th August 2023. We identified 35 eligible papers; however, we excluded 6 studies which did not describe the sleep assessment. We used a random-effects meta-analysis model to estimate the pooled prevalence of sleep disturbances.<br><br>RESULTS: 29 studies involved 13,935 long COVID-19 patients; approximately 39% of participants were male aged 18 to 97&#xa0;years. The overall pooled prevalence of sleep disturbance was 46% (95% CI: 38-54%). Subgroup analyses revealed that the pooled prevalence of poor sleep quality was 56% (95% CI: 47-65%). The pooled prevalence of insomnia was 38% (95% CI: 28-48%). Finally, the pooled prevalence of excessive daytime sleepiness was 14% (95% CI: 0-29%).<br><br>CONCLUSION: Sleep disturbances are common in long COVID-19 patients. The healthcare sector should recognise these sleep issues and provide an early, effective treatment to prevent long-term sequelae of sleep problems.}, }
@article {pmid37906246, year = {2024}, author = {Constantinidou, F and Sander, A and Bergquist, T and Zimmerman, AS and Kingsley, K}, title = {Strategies to Manage the Thinking and Emotional Difficulties of Long COVID: A Guide for Patients and Families.}, journal = {Archives of physical medicine and rehabilitation}, volume = {105}, number = {9}, pages = {1809-1812}, doi = {10.1016/j.apmr.2023.09.014}, pmid = {37906246}, issn = {1532-821X}, mesh = {Humans ; *COVID-19/psychology ; SARS-CoV-2 ; Emotions ; Post-Acute COVID-19 Syndrome ; Thinking ; Family/psychology ; }, }
@article {pmid37907497, year = {2023}, author = {Li, J and Zhou, Y and Ma, J and Zhang, Q and Shao, J and Liang, S and Yu, Y and Li, W and Wang, C}, title = {The long-term health outcomes, pathophysiological mechanisms and multidisciplinary management of long COVID.}, journal = {Signal transduction and targeted therapy}, volume = {8}, number = {1}, pages = {416}, pmid = {37907497}, issn = {2059-3635}, support = {2021M692309, 2022T150451//China Postdoctoral Science Foundation/ ; 2020HXBH084, CGZH21009//Sichuan University (SCU)/ ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Outcome Assessment, Health Care ; }, abstract = {There have been hundreds of millions of cases of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the growing population of recovered patients, it is crucial to understand the long-term consequences of the disease and management strategies. Although COVID-19 was initially considered an acute respiratory illness, recent evidence suggests that manifestations including but not limited to those of the cardiovascular, respiratory, neuropsychiatric, gastrointestinal, reproductive, and musculoskeletal systems may persist long after the acute phase. These persistent manifestations, also referred to as long COVID, could impact all patients with COVID-19 across the full spectrum of illness severity. Herein, we comprehensively review the current literature on long COVID, highlighting its epidemiological understanding, the impact of vaccinations, organ-specific sequelae, pathophysiological mechanisms, and multidisciplinary management strategies. In addition, the impact of psychological and psychosomatic factors is also underscored. Despite these crucial findings on long COVID, the current diagnostic and therapeutic strategies based on previous experience and pilot studies remain inadequate, and well-designed clinical trials should be prioritized to validate existing hypotheses. Thus, we propose the primary challenges concerning biological knowledge gaps and efficient remedies as well as discuss the corresponding recommendations.}, }
@article {pmid37919074, year = {2023}, author = {Marschalek, R}, title = {SARS-CoV-2: The Virus, Its Biology and COVID-19 Disease-Counteracting Possibilities.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {28}, number = {10}, pages = {273}, doi = {10.31083/j.fbl2810273}, pmid = {37919074}, issn = {2768-6698}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Biology ; Drug Combinations ; Lactams ; Leucine ; Nitriles ; Proline ; Ritonavir ; }, abstract = {Since the end of 2019, the SARS-CoV-2 virus started to spread in different countries, leading to a world-wide pandemia, with today's infection numbers of more than 690 million and with a case fatality rate of more than 6.9 million. In addition, about 65 million patients suffer from post/long-Covid syndromes after having infections with the SARS-CoV-2 virus or variants thereof. This review highlights the biology of the virus, summarizes our knowledge of some of the viral mechanisms that counteract our immune responses, and finally also discusses the different vaccines and their specific safety profiles. Also, the possibility to fight this virus with recently available drugs (Veklury, Lagevrio and Paxlovid) will be discussed. All these data clearly argue that SARS-CoV-2 variants still exhibit a dangerous potential-although with a lower case fatality rate-and that vaccination in combination with drug intake upon infection may help to lower the risk of developing chronic or temporary autoimmune diseases.}, }
@article {pmid37926103, year = {2023}, author = {Gorst, SL and Seylanova, N and Dodd, SR and Harman, NL and O'Hara, M and Terwee, CB and Williamson, PR and Needham, DM and Munblit, D and Nicholson, TR and , }, title = {Core outcome measurement instruments for use in clinical and research settings for adults with post-COVID-19 condition: an international Delphi consensus study.}, journal = {The Lancet. Respiratory medicine}, volume = {11}, number = {12}, pages = {1101-1114}, doi = {10.1016/S2213-2600(23)00370-3}, pmid = {37926103}, issn = {2213-2619}, support = {MC_PC_20050/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; Adult ; Delphi Technique ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Research Design ; Outcome Assessment, Health Care ; Treatment Outcome ; }, abstract = {Post-COVID-19 condition (also known as long COVID) is a new, complex, and poorly understood disorder. A core outcome set (COS) for post-COVID-19 condition in adults has been developed and agreement is now required on the most appropriate measurement instruments for these core outcomes. We conducted an international consensus study involving multidisciplinary experts and people with lived experience of long COVID. The study comprised a literature review to identify measurement instruments for the core outcomes, a three-round online modified Delphi process, and an online consensus meeting to generate a core outcome measurement set (COMS). 594 individuals from 58 countries participated. The number of potential instruments for the 12 core outcomes was reduced from 319 to 19. Consensus was reached for inclusion of the modified Medical Research Council Dyspnoea Scale for respiratory outcomes. Measures for two relevant outcomes from a previously published COS for acute COVID-19 were also included: time until death, for survival, and the Recovery Scale for COVID-19, for recovery. Instruments were suggested for consideration for the remaining nine core outcomes: fatigue or exhaustion, pain, post-exertion symptoms, work or occupational and study changes, and cardiovascular, nervous system, cognitive, mental health, and physical outcomes; however, consensus was not achieved for instruments for these outcomes. The recommended COMS and instruments for consideration provide a foundation for the evaluation of post-COVID-19 condition in adults, which should help to optimise clinical care and accelerate research worldwide. Further assessment of this COMS is warranted as new data emerge on existing and novel measurement instruments.}, }
@article {pmid37927339, year = {2023}, author = {Matveeva, N and Kiselev, I and Baulina, N and Semina, E and Kakotkin, V and Agapov, M and Kulakova, O and Favorova, O}, title = {Shared genetic architecture of COVID-19 and Alzheimer's disease.}, journal = {Frontiers in aging neuroscience}, volume = {15}, number = {}, pages = {1287322}, pmid = {37927339}, issn = {1663-4365}, abstract = {The severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and the сoronavirus disease 2019 (COVID-19) have become a global health threat. At the height of the pandemic, major efforts were focused on reducing COVID-19-associated morbidity and mortality. Now is the time to study the long-term effects of the pandemic, particularly cognitive impairment associated with long COVID. In recent years much attention has been paid to the possible relationship between COVID-19 and Alzheimer's disease, which is considered a main cause of age-related cognitive impairment. Genetic predisposition was shown for both COVID-19 and Alzheimer's disease. However, the analysis of the similarity of the genetic architecture of these diseases is usually limited to indicating a positive genetic correlation between them. In this review, we have described intrinsic linkages between COVID-19 and Alzheimer's disease, pointed out shared susceptibility genes that were previously identified in genome-wide association studies of both COVID-19 and Alzheimer's disease, and highlighted a panel of SNPs that includes candidate genetic risk markers of the long COVID-associated cognitive impairment.}, }
@article {pmid37931841, year = {2024}, author = {Borczuk, AC}, title = {Pathogenesis of Pulmonary Long COVID-19.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {37}, number = {2}, pages = {100378}, doi = {10.1016/j.modpat.2023.100378}, pmid = {37931841}, issn = {1530-0285}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Lung ; Complement Activation ; }, abstract = {COVID-19 is characterized by an acute respiratory illness that, in some patients, progresses to respiratory failure, largely demonstrating a pattern of acute respiratory distress syndrome. Excluding fatal cases, the outcome of this severe illness ranges from complete resolution to persistent respiratory dysfunction. This subacute-to-chronic respiratory illness has different manifestations and is collectively termed as "long COVID." The pathogenesis of organ dysfunction in acute injury stems from exaggerated innate immune response, complement activation, and monocyte influx, with a shift toward an organ injury state with abnormalities in cellular maturation. Although the increased rate of thrombosis observed in acute COVID-19 does not appear to persist, interestingly, ongoing symptomatic COVID-19 and post-COVID pathogeneses appear to reflect the persistence of immune and cellular disturbances triggered by the acute and subacute periods.}, }
@article {pmid37936547, year = {2023}, author = {Wolff, D and Drewitz, KP and Ulrich, A and Siegels, D and Deckert, S and Sprenger, AA and Kuper, PR and Schmitt, J and Munblit, D and Apfelbacher, C}, title = {Allergic diseases as risk factors for Long-COVID symptoms: Systematic review of prospective cohort studies.}, journal = {Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology}, volume = {53}, number = {11}, pages = {1162-1176}, doi = {10.1111/cea.14391}, pmid = {37936547}, issn = {1365-2222}, support = {//Bundesministerium f&#xfc;r Bildung und Forschung/ ; }, mesh = {Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Prospective Studies ; *Rhinitis ; *Asthma/epidemiology/etiology ; Risk Factors ; }, abstract = {OBJECTIVE: The role of allergy as a risk factor for Long-COVID (LC) is unclear and has not been thoroughly examined yet. We aimed to systematically review and appraise the epidemiological evidence on allergic diseases as risk factors for LC.<br><br>DESIGN: This is an initial systematic review. Two reviewers independently performed the study selection and data extraction using Covidence. Risk of bias (RoB) and certainty of evidence (GRADE) were assessed. Random effects meta-analyses were used to pool unadjusted ORs within homogeneous data subsets.<br><br>DATA SOURCES: We retrieved articles published between January 1st, 2020 and January 19th, 2023 from MEDLINE via PubMed, Scopus, the WHO-COVID-19 database and the LOVE platform (Epistemonikos Foundation). In addition, citations and reference lists were searched.<br><br>ELIGIBILITY CRITERIA: We included prospective cohort studies recruiting individuals of all ages with confirmed SARS-CoV-2 infection that were followed up for at least 12&#x2009;months for LC symptoms where information on pre-existing allergic diseases was available. We excluded all study designs that were not prospective cohort studies and all publication types that were not original articles.<br><br>RESULTS: We identified 13 studies (9967 participants, range 39-1950 per study), all assessed as high RoB, due to population selection and methods used to ascertain the exposures and the outcome. Four studies did not provide sufficient data to calculate Odds Ratios. The evidence supported a possible relationship between LC and allergy, but was very uncertain. For example, pre-existing asthma measured in hospital-based populations (6 studies, 4019 participants) may be associated with increased risk of LC (Odds Ratio 1.94, 95% CI 1.08, 3.50) and findings were similar for pre-existing rhinitis (3 studies, 1141 participants; Odds Ratio 1.96, 95% CI 1.61, 2.39), both very low certainty evidence.<br><br>CONCLUSIONS: Pre-existing asthma or rhinitis may increase the risk of LC.}, }
@article {pmid37942323, year = {2023}, author = {Müller, L and Di Benedetto, S}, title = {From aging to long COVID: exploring the convergence of immunosenescence, inflammaging, and autoimmunity.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1298004}, pmid = {37942323}, issn = {1664-3224}, mesh = {Humans ; Aged ; *Immunosenescence ; Autoimmunity ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Aging ; *Autoimmune Diseases ; Inflammation ; }, abstract = {The process of aging is accompanied by a dynamic restructuring of the immune response, a phenomenon known as immunosenescence. This mini-review navigates through the complex landscape of age-associated immune changes, chronic inflammation, age-related autoimmune tendencies, and their potential links with immunopathology of Long COVID. Immunosenescence serves as an introductory departure point, elucidating alterations in immune cell profiles and their functional dynamics, changes in T-cell receptor signaling, cytokine network dysregulation, and compromised regulatory T-cell function. Subsequent scrutiny of chronic inflammation, or "inflammaging," highlights its roles in age-related autoimmune susceptibilities and its potential as a mediator of the immune perturbations observed in Long COVID patients. The introduction of epigenetic facets further amplifies the potential interconnections. In this compact review, we consider the dynamic interactions between immunosenescence, inflammation, and autoimmunity. We aim to explore the multifaceted relationships that link these processes and shed light on the underlying mechanisms that drive their interconnectedness. With a focus on understanding the immunological changes in the context of aging, we seek to provide insights into how immunosenescence and inflammation contribute to the emergence and progression of autoimmune disorders in the elderly and may serve as potential mediator for Long COVID disturbances.}, }
@article {pmid37943302, year = {2023}, author = {Bhattacharjee, N and Sarkar, P and Sarkar, T}, title = {Beyond the acute illness: Exploring long COVID and its impact on multiple organ systems.}, journal = {Physiology international}, volume = {110}, number = {4}, pages = {291-310}, doi = {10.1556/2060.2023.00256}, pmid = {37943302}, issn = {2498-602X}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Acute Disease ; Pandemics ; SARS-CoV-2 ; }, abstract = {Unprecedented worldwide health catastrophe due to the COVID-19 pandemic has ended up resulting in high morbidity and mortality rates. Even though many people recover from acute infection, there is rising concern regarding post-COVID-19 conditions (PCCs), often referred to as post-acute sequelae of SARS-CoV-2 infection (PASC) or "long COVID." The respiratory, cardiovascular, neurological, and endocrine systems are just a few of the many organ systems that can be impacted by this multifarious, complicated illness. The clinical manifestations of long COVID can vary among individuals and may include fatigue, dyspnea, chest pain, cognitive impairment, and new-onset diabetes, among others. Although the underlying processes of long COVID are not fully understood, they probably involve unregulated immune response, persistent generation of pro-inflammatory cytokines (chronic inflammation), autoimmune-like reactions, persistent viral replication, and micro-clot formation. To create successful treatments and care plans, it is essential to comprehend the immunological mechanisms causing these difficulties. The pathogenesis of long COVID should be clarified and potential biomarkers to help with diagnosis and treatment should be sought after. To reduce the burden of long COVID on people and healthcare systems around the world, the need for long-term monitoring and management of long COVID problems should be emphasized. It also underscores the significance of a multidisciplinary approach to patient care. The goal of this review is to carefully evaluate the clinical signs and symptoms of long COVID, their underlying causes, and any potential immunological implications.}, }
@article {pmid37947962, year = {2023}, author = {Hira, R and Karalasingham, K and Baker, JR and Raj, SR}, title = {Autonomic Manifestations of Long-COVID Syndrome.}, journal = {Current neurology and neuroscience reports}, volume = {23}, number = {12}, pages = {881-892}, pmid = {37947962}, issn = {1534-6293}, support = {UL1 TR000445/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; Pandemics ; *COVID-19/complications/epidemiology ; *Autonomic Nervous System Diseases/epidemiology/etiology ; Autonomic Nervous System ; *Postural Orthostatic Tachycardia Syndrome/diagnosis/epidemiology ; }, abstract = {PURPOSE OF REVIEW: Long-COVID is a novel condition emerging from the COVID-19 pandemic. Long-COVID is characterized by symptoms commonly seen in autonomic disorders including fatigue, brain fog, light-headedness, and palpitations. This article will critically evaluate recent findings and studies on Long-COVID and its physiological autonomic manifestations.<br><br>RECENT FINDINGS: Studies have reported on the prevalence of different symptoms and autonomic disorders in Long-COVID cohorts. Autonomic nervous system function, including both the parasympathetic and sympathetic limbs, has been studied using different testing techniques in Long-COVID patients. While numerous mechanisms may contribute to Long-COVID autonomic pathophysiology, it is currently unclear which ones lead to a Long-COVID presentation. To date, studies have not tested treatment options for autonomic disorders in Long-COVID patients. Long-COVID is associated with autonomic abnormalities. There is a high prevalence of clinical autonomic disorders among Long-COVID patients, with limited knowledge of the underlying mechanisms and the effectiveness of treatment options.}, }
@article {pmid37948194, year = {2023}, author = {Grand, RJ}, title = {SARS-CoV-2 and the DNA damage response.}, journal = {The Journal of general virology}, volume = {104}, number = {11}, pages = {}, pmid = {37948194}, issn = {1465-2099}, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Genomic Instability ; DNA Damage ; }, abstract = {The recent coronavirus disease 2019 (COVID-19) pandemic was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is characterized by respiratory distress, multiorgan dysfunction and, in some cases, death. The virus is also responsible for post-COVID-19 condition (commonly referred to as 'long COVID'). SARS-CoV-2 is a single-stranded, positive-sense RNA virus with a genome of approximately 30 kb, which encodes 26 proteins. It has been reported to affect multiple pathways in infected cells, resulting, in many cases, in the induction of a 'cytokine storm' and cellular senescence. Perhaps because it is an RNA virus, replicating largely in the cytoplasm, the effect of SARS-Cov-2 on genome stability and DNA damage responses (DDRs) has received relatively little attention. However, it is now becoming clear that the virus causes damage to cellular DNA, as shown by the presence of micronuclei, DNA repair foci and increased comet tails in infected cells. This review considers recent evidence indicating how SARS-CoV-2 causes genome instability, deregulates the cell cycle and targets specific components of DDR pathways. The significance of the virus's ability to cause cellular senescence is also considered, as are the implications of genome instability for patients suffering from long COVID.}, }
@article {pmid37950846, year = {2023}, author = {Ocampo, FF and Promsena, P and Chan, P}, title = {Update on Central Nervous System Effects of the Intersection of HIV-1 and SARS-CoV-2.}, journal = {Current HIV/AIDS reports}, volume = {20}, number = {6}, pages = {345-356}, pmid = {37950846}, issn = {1548-3576}, mesh = {Humans ; SARS-CoV-2 ; *COVID-19/complications ; *HIV-1 ; *HIV Infections/complications/drug therapy ; *HIV Seropositivity ; Central Nervous System ; }, abstract = {PURPOSE OF REVIEW: Research has shown myriad neurologic and mental health manifestations during the acute and subsequent stages of COVID-19 in people with HIV (PWH). This review summarizes the updates on central nervous system (CNS) outcomes following SARS-CoV-2 infection in PWH and highlight the existing knowledge gaps in this area.<br><br>RECENT FINDINGS: Studies leveraging electronic record systems have highlighted the excess risk of developing acute and lingering neurological complications of COVID-19 in PWH compared to people without HIV (PWoH). However, there is a notable scarcity of neuroimaging as well as blood and cerebrospinal fluid (CSF) marker studies that can confirm the potential synergy between these two infections, particularly in PWH receiving suppressive antiretroviral therapy. Considering the unclear potential interaction between SARS-CoV-2 and HIV, clinicians should remain vigilant regarding new-onset or worsening neurological symptoms in PWH following COVID-19, as they could be linked to either infection.}, }
@article {pmid37951572, year = {2024}, author = {Theoharides, TC and Twahir, A and Kempuraj, D}, title = {Mast cells in the autonomic nervous system and potential role in disorders with dysautonomia and neuroinflammation.}, journal = {Annals of allergy, asthma &amp; immunology : official publication of the American College of Allergy, Asthma, &amp; Immunology}, volume = {132}, number = {4}, pages = {440-454}, doi = {10.1016/j.anai.2023.10.032}, pmid = {37951572}, issn = {1534-4436}, mesh = {Humans ; Mast Cells ; Neuroinflammatory Diseases ; *Autism Spectrum Disorder ; Post-Acute COVID-19 Syndrome ; Autonomic Nervous System ; *Postural Orthostatic Tachycardia Syndrome ; }, abstract = {Mast cells (MC) are ubiquitous in the body, and they are critical for not only in allergic diseases but also in immunity and inflammation, including having potential involvement in the pathophysiology of dysautonomias and neuroinflammatory disorders. MC are located perivascularly close to nerve endings and sites such as the carotid bodies, heart, hypothalamus, the pineal gland, and the adrenal gland that would allow them not only to regulate but also to be affected by the autonomic nervous system (ANS). MC are stimulated not only by allergens but also many other triggers including some from the ANS that can affect MC release of neurosensitizing, proinflammatory, and vasoactive mediators. Hence, MC may be able to regulate homeostatic functions that seem to be dysfunctional in many conditions, such as postural orthostatic tachycardia syndrome, autism spectrum disorder, myalgic encephalomyelitis/chronic fatigue syndrome, and Long-COVID syndrome. The evidence indicates that there is a possible association between these conditions and diseases associated with MC activation. There is no effective treatment for any form of these conditions other than minimizing symptoms. Given the many ways MC could be activated and the numerous mediators released, it would be important to develop ways to inhibit stimulation of MC and the release of ANS-relevant mediators.}, }
@article {pmid37953801, year = {2023}, author = {Marwaha, B}, title = {Role of Tau protein in long COVID and potential therapeutic targets.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1280600}, pmid = {37953801}, issn = {2235-2988}, mesh = {Animals ; Humans ; Rats ; *COVID-19 ; *Post-Acute COVID-19 Syndrome ; *tau Proteins/metabolism ; Tauopathies/diagnosis/drug therapy/metabolism ; }, abstract = {INTRODUCTION: Long COVID is an emerging public health burden and has been defined as a syndrome with common symptoms of fatigue, shortness of breath, cognitive dysfunction, and others impacting day-to-day life, fluctuating or relapsing over, occurring for at least two months in patients with a history of probable or confirmed SARS CoV-2 infection; usually three months from the onset of illness and cannot be explained by an alternate diagnosis. The actual prevalence of long-term COVID-19 is unknown, but it is believed that more than 17 million patients in Europe may have suffered from it during pandemic.<br><br>PATHOPHYSIOLOGY: Currently, there is limited understanding of the pathophysiology of this syndrome, and multiple hypotheses have been proposed. Our literature review has shown studies reporting tau deposits in tissue samples of the brain from autopsies of COVID-19 patients compared to the control group, and the in-vitro human brain organoid model has shown aberrant phosphorylation of tau protein in response to SARS-CoV-2 infection. Tauopathies, a group of neurodegenerative disorders with the salient features of tau deposits, can manifest different symptoms based on the anatomical region of brain involvement and have been shown to affect the peripheral nervous system as well and explained even in rat model studies. Long COVID has more than 203 symptoms, with predominant symptoms of fatigue, dyspnea, and cognitive dysfunction, which tauopathy-induced CNS and peripheral nervous system dysfunction can explain. There have been no studies up till now to reveal the pathophysiology of long COVID. Based on our literature review, aberrant tau phosphorylation is a promising hypothesis that can be explored in future studies. Therapeutic approaches for tauopathies have multidimensional aspects, including targeting post-translational modifications, tau aggregation, and tau clearance through the autophagy process with the help of lysosomes, which can be potential targets for developing therapeutic interventions for the long COVID. In addition, future studies can attempt to find the tau proteins in CSF and use those as biomarkers for the long COVID.}, }
@article {pmid37957515, year = {2024}, author = {Gomaa, AA and Abdel-Wadood, YA and Thabet, RH and Gomaa, GA}, title = {Pharmacological evaluation of vitamin D in COVID-19 and long COVID-19: recent studies confirm clinical validation and highlight metformin to improve VDR sensitivity and efficacy.}, journal = {Inflammopharmacology}, volume = {32}, number = {1}, pages = {249-271}, pmid = {37957515}, issn = {1568-5608}, mesh = {Animals ; Humans ; Chronic Disease ; *COVID-19 ; Observational Studies as Topic ; Post-Acute COVID-19 Syndrome ; Randomized Controlled Trials as Topic ; Receptors, Calcitriol ; SARS-CoV-2 ; *Vitamin D/pharmacology/therapeutic use ; *Vitamins/pharmacology/therapeutic use ; }, abstract = {Nearly four years after its first appearance, and having gone from pandemic to endemic, the SARS-CoV-2 remains out of control globally. The purpose of this study was to evaluate the clinical efficacy of vitamin D (VD) in COVID-19 and long COVID-19, explain the discrepancy in clinical outcomes and highlight the potential impact of metformin on VD efficacy in recent articles. Articles from January 2022 to August 2023 were selected for this review. The objective of this study was achieved by reviewing, analyzing, and discussing articles demonstrating (1) the mechanism of action of VD (2) observational or randomized clinical trials (RCTs) that support or not the beneficial clinical effects of VD in COVID-19 or long COVID. (3) genetic and non-genetic reasons for the variation in the effects of VD. Articles were collected from electronic databases such as PubMed, Scopus, MEDLINE, Google Scholar, Egyptian Knowledge Bank, Science Direct, and Cochrane Database of Systematic Reviews. Twenty three studies conducted in vitro or in animal models indicated that VD may act in COVID-19 through protecting the respiratory system by antimicrobial peptide cathelicidins, reducing lung inflammation, regulating innate and adaptive immune functions and up regulation of autophagy gene activity. Our review identified 58 clinical studies that met the criteria. The number of publications supporting a beneficial clinical activity of VD in treating COVID-19 was 49 (86%), including 12 meta-analyses. Although the total patients included in all articles was 14,071,273, patients included in publications supporting a beneficial role of VD in COVID-19 were 14,029,411 (99.7%). Collectively, extensive observational studies indicated a decisive relationship between low VD levels and the severity of COVID-19 and mortality outcomes. Importantly, evidence from intervention studies has demonstrated the effectiveness of VD supplements in treating COVID-19. Furthermore, the results of 4 observational studies supported the beneficial role of VD in alleviating symptoms of long COVID-19 disease. However, eight RCTs and one meta-analysis of RCTs may contain low-grade evidence against a beneficial role of VD in COVID-19. Twenty-five articles have addressed the association between VDR and DBP genetic polymorphisms and treatment failure of VD in COVID-19. Impaired VDR signaling may underlie the variability of VD effects as non-genetic mechanisms. Interestingly, in recent studies, metformin has a beneficial therapeutic role in COVID-19 and long COVID-19, possibly by improving AMPK signaling of the VDR and enhancing the efficacy of the VD. In conclusion, evidence has been significantly strengthened over the past 18 months, with several meta-analyses and RCTs reporting conclusive beneficial effects of VD supplementation against COVID-19 and highlighting metformin to improve VDR sensitivity and efficacy in treating COVID-19 and long COVID-19.}, }
@article {pmid37958264, year = {2023}, author = {Luchian, ML and Higny, J and Benoit, M and Robaye, B and Berners, Y and Henry, JP and Colle, B and Xhaët, O and Blommaert, D and Droogmans, S and Motoc, AI and Cosyns, B and Gabriel, L and Guedes, A and Demeure, F}, title = {Unmasking Pandemic Echoes: An In-Depth Review of Long COVID's Unabated Cardiovascular Consequences beyond 2020.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {21}, pages = {}, pmid = {37958264}, issn = {2075-4418}, abstract = {At the beginning of 2020, coronavirus disease 2019 (COVID-19) emerged as a new pandemic, leading to a worldwide health crisis and overwhelming healthcare systems due to high numbers of hospital admissions, insufficient resources, and a lack of standardized therapeutic protocols. Multiple genetic variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been detected since its first public declaration in 2020, some of them being considered variants of concern (VOCs) corresponding to several pandemic waves. Nevertheless, a growing number of COVID-19 patients are continuously discharged from hospitals, remaining symptomatic even months after their first episode of COVID-19 infection. Long COVID-19 or 'post-acute COVID-19 syndrome' emerged as the new pandemic, being characterized by a high variability of clinical manifestations ranging from cardiorespiratory and neurological symptoms such as chest pain, exertional dyspnoea or cognitive disturbance to psychological disturbances, e.g., depression, anxiety or sleep disturbance with a crucial impact on patients' quality of life. Moreover, Long COVID is viewed as a new cardiovascular risk factor capable of modifying the trajectory of current and future cardiovascular diseases, altering the patients' prognosis. Therefore, in this review we address the current definitions of Long COVID and its pathophysiology, with a focus on cardiovascular manifestations. Furthermore, we aim to review the mechanisms of acute and chronic cardiac injury and the variety of cardiovascular sequelae observed in recovered COVID-19 patients, in addition to the potential role of Long COVID clinics in the medical management of this new condition. We will further address the role of future research for a better understanding of the actual impact of Long COVID and future therapeutic directions.}, }
@article {pmid37964554, year = {2023}, author = {Pierre, V and Draica, F and Di Fusco, M and Yang, J and Nunez-Gonzalez, S and Kamar, J and Lopez, S and Moran, MM and Nguyen, J and Alvarez, P and Cha-Silva, A and Gavaghan, M and Yehoshua, A and Stapleton, N and Burnett, H}, title = {The impact of vaccination and outpatient treatment on the economic burden of Covid-19 in the United States omicron era: a systematic literature review.}, journal = {Journal of medical economics}, volume = {26}, number = {1}, pages = {1519-1531}, doi = {10.1080/13696998.2023.2281882}, pmid = {37964554}, issn = {1941-837X}, mesh = {Humans ; *COVID-19/prevention &amp; control ; Financial Stress ; Post-Acute COVID-19 Syndrome ; Outpatients ; Vaccination ; *Vaccines ; }, abstract = {AIMS: To identify and synthesize evidence regarding how coronavirus disease 2019 (COVID-19) interventions, including vaccines and outpatient treatments, have impacted healthcare resource use (HCRU) and costs in the United States (US) during the Omicron era.<br><br>MATERIALS AND METHODS: A systematic literature review (SLR) was performed to identify articles published between 1 January 2021 and 10 March 2023 that assessed the impact of vaccination and outpatient treatment on costs and HCRU outcomes associated with COVID-19. Screening was performed by two independent researchers using predefined inclusion/exclusion criteria.<br><br>RESULTS: Fifty-eight unique studies were included in the SLR, of which all reported HCRU outcomes, and one reported costs. Overall, there was a significant reduction in the risk of COVID-19-related hospitalization for patients who received an original monovalent primary series vaccine plus booster dose vs. no vaccination. Moreover, receipt of a booster vaccine was associated with a lower risk of hospitalization vs. primary series vaccination. Evidence also indicated a significantly reduced risk of hospitalizations among recipients of nirmatrelvir/ritonavir (NMV/r), remdesivir, sotrovimab, and molnupiravir compared to non-recipients. Treated and/or vaccinated patients also experienced reductions in intensive care unit (ICU) admissions, length of stay, and emergency department (ED)/urgent care clinic encounters.<br><br>LIMITATIONS: The identified studies may not represent unique patient populations as many utilized the same regional/national data sources. Synthesis of the evidence was also limited by differences in populations, outcome definitions, and varying duration of follow-up across studies. Additionally, significant gaps, including HCRU associated with long COVID and various high-risk populations and cost data, were observed.<br><br>CONCLUSIONS: Despite evidence gaps, findings from the SLR highlight the significant positive impact that vaccination and outpatient treatment have had on HCRU in the US, including periods of Omicron predominance. Continued research is needed to inform clinical and policy decision-making in the US as COVID-19 continues to evolve as an endemic disease.}, }
@article {pmid37985854, year = {2024}, author = {Sievers, BL and Cheng, MTK and Csiba, K and Meng, B and Gupta, RK}, title = {SARS-CoV-2 and innate immunity: the good, the bad, and the "goldilocks".}, journal = {Cellular &amp; molecular immunology}, volume = {21}, number = {2}, pages = {171-183}, pmid = {37985854}, issn = {2042-0226}, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19 ; COVID-19 Vaccines ; Post-Acute COVID-19 Syndrome ; Immunity, Innate ; }, abstract = {An ancient conflict between hosts and pathogens has driven the innate and adaptive arms of immunity. Knowledge about this interplay can not only help us identify biological mechanisms but also reveal pathogen vulnerabilities that can be leveraged therapeutically. The humoral response to SARS-CoV-2 infection has been the focus of intense research, and the role of the innate immune system has received significantly less attention. Here, we review current knowledge of the innate immune response to SARS-CoV-2 infection and the various means SARS-CoV-2 employs to evade innate defense systems. We also consider the role of innate immunity in SARS-CoV-2 vaccines and in the phenomenon of long COVID.}, }
@article {pmid37987274, year = {2023}, author = {Sánchez-García, JC and Reinoso-Cobo, A and Piqueras-Sola, B and Cortés-Martín, J and Menor-Rodríguez, MJ and Alabau-Dasi, R and Rodríguez-Blanque, R}, title = {Long COVID and Physical Therapy: A Systematic Review.}, journal = {Diseases (Basel, Switzerland)}, volume = {11}, number = {4}, pages = {}, pmid = {37987274}, issn = {2079-9721}, abstract = {Prolonged COVID is a persistent condition following the initial COVID-19 infection, which is characterized by a variety of symptoms that may include fatigue, muscle pain, sleep disturbances, "brain fog", respiratory, cardiovascular, digestive, neurological and dermatological symptoms. Physical therapy has been identified as a crucial aspect of the management of patients with long COVID, as it can help improve symptoms and overall physical function. The investigation of long COVID poses significant challenges due to the diversity and variability of symptoms, lack of clear diagnostic criteria, and limited understanding of the underlying mechanisms. The aim of this study is to conduct a systematic review of studies conducted in patients with long COVID in conjunction with interventions targeting respiratory function, particularly involving physical activity. To this end, we conducted a systematic review to analyze studies conducted on treatment programs for long COVID based on some form of physical activity. The protocol of the review was registered in the PROSPERO website, and the databases PubMed, Scopus, CINAHL and WOS were searched. Of the 62 initial articles, six were included in the review. The results obtained have positive implications for the advancement of physical activity as a therapeutic intervention for individuals with long COVID-19 and the conceptualization of evidence-based treatment protocols. Statistically significant results have been observed in studies of at least 6 weeks duration, in which inspiratory muscle training exercises are proposed. Further research is needed to better understand long COVID and develop effective treatment strategies.}, }
@article {pmid38002002, year = {2023}, author = {Hu, Y and Liu, Y and Zheng, H and Liu, L}, title = {Risk Factors for Long COVID in Older Adults.}, journal = {Biomedicines}, volume = {11}, number = {11}, pages = {}, pmid = {38002002}, issn = {2227-9059}, support = {32070923//National Natural Science Foundation of China/ ; 2022SCP010//The High-level Talent Promotion and Training Project of Kunming/ ; 2021-I2M-1-043//CAMS Innovation Fund for Medical Sciences/ ; }, abstract = {As time has passed following the COVID-19 pandemic, individuals infected with SARS-CoV-2 have gradually exhibited a variety of symptoms associated with long COVID in the postacute phase of infection. Simultaneously, in many countries worldwide, the process of population aging has been accelerating. Within this context, the elderly population has not only become susceptible and high-risk during the acute phase of COVID-19 but also has considerable risks when confronting long COVID. Elderly individuals possess specific immunological backgrounds, and during the process of aging, their immune systems can enter a state known as "immunosenescence". This further exacerbates "inflammaging" and the development of various comorbidities in elderly individuals, rendering them more susceptible to long COVID. Additionally, long COVID can inflict both physical and mental harm upon elderly people, thereby reducing their overall quality of life. Consequently, the impact of long COVID on elderly people should not be underestimated. This review seeks to summarize the infection characteristics and intrinsic factors of older adults during the COVID-19 pandemic, with a focus on the physical and mental impact of long COVID. Additionally, it aims to explore potential strategies to mitigate the risk of long COVID or other emerging infectious diseases among older adults in the future.}, }
@article {pmid38004261, year = {2023}, author = {Mohan, A and Iyer, VA and Kumar, D and Batra, L and Dahiya, P}, title = {Navigating the Post-COVID-19 Immunological Era: Understanding Long COVID-19 and Immune Response.}, journal = {Life (Basel, Switzerland)}, volume = {13}, number = {11}, pages = {}, pmid = {38004261}, issn = {2075-1729}, abstract = {The COVID-19 pandemic has affected the world unprecedentedly, with both positive and negative impacts. COVID-19 significantly impacted the immune system, and understanding the immunological consequences of COVID-19 is essential for developing effective treatment strategies. The purpose of this review is to comprehensively explore and provide insights into the immunological aspects of long COVID-19, a phenomenon where individuals continue to experience a range of symptoms and complications, even after the acute phase of COVID-19 infection has subsided. The immune system responds to the initial infection by producing various immune cells and molecules, including antibodies, T cells, and cytokines. However, in some patients, this immune response becomes dysregulated, leading to chronic inflammation and persistent symptoms. Long COVID-19 encompasses diverse persistent symptoms affecting multiple organ systems, including the respiratory, cardiovascular, neurological, and gastrointestinal systems. In the post-COVID-19 immunological era, long COVID-19 and its impact on immune response have become a significant concern. Post-COVID-19 immune pathology, including autoimmunity and immune-mediated disorders, has also been reported in some patients. This review provides an overview of the current understanding of long COVID-19, its relationship to immunological responses, and the impact of post-COVID-19 immune pathology on patient outcomes. Additionally, the review addresses the current and potential treatments for long COVID-19, including immunomodulatory therapies, rehabilitation programs, and mental health support, all of which aim to improve the quality of life for individuals with long COVID-19. Understanding the complex interplay between the immune system and long COVID-19 is crucial for developing targeted therapeutic strategies and providing optimal care in the post-COVID-19 era.}, }
@article {pmid38014645, year = {2024}, author = {Volk, P and Rahmani Manesh, M and Warren, ME and Besko, K and Gonçalves de Andrade, E and Wicki-Stordeur, LE and Swayne, LA}, title = {Long-term neurological dysfunction associated with COVID-19: Lessons from influenza and inflammatory diseases?.}, journal = {Journal of neurochemistry}, volume = {168}, number = {10}, pages = {3500-3511}, doi = {10.1111/jnc.16016}, pmid = {38014645}, issn = {1471-4159}, support = {GA4-177766//CIHR/Canada ; PJT 185887//CIHR/Canada ; GA4-177766//CIHR/Canada ; PJT 185887//CIHR/Canada ; }, mesh = {Humans ; *COVID-19/complications ; *Influenza, Human/complications/epidemiology ; Nervous System Diseases/etiology ; SARS-CoV-2/pathogenicity ; Cognitive Dysfunction/etiology ; Inflammation ; Fatigue/etiology ; }, abstract = {As the COVID-19 pandemic persists, SARS-CoV-2 infection is increasingly associated with long-term neurological side effects including cognitive impairment, fatigue, depression, and anxiety, colloquially known as "long-COVID." While the full extent of long-COVID neuropathology across years or even decades is not yet known, we can perhaps take direction from long-standing research into other respiratory diseases, such as influenza, that can present with similar long-term neurological consequences. In this review, we highlight commonalities in the neurological impacts of influenza and COVID-19. We first focus on the common potential mechanisms underlying neurological sequelae of long-COVID and influenza, namely (1) viral neurotropism and (2) dysregulated peripheral inflammation. The latter, namely heightened peripheral inflammation leading to central nervous system dysfunction, is emerging as a shared mechanism in various peripheral inflammatory or inflammation-associated diseases and conditions. We then discuss historical and modern examples of influenza- and COVID-19-associated cognitive impairment, depression, anxiety, and fatigue, revealing key similarities in their neurological sequelae. Although we are learning that the effects of influenza and COVID differ somewhat in terms of their influence on the brain, as the impacts of long-COVID grow, such comparisons will likely prove valuable in guiding ongoing research into long-COVID, and perhaps foreshadow what could be in store for individuals with COVID-19 and their brain health.}, }
@article {pmid38017426, year = {2023}, author = {Guo, B and Zhao, C and He, MZ and Senter, C and Zhou, Z and Peng, J and Li, S and Fitzpatrick, AL and Lindström, S and Stebbins, RC and Noppert, GA and Li, C}, title = {Identifying patterns of reported findings on long-term cardiac complications of COVID-19: a systematic review and meta-analysis.}, journal = {BMC medicine}, volume = {21}, number = {1}, pages = {468}, pmid = {38017426}, issn = {1741-7015}, support = {R01 AG075719/AG/NIA NIH HHS/United States ; R00AG062749/GF/NIH HHS/United States ; R01AG075719/GF/NIH HHS/United States ; T32 HD049311/HD/NICHD NIH HHS/United States ; R00 AG062749/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/complications/epidemiology ; Cross-Sectional Studies ; Arrhythmias, Cardiac/epidemiology/etiology ; Chest Pain ; }, abstract = {INTRODUCTION: Prior reviews synthesized findings of studies on long-term cardiac complications of COVID-19. However, the reporting and methodological quality of these studies has not been systematically evaluated. Here, we conducted a systematic review and meta-analysis on long-term cardiac complications of COVID-19 and examined patterns of reported findings by study quality and characteristics.<br><br>METHODS: We searched for studies examining long-term cardiac complications of COVID-19 that persisted for 4&#xa0;weeks and over. A customized Newcastle-Ottawa scale (NOS) was used to evaluate the quality of included studies. Meta-analysis was performed to generate prevalence estimates of long-term cardiac complications across studies. Stratified analyses were further conducted to examine the prevalence of each complication by study quality and characteristics. The GRADE approach was used to determine the level of evidence for complications included in the meta-analysis.<br><br>RESULTS: A total number of 150 studies describing 57 long-term cardiac complications were included in this review, and 137 studies reporting 17 complications were included in the meta-analysis. Only 25.3% (n&#x2009;=&#x2009;38) of studies were of high quality based on the NOS quality assessment. Chest pain and arrhythmia were the most widely examined long-term complications. When disregarding study quality and characteristics, summary prevalence estimates for chest and arrhythmia were 9.79% (95% CI 7.24-13.11) and 8.22% (95% CI 6.46-10.40), respectively. However, stratified analyses showed that studies with low-quality scores, small sample sizes, unsystematic sampling methods, and cross-sectional design were more likely to report a higher prevalence of complications. For example, the prevalence of chest pain was 22.17% (95% CI 14.40-32.55), 11.08% (95% CI 8.65-14.09), and 3.89% (95% CI 2.49-6.03) in studies of low, medium, and high quality, respectively. Similar patterns were observed for arrhythmia and other less examined long-term cardiac complications.<br><br>CONCLUSION: There is a wide spectrum of long-term cardiac complications of COVID-19. Reported findings from previous studies are strongly related to study quality, sample sizes, sampling methods, and designs, underscoring the need for high-quality epidemiologic studies to characterize these complications and understand their etiology.}, }
@article {pmid38018136, year = {2023}, author = {Boccatonda, A and Campello, E and Simion, C and Simioni, P}, title = {Long-term hypercoagulability, endotheliopathy and inflammation following acute SARS-CoV-2 infection.}, journal = {Expert review of hematology}, volume = {16}, number = {12}, pages = {1035-1048}, doi = {10.1080/17474086.2023.2288154}, pmid = {38018136}, issn = {1747-4094}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Endothelial Cells/metabolism ; Inflammation ; *Thrombosis/etiology/metabolism ; *Thrombophilia/etiology ; }, abstract = {INTRODUCTION: both symptomatic and asymptomatic SARS-CoV-2 infections - coined Coronavirus disease 2019 (COVID-19) - have been linked to a higher risk of cardiovascular events after recovery.<br><br>AREAS COVERED: our review aims to summarize the latest evidence on the increased thrombotic and cardiovascular risk in recovered COVID-19 patients and to examine the pathophysiological mechanisms underlying the interplay among endothelial dysfunction, inflammatory response and coagulation in long-COVID. We performed a systematic search of studies on hypercoagulability, endothelial dysfunction and inflammation after SARS-CoV-2 infection.<br><br>EXPERT OPINION: endothelial dysfunction is a major pathophysiological mechanism responsible for most clinical manifestations in COVID-19. The pathological activation of endothelial cells by a virus infection results in a pro-adhesive and chemokine-secreting phenotype, which in turn promotes the recruitment of circulating leukocytes. Cardiovascular events after COVID-19 appear to be related to persistent immune dysregulation. Patients with long-lasting symptoms display higher amounts of proinflammatory molecules such as tumor necrosis factor-&#x3b1;, interferon &#x3b3; and interleukins 2 and 6. Immune dysregulation can trigger the activation of the coagulation pathway. The formation of extensive microclots in vivo, both during acute COVID-19 and in long-COVID-19, appears to be a relevant mechanism responsible for persistent symptoms and cardiovascular events.}, }
@article {pmid38019841, year = {2023}, author = {Hoshijima, H and Mihara, T and Seki, H and Hyuga, S and Kuratani, N and Shiga, T}, title = {Incidence of long-term post-acute sequelae of SARS-CoV-2 infection related to pain and other symptoms: A systematic review and meta-analysis.}, journal = {PloS one}, volume = {18}, number = {11}, pages = {e0250909}, pmid = {38019841}, issn = {1932-6203}, mesh = {Humans ; *COVID-19/complications/epidemiology ; Post-Acute COVID-19 Syndrome ; Incidence ; Anosmia ; SARS-CoV-2 ; Headache/epidemiology/etiology ; Dyspnea/epidemiology ; }, abstract = {BACKGROUND: Persistent symptoms are reported in patients who survive the initial stage of COVID-19, often referred to as "long COVID" or "post-acute sequelae of SARS-CoV-2 infection" (PASC); however, evidence on their incidence is still lacking, and symptoms relevant to pain are yet to be assessed.<br><br>METHODS: A literature search was performed using the electronic databases PubMed, EMBASE, Scopus, and CHINAL and preprint servers MedR&#x3c7;iv and BioR&#x3c7;iv through January 15, 2021. The primary outcome was pain-related symptoms such as headache or myalgia. Secondary outcomes were symptoms relevant to pain (depression or muscle weakness) and symptoms frequently reported (anosmia and dyspnea). Incidence rates of symptoms were pooled using inverse variance methods with a DerSimonian-Laird random-effects model. The source of heterogeneity was explored using meta-regression, with follow-up period, age and sex as covariates.<br><br>RESULTS: In total, 38 studies including 19,460 patients were eligible. Eight pain-related symptoms and 26 other symptoms were identified. The highest pooled incidence among pain-related symptoms was chest pain (17%, 95% confidence interval [CI], 11%-24%), followed by headache (16%, 95% CI, 9%-27%), arthralgia (13%, 95% CI, 7%-24%), neuralgia (12%, 95% CI, 3%-38%) and abdominal pain (11%, 95% CI, 7%-16%). The highest pooled incidence among other symptoms was fatigue (44%, 95% CI, 32%-57%), followed by insomnia (27%, 95% CI, 10%-55%), dyspnea (26%, 95% CI, 17%-38%), weakness (25%, 95% CI, 8%-56%) and anosmia (19%, 95% CI, 13%-27%). Substantial heterogeneity was identified (I2, 50-100%). Meta-regression analyses partially accounted for the source of heterogeneity, and yet, 53% of the symptoms remained unexplained.<br><br>CONCLUSIONS: The current meta-analysis may provide a complete picture of incidence in PASC. It remains unclear, however, whether post-COVID symptoms progress or regress over time or to what extent PASC are associated with age or sex.}, }
@article {pmid38020714, year = {2023}, author = {Wu, J and Yang, H and Yu, D and Yang, X}, title = {Blood-derived product therapies for SARS-CoV-2 infection and long COVID.}, journal = {MedComm}, volume = {4}, number = {6}, pages = {e426}, pmid = {38020714}, issn = {2688-2663}, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is capable of large-scale transmission and has caused the coronavirus disease 2019 (COVID-19) pandemic. Patients with COVID-19 may experience persistent long-term health issues, known as long COVID. Both acute SARS-CoV-2 infection and long COVID have resulted in persistent negative impacts on global public health. The effective application and development of blood-derived products are important strategies to combat the serious damage caused by COVID-19. Since the emergence of COVID-19, various blood-derived products that target or do not target SARS-CoV-2 have been investigated for therapeutic applications. SARS-CoV-2-targeting blood-derived products, including COVID-19 convalescent plasma, COVID-19 hyperimmune globulin, and recombinant anti-SARS-CoV-2 neutralizing immunoglobulin G, are virus-targeting and can provide immediate control of viral infection in the short term. Non-SARS-CoV-2-targeting blood-derived products, including intravenous immunoglobulin and human serum albumin exhibit anti-inflammatory, immunomodulatory, antioxidant, and anticoagulatory properties. Rational use of these products can be beneficial to patients with SARS-CoV-2 infection or long COVID. With evidence accumulated since the pandemic began, we here summarize the progress of blood-derived product therapies for COVID-19, discuss the effective methods and scenarios regarding these therapies, and provide guidance and suggestions for clinical treatment.}, }
@article {pmid38024037, year = {2023}, author = {Hulscher, N and Procter, BC and Wynn, C and McCullough, PA}, title = {Clinical Approach to Post-acute Sequelae After COVID-19 Infection and Vaccination.}, journal = {Cureus}, volume = {15}, number = {11}, pages = {e49204}, pmid = {38024037}, issn = {2168-8184}, abstract = {The spike protein of SARS-CoV-2 has been found to exhibit pathogenic characteristics and be a possible cause of post-acute sequelae after SARS-CoV-2 infection or COVID-19 vaccination. COVID-19 vaccines utilize a modified, stabilized prefusion spike protein that may share similar toxic effects with its viral counterpart. The aim of this study is to investigate possible mechanisms of harm to biological systems from SARS-CoV-2 spike protein and vaccine-encoded spike protein and to propose possible mitigation strategies. We searched PubMed, Google Scholar, and 'grey literature' to find studies that (1) investigated the effects of the spike protein on biological systems, (2) helped differentiate between viral and vaccine-generated spike proteins, and (3) identified possible spike protein detoxification protocols and compounds that had signals of benefit and acceptable safety profiles. We found abundant evidence that SARS-CoV-2 spike protein may cause damage in the cardiovascular, hematological, neurological, respiratory, gastrointestinal, and immunological systems. Viral and vaccine-encoded spike proteins have been shown to play a direct role in cardiovascular and thrombotic injuries from both SARS-CoV-2 and vaccination. Detection of spike protein for at least 6-15 months after vaccination and infection in those with post-acute sequelae indicates spike protein as a possible primary contributing factor to long COVID. We rationalized that these findings give support to the potential benefit of spike protein detoxification protocols in those with long-term post-infection and/or vaccine-induced complications. We propose a base spike detoxification protocol, composed of oral nattokinase, bromelain, and curcumin. This approach holds immense promise as a base of clinical care, upon which additional therapeutic agents are applied with the goal of aiding in the resolution of post-acute sequelae after SARS-CoV-2 infection and COVID-19 vaccination. Large-scale, prospective, randomized, double-blind, placebo-controlled trials are warranted in order to determine the relative risks and benefits of the base spike detoxification protocol.}, }
@article {pmid38025440, year = {2023}, author = {Perea-Flórez, F and Javier-Murillo, N and Lapeyre-Rivera, A and Gamonal, B and Cabanillas-Lazo, M and Velásquez-Rimachi, V and Alva-Diaz, C}, title = {Prevalence and incidence of neuropsychiatric disorders in post hospitalized COVID-19 patients in South America: a systematic review and meta-analysis.}, journal = {Frontiers in psychiatry}, volume = {14}, number = {}, pages = {1163989}, pmid = {38025440}, issn = {1664-0640}, abstract = {INTRODUCTION: There are multiple reports of neuropsychiatric disorders (NDs) such as stress, depression, post-traumatic stress disorder (PTSD), or anxiety, in patients who have survived the acute phase of COVID-19, being even more frequent in people who were hospitalized with moderate or severe disease. South America (SA) was one of the most affected continents during this time due to its health, social, political and economic context. We aimed to determine the prevalence and incidence of NDs in patients following hospitalization for COVID-19 in SA.<br><br>MATERIALS AND METHODS: We searched in PubMed, Embase, Scopus, Web of Science, LILACS, SciELO, and Google Scholar databases up to October 2022. We performed proportion meta-analysis with a random-effect model and Freeman-Tukey Double Arcsine transformation using the STATA 16.1 program. Finally, we evaluated heterogeneity by subgroup analysis and certainty of evidence with the GRADE approach.<br><br>RESULTS: We included eight studies from four countries. We only pooled six studies with prevalence measures. The estimated prevalence of all NDs was 31.48% (two-studies, 95%CI: 25.82-37.43). Depression, anxiety, insomnia, PTSD, and memory alterations had a pooled prevalence of 16.23% (three-studies, 95%CI: 7.18-27.93, I2: 94.22), 18.72% (three-studies, 95%CI: 11.65-26.97, I2: 87.56), 43.07% (three-studies, 95%CI: 32.77-53.37, I2: 92.61), 31.78% (three-studies, 95%CI: 14.33-52.40, I2: 97.96), and 38.24% (two-studies, 95%CI: 35.5-40.97), respectively. The evidence included was deemed as moderate to high certainty.<br><br>CONCLUSION: We suggest that NDs should be prioritized in research and care in South America with public policies that can support their identification and prompt management to improve the quality of life of patients. More studies are needed to adequately study the prevalence of NDs in South America, their associated factors, and evaluate the causes of heterogeneity.<br><br>https://doi.org/10.6084/m9.figshare.21901041.v1.}, }
@article {pmid38043758, year = {2024}, author = {Kitselman A, K and Bédard-Matteau, J and Rousseau, S and Tabrizchi, R and Daneshtalab, N}, title = {Sex differences in vascular endothelial function related to acute and long COVID-19.}, journal = {Vascular pharmacology}, volume = {154}, number = {}, pages = {107250}, doi = {10.1016/j.vph.2023.107250}, pmid = {38043758}, issn = {1879-3649}, mesh = {Humans ; Female ; Male ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Fatigue Syndrome, Chronic/epidemiology ; Sex Characteristics ; *Vascular Diseases ; }, abstract = {The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has been at the forefront of health sciences research since its emergence in China in 2019 that quickly led to a global pandemic. As a result of this research, and the large numbers of infected patients globally, there were rapid enhancements made in our understanding of Coronavirus disease 2019 (COVID-19) pathology, including its role in the development of uncontrolled immune responses and its link to the development of endotheliitis and endothelial dysfunction. There were also some noted differences in the rate and severity of infection between males and females with acute COVID. Some individuals infected with SARS-CoV-2 also experience long-COVID, an important hallmark symptom of this being Myalgic Encephalomyelitis-Chronic Fatigue Syndrome (ME-CFS), also experienced differently between males and females. The purpose of this review is to discuss the impact of sex on the vasculature during acute and long COVID-19, present any link between ME-CFS and endothelial dysfunction, and provide evidence for the relationship between ME-CFS and the immune system. We also will delineate biological sex differences observed in other post viral infections and, assess if sex differences exist in how the immune system responds to viral infection causing ME-CFS.}, }
@article {pmid38054899, year = {2023}, author = {Chilosi, M and Doglioni, C and Ravaglia, C and Piciucchi, S and Dubini, A and Stefanizzi, L and Poletti, V}, title = {COVID-19. Biology, pathophysiology, and immunology: a pathologist view.}, journal = {Pathologica}, volume = {115}, number = {5}, pages = {248-256}, pmid = {38054899}, issn = {1591-951X}, mesh = {Humans ; *COVID-19 ; Pathologists ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Biology ; }, abstract = {Even if the SARS-CoV-2 pandemic has been declared over, several risks and clinical problems remain to be faced, including long-COVID sequelae and possible outbreaks of pathogenic variants. Intense research on COVID-19 has provided in these few years a striking amount of data covering different fields and disciplines, which can help to provide a knowledge shield against new potential infective spreads, and may also potentially be applied to other fields of medicine, including oncology and neurology. Nevertheless, areas of uncertainty still remain regarding the pathogenic mechanisms that subtend the multifaceted manifestations of the disease. To better clarify the pathogenesis of the disease, a systematic multidisciplinary evaluation of the many mechanisms involved in COVID-19 is mandatory, including clinical, physiological, radiological, immunological and pathological studies. In COVID-19 syndrome the pathological studies have been mainly performed on autopsy cases, and only a few studies are available on biopsies. Nevertheless, these studies have provided relevant information that can substantially contribute to decipher the complex scenario characterizing the different forms of COVID-19 and long-COVID-19. In this review the data provided by pathological investigations are recapitulated and discussed, in the light of different hypothesis and data provided by clinical, physiological and immunological data.}, }
@article {pmid38054902, year = {2023}, author = {Olteanu, GE and Pezzuto, F and Lunardi, F and Fortarezza, F and Dubini, A and Calabrese, F}, title = {Exploring the pathologist's role in understanding COVID-19: from pneumonia to long-COVID lung sequelae.}, journal = {Pathologica}, volume = {115}, number = {5}, pages = {275-283}, pmid = {38054902}, issn = {1591-951X}, mesh = {Humans ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; Artificial Intelligence ; Pathologists ; SARS-CoV-2 ; *Pneumonia ; Lung/diagnostic imaging ; }, abstract = {The crucial role of pathologists in enhancing our understanding of SARS-CoV-2-related disease, from initial pneumonia manifestations to persistent long COVID lung symptoms, is the focus of this review. Pathological explorations have offered unprecedented insights into the early stages of severe COVID-19, shedding light on the interplay between the virus and subsequent complications, thereby shaping clinical approaches. Growing interest is directed to residual lung abnormalities of COVID-19 survivors. Although various radiological studies reported long-lasting pulmonary changes (e.g., ground glass opacities, reticulations, and bronchiectasis), the true incidence of pulmonary fibrosis and corresponding pathological findings in these patients remains largely unknown. There are a few high-impact and knowledgeable works on late complications in COVID-19 survivors, several coming from explant or autopsy cases, and rare cases from in vivo sampling. The study of biopsy samples has further deepened our knowledge of the aftermath of COVID-19 on lung tissue, uncovering alterations at the cellular level and shifts in vascular and epithelial dynamics. Despite the substantial progress made, future research is needed to devise a uniform strategy for interpreting lung biopsies, with a focus on leveraging advanced tools such as molecular and digital pathology techniques, along with artificial intelligence.}, }
@article {pmid38055113, year = {2024}, author = {Rayner, DG and Wang, E and Su, C and Patel, OD and Aleluya, S and Giglia, A and Zhu, E and Siddique, M}, title = {Risk factors for long COVID in children and adolescents: a systematic review and meta-analysis.}, journal = {World journal of pediatrics : WJP}, volume = {20}, number = {2}, pages = {133-142}, pmid = {38055113}, issn = {1867-0687}, mesh = {Humans ; *COVID-19/epidemiology ; Child ; Risk Factors ; Adolescent ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The long-term sequelae of COVID-19 in children and adolescents remain poorly understood and characterized. This systematic review and meta-analysis sought to summarize the risk factors for long COVID in the pediatric population.<br><br>METHODS: We searched six databases from January 2020 to May 2023 for observational studies reporting on risk factors for long COVID or persistent symptoms those were present 12 or more weeks post-infection using multivariable regression analyses. Trial registries, reference lists of included studies, and preprint servers were hand-searched for relevant studies. Random-effects meta-analyses were conducted to pool odds ratios for each risk factor. Individual study risk of bias was rated using QUIPS, and the GRADE framework was used to assess the certainty of evidence for each unique factor.<br><br>RESULTS: Sixteen observational studies (N&#x2009;=&#x2009;46,262) were included, and 19 risk factors were amenable to meta-analysis. With moderate certainty in the evidence, age (per 2-year increase), allergic rhinitis, obesity, previous respiratory diseases, hospitalization, severe acute COVID-19, and symptomatic acute COVID-19 are probably associated with an increased risk of long COVID. Female sex, asthma, comorbidity, and heart diseases may be associated with an increased risk of long COVID, and Asian and Black races may be associated with a decreased risk of long COVID. We did not observe any credible subgroup effects for any risk factor.<br><br>CONCLUSIONS: The current body of literature presents several compelling risk factors for the development of long COVID in the pediatric population. Further research is necessary to elucidate the pathophysiology of long COVID.}, }
@article {pmid38057315, year = {2023}, author = {Liu, X and Xiong, W and Ye, M and Lu, T and Yuan, K and Chang, S and Han, Y and Wang, Y and Lu, L and Bao, Y}, title = {Non-coding RNAs expression in SARS-CoV-2 infection: pathogenesis, clinical significance, and therapeutic targets.}, journal = {Signal transduction and targeted therapy}, volume = {8}, number = {1}, pages = {441}, pmid = {38057315}, issn = {2059-3635}, mesh = {Humans ; *COVID-19/genetics ; Post-Acute COVID-19 Syndrome ; Clinical Relevance ; SARS-CoV-2/genetics ; RNA, Untranslated/genetics ; Biomarkers ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic has been looming globally for three years, yet the diagnostic and treatment methods for COVID-19 are still undergoing extensive exploration, which holds paramount importance in mitigating future epidemics. Host non-coding RNAs (ncRNAs) display aberrations in the context of COVID-19. Specifically, microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) exhibit a close association with viral infection and disease progression. In this comprehensive review, an overview was presented of the expression profiles of host ncRNAs following SARS-CoV-2 invasion and of the potential functions in COVID-19 development, encompassing viral invasion, replication, immune response, and multiorgan deficits which include respiratory system, cardiac system, central nervous system, peripheral nervous system as well as long COVID. Furthermore, we provide an overview of several promising host ncRNA biomarkers for diverse clinical scenarios related to COVID-19, such as stratification biomarkers, prognostic biomarkers, and predictive biomarkers for treatment response. In addition, we also discuss the therapeutic potential of ncRNAs for COVID-19, presenting ncRNA-based strategies to facilitate the development of novel treatments. Through an in-depth analysis of the interplay between ncRNA and COVID-19 combined with our bioinformatic analysis, we hope to offer valuable insights into the stratification, prognosis, and treatment of COVID-19.}, }
@article {pmid38057338, year = {2023}, author = {Frallonardo, L and Segala, FV and Chhaganlal, KD and Yelshazly, M and Novara, R and Cotugno, S and Guido, G and Papagni, R and Colpani, A and De Vito, A and Barbagallo, M and Madeddu, G and Babudieri, S and Lochoro, P and Ictho, J and Putoto, G and Veronese, N and Saracino, A and Di Gennaro, F}, title = {Incidence and burden of long COVID in Africa: a systematic review and meta-analysis.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {21482}, pmid = {38057338}, issn = {2045-2322}, mesh = {Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Incidence ; *Mental Disorders/epidemiology ; Africa/epidemiology ; }, abstract = {Long COVID, also known as "post-acute sequelae of COVID-19," affects at least 65 million individuals worldwide with a wide spectrum of symptoms that may last weeks, months, or permanently. Its epidemiology and burden in Africa are unclear. This meta-analysis examines long-term COVID-19 effects in the WHO African Region. A systematic search in several databases was carried out up to 12 February 2023 including observational studies from African countries reporting the cumulative incidence of long COVID signs and symptoms. Only studies conducted in African countries were included. Several sensitivity and meta-regression analyses were performed. Among 1547 papers initially screened, 25 were included, consisting of 29,213 participants. The incidence of any long COVID symptomatology was 48.6% (95% CI 37.4-59.8) as psychiatric conditions were the most frequent, particularly post-traumatic stress disorder reaching a cumulative incidence of 25% (95% CI 21.1-30.4). Higher age (p = 0.027) and hospitalization (p = 0.05) were associated with a higher frequency of long COVID. Long COVID poses a significant burden in Africa, particularly concerning psychiatric conditions. The study recommends identifying at-risk people and defining treatment strategies and recommendations for African long-COVID patients. High-quality studies addressing this condition in African setting are urgently needed.}, }
@article {pmid38063359, year = {2023}, author = {Ghram, A and Latiri, I and Methnani, J and Souissi, A and Benzarti, W and Toulgui, E and Ben Saad, H}, title = {Effects of cardiorespiratory rehabilitation program on submaximal exercise in patients with long-COVID-19 conditions: a systematic review of randomized controlled trials and recommendations for future studies.}, journal = {Expert review of respiratory medicine}, volume = {17}, number = {12}, pages = {1095-1124}, doi = {10.1080/17476348.2023.2293226}, pmid = {38063359}, issn = {1747-6356}, mesh = {Humans ; *Cardiac Rehabilitation/methods ; *COVID-19/rehabilitation ; Exercise Therapy/methods ; *Exercise Tolerance ; Post-Acute COVID-19 Syndrome ; *Randomized Controlled Trials as Topic ; SARS-CoV-2 ; Walk Test ; }, abstract = {INTRODUCTION: Long-COVID-19 patients (LC19Ps) often experience cardiovascular and respiratory complications. Cardiorespiratory rehabilitation programs (CRRPs) have emerged as promising interventions to enhance exercise capacity in this population. This systematic review aimed to assess the impact of CRRPs on submaximal exercise performance, specifically the 6-minute walk test (6MWT) outcomes, in LC19Ps through an analysis of available randomized controlled trials (RCTs).<br><br>METHODS: A systematic search was conducted in PubMed/Medline and Scopus to identify relevant RCTs. Six RCTs meeting inclusion criteria were included in this review, investigating the effects of CRRPs on 6MWT outcomes in LC19Ps.<br><br>RESULTS: The findings from the included RCTs provide compelling evidence supporting the effectiveness of CRRPs in improving submaximal exercise performance in LC19Ps. These results underscore the potential of CRRPs to enhance submaximal exercise capacity and overall functional well-being in this population. However, future research is imperative to determine optimal CRRPs, including duration, intensity, and specific intervention components. Additionally, the long-term sustainability and durability of CRRP-induced improvements warrant further exploration. Future studies should prioritize patient-centric outcomes and address potential implementation barriers.<br><br>CONCLUSION: CRRPs show promise in ameliorating submaximal exercise performance among LC19Ps. Further research is needed to refine these programs and ensure their lasting impact on this patient group.<br><br>https://doi.org/10.17605/OSF.IO/HMN38. [Figure: see text].}, }
@article {pmid38063895, year = {2024}, author = {Shil, RSK and Hughes, TW and Sargent, BF and Huang, Y and Tamborska, AA and Frank, B and Ellul, MA and Michael, BD}, title = {A clinical approach to the investigation and management of long COVID associated neuropathic pain.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {274}, number = {8}, pages = {1787-1795}, pmid = {38063895}, issn = {1433-8491}, support = {MC_PC_19059/MRF/MRF/United Kingdom ; MR/V007181/1/MRF/MRF/United Kingdom ; MR/V03605X/1/MRF/MRF/United Kingdom ; ISSF201902/3/WT_/Wellcome Trust/United Kingdom ; MR/V007181/1/MRC_/Medical Research Council/United Kingdom ; MR/T028750/1/MRC_/Medical Research Council/United Kingdom ; NIHR133599//National Institute for Health and Care Research/ ; MC_PC_19059/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; MR/V03605X/1/MRC_/Medical Research Council/United Kingdom ; MRF-CPP-R2-2022-100003/MRF/MRF/United Kingdom ; MR/T028750/1/MRF/MRF/United Kingdom ; }, mesh = {Humans ; *COVID-19/complications ; *Neuralgia/etiology/therapy ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {COVID-19 has been associated with a wide range of ongoing symptoms following recovery from the acute SARS-CoV-2 infection. Around one in three people with COVID-19 develop neurological symptoms with many reporting neuropathic pain and associated symptoms, including paraesthesia, numbness, and dysesthesia. Whilst the pathophysiology of long COVID-19-associated neuropathic pain remains unclear, it is likely to be multifactorial. Early identification, exclusion of common alternative causes, and a biopsychosocial approach to the management of the symptoms can help in relieving the burden of disease and improving the quality of life for patients.}, }
@article {pmid38068427, year = {2023}, author = {Choi, YJ and Seo, YB and Seo, JW and Lee, J and Nham, E and Seong, H and Yoon, JG and Noh, JY and Cheong, HJ and Kim, WJ and Kim, EJ and Song, JY}, title = {Effectiveness of Antiviral Therapy on Long COVID: A Systematic Review and Meta-Analysis.}, journal = {Journal of clinical medicine}, volume = {12}, number = {23}, pages = {}, pmid = {38068427}, issn = {2077-0383}, support = {HD22C2045//Korea Health Industry Development Institute/Republic of Korea ; }, abstract = {Antiviral treatment reduces the severity and mortality of SARS-CoV-2 infection; however, its effectiveness against long COVID-19 is unclear. This study aimed to evaluate the effectiveness of antiviral drugs in preventing long COVID and related hospitalizations/deaths. Scientific and medical databases were searched from 1 January 2020 to 30 June 2023. We included observational cohort studies comparing individuals receiving early antiviral therapy for COVID-19 and those receiving supportive treatment. A fixed-effects model was used to merge the effects reported in two or more studies. The risk of post-acute sequelae of COVID-19 (PASC) was combined as an odds ratio (OR). Six studies were selected, including a total of 3,352,235 participants. The occurrence of PASC was 27.5% lower in patients who received antiviral drugs during the early stages of SARS-CoV-2 infection (OR = 0.725; 95% confidence interval [CI] = 0.409-0.747) than in the supportive treatment group. Moreover, the risk of PASC-associated hospitalization and mortality was 29.7% lower in patients receiving early antiviral therapy than in the supportive treatment group (OR = 0.721; 95% CI = 0.697-0.794). Early antiviral therapy was associated with a reduced risk of PASC and related hospitalization or death. Thus, early antiviral therapy is recommended for at-risk individuals.}, }
@article {pmid38069140, year = {2023}, author = {Pietraszko, P and Zorawski, M and Bielecka, E and Sielatycki, P and Zbroch, E}, title = {Mid-Regional Proadrenomedullin in COVID-19-May It Act as a Predictor of Prolonged Cardiovascular Complications?.}, journal = {International journal of molecular sciences}, volume = {24}, number = {23}, pages = {}, pmid = {38069140}, issn = {1422-0067}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; SARS-CoV-2 ; Biomarkers ; Adrenomedullin ; *Cardiovascular Diseases/etiology ; Protein Precursors ; }, abstract = {The rising prevalence of cardiovascular disease (CVD) and the impact of the SARS-CoV-2 pandemic have both led to increased mortality rates, affecting public health and the global economy. Therefore, it is essential to find accessible, non-invasive prognostic markers capable of identifying patients at high risk. One encouraging avenue of exploration is the potential of mid-regional proadrenomedullin (MR-proADM) as a biomarker in various health conditions, especially in the context of CVD and COVID-19. MR-proADM presents the ability to predict mortality, heart failure, and adverse outcomes in CVD, offering promise for improved risk assessment and treatment strategies. On the other hand, an elevated MR-proADM level is associated with disease severity and cytokine storms in patients with COVID-19, making it a predictive indicator for intensive care unit admissions and mortality rates. Moreover, MR-proADM may have relevance in long COVID, aiding in the risk assessment, triage, and monitoring of individuals at increased risk of developing prolonged cardiac issues. Our review explores the potential of MR-proADM as a predictor of enduring cardiovascular complications following COVID-19 infection.}, }
@article {pmid38069362, year = {2023}, author = {Scheim, DE and Vottero, P and Santin, AD and Hirsh, AG}, title = {Sialylated Glycan Bindings from SARS-CoV-2 Spike Protein to Blood and Endothelial Cells Govern the Severe Morbidities of COVID-19.}, journal = {International journal of molecular sciences}, volume = {24}, number = {23}, pages = {}, pmid = {38069362}, issn = {1422-0067}, support = {UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Humans ; *COVID-19 ; Spike Glycoprotein, Coronavirus/metabolism ; SARS-CoV-2/metabolism ; Post-Acute COVID-19 Syndrome ; Endothelial Cells/metabolism ; *Common Cold ; Angiotensin-Converting Enzyme 2/metabolism ; Polysaccharides/metabolism ; Morbidity ; Hypoxia ; Mammals/metabolism ; }, abstract = {Consistent with well-established biochemical properties of coronaviruses, sialylated glycan attachments between SARS-CoV-2 spike protein (SP) and host cells are key to the virus's pathology. SARS-CoV-2 SP attaches to and aggregates red blood cells (RBCs), as shown in many pre-clinical and clinical studies, causing pulmonary and extrapulmonary microthrombi and hypoxia in severe COVID-19 patients. SARS-CoV-2 SP attachments to the heavily sialylated surfaces of platelets (which, like RBCs, have no ACE2) and endothelial cells (having minimal ACE2) compound this vascular damage. Notably, experimentally induced RBC aggregation in vivo causes the same key morbidities as for severe COVID-19, including microvascular occlusion, blood clots, hypoxia and myocarditis. Key risk factors for COVID-19 morbidity, including older age, diabetes and obesity, are all characterized by markedly increased propensity to RBC clumping. For mammalian species, the degree of clinical susceptibility to COVID-19 correlates to RBC aggregability with p = 0.033. Notably, of the five human betacoronaviruses, the two common cold strains express an enzyme that releases glycan attachments, while the deadly SARS, SARS-CoV-2 and MERS do not, although viral loads for COVID-19 and the two common cold infections are similar. These biochemical insights also explain the previously puzzling clinical efficacy of certain generics against COVID-19 and may support the development of future therapeutic strategies for COVID-19 and long COVID patients.}, }
@article {pmid38083997, year = {2024}, author = {Collins, E and Philippe, E and Gravel, CA and Hawken, S and Langlois, MA and Little, J}, title = {Serological markers and long COVID-A rapid systematic review.}, journal = {European journal of clinical investigation}, volume = {54}, number = {4}, pages = {e14149}, doi = {10.1111/eci.14149}, pmid = {38083997}, issn = {1365-2362}, support = {//CIHR/ ; }, mesh = {Humans ; *COVID-19/immunology/blood ; *Immunoglobulin G/blood/immunology ; *Biomarkers/blood ; *SARS-CoV-2/immunology ; Post-Acute COVID-19 Syndrome ; Antibodies, Viral/blood ; Spike Glycoprotein, Coronavirus/immunology ; }, abstract = {BACKGROUND: Long COVID is highly heterogeneous, often debilitating, and may last for years after infection. The aetiology of long COVID remains uncertain. Examination of potential serological markers of long COVID, accounting for clinical covariates, may yield emergent pathophysiological insights.<br><br>METHODS: In adherence to PRISMA guidelines, we carried out a rapid review of the literature. We searched Medline and Embase for primary observational studies that compared IgG response in individuals who experienced COVID-19 symptoms persisting &#x2265;12&#x2009;weeks post-infection with those who did not. We examined relationships between serological markers and long COVID status and investigated sources of inter-study variability, such as severity of acute illness, long COVID symptoms assessed and target antigen(s).<br><br>RESULTS: Of 8018 unique records, we identified 29 as being eligible for inclusion in synthesis. Definitions of long COVID varied. In studies that reported anti-nucleocapsid (N) IgG (n&#x2009;=&#x2009;10 studies; n&#x2009;=&#x2009;989 participants in aggregate), full or partial anti-Spike IgG (i.e. the whole trimer, S1 or S2 subgroups, or receptor binding domain, n&#x2009;=&#x2009;19 studies; n&#x2009;=&#x2009;2606 participants), or neutralizing response (n&#x2009;=&#x2009;7 studies; n&#x2009;=&#x2009;1123 participants), we did not find strong evidence to support any difference in serological markers between groups with and without persisting symptoms. However, most studies did not account for severity or level of care required during acute illness, and other potential confounders.<br><br>CONCLUSIONS: Pooling of studies would enable more robust exploration of clinical and serological predictors among diverse populations. However, substantial inter-study variations hamper comparability. Standardized reporting practices would improve the quality, consistency and comprehension of study findings.}, }
@article {pmid38091027, year = {2024}, author = {Rana, P and Patial, S and Soni, V and Singh, P and Khosla, A and Thakur, S and Hussaisn, CM and de Carvalho Nagliate, P and Meili, L and Selvasembian, R and Raizada, P}, title = {"Long COVID" and Its Impact on The Environment: Emerging Concerns and Perspectives.}, journal = {Environmental management}, volume = {73}, number = {3}, pages = {471-480}, pmid = {38091027}, issn = {1432-1009}, mesh = {Humans ; *Air Pollution/analysis ; *COVID-19/epidemiology ; Pandemics ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {The COVID-19 pandemic has caused unprecedented global health and economic crises. The emergence of long COVID-19 has raised concerns about the interplay between SARS-CoV-2 infections, climate change, and the environment. In this context, a concise analysis of the potential long-term effects of the COVID-19 epidemic along with the awareness aboutenvironmental issues are realized. While COVID-19 effects in the short-term have reduced environmental air pollutants and pressures, CO2 emissions are projected to increase as the economy recovers and growth rates return to pre-COVID-19 levels. This review discusses the systematic effects of both the short-term and long-term effects of the pandemic on the clean energy revolution and environmental issues. This article also discusses opportunities to achieve long-term environmental benefits and emphasizes the importance of future policies in promoting global environmental sustainability. Future directions for growth and recovery are presented to cope with long COVID-19 epidemic along with the critical findings focussing on various aspects: waste management, air quality improvement.}, }
@article {pmid38098317, year = {2024}, author = {El-Baky, NA and Amara, AA and Uversky, VN and Redwan, EM}, title = {Intrinsic factors behind long COVID: III. Persistence of SARS-CoV-2 and its components.}, journal = {Journal of cellular biochemistry}, volume = {125}, number = {1}, pages = {22-44}, doi = {10.1002/jcb.30514}, pmid = {38098317}, issn = {1097-4644}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Intrinsic Factor ; *COVID-19 ; RNA, Viral/genetics ; }, abstract = {Considerable research has been done in investigating SARS-CoV-2 infection, its characteristics, and host immune response. However, debate is still ongoing over the emergence of post-acute sequelae of SARS-CoV-2 infection (PASC). A multitude of long-lasting symptoms have been reported several weeks after the primary acute SARS-CoV-2 infection that resemble several other viral infections. Thousands of research articles have described various post-COVID-19 conditions. Yet, the evidence around these ongoing health problems, the reasons behind them, and their molecular underpinnings are scarce. These persistent symptoms are also known as long COVID-19. The persistence of SARS-CoV-2 and/or its components in host tissues can lead to long COVID. For example, the presence of viral nucleocapsid protein and RNA was detected in the skin, appendix, and breast tissues of some long COVID patients. The persistence of viral RNA was reported in multiple anatomic sites, including non-respiratory tissues such as the adrenal gland, ocular tissue, small intestine, lymph nodes, myocardium, and sciatic nerve. Distinctive viral spike sequence variants were also found in non-respiratory tissues. Interestingly, prolonged detection of viral subgenomic RNA was observed across all tissues, sometimes in multiple tissues of the same patient, which likely reflects recent but defective viral replication. Moreover, the persistence of SARS-CoV-2 RNA was noticed throughout the brain at autopsy, as late as 230 days following symptom onset among unvaccinated patients who died of severe infection. Here, we review the persistence of SARS-CoV-2 and its components as an intrinsic factor behind long COVID. We also highlight the immunological consequences of this viral persistence.}, }
@article {pmid38113020, year = {2024}, author = {Fernández-de-Las-Peñas, C and Torres-Macho, J and Catahay, JA and Macasaet, R and Velasco, JV and Macapagal, S and Caldararo, M and Henry, BM and Lippi, G and Franco-Moreno, A and Notarte, KI}, title = {Is antiviral treatment at the acute phase of COVID-19 effective for decreasing the risk of long-COVID? A systematic review.}, journal = {Infection}, volume = {52}, number = {1}, pages = {43-58}, pmid = {38113020}, issn = {1439-0973}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Ritonavir ; SARS-CoV-2 ; Antiviral Agents/therapeutic use ; Dexamethasone/therapeutic use ; *Metformin ; }, abstract = {PURPOSE: Preliminary evidence suggests a potential effect of antiviral medication used during the acute COVID-19 phase for preventing long-COVID. This review investigates if having received pharmacological treatment during acute SARS-CoV-2 infection may reduce the risk of long-COVID.<br><br>METHODS: MEDLINE, CINAHL, PubMed, EMBASE, Web of Science databases, as well as medRxiv/bioRxiv preprint servers were searched up to July 15th, 2023. Articles comparing the presence of long-COVID symptoms between individuals who received or not a specific medication, particularly antivirals, during the acute phase of SARS-CoV-2 infection were included. Methodological quality was assessed using the Newcastle-Ottawa Scale or Cochrane's Risk of Bias (Rob) tool.<br><br>RESULTS: From 517 studies identified, 6 peer-reviewed studies and one preprint met all inclusion criteria. The sample included 2683 (n&#x2009;=&#x2009;4) hospitalized COVID-19 survivors and 307,409 (n&#x2009;=&#x2009;3) non-hospitalized patients. The methodological quality was high in 71% of studies (n&#x2009;=&#x2009;5/7). Two studies investigating the effects of Nirmaltrevir/Ritonavir and three studies the effect of Remdesivir reported conflicting results on effectiveness for preventing long-COVID. Three studies investigating the effects of other medication such as Dexamethasone (n&#x2009;=&#x2009;2) or Metformin (n&#x2009;=&#x2009;1) found positive results of these medications for preventing long-COVID.<br><br>CONCLUSION: Available evidence about the effect of medication treatment with antivirals during acute COVID-19 and reduced risk of developing long-COVID is conflicting. Heterogeneous evidence suggests that Remdesivir or Nirmaltrevir/Ritonavir could have a potential protective effect for long-COVID. A limited number of studies demonstrated a potential benefit of other medications such as Dexamethasone or Metformin, but more studies are needed.}, }
@article {pmid38117308, year = {2024}, author = {da Silva, LNM and Filho, AGO and Guimarães, JB}, title = {Musculoskeletal manifestations of COVID-19.}, journal = {Skeletal radiology}, volume = {53}, number = {10}, pages = {2009-2022}, pmid = {38117308}, issn = {1432-2161}, mesh = {Humans ; *COVID-19/complications/diagnostic imaging ; *Musculoskeletal Diseases/diagnostic imaging/etiology ; *SARS-CoV-2 ; }, abstract = {During the COVID-19 pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected millions of people worldwide, with acute respiratory distress syndrome (ARDS) being the most common severe condition of pulmonary involvement. Despite its involvement in the lungs, SARS-CoV-2 causes multiple extrapulmonary manifestations, including manifestations in the musculoskeletal system. Several cases involving bone, joint, muscle, neurovascular and soft tissues were reported shortly after pandemic onset. Even after the acute infection has resolved, many patients experience persistent symptoms and a decrease in quality of life, a condition known as post-COVID syndrome or long COVID. COVID-19 vaccines have been widely available since December 2020, preventing millions of deaths during the pandemic. However, adverse reactions, including those involving the musculoskeletal system, have been reported in the literature. Therefore, the primary goal of this article is to review the main imaging findings of SARS-CoV-2 involvement in the musculoskeletal system, including acute, subacute, chronic and postvaccination manifestations.}, }
@article {pmid38123233, year = {2023}, author = {Singh, SJ and Daynes, E and McAuley, HJC and Raman, B and Greening, NJ and Chalder, T and Elneima, O and Evans, RA and Bolton, CE}, title = {Balancing the value and risk of exercise-based therapy post-COVID-19: a narrative review.}, journal = {European respiratory review : an official journal of the European Respiratory Society}, volume = {32}, number = {170}, pages = {}, pmid = {38123233}, issn = {1600-0617}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *COVID-19 ; Exercise Therapy/adverse effects ; Exercise ; Fatigue ; Dyspnea ; }, abstract = {Coronavirus disease 2019 (COVID-19) can lead to ongoing symptoms such as breathlessness, fatigue and muscle pain, which can have a substantial impact on an individual. Exercise-based rehabilitation programmes have proven beneficial in many long-term conditions that share similar symptoms. These programmes have favourably influenced breathlessness, fatigue and pain, while also increasing functional capacity. Exercise-based rehabilitation may benefit those with ongoing symptoms following COVID-19. However, some precautions may be necessary prior to embarking on an exercise programme. Areas of concern include ongoing complex lung pathologies, such as fibrosis, cardiovascular abnormalities and fatigue, and concerns regarding post-exertional symptom exacerbation. This article addresses these concerns and proposes that an individually prescribed, symptom-titrated exercise-based intervention may be of value to individuals following infection with severe acute respiratory syndrome coronavirus 2.}, }
@article {pmid38124476, year = {2024}, author = {Shetty, AJ and Banerjee, M and Prasad, TN and Bhadada, SK and Pal, R}, title = {Do vitamin D levels or supplementation play A role in COVID-19 outcomes?-a narrative review.}, journal = {Annals of palliative medicine}, volume = {13}, number = {1}, pages = {162-177}, doi = {10.21037/apm-23-113}, pmid = {38124476}, issn = {2224-5839}, mesh = {Humans ; *COVID-19 ; Dietary Supplements ; SARS-CoV-2 ; Vitamin D/therapeutic use ; *Vitamin D Deficiency/complications ; }, abstract = {BACKGROUND AND OBJECTIVE: Hypovitaminosis D has been proposed as a risk factor for increased susceptibility to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and severe outcomes in coronavirus disease 2019 (COVID-19). Likewise, vitamin D supplementation has been proposed as an effective means for preventing and improving clinical outcomes in COVID-19. Nevertheless, available data are markedly inconsistent and contradictory. Considering the heterogeneity in the available clinical evidence, we planned to undertake a narrative review and provide a precise summary of the role of vitamin D in COVID-19.<br><br>METHODS: PubMed/MEDLINE database was searched from inception till September 30, 2023 using appropriate MeSH terms. The initial search revealed 900 results. Thereafter, titles and abstracts were scanned and commentaries, letters, and editorials were excluded. Relevant observational studies and clinical trials/randomized controlled trials (RCTs) were full-text assessed and pertinent data were extracted for this narrative review.<br><br>KEY CONTENT AND FINDINGS: Data from observational and ecological studies suggest that hypovitaminosis D is associated with a higher risk of acquiring COVID-19. Similarly, evidence support a negative association between 25-hydroxyvitamin D levels and COVID-19 severity, nevertheless, causality remains to be established. With regard to vitamin D supplementation and COVID-19-related health outcomes, data from observational studies and RCTs are contradictory. Even in moderate-to-severe/severe COVID-19, vitamin D supplementation has not been shown to be beneficial. Besides, data suggest that vitamin D levels might alter COVID-19 vaccine efficacy and be associated with long COVID.<br><br>CONCLUSIONS: Vitamin D deficiency is linked to an increased risk of acquiring SARS-CoV-2 infection and poor COVID-19 prognosis, however, available evidence with regard to improved clinical outcomes with vitamin D supplementation is inconsistent.}, }
@article {pmid38126937, year = {2024}, author = {Razzaq, A and Disoma, C and Zhou, Y and Tao, S and Chen, Z and Liu, S and Zheng, R and Zhang, Y and Liao, Y and Chen, X and Liu, S and Dong, Z and Xu, L and Deng, X and Li, S and Xia, Z}, title = {Targeting epidermal growth factor receptor signalling pathway: A promising therapeutic option for COVID-19.}, journal = {Reviews in medical virology}, volume = {34}, number = {1}, pages = {e2500}, doi = {10.1002/rmv.2500}, pmid = {38126937}, issn = {1099-1654}, mesh = {Humans ; Antiviral Agents/therapeutic use/pharmacology ; *COVID-19 ; COVID-19 Drug Treatment ; *ErbB Receptors/genetics/metabolism ; Erlotinib Hydrochloride/therapeutic use ; Post-Acute COVID-19 Syndrome ; Pulmonary Fibrosis/metabolism ; SARS-CoV-2/metabolism ; *Signal Transduction/drug effects ; }, abstract = {The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously producing new variants, necessitating effective therapeutics. Patients are not only confronted by the immediate symptoms of infection but also by the long-term health issues linked to long COVID-19. Activation of epidermal growth factor receptor (EGFR) signalling during SARS-CoV-2 infection promotes virus propagation, mucus hyperproduction, and pulmonary fibrosis, and suppresses the host's antiviral response. Over the long term, EGFR activation in COVID-19, particularly in COVID-19-induced pulmonary fibrosis, may be linked to the development of lung cancer. In this review, we have summarised the significance of EGFR signalling in the context of SARS-CoV-2 infection. We also discussed the targeting of EGFR signalling as a promising strategy for COVID-19 treatment and highlighted erlotinib as a superior option among EGFR inhibitors. Erlotinib effectively blocks EGFR and AAK1, thereby preventing SARS-CoV-2 replication, reducing mucus hyperproduction, TNF-α expression, and enhancing the host's antiviral response. Nevertheless, to evaluate the antiviral efficacy of erlotinib, relevant clinical trials involving an appropriate patient population should be designed.}, }
@article {pmid38128935, year = {2023}, author = {Fyffe, I and Sorensen, J and Carroll, S and MacPhee, M and Andrews-Paul, A and Crooks, VA and Freeman, S and Davison, K and Walls, J and Berndt, A and Shams, B and Sivan, M and Mithani, A}, title = {Long COVID in long-term care: a rapid realist review.}, journal = {BMJ open}, volume = {13}, number = {12}, pages = {e076186}, pmid = {38128935}, issn = {2044-6055}, mesh = {Humans ; *COVID-19/therapy ; Delivery of Health Care ; Long-Term Care ; *Post-Acute COVID-19 Syndrome ; Quality of Life ; }, abstract = {OBJECTIVES: The goals of this rapid realist review were to ask: (a) what are the key mechanisms that drive successful interventions for long COVID in long-term care (LTC) and (b) what are the critical contexts that determine whether the mechanisms produce the intended outcomes?<br><br>DESIGN: Rapid realist review.<br><br>DATA SOURCES: Medline, CINAHL, Embase, PsycINFO and Web of Science for peer-reviewed literature and Google for grey literature were searched up to 23 February 2023.<br><br>ELIGIBILITY CRITERIA: We included sources focused on interventions, persons in LTC, long COVID or post-acute phase at least 4&#x2009;weeks following initial COVID-19 infection and ones that had a connection with source materials.<br><br>DATA EXTRACTION AND SYNTHESIS: Three independent reviewers searched, screened and coded studies. Two independent moderators resolved conflicts. A data extraction tool organised relevant data into context-mechanism-outcome configurations using realist methodology. Twenty-one sources provided 51 intervention data excerpts used to develop our programme theory. Synthesised findings were presented to a reference group and expert panel for confirmatory purposes.<br><br>RESULTS: Fifteen peer-reviewed articles and six grey literature sources were eligible for inclusion. Eleven context-mechanism-outcome configurations identify those contextual factors and underlying mechanisms associated with desired outcomes, such as clinical care processes and policies that ensure timely access to requisite resources for quality care delivery, and resident-centred assessments and care planning to address resident preferences and needs. The underlying mechanisms associated with enhanced outcomes for LTC long COVID survivors were: awareness, accountability, vigilance and empathetic listening.<br><br>CONCLUSIONS: Although the LTC sector struggles with organisational capacity issues, they should be aware that comprehensively assessing and monitoring COVID-19 survivors and providing timely interventions to those with long COVID is imperative. This is due to the greater care needs of residents with long COVID, and coordinated efficient care is required to optimise their quality of life.}, }
@article {pmid38131885, year = {2023}, author = {Sideratou, CM and Papaneophytou, C}, title = {Persisting Shadows: Unraveling the Impact of Long COVID-19 on Respiratory, Cardiovascular, and Nervous Systems.}, journal = {Infectious disease reports}, volume = {15}, number = {6}, pages = {806-830}, pmid = {38131885}, issn = {2036-7430}, abstract = {The coronavirus disease 2019 (COVID-19), instigated by the zoonotic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), rapidly transformed from an outbreak in Wuhan, China, into a widespread global pandemic. A significant post-infection condition, known as 'long- COVID-19' (or simply 'long- COVID'), emerges in a substantial subset of patients, manifesting with a constellation of over 200 reported symptoms that span multiple organ systems. This condition, also known as 'post-acute sequelae of SARS-CoV-2 infection' (PASC), presents a perplexing clinical picture with far-reaching implications, often persisting long after the acute phase. While initial research focused on the immediate pulmonary impact of the virus, the recognition of COVID-19 as a multiorgan disruptor has unveiled a gamut of protracted and severe health issues. This review summarizes the primary effects of long COVID on the respiratory, cardiovascular, and nervous systems. It also delves into the mechanisms underlying these impacts and underscores the critical need for a comprehensive understanding of long COVID's pathogenesis.}, }
@article {pmid38132646, year = {2023}, author = {Zimmermann, P and Sourij, H and Aberer, F and Rilstone, S and Schierbauer, J and Moser, O}, title = {SGLT2 Inhibitors in Long COVID Syndrome: Is There a Potential Role?.}, journal = {Journal of cardiovascular development and disease}, volume = {10}, number = {12}, pages = {}, pmid = {38132646}, issn = {2308-3425}, abstract = {The coronavirus disease (COVID)-19 has turned into a pandemic causing a global public health crisis. While acute COVID-19 mainly affects the respiratory system and can cause acute respiratory distress syndrome, an association with persistent inflammatory stress affecting different organ systems has been elucidated in long COVID syndrome (LCS). Increased severity and mortality rates have been reported due to cardiophysiological and metabolic systemic disorders as well as multiorgan failure in COVID-19, additionally accompanied by chronic dyspnea and fatigue in LCS. Hence, novel therapies have been tested to improve the outcomes of LCS of which one potential candidate might be sodium-glucose cotransporter 2 (SGLT2) inhibitors. The aim of this narrative review was to discuss rationales for investigating SGLT2 inhibitor therapy in people suffering from LCS. In this regard, we discuss their potential positive effects-next to the well described "cardio-renal-metabolic" conditions-with a focus on potential anti-inflammatory and beneficial systemic effects in LCS. However, potential beneficial as well as potential disadvantageous effects of SGLT2 inhibitors on the prevalence and long-term outcomes of COVID-19 will need to be established in ongoing research.}, }
@article {pmid38138102, year = {2023}, author = {Fernández-de-Las-Peñas, C and Raveendran, AV and Giordano, R and Arendt-Nielsen, L}, title = {Long COVID or Post-COVID-19 Condition: Past, Present and Future Research Directions.}, journal = {Microorganisms}, volume = {11}, number = {12}, pages = {}, pmid = {38138102}, issn = {2076-2607}, abstract = {The presence of symptoms after an acute SARS-CoV-2 infection (long-COVID) has become a worldwide healthcare emergency but remains underestimated and undertreated due to a lack of recognition of the condition and knowledge of the underlying mechanisms. In fact, the prevalence of post-COVID symptoms ranges from 50% during the first months after the infection up to 20% two-years after. This perspective review aimed to map the existing literature on post-COVID symptoms and to identify gaps in the literature to guide the global effort toward an improved understanding of long-COVID and suggest future research directions. There is a plethora of symptomatology that can be due to COVID-19; however, today, there is no clear classification and definition of this condition, termed long-COVID or post-COVID-19 condition. The heterogeneity in the symptomatology has led to the presence of groups/clusters of patients, which could exhibit different risk factors and different mechanisms. Viral persistence, long-lasting inflammation, immune dysregulation, autoimmune reactions, reactivation of latent infections, endothelial dysfunction and alteration in gut microbiota have been proposed as potential mechanisms explaining the complexity of long-COVID. In such an equation, viral biology (e.g., re-infections, SARS-CoV-2 variants), host biology (e.g., genetics, epigenetics) and external factors (e.g., vaccination) should be also considered. These various factors will be discussed in the current perspective review and future directions suggested.}, }
@article {pmid38139027, year = {2023}, author = {Ailioaie, LM and Ailioaie, C and Litscher, G}, title = {Gut Microbiota and Mitochondria: Health and Pathophysiological Aspects of Long COVID.}, journal = {International journal of molecular sciences}, volume = {24}, number = {24}, pages = {}, pmid = {38139027}, issn = {1422-0067}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Gastrointestinal Microbiome ; Inflammation ; Dysbiosis ; }, abstract = {The current understanding of long COVID (LC) is still limited. This review highlights key findings regarding the role of gut microbiota, mitochondria, and the main pathophysiological aspects of LC revealed by clinical studies, related to the complex interplay between infection, intestinal dysbiosis, dysfunctional mitochondria, and systemic inflammation generated in a vicious circle, reflecting the molecular and cellular processes from the "leaky gut" to the "leaky electron transport chain (ETC)" into a quantum leap. The heterogeneity of LC has hindered progress in deciphering all the pathophysiological mechanisms, and therefore, the approach must be multidisciplinary, with a special focus not only on symptomatic management but also on addressing the underlying health problems of the patients. It is imperative to further assess and validate the effects of COVID-19 and LC on the gut microbiome and their relationship to infections with other viral agents or pathogens. Further studies are needed to better understand LC and expand the interdisciplinary points of view that are required to accurately diagnose and effectively treat this heterogeneous condition. Given the ability of SARS-CoV-2 to induce autoimmunity in susceptible patients, they should be monitored for symptoms of autoimmune disease after contracting the viral infection. One question remains open, namely, whether the various vaccines developed to end the pandemic will also induce autoimmunity. Recent data highlighted in this review have revealed that the persistence of SARS-CoV-2 and dysfunctional mitochondria in organs such as the heart and, to a lesser extent, the kidneys, liver, and lymph nodes, long after the organism has been able to clear the virus from the lungs, could be an explanation for LC.}, }
@article {pmid38139400, year = {2023}, author = {Gostimirovic, M and Rajkovic, J and Bukarica, A and Simanovic, J and Gojkovic-Bukarica, L}, title = {Resveratrol and Gut Microbiota Synergy: Preventive and Therapeutic Effects.}, journal = {International journal of molecular sciences}, volume = {24}, number = {24}, pages = {}, pmid = {38139400}, issn = {1422-0067}, support = {NA//Ministry of Science, Technological Development and Innovations of Republic of Serbia/ ; }, mesh = {Humans ; Resveratrol/pharmacology/therapeutic use ; *Gastrointestinal Microbiome/physiology ; *Noncommunicable Diseases ; Quality of Life ; Diet, High-Fat ; *COVID-19 ; }, abstract = {The role of an imbalanced high-fat diet in the pathophysiology of common chronic noncommunicable diseases has been known for years. More recently, the concept of 'gut microbiota' and the interaction between their composition and gut metabolites produced from the intake of dietary products have gained the focus of researchers, mostly from the perspective of the prevention of cardiovascular and metabolic disorders, which are still the leading cause of death globally. The aim of this work is to highlight the health benefits of the interaction between resveratrol (RSV), red grape polyphenol, and gut microbiota, through aspects of their therapeutic and preventive potentials. Since changed microbiota (mostly as a consequence of antibiotic overuse) contribute to the persistence of post ('long')-COVID-19 symptoms, these aspects will be covered too. Data were obtained from the electronic databases (MedLine/PubMed), according to specific keywords regarding the protective role of resveratrol, the gut microbiota, and their synergy. RSV exerts beneficial properties in the modulation of cardiovascular, metabolic, and post-COVID-19-related disorders. In healthy individuals, it maintains an ergogenic capacity, prevents oxidative stress, and modulates the inflammatory response. Overall, it improves quality of life. The RSV-gut-microbiota interaction is beneficial in terms of maintaining human health. Along with physical activity, it is key for the prevention of chronic noncommunicable diseases.}, }
@article {pmid38140991, year = {2024}, author = {Brigido, S and Manes, MT and Ingianni, N and Lanni, F and Cutolo, A and La Rovere, MT and Pavan, D and , }, title = {[Gender cardiology: focus on clinical and pathophysiological peculiarities in women with long COVID syndrome].}, journal = {Giornale italiano di cardiologia (2006)}, volume = {25}, number = {1}, pages = {6-13}, doi = {10.1714/4165.41585}, pmid = {38140991}, issn = {1972-6481}, mesh = {Female ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Cardiovascular System ; *Cardiology ; *Vascular Diseases ; }, abstract = {Long COVID is a clinical syndrome characterized by the persistence or development of symptoms due to COVID-19 at least 12 weeks after initial infection. More than 200 different symptoms have been ascribed to long COVID, the most common being fatigue, shortness of breath, and muscle weakness. Women have a three-fold higher risk of being diagnosed with long COVID, and the symptoms more often described are persistent weakness, chest pain, altered smell and taste, palpitations or muscle pain, as well as neurological, gastrointestinal and rheumatologic symptoms. Long COVID features are influenced by immune function, endothelial dysfunction and sex hormones. Moreover, it leads to systemic dysfunction, so various therapeutic strategies have been explored and still different trials are ongoing, mainly regarding anticoagulation and immuno-modulators. Nowadays the most quoted interventions are focused rehabilitation programs and pharmacological selected treatments in specifical cases. The aim of this review will be focusing the clinical and pathophysiological sex-related peculiarities to understand the different long COVID phenotypes and possibly address a better tailored approach and treatment.}, }
@article {pmid38143784, year = {2023}, author = {Peterson, BM and Unger, I and Sun, S and Park, JY and Kim, J and Gunasekera, RS and Wilson, J and Galbadage, T}, title = {The vital role of exercise and nutrition in COVID-19 rehabilitation: synergizing strength.}, journal = {Frontiers in sports and active living}, volume = {5}, number = {}, pages = {1305175}, pmid = {38143784}, issn = {2624-9367}, abstract = {Since the outset of the COVID-19 pandemic, the global healthcare community has faced the challenge of understanding and addressing the ongoing and multi-faceted SARS-CoV-2 infection outcomes. As millions of individuals worldwide continue to navigate the complexities of post-hospitalization recovery, reinfection rates, and the increasing prevalence of Long-COVID symptoms, comprehensive COVID-19 rehabilitation strategies are greatly needed. Previous studies have highlighted the potential synergy between exercise and nutrition, suggesting that their integration into patient rehabilitation programs may yield improved clinical outcomes for survivors of COVID-19. Our group aimed to consolidate existing knowledge following the implementation of patient, intervention, comparison, and outcome (PICO) search strategies on the distinct and combined impacts of exercise and nutrition interventions in facilitating the recovery of COVID-19 patients following hospitalization, with a specific focus on their implications for both public health and clinical practice. The incorporation of targeted nutritional strategies alongside exercise-based programs may expedite patient recovery, ultimately promoting independence in performing activities of daily living (ADLs). Nonetheless, an imperative for expanded scientific inquiry remains, particularly in the realm of combined interventions. This mini-review underscores the compelling prospects offered by an amalgamated approach, advocating for the seamless integration of exercise and nutrition as integral components of post-hospitalization COVID-19 rehabilitation. The pursuit of a comprehensive understanding of the synergistic effects and effectiveness of exercise and nutrition stands as a crucial objective in advancing patient care and refining recovery strategies in the wake of this enduring global health crisis.}, }
@article {pmid38156008, year = {2023}, author = {He, KY and Lei, XY and Zhang, L and Wu, DH and Li, JQ and Lu, LY and Laila, UE and Cui, CY and Xu, ZX and Jian, YP}, title = {Development and management of gastrointestinal symptoms in long-term COVID-19.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1278479}, pmid = {38156008}, issn = {1664-302X}, abstract = {BACKGROUND: Emerging evidence reveals that SARS-CoV-2 possesses the capability to disrupt the gastrointestinal (GI) homeostasis, resulting in the long-term symptoms such as loss of appetite, diarrhea, gastroesophageal reflux, and nausea. In the current review, we summarized recent reports regarding the long-term effects of COVID-19 (long COVID) on the gastrointestine.<br><br>OBJECTIVE: To provide a narrative review of abundant clinical evidence regarding the development and management of long-term GI symptoms in COVID-19 patients.<br><br>RESULTS: Long-term persistent digestive symptoms are exhibited in a majority of long-COVID patients. SARS-CoV-2 infection of intestinal epithelial cells, cytokine storm, gut dysbiosis, therapeutic drugs, psychological factors and exacerbation of primary underlying diseases lead to long-term GI symptoms in COVID-19 patients. Interventions like probiotics, prebiotics, fecal microbiota transplantation, and antibiotics are proved to be beneficial in preserving intestinal microecological homeostasis and alleviating GI symptoms.<br><br>CONCLUSION: Timely diagnosis and treatment of GI symptoms in long-COVID patients hold great significance as they may contribute to the mitigation of severe conditions and ultimately lead to the improvement of outcomes of the patients.}, }
@article {pmid38159046, year = {2024}, author = {Lui, KO and Ma, Z and Dimmeler, S}, title = {SARS-CoV-2 induced vascular endothelial dysfunction: direct or indirect effects?.}, journal = {Cardiovascular research}, volume = {120}, number = {1}, pages = {34-43}, doi = {10.1093/cvr/cvad191}, pmid = {38159046}, issn = {1755-3245}, mesh = {Animals ; Humans ; SARS-CoV-2/metabolism ; *COVID-19 ; Angiotensin-Converting Enzyme 2/metabolism ; Endothelial Cells/metabolism ; Post-Acute COVID-19 Syndrome ; Peptidyl-Dipeptidase A/metabolism ; *Vascular Diseases ; Mammals/metabolism ; }, abstract = {Clinical evidence reveals that manifestations of endothelial dysfunction are widely observed in COVID-19 and long-COVID patients. However, whether these detrimental effects are caused by direct infection of the endothelium or are indirectly mediated by systemic inflammation has been a matter of debate. It has been well acknowledged that endothelial cells (ECs) of the cardiovascular system ubiquitously express the SARS-CoV-2 entry receptor angiotensin-converting enzyme 2 (ACE2), yet accumulating evidence suggests that it is more predominantly expressed by pericytes and vascular smooth muscle cells of the mammalian blood vessel. Besides, replicative infection of ECs by SARS-CoV-2 has yet to be demonstrated both in vitro and in vivo. In this study, we review latest research on endothelial ACE2 expression in different vascular beds, and the heterogeneity in various EC subsets with differential ACE2 expression in response to SARS-CoV-2. We also discuss ACE2-independent alternative mechanisms underlying endothelial activation in COVID-19, and the clinical manifestations of SARS-CoV-2-induced endothelial dysfunction. Altogether, understanding ACE2-dependent and ACE2-independent mechanisms driving SARS-CoV-2-induced vascular dysfunction would shed light on strategies of more effective therapies targeting cardiovascular complications associated with COVID-19.}, }
@article {pmid38163814, year = {2024}, author = {Fedorowski, A and Fanciulli, A and Raj, SR and Sheldon, R and Shibao, CA and Sutton, R}, title = {Cardiovascular autonomic dysfunction in post-COVID-19 syndrome: a major health-care burden.}, journal = {Nature reviews. Cardiology}, volume = {21}, number = {6}, pages = {379-395}, pmid = {38163814}, issn = {1759-5010}, mesh = {Humans ; *COVID-19/complications/physiopathology/epidemiology ; *Autonomic Nervous System Diseases/physiopathology/etiology/diagnosis ; *Cardiovascular Diseases/physiopathology/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {Cardiovascular autonomic dysfunction (CVAD) is a malfunction of the cardiovascular system caused by deranged autonomic control of circulatory homeostasis. CVAD is an important component of post-COVID-19 syndrome, also termed long COVID, and might affect one-third of highly symptomatic patients with COVID-19. The effects of CVAD can be seen at both the whole-body level, with impairment of heart rate and blood pressure control, and in specific body regions, typically manifesting as microvascular dysfunction. Many severely affected patients with long COVID meet the diagnostic criteria for two common presentations of CVAD: postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia. CVAD can also manifest as disorders associated with hypotension, such as orthostatic or postprandial hypotension, and recurrent reflex syncope. Advances in research, accelerated by the COVID-19 pandemic, have identified new potential pathophysiological mechanisms, diagnostic methods and therapeutic targets in CVAD. For clinicians who daily see patients with CVAD, knowledge of its symptomatology, detection and appropriate management is more important than ever. In this Review, we define CVAD and its major forms that are encountered in post-COVID-19 syndrome, describe possible CVAD aetiologies, and discuss how CVAD, as a component of post-COVID-19 syndrome, can be diagnosed and managed. Moreover, we outline directions for future research to discover more efficient ways to cope with this prevalent and long-lasting condition.}, }
@article {pmid38169007, year = {2024}, author = {Munro, APS and Jones, CE and Faust, SN}, title = {Vaccination against COVID-19 - risks and benefits in children.}, journal = {European journal of pediatrics}, volume = {183}, number = {3}, pages = {1107-1112}, pmid = {38169007}, issn = {1432-1076}, mesh = {Adolescent ; Adult ; Child ; Humans ; Male ; *COVID-19/prevention &amp; control/complications ; *COVID-19 Vaccines/adverse effects ; *Myocarditis/etiology ; Risk Assessment ; SARS-CoV-2 ; Syndrome ; *Systemic Inflammatory Response Syndrome ; Vaccination/adverse effects ; }, abstract = {Countries in Europe and around the world have taken varying approaches to their policies on COVID-19 vaccination for children. The low risk of severe illness from COVID-19 means that even small risks from vaccination warrant careful consideration. Vaccination appears to result in a decreased risk of severe illness including the paediatric multi-system inflammatory syndrome known to be associated with COVID-19. These risks have already decreased significantly with the emergence of the Omicron variant and its subvariants, and due to widespread population immunity through previous infection. There is a relatively high risk of myocarditis following second doses of mRNA vaccines in adolescent males, although the general course of this condition appears mild. Conclusion: COVID-19 vaccination only provides a transient reduction in transmission. Currently, insufficient evidence exists to determine the impact of vaccination on post-acute COVID syndromes in children, which are uncommon. What is Known: • Vaccines against COVID-19 have significantly reduced morbidity and mortality around the world. • Whilst countries have universally recommended vaccines for adults and continue to recommend them for vulnerable populations, there has been more variability in recommendations for children. What is New: • In the setting of near universal existing immunity from infection, the majority of the initial benefit in protecting against severe illness has been eroded. • The risks of myocarditis following mRNA vaccination for children is low, but an important consideration given the modest benefits.}, }
@article {pmid38172332, year = {2024}, author = {Helbing, DL and Dommaschk, EM and Danyeli, LV and Liepinsh, E and Refisch, A and Sen, ZD and Zvejniece, L and Rocktäschel, T and Stabenow, LK and Schiöth, HB and Walter, M and Dambrova, M and Besteher, B}, title = {Conceptual foundations of acetylcarnitine supplementation in neuropsychiatric long COVID syndrome: a narrative review.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {274}, number = {8}, pages = {1829-1845}, pmid = {38172332}, issn = {1433-8491}, support = {857394 (FAT4BRAIN)//Horizon 2020 Framework Programme/ ; }, mesh = {Humans ; *Acetylcarnitine/pharmacology/therapeutic use ; *COVID-19/complications ; *Dietary Supplements ; *Post-Acute COVID-19 Syndrome ; Fatigue Syndrome, Chronic/drug therapy ; }, abstract = {Post-acute sequelae of COVID-19 can present as multi-organ pathology, with neuropsychiatric symptoms being the most common symptom complex, characterizing long COVID as a syndrome with a significant disease burden for affected individuals. Several typical symptoms of long COVID, such as fatigue, depressive symptoms and cognitive impairment, are also key features of other psychiatric disorders such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and major depressive disorder (MDD). However, clinically successful treatment strategies are still lacking and are often inspired by treatment options for diseases with similar clinical presentations, such as ME/CFS. Acetylcarnitine, the shortest metabolite of a class of fatty acid metabolites called acylcarnitines and one of the most abundant blood metabolites in humans can be used as a dietary/nutritional supplement with proven clinical efficacy in the treatment of MDD, ME/CFS and other neuropsychiatric disorders. Basic research in recent decades has established acylcarnitines in general, and acetylcarnitine in particular, as important regulators and indicators of mitochondrial function and other physiological processes such as neuroinflammation and energy production pathways. In this review, we will compare the clinical basis of neuropsychiatric long COVID with other fatigue-associated diseases. We will also review common molecular disease mechanisms associated with altered acetylcarnitine metabolism and the potential of acetylcarnitine to interfere with these as a therapeutic agent. Finally, we will review the current evidence for acetylcarnitine as a supplement in the treatment of fatigue-associated diseases and propose future research strategies to investigate the potential of acetylcarnitine as a treatment option for long COVID.}, }
@article {pmid38185377, year = {2024}, author = {Rischard, F and Altman, N and Szmuszkovicz, J and Sciurba, F and Berman-Rosenzweig, E and Lee, S and Krishnan, S and Truong, N and Wood, J and Finn, AV and , }, title = {Long-Term Effects of COVID-19 on the Cardiopulmonary System in Adults and Children: Current Status and Questions to be Resolved by the National Institutes of Health Researching COVID to Enhance Recovery Initiative.}, journal = {Chest}, volume = {165}, number = {4}, pages = {978-989}, pmid = {38185377}, issn = {1931-3543}, support = {OTA-21-015A/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Humans ; Child ; United States/epidemiology ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Dyspnea ; Lung ; }, abstract = {TOPIC IMPORTANCE: Long COVID may occur in at least 10% of patients recovering from SARS-CoV-2 infection and often is associated with debilitating symptoms. Among the organ systems that might be involved in its pathogenesis, the respiratory and cardiovascular systems may be central to common symptoms seen in survivors of COVID-19, including fatigue, dyspnea, chest pain, cough, and exercise intolerance. Understand the exact symptomatology, causes, and effects of long COVID on the heart and lungs may help us to discover new therapies. To that end, the National Institutes of Health is sponsoring a national study population of diverse volunteers to support large-scale studies on the long-term effects of COVID-19.<br><br>REVIEW FINDINGS: The National Institutes of Health Researching COVID to Enhance Recovery (RECOVER) initiative currently is recruiting participants in the United States to answer critical questions about long COVID. The study comprises adult and pediatric cohorts as well as an electronic health record cohort. Based on symptoms, individuals undergo prespecified medical testing to understand whether abnormalities can be detected and are followed up longitudinally. Herein, we outline current understanding of the clinical symptoms and pathophysiologic features of long COVID with respect to the cardiopulmonary system in adults and children and then determine how the clinical, electronic health record, and autopsy cohorts of the RECOVER initiative will attempt to answer the most pressing questions surrounding the long-term effects of COVID-19.<br><br>SUMMARY: Data generated from the RECOVER initiative will provide guidance about missing gaps in our knowledge about long COVID and how they might be filled by data gathered through the RECOVER initiative.}, }
@article {pmid38187378, year = {2023}, author = {Noonong, K and Chatatikun, M and Surinkaew, S and Kotepui, M and Hossain, R and Bunluepuech, K and Noothong, C and Tedasen, A and Klangbud, WK and Imai, M and Kawakami, F and Kubo, M and Kitagawa, Y and Ichikawa, H and Kanekura, T and Sukati, S and Somsak, V and Udomwech, L and Ichikawa, T and Nissapatorn, V and Tangpong, J and Indo, HP and Majima, HJ}, title = {Mitochondrial oxidative stress, mitochondrial ROS storms in long COVID pathogenesis.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1275001}, pmid = {38187378}, issn = {1664-3224}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Reactive Oxygen Species ; Mitochondria ; Oxidative Stress ; }, abstract = {SIGNIFICANCE: This review discusses the coronavirus disease 2019 (COVID-19) pathophysiology in the context of diabetes and intracellular reactions by COVID-19, including mitochondrial oxidative stress storms, mitochondrial ROS storms, and long COVID.<br><br>RECENT ADVANCES: The long COVID is suffered in ~10% of the COVID-19 patients. Even the virus does not exist, the patients suffer the long COVID for even over a year, This disease could be a mitochondria dysregulation disease.<br><br>CRITICAL ISSUES: Patients who recover from COVID-19 can develop new or persistent symptoms of multi-organ complications lasting weeks or months, called long COVID. The underlying mechanisms involved in the long COVID is still unclear. Once the symptoms of long COVID persist, they cause significant damage, leading to numerous, persistent symptoms.<br><br>FUTURE DIRECTIONS: A comprehensive map of the stages and pathogenetic mechanisms related to long COVID and effective drugs to treat and prevent it are required, which will aid the development of future long COVID treatments and symptom relief.}, }
@article {pmid38197253, year = {2024}, author = {Hitchcock, S and Cintron, SA and Kasuske, L and J Diaz, F and Pierce, J}, title = {Post-COVID-19 Condition in Military Personnel.}, journal = {Military medicine}, volume = {189}, number = {5-6}, pages = {e1277-e1281}, doi = {10.1093/milmed/usad453}, pmid = {38197253}, issn = {1930-613X}, support = {11189-N23-B01//Tri-Service Nursing Research Program/ ; }, mesh = {Humans ; *COVID-19/epidemiology ; *Military Personnel/statistics &amp; numerical data ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Prevalence ; Pandemics ; }, abstract = {INTRODUCTION: During the COVID-19 pandemic, a significant number of individuals experienced persistent symptoms, collectively termed post-COVID-19 condition (PCC) by the World Health Organization. While civilian prevalence has been extensively studied, little is known about PCC in military personnel. This article highlights the need for increased awareness, documentation, and research on PCC within the military context, utilizing the Defense Health Agency database.<br><br>MATERIALS AND METHODS: A keyword search of the PubMed, CINAHL, and Web of Science databases was performed utilizing the keywords: military, post-COVID conditions, long COVID-19, and post-COVID19 syndrome. A five-stage integrative review framework was used to analyze 40 reports and research articles published from 2019 to 2023 to assess the current state of PCC research, including epidemiology, severe acute respiratory syndrome coronavirus 2 variants, pathophysiology, and prevalence in military personnel.<br><br>RESULTS: Our review revealed a notable gap in research on PCC within the military population, with only a few mentions in the literature. A key finding was the association between immunization status, symptom severity, and ethnicity in PCC development.<br><br>CONCLUSION: To comprehensively address PCC in military personnel, it is imperative to foster both awareness and documentation. Creating a centralized Defense Health Agency-DoD repository for active duty service members with PCC diagnoses offers a valuable opportunity to conduct trend analysis, identify missed cases, and better understand the individual and military readiness implications of this condition. Additionally, to address the educational needs of clinicians, it is essential to develop continuing medical education and continuing nursing education programs focusing on PCC signs, symptoms, and their impact on readiness. Furthermore, randomized controlled trials and longitudinal experimental clinical trials are essential for monitoring service members over time, providing valuable insights into the course of PCC and potential interventions. These research endeavors collectively contribute to improving the health, readiness, and care of military personnel affected by PCC.}, }
@article {pmid38202234, year = {2023}, author = {Scott, C and Hall, S and Zhou, J and Lehmann, C}, title = {Cannabinoids and the Endocannabinoid System in Early SARS-CoV-2 Infection and Long COVID-19-A Scoping Review.}, journal = {Journal of clinical medicine}, volume = {13}, number = {1}, pages = {}, pmid = {38202234}, issn = {2077-0383}, abstract = {Coronavirus disease-19 (COVID-19) is a highly contagious illness caused by the SARS-CoV-2 virus. The clinical presentation of COVID-19 is variable, often including symptoms such as fever, cough, headache, fatigue, and an altered sense of smell and taste. Recently, post-acute "long" COVID-19 has emerged as a concern, with symptoms persisting beyond the acute infection. Vaccinations remain one of the most effective preventative methods against severe COVID-19 outcomes and the development of long-term COVID-19. However, individuals with underlying health conditions may not mount an adequate protective response to COVID-19 vaccines, increasing the likelihood of severe symptoms, hospitalization, and the development of long-term COVID-19 in high-risk populations. This review explores the potential therapeutic role of cannabinoids in limiting the susceptibility and severity of infection, both pre- and post-SARS-CoV-19 infection. Early in the SARS-CoV-19 infection, cannabinoids have been shown to prevent viral entry, mitigate oxidative stress, and alleviate the associated cytokine storm. Post-SARS-CoV-2 infection, cannabinoids have shown promise in treating symptoms associated with post-acute long COVID-19, including depression, anxiety, post-traumatic stress injury, insomnia, pain, and decreased appetite. While current research primarily focuses on potential treatments for the acute phase of COVID-19, there is a gap in research addressing therapeutics for the early and post-infectious phases. This review highlights the potential for future research to bridge this gap by investigating cannabinoids and the endocannabinoid system as a potential treatment strategy for both early and post-SARS-CoV-19 infection.}, }
@article {pmid38203577, year = {2023}, author = {Constantinescu-Bercu, A and Lobiuc, A and Căliman-Sturdza, OA and Oiţă, RC and Iavorschi, M and Pavăl, NE and Șoldănescu, I and Dimian, M and Covasa, M}, title = {Long COVID: Molecular Mechanisms and Detection Techniques.}, journal = {International journal of molecular sciences}, volume = {25}, number = {1}, pages = {}, pmid = {38203577}, issn = {1422-0067}, support = {PN-III-Pl-1.1-PD-2021-0273, within PNCDI III//Ministry of Research, Innovation and Digitization, CNCS - UEFISCDI/ ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Pandemics ; SARS-CoV-2 ; Disease Progression ; }, abstract = {Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), has emerged as a significant health concern following the COVID-19 pandemic. Molecular mechanisms underlying the occurrence and progression of long COVID include viral persistence, immune dysregulation, endothelial dysfunction, and neurological involvement, and highlight the need for further research to develop targeted therapies for this condition. While a clearer picture of the clinical symptomatology is shaping, many molecular mechanisms are yet to be unraveled, given their complexity and high level of interaction with other metabolic pathways. This review summarizes some of the most important symptoms and associated molecular mechanisms that occur in long COVID, as well as the most relevant molecular techniques that can be used in understanding the viral pathogen, its affinity towards the host, and the possible outcomes of host-pathogen interaction.}, }
@article {pmid38203745, year = {2024}, author = {Mantle, D and Hargreaves, IP and Domingo, JC and Castro-Marrero, J}, title = {Mitochondrial Dysfunction and Coenzyme Q10 Supplementation in Post-Viral Fatigue Syndrome: An Overview.}, journal = {International journal of molecular sciences}, volume = {25}, number = {1}, pages = {}, pmid = {38203745}, issn = {1422-0067}, mesh = {Humans ; *Fatigue Syndrome, Chronic/drug therapy/etiology ; Post-Acute COVID-19 Syndrome ; *Fibromyalgia/drug therapy/etiology ; Myalgia ; *Mitochondrial Diseases ; Dietary Supplements ; Ubiquinone/*analogs &amp; derivatives ; }, abstract = {Post-viral fatigue syndrome (PVFS) encompasses a wide range of complex neuroimmune disorders of unknown causes characterised by disabling post-exertional fatigue, myalgia and joint pain, cognitive impairments, unrefreshing sleep, autonomic dysfunction, and neuropsychiatric symptoms. It includes myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS); fibromyalgia (FM); and more recently post-COVID-19 condition (long COVID). To date, there are no definitive clinical case criteria and no FDA-approved pharmacological therapies for PVFS. Given the current lack of effective treatments, there is a need to develop novel therapeutic strategies for these disorders. Mitochondria, the cellular organelles responsible for tissue energy production, have recently garnered attention in research into PVFS due to their crucial role in cellular bioenergetic metabolism in these conditions. The accumulating literature has identified a link between mitochondrial dysfunction and low-grade systemic inflammation in ME/CFS, FM, and long COVID. To address this issue, this article aims to critically review the evidence relating to mitochondrial dysfunction in the pathogenesis of these disorders; in particular, it aims to evaluate the effectiveness of coenzyme Q10 supplementation on chronic fatigue and pain symptoms as a novel therapeutic strategy for the treatment of PVFS.}, }
@article {pmid38204779, year = {2023}, author = {Tseng, AA}, title = {Effectiveness of Meditation-based Interventions on Health Problems Caused by COVID-19 Pandemic: Narrative Review.}, journal = {International journal of yoga}, volume = {16}, number = {2}, pages = {72-78}, pmid = {38204779}, issn = {0973-6131}, abstract = {This article provides a quantitative review of the potential applications of meditation-based interventions (MBIs) in addressing the major health issues arising from the COVID-19 pandemic. The review assesses the effectiveness of MBIs on five prevalent disorders during the pandemic, namely depression, anxiety, stress, insomnia, and long COVID. This is achieved by selecting and scrutinizing seven studies that involve various types of online randomized controlled trials and utilize control group outcomes for effectiveness evaluation. The findings reveal a significant impact of MBIs on overall distress disorder, encompassing symptoms of depression, anxiety, and stress, with effectiveness ranging from 20.5% to 68.8%. The interventions also show moderate effectiveness on insomnia disorder with improvements between 5.2% and 38.5%. However, the effectiveness on long COVID disorder presents a mixed picture, with improvements varying from 0.0% to 71.2% across 13 related symptoms or qualities examined. This review offers compelling evidence supporting the effectiveness of MBIs in alleviating these five prevalent disorders resulting from the COVID-19 pandemic.}, }
@article {pmid38212633, year = {2024}, author = {Goldstein, DS}, title = {Post-COVID dysautonomias: what we know and (mainly) what we don't know.}, journal = {Nature reviews. Neurology}, volume = {20}, number = {2}, pages = {99-113}, pmid = {38212633}, issn = {1759-4766}, support = {/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; Pandemics ; *COVID-19 ; SARS-CoV-2 ; *Autonomic Nervous System Diseases ; Disease Progression ; }, abstract = {Following on from the COVID-19 pandemic is another worldwide public health challenge that is referred to variously as long COVID, post-COVID syndrome or post-acute sequelae of SARS-CoV-2 infection (PASC). PASC comes in many forms and affects all body organs. This heterogeneous presentation suggests involvement of the autonomic nervous system (ANS), which has numerous roles in the maintenance of homeostasis and coordination of responses to various stressors. Thus far, studies of ANS dysregulation in people with PASC have been largely observational and descriptive, based on symptom inventories or objective but indirect measures of cardiovascular function, and have paid little attention to the adrenomedullary, hormonal and enteric nervous components of the ANS. Such investigations do not consider the syndromic nature of autonomic dysfunction. This Review provides an update on the literature relating to ANS abnormalities in people with post-COVID syndrome and presents a theoretical perspective on how the ANS might participate in common features of PASC.}, }
@article {pmid38212781, year = {2024}, author = {Azzam, A and Khaled, H and Refaey, N and Mohsen, S and El-Emam, OA and Dawood, N and Ahmed, HA and Soliman, OA and Mostafa, S and Ramadan, H and Mosa, M and Elmowafy, AOI and Rizk, SMA and Zaki, A and Hussien, M and Ahmed, A and Ezzat, AA and Hassan, FE}, title = {The burden of persistent symptoms after COVID-19 (long COVID): a meta-analysis of controlled studies in children and adults.}, journal = {Virology journal}, volume = {21}, number = {1}, pages = {16}, pmid = {38212781}, issn = {1743-422X}, mesh = {Adult ; Child ; Humans ; Ageusia/etiology ; Anosmia/etiology ; *COVID-19/complications/epidemiology ; *Post-Acute COVID-19 Syndrome/complications/epidemiology ; }, abstract = {BACKGROUND: Previous meta-analyses estimating the prevalence of the post-COVID-19 condition (PCC) were confounded by the lack of negative control groups. This may result in an overestimation of the prevalence of those experiencing PCC, as these symptoms are non-specific and common in the general population. In this study, we aimed to compare the burden of persistent symptoms among COVID-19 survivors relative to COVID-19-negative controls.<br><br>METHODS: A systematic literature search was conducted using the following databases (PubMed, Web of Science, and Scopus) until July 2023 for comparative studies that examined the prevalence of persistent symptoms in COVID-19 survivors. Given that many of the symptoms among COVID-19 survivors overlap with post-hospitalization syndrome and post-intensive care syndrome, we included studies that compare the prevalence of persistent symptoms in hospitalized COVID-19 patients relative to non-COVID-19 hospitalized patients and in non-hospitalized COVID-19 patients relative to healthy controls that reported outcomes after at least 3 months since infection. The results of the meta-analysis were reported as odds ratios with a 95% confidence interval based on the random effects model.<br><br>RESULTS: Twenty articles were included in this study. Our analysis of symptomatology in non-hospitalized COVID-19 patients compared to negative controls revealed that the majority of symptoms examined were not related to COVID-19 infection and appeared equally prevalent in both cohorts. However, non-COVID-19 hospitalized patients had higher odds of occurrence of certain symptoms like anosmia, ageusia, fatigue, dyspnea, and brain fog (P&#x2009;<&#x2009;0.05). Particularly, anosmia and ageusia showed substantially elevated odds relative to the negative control group at 11.27 and 9.76, respectively, P&#x2009;<&#x2009;0.05. In contrast, analysis of hospitalized COVID-19 patients compared to those hospitalized for other indications did not demonstrate significantly higher odds for the tested symptoms.<br><br>CONCLUSIONS: The persistent symptoms in COVID-19 survivors may result from hospitalization for causes unrelated to COVID-19 and are commonly reported among the general population. Although certain symptoms exhibited higher odds in non-hospitalized COVID-19 patients relative to controls, these symptoms are common post-viral illnesses. Therefore, the persistent symptoms after COVID-19 may not be unique to SARS-CoV-2. Future studies including well-matched control groups when investigating persistent symptoms in COVID-19 survivors are warranted to draw a firm conclusion.}, }
@article {pmid38214724, year = {2024}, author = {Ludwig, M and Schneider, K and Heß, S and Broich, K}, title = {[Establishment of the new "Health Data Lab" to provide data for science].}, journal = {Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz}, volume = {67}, number = {2}, pages = {131-138}, pmid = {38214724}, issn = {1437-1588}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Germany ; *Delivery of Health Care ; Electronic Health Records ; }, abstract = {The analysis of real-world data (RWD) has become increasingly important in health research in recent years. With the BfArM Health Data Lab (HDL), which is currently being set up, researchers will in future be able to gain access to routine data from the statutory health insurance of around 74 million people in Germany. Data from electronic patient records can also be made available for research prospectively. In doing so, the Health Data Lab guarantees the highest data protection and IT security standards. The digital application process, the provision of data in secure processing environments as well as the features supporting the analyses such as catalogues of coding systems, a point-and-click analysis tool and predefined standard analyses increase user-friendliness for researchers. The use of the extensive health data accessible at HDL will open a wide range of future possibilities for improving the health system and the quality of care. This article begins by highlighting the advantages of the HDL and outlining the opportunities that the RWD offers for research in healthcare and for the population. The structure and central aspects of the HDL are explained afterwards. An outlook on the opportunities of linking different data is given. What the application and data usage processes at the HDL will look like is illustrated using the example of fictitious possibilities for analysing long COVID based on the routine data available at the HDL in the future.}, }
@article {pmid38218363, year = {2024}, author = {Skok, M}, title = {The role of α7 nicotinic acetylcholine receptors in post-acute sequelae of covid-19.}, journal = {The international journal of biochemistry &amp; cell biology}, volume = {168}, number = {}, pages = {106519}, doi = {10.1016/j.biocel.2024.106519}, pmid = {38218363}, issn = {1878-5875}, mesh = {Humans ; alpha7 Nicotinic Acetylcholine Receptor ; Post-Acute COVID-19 Syndrome ; RNA, Viral ; *COVID-19/complications ; SARS-CoV-2 ; Antibodies ; *Receptors, Nicotinic ; }, abstract = {Post-Acute Sequelae of COVID-19 or Long COVID becomes evident some weeks to months following acute COVID-19. Symptoms include cognitive impairment and varying degrees of memory loss with no definitive etiologies or efficacious therapies forthcoming even after four years of the SARS-Cov2 pandemic virus. The aim of this review is to demonstrate the important role of α7 nicotinic acetylcholine receptors in both acute COVID-19 and Long COVID. Evidence presented implicates immune mechanisms stimulated by SARS-Cov-2 S-protein fragment 674-685 that possesses homology with α7-specific ligands. Cognitive dysfunctions observed in Long COVID patients may be derived from anti-idiotypic α7-specific antibodies stimulated by (674-685)-specific antibodies. Therapeutic interventions capable of neutralizing these antibodies and restoring full functions of α7 nicotinic acetylcholine receptors appear to be of paramount importance in post-acute sequelae of COVID-19.}, }
@article {pmid38219763, year = {2024}, author = {Català, M and Mercadé-Besora, N and Kolde, R and Trinh, NTH and Roel, E and Burn, E and Rathod-Mistry, T and Kostka, K and Man, WY and Delmestri, A and Nordeng, HME and Uusküla, A and Duarte-Salles, T and Prieto-Alhambra, D and Jödicke, AM}, title = {The effectiveness of COVID-19 vaccines to prevent long COVID symptoms: staggered cohort study of data from the UK, Spain, and Estonia.}, journal = {The Lancet. Respiratory medicine}, volume = {12}, number = {3}, pages = {225-236}, doi = {10.1016/S2213-2600(23)00414-9}, pmid = {38219763}, issn = {2213-2619}, mesh = {Adult ; Humans ; BNT162 Vaccine ; Cohort Studies ; *COVID-19/epidemiology/prevention &amp; control ; *COVID-19 Vaccines/therapeutic use ; Estonia ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Spain ; United Kingdom/epidemiology ; }, abstract = {BACKGROUND: Although vaccines have proved effective to prevent severe COVID-19, their effect on preventing long-term symptoms is not yet fully understood. We aimed to evaluate the overall effect of vaccination to prevent long COVID symptoms and assess comparative effectiveness of the most used vaccines (ChAdOx1 and BNT162b2).<br><br>METHODS: We conducted a staggered cohort study using primary care records from the UK (Clinical Practice Research Datalink [CPRD] GOLD and AURUM), Catalonia, Spain (Information System for Research in Primary Care [SIDIAP]), and national health insurance claims from Estonia (CORIVA database). All adults who were registered for at least 180 days as of Jan 4, 2021 (the UK), Feb 20, 2021 (Spain), and Jan 28, 2021 (Estonia) comprised the source population. Vaccination status was used as a time-varying exposure, staggered by vaccine rollout period. Vaccinated people were further classified by vaccine brand according to their first dose received. The primary outcome definition of long COVID was defined as having at least one of 25 WHO-listed symptoms between 90 and 365 days after the date of a PCR-positive test or clinical diagnosis of COVID-19, with no history of that symptom 180 days before SARS-Cov-2 infection. Propensity score overlap weighting was applied separately for each cohort to minimise confounding. Sub-distribution hazard ratios (sHRs) were calculated to estimate vaccine effectiveness against long COVID, and empirically calibrated using negative control outcomes. Random effects meta-analyses across staggered cohorts were conducted to pool overall effect estimates.<br><br>FINDINGS: A total of 1&#x2009;618 395 (CPRD GOLD), 5&#x2009;729 800 (CPRD AURUM), 2&#x2009;744&#x2009;821 (SIDIAP), and 77&#x2009;603 (CORIVA) vaccinated people and 1&#x2009;640&#x2009;371 (CPRD GOLD), 5&#x2009;860&#x2009;564 (CPRD AURUM), 2&#x2009;588&#x2009;518 (SIDIAP), and 302&#x2009;267 (CORIVA) unvaccinated people were included. Compared with unvaccinated people, overall HRs for long COVID symptoms in people vaccinated with a first dose of any COVID-19 vaccine were 0&#xb7;54 (95% CI 0&#xb7;44-0&#xb7;67) in CPRD GOLD, 0&#xb7;48 (0&#xb7;34-0&#xb7;68) in CPRD AURUM, 0&#xb7;71 (0&#xb7;55-0&#xb7;91) in SIDIAP, and 0&#xb7;59 (0&#xb7;40-0&#xb7;87) in CORIVA. A slightly stronger preventative effect was seen for the first dose of BNT162b2 than for ChAdOx1 (sHR 0&#xb7;85 [0&#xb7;60-1&#xb7;20] in CPRD GOLD and 0&#xb7;84 [0&#xb7;74-0&#xb7;94] in CPRD AURUM).<br><br>INTERPRETATION: Vaccination against COVID-19 consistently reduced the risk of long COVID symptoms, which highlights the importance of vaccination to prevent persistent COVID-19 symptoms, particularly in adults.<br><br>FUNDING: National Institute for Health and Care Research.}, }
@article {pmid38233059, year = {2024}, author = {Rofail, D and Somersan-Karakaya, S and Choi, JY and Przydzial, K and Zhao, Y and Hussein, M and Norton, TD and Podolanczuk, AJ and Mylonakis, E and Geba, GP}, title = {Thematic analysis to explore patients' experiences with long COVID-19: a conceptual model of symptoms and impacts on daily lives.}, journal = {BMJ open}, volume = {14}, number = {1}, pages = {e076992}, pmid = {38233059}, issn = {2044-6055}, mesh = {Adult ; Humans ; Female ; Male ; *Quality of Life/psychology ; Post-Acute COVID-19 Syndrome ; Activities of Daily Living ; Prospective Studies ; *COVID-19 ; Qualitative Research ; }, abstract = {OBJECTIVES: There is limited qualitative research on patients' experiences with long COVID-19, and how specific symptoms impact their daily lives. The study aimed to understand patients' lived experiences of long COVID-19 and to develop a conceptual model representing the symptoms and their impact on overall quality of life.<br><br>SETTING: Qualitative study consisting of a comprehensive literature review, and in-depth clinician and patient semistructured interviews.<br><br>PARTICIPANTS: Forty-one adult patients with long COVID-19, of whom 18 (44%) were recruited through Regeneron Pharmaceuticals's clinical trials and 23 (56%) through recruitment agencies; 85.4% were female and 73.2% were White. Five independent clinicians treating patients with long COVID-19 were interviewed. Concept saturation was also assessed.<br><br>Interview transcripts were analysed thematically to identify concepts of interest spontaneously mentioned by patients, including symptoms and their impacts on daily life, to guide the development of the conceptual model.<br><br>RESULTS: Findings from the literature review and clinician and patient interviews resulted in the development of a conceptual model comprising two overarching domains: symptoms (upper respiratory tract, lower respiratory tract, smell and taste, systemic, gastrointestinal, neurocognitive and other) and impacts (activities of daily living, instrumental activities of daily living, physical impacts, emotional, social/leisure activities and professional impacts). Saturation was achieved for the reported impacts. The symptoms reported were heterogenic; neurocognitive symptoms, such as numbness, ringing in ears, haziness, confusion, forgetfulness/memory problems, brain fog, concentration, difficulties finding the right word and challenges with fine motor skills, were particularly pertinent for several months.<br><br>CONCLUSION: The conceptual model, developed based on patient experience data of long COVID-19, highlighted numerous symptoms that impact patients' physical and mental well-being, and suggests humanistic unmet needs. Prospective real-world studies are warranted to understand the pattern of long COVID-19 experienced in larger samples over longer periods of time.}, }
@article {pmid38235010, year = {2023}, author = {Shibafar, S and Jafarlou, F}, title = {A review on the impacts of COVID-19 on the auditory system: Implications for public health promotion research.}, journal = {Health promotion perspectives}, volume = {13}, number = {4}, pages = {280-289}, pmid = {38235010}, issn = {2228-6497}, abstract = {BACKGROUND: Currently, there are few studies on the relationship between COVID-19 and the auditory system. In the current study, a review of the studies conducted in the fields of etiopathology, clinical manifestations, research, and treatment of hearing loss caused byCOVID-19 was conducted, which can be used as a baseline for future studies.<br><br>METHODS: We utilized the research approach suggested by Arksey and O'Malley to carry out this scoping review. Search was conducted in Farsi and English with a focus on the onset of hearing loss in patients with COVID-19 through Medline and PubMed, and Google Scholar search engine. Studies included were those involving adult patients diagnosed with COVID-19 who experienced hearing loss, ear pain, ear discharge, and otitis media. Studies were eligible for inclusion if there was a description of the otologic dysfunction, specifically onset, duration, or clinical outcomes.<br><br>RESULTS: Among 90 studies identified, 35 studies were included in the review process. Our findings suggest several possible mechanisms for sudden sensorineural hearing loss (SSNHL) in COVID-19 patients, and COVID-19 infection could have deleterious effects on the inner ear, specifically on the hair cells of the cochlea despite patients being asymptomatic and early identification of SSNHL in COVID-19patients can save the hearing and also patient.<br><br>CONCLUSION: Hearing loss in COVID-19 infection has not received much attention by health care professionals. Sensorineural hearing loss (SNHL), tinnitus, and/or vertigo have been shown to occur during and following COVID-19 infection. Due to lack of research studies, and the inconsistency and even contradictory of the findings, it remains questionable whether COVID-19 contributes to the high incidence of hearing loss. The proper understanding of the mechanisms behind hearing loss in COVID-19 infections needs further research. However, it seems likely that SNHL could be included among the manifestations of those-called "long COVID" syndrome.}, }
@article {pmid38246521, year = {2024}, author = {Daynes, E and Mills, G and Hull, JH and Bishop, NC and Bakali, M and Burtin, C and McAuley, HJC and Singh, SJ and Greening, NJ}, title = {Pulmonary Rehabilitation for People With Persistent Symptoms After COVID-19.}, journal = {Chest}, volume = {166}, number = {3}, pages = {461-471}, doi = {10.1016/j.chest.2024.01.029}, pmid = {38246521}, issn = {1931-3543}, mesh = {Humans ; *COVID-19/rehabilitation/complications ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Exercise Therapy/methods ; }, abstract = {TOPIC IMPORTANCE: COVID-19 can cause ongoing and persistent symptoms (such as breathlessness and fatigue) that lead to reduced functional capacity. There are parallels in symptoms and functional limitations in adults with post-COVID symptoms and adults with chronic respiratory diseases. Pulmonary rehabilitation is a key treatment for adults with chronic respiratory diseases, with the aims to improve symptom management and increase functional capacity. Given the similarities in presentation and aims, a pulmonary rehabilitation program may be optimal to meet the needs of those with ongoing symptoms after COVID-19.<br><br>REVIEW FINDINGS: Aerobic and strength training has shown benefit for adults living with long COVID, although there is little evidence on structured education in this population. Breathing pattern disorder is common in adults with long COVID, and considerations on treatment before rehabilitation, or alongside rehabilitation, are necessary. Considerations on postexertional malaise are important in this population, and evidence from the chronic fatigue syndrome literature supports the need for individualization of exercise programs, and considerations for those who have an adverse reaction to activity and/or exercise.<br><br>SUMMARY: This narrative review summarizes the current evidence on pulmonary rehabilitation programs in a long-COVID population. Where the evidence is lacking in long COVID the supporting evidence of these programs in chronic respiratory diseases has highlighted the importance of aerobic and strength training, considerations for fatigue, potential mechanisms for immunology improvement, and management of breathing pattern disorders in these programs.}, }
@article {pmid38248798, year = {2024}, author = {Trofor, AC and Robu Popa, D and Melinte, OE and Trofor, L and Vicol, C and Grosu-Creangă, IA and Crișan Dabija, RA and Cernomaz, AT}, title = {Looking at the Data on Smoking and Post-COVID-19 Syndrome-A Literature Review.}, journal = {Journal of personalized medicine}, volume = {14}, number = {1}, pages = {}, pmid = {38248798}, issn = {2075-4426}, abstract = {Long COVID is a recently described entity that is responsible for significant morbidity and that has consequences ranging from mild to life-threatening. The underlying mechanisms are not completely understood, and treatment options are currently limited, as existing data focus more on risk factors and predictors. Smoking has been reported as a risk factor for poor outcomes of acute SARS-CoV-2 infection and seems to also play a role in mediating post-COVID-19 symptoms. We aimed to review relevant work addressing the interaction between smoking and long COVID in order to characterize smoking's role as a risk factor and possibly identify new research directions. Methods: The PubMed/MEDLINE database was searched using the keywords 'smoking', 'long COVID', and 'post-acute COVID' to identify relevant English-language articles published up to October 2023. Results and conclusions: From the 374 initial hits, a total of 36 papers were deemed relevant to the aim of the review. There was significant variability concerning the ways in which tobacco usage was quantified and reported; still, there is compelling evidence linking smoking to an increased risk of developing manifestations of post-acute-COVID disease. Some clinical conditions, such as dyspnea, cardiovascular symptoms, and cognitive or mental-health impairment, seem to be relatively strongly associated with smoking, while the connection between smoking and upper-airway involvement seems less certain. The available data support recommending smoking cessation as a clinical tool for the prevention of long COVID.}, }
@article {pmid38253027, year = {2024}, author = {Untersmayr, E and Venter, C and Smith, P and Rohrhofer, J and Ndwandwe, C and Schwarze, J and Shannon, E and Sokolowska, M and Sadlier, C and O'Mahony, L}, title = {Immune Mechanisms Underpinning Long COVID: Collegium Internationale Allergologicum Update 2024.}, journal = {International archives of allergy and immunology}, volume = {185}, number = {5}, pages = {489-502}, doi = {10.1159/000535736}, pmid = {38253027}, issn = {1423-0097}, mesh = {Humans ; *COVID-19/immunology ; *SARS-CoV-2/immunology ; *Post-Acute COVID-19 Syndrome ; Dysbiosis/immunology ; Autoimmunity ; }, abstract = {BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in a prolonged multisystem disorder termed long COVID, which may affect up to 10% of people following coronavirus disease 2019 (COVID-19). It is currently unclear why certain individuals do not fully recover following SARS-CoV-2 infection.<br><br>SUMMARY: In this review, we examine immunological mechanisms that may underpin the pathophysiology of long COVID. These mechanisms include an inappropriate immune response to acute SARS-CoV-2 infection, immune cell exhaustion, immune cell metabolic reprogramming, a persistent SARS-CoV-2 reservoir, reactivation of other viruses, inflammatory responses impacting the central nervous system, autoimmunity, microbiome dysbiosis, and dietary factors.<br><br>KEY MESSAGES: Unfortunately, the currently available diagnostic and treatment options for long COVID are inadequate, and more clinical trials are needed that match experimental interventions to underlying immunological mechanisms.}, }
@article {pmid38255826, year = {2024}, author = {Müller, L and Di Benedetto, S}, title = {Immunosenescence and Cytomegalovirus: Exploring Their Connection in the Context of Aging, Health, and Disease.}, journal = {International journal of molecular sciences}, volume = {25}, number = {2}, pages = {}, pmid = {38255826}, issn = {1422-0067}, mesh = {Aged ; Humans ; Cytomegalovirus ; Post-Acute COVID-19 Syndrome ; Aging ; *Immunosenescence ; *Cytomegalovirus Infections ; *COVID-19 ; *Latent Infection ; }, abstract = {Aging induces numerous physiological alterations, with immunosenescence emerging as a pivotal factor. This phenomenon has attracted both researchers and clinicians, prompting profound questions about its implications for health and disease. Among the contributing factors, one intriguing actor in this complex interplay is human cytomegalovirus (CMV), a member of the herpesvirus family. Latent CMV infection exerts a profound influence on the aging immune system, potentially contributing to age-related diseases. This review delves into the intricate relationship between immunosenescence and CMV, revealing how chronic viral infection impacts the aging immune landscape. We explore the mechanisms through which CMV can impact both the composition and functionality of immune cell populations and induce shifts in inflammatory profiles with aging. Moreover, we examine the potential role of CMV in pathologies such as cardiovascular diseases, cancer, neurodegenerative disorders, COVID-19, and Long COVID. This review underlines the importance of understanding the complex interplay between immunosenescence and CMV. It offers insights into the pathophysiology of aging and age-associated diseases, as well as COVID-19 outcomes among the elderly. By unraveling the connections between immunosenescence and CMV, we gain a deeper understanding of aging's remarkable journey and the profound role that viral infections play in transforming the human immune system.}, }
@article {pmid38256558, year = {2024}, author = {Kao, CM}, title = {Overview of COVID-19 Infection, Treatment, and Prevention in Children.}, journal = {Journal of clinical medicine}, volume = {13}, number = {2}, pages = {}, pmid = {38256558}, issn = {2077-0383}, abstract = {Coronavirus disease 2019 (COVID-19), caused by the novel respiratory virus-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-was declared a global pandemic by the World Health Organization on 11 March 2020. Since then, substantial gains have been made in our understanding of COVID-19 epidemiology, disease presentation, and management. While children tend to have less severe disease courses compared to adults, children can still develop severe COVID-19 infections, particularly in those with underlying medical conditions such as obesity, chronic lung disease, or prematurity. In addition, children are at risk of severe complications of COVID-19 infection, such as multisystem inflammatory syndrome in children (MIS-C) or long COVID. The case definitions of MIS-C and long COVID have continued to evolve with the increased understanding of these new entities; however, improved methods of diagnosis and determination of the optimal management are still needed. Furthermore, with the continued circulation of SARS-CoV-2 variants, there remains a need for clinicians to remain up-to-date on the latest treatment and prevention options. The purpose of this review is to provide an evidence-based review of what we have learned about COVID-19 in children since the start of the pandemic and how best to counsel children and their families on the best methods of prevention.}, }
@article {pmid38257728, year = {2023}, author = {Len, JS and Koh, CWT and Chan, KR}, title = {The Functional Roles of MDSCs in Severe COVID-19 Pathogenesis.}, journal = {Viruses}, volume = {16}, number = {1}, pages = {}, pmid = {38257728}, issn = {1999-4915}, support = {MOH-000610-00//National Medical Research Council/ ; }, mesh = {Aged ; Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; *Myeloid-Derived Suppressor Cells ; Gene Expression Profiling ; Immunocompromised Host ; }, abstract = {Severe COVID-19 is a major cause of morbidity and mortality worldwide, especially among those with co-morbidities, the elderly, and the immunocompromised. However, the molecular determinants critical for severe COVID-19 progression remain to be fully elucidated. Meta-analyses of transcriptomic RNAseq and single-cell sequencing datasets comparing severe and mild COVID-19 patients have demonstrated that the early expansion of myeloid-derived suppressor cells (MDSCs) could be a key feature of severe COVID-19 progression. Besides serving as potential early prognostic biomarkers for severe COVID-19 progression, several studies have also indicated the functional roles of MDSCs in severe COVID-19 pathogenesis and possibly even long COVID. Given the potential links between MDSCs and severe COVID-19, we examine the existing literature summarizing the characteristics of MDSCs, provide evidence of MDSCs in facilitating severe COVID-19 pathogenesis, and discuss the potential therapeutic avenues that can be explored to reduce the risk and burden of severe COVID-19. We also provide a web app where users can visualize the temporal changes in specific genes or MDSC-related gene sets during severe COVID-19 progression and disease resolution, based on our previous study.}, }
@article {pmid38257821, year = {2024}, author = {Panagiotides, NG and Poledniczek, M and Andreas, M and Hülsmann, M and Kocher, AA and Kopp, CW and Piechota-Polanczyk, A and Weidenhammer, A and Pavo, N and Wadowski, PP}, title = {Myocardial Oedema as a Consequence of Viral Infection and Persistence-A Narrative Review with Focus on COVID-19 and Post COVID Sequelae.}, journal = {Viruses}, volume = {16}, number = {1}, pages = {}, pmid = {38257821}, issn = {1999-4915}, mesh = {Humans ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Virus Diseases ; Disease Progression ; Edema ; }, abstract = {Microvascular integrity is a critical factor in myocardial fluid homeostasis. The subtle equilibrium between capillary filtration and lymphatic fluid removal is disturbed during pathological processes leading to inflammation, but also in hypoxia or due to alterations in vascular perfusion and coagulability. The degradation of the glycocalyx as the main component of the endothelial filtration barrier as well as pericyte disintegration results in the accumulation of interstitial and intracellular water. Moreover, lymphatic dysfunction evokes an increase in metabolic waste products, cytokines and inflammatory cells in the interstitial space contributing to myocardial oedema formation. This leads to myocardial stiffness and impaired contractility, eventually resulting in cardiomyocyte apoptosis, myocardial remodelling and fibrosis. The following article reviews pathophysiological inflammatory processes leading to myocardial oedema including myocarditis, ischaemia-reperfusion injury and viral infections with a special focus on the pathomechanisms evoked by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In addition, clinical implications including potential long-term effects due to viral persistence (long COVID), as well as treatment options, are discussed.}, }
@article {pmid38258769, year = {2024}, author = {Hodel, K and Fonseca, A and Barbosa, I and Medina, C and Alves, B and Maciel, C and Nascimento, D and Oliveira-Junior, G and Pedreira, L and de Souza, M and Godoy, AL}, title = {Obesity and its Relationship with Covid-19: A Review of the Main Pharmaceutical Aspects.}, journal = {Current pharmaceutical biotechnology}, volume = {25}, number = {13}, pages = {1651-1663}, pmid = {38258769}, issn = {1873-4316}, mesh = {Humans ; *Obesity/metabolism ; *COVID-19/complications ; *COVID-19 Drug Treatment ; *SARS-CoV-2 ; Antiviral Agents/therapeutic use/pharmacokinetics ; COVID-19 Vaccines ; }, abstract = {Important physiological changes are observed in patients with obesity, such as intestinal permeability, gastric emptying, cardiac output, and hepatic and renal function. These differences can determine variations in the pharmacokinetics of different drugs and can generate different concentrations at the site of action, which can lead to sub therapeutic or toxic concentrations. Understanding the physiological and immunological processes that lead to the clinical manifestations of COVID-19 is essential to correlate obesity as a risk factor for increasing the prevalence, severity, and lethality of the disease. Several drugs have been suggested to control COVID- 19 like Lopinavir, Ritonavir, Ribavirin, Sofosbuvir, Remdesivir, Oseltamivir, Oseltamivir phosphate, Oseltamivir carboxylate, Hydroxychloroquine, Chloroquine, Azithromycin, Teicoplanin, Tocilizumab, Anakinra, Methylprednisolone, Prednisolone, Ciclesonide and Ivermectin. Similarly, these differences between healthy people and obese people can be correlated to mechanical factors, such as insufficient doses of the vaccine for high body mass, impairing the absorption and distribution of the vaccine that will be lower than desired or can be linked to the inflammatory state in obese patients, which can influence the humoral immune response. Additionally, different aspects make the obese population more prone to persistent symptoms of the disease (long COVID), which makes understanding these mechanisms fundamental to addressing the implications of the disease. Thus, this review provides an overview of the relationship between COVID-19 and obesity, considering aspects related to pharmacokinetics, immunosuppression, immunization, and possible implications of long COVID in these individuals.}, }
@article {pmid38269219, year = {2023}, author = {Schaefer, J and Khanna, D}, title = {Nutritional and Wellness Strategies for Neurological and Psychiatric Recovery From Post-COVID Syndrome and Post-acute Sequelae of COVID-19.}, journal = {Cureus}, volume = {15}, number = {12}, pages = {e51076}, pmid = {38269219}, issn = {2168-8184}, abstract = {The post-COVID syndrome was officially recognized as a disability under the Americans with Disabilities Act, indicating that this syndrome has made a significant impact on our populace. Also, post-acute sequelae of COVID-19 (PASC) is a term that describes the long-term health problems that some people experience after being infected with the virus that causes COVID-19. These problems can last for weeks, months, or even years, and can affect various parts of the body, such as the heart, lungs, brain, and blood vessels. This narrative review paper utilized the PubMed database to explore the pathophysiology of post-COVID syndrome's neurological and psychiatric symptoms and PASC and make therapeutic connections to the known mechanisms of various nutritional, supplemental, and wellness approaches. Searches were queried on the PubMed database between March 29 and April 16, 2022, using the phrases "long-covid," "post-COVID syndrome," "Vitamin D covid," "vitamin C covid," "omega-3 covid," "kynurenine covid," "whole-body hyperthermia," "mushrooms immunity," "n-acetyl cysteine covid," "mushrooms cognition," "sugar consumption inflammation," and "covid microbiome." Articles were screened for their relevance to the discussion of post-COVID syndrome's neurological and psychiatric pathophysiology at the discretion of the principal researcher. There were no limitations regarding publication years, but articles from 2005 to April 2022 were cited. Micro-ischemic disease, neuropathy, autoimmune processes, mast-cell activation, and impaired blood-brain barriers have all been implicated in the pathological processes of this syndrome with varying degrees of supportive evidence. The common denominators, however, are inflammation and oxidative stress. Therefore, a beneficial approach to dealing with the complications of post-COVID syndrome would be to reduce the exacerbations of these common denominators with lifestyle and nutritional changes. Replenishing nutritional deficiencies, supplementing with N-acetylcysteine, decreasing consumption of refined sugars, preventing dysbiosis of the microbiome, performing exercises, increasing dietary intake of mushrooms, utilizing beneficial herbs such as rosemary, and increasing the core body temperature through whole-body hyperthermia seem to show potential for efficacy in this pursuit. Considering the safety and evidence-based connections of the therapies explored for dealing with the post-Covid syndrome, it could be of great benefit and of little harm to our patients to include these considerations in formulating post-Covid treatment plans.}, }
@article {pmid38274052, year = {2023}, author = {Ahmad, I and Amelio, A and Merla, A and Scozzari, F}, title = {A survey on the role of artificial intelligence in managing Long COVID.}, journal = {Frontiers in artificial intelligence}, volume = {6}, number = {}, pages = {1292466}, pmid = {38274052}, issn = {2624-8212}, abstract = {In the last years, several techniques of artificial intelligence have been applied to data from COVID-19. In addition to the symptoms related to COVID-19, many individuals with SARS-CoV-2 infection have described various long-lasting symptoms, now termed Long COVID. In this context, artificial intelligence techniques have been utilized to analyze data from Long COVID patients in order to assist doctors and alleviate the considerable strain on care and rehabilitation facilities. In this paper, we explore the impact of the machine learning methodologies that have been applied to analyze the many aspects of Long COVID syndrome, from clinical presentation through diagnosis. We also include the text mining techniques used to extract insights and trends from large amounts of text data related to Long COVID. Finally, we critically compare the various approaches and outline the work that has to be done to create a robust artificial intelligence approach for efficient diagnosis and treatment of Long COVID.}, }
@article {pmid38274511, year = {2023}, author = {Martínez-Borba, V and Martínez-García, L and Peris-Baquero, &#xd3; and Osma, J and Del Corral-Beamonte, E}, title = {Guiding future research on psychological interventions in people with COVID-19 and post COVID syndrome and comorbid emotional disorders based on a systematic review.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1305463}, pmid = {38274511}, issn = {2296-2565}, mesh = {Adult ; Humans ; Psychosocial Intervention ; Post-Acute COVID-19 Syndrome ; Pandemics ; *COVID-19/epidemiology ; *Cognitive Behavioral Therapy/methods ; }, abstract = {OBJECTIVE: The COVID-19 pandemic has been emotionally challenging for the entire population and especially for people who contracted the illness. This systematic review summarizes psychological interventions implemented in COVID-19 and long COVID-19 patients who presented comorbid emotional disorders.<br><br>METHODS AND MEASURES: 3,839 articles were identified in 6 databases and 43 of them were included in this work. Two independent researchers selected the articles and assessed their quality.<br><br>RESULTS: 2,359 adults were included in this review. Severity of COVID-19 symptoms ranged from asymptomatic to hospitalized patients; only 3 studies included long COVID-19 populations. Similar number of randomized controlled studies (n&#x2009;=&#x2009;15) and case studies (n&#x2009;=&#x2009;14) were found. Emotional disorders were anxiety and/or depressive symptoms (n&#x2009;=&#x2009;39) and the psychological intervention most represented had a cognitive behavioral approach (n&#x2009;=&#x2009;10). Length of psychological programs ranged from 1-5 sessions (n&#x2009;=&#x2009;6) to 16 appointments (n&#x2009;=&#x2009;2). Some programs were distributed on a daily (n&#x2009;=&#x2009;4) or weekly basis (n&#x2009;=&#x2009;2), but other proposed several sessions a week (n&#x2009;=&#x2009;4). Short (5-10&#x2009;min, n&#x2009;=&#x2009;4) and long sessions (60-90&#x2009;min, n&#x2009;=&#x2009;3) are proposed. Most interventions were supported by the use of technologies (n&#x2009;=&#x2009;18). Important risk of bias was present in several studies.<br><br>CONCLUSION: Promising results in the reduction of depressive, anxiety and related disorders have been found. However, important limitations in current psychological interventions were detected (i.e., duration, format, length, and efficacy of interventions were not consistently established across investigations). The results derived from our work may help to understand clinical practices in the context of pandemics and could guide future efforts to manage emotional suffering in COVID-19 patients. A stepped model of care could help to determine the dosage, length and format of delivery for each patient.Systematic review registration: PROSPERO 2022 CRD42022367227. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022367227.}, }
@article {pmid38275749, year = {2023}, author = {León-Moreno, LC and Reza-Zaldívar, EE and Hernández-Sapiéns, MA and Villafaña-Estarrón, E and García-Martin, M and Ojeda-Hernández, DD and Matias-Guiu, JA and Gomez-Pinedo, U and Matias-Guiu, J and Canales-Aguirre, AA}, title = {Mesenchymal Stem Cell-Based Therapies in the Post-Acute Neurological COVID Syndrome: Current Landscape and Opportunities.}, journal = {Biomolecules}, volume = {14}, number = {1}, pages = {}, pmid = {38275749}, issn = {2218-273X}, support = {9790-2021.//Fondo de Desarrollo Cient&#xed;fico de Jalisco/ ; }, mesh = {Humans ; *COVID-19/therapy ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Mesenchymal Stem Cells/physiology ; Central Nervous System ; }, abstract = {One of the main concerns related to SARS-CoV-2 infection is the symptoms that could be developed by survivors, known as long COVID, a syndrome characterized by persistent symptoms beyond the acute phase of the infection. This syndrome has emerged as a complex and debilitating condition with a diverse range of manifestations affecting multiple organ systems. It is increasingly recognized for affecting the Central Nervous System, in which one of the most prevalent manifestations is cognitive impairment. The search for effective therapeutic interventions has led to growing interest in Mesenchymal Stem Cell (MSC)-based therapies due to their immunomodulatory, anti-inflammatory, and tissue regenerative properties. This review provides a comprehensive analysis of the current understanding and potential applications of MSC-based interventions in the context of post-acute neurological COVID-19 syndrome, exploring the underlying mechanisms by which MSCs exert their effects on neuroinflammation, neuroprotection, and neural tissue repair. Moreover, we discuss the challenges and considerations specific to employing MSC-based therapies, including optimal delivery methods, and functional treatment enhancements.}, }
@article {pmid38277732, year = {2024}, author = {Gamero-de-Luna, EJ and Sánchez-Jaén, MR}, title = {[Genetic factors associated with long COVID].}, journal = {Semergen}, volume = {50}, number = {2}, pages = {102187}, doi = {10.1016/j.semerg.2023.102187}, pmid = {38277732}, issn = {1578-8865}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/genetics ; Forkhead Transcription Factors ; }, abstract = {INTRODUCTION: The variability in expression and evolution of COVID is not completely explained by clinical factors. In fact, genetic factors play an important role. Moreover, it is unknown whether the genetic factor that contribute to susceptibility and severity are also involved in the onset and evolution of long-COVID. The objective of this review is to gather information from literature to understand which genetic factors are involved in the onset of persistent COVID.<br><br>MATERIAL AND METHODS: Systematic review in PubMed and bioRxiv and medRxiv repositories based on MeSH-descriptors and MeSH-terms related to COVID and genetic factors. Using these terms 2715 articles were pooled. An initial screening performed by authors independently, selected 205 articles of interest. A final deeper screening a total of 85 articles were chosen for complete reading and summarized in this review.<br><br>RESULTS: Although ACE2 and TMPSS6 are involved in COVID susceptibility, their involvement in long-COVID has not been found. On the other hand, the severity of the disease and the onset of long-COVID has been associated with different genes involved in the inflammatory and immune response. Particularly interesting has been the association found with the FOXP4 locus.<br><br>CONCLUSIONS: Although studies on long-COVID are insufficient to fully comprehend the cause, it is clear that the current identified genetic factors do not fully explain the progression and onset of long-COVID. Other factors such as polygenic action, pleiotropic genes, the microbiota and epigenetic changes must be considered and studied.}, }
@article {pmid38277734, year = {2024}, author = {Suárez, D and Pascual, E and Soravilla, JR}, title = {[Long covid and disability].}, journal = {Semergen}, volume = {50}, number = {2}, pages = {102189}, doi = {10.1016/j.semerg.2023.102189}, pmid = {38277734}, issn = {1578-8865}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; SARS-CoV-2 ; Anxiety ; Pandemics ; }, abstract = {Long covid is a health problem that will entail a high hidden cost attributable to the pandemic years after it because it affects the work capacity of many workers. Given the millions of covid-19 cases worldwide and current research showing that one in 7covid-19 patients remain symptomatic at 12 weeks, the number of long covid patients is likely to be substantial. Long covid is characterized by heterogeneous sequelae that often affect multiple systems, organs with an impact on the functioning and capacity of the worker. Workers with long covid symptoms can return to their occupation but this involves a complex individualized approach to the impact of symptoms on work, adjustments and modifications to the workplace. Patients with long covid typically report prolonged multisystem involvement and signicant disability. The psychological cost to the worker must also be addressed. A survey by the Community of Madrid (CCOO, SATSE, CSIF, AMYTS) in 2022 reveals that 24.5% of those affected by long covid were sick for more than 12 months; 30% of those affected by persistent covid need and adaption to their workplace. In Spain, more than 10million people infected with SARS-CoV-2 have been reported since the pandemic began, so it is estimated that there could be one million people with persistent covid. In 2021 alone there were more than 2.6 million sick leave due to covid-19 in Spain, the average duration of which was 10 days. One hundred million people around the world suffer from persistent covid, but few countries officially count them, nor do they help those affected with employment. In advanced countries, like the United States, long covid is treated as a disability,and the number of people with disabilities working or looking for work increased by 1.36 million, an increase of 23%, between January 2021 and January 2022. In the United Kingdom, some 200,000 people are not working or are not looking for work due to long-term health problems attributable to long covid, since the pandemic began.}, }
@article {pmid38279014, year = {2024}, author = {Toepfner, N and Brinkmann, F and Augustin, S and Stojanov, S and Behrends, U}, title = {Long COVID in pediatrics-epidemiology, diagnosis, and management.}, journal = {European journal of pediatrics}, volume = {183}, number = {4}, pages = {1543-1553}, pmid = {38279014}, issn = {1432-1076}, mesh = {Adolescent ; Humans ; Child ; Infant, Newborn ; Post-Acute COVID-19 Syndrome ; *Fatigue Syndrome, Chronic ; *COVID-19/diagnosis/epidemiology/therapy ; Quality of Life ; SARS-CoV-2 ; Disease Progression ; COVID-19 Testing ; }, abstract = {This review summarizes current knowledge on post-acute sequelae of COVID-19 (PASC) and post-COVID-19 condition (PCC) in children and adolescents. A literature review was performed to synthesize information from clinical studies, expert opinions, and guidelines. PASC also termed Long COVID - at any age comprise a plethora of unspecific symptoms present later than 4 weeks after confirmed or probable infection with severe respiratory syndrome corona virus type 2 (SARS-CoV-2), without another medical explanation. PCC in children and adolescents was defined by the WHO as PASC occurring within 3 months of acute coronavirus disease 2019 (COVID-19), lasting at least 2 months, and limiting daily activities. Pediatric PASC mostly manifest after mild courses of COVID-19 and in the majority of cases remit after few months. However, symptoms can last for more than 1 year and may result in significant disability. Frequent symptoms include fatigue, exertion intolerance, and anxiety. Some patients present with postural tachycardia syndrome (PoTS), and a small number of cases fulfill the clinical criteria of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). To date, no diagnostic marker has been established, and differential diagnostics remains challenging. Therapeutic approaches include appropriate self-management as well as the palliation of symptoms by non-pharmaceutical and pharmaceutical strategies. Conclusion: PASC in pediatrics present with heterogenous severity and duration. A stepped, interdisciplinary, and individualized approach is essential for appropriate clinical management. Current health care structures have to be adapted, and research was extended to meet the medical and psychosocial needs of young people with PASC or similar conditions. What is Known: • Post-acute sequelae of coronavirus 2019 (COVID-19) (PASC) - also termed Long COVID - in children and adolescents can lead to activity limitation and reduced quality of life. • PASC belongs to a large group of similar post-acute infection syndromes (PAIS). Specific biomarkers and causal treatment options are not yet available. What is New: • In February 2023, a case definition for post COVID-19 condition (PCC) in children and adolescents was provided by the World Health Organization (WHO), indicating PASC with duration of at least 2 months and limitation of daily activities. PCC can present as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). • Interdisciplinary collaborations are necessary and have been established worldwide to offer harmonized, multimodal approaches to diagnosis and management of PASC/PCC in children and adolescents.}, }
@article {pmid38279329, year = {2024}, author = {Álvarez-Santacruz, C and Tyrkalska, SD and Candel, S}, title = {The Microbiota in Long COVID.}, journal = {International journal of molecular sciences}, volume = {25}, number = {2}, pages = {}, pmid = {38279329}, issn = {1422-0067}, support = {00006/COVI/20//Fundaci&#xf3;n S&#xe9;neca - Agencia de Ciencia y Tecnolog&#xed;a de la Regi&#xf3;n de Murcia/ ; 21118/SF/19//Fundaci&#xf3;n S&#xe9;neca - Agencia de Ciencia y Tecnolog&#xed;a de la Regi&#xf3;n de Murcia/ ; Juan de la Cierva-Incorporaci&#xf3;n//Ministerio de Ciencia e Innovaci&#xf3;n/ ; }, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; Dysbiosis ; *Microbiota ; *Vaccines ; }, abstract = {Interest in the coronavirus disease 2019 (COVID-19) has progressively decreased lately, mainly due to the great effectivity of vaccines. Furthermore, no new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants able to circumvent the protection of these vaccines, while presenting high transmissibility and/or lethality, have appeared. However, long COVID has emerged as a huge threat to human health and economy globally. The human microbiota plays an important role in health and disease, participating in the modulation of innate and adaptive immune responses. Thus, multiple studies have found that the nasopharyngeal microbiota is altered in COVID-19 patients, with these changes associated with the onset and/or severity of the disease. Nevertheless, although dysbiosis has also been reported in long COVID patients, mainly in the gut, little is known about the possible involvement of the microbiota in the development of this disease. Therefore, in this work, we aim to fill this gap in the knowledge by discussing and comparing the most relevant studies that have been published in this field up to this point. Hence, we discuss that the relevance of long COVID has probably been underestimated, and that the available data suggest that the microbiota could be playing a pivotal role on the pathogenesis of the disease. Further research to elucidate the involvement of the microbiota in long COVID will be essential to explore new therapeutic strategies based on manipulation of the microbiota.}, }
@article {pmid38284464, year = {2024}, author = {Çulha, Y and Büyükyılmaz, F and Çulha, MG}, title = {The effect of long-term COVID-19 on aetiological factors related to nocturia.}, journal = {Journal of clinical nursing}, volume = {33}, number = {3}, pages = {1161-1168}, doi = {10.1111/jocn.17037}, pmid = {38284464}, issn = {1365-2702}, mesh = {Humans ; *Nocturia/etiology/drug therapy ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; *Urinary Bladder, Overactive/complications/drug therapy ; Urinary Bladder ; }, abstract = {AIMS AND OBJECTIVES: This study was conducted to examine the possible aetiology of nocturia in patients with long-term COVID-19.<br><br>BACKGROUND: Physical and neuropsychiatric symptoms, an increase in overactive bladder symptoms, especially from urinary system complaints, has been reported in patients with COVID-19, 10-14&#x2009;weeks after the illness.<br><br>DESIGN: A descriptive design.<br><br>METHODS: The study consisted of 70 patients who had experienced COVID-19, had nocturia, and were followed in the State Hospital between April and July 2022. Data were collected using a patient information form, the 'TANGO' nocturia screening tool, and the Visual Analog Scale. This study was created in accordance with the STROBE Statement Checklist.<br><br>RESULTS: When the nocturia effects of long-term COVID-19 were examined it was determined that the urinary tract was the 'priority' aetiological condition. It was observed that there was a significant difference between the aetiological factor groups in terms of the mean age of the patients and the number of nocturia (p&#x2009;<&#x2009;.05). According to post-hoc analysis, the mean age of patients with a dominant cardio-metabolic factor was found to be significantly younger (p&#x2009;<&#x2009;.05). In addition, when comparing the number of nocturia according to the aetiological factors of the patients, it was observed that the number of nocturia was significantly frequent in the patients with a dominant sleep factor (p&#x2009;<&#x2009;.05).<br><br>CONCLUSIONS: It was found that the urinary tract aetiological factor was dominant in patients with long-term COVID-19 and nocturia, patients with a dominant cardiovascular aetiological factor were younger, and that the number of nocturia was higher in patients with a dominant sleep factor.<br><br>Identification of the early signs and symptoms and underlying causes of nocturia in individuals with post-COVID-19 syndrome will enable nurses and health professionals to guide the early identification of different underlying problems, as well as the implementation of approaches to treat and eliminate nocturia.<br><br>The patients contributed to the study by agreeing to participate in the evaluation of nocturia complaints after COVID-19 infection.}, }
@article {pmid38285646, year = {2026}, author = {McMaster, MW and Dey, S and Fishkin, T and Wang, A and Frishman, WH and Aronow, WS}, title = {The Impact of Long COVID-19 on the Cardiovascular System.}, journal = {Cardiology in review}, volume = {34}, number = {1}, pages = {11-18}, doi = {10.1097/CRD.0000000000000654}, pmid = {38285646}, issn = {1538-4683}, mesh = {Humans ; *COVID-19/complications/physiopathology ; *Cardiovascular Diseases/physiopathology/etiology/virology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long coronavirus disease (COVID) is the development or persistence of symptoms after an acute SARS-CoV-2 (COVID-19) infection. Fewer patients are developing acute COVID-19 infections, but patients with long COVID continue to have alarming long-term sequelae. Many cardiac magnetic resonance imaging studies show significant changes in cardiac structure after a COVID-19 infection, suggestive of an increased burden of many cardiovascular diseases, notably myocarditis. The pathophysiology of COVID-19 requires viral binding to angiotensin-converting enzyme 2 protein receptors throughout the body, which are upregulated by inflammation. Consequently, the numerous preexisting conditions that worsen or prolong inflammation enhance this binding and have differing effects on patients based on their unique immune systems. These pathophysiological changes drive long COVID cardiac sequelae such as inappropriate sinus tachycardia, postural orthostatic tachycardia, and other types of orthostatic intolerance. Increased screening for long COVID and low-risk interventions such as exercise regimens could alleviate the suffering endured by patients with long COVID. Many studies such as the Researching COVID to Enhance Recovery Initiative (RECOVER) trials at the National Institutes of Health are exploring potential treatments for long COVID patients.}, }
@article {pmid38294616, year = {2024}, author = {Kelleni, MT}, title = {Repurposing metformin to manage idiopathic or long COVID Tinnitus: self-report adopting a pathophysiological and pharmacological approach.}, journal = {Inflammopharmacology}, volume = {32}, number = {2}, pages = {945-948}, pmid = {38294616}, issn = {1568-5608}, mesh = {Male ; Humans ; Self Report ; Post-Acute COVID-19 Syndrome ; *Tinnitus/drug therapy ; *COVID-19 ; }, abstract = {Chronic tinnitus is a common neurological disorder that affects millions of patients globally with no available successful pharmacotherapy. It can be extremely bothersome to some patients to the extent that it occasionally qualifies as a disability that can hinder them from leading a normal life. In this short communication, the author discusses how he suffered from idiopathic tinnitus and how he managed to adopt a combined pathophysiological and pharmacological approach to the reason for the first time in the medical literature that low-dose metformin might be safely and effectively repurposed to manage at least a subset of tinnitus patients while discussing the potential role of adenosine receptor agonists as potential future tinnitus therapeutics.}, }
@article {pmid38299237, year = {2024}, author = {Lempesis, IG and Georgakopoulou, VE and Reiter, RJ and Spandidos, DA}, title = {A mid‑pandemic night's dream: Melatonin, from harbinger of anti‑inflammation to mitochondrial savior in acute and long COVID‑19 (Review).}, journal = {International journal of molecular medicine}, volume = {53}, number = {3}, pages = {}, pmid = {38299237}, issn = {1791-244X}, mesh = {Humans ; Antioxidants/pharmacology/therapeutic use/metabolism ; *COVID-19 ; *Melatonin/pharmacology/therapeutic use/metabolism ; Pandemics ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2/metabolism ; }, abstract = {Coronavirus disease 2019 (COVID‑19), a systemic illness caused by severe acute respiratory distress syndrome 2 (SARS‑CoV‑2), has triggered a worldwide pandemic with symptoms ranging from asymptomatic to chronic, affecting practically every organ. Melatonin, an ancient antioxidant found in all living organisms, has been suggested as a safe and effective therapeutic option for the treatment of SARS‑CoV‑2 infection due to its good safety characteristics and broad‑spectrum antiviral medication properties. Melatonin is essential in various metabolic pathways and governs physiological processes, such as the sleep‑wake cycle and circadian rhythms. It exhibits oncostatic, anti‑inflammatory, antioxidant and anti‑aging properties, exhibiting promise for use in the treatment of numerous disorders, including COVID‑19. The preventive and therapeutic effects of melatonin have been widely explored in a number of conditions and have been well‑established in experimental ischemia/reperfusion investigations, particularly in coronary heart disease and stroke. Clinical research evaluating the use of melatonin in COVID‑19 has shown various improved outcomes, including reduced hospitalization durations; however, the trials are small. Melatonin can alleviate mitochondrial dysfunction in COVID‑19, improve immune cell function and provide antioxidant properties. However, its therapeutic potential remains underexplored due to funding limitations and thus further investigations are required.}, }
@article {pmid38306758, year = {2024}, author = {Ahmed, S and Ahmad, E and Ahmad, B and Arif, MH and Ilyas, HMA and Hashmi, N and Ahmad, S}, title = {Long COVID-19 and primary care: Challenges, management and recommendations.}, journal = {Semergen}, volume = {50}, number = {3}, pages = {102188}, doi = {10.1016/j.semerg.2023.102188}, pmid = {38306758}, issn = {1578-8865}, mesh = {Humans ; *COVID-19/therapy ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Chronic Disease ; Primary Health Care ; Disease Progression ; }, abstract = {Long COVID-19, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by persistent symptoms after COVID-19 onset. This article explores the challenges, management strategies, and recommendations for addressing long COVID-19 in primary care settings. The epidemiology of long COVID-19 reveals significant variability, with a substantial portion of COVID-19 survivors experiencing post-acute symptoms. Pathophysiological mechanisms include viral persistence, endothelial dysfunction, autoimmunity, neurological dysregulation, and gastrointestinal dysbiosis. Multiple risk factors, including age, sex, pre-existing comorbidities, smoking, BMI, and acute COVID-19 severity, influence the development of long COVID-19. Effective management requires proactive measures such as vaccination, identification of high-risk populations, public awareness, and post-infection vaccination. Collaboration of primary care physicians with specialists is essential for holistic and individualized patient care. This article underscores the role of primary care physicians in diagnosing, managing, and mitigating the long-term effects of COVID-19.}, }
@article {pmid38316434, year = {2024}, author = {Laskowski, NM and Brandt, G and Paslakis, G}, title = {[Gender Inequalities of the COVID-19 Pandemic: A Synthesis of Systematic Reviews with a Focus on Sexual and Gender Minorities].}, journal = {Psychotherapie, Psychosomatik, medizinische Psychologie}, volume = {74}, number = {2}, pages = {57-69}, doi = {10.1055/a-2228-6244}, pmid = {38316434}, issn = {1439-1058}, mesh = {Male ; Humans ; Female ; *COVID-19/epidemiology ; Pandemics ; Gender Equity ; Post-Acute COVID-19 Syndrome ; Systematic Reviews as Topic ; *Sexual and Gender Minorities ; Gender Identity ; }, abstract = {OBJECTIVE: From the very beginning of the COVID-19 pandemic, gender was shown to play a significant role in how people were affected by it, while aspects related to sexual and gender minorities (SGM) have been rather understudied. The aim of this review was to synthesize systematic reviews and meta-analyses that explicitly addressed the impact of gender within the context of the pandemic, with a focus on SGM.<br><br>METHODS: We based the narrative synthesis of results on a literature search of PubMed. We included systematic reviews and meta-analyses as of 2019 with an identifiable gender comparison or SGM reference and a specified clinical outcome.<br><br>RESULTS: The search yielded 2 658 hits; 29 systematic reviews were included for content synthesis. Of these, we identified 23 systematic reviews with gender comparisons and 8 related to SGM. Men showed higher prevalence, severity, and mortality of COVID-19 compared with women, but the psychological consequences of the COVID-19 pandemic affected women more compared with men. Evidence suggests that women are at higher risk for Long-COVID-19. SGM experienced increased mental health problems during the COVID-19 pandemic compared to the general population.<br><br>DISCUSSION: It appears that biological and social risks led to differential susceptibility to infection and manifestation of COVID-19 disease and also accounted for differences in mortality between men and women. Insights on prevalence, disease burden, and mortality among SGM during the COVID-19 pandemic are lacking. This suggests an underrepresentation of SGM in COVID-19-related research. Despite the abundance of COVID-19 publications, gender effects have not often been explicitly and adequately studied.<br><br>CONCLUSION: Future studies should examine gender differences and needs and concerns of SGM in mental disorders and further understudied entities like Long-COVID-19, to gain insights and help to provide preventive measures and adequate treatments for all, for potential future pandemics as well.}, }
@article {pmid38321404, year = {2024}, author = {Seighali, N and Abdollahi, A and Shafiee, A and Amini, MJ and Teymouri Athar, MM and Safari, O and Faghfouri, P and Eskandari, A and Rostaii, O and Salehi, AH and Soltani, H and Hosseini, M and Abhari, FS and Maghsoudi, MR and Jahanbakhshi, B and Bakhtiyari, M}, title = {The global prevalence of depression, anxiety, and sleep disorder among patients coping with Post COVID-19 syndrome (long COVID): a systematic review and meta-analysis.}, journal = {BMC psychiatry}, volume = {24}, number = {1}, pages = {105}, pmid = {38321404}, issn = {1471-244X}, mesh = {Humans ; *Anxiety/epidemiology ; Coping Skills ; *Depression/epidemiology ; *Post-Acute COVID-19 Syndrome/psychology ; Prevalence ; *Sleep Wake Disorders/epidemiology ; }, abstract = {BACKGROUND: Post COVID-19 syndrome, also known as "Long COVID," is a complex and multifaceted condition that affects individuals who have recovered from SARS-CoV-2 infection. This systematic review and meta-analysis aim to comprehensively assess the global prevalence of depression, anxiety, and sleep disorder in individuals coping with Post COVID-19 syndrome.<br><br>METHODS: A rigorous search of electronic databases was conducted to identify original studies until 24 January 2023. The inclusion criteria comprised studies employing previously validated assessment tools for depression, anxiety, and sleep disorders, reporting prevalence rates, and encompassing patients of all age groups and geographical regions for subgroup analysis Random effects model was utilized for the meta-analysis. Meta-regression analysis was done.<br><br>RESULTS: The pooled prevalence of depression and anxiety among patients coping with Post COVID-19 syndrome was estimated to be 23% (95% CI: 20%-26%; I2&#x2009;=&#x2009;99.9%) based on data from 143 studies with 7,782,124 participants and 132 studies with 9,320,687 participants, respectively. The pooled prevalence of sleep disorder among these patients, derived from 27 studies with 15,362 participants, was estimated to be 45% (95% CI: 37%-53%; I2&#x2009;=&#x2009;98.7%). Subgroup analyses based on geographical regions and assessment scales revealed significant variations in prevalence rates. Meta-regression analysis showed significant correlations between the prevalence and total sample size of studies, the age of participants, and the percentage of male participants. Publication bias was assessed using Doi plot visualization and the Peters test, revealing a potential source of publication bias for depression (p&#x2009;=&#x2009;0.0085) and sleep disorder (p&#x2009;=&#x2009;0.02). However, no evidence of publication bias was found for anxiety (p&#x2009;=&#x2009;0.11).<br><br>CONCLUSION: This systematic review and meta-analysis demonstrate a considerable burden of mental health issues, including depression, anxiety, and sleep disorders, among individuals recovering from COVID-19. The findings emphasize the need for comprehensive mental health support and tailored interventions for patients experiencing persistent symptoms after COVID-19 recovery.}, }
@article {pmid38321938, year = {2024}, author = {Rao, S and Gross, RS and Mohandas, S and Stein, CR and Case, A and Dreyer, B and Pajor, NM and Bunnell, HT and Warburton, D and Berg, E and Overdevest, JB and Gorelik, M and Milner, J and Saxena, S and Jhaveri, R and Wood, JC and Rhee, KE and Letts, R and Maughan, C and Guthe, N and Castro-Baucom, L and Stockwell, MS}, title = {Postacute Sequelae of SARS-CoV-2 in Children.}, journal = {Pediatrics}, volume = {153}, number = {3}, pages = {}, pmid = {38321938}, issn = {1098-4275}, support = {K23 DC019678/DC/NIDCD NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; P30 DK111022/DK/NIDDK NIH HHS/United States ; }, mesh = {Child ; Humans ; *Autoimmune Diseases ; *COVID-19/complications/epidemiology ; Disease Progression ; Observational Studies as Topic ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Systemic Inflammatory Response Syndrome ; United States ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic has caused significant medical, social, and economic impacts globally, both in the short and long term. Although most individuals recover within a few days or weeks from an acute infection, some experience longer lasting effects. Data regarding the postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC) in children, or long COVID, are only just emerging in the literature. These symptoms and conditions may reflect persistent symptoms from acute infection (eg, cough, headaches, fatigue, and loss of taste and smell), new symptoms like dizziness, or exacerbation of underlying conditions. Children may develop conditions de novo, including postural orthostatic tachycardia syndrome, myalgic encephalomyelitis/chronic fatigue syndrome, autoimmune conditions and multisystem inflammatory syndrome in children. This state-of-the-art narrative review provides a summary of our current knowledge about PASC in children, including prevalence, epidemiology, risk factors, clinical characteristics, underlying mechanisms, and functional outcomes, as well as a conceptual framework for PASC based on the current National Institutes of Health definition. We highlight the pediatric components of the National Institutes of Health-funded Researching COVID to Enhance Recovery Initiative, which seeks to characterize the natural history, mechanisms, and long-term health effects of PASC in children and young adults to inform future treatment and prevention efforts. These initiatives include electronic health record cohorts, which offer rapid assessments at scale with geographical and demographic diversity, as well as longitudinal prospective observational cohorts, to estimate disease burden, illness trajectory, pathobiology, and clinical manifestations and outcomes.}, }
@article {pmid38335908, year = {2024}, author = {Bronowicka-Szydełko, A and Gostomska-Pampuch, K and Kuzan, A and Pietkiewicz, J and Krzystek-Korpacka, M and Gamian, A}, title = {Effect of advanced glycation end-products in a wide range of medical problems including COVID-19.}, journal = {Advances in medical sciences}, volume = {69}, number = {1}, pages = {36-50}, doi = {10.1016/j.advms.2024.01.003}, pmid = {38335908}, issn = {1898-4002}, mesh = {*Glycation End Products, Advanced/metabolism ; Humans ; *COVID-19/metabolism/virology ; *SARS-CoV-2/isolation &amp; purification/metabolism ; Diabetes Complications/metabolism ; Atherosclerosis/metabolism ; Neurodegenerative Diseases/metabolism ; }, abstract = {Glycation is a physiological process that determines the aging of the organism, while in states of metabolic disorders it is significantly intensified. High concentrations of compounds such as reducing sugars or reactive aldehydes derived from lipid oxidation, occurring for example in diabetes, atherosclerosis, dyslipidemia, obesity or metabolic syndrome, lead to increased glycation of proteins, lipids and nucleic acids. The level of advanced glycation end-products (AGEs) in the body depends on rapidity of their production and the rate of their removal by the urinary system. AGEs, accumulated in the extracellular matrix of the blood vessels and other organs, cause irreversible changes in the biochemical and biomechanical properties of tissues. As a consequence, micro- and macroangiopathies appear in the system, and may contribute to the organ failure, like kidneys and heart. Elevated levels of AGEs also increase the risk of Alzheimer's disease and various cancers. In this paper, we propose a new classification due to modified amino acid residues: arginyl-AGEs, monolysyl-AGEs and lysyl-arginyl-AGEs and dilysyl-AGEs. Furthermore, we describe in detail the effect of AGEs on the pathogenesis of metabolic and old age diseases, such as diabetic complications, atherosclerosis and neurodegenerative diseases. We summarize the currently available data on the diagnostic value of AGEs and present the AGEs as a therapeutic goal in a wide range of medical problems, including SARS-CoV-2 infection and so-called long COVID.}, }
@article {pmid38337760, year = {2024}, author = {Negrut, N and Menegas, G and Kampioti, S and Bourelou, M and Kopanyi, F and Hassan, FD and Asowed, A and Taleouine, FZ and Ferician, A and Marian, P}, title = {The Multisystem Impact of Long COVID: A Comprehensive Review.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {3}, pages = {}, pmid = {38337760}, issn = {2075-4418}, abstract = {(1) Background: COVID-19 was responsible for the latest pandemic, shaking and reshaping healthcare systems worldwide. Its late clinical manifestations make it linger in medical memory as a debilitating illness over extended periods. (2) Methods: the recent literature was systematically analyzed to categorize and examine the symptomatology and pathophysiology of Long COVID across various bodily systems, including pulmonary, cardiovascular, gastrointestinal, neuropsychiatric, dermatological, renal, hematological, and endocrinological aspects. (3) Results: The review outlines the diverse clinical manifestations of Long COVID across multiple systems, emphasizing its complexity and challenges in diagnosis and treatment. Factors such as pre-existing conditions, initial COVID-19 severity, vaccination status, gender, and age were identified as influential in the manifestation and persistence of Long COVID symptoms. This condition is highlighted as a debilitating disease capable of enduring over an extended period and presenting new symptoms over time. (4) Conclusions: Long COVID emerges as a condition with intricate multi-systemic involvement, complicating its diagnosis and treatment. The findings underscore the necessity for a nuanced understanding of its diverse manifestations to effectively manage and address the evolving nature of this condition over time.}, }
@article {pmid38339115, year = {2024}, author = {Bielecka, E and Sielatycki, P and Pietraszko, P and Zapora-Kurel, A and Zbroch, E}, title = {Elevated Arterial Blood Pressure as a Delayed Complication Following COVID-19-A Narrative Review.}, journal = {International journal of molecular sciences}, volume = {25}, number = {3}, pages = {}, pmid = {38339115}, issn = {1422-0067}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Arterial Pressure ; Angiotensin-Converting Enzyme Inhibitors ; Renin-Angiotensin System ; *Hypertension ; Blood Pressure/physiology ; }, abstract = {Arterial hypertension is one of the most common and significant cardiovascular risk factors. There are many well-known and identified risk factors for its development. In recent times, there has been growing concern about the potential impact of COVID-19 on the cardiovascular system and its relation to arterial hypertension. Various theories have been developed that suggest a connection between COVID-19 and elevated blood pressure. However, the precise link between SARS-CoV-2 infection and the long-term risk of developing hypertension remains insufficiently explored. Therefore, the primary objective of our study was to investigate the influence of COVID-19 infection on blood pressure elevation and the subsequent risk of developing arterial hypertension over an extended period. To accomplish this, we conducted a thorough search review of relevant papers in the PubMed and SCOPUS databases up to 3 September 2023. Our analysis encompassed a total of 30 eligible articles. Out of the 30 papers we reviewed, 19 of them provided substantial evidence showing a heightened risk of developing arterial hypertension following COVID-19 infection. Eight of the studies showed that blood pressure values increased after the infection, while three of the qualified studies did not report any notable impact of COVID-19 on blood pressure levels. The precise mechanism behind the development of hypertension after COVID-19 remains unclear, but it is suggested that endothelial injury and dysfunction of the renin-angiotensin-aldosterone system may be contributory. Additionally, changes in blood pressure following COVID-19 infection could be linked to lifestyle alterations that often occur alongside the illness. Our findings emphasize the pressing requirement for thorough research into the relationship between COVID-19 and hypertension. These insights are essential for the development of effective prevention and management approaches for individuals who have experienced COVID-19 infection.}, }
@article {pmid38347167, year = {2024}, author = {Lui, DTW and Lee, CH and Woo, YC and Hung, IFN and Lam, KSL}, title = {Thyroid dysfunction in COVID-19.}, journal = {Nature reviews. Endocrinology}, volume = {20}, number = {6}, pages = {336-348}, pmid = {38347167}, issn = {1759-5037}, mesh = {Humans ; *COVID-19/complications/epidemiology/physiopathology ; *Thyroid Diseases/epidemiology/physiopathology ; *SARS-CoV-2 ; COVID-19 Vaccines ; Thyroid Gland/physiopathology ; }, abstract = {The COVID-19 pandemic has affected over 772 million people globally. While lung damage is the major contributor to the morbidity and mortality of this disease, the involvement of multiple organs, including the endocrine glands, has been reported. This Review aims to provide an updated summary of evidence regarding COVID-19 and thyroid dysfunction, incorporating highlights of recent advances in the field, particularly in relation to long COVID and COVID-19 vaccination. Since subacute thyroiditis following COVID-19 was first reported in May 2020, thyroid dysfunction associated with COVID-19 has been increasingly recognized, secondary to direct and indirect effects on the hypothalamic-pituitary-thyroid axis. Here, we summarize the epidemiological evidence, pattern and clinical course of thyroid dysfunction following COVID-19 and examine radiological, molecular and histological evidence of thyroid involvement in SARS-CoV-2 infection. Beyond acute SARS-CoV-2 infection, it is also timely to examine the course and implication of thyroid dysfunction in the context of long COVID owing to the large population of survivors of COVID-19 worldwide. This Review also analyses the latest evidence on the relationship between the therapeutics and vaccination for COVID-19 and thyroid dysfunction. To conclude, evidence-based practice recommendations for thyroid function testing during and following COVID-19 and concerning COVID-19 vaccination are proposed.}, }
@article {pmid38349116, year = {2024}, author = {Eltayeb, A and Al-Sarraj, F and Alharbi, M and Albiheyri, R and Mattar, EH and Abu Zeid, IM and Bouback, TA and Bamagoos, A and Uversky, VN and Rubio-Casillas, A and Redwan, EM}, title = {Intrinsic factors behind long COVID: IV. Hypothetical roles of the SARS-CoV-2 nucleocapsid protein and its liquid-liquid phase separation.}, journal = {Journal of cellular biochemistry}, volume = {125}, number = {3}, pages = {e30530}, doi = {10.1002/jcb.30530}, pmid = {38349116}, issn = {1097-4644}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Coronavirus Nucleocapsid Proteins ; Endothelial Cells ; Phase Separation ; Nucleocapsid Proteins ; }, abstract = {When the SARS-CoV-2 virus infects humans, it leads to a condition called COVID-19 that has a wide spectrum of clinical manifestations, from no symptoms to acute respiratory distress syndrome. The virus initiates damage by attaching to the ACE-2 protein on the surface of endothelial cells that line the blood vessels and using these cells as hosts for replication. Reactive oxygen species levels are increased during viral replication, which leads to oxidative stress. About three-fifths (~60%) of the people who get infected with the virus eradicate it from their body after 28 days and recover their normal activity. However, a large fraction (~40%) of the people who are infected with the virus suffer from various symptoms (anosmia and/or ageusia, fatigue, cough, myalgia, cognitive impairment, insomnia, dyspnea, and tachycardia) beyond 12 weeks and are diagnosed with a syndrome called long COVID. Long-term clinical studies in a group of people who contracted SARS-CoV-2 have been contrasted with a noninfected matched group of people. A subset of infected people can be distinguished by a set of cytokine markers to have persistent, low-grade inflammation and often self-report two or more bothersome symptoms. No medication can alleviate their symptoms efficiently. Coronavirus nucleocapsid proteins have been investigated extensively as potential drug targets due to their key roles in virus replication, among which is their ability to bind their respective genomic RNAs for incorporation into emerging virions. This review highlights basic studies of the nucleocapsid protein and its ability to undergo liquid-liquid phase separation. We hypothesize that this ability of the nucleocapsid protein for phase separation may contribute to long COVID. This hypothesis unlocks new investigation angles and could potentially open novel avenues for a better understanding of long COVID and treating this condition.}, }
@article {pmid38359962, year = {2024}, author = {Seylanova, N and Chernyavskaya, A and Degtyareva, N and Mursalova, A and Ajam, A and Xiao, L and Aktulaeva, K and Roshchin, P and Bobkova, P and Aiyegbusi, OL and Anbu, AT and Apfelbacher, C and Asadi-Pooya, AA and Ashkenazi-Hoffnung, L and Brackel, C and Buonsenso, D and de Groote, W and Diaz, JV and Dona, D and Dunn Galvin, A and Genuneit, J and Goss, H and Hughes, SE and Jones, CJ and Kuppalli, K and Malone, LA and McFarland, S and Needham, DM and Nekliudov, N and Nicholson, TR and Oliveira, CR and Schiess, N and Segal, TY and Sigfrid, L and Thorne, C and Vijverberg, S and Warner, JO and Were, WM and Williamson, PR and Munblit, D and , }, title = {Core outcome measurement set for research and clinical practice in post-COVID-19 condition (long COVID) in children and young people: an international Delphi consensus study "PC-COS Children".}, journal = {The European respiratory journal}, volume = {63}, number = {3}, pages = {}, pmid = {38359962}, issn = {1399-3003}, support = {001/WHO_/World Health Organization/International ; K23 AI159518/AI/NIAID NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; }, mesh = {Adolescent ; Child ; Humans ; *COVID-19 ; Delphi Technique ; Outcome Assessment, Health Care ; *Post-Acute COVID-19 Syndrome ; Research Design ; Treatment Outcome ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic substantially impacted different age groups, with children and young people not exempted. Many have experienced enduring health consequences. Presently, there is no consensus on the health outcomes to assess in children and young people with post-COVID-19 condition. Furthermore, it is unclear which measurement instruments are appropriate for use in research and clinical management of children and young people with post-COVID-19. To address these unmet needs, we conducted a consensus study, aiming to develop a core outcome set (COS) and an associated core outcome measurement set (COMS) for evaluating post-COVID-19 condition in children and young people. Our methodology comprised of two phases. In phase 1 (to create a COS), we performed an extensive literature review and categorisation of outcomes, and prioritised those outcomes in a two-round online modified Delphi process followed by a consensus meeting. In phase 2 (to create the COMS), we performed another modified Delphi consensus process to evaluate measurement instruments for previously defined core outcomes from phase 1, followed by an online consensus workshop to finalise recommendations regarding the most appropriate instruments for each core outcome. In phase 1, 214 participants from 37 countries participated, with 154 (72%) contributing to both Delphi rounds. The subsequent online consensus meeting resulted in a final COS which encompassed seven critical outcomes: fatigue; post-exertion symptoms; work/occupational and study changes; as well as functional changes, symptoms, and conditions relating to cardiovascular, neuro-cognitive, gastrointestinal and physical outcomes. In phase 2, 11 international experts were involved in a modified Delphi process, selecting measurement instruments for a subsequent online consensus workshop where 30 voting participants discussed and independently scored the selected instruments. As a result of this consensus process, four instruments met a priori consensus criteria for inclusion: PedsQL multidimensional fatigue scale for "fatigue"; PedsQL gastrointestinal symptom scales for "gastrointestinal"; PedsQL cognitive functioning scale for "neurocognitive" and EQ-5D for "physical functioning". Despite proposing outcome measurement instruments for the remaining three core outcomes ("cardiovascular", "post-exertional malaise", "work/occupational and study changes"), a consensus was not achieved. Our international, consensus-based initiative presents a robust framework for evaluating post-COVID-19 condition in children and young people in research and clinical practice via a rigorously defined COS and associated COMS. It will aid in the uniform measurement and reporting of relevant health outcomes worldwide.}, }
@article {pmid38366966, year = {2024}, author = {Fernández-de-Las-Peñas, C and Torres-Macho, J and Macasaet, R and Velasco, JV and Ver, AT and Culasino Carandang, THD and Guerrero, JJ and Franco-Moreno, A and Chung, W and Notarte, KI}, title = {Presence of SARS-CoV-2 RNA in COVID-19 survivors with post-COVID symptoms: a systematic review of the literature.}, journal = {Clinical chemistry and laboratory medicine}, volume = {62}, number = {6}, pages = {1044-1052}, pmid = {38366966}, issn = {1437-4331}, mesh = {Humans ; *COVID-19/virology/diagnosis ; *RNA, Viral/analysis ; *SARS-CoV-2/isolation &amp; purification/genetics ; Survivors ; Feces/virology/chemistry ; Female ; }, abstract = {INTRODUCTION: Viral persistence is one of the main hypotheses explaining the presence of post-COVID symptoms. This systematic review investigated the presence of SARS-CoV-2 RNA in plasma, stool, urine, and nasal/oral swab samples in individuals with post-COVID symptomatology.<br><br>CONTENT: MEDLINE, CINAHL, PubMed, EMBASE, Web of Science databases, as well as medRxiv/bioRxiv preprint servers were searched up to November 25th, 2023. Articles investigating the persistence of SARS-CoV-2 RNA in plasma, stool, urine or nasal/oral swab samples in patients with post-COVID symptoms were included. Methodological quality was assessed using the Newcastle-Ottawa Scale or Cochrane's Risk of Bias (Rob) tool.<br><br>SUMMARY: From 322 studies identified, six studies met all inclusion criteria. The sample included 678 COVID-19 survivors (52&#x202f;% female, aged from 29 to 66 years). The methodological quality was moderate in 88&#x202f;% of the studies (n=5/6). Three papers investigated the presence of SARS-CoV-2 RNA in plasma, three studies in nasal/oral swabs, two studies in stool samples, one in urine and one in saliva. The follow-up was shorter than two months (<60 days after) in 66&#x202f;% of the studies (n=4/6). The prevalence of SARS-CoV-2 RNA ranged from 5 to 59&#x202f;% in patients with post-COVID symptoms the first two months after infection, depending on the sample tested, however, SARS-CoV-2 RNA was also identified in COVID-19 survivors without post-COVID symptoms (one study).<br><br>OUTLOOK: Available evidence can suggest the presence of persistent SARS-CoV-2 RNA in post-COVID patients in the short term, although the biases within the studies do not permit us to make firm assumptions. The association between post-COVID symptoms and SARS-CoV-2 RNA in the samples tested is also conflicting. The lack of comparative group without post-COVID symptoms limits the generalizability of viral persistence in post-COVID-19 condition.}, }
@article {pmid38372528, year = {2024}, author = {Maybin, JA and Watters, M and Rowley, B and Walker, CA and Sharp, GC and Alvergne, A}, title = {COVID-19 and abnormal uterine bleeding: potential associations and mechanisms.}, journal = {Clinical science (London, England : 1979)}, volume = {138}, number = {4}, pages = {153-171}, pmid = {38372528}, issn = {1470-8736}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Female ; Humans ; *Endometrium ; Post-Acute COVID-19 Syndrome ; Quality of Life ; COVID-19 Vaccines ; *COVID-19/complications ; SARS-CoV-2 ; Menstruation/physiology ; Uterine Hemorrhage/etiology ; Menstruation Disturbances/complications ; }, abstract = {The impact of COVID-19 on menstruation has received a high level of public and media interest. Despite this, uncertainty exists about the advice that women and people who menstruate should receive in relation to the expected impact of SARS-CoV-2 infection, long COVID or COVID-19 vaccination on menstruation. Furthermore, the mechanisms leading to these reported menstrual changes are poorly understood. This review evaluates the published literature on COVID-19 and its impact on menstrual bleeding, discussing the strengths and limitations of these studies. We present evidence consistent with SARS-CoV-2 infection and long COVID having an association with changes in menstrual bleeding parameters and that the impact of COVID vaccination on menstruation appears less significant. An overview of menstrual physiology and known causes of abnormal uterine bleeding (AUB) is provided before discussing potential mechanisms which may underpin the menstrual disturbance reported with COVID-19, highlighting areas for future scientific study. Finally, consideration is given to the effect that menstruation may have on COVID-19, including the impact of the ovarian sex hormones on acute COVID-19 severity and susceptibility and reported variation in long COVID symptoms across the menstrual cycle. Understanding the current evidence and addressing gaps in our knowledge in this area are essential to inform public health policy, direct the treatment of menstrual disturbance and facilitate development of new therapies, which may reduce the severity of COVID-19 and improve quality of life for those experiencing long COVID.}, }
@article {pmid38375735, year = {2024}, author = {Ribeiro, J and Caldeira, D and Dores, H}, title = {Long-term manifestations of COVID-19 in athletes: a narrative review.}, journal = {The Physician and sportsmedicine}, volume = {52}, number = {5}, pages = {452-459}, doi = {10.1080/00913847.2024.2321629}, pmid = {38375735}, issn = {2326-3660}, mesh = {Humans ; *COVID-19/complications/epidemiology/physiopathology ; *Athletes ; *Return to Sport ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Athletic Performance/physiology ; Fatigue/physiopathology/etiology ; }, abstract = {BACKGROUND: Long COVID is a condition where symptoms or complications persist beyond 3 months after COVID-19 infection. Although most athletes experience mild symptoms, those involved in sports with higher cardiovascular demands can develop long COVID, which can negatively impact sports performance. This narrative review aimed to analyze the long COVID in athletes, especially cardiovascular effects; to alert medical and sporting community for the clinical aftermaths of COVID-19, focusing on physical activity; and to discuss the potential return-to-play strategies for these athletes.<br><br>METHODS: An electronic search in PubMed database for articles published between January/2020 and February/2023 was performed including athletic populations with COVID-19, emphasizing long-term complications, especially the cardiovascular effects.<br><br>RESULTS AND CONCLUSIONS: While severe cardiac complications are rare, athletes with long COVID often experience symptoms such as fatigue, dyspnea, palpitations, and exercise intolerance. To manage athletes with long COVID, individualized and structured return-to-play programs with the involvement of multidisciplinary teams are crucial. This underscores the importance of recognizing long COVID in athletes, raising awareness of its potential impacts, and implementing strategies to ensure a safe return to play.}, }
@article {pmid38378550, year = {2024}, author = {Valencia, I and Lumpuy-Castillo, J and Magalhaes, G and Sánchez-Ferrer, CF and Lorenzo, &#xd3; and Peiró, C}, title = {Mechanisms of endothelial activation, hypercoagulation and thrombosis in COVID-19: a link with diabetes mellitus.}, journal = {Cardiovascular diabetology}, volume = {23}, number = {1}, pages = {75}, pmid = {38378550}, issn = {1475-2840}, support = {CD22/00101//Instituto de Salud Carlos III/ ; FPI-UAM//Universidad Aut&#xf3;noma de Madrid/ ; Maria Zambrano postdoctoral grant//European Union-Next Generation EU/ ; SAF2017-84776-R//Ministerio de Econom&#xed;a y Competitividad/ ; P120/00923//Instituto de Salud Carlos III and Fondo de Investigaciones Sanitarias/ ; SPACE2-CV-COVID-CM//REACT-EU-Comunidad de Madrid and the European Regional Development Fund/ ; }, mesh = {Humans ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; Pandemics ; SARS-CoV-2 ; *Thrombophilia/diagnosis/drug therapy ; *Thrombosis ; *Diabetes Mellitus/diagnosis/drug therapy/epidemiology ; Endothelium ; }, abstract = {Early since the onset of the COVID-19 pandemic, the medical and scientific community were aware of extra respiratory actions of SARS-CoV-2 infection. Endothelitis, hypercoagulation, and hypofibrinolysis were identified in COVID-19 patients as subsequent responses of endothelial dysfunction. Activation of the endothelial barrier may increase the severity of the disease and contribute to long-COVID syndrome and post-COVID sequelae. Besides, it may cause alterations in primary, secondary, and tertiary hemostasis. Importantly, these responses have been highly decisive in the evolution of infected patients also diagnosed with diabetes mellitus (DM), who showed previous endothelial dysfunction. In this review, we provide an overview of the potential triggers of endothelial activation related to COVID-19 and COVID-19 under diabetic milieu. Several mechanisms are induced by both the viral particle itself and by the subsequent immune-defensive response (i.e., NF-κB/NLRP3 inflammasome pathway, vasoactive peptides, cytokine storm, NETosis, activation of the complement system). Alterations in coagulation mediators such as factor VIII, fibrin, tissue factor, the von Willebrand factor: ADAMST-13 ratio, and the kallikrein-kinin or plasminogen-plasmin systems have been reported. Moreover, an imbalance of thrombotic and thrombolytic (tPA, PAI-I, fibrinogen) factors favors hypercoagulation and hypofibrinolysis. In the context of DM, these mechanisms can be exacerbated leading to higher loss of hemostasis. However, a series of therapeutic strategies targeting the activated endothelium such as specific antibodies or inhibitors against thrombin, key cytokines, factor X, complement system, the kallikrein-kinin system or NETosis, might represent new opportunities to address this hypercoagulable state present in COVID-19 and DM. Antidiabetics may also ameliorate endothelial dysfunction, inflammation, and platelet aggregation. By improving the microvascular pathology in COVID-19 and post-COVID subjects, the associated comorbidities and the risk of mortality could be reduced.}, }
@article {pmid38380482, year = {2024}, author = {Warnaerts, N and Beeckmans, K and Morrens, M and De Picker, L}, title = {[Impairments in neurocognitive functions in patients with long COVID: A systematic review].}, journal = {Tijdschrift voor psychiatrie}, volume = {66}, number = {1}, pages = {12-18}, pmid = {38380482}, issn = {0303-7339}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Neuropsychological Tests ; Case-Control Studies ; *COVID-19/complications ; Executive Function ; }, abstract = {BACKGROUND: Studies have shown impairments in neurocognitive functions which persist more than 3 months after COVID-19 (long COVID). It remains unclear what these impairments entail, how long they persist and what proportion of the patients exhibit them.<br><br>AIM: To define the specific neurocognitive profile and to determine the proportion of deficits in at least one cognitive domain in patients with long COVID.<br><br>METHOD: We conducted a systematic search in PubMed according to PRISMA 2020 guidelines with the following inclusion criteria: peer reviewed publications in which patients were assessed more than 3 months following acute COVID-19 by means of a test battery for different domains of neurocognition.<br><br>RESULTS: We found a total of 1178 papers, of which 7 cohort studies and 1 case-control study were selected. The proportion of patients having deficits in at least one domain of neurocognition ranged from 23% to 100%. Most frequent impairments were found in attention and speed of information processing, anterograde memory, working memory and executive function. Quality of the included studies was moderate.<br><br>CONCLUSION: Impairments in neurocognitive functions are highly prevalent among patients with long COVID and include various cognitive domains. We encourage further research to continue studying the complex interaction of COVID-19, neurocognitive impairments and neuropsychiatric syndromes.}, }
@article {pmid38381595, year = {2025}, author = {Tsampasian, V and Bäck, M and Bernardi, M and Cavarretta, E and Dębski, M and Gati, S and Hansen, D and Kränkel, N and Koskinas, KC and Niebauer, J and Spadafora, L and Frias Vargas, M and Biondi-Zoccai, G and Vassiliou, VS}, title = {Cardiovascular disease as part of Long COVID: a systematic review.}, journal = {European journal of preventive cardiology}, volume = {32}, number = {6}, pages = {485-498}, doi = {10.1093/eurjpc/zwae070}, pmid = {38381595}, issn = {2047-4881}, mesh = {Humans ; *COVID-19/complications/epidemiology/diagnosis ; *Cardiovascular Diseases/epidemiology/diagnosis/therapy/etiology/physiopathology ; SARS-CoV-2 ; Risk Factors ; Risk Assessment ; Heart Disease Risk Factors ; }, abstract = {AIMS: Long COVID syndrome has had a major impact on million patients' lives worldwide. The cardiovascular system is an important aspect of this multifaceted disease that may manifest in many ways. We have hereby performed a narrative review in order to identify the extent of the cardiovascular manifestations of the Long COVID syndrome.<br><br>METHODS AND RESULTS: An in-depth systematic search of the literature has been conducted for this narrative review. The systematic search of PubMed and Cochrane databases yielded 3993 articles, of which 629 underwent full-text screening. A total of 78 studies were included in the final qualitative synthesis and data evaluation. The pathophysiology of the cardiovascular sequelae of Long COVID syndrome and the cardiac manifestations and complications of Long COVID syndrome are critically evaluated. In addition, potential cardiovascular risk factors are assessed, and preventive methods and treatment options are examined in this review.<br><br>CONCLUSION: This systematic review poignantly summarizes the evidence from the available literature regarding the cardiovascular manifestations of Long COVID syndrome and reviews potential mechanistic pathways, diagnostic approaches, preventive measures, and treatment options.}, }
@article {pmid38383157, year = {2024}, author = {Steinruecke, M and Mason, I and Keen, M and McWhirter, L and Carson, AJ and Stone, J and Hoeritzauer, I}, title = {Pain and functional neurological disorder: a systematic review and meta-analysis.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {95}, number = {9}, pages = {874-885}, pmid = {38383157}, issn = {1468-330X}, mesh = {Humans ; *Nervous System Diseases/complications ; *Chronic Pain ; }, abstract = {BACKGROUND: Functional neurological disorder (FND) is characterised by neurological symptoms, such as seizures and abnormal movements. Despite its significance to patients, the clinical features of chronic pain in people with FND, and of FND in people with chronic pain, have not been comprehensively studied.<br><br>METHODS: We systematically reviewed PubMed, Embase and PsycINFO for studies of chronic pain in adults with FND and FND in patients with chronic pain. We described the proportions of patients reporting pain, pain rating and timing, pain-related diagnoses and responsiveness to treatment. We performed random effects meta-analyses of the proportions of patients with FND who reported pain or were diagnosed with pain-related disorders.<br><br>RESULTS: Seven hundred and fifteen articles were screened and 64 were included in the analysis. Eight case-control studies of 3476 patients described pain symptoms in a higher proportion of patients with FND than controls with other neurological disorders. A random effects model of 30 cohorts found that an estimated 55% (95% CI 46% to 64%) of 4272 patients with FND reported pain. Random effects models estimated diagnoses of complex regional pain syndrome in 22% (95% CI 6% to 39%) of patients, irritable bowel syndrome in 16% (95% CI 9% to 24%) and fibromyalgia in 10% (95% CI 8% to 13%). Five studies of FND diagnoses among 361 patients with chronic pain were identified. Most interventions for FND did not ameliorate pain, even when other symptoms improved.<br><br>CONCLUSIONS: Pain symptoms and pain-related diagnoses are common in FND. Classification systems and treatments should routinely consider pain as a comorbidity in patients with FND.}, }
@article {pmid38384747, year = {2024}, author = {Lammers, N and Beese, F and Hoebel, J and Poethko-Müller, C and Wachtler, B}, title = {Social Inequalities in Long-Term Health Effects After COVID-19-A Scoping Review.}, journal = {International journal of public health}, volume = {69}, number = {}, pages = {1606739}, pmid = {38384747}, issn = {1661-8564}, mesh = {Humans ; *COVID-19/epidemiology ; *Socioeconomic Factors ; *SARS-CoV-2 ; Health Status Disparities ; Post-Acute COVID-19 Syndrome ; }, abstract = {Objectives: We aimed to map and synthesize evidence about social inequalities in long-term health effects after COVID-19 (LTHE), often referred to as "long COVID" or "post-COVID-19 conditions." Methods: We conducted a scoping review of peer-reviewed articles by searching the databases Embase and Scopus. According to predefined inclusion criteria, titles/abstracts and full texts were screened for eligibility. Additionally, reference lists of all included studies were hand-searched for eligible studies. This study followed the PRISMA guidelines for scoping reviews. Results: Nineteen articles were included. LTHE were analysed according to ethnicity, education, income, employment and deprivation indices. The studies varied significantly in their definitions of LTHE. Eighty-two analyses showed no statistically significant associations. At least 12 studies had a high risk of type II errors. Only studies associating deprivation indices and long COVID tended to show a higher prevalence of LTHE in deprived areas. Conclusion: Although some studies indicated social inequalities in LTHE, evidence was generally weak and inconclusive. Further studies with larger sample sizes specifically designed to detect social inequalities regarding LTHE are needed to inform future healthcare planning and public health policies.}, }
@article {pmid38389299, year = {2024}, author = {Martínez-Pozas, O and Meléndez-Oliva, E and Rolando, LM and Rico, JAQ and Corbellini, C and Sánchez Romero, EA}, title = {The pulmonary rehabilitation effect on long covid-19 syndrome: A systematic review and meta-analysis.}, journal = {Physiotherapy research international : the journal for researchers and clinicians in physical therapy}, volume = {29}, number = {2}, pages = {e2077}, doi = {10.1002/pri.2077}, pmid = {38389299}, issn = {1471-2865}, support = {//Award for Best Research Project in post-COVID-19 sequelae/ ; //the Ilustre Colegio Profesional de Fisioterapeutas de la Comunidad de Madrid, December 2021/ ; }, mesh = {Adult ; Humans ; *Quality of Life ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Fatigue ; Dyspnea ; }, abstract = {OBJECTIVES: This systematic review and meta-analysis aims to evaluate the efficacy of pulmonary rehabilitation (PR) in improving dyspnea, fatigue, physical activity, quality of life, anxiety and depression in patients with Long COVID-19 (LC). The impact of PR on LC and a comparison of face-to-face and telerehabilitation approaches was explored.<br><br>METHODS: This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO. A literature search included PubMed, Web of Science, and Cochrane Library until January 2023. No language filters were applied. Randomized controlled trials, non-randomized controlled trials, and observational studies were included. The risk of bias was assessed using appropriate tools. Descriptive analysis and meta-analysis were performed. Forest plots presented results. Statistical analyses were conducted using the Metafor Package in R v.3.4.2.<br><br>RESULTS/FINDINGS: This systematic review and meta-analysis included 16 studies on PR in LC patients. A total of 1027 adults were included. The studies varied in design, with seven observational studies, three quasi-experimental studies, and six randomized controlled trials. Dyspnea, physical function, quality of life, psychological state, and fatigue were assessed as outcomes. The review found that pulmonary rehabilitation had a significant positive effect on dyspnea, physical function, quality of life (both global and physical domain), anxiety, and depression. However, the effect on fatigue was not significant. Heterogeneity was observed in some analyses, and publication bias was found in certain outcomes. Age and study design were identified as potential moderators. Both face-to-face and telerehabilitation interventions improved the studied outcomes, with only differences in the physical domain of quality of life favoring the face-to-face group.<br><br>PR improved dyspnea, physical function, quality of life, and psychological state in LC patients, but not fatigue. Face-to-face and telerehabilitation have similar effects, except for physical quality of life.}, }
@article {pmid38390594, year = {2024}, author = {Adler, BL and Chung, T and Rowe, PC and Aucott, J}, title = {Dysautonomia following Lyme disease: a key component of post-treatment Lyme disease syndrome?.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1344862}, pmid = {38390594}, issn = {1664-2295}, abstract = {Dysautonomia, or dysfunction of the autonomic nervous system (ANS), may occur following an infectious insult and can result in a variety of debilitating, widespread, and often poorly recognized symptoms. Dysautonomia is now widely accepted as a complication of COVID-19 and is an important component of Post-Acute Sequelae of COVID-19 (PASC or long COVID). PASC shares many overlapping clinical features with other infection-associated chronic illnesses including Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Post-Treatment Lyme Disease Syndrome (PTLDS), suggesting that they may share common underlying mechanisms including autonomic dysfunction. Despite the recognition of this complication of Lyme disease in the care of patients with PTLD, there has been a scarcity of research in this field and dysautonomia has not yet been established as a complication of Lyme disease in the medical literature. In this review, we discuss the evidence implicating Borrelia burgdorferi as a cause of dysautonomia and the related symptoms, propose potential pathogenic mechanisms given our knowledge of Lyme disease and mechanisms of PASC and ME/CFS, and discuss the diagnostic evaluation and treatments of dysautonomia. We also outline gaps in the literature and priorities for future research.}, }
@article {pmid38391754, year = {2024}, author = {Leão Batista Simões, J and Webler Eichler, S and Raitz Siqueira, ML and de Carvalho Braga, G and Bagatini, MD}, title = {Amyotrophic Lateral Sclerosis in Long-COVID Scenario and the Therapeutic Potential of the Purinergic System in Neuromodulation.}, journal = {Brain sciences}, volume = {14}, number = {2}, pages = {}, pmid = {38391754}, issn = {2076-3425}, support = {Proj. No 404256/2021-0 and 310606/2021-7).//National Council for Scientific and Technological Development/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) involves the degeneration of motor neurons and debilitating and possibly fatal symptoms. The COVID-19 pandemic directly affected the quality of life of this group, and the SARS-CoV-2 infection accelerated the present neuroinflammatory process. Furthermore, studies indicate that the infection may have led to the development of the pathology. Thus, the scenario after this pandemic presents "long-lasting COVID" as a disease that affects people who have been infected. From this perspective, studying the pathophysiology behind ALS associated with SARS-CoV-2 infection and possible supporting therapies becomes necessary when we understand the impact on the quality of life of these patients. Thus, the purinergic system was trained to demonstrate how its modulation can add to the treatment, reduce disease progression, and result in better prognoses. From our studies, we highlight the P2X7, P2X4, and A2AR receptors and how their activity can directly influence the ALS pathway.}, }
@article {pmid38391826, year = {2024}, author = {Daniels, K and Mourad, J and Bonnechère, B}, title = {Exploring the Use of Mobile Health for the Rehabilitation of Long COVID Patients: A Scoping Review.}, journal = {Healthcare (Basel, Switzerland)}, volume = {12}, number = {4}, pages = {}, pmid = {38391826}, issn = {2227-9032}, abstract = {The COVID-19 pandemic has led to a substantial revolution in the incorporation of digital solutions in healthcare. This systematic review investigates the enduring physical and psychological consequences individuals experience up to two years post-recovery. Additionally, it focuses on examining the influence of mHealth interventions on these effects. Significantly, 41.7% of survivors experience lingering symptoms that have not been addressed, while 14.1% encounter difficulties in returning to work. The presence of anxiety, compromised respiratory functioning, and persistent symptoms highlight the immediate requirement for specific therapies. Telehealth, particularly telerehabilitation, presents itself as a possible way to address these difficulties. The study thoroughly examines 10 studies encompassing 749 COVID-19 patients, investigating the efficacy of telerehabilitation therapies in addressing various health markers. Telerehabilitation-based breathing exercises yield substantial enhancements in functional performance, dyspnea, and overall well-being. The results emphasize the potential of telerehabilitation to have a favorable effect on patient outcomes; however, more research is needed to strengthen the existing evidence base, as one of the most important limitations is the limited number of trials and the evaluation of varied therapies. This analysis highlights the significance of digital solutions in post-COVID care and calls for ongoing research to improve the comprehension and implementation of telehealth interventions in a swiftly changing healthcare environment.}, }
@article {pmid38392036, year = {2024}, author = {Taieb, A and Nassim, BHS and Asma, G and Jabeur, M and Ghada, S and Asma, BA}, title = {The Growing Understanding of the Pituitary Implication in the Pathogenesis of Long COVID-19 Syndrome: A Narrative Review.}, journal = {Advances in respiratory medicine}, volume = {92}, number = {1}, pages = {96-109}, pmid = {38392036}, issn = {2543-6031}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; Pituitary Gland ; Fatigue/etiology ; }, abstract = {Long COVID-19, also known as post-acute sequelae of SARS-CoV-2 infection, is a condition where individuals who have recovered from the acute phase of COVID-19 continue to experience a range of symptoms for weeks or even months afterward. While it was initially thought to primarily affect the respiratory system, it has become clear that Long COVID-19 can involve various organs and systems, including the endocrine system, which includes the pituitary gland. In the context of Long COVID-19, there is a growing understanding of the potential implications for the pituitary gland. The virus can directly affect the pituitary gland, leading to abnormalities in hormone production and regulation. This can result in symptoms such as fatigue, changes in appetite, and mood disturbances. Long COVID-19, the persistent and often debilitating condition following acute COVID-19 infection, may be explained by deficiencies in ACTH and Growth hormone production from the pituitary gland. Corticotropin insufficiency can result in the dysregulation of the body's stress response and can lead to prolonged feelings of stress, fatigue, and mood disturbances in Long COVID-19 patients. Simultaneously, somatotropin insufficiency can affect growth, muscle function, and energy metabolism, potentially causing symptoms such as muscle weakness, exercise intolerance, and changes in body composition. Recently, some authors have suggested the involvement of the pituitary gland in Post COVID-19 Syndrome. The exact mechanisms of viral action on infected cells remain under discussion, but inflammatory and autoimmune mechanisms are primarily implicated. The aim of our study will be to review the main pituitary complications following COVID-19 infection. Moreover, we will explain the possible involvement of the pituitary gland in the persistence of Post COVID-19 Syndrome.}, }
@article {pmid38393096, year = {2024}, author = {Nederlof, RA and de la Garza, MA and Bakker, J}, title = {Perspectives on SARS-CoV-2 Cases in Zoological Institutions.}, journal = {Veterinary sciences}, volume = {11}, number = {2}, pages = {}, pmid = {38393096}, issn = {2306-7381}, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in a zoological institution were initially reported in March 2020. Since then, at least 94 peer-reviewed cases have been reported in zoos worldwide. Among the affected animals, nonhuman primates, carnivores, and artiodactyls appear to be most susceptible to infection, with the Felidae family accounting for the largest number of reported cases. Clinical symptoms tend to be mild across taxa; although, certain species exhibit increased susceptibility to disease. A variety of diagnostic tools are available, allowing for initial diagnostics and for the monitoring of infectious risk. Whilst supportive therapy proves sufficient in most cases, monoclonal antibody therapy has emerged as a promising additional treatment option. Effective transmission of SARS-CoV-2 in some species raises concerns over potential spillover and the formation of reservoirs. The occurrence of SARS-CoV-2 in a variety of animal species may contribute to the emergence of variants of concern due to altered viral evolutionary constraints. Consequently, this review emphasizes the need for effective biosecurity measures and surveillance strategies to prevent and control SARS-CoV-2 infections in zoological institutions.}, }
@article {pmid38393535, year = {2024}, author = {Pszczołowska, M and Walczak, K and Misków, W and Antosz, K and Batko, J and Karska, J and Leszek, J}, title = {Molecular cross-talk between long COVID-19 and Alzheimer's disease.}, journal = {GeroScience}, volume = {46}, number = {3}, pages = {2885-2899}, pmid = {38393535}, issn = {2509-2723}, mesh = {Humans ; *Alzheimer Disease/metabolism ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Amyloid beta-Peptides ; Chronic Disease ; }, abstract = {The long COVID (coronavirus disease), a multisystemic condition following severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, is one of the widespread problems. Some of its symptoms affect the nervous system and resemble symptoms of Alzheimer's disease (AD)-a neurodegenerative condition caused by the accumulation of amyloid beta and hyperphosphorylation of tau proteins. Multiple studies have found dependence between these two conditions. Patients with Alzheimer's disease have a greater risk of SARS-CoV-2 infection due to increased levels of angiotensin-converting enzyme 2 (ACE2), and the infection itself promotes amyloid beta generation which enhances the risk of AD. Also, the molecular pathways are alike-misregulations in folate-mediated one-carbon metabolism, a deficit of Cq10, and disease-associated microglia. Medical imaging in both of these diseases shows a decrease in the volume of gray matter, global brain size reduction, and hypometabolism in the parahippocampal gyrus, thalamus, and cingulate cortex. In some studies, a similar approach to applied medication can be seen, including the use of amino adamantanes and phenolic compounds of rosemary. The significance of these connections and their possible application in medical practice still needs further study but there is a possibility that they will help to better understand long COVID.}, }
@article {pmid38396973, year = {2024}, author = {Nakane, S and Koike, H and Hayashi, T and Nakatsuji, Y}, title = {Autoimmune Autonomic Neuropathy: From Pathogenesis to Diagnosis.}, journal = {International journal of molecular sciences}, volume = {25}, number = {4}, pages = {}, pmid = {38396973}, issn = {1422-0067}, support = {22FC1007//Ministry of Health Labour and Welfare/ ; }, mesh = {Humans ; Ganglia, Autonomic ; Post-Acute COVID-19 Syndrome ; *Autoimmune Diseases of the Nervous System ; Autonomic Nervous System ; *Autonomic Nervous System Diseases/diagnosis/etiology ; *Autoimmune Diseases/diagnosis/pathology ; *Peripheral Nervous System Diseases/pathology ; Autoantibodies ; }, abstract = {Autoimmune autonomic ganglionopathy (AAG) is a disease of autonomic failure caused by ganglionic acetylcholine receptor (gAChR) autoantibodies. Although the detection of autoantibodies is important for distinguishing the disease from other neuropathies that present with autonomic dysfunction, other factors are important for accurate diagnosis. Here, we provide a comprehensive review of the clinical features of AAG, highlighting differences in clinical course, clinical presentation, and laboratory findings from other neuropathies presenting with autonomic symptoms. The first step in diagnosing AAG is careful history taking, which should reveal whether the mode of onset is acute or chronic, followed by an examination of the time course of disease progression, including the presentation of autonomic and extra-autonomic symptoms. AAG is a neuropathy that should be differentiated from other neuropathies when the patient presents with autonomic dysfunction. Immune-mediated neuropathies, such as acute autonomic sensory neuropathy, are sometimes difficult to differentiate, and therefore, differences in clinical and laboratory findings should be well understood. Other non-neuropathic conditions, such as postural orthostatic tachycardia syndrome, chronic fatigue syndrome, and long COVID, also present with symptoms similar to those of AAG. Although often challenging, efforts should be made to differentiate among the disease candidates.}, }
@article {pmid38398460, year = {2024}, author = {Parzen-Johnson, S and Katz, BZ}, title = {Navigating the Spectrum of Two Pediatric COVID-19 Complications: Multi-System Inflammatory Syndrome in Children and Post-Acute Sequelae of SARS-CoV-2 Infection.}, journal = {Journal of clinical medicine}, volume = {13}, number = {4}, pages = {}, pmid = {38398460}, issn = {2077-0383}, abstract = {PURPOSE: This review summarizes the current scope of understanding associated with two common post-infectious complications associated with COVID-19 infection: Multi-System Inflammatory Syndrome in Children (MIS-C) and Post-Acute Sequelae of SARS-CoV-2 infection (PASC). It identifies current gaps in the knowledge and issues that may limit the ability to fill these gaps. This review provides a framework to drive continued research.<br><br>METHODS: A comprehensive review of the current literature was performed, identifying seminal articles describing the emergence of MIS-C and PASC, and works from the literature focused on the clinical implications and pathophysiologic understanding of these disorders.<br><br>FINDINGS: Although pediatric patients experienced few severe cases of acute COVID-19 infection, the burden of disease from post-infectious sequelae is substantial. Mortality is low, but morbidity is significant. There are still numerous unknowns about the pathophysiology of both MIS-C and PASC; however, with widespread immunity developing after increased vaccination and prior infection, it may be difficult to perform adequate prospective studies to answer pathophysiologic questions. Long-term sequalae of MIS-C seem to be minimal whereas, by definition, PASC is an ongoing problem and may be severe.<br><br>IMPLICATIONS: The rapid sharing of information regarding novel conditions such as MIS-C and PASC are key to interventions related to future post-infectious sequelae outside of those stemming from COVID-19. Although MIS-C seems unlikely to return as a clinical condition in substantial numbers, there is still significant learning that can be gleaned from existing patients about general aspects of epidemiology, equity, and pathophysiology. There is significant morbidity associated with PASC and additional resources need to be dedicated to determining appropriate and effective therapies moving forward.}, }
@article {pmid38399736, year = {2024}, author = {Liu, S and Zhong, M and Wu, H and Su, W and Wang, Y and Li, P}, title = {Potential Beneficial Effects of Naringin and Naringenin on Long COVID-A Review of the Literature.}, journal = {Microorganisms}, volume = {12}, number = {2}, pages = {}, pmid = {38399736}, issn = {2076-2607}, support = {2023A1515011953//Natural Science Foundation of Guangdong Province/ ; 2022SDZG07//Open Competition Program of Ten Major Directions of Agricultural Science and Technology Innovation for the 14th Five-Year Plan of Guangdong Province/ ; 2022ZD006//Research Fund of Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture/ ; }, abstract = {Coronavirus disease 2019 (COVID-19) caused a severe epidemic due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Recent studies have found that patients do not completely recover from acute infections, but instead, suffer from a variety of post-acute sequelae of SARS-CoV-2 infection, known as long COVID. The effects of long COVID can be far-reaching, with a duration of up to six months and a range of symptoms such as cognitive dysfunction, immune dysregulation, microbiota dysbiosis, myalgic encephalomyelitis/chronic fatigue syndrome, myocarditis, pulmonary fibrosis, cough, diabetes, pain, reproductive dysfunction, and thrombus formation. However, recent studies have shown that naringenin and naringin have palliative effects on various COVID-19 sequelae. Flavonoids such as naringin and naringenin, commonly found in fruits and vegetables, have various positive effects, including reducing inflammation, preventing viral infections, and providing antioxidants. This article discusses the molecular mechanisms and clinical effects of naringin and naringenin on treating the above diseases. It proposes them as potential drugs for the treatment of long COVID, and it can be inferred that naringin and naringenin exhibit potential as extended long COVID medications, in the future likely serving as nutraceuticals or clinical supplements for the comprehensive alleviation of the various manifestations of COVID-19 complications.}, }
@article {pmid38400172, year = {2024}, author = {Man, MA and Rosca, D and Bratosin, F and Fira-Mladinescu, O and Ilie, AC and Burtic, SR and Fildan, AP and Fizedean, CM and Jianu, AM and Negrean, RA and Marc, MS}, title = {Impact of Pre-Infection COVID-19 Vaccination on the Incidence and Severity of Post-COVID Syndrome: A Systematic Review and Meta-Analysis.}, journal = {Vaccines}, volume = {12}, number = {2}, pages = {}, pmid = {38400172}, issn = {2076-393X}, abstract = {This systematic review critically evaluated the impact of a pre-infection COVID-19 vaccination on the incidence and severity of post-COVID-19 syndrome and aimed to assess the potential protective effect across different vaccines and patient demographics. This study hypothesized that vaccination before infection substantially reduces the risk and severity of post-COVID-19 syndrome. In October 2023, a comprehensive literature search was conducted across three databases, PubMed, Embase, and Scopus, focusing on studies published up to that date. Utilizing a wide array of keywords, the search strategy adhered to the PRISMA guidelines and was registered in the Open Science Framework. The inclusion criteria comprised studies focusing on patients with a breakthrough SARS-CoV-2 infection who developed post-COVID-19 syndrome. We included a total of 13 articles that met the inclusion criteria, analyzing more than 10 million patients with a mean age of 50.6 years, showing that the incidence of intensive care unit (ICU) admissions post-vaccination was as low as 2.4%, with a significant reduction in mortality risk (OR 0.66, 95% CI 0.58-0.74). The prevalence of post-COVID-19 syndrome symptoms was lower in vaccinated individuals (9.5%) compared to unvaccinated (14.6%), with a notable decrease in activity-limiting symptoms (adjusted OR 0.59, 95% CI 0.48-0.73). Vaccinated patients also showed a quicker recovery and return to work (HR 1.37, 95% CI 1.04-1.79). The pooled odds ratio of 0.77 indicates that vaccination is associated with a 23% reduction in the risk of developing post-COVID-19 syndrome (95% CI 0.75-0.79). Despite the protective effects observed, a substantial heterogeneity among the studies was noted. In conclusion, a pre-infection COVID-19 vaccination is associated with a significant reduction in the risk and severity of post-COVID-19 syndrome. However, the observed heterogeneity across studies suggests a need for further research with standardized methods to fully comprehend vaccine efficacy against long COVID.}, }
@article {pmid38405190, year = {2024}, author = {Chu, XJ and Song, DD and Zhou, MH and Chen, XZ and Chu, N and Li, M and Li, BZ and Liu, SH and Hou, S and Wu, JB and Gong, L}, title = {Perturbations in gut and respiratory microbiota in COVID-19 and influenza patients: a systematic review and meta-analysis.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1301312}, pmid = {38405190}, issn = {2296-858X}, abstract = {OBJECTIVES: Coronavirus disease-19 (COVID-19)/influenza poses unprecedented challenges to the global economy and healthcare services. Numerous studies have described alterations in the microbiome of COVID-19/influenza patients, but further investigation is needed to understand the relationship between the microbiome and these diseases. Herein, through systematic comparison between COVID-19 patients, long COVID-19 patients, influenza patients, no COVID-19/influenza controls and no COVID-19/influenza patients, we conducted a comprehensive review to describe the microbial change of respiratory tract/digestive tract in COVID-19/influenza patients.<br><br>METHODS: We systematically reviewed relevant literature by searching the PubMed, Embase, and Cochrane Library databases from inception to August 12, 2023. We conducted a comprehensive review to explore microbial alterations in patients with COVID-19/influenza. In addition, the data on &#x3b1;-diversity were summarized and analyzed by meta-analysis.<br><br>RESULTS: A total of 134 studies comparing COVID-19 patients with controls and 18 studies comparing influenza patients with controls were included. The Shannon indices of the gut and respiratory tract microbiome were slightly decreased in COVID-19/influenza patients compared to no COVID-19/influenza controls. Meanwhile, COVID-19 patients with more severe symptoms also exhibited a lower Shannon index versus COVID-19 patients with milder symptoms. The intestinal microbiome of COVID-19 patients was characterized by elevated opportunistic pathogens along with reduced short-chain fatty acid (SCFAs)-producing microbiota. Moreover, Enterobacteriaceae (including Escherichia and Enterococcus) and Lactococcus, were enriched in the gut and respiratory tract of COVID-19 patients. Conversely, Haemophilus and Neisseria showed reduced abundance in the respiratory tract of both COVID-19 and influenza patients.<br><br>CONCLUSION: In this systematic review, we identified the microbiome in COVID-19/influenza patients in comparison with controls. The microbial changes in influenza and COVID-19 are partly similar.}, }
@article {pmid38406111, year = {2024}, author = {Assiri, AM and Alamaa, T and Elenezi, F and Alsagheir, A and Alzubaidi, L and TIeyjeh, I and Alhomod, AS and Gaffas, EM and Amer, SA}, title = {Unveiling the Clinical Spectrum of Post-COVID-19 Conditions: Assessment and Recommended Strategies.}, journal = {Cureus}, volume = {16}, number = {1}, pages = {e52827}, pmid = {38406111}, issn = {2168-8184}, abstract = {SARS-CoV-2 caused the pandemic of the rapidly evolving COVID-19. As of December 6, 2023, there were 765,152,854 COVID-19-recovering cases. Long-term consequences known as "long COVID" and "post-COVID-19 conditions" (PCCs) or "post-acute COVID-19 syndrome" are being reported more frequently in a subset of recovering patients. Systemic, neuropsychiatric, cardio-respiratory, and gastrointestinal symptoms are the most prevalent. The management of PCCs poses unique challenges due to the lack of official guidelines and the complex nature of the illness. This abstract highlights key principles derived from recent reviews and expert recommendations to provide healthcare professionals with a comprehensive approach to manage post-COVID-19 patients. Preventive medicine plays a crucial role in managing PCCs. While no specific medications are available for treatment, preventive measures such as COVID-19 vaccination, adherence to precautionary measures, regular consultations with medical professionals, monitoring symptoms and progress, and seeking information on symptom management are essential to assist patients in their recovery and improve their quality of life. Medical management requires transparent goal-setting and collaborative decision-making based on the patient's symptoms, comorbidities, and treatment objectives. Treatment plans for post-COVID-19 patients should focus on patient education, using registries and calendars to track symptoms and triggers, providing support and reassurance, and offering holistic support through peer networks and supportive psychotherapy techniques. Symptomatic and rehabilitative care, including well-established symptom management techniques, physical rehabilitation programs, and addressing mental health and well-being, are vital components of post-COVID-19 management. Lifestyle factors such as stress reduction, nutrition, and sleep should be incorporated into managing underlying medical conditions in post-COVID-19 patients. Regular follow-up visits and referrals to specialists are recommended to monitor the patient's progress and address specific organ system involvement or additional care needs. In summary, for the effective management of PCCs, a holistic approach should include preventive measures, patient education, supportive psychotherapy, symptomatic and rehabilitative care, medical management, counseling on lifestyle elements, and appropriate follow-up plans. However, it is crucial to stay updated with evolving guidelines and recommendations from healthcare authorities to provide the most effective and evidence-based care to post-COVID-19 patients.}, }
@article {pmid38413389, year = {2024}, author = {Lopuhaä, B and Voorham, QJM and van Kemenade, FJ and von der Thüsen, JH}, title = {COVID-19 in the Netherlands: lessons from a nationwide query of dutch autopsy, histology, and cytology pathological reports.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {484}, number = {3}, pages = {429-439}, pmid = {38413389}, issn = {1432-2307}, support = {10430012010016/ZONMW_/ZonMw/Netherlands ; }, mesh = {Female ; Humans ; Pregnancy ; Autopsy ; *COVID-19/pathology ; Lung/pathology ; Netherlands/epidemiology ; Pandemics ; *Pregnancy Complications, Infectious/pathology ; SARS-CoV-2 ; *Thrombosis/pathology ; }, abstract = {Since the onset of the COVID-19 pandemic, autopsies have played a valuable role in understanding the pathophysiology of COVID-19. In this study, we have analyzed COVID-19-related pathology reports from autopsies, histology, and cytology on a nationwide level. Pathology reports from all 43 pathology laboratories in the Netherlands stating "COVID," "Corona," and/or "SARS" were queried from the Dutch Nationwide Pathology Database (Palga). Consecutive reports of the included patients were also retrieved. Out of 5065 entries, a total of 1833 eligible COVID-19-related pathology reports between January 2020 and June 2021 were included in this collection of reports. Lung histopathology reports reflected differences in the severity of abnormalities (acute diffuse alveolar damage, alveolar histiocytes, and thrombi during the first three pandemic waves (Wuhan variant) versus the fourth wave (alpha variant)). Autopsy reports from 2020 state significantly shorter disease duration and younger age of death compared to autopsy reports from 2021. All reports together reflected a more granular pathology with comorbidities such as chronic histiocytic intervillositis, perniosis, and thrombi found in a variety of organs (lungs, kidneys, and small and large intestines). This nationwide overview of pathology reports provides data related to deaths as well as comorbidities in a clinical setting of COVID-19. Certain findings reported in SARS-CoV-infected lungs and placentas were also reported in post-COVID-19 tissue of the same kind. Consecutive reports after the earliest reports with COVID-19 allowed for follow-up reports. These follow-up reports can help with post-viral studies regarding long-term effects of COVID-19 as well as identifying the effects of different SARS-CoV-2 variants.}, }
@article {pmid38415507, year = {2024}, author = {Xiao, J and Luo, Y and Li, Y and Yao, X}, title = {The characteristics of BCR-CDR3 repertoire in COVID-19 patients and SARS-CoV-2 vaccinated volunteers.}, journal = {Journal of medical virology}, volume = {96}, number = {3}, pages = {e29488}, doi = {10.1002/jmv.29488}, pmid = {38415507}, issn = {1096-9071}, support = {82160279//National Natural Science Foundation of China/ ; (2018) 5637//Guizhou Provincial Hundred Level Talent Fund/ ; }, mesh = {Humans ; *SARS-CoV-2/genetics ; *COVID-19/prevention &amp; control ; COVID-19 Vaccines ; Post-Acute COVID-19 Syndrome ; Pandemics ; Antibodies, Neutralizing ; Antibodies, Viral ; }, abstract = {The global COVID-19 pandemic has caused more than 1 billion infections, and numerous SARS-CoV-2 vaccines developed rapidly have been administered over 10 billion doses. The world is continuously concerned about the cytokine storms induced by the interaction between SARS-CoV-2 and host, long COVID, breakthrough infections postvaccination, and the impact of SARS-CoV-2 variants. BCR-CDR3 repertoire serves as a molecular target for monitoring the antiviral response "trace" of B cells, evaluating the effects, mechanisms, and memory abilities of individual responses to B cells, and has been successfully applied in analyzing the infection mechanisms, vaccine improvement, and neutralizing antibodies preparation of influenza virus, HIV, MERS, and Ebola virus. Based on research on BCR-CDR3 repertoire of COVID-19 patients and volunteers who received different SARS-CoV-2 vaccines in multiple laboratories worldwide, we focus on analyzing the characteristics and changes of BCR-CDR3 repertoire, such as diversity, clonality, V&amp;J genes usage and pairing, SHM, CSR, shared CDR3 clones, as well as the summary on BCR sequences targeting virus-specific epitopes in the preparation and application research of SARS-CoV-2 potential therapeutic monoclonal antibodies. This review provides comparative data and new research schemes for studying the possible mechanisms of differences in B cell response between SARS-CoV-2 infection or vaccination, and supplies a foundation for improving vaccines after SARS-CoV-2 mutations and potential antibody therapy for infected individuals.}, }
@article {pmid38417766, year = {2024}, author = {Faghy, MA and Tatler, A and Chidley, C and Fryer, S and Stoner, L and Laddu, D and Arena, R and Ashton, RE}, title = {The physiologic benefits of optimizing cardiorespiratory fitness and physical activity - From the cell to systems level in a post-pandemic world.}, journal = {Progress in cardiovascular diseases}, volume = {83}, number = {}, pages = {49-54}, doi = {10.1016/j.pcad.2024.02.006}, pmid = {38417766}, issn = {1873-1740}, support = {MRF-009-0001-RG-TATLE/MRF_/MRF_/United Kingdom ; }, mesh = {Humans ; *Cardiorespiratory Fitness ; *COVID-19/epidemiology ; *Exercise/physiology ; *Cardiovascular Diseases/epidemiology/physiopathology/prevention &amp; control ; SARS-CoV-2 ; Quality of Life ; }, abstract = {Cardiovascular (CV) disease (CVD) is a leading cause of premature death and hospitalization which places a significant strain on health services and economies around the World. Evidence from decades of empirical and observational research demonstrates clear associations between physical activity (PA) and cardiorespiratory fitness (CRF) which can offset the risk of mortality and increase life expectancy and the quality of life in patients. Whilst well documented, the narrative of increased CRF remained pertinent during the coronavirus disease 2019 (COVID-19) pandemic, where individuals with lower levels of CRF had more than double the risk of dying from COVID-19 compared to those with a moderate or high CRF. The need to better understand the mechanisms associated with COVID-19 and those that continue to be affected with persistent symptoms following infection (Long COVID), and CV health is key if we are to be able to effectively target the use of CRF and PA to improve the lives of those suffering its afflictions. Whilst there is a long way to go to optimise PA and CRF for improved health at a population level, particularly in a post-pandemic world, increasing the understanding using a cellular-to-systems approach, we hope to provide further insight into the benefits of engaging in PA.}, }
@article {pmid38417769, year = {2024}, author = {Faghy, MA and Dalton, C and Duncan, R and Arena, R and Ashton, REM}, title = {Using cardiorespiratory fitness assessment to identify pathophysiology in long COVID - Best practice approaches.}, journal = {Progress in cardiovascular diseases}, volume = {83}, number = {}, pages = {55-61}, doi = {10.1016/j.pcad.2024.02.005}, pmid = {38417769}, issn = {1873-1740}, mesh = {Humans ; *Cardiorespiratory Fitness ; *COVID-19/physiopathology/diagnosis/epidemiology/therapy ; Exercise Test ; *Post-Acute COVID-19 Syndrome ; }, abstract = {Cardio-respiratory fitness (CRF) is well-established in the clinical domains as an integrative measure of the body's physiological capability and capacity to transport and utilise oxygen during controlled bouts of physical exertion. Long COVID is associated with >200 different symptoms and is estimated to affect ∼150 million people worldwide. The most widely reported impact is reduced quality of life and functional status due to highly sensitive and cyclical symptoms that manifest and are augmented following exposure to physical, emotional, orthostatic, and cognitive stimuli, more commonly known as post-exertional symptom exacerbation (PESE) which prevents millions from engaging in routine daily activities. The use of cardiopulmonary exercise testing (CPET) is commonplace in the assessment of integrated physiology; CPET will undoubtedly play an integral role in furthering the pathophysiology and mechanistic knowledge that will inform bespoke Long COVID treatment and management strategies. An inherent risk of previous attempts to utilise CPET protocols in patients with chronic disease is that these are compounded by PESE and have induced a worsening of symptoms for patients that can last for days or weeks. To do this effectively and to meet the global need, the complex multi-system pathophysiology of Long COVID must be considered to ensure the design and implementation of research that is both safe for participants and capable of advancing mechanistic understanding.}, }
@article {pmid38421118, year = {2024}, author = {Mattioli, LB and Frosini, M and Corazza, I and Fiorino, S and Zippi, M and Micucci, M and Budriesi, R}, title = {Long COVID-19 gastrointestinal related disorders and traditional Chinese medicine: A network target-based approach.}, journal = {Phytotherapy research : PTR}, volume = {38}, number = {5}, pages = {2323-2346}, doi = {10.1002/ptr.8163}, pmid = {38421118}, issn = {1099-1573}, mesh = {Humans ; *Medicine, Chinese Traditional/methods ; *COVID-19/epidemiology ; *Gastrointestinal Diseases/drug therapy ; *Drugs, Chinese Herbal/therapeutic use ; SARS-CoV-2 ; COVID-19 Drug Treatment ; Pandemics ; }, abstract = {The significant number of individuals impacted by the pandemic makes prolonged symptoms after COVID-19 a matter of considerable concern. These are numerous and affect multiple organ systems. According to the World Health Organization (WHO), prolonged gastrointestinal issues are a crucial part of post-COVID-19 syndrome. The resulting disruption of homeostasis underscores the need for a therapeutic approach based on compounds that can simultaneously affect more than one target/node. The present review aimed to check for nutraceuticals possessing multiple molecular mechanisms helpful in relieving Long COVID-19-specific gastrointestinal symptoms. Specific plants used in Keywords Chinese Medicine (TCM) expected to be included in the WHO Global Medical Compendium were selected based on the following criteria: (1) they are widely used in the Western world as natural remedies and complementary medicine adjuvants; (2) their import and trade are regulated by specific laws that ensure quality and safety (3) have the potential to be beneficial in alleviating intestinal issues associated with Long COVID-19. Searches were performed in PubMed, Elsevier, Google Scholar, Scopus, Science Direct, and ResearchGate up to 2023. Cinnamomum cassia, Glycyrrhiza uralensis, Magnolia officinalis, Poria cocos, Salvia miltiorrhiza, Scutellaria baicalensis, and Zingiber officinalis were identified as the most promising for their potential impact on inflammation and oxidative stress. Based on the molecular mechanisms of the phytocomplexes and isolated compounds of the considered plants, their clinical use may lead to benefits in gastrointestinal diseases associated with Long COVID-19, thanks to a multiorgan and multitarget approach.}, }
@article {pmid38423894, year = {2025}, author = {Johnston, R and Sonnappa, S and Goddings, AL and Whittaker, E and Segal, TY}, title = {A review of post COVID syndrome pathophysiology, clinical presentation and management in children and young people.}, journal = {Paediatric respiratory reviews}, volume = {53}, number = {}, pages = {14-22}, doi = {10.1016/j.prrv.2024.01.002}, pmid = {38423894}, issn = {1526-0550}, mesh = {Humans ; *COVID-19/complications/physiopathology/therapy/epidemiology ; Child ; SARS-CoV-2 ; Adolescent ; Post-Acute COVID-19 Syndrome ; }, abstract = {Post Covid Syndrome (PCS) is a complex multi-system disorder with a spectrum of presentations. Severity ranges from mild to very severe with variable duration of illness and recovery. This paper discusses the difficulties defining and describing PCS. We review the current understanding of PCS, epidemiology, and predisposing factors. We consider potential mechanisms including viral persistence, clotting dysfunction and immunity. We review presentation and diagnosis and finally consider management strategies including addressing symptom burden, rehabilitation, and novel therapies.}, }
@article {pmid38425701, year = {2024}, author = {Leonel, JW and Ciurleo, GCV and Formiga, AM and Vasconcelos, TMF and de Andrade, MH and Feitosa, WLQ and Sobreira-Neto, AA and Portugal, CG and Morais, LM and Marinho, SC and Gomes, EABM and Feitosa, EAAF and Sobreira, EST and Oriá, RB and Sobreira-Neto, MA and Braga-Neto, P}, title = {Long COVID: neurological manifestations - an updated narrative review.}, journal = {Dementia &amp; neuropsychologia}, volume = {18}, number = {}, pages = {e20230076}, pmid = {38425701}, issn = {1980-5764}, abstract = {Infection with the SARS-CoV-2 virus can lead to neurological symptoms in the acute phase and in the Long COVID phase. These symptoms usually involve cognition, sleep, smell disorders, psychiatric manifestations, headache and others. This condition is more commonly described in young adults and women. This symptomatology can follow severe or mild cases of the disease. The importance of this issue resides in the high prevalence of neurological symptoms in the Long COVID phase, which entails significant morbidity in this population. In addition, such a condition is associated with high health care costs, with some estimates hovering around 3.7 trillion US dollars. In this review, we will sequentially describe the current knowledge about the most prevalent neurological symptoms in Long COVID, as well as their pathophysiology and possible biomarkers.}, }
@article {pmid38428523, year = {2024}, author = {Banerjee, A}, title = {Disparities by Social Determinants of Health: Links Between Long COVID and Cardiovascular Disease.}, journal = {The Canadian journal of cardiology}, volume = {40}, number = {6}, pages = {1123-1134}, doi = {10.1016/j.cjca.2024.02.017}, pmid = {38428523}, issn = {1916-7075}, mesh = {Humans ; *Social Determinants of Health ; *COVID-19/epidemiology ; *Cardiovascular Diseases/epidemiology/therapy ; Post-Acute COVID-19 Syndrome ; Risk Factors ; Healthcare Disparities ; Socioeconomic Factors ; Health Status Disparities ; SARS-CoV-2 ; }, abstract = {Long COVID has been defined by the World Health Organisation as "continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation." Cardiovascular disease is implicated as a risk factor, concomitant condition, and consequence of long COVID. As well as heterogeneity in definition, presentation, and likely underlying pathophysiology of long COVID, disparities by social determinants of health, extensively studied and described in cardiovascular disease, have been observed in 3 ways. First, underlying long-term conditions, such as cardiovascular disease and its risk factors, are associated with incidence and severity of long COVID, and previously described socioeconomic disparities in these factors are important in exacerbating disparities in long COVID. Second, socioeconomic disparities in management of COVID-19 may themselves lead to distal disparities in long COVID. Third, there are socioeconomic disparities in the way that long COVID is diagnosed, managed, and prevented. Together, factors such as age, sex, deprivation, and ethnicity have far-reaching implications in this new postviral syndrome across its management spectrum. There are similarities and differences compared with disparities for cardiovascular disease. Some of these disparities are in fact, inequalities, that is, rather than simply observed variations, they represent injustices with costs to individuals, communities, and economies. This review of current literature considers opportunities to prevent or at least attenuate these socioeconomic disparities in long COVID and cardiovascular disease, with special challenges for research, clinical practice, public health, and policy in a new disease which is evolving.}, }
@article {pmid38432584, year = {2024}, author = {Powell, AA and Dowell, AC and Moss, P and Ladhani, SN and , }, title = {Current state of COVID-19 in children: 4 years on.}, journal = {The Journal of infection}, volume = {88}, number = {5}, pages = {106134}, doi = {10.1016/j.jinf.2024.106134}, pmid = {38432584}, issn = {1532-2742}, mesh = {Humans ; *COVID-19/epidemiology/prevention &amp; control/*complications ; Child ; *SARS-CoV-2 ; *COVID-19 Vaccines/administration &amp; dosage ; United Kingdom/epidemiology ; Systemic Inflammatory Response Syndrome/epidemiology ; Child, Preschool ; Vaccination ; Adolescent ; }, abstract = {Children have been disproportionately affected by the COVID-19 pandemic. Despite evidence of a very low risk of severe disease, children were subjected to extensive lockdown, restriction and mitigation measures, including school closures, to control the rapid spread of SARS-CoV-2 in most parts of the world. In this review we summarise the UK experience of COVID-19 in children four years into the largest and longest pandemic of this century. We address the risks of SARS-CoV-2 infection, immunity, transmission, severity and outcomes in children. We also assess the implementation, uptake, effectiveness and impact of COVID-19 vaccination, as well as the emergence, evolution and near disappearance of PIMS-TS (paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2) and current understanding of long COVID in children. This review consolidates current knowledge on childhood COVID-19 and emphasises the importance of continued research and the need for research-driven public health actions and policy decisions, especially in the context of new variants and future vaccines.}, }
@article {pmid38432691, year = {2024}, author = {Ordaya, EE and Razonable, RR}, title = {Emerging anti-spike monoclonal antibodies against SARS-CoV-2.}, journal = {Expert opinion on biological therapy}, volume = {24}, number = {3}, pages = {191-201}, doi = {10.1080/14712598.2024.2326647}, pmid = {38432691}, issn = {1744-7682}, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Neutralizing/therapeutic use ; }, abstract = {INTRODUCTION: Anti-spike monoclonal antibodies (mAbs) were previously authorized for the prevention and treatment of COVID-19 in immunocompromised patients. However, they are no longer authorized in the U.S. due to their lack of neutralizing activity against current circulating SARS-CoV-2 Omicron variants.<br><br>AREAS COVERED: We summarized the available data on emergent mAbs in the early stages of clinical development. Consistent with data on prior mAbs, these novel agents have been well tolerated and demonstrated a good safety profile in early clinical trials. Additionally, many of them have been engineered to ensure prolonged half-life and combined with other mAbs to overcome the potential for emerging resistant mutants. Interestingly, one of these agents has been evaluated using an inhaled route of administration, and another agent is being evaluated for treatment of long COVID.<br><br>EXPERT OPINION: Although the available data of novel mAbs holds promise, we anticipate that these agents will face similar challenges encountered by prior authorized agents, including the continued evolution of SARS-CoV-2 and emergence of new escape mutations. Strategies to potentially mitigate this are discussed. Based on prior successful experience, immunocompromised patients will certainly benefit from the utilization of mAbs for the prevention and treatment of COVID-19; thus, we need to design potential interventions to ensure the sustained activity of these agents.}, }
@article {pmid38442116, year = {2024}, author = {Cruickshank, M and Brazzelli, M and Manson, P and Torrance, N and Grant, A}, title = {What is the impact of long-term COVID-19 on workers in healthcare settings? A rapid systematic review of current evidence.}, journal = {PloS one}, volume = {19}, number = {3}, pages = {e0299743}, pmid = {38442116}, issn = {1932-6203}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Health Facilities ; Health Resources ; Health Personnel ; Chronic Disease ; Dyspnea ; }, abstract = {BACKGROUND: Long COVID is a devastating, long-term, debilitating illness which disproportionately affects healthcare workers, due to the nature of their work. There is currently limited evidence specific to healthcare workers about the experience of living with Long COVID, or its prevalence, pattern of recovery or impact on healthcare.<br><br>OBJECTIVE: Our objective was to assess the effects of Long COVID among healthcare workers and its impact on health status, working lives, personal circumstances, and use of health service resources.<br><br>METHODS: We conducted a systematic rapid review according to current methodological standards and reported it in adherence to the PRISMA 2020 and ENTREQ statements.<br><br>RESULTS: We searched relevant electronic databases and identified 3770 articles of which two studies providing qualitative evidence and 28 survey studies providing quantitative evidence were eligible. Thematic analysis of the two qualitative studies identified five themes: uncertainty about symptoms, difficulty accessing services, importance of being listened to and supported, patient versus professional identity and suggestions to improve communication and services for people with Long COVID. Common long-term symptoms in the survey studies included fatigue, headache, loss of taste and/or smell, breathlessness, dyspnoea, difficulty concentrating, depression and anxiety.<br><br>CONCLUSION: Healthcare workers struggled with their dual identity (patient/doctor) and felt dismissed or not taken seriously by their doctors. Our findings are in line with those in the literature showing that there are barriers to healthcare professionals accessing healthcare and highlighting the challenges of receiving care due to their professional role. A more representative approach in Long COVID research is needed to reflect the diverse nature of healthcare staff and their occupations. This rapid review was conducted using robust methods with the codicil that the pace of research into Long COVID may mean relevant evidence was not identified.}, }
@article {pmid38443223, year = {2024}, author = {Annesley, SJ and Missailidis, D and Heng, B and Josev, EK and Armstrong, CW}, title = {Unravelling shared mechanisms: insights from recent ME/CFS research to illuminate long COVID pathologies.}, journal = {Trends in molecular medicine}, volume = {30}, number = {5}, pages = {443-458}, doi = {10.1016/j.molmed.2024.02.003}, pmid = {38443223}, issn = {1471-499X}, mesh = {Humans ; *COVID-19/complications/virology ; *Fatigue Syndrome, Chronic/virology ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome ; }, abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic illness often triggered by an initiating acute event, mainly viral infections. The transition from acute to chronic disease remains unknown, but interest in this phenomenon has escalated since the COVID-19 pandemic and the post-COVID-19 illness, termed 'long COVID' (LC). Both ME/CFS and LC share many clinical similarities. Here, we present recent findings in ME/CFS research focussing on proposed disease pathologies shared with LC. Understanding these disease pathologies and how they influence each other is key to developing effective therapeutics and diagnostic tests. Given that ME/CFS typically has a longer disease duration compared with LC, with symptoms and pathologies evolving over time, ME/CFS may provide insights into the future progression of LC.}, }
@article {pmid38444741, year = {2024}, author = {Verma, A and Manojkumar, A and Dhasmana, A and Tripathi, MK and Jaggi, M and Chauhan, SC and Chauhan, DS and Yallapu, MM}, title = {Recurring SARS-CoV-2 variants: an update on post-pandemic, co-infections and immune response.}, journal = {Nanotheranostics}, volume = {8}, number = {2}, pages = {247-269}, pmid = {38444741}, issn = {2206-7418}, mesh = {Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Coinfection ; Pandemics ; Protein Subunit Vaccines ; }, abstract = {The post-pandemic era following the global spread of the SARS-CoV-2 virus has brought about persistent concerns regarding recurring coinfections. While significant strides in genome mapping, diagnostics, and vaccine development have controlled the pandemic and reduced fatalities, ongoing virus mutations necessitate a deeper exploration of the interplay between SARS-CoV-2 mutations and the host's immune response. Various vaccines, including RNA-based ones like Pfizer and Moderna, viral vector vaccines like Johnson &amp; Johnson and AstraZeneca, and protein subunit vaccines like Novavax, have played critical roles in mitigating the impact of COVID-19. Understanding their strengths and limitations is crucial for tailoring future vaccines to specific variants and individual needs. The intricate relationship between SARS-CoV-2 mutations and the immune response remains a focus of intense research, providing insights into personalized treatment strategies and long-term effects like long-COVID. This article offers an overview of the post-pandemic landscape, highlighting emerging variants, summarizing vaccine platforms, and delving into immunological responses and the phenomenon of long-COVID. By presenting clinical findings, it aims to contribute to the ongoing understanding of COVID-19's progression in the aftermath of the pandemic.}, }
@article {pmid38447388, year = {2024}, author = {van der Feltz-Cornelis, C and Turk, F and Sweetman, J and Khunti, K and Gabbay, M and Shepherd, J and Montgomery, H and Strain, WD and Lip, GYH and Wootton, D and Watkins, CL and Cuthbertson, DJ and Williams, N and Banerjee, A}, title = {Prevalence of mental health conditions and brain fog in people with long COVID: A systematic review and meta-analysis.}, journal = {General hospital psychiatry}, volume = {88}, number = {}, pages = {10-22}, doi = {10.1016/j.genhosppsych.2024.02.009}, pmid = {38447388}, issn = {1873-7714}, mesh = {Humans ; *COVID-19/epidemiology ; Prevalence ; *Post-Acute COVID-19 Syndrome ; Cognitive Dysfunction/epidemiology/etiology ; Mental Disorders/epidemiology ; }, abstract = {OBJECTIVE: Long COVID can include impaired cognition ('brain fog'; a term encompassing multiple symptoms) and mental health conditions. We performed a systematic review and meta-analysis to estimate their prevalence and to explore relevant factors associated with the incidence of impaired cognition and mental health conditions.<br><br>METHODS: Searches were conducted in Medline and PsycINFO to cover the start of the pandemic until August 2023. Included studies reported prevalence of mental health conditions and brain fog in adults with long COVID after clinically-diagnosed or PCR-confirmed SARS-CoV-2 infection.<br><br>FINDINGS: 17 studies were included, reporting 41,249 long COVID patients. Across all timepoints (3-24&#xa0;months), the combined prevalence of mental health conditions and brain fog was 20&#xb7;4% (95% CI 11&#xb7;1%-34&#xb7;4%), being lower among those previously hospitalised than in community-managed patients(19&#xb7;5 vs 29&#xb7;7% respectively; p&#xa0;=&#xa0;0&#xb7;047). The odds of mental health conditions and brain fog increased over time and when validated instruments were used. Odds of brain fog significantly decreased with increasing vaccination rates (p&#xa0;=&#xa0;&#xb7;000).<br><br>CONCLUSIONS: Given the increasing prevalence of mental health conditions and brain fog over time, preventive interventions and treatments are needed. Research is needed to explore underlying mechanisms that could inform further research in development of effective treatments. The reduced risk of brain fog associated with vaccination emphasizes the need for ongoing vaccination programs.}, }
@article {pmid38449882, year = {2024}, author = {Katz, AA and Wainwright, S and Kelly, MP and Albert, P and Byrne, R}, title = {Hyperbaric oxygen effectively addresses the pathophysiology of long COVID: clinical review.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1354088}, pmid = {38449882}, issn = {2296-858X}, abstract = {BACKGROUND: The World Health Organization defines long COVID as "the continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation." Estimations of approximately 50 million individuals suffer from long COVID, reporting low health-related quality of life. Patients develop ongoing persistent symptoms that continue for more than 12 weeks that are not explained by another alternative diagnosis. To date, no current therapeutics are effective in treating the underlying pathophysiology of long COVID.<br><br>DISCUSSION: A comprehensive literature search using PubMed and Google Scholar was conducted and all available articles from November 2021 to January 2024 containing keywords long covid and hyperbaric oxygen were reviewed. These published studies, including case series and randomized trials, demonstrate that utilizing Hyperbaric Oxygen Therapy (HBO) provided significant improvement in patients with long COVID.<br><br>CONCLUSION: A large cohort of patients suffer from long COVID or post-COVID-19 syndrome after recovery from their acute infection with no effective treatment options. HBO is a safe treatment and may provide benefit for this population and should continue to be researched for adjunctive treatment of long COVID.}, }
@article {pmid38455739, year = {2024}, author = {Zhang, J and Kuang, T and Liu, X}, title = {Advances in researches on long coronavirus disease in children: a narrative review.}, journal = {Translational pediatrics}, volume = {13}, number = {2}, pages = {318-328}, pmid = {38455739}, issn = {2224-4344}, abstract = {BACKGROUND AND OBJECTIVE: In the context of the global pandemic of coronavirus disease 2019 (COVID-19), more than 700 million infections and millions of deaths have occurred in countries around the world. Currently, two main sequelae of this disease are considered to occur in children, namely, multi-system inflammatory syndrome in children and long COVID. Among these two, the incidence of long COVID is higher and its impact on the population is more extensive, which is the focus of us. However, due to the lack of relevant studies and the limitations of most studies, the studies on sequelae of COVID-19 infection lag behind those of adults, but they have begun to attract the attention of some clinicians and researchers. We aim to summarize the current knowledge of long COVID in children, helping pediatricians and researchers to better understand this disease and providing guidance on research and clinical treatment of it.<br><br>METHODS: We reviewed all the studies on "long COVID", pediatric, children, adolescent, post-COVID syndrome in PubMed published after 2019.<br><br>KEY CONTENT AND FINDINGS: This review summarizes the latest researches on epidemiology, pathogenesis, clinical manifestations, prevention and treatment of long COVID in children. Based on the existing research data, we summarized and analyzed the characteristics of long COVID in children, discovering the means to decipher the diagnosis of COVID-19 in children and some potential therapeutic treatments.<br><br>CONCLUSIONS: We aim to summarize existing research on long COVID in children and help pediatricians and government agencies quickly understand the disease so that it can be used for clinical diagnosis, treatment and prevention in the population. In addition, providing a research basis for further researches on the cellular and even molecular level to explain the occurrence and development of diseases, and has a guiding role for future research direction.}, }
@article {pmid38455892, year = {2023}, author = {Gómez Bravo, R and Infanti, A and Billieux, J and Ritzen, M and ,  and Vögele, C and Benoy, C}, title = {The psychological syndrome associated with Long-COVID: A study protocol.}, journal = {Frontiers in epidemiology}, volume = {3}, number = {}, pages = {1193369}, pmid = {38455892}, issn = {2674-1199}, abstract = {INTRODUCTION: Chronic post-viral syndromes, including Long-COVID, are characterized by a range of persistent symptoms that occur following a viral infection. Psychological symptoms are prevalent in Long-COVID patients and can have a significant impact on their quality of life. However, the specific patterns of psychological symptoms, their associations with physical symptoms, and the factors predicting their severity remain poorly understood.<br><br>AIMS: This study aims to explore and systematically assess psychological symptoms in Long-COVID, to identify syndrome clusters based on these symptoms, to examine their relationship with physical symptoms, and to investigate the influence of pandemic-related variables.<br><br>METHODS: Descriptive, cross-sectional study with data collected through an online questionnaire across several EU countries, from February 2020 to December 2022. Participants were recruited using public relations, the social media and information campaigns directed at the public and health professionals using snowball sampling.<br><br>RESULTS: The findings will allow to phenotype Long-COVID related psychological symptom clusters based on self-reports. facilitating improved assessment and treatment approaches.<br><br>CONCLUSIONS: The results will provide important knowledge for the public health management of the public healh management of Long COVID. The findings will contribute to a better understanding of the psychological symptoms associated with Long-COVID and the development of specific treatment guidelines for psychological burden associated with Long-COVID, thereby supporting management strategies to combat the after-effects of the COVID-19 pandemic, enhancing their overall well-being and quality of life.}, }
@article {pmid38460395, year = {2024}, author = {Peluso, MJ and Abdel-Mohsen, M and Henrich, TJ and Roan, NR}, title = {Systems analysis of innate and adaptive immunity in Long COVID.}, journal = {Seminars in immunology}, volume = {72}, number = {}, pages = {101873}, doi = {10.1016/j.smim.2024.101873}, pmid = {38460395}, issn = {1096-3618}, support = {L30 AI147159/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Pandemics ; SARS-CoV-2 ; Adaptive Immunity ; Systems Analysis ; Immunity, Innate ; }, abstract = {Since the onset of the COVID-19 pandemic, significant progress has been made in developing effective preventive and therapeutic strategies against severe acute SARS-CoV-2 infection. However, the management of Long COVID (LC), an infection-associated chronic condition that has been estimated to affect 5-20% of individuals following SARS-CoV-2 infection, remains challenging due to our limited understanding of its mechanisms. Although LC is a heterogeneous disease that is likely to have several subtypes, immune system disturbances appear common across many cases. The extent to which these immune perturbations contribute to LC symptoms, however, is not entirely clear. Recent advancements in multi-omics technologies, capable of detailed, cell-level analysis, have provided valuable insights into the immune perturbations associated with LC. Although these studies are largely descriptive in nature, they are the crucial first step towards a deeper understanding of the condition and the immune system's role in its development, progression, and resolution. In this review, we summarize the current understanding of immune perturbations in LC, covering both innate and adaptive immune responses, and the cytokines and analytes involved. We explore whether these findings support or challenge the primary hypotheses about LC's underlying mechanisms. We also discuss the crosstalk between various immune system components and how it can be disrupted in LC. Finally, we emphasize the need for more tissue- and subtype-focused analyses of LC, and for enhanced collaborative efforts to analyze common specimens from large cohorts, including those undergoing therapeutic interventions. These collective efforts are vital to unravel the fundaments of this new disease, and could also shed light on the prevention and treatment of the larger family of chronic illnesses linked to other microbial infections.}, }
@article {pmid38460898, year = {2024}, author = {Faghy, MA and Duncan, R and Hume, E and Gough, L and Roscoe, C and Laddu, D and Arena, R and Asthon, REM and Dalton, C}, title = {Developing effective strategies to optimize physical activity and cardiorespiratory fitness in the long Covid population- The need for caution and objective assessment.}, journal = {Progress in cardiovascular diseases}, volume = {83}, number = {}, pages = {62-70}, doi = {10.1016/j.pcad.2024.03.003}, pmid = {38460898}, issn = {1873-1740}, mesh = {Humans ; *Cardiorespiratory Fitness ; COVID-19/complications ; *Exercise ; *Post-Acute COVID-19 Syndrome/diagnosis/pathology/therapy ; Quality of Life ; }, abstract = {The Post Covid-19 Condition (commonly known as Long Covid) has been defined by the World Health Organisation as occurring in individuals with a history of probable or confirmed SARS CoV 2 infection, usually within 3 months from the onset of acute Covid-19 infection with symptoms that last for at least two months which cannot be explained by an alternative diagnosis. Long Covid is associated with over two hundred recognised symptoms and affects tens of millions of people worldwide. Widely reported reductions in quality of life(QoL) and functional status are caused by extremely sensitive and cyclical symptom profiles that are augmented following exposure to physical, emotional, orthostatic, and cognitive stimuli. This manifestation prevents millions of people from engaging in routine activities of daily living (ADLs) and has important health and well-being, social and economic impacts. Post-exertional symptom exacerbation (PESE) (also known as post-exertional malaise) is an exacerbation in the severity of fatigue and other symptoms following physical, emotional, orthostatic and cognitive tasks. Typically, this will occur 24-72 h after "over-exertion" and can persist for several days and even weeks. It is a hallmark symptom of Long Covid with a reported prevalence of 86%. The debilitating nature of PESE prevents patients from engaging in physical activity which impacts functional status and QoL. In this review, the authors present an update to the literature relating to PESE in Long Covid and make the case for evidence-based guidelines that support the design and implementation of safe rehabilitation approaches for people with Long Covid. This review also considers the role of objective monitoring to quantify a patient's response to external stimuli which can be used to support the safe management of Long Covid and inform decisions relating to engagement with any stimuli that could prompt an exacerbation of symptoms.}, }
@article {pmid38461701, year = {2024}, author = {van der Knaap, N and Ariës, MJH and van der Horst, ICC and Jansen, JFA}, title = {On the merits and potential of advanced neuroimaging techniques in COVID-19: A scoping review.}, journal = {NeuroImage. Clinical}, volume = {42}, number = {}, pages = {103589}, pmid = {38461701}, issn = {2213-1582}, mesh = {Humans ; *COVID-19/diagnostic imaging/complications ; *Neuroimaging/methods ; *Brain/diagnostic imaging/pathology ; SARS-CoV-2 ; }, abstract = {Many Coronavirus Disease 2019 (COVID-19) patients are suffering from long-term neuropsychological sequelae. These patients may benefit from a better understanding of the underlying neuropathophysiological mechanisms and identification of potential biomarkers and treatment targets. Structural clinical neuroimaging techniques have limited ability to visualize subtle cerebral abnormalities and to investigate brain function. This scoping review assesses the merits and potential of advanced neuroimaging techniques in COVID-19 using literature including advanced neuroimaging or postmortem analyses in adult COVID-19 patients published from the start of the pandemic until December 2023. Findings were summarized according to distinct categories of reported cerebral abnormalities revealed by different imaging techniques. Although no unified COVID-19-specific pattern could be subtracted, a broad range of cerebral abnormalities were revealed by advanced neuroimaging (likely attributable to hypoxic, vascular, and inflammatory pathology), even in absence of structural clinical imaging findings. These abnormalities are validated by postmortem examinations. This scoping review emphasizes the added value of advanced neuroimaging compared to structural clinical imaging and highlights implications for brain functioning and long-term consequences in COVID-19.}, }
@article {pmid38463084, year = {2024}, author = {Tariq, M and Mahak, F and Kumar, R and Kumar, A and Kumar, A and Khan, J and Muhammad, MA and Memon, U and Maqsood, KM and Tanveer, FS and Gill, A and Jawed, A and Shrestha, S and Waheed, MH}, title = {Unmasking the long-term effects: unravelling neuropsychiatric and neurological consequences of COVID-19.}, journal = {Annals of medicine and surgery (2012)}, volume = {86}, number = {3}, pages = {1490-1495}, pmid = {38463084}, issn = {2049-0801}, abstract = {The COVID-19 pandemic has not only burdened healthcare systems but has also led to a new emerging medical enigma that is post-COVID-19 syndrome or "long COVID." Characterized by persistent symptoms that extend beyond the acute phase of the illness, long COVID has rapidly become a public health concern with ambiguous neurological and neuropsychiatric dimensions. This narrative review aims at synthesizing available research to decode the long-term impacts of COVID-19 on neurological and mental health. Drawing from a multitude of studies, this review synthesizes evidence on various neuropsychiatric and neurological symptoms, including cognitive deficits, mood disorders, and more. The narrative delves into potential pathogenic mechanisms, hoping to fill existing research gaps and offering directions for future inquiry. The objective is not just academic; it has immediate real-world implications. Understanding these long-term effects is crucial for developing effective treatments and interventions, thereby better serving the millions of individuals living with these lingering symptoms. As healthcare systems continue to grapple with the fallout from the pandemic, this review provides much-needed context and insights into an area that demands urgent research and action.}, }
@article {pmid38463416, year = {2024}, author = {Agoston, DV}, title = {Traumatic Brain Injury in the Long-COVID Era.}, journal = {Neurotrauma reports}, volume = {5}, number = {1}, pages = {81-94}, pmid = {38463416}, issn = {2689-288X}, abstract = {Major determinants of the biological background or reserve, such as age, biological sex, comorbidities (diabetes, hypertension, obesity, etc.), and medications (e.g., anticoagulants), are known to affect outcome after traumatic brain injury (TBI). With the unparalleled data richness of coronavirus disease 2019 (COVID-19; ∼375,000 and counting!) as well as the chronic form, long-COVID, also called post-acute sequelae SARS-CoV-2 infection (PASC), publications (∼30,000 and counting) covering virtually every aspect of the diseases, pathomechanisms, biomarkers, disease phases, symptomatology, etc., have provided a unique opportunity to better understand and appreciate the holistic nature of diseases, interconnectivity between organ systems, and importance of biological background in modifying disease trajectories and affecting outcomes. Such a holistic approach is badly needed to better understand TBI-induced conditions in their totality. Here, I briefly review what is known about long-COVID/PASC, its underlying-suspected-pathologies, the pathobiological changes induced by TBI, in other words, the TBI endophenotypes, discuss the intersection of long-COVID/PASC and TBI-induced pathobiologies, and how by considering some of the known factors affecting the person's biological background and the inclusion of mechanistic molecular biomarkers can help to improve the clinical management of TBI patients.}, }
@article {pmid38468535, year = {2025}, author = {Balzanelli, MG and Rastmanesh, R and Distratis, P and Lazzaro, R and Inchingolo, F and Del Prete, R and Pham, VH and Aityan, SK and Cong, TT and Nguyen, KCD and Isacco, CG}, title = {The Role of SARS-CoV-2 Spike Protein in Long-term Damage of Tissues and Organs, the Underestimated Role of Retrotransposons and Stem Cells, a Working Hypothesis.}, journal = {Endocrine, metabolic &amp; immune disorders drug targets}, volume = {25}, number = {2}, pages = {85-98}, pmid = {38468535}, issn = {2212-3873}, mesh = {Humans ; *Spike Glycoprotein, Coronavirus/metabolism/genetics/physiology ; COVID-19 ; SARS-CoV-2 ; *Retroelements/physiology/genetics ; *Stem Cells/virology/metabolism ; Pandemics ; *Betacoronavirus/metabolism/genetics ; *Coronavirus Infections/virology/genetics ; *Pneumonia, Viral/virology/genetics ; Animals ; }, abstract = {Coronavirus disease-2019 (COVID-19) is a respiratory disease in which Spike protein from SARS-CoV-2 plays a key role in transferring virus genomic code into target cells. Spike protein, which is found on the surface of the SARS-CoV-2 virus, latches onto angiotensin-converting enzyme 2 receptors (ACE2r) on target cells. The RNA genome of coronaviruses, with an average length of 29 kb, is the longest among all RNA viruses and comprises six to ten open reading frames (ORFs) responsible for encoding replicase and structural proteins for the virus. Each component of the viral genome is inserted into a helical nucleocapsid surrounded by a lipid bilayer. The Spike protein is responsible for damage to several organs and tissues, even leading to severe impairments and long-term disabilities. Spike protein could also be the cause of the long-term post-infectious conditions known as Long COVID-19, characterized by a group of unresponsive idiopathic severe neuro- and cardiovascular disorders, including strokes, cardiopathies, neuralgias, fibromyalgia, and Guillaume- Barret's like-disease. In this paper, we suggest a pervasive mechanism whereby the Spike proteins either from SARS-CoV-2 mRNA or mRNA vaccines, tend to enter the mature cells, and progenitor, multipotent, and pluripotent stem cells (SCs), altering the genome integrity. This will eventually lead to the production of newly affected clones and mature cells. The hypothesis presented in this paper proposes that the mRNA integration into DNA occurs through several components of the evolutionarily genetic mechanism such as retrotransposons and retrotransposition, LINE-1 or L1 (long interspersed element-1), and ORF-1 and 2 responsible for the generation of retrogenes. Once the integration phase is concluded, somatic cells, progenitor cells, and SCs employ different silencing mechanisms. DNA methylation, followed by histone modification, begins to generate unlimited lines of affected cells and clones that form affected tissues characterized by abnormal patterns that become targets of systemic immune cells, generating uncontrolled inflammatory conditions, as observed in both Long COVID-19 syndrome and the mRNA vaccine.}, }
@article {pmid38469293, year = {2024}, author = {Collins, CP and Longo, DL and Murphy, WJ}, title = {The immunobiology of SARS-CoV-2 infection and vaccine responses: potential influences of cross-reactive memory responses and aging on efficacy and off-target effects.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1345499}, pmid = {38469293}, issn = {1664-3224}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Vaccines ; Aging ; Immunoglobulin Idiotypes ; }, abstract = {Immune responses to both SARS-CoV-2 infection and its associated vaccines have been highly variable within the general population. The increasing evidence of long-lasting symptoms after resolution of infection, called post-acute sequelae of COVID-19 (PASC) or "Long COVID," suggests that immune-mediated mechanisms are at play. Closely related endemic common human coronaviruses (hCoV) can induce pre-existing and potentially cross-reactive immunity, which can then affect primary SARS-CoV-2 infection, as well as vaccination responses. The influence of pre-existing immunity from these hCoVs, as well as responses generated from original CoV2 strains or vaccines on the development of new high-affinity responses to CoV2 antigenic viral variants, needs to be better understood given the need for continuous vaccine adaptation and application in the population. Due in part to thymic involution, normal aging is associated with reduced naïve T cell compartments and impaired primary antigen responsiveness, resulting in a reliance on the pre-existing cross-reactive memory cell pool which may be of lower affinity, restricted in diversity, or of shorter duration. These effects can also be mediated by the presence of down-regulatory anti-idiotype responses which also increase in aging. Given the tremendous heterogeneity of clinical data, utilization of preclinical models offers the greatest ability to assess immune responses under a controlled setting. These models should now involve prior antigen/viral exposure combined with incorporation of modifying factors such as age on immune responses and effects. This will also allow for mechanistic dissection and understanding of the different immune pathways involved in both SARS-CoV-2 pathogen and potential vaccine responses over time and how pre-existing memory responses, including potential anti-idiotype responses, can affect efficacy as well as potential off-target effects in different tissues as well as modeling PASC.}, }
@article {pmid38474072, year = {2024}, author = {Smith, MM and Melrose, J}, title = {Lumican, a Multifunctional Cell Instructive Biomarker Proteoglycan Has Novel Roles as a Marker of the Hypercoagulative State of Long Covid Disease.}, journal = {International journal of molecular sciences}, volume = {25}, number = {5}, pages = {}, pmid = {38474072}, issn = {1422-0067}, support = {n/a//Melrose Personal Research Fund, Sydney, Australia/ ; }, mesh = {Humans ; *Proteoglycans ; Lumican ; Post-Acute COVID-19 Syndrome ; Chondroitin Sulfate Proteoglycans/metabolism ; *COVID-19 ; Biomarkers ; }, abstract = {This study has reviewed the many roles of lumican as a biomarker of tissue pathology in health and disease. Lumican is a structure regulatory proteoglycan of collagen-rich tissues, with cell instructive properties through interactions with a number of cell surface receptors in tissue repair, thereby regulating cell proliferation, differentiation, inflammation and the innate and humoral immune systems to combat infection. The exponential increase in publications in the last decade dealing with lumican testify to its role as a pleiotropic biomarker regulatory protein. Recent findings show lumican has novel roles as a biomarker of the hypercoagulative state that occurs in SARS CoV-2 infections; thus, it may also prove useful in the delineation of the complex tissue changes that characterize COVID-19 disease. Lumican may be useful as a prognostic and diagnostic biomarker of long COVID disease and its sequelae.}, }
@article {pmid38481207, year = {2024}, author = {Duan, C and Liu, L and Wang, T and Wang, G and Jiang, Z and Li, H and Zhang, G and Ye, L and Li, C and Cao, Y}, title = {Evidence linking COVID-19 and the health/well-being of children and adolescents: an umbrella review.}, journal = {BMC medicine}, volume = {22}, number = {1}, pages = {116}, pmid = {38481207}, issn = {1741-7015}, support = {National Natural Science Foundation of China//National Natural Science Foundation of China/ ; 24NSFSC3535//Natural Science Foundation of Sichuan Province/ ; RD-02-202409//West China School of Stomatology, Sichuan University/ ; }, mesh = {Adolescent ; Child ; Humans ; *COVID-19/epidemiology ; COVID-19 Vaccines ; Post-Acute COVID-19 Syndrome ; Quality of Life ; Systematic Reviews as Topic ; }, abstract = {BACKGROUND: Experiences during childhood and adolescence have enduring impacts on physical and mental well-being, overall quality of life, and socioeconomic status throughout one's lifetime. This underscores the importance of prioritizing the health of children and adolescents to establish an impactful healthcare system that benefits both individuals and society. It is crucial for healthcare providers and policymakers to examine the relationship between COVID-19 and the health of children and adolescents, as this understanding will guide the creation of interventions and policies for the long-term management of the virus.<br><br>METHODS: In this umbrella review (PROSPERO ID: CRD42023401106), systematic reviews were identified from the Cochrane Database of Systematic Reviews; EMBASE (OvidSP); and MEDLINE (OvidSP) from December 2019 to February 2023. Pairwise and single-arm meta-analyses were extracted from the included systematic reviews. The methodological quality appraisal was completed using the AMSTAR-2 tool. Single-arm meta-analyses were re-presented under six domains associated with COVID-19 condition. Pairwise meta-analyses were classified into five domains according to the evidence classification criteria. Rosenberg's FSN was calculated for both binary and continuous measures.<br><br>RESULTS: We identified 1551 single-arm and 301 pairwise meta-analyses from 124 systematic reviews that met our predefined criteria for inclusion. The focus of the meta-analytical evidence was predominantly on the physical outcomes of COVID-19, encompassing both single-arm and pairwise study designs. However, the quality of evidence and methodological rigor were suboptimal. Based on the evidence gathered from single-arm meta-analyses, we constructed an illustrative representation of the disease severity, clinical manifestations, laboratory and radiological findings, treatments, and outcomes from 2020 to 2022. Additionally, we discovered 17 instances of strong or highly suggestive pairwise meta-analytical evidence concerning long-COVID, pediatric comorbidity, COVID-19 vaccines, mental health, and depression.<br><br>CONCLUSIONS: The findings of our study advocate for the implementation of surveillance systems to track health consequences associated with COVID-19 and the establishment of multidisciplinary collaborative rehabilitation programs for affected younger populations. In future research endeavors, it is important to prioritize the investigation of non-physical outcomes to bridge the gap between research findings and clinical application in this field.}, }
@article {pmid38482000, year = {2024}, author = {Bohmwald, K and Diethelm-Varela, B and Rodríguez-Guilarte, L and Rivera, T and Riedel, CA and González, PA and Kalergis, AM}, title = {Pathophysiological, immunological, and inflammatory features of long COVID.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1341600}, pmid = {38482000}, issn = {1664-3224}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Pandemics ; Kinetics ; Persistent Infection ; }, abstract = {The COVID-19 pandemic continues to cause severe global disruption, resulting in significant excess mortality, overwhelming healthcare systems, and imposing substantial social and economic burdens on nations. While most of the attention and therapeutic efforts have concentrated on the acute phase of the disease, a notable proportion of survivors experience persistent symptoms post-infection clearance. This diverse set of symptoms, loosely categorized as long COVID, presents a potential additional public health crisis. It is estimated that 1 in 5 COVID-19 survivors exhibit clinical manifestations consistent with long COVID. Despite this prevalence, the mechanisms and pathophysiology of long COVID remain poorly understood. Alarmingly, evidence suggests that a significant proportion of cases within this clinical condition develop debilitating or disabling symptoms. Hence, urgent priority should be given to further studies on this condition to equip global public health systems for its management. This review provides an overview of available information on this emerging clinical condition, focusing on the affected individuals' epidemiology, pathophysiological mechanisms, and immunological and inflammatory profiles.}, }
@article {pmid38483046, year = {2024}, author = {Pietrangelo, T and Cagnin, S and Bondi, D and Santangelo, C and Marramiero, L and Purcaro, C and Bonadio, RS and Di Filippo, ES and Mancinelli, R and Fulle, S and Verratti, V and Cheng, X}, title = {Myalgic encephalomyelitis/chronic fatigue syndrome from current evidence to new diagnostic perspectives through skeletal muscle and metabolic disturbances.}, journal = {Acta physiologica (Oxford, England)}, volume = {240}, number = {4}, pages = {e14122}, doi = {10.1111/apha.14122}, pmid = {38483046}, issn = {1748-1716}, support = {R21 NS139044/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Fatigue Syndrome, Chronic/diagnosis/epidemiology ; Post-Acute COVID-19 Syndrome ; Pandemics ; Muscle, Skeletal/metabolism ; }, abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a demanding medical condition for patients and society. It has raised much more public awareness after the COVID-19 pandemic since ME/CFS and long-COVID patients share many clinical symptoms such as debilitating chronic fatigue. However, unlike long COVID, the etiopathology of ME/CFS remains a mystery despite several decades' research. This review moves from pathophysiology of ME/CFS through the compelling evidence and most interesting hypotheses. It focuses on the pathophysiology of skeletal muscle by proposing the hypothesis that skeletal muscle tissue offers novel opportunities for diagnosis and treatment of this syndrome and that new evidence can help resolve the long-standing debate on terminology.}, }
@article {pmid38491011, year = {2024}, author = {Aldridge, SJ and Agrawal, U and Murphy, S and Millington, T and Akbari, A and Almaghrabi, F and Anand, SN and Bedston, S and Goudie, R and Griffiths, R and Joy, M and Lowthian, E and de Lusignan, S and Patterson, L and Robertson, C and Rudan, I and Bradley, DT and Lyons, RA and Sheikh, A and Owen, RK}, title = {Uptake of COVID-19 vaccinations amongst 3,433,483 children and young people: meta-analysis of UK prospective cohorts.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {2363}, pmid = {38491011}, issn = {2041-1723}, support = {MC_PC_20058/MRC_/Medical Research Council/United Kingdom ; SBF006\1122/DUK_/Diabetes UK/United Kingdom ; }, mesh = {Adolescent ; Child ; Humans ; *COVID-19/epidemiology/prevention &amp; control ; *COVID-19 Vaccines ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; SARS-CoV-2 ; United Kingdom/epidemiology ; Vaccination ; Child, Preschool ; }, abstract = {SARS-CoV-2 infection in children and young people (CYP) can lead to life-threatening COVID-19, transmission within households and schools, and the development of long COVID. Using linked health and administrative data, we investigated vaccine uptake among 3,433,483 CYP aged 5-17 years across all UK nations between 4th August 2021 and 31st May 2022. We constructed national cohorts and undertook multi-state modelling and meta-analysis to identify associations between demographic variables and vaccine uptake. We found that uptake of the first COVID-19 vaccine among CYP was low across all four nations compared to other age groups and diminished with subsequent doses. Age and vaccination status of adults living in the same household were identified as important risk factors associated with vaccine uptake in CYP. For example, 5-11 year-olds were less likely to receive their first vaccine compared to 16-17 year-olds (adjusted Hazard Ratio [aHR]: 0.10 (95%CI: 0.06-0.19)), and CYP in unvaccinated households were less likely to receive their first vaccine compared to CYP in partially vaccinated households (aHR: 0.19, 95%CI 0.13-0.29).}, }
@article {pmid38495122, year = {2024}, author = {Qiu, Y and Mo, C and Chen, L and Ye, W and Chen, G and Zhu, T}, title = {Alterations in microbiota of patients with COVID-19: implications for therapeutic interventions.}, journal = {MedComm}, volume = {5}, number = {4}, pages = {e513}, pmid = {38495122}, issn = {2688-2663}, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently caused a global pandemic, resulting in more than 702 million people being infected and over 6.9 million deaths. Patients with coronavirus disease (COVID-19) may suffer from diarrhea, sleep disorders, depression, and even cognitive impairment, which is associated with long COVID during recovery. However, there remains no consensus on effective treatment methods. Studies have found that patients with COVID-19 have alterations in microbiota and their metabolites, particularly in the gut, which may be involved in the regulation of immune responses. Consumption of probiotics may alleviate the discomfort caused by inflammation and oxidative stress. However, the pathophysiological process underlying the alleviation of COVID-19-related symptoms and complications by targeting the microbiota remains unclear. In the current study, we summarize the latest research and evidence on the COVID-19 pandemic, together with symptoms of SARS-CoV-2 and vaccine use, with a focus on the relationship between microbiota alterations and COVID-19-related symptoms and vaccine use. This work provides evidence that probiotic-based interventions may improve COVID-19 symptoms by regulating gut microbiota and systemic immunity. Probiotics may also be used as adjuvants to improve vaccine efficacy.}, }
@article {pmid38495940, year = {2024}, author = {Mostafa, RH and Moustafa, A}, title = {Beyond acute infection: molecular mechanisms underpinning cardiovascular complications in long COVID.}, journal = {Frontiers in cardiovascular medicine}, volume = {11}, number = {}, pages = {1268571}, pmid = {38495940}, issn = {2297-055X}, abstract = {SARS-CoV-2, responsible for the global COVID-19 pandemic, has manifested significant cardiovascular implications for the infected population. These cardiovascular repercussions not only linger beyond the initial phase of illness but have also been observed in individuals who remain asymptomatic. This extended and pervasive impact is often called the post-acute COVID-19 syndrome (PACS) or "Long COVID". With the number of confirmed global cases approaching an alarming 756 million, the multifaceted challenges of Long COVID are undeniable. These challenges span from individual health complications to considerable burdens on worldwide healthcare systems. Our review comprehensively examines the complications of the persistent cardiovascular complications associated with COVID-19. Furthermore, we shed light on emerging therapeutic strategies that promise to manage and possibly mitigate these complications. We also introduce and discuss the profound concerns regarding the potential transgenerational repercussions of SARS-CoV-2, emphasizing the need for a proactive and informed approach to future research and clinical practice.}, }
@article {pmid38500880, year = {2024}, author = {Gheorghita, R and Soldanescu, I and Lobiuc, A and Caliman Sturdza, OA and Filip, R and Constantinescu-Bercu, A and Dimian, M and Mangul, S and Covasa, M}, title = {The knowns and unknowns of long COVID-19: from mechanisms to therapeutical approaches.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1344086}, pmid = {38500880}, issn = {1664-3224}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Disease Management ; Disease Progression ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has been defined as the greatest global health and socioeconomic crisis of modern times. While most people recover after being infected with the virus, a significant proportion of them continue to experience health issues weeks, months and even years after acute infection with SARS-CoV-2. This persistence of clinical symptoms in infected individuals for at least three months after the onset of the disease or the emergence of new symptoms lasting more than two months, without any other explanation and alternative diagnosis have been named long COVID, long-haul COVID, post-COVID-19 conditions, chronic COVID, or post-acute sequelae of SARS-CoV-2 (PASC). Long COVID has been characterized as a constellation of symptoms and disorders that vary widely in their manifestations. Further, the mechanisms underlying long COVID are not fully understood, which hamper efficient treatment options. This review describes predictors and the most common symptoms related to long COVID's effects on the central and peripheral nervous system and other organs and tissues. Furthermore, the transcriptional markers, molecular signaling pathways and risk factors for long COVID, such as sex, age, pre-existing condition, hospitalization during acute phase of COVID-19, vaccination, and lifestyle are presented. Finally, recommendations for patient rehabilitation and disease management, as well as alternative therapeutical approaches to long COVID sequelae are discussed. Understanding the complexity of this disease, its symptoms across multiple organ systems and overlapping pathologies and its possible mechanisms are paramount in developing diagnostic tools and treatments.}, }
@article {pmid38506116, year = {2024}, author = {Khullar, V and Lemmon, B and Acar, O and Abrams, P and Vahabi, B}, title = {Does COVID-19 cause or worsen LUT dysfunction, what are the mechanisms and possible treatments? ICI-RS 2023.}, journal = {Neurourology and urodynamics}, volume = {43}, number = {6}, pages = {1458-1463}, doi = {10.1002/nau.25441}, pmid = {38506116}, issn = {1520-6777}, mesh = {Humans ; *COVID-19/complications/physiopathology ; *Lower Urinary Tract Symptoms/physiopathology/etiology/therapy ; SARS-CoV-2 ; }, abstract = {INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and produced a worldwide pandemic in 2020. There have been 770,875,433 confirmed cases and 6,959,316 attributed deaths worldwide until September 19, 2023. The virus can also affect the lower urinary tract (LUT) leading to bladder inflammation and producing lower urinary tract symptoms (LUTS) in both the acute and chronic phases of disease.<br><br>METHODS: At the 2023 meeting of the International Consultation on Incontinence-Research Society (ICI-RS), the literature relating to COVID-19 and bladder dysfunction was reviewed. The LUTS&#xa0;reported, as well as the pathophysiology of these bladder symptoms, were the subject of considerable discussion. A number of different topics were discussed including lower LUTS reported in COVID-19, how SARS-CoV-2 may infect and affect the urinary tract, and proposed mechanisms for how viral infection result in new, worsened, and in some persisting LUTS.<br><br>CONCLUSIONS: The workshop discussed the interaction between the virus and the immune system, covering current evidence supporting theories underlying the causes of acute and chronic LUTS related to COVID-19 infection. Research questions for further investigation were suggested and identified.}, }
@article {pmid38508059, year = {2024}, author = {Srivastava, A and Nalroad Sundararaj, S and Bhatia, J and Singh Arya, D}, title = {Understanding long COVID myocarditis: A comprehensive review.}, journal = {Cytokine}, volume = {178}, number = {}, pages = {156584}, doi = {10.1016/j.cyto.2024.156584}, pmid = {38508059}, issn = {1096-0023}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Myocarditis/etiology ; *Heart Failure ; *Zika Virus ; *Zika Virus Infection ; }, abstract = {Infectious diseases are a cause of major concern in this twenty-first century. There have been reports of various outbreaks like severe acute respiratory syndrome (SARS) in 2003, swine flu in 2009, Zika virus disease in 2015, and Middle East Respiratory Syndrome (MERS) in 2012, since the start of this millennium. In addition to these outbreaks, the latest infectious disease to result in an outbreak is the SARS-CoV-2 infection. A viral infection recognized as a respiratory illness at the time of emergence, SARS-CoV-2 has wreaked havoc worldwide because of its long-lasting implications like heart failure, sepsis, organ failure, etc., and its significant impact on the global economy. Besides the acute illness, it also leads to symptoms months later which is called long COVID or post-COVID-19 condition. Due to its ever-increasing prevalence, it has been a significant challenge to treat the affected individuals and manage the complications as well. Myocarditis, a long-term complication of coronavirus disease 2019 (COVID-19) is an inflammatory condition involving the myocardium of the heart, which could even be fatal in the long term in cases of progression to ventricular dysfunction and heart failure. Thus, it is imperative to diagnose early and treat this condition in the affected individuals. At present, there are numerous studies which are in progress, investigating patients with COVID-19-related myocarditis and the treatment strategies. This review focuses primarily on myocarditis, a life-threatening complication of COVID-19 illness, and endeavors to elucidate the pathogenesis, biomarkers, and management of long COVID myocarditis along with pipeline drugs in detail.}, }
@article {pmid38510743, year = {2024}, author = {Gonjilashvili, A and Tatishvili, S}, title = {The interplay between Sars-Cov-2 infection related cardiovascular diseases and depression. Common mechanisms, shared symptoms.}, journal = {American heart journal plus : cardiology research and practice}, volume = {38}, number = {}, pages = {100364}, pmid = {38510743}, issn = {2666-6022}, abstract = {In 2020 the World Health organization announced a pandemic due to the outbreak of the Coronavirus disease 19. Pneumonia was the most common manifestation of the Sars-Cov-2 infection, however, clinical papers describe Sars-Cov-2 associated cardiovascular pathologies, such as ACS, myopericarditis, cardiomyopathies, dysrhythmias, as leading causes of increased morbidity and mortality. The short and long term prognosis of Sars-Cov-2-related cardiovascular diseases was defined not only by the disease severity itself but also by associated conditions and complications, among which mental health issues (stress, depression and anxiety) have a negative impact. The interplay between Sars-Cov-2 infection, cardiovascular disease and depression may be explained by hyperinflammation, unhealthy lifestyle and inter-organ communication, mediated by extracellular vesicles (EV) and non-coding MicroRNA (miRNA). The long Covid syndrome is characterized with orthostatic hypotension, impaired cardiac and cerebral perfusion, postural orthostatic tachycardia syndrome (POTS), syncope, chest pain, dyspnea, palpitation, chronic fatigue syndrome, 'brain fog', memory, cognitive and sleep difficulties, depression and anxiety. From a clinical point of view these symptoms may be considered as common symptoms representing not only a cardiac but also a neurological/psychiatric problem. Consequently assessment of these symptoms are of paramount importance. Due to their complexity, management of these patients requires multidisciplinary care.}, }
@article {pmid38518038, year = {2024}, author = {Kavanagh, KT and Cormier, LE and Pontus, C and Bergman, A and Webley, W}, title = {Long COVID's Impact on Patients, Workers, &amp; Society: A review.}, journal = {Medicine}, volume = {103}, number = {12}, pages = {e37502}, pmid = {38518038}, issn = {1536-5964}, mesh = {Adult ; Child ; Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Disease Outbreaks ; }, abstract = {The incidence of long COVID in adult survivors of an acute SARS-CoV-2 infection is approximately 11%. Of those afflicted, 26% have difficulty with day-to-day activities. The majority of long COIVD cases occur after mild or asymptomatic acute infection. Children can spread SARS-CoV-2 infections and can also develop long-term neurological, endocrine (type I diabetes), and immunological sequelae. Immunological hypofunction is exemplified by the recent large outbreaks of respiratory syncytial virus and streptococcal infections. Neurological manifestations are associated with anatomical brain damage demonstrated on brain scans and autopsy studies. The prefrontal cortex is particularly susceptible. Common symptoms include brain fog, memory loss, executive dysfunction, and personality changes. The impact on society has been profound. Fewer than half of previously employed adults who develop long COVID are working full-time, and 42% of patients reported food insecurity and 20% reported difficulties paying rent. Vaccination not only helps prevent severe COVID-19, but numerous studies have found beneficial effects in preventing and mitigating long COVID. There is also evidence that vaccination after an acute infection can lessen the symptoms of long COVID. Physical and occupational therapy can also help patients regain function, but the approach must be "low and slow." Too much physical or mental activity can result in post-exertional malaise and set back the recovery process by days or weeks. The complexity of long COVID presentations coupled with rampant organized disinformation, have caused significant segments of the public to ignore sound public health advice. Further research is needed regarding treatment and effective public communication.}, }
@article {pmid38518814, year = {2024}, author = {McClelland, AC and Benitez, SJ and Burns, J}, title = {COVID-19 Neuroimaging Update: Pathophysiology, Acute Findings, and Post-Acute Developments.}, journal = {Seminars in ultrasound, CT, and MR}, volume = {45}, number = {4}, pages = {318-331}, doi = {10.1053/j.sult.2024.03.003}, pmid = {38518814}, issn = {1558-5034}, mesh = {Humans ; *COVID-19/diagnostic imaging/physiopathology ; *Neuroimaging/methods ; *SARS-CoV-2 ; Brain/diagnostic imaging/physiopathology ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19 has prominent effects on the nervous system with important manifestations on neuroimaging. In this review, we discuss the neuroimaging appearance of acute COVID-19 that became evident during the early stages of the pandemic. We highlight the underlying pathophysiology mediating nervous system effects and neuroimaging appearances including systemic inflammatory response such as cytokine storm, coagulopathy, and para/post-infections immune mediated phenomena. We also discuss the nervous system manifestations of COVID-19 and the role of imaging as the pandemic has evolved over time, including related to the development of vaccines and the emergence of post-acute sequalae such as long COVID.}, }
@article {pmid38520374, year = {2024}, author = {Garmoe, W and Rao, K and Gorter, B and Kantor, R}, title = {Neurocognitive Impairment in Post-COVID-19 Condition in Adults: Narrative Review of the Current Literature.}, journal = {Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists}, volume = {39}, number = {3}, pages = {276-289}, doi = {10.1093/arclin/acae017}, pmid = {38520374}, issn = {1873-5843}, mesh = {Adult ; Humans ; *Cognitive Dysfunction/etiology ; COVID-19/complications ; SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome/physiopathology ; Neuropsychology ; }, abstract = {The severe acute respiratory syndrome coronavirus 2 virus has, up to the time of this article, resulted in >770 million cases of COVID-19 illness worldwide, and approximately 7 million deaths, including >1.1 million in the United States. Although defined as a respiratory virus, early in the pandemic, it became apparent that considerable numbers of people recovering from COVID-19 illness experienced persistence or new onset of multi-system health problems, including neurologic and cognitive and behavioral health concerns. Persistent multi-system health problems are defined as Post-COVID-19 Condition (PCC), Post-Acute Sequelae of COVID-19, or Long COVID. A significant number of those with PCC report cognitive problems. This paper reviews the current state of scientific knowledge on persisting cognitive symptoms in adults following COVID-19 illness. A brief history is provided of the emergence of concerns about persisting cognitive problems following COVID-19 illness and the definition of PCC. Methodologic factors that complicate clear understanding of PCC are reviewed. The review then examines research on patterns of cognitive impairment that have been found, factors that may contribute to increased risk, behavioral health variables, and interventions being used to ameliorate persisting symptoms. Finally, recommendations are made about ways neuropsychologists can improve the quality of existing research.}, }
@article {pmid38527781, year = {2024}, author = {Seo, JW and Kim, SE and Kim, Y and Kim, EJ and Kim, T and Kim, T and Lee, SH and Lee, E and Lee, J and Seo, YB and Jeong, YH and Jung, YH and Choi, YJ and Song, JY}, title = {Updated Clinical Practice Guidelines for the Diagnosis and Management of Long COVID.}, journal = {Infection &amp; chemotherapy}, volume = {56}, number = {1}, pages = {122-157}, pmid = {38527781}, issn = {2093-2340}, support = {HD22C2045//Korea Health Industry Development Institute/Republic of Korea ; }, abstract = {"Long COVID" is a term used to describe a condition when the symptoms and signs associated with coronavirus disease 2019 (COVID-19) persist for more than three months among patients infected with COVID-19; this condition has been reported globally and poses a serious public health issue. Long COVID can manifest in various forms, highlighting the need for appropriate evaluation and management by experts from various fields. However, due to the lack of clear clinical definitions, knowledge of pathophysiology, diagnostic methods, and treatment protocols, it is necessary to develop the best standard clinical guidelines based on the scientific evidence reported to date. We developed this clinical guideline for diagnosing and treating long COVID by analyzing the latest research data collected from the start of the COVID-19 pandemic until June 2023, along with the consensus of expert opinions. This guideline provides recommendations for diagnosis and treatment that can be applied in clinical practice, based on a total of 32 key questions related to patients with long COVID. The evaluation of patients with long COVID should be comprehensive, including medical history, physical examination, blood tests, imaging studies, and functional tests. To reduce the risk of developing long COVID, vaccination and antiviral treatment during the acute phase are recommended. This guideline will be revised when there is a reasonable need for updates based on the availability of new knowledge on the diagnosis and treatment of long COVID.}, }
@article {pmid38534740, year = {2024}, author = {Kemerley, A and Gupta, A and Thirunavukkarasu, M and Maloney, M and Burgwardt, S and Maulik, N}, title = {COVID-19 Associated Cardiovascular Disease-Risks, Prevention and Management: Heart at Risk Due to COVID-19.}, journal = {Current issues in molecular biology}, volume = {46}, number = {3}, pages = {1904-1920}, pmid = {38534740}, issn = {1467-3045}, abstract = {The SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) virus and the resulting COVID-19 pandemic have had devastating and lasting impact on the global population. Although the main target of the disease is the respiratory tract, clinical outcomes, and research have also shown significant effects of infection on other organ systems. Of interest in this review is the effect of the virus on the cardiovascular system. Complications, including hyperinflammatory syndrome, myocarditis, and cardiac failure, have been documented in the context of COVID-19 infection. These complications ultimately contribute to worse patient outcomes, especially in patients with pre-existing conditions such as hypertension, diabetes, or cardiovascular disease (CVD). Importantly and interestingly, reports have demonstrated that COVID-19 also causes myocardial injury in adults without pre-existing conditions and contributes to systemic complications in pediatric populations, such as the development of multisystem inflammatory syndrome in children (MIS-C). Although there is still a debate over the exact mechanisms by which such complications arise, understanding the potential paths by which the virus can influence the cardiovascular system to create an inflammatory environment may clarify how SARS-CoV-2 interacts with human physiology. In addition to describing the mechanisms of disease propagation and patient presentation, this review discusses the diagnostic findings and treatment strategies and the evolution of management for patients presenting with cardiovascular complications, focusing on disease treatment and prevention.}, }
@article {pmid38535041, year = {2024}, author = {Babar, M and Jamil, H and Mehta, N and Moutwakil, A and Duong, TQ}, title = {Short- and Long-Term Chest-CT Findings after Recovery from COVID-19: A Systematic Review and Meta-Analysis.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {6}, pages = {}, pmid = {38535041}, issn = {2075-4418}, abstract = {While ground-glass opacity, consolidation, and fibrosis in the lungs are some of the hallmarks of acute SAR-CoV-2 infection, it remains unclear whether these pulmonary radiological findings would resolve after acute symptoms have subsided. We conducted a systematic review and meta-analysis to evaluate chest computed tomography (CT) abnormalities stratified by COVID-19 disease severity and multiple timepoints post-infection. PubMed/MEDLINE was searched for relevant articles until 23 May 2023. Studies with COVID-19-recovered patients and follow-up chest CT at least 12 months post-infection were included. CT findings were evaluated at short-term (1-6 months) and long-term (12-24 months) follow-ups and by disease severity (severe and non-severe). A generalized linear mixed-effects model with random effects was used to estimate event rates for CT findings. A total of 2517 studies were identified, of which 43 met the inclusion (N = 8858 patients). Fibrotic-like changes had the highest event rate at short-term (0.44 [0.3-0.59]) and long-term (0.38 [0.23-0.56]) follow-ups. A meta-regression showed that over time the event rates decreased for any abnormality (β = -0.137, p = 0.002), ground-glass opacities (β = -0.169, p < 0.001), increased for honeycombing (β = 0.075, p = 0.03), and did not change for fibrotic-like changes, bronchiectasis, reticulation, and interlobular septal thickening (p > 0.05 for all). The severe subgroup had significantly higher rates of any abnormalities (p < 0.001), bronchiectasis (p = 0.02), fibrotic-like changes (p = 0.03), and reticulation (p < 0.001) at long-term follow-ups when compared to the non-severe subgroup. In conclusion, significant CT abnormalities remained up to 2 years post-COVID-19, especially in patients with severe disease. Long-lasting pulmonary abnormalities post-SARS-CoV-2 infection signal a future public health concern, necessitating extended monitoring, rehabilitation, survivor support, vaccination, and ongoing research for targeted therapies.}, }
@article {pmid38535608, year = {2024}, author = {Agouridis, AP and Mastori-Kourmpani, C and Antoniou, P and Konstantinou, P and Rizos, EC and Tsioutis, C}, title = {Beau's Lines and COVID-19; A Systematic Review on Their Association.}, journal = {Pathogens (Basel, Switzerland)}, volume = {13}, number = {3}, pages = {}, pmid = {38535608}, issn = {2076-0817}, mesh = {Humans ; *COVID-19/epidemiology/immunology/prevention &amp; control ; *SARS-CoV-2/immunology ; *Nail Diseases/virology/epidemiology ; COVID-19 Vaccines/administration &amp; dosage ; Nails/virology ; Vaccination ; Male ; Female ; }, abstract = {BACKGROUND: Beau's lines are transverse grooves in the nail plate that result from transient interruption of the growth of the proximal nail matrix after severe disease. The aim of this study is to systematically report all evidence on the association of Beau's lines with COVID-19 infection or vaccination against COVID-19.<br><br>METHODS: PubMed and Scopus databases were searched up to January 2024 for articles reporting Beau's lines associated with COVID-19 infection or vaccination for COVID-19.<br><br>PROSPERO ID: CRD42024496830.<br><br>RESULTS: PubMed search identified 299 records while Scopus search identified 18 records. After screening the bibliography, nine studies including 35 cases were included in our systematic review. The studies were reported from different areas around the world. Included studies documented Beau's lines following COVID-19 vaccination (two studies) or after COVID-19 infection (seven studies). High variability was recorded in onset and resolution times among included cases, averaging 3 months and 6 months after COVID-19 infection, respectively. In the two studies reporting Beau's lines after vaccination, onset was at 7 days and 6 weeks and resolution occurred after 8 and 17 weeks, respectively.<br><br>CONCLUSIONS: To the best of our knowledge, this is the first systematic review reporting the association of Beau's lines with COVID-19 infection and vaccination. Severe immune response can result in the formation of these nail disorders. Of importance, Beau's lines represent a potential indicator of prior severe COVID-19 infection or vaccination for COVID-19, as well as a sign of long COVID-19 syndrome.}, }
@article {pmid38537538, year = {2024}, author = {Bhattacharya, M and Chatterjee, S and Saxena, S and Nandi, SS and Lee, SS and Chakraborty, C}, title = {Current landscape of long COVID clinical trials.}, journal = {International immunopharmacology}, volume = {132}, number = {}, pages = {111930}, doi = {10.1016/j.intimp.2024.111930}, pmid = {38537538}, issn = {1878-1705}, mesh = {Humans ; *Clinical Trials as Topic ; *COVID-19/therapy ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome ; COVID-19 Drug Treatment ; }, abstract = {Long COVID was reported as a multi-systemic condition after the infection of SARS-CoV-2, and more than 65 million people are suffering from this disease. It has been noted that around 10% of severe SARS-CoV-2 infected individuals are suffering from the enduring effects of long COVID. The symptoms of long COVID have also been noted in several mild or asymptomatic SARS-CoV-2 infected individuals. While limited reports on clinical trials investigating new therapeutics for long COVID exist, there is an abundance of scattered information available regarding these trials. This review explores the extensive literature search, and complete clinical trial database search to map the current status of long COVID clinical trials worldwide. The study listed about 110 long COVID clinical trials. In addition to conducting extensive long COVID clinical trials, we have comprehensively presented an overview of the condition, its symptoms, notable manifestations, associated clinical trials, the unique challenges it poses, and our recommendations for addressing long COVID.}, }
@article {pmid38540252, year = {2024}, author = {Lazar, M and Sandulescu, M and Barbu, EC and Chitu-Tisu, CE and Andreescu, DI and Anton, AN and Erculescu, TM and Petre, AM and Duca, GT and Simion, V and Padiu, IF and Pacurar, CG and Rosca, R and Simian, TM and Oprea, CA and Ion, DA}, title = {The Role of Cytokines and Molecular Pathways in Lung Fibrosis Following SARS-CoV-2 Infection: A Physiopathologic (Re)view.}, journal = {Biomedicines}, volume = {12}, number = {3}, pages = {}, pmid = {38540252}, issn = {2227-9059}, abstract = {SARS-CoV-2 infection is a significant health concern that needs to be addressed not only during the initial phase of infection but also after hospitalization. This is the consequence of the various pathologies associated with long COVID-19, which are still being studied and researched. Lung fibrosis is an important complication after COVID-19, found in up to 71% of patients after discharge. Our research is based on scientific articles indexed in PubMed; in the selection process, we used the following keywords: "lung fibrosis", "fibrosis mediators", "fibrosis predictors", "COVID-19", "SARS-CoV-2 infection", and "long COVID-19". In this narrative review, we aimed to discuss the current understanding of the mechanisms of initiation and progression of post-COVID-19 lung fibrosis (PC-19-LF) and the risk factors for its occurrence. The pathogenesis of pulmonary fibrosis involves various mediators such as TGF-β, legumain, osteopontin, IL-4, IL-6, IL-13, IL-17, TNF-α, Gal-1, Gal-3, PDGF, and FGFR-1. The key cellular effectors involved in COVID-19 lung fibrosis are macrophages, epithelial alveolar cells, neutrophils, and fibroblasts. The main fibrosis pathways in SARS-CoV-2 infection include hypoxemia-induced fibrosis, macrophage-induced fibrosis, and viral-fibroblast interaction-induced fibrosis.}, }
@article {pmid38541324, year = {2024}, author = {Sweis, JJG and Alnaimat, F and Esparza, V and Prasad, S and Azam, A and Modi, Z and Al-Awqati, M and Jetanalin, P and Sweis, NJ and Ascoli, C and Novak, RM and Rubinstein, I and Papanikolaou, IC and Sweiss, N}, title = {From Acute Infection to Prolonged Health Consequences: Understanding Health Disparities and Economic Implications in Long COVID Worldwide.}, journal = {International journal of environmental research and public health}, volume = {21}, number = {3}, pages = {}, pmid = {38541324}, issn = {1660-4601}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Pandemics ; SARS-CoV-2 ; Health Inequities ; }, abstract = {The COVID-19 pandemic has resulted in a growing number of patients experiencing persistent symptoms and physiological changes after recovering from acute SARS-CoV-2 infection, known as Long COVID. Long COVID is characterized by recurring symptoms and inflammation across multiple organ systems. Diagnosis can be challenging, influenced by factors like demographics, comorbidities, and immune responses. Long COVID impacts various organ systems and can have neuropsychological effects. Health disparities, particularly related to race, contribute to a higher burden of infection and ongoing symptoms in minority populations. Managing Long COVID entails addressing a spectrum of symptoms that encompass physical, cognitive, and psychological aspects. The recovery period for patients with Long COVID can vary significantly, influenced by factors like the severity of the disease, hospitalization, comorbidities, and age. Currently, there are no universally effective treatments, although certain interventions show promise, necessitating further research. Self-management and rehabilitation programs can provide relief, but more research is needed to establish their effectiveness. Preventive measures such as vaccination and the use of antiviral medications and metformin. It is imperative to conduct further research to develop evidence-based guidelines and gain a better understanding of the long-term implications of COVID-19. Long COVID could have substantial economic impact on the labor market, productivity, healthcare expenditures, and overall economic growth. To address the challenges patients with long-term complications face, there is a focus on strategies like promoting telework and flexible work arrangements to accommodate diverse symptoms, particularly chronic fatigue and other Long COVID effects. In conclusion, this review emphasizes the multifaceted complexity of Long COVID and the ongoing need to address its potential long-term health and economic impacts.}, }
@article {pmid38542177, year = {2024}, author = {Ricardi, C and Barachini, S and Consoli, G and Marazziti, D and Polini, B and Chiellini, G}, title = {Beta-Caryophyllene, a Cannabinoid Receptor Type 2 Selective Agonist, in Emotional and Cognitive Disorders.}, journal = {International journal of molecular sciences}, volume = {25}, number = {6}, pages = {}, pmid = {38542177}, issn = {1422-0067}, mesh = {Humans ; Adolescent ; *Cannabinoid Receptor Agonists/pharmacology/therapeutic use ; Pandemics ; Post-Acute COVID-19 Syndrome ; *Cognitive Dysfunction ; Receptors, Cannabinoid ; Anti-Inflammatory Agents/pharmacology/therapeutic use ; Receptor, Cannabinoid, CB2 ; *Polycyclic Sesquiterpenes ; }, abstract = {Mental disorders account for one of the most prevalent categories of the burden of disease worldwide, with depression expected to be the largest contributor by 2030, closely followed by anxiety. The COVID-19 pandemic possibly exacerbated these challenges, especially amongst adolescents, who experienced isolation, disrupted routines, and limited healthcare access. Notably, the pandemic has been associated with long-term neurological effects known as "long-COVID", characterized by both cognitive and psychopathological symptoms. In general, psychiatric disorders, including those related to long-COVID, are supposed to be due to widespread inflammation leading to neuroinflammation. Recently, the endocannabinoid system (ECS) emerged as a potential target for addressing depression and anxiety pathophysiology. Specifically, natural or synthetic cannabinoids, able to selectively interact with cannabinoid type-2 receptor (CB2R), recently revealed new therapeutic potential in neuropsychiatric disorders with limited or absent psychotropic activity. Among the most promising natural CB2R ligands, the bicyclic sesquiterpene β-caryophyllene (BCP) has emerged as an excellent anti-inflammatory and antioxidant therapeutic agent. This review underscores BCP's immunomodulatory and anti-inflammatory properties, highlighting its therapeutic potential for the management of depression and anxiety.}, }
@article {pmid38543736, year = {2024}, author = {Giovanetti, M and Pannella, G and Altomare, A and Rocchi, G and Guarino, M and Ciccozzi, M and Riva, E and Gherardi, G}, title = {Exploring the Interplay between COVID-19 and Gut Health: The Potential Role of Prebiotics and Probiotics in Immune Support.}, journal = {Viruses}, volume = {16}, number = {3}, pages = {}, pmid = {38543736}, issn = {1999-4915}, mesh = {Humans ; Prebiotics ; *COVID-19/therapy ; Post-Acute COVID-19 Syndrome ; Pandemics ; SARS-CoV-2 ; *Probiotics/therapeutic use ; Inflammation ; }, abstract = {The COVID-19 pandemic has profoundly impacted global health, leading to extensive research focused on developing strategies to enhance outbreak response and mitigate the disease's severity. In the aftermath of the pandemic, attention has shifted towards understanding and addressing long-term health implications, particularly in individuals experiencing persistent symptoms, known as long COVID. Research into potential interventions to alleviate long COVID symptoms has intensified, with a focus on strategies to support immune function and mitigate inflammation. One area of interest is the gut microbiota, which plays a crucial role in regulating immune responses and maintaining overall health. Prebiotics and probiotics, known for their ability to modulate the gut microbiota, have emerged as potential therapeutic agents in bolstering immune function and reducing inflammation. This review delves into the intricate relationship between long COVID, the gut microbiota, and immune function, with a specific focus on the role of prebiotics and probiotics. We examine the immune response to long COVID, emphasizing the importance of inflammation and immune regulation in the persistence of symptoms. The potential of probiotics in modulating immune responses, including their mechanisms in combating viral infections such as COVID-19, is discussed in detail. Clinical evidence supporting the use of probiotics in managing long COVID symptoms is summarized, highlighting their role as adjunctive therapy in addressing various aspects of SARS-CoV-2 infection and its aftermath.}, }
@article {pmid38549864, year = {2024}, author = {Bocquet-Garçon, A}, title = {Impact of the SARS-CoV-2 Spike Protein on the Innate Immune System: A Review.}, journal = {Cureus}, volume = {16}, number = {3}, pages = {e57008}, pmid = {38549864}, issn = {2168-8184}, abstract = {The Spike protein enables the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by binding to multiple receptors, including the angiotensin-converting enzyme 2 (ACE2). Scientific studies also indicate that Spike is involved in severe forms of coronavirus disease 2019 (COVID-19), "long-haul COVID diseases" - also known as "long COVID syndromes" or "post-acute sequelae of SARS-CoV-2 infection" (PACS) - or, recently, in adverse reactions to lipid nanoparticle-messenger ribonucleic acid (mRNA) vaccines or other anti-COVID19 products. Numerous mutations, notably within the subunit 1 of Spike (S1), prevent neutralization by antibodies, but more generally, the virus has developed numerous strategies to avoid immune system surveillance, especially type-I interferons (IFN-I). Meanwhile, a "hyperinflammatory" state, named "cytokine storm," sets in. However, what role does the Spike protein play in the immune escape mechanisms? Can its inflammatory activities affect IFN-I? Does Spike block IFN-I or hijack them for the virus benefits? What are the other potential consequences? This article was written to provide an up-to-date and more general overview of the impact of the Spike protein on the innate immune system and its effectors at the molecular level.}, }
@article {pmid38555403, year = {2024}, author = {Naidu, AS and Wang, CK and Rao, P and Mancini, F and Clemens, RA and Wirakartakusumah, A and Chiu, HF and Yen, CH and Porretta, S and Mathai, I and Naidu, SAG}, title = {Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID.}, journal = {NPJ science of food}, volume = {8}, number = {1}, pages = {19}, pmid = {38555403}, issn = {2396-8370}, abstract = {SARS-CoV-2, the etiological agent of COVID-19, is devoid of any metabolic capacity; therefore, it is critical for the viral pathogen to hijack host cellular metabolic machinery for its replication and propagation. This single-stranded RNA virus with a 29.9 kb genome encodes 14 open reading frames (ORFs) and initiates a plethora of virus-host protein-protein interactions in the human body. These extensive viral protein interactions with host-specific cellular targets could trigger severe human metabolic reprogramming/dysregulation (HMRD), a rewiring of sugar-, amino acid-, lipid-, and nucleotide-metabolism(s), as well as altered or impaired bioenergetics, immune dysfunction, and redox imbalance in the body. In the infectious process, the viral pathogen hijacks two major human receptors, angiotensin-converting enzyme (ACE)-2 and/or neuropilin (NRP)-1, for initial adhesion to cell surface; then utilizes two major host proteases, TMPRSS2 and/or furin, to gain cellular entry; and finally employs an endosomal enzyme, cathepsin L (CTSL) for fusogenic release of its viral genome. The virus-induced HMRD results in 5 possible infectious outcomes: asymptomatic, mild, moderate, severe to fatal episodes; while the symptomatic acute COVID-19 condition could manifest into 3 clinical phases: (i) hypoxia and hypoxemia (Warburg effect), (ii) hyperferritinemia ('cytokine storm'), and (iii) thrombocytosis (coagulopathy). The mean incubation period for COVID-19 onset was estimated to be 5.1 days, and most cases develop symptoms after 14 days. The mean viral clearance times were 24, 30, and 39 days for acute, severe, and ICU-admitted COVID-19 patients, respectively. However, about 25-70% of virus-free COVID-19 survivors continue to sustain virus-induced HMRD and exhibit a wide range of symptoms that are persistent, exacerbated, or new 'onset' clinical incidents, collectively termed as post-acute sequelae of COVID-19 (PASC) or long COVID. PASC patients experience several debilitating clinical condition(s) with >200 different and overlapping symptoms that may last for weeks to months. Chronic PASC is a cumulative outcome of at least 10 different HMRD-related pathophysiological mechanisms involving both virus-derived virulence factors and a multitude of innate host responses. Based on HMRD and virus-free clinical impairments of different human organs/systems, PASC patients can be categorized into 4 different clusters or sub-phenotypes: sub-phenotype-1 (33.8%) with cardiac and renal manifestations; sub-phenotype-2 (32.8%) with respiratory, sleep and anxiety disorders; sub-phenotype-3 (23.4%) with skeleto-muscular and nervous disorders; and sub-phenotype-4 (10.1%) with digestive and pulmonary dysfunctions. This narrative review elucidates the effects of viral hijack on host cellular machinery during SARS-CoV-2 infection, ensuing detrimental effect(s) of virus-induced HMRD on human metabolism, consequential symptomatic clinical implications, and damage to multiple organ systems; as well as chronic pathophysiological sequelae in virus-free PASC patients. We have also provided a few evidence-based, human randomized controlled trial (RCT)-tested, precision nutrients to reset HMRD for health recovery of PASC patients.}, }
@article {pmid38557961, year = {2024}, author = {Namjoshi, SS and Mast, A and Patel, AS}, title = {Review of long COVID in pediatric gastroenterology, hepatology, &amp; nutrition.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {78}, number = {6}, pages = {1210-1212}, doi = {10.1002/jpn3.12199}, pmid = {38557961}, issn = {1536-4801}, support = {//None/ ; }, mesh = {Humans ; *COVID-19/prevention &amp; control ; *Gastroenterology/organization &amp; administration/methods ; Child ; *Pediatrics/methods/organization &amp; administration ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, }
@article {pmid38560644, year = {2024}, author = {Chen, DY and Huang, PI and Tang, KT}, title = {Characteristics of long COVID in patients with autoimmune rheumatic diseases: a systematic review and meta-analysis.}, journal = {Rheumatology advances in practice}, volume = {8}, number = {2}, pages = {rkae027}, pmid = {38560644}, issn = {2514-1775}, abstract = {OBJECTIVES: Numerous cases of long coronavirus disease (long COVID) have been reported in patients with autoimmune rheumatic diseases (ARDs). Despite the reviews on clinical manifestations of long COVID in the general population, systematic reviews on ARD patients are scarce. Herein, we conducted a systematic review and meta-analysis on the prevalence and characteristics of long COVID in ARD patients.<br><br>METHODS: We searched the literature in PubMed and Embase as of 27 December 2022. Cohort, cross-sectional and case-control studies relevant to long COVID in ARD patients were collected. Stratification based on the severity of COVID infection and subtypes of rheumatic diseases [systemic autoimmune rheumatic disease (SARD) vs non-autoimmune rheumatic disease (NARD)] was also undertaken. A random-effects model was used in the meta-analysis.<br><br>RESULTS: A total of 15 relevant studies were identified from the literature. The prevalence of long COVID was 56% (95% CI 34, 76) in 2995 patients. Hospitalized COVID patients had a higher proportion of long COVID than non-hospitalized patients. The prevalence of long COVID was similar between SARD and NARD patients. In terms of symptoms, fatigue, arthralgia and pain were commonly reported in long COVID patients with ARDs.<br><br>CONCLUSION: The characteristics of long COVID in ARD patients are generally similar to those in the general population despite a higher prevalence and a higher proportion of arthralgia and pain.}, }
@article {pmid38561114, year = {2024}, author = {Faghy, PMA and Ashton, DRE and McNelis, MR and Arena, R and Duncan, DR}, title = {Attenuating post-exertional malaise in Myalgic encephalomyelitis/chronic fatigue syndrome and long-COVID: Is blood lactate monitoring the answer?.}, journal = {Current problems in cardiology}, volume = {49}, number = {6}, pages = {102554}, doi = {10.1016/j.cpcardiol.2024.102554}, pmid = {38561114}, issn = {1535-6280}, mesh = {Humans ; *Fatigue Syndrome, Chronic/blood/diagnosis ; *COVID-19/complications ; *Lactic Acid/blood ; SARS-CoV-2 ; Biomarkers/blood ; }, }
@article {pmid38561236, year = {2024}, author = {Nlandu, Y and Tannor, EK and Bafemika, T and Makulo, JR}, title = {Kidney damage associated with COVID-19: from the acute to the chronic phase.}, journal = {Renal failure}, volume = {46}, number = {1}, pages = {2316885}, pmid = {38561236}, issn = {1525-6049}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Kidney/pathology ; *Acute Kidney Injury/etiology/pathology ; Inflammation/pathology ; }, abstract = {Severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) infection is well established as a systemic disease including kidney damage. The entry point into the renal cell remains the angiotensin-converting enzyme 2 (ACE-2) receptor and the spectrum of renal lesions is broad, with a clear predominance of structural and functional tubular lesions. The most common form of glomerular injury is collapsing glomerulopathy (CG), which is strongly associated with apolipoprotein L1(APOL-1) risk variants. These acute lesions, which are secondary to the direct or indirect effects of SARS-CoV-2, can progress to chronicity and are specific to long COVID-19 in the absence of any other cause. Residual inflammation associated with SARS-CoV-2 infection, in addition to acute kidney injury (AKI) as a transitional state with or without severe histological lesions, may be responsible for greater kidney function decline in mild-to-moderate COVID-19. This review discusses the evidence for renal histological markers of chronicity in COVID-19 patients and triggers of low-grade inflammation that may explain the decline in kidney function in the post-COVID-19 period.}, }
@article {pmid38568321, year = {2024}, author = {Jiang, Y and Sadun, RE}, title = {What the SARS-CoV-2 Pandemic Has Taught Us About Immunosuppression, Vaccinations, and Immune Dysregulation: The Rheumatology Experience.}, journal = {Current allergy and asthma reports}, volume = {24}, number = {4}, pages = {221-232}, pmid = {38568321}, issn = {1534-6315}, support = {T32 HD094671/HD/NICHD NIH HHS/United States ; }, mesh = {Child ; Humans ; United States ; SARS-CoV-2 ; *COVID-19/epidemiology/prevention &amp; control/*complications ; *Rheumatology ; Pandemics/prevention &amp; control ; COVID-19 Vaccines/therapeutic use ; Post-Acute COVID-19 Syndrome ; Immunosuppression Therapy ; Vaccination ; *Systemic Inflammatory Response Syndrome ; }, abstract = {PURPOSE OF REVIEW: This review reflects on the impact of the COVID-19 pandemic on the field of rheumatology, emphasizing resulting insights related to the risks of viral infections in immunosuppressed patients, vaccine immunogenicity in immunocompromised patients, and immune dysregulation in the setting of viral infection.<br><br>RECENT FINDINGS: During the pandemic, global patient registries provided real-time insights into the risk factors associated with severe COVID-19 outcomes in rheumatology patients. Updated evidence-based recommendations from the American College of Rheumatology (ACR) guided rheumatology practice&#xa0;during a time of considerable&#xa0;uncertainty. Studies on COVID-19 vaccines in immunocompromised populations enhanced our&#xa0;understanding of specific immunosuppressive therapies on vaccine efficacy. The immune dysregulation seen in severe COVID-19 underscored a role for immunomodulation in this and other severe infections. Furthermore, novel post-infectious conditions, namely multisystem inflammatory syndrome in children (MIS-C) and Long COVID, reshaped our understanding of post-viral syndromes and revealed novel pathological mechanisms. Lessons from the COVID-19 pandemic demonstrate the power of collaborative research. The scientific revelations from this dreadful time will, nonetheless, benefit the practice of rheumatology for years to come.}, }
@article {pmid38576710, year = {2024}, author = {Peng, Z and Zheng, Y and Yang, Z and Zhang, H and Li, Z and Xu, M and Cui, S and Lin, R}, title = {Acupressure: a possible therapeutic strategy for anxiety related to COVID-19: a meta-analysis of randomized controlled trials.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1341072}, pmid = {38576710}, issn = {2296-858X}, abstract = {BACKGROUND: From the end of 2019 to December 2023, the world grappled with the COVID-19 pandemic. The scope and ultimate repercussions of the pandemic on global health and well-being remained uncertain, ushering in a wave of fear, anxiety, and worry. This resulted in many individuals succumbing to fear and despair. Acupoint massage emerged as a safe and effective alternative therapy for anxiety relief. However, its efficacy was yet to be extensively backed by evidence-based medicine. This study aimed to enhance the clinical effectiveness of acupoint massage and extend its benefits to a wider population. It undertakes a systematic review of the existing randomized controlled trials (RCTs) assessing the impact of acupoint massage on anxiety treatment, discussing its potential benefits and implications. This research aims to furnish robust evidence supporting anxiety treatment strategies for patients afflicted with COVID-19 disease and spark new approaches to anxiety management.<br><br>OBJECTIVES: This study evaluates the evidence derived from randomised controlled trials (RCTs), quantifies the impact of acupressure on anxiety manifestations within the general population, and proposes viable supplementary intervention strategies for managing COVID-19 related anxiety.<br><br>MATERIALS AND METHODS: This review included RCTs published between February 2014 and July 2023, that compared the effects of acupressure with sham control in alleviating anxiety symptomatology as the outcome measure. The studies were sourced from the multiple databases, including CINAHL, EBM Reviews, Embase, Medline, PsycINFO, Scopus and Web of Science. A meta-analysis was performed on the eligible studies, and an overall effect size was computed specifically for the anxiety outcome. The Cochrane Collaboration Bias Risk Assessment Tool (RevMan V5.4) was employed to assess bias risk, data integration, meta-analysis, and subgroup analysis. The mean difference, standard mean deviation, and binary data were used to represent continuous outcomes.<br><br>RESULTS: Of 1,110 studies of potential relevance, 39 met the criteria for inclusion in the meta-analysis. The majority of the studies reported a positive effect of acupressure in assuaging anticipatory anxiety about treatment. Eighteen studies were evaluated using the STAI scale. The acupressure procedures were thoroughly documented, and studies exhibited a low risk of bias. The cumulative results of the 18 trials showcased a more substantial reduction in anxiety in the acupressure group compared to controls (SMD =&#x2009;-5.39, 95% CI -5.61 to -5.17, p&#x2009;<&#x2009;0.01). A subsequent subgroup analysis, based on different interventions in the control group, demonstrated improvement in anxiety levels with sham acupressure in improving changes in anxiety levels (SMD -1.61, 95% CI: -2.34 to -0.87, p&#x2009;<&#x2009;0.0001), and blank controls (SMD -0.92, 95% CI: -2.37 to 0.53, p&#x2009;=&#x2009;0.22).<br><br>CONCLUSION: In the clinical research of traditional Chinese medicine treatment of anxiety, acupressure demonstrated effectiveness in providing instant relief from anxiety related to multiple diseases with a medium effect size. Considering the increasing incidence of anxiety caused by long COVID, the widespread application of acupressure appears feasible. However, the results were inconsistent regarding improvements on physiological indicators, calling for more stringent reporting procedures, including allocation concealment, to solidify the findings.}, }
@article {pmid38590789, year = {2024}, author = {Kikinis, Z and Castañeyra-Perdomo, A and González-Mora, JL and Rushmore, RJ and Toppa, PH and Haggerty, K and Papadimitriou, G and Rathi, Y and Kubicki, M and Kikinis, R and Heller, C and Yeterian, E and Besteher, B and Pallanti, S and Makris, N}, title = {Investigating the structural network underlying brain-immune interactions using combined histopathology and neuroimaging: a critical review for its relevance in acute and long COVID-19.}, journal = {Frontiers in psychiatry}, volume = {15}, number = {}, pages = {1337888}, pmid = {38590789}, issn = {1664-0640}, support = {K24 MH116366/MH/NIMH NIH HHS/United States ; R01 MH112748/MH/NIMH NIH HHS/United States ; R21 DA042271/DA/NIDA NIH HHS/United States ; R01 MH125860/MH/NIMH NIH HHS/United States ; R01 NS125307/NS/NINDS NIH HHS/United States ; R01 AG042512/AG/NIA NIH HHS/United States ; R01 MH111917/MH/NIMH NIH HHS/United States ; }, abstract = {Current views on immunity support the idea that immunity extends beyond defense functions and is tightly intertwined with several other fields of biology such as virology, microbiology, physiology and ecology. It is also critical for our understanding of autoimmunity and cancer, two topics of great biological relevance and for critical public health considerations such as disease prevention and treatment. Central to this review, the immune system is known to interact intimately with the nervous system and has been recently hypothesized to be involved not only in autonomic and limbic bio-behaviors but also in cognitive function. Herein we review the structural architecture of the brain network involved in immune response. Furthermore, we elaborate upon the implications of inflammatory processes affecting brain-immune interactions as reported recently in pathological conditions due to SARS-Cov-2 virus infection, namely in acute and post-acute COVID-19. Moreover, we discuss how current neuroimaging techniques combined with ad hoc clinical autopsies and histopathological analyses could critically affect the validity of clinical translation in studies of human brain-immune interactions using neuroimaging. Advances in our understanding of brain-immune interactions are expected to translate into novel therapeutic avenues in a vast array of domains including cancer, autoimmune diseases or viral infections such as in acute and post-acute or Long COVID-19.}, }
@article {pmid38596351, year = {2024}, author = {Barilaite, E and Watson, H and Hocaoglu, MB}, title = {Understanding Patient-Reported Outcome Measures Used in Adult Survivors Experiencing Long-Term Effects After COVID-19 Infection: A Rapid Review.}, journal = {Journal of patient-centered research and reviews}, volume = {11}, number = {1}, pages = {36-50}, pmid = {38596351}, issn = {2330-0698}, abstract = {PURPOSE: Patient-reported outcome measures (PROMs) are used in individuals experiencing long-term effects from COVID-19 infection, or Long COVID, to evaluate the quality of life and functional status of these individuals. However, little is known about which PROMs are being utilised and the psychometric properties of these PROMs. Our purpose was thus to explore which PROMs are used in Long COVID patients and to discuss the psychometric properties of the PROMs.<br><br>METHODS: For this rapid review, a systematic literature search was performed in the PubMed, Embase, and CINAHL databases. The found studies were screened using the PRISMA flowchart. We then performed study quality appraisal and assessed the psychometric properties of the found PROMs.<br><br>RESULTS: Per the systematic literature search and after removal of duplicates, 157 publications were identified for individual screening. After screening and eligibility assessment, 74 articles were selected for our review. In total, 74 PROMs were used and primarily comprised quality of life, fatigue, breathlessness, mental health, and smell/taste issues in COVID "long haulers." Five studies used newly developed, COVID-19-specific PROMs. We assessed the psychometric properties of the 10 most-used PROMs. The majority were found to be reliable and valid instruments. EQ-5D-5L was the most popular and highly rated PROM.<br><br>CONCLUSIONS: We assessed PROMs used in Long COVID patients and evaluated their psychometric properties. EQ-5D-5L was the most favourably rated PROM. PROMs addressing mental health issues are crucial in managing anxiety and depression in Long COVID patients. New COVID-specific PROMs assess functional status and smell/taste perception and show great utilisation potential in olfactory training at COVID smell clinics. However, many reviewed PROMs currently lack sufficient analysis of their psychometric properties. Therefore, future research needs to examine these measures.}, }
@article {pmid38605011, year = {2024}, author = {Jiao, T and Huang, Y and Sun, H and Yang, L}, title = {Research progress of post-acute sequelae after SARS-CoV-2 infection.}, journal = {Cell death &amp; disease}, volume = {15}, number = {4}, pages = {257}, pmid = {38605011}, issn = {2041-4889}, support = {81970663//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Disease Progression ; }, abstract = {SARS-CoV-2 has spread rapidly worldwide and infected hundreds of millions of people worldwide. With the increasing number of COVID-19 patients discharged from hospitals, the emergence of its associated complications, sequelae, has become a new global health crisis secondary to acute infection. For the time being, such complications and sequelae are collectively called "Post-acute sequelae after SARS-CoV-2 infection (PASC)", also referred to as "long COVID" syndrome. Similar to the acute infection period of COVID-19, there is also heterogeneity in PASC. This article reviews the various long-term complications and sequelae observed in multiple organ systems caused by COVID-19, pathophysiological mechanisms, diagnosis, and treatment of PASC, aiming to raise awareness of PASC and optimize management strategies.}, }
@article {pmid38611624, year = {2024}, author = {Makhluf, H and Madany, H and Kim, K}, title = {Long COVID: Long-Term Impact of SARS-CoV2.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {7}, pages = {}, pmid = {38611624}, issn = {2075-4418}, abstract = {Four years post-pandemic, SARS-CoV-2 continues to affect many lives across the globe. An estimated 65 million people suffer from long COVID, a term used to encapsulate the post-acute sequelae of SARS-CoV-2 infections that affect multiple organ systems. Known symptoms include chronic fatigue syndrome, brain fog, cardiovascular issues, autoimmunity, dysautonomia, and clotting due to inflammation. Herein, we review long COVID symptoms, the proposed theories behind the pathology, diagnostics, treatments, and the clinical trials underway to explore treatments for viral persistence, autonomic and cognitive dysfunctions, sleep disturbances, fatigue, and exercise intolerance.}, }
@article {pmid38612629, year = {2024}, author = {Chagas, LDS and Serfaty, CA}, title = {The Influence of Microglia on Neuroplasticity and Long-Term Cognitive Sequelae in Long COVID: Impacts on Brain Development and Beyond.}, journal = {International journal of molecular sciences}, volume = {25}, number = {7}, pages = {}, pmid = {38612629}, issn = {1422-0067}, support = {E-26/201.004/2021//Funda&#xe7;&#xe3;o Carlos Chagas Filho de Amparo &#xe0; Pesquisa do Estado do Rio de Janeiro/ ; }, mesh = {Adult ; Child ; Humans ; *Microglia ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Neuronal Plasticity ; Brain ; Disease Progression ; Cognition ; }, abstract = {Microglial cells, the immune cells of the central nervous system, are key elements regulating brain development and brain health. These cells are fully responsive to stressors, microenvironmental alterations and are actively involved in the construction of neural circuits in children and the ability to undergo full experience-dependent plasticity in adults. Since neuroinflammation is a known key element in the pathogenesis of COVID-19, one might expect the dysregulation of microglial function to severely impact both functional and structural plasticity, leading to the cognitive sequelae that appear in the pathogenesis of Long COVID. Therefore, understanding this complex scenario is mandatory for establishing the possible molecular mechanisms related to these symptoms. In the present review, we will discuss Long COVID and its association with reduced levels of BDNF, altered crosstalk between circulating immune cells and microglia, increased levels of inflammasomes, cytokines and chemokines, as well as the alterations in signaling pathways that impact neural synaptic remodeling and plasticity, such as fractalkines, the complement system, the expression of SIRPα and CD47 molecules and altered matrix remodeling. Together, these complex mechanisms may help us understand consequences of Long COVID for brain development and its association with altered brain plasticity, impacting learning disabilities, neurodevelopmental disorders, as well as cognitive decline in adults.}, }
@article {pmid38614374, year = {2024}, author = {Guarnieri, JW and Haltom, JA and Albrecht, YES and Lie, T and Olali, AZ and Widjaja, GA and Ranshing, SS and Angelin, A and Murdock, D and Wallace, DC}, title = {SARS-CoV-2 mitochondrial metabolic and epigenomic reprogramming in COVID-19.}, journal = {Pharmacological research}, volume = {204}, number = {}, pages = {107170}, doi = {10.1016/j.phrs.2024.107170}, pmid = {38614374}, issn = {1096-1186}, support = {R01 AG078814/AG/NIA NIH HHS/United States ; R01 CA259635/CA/NCI NIH HHS/United States ; W81XWH-21-1-0128//DOD/ ; }, mesh = {Humans ; *COVID-19/metabolism/genetics/virology ; *SARS-CoV-2 ; *Mitochondria/metabolism/genetics ; *Oxidative Phosphorylation ; Reactive Oxygen Species/metabolism ; Epigenesis, Genetic ; Energy Metabolism ; Epigenomics ; Animals ; }, abstract = {To determine the effects of SARS-CoV-2 infection on cellular metabolism, we conducted an exhaustive survey of the cellular metabolic pathways modulated by SARS-CoV-2 infection and confirmed their importance for SARS-CoV-2 propagation by cataloging the effects of specific pathway inhibitors. This revealed that SARS-CoV-2 strongly inhibits mitochondrial oxidative phosphorylation (OXPHOS) resulting in increased mitochondrial reactive oxygen species (mROS) production. The elevated mROS stabilizes HIF-1α which redirects carbon molecules from mitochondrial oxidation through glycolysis and the pentose phosphate pathway (PPP) to provide substrates for viral biogenesis. mROS also induces the release of mitochondrial DNA (mtDNA) which activates innate immunity. The restructuring of cellular energy metabolism is mediated in part by SARS-CoV-2 Orf8 and Orf10 whose expression restructures nuclear DNA (nDNA) and mtDNA OXPHOS gene expression. These viral proteins likely alter the epigenome, either by directly altering histone modifications or by modulating mitochondrial metabolite substrates of epigenome modification enzymes, potentially silencing OXPHOS gene expression and contributing to long-COVID.}, }
@article {pmid38619233, year = {2024}, author = {Tomasiewicz, K and Woron, J and Kobayashi, A and Krasinski, Z and Rydzewska, G and Szymanski, FM}, title = {Post-COVID-19 syndrome in everyday clinical practice: interdisciplinary expert position statement endorsed by the Polish Society of Civilization Diseases.}, journal = {Polish archives of internal medicine}, volume = {134}, number = {5}, pages = {}, doi = {10.20452/pamw.16728}, pmid = {38619233}, issn = {1897-9483}, mesh = {Humans ; *COVID-19/complications/therapy ; Poland ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {Post-COVID-19 syndrome, also known as long COVID-19 syndrome, is a complex set of symptoms that persist for weeks or months after recovery from an acute phase of COVID-19. These symptoms can affect various body systems, including the respiratory, nervous, cardiovascular, and digestive systems. The most common complaints are fatigue, shortness of breath, joint pain, taste and smell disorders, as well as problems with memory and concentration. Pathogenesis of post-COVID-19 syndrome is complicated and not fully understood, but it is likely related to an overactive immune system, disturbances in the intestinal microbiome, and cell and tissue damage caused by the virus. Incorporating a multidisciplinary approach to treating and rehabilitating patients and further research into this syndrome's underlying mechanisms and therapy are crucial for understanding and effectively treating this complex and multifaceted condition.}, }
@article {pmid38620971, year = {2021}, author = {Membrilla, JA and Caronna, E and Trigo-López, J and González-Martínez, A and Layos-Romero, A and Pozo-Rosich, P and Guerrero-Peral, &#xc1; and Gago-Veiga, AB and Andrés-López, A and Díaz de Terán, J}, title = {Persistent headache after COVID-19: Pathophysioloy, clinic and treatment.}, journal = {Neurology perspectives}, volume = {1}, number = {}, pages = {S31-S36}, pmid = {38620971}, issn = {2667-0496}, abstract = {SARS-CoV-2 is the virus responsible for the COVID-19 pandemic. The acute infection is characterised not only by respiratory symptoms, but also by multiple systemic manifestations, including neurological symptoms. Among these, headache is a frequent complaint. As the pandemic progresses and the population of patients recovering from COVID-19 grows, it is becoming apparent that the headache present in the acute stage of the infection may persist for an indeterminate period, becoming a major problem for the patient and potentially leading to disability. In this review we describe the pathophysiological and clinical aspects of persistent headache after COVID-19 based on the information currently available in the literature and the authors' clinical experience.}, }
@article {pmid38622352, year = {2024}, author = {Chan, JF and Yuan, S and Chu, H and Sridhar, S and Yuen, KY}, title = {COVID-19 drug discovery and treatment options.}, journal = {Nature reviews. Microbiology}, volume = {22}, number = {7}, pages = {391-407}, pmid = {38622352}, issn = {1740-1534}, mesh = {Humans ; *Antiviral Agents/therapeutic use/pharmacology ; *COVID-19 Drug Treatment ; *Drug Discovery ; *SARS-CoV-2/drug effects ; *COVID-19/virology ; Animals ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused substantial morbidity and mortality, and serious social and economic disruptions worldwide. Unvaccinated or incompletely vaccinated older individuals with underlying diseases are especially prone to severe disease. In patients with non-fatal disease, long COVID affecting multiple body systems may persist for months. Unlike SARS-CoV and Middle East respiratory syndrome coronavirus, which have either been mitigated or remained geographically restricted, SARS-CoV-2 has disseminated globally and is likely to continue circulating in humans with possible emergence of new variants that may render vaccines less effective. Thus, safe, effective and readily available COVID-19 therapeutics are urgently needed. In this Review, we summarize the major drug discovery approaches, preclinical antiviral evaluation models, representative virus-targeting and host-targeting therapeutic options, and key therapeutics currently in clinical use for COVID-19. Preparedness against future coronavirus pandemics relies not only on effective vaccines but also on broad-spectrum antivirals targeting conserved viral components or universal host targets, and new therapeutics that can precisely modulate the immune response during infection.}, }
@article {pmid38631806, year = {2024}, author = {Kane, AS and Godfrey, M and Noval Rivas, M and Arditi, M and Fasano, A and Yonker, LM}, title = {The Spectrum of Postacute Sequelae of COVID-19 in Children: From MIS-C to Long COVID.}, journal = {Annual review of virology}, volume = {11}, number = {1}, pages = {327-341}, pmid = {38631806}, issn = {2327-0578}, support = {R01 HL173059/HL/NHLBI NIH HHS/United States ; R56 AI169645/AI/NIAID NIH HHS/United States ; R01 AI072726/AI/NIAID NIH HHS/United States ; R01 DK104344/DK/NIDDK NIH HHS/United States ; K08 HL143183/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/complications/immunology/virology ; *Systemic Inflammatory Response Syndrome/diagnosis/virology ; Child ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; *Dysbiosis ; Gastrointestinal Microbiome ; }, abstract = {The effects of SARS-CoV-2 infection on children continue to evolve following the onset of the COVID-19 pandemic. Although life-threatening multisystem inflammatory syndrome in children (MIS-C) has become rare, long-standing symptoms stemming from persistent immune activation beyond the resolution of acute SARS-CoV-2 infection contribute to major health sequelae and continue to pose an economic burden. Shared pathophysiologic mechanisms place MIS-C and long COVID within a vast spectrum of postinfectious conditions characterized by intestinal dysbiosis, increased gut permeability, and varying degrees of immune dysregulation. Insights obtained from MIS-C will help shape our understanding of the more indolent and prevalent postacute sequelae of COVID and ultimately guide efforts to improve diagnosis and management of postinfectious complications of SARS-CoV-2 infection in children.}, }
@article {pmid38638307, year = {2024}, author = {Zhao, J and Xia, F and Jiao, X and Lyu, X}, title = {Long COVID and its association with neurodegenerative diseases: pathogenesis, neuroimaging, and treatment.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1367974}, pmid = {38638307}, issn = {1664-2295}, abstract = {Corona Virus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has presented unprecedented challenges to the world. Changes after acute COVID-19 have had a significant impact on patients with neurodegenerative diseases. This study aims to explore the mechanism of neurodegenerative diseases by examining the main pathways of central nervous system infection of SARS-CoV-2. Research has indicated that chronic inflammation and abnormal immune response are the primary factors leading to neuronal damage and long-term consequences of COVID-19. In some COVID-19 patients, the concurrent inflammatory response leads to increased release of pro-inflammatory cytokines, which may significantly impact the prognosis. Molecular imaging can accurately assess the severity of neurodegenerative diseases in patients with COVID-19 after the acute phase. Furthermore, the use of FDG-PET is advocated to quantify the relationship between neuroinflammation and psychiatric and cognitive symptoms in patients who have recovered from COVID-19. Future development should focus on aggressive post-infection control of inflammation and the development of targeted therapies that target ACE2 receptors, ERK1/2, and Ca[2+].}, }
@article {pmid38641397, year = {2024}, author = {Wills, CP and Perez, B and Moore, J}, title = {Coronavirus Disease 2019: Past, Present, and Future.}, journal = {Emergency medicine clinics of North America}, volume = {42}, number = {2}, pages = {415-442}, doi = {10.1016/j.emc.2024.02.002}, pmid = {38641397}, issn = {1558-0539}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 is one of the most impactful diseases experienced in the past century. While the official national health emergency concluded in May of 2023, coronavirus disease 2019 (COVID-19) continues to mutate. As the summer of 2023, all countries were experiencing a new surge of cases from the EG.5 Omicron variant. Additionally, a new genetically distinct Omicron descendant BA2.86 had been detected in multiple countries including the United States. This article seeks to offer lessons learned from the pandemic, summarize best evidence for current management of patients with COVID-19, and give insights into future directions with this disease.}, }
@article {pmid38651133, year = {2024}, author = {Staub, K and Ballouz, T and Puhan, M}, title = {An Unwanted but Long-Known Company: Post-Viral Symptoms in the Context of Past Pandemics in Switzerland (and Beyond).}, journal = {Public health reviews}, volume = {45}, number = {}, pages = {1606966}, pmid = {38651133}, issn = {0301-0422}, abstract = {Objectives: Some people do not fully recover from an acute viral infection and experience persistent symptoms or incomplete recovery for months or even years. This is not unique to the SARS-CoV-2 virus and history shows that post-viral conditions like post COVID-19 condition, also referred to as Long Covid, are not new. In particular, during and after pandemics caused by respiratory viruses in which large parts of the population were infected or exposed, professional and public attention was increased, not least because of the large number of people affected. Methods: Given the current relevance of the topic, this article aims to narratively review and summarize the literature on post-viral symptoms during past pandemics and to supplement and illustrate it with Swiss examples from the pandemics of 1890, 1918-1920 and later. Results: Post-viral diseases were an increasingly emphasised health topic during and after past pandemics triggered by respiratory infections over the last 150 years. Conclusion: In the next pandemic, it should not be surprising that post-viral conditions will again play a role, and pandemic plans should reflect this.}, }
@article {pmid38652364, year = {2024}, author = {Jasiczek, J and Doroszko, A and Trocha, T and Trocha, M}, title = {Role of the RAAS in mediating the pathophysiology of COVID-19.}, journal = {Pharmacological reports : PR}, volume = {76}, number = {3}, pages = {475-486}, pmid = {38652364}, issn = {2299-5684}, mesh = {Humans ; *Renin-Angiotensin System/physiology ; *COVID-19/physiopathology/metabolism ; *Angiotensin-Converting Enzyme 2/metabolism ; SARS-CoV-2 ; Animals ; }, abstract = {The renin-angiotensin-aldosterone system (RAAS) holds a position of paramount importance as enzymatic and endocrine homeostatic regulator concerning the water-electrolyte and acid-base balance. Nevertheless, its intricacy is influenced by the presence of various complementary angiotensins and their specific receptors, thereby modifying the primary RAAS actions. Angiotensin-converting enzyme 2 (ACE2) acts as a surface receptor for SARS-CoV-2, establishing an essential connection between RAAS and COVID-19 infection. Despite the recurring exploration of the RAAS impact on the trajectory of COVID-19 along with the successful resolution of many inquiries, its complete role in the genesis of delayed consequences encompassing long COVID and cardiovascular thrombotic outcomes during the post-COVID phase as well as post-vaccination, remains not fully comprehended. Particularly noteworthy is the involvement of the RAAS in the molecular mechanisms underpinning procoagulant processes throughout COVID-19. These processes significantly contribute to the pathogenesis of organ complications as well as determine clinical outcomes and are discussed in this manuscript.}, }
@article {pmid38656063, year = {2024}, author = {Martins, WRM and Cardoso, TV and Oliveira, AL and Fernandes, GS and Fontes, IFL and Dantas, JG and Miranda, JS and Martins, JE and Antunes, LN and Leite, TG}, title = {Long COVID-19 and mnemonic effects: an integrative literature review.}, journal = {Revista da Associacao Medica Brasileira (1992)}, volume = {70}, number = {5}, pages = {e20231211}, pmid = {38656063}, issn = {1806-9282}, mesh = {Humans ; *COVID-19/prevention &amp; control ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, }
@article {pmid38657468, year = {2024}, author = {Rusu, EC and Monfort-Lanzas, P and Bertran, L and Barrientos-Riosalido, A and Solé, E and Mahmoudian, R and Aguilar, C and Briansó, S and Mohamed, F and Garcia, S and Camaron, J and Auguet, T}, title = {Towards understanding post-COVID-19 condition: A systematic meta-analysis of transcriptomic alterations with sex-specific insights.}, journal = {Computers in biology and medicine}, volume = {175}, number = {}, pages = {108507}, doi = {10.1016/j.compbiomed.2024.108507}, pmid = {38657468}, issn = {1879-0534}, mesh = {Humans ; *COVID-19/genetics ; *Transcriptome/genetics ; Male ; Female ; *SARS-CoV-2/genetics ; Sex Factors ; Post-Acute COVID-19 Syndrome ; Gene Expression Profiling ; }, abstract = {BACKGROUND: Post COVID-19 Condition (PCC), characterized by lingering symptoms post-acute COVID-19, poses clinical challenges, highlighting the need to understand its underlying molecular mechanisms. This meta-analysis aims to shed light on the transcriptomic landscapes and sex-specific molecular dynamics intrinsic to PCC.<br><br>METHODS: A systematic review identified three studies suitable for comprehensive meta-analysis, encompassing 135 samples (57 PCC subjects and 78 recovered subjects). We performed meta-analysis on differential gene expression, a gene set enrichment analysis of Reactome pathways, and weighted gene co-expression network analysis (WGCNA). We performed a drug and disease enrichment analysis and also assessed sex-specific differences in expression patterns.<br><br>KEY FINDINGS: A clear difference was observed in the transcriptomic profiles of PCC subjects, with 530 differentially expressed genes (DEGs) identified. Enrichment analysis revealed that the altered pathways were predominantly implicated in cell cycle processes, immune dysregulation and histone modifications. Antioxidant compounds such as hesperitin were predominantly linked to the hub genes of the DEGs. Sex-specific analyses highlighted disparities in DEGs and altered pathways in male and female PCC patients, revealing a difference in the expression of ribosomal proteins. PCC in men was mostly linked to neuro-cardiovascular disorders, while women exhibited more diverse disorders, with a high index of respiratory conditions.<br><br>CONCLUSION: Our study reveals the intricate molecular processes underlying PCC, highlighting that the differences in molecular dynamics between males and females could be key to understanding and effectively managing the varied symptomatology of this condition.}, }
@article {pmid38666878, year = {2024}, author = {Paradiso, B and Pauza, DH and Limback, C and Ottaviani, G and Thiene, G}, title = {From Psychostasis to the Discovery of Cardiac Nerves: The Origins of the Modern Cardiac Neuromodulation Concept.}, journal = {Biology}, volume = {13}, number = {4}, pages = {}, pmid = {38666878}, issn = {2079-7737}, abstract = {This review explores the historical development of cardiology knowledge, from ancient Egyptian psychostasis to the modern comprehension of cardiac neuromodulation. In ancient Egyptian religion, psychostasis was the ceremony in which the deceased was judged before gaining access to the afterlife. This ritual was also known as the "weighing of the heart" or "weighing of the soul". The Egyptians believed that the heart, not the brain, was the seat of human wisdom, emotions, and memory. They were the first to recognize the cardiocentric nature of the body, identifying the heart as the center of the circulatory system. Aristotle (fourth century BC) considered the importance of the heart in human physiology in his philosophical analyses. For Galen (third century AD), the heart muscle was the site of the vital spirit, which regulated body temperature. Cardiology knowledge advanced significantly in the 15th century, coinciding with Leonardo da Vinci and Vesalius's pioneering anatomical and physiological studies. It was William Harvey, in the 17th century, who introduced the concept of cardiac circulation. Servet's research and Marcello Malpighi's discovery of arterioles and capillaries provided a more detailed understanding of circulation. Richard Lower emerged as the foremost pioneer of experimental cardiology in the late 17th century. He demonstrated the heart's neural control by tying off the vagus nerve. In 1753, Albrecht von Haller, a professor at Göttingen, was the first to discover the heart's automaticity and the excitation of muscle fibers. Towards the end of the 18th century, Antonio Scarpa challenged the theories of Albrecht von Haller and Johann Bernhard Jacob Behrends, who maintained that the myocardium possessed its own "irritability", on which the heartbeat depended, and was independent of neuronal sensitivity. Instead, Scarpa argued that the heart required innervation to maintain life, refuting Galenic notions. In contemporary times, the study of cardiac innervation has regained prominence, particularly in understanding the post-acute sequelae of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection (PASC), which frequently involves cardiorespiratory symptoms and dysregulation of the intrinsic cardiac innervation. Recently, it has been recognized that post-acute sequelae of acute respiratory infections (ARIs) due to other pathogens can also be a cause of long-term vegetative and somatic symptoms. Understanding cardiac innervation and modulation can help to recognize and treat long COVID and long non-COVID-19 (coronavirus disease 2019) ARIs. This analysis explores the historical foundations of cardiac neuromodulation and its contemporary relevance. By focusing on this concept, we aim to bridge the gap between historical understanding and modern applications. This will illuminate the complex interplay between cardiac function, neural modulation, cardiovascular health, and disease management in the context of long-term cardiorespiratory symptoms and dysregulation of intrinsic cardiac innervations.}, }
@article {pmid38668125, year = {2024}, author = {Rudroff, T}, title = {Decoding Post-Viral Fatigue: The Basal Ganglia's Complex Role in Long-COVID.}, journal = {Neurology international}, volume = {16}, number = {2}, pages = {380-393}, pmid = {38668125}, issn = {2035-8385}, abstract = {Long-COVID afflicts millions with relentless fatigue, disrupting daily life. The objective of this narrative review is to synthesize current evidence on the role of the basal ganglia in long-COVID fatigue, discuss potential mechanisms, and highlight promising therapeutic interventions. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science databases. Mounting evidence from PET, MRI, and functional connectivity data reveals basal ganglia disturbances in long-COVID exhaustion, including inflammation, metabolic disruption, volume changes, and network alterations focused on striatal dopamine circuitry regulating motivation. Theories suggest inflammation-induced signaling disturbances could impede effort/reward valuation, disrupt cortical-subcortical motivational pathways, or diminish excitatory input to arousal centers, attenuating drive initiation. Recent therapeutic pilots targeting basal ganglia abnormalities show provisional efficacy. However, heterogeneous outcomes, inconsistent metrics, and perceived versus objective fatigue discrepancies temper insights. Despite the growing research, gaps remain in understanding the precise pathways linking basal ganglia dysfunction to fatigue and validating treatment efficacy. Further research is needed to advance understanding of the basal ganglia's contribution to long-COVID neurological sequelae and offer hope for improving function across the expanding affected population.}, }
@article {pmid38668888, year = {2024}, author = {Molnar, T and Lehoczki, A and Fekete, M and Varnai, R and Zavori, L and Erdo-Bonyar, S and Simon, D and Berki, T and Csecsei, P and Ezer, E}, title = {Mitochondrial dysfunction in long COVID: mechanisms, consequences, and potential therapeutic approaches.}, journal = {GeroScience}, volume = {46}, number = {5}, pages = {5267-5286}, pmid = {38668888}, issn = {2509-2723}, mesh = {Humans ; *COVID-19/complications/physiopathology/therapy ; *Post-Acute COVID-19 Syndrome ; *Mitochondria/metabolism ; SARS-CoV-2 ; Oxidative Stress/physiology ; Mitochondrial Diseases/therapy/physiopathology ; }, abstract = {The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has introduced the medical community to the phenomenon of long COVID, a condition characterized by persistent symptoms following the resolution of the acute phase of infection. Among the myriad of symptoms reported by long COVID sufferers, chronic fatigue, cognitive disturbances, and exercise intolerance are predominant, suggesting systemic alterations beyond the initial viral pathology. Emerging evidence has pointed to mitochondrial dysfunction as a potential underpinning mechanism contributing to the persistence and diversity of long COVID symptoms. This review aims to synthesize current findings related to mitochondrial dysfunction in long COVID, exploring its implications for cellular energy deficits, oxidative stress, immune dysregulation, metabolic disturbances, and endothelial dysfunction. Through a comprehensive analysis of the literature, we highlight the significance of mitochondrial health in the pathophysiology of long COVID, drawing parallels with similar clinical syndromes linked to post-infectious states in other diseases where mitochondrial impairment has been implicated. We discuss potential therapeutic strategies targeting mitochondrial function, including pharmacological interventions, lifestyle modifications, exercise, and dietary approaches, and emphasize the need for further research and collaborative efforts to advance our understanding and management of long COVID. This review underscores the critical role of mitochondrial dysfunction in long COVID and calls for a multidisciplinary approach to address the gaps in our knowledge and treatment options for those affected by this condition.}, }
@article {pmid38671455, year = {2024}, author = {Ghasemiyeh, P and Mohammadi-Samani, S}, title = {Lessons we learned during the past four challenging years in the COVID-19 era: pharmacotherapy, long COVID complications, and vaccine development.}, journal = {Virology journal}, volume = {21}, number = {1}, pages = {98}, pmid = {38671455}, issn = {1743-422X}, mesh = {Humans ; *COVID-19/prevention &amp; control/immunology ; *COVID-19 Vaccines/immunology/adverse effects/administration &amp; dosage ; *SARS-CoV-2/immunology ; *Vaccine Development ; COVID-19 Drug Treatment ; Antiviral Agents/therapeutic use ; Post-Acute COVID-19 Syndrome ; Drug Repositioning ; }, abstract = {About four years have passed since the detection of the first cases of COVID-19 in China. During this lethal pandemic, millions of people have lost their lives around the world. Since the first waves of COVID-19 infection, various pharmacotherapeutic agents have been examined in the management of COVID-19. Despite all these efforts in pharmacotherapy, drug repurposing, and design and development of new drugs, multiple organ involvement and various complications occurred during COVID-19. Some of these complications became chronic and long-lasting which led to the "long COVID" syndrome appearance. Therefore, the best way to eradicate this pandemic is prophylaxis through mass vaccination. In this regard, various vaccine platforms including inactivated vaccines, nucleic acid-based vaccines (mRNA and DNA vaccines), adenovirus-vectored vaccines, and protein-based subunit vaccines have been designed and developed to prevent or reduce COVID-19 infection, hospitalization, and mortality rates. In this focused review, at first, the most commonly reported clinical presentations of COVID-19 during these four years have been summarized. In addition, different therapeutic regimens and their latest status in COVID-19 management have been listed. Furthermore, the "long COVID" and related signs, symptoms, and complications have been mentioned. At the end, the effectiveness of available COVID-19 vaccines with different platforms against early SARS-CoV-2 variants and currently circulating variants of interest (VOI) and the necessity of booster vaccine shots have been summarized and discussed in more detail.}, }
@article {pmid38672163, year = {2024}, author = {Maniaci, A and Lavalle, S and Masiello, E and Lechien, JR and Vaira, L and Boscolo-Rizzo, P and Musa, M and Gagliano, C and Zeppieri, M}, title = {Platelet-Rich Plasma (PRP) in the Treatment of Long COVID Olfactory Disorders: A Comprehensive Review.}, journal = {Biomedicines}, volume = {12}, number = {4}, pages = {}, pmid = {38672163}, issn = {2227-9059}, abstract = {Background: Long COVID has brought numerous challenges to healthcare, with olfactory dysfunction (OD) being a particularly distressing outcome for many patients. The persistent loss of smell significantly diminishes the affected individual's quality of life. Recent attention has been drawn to the potential of platelet-rich plasma (PRP) therapy as a treatment for OD. This comprehensive review aims to evaluate the effectiveness of PRP therapy in ameliorating OD, especially when associated with long-term COVID-19. Methods: We executed a comprehensive search of the literature, encompassing clinical trials and observational studies that utilized PRP in treating OD limited to COVID-19. We retrieved and comprehensively discussed data such as design, participant demographics, and reported outcomes, focusing on the efficacy and safety of PRP therapy for OD in COVID-19 patients. Results: Our comprehensive analysis interestingly found promising perspectives for PRP in OD following COVID-19 infection. The collective data indicate that PRP therapy contributed to a significant improvement in olfactory function after COVID-19 infection. Conclusions: The evidence amassed suggests that PRP is a promising and safe therapeutic option for OD, including cases attributable to Long COVID-19. The observed uniform enhancement of olfactory function in patients receiving PRP highlights the necessity for well-designed, controlled trials. Such studies would help to refine treatment protocols and more definitively ascertain the efficacy of PRP in a broader, more varied patient cohort.}, }
@article {pmid38672245, year = {2024}, author = {Kell, DB and Lip, GYH and Pretorius, E}, title = {Fibrinaloid Microclots and Atrial Fibrillation.}, journal = {Biomedicines}, volume = {12}, number = {4}, pages = {}, pmid = {38672245}, issn = {2227-9059}, abstract = {Atrial fibrillation (AF) is a comorbidity of a variety of other chronic, inflammatory diseases for which fibrinaloid microclots are a known accompaniment (and in some cases, a cause, with a mechanistic basis). Clots are, of course, a well-known consequence of atrial fibrillation. We here ask the question whether the fibrinaloid microclots seen in plasma or serum may in fact also be a cause of (or contributor to) the development of AF. We consider known 'risk factors' for AF, and in particular, exogenous stimuli such as infection and air pollution by particulates, both of which are known to cause AF. The external accompaniments of both bacterial (lipopolysaccharide and lipoteichoic acids) and viral (SARS-CoV-2 spike protein) infections are known to stimulate fibrinaloid microclots when added in vitro, and fibrinaloid microclots, as with other amyloid proteins, can be cytotoxic, both by inducing hypoxia/reperfusion and by other means. Strokes and thromboembolisms are also common consequences of AF. Consequently, taking a systems approach, we review the considerable evidence in detail, which leads us to suggest that it is likely that microclots may well have an aetiological role in the development of AF. This has significant mechanistic and therapeutic implications.}, }
@article {pmid38672267, year = {2024}, author = {Golzardi, M and Hromić-Jahjefendić, A and Šutković, J and Aydin, O and Ünal-Aydın, P and Bećirević, T and Redwan, EM and Rubio-Casillas, A and Uversky, VN}, title = {The Aftermath of COVID-19: Exploring the Long-Term Effects on Organ Systems.}, journal = {Biomedicines}, volume = {12}, number = {4}, pages = {}, pmid = {38672267}, issn = {2227-9059}, abstract = {BACKGROUND: Post-acute sequelae of SARS-CoV-2 infection (PASC) is a complicated disease that affects millions of people all over the world. Previous studies have shown that PASC impacts 10% of SARS-CoV-2 infected patients of which 50-70% are hospitalised. It has also been shown that 10-12% of those vaccinated against COVID-19 were affected by PASC and its complications. The severity and the later development of PASC symptoms are positively associated with the early intensity of the infection.<br><br>RESULTS: The generated health complications caused by PASC involve a vast variety of organ systems. Patients affected by PASC have been diagnosed with neuropsychiatric and neurological symptoms. The cardiovascular system also has been involved and several diseases such as myocarditis, pericarditis, and coronary artery diseases were reported. Chronic hematological problems such as thrombotic endothelialitis and hypercoagulability were described as conditions that could increase the risk of clotting disorders and coagulopathy in PASC patients. Chest pain, breathlessness, and cough in PASC patients were associated with the respiratory system in long-COVID causing respiratory distress syndrome. The observed immune complications were notable, involving several diseases. The renal system also was impacted, which resulted in raising the risk of diseases such as thrombotic issues, fibrosis, and sepsis. Endocrine gland malfunction can lead to diabetes, thyroiditis, and male infertility. Symptoms such as diarrhea, nausea, loss of appetite, and taste were also among reported observations due to several gastrointestinal disorders. Skin abnormalities might be an indication of infection and long-term implications such as persistent cutaneous complaints linked to PASC.<br><br>CONCLUSIONS: Long-COVID is a multidimensional syndrome with considerable public health implications, affecting several physiological systems and demanding thorough medical therapy, and more study to address its underlying causes and long-term effects is needed.}, }
@article {pmid38672710, year = {2024}, author = {Wu, BQ and Liu, DY and Shen, TC and Lai, YR and Yu, TL and Hsu, HL and Lee, HM and Liao, WC and Hsia, TC}, title = {Effects of Hyperbaric Oxygen Therapy on Long COVID: A Systematic Review.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {4}, pages = {}, pmid = {38672710}, issn = {2075-1729}, abstract = {The coronavirus disease (COVID-19) pandemic has resulted in an increasing population that is experiencing a wide range of long-lasting symptoms after recovery from the acute infection. Long COVID refers to this specific condition and is associated with diverse symptoms, such as fatigue, myalgias, dyspnea, headache, cognitive impairment, neurodegenerative symptoms, anxiety, depression, and a sense of despair. The potential of hyperbaric oxygen therapy (HBOT) to improve chronic fatigue, cognitive impairments, and neurological disorders has been established; therefore, the use of HBOT to treat long COVID has also been studied. We conducted a literature search between 1 January 2019 and 30 October 2023, focusing on the clinical efficacy and utility of HBOT for treating long COVID and found ten clinical studies that fit the review topic, including one case report, five one-group pretest-posttest design studies, one safety report from a randomized controlled trial (RCT), and three complete reports of RCTs. Most studies found that HBOT can improve quality of life, fatigue, cognition, neuropsychiatric symptoms, and cardiopulmonary function. Although HBOT has shown some benefits for long COVID symptoms, further rigorous large-scale RCTs are required to establish precise indications, protocols, and post-treatment evaluations.}, }
@article {pmid38672973, year = {2024}, author = {Ferous, S and Siafakas, N and Boufidou, F and Patrinos, GP and Tsakris, A and Anastassopoulou, C}, title = {Investigating ABO Blood Groups and Secretor Status in Relation to SARS-CoV-2 Infection and COVID-19 Severity.}, journal = {Journal of personalized medicine}, volume = {14}, number = {4}, pages = {}, pmid = {38672973}, issn = {2075-4426}, abstract = {The ABO blood groups, Lewis antigens, and secretor systems are important components of transfusion medicine. These interconnected systems have been also shown to be associated with differing susceptibility to bacterial and viral infections, likely as the result of selection over the course of evolution and the constant tug of war between humans and infectious microbes. This comprehensive narrative review aimed to explore the literature and to present the current state of knowledge on reported associations of the ABO, Lewis, and secretor blood groups with SARS-CoV-2 infection and COVID-19 severity. Our main finding was that the A blood group may be associated with increased susceptibility to SARS-CoV-2 infection, and possibly also with increased disease severity and overall mortality. The proposed pathophysiological pathways explaining this potential association include antibody-mediated mechanisms and increased thrombotic risk amongst blood group A individuals, in addition to altered inflammatory cytokine expression profiles. Preliminary evidence does not support the association between ABO blood groups and COVID-19 vaccine response, or the risk of developing long COVID. Even though the emergency state of the pandemic is over, further research is needed especially in this area since tens of millions of people worldwide suffer from lingering COVID-19 symptoms.}, }
@article {pmid38673384, year = {2024}, author = {Diar Bakerly, N and Smith, N and Darbyshire, JL and Kwon, J and Bullock, E and Baley, S and Sivan, M and Delaney, B}, title = {Pathophysiological Mechanisms in Long COVID: A Mixed Method Systematic Review.}, journal = {International journal of environmental research and public health}, volume = {21}, number = {4}, pages = {}, pmid = {38673384}, issn = {1660-4601}, mesh = {Humans ; *COVID-19/physiopathology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Long COVID (LC) is a global public health crisis affecting more than 70 million people. There is emerging evidence of different pathophysiological mechanisms driving the wide array of symptoms in LC. Understanding the relationships between mechanisms and symptoms helps in guiding clinical management and identifying potential treatment targets.<br><br>METHODS: This was a mixed-methods systematic review with two stages: Stage one (Review 1) included only existing systematic reviews (meta-review) and Stage two (Review 2) was a review of all primary studies. The search strategy involved Medline, Embase, Emcare, and CINAHL databases to identify studies that described symptoms and pathophysiological mechanisms with statistical analysis and/or discussion of plausible causal relationships between mechanisms and symptoms. Only studies that included a control arm for comparison were included. Studies were assessed for quality using the National Heart, Lung, and Blood Institute quality assessment tools.<br><br>RESULTS: 19 systematic reviews were included in Review 1 and 46 primary studies in Review 2. Overall, the quality of reporting across the studies included in this second review was moderate to poor. The pathophysiological mechanisms with strong evidence were immune system dysregulation, cerebral hypoperfusion, and impaired gas transfer in the lungs. Other mechanisms with moderate to weak evidence were endothelial damage and hypercoagulation, mast cell activation, and auto-immunity to vascular receptors.<br><br>CONCLUSIONS: LC is a complex condition affecting multiple organs with diverse clinical presentations (or traits) underpinned by multiple pathophysiological mechanisms. A 'treatable trait' approach may help identify certain groups and target specific interventions. Future research must include understanding the response to intervention based on these mechanism-based traits.}, }
@article {pmid38675914, year = {2024}, author = {Nunes, JM and Kell, DB and Pretorius, E}, title = {Herpesvirus Infection of Endothelial Cells as a Systemic Pathological Axis in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.}, journal = {Viruses}, volume = {16}, number = {4}, pages = {}, pmid = {38675914}, issn = {1999-4915}, support = {142142//National Research Foundation/ ; NNF10CC1016517//Novo Nordisk Foundation/ ; }, mesh = {Humans ; *Endothelial Cells/virology ; *Fatigue Syndrome, Chronic/virology/physiopathology ; Herpesviridae/physiology ; *Herpesviridae Infections/virology ; Virus Latency ; Post-Acute COVID-19 Syndrome/pathology/physiopathology ; }, abstract = {Understanding the pathophysiology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is critical for advancing treatment options. This review explores the novel hypothesis that a herpesvirus infection of endothelial cells (ECs) may underlie ME/CFS symptomatology. We review evidence linking herpesviruses to persistent EC infection and the implications for endothelial dysfunction, encompassing blood flow regulation, coagulation, and cognitive impairment-symptoms consistent with ME/CFS and Long COVID. This paper provides a synthesis of current research on herpesvirus latency and reactivation, detailing the impact on ECs and subsequent systemic complications, including latent modulation and long-term maladaptation. We suggest that the chronicity of ME/CFS symptoms and the multisystemic nature of the disease may be partly attributable to herpesvirus-induced endothelial maladaptation. Our conclusions underscore the necessity for further investigation into the prevalence and load of herpesvirus infection within the ECs of ME/CFS patients. This review offers conceptual advances by proposing an endothelial infection model as a systemic mechanism contributing to ME/CFS, steering future research toward potentially unexplored avenues in understanding and treating this complex syndrome.}, }
@article {pmid38692805, year = {2024}, author = {Borczuk, AC}, title = {Pathology of COVID-19 Lung Disease.}, journal = {Surgical pathology clinics}, volume = {17}, number = {2}, pages = {203-214}, doi = {10.1016/j.path.2023.11.006}, pmid = {38692805}, issn = {1875-9157}, mesh = {Humans ; *COVID-19/pathology/complications ; *Lung/pathology ; *SARS-CoV-2 ; Lung Diseases/pathology ; }, abstract = {The pathology of severe COVID-19 lung injury is predominantly diffuse alveolar damage, with other reported patterns including acute fibrinous organizing pneumonia, organizing pneumonia, and bronchiolitis. Lung injury was caused by primary viral injury, exaggerated immune responses, and superinfection with bacteria and fungi. Although fatality rates have decreased from the early phases of the pandemic, persistent pulmonary dysfunction occurs and its pathogenesis remains to be fully elucidated.}, }
@article {pmid38693436, year = {2024}, author = {Văcăraş, V and Vulturar, R and Chiş, A and Damian, L}, title = {Inclusion body myositis, viral infections, and TDP-43: a narrative review.}, journal = {Clinical and experimental medicine}, volume = {24}, number = {1}, pages = {91}, pmid = {38693436}, issn = {1591-9528}, mesh = {*Myositis, Inclusion Body/virology ; Humans ; *Virus Diseases/immunology/virology ; *DNA-Binding Proteins/genetics/metabolism ; }, abstract = {The ubiquitous RNA-processing molecule TDP-43 is involved in neuromuscular diseases such as inclusion body myositis, a late-onset acquired inflammatory myopathy. TDP-43 solubility and function are disrupted in certain viral infections. Certain viruses, high viremia, co-infections, reactivation of latent viruses, and post-acute expansion of cytotoxic T cells may all contribute to inclusion body myositis, mainly in an age-shaped immune landscape. The virally induced senescent, interferon gamma-producing cytotoxic CD8+ T cells with increased inflammatory, and cytotoxic features are involved in the occurrence of inclusion body myositis in most such cases, in a genetically predisposed host. We discuss the putative mechanisms linking inclusion body myositis, TDP-43, and viral infections untangling the links between viruses, interferon, and neuromuscular degeneration could shed a light on the pathogenesis of the inclusion body myositis and other TDP-43-related neuromuscular diseases, with possible therapeutic implications.}, }
@article {pmid38693641, year = {2024}, author = {Apostolou, E and Rosén, A}, title = {Epigenetic reprograming in myalgic encephalomyelitis/chronic fatigue syndrome: A narrative of latent viruses.}, journal = {Journal of internal medicine}, volume = {296}, number = {1}, pages = {93-115}, doi = {10.1111/joim.13792}, pmid = {38693641}, issn = {1365-2796}, support = {4.3-2019-00201 GD-2020-138//Swedish Research Council/ ; 211832Pj01H2//Swedish Cancer Society/ ; }, mesh = {Humans ; *Fatigue Syndrome, Chronic/virology/genetics ; *Epigenesis, Genetic ; Virus Latency/genetics ; Herpesvirus 4, Human ; }, abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic disease presenting with severe fatigue, post-exertional malaise, and cognitive disturbances-among a spectrum of symptoms-that collectively render the patient housebound or bedbound. Epigenetic studies in ME/CFS collectively confirm alterations and/or malfunctions in cellular and organismal physiology associated with immune responses, cellular metabolism, cell death and proliferation, and neuronal and endothelial cell function. The sudden onset of ME/CFS follows a major stress factor that, in approximately 70% of cases, involves viral infection, and ME/CFS symptoms overlap with those of long COVID. Viruses primarily linked to ME/CFS pathology are the symbiotic herpesviruses, which follow a bivalent latent-lytic lifecycle. The complex interaction between viruses and hosts involves strategies from both sides: immune evasion and persistence by the viruses, and immune activation and viral clearance by the host. This dynamic interaction is imperative for herpesviruses that facilitate their persistence through epigenetic regulation of their own and the host genome. In the current article, we provide an overview of the epigenetic signatures demonstrated in ME/CFS and focus on the potential strategies that latent viruses-particularly Epstein-Barr virus-may employ in long-term epigenetic reprograming in ME/CFS. Epigenetic studies could aid in elucidating relevant biological pathways impacted in ME/CFS and reflect the physiological variations among the patients that stem from environmental triggers, including exogenous viruses and/or altered viral activity.}, }
@article {pmid38695969, year = {2024}, author = {Gorenshtein, A and Liba, T and Leibovitch, L and Stern, S and Stern, Y}, title = {Intervention modalities for brain fog caused by long-COVID: systematic review of the literature.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {7}, pages = {2951-2968}, pmid = {38695969}, issn = {1590-3478}, mesh = {Humans ; Brain ; *Cognitive Dysfunction/etiology/therapy/physiopathology ; COVID-19/complications ; Hyperbaric Oxygenation/methods ; *Post-Acute COVID-19 Syndrome/therapy ; SARS-CoV-2 ; Transcranial Direct Current Stimulation/methods ; Transcranial Magnetic Stimulation/methods ; *Mental Fatigue/therapy ; }, abstract = {Individuals suffering from long-COVID can present with "brain fog", which is characterized by a range of cognitive impairments, such as confusion, short-term memory loss, and difficulty concentrating. To date, several potential interventions for brain fog have been considered. Notably, no systematic review has comprehensively discussed the impact of each intervention type on brain fog symptoms. We included studies on adult (aged > 18 years) individuals with proven long- COVID brain-fog symptoms from PubMed, MEDLINE, Central, Scopus, and Embase. A search limit was set for articles published between 01/2020 and 31/12/2023. We excluded studies lacking an objective assessment of brain fog symptoms and patients with preexisting neurological diseases that affected cognition before COVID-19 infection. This review provided relevant information from 17 studies. The rehabilitation studies utilized diverse approaches, leading to a range of outcomes in terms of the effectiveness of the interventions. Six studies described noninvasive brain stimulation, and all showed improvement in cognitive ability. Three studies described hyperbaric oxygen therapy, all of which showed improvements in cognitive assessment tests and brain perfusion. Two studies showed that the use of Palmitoylethanolamide and Luteolin (PEA-LUT) improved cognitive impairment. Noninvasive brain stimulation and hyperbaric oxygen therapy showed promising results in the treatment of brain fog symptoms caused by long-COVID, with improved perfusion and cortical excitability. Furthermore, both rehabilitation strategies and PEA-LUT administration have been associated with improvements in symptoms of brain fog. Future studies should explore combinations of interventions and include longer follow-up periods to assess the long-term effects of these treatments.}, }
@article {pmid38696415, year = {2024}, author = {Hua, MJ and Butera, G and Akinyemi, O and Porterfield, D}, title = {Biases and limitations in observational studies of Long COVID prevalence and risk factors: A rapid systematic umbrella review.}, journal = {PloS one}, volume = {19}, number = {5}, pages = {e0302408}, pmid = {38696415}, issn = {1932-6203}, mesh = {Humans ; *COVID-19/epidemiology ; Risk Factors ; Prevalence ; *SARS-CoV-2/isolation &amp; purification ; *Observational Studies as Topic ; Bias ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Observational studies form the foundation of Long COVID knowledge, however combining data from Long COVID observational studies has multiple methodological challenges. This umbrella review synthesizes estimates of Long COVID prevalence and risk factors as well as biases and limitations in the primary and review literatures.<br><br>METHODS AND FINDINGS: A systematic literature search was conducted using multiple electronic databases (PubMed, EMBASE, LitCOVID) from Jan 1, 2019 until June 9, 2023. Eligible studies were systematic reviews including adult populations assessed for at least one Long COVID symptom four weeks or more after SARS-CoV-2 infection. Overall and subgroup prevalence and risk factors as well as risk of bias (ROB) assessments were extracted and descriptively analyzed. The protocol was registered with PROSPERO (CRD42023434323). Fourteen reviews of 5-196 primary studies were included: 8 reported on Long COVID prevalence, 5 on risk/protective factors, and 1 on both. Prevalence of at least 1 Long COVID symptom ranged from 21% (IQR: 8.9%-35%) to 74.5% (95% CI: 55.6%-78.0%). Risk factor reviews found significant associations between vaccination status, sex, acute COVID-19 severity, and comorbidities. Both prevalence and risk factor reviews frequently identified selection and ascertainment biases. Using the AMSTAR 2 criteria, the quality of included reviews, particularly the prevalence reviews, were concerning for the adequacy of ROB assessments and justifications for conducting meta-analysis.<br><br>CONCLUSION: A high level of heterogeneity render the interpretation of pooled prevalence estimates of Long COVID challenging, further hampered by the lack of robust critical appraisals in the included reviews. Risk factor reviews were of higher quality overall and suggested consistent associations between Long COVID risk and patient characteristics.}, }
@article {pmid38700307, year = {2023}, author = {Karuturi, S}, title = {Long COVID-19: A Systematic Review.}, journal = {The Journal of the Association of Physicians of India}, volume = {71}, number = {9}, pages = {82-94}, doi = {10.59556/japi.71.0337}, pmid = {38700307}, issn = {0004-5772}, mesh = {Humans ; COVID-19/epidemiology ; *Post-Acute COVID-19 Syndrome/epidemiology/pathology/therapy ; SARS-CoV-2 ; }, abstract = {Coronavirus disease 2019's (COVID-19's) wide dissemination casts long-term health jeopardy for millions. Long COVID-19, a lingering multisystem malady, weaves a complex array of symptoms. Understanding its full impact requires extensive research over months or years. The pace of recovery remains uncertain, challenging healthcare systems. An evidence-based symphony of medical care and support is urgently needed for long haulers. Understanding long COVID's genesis and advocating for patients is vital. Our comprehension remains limited, prompting a systematic scoping study to explore the existing knowledge and pave the way for future research, illuminating the enigma of "long COVID" and guiding the path towards understanding this relentless condition. How to cite this article: Karuturi S. Long COVID-19: A Systematic Review. J Assoc Physicians India 2023;71(9):82-94.}, }
@article {pmid38700879, year = {2024}, author = {Cogliandro, V and Bonfanti, P}, title = {Long COVID: lights and shadows on the clinical characterization of this emerging pathology.}, journal = {The new microbiologica}, volume = {47}, number = {1}, pages = {15-27}, pmid = {38700879}, issn = {1121-7138}, mesh = {Humans ; *COVID-19/epidemiology/virology ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome ; Fatigue Syndrome, Chronic/virology ; Risk Factors ; Quality of Life ; Postural Orthostatic Tachycardia Syndrome/physiopathology ; }, abstract = {More than 800 million individuals have contracted SARSCOV2 infection worldwide. It was estimated that almost 10-20% of these might suffer from Long COVID. It is a multisystemic syndrome, which negatively affects the quality of life with a significant burden of health loss compared to COVID negative individuals. Moreover, the risk of sequelae still remains high at 2 years in both nonhospitalized and hospitalized individuals. This review summarizes studies regarding long COVID and clarifies the definitions, the risk factors and the management of this syndrome. Finally, it delves into the most frequent long-term outcomes, especially postural orthostatic tachycardia syndrome" (POTS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), brain fog, and their therapeutical possibilities.}, }
@article {pmid38704055, year = {2024}, author = {Altmayer, S and Leung, AN and de Oliveira, GS and Prodigios, J and Patel, P and Mohammed, TL and Verma, N and Hochhegger, B}, title = {Chronic Chest Computed Tomography Findings Following COVID-19 Pneumonia.}, journal = {Seminars in ultrasound, CT, and MR}, volume = {45}, number = {4}, pages = {298-308}, doi = {10.1053/j.sult.2024.02.008}, pmid = {38704055}, issn = {1558-5034}, mesh = {Humans ; *COVID-19/diagnostic imaging/complications ; *Tomography, X-Ray Computed/methods ; *SARS-CoV-2 ; *Lung/diagnostic imaging ; Radiography, Thoracic/methods ; }, abstract = {Respiratory symptoms are a frequent manifestation of patients with post-acute sequela of SARS-CoV-2 (PASC), also known as long-COVID. Many cohorts of predominantly hospitalized patients have shown that a significant subset may have persistent chest computed tomography findings for more than 12 months after the acute infection. Proper understanding of the evolving long-term imaging findings and terminology is crucial for accurate imaging interpretation and patient care. The goal of this article is to review the chronic chest computed tomography findings of patients with PASC and common pitfalls.}, }
@article {pmid38711990, year = {2024}, author = {Zifko, U and Guendling, K and Seet, R and Kasper, S}, title = {Management of cognitive impairment associated with post-COVID-19 syndrome: recommendations for primary care.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1338235}, pmid = {38711990}, issn = {1663-9812}, abstract = {Introduction: Although post-COVID-19 syndrome (PCS) with cognitive impairment is increasingly encountered in primary care, evidence-based recommendations for its appropriate management are lacking. Methods: A systematic literature search evaluating the diagnosis and treatment of cognitive impairment associated with PCS was conducted. Practical recommendations for the management of PCS-associated cognitive impairment in primary care are summarized, based on an evaluation of pharmacological plausibility and clinical applications. Results: Currently, the pathology of cognitive impairment associated with PCS remains unclear with no high-quality data to support targeted interventions. Existing treatment approaches are directed towards symptom relief where counseling on the chronicity of the disease and regular reassessments at 4- to 8-week intervals is considered reasonable. Patients should be informed and encouraged to adopt a healthy lifestyle that centers around balanced nutrition and appropriate physical activities. They may also benefit from the intake of vitamins, micronutrients, and probiotics. The administration of Ginkgo biloba extract could offer a safe and potentially beneficial treatment option. Other non-pharmacological measures include physiotherapy, digitally supported cognitive training, and, if indicated, ergotherapy or speech therapy. In most patients, symptoms improve within 8 weeks. If serious, ambiguous, or when new symptoms occur, specialized diagnostic measures such as comprehensive neurocognitive testing or neuroimaging should be initiated. Very few patients would require inpatient rehabilitation. Conclusion: PCS with cognitive impairment is a debilitating condition that could affect daily functioning and reduce work productivity. Management in primary care should adopt a multidisciplinary approach, centering around physical, cognitive, and pharmacological therapies.}, }
@article {pmid38732160, year = {2024}, author = {Riou, M and Coste, F and Meyer, A and Enache, I and Talha, S and Charloux, A and Reboul, C and Geny, B}, title = {Mechanisms of Pulmonary Vasculopathy in Acute and Long-Term COVID-19: A Review.}, journal = {International journal of molecular sciences}, volume = {25}, number = {9}, pages = {}, pmid = {38732160}, issn = {1422-0067}, mesh = {Humans ; *COVID-19/complications/virology/pathology ; *SARS-CoV-2/pathogenicity ; Lung/blood supply/pathology/virology ; Pulmonary Embolism/virology/etiology ; Hypertension, Pulmonary/etiology/physiopathology/virology/pathology ; Post-Acute COVID-19 Syndrome ; Thrombosis/virology/etiology/pathology ; }, abstract = {Despite the end of the pandemic, coronavirus disease 2019 (COVID-19) remains a major public health concern. The first waves of the virus led to a better understanding of its pathogenesis, highlighting the fact that there is a specific pulmonary vascular disorder. Indeed, COVID-19 may predispose patients to thrombotic disease in both venous and arterial circulation, and many cases of severe acute pulmonary embolism have been reported. The demonstrated presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within the endothelial cells suggests that direct viral effects, in addition to indirect effects of perivascular inflammation and coagulopathy, may contribute to pulmonary vasculopathy in COVID-19. In this review, we discuss the pathological mechanisms leading to pulmonary vascular damage during acute infection, which appear to be mainly related to thromboembolic events, an impaired coagulation cascade, micro- and macrovascular thrombosis, endotheliitis and hypoxic pulmonary vasoconstriction. As many patients develop post-COVID symptoms, including dyspnea, we also discuss the hypothesis of pulmonary vascular damage and pulmonary hypertension as a sequela of the infection, which may be involved in the pathophysiology of long COVID.}, }
@article {pmid38732592, year = {2024}, author = {Sinopoli, A and Sciurti, A and Isonne, C and Santoro, MM and Baccolini, V}, title = {The Efficacy of Multivitamin, Vitamin A, Vitamin B, Vitamin C, and Vitamin D Supplements in the Prevention and Management of COVID-19 and Long-COVID: An Updated Systematic Review and Meta-Analysis of Randomized Clinical Trials.}, journal = {Nutrients}, volume = {16}, number = {9}, pages = {}, pmid = {38732592}, issn = {2072-6643}, mesh = {Humans ; *Dietary Supplements ; *COVID-19/prevention &amp; control/mortality ; *Vitamins/therapeutic use ; *Vitamin D/therapeutic use/administration &amp; dosage ; *Randomized Controlled Trials as Topic ; *Ascorbic Acid/therapeutic use/administration &amp; dosage ; *SARS-CoV-2 ; *Vitamin A/therapeutic use/administration &amp; dosage ; COVID-19 Drug Treatment ; Vitamin B Complex/therapeutic use ; }, abstract = {This review aims to evaluate the efficacy of any vitamin administration(s) in preventing and managing COVID-19 and/or long-COVID. Databases were searched up to May 2023 to identify randomized clinical trials comparing data on the effects of vitamin supplementation(s) versus placebo or standard of care on the two conditions of interest. Inverse-variance random-effects meta-analyses were conducted to estimate pooled risk ratios (RRs) and 95% confidence intervals (CIs) for all-cause mortality between supplemented and non-supplemented individuals. Overall, 37 articles were included: two regarded COVID-19 and long-COVID prevention and 35 records the COVID-19 management. The effects of vitamin D in preventing COVID-19 and long-COVID were contrasting. Similarly, no conclusion could be drawn on the efficacy of multivitamins, vitamin A, and vitamin B in COVID-19 management. A few positive findings were reported in some vitamin C trials but results were inconsistent in most outcomes, excluding all-cause mortality (RR = 0.84; 95% CI: 0.72-0.97). Vitamin D results were mixed in most aspects, including mortality, in which benefits were observed in regular administrations only (RR = 0.67; 95% CI: 0.49-0.91). Despite some benefits, results were mostly contradictory. Variety in recruitment and treatment protocols might explain this heterogeneity. Better-designed studies are needed to clarify these vitamins' potential effects against SARS-CoV-2.}, }
@article {pmid38745394, year = {2024}, author = {Brainin, M and Teuschl, Y and Gelpi, E}, title = {"Spanish flu," encephalitis lethargica, and COVID-19: Progress made, lessons learned, and directions for future research.}, journal = {European journal of neurology}, volume = {31}, number = {11}, pages = {e16312}, pmid = {38745394}, issn = {1468-1331}, mesh = {Humans ; *COVID-19/epidemiology ; History, 20th Century ; Parkinson Disease, Postencephalitic/history/therapy/epidemiology ; Influenza, Human/epidemiology/history/prevention &amp; control/therapy ; Pandemics ; }, abstract = {One hundred years ago, an influenza pandemic swept across the globe that coincided with the development of a neurological condition, named "encephalitis lethargica" for the occurrence of its main symptom, the sudden onset of sleepiness that either developed into coma or gradually receded. Between 1917 and 1920, mortality of the flu was >20 million and of encephalitis lethargica approximately 1 million. For lessons to be learned from this pandemic, it makes sense to compare it with the COVID-19 pandemic, which occurred 100 years later. Biomedical progress had enabled testing, vaccinations, and drug therapies accompanied by public health measures such as social distancing, contact tracing, wearing face masks, and frequent hand washing. From todays' perspective, these public health measures are time honored but not sufficiently proven effective, especially when applied in the context of a vaccination strategy. Also, the protective effects of lockdowns of schools, universities, and other institutions and the restrictions on travel and personal visits to hospitals or old-age homes are not precisely known. Preparedness is still a demand for a future pandemic. Clinical trials should determine the comparative effectiveness of such public health measures, especially for their use as a combination strategy with vaccination and individual testing of asymptomatic individuals. It is important for neurologists to realize that during a pandemic the treatment possibilities for acute stroke and other neurological emergencies are reduced, which has previously led to an increase of mortality and suffering. To increase preparedness for a future pandemic, neurologists play an important role, as the case load of acute and chronic neurological patients will be higher as well as the needs for rehabilitation. Finally, new chronic forms of postviral disease will likely be added, as was the case for postencephalitic parkinsonism a century ago and now has occurred as long COVID.}, }
@article {pmid38746044, year = {2024}, author = {Chen, XY and Lu, CL and Wang, QY and Pan, XR and Zhang, YY and Wang, JL and Liao, JY and Hu, NC and Wang, CY and Duan, BJ and Liu, XH and Jin, XY and Hunter, J and Liu, JP}, title = {Traditional, complementary and integrative medicine for fatigue post COVID-19 infection: A systematic review of randomized controlled trials.}, journal = {Integrative medicine research}, volume = {13}, number = {2}, pages = {101039}, pmid = {38746044}, issn = {2213-4220}, abstract = {BACKGROUND: Chronic fatigue is a predominant symptom of post COVID-19 condition, or long COVID. We aimed to evaluate the efficacy and safety of Traditional, Complementary and Integrative Medicine (TCIM) for fatigue post COVID-19 infection.<br><br>METHODS: Ten English and Chinese language databases and grey literature were searched up to 12 April 2023 for randomized controlled trials (RCTs). Cochrane "Risk of bias" (RoB) tool was applied. Evidence certainty was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Effect estimates were presented as risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI).<br><br>RESULTS: Thirteen RCTs with 1632 participants were included. One RCT showed that Bufei Huoxue herbal capsules reduced fatigue (n=129, MD -14.90, 95%CI -24.53 to -5.27), one RCT reported that Ludangshen herbal liquid lowered fatigue (n=184, MD -1.90, 95%CI -2.38 to -1.42), and the other one RCT shown that fatigue disappearance rate was higher with Ludangshen herbal liquid (n=184, RR 4.19, 95%CI 2.06 to 8.53). Compared to traditional Chinese medicine rehabilitation (TCM-rahab) alone, one RCT showed that fatigue symptoms were lower following Qingjin Yiqi granules plus TCM-rehab (n=388, MD -0.48, 95%CI -0.50 to -0.46). Due to concerns with RoB and/or imprecision, the certainty in this evidence was low to very low. No serious adverse events was reported.<br><br>CONCLUSIONS: Limited evidence suggests that various TCIM interventions might reduce post COVID-19 fatigue. Larger, high quality RCTs of longer duration are required to confirm these preliminary findings.<br><br>STUDY REGISTRATION: The protocol of this review has been registered at PROSPERO: CRD42022384136.}, }
@article {pmid38749402, year = {2024}, author = {Anastassopoulou, C and Davaris, N and Ferous, S and Siafakas, N and Boufidou, F and Anagnostopoulos, K and Tsakris, A}, title = {The Molecular Basis of Olfactory Dysfunction in COVID-19 and Long COVID.}, journal = {Lifestyle genomics}, volume = {17}, number = {1}, pages = {42-56}, doi = {10.1159/000539292}, pmid = {38749402}, issn = {2504-3188}, mesh = {*COVID-19/complications ; Humans ; *SARS-CoV-2 ; *Olfaction Disorders/physiopathology ; Anosmia/physiopathology ; Post-Acute COVID-19 Syndrome ; Olfactory Mucosa/virology/pathology ; Olfactory Receptor Neurons ; }, abstract = {Olfactory dysfunction (OD) is not uncommon following viral infection. Herein, we explore the interplay of host genetics with viral correlates in coronavirus disease 2019 (COVID-19)- and long COVID-related OD, and its diagnosis and treatment that remain challenging. Two genes associated with olfaction, UGT2A1 and UGT2A2, appear to be involved in COVID-19-related anosmia, a hallmark symptom of acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), particularly in the early stages of the pandemic. SARS-CoV-2 infects olfactory support cells, sustentacular and Bowman gland cells, that surround olfactory sensory neurons (OSNs) in the olfactory epithelium (OE) where the initial step of odor detection takes place. Anosmia primarily arises from the infection of support cells of the OE, followed by the deciliation and disruption of OE integrity, typically without OSN infection. Through the projected axons of OSNs, the virus could theoretically reach the olfactory bulb and brain, but current evidence points against this route. Intriguingly, SARS-CoV-2 infection of support cells leads to profound alterations in the nuclear architecture of OSNs, leading to the downregulation of odorant receptor-related genes, e.g., of Adcy3. Viral factors associated with the development of OD include spike protein aminoacidic changes, e.g., D614G, the first substitution that was selected early during SARS-CoV-2 evolution. More recent variants of the Omicron family are less likely to cause OD compared to Delta or Alpha, although OD has been associated with a milder disease course. OD is one of the most prevalent post-acute neurologic symptoms of SARS-CoV-2 infection. The tens of millions of people worldwide who have lingering problems with OD wait eagerly for effective new treatments that will restore their sense of smell which adds value to their quality of life.}, }
@article {pmid38761526, year = {2024}, author = {Goldenberg, DL}, title = {How to understand the overlap of long COVID, chronic fatigue syndrome/myalgic encephalomyelitis, fibromyalgia and irritable bowel syndromes.}, journal = {Seminars in arthritis and rheumatism}, volume = {67}, number = {}, pages = {152455}, doi = {10.1016/j.semarthrit.2024.152455}, pmid = {38761526}, issn = {1532-866X}, mesh = {Humans ; *Irritable Bowel Syndrome/physiopathology ; *Fibromyalgia/physiopathology ; *Fatigue Syndrome, Chronic/virology/physiopathology ; *COVID-19/complications ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {Long COVID should be limited to patients with multiple, persistent symptoms not related to well-defined organ damage. Once redefined, a focused review of long COVID demonstrates striking similarity to chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), fibromyalgia (FM) and irritable bowel syndrome (IBS). Research in long COVID has revealed similar findings to those noted in CFS/ME and FM, characterized by central nervous system organ dysfunction. Long COVID, like CFS/ME, FM and IBS, is best understood as a bidirectional mind-body, neuroimmune illness.}, }
@article {pmid38765079, year = {2024}, author = {Ho, WY and Shen, ZH and Chen, Y and Chen, TH and Lu, X and Fu, YS}, title = {Therapeutic implications of quercetin and its derived-products in COVID-19 protection and prophylactic.}, journal = {Heliyon}, volume = {10}, number = {9}, pages = {e30080}, pmid = {38765079}, issn = {2405-8440}, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel human coronavirus, which has triggered a global pandemic of the coronavirus infectious disease 2019 (COVID-19). Outbreaks of emerging infectious diseases continue to challenge human health worldwide. The virus conquers human cells through the angiotensin-converting enzyme 2 receptor-driven pathway by mostly targeting the human respiratory tract. Quercetin is a natural flavonoid widely represented in the plant kingdom. Cumulative evidence has demonstrated that quercetin and its derivatives have various pharmacological properties including anti-cancer, anti-hypertension, anti-hyperlipidemia, anti-hyperglycemia, anti-microbial, antiviral, neuroprotective, and cardio-protective effects, because it is a potential treatment for severe inflammation and acute respiratory distress syndrome. Furthermore, it is the main life-threatening condition in patients with COVID-19. This article provides a comprehensive review of the primary literature on the predictable effectiveness of quercetin and its derivatives docked to multi-target of SARS-CoV-2 and host cells via in silico and some of validation through in vitro, in vivo, and clinically to fight SARS-CoV-2 infections, contribute to the reduction of inflammation, which suggests the preventive and therapeutic latency of quercetin and its derived-products against COVID-19 pandemic, multisystem inflammatory syndromes (MIS), and long-COVID.}, }
@article {pmid38768458, year = {2024}, author = {Chou, R and Herman, E and Ahmed, A and Anderson, J and Selph, S and Dana, T and Williams, L and Ivlev, I}, title = {Long COVID Definitions and Models of Care : A Scoping Review.}, journal = {Annals of internal medicine}, volume = {177}, number = {7}, pages = {929-940}, doi = {10.7326/M24-0677}, pmid = {38768458}, issn = {1539-3704}, mesh = {Humans ; *COVID-19/diagnosis/epidemiology/therapy ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome ; Terminology as Topic ; Delivery of Health Care/organization &amp; administration ; }, abstract = {BACKGROUND: Definitions of long COVID are evolving, and optimal models of care are uncertain.<br><br>PURPOSE: To perform a scoping review on definitions of long COVID and provide an overview of care models, including a proposed framework to describe and distinguish models.<br><br>DATA SOURCES: English-language articles from Ovid MEDLINE, PsycINFO, the Cochrane Library, SocINDEX, Scopus, Embase, and CINAHL published between January 2021 and November 2023; gray literature; and discussions with 18 key informants.<br><br>STUDY SELECTION: Publications describing long COVID definitions or models of care, supplemented by models described by key informants.<br><br>DATA EXTRACTION: Data were extracted by one reviewer and verified for accuracy by another reviewer.<br><br>DATA SYNTHESIS: Of 1960 screened citations, 38 were included. Five clinical definitions of long COVID varied with regard to timing since symptom onset and the minimum duration required for diagnosis; 1 additional definition was symptom score-based. Forty-nine long COVID care models were informed by 5 key principles: a core "lead" team, multidisciplinary expertise, comprehensive access to diagnostic and therapeutic services, a patient-centered approach, and providing capacity to meet demand. Seven characteristics provided a framework for distinguishing models: home department or clinical setting, clinical lead, collocation of other specialties, primary care role, population managed, use of teleservices, and whether the model was practice- or systems-based. Using this framework, 10 representative practice-based and 3 systems-based models of care were identified.<br><br>LIMITATIONS: Published literature often lacked key model details, data were insufficient to assess model outcomes, and there was overlap between and variability within models.<br><br>CONCLUSION: Definitions of long COVID and care models are evolving. Research is needed to optimize models and evaluate outcomes of different models.<br><br>PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (Protocol posted at https://effectivehealthcare.ahrq.gov/products/long-covid-models-care/protocol.).}, }
@article {pmid38771409, year = {2024}, author = {Baig, AM and Rosko, S and Jaeger, B and Gerlach, J and Rausch, H}, title = {Unraveling the enigma of long COVID: novel aspects in pathogenesis, diagnosis, and treatment protocols.}, journal = {Inflammopharmacology}, volume = {32}, number = {4}, pages = {2075-2090}, pmid = {38771409}, issn = {1568-5608}, mesh = {Humans ; *COVID-19 ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2/pathogenicity ; Genetic Predisposition to Disease ; COVID-19 Drug Treatment ; Autoimmunity ; }, abstract = {Long COVID, now unmistakably identified as a syndromic entity encompassing a complex spectrum of symptoms, demands immediate resolution of its elusive pathogenic underpinnings. The intricate interplay of diverse factors presents a complex puzzle, difficult to resolve, and thus poses a substantial challenge. As instances of long COVID manifest by repeated infections of SARS-CoV-2 and genetic predisposition, a detailed understanding in this regard is needed. This endeavor is a comprehensive exploration and analysis of the cascading pathogenetic events driven by viral persistence and replication. Beyond its morbidity, long COVID, more disabling than fatal, exacts one of the most substantial tolls on public health in contemporary times, with the potential to cripple national economies. The paper introduces a unified theory of long COVID, detailing a novel pathophysiological framework that interlinks persistent SARS-CoV-2 infection, autoimmunity, and systemic vascular pathology. We posit a model where viral reservoirs, immune dysregulation, and genetic predispositions converge to perpetuate disease. It challenges prevailing hypotheses with new evidence, suggesting innovative diagnostic and therapeutic approaches. The paper aims to shift the paradigm in long COVID research by providing an integrative perspective that encapsulates the multifaceted nature of the condition. We explain the immunological mechanisms, hypercoagulability states, and viral reservoirs in the skull that feed NeuroCOVID in patients with long COVID. Also, this study hints toward a patient approach and how to prioritize treatment sequences in long COVID patients in hospitals and clinics.}, }
@article {pmid38772083, year = {2024}, author = {Silva-Passadouro, B and Tamasauskas, A and Khoja, O and Casson, AJ and Delis, I and Brown, C and Sivan, M}, title = {A systematic review of quantitative EEG findings in Fibromyalgia, Chronic Fatigue Syndrome and Long COVID.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {163}, number = {}, pages = {209-222}, doi = {10.1016/j.clinph.2024.04.019}, pmid = {38772083}, issn = {1872-8952}, support = {MR/N013840/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Fatigue Syndrome, Chronic/physiopathology/diagnosis ; *Fibromyalgia/physiopathology/diagnosis ; *COVID-19/physiopathology/complications ; *Electroencephalography/methods ; Brain/physiopathology ; }, abstract = {Fibromyalgia Syndrome (FMS), Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID (LC) are similar multisymptom clinical syndromes but with difference in dominant symptoms in each individual. There is existing and emerging literature on possible functional alterations of the central nervous system in these conditions. This review aims to synthesise and appraise the literature on resting-state quantitative EEG (qEEG) in FMS, ME/CFS and LC, drawing on previous research on FMS and ME/CFS to help understand neuropathophysiology of the new condition LC. A systematic search of MEDLINE, Embase, CINHAL, PsycINFO and Web of Science databases for articles published between December 1994 and September 2023 was performed. Out of the initial 2510 studies identified, 17 articles were retrieved that met all the predetermined selection criteria, particularly of assessing qEEG changes in one of the three conditions compared to healthy controls. All studies scored moderate to high quality on the Newcastle-Ottawa scale. There was a general trend for decreased low-frequency EEG band activity (delta, theta, and alpha) and increased high-frequency EEG beta activity in FMS, differing to that found in ME/CFS. The limited LC studies included in this review focused mainly on cognitive impairments and showed mixed findings not consistent with patterns observed in FMS and ME/CFS. Our findings suggest different patterns of qEEG brainwave activity in FMS and ME/CFS. Further research is required to explore whether there are phenotypes within LC that have EEG signatures similar to FMS or ME/CFS. This could inform identification of reliable diagnostic markers and possible targets for neuromodulation therapies tailored to each clinical syndrome.}, }
@article {pmid38774167, year = {2024}, author = {Olumuyide, E and Agwuegbo, CC and Ahmed, EN}, title = {Exploring the Heart Failure Connection in Long COVID Patients: A Narrative Review.}, journal = {Cureus}, volume = {16}, number = {4}, pages = {e58694}, pmid = {38774167}, issn = {2168-8184}, abstract = {In this narrative review, we explore the relationship between long COVID patients and their risk of developing heart failure (HF). Patients with long COVID face a heightened risk of HF, a critical cardiovascular complication linked to the prolonged effects of COVID-19. Clinical manifestations of long COVID-associated HF present diagnostic challenges, complicating patient management. Multidisciplinary care is essential to address these complexities effectively. We found that long COVID can result in various cardiovascular issues including HF. The current view is long COVID leads to HF by activating systemic inflammation by causing endothelial dysfunction, which leads to activation of the complement pathways, tissue factor pathways, and Von Willebrand factor; activation of all these factors leads to venous and arterial thrombosis, which could lead to clogging of blood vessel of the heart leading to cardiovascular complications. The association between long COVID and HF can be challenging despite being recognized as comorbidity because biomarkers are not dependable in determining whether a patient had HF before or after contracting COVID-19. Emerging therapeutic modalities offer hope for improving outcomes, but further research is needed to refine management strategies and mitigate long-term cardiovascular consequences of COVID-19.}, }
@article {pmid38775379, year = {2024}, author = {Li, AY and Li, WX and Li, J}, title = {Emerging trends in management of long COVID with a focus on pulmonary rehabilitation: A review.}, journal = {The clinical respiratory journal}, volume = {18}, number = {5}, pages = {e13777}, pmid = {38775379}, issn = {1752-699X}, mesh = {Humans ; *COVID-19/epidemiology/rehabilitation ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; Quality of Life ; Telemedicine/trends ; Dyspnea/etiology/rehabilitation ; Exercise Therapy/methods ; Critical Illness ; }, abstract = {Long COVID, or post-acute sequelae of COVID-19 (PASC), represents a complex condition with persistent symptoms following SARS-Cov-2 infection. The symptoms include fatigue, dyspnoea, cognitive impairment, decreased quality of life in variable levels of severity. Potential mechanisms behind long COVID include vascular damage, immune dysregulation and viral persistence. Diagnosing long COVID involves medical evaluation by multidisciplinary team and assessment of persistent symptoms with scoring systems in development. Treatment strategies are symptom-focused, encompassing multidisciplinary care, rehabilitation and tailored exercise programmes. Pulmonary rehabilitation, an effective and critical component of long COVID management, has shown promise, particularly for patients with respiratory symptoms such as dyspnoea. These programmes, which combine exercise, breathing techniques, education and psychological support, improve symptoms, quality of life and overall recovery. Innovative technologies, such as telemedicine, wearable devices, telerehabilitation, are transforming long COVID management. Telemedicine facilitates consultations and interventions, eliminating healthcare access barriers. Wearable devices enable remote and continuous monitoring of patients during their rehabilitation activities. Telerehabilitation has proven to be safe and feasible and to have high potential for COVID-19 recovery. This review provides a concise overview of long COVID, encompassing its definition, prevalence, mechanisms, clinical manifestations, diagnosis and management approaches. It emphasizes the significance of multidisciplinary approach in diagnosis and treatment of long COVID, with focus on pulmonary rehabilitation and innovative technology advances to effectively address the management of long COVID.}, }
@article {pmid38776716, year = {2024}, author = {Svensson Akusjärvi, S and Zanoni, I}, title = {Yin and yang of interferons: lessons from the coronavirus disease 2019 (COVID-19) pandemic.}, journal = {Current opinion in immunology}, volume = {87}, number = {}, pages = {102423}, pmid = {38776716}, issn = {1879-0372}, support = {R01 AI121066/AI/NIAID NIH HHS/United States ; R01 AI165505/AI/NIAID NIH HHS/United States ; R01 AI170632/AI/NIAID NIH HHS/United States ; R01 DK115217/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/immunology ; *Interferons/immunology/metabolism ; *SARS-CoV-2/immunology ; Pandemics ; Animals ; Yin-Yang ; }, abstract = {The host immune response against severe acute respiratory syndrome coronavirus 2 includes the induction of a group of natural antiviral cytokines called interferons (IFNs). Although originally recognized for their ability to potently counteract infections, the mechanistic functions of IFNs in patients with varying severities of coronavirus disease 2019 (COVID-19) have highlighted a more complex scenario. Cellular and molecular analyses have revealed that timing, location, and subtypes of IFNs produced during severe acute respiratory syndrome coronavirus 2 infection play a major role in determining disease progression and severity. In this review, we summarize what the COVID-19 pandemic has taught us about the protective and detrimental roles of IFNs during the inflammatory response elicited against a new respiratory virus across different ages and its longitudinal consequences in driving the development of long COVID-19.}, }
@article {pmid38779550, year = {2024}, author = {Tunnell, NC and Corner, SE and Roque, AD and Kroll, JL and Ritz, T and Meuret, AE}, title = {Biobehavioral approach to distinguishing panic symptoms from medical illness.}, journal = {Frontiers in psychiatry}, volume = {15}, number = {}, pages = {1296569}, pmid = {38779550}, issn = {1664-0640}, abstract = {Panic disorder is a common psychiatric diagnosis characterized by acute, distressing somatic symptoms that mimic medically-relevant symptoms. As a result, individuals with panic disorder overutilize personal and healthcare resources in an attempt to diagnose and treat physical symptoms that are often medically benign. A biobehavioral perspective on these symptoms is needed that integrates psychological and medical knowledge to avoid costly treatments and prolonged suffering. This narrative review examines six common somatic symptoms of panic attacks (non-cardiac chest pain, palpitations, dyspnea, dizziness, abdominal distress, and paresthesia), identified in the literature as the most severe, prevalent, or critical for differential diagnosis in somatic illness, including long COVID. We review somatic illnesses that are commonly comorbid or produce panic-like symptoms, their relevant risk factors, characteristics that assist in distinguishing them from panic, and treatment approaches that are typical for these conditions. Additionally, this review discusses key factors, including cultural considerations, to assist healthcare professionals in differentiating benign from medically relevant symptoms in panic sufferers.}, }
@article {pmid38782355, year = {2024}, author = {Ramonfaur, D and Ayad, N and Liu, PHZ and Zhou, J and Wu, Y and Li, J and Chen, G}, title = {The global clinical studies of long COVID.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {146}, number = {}, pages = {107105}, doi = {10.1016/j.ijid.2024.107105}, pmid = {38782355}, issn = {1878-3511}, mesh = {Humans ; *COVID-19/epidemiology/therapy ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Clinical Trials as Topic ; Global Health ; COVID-19 Drug Treatment ; United States/epidemiology ; }, abstract = {People with long COVID are those who still have symptoms, signs, and conditions after the initial phase of infection of SARS-CoV-2. The incidence of long COVID varies among regions-31% in North America, 44% in Europe, and 51% in Asia, which is challenging the healthcare system, but there is limited guidelines for its treatment. With more and more nationwide projects funded by the government such as the RECOVER initiative in the United States and National Institute for Health Research funding in the United Kingdom, an increasing number of ongoing clinical trials are investigating the efficacy of diverse therapies on reversing long COVID. After searching the World Health Organization International Clinical Trial Registry Platform, 587 clinical studies are identified as long COVID studies. Among these, 312 studies (53.2%) are testing potential therapies. Most of the long COVID trials were conducted in the United States (58 trials [18.6%]), followed by India (55 trials [17.6%]), and Spain (20 trials [6.4%]). Interventions in these clinical trials include physical exercise, rehabilitation therapy, behavioral therapy, and pharmacological therapies including herbs, paxlovid, and fluvoxamine. These trials are aiming to deal with these long COVID symptoms and signs including fatigue, decreased pulmonary function, reduced cognitive function, and others. To date, only 11 of these 312 studies have published their results that were not confirmative, unfortunately. Future studies should be designed to address sleep disorders which were seldomly included in registered clinical studies. Moreover, interventions aimed at treating the underlying pathophysiology of long COVID are also necessary but currently lacking.}, }
@article {pmid38785750, year = {2024}, author = {Calcaterra, V and Zanelli, S and Foppiani, A and Verduci, E and Benatti, B and Bollina, R and Bombaci, F and Brucato, A and Cammarata, S and Calabrò, E and Cirnigliaro, G and Della Torre, S and Dell'osso, B and Moltrasio, C and Marzano, AV and Nostro, C and Romagnuolo, M and Trotta, L and Savasi, V and Smiroldo, V and Zuccotti, G}, title = {Long COVID in Children, Adults, and Vulnerable Populations: A Comprehensive Overview for an Integrated Approach.}, journal = {Diseases (Basel, Switzerland)}, volume = {12}, number = {5}, pages = {}, pmid = {38785750}, issn = {2079-9721}, abstract = {Long COVID affects both children and adults, including subjects who experienced severe, mild, or even asymptomatic SARS-CoV-2 infection. We have provided a comprehensive overview of the incidence, clinical characteristics, risk factors, and outcomes of persistent COVID-19 symptoms in both children and adults, encompassing vulnerable populations, such as pregnant women and oncological patients. Our objective is to emphasize the critical significance of adopting an integrated approach for the early detection and appropriate management of long COVID. The incidence and severity of long COVID symptoms can have a significant impact on the quality of life of patients and the course of disease in the case of pre-existing pathologies. Particularly, in fragile and vulnerable patients, the presence of PASC is related to significantly worse survival, independent from pre-existing vulnerabilities and treatment. It is important try to achieve an early recognition and management. Various mechanisms are implicated, resulting in a wide range of clinical presentations. Understanding the specific mechanisms and risk factors involved in long COVID is crucial for tailoring effective interventions and support strategies. Management approaches involve comprehensive biopsychosocial assessments and treatment of symptoms and comorbidities, such as autonomic dysfunction, as well as multidisciplinary rehabilitation. The overall course of long COVID is one of gradual improvement, with recovery observed in the majority, though not all, of patients. As the research on long-COVID continues to evolve, ongoing studies are likely to shed more light on the intricate relationship between chronic diseases, such as oncological status, cardiovascular diseases, psychiatric disorders, and the persistent effects of SARS-CoV-2 infection. This information could guide healthcare providers, researchers, and policymakers in developing targeted interventions.}, }
@article {pmid38791759, year = {2024}, author = {Gebremeskel, TG and Romeo, F and Shama, AT and Bonevski, B and Trigg, J}, title = {Facilitators and Barriers to Lung Cancer Screening during Long COVID: A Global Systematic Review and Meta-Study Synthesis of Qualitative Research.}, journal = {International journal of environmental research and public health}, volume = {21}, number = {5}, pages = {}, pmid = {38791759}, issn = {1660-4601}, mesh = {Humans ; *Lung Neoplasms/diagnosis/psychology ; *COVID-19/psychology ; *Early Detection of Cancer/psychology ; *Qualitative Research ; SARS-CoV-2 ; }, abstract = {Background: Participation in targeted screening reduces lung cancer mortality by 30-60%, but screening is not universally available. Therefore, the study aimed to synthesize the evidence and identify facilitators and barriers to lung cancer screening participation globally. Methods: Two reviewers screened primary studies using qualitative methods published up to February 2023. We used two-phase synthesis consistent with a meta-study methodology to create an interpretation of lung cancer screening decisions grounded in primary studies, carried out a thematic analysis of group themes as specific facilitators and barriers, systematically compared investigations for similarities and differences, and performed meta-synthesis to generate an expanded theory of lung cancer screening participation. We used the Social Ecological Model to organize and interpret the themes: individual, interpersonal, social/cultural, and organizational/structural levels. Results: Fifty-two articles met the final inclusion criteria. Themes identified as facilitating lung cancer screening included prioritizing patient education, quality of communication, and quality of provider-initiated encounter/coordination of care (individual patient and provider level), quality of the patient-provider relationship (interpersonal group), perception of a life's value and purpose (cultural status), quality of tools designed, and care coordination (and organizational level). Themes coded as barriers included low awareness, fear of cancer diagnosis, low perceived benefit, high perceived risk of low-dose computerized tomography, concern about cancer itself, practical obstacle, futility, stigma, lack of family support, COVID-19 fear, disruptions in cancer care due to COVID-19, inadequate knowledge of care providers, shared decision, and inadequate time (individual level), patient misunderstanding, poor rapport, provider recommendation, lack of established relationship, and confusing decision aid tools (interpersonal group), distrust in the service, fatalistic beliefs, and perception of aging (cultural level), and lack of institutional policy, lack of care coordinators, inadequate infrastructure, absence of insurance coverage, and costs (and organizational status). Conclusions: This study identified critical barriers, facilitators, and implications to lung cancer screening participation. Therefore, we employed strategies for a new digital medicine (artificial intelligence) screening method to balance the cost-benefit, "workdays" lost in case of disease, and family hardship, which is essential to improve lung cancer screening uptake.}, }
@article {pmid38793710, year = {2024}, author = {Kumar, A and Tripathi, P and Kumar, P and Shekhar, R and Pathak, R}, title = {From Detection to Protection: Antibodies and Their Crucial Role in Diagnosing and Combatting SARS-CoV-2.}, journal = {Vaccines}, volume = {12}, number = {5}, pages = {}, pmid = {38793710}, issn = {2076-393X}, abstract = {Understanding the antibody response to SARS-CoV-2, the virus responsible for COVID-19, is crucial to comprehending disease progression and the significance of vaccine and therapeutic development. The emergence of highly contagious variants poses a significant challenge to humoral immunity, underscoring the necessity of grasping the intricacies of specific antibodies. This review emphasizes the pivotal role of antibodies in shaping immune responses and their implications for diagnosing, preventing, and treating SARS-CoV-2 infection. It delves into the kinetics and characteristics of the antibody response to SARS-CoV-2 and explores current antibody-based diagnostics, discussing their strengths, clinical utility, and limitations. Furthermore, we underscore the therapeutic potential of SARS-CoV-2-specific antibodies, discussing various antibody-based therapies such as monoclonal antibodies, polyclonal antibodies, anti-cytokines, convalescent plasma, and hyperimmunoglobulin-based therapies. Moreover, we offer insights into antibody responses to SARS-CoV-2 vaccines, emphasizing the significance of neutralizing antibodies in order to confer immunity to SARS-CoV-2, along with emerging variants of concern (VOCs) and circulating Omicron subvariants. We also highlight challenges in the field, such as the risks of antibody-dependent enhancement (ADE) for SARS-CoV-2 antibodies, and shed light on the challenges associated with the original antigenic sin (OAS) effect and long COVID. Overall, this review intends to provide valuable insights, which are crucial to advancing sensitive diagnostic tools, identifying efficient antibody-based therapeutics, and developing effective vaccines to combat the evolving threat of SARS-CoV-2 variants on a global scale.}, }
@article {pmid38800038, year = {2024}, author = {Sadowski, J and Klaudel, T and Rombel-Bryzek, A and Bułdak, RJ}, title = {Cognitive dysfunctions in the course of SARS‑CoV‑2 virus infection, including NeuroCOVID, frontal syndrome and cytokine storm (Review).}, journal = {Biomedical reports}, volume = {21}, number = {1}, pages = {103}, pmid = {38800038}, issn = {2049-9442}, abstract = {During the coronavirus disease 2019 (COVID-19) pandemic, cognitive impairment of varying degrees of severity began to be observed in a significant percentage of patients. The present study discussed the impact of immunological processes on structural and functional changes in the central nervous system and the related cognitive disorders. The purpose of the present review was to analyse and discuss available information from the scientific literature considering the possible relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection and cognitive impairment, including NeuroCOVID, frontal syndrome and cytokine storm. A systematic literature review was conducted using: Google Scholar, Elsevier and the PubMed database. When searching for materials, the following keywords were used: 'cognitive dysfunctions', 'SARS-CoV-2', 'COVID-19', 'Neuro-SARS2', 'NeuroCOVID', 'frontal syndrome', 'cytokine storm', 'Long COVID-19'. A total of 96 articles were included in the study. The analysis focused on the characteristics of each study's materials, methods, results and conclusions. SARS-CoV-2 infection may induce or influence existing cognitive disorders of various nature and severity. The influence of immunological factors related to the response against SARS-CoV-2 on the disturbance of cerebral perfusion, the functioning of nerve cells and the neuroprotective effect has been demonstrated. Particular importance is attached to the cytokine storm and the related difference between pro- and anti-inflammatory effects, oxidative stress, disturbances in the regulation of the hypothalamic-pituitary-adrenal axis and the stress response of the body.}, }
@article {pmid38800959, year = {2024}, author = {Calvache-Mateo, A and Reychler, G and Heredia-Ciuró, A and Martín-Núñez, J and Ortiz-Rubio, A and Navas-Otero, A and Valenza, MC}, title = {Respiratory training effects in Long COVID-19 patients: a systematic review and meta-analysis.}, journal = {Expert review of respiratory medicine}, volume = {18}, number = {3-4}, pages = {207-217}, doi = {10.1080/17476348.2024.2358933}, pmid = {38800959}, issn = {1747-6356}, mesh = {Humans ; *COVID-19 ; *Breathing Exercises ; *Muscle Strength ; *Respiratory Muscles/physiopathology ; Dyspnea/physiopathology ; SARS-CoV-2 ; Randomized Controlled Trials as Topic ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: To date, it is unknown whether respiratory training interventions can benefit Long COVID-19 patients. The main objective was to analyze the effects of respiratory training on patients with Long COVID-19, concretely on respiratory muscle strength, lung function, dyspnea, and functional capacity.<br><br>METHODS: We performed a systematic review following PRISMA statement using PubMed, Scopus, and PEDro (last search November 2023). The risk of bias was assessed using the Cochrane tool. We included randomized controlled trials testing the effect of respiratory training interventions in Long COVID-19 patients versus no intervention, control, or placebo intervention. The data was pooled, and a meta-analysis was complete.<br><br>RESULTS: We selected 7 studies, which included 572 patients. Meta-analysis results show significant differences in favor of respiratory training in respiratory muscle strength (MD&#x2009;=&#x2009;13.71; 95% CI&#x2009;=&#x2009;5.41; 22; p&#x2009;=&#x2009;0.001), dyspnea (SDM&#x2009;=&#x2009;1.39; 95% CI&#x2009;=&#x2009;0.33; 2.46; p&#x2009;=&#x2009;0.01) and functional capacity (SDM&#x2009;=&#x2009;0.90; 95% CI&#x2009;=&#x2009;0.37; 1.43; p&#x2009;=&#x2009;0.0009), but not in lung function (MD&#x2009;=&#x2009;0.28; 95%CI&#x2009;=&#x2009;-0.27; 0.83; p&#x2009;=&#x2009;0.32).<br><br>CONCLUSION: The results of this systematic review with meta-analysis suggest that respiratory training improves respiratory muscle strength and functional capacity in Long COVID-19 patients, as well as dyspnea if combined with therapeutic exercise. However, respiratory training does not improve lung function in these patients.<br><br>CRD42022371820.}, }
@article {pmid38802702, year = {2024}, author = {Dehhaghi, M and Heydari, M and Panahi, HKS and Lewin, SR and Heng, B and Brew, BJ and Guillemin, GJ}, title = {The roles of the kynurenine pathway in COVID-19 neuropathogenesis.}, journal = {Infection}, volume = {52}, number = {5}, pages = {2043-2059}, pmid = {38802702}, issn = {1439-0973}, support = {Macquarie University Research Excellence Scholarship//Macquarie University/ ; APP1176660//National Health and Medical Research Council/ ; }, mesh = {*Kynurenine/metabolism ; Humans ; *COVID-19/metabolism ; *SARS-CoV-2 ; Cytokines/metabolism ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism ; Cytokine Release Syndrome ; Post-Acute COVID-19 Syndrome ; Tryptophan/metabolism ; }, abstract = {The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the highly contagious respiratory disease Corona Virus Disease 2019 (COVID-19) that may lead to various neurological and psychological disorders that can be acute, lasting days to weeks or months and possibly longer. The latter is known as long-COVID or more recently post-acute sequelae of COVID (PASC). During acute COVID-19 infection, a strong inflammatory response, known as the cytokine storm, occurs in some patients. The levels of interferon-γ (IFN-γ), interferon-β (IFN-β), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) are particularly increased. These cytokines are known to activate the enzyme indoleamine 2,3-dioxygenase 1 (IDO-1), catalysing the first step of tryptophan (Trp) catabolism through the kynurenine pathway (KP) leading to the production of several neurotoxic and immunosuppressive metabolites. There is already data showing elevation in KP metabolites both acutely and in PASC, especially regarding cognitive impairment. Thus, it is likely that KP involvement is significant in SARS-CoV-2 pathogenesis especially neurologically.}, }
@article {pmid38807958, year = {2024}, author = {Antonelli, M and Donelli, D}, title = {Evaluating qigong as integrative support for COVID-19 and Long-COVID-19 rehabilitation: a systematic review.}, journal = {Frontiers in psychology}, volume = {15}, number = {}, pages = {1403130}, pmid = {38807958}, issn = {1664-1078}, abstract = {INTRODUCTION: Amidst the ongoing global impact of COVID-19 on public health, there is an increasing focus on holistic strategies encompassing integrative therapies and rehabilitation techniques, particularly in addressing the challenges posed by Long-COVID-19. This review investigates the potential of Qigong, an ancient Chinese practice characterized by gentle movements, controlled breathing, and meditative elements, within the context of COVID-19.<br><br>METHODS: A systematic search of PubMed, EMBASE, Web of Science, Scopus, and Google Scholar was conducted to identify pertinent clinical studies.<br><br>RESULTS: Following thorough database scrutiny, nine studies were identified as meeting the eligibility criteria. Across the spectrum of COVID-19 severity, individuals engaging in qigong practice exhibited notable enhancements in both physical and psychological wellbeing, evidenced by ameliorated respiratory symptoms, reduced anxiety levels, enhanced sleep quality, bolstered mental wellbeing, and augmented health-related quality of life. Moreover, qigong training, whether employed independently or in conjunction with other therapies, demonstrated beneficial effects on Long-COVID-19 symptoms, encompassing persistent respiratory issues, dizziness, sleep disturbances, and compromised health-related quality of life.<br><br>DISCUSSION: This review underscores the necessity for further investigation to quantify and standardize the contribution of Qigong to COVID-19 recovery and rehabilitation. Such endeavors aim to integrate this accessible and low-impact practice into public health strategies and comprehensive treatment regimens.<br><br>The review protocol was registered in the Open Science Framework under the following doi: 10.17605/OSF.IO/7K5X6 (URL: https://osf.io/7k5x6).}, }
@article {pmid38808005, year = {2024}, author = {Dhiman, NR and Joshi, D and Singh, R and Gyanpuri, V and Kumar, A}, title = {Post-COVID-19 headache- NDPH phenotype: a systematic review of case reports.}, journal = {Frontiers in pain research (Lausanne, Switzerland)}, volume = {5}, number = {}, pages = {1376506}, pmid = {38808005}, issn = {2673-561X}, abstract = {BACKGROUND AND OBJECTIVES: Post-acute COVID-19 syndrome or "long COVID" affects patients even after the recovery from Covid infection in various ways. Persistent headache or New Daily Persistent Headache (NDPH) is one of such symptoms. In this review, we will discuss about the case-reports of post covid-19 headache- NDPH phenotype both after and in the course of COVID-19 infection.<br><br>METHODS: Case reports/studies talked about patients having NDPH around the disease either immediately or late post COVID were included. Data was taken from the source and synthesised on a qualitative basis.<br><br>RESULTS: Literature search showed 3,538 articles, out of which 12 were screened as per the eligibility criteria and finally, 4 case reports on NDPH and Covid-19 were chosen for analysis from the database and by human search. All case reports justify the criteria for acceptability in quality for this systematic review.<br><br>CONCLUSION: NDPH in and around Covid 19 infection is something that is currently an ingenious debated topic in the scientific community. More case studies should be written and published on the same subject so that a large systematic review could be conducted.<br><br>The review is registered in Prospero with no. Identifier (CRD42022354912).<br><br>https://www.crd.york.ac.uk/, PROSPERO (CRD42022354912).}, }
@article {pmid38818469, year = {2024}, author = {Li, J and Huang, Q and Liang, Y and Jiang, J and Yang, Y and Feng, J and Tan, X and Li, T}, title = {The Potential Mechanisms of Arrhythmia in Coronavirus disease-2019.}, journal = {International journal of medical sciences}, volume = {21}, number = {7}, pages = {1366-1377}, pmid = {38818469}, issn = {1449-1907}, mesh = {Humans ; *COVID-19/complications/immunology/virology ; *Arrhythmias, Cardiac/etiology/virology/physiopathology ; *SARS-CoV-2 ; }, abstract = {Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) leads to coronavirus disease-2019 (COVID-19) which can cause severe cardiovascular complications including myocardial injury, arrhythmias, acute coronary syndrome and others. Among these complications, arrhythmias are considered serious and life-threatening. Although arrhythmias have been associated with factors such as direct virus invasion leading to myocardial injury, myocarditis, immune response disorder, cytokine storms, myocardial ischemia/hypoxia, electrolyte abnormalities, intravascular volume imbalances, drug interactions, side effects of COVID-19 vaccines and autonomic nervous system dysfunction, the exact mechanisms of arrhythmic complications in patients with COVID-19 are complex and not well understood. In the present review, the literature was extensively searched to investigate the potential mechanisms of arrhythmias in patients with COVID-19. The aim of the current review is to provide clinicians with a comprehensive foundation for the prevention and treatment of arrhythmias associated with long COVID-19.}, }
@article {pmid38819890, year = {2024}, author = {Dalko, K and Elsuson, HA and Kalter, I and Zilezinski, M and Hofstetter, S and Stoevesandt, D and Paulicke, D and Jahn, P}, title = {Virtual Reality Applications for the Implementation of Domestic Respiratory Rehabilitation Programs for Patients With Long COVID and Post-COVID Condition: Scoping Review.}, journal = {JMIR serious games}, volume = {12}, number = {}, pages = {e52309}, pmid = {38819890}, issn = {2291-9279}, abstract = {BACKGROUND: Due to a high number of patients affected by long COVID or post-COVID condition, an essential step to address the long-term effects of COVID-19 lies in the development and implementation of flexible and accessible rehabilitation programs. Virtual reality (VR) technologies offer the potential to support traditional therapies with individualized at-home programs.<br><br>OBJECTIVE: This study aims to provide an overview of existing scientific evidence on the development and implementation of VR-assisted respiratory rehabilitation programs for patients with long COVID and post-COVID condition and to synthesize the results.<br><br>METHODS: We conducted a scoping review of studies from 6 databases. PubMed, CINAHL, Cochrane, ScienceDirect, Web of Science Social Sciences Citation Index, and PEDro were searched using an exploratory search strategy. The search, which was last updated in February 2024, included peer-reviewed studies on immersive VR applications providing respiratory rehabilitation programs for patients with chronic obstructive pulmonary disease and long COVID or post-COVID condition. Exclusion criteria were studies in clinical or inpatient settings, telemedicine, nonimmersive VR applications, and gray literature. Nine publications were included in this review. Findings were extracted and summarized from the studies according to the JBI (Joanna Briggs Institute) method and thematically categorized. Topics covered were study characteristics, physiotherapeutic concept, clinical parameters, as well as usability and acceptability.<br><br>RESULTS: The 9 publications included in the qualitative analysis were published in 2019-2023. Eight empirical studies were included: 4 followed a mixed methods design, 3 were qualitative studies, and 1 followed a quantitative method. One scoping review was included in the data analyses. Four of the included studies were on patients with chronic obstructive pulmonary disease. The 9 studies demonstrated that VR-supported respiratory rehabilitation programs result in positive initial outcomes in terms of physical as well as psychological parameters. Particularly noteworthy was the increased motivation and compliance of patients. However, adverse effects and lack of usability are the barriers to the implementation of this innovative approach.<br><br>CONCLUSIONS: Overall, VR is a promising technology for the implementation of individualized and flexible respiratory rehabilitation programs for patients with long COVID and post-COVID condition. Nevertheless, corresponding approaches are still under development and need to be more closely adapted to the needs of users. Further, the evidence was limited to pilot studies or a small number of patients, and no randomized controlled trials or long-term studies were part of the study selection. The included studies were performed by 4 groups of researchers: 3 from Europe and 1 from the United States.}, }
@article {pmid38826995, year = {2024}, author = {Prusinski, C and Yan, D and Klasova, J and McVeigh, KH and Shah, SZ and Fermo, OP and Kubrova, E and Farr, EM and Williams, LC and Gerardo-Manrique, G and Bergquist, TF and Pham, SM and Engelberg-Cook, E and Hare, JM and March, KL and Caplan, AI and Qu, W}, title = {Multidisciplinary Management Strategies for Long COVID: A Narrative Review.}, journal = {Cureus}, volume = {16}, number = {5}, pages = {e59478}, pmid = {38826995}, issn = {2168-8184}, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of infections to date and has led to a worldwide pandemic. Most patients had a complete recovery from the acute infection, however, a large number of the affected individuals experienced symptoms that persisted more than 3 months after diagnosis. These symptoms most commonly include fatigue, memory difficulties, brain fog, dyspnea, cough, and other less common ones such as headache, chest pain, paresthesias, mood changes, muscle pain, and weakness, skin rashes, and cardiac, endocrine, renal and hepatic manifestations. The treatment of this syndrome remains challenging. A multidisciplinary approach to address combinations of symptoms affecting multiple organ systems has been widely adopted. This narrative review aims to bridge the gap surrounding the broad treatment approaches by providing an overview of multidisciplinary management strategies for the most common long COVID conditions.}, }
@article {pmid38827572, year = {2021}, author = {Montes de Oca-B, P}, title = {Evidence of mitochondria origin of SARS-CoV-2 double-membrane vesicles: a review.}, journal = {F1000Research}, volume = {10}, number = {}, pages = {1009}, pmid = {38827572}, issn = {2046-1402}, mesh = {Humans ; *SARS-CoV-2/physiology ; *COVID-19/virology ; *Mitochondria/metabolism/virology ; Virus Replication ; *Mitochondrial Membranes/virology/metabolism ; }, abstract = {Coronavirus Disease-19 (COVID-19) pandemic is caused by SARS-CoV-2 that has infected more than 600 million people and killed more than 6 million people worldwide. This infection affects mainly certain groups of people that have high susceptibility to present severe COVID-19 due to comorbidities. Moreover, the long-COVID-19 comprises a series of symptoms that may remain in some patients for months after infection that further compromises their health. Thus, since this pandemic is profoundly affecting health, economy, and social life of societies, a deeper understanding of viral replication cycle could help to envisage novel therapeutic alternatives that limit or stop COVID-19. Several findings have unexpectedly discovered that mitochondria play a critical role in SARS-CoV-2 cell infection. Indeed, it has been suggested that this organelle could be the origin of its replication niches, the double membrane vesicles (DMV). In this regard, mitochondria derived vesicles (MDV), involved in mitochondria quality control, discovered almost 15 years ago, comprise a subpopulation characterized by a double membrane. MDV shedding is induced by mitochondrial stress, and it has a fast assembly dynamic, reason that perhaps has precluded their identification in electron microscopy or tomography studies. These and other features of MDV together with recent SARS-CoV-2 protein interactome and other findings link SARS-CoV-2 to mitochondria and support that these vesicles are the precursors of SARS-CoV-2 induced DMV. In this work, the morphological, biochemical, molecular, and cellular evidence that supports this hypothesis is reviewed and integrated into the current model of SARS-CoV-2 cell infection. In this scheme, some relevant questions are raised as pending topics for research that would help in the near future to test this hypothesis. The intention of this work is to provide a novel framework that could open new possibilities to tackle SARS-CoV-2 pandemic through mitochondria and DMV targeted therapies.}, }
@article {pmid38827682, year = {2024}, author = {Ranjan, A and Agarwal, R and Mudgal, SK and Bhattacharya, S and Kumar, B}, title = {Young hearts at risk: Unveiling novel factors in myocardial infarction susceptibility and prevention.}, journal = {Journal of family medicine and primary care}, volume = {13}, number = {4}, pages = {1200-1205}, pmid = {38827682}, issn = {2249-4863}, abstract = {The increasing incidence of acute myocardial infarction (AMI) among the young population represents a significant and emerging health concern, contributing substantially to both mortality and morbidity. Unlike myocardial infarctions occurring in older individuals, traditional risk factors such as diabetes and hypertension exhibit a weaker association in the younger demographic. Consequently, there is a pressing need for a deeper understanding of novel risk factors that contribute to AMI in young patients. In this review, we explore distinct risk factor profiles associated with young-onset AMI in comparison to older patients. Special attention is given to novel risk factors, examining their susceptibility factors and exploring preventive measures. The comprehensive risk profile of extremely young South Asians who develop early coronary arterial disease is not yet fully understood. There are many novel evolving risk factors associated with young AMI which need intervention to reduce morbidity and mortality. It has been seen that established inflammatory markers like lipoprotein (a), dyslipidaemia, long COVID, and new emerging risk factors like air pollution (micro- and nanoplastics), periodontitis, acute stress, energy drinks, misuse of recreational drugs may increase risk and influence treatment, and outcomes of AMI in this young population. Screening of emerging novel risk markers and their optimization is important in preventing young patients with AMI. The role of conventional risk factors should not be overlooked and should be treated aggressively. Sex and geographic-specific base approaches are required to reduce risk factors and prevent AMI in young. More prospective studies are needed to evaluate the increasing incidence of young AMI and its associated novel risk factors.}, }
@article {pmid38829253, year = {2024}, author = {Julide, T and Cigdem, T and Baris, T}, title = {Cognitive impairment in long-COVID.}, journal = {Ideggyogyaszati szemle}, volume = {77}, number = {5-6}, pages = {151-159}, doi = {10.18071/isz.77.0151}, pmid = {38829253}, issn = {0019-1442}, mesh = {Humans ; *COVID-19/complications/psychology ; *Cognitive Dysfunction/etiology/physiopathology/virology ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Risk Factors ; }, abstract = {Long Covid is a complex condition characterised by symptoms that persist for weeks and months after the Covid infection, accompanied by cognitive impairment that negatively affects daily life. Understanding this complex condition is important for the development of diagnostic and therapeutic strategies.This article aims to provide a comprehensive overview of cognitive impairment in long-COVID, including its definition, symptoms, pathophysiology, risk factors, assessment tools, imaging abnormalities, potential biomarkers, management strategies, long-term outcomes, and future directions for research.Methods - The search methodology used in this review aimed to include a wide range of research on cognitive impairment related to both COVID-19 and long-COVID. Systematic searches of PubMed and Google Scholar databases were conducted using a mixture of MeSH terms and keywords including 'cognition', 'cognitive impairment', 'brain fog', 'COVID-19' and 'long-COVID'. The search was restricted to studies published in English between 1 January 2019 and 11 February 2024, which presented findings on neurological manifestations in human participants. Results - Long-COVID is characterized by persistent symptoms following COVID-19 infection, with cognitive impairment being a prominent feature. Symptoms include brain fog, difficulties with concentration, memory issues, and executive function deficits. Pathophysiological mechanisms involve viral persistence, immune responses, and vascular damage. Risk factors include age, pre-existing conditions, and disease severity. Cognitive assessment tools such as the Montreal Cognitive Assessment (MoCA) are essential for diagnosis. Imaging studies, including MRI, PET, and SPECT, reveal structural and functional brain alterations. Potential biomarkers include C-reactive protein, interleukin-6, and neuron-specific enolase. Management strategies encompass cognitive rehabilitation, occupational therapy, medications, and lifestyle modifications. Conclusion - Long-COVID poses a multifaceted challenge, and cognitive impairment significantly impacts patients' lives. A multidisciplinary approach, including cognitive rehabilitation and medication when appropriate, is essential for effective management. Future research should focus on validating biomarkers and understanding long-term cognitive outcomes. Conclusion - Long-COVID is a global health concern, and cognitive impairment is a distressing symptom. While pharmacological interventions have potential, they require careful consideration. Continued research is crucial for improving the understanding and treatment of cognitive impairment in long-COVID.}, }
@article {pmid38831890, year = {2024}, author = {Zou, XY and Liu, XH and Lu, CL and Jin, XY and He, BX and Liao, YL and Liu, T and Dai, YD and Qi, SH and Sheng, ZJ and Yan, ZF and Yang, GY and Stub, T and Liu, JP}, title = {Traditional Chinese medicine for post-viral olfactory dysfunction: A systematic review.}, journal = {Integrative medicine research}, volume = {13}, number = {2}, pages = {101045}, pmid = {38831890}, issn = {2213-4220}, abstract = {BACKGROUND: Post-viral olfactory dysfunction (PVOD) is the common symptoms of long COVID, lacking of effective treatments. Traditional Chinese medicine (TCM) is claimed to be effective in treating olfactory dysfunction, but the evidence has not yet been critically appraised. We conducted a systematic review to evaluate the effectiveness and safety of TCM for PVOD.<br><br>METHODS: We searched eight databases to identified clinical controlled studies about TCM for PVOD. The Cochrane risk of bias tools and GRADE were used to evaluate the quality of evidence. Risk ratio (RR), mean differences (MD), and 95 % confidence interval (CI), were used for effect estimation and RevMan 5.4.1 was used for data analysis.<br><br>RESULTS: Six randomized controlled trials (RCTs) (545 participants), two non-randomized controlled trials (non-RCTs) (112 participants), and one retrospective cohort study (30 participants) were included. The overall quality of included studies was low. Acupuncture (n = 8) and acupoint injection (n = 3) were the mainly used TCM therapies. Five RCTs showed a better effect in TCM group. Four trials used acupuncture, and three trials used acupoint injection. The results of two non-RCTs and one cohort study were not statistically significant. Two trials reported mild to moderate adverse events (pain and brief syncope caused by acupuncture or acupoint injection).<br><br>CONCLUSIONS: Limited evidence focus on acupuncture and acupoint injection for PVOD and suggests that acupuncture and acupoint injection may be effective in improving PVOD. More well-designed trials should focus on acupuncture to confirm the benefit.<br><br>PROTOCOL REGISTRATION: The protocol of this review was registered at PROSPERO: CRD42022366776.}, }
@article {pmid38831970, year = {2024}, author = {Dutra, LS and Shigaeff, N}, title = {Proposed protocol for post COVID-19 cognitive rehabilitation for attention and memory.}, journal = {Dementia &amp; neuropsychologia}, volume = {18}, number = {}, pages = {e20230109}, pmid = {38831970}, issn = {1980-5764}, abstract = {UNLABELLED: Since the beginning of the COVID-19 pandemic, many people suffered from Long Covid Syndrome, in which affected individuals do not recover immediately after the end of the infectious and inflammatory process caused by the virus. The most common neuropsychological symptoms of this syndrome are: memory decline, lack of attention, anxiety and depression.<br><br>OBJECTIVE: The purpose of this study was to develop a proposed cognitive rehabilitation protocol for post-COVID individuals with cognitive symptoms.<br><br>METHODS: A rehabilitation proposed protocol focusing on attention and memory was developed, based on the tests used in the neuropsychological evaluation of affected patients. Researchers held weekly sessions for six months, each lasting 60 minutes. Homework activities were also assigned and corrected in the following session. The attention and memory sessions were conducted with activities based on the applied tests.<br><br>RESULTS: Despite the methodological separation of attention and memory, the activities indirectly affect other cognitive functions and abilities, such as executive function, language, reasoning, execution strategies, and cognitive flexibility. A computer, a sheet of paper, and a pen were used to present the slides for the activities. Attention training included all types of attention: sustained, alternating, selective and divided. Memory training sessions included activities that stimulated both short-term and long-term memory. With each session, the difficulty of the activities was gradually increased.<br><br>CONCLUSION: Cognitive rehabilitation already has more consolidated evidence about its effectiveness for the treatment of other pathologies, so it can be thought that it will also be a promising strategy for COVID-19 too.}, }
@article {pmid38841775, year = {2024}, author = {Ronconi, G and Codazza, S and Ariani, M and LA Cagnina, F and Scrima, R and Coraci, D and Ferrara, PE}, title = {An update of the literature about rehabilitation tools used in the treatment of COVID-19-related disabilities: a systematic review of literature.}, journal = {Panminerva medica}, volume = {66}, number = {3}, pages = {309-316}, doi = {10.23736/S0031-0808.24.05098-5}, pmid = {38841775}, issn = {1827-1898}, mesh = {Humans ; *COVID-19/complications/rehabilitation ; Quality of Life ; Telerehabilitation ; Exercise Therapy/methods ; SARS-CoV-2 ; Electric Stimulation Therapy/methods ; Treatment Outcome ; Randomized Controlled Trials as Topic ; Physical Therapy Modalities ; Virtual Reality ; }, abstract = {INTRODUCTION: The role of rehabilitation during and after the COVID-19 pandemia was influenced by the progressive acquisition of knowledge on the pathology with the adaptation of the rehabilitative instruments to the heterogeneous impairments of the patients. The aim of this systematic review is to describe the effects of the rehabilitation tools applied in the last three years in the different phases of the COVID-19 disease.<br><br>EVIDENCE ACQUISITION: A literature search of MEDLINE (PubMed), Scopus and Physiotherapy Evidence Database (PEDro) was conducted. 2994 participants were included in this systematic review: 1225 patients for acute-COVID, 1331 patients for post-COVID, 438 patients for long-COVID.<br><br>EVIDENCE SYNTHESIS: Of the initial 907 hits only 45 randomized controlled trials were included. The Cochrane library assessment tool was used to evaluate the risk of bias. The trials selected studied the effects of respiratory rehabilitation alone or in association with exercises, tele-rehabilitation, endurance training, virtual reality, electrostimulations in different settings and phases of the infection with the evaluation of clinical, quality of life and impairment outcome measures.<br><br>CONCLUSIONS: All the rehabilitations tool were used based on the experts' opinion and on the rules of good clinical practice, during and after the pandemic period. Despite the heterogeneity of the studies, the different outcome measures and the small sample sizes, pulmonary rehabilitation, tele-rehabilitation and low/moderate intensity aerobic and endurance exercises seemed to improve clinical and quality of life outcomes at short (8 weeks) and mean time (2 months) after treatments in all phases of the infection.}, }
@article {pmid38846354, year = {2024}, author = {Zhang, Y and Chen, S and Tian, Y and Fu, X}, title = {Host factors of SARS-CoV-2 in infection, pathogenesis, and long-term effects.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1407261}, pmid = {38846354}, issn = {2235-2988}, mesh = {Humans ; *COVID-19/virology ; *SARS-CoV-2/pathogenicity ; *Virus Replication ; *Host-Pathogen Interactions ; Antiviral Agents/therapeutic use ; Host Microbial Interactions ; }, abstract = {SARS-CoV-2 is the causative virus of the devastating COVID-19 pandemic that results in an unparalleled global health and economic crisis. Despite unprecedented scientific efforts and therapeutic interventions, the fight against COVID-19 continues as the rapid emergence of different SARS-CoV-2 variants of concern and the increasing challenge of long COVID-19, raising a vast demand to understand the pathomechanisms of COVID-19 and its long-term sequelae and develop therapeutic strategies beyond the virus per se. Notably, in addition to the virus itself, the replication cycle of SARS-CoV-2 and clinical severity of COVID-19 is also governed by host factors. In this review, we therefore comprehensively overview the replication cycle and pathogenesis of SARS-CoV-2 from the perspective of host factors and host-virus interactions. We sequentially outline the pathological implications of molecular interactions between host factors and SARS-CoV-2 in multi-organ and multi-system long COVID-19, and summarize current therapeutic strategies and agents targeting host factors for treating these diseases. This knowledge would be key for the identification of new pathophysiological aspects and mechanisms, and the development of actionable therapeutic targets and strategies for tackling COVID-19 and its sequelae.}, }
@article {pmid38848177, year = {2024}, author = {Tavares-Júnior, JWL and Ciurleo, GCV and Feitosa, EAAF and Oriá, RB and Braga-Neto, P}, title = {The Clinical Aspects of COVID and Alzheimer's Disease: A Round-Up of Where Things Stand and Are Headed.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {99}, number = {4}, pages = {1159-1171}, doi = {10.3233/JAD-231368}, pmid = {38848177}, issn = {1875-8908}, mesh = {Humans ; *Alzheimer Disease ; *COVID-19/complications/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Cognitive Dysfunction/etiology ; }, abstract = {The link between long COVID-19 and brain/cognitive impairments is concerning and may foster a worrisome worldwide emergence of novel cases of neurodegenerative diseases with aging. This review aims to update the knowledge, crosstalk, and possible intersections between the Post-COVID Syndrome (PCS) and Alzheimer's disease (AD). References included in this review were obtained from PubMed searches conducted between October 2023 and November 2023. PCS is a very heterogenous and poorly understood disease with recent evidence of a possible association with chronic diseases such as AD. However, more scientific data is required to establish the link between PCS and AD.}, }
@article {pmid38850628, year = {2025}, author = {Panagea, E and Messinis, L and Petri, MC and Liampas, I and Anyfantis, E and Nasios, G and Patrikelis, P and Kosmidis, M}, title = {Neurocognitive Impairment in Long COVID: A Systematic Review.}, journal = {Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists}, volume = {40}, number = {1}, pages = {125-149}, pmid = {38850628}, issn = {1873-5843}, mesh = {Humans ; *COVID-19/complications/psychology ; *Cognitive Dysfunction/etiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {OBJECTIVE: Although Coronavirus disease 2019 (COVID-19) is primarily a respiratory infectious disease, it has also been associated with a wide range of other clinical manifestations. It is widely accepted in the scientific community that many patients after recovery continue to experience COVID-19-related symptoms, including cognitive impairment. The aim of this systematic review was to investigate the cognitive profile of patients with long-COVID syndrome.<br><br>METHODS: A systematic search of empirical studies was conducted through the PubMed/Medline and Scopus electronic databases. Cross-sectional and longitudinal studies published between 2020 and 2023 were included.<br><br>RESULTS: Of the 516 studies assessed for eligibility, 36 studies met the inclusion criteria. All included studies support the presence of persistent cognitive changes after COVID-19 disease. Executive function, memory, attention, and processing speed appear to be the cognitive domains that are predominantly associated with long-COVID syndrome, whereas language is an area that has not been sufficiently investigated.<br><br>CONCLUSIONS: In this review, the high frequency of cognitive impairment after COVID-19 is evident. If we consider that cognitive functioning affects our ability to live independently and is a key determinant of our quality of life, it is imperative to precisely define those factors that may induce cognitive impairment in COVID-19 survivors, with the ultimate goal of early diagnosis of cognitive changes and, consequently, the development of targeted rehabilitation interventions to address them.}, }
@article {pmid38855286, year = {2024}, author = {Kim, S and Finlay, JB and Ko, T and Goldstein, BJ}, title = {Long-term olfactory loss post-COVID-19: Pathobiology and potential therapeutic strategies.}, journal = {World journal of otorhinolaryngology - head and neck surgery}, volume = {10}, number = {2}, pages = {148-155}, pmid = {38855286}, issn = {2589-1081}, support = {R01 DC016859/DC/NIDCD NIH HHS/United States ; R25 DC020172/DC/NIDCD NIH HHS/United States ; }, abstract = {An acute loss of smell emerged as a striking symptom present in roughly half of the people infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus in the early phases of the COVID-19 pandemic. In most COVID-19 patients, olfaction recovers over the course of a few weeks. However, a lasting partial or complete loss of smell, often associated with distorted olfactory perceptions termed parosmia, has emerged as a widespread problem impacting at least 5%-10% of those who experience anosmia due to COVID-19. Our inability to offer effective therapies to this hyposmic or anosmic population, comprising millions of patients, highlights an enormous unmet need for the medical system. Here, we summarize the current understanding of the pathobiology causing acute olfactory loss due to SARS-CoV-2 infection, focusing on how the virus interacts with the peripheral olfactory system, a major site of viral infection. We also explore the problem of long-COVID olfactory dysfunction, which may accompany other persistent systemic disorders collectively termed postacute sequelae of COVID-19. Specifically, we discuss an emerging model focused on unresolved immune cell activity driving ongoing dysfunction. Finally, we review current and future therapeutic approaches aimed at restoring olfactory function.}, }
@article {pmid38862591, year = {2024}, author = {Prasanth, MI and Wannigama, DL and Reiersen, AM and Thitilertdecha, P and Prasansuklab, A and Tencomnao, T and Brimson, S and Brimson, JM}, title = {A systematic review and meta-analysis, investigating dose and time of fluvoxamine treatment efficacy for COVID-19 clinical deterioration, death, and Long-COVID complications.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {13462}, pmid = {38862591}, issn = {2045-2322}, support = {Sys_66_007_3700_001//the Ratchadaprisk Sompoch Endowment Fund (2023) Chulalongkorn University/ ; }, mesh = {*Fluvoxamine/therapeutic use ; Humans ; *COVID-19 Drug Treatment ; *COVID-19/mortality ; *SARS-CoV-2/isolation &amp; purification/drug effects ; Treatment Outcome ; Clinical Deterioration ; Selective Serotonin Reuptake Inhibitors/therapeutic use/adverse effects/administration &amp; dosage ; }, abstract = {There have been 774,075,242 cases of COVID-19 and 7,012,986 deaths worldwide as of January 2024. In the early stages of the pandemic, there was an urgent need to reduce the severity of the disease and prevent the need for hospitalization to avoid stress on healthcare systems worldwide. The repurposing of drugs to prevent clinical deterioration of COVID-19 patients was trialed in many studies using many different drugs. Fluvoxamine (an SSRI and sigma-1 receptor agonist) was initially identified to potentially provide beneficial effects in COVID-19-infected patients, preventing clinical deterioration and the need for hospitalization. Fourteen clinical studies have been carried out to date, with seven of those being randomized placebo-controlled studies. This systematic review and meta-analysis covers the literature from the outbreak of SARS-CoV-2 in late 2019 until January 2024. Search terms related to fluvoxamine, such as its trade names and chemical names, along with words related to COVID-19, such as SARS-CoV-2 and coronavirus, were used in literature databases including PubMed, Google Scholar, Scopus, and the ClinicalTrials.gov database from NIH, to identify the trials used in the subsequent analysis. Clinical deterioration and death data were extracted from these studies where available and used in the meta-analysis. A total of 7153 patients were studied across 14 studies (both open-label and double-blind placebo-controlled). 681 out of 3553 (19.17%) in the standard care group and 255 out of 3600 (7.08%) in the fluvoxamine-treated group experienced clinical deterioration. The estimated average log odds ratio was 1.087 (95% CI 0.200 to 1.973), which differed significantly from zero (z = 2.402, p = 0.016). The seven placebo-controlled studies resulted in a log odds ratio of 0.359 (95% CI 0.1111 to 0.5294), which differed significantly from zero (z = 3.103, p = 0.002). The results of this study identified fluvoxamine as effective in preventing clinical deterioration, and subgrouping analysis suggests that earlier treatment with a dose of 200 mg or above provides the best outcomes. We hope the outcomes of this study can help design future studies into respiratory viral infections and potentially improve clinical outcomes.}, }
@article {pmid38863829, year = {2024}, author = {Raj, ST and Bruce, AW and Anbalagan, M and Srinivasan, H and Chinnappan, S and Rajagopal, M and Khanna, K and Chandramoorthy, HC and Mani, RR}, title = {COVID-19 influenced gut dysbiosis, post-acute sequelae, immune regulation, and therapeutic regimens.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1384939}, pmid = {38863829}, issn = {2235-2988}, mesh = {*COVID-19/immunology/complications/therapy ; Humans ; *Dysbiosis ; *Gastrointestinal Microbiome ; *SARS-CoV-2/immunology ; Post-Acute COVID-19 Syndrome ; Probiotics/therapeutic use ; Gastrointestinal Tract/microbiology ; COVID-19 Drug Treatment ; }, abstract = {The novel coronavirus disease 2019 (COVID-19) pandemic outbreak caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has garnered unprecedented global attention. It caused over 2.47 million deaths through various syndromes such as acute respiratory distress, hypercoagulability, and multiple organ failure. The viral invasion proceeds through the ACE2 receptor, expressed in multiple cell types, and in some patients caused serious damage to tissues, organs, immune cells, and the microbes that colonize the gastrointestinal tract (GIT). Some patients who survived the SARS-CoV-2 infection have developed months of persistent long-COVID-19 symptoms or post-acute sequelae of COVID-19 (PASC). Diagnosis of these patients has revealed multiple biological effects, none of which are mutually exclusive. However, the severity of COVID-19 also depends on numerous comorbidities such as obesity, age, diabetes, and hypertension and care must be taken with respect to other multiple morbidities, such as host immunity. Gut microbiota in relation to SARS-CoV-2 immunopathology is considered to evolve COVID-19 progression via mechanisms of biochemical metabolism, exacerbation of inflammation, intestinal mucosal secretion, cytokine storm, and immunity regulation. Therefore, modulation of gut microbiome equilibrium through food supplements and probiotics remains a hot topic of current research and debate. In this review, we discuss the biological complications of the physio-pathological effects of COVID-19 infection, GIT immune response, and therapeutic pharmacological strategies. We also summarize the therapeutic targets of probiotics, their limitations, and the efficacy of preclinical and clinical drugs to effectively inhibit the spread of SARS-CoV-2.}, }
@article {pmid38868283, year = {2024}, author = {Rathod, N and Kumar, S and Chavhan, R and Acharya, S and Rathod, S}, title = {Navigating the Long Haul: A Comprehensive Review of Long-COVID Sequelae, Patient Impact, Pathogenesis, and Management.}, journal = {Cureus}, volume = {16}, number = {5}, pages = {e60176}, pmid = {38868283}, issn = {2168-8184}, abstract = {Long COVID, characterized by persistent symptoms following a SARS-CoV-2 infection, presents a significant public health challenge with wide-ranging implications. This comprehensive review explores the epidemiology, clinical manifestations, pathogenesis, risk factors, diagnosis, patient impact, management strategies, and long-term prognosis of COVID. Despite a varied symptomatology that spans multiple organ systems, including respiratory, neurological, and cardiovascular systems, this condition is primarily associated with chronic inflammation and potential viral persistence. Prevalence varies, influenced by the initial infection severity, demographic factors, and pre-existing conditions. The review emphasizes the necessity for healthcare systems to adapt to the needs of long-COVID patients by developing standardized diagnostic criteria and personalized, multidisciplinary treatment approaches. Current research gaps and future directions are identified, highlighting the urgent need for further studies on pathophysiological mechanisms and effective therapeutic interventions. This review aims to inform healthcare providers, researchers, and policymakers, enhancing patient care and guiding ongoing and future research initiatives. The continuing global focus and collaborative efforts offer hope for improved outcomes for those affected by long COVID, marking an essential step towards addressing this emergent condition comprehensively.}, }
@article {pmid38874693, year = {2024}, author = {Russell, SJ and Parker, K and Lehoczki, A and Lieberman, D and Partha, IS and Scott, SJ and Phillips, LR and Fain, MJ and Nikolich, J&#x17d;}, title = {Post-acute sequelae of SARS-CoV-2 infection (Long COVID) in older adults.}, journal = {GeroScience}, volume = {46}, number = {6}, pages = {6563-6581}, pmid = {38874693}, issn = {2509-2723}, support = {R25AG076387/AG/NIA NIH HHS/United States ; R37AG020719/AG/NIA NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; R25 AG076387/AG/NIA NIH HHS/United States ; OT2HL161847/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/epidemiology/complications ; *Post-Acute COVID-19 Syndrome ; Aged ; SARS-CoV-2 ; Aging/physiology ; }, abstract = {Long COVID, also known as PASC (post-acute sequelae of SARS-CoV-2), is a complex infection-associated chronic condition affecting tens of millions of people worldwide. Many aspects of this condition are incompletely understood. Among them is how this condition may manifest itself in older adults and how it might impact the older population. Here, we briefly review the current understanding of PASC in the adult population and examine what is known on its features with aging. Finally, we outline the major gaps and areas for research most germane to older adults.}, }
@article {pmid38881113, year = {2024}, author = {Muley, A and Mitra, S and Bhaliya, B and Soni, S and Joshi, A}, title = {A Systematic Review and Meta-analysis to Identify Risk Factors for Developing Long COVID-19.}, journal = {The Journal of the Association of Physicians of India}, volume = {72}, number = {5}, pages = {68-74}, doi = {10.59556/japi.72.0528}, pmid = {38881113}, issn = {0004-5772}, mesh = {Humans ; *COVID-19/epidemiology ; Risk Factors ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Sex Factors ; }, abstract = {AIM: This systematic review and meta-analysis was undertaken to identify the risk factors of long coronavirus disease 2019 (COVID-19) to provide insight for selecting cases for more aggressive monitoring and treatment after COVID-19 infection and reduce morbidity due to long COVID-19.<br><br>MATERIALS AND METHODS: All relevant studies published till July 2022 were searched for in PubMed, Trip database, and the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library). Reference lists of the studies selected for appraisal were also considered. The National Institute of Health Clinical Database and Google Scholar were searched for unpublished studies. All cohort studies which studied risk factors for long COVID-19 in adults (>18 years age-group) were included. Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were used for data extraction and bias assessment were. The outcomes were risk factors identified as being related with persistent symptoms 3 months after recovery from COVID-19. Random-effects model (RevMan 5.3) was used to pool the data.<br><br>RESULTS: Total nine studies were included with overall quality scores ranging from 16 to 19 out of the maximum 22. Pooled results demonstrated statistically significant association of long COVID-19 with female gender [odds ratio (OR) -1.67; 95% confidence interval (CI) 1.33-2.09], need of hospitalization (OR -1.80; 95% CI 1.22-2.64), and hospital stay (OR 2.41; 95% CI 0.75-4.07).<br><br>CONCLUSION: Female gender, need for hospitalization and duration of hospitalization during acute COVID-19 infection are the risk factors for later development of long COVID-19. There should be specific guidelines for monitoring and treatment of this population after acute COVID-19 infection.}, }
@article {pmid38887284, year = {2024}, author = {Arron, HE and Marsh, BD and Kell, DB and Khan, MA and Jaeger, BR and Pretorius, E}, title = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: the biology of a neglected disease.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1386607}, pmid = {38887284}, issn = {1664-3224}, mesh = {*Fatigue Syndrome, Chronic/diagnosis/immunology/therapy/etiology ; Humans ; Neglected Diseases ; Dysbiosis ; Animals ; Gastrointestinal Microbiome/immunology ; }, abstract = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic, debilitating disease characterised by a wide range of symptoms that severely impact all aspects of life. Despite its significant prevalence, ME/CFS remains one of the most understudied and misunderstood conditions in modern medicine. ME/CFS lacks standardised diagnostic criteria owing to variations in both inclusion and exclusion criteria across different diagnostic guidelines, and furthermore, there are currently no effective treatments available. Moving beyond the traditional fragmented perspectives that have limited our understanding and management of the disease, our analysis of current information on ME/CFS represents a significant paradigm shift by synthesising the disease's multifactorial origins into a cohesive model. We discuss how ME/CFS emerges from an intricate web of genetic vulnerabilities and environmental triggers, notably viral infections, leading to a complex series of pathological responses including immune dysregulation, chronic inflammation, gut dysbiosis, and metabolic disturbances. This comprehensive model not only advances our understanding of ME/CFS's pathophysiology but also opens new avenues for research and potential therapeutic strategies. By integrating these disparate elements, our work emphasises the necessity of a holistic approach to diagnosing, researching, and treating ME/CFS, urging the scientific community to reconsider the disease's complexity and the multifaceted approach required for its study and management.}, }
@article {pmid38892110, year = {2024}, author = {Paroli, M and Gioia, C and Accapezzato, D and Caccavale, R}, title = {Inflammation, Autoimmunity, and Infection in Fibromyalgia: A Narrative Review.}, journal = {International journal of molecular sciences}, volume = {25}, number = {11}, pages = {}, pmid = {38892110}, issn = {1422-0067}, mesh = {Animals ; Humans ; Autoimmune Diseases/immunology/complications ; *Autoimmunity ; *COVID-19/immunology/complications/virology ; *Fibromyalgia/immunology ; *Inflammation/immunology ; SARS-CoV-2/immunology ; }, abstract = {Fibromyalgia (FM) is a chronic disease characterized by widespread musculoskeletal pain of unknown etiology. The condition is commonly associated with other symptoms, including fatigue, sleep disturbances, cognitive impairment, and depression. For this reason, FM is also referred to as FM syndrome. The nature of the pain is defined as nociplastic according to the latest international classification and is characterized by altered nervous sensitization both centrally and peripherally. Psychosocial conditions have traditionally been considered critical in the genesis of FM. However, recent studies in animal models and humans have provided new evidence in favor of an inflammatory and/or autoimmune pathogenesis. In support of this hypothesis are epidemiological data of an increased female prevalence, similar to that of autoimmune diseases, and the frequent association with immune-mediated inflammatory disorders. In addition, the observation of an increased incidence of this condition during long COVID revived the hypothesis of an infectious pathogenesis. This narrative review will, therefore, discuss the evidence supporting the immune-mediated pathogenesis of FM in light of the most current data available in the literature.}, }
@article {pmid38892479, year = {2024}, author = {Jurek, JM and Castro-Marrero, J}, title = {A Narrative Review on Gut Microbiome Disturbances and Microbial Preparations in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Implications for Long COVID.}, journal = {Nutrients}, volume = {16}, number = {11}, pages = {}, pmid = {38892479}, issn = {2072-6643}, mesh = {Humans ; *Fatigue Syndrome, Chronic/therapy ; *Gastrointestinal Microbiome ; *COVID-19/complications/immunology ; *Probiotics/therapeutic use ; *Dysbiosis ; SARS-CoV-2 ; Dietary Supplements ; Synbiotics/administration &amp; dosage ; Brain-Gut Axis ; }, abstract = {Myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS), and long COVID are complex, multisystemic and long-term disabling conditions characterized by debilitating post-exertional malaise and other core symptoms related to immune dysregulation resultant from post-viral infection, including mitochondrial dysfunction, chronic neuroinflammation and gut dysbiosis. The reported associations between altered microbiota composition and cardinal symptoms of ME/CFS and long COVID suggest that the use of microbial preparations, such as probiotics, by restoring the homeostasis of the brain-immune-gut axis, may help in the management of symptoms in both conditions. Therefore, this review aims to investigate the implications of alerted gut microbiome and assess the evidence supporting use of microbial-based preparations, including probiotics, synbiotics, postbiotics alone and/or in combination with other nutraceuticals in the management of fatigue, inflammation and neuropsychiatric and gastrointestinal symptoms among patients with ME/CFS and long COVID.}, }
@article {pmid38893693, year = {2024}, author = {Song, X and Song, W and Cui, L and Duong, TQ and Pandy, R and Liu, H and Zhou, Q and Sun, J and Liu, Y and Li, T}, title = {A Comprehensive Review of the Global Epidemiology, Clinical Management, Socio-Economic Impacts, and National Responses to Long COVID with Future Research Directions.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {11}, pages = {}, pmid = {38893693}, issn = {2075-4418}, abstract = {Background: Long COVID, characterized by a persistent symptom spectrum following SARS-CoV-2 infection, poses significant health, social, and economic challenges. This review aims to consolidate knowledge on its epidemiology, clinical features, and underlying mechanisms to guide global responses; Methods: We conducted a literature review, analyzing peer-reviewed articles and reports to gather comprehensive data on long COVID's epidemiology, symptomatology, and management approaches; Results: Our analysis revealed a wide array of long COVID symptoms and risk factors, with notable demographic variability. The current understanding of its pathophysiology suggests a multifactorial origin yet remains partially understood. Emerging diagnostic criteria and potential therapeutic strategies were identified, highlighting advancements in long COVID management; Conclusions: This review highlights the multifaceted nature of long COVID, revealing a broad spectrum of symptoms, diverse risk factors, and the complex interplay of physiological mechanisms underpinning the condition. Long COVID symptoms and disorders will continue to weigh on healthcare systems in years to come. Addressing long COVID requires a holistic management strategy that integrates clinical care, social support, and policy initiatives. The findings underscore the need for increased international cooperation in research and health planning to address the complex challenges of long COVID. There is a call for continued refinement of diagnostic and treatment modalities, emphasizing a multidisciplinary approach to manage the ongoing and evolving impacts of the condition.}, }
@article {pmid38900132, year = {2025}, author = {Sunami, Y and Sugaya, K and Takahashi, K}, title = {G protein-coupled receptors related to autoimmunity in postural orthostatic tachycardia syndrome.}, journal = {Immunological medicine}, volume = {48}, number = {2}, pages = {141-148}, doi = {10.1080/25785826.2024.2370079}, pmid = {38900132}, issn = {2578-5826}, mesh = {Humans ; *Postural Orthostatic Tachycardia Syndrome/immunology ; Autoantibodies/immunology ; *Autoimmunity ; *Receptors, G-Protein-Coupled/immunology ; *COVID-19/immunology/complications ; SARS-CoV-2/immunology ; }, abstract = {Postural orthostatic tachycardia syndrome (POTS) is characterized by exaggerated orthostatic tachycardia in the absence of orthostatic hypotension. The pathophysiology of POTS may involve hypovolemia, autonomic neuropathy, a hyperadrenergic state, and cardiovascular deconditioning, any of which can co-occur in the same patient. Furthermore, there is growing evidence of the role of autoimmunity in a subset of POTS cases. In recent years, investigators have described an increased rate of autoimmune comorbidities as evidenced by the finding of several types of neural receptor autoantibody and non-specific autoimmune marker in patients with POTS. In particular, the association of the disease with several types of anti-G protein-coupled receptor (GPCR) antibodies and POTS has frequently been noted. A previous study reported that autoantibodies to muscarinic AChRs may play an important role in POTS with persistent, gastrointestinal symptoms. To date, POTS is recognized as one of the sequelae of coronavirus disease 2019 (COVID-19) and its frequency and pathogenesis are still largely unknown. Multiple autoantibody types occur in COVID-related, autonomic disorders, suggesting the presence of autoimmune pathology in these disorders. Herein, we review the association of anti-GPCR autoantibodies with disorders of the autonomic nervous system, in particular POTS, and provide a new perspective for understanding POTS-related autoimmunity.}, }
@article {pmid38904974, year = {2024}, author = {Rocker, J and Weiss, C}, title = {COVID-19, MIS-C, and long COVID in pediatric patients: an update.}, journal = {Pediatric emergency medicine practice}, volume = {21}, number = {7}, pages = {1-28}, pmid = {38904974}, issn = {1549-9669}, mesh = {Humans ; *COVID-19/complications/therapy ; *Systemic Inflammatory Response Syndrome/therapy/diagnosis ; Child ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19, the disease caused by SARS-CoV-2, has been disruptive worldwide. It was primarily a respiratory disease that affected many of the medically vulnerable, but the true impact of postacute sequelae of SARS-CoV-2 (PASC), which has been demonstrated to involve all organ systems, is now coming to light. In addition, a new disease entity emerged, multisystem inflammatory syndrome in children (MIS-C), which has had significant morbidity and mortality associated with it. This issue reviews the presentation, evaluation, and management of patients with COVID-19, MIS-C, and PASC. Additionally, the current literature supporting public health measures, as well as COVID-19 vaccinations and their complications are discussed.}, }
@article {pmid38911850, year = {2024}, author = {Carvajal, JJ and García-Castillo, V and Cuellar, SV and Campillay-Véliz, CP and Salazar-Ardiles, C and Avellaneda, AM and Muñoz, CA and Retamal-Díaz, A and Bueno, SM and González, PA and Kalergis, AM and Lay, MK}, title = {New insights into the pathogenesis of SARS-CoV-2 during and after the COVID-19 pandemic.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1363572}, pmid = {38911850}, issn = {1664-3224}, mesh = {Humans ; *COVID-19/immunology/epidemiology ; *SARS-CoV-2 ; Angiotensin-Converting Enzyme 2/metabolism ; Pandemics ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the respiratory distress condition known as COVID-19. This disease broadly affects several physiological systems, including the gastrointestinal, renal, and central nervous (CNS) systems, significantly influencing the patient's overall quality of life. Additionally, numerous risk factors have been suggested, including gender, body weight, age, metabolic status, renal health, preexisting cardiomyopathies, and inflammatory conditions. Despite advances in understanding the genome and pathophysiological ramifications of COVID-19, its precise origins remain elusive. SARS-CoV-2 interacts with a receptor-binding domain within angiotensin-converting enzyme 2 (ACE2). This receptor is expressed in various organs of different species, including humans, with different abundance. Although COVID-19 has multiorgan manifestations, the main pathologies occur in the lung, including pulmonary fibrosis, respiratory failure, pulmonary embolism, and secondary bacterial pneumonia. In the post-COVID-19 period, different sequelae may occur, which may have various causes, including the direct action of the virus, alteration of the immune response, and metabolic alterations during infection, among others. Recognizing the serious adverse health effects associated with COVID-19, it becomes imperative to comprehensively elucidate and discuss the existing evidence surrounding this viral infection, including those related to the pathophysiological effects of the disease and the subsequent consequences. This review aims to contribute to a comprehensive understanding of the impact of COVID-19 and its long-term effects on human health.}, }
@article {pmid38912617, year = {2024}, author = {Pietrzak, P and Hanke, W}, title = {The long COVID and its mental health manifestations - the review of literature.}, journal = {International journal of occupational medicine and environmental health}, volume = {37}, number = {3}, pages = {360-380}, pmid = {38912617}, issn = {1896-494X}, mesh = {Humans ; *COVID-19/psychology/epidemiology ; SARS-CoV-2 ; Depression/epidemiology ; Anxiety/epidemiology ; Mental Disorders/epidemiology ; Suicide, Attempted/statistics &amp; numerical data/psychology ; Post-Acute COVID-19 Syndrome ; Mental Health ; Prevalence ; }, abstract = {This article aims to present the overview of the situation during the coronavirus disease 2019 (COVID-19) pandemic about issues concerning the prevalence of mental disorders such as depression, anxiety, rate of suicide attempts, and long COVID (LC) infections in the general population during COVID-19 pandemic. Analysis of the literature (in English, Polish and Spanish language) on topics related to COVID-19, mental disorders (suicide attempts, depression, anxiety) and LC infection published during the 4 years (2020-2023) was done using Pubmed and PubMed Central search engine. Keywords such as "COVID-19," "mental disorders," "long COVID infection," "depression," "anxiety," "suicide attempts" were used during the search. The conduct of this review/comment followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) protocol, which corresponds to a checklist of 27 items designed to facilitate the development and reporting of a robust protocol for systematic reviews or meta-analyses. Overall 35 studies were selected and analyzed in the review on topics: including among others LC (14 studies), suicide attempts (7 studies), mental disorders (depression, anxiety) (14 studies). The main issues raised in the articles were: higher risk of LC symptoms in women, fatigue and brain fog listed as frequently encountered patient's complaints together with anxiety, depression, loneliness, especially in younger age groups and in women. Issues regarding LC, mental disorders and suicide attempts requires further research as the results vary in different countries. Int J Occup Med Environ Health. 2024;37(3):360-80.}, }
@article {pmid38928096, year = {2024}, author = {Gusev, E and Sarapultsev, A}, title = {Exploring the Pathophysiology of Long COVID: The Central Role of Low-Grade Inflammation and Multisystem Involvement.}, journal = {International journal of molecular sciences}, volume = {25}, number = {12}, pages = {}, pmid = {38928096}, issn = {1422-0067}, support = {122020900136-4//Institute of Immunology and Physiology/ ; }, mesh = {Humans ; *COVID-19/physiopathology/complications/virology/pathology ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; *Inflammation ; }, abstract = {Long COVID (LC), also referred to as Post COVID-19 Condition, Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), and other terms, represents a complex multisystem disease persisting after the acute phase of COVID-19. Characterized by a myriad of symptoms across different organ systems, LC presents significant diagnostic and management challenges. Central to the disorder is the role of low-grade inflammation, a non-classical inflammatory response that contributes to the chronicity and diversity of symptoms observed. This review explores the pathophysiological underpinnings of LC, emphasizing the importance of low-grade inflammation as a core component. By delineating the pathogenetic relationships and clinical manifestations of LC, this article highlights the necessity for an integrated approach that employs both personalized medicine and standardized protocols aimed at mitigating long-term consequences. The insights gained not only enhance our understanding of LC but also inform the development of therapeutic strategies that could be applicable to other chronic conditions with similar pathophysiological features.}, }
@article {pmid38928587, year = {2024}, author = {Rudroff, T}, title = {Long COVID in Brain Health Research: A Call to Action.}, journal = {Brain sciences}, volume = {14}, number = {6}, pages = {}, pmid = {38928587}, issn = {2076-3425}, abstract = {The COVID-19 pandemic has brought attention to the long-term consequences of the virus, particularly the persistent symptoms that characterize long COVID. This syndrome, which can last for months after the initial infection, includes a range of neurological and neuropsychiatric manifestations that have significant implications for brain health and dementia research. This review explores the current understanding of long COVID's cognitive, neurological, and psychiatric symptoms and their potential impact on brain stimulation and neuroimaging studies. It argues that researchers must adapt their study designs and screening processes to account for the confounding effects of long COVID and ensure the accuracy and reliability of their findings. To advance the understanding of this condition and its long-term effects on brain health, the review proposes a series of strategies, including the development of standardized screening tools, the investigation of underlying mechanisms, and the identification of risk factors and protective factors. It also emphasizes the importance of collaborative research efforts and international data sharing platforms in accelerating the pace of discovery and developing targeted interventions for individuals with long COVID. As the prevalence of this condition continues to grow, it is imperative that the neuroscience community comes together to address this challenge and support those affected by long COVID.}, }
@article {pmid38930148, year = {2024}, author = {Nantakool, S and Sa-Nguanmoo, P and Konghakote, S and Chuatrakoon, B}, title = {Effects of Exercise Rehabilitation on Cardiorespiratory Fitness in Long-COVID-19 Survivors: A Meta-Analysis.}, journal = {Journal of clinical medicine}, volume = {13}, number = {12}, pages = {}, pmid = {38930148}, issn = {2077-0383}, abstract = {Background: Poor cardiorespiratory fitness poses the highest risk of mortality. Long-COVID-19 survivors exhibit a reduced cardiorespiratory fitness (CRF). While exercise rehabilitation, such as cardiopulmonary exercise, is used for long-COVID-19 survivors, the effects of exercise on CRF in this population remain inconclusive. In this study, we aim to systematically summarise and synthesise whether exercise rehabilitation improves CRF among long-COVID-19 survivors. Methods: A comprehensive search was performed through PubMed, CINAHL, Embase, Scopus, and the Cochrane Library (since their inception to November 2023) and study reference lists. Studies presenting the effects of exercise rehabilitation on CRF (peak oxygen consumption (VO2peak) and six-minute walk distance (6MWD)) in long-COVID-19 survivors were identified. The standardised mean difference (SMD), mean difference (MD), and 95% confidence interval (CI) were used for analyses. The certainty of evidence was measured using a Grading of Recommendation Assessment, Development and Evaluation approach. Results: Twelve eligible studies (five RCTs and seven non-RCTs) with 682 participants were analysed. The meta-analysis showed significantly improved 6MWDs (MD 76.47, 95% CI 59.19-93.71, low certainty) and significantly greater 6MWDs (SMD 0.85, 95% CI 0.11-1.59, very low certainty) in the exercise rehabilitation group compared to the control group. A significantly improved 6MWD was found in subgroups of young to middle-aged adults and subgroups of patients who undertook aerobic exercise combined with resistance and respiratory exercise and centre-based training programs. Conclusions: Exercise rehabilitation is effective for improving CRF, as measured by the 6MWD in long-COVID-19 survivors. Improvements are likely to be more pronounced in specific subgroups of young to middle-aged adults and patients undertaking aerobic exercise combined with resistance and respiratory exercise and centre-based training programs. However, recommendations for clinical practice are limited due to the very low evidence certainty.}, }
@article {pmid38932130, year = {2024}, author = {Elumalai, N and Hussain, H and Sampath, N and Shamaladevi, N and Hajjar, R and Druyan, BZ and Rashed, AB and Ramamoorthy, R and Kenyon, NS and Jayakumar, AR and Paidas, MJ}, title = {SPIKENET: An Evidence-Based Therapy for Long COVID.}, journal = {Viruses}, volume = {16}, number = {6}, pages = {}, pmid = {38932130}, issn = {1999-4915}, support = {0000//University of Miami Miller School of Medicine Department Obstetrics, Gynecology and Repro-ductive Sciences/ ; 0000//Muriel, Murray &amp; Robert Smith Foundation COVID-19 Research Fund/ ; 0000//University of Miami Miller School of Medicine Team Science Award/ ; 0000//Charles M. Vallee Foundation/ ; }, mesh = {*SARS-CoV-2/drug effects ; Humans ; *COVID-19/therapy/virology ; Animals ; *Spike Glycoprotein, Coronavirus/metabolism/genetics ; Mice ; Post-Acute COVID-19 Syndrome ; Angiotensin-Converting Enzyme 2/metabolism ; Peptides/therapeutic use ; Antiviral Agents/therapeutic use ; COVID-19 Drug Treatment ; }, abstract = {The COVID-19 pandemic has been one of the most impactful events in our lifetime, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Multiple SARS-CoV-2 variants were reported globally, and a wide range of symptoms existed. Individuals who contract COVID-19 continue to suffer for a long time, known as long COVID or post-acute sequelae of COVID-19 (PASC). While COVID-19 vaccines were widely deployed, both unvaccinated and vaccinated individuals experienced long-term complications. To date, there are no treatments to eradicate long COVID. We recently conceived a new approach to treat COVID in which a 15-amino-acid synthetic peptide (SPIKENET, SPK) is targeted to the ACE2 receptor binding domain of SARS-CoV-2, which prevents the virus from attaching to the host. We also found that SPK precludes the binding of spike glycoproteins with the receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) of a coronavirus, murine hepatitis virus-1 (MHV-1), and with all SARS-CoV-2 variants. Further, SPK reversed the development of severe inflammation, oxidative stress, tissue edema, and animal death post-MHV-1 infection in mice. SPK also protects against multiple organ damage in acute and long-term post-MHV-1 infection. Our findings collectively suggest a potential therapeutic benefit of SPK for treating COVID-19.}, }
@article {pmid38936313, year = {2024}, author = {Gomes-Neto, M and Almeida, KO and Correia, HF and Santos, JC and Gomes, VA and Serra, JPC and Durães, AR and Carvalho, VO}, title = {Determinants of cardiorespiratory fitness measured by cardiopulmonary exercise testing in COVID-19 survivors: a systematic review with meta-analysis and meta‑regression.}, journal = {Brazilian journal of physical therapy}, volume = {28}, number = {4}, pages = {101089}, pmid = {38936313}, issn = {1809-9246}, mesh = {Humans ; *Cardiorespiratory Fitness/physiology ; *COVID-19/physiopathology ; *Exercise Test/methods ; Oxygen Consumption/physiology ; SARS-CoV-2 ; *Survivors ; }, abstract = {BACKGROUND: The relationship between cardiorespiratory fitness and its possible determinants in post-COVID-19 survivors has not been systematically assessed.<br><br>OBJECTIVES: To identify and summarize studies comparing cardiorespiratory fitness measured by cardiopulmonary exercise testing in COVID-19 survivors versus non-COVID-19 controls, as well as to determine the influence of potential moderating factors.<br><br>METHODS: We conducted a systematic search of MEDLINE/PubMed, Cochrane Library, EMBASE, Google Scholar, and SciELO since their inceptions until June 2022. Mean differences (MD), standard mean differences (SMD), and 95% confidence intervals (CI) were calculated. Subgroup and meta-regression analyses were used to evaluate potential moderating factors.<br><br>RESULTS: 48 studies (3372 participants, mean age 42 years, and with a mean testing time of 4 months post-COVID-19) were included, comprising a total of 1823 COVID-19 survivors and 1549 non-COVID-19 controls. After data pooling, VO2 peak (SMD=1.0 95% CI: 0.5, 1.5; 17 studies; N = 1273) was impaired in COVID-19 survivors. In 15 studies that reported VO2 peak values in mL/min/kg, non-COVID-19 controls had higher peak VO2 values than COVID-19 survivors (MD=6.2, 95% CI: 3.5, 8.8; N = 905; I[2]=84%). In addition, VO2 peak was associated with age, time post-COVID-19, disease severity, presence of dyspnea, and reduced exercise capacity.<br><br>CONCLUSION: This systematic review provides evidence that cardiorespiratory fitness may be impaired in COVID-19 survivors, especially for those with severe disease, presence of dyspnea, and reduced exercise capacity. Furthermore, the degree of reduction of VO2 peak is inversely associated with age and time post-COVID.}, }
@article {pmid38941608, year = {2024}, author = {Malireddi, RKS and Sharma, BR and Kanneganti, TD}, title = {Innate Immunity in Protection and Pathogenesis During Coronavirus Infections and COVID-19.}, journal = {Annual review of immunology}, volume = {42}, number = {1}, pages = {615-645}, pmid = {38941608}, issn = {1545-3278}, support = {R35 CA253095/CA/NCI NIH HHS/United States ; R01 AI101935/AI/NIAID NIH HHS/United States ; R01 AI124346/AI/NIAID NIH HHS/United States ; R37 AI101935/AI/NIAID NIH HHS/United States ; R01 AI160179/AI/NIAID NIH HHS/United States ; R01 AR056296/AR/NIAMS NIH HHS/United States ; }, mesh = {Humans ; *Immunity, Innate ; *COVID-19/immunology ; *SARS-CoV-2/immunology/physiology ; Cytokine Release Syndrome/immunology ; Cytokines/metabolism ; Animals ; Coronavirus Infections/immunology/virology/prevention &amp; control ; Immune Evasion ; }, abstract = {The COVID-19 pandemic was caused by the recently emerged β-coronavirus SARS-CoV-2. SARS-CoV-2 has had a catastrophic impact, resulting in nearly 7 million fatalities worldwide to date. The innate immune system is the first line of defense against infections, including the detection and response to SARS-CoV-2. Here, we discuss the innate immune mechanisms that sense coronaviruses, with a focus on SARS-CoV-2 infection and how these protective responses can become detrimental in severe cases of COVID-19, contributing to cytokine storm, inflammation, long-COVID, and other complications. We also highlight the complex cross talk among cytokines and the cellular components of the innate immune system, which can aid in viral clearance but also contribute to inflammatory cell death, cytokine storm, and organ damage in severe COVID-19 pathogenesis. Furthermore, we discuss how SARS-CoV-2 evades key protective innate immune mechanisms to enhance its virulence and pathogenicity, as well as how innate immunity can be therapeutically targeted as part of the vaccination and treatment strategy. Overall, we highlight how a comprehensive understanding of innate immune mechanisms has been crucial in the fight against SARS-CoV-2 infections and the development of novel host-directed immunotherapeutic strategies for various diseases.}, }
@article {pmid38944141, year = {2025}, author = {Joyce, MKP and Uchendu, S and Arnsten, AFT}, title = {Stress and Inflammation Target Dorsolateral Prefrontal Cortex Function: Neural Mechanisms Underlying Weakened Cognitive Control.}, journal = {Biological psychiatry}, volume = {97}, number = {4}, pages = {359-371}, pmid = {38944141}, issn = {1873-2402}, support = {R01 MH130538/MH/NIMH NIH HHS/United States ; RF1 AG083090/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Inflammation/physiopathology ; *Stress, Psychological/physiopathology/metabolism ; *Dorsolateral Prefrontal Cortex/physiopathology/metabolism ; Animals ; Memory, Short-Term/physiology ; *Prefrontal Cortex/physiopathology ; }, abstract = {Most mental disorders involve dysfunction of the dorsolateral prefrontal cortex (dlPFC), a recently evolved brain region that subserves working memory, abstraction, and the thoughtful regulation of attention, action, and emotion. For example, schizophrenia, depression, long COVID, and Alzheimer's disease are all associated with dlPFC dysfunction, with neuropathology often being focused in layer III. The dlPFC has extensive top-down projections, e.g., to the posterior association cortices to regulate attention and to the subgenual cingulate cortex via the rostral and medial PFC to regulate emotional responses. However, the dlPFC is particularly dependent on arousal state and is very vulnerable to stress and inflammation, which are etiological and/or exacerbating factors for most mental disorders. The cellular mechanisms by which stress and inflammation impact the dlPFC are a topic of current research and are summarized in this review. For example, the layer III dlPFC circuits that generate working memory-related neuronal firing have unusual neurotransmission, depending on NMDA receptor and nicotinic α7 receptor actions that are blocked under inflammatory conditions by kynurenic acid. These circuits also have unusual neuromodulation, with the molecular machinery to magnify calcium signaling in spines needed to support persistent firing, which must be tightly regulated to prevent toxic calcium actions. Stress rapidly weakens layer III connectivity by driving feedforward calcium-cAMP (cyclic adenosine monophosphate) opening of potassium channels on spines. This is regulated by postsynaptic noradrenergic α2A adrenergic receptor and mGluR3 (metabotropic glutamate receptor 3) signaling but dysregulated by inflammation and/or chronic stress exposure, which contribute to spine loss. Treatments that strengthen the dlPFC via pharmacological (the α2A adrenergic receptor agonist, guanfacine) or repetitive transcranial magnetic stimulation manipulation provide a rational basis for therapy.}, }
@article {pmid38945306, year = {2024}, author = {Shafqat, A and Masters, MC and Tripathi, U and Tchkonia, T and Kirkland, JL and Hashmi, SK}, title = {Long COVID as a disease of accelerated biological aging: An opportunity to translate geroscience interventions.}, journal = {Ageing research reviews}, volume = {99}, number = {}, pages = {102400}, doi = {10.1016/j.arr.2024.102400}, pmid = {38945306}, issn = {1872-9649}, mesh = {Humans ; *COVID-19 ; *Aging ; SARS-CoV-2 ; Geroscience ; Post-Acute COVID-19 Syndrome ; }, abstract = {It has been four years since long COVID-the protracted consequences that survivors of COVID-19 face-was first described. Yet, this entity continues to devastate the quality of life of an increasing number of COVID-19 survivors without any approved therapy and a paucity of clinical trials addressing its biological root causes. Notably, many of the symptoms of long COVID are typically seen with advancing age. Leveraging this similarity, we posit that Geroscience-which aims to target the biological drivers of aging to prevent age-associated conditions as a group-could offer promising therapeutic avenues for long COVID. Bearing this in mind, this review presents a translational framework for studying long COVID as a state of effectively accelerated biological aging, identifying research gaps and offering recommendations for future preclinical and clinical studies.}, }
@article {pmid38947233, year = {2024}, author = {Dietz, TK and Brondstater, KN}, title = {Long COVID management: a mini review of current recommendations and underutilized modalities.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1430444}, pmid = {38947233}, issn = {2296-858X}, abstract = {Long COVID is a condition that develops in a subset of patients after COVID-19 infection comprising of symptoms of varying severity encompassing multiple organ systems. Currently, long COVID is without consensus on a formal definition, identifiable biomarkers, and validated treatment. Long COVID is expected to be a long-term chronic condition for a subset of patients and is associated with suffering and incapacity. There is an urgent need for clear management guidelines for the primary care provider, who is essential in bridging the gap with more specialized care to improve quality of life and functionality in their patients living with long COVID. The purpose of this mini review is to provide primary care providers with the latest highlights from existing literature regarding the most common long COVID symptoms and current management recommendations. This review also highlights the underutilized interventions of stellate ganglion blocks and low-dose naltrexone, both with well-established safety profiles demonstrated to improve quality of life and functionality for patients suffering with some symptoms of long COVID, and encourages prompt referral to interventional pain management.}, }
@article {pmid38958890, year = {2024}, author = {Chikopela, T and Mwesigwa, N and Masenga, SK and Kirabo, A and Shibao, CA}, title = {The Interplay of HIV and Long COVID in Sub-Saharan Africa: Mechanisms of Endothelial Dysfunction.}, journal = {Current cardiology reports}, volume = {26}, number = {9}, pages = {859-871}, pmid = {38958890}, issn = {1534-3170}, support = {AHA 967054//American Heart Association/ ; }, mesh = {Humans ; *HIV Infections/physiopathology/complications/epidemiology ; *COVID-19/physiopathology/epidemiology/complications ; *Endothelium, Vascular/physiopathology ; Africa South of the Sahara/epidemiology ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Oxidative Stress ; Cardiovascular Diseases/physiopathology/epidemiology ; }, abstract = {PURPOSE OF REVIEW: Long COVID affects approximately 5 million people in Africa. This disease is characterized by persistent symptoms or new onset of symptoms after an acute SARS-CoV-2 infection. Specifically, the most common symptoms include a range of cardiovascular problems such as chest pain, orthostatic intolerance, tachycardia, syncope, and uncontrolled hypertension. Importantly, these conditions appear to have endothelial dysfunction as the common denominator, which is often due to impaired nitric oxide (NO) mechanisms. This review discusses the role of mechanisms contributing to endothelial dysfunction in Long COVID, particularly in people living with HIV.<br><br>RECENT FINDINGS: Recent studies have reported that increased inflammation and oxidative stress, frequently observed in Long COVID, may contribute to NO dysfunction, ultimately leading to decreased vascular reactivity. These mechanisms have also been reported in people living with HIV. In regions like Africa, where HIV infection is still a major public health challenge with a prevalence of approximately 26&#xa0;million people in 2022. Specifically, endothelial dysfunction has been reported as a major mechanism that appears to contribute to cardiovascular diseases and the intersection with Long COVID mechanisms is of particular concern. Further, it is well established that this population is more likely to develop Long COVID following infection with SARS-CoV-2. Therefore, concomitant infection with SARS-CoV-2 may lead to accelerated cardiovascular disease. We outline the details of the worsening health problems caused by Long COVID, which exacerbate pre-existing conditions such as endothelial dysfunction. The overlapping mechanisms of HIV and SARS-CoV-2, particularly the prolonged inflammatory response and chronic hypoxia, may increase susceptibility to Long COVID. Addressing these overlapping health issues is critical as it provides clinical entry points for interventions that could improve and enhance outcomes and quality of life for those affected by both HIV and Long COVID in the region.}, }
@article {pmid38960014, year = {2024}, author = {Oscoz-Ochandorena, S and Legarra-Gorgoñon, G and García-Alonso, Y and García-Alonso, N and Izquierdo, M and Ramírez-Vélez, R}, title = {Reduced autonomic function in patients with long-COVID-19 syndrome is mediated by cardiorespiratory fitness.}, journal = {Current problems in cardiology}, volume = {49}, number = {9}, pages = {102732}, doi = {10.1016/j.cpcardiol.2024.102732}, pmid = {38960014}, issn = {1535-6280}, mesh = {Humans ; *Cardiorespiratory Fitness/physiology ; Male ; Female ; *COVID-19/physiopathology/complications ; Middle Aged ; *Heart Rate/physiology ; *Post-Acute COVID-19 Syndrome ; *Autonomic Nervous System/physiopathology ; SARS-CoV-2 ; Adult ; Case-Control Studies ; Exercise Tolerance/physiology ; Muscle Strength/physiology ; Autonomic Nervous System Diseases/physiopathology/diagnosis/etiology ; Oxygen Consumption/physiology ; }, abstract = {BACKGROUND: Long-COVID-19 syndrome (LCS) exhibits neurological problems such as peripheral neuropathy and autonomic nervous system (ANS) dysfunction. Exercise intolerance and, consequently, low cardiorespiratory fitness (CRF) are some of the most common symptoms of LCS. We describe a series of individuals exhibiting LCS symptoms compared to a control group and posit that this condition may be related to the exercise capacity-mediated disruption of the ANS resulting particularly in exercise intolerance.<br><br>METHODS: This study included 87 individuals with LCS and 71 control participants without COVID-19 diagnoses. Heart rate variability (HRV) in supine position is commonly measured to diagnose autonomic dysregulation and subsequently analyzed using the Kubios software (Kuopio, Finland). CRF (peak VO2), post-COVID-19 patient-reported symptoms, maximal muscle strength (grip strength, bilateral leg press, leg extension, pectoral press, and back press exercises), and body composition were also measured. Analysis of covariance (ANCOVA) and mediation analysis were employed to assess the associations among LCS, peak VO2, and HRV indicators. Two-sided p < 0.05 was considered as significant.<br><br>RESULTS: The HRV parameters-RR interval, RMSSD, SDNN, PNS index, LF, HF, total power, SD1, and SD2-were significantly elevated (p < 0.05) in the control group when compared to the LCS patients. In contrast, the HR, stress index, and SNS index parameters were significantly higher (p < 0.05) in the LCS group. When adjusted for RR intervals, these parameters remained statistically significant (p < 0.05). A partially mediated effect was found between peak VO2 and RMSSD (mediation effect = 24.4%) as well as peak VO2 and SDNN (mediation effect = 25.1%) in the LCS patients.<br><br>CONCLUSIONS: These findings contribute new insights on the interplay between CRF and HRV indicators as well as endorse that dysautonomia may be related to the low peak VO2 observed in long COVID-19 patients.}, }
@article {pmid38965510, year = {2024}, author = {Sk Abd Razak, R and Ismail, A and Abdul Aziz, AF and Suddin, LS and Azzeri, A and Sha'ari, NI}, title = {Post-COVID syndrome prevalence: a systematic review and meta-analysis.}, journal = {BMC public health}, volume = {24}, number = {1}, pages = {1785}, pmid = {38965510}, issn = {1471-2458}, mesh = {Humans ; *COVID-19/epidemiology ; Prevalence ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Since the Coronavirus disease 2019 (COVID-19) pandemic began, the number of individuals recovering from COVID-19 infection have increased. Post-COVID Syndrome, or PCS, which is defined as signs and symptoms that develop during or after infection in line with COVID-19, continue beyond 12 weeks, and are not explained by an alternative diagnosis, has also gained attention. We systematically reviewed and determined the pooled prevalence estimate of PCS worldwide based on published literature.<br><br>METHODS: Relevant articles from the Web of Science, Scopus, PubMed, Cochrane Library, and Ovid MEDLINE databases were screened using a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-guided systematic search process. The included studies were in English, published from January 2020 to April 2024, had overall PCS prevalence as one of the outcomes studied, involved a human population with confirmed COVID-19 diagnosis and undergone assessment at 12&#xa0;weeks post-COVID infection or beyond. As the primary outcome measured, the pooled prevalence of PCS was estimated from a meta-analysis of the PCS prevalence data extracted from individual studies, which was conducted via the random-effects model. This study has been registered on PROSPERO (CRD42023435280).<br><br>RESULTS: Forty eight studies met the eligibility criteria and were included in this review. 16 were accepted for meta-analysis to estimate the pooled prevalence for PCS worldwide, which was 41.79% (95% confidence interval [CI] 39.70-43.88%, I[2]&#x2009;=&#x2009;51%, p&#x2009;=&#x2009;0.03). Based on different assessment or follow-up timepoints after acute COVID-19 infection, PCS prevalence estimated at&#x2009;&#x2265;&#x2009;3rd,&#x2009;&#x2265;&#x2009;6th, and&#x2009;&#x2265;&#x2009;12th months timepoints were each 45.06% (95% CI: 41.25-48.87%), 41.30% (95% CI: 34.37-48.24%), and 41.32% (95% CI: 39.27-43.37%), respectively. Sex-stratified PCS prevalence was estimated at 47.23% (95% CI: 44.03-50.42%) in male and 52.77% (95% CI: 49.58-55.97%) in female. Based on continental regions, pooled PCS prevalence was estimated at 46.28% (95% CI: 39.53%-53.03%) in Europe, 46.29% (95% CI: 35.82%-56.77%) in America, 49.79% (95% CI: 30.05%-69.54%) in Asia, and 42.41% (95% CI: 0.00%-90.06%) in Australia.<br><br>CONCLUSION: The prevalence estimates in this meta-analysis could be used in further comprehensive studies on PCS, which might enable the development of better PCS management plans to reduce the effect of PCS on population health and the related economic burden.}, }
@article {pmid38966504, year = {2024}, author = {Sarfraz, A and Sarfraz, Z and Bano, S and Sarfraz, M and Jaan, A and Minhas, A and Razzack, AA and Patel, G and Manish, KC and Makkar, SS and Garimella, R and Pandav, K and Almonte, J and Paul, T and Almonte, T and Jimenez, L and Pantoga, JC and El Mazboudi, N and Yatzkan, G and Michel, G and Michel, J}, title = {Global Perspective on COVID-19 Therapies, Cardiovascular Outcomes, and Implications for Long COVID: A State-of-the-Art Review.}, journal = {Journal of community hospital internal medicine perspectives}, volume = {14}, number = {2}, pages = {58-66}, pmid = {38966504}, issn = {2000-9666}, abstract = {The COVID-19 pandemic has resulted in many therapies, of which many are repurposed and used for other diseases in the last decade such in Influenza and Ebola. We intend to provide a robust foundation for cardiovascular outcomes of the therapies to better understand the rationale for the clinical trials that were conducted during the COVID-19 pandemic, and to gain more clarity on the steps moving forward should the repurposing provide clinical benefit in pandemic situations. With this state-of-the-art review, we aim to improve the understanding of the cardiovascular involvement of the therapies prior to, during, and after the COVID-19 pandemic to provide meaningful findings to the cardiovascular specialists and clinical trials for therapies, moving on from the period of pandemic urgency.}, }
@article {pmid38967606, year = {2024}, author = {Marcinkiewicz, J}, title = {Increase in the incidence of invasive bacterial infections following the COVID-19 pandemic: potential links with decreased herd trained immunity - a novel concept in medicine.}, journal = {Polish archives of internal medicine}, volume = {134}, number = {9}, pages = {}, doi = {10.20452/pamw.16794}, pmid = {38967606}, issn = {1897-9483}, mesh = {Humans ; *COVID-19/immunology/epidemiology ; Incidence ; Immunity, Herd ; Immunity, Innate ; Bacterial Infections/immunology/epidemiology ; SARS-CoV-2/immunology ; Pandemics ; Streptococcal Infections/immunology/epidemiology ; Streptococcus pyogenes/immunology ; Trained Immunity ; }, abstract = {A global increase in the incidence of various infectious diseases has been observed since the end of the COVID‑19 pandemic. This may be due to 2 independent phenomena. One of them is impaired immunity of long‑COVID patients. The second (major) one is associated with long‑term isolation of many people during the global pandemic‑related lockdown, resulting in an extreme reduction of exposure to natural environmental human microbiota. This, in turn, led to a silencing state of the body's defense systems, including a decline of the prepandemic trained immunity (innate memory), which only persists for weeks to months after exposure to a pathogen. This decrease in the performance of trained immunity may be especially important for morbidity of infectious diseases without currently available vaccines, such as invasive group A Streptococcus pyogenes (GAS) infections, primarily streptococcal toxic shock syndrome. This review discusses data that support an important role of trained macrophages in host defense, and demonstrates the potential clinical implications of β‑glucan, the major inducer of trained macrophages, for prophylactic and therapeutic use in individuals with impaired personal innate immunity. Altogether, it might be speculated that trained innate immunity within an entire population can lead to the development of herd trained immunity (HTI), a newly‑coined medical term. HTI can supplement classic, antigen‑specific herd immunity (memory B and T cells), and it plays a key role in preventing the spread of various infectious diseases, including invasive GAS infections. Unfortunately, the global HTI has been overthrown during the COVID‑19 pandemic; however, it should be restored shortly.}, }
@article {pmid38969238, year = {2024}, author = {Halme, ALE and Laakkonen, S and Rutanen, J and Nevalainen, OPO and Sinisalo, M and Horstia, S and Mustonen, JMJ and Pourjamal, N and Vanhanen, A and ,  and Rosberg, T and Renner, A and Perola, M and Paukkeri, EL and Patovirta, RL and Parkkila, S and Paajanen, J and Nykänen, T and Mäntylä, J and Myllärniemi, M and Mattila, T and Leinonen, MK and Külmäsu, A and Kuutti, P and Kuitunen, I and Kreivi, HR and Kilpeläinen, TP and Kauma, H and Kalliala, IEJ and Järvinen, P and Hankkio, R and Hammarén, T and Feuth, T and Ansakorpi, H and Ala-Karvia, R and Guyatt, GH and Tikkinen, KAO}, title = {Short- and long-term effects of imatinib in hospitalized COVID-19 patients: A randomized trial.}, journal = {The Journal of infection}, volume = {89}, number = {3}, pages = {106217}, doi = {10.1016/j.jinf.2024.106217}, pmid = {38969238}, issn = {1532-2742}, mesh = {Humans ; *Imatinib Mesylate/therapeutic use ; Female ; Male ; Middle Aged ; *Quality of Life ; *COVID-19/mortality ; *Hospitalization/statistics &amp; numerical data ; Aged ; *SARS-CoV-2 ; *COVID-19 Drug Treatment ; Treatment Outcome ; Adult ; }, abstract = {OBJECTIVES: We studied the short- and long-term effects of imatinib in hospitalized COVID-19 patients.<br><br>METHODS: Participants were randomized to receive standard of care (SoC) or SoC with imatinib. Imatinib dosage was 400&#xa0;mg daily until discharge (max 14 days). Primary outcomes were mortality at 30 days and 1 year. Secondary outcomes included recovery, quality of life and long COVID symptoms at 1 year. We also performed a systematic review and meta-analysis of randomized trials studying imatinib for 30-day mortality in hospitalized COVID-19 patients.<br><br>RESULTS: We randomized 156 patients (73 in SoC and 83 in imatinib). Among patients on imatinib, 7.2% had died at 30 days and 13.3% at 1 year, and in SoC, 4.1% and 8.2% (adjusted HR 1.35, 95% CI 0.47-3.90). At 1 year, self-reported recovery occurred in 79.0% in imatinib and in 88.5% in SoC (RR 0.91, 0.78-1.06). We found no convincing difference in quality of life or symptoms. Fatigue (24%) and sleep issues (20%) frequently bothered patients at one year. In the meta-analysis, imatinib was associated with a mortality risk ratio of 0.73 (0.32-1.63; low certainty evidence).<br><br>CONCLUSIONS: The evidence raises doubts regarding benefit of imatinib in reducing mortality, improving recovery and preventing long COVID symptoms in hospitalized COVID-19 patients.}, }
@article {pmid38970055, year = {2024}, author = {Löhn, M and Wirth, KJ}, title = {Potential pathophysiological role of the ion channel TRPM3 in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and the therapeutic effect of low-dose naltrexone.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {630}, pmid = {38970055}, issn = {1479-5876}, mesh = {Humans ; *Fatigue Syndrome, Chronic/drug therapy ; *TRPM Cation Channels/metabolism ; *Naltrexone/therapeutic use/pharmacology/administration &amp; dosage ; Animals ; Dose-Response Relationship, Drug ; Treatment Outcome ; }, abstract = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease with a broad overlap of symptomatology with Post-COVID Syndrome (PCS). Despite the severity of symptoms and various neurological, cardiovascular, microvascular, and skeletal muscular findings, no biomarkers have been identified. The Transient receptor potential melastatin 3 (TRPM3) channel, involved in pain transduction, thermosensation, transmitter and neuropeptide release, mechanoregulation, vasorelaxation, and immune defense, shows altered function in ME/CFS. Dysfunction of TRPM3 in natural killer (NK) cells, characterized by reduced calcium flux, has been observed in ME/CFS and PCS patients, suggesting a role in ineffective pathogen clearance and potential virus persistence and autoimmunity development. TRPM3 dysfunction in NK cells can be improved by naltrexone in vitro and ex vivo, which may explain the moderate clinical efficacy of low-dose naltrexone (LDN) treatment. We propose that TRPM3 dysfunction may have a broader involvement in ME/CFS pathophysiology, affecting other organs. This paper discusses TRPM3's expression in various organs and its potential impact on ME/CFS symptoms, with a focus on small nerve fibers and the brain, where TRPM3 is involved in presynaptic GABA release.}, }
@article {pmid38973985, year = {2024}, author = {Dalmau, R and Alanazi, AM and Arora, M and Banerjee, A and Bianco, E and Gaalema, DE and Goma, FM and Hasegawa, K and Komiyama, M and Pérez Ríos, M and Willett, J and Wang, Y}, title = {A Complex Interplay: Navigating the Crossroads of Tobacco Use, Cardiovascular Disease, and the COVID-19 Pandemic: A WHF Policy Brief.}, journal = {Global heart}, volume = {19}, number = {1}, pages = {55}, pmid = {38973985}, issn = {2211-8179}, mesh = {Humans ; *COVID-19/epidemiology/prevention &amp; control ; *Cardiovascular Diseases/epidemiology/prevention &amp; control ; *Tobacco Use/epidemiology ; *SARS-CoV-2 ; Pandemics ; Risk Factors ; Health Policy ; }, abstract = {The Coronavirus Disease 2019, commonly referred to as COVID-19, is responsible for one of the deadliest pandemics in human history. The direct, indirect and lasting repercussions of the COVID-19 pandemic on individuals and public health, as well as health systems can still be observed, even today. In the midst of the initial chaos, the role of tobacco as a prognostic factor for unfavourable COVID-19 outcomes was largely neglected. As of 2023, numerous studies have confirmed that use of tobacco, a leading risk factor for cardiovascular and other diseases, is strongly associated with increased risks of severe COVID-19 complications (e.g., hospitalisation, ICU admission, need for mechanical ventilation, long COVID, etc.) and deaths from COVID-19. In addition, evidence suggests that COVID-19 directly affects multiple organs beyond the respiratory system, disproportionately impacting individuals with comorbidities. Notably, people living with cardiovascular disease are more prone to experiencing worse outcomes, as COVID-19 often inherently manifests as thrombotic cardiovascular complications. As such, the triad of tobacco, COVID-19 and cardiovascular disease constitutes a dangerous cocktail. The lockdowns and social distancing measures imposed by governments have also had adverse effects on our lifestyles (e.g., shifts in diets, physical activity, tobacco consumption patterns, etc.) and mental well-being, all of which affect cardiovascular health. In particular, vulnerable populations are especially susceptible to tobacco use, cardiovascular disease and the psychological fallout from the pandemic. Therefore, national pandemic responses need to consider health equity as well as the social determinants of health. The pandemic has also had catastrophic impacts on many health systems, bringing some to the brink of collapse. As a result, many health services, such as services for cardiovascular disease or tobacco cessation, were severely disrupted due to fears of transmission and redirection of resources for COVID-19 care. Unfortunately, the return to pre-pandemic levels of cardiovascular disease care activity has stagnated. Nevertheless, digital solutions, such as telemedicine and apps, have flourished, and may help reduce the gaps. Advancing tobacco control was especially challenging due to interference from the tobacco industry. The industry exploited lingering uncertainties to propagate misleading information on tobacco and COVID-19 in order to promote its products. Regrettably, the links between tobacco use and risk of SARS-CoV-2 infection remain inconclusive. However, a robust body of evidence has, since then, demonstrated that tobacco use is associated with more severe COVID-19 illness and complications. Additionally, the tobacco industry also repeatedly attempted to forge partnerships with governments under the guise of corporate social responsibility. The implementation of the WHO Framework Convention on Tobacco Control could address many of the aforementioned challenges and alleviate the burden of tobacco, COVID-19, and cardiovascular disease. In particular, the implementation of Article 5.3 could protect public health policies from the vested interests of the industry. The world can learn from the COVID-19 pandemic to better prepare for future health emergencies of international concern. In light of the impact of tobacco on the COVID-19 pandemic, it is imperative that tobacco control remains a central component in pandemic preparedness and response plans.}, }
@article {pmid38987743, year = {2024}, author = {Sha'ari, NI and Ismail, A and Abdul Aziz, AF and Suddin, LS and Azzeri, A and Sk Abd Razak, R and Mad Tahir, NS}, title = {Cardiovascular diseases as risk factors of post-COVID syndrome: a systematic review.}, journal = {BMC public health}, volume = {24}, number = {1}, pages = {1846}, pmid = {38987743}, issn = {1471-2458}, support = {FRGS/1/2022/SKK04/UKM/02/2//Fundamental Research Grant Scheme (FRGS) under Ministry of Higher Education (MoHE) Malaysia/ ; FRGS/1/2022/SKK04/UKM/02/2//Fundamental Research Grant Scheme (FRGS) under Ministry of Higher Education (MoHE) Malaysia/ ; FRGS/1/2022/SKK04/UKM/02/2//Fundamental Research Grant Scheme (FRGS) under Ministry of Higher Education (MoHE) Malaysia/ ; FRGS/1/2022/SKK04/UKM/02/2//Fundamental Research Grant Scheme (FRGS) under Ministry of Higher Education (MoHE) Malaysia/ ; FRGS/1/2022/SKK04/UKM/02/2//Fundamental Research Grant Scheme (FRGS) under Ministry of Higher Education (MoHE) Malaysia/ ; FRGS/1/2022/SKK04/UKM/02/2//Fundamental Research Grant Scheme (FRGS) under Ministry of Higher Education (MoHE) Malaysia/ ; FRGS/1/2022/SKK04/UKM/02/2//Fundamental Research Grant Scheme (FRGS) under Ministry of Higher Education (MoHE) Malaysia/ ; }, mesh = {Humans ; *COVID-19/epidemiology/complications ; *Cardiovascular Diseases/epidemiology ; Risk Factors ; Post-Acute COVID-19 Syndrome ; Survivors/statistics &amp; numerical data ; }, abstract = {BACKGROUND: A growing proportion of people experience incomplete recovery months after contracting coronavirus disease 2019 (COVID-19). These COVID-19 survivors develop a condition known as post-COVID syndrome (PCS), where COVID-19 symptoms persist for > 12 weeks after acute infection. Limited studies have investigated PCS risk factors that notably include pre-existing cardiovascular diseases (CVD), which should be examined considering the most recent PCS data. This review aims to identify CVD as a risk factor for PCS development in COVID-19 survivors.<br><br>METHODS: Following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) checklist, systematic literature searches were performed in the PubMed, Scopus, and Web of Science databases from the earliest date available to June 2023. Data from observational studies in English that described the association between CVD and PCS in adults (&#x2265;&#x2009;18 years old) were included. A minimum of two authors independently performed the screening, study selection, data extraction, data synthesis, and quality assessment (Newcastle-Ottawa Scale). The protocol of this review was registered under PROSPERO (ID: CRD42023440834).<br><br>RESULTS: In total, 594 studies were screened after duplicates and non-original articles had been removed. Of the 11 included studies, CVD including hypertension (six studies), heart failure (three studies), and others (two studies) were significantly associated with PCS development with different factors considered. The included studies were of moderate to high methodological quality.<br><br>CONCLUSION: Our review highlighted that COVID-19 survivors with pre-existing CVD have a significantly greater risk of developing PCS symptomology than survivors without pre-existing CVD. As heart failure, hypertension and other CVD are associated with a higher risk of developing PCS, comprehensive screening and thorough examinations are essential to minimise the impact of PCS and improve patients' disease progression.}, }
@article {pmid38988667, year = {2024}, author = {Müller, L and Di Benedetto, S}, title = {Inflammaging, immunosenescence, and cardiovascular aging: insights into long COVID implications.}, journal = {Frontiers in cardiovascular medicine}, volume = {11}, number = {}, pages = {1384996}, pmid = {38988667}, issn = {2297-055X}, abstract = {Aging leads to physiological changes, including inflammaging-a chronic low-grade inflammatory state with significant implications for various physiological systems, particularly for cardiovascular health. Concurrently, immunosenescence-the age-related decline in immune function, exacerbates vulnerabilities to cardiovascular pathologies in older individuals. Examining the dynamic connections between immunosenescence, inflammation, and cardiovascular aging, this mini-review aims to disentangle some of these interactions for a better understanding of their complex interplay. In the context of cardiovascular aging, the chronic inflammatory state associated with inflammaging compromises vascular integrity and function, contributing to atherosclerosis, endothelial dysfunction, arterial stiffening, and hypertension. The aging immune system's decline amplifies oxidative stress, fostering an environment conducive to atherosclerotic plaque formation. Noteworthy inflammatory markers, such as the high-sensitivity C-reactive protein, interleukin-6, interleukin-1β, interleukin-18, and tumor necrosis factor-alpha emerge as key players in cardiovascular aging, triggering inflammatory signaling pathways and intensifying inflammaging and immunosenescence. In this review we aim to explore the molecular and cellular mechanisms underlying inflammaging and immunosenescence, shedding light on their nuanced contributions to cardiovascular diseases. Furthermore, we explore the reciprocal relationship between immunosenescence and inflammaging, revealing a self-reinforcing cycle that intensifies cardiovascular risks. This understanding opens avenues for potential therapeutic targets to break this cycle and mitigate cardiovascular dysfunction in aging individuals. Furthermore, we address the implications of Long COVID, introducing an additional layer of complexity to the relationship between aging, immunosenescence, inflammaging, and cardiovascular health. Our review aims to stimulate continued exploration and advance our understanding within the realm of aging and cardiovascular health.}, }
@article {pmid38996944, year = {2024}, author = {Loo, C and Treacy, MG and Toerien, L and Msellati, A and Catanzano, T}, title = {Emergency Presentations of Coronavirus Disease (COVID-19): A Review of the Literature and Radiologic Perspective.}, journal = {Seminars in ultrasound, CT, and MR}, volume = {45}, number = {4}, pages = {332-338}, doi = {10.1053/j.sult.2024.07.003}, pmid = {38996944}, issn = {1558-5034}, mesh = {Humans ; *COVID-19/diagnostic imaging ; *SARS-CoV-2 ; Tomography, X-Ray Computed/methods ; Emergency Service, Hospital ; Pandemics ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the debilitating global pandemic known as Coronavirus disease (COVID-19). In this paper, we highlight the widespread manifestations and complications across disease systems. In addition, we present their relevant imaging findings to inform appropriate investigations and management in patients presenting to the Emergency Department with COVID-19 and its respective sequalae. Of note, we outline considerations for diagnosis of long COVID, an important medium to long term sequalae in patients with previous COVID-19 infections.}, }
@article {pmid39002665, year = {2024}, author = {Sun, G and Lin, K and Ai, J and Zhang, W}, title = {The efficacy of antivirals, corticosteroids, and monoclonal antibodies as acute COVID-19 treatments in reducing the incidence of long COVID: a systematic review and meta-analysis.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {30}, number = {12}, pages = {1505-1513}, doi = {10.1016/j.cmi.2024.07.006}, pmid = {39002665}, issn = {1469-0691}, mesh = {Aged ; Female ; Humans ; Male ; *Adrenal Cortex Hormones/therapeutic use ; *Antibodies, Monoclonal/therapeutic use ; *Antiviral Agents/therapeutic use ; *COVID-19/complications/immunology/virology ; *COVID-19 Drug Treatment/methods ; Incidence ; *Post-Acute COVID-19 Syndrome/epidemiology/immunology/prevention &amp; control/virology ; SARS-CoV-2/immunology ; Treatment Outcome ; }, abstract = {BACKGROUND: Whether treatment during acute COVID-19 results in protective efficacy against long COVID incidence remains unclear.<br><br>OBJECTIVES: To assess the relationship between acute COVID-19 treatments of antivirals, corticosteroids, and monoclonal antibodies (mAbs) and long COVID incidence, and their effects in different populations and individual symptoms.<br><br>METHODS: A systematic review and meta-analysis.<br><br>DATA SOURCES: Searches were conducted up to January 29, 2024 in PubMed, Medline, Web of Science, and Embase.<br><br>STUDY ELIGIBILITY CRITERIA: Articles that reported long COVID incidence post-acute COVID with a follow-up of at least 30&#xa0;days with no language restrictions.<br><br>PARTICIPANTS: Patients with a COVID-19 diagnosis history.<br><br>INTERVENTIONS: Patients treated with antivirals, corticosteroids or mAbs.<br><br>ASSESSMENT OF RISK OF BIAS: Quality assessment was based on the Newcastle-Ottawa scale, risk of bias in nonrandomized studies of interventions-I and Cochrane risk of bias tool.<br><br>METHODS OF DATA SYNTHESIS: Basic characteristics were documented for each study. Random forest model and meta-regression were used to evaluate the correlation between treatments and long COVID.<br><br>RESULTS: Our search identified 2363 records, 32 of which were included in the qualitative synthesis and 25 included into the meta-analysis. Effect size from 14 papers investigating acute COVID-19 antiviral treatment concluded its protective efficacy against long COVID (OR, 0.61; 95% CI, 0.48-0.79; p 0.0002); however, corticosteroid (OR, 1.57; 95% CI, 0.80-3.09; p 0.1913), and mAbs treatments (OR, 0.94; 95% CI, 0.56-1.56; p 0.8012) did not generate such effect. Subsequent subgroup analysis revealed that antivirals provided stronger protection in the aged, male, unvaccinated and nondiabetic populations. Furthermore, antivirals effectively reduced 8 out of the 22 analysed long COVID symptoms.<br><br>CONCLUSIONS: Our meta-analysis determined that antivirals reduced long COVID incidence across populations and should thus be recommended for acute COVID-19 treatment. There was no relationship between mAbs treatment and long COVID, but studies should be conducted to clarify acute COVID-19 corticosteroids' potential harmful effects on the post-acute phase of COVID-19.}, }
@article {pmid39003005, year = {2024}, author = {Broussard, CA and Azola, A and Rowe, PC}, title = {Post-Acute Sequelae of SARS-CoV-2 Infection and Its Impact on Adolescents and Young Adults.}, journal = {Pediatric clinics of North America}, volume = {71}, number = {4}, pages = {613-630}, doi = {10.1016/j.pcl.2024.04.004}, pmid = {39003005}, issn = {1557-8240}, mesh = {Humans ; *COVID-19/complications/epidemiology ; Adolescent ; Young Adult ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {This review discusses the varying definitions for post-acute sequelae of SARS CoV-2 infection (PASC) in adolescents and young adults (AYAs), symptom profiles of AYAs with PASC, and assessment and management strategies when AYAs present with symptoms concerning for PASC. Additionally, it reviews the impact that PASC can have on AYAs and includes strategies for providers to support AYAs with PASC. Finally, it concludes with a discussion around equity in the care of AYAs with possible PASC.}, }
@article {pmid39022666, year = {2024}, author = {Zheng, C and Chen, JJ and Dai, ZH and Wan, KW and Sun, FH and Huang, JH and Chen, XK}, title = {Physical exercise-related manifestations of long COVID: A systematic review and meta-analysis.}, journal = {Journal of exercise science and fitness}, volume = {22}, number = {4}, pages = {341-349}, pmid = {39022666}, issn = {1728-869X}, abstract = {OBJECTIVE: This study aims to systematically assess physical exercise-related symptoms of post-acute sequelae of SARS-CoV-2 infection (PASC or long COVID) in coronavirus disease 2019 (COVID-19) survivors.<br><br>METHODS: Eight databases were systematically searched on March 03, 2024. Original studies that compared physical exercise-related parameters measured by exercise testing between COVID-19 survivors who recovered from SARS-CoV-2 infection over 3 months and non-COVID-19 controls were included. A random-effects model was utilized to determine the mean differences (MDs) or standardized MDs in the meta-analysis.<br><br>RESULTS: A total of 40 studies with 6241 COVID-19 survivors were included. The 6-min walk test, maximal oxygen consumption (VO2max), and anaerobic threshold were impaired in COVID-19 survivors 3 months post-infection compared with non-COVID-19 controls in exercise testing, while VO2 were comparable between the two groups at rest. In contrast, no differences were observed in SpO2, heart rate, blood pressure, fatigue, and dyspnea between COVID-19 survivors and non-COVID-19 controls in exercise testing.<br><br>CONCLUSION: The findings suggest an underestimation of the manifestations of PASC. COVID-19 survivors also harbor physical exercise-related symptoms of PASC that can be determined by the exercise testing and are distinct from those observed at rest. Exercise testing should be included while evaluating the symptoms of PASC in COVID-19 survivors.}, }
@article {pmid39029739, year = {2024}, author = {Nugent, K and Berdine, G}, title = {Dyspnea and long COVID patients.}, journal = {The American journal of the medical sciences}, volume = {368}, number = {4}, pages = {399-404}, doi = {10.1016/j.amjms.2024.07.024}, pmid = {39029739}, issn = {1538-2990}, mesh = {Humans ; *COVID-19/complications/physiopathology ; *Dyspnea/etiology/physiopathology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Respiratory Function Tests ; Exercise Test ; }, abstract = {Patients with prior COVID-19 infections often develop chronic post-COVID symptoms, such as fatigue and dyspnea. Some patients have residual pulmonary disorders with abnormal pulmonary function tests and/or chest radiographs to explain their dyspnea. However, other patients appear to have dyspnea that is out of proportion to any measurable change in lung function. Some of these patients have abnormal cardiopulmonary exercise testing with definite cardiac or respiratory limits. However, others have normal cardiopulmonary exercise testing based on VO2 measurement but pronounced dyspnea during this testing. These patients often have abnormal respiratory patterns, referred to as dysfunctional breathing, with irregular and variable respiratory rates and/or tidal volumes. Consequently, their control of breathing is impaired, and this may represent residual effects from prior COVID-19 infection involving the central nervous system. Alternatively, patients may have acquired "a memory" of respiratory symptoms during their infection which persists post-infection. These patients should participate in pulmonary rehabilitation and breathing retraining.}, }
@article {pmid39035011, year = {2024}, author = {Notarte, KI and Carandang, THDC and Velasco, JV and Pastrana, A and Ver, AT and Manalo, GN and Ng, JA and Grecia, S and Lippi, G and Henry, BM and Fernández-de-Las-Peñas, C}, title = {Autoantibodies in COVID-19 survivors with post-COVID symptoms: a systematic review.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1428645}, pmid = {39035011}, issn = {1664-3224}, mesh = {Humans ; *COVID-19/immunology ; *Autoantibodies/immunology/blood ; *SARS-CoV-2/immunology ; *Survivors ; }, abstract = {OBJECTIVE: The long-lasting persistence of autoantibodies stands as one of the hypotheses explaining the multisystemic manifestations seen in individuals with post-COVID-19 condition. The current review offers restricted insights into the persistence of autoantibodies in plasma/serum in people with post-COVID symptoms.<br><br>METHODS: PubMed/MEDLINE, CINAHL, EMBASE, and Web of Science databases, as well as on medRxiv and bioRxiv preprint servers were searched up to January 5[th], 2024. Papers investigating the presence of autoantibodies in plasma/serum samples in people with post-COVID symptoms were included. The Newcastle-Ottawa Scale (NOS) was used to assess methodological quality.<br><br>RESULTS: From 162 identified records, five articles met all inclusion criteria; four studies included infected controls with no post-COVID symptoms whereas all five studies included non-infected controls (410 COVID-19 survivors with post-COVID symptoms, 223 COVID-19 survivors with no post-COVID symptoms as controls and 266 non-infected healthy controls). Four studies concluded that the presence of autoantibodies had a potential (but small) role in post-COVID-19 condition whereas one study concluded that autoantibodies were not associated. Quality assessment showed all studies had high methodological quality.<br><br>CONCLUSION: Although evidence suggests that persistent autoantibodies can be associated with post-COVID symptoms, the clinical relevance of their presence seems modest at this stage. Current results highlight further research to clarify the role of autoantibodies in the development of post-COVID symptoms, guiding the development of tailored diagnostic and treatment approaches to enhance patient outcomes.<br><br>https://osf.io/vqz28.}, }
@article {pmid39038507, year = {2024}, author = {Wesley, UV and Dempsey, RJ}, title = {Neuro-molecular perspectives on long COVID-19 impacted cerebrovascular diseases - a role for dipeptidyl peptidase IV.}, journal = {Experimental neurology}, volume = {380}, number = {}, pages = {114890}, doi = {10.1016/j.expneurol.2024.114890}, pmid = {39038507}, issn = {1090-2430}, mesh = {Humans ; *Dipeptidyl Peptidase 4/metabolism ; *COVID-19/complications ; *Cerebrovascular Disorders ; *SARS-CoV-2/pathogenicity ; Post-Acute COVID-19 Syndrome ; Animals ; }, abstract = {The coronavirus disease 2019 (COVID-19) has caused immense devastation globally with many outcomes that are now extending to its long-term sequel called long COVID. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects not only lungs, but also the brain and heart in association with endothelial cell dysfunction, coagulation abnormalities, and thrombosis leading to cardio-cerebrovascular health issues. Fatigue, cognitive decline, and brain fog are common neurological symptoms in persisting long COVID. Neurodegenerative processes and SARS-CoV-2 infection manifest overlapping molecular mechanisms, such as cytokine dysregulation, inflammation, protein aggregation, mitochondrial dysfunction, and oxidative stress. Identifying the key molecules in these processes is of importance for prevention and treatment of this disease. In particular, Dipeptidyl peptidase IV (DPPIV), a multifunctional peptidase has recently drawn attention as a potential co-receptor for SARS-CoV-2 infection and cellular entry. DPPIV is a known co-receptor for some other COVID viruses including MERS-Co-V. DPPIV regulates the immune responses, obesity, glucose metabolism, diabetes, and hypertension that are associated with cerebrovascular manifestations including stroke. DPPIV likely worsens persisting COVID-19 by disrupting inflammatory signaling pathways and the neurovascular system. This review highlights the neurological, cellular and molecular processes concerning long COVID, and DPPIV as a potential key factor contributing to cerebrovascular dysfunctions following SARS-CoV-2 infection.}, }
@article {pmid39044822, year = {2024}, author = {Ruiz-Pablos, M and Paiva, B and Zabaleta, A}, title = {Hypocortisolemic ASIA: a vaccine- and chronic infection-induced syndrome behind the origin of long COVID and myalgic encephalomyelitis.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1422940}, pmid = {39044822}, issn = {1664-3224}, mesh = {Humans ; *COVID-19 Vaccines/adverse effects/immunology ; *Fatigue Syndrome, Chronic/immunology/etiology/virology ; HLA-DRB1 Chains/genetics/immunology ; *Post-Acute COVID-19 Syndrome/immunology ; }, abstract = {Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), long COVID (LC) and post-COVID-19 vaccine syndrome show similarities in their pathophysiology and clinical manifestations. These disorders are related to viral or adjuvant persistence, immunological alterations, autoimmune diseases and hormonal imbalances. A developmental model is postulated that involves the interaction between immune hyperactivation, autoimmune hypophysitis or pituitary hypophysitis, and immune depletion. This process might begin with a deficient CD4 T-cell response to viral infections in genetically predisposed individuals (HLA-DRB1), followed by an uncontrolled immune response with CD8 T-cell hyperactivation and elevated antibody production, some of which may be directed against autoantigens, which can trigger autoimmune hypophysitis or direct damage to the pituitary, resulting in decreased production of pituitary hormones, such as ACTH. As the disease progresses, prolonged exposure to viral antigens can lead to exhaustion of the immune system, exacerbating symptoms and pathology. It is suggested that these disorders could be included in the autoimmune/adjuvant-induced inflammatory syndrome (ASIA) because of their similar clinical manifestations and possible relationship to genetic factors, such as polymorphisms in the HLA-DRB1 gene. In addition, it is proposed that treatment with antivirals, corticosteroids/ginseng, antioxidants, and metabolic precursors could improve symptoms by modulating the immune response, pituitary function, inflammation and oxidative stress. Therefore, the purpose of this review is to suggest a possible autoimmune origin against the adenohypophysis and a possible improvement of symptoms after treatment with corticosteroid replacement therapy.}, }
@article {pmid39052056, year = {2025}, author = {Gutzeit, J and Weiß, M and Nürnberger, C and Lemhöfer, C and Appel, KS and Pracht, E and Reese, JP and Lehmann, C and Polidori, MC and Hein, G and Deckert, J}, title = {Definitions and symptoms of the post-COVID syndrome: an updated systematic umbrella review.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {275}, number = {1}, pages = {129-140}, pmid = {39052056}, issn = {1433-8491}, mesh = {Humans ; *COVID-19/complications/physiopathology ; Post-Acute COVID-19 Syndrome ; *Fatigue/etiology/physiopathology/diagnosis ; }, abstract = {Post-COVID syndrome (PCS) describes a persistent complex of symptoms following a COVID-19 episode, lasting at least 4 to 12 weeks, depending on the specific criteria used for its definition. It is often associated with moderate to severe impairments of daily life and represents a major burden for many people worldwide. However, especially during the first two years of the COVID-19 pandemic, therapeutic and diagnostic uncertainties were prominent due to the novelty of the disease and non-specific definitions that overlooked functional deficits and lacked objective assessment. The present work comprehensively examines the status of PCS definitions as depicted in recent reviews and meta-analyses, alongside exploring associated symptoms and functional impairments. We searched the database Pubmed for reviews and meta-analysis evaluating PCS in the period between May 31, 2022, to December 31, 2023. Out of 95 studies, 33 were selected for inclusion in our analyses. Furthermore, we extended upon prior research by systematically recording the symptoms linked with PCS as identified in the studies. We found that fatigue, neurological complaints, and exercise intolerance were the most frequently reported symptoms. In conclusion, over the past eighteen months, there has been a notable increase in quantity and quality of research studies on PCS. However, there still remains a clear need for improvement, particularly with regard to the definition of the symptoms necessary for diagnosing this syndrome. Enhancing this aspect will render future research more comparable and precise, thereby advancing and understanding PCS.}, }
@article {pmid39062061, year = {2024}, author = {Saloň, A and De Boever, P and Goswami, N}, title = {Microvascular Changes during Viral Infections: A Systematic Review of Studies Using Retinal Vessel Diameter Assessments.}, journal = {Biomedicines}, volume = {12}, number = {7}, pages = {}, pmid = {39062061}, issn = {2227-9059}, abstract = {Viral infection frequently affects the cardiovascular system, and vascular disturbances in patients can lead to health complications. One essential component of the cardiovascular system that is vulnerable to the inflammatory effects of viral infections is the microcirculatory system. As a suitable and practical non-invasive method to assess the structure and function of the retinal microcirculation, a proxy for the microcirculatory system, retinal fundus imaging can be used. We examined the impact of viral infections on retinal vessel diameters and performed a systematic analysis of the literature. Our search was carried out on PubMed using predefined search queries. After a methodological filtering process, we were able to reduce the corpus of 363 publications to 16 studies that met the search parameters. We used a narrative review style to summarise the observations. Six studies covered COVID-19, seven described HIV, and three were included in the subgroup called others, covering viruses, such as Dengue Fever and Crimean-Congo Haemorrhagic Fever. Analysis of the literature showed that viral infections are associated with alterations in the retinal vessels' vasoactivity. COVID-19 and other infections cause inflammation-associated the vasodilatation of microvasculature as a short-term effect of the infection. Long COVID-19 as well as HIV are the cause of chronic inflammation impacting microvascular morphology via retinal vessel diameter narrowing. The review emphasises the importance of the understudied area of viral infections' effects on retinal microcirculation. Continuous research in this area is needed to further verify retinal fundus imaging as an innovative tool for the optimal diagnosis of microvascular changes. As changes in the microvasculature precede changes in bigger arteries, the early detection of microvascular changes can go a long way in reducing the morbidity and mortality associated with cardiovascular diseases.}, }
@article {pmid39062549, year = {2024}, author = {Ashmawy, R and Hammouda, EA and El-Maradny, YA and Aboelsaad, I and Hussein, M and Uversky, VN and Redwan, EM}, title = {Interplay between Comorbidities and Long COVID: Challenges and Multidisciplinary Approaches.}, journal = {Biomolecules}, volume = {14}, number = {7}, pages = {}, pmid = {39062549}, issn = {2218-273X}, mesh = {Humans ; *COVID-19/epidemiology/immunology ; *Comorbidity ; *SARS-CoV-2/immunology ; *Post-Acute COVID-19 Syndrome ; Autoantibodies/immunology ; }, abstract = {Long COVID, a name often given to the persistent symptoms following acute SARS-CoV-2 infection, poses a multifaceted challenge for health. This review explores the intrinsic relationship between comorbidities and autoimmune responses in shaping the trajectory of long COVID. Autoantibodies have emerged as significant players in COVID-19 pathophysiology, with implications for disease severity and progression. Studies show immune dysregulation persisting months after infection, marked by activated innate immune cells and high cytokine levels. The presence of autoantibodies against various autoantigens suggests their potential as comorbid factors in long COVID. Additionally, the formation of immune complexes may lead to severe disease progression, highlighting the urgency for early detection and intervention. Furthermore, long COVID is highly linked to cardiovascular complications and neurological symptoms, posing challenges in diagnosis and management. Multidisciplinary approaches, including vaccination, tailored rehabilitation, and pharmacological interventions, are used for mitigating long COVID's burden. However, numerous challenges persist, from evolving diagnostic criteria to addressing the psychosocial impact and predicting disease outcomes. Leveraging AI-based applications holds promise in enhancing patient management and improving our understanding of long COVID. As research continues to unfold, unravelling the complexities of long COVID remains paramount for effective intervention and patient care.}, }
@article {pmid39062904, year = {2024}, author = {Pacheco-García, U and Varela-López, E and Serafín-López, J}, title = {Immune Stimulation with Imiquimod to Best Face SARS-CoV-2 Infection and Prevent Long COVID.}, journal = {International journal of molecular sciences}, volume = {25}, number = {14}, pages = {}, pmid = {39062904}, issn = {1422-0067}, support = {Not applied//Instituto Nacional de Cardiolog&#xed;a Ignacio Ch&#xe1;vez/ ; Not Applied//Instituto Nacional de Cardiolog&#xed;a Ignacio Ch&#xe1;vez/ ; }, mesh = {Humans ; *Imiquimod ; *COVID-19/immunology/prevention &amp; control/complications ; *SARS-CoV-2/immunology ; Post-Acute COVID-19 Syndrome ; Adjuvants, Immunologic/therapeutic use ; Cytokines/metabolism ; COVID-19 Vaccines/immunology ; }, abstract = {Through widespread immunization against SARS-CoV-2 prior to or post-infection, a substantial segment of the global population has acquired both humoral and cellular immunity, and there has been a notable reduction in the incidence of severe and fatal cases linked to this virus and accelerated recovery times for those infected. Nonetheless, a significant demographic, comprising around 20% to 30% of the adult population, remains unimmunized due to diverse factors. Furthermore, alongside those recovered from the infection, there is a subset of the population experiencing persistent symptoms referred to as Long COVID. This condition is more prevalent among individuals with underlying health conditions and immune system impairments. Some Long COVID pathologies stem from direct damage inflicted by the viral infection, whereas others arise from inadequate immune system control over the infection or suboptimal immunoregulation. There are differences in the serum cytokines and miRNA profiles between infected individuals who develop severe COVID-19 or Long COVID and those who control adequately the infection. This review delves into the advantages and constraints associated with employing imiquimod in human subjects to enhance the immune response during SARS-CoV-2 immunization. Restoration of the immune system can modify it towards a profile of non-susceptibility to SARS-CoV-2. An adequate immune system has the potential to curb viral propagation, mitigate symptoms, and ameliorate the severe consequences of the infection.}, }
@article {pmid39066223, year = {2024}, author = {Donald, J and Bilasy, SE and Yang, C and El-Shamy, A}, title = {Exploring the Complexities of Long COVID.}, journal = {Viruses}, volume = {16}, number = {7}, pages = {}, pmid = {39066223}, issn = {1999-4915}, mesh = {Humans ; *COVID-19/epidemiology ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; Risk Factors ; Comorbidity ; Prevalence ; Female ; Male ; Dysbiosis ; }, abstract = {Since the emergence of the SARS-CoV-2 virus in 2019, nearly 700 million COVID-19 cases and 7 million deaths have been reported globally. Despite most individuals recovering within four weeks, the Center for Disease Control (CDC) estimates that 7.5% to 41% develop post-acute infection syndrome (PAIS), known as 'Long COVID'. This review provides current statistics on Long COVID's prevalence, explores hypotheses concerning epidemiological factors, such as age, gender, comorbidities, initial COVID-19 severity, and vaccine interactions, and delves into potential mechanisms, including immune responses, viral persistence, and gut dysbiosis. Moreover, we conclude that women, advanced age, comorbidities, non-vaccination, and low socioeconomic status all appear to be risk factors. The reasons for these differences are still not fully understood and likely involve a complex relationship between social, genetic, hormonal, and other factors. Furthermore, individuals with Long COVID-19 seem more likely to endure economic hardship due to persistent symptoms. In summary, our findings further illustrate the multifaceted nature of Long COVID and underscore the importance of understanding the epidemiological factors and potential mechanisms needed to develop effective therapeutic strategies and interventions.}, }
@article {pmid39066303, year = {2024}, author = {Maham, S and Yoon, MS}, title = {Clinical Spectrum of Long COVID: Effects on Female Reproductive Health.}, journal = {Viruses}, volume = {16}, number = {7}, pages = {}, pmid = {39066303}, issn = {1999-4915}, support = {No. HV22C0128//the Korea Health Industry Development Institute (KHIDI)/ ; GCU-202103040001//Gachon University Research Fund of 2020/ ; }, mesh = {Humans ; Female ; *COVID-19/epidemiology/virology/immunology ; *Reproductive Health ; *SARS-CoV-2 ; Menstrual Cycle ; Post-Acute COVID-19 Syndrome ; Fertility ; }, abstract = {The COVID-19 pandemic caused by SARS-CoV-2 has presented numerous health challenges, including long-term COVID, which affects female reproductive health. This review consolidates the current research on the impact of SARS-CoV-2 on the menstrual cycle, ovarian function, fertility, and overall gynecological health. This study emphasizes the role of angiotensin-converting enzyme receptors in viral entry and the subsequent tissue-specific pathological effects. It also explores the potential influence of long COVID on hormonal balance and immune responses, contributing to menstrual irregularities and impaired ovarian function. The findings indicate a higher prevalence of long-term COVID-19 among women, highlighting the substantial implications for reproductive health and the need for sex-sensitive longitudinal studies. Enhanced surveillance and targeted research are essential to develop effective interventions that prioritize women's reproductive well-being following SARS-CoV-2 infection. This review advocates for a sex-informed approach to ongoing COVID-19 research and healthcare strategies, aiming to provide up-to-date and pertinent data for healthcare providers and the general public, ultimately improving outcomes for females affected by long COVID.}, }
@article {pmid39069330, year = {2024}, author = {Okuducu, YK and Mall, MA and Yonker, LM}, title = {COVID-19 in Pediatric Populations.}, journal = {Clinics in chest medicine}, volume = {45}, number = {3}, pages = {675-684}, doi = {10.1016/j.ccm.2024.02.019}, pmid = {39069330}, issn = {1557-8216}, support = {R01 HL173059/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/epidemiology/complications ; Child ; *SARS-CoV-2 ; Systemic Inflammatory Response Syndrome/epidemiology/therapy ; Child, Preschool ; Risk Factors ; Age Factors ; }, abstract = {The COVID-19 pandemic reshaped the landscape of respiratory viral illnesses, causing common viruses to fade as SARS-CoV-2 took precedence. By 2023, more than 96% of the children in the United States were estimated to have been infected with SARS-CoV-2, with certain genetic predispositions and underlying health conditions posing risk factors for severe disease in children. Children, in general though, exhibit immunity advantages, protecting against aspects of the SARS-CoV-2 infection known to drive increased severity in older adults. Post-COVID-19 complications such as multisystem inflammatory syndrome in children and long COVID have emerged, underscoring the importance of vaccination. Here, we highlight the risks of severe pediatric COVID-19, age-specific immunoprotection, comparisons of SARS-CoV-2 with other respiratory viruses, and factors contributing to post-COVID-19 complications in children.}, }
@article {pmid39069361, year = {2024}, author = {Gott, D and Orsillo, K and Ticotsky, A}, title = {Connecting the Dots: Unveiling the Overlapping Realities of Long Coronavirus Disease and Post-Intensive Care Syndrome.}, journal = {Critical care nursing clinics of North America}, volume = {36}, number = {3}, pages = {427-436}, doi = {10.1016/j.cnc.2023.12.006}, pmid = {39069361}, issn = {1558-3481}, mesh = {Humans ; *COVID-19 ; Intensive Care Units ; Post-Acute COVID-19 Syndrome ; Critical Care Nursing ; Critical Care ; Critical Illness ; }, abstract = {Critical care areas saw an unprecedented number of patients throughout the coronavirus disease 2019 (COVID-19) pandemic. Unfortunately, many of these patients continue to experience lingering symptoms long after their discharge from the intensive care unit, related to post-intensive care syndrome and/or post-acute sequelae of COVID-19. Nurses should be aware of these often invisible illnesses and attentive to the fact that this patient population requires ongoing support via multidisciplinary, coordinated care.}, }
@article {pmid39076856, year = {2023}, author = {Kusumawardhani, NY and Putra, ICS and Kamarullah, W and Afrianti, R and Pramudyo, M and Iqbal, M and Prameswari, HS and Achmad, C and Tiksnadi, BB and Akbar, MR}, title = {Cardiovascular Disease in Post-Acute COVID-19 Syndrome: A Comprehensive Review of Pathophysiology and Diagnosis Approach.}, journal = {Reviews in cardiovascular medicine}, volume = {24}, number = {1}, pages = {28}, pmid = {39076856}, issn = {2153-8174}, abstract = {Long COVID or post-acute Coronavirus disease 2019 (COVID-19), a malady defined by the persistence of COVID-19 symptoms for weeks or even months, is expected to affect the lives of millions of individuals worldwide significantly. Cardiopulmonary symptoms such as chest discomfort, shortness of breath, fatigue, and autonomic manifestations such as postural orthostatic tachycardia syndrome, and arrhythmias are prevalent and widely recognized. A variety of cardiovascular problems, including myocardial inflammation, myocardial infarction, ventricular dysfunction, and endothelial dysfunction, have been described in individuals following the initial acute phase. With over 10,000 published publications on COVID-19 and the cardiovascular system, presenting an unbiased thorough analysis of how SARS-CoV-2 affects the system is essentially challenging. This review will provide an overview of frequent cardiovascular manifestations, emphasizing consequences, proposed pathophysiology, and clinical diagnostic manifestation strategy.}, }
@article {pmid39081420, year = {2024}, author = {Gollapudi, S and Chimurkar, V}, title = {Comprehensive Insights Into the Multi-faceted Manifestations of COVID-19: A Narrative Review.}, journal = {Cureus}, volume = {16}, number = {6}, pages = {e63493}, pmid = {39081420}, issn = {2168-8184}, abstract = {The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the ensuing COVID-19 pandemic had far-reaching and multifaceted effects on global health. This paper provides a comprehensive overview of the physical, extrapulmonary, and psychological manifestations associated with COVID-19. It highlights the wide-ranging impact of the virus on various organ systems, including the respiratory, cardiovascular, renal, gastrointestinal, ocular, dermatologic, and nervous systems. Additionally, it explores the complex connections between COVID-19 infection and neuropsychiatric symptoms, shedding light on the potential underlying mechanisms. The paper also delves into the phenomenon of "long COVID," a condition characterized by persistent symptoms extending well beyond the disease's acute phase. It discusses the diverse and often debilitating symptoms that individuals with long COVID may experience, encompassing physical, cognitive, and psychological aspects. The complexity and variability of long COVID underscore the challenges it poses to healthcare professionals and the importance of ongoing research to understand its underlying mechanisms. Furthermore, the paper touches on the current state of knowledge regarding the aetiology of long COVID and the various approaches to symptom management and treatment. While a definitive cure remains elusive, efforts are underway to alleviate the burden of long COVID through pharmacological interventions, physical therapy, cognitive-behavioral therapy, and support networks. This paper comprehensively explores COVID-19's far-reaching effects, emphasizing the need for a holistic and interdisciplinary approach to understanding and managing the diverse manifestations of this global health challenge. Ongoing research and collaborative efforts are essential in addressing the complex and evolving nature of COVID-19 and its aftermath.}, }
@article {pmid39083202, year = {2024}, author = {Huang, Y and Wang, W and Liu, Y and Wang, Z and Cao, B}, title = {COVID-19 vaccine updates for people under different conditions.}, journal = {Science China. Life sciences}, volume = {67}, number = {11}, pages = {2323-2343}, pmid = {39083202}, issn = {1869-1889}, mesh = {Humans ; *COVID-19 Vaccines/immunology/administration &amp; dosage ; *COVID-19/prevention &amp; control/immunology/epidemiology ; *SARS-CoV-2/immunology ; Vaccine Efficacy ; Immunocompromised Host/immunology ; }, abstract = {SARS-CoV-2 has caused global waves of infection since December 2019 and continues to persist today. The emergence of SARS-CoV-2 variants with strong immune evasion capabilities has compromised the effectiveness of existing vaccines against breakthrough infections. Therefore, it is important to determine the best utilization strategies for different demographic groups given the variety of vaccine options available. In this review, we will discuss the protective efficacy of vaccines during different stages of the epidemic and emphasize the importance of timely updates to target prevalent variants, which can significantly improve immune protection. While it is recognized that vaccine effectiveness may be lower in certain populations such as the elderly, individuals with chronic comorbidities (e.g., diabetes with poor blood glucose control, those on maintenance dialysis), or those who are immunocompromised compared to the general population, administering multiple doses can result in a strong protective immune response that outweighs potential risks. However, caution should be exercised when considering vaccines that might trigger an intense immune response in populations prone to inflammatory flare or other complications. In conclusion, individuals with special conditions require enhanced and more effective immunization strategies to prevent infection or reinfection, as well as to avoid the potential development of long COVID.}, }
@article {pmid39084516, year = {2024}, author = {Li, B and Bai, J and Xiong, Y and Guo, D and Fu, B and Deng, G and Wu, H}, title = {Understanding the mechanisms and treatments of long COVID to address future public health risks.}, journal = {Life sciences}, volume = {353}, number = {}, pages = {122938}, doi = {10.1016/j.lfs.2024.122938}, pmid = {39084516}, issn = {1879-0631}, mesh = {Humans ; *COVID-19/therapy ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome ; *Public Health ; }, abstract = {The 2019 coronavirus disease (COVID-19), triggered by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), has seen numerous individuals undergo and recover from it, drawing extensive attention to their health conditions. Extensive studies indicate that even after surpassing the acute phase of infection, patients continue to experience persistent symptoms such as fatigue, pain, depression, weakening, and anosmia. COVID-19 appears not to have concluded but rather to persist long-term in certain individuals, termed as "long COVID." This represents a heterogeneous ailment involving multiple organ systems, with a perceived complex and still elusive pathogenesis. Among patients with long COVID, observations reveal immune dysregulation, coagulation impairments, and microbial dysbiosis, considered potential mechanisms explaining sustained adverse outcomes post COVID-19. Based on the multifactorial nature, varied symptoms, and heterogeneity of long COVID, we have summarized several categories of current therapeutic approaches. Furthermore, the symptoms of long COVID resemble those of other viral illnesses, suggesting that existing knowledge may offer novel insights into long-term COVID implications. Here, we provide an overview of existing literature associated with long COVID and summarize potential mechanisms, treatment modalities, and other analogous conditions. Lastly, we underscore the inadequacies in long COVID treatment approaches and emphasize the significance of conducting further research and clinical trials.}, }
@article {pmid39085687, year = {2025}, author = {Za, P and Papalia, GF and Gregori, P and Vasta, S and Papalia, R}, title = {Osteonecrosis as a manifestation of Long-COVID Syndrome: a systematic review.}, journal = {Musculoskeletal surgery}, volume = {109}, number = {1}, pages = {1-7}, pmid = {39085687}, issn = {2035-5114}, mesh = {Humans ; *COVID-19/complications ; *Osteonecrosis/etiology/diagnostic imaging/virology/drug therapy ; SARS-CoV-2 ; }, abstract = {Purpose SARS-CoV-2 is an RNA virus responsible for COVID-19 pandemic. Some authors described the set of persistent symptoms COVID-related as "Long-COVID Syndrome." Several cases of post-COVID-19 osteonecrosis (ON) are described. Our primary aim was to study the hypothetical correlation between SARS-CoV-2 infection and ON; our secondary aim was to understand if ON can be considered part of Long-COVID. Materials and methods We performed a systematic review following the Preferred Reporting Items for Systematic Reviewers and Meta-analysis (PRISMA) guidelines. Because COVID-19 is a recently described disease, we included all levels of evidence studies. We excluded studies lacking specification regarding the use of corticosteroids (CCS) and studies not related to COVID-19. The variables extracted were age, sex, risk factors, affected joints, signs and symptoms, magnetic resonance imaging (MRI) and X-ray features, histology, treatment of COVID-19, dose and duration of treatment with CCS, treatment of ON, follow-up, and treatment outcome. Results A total of 13 studies were included, involving 95 patients and 159 joints. Time between the diagnosis of COVID-19 and the onset of symptoms related to ON was 16 weeks on average. Time between the onset of symptoms and the MRI was 6 weeks. An average of 926.4 mg of prednisolone equivalent per patient were administered. On average, CCS were administered for 20.6 days. Conclusions Patients with a history of COVID-19 infection developed osteonecrosis prematurely and with a lower dose of CCS than usually reported in the literature. Symptoms of osteonecrosis occur within the interval of the period described as Long-COVID. Surgeons should not underestimate the persistence of arthralgia when a history of SARS-CoV-2 infection and use of CCS is reported.}, }
@article {pmid39086937, year = {2024}, author = {Lofrano-Porto, A and D'Isabel, S and Smith, DL}, title = {Developing a clinical-pathological framework of long COVID-related fatigue applied to public safety workers.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1387499}, pmid = {39086937}, issn = {2296-858X}, abstract = {In the wake of the COVID-19 pandemic, millions worldwide are still struggling with persistent or recurring symptoms known as long COVID. Fatigue is one of the most prevalent symptoms associated with long COVID, and for many it can be debilitating. Understanding the potential pathological processes that link fatigue to long COVID is critical to better guide treatment. Challenges with diagnosis and treatment are reviewed, recognizing that post-COVID fatigue does not always present with corroborating clinical evidence, a situation that is frustrating for both patients and healthcare providers. Firefighters are a group of public safety workers who are particularly impacted by long COVID-related fatigue. Firefighters must be able to engage in strenuous physical activity and deal with demanding psychological situations, both of which may be difficult for those suffering from fatigue. Disruption in public safety worker health can potentially impact community welfare. This review creates a framework to explain the clinical-pathological features of fatigue resulting from long COVID, addresses diagnosis and treatment challenges, and explores the unique impact fatigue may pose for public safety workers and their organizations.}, }
@article {pmid39087973, year = {2024}, author = {Ren, Y and Zhang, Z and Li, HP and Zhang, PJ and Duo, J and Kong, H}, title = {A Comprehensive Overview of the Stellate Ganglion Block Throughout the Past Three Decades: A Bibliometric Analysis.}, journal = {Pain physician}, volume = {27}, number = {5}, pages = {E597-E610}, pmid = {39087973}, issn = {2150-1149}, mesh = {*Bibliometrics ; *Stellate Ganglion ; Humans ; *Autonomic Nerve Block/methods ; }, abstract = {BACKGROUND: Over the past 3 decades, clinicians and scholars have used and studied the stellate ganglion block (SGB) extensively, making this field a highly anticipated research hot spot. To the best of our knowledge, there has been no bibliometric analysis of the SGB until now.<br><br>OBJECTIVE: Our study aimed to complete multiple tasks regarding SGB research: identify the collaboration and impact of countries, institutions, journals, and authors, evaluate the knowledge base, trace the trends in hot spots, and explore the emerging topics relevant to the field.<br><br>STUDY DESIGN: A bibliometric analysis.<br><br>METHODS: Publications that were associated with the SGB and published between the years of 1993 and 2022 were retrieved from the Web of Science Core Collection on September 21st, 2023. CiteSpace 6.1.R6 and VOSviewer 1.6.18 were used to perform bibliometric and knowledge-map analyses.<br><br>RESULTS: This study found a total of 837 publications originating from 51 countries and 1006 institutions. These articles were published in 393 journals. The United States was the country that produced the most articles focused on SGB, and the University of California, Los Angeles was the institution associated with the greatest number of publications. The anesthesiology and cardiology journals surveyed for this study published the most articles and received the most citations. Among the authors whose works were examined, Kitajima T had the greatest number of published articles, and Lipov E was the most frequently cited co-author. Five main domains of SGB research included electrical storm and refractory ventricular arrhythmia, breast cancer and climacteric medicine, post-traumatic stress disorder, pain management, and cerebrovascular diseases. The latest hot topics involving this field focused on SGB's anti-arrhythmic and anti-cerebral vasospasm effects and its treatment of long COVID syndrome.<br><br>LIMITATIONS: Data were retrieved only from the WoSCC; therefore, publications in other databases might have been missed.<br><br>CONCLUSION: This comprehensive bibliometric analysis conducted a complete overview of SGB research, which was helpful in furthering our understanding of research trends and locating research hot spots and gaps in this domain. This field is developing rapidly and will garner significant and continuous attention from future scholars.}, }
@article {pmid39096925, year = {2024}, author = {Greenhalgh, T and Sivan, M and Perlowski, A and Nikolich, J&#x17d;}, title = {Long COVID: a clinical update.}, journal = {Lancet (London, England)}, volume = {404}, number = {10453}, pages = {707-724}, doi = {10.1016/S0140-6736(24)01136-X}, pmid = {39096925}, issn = {1474-547X}, mesh = {Humans ; *COVID-19/epidemiology ; *Post-Acute COVID-19 Syndrome/epidemiology/physiopathology/therapy ; }, abstract = {Post-COVID-19 condition (also known as long COVID) is generally defined as symptoms persisting for 3 months or more after acute COVID-19. Long COVID can affect multiple organ systems and lead to severe and protracted impairment of function as a result of organ damage. The burden of this disease, both on the individual and on health systems and national economies, is high. In this interdisciplinary Review, with a coauthor with lived experience of severe long COVID, we sought to bring together multiple streams of literature on the epidemiology, pathophysiology (including the hypothesised mechanisms of organ damage), lived experience and clinical manifestations, and clinical investigation and management of long COVID. Although current approaches to long COVID care are largely symptomatic and supportive, recent advances in clinical phenotyping, deep molecular profiling, and biomarker identification might herald a more mechanism-informed and personally tailored approach to clinical care. We also cover the organisation of services for long COVID, approaches to preventing long COVID, and suggestions for future research.}, }
@article {pmid39098596, year = {2024}, author = {Strongin, SR and Stelson, E and Soares, L and Sukhatme, V and Dasher, P and Schito, M and Challa, AP and Geng, LN and Walker, TA}, title = {Using real-world data to accelerate the search for long COVID therapies.}, journal = {Life sciences}, volume = {353}, number = {}, pages = {122940}, doi = {10.1016/j.lfs.2024.122940}, pmid = {39098596}, issn = {1879-0631}, mesh = {Humans ; *COVID-19/therapy ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome ; COVID-19 Drug Treatment ; Antiviral Agents/therapeutic use ; Clinical Trials as Topic ; Quality of Life ; }, abstract = {Long COVID, a spectrum of symptoms and syndromes that can develop after SARS-COV-2 infection, can significantly affect patients' health, quality of life and impact their ability to productively function in society. There is currently no approved therapy for Long COVID and there is an urgent need for rigorous clinical trials to find such treatments. Although research into the pathophysiology of Long COVID is advancing, investigations into treatment for patients remain underfunded and, as a result, understudied. Owing to the urgency of the Long COVID pandemic and as a research collaborative across a diversity of biomedical innovation value propositions, we are calling for a new approach that parallelizes pathophysiologic and therapeutic research into this condition, leveraging patient-centered research and real-world data to generate hypotheses to assess the effectiveness of existing FDA approved drugs. Accelerated discovery of therapeutics for Long COVID can then be confirmed through efficient and cost-effective adaptive platform clinical trials.}, }
@article {pmid39099786, year = {2024}, author = {Lam, WC and Wei, D and Li, H and Yao, L and Zhang, S and Lai, MXY and Zheng, Y and Yeung, JWF and Lau, AYL and Lyu, A and Bian, Z and Cheung, AM and Zhong, LLD}, title = {The use of acupuncture for addressing neurological and neuropsychiatric symptoms in patients with long COVID: a systematic review and meta-analysis.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1406475}, pmid = {39099786}, issn = {1664-2295}, abstract = {IMPORTANCE: Acupuncture has been used to treat neurological and neuropsychiatric symptoms in China and other parts of the world. These symptoms, such as fatigue, headache, cognitive impairment, anxiety, depression, and insomnia, are common in people experiencing long COVID.<br><br>OBJECTIVE: This study aims to explore the feasibility of acupuncture in the treatment of neurological and neuropsychiatric symptoms in long COVID patients.<br><br>DATA SOURCES: A systematic search was conducted in four English and four Chinese databases from inception to 23 June 2023. Literature selection and data extraction were conducted by two pairs of independent reviewers.<br><br>STUDY SELECTION: Randomized controlled trials (RCTs) that explored the effect of acupuncture on fatigue, depression, anxiety, cognitive abnormalities, headache, and insomnia were included.<br><br>DATA EXTRACTION AND SYNTHESIS: RCTs that explored the effect of acupuncture on fatigue, depression, anxiety, cognitive abnormalities, headache, and insomnia were included. A meta-analysis was performed using R software. Heterogeneity was measured using I[2]. Subgroup analyses were performed focusing on the duration of treatment and acupuncture modalities. The systematic review protocol was registered on PROSPERO (registration number: CRD42022354940).<br><br>MAIN OUTCOMES AND MEASURES: Widely adopted clinical outcome scales included the Fatigue Scale for assessing fatigue, the Hamilton Depression Rating Scale for evaluating depression, the Mini-Mental State Examination for assessing cognitive impairment, the Visual Analog Scale for headache severity, and the Pittsburgh Sleep Quality Index for measuring insomnia.<br><br>RESULTS: A total of 110 RCTs were included in the systematic review and meta-analysis. Overall, acupuncture was found to improve the scores of the Fatigue Scale (vs. medication: mean differences (MD): -2.27, P < 0.01; vs. sham acupuncture: MD: -3.36, P < 0.01), the Hamilton Depression Rating Scale (vs. medication: MD: -1.62, 95%, P < 0.01; vs. sham acupuncture: MD: -9.47, P < 0.01), the Mini-Mental State Examination (vs. medication: MD: 1.15, P < 0.01; vs. sham acupuncture: MD: 1.20, P < 0.01), the Visual Analog Scale (vs. medication: MD: -1.05, P < 0.01; vs. waitlist: MD: -0.48, P=0.04), and the Pittsburgh Sleep Quality Index (vs. medication: MD: -2.33, P < 0.01; vs. sham acupuncture: MD: -4.19, P < 0.01).<br><br>CONCLUSION AND RELEVANCE: This systematic review suggested acupuncture as a potentially beneficial approach for the treatment of neurological and neuropsychiatric symptoms, as assessed using clinical scales, and it may have applicability in long COVID patients. Further well-designed clinical studies specifically targeting long COVID patients are needed to validate the role of acupuncture in alleviating long COVID symptoms.<br><br>PROSPERO, identifier [CRD42022354940].}, }
@article {pmid39102189, year = {2024}, author = {Sher, L}, title = {Long COVID-19 and Suicide.}, journal = {Advances in experimental medicine and biology}, volume = {1458}, number = {}, pages = {51-57}, pmid = {39102189}, issn = {0065-2598}, mesh = {Humans ; *COVID-19/psychology/epidemiology/complications ; *Suicide/psychology/statistics &amp; numerical data ; *SARS-CoV-2/pathogenicity ; Suicidal Ideation ; Risk Factors ; Suicide Prevention ; Post-Acute COVID-19 Syndrome ; Depression/psychology/epidemiology ; Anxiety/psychology/epidemiology ; Mental Disorders/psychology/epidemiology ; }, abstract = {Suicide is a significant public health problem around the world. More than 90% of individuals who die by suicide have a diagnosable psychiatric disorder, and most persons who attempt suicide also have a psychiatric illness. Depression, anxiety, posttraumatic symptoms, sleep disturbances, decreased energy, and cognitive abnormalities are the most frequently reported psychiatric symptoms of long COVID. All these conditions are associated with suicidal ideation and behavior. Therefore, individuals with long COVID may be at increased risk of suicide. Recent studies of patients with long COVID confirm that individuals with long COVID are at increased suicide risk. It is vital to educate clinicians taking care of long COVID individuals that patients with long COVID may be suicidal, that it is essential to screen patients with long COVID for suicidality, and if needed, suicide prevention interventions should be employed.}, }
@article {pmid39102196, year = {2024}, author = {Fuller, H and King-Okoye, M}, title = {Improving Pathways to Care for Ethnic Minority Communities.}, journal = {Advances in experimental medicine and biology}, volume = {1458}, number = {}, pages = {157-173}, pmid = {39102196}, issn = {0065-2598}, mesh = {Humans ; *COVID-19/epidemiology/prevention &amp; control/therapy ; COVID-19 Vaccines/therapeutic use ; *Ethnic and Racial Minorities ; *Health Services Accessibility ; *Healthcare Disparities ; Pandemics/prevention &amp; control ; *Social Determinants of Health ; }, abstract = {It is well established that the COVID-19 pandemic has had a substantial impact on ethnic minority communities and has worsened existing health inequalities experienced by these populations globally. Individuals from ethnic minority backgrounds have not only been more likely to become infected with COVID-19 throughout the pandemic, but they have also higher risk of adverse symptoms and death following infection. Factors responsible for these discrepancies are wide reaching and encompass all aspects of the social determinants of health (SDoH). Although always an area of concern among healthcare professionals, barriers to health care experienced by ethnic minority populations became a more pertinent issue during the COVID-19 pandemic when all individuals required sufficient and sustained access to a healthcare system (whether this be for COVID-19 testing, vaccination or treatment). These healthcare barriers exacerbated the increased COVID-19 burden experienced by minority populations and will continue to detrimentally impact the health of these populations during future COVID-19 waves or indeed, future novel pandemics. This chapter aims to summarise the major healthcare barriers experienced by minority populations throughout the COVID-19 pandemic, including COVID-19 prevention, vaccine rollout, care during hospitalisation and post-COVID care for long COVID patients. To end, this chapter will summarise lessons learned and future directions that need to be taken to improve health disparities and healthcare access for minority populations in relation to the COVID pandemic and beyond.}, }
@article {pmid39103645, year = {2024}, author = {Thomas, C and Faghy, MA and Chidley, C and Phillips, BE and Bewick, T and Ashton, RE}, title = {Blood Biomarkers of Long COVID: A Systematic Review.}, journal = {Molecular diagnosis &amp; therapy}, volume = {28}, number = {5}, pages = {537-574}, pmid = {39103645}, issn = {1179-2000}, mesh = {Humans ; *COVID-19/blood/diagnosis ; *Biomarkers/blood ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long coronavirus disease (COVID; LC) affects millions of people worldwide. The exact mechanisms which result in a broad, undulating and detrimental symptom profile remain unknown. Blood biomarkers associated with LC have been described; however, consensus on these remains elusive, in part due to a lack of continuity between studies on a universally accepted definition of LC. This systematic review aimed to consolidate current knowledge of blood biomarkers associated with the prevalence of LC on the basis of the World Health Organisation (WHO) clinical definition of this condition.<br><br>Observational, cross-sectional, and randomised control studies published in the English language that studied blood biomarkers associated with the WHO definition of LC. All studies included participants who were &#x2265; 18 years old and group sizes &#x2265; 10 participants, and were compared against a control group without any known co-morbidities.<br><br>METHODS: A systematic literature search was conducted according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and prospectively registered on Prospero (ID: CRD42022373121). The Cochrane, Embase, PubMed and Web of Science databases were searched from inception to January 2024. Search results were gathered using Rayyan software and data extracted using Microsoft Excel. The reporting recommendations for tumour markers prognostic studies (REMARK) questionnaire was used to assess the quality of the included studies.<br><br>RESULTS: A total of 45 observational and one interventional study comprising 4415 participants were included in this review which identified 525 blood biomarkers thought to be associated with LC. Three blood biomarker subtypes were associated with the development of LC: (1) immunological and inflammatory dysfunction, (2) endothelial/vascular dysfunction and (3) metabolic and clotting abnormalities.<br><br>DISCUSSION AND CONCLUSIONS: Our data are consistent with previous findings; however, no single biomarker was sufficiently associated with LC prevalence and instead a profile of biomarkers across various physiological systems may be more clinically useful. In all, 196 studies were excluded due to a lack of an adequately healthy comparator group and/or failure to meet the WHO LC definition. This demonstrates a need for further research incorporating a universal LC definition across all disease severity groups and symptom profiles, and longitudinal data reflecting the relapsing and remitting nature of this condition. Further investigation into blood biomarkers of LC, including clear reporting of healthy comparator groups and the investigation of acute and chronic biomarker changes, within the context of medical practice, may support the development of curative/restorative approaches.}, }
@article {pmid39120242, year = {2024}, author = {Jia, G and Su, CH}, title = {Tailored Physical Activity Interventions for Long COVID: Current Approaches and Benefits-A Narrative Review.}, journal = {Healthcare (Basel, Switzerland)}, volume = {12}, number = {15}, pages = {}, pmid = {39120242}, issn = {2227-9032}, support = {Grant No. HXXM-18-10-006//Beijing Jingti da Culture Development Co. , Ltd./ ; }, abstract = {This narrative review explores the essential role of physical activity in managing long COVID, which is characterized by persistent symptoms such as fatigue, breathlessness, and cognitive impairments following SARS-CoV-2 infection. In this context, "physical activity" includes various exercises, such as aerobic and resistance training, as well as flexibility and balance exercises, thereby encompassing the subset known as "exercise". The methodology involved a comprehensive literature search across PubMed, EBSCO (EDS), and Google Scholar, selecting peer-reviewed articles from December 2019 to June 2024 focusing on long COVID physical activity interventions. The review highlights that tailored exercise programs, adjusted to individual health status and abilities, significantly alleviate symptoms and enhance psychological well-being. Key findings emphasize the importance of personalized exercise prescriptions due to the variability in patient responses and the need for a multidisciplinary approach in developing and monitoring interventions. Despite promising outcomes, the review identifies research gaps, including the need for long-term studies, randomized controlled trials, and deeper mechanistic insights. It suggests that standardized reporting, templates like the Consensus on Exercise Reporting Template (CERT), and integrating digital health tools are essential for optimizing interventions. Overall, the review advocates including personalized physical activity or exercise programs in standard care for long COVID to improve patient outcomes and quality of life.}, }
@article {pmid39122965, year = {2024}, author = {Al-Aly, Z and Davis, H and McCorkell, L and Soares, L and Wulf-Hanson, S and Iwasaki, A and Topol, EJ}, title = {Long COVID science, research and policy.}, journal = {Nature medicine}, volume = {30}, number = {8}, pages = {2148-2164}, pmid = {39122965}, issn = {1546-170X}, mesh = {Humans ; *COVID-19/epidemiology ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome ; Health Policy ; Global Health ; Biomedical Research/trends ; }, abstract = {Long COVID represents the constellation of post-acute and long-term health effects caused by SARS-CoV-2 infection; it is a complex, multisystem disorder that can affect nearly every organ system and can be severely disabling. The cumulative global incidence of long COVID is around 400 million individuals, which is estimated to have an annual economic impact of approximately $1 trillion-equivalent to about 1% of the global economy. Several mechanistic pathways are implicated in long COVID, including viral persistence, immune dysregulation, mitochondrial dysfunction, complement dysregulation, endothelial inflammation and microbiome dysbiosis. Long COVID can have devastating impacts on individual lives and, due to its complexity and prevalence, it also has major ramifications for health systems and economies, even threatening progress toward achieving the Sustainable Development Goals. Addressing the challenge of long COVID requires an ambitious and coordinated-but so far absent-global research and policy response strategy. In this interdisciplinary review, we provide a synthesis of the state of scientific evidence on long COVID, assess the impacts of long COVID on human health, health systems, the economy and global health metrics, and provide a forward-looking research and policy roadmap.}, }
@article {pmid39125722, year = {2024}, author = {Chung, YS and Lam, CY and Tan, PH and Tsang, HF and Wong, SC}, title = {Comprehensive Review of COVID-19: Epidemiology, Pathogenesis, Advancement in Diagnostic and Detection Techniques, and Post-Pandemic Treatment Strategies.}, journal = {International journal of molecular sciences}, volume = {25}, number = {15}, pages = {}, pmid = {39125722}, issn = {1422-0067}, mesh = {Humans ; *COVID-19/epidemiology/diagnosis/virology ; *SARS-CoV-2/isolation &amp; purification ; Pandemics ; COVID-19 Testing/methods ; }, abstract = {At present, COVID-19 remains a public health concern due to the ongoing evolution of SARS-CoV-2 and its prevalence in particular countries. This paper provides an updated overview of the epidemiology and pathogenesis of COVID-19, with a focus on the emergence of SARS-CoV-2 variants and the phenomenon known as 'long COVID'. Meanwhile, diagnostic and detection advances will be mentioned. Though many inventions have been made to combat the COVID-19 pandemic, some outstanding ones include multiplex RT-PCR, which can be used for accurate diagnosis of SARS-CoV-2 infection. ELISA-based antigen tests also appear to be potential diagnostic tools to be available in the future. This paper also discusses current treatments, vaccination strategies, as well as emerging cell-based therapies for SARS-CoV-2 infection. The ongoing evolution of SARS-CoV-2 underscores the necessity for us to continuously update scientific understanding and treatments for it.}, }
@article {pmid39127088, year = {2024}, author = {Almulla, AF and Thipakorn, Y and Zhou, B and Vojdani, A and Maes, M}, title = {Immune activation and immune-associated neurotoxicity in Long-COVID: A systematic review and meta-analysis of 103 studies comprising 58 cytokines/chemokines/growth factors.}, journal = {Brain, behavior, and immunity}, volume = {122}, number = {}, pages = {75-94}, doi = {10.1016/j.bbi.2024.07.036}, pmid = {39127088}, issn = {1090-2139}, mesh = {Humans ; C-Reactive Protein/metabolism ; *Chemokines/immunology ; *COVID-19/immunology ; *Cytokines/immunology ; *Intercellular Signaling Peptides and Proteins/metabolism ; Neurotoxicity Syndromes/immunology ; *Post-Acute COVID-19 Syndrome/immunology ; }, abstract = {BACKGROUND: Multiple studies have shown that Long COVID (LC) disease is associated with heightened immune activation, as evidenced by elevated levels of inflammatory mediators. However, there is no comprehensive meta-analysis focusing on activation of the immune inflammatory response system (IRS) and the compensatory immunoregulatory system (CIRS) along with other immune phenotypes in LC patients.<br><br>OBJECTIVES: This meta-analysis is designed to explore the IRS and CIRS profiles in LC patients, the individual cytokines, chemokines, growth factors, along with C-reactive protein (CRP) and immune-associated neurotoxicity.<br><br>METHODS: To gather relevant studies for our research, we conducted a thorough search using databases such as PubMed, Google Scholar, and SciFinder, covering all available literature up to July 5th, 2024.<br><br>RESULTS: The current meta-analysis encompassed 103 studies that examined multiple immune profiles, C-reactive protein, and 58 cytokines/chemokines/growth factors in 5502 LC patients versus 5962 normal controls (NC). LC patients showed significant increases in IRS/CIRS ratio (standardized mean difference (SMD: 0.156, confidence interval (CI): 0.062;0.250), IRS (SMD: 0.338, CI: 0.236;0.440), M1 macrophage (SMD: 0.371, CI: 0.263;0.480), T helper (Th)1 (SMD: 0.316, CI: 0.185;0.446), Th17 (SMD: 0.439, CI: 0.302;0.577) and immune-associated neurotoxicity (SMD: 0.384, CI: 0.271;0.497). In addition, CRP and 21 different cytokines displayed significantly elevated levels in LC patients compared to NC.<br><br>CONCLUSION: LC disease is characterized by IRS activation and increased immune-associated neurotoxicity.}, }
@article {pmid39127446, year = {2024}, author = {Shrestha, A and Chen, R and Kunasekaran, M and Honeyman, D and Notaras, A and Sutton, B and Quigley, A and MacIntyre, CR}, title = {The risk of cognitive decline and dementia in older adults diagnosed with COVID-19: A systematic review and meta-analysis.}, journal = {Ageing research reviews}, volume = {101}, number = {}, pages = {102448}, doi = {10.1016/j.arr.2024.102448}, pmid = {39127446}, issn = {1872-9649}, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; *Cognitive Dysfunction/epidemiology/psychology/diagnosis/etiology ; *COVID-19/psychology/complications/epidemiology ; *Dementia/diagnosis/epidemiology/etiology/psychology ; Risk Factors ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Cognitive impairment can be caused by infections with various pathogens, including SARS-CoV-2. Research has yet to determine the true incidence and course of cognitive impairment in older adults following COVID-19. Furthermore, research has theorised that COVID-19 is associated with dementia progression and diagnosis but this association has yet to be fully described.<br><br>METHODS: A systematic review was registered in Prospero and conducted on the databases PubMed, Embase, Ovid, CENTRAL and Cochrane Library. Studies reporting cognitive impairment and dementia outcomes in post-acute and post-COVID-19 patients aged &#x2265;65 years, and which included control data, were included in this review.<br><br>RESULTS: 15,124 articles were identified by the search strategy. After eliminating duplicate titles and completing title, abstracts and full-text review, 18 studies were included comprising of 412,957 patients with COVID-19 (46.63&#x202f;% male) and 411,929 patients without COVID-19 (46.59&#x202f;% male). The overall mean Montreal Cognitive Assessment (MoCA) score in COVID-19 patients was 23.34 out of 30 (95&#x202f;% CI [22.24, 24.43]). indicating cognitive impairment. The overall proportion of patients identified as having new onset cognitive impairment was 65&#x202f;% (95&#x202f;% CI [44,81]). Subgroup analyses indicated that time since infection significantly improves overall MoCA score and reduces proportion of patients with cognitive impairment.<br><br>CONCLUSION: This study indicates that cognitive impairment may be an important sequela of COVID-19. Further research with adequate sample sizes is warranted regarding COVID-19's association with new-onset dementia and dementia progression, and the effect of repeat infections. There is a need for development of diagnostic and management protocols for COVID-19 patients with cognitive impairment.}, }
@article {pmid39129538, year = {2024}, author = {Xu, Z and Wang, W and Zhang, D and Tam, KW and Li, Y and Chan, DCC and Yang, Z and Wong, SYS}, title = {Excess risks of long COVID symptoms compared with identical symptoms in the general population: A systematic review and meta-analysis of studies with control groups.}, journal = {Journal of global health}, volume = {14}, number = {}, pages = {05022}, pmid = {39129538}, issn = {2047-2986}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: It is important to understand the excess risks of symptoms of long COVID when compared to the same symptoms in the general population. We aimed to evaluate the association between coronavirus disease 2019 (COVID-19) infection and various long-term symptoms.<br><br>METHODS: We conducted a systematic review and meta-analysis of studies measuring long COVID symptoms lasting for at least three months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in comparison to non-COVID-19 control groups. We searched MEDLINE and Embase (via Ovid), CINAHL (via EBSCOhost), the ProQuest Coronavirus Research Database, and the World Health Organization COVID-19 Research Database for relevant literature on 14 February 2023. The symptom list had 10 categories with 29 symptoms, including general, neurologic, respiratory, cardiac, dermatologic, eye, ear, musculoskeletal, psychiatric, and gastrointestinal symptoms. We performed random-effects meta-analysis and summarised the results using odds ratios (OR) and 95% confidence intervals (CI), after which we conducted subgroup analyses.<br><br>RESULTS: We included 51 studies with 17&#x2009;901&#x2009;204 participants (range of mean age: 5.9-65.4 years; range of proportion of women: 11.2-96.0%). In the primary analysis, participants with COVID-19 had a significantly higher risk of having at least one long COVID symptom (OR&#x2009;=&#x2009;2.032; 95% CI&#x2009;=&#x2009;1.787-2.310). Specifically, they had higher risks of 25 symptoms, the highest of which were for smell (OR&#x2009;=&#x2009;8.474; 95% CI&#x2009;=&#x2009;6.357-11.295), taste (OR&#x2009;=&#x2009;5.881; 95% CI&#x2009;=&#x2009;3.818-9.059), post-exertional malaise (OR&#x2009;=&#x2009;3.187; 95% CI&#x2009;=&#x2009;2.602-3.904), shortness of breath (OR&#x2009;=&#x2009;2.497; 95% CI&#x2009;=&#x2009;2.125-2.935), brain fog (OR&#x2009;=&#x2009;2.093; 95% CI&#x2009;=&#x2009;1.362-3.218), hair loss (OR&#x2009;=&#x2009;2.082; 95% CI&#x2009;=&#x2009;1.291-3.358), chest pain (OR&#x2009;=&#x2009;2.056; 95% CI&#x2009;=&#x2009;1.692-2.498), cognitive decline (OR&#x2009;=&#x2009;1.992; 95% CI&#x2009;=&#x2009;1.560-2.544), palpitations (OR&#x2009;=&#x2009;1.986; 95% CI&#x2009;=&#x2009;1.647-2.395), and fatigue (OR&#x2009;=&#x2009;1.971; 95% CI&#x2009;=&#x2009;1.781-2.182). We found significant differences between studies with different follow-up times in cognitive decline, dizziness, palpitations, and sleep problems (P&#x2009;<&#x2009;0.05). Adults had significantly higher risks of cognitive decline, hair loss, and joint pain than children (P&#x2009;<&#x2009;0.05).<br><br>CONCLUSIONS: We found that COVID-19 can significantly increase the risk of many long COVID symptoms, without differences due to gender, age, or decrease over time after three months post-infection. This highlights that services and interventions for long COVID symptoms are needed.<br><br>REGISTRATION: PROSPERO (CRD42023409847).}, }
@article {pmid39133434, year = {2025}, author = {Saxena, A and Mautner, J}, title = {A Disease Hidden in Plain Sight: Pathways and Mechanisms of Neurological Complications of Post-acute Sequelae of COVID-19 (NC-PASC).}, journal = {Molecular neurobiology}, volume = {62}, number = {2}, pages = {2530-2547}, pmid = {39133434}, issn = {1559-1182}, mesh = {Humans ; *COVID-19/complications ; *Nervous System Diseases/etiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {The global impact of coronavirus disease 2019 (COVID-19) marked by numerous pandemic peaks is attributed to its high variability and infectious nature, transforming it into a persistent global public health concern. With hundreds of millions of cases reported globally, the illness is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite its initial classification as an acute respiratory illness, recent evidence indicates that lingering effects on various bodily systems, such as cardiovascular, pulmonary, nervous, gastrointestinal (GI), and musculoskeletal, may endure well beyond the acute phase. These persistent manifestations following COVID-19, commonly known as long COVID, have the potential to affect individuals across the entire range of illness severity, with a tendency to be more prevalent in mild to moderate cases. At present, there are no established criteria for diagnosing long COVID. Nonetheless, it is conceptualized as a multi-organ disorder encompassing a diverse array of clinical manifestations. The most common, persistent, and debilitating symptoms of long COVID may be neurological, known as neurological complications of post-acute sequelae of COVID-19 (NC-PASC). More than one-third of individuals with a prior SARS-CoV-2 infection show involvement of both the central nervous system (CNS) and peripheral nervous system (PNS), as evidenced by an approximately threefold higher incidence of neurological symptoms in observational studies. The persistent neurological symptoms of long COVID encompass fatigue, headache, cognitive decline, "brain fog", dysautonomia, neuropsychiatric issues, loss of smell (anosmia), loss of taste (ageusia), and peripheral nerve problems (peripheral neuropathy). Reported pathogenic mechanisms encompass viral persistence and neuro-invasion by SARS-CoV-2, neuroinflammation, autoimmunity, coagulopathy, and endotheliopathy. Raising awareness of potential complications is crucial for preventing and alleviating the long-term effects of long COVID and enhancing the prognosis for affected patients. This review explores the hypothetical pathophysiological mechanisms and pathways of NC-PASC with a sole aim to increase awareness about this crippling disease.}, }
@article {pmid39138793, year = {2025}, author = {Fekete, M and Liotta, EM and Molnar, T and Fülöp, GA and Lehoczki, A}, title = {The role of atrial fibrillation in vascular cognitive impairment and dementia: epidemiology, pathophysiology, and preventive strategies.}, journal = {GeroScience}, volume = {47}, number = {1}, pages = {287-300}, pmid = {39138793}, issn = {2509-2723}, support = {RRF-2.3.1-21-2022-00003//Nemzeti Kutat&#xe1;si, Fejleszt&#xe9;si &#xe9;s Innovaci&#xf3;s Alap/ ; }, mesh = {Humans ; *Atrial Fibrillation/epidemiology/complications/physiopathology ; *COVID-19/epidemiology ; *Cognitive Dysfunction/epidemiology/etiology/prevention &amp; control/physiopathology ; *Dementia, Vascular/epidemiology/prevention &amp; control/physiopathology/etiology ; SARS-CoV-2 ; Aged ; Risk Factors ; Europe/epidemiology ; }, abstract = {The aging population in Europe faces a substantial burden from dementia, with vascular cognitive impairment and dementia (VCID) being a preventable cause. Atrial fibrillation (AF), a common cardiac arrhythmia, increases the risk of VCID through mechanisms such as thromboembolism, cerebral hypoperfusion, and inflammation. This review explores the epidemiology, pathophysiology, and preventive strategies for AF-related VCID. Epidemiological data indicate that AF prevalence rises with age, affecting up to 12% of individuals over 80. Neuroimaging studies reveal chronic brain changes in AF patients, including strokes, lacunar strokes, white matter hyperintensities (WMHs), and cerebral microbleeds (CMHs), while cognitive assessments show impairments in memory, executive function, and attention. The COVID-19 pandemic has exacerbated the underdiagnosis of AF, leading to an increase in undiagnosed strokes and cognitive impairment. Many elderly individuals did not seek medical care due to fear of exposure, resulting in delayed diagnoses. Additionally, reduced family supervision during the pandemic contributed to missed opportunities for early detection of AF and related complications. Emerging evidence suggests that long COVID may also elevate the risk of AF, further complicating the management of this condition. This review underscores the importance of early detection and comprehensive management of AF to mitigate cognitive decline. Preventive measures, including public awareness campaigns, patient education, and the use of smart devices for early detection, are crucial. Anticoagulation therapy, rate and rhythm control, and addressing comorbid conditions are essential therapeutic strategies. Recognizing and addressing the cardiovascular and cognitive impacts of AF, especially in the context of the COVID-19 pandemic, is essential for advancing public health.}, }
@article {pmid39142505, year = {2024}, author = {Vogel, JM and Pollack, B and Spier, E and McCorkell, L and Jaudon, TW and Fitzgerald, M and Davis, H and Cohen, AK}, title = {Designing and optimizing clinical trials for long COVID.}, journal = {Life sciences}, volume = {355}, number = {}, pages = {122970}, doi = {10.1016/j.lfs.2024.122970}, pmid = {39142505}, issn = {1879-0631}, mesh = {Humans ; *COVID-19/epidemiology/therapy ; *Clinical Trials as Topic ; *Research Design ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; COVID-19 Drug Treatment ; Drug Repositioning/methods ; }, abstract = {Long COVID is a debilitating, multisystemic illness following a SARS-CoV-2 infection whose duration may be indefinite. Over four years into the pandemic, little knowledge has been generated from clinical trials. We analyzed the information available on ClinicalTrials.gov, and found that the rigor and focus of trials vary widely, and that the majority test non-pharmacological interventions with insufficient evidence. We highlight promising trials underway, and encourage the proliferation of clinical trials for treating Long COVID and other infection-associated chronic conditions and illnesses (IACCIs). We recommend several guidelines for Long COVID trials: First, pharmaceutical trials with potentially curative, primary interventions should be prioritized, and both drug repurposing and new drug development should be pursued. Second, study designs should be both rigorous and accessible, e.g., triple-blinded randomized trials that can be conducted remotely, without participants needing to leave their homes. Third, studies should have multiple illness comparator cohorts for IACCIs such as myalgic encephalomyelitis (ME/CFS) and dysautonomia, and screen for the full spectrum of symptomatology and pathologies of these illnesses. Fourth, studies should consider inclusion/exclusion criteria with an eye towards equity and breadth of representation, including participants of all races, ethnicities, and genders most impacted by COVID-19, and including all levels of illness severity. Fifth, involving patient-researchers in all aspects of studies brings immensely valuable perspectives that will increase the impact of trials. We also encourage the development of efficient clinical trial designs including methods to study several therapies in parallel.}, }
@article {pmid39142509, year = {2024}, author = {Brode, WM and Melamed, E}, title = {A practical framework for Long COVID treatment in primary care.}, journal = {Life sciences}, volume = {354}, number = {}, pages = {122977}, doi = {10.1016/j.lfs.2024.122977}, pmid = {39142509}, issn = {1879-0631}, mesh = {Humans ; *COVID-19/therapy ; *Primary Health Care ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; }, abstract = {Long COVID is a complex, multisystem illness with a poorly understood pathophysiology, absence of specific diagnostic tests or criteria, or evidence-based treatments. With over 200 identified symptoms and approximately 10% of COVID-19 cases resulting in Long COVID, it is a challenge to provide comprehensive treatment at a scale commensurate with the illness burden. The diverse manifestations of Long COVID, encompassing numerous medical specialties, typically place primary care providers (PCPs) at the forefront of management, navigating an evolving landscape of research and lack of evidence-based guidelines. This paper presents a pragmatic, structured framework for Long COVID management in primary care, integrating current knowledge and best practices. The approach is individualized, addressing Long COVID's broad symptomatology through a four-step framework. The first step focuses on energy management strategies, emphasizing the prevention of post-exertional malaise, a cardinal feature of Long COVID. The second step, intentional rehabilitation, employs carefully titrated multidisciplinary modalities to address physical, cognitive, and emotional domains. The third step utilizes symptomatic management through both pharmacological and non-pharmacological interventions, targeting debilitating symptoms like fatigue, insomnia, and chronic pain. The fourth step outlines an approach to trialing experimental, targeted therapies that may impact Long COVID's underlying pathophysiology. These treatments, while experimental and lacking quality evidence in Long COVID, may be available off-label on an individual basis following a thorough risk-benefit discussion. This stepwise framework can equip PCPs to effectively address the most common and disabling symptoms of Long COVID, individualize care, and remain attuned to the evolving scientific understanding of the condition.}, }
@article {pmid39150062, year = {2024}, author = {Gordon, JI and Brummel, NE}, title = {Implications of frailty before and after intensive care unit admission.}, journal = {Current opinion in critical care}, volume = {30}, number = {5}, pages = {472-478}, doi = {10.1097/MCC.0000000000001197}, pmid = {39150062}, issn = {1531-7072}, support = {T32 HS029590/HS/AHRQ HHS/United States ; }, mesh = {Humans ; *COVID-19/epidemiology ; *Intensive Care Units ; *Frailty ; *Delirium ; *Critical Illness ; *SARS-CoV-2 ; Aged ; Frail Elderly ; Geriatric Assessment/methods ; }, abstract = {PURPOSE OF REVIEW: In the decade since the first publications related to frailty in those with critical illness, the study of frailty has rapidly increased. The purpose of this review is to update the reader on recent advances across several important areas of frailty research: how best to identify frailty in those with critical illness, studies describing the relationship between frailty and delirium, and how frailty affects outcomes for those with coronavirus disease 2019 (COVID-19), which, despite rates and severity of acute infection declining, still tremendously impacts patients long after the acute infection, resulting in symptoms of long COVID-19.<br><br>RECENT FINDINGS: A number of frailty assessment tools exist, to date, the Clinical Frailty Scale based on the deficit accumulation approach to defining frailty, is the most commonly used in ICU studies. Several novel frailty instruments for the ICU are being developed. Because tools assessing frailty by the phenotypic and deficit accumulation approaches identify different populations, careful choice of a frailty assessment tool is warranted.Frailty and delirium are hypothesized to represent different clinical expressions of a similar underlying vulnerability, thus identifying frailty may be a useful means by which to identify patients at high risk of becoming delirious. Recent studies show that frailty at ICU admission is a predictor of the development of delirium.Finally, frailty and its outcomes were studied in patients with COVID-19. As with other causes of critical illness, frailty was highly prevalent in those admitted to the ICU and is associated with greater mortality. Frailty was also associated with increased decisions to limit life support treatments, but these decisions were not different among those admitted with COVID-19 or for other reasons.<br><br>SUMMARY: Frailty in those with critical illness is an emerging field of study. Future work to define the optimal means by which to identify this syndrome and how best to manage critically ill patients with frailty are needed.}, }
@article {pmid39154330, year = {2024}, author = {Kupovits, TR}, title = {[Symptoms and options in rehabilitation of post-COVID-19 syndrome (long-COVID)].}, journal = {Orvosi hetilap}, volume = {165}, number = {33}, pages = {1266-1274}, doi = {10.1556/650.2024.33107}, pmid = {39154330}, issn = {1788-6120}, mesh = {Humans ; Pandemics ; *Post-Acute COVID-19 Syndrome/diagnosis/epidemiology/rehabilitation/virology ; SARS-CoV-2 ; }, abstract = {Today we live in the age of epidemics. More and more serious epidemics are appearing. Coronavirus disease 2019 (COVID–19) is a highly contagious disease caused by the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2). The virus probably spread from bats to humans. One virus of Rhinolophus sinicus showed 80% similarity, while the virus strain of Rhinolophus affinis showed 96% similarity with SARS-CoV-2. Human-to-human transmission of the COVID–19 infection has led to the isolation of patients. Due to globalized travel, it has spread worldwide, the World Health Organization (WHO) declared it a pandemic, and today it is considered a major public health problem. Besides the acute symptoms after infection, patients and society are also being challenged by long-term health complications associated with COVID–19 including the post-COVID–19 syndrome, also known as long-COVID. Within the post-acute COVID–19 syndrome, two stages are distinguished: subacute COVID–19 between 4 and 12 weeks after acute infection and post-COVID–19 syndrome characterized by symptoms that persist beyond 12 weeks. It is characterized by a wide range of symptoms that affect several organ systems. Treatment of complaints consists primarily of symptomatic treatment and multidisciplinary rehabilitation. Vaccination against COVID–19 is one of the most important means of mitigating the pandemic. Extensive research in recent years has confirmed the effectiveness of the COVID–19 vaccines. International studies have shown that the vaccine has proven to be a protective factor against long-lasting COVID symptoms. In this review, the symptoms, epidemiology, transmission, pathogenesis of COVID–19 as well as the effects of the post-COVID–19 syndrome on certain organ systems, its rehabilitation, and the effect of vaccines on the development of symptoms are highlighted. Orv Hetil. 2024; 165(33): 1266–1274.}, }
@article {pmid39154907, year = {2024}, author = {Tavee, J}, title = {Current concepts in long COVID-19 brain fog and postural orthostatic tachycardia syndrome.}, journal = {Annals of allergy, asthma &amp; immunology : official publication of the American College of Allergy, Asthma, &amp; Immunology}, volume = {133}, number = {5}, pages = {522-530}, doi = {10.1016/j.anai.2024.08.008}, pmid = {39154907}, issn = {1534-4436}, mesh = {Humans ; *Postural Orthostatic Tachycardia Syndrome/physiopathology/therapy ; *COVID-19/complications/physiopathology ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; Cognitive Dysfunction/etiology/physiopathology ; Quality of Life ; Cognitive Behavioral Therapy ; }, abstract = {Neurologic complications of long COVID-19 syndrome are one of the leading causes of global disability. In particular, post-COVID-19 cognitive dysfunction and dysautonomia in the form of postural orthostatic tachycardia syndrome (POTS) markedly affect patient quality of life and ability to return to work. The underlying pathophysiology of post-COVID-19 neurologic complications is unknown but is likely multifactorial with immune dysregulation and microvascular dysfunction playing central roles. Specific pathogenic factors with supportive evidence to date include cytokine-mediated inflammation, autoantibodies, immune exhaustion, disruption of the renin-angiotensin system, reduced serotonin levels, and microglial activation. The prevalence of post-COVID-19 cognitive dysfunction ranges from 10% to 88% and is affected by viral variant and hospitalization status among other factors, whereas that of long COVID-19 POTS is unknown due to referral bias and varying definitions. Treatment is largely supportive and often incorporates combined modalities. Marginal benefits with cognitive behavioral therapy, hyperbaric oxygen therapy, and supplements have been found for post-COVID-19 brain fog, whereas established POTS therapies aimed at improving venous return and reducing heart rate may reduce symptoms of long COVID-19 POTS. Although significant recovery has been noted for many cases of post-COVID-19 brain fog and POTS, prospective studies have revealed evidence of persistent symptoms and neurologic deficits a year after infection in some patients. Further studies that provide insight into the underlying pathophysiology of long COVID-19 are needed for development of target directed therapy.}, }
@article {pmid39159607, year = {2025}, author = {Gorenshtein, A and Leibovitch, L and Liba, T and Stern, S and Stern, Y}, title = {Gender Disparities in Neurological Symptoms of Long COVID: A Systematic Review and Meta-Analysis.}, journal = {Neuroepidemiology}, volume = {59}, number = {4}, pages = {426-440}, pmid = {39159607}, issn = {1423-0208}, mesh = {Humans ; *COVID-19/complications/epidemiology ; Female ; Sex Factors ; *Nervous System Diseases/epidemiology/etiology ; Male ; Fatigue/epidemiology ; Post-Acute COVID-19 Syndrome ; Risk Factors ; }, abstract = {BACKGROUND: Female gender is a known risk factor for long COVID. With the increasing number of COVID-19 cases, the corresponding number of survivors is also expected to rise. To the best of our knowledge, no systematic review has specifically addressed the gender differences in neurological symptoms of long COVID.<br><br>METHODS: We included studies on female individuals who presented with specific neurological symptoms at least 12 weeks after confirmed COVID-19 diagnosis from PubMed, Central, Scopus, and Web of Science. The search limit was put for after January 2020 until June 15, 2024. We excluded studies that did not provide sex-specific outcome data, those not in English, case reports, case series, and review articles Results: A total of 5,632 eligible articles were identified. This article provides relevant information from 12 studies involving 6,849 patients, of which 3,414 were female. The sample size ranged from 70 to 2,856, with a maximum follow-up period of 18 months. The earliest publication date was September 16, 2021, while the latest was June 11, 2024. The following neurological symptoms had a significant difference in the risk ratio (RR) for female gender: fatigue RR 1.40 (95% confidence interval [CI]: 1.22-1.60, p < 0.001), headache RR 1.37 (95% CI: 1.12-1.67, p = 0.002), brain-fog RR 1.38 (95% CI 1.08-1.76, p = 0.011) depression RR 1.49 (95% CI: 1.2-1.86, p < 0.001), and anosmia RR 1.61 (95% CI: 1.36-1.90, p < 0.001). High heterogenicity was found for fatigue, brain fog, and anxiety due to the diverse methodologies employed in the studies.<br><br>CONCLUSION: Our findings suggest that women are at a higher risk for long-COVID neurological symptoms, including fatigue, headaches, brain fog, depression, and anosmia, compared to men. The prevalence of these symptoms decreases after 1 year, based on limited data from the small number of studies available beyond this period.}, }
@article {pmid39171285, year = {2023}, author = {Liu, Y and Gu, X and Li, H and Zhang, H and Xu, J}, title = {Mechanisms of long COVID: An updated review.}, journal = {Chinese medical journal pulmonary and critical care medicine}, volume = {1}, number = {4}, pages = {231-240}, pmid = {39171285}, issn = {2772-5588}, abstract = {The coronavirus disease 2019 (COVID-19) pandemic has been ongoing for more than 3 years, with an enormous impact on global health and economies. In some patients, symptoms and signs may remain after recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which cannot be explained by an alternate diagnosis; this condition has been defined as long COVID. Long COVID may exist in patients with both mild and severe disease and is prevalent after infection with different SARS-CoV-2 variants. The most common symptoms include fatigue, dyspnea, and other symptoms involving multiple organs. Vaccination results in lower rates of long COVID. To date, the mechanisms of long COVID remain unclear. In this narrative review, we summarized the clinical presentations and current evidence regarding the pathogenesis of long COVID.}, }
@article {pmid39177216, year = {2025}, author = {Koterba, CH and Considine, CM and Becker, JH and Hoskinson, KR and Ng, R and Vargas, G and Basso, MR and Puente, AE and Lippa, SM and Whiteside, DM}, title = {Neuropsychology practice guidance for the neuropsychiatric aspects of Long COVID.}, journal = {The Clinical neuropsychologist}, volume = {39}, number = {4}, pages = {870-898}, doi = {10.1080/13854046.2024.2392943}, pmid = {39177216}, issn = {1744-4144}, mesh = {Humans ; *COVID-19/complications/psychology ; *Neuropsychology/standards/methods ; *Mental Disorders/etiology/therapy ; *Practice Guidelines as Topic ; SARS-CoV-2 ; Adult ; }, abstract = {Objective: The coronavirus disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has had a profound global impact on individual health and well-being in adults and children. While most fully recover from COVID-19, a relatively large subgroup continues to experience persistent physical, cognitive, and emotional/behavioral symptoms beyond the initial infection period. The World Health Organization has termed this phenomenon "Post-COVID-19 Condition" (PCC), better known as "Long COVID." Due to the cognitive and psychosocial symptoms, neuropsychologists often assess and recommend treatment for individuals with Long COVID. However, guidance for neuropsychologists' involvement in clinical care, policy-making, and research has not yet been developed. The authors of this manuscript convened to address this critical gap and develop guidance for clinical neuropsychologists working with patients presenting with Long COVID. Method: Authors include pediatric and adult neuropsychologists with expertise in Long COVID and behavioral health. All authors have been engaged in clinical and research efforts examining the impact of COVID-19. Authors summarized the literature-to-date pertinent to the neuropsychiatric sequelae of Long COVID and developed guidance for neuropsychologists working with individuals with Long COVID. Conclusions: Research findings regarding neuropsychiatric symptoms associated with Long COVID are mixed and limited by methodological differences. As they practice and conduct research, neuropsychologists should remain mindful of the evolving and tenuous nature of the literature.}, }
@article {pmid39179099, year = {2024}, author = {Elliott, MR and O'Connor, AE and Marshall, GD}, title = {Inflammatory pathways in patients with post-acute sequelae of COVID-19: The role of the clinical immunologist.}, journal = {Annals of allergy, asthma &amp; immunology : official publication of the American College of Allergy, Asthma, &amp; Immunology}, volume = {133}, number = {5}, pages = {507-515}, pmid = {39179099}, issn = {1534-4436}, support = {OT2 HL161847/HL/NHLBI NIH HHS/United States ; U19 AT010838/AT/NCCIH NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/immunology/complications ; *SARS-CoV-2/immunology ; *Post-Acute COVID-19 Syndrome ; *Inflammation/immunology ; }, abstract = {As the SARS-CoV-2 pandemic progressed, some survivors noted prolonged symptoms after acute infection, termed post-acute sequelae of COVID-19 (PASC) or "long COVID." PASC is a significant clinical and public health concern that adversely affects patients' quality of life, income, and health care expenses. Moreover, PASC symptoms are highly heterogeneous, the most common being fatigue and cognitive impairment, and they likely reflect a spectrum of clinical phenotypes. The proposed role of persistent inflammation is one of leading pathophysiological theories. This review article addresses these proposed mechanisms of persistent and aberrant inflammation, their clinical evaluation, and theoretical approaches to management. A review of public databases was used to collect literature for the review. The literature supports a prominent role of persistent and aberrant inflammation as a major contributor to the symptoms of PASC. Proposed mechanisms for persistent inflammation include reactivation of latent viruses, viral persistence, loss of immunoregulatory pathways, autoimmune mechanisms, and/or mast cell dysregulation. Persistent inflammation may result in constitutional symptoms such as fatigue, brain fog, body aches, and/or organ-specific dysfunction, such as gastrointestinal dysregulation and myocardial inflammation. There are no approved or even proven therapies for PASC at this time, but some studies have identified therapeutic options that may either reduce the risk for progression to PASC or decrease symptom burden. Laboratory evaluation and therapeutic options are limited and require further investigation to establish their clinical value. A more refined definition of PASC is needed to address the wide variety of clinical presentations, pathophysiology, and therapeutic options.}, }
@article {pmid39179487, year = {2025}, author = {Hromić-Jahjefendić, A and Mahmutović, L and Sezer, A and Bećirević, T and Rubio-Casillas, A and Redwan, EM and Uversky, VN}, title = {The intersection of microbiome and autoimmunity in long COVID-19: Current insights and future directions.}, journal = {Cytokine &amp; growth factor reviews}, volume = {82}, number = {}, pages = {43-54}, doi = {10.1016/j.cytogfr.2024.08.002}, pmid = {39179487}, issn = {1879-0305}, mesh = {Humans ; *COVID-19/immunology/microbiology/complications ; *Autoimmunity/immunology ; *SARS-CoV-2/immunology ; *Microbiota/immunology ; *Autoimmune Diseases/immunology/microbiology ; Autoantibodies/immunology ; Probiotics/therapeutic use ; Gastrointestinal Microbiome/immunology ; Extracellular Traps/immunology ; Post-Acute COVID-19 Syndrome ; Prebiotics ; }, abstract = {Long COVID-19 affects a significant percentage of patients and is characterized by a wide range of symptoms, including weariness and mental fog as well as emotional symptoms like worry and sadness. COVID-19 is closely linked to the autoimmune disorders that are becoming more prevalent worldwide and are linked to immune system hyperactivation, neutrophil extracellular trap (NET) development, and molecular mimicry pathways. Long-term COVID-related autoimmune responses include a watchful immune system referring to the ability of immune system to constantly monitor the body for signs of infection, disease, or abnormal cells; altered innate and adaptive immune cells, autoantigens secreted by living or dead neutrophils, and high concentrations of autoantibodies directed against different proteins. The microbiome, which consists of billions of bacteria living in the human body, is essential for controlling immune responses and supporting overall health. The microbiome can affect the course of long COVID-associated autoimmunity, including the degree of illness, the rate of recovery, and the onset of autoimmune reactions. Although the precise role of the microbiome in long COVID autoimmunity is still being investigated, new studies indicate that probiotics, prebiotics, and dietary changes-interventions that target the microbiome-may be able to reduce autoimmune reactions and enhance long-term outcomes for COVID-19 survivors. More research is required to precisely understand how the microbiome affects COVID-19-related autoimmunity and to create tailored treatment plans.}, }
@article {pmid39180511, year = {2024}, author = {Smith, MM and Melrose, J}, title = {Impaired instructive and protective barrier functions of the endothelial cell glycocalyx pericellular matrix is impacted in COVID-19 disease.}, journal = {Journal of cellular and molecular medicine}, volume = {28}, number = {16}, pages = {e70033}, pmid = {39180511}, issn = {1582-4934}, support = {//Melrose Personal Research Fund/ ; }, mesh = {Humans ; *Glycocalyx/metabolism ; *COVID-19/metabolism/pathology/virology ; *Endothelial Cells/metabolism/pathology ; *SARS-CoV-2/metabolism/drug effects ; *Blood-Brain Barrier/metabolism/drug effects ; Glycosaminoglycans/metabolism ; }, abstract = {The aim of this study was to review the roles of endothelial cells in normal tissue function and to show how COVID-19 disease impacts on endothelial cell properties that lead to much of its associated symptomatology. This places the endothelial cell as a prominent cell type to target therapeutically in the treatment of this disorder. Advances in glycosaminoglycan analytical techniques and functional glycomics have improved glycosaminoglycan mimetics development, providing agents that can more appropriately target various aspects of the behaviour of the endothelial cell in-situ and have also provided polymers with potential to prevent viral infection. Thus, promising approaches are being developed to combat COVID-19 disease and the plethora of symptoms this disease produces. Glycosaminoglycan mimetics that improve endothelial glycocalyx boundary functions have promising properties in the prevention of viral infection, improve endothelial cell function and have disease-modifying potential. Endothelial cell integrity, forming tight junctions in cerebral cell populations in the blood-brain barrier, prevents the exposure of the central nervous system to circulating toxins and harmful chemicals, which may contribute to the troublesome brain fogging phenomena reported in cognitive processing in long COVID disease.}, }
@article {pmid39183058, year = {2024}, author = {Dempsey, B and Madan, I and Stevelink, SAM and Lamb, D}, title = {Long COVID among healthcare workers: a narrative review of definitions, prevalence, symptoms, risk factors and impacts.}, journal = {British medical bulletin}, volume = {151}, number = {1}, pages = {16-35}, pmid = {39183058}, issn = {1471-8391}, support = {NIHR300592//National Institute for Health and Care Research/ ; //Maudsley NHS Foundation Trust/ ; //National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre/ ; CF/01/22//Colt Foundation/ ; }, mesh = {Humans ; *Health Personnel/statistics &amp; numerical data ; *Post-Acute COVID-19 Syndrome/diagnosis/epidemiology ; Prevalence ; Risk Factors ; SARS-CoV-2 ; }, abstract = {INTRODUCTION: Long COVID (LC) occurs when people experience symptoms for weeks, months or even years after a COVID-19 infection. This review looks at research exploring the LC definitions, prevalence, symptoms, risk factors, and associated impacts in research on healthcare workers (HCWs).<br><br>DATA SOURCES: We systematically searched five electronic databases (CINAHL, EMBASE, Medline, PsycInfo and PubMed) and compiled a narrative literature review based on 56 relevant studies.<br><br>AREAS OF AGREEMENT: LC is prevalent among HCWs who become infected by COVID-19. Many of the most frequent symptoms associated with LC in the general population are also reported among HCWs. Some risk factors for LC are also similar to those in the general population, such as female sex, older age, and having a pre-existing respiratory illness.<br><br>AREAS OF CONTROVERSY: The mechanism(s) responsible for LC remains unknown. A variety of terms, timeframes and symptoms are used to define LC, creating difficulties in comparing results across studies. Much of the research is cross-sectional and fails to explore the impacts that prolonged symptoms have on HCWs' personal and professional lives.<br><br>GROWING POINTS: The need to support HCWs with LC is clear. Identifying the mechanism(s) responsible for LC is a key priority, as this will inform treatments.<br><br>AREAS FOR DEVELOPING RESEARCH: Future research should move towards a standard definition for LC. Greater attention should be paid to longitudinal and qualitative studies, which could give insights into prognosis, lived experience and work participation. Finally, studies evaluating treatments suitable for people with LC are timely.}, }
@article {pmid39186150, year = {2024}, author = {Ejalonibu, H and Amah, A and Aburub, A and Kumar, P and Frederick, DE and Groot, G}, title = {A review of Patient Reported Outcome Measures (PROMs) for characterizing Long COVID (LC)-merits, gaps, and recommendations.}, journal = {Journal of patient-reported outcomes}, volume = {8}, number = {1}, pages = {101}, pmid = {39186150}, issn = {2509-8020}, support = {Strategy for Patient-Oriented Research//Strategy for Patient-Oriented Research/ ; }, mesh = {*Patient Reported Outcome Measures ; Humans ; *COVID-19/epidemiology/psychology ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Psychometrics/methods/instrumentation ; Quality of Life ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Individuals may experience a range of symptoms after the clearance of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This condition is termed long COVID (LC) or Post-COVID-19 condition (PCC). Despite the appreciable number of symptoms documented to date, one key challenge remains in the robust characterization of LC outcomes. This review aimed to assess the properties, identify gaps, and provide recommendations for relevant descriptive and evaluative Patient-Reported Outcome Measurement (PROM) instruments that can be used to comprehensively characterize LC.<br><br>METHODS: To achieve this objective, we identified and reviewed descriptive and evaluative PROM instruments that have been developed and validated to date with people living with LC. Our review assessed their properties, identified gaps, and recommended PROMs suitable for characterizing LC. To ensure a comprehensive and robust characterization of LC, we next identified, reviewed, and selected (with the input of patient partners) PROMs associated with the most frequently reported LC symptoms. The evaluation criteria included psychometric evidence, mode of delivery, cost, and administration time.<br><br>RESULTS: Traditional matrix mapping revealed Post-COVID Functional Status Scale (PCFS) as a choice instrument for capturing LC outcomes largely because of the comprehensive domains it covered, and the number of psychometric evidence reported in literatures. This instrument can be effectively paired with the Fatigue Severity Scale (FSS), Montreal Cognitive Assessment (MoCA), Patient Health Questionnaire (PHQ-9), Headache Impact Test (HIT), Pittsburgh Sleep Quality Index (PSQI), and DePaul Symptom Questionnaire (DSQ-PEM) to characterize fatigue, cognitive impairment, depression/anxiety, headache, sleeplessness, and post-exertional malaise respectively.<br><br>CONCLUSION: Our paper identified appropriate PROM instruments that can effectively capture the diverse impacts of LC. By utilizing these validated instruments, we can better understand and manage LC.}, }
@article {pmid39187064, year = {2024}, author = {Snowden, J and Weakley, K}, title = {Diagnosing, managing, and studying long-COVID syndromes in children and adolescents in rural and underserved populations.}, journal = {Annals of allergy, asthma &amp; immunology : official publication of the American College of Allergy, Asthma, &amp; Immunology}, volume = {133}, number = {5}, pages = {516-521}, doi = {10.1016/j.anai.2024.08.028}, pmid = {39187064}, issn = {1534-4436}, mesh = {Humans ; *COVID-19/epidemiology/diagnosis/therapy ; Child ; Adolescent ; *Rural Population ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; *Vulnerable Populations ; Health Services Accessibility ; Medically Underserved Area ; Pandemics ; }, abstract = {The COVID-19 pandemic has arguably had its greatest impact in rural and other historically hard-to-reach populations. Families in rural and underserved communities experienced COVID-19 infections at a higher rate than did their peers in other groups and experienced disproportionate morbidity and mortality. Without careful design and implementation of resources, children in these areas are also at risk of being disproportionately affected by long-term sequelae of SARS-CoV-2 infections, such as "long COVID" syndromes. Increased frequency and severity of COVID-19 infections, decreased access to health care and supporting services, environmental and social structure factors that exacerbate post-acute sequelae of COVID-19, and increased baseline frequency of health disorders that may complicate post-COVID issues, such as higher rates of obesity, asthma, diabetes, and mental health disorders, all place children and adolescents in under-resourced areas at significant risk. Unfortunately, children and adolescents in these areas have been historically under-represented in clinical research. Not only are fewer studies published with participants in rural and underserved communities, but these studies more often exhibit lower quality, with fewer randomized controlled trials and multicenter studies. This gap not only deprives people in rural and underserved areas of the country of access to cutting-edge therapy, but it also risks "evidence-based" solutions that are not generalizable because they cannot be implemented in the areas disproportionately affected by many health conditions such as long COVID. These factors significantly impede our ability to provide appropriate medical care for underserved communities. This review will discuss the impact of COVID-19 in rural and underserved communities and the factors that must be considered in designing evidence-based long-COVID solutions for children and adolescents in these areas.}, }
@article {pmid39188336, year = {2024}, author = {Motilal, S and Rampersad, R and Adams, M and Goon Lun, S and Ramdhanie, A and Ruiz, T and Shah, A and Wilkinson, A and Lewis, J}, title = {Randomized Controlled Trials for Post-COVID-19 Conditions: A Systematic Review.}, journal = {Cureus}, volume = {16}, number = {8}, pages = {e67603}, pmid = {39188336}, issn = {2168-8184}, abstract = {Post-coronavirus disease 2019 (COVID-19) syndrome or condition (PCS) is defined as new onset symptoms for at least three months following COVID-19 infection that has persisted for at least two months. Given the global sequelae of COVID-19, there is an urgent need for effective PCS interventions. The aim of this study was to systematically review all interventions for PCS tested in randomized controlled trials. In this International Prospective Register of Systematic Reviews (PROSPERO) registered (CRD42023415835) systematic review, PubMed, Google Scholar, and ClinicalTrials.gov databases were searched between 1st January 2020 and 30th April 2023. Inclusion criteria were (1) randomized controlled trials that tested interventions for (2) PCS as defined above. Studies were independently reviewed, and final decisions regarding extracted data and risk of bias were made by consensus. Trial findings were summarized qualitatively. The review included 23 trials with 1,916 subjects (mean age 44.9, 25.8% males) from 10 countries. The predominant symptom or function targeted by the interventions were general long COVID-19 symptoms (35%), fatigue (30%), breathlessness (17%), olfactory (17%), and brain function (9%). Overall, the majority of trials (74%) were at high risk of bias. A range of interventions were identified, including physical therapies, dietary and regenerative treatments, electrical stimulation, and digital wellness programs with variable effects. While a diverse range of interventions for PCS have been tested, their effectiveness varies, with threats to validity in most studies. Trials focusing on PCS mental health disorders, musculoskeletal complaints, and children are needed. Well-designed RCTs are needed to establish definitive interventions for PCS.}, }
@article {pmid39188722, year = {2024}, author = {Jang, S and Hong, W and Moon, Y}, title = {Obesity-compromised immunity in post-COVID-19 condition: a critical control point of chronicity.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1433531}, pmid = {39188722}, issn = {1664-3224}, mesh = {Humans ; *COVID-19/immunology/complications ; *Obesity/immunology/complications ; *SARS-CoV-2/immunology/physiology ; Inflammation/immunology ; Chronic Disease ; Adipose Tissue/immunology/metabolism ; T-Lymphocytes/immunology ; Immunity, Humoral ; }, abstract = {Post-COVID-19 condition is recognized as a multifactorial disorder, with persistent presence of viral antigens, discordant immunity, delayed viral clearance, and chronic inflammation. Obesity has emerged as an independent risk factor for both SARS-CoV-2 infection and its subsequent sequelae. In this study, we aimed to predict the molecular mechanisms linking obesity and post-COVID-19 distress. Viral antigen-exposed adipose tissues display remarkable levels of viral receptors, facilitating viral entry, deposition, and chronic release of inflammatory mediators and cells in patients. Subsequently, obesity-associated inflammatory insults are predicted to disturb cellular and humoral immunity by triggering abnormal cell differentiation and lymphocyte exhaustion. In particular, the decline in SARS-CoV-2 antibody titers and T-cell exhaustion due to chronic inflammation may account for delayed virus clearance and persistent activation of inflammatory responses. Taken together, obesity-associated defective immunity is a critical control point of intervention against post-COVID-19 progression, particularly in subjects with chronic metabolic distress.}, }
@article {pmid39189008, year = {2024}, author = {Krishna, BA and Metaxaki, M and Sithole, N and Landín, P and Martín, P and Salinas-Botrán, A}, title = {Cardiovascular disease and covid-19: A systematic review.}, journal = {International journal of cardiology. Heart &amp; vasculature}, volume = {54}, number = {}, pages = {101482}, pmid = {39189008}, issn = {2352-9067}, abstract = {BACKGROUND: Cardiovascular complications of COVID-19 are numerous and aspects of this phenomenon are not well known. The main objective of this manuscript is a systematic review of the acute and chronic cardiovascular complications secondary to COVID-19.<br><br>METHODS: A systematic review of the literature through Medline via PubMed was conducted (2020-2024).<br><br>RESULTS: There is a plethora of effects of COVID-19 on the heart in the acute setting. Here we discuss pathophysiology, myocardial infarctions, heart failure, Takotsubo Cardiomyopathy, myocardial injury, myocarditis and arrhythmias that are caused by COVID-19. Additionally, these cardiovascular injuries can linger and may be an underlying cause of some Long COVID symptoms.<br><br>CONCLUSIONS: Cardiovascular complications of COVID-19 are numerous and life-threatening. Long COVID can affect cardiovascular health. Microclotting induced by SARS-CoV-2 infection could be a therapeutic target for some aspects of Long Covid.}, }
@article {pmid39189651, year = {2024}, author = {Thierry, AR and Salmon, D}, title = {Inflammation-, immunothrombosis,- and autoimmune-feedback loops may lead to persistent neutrophil self-stimulation in long COVID.}, journal = {Journal of medical virology}, volume = {96}, number = {8}, pages = {e29887}, doi = {10.1002/jmv.29887}, pmid = {39189651}, issn = {1096-9071}, support = {//SIRIC Montpellier Cancer/ ; //Soci&#xe9;t&#xe9; Fran&#xe7;aise des Acides Nucl&#xe9;iques Circulants/ ; //INSERM/ ; }, mesh = {*Inflammation/immunology ; *Thromboinflammation/immunology ; *Autoimmunity ; *Feedback, Physiological ; *Neutrophils/immunology ; *Post-Acute COVID-19 Syndrome/immunology/physiopathology ; Extracellular Traps/immunology ; Communicable Diseases/pathology ; }, abstract = {Understanding the pathophysiology of long COVID is one of the most intriguing challenges confronting contemporary medicine. Despite observations recently made in the relevant molecular, cellular, and physiological domains, it is still difficult to say whether the post-acute sequelae of COVID-19 directly correspond to the consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This work hypothesizes that neutrophils and neutrophil extracellular traps (NETs) production are at the interconnection of three positive feedback loops which are initiated in the acute phase of SARS-CoV-2 infection, and which involve inflammation, immunothrombosis, and autoimmunity. This phenomenon could be favored by the fact that SARS-CoV-2 may directly bind and penetrate neutrophils. The ensuing strong neutrophil stimulation leads to a progressive amplification of an exacerbated and uncontrolled NETs production, potentially persisting for months beyond the acute phase of infection. This continuous self-stimulation of neutrophils leads, in turn, to systemic inflammation, micro-thromboses, and the production of autoantibodies, whose significant consequences include the persistence of endothelial and multiorgan damage, and vascular complications.}, }
@article {pmid39195858, year = {2024}, author = {Tsai, DH and Harmon, E and Goelen, J and Barry, HE and Chen, LY and Hsia, Y}, title = {Evaluating the Risk-Benefit Profile of Corticosteroid Therapy for COVID-19 Patients: A Scoping Review.}, journal = {Pharmacy (Basel, Switzerland)}, volume = {12}, number = {4}, pages = {}, pmid = {39195858}, issn = {2226-4787}, abstract = {BACKGROUND: The 2019 coronavirus (COVID-19) outbreak was declared a global pandemic in March 2020. It quickly spread across all continents, causing significant social, environmental, health, and economic impacts. During the pandemic, there has been consideration of repurposing and repositioning of medications, such as corticosteroids, for the treatment of hospitalised COVID-19 patients.<br><br>OBJECTIVE: To assess and summarise corticosteroid regimens used for hospitalised COVID-19 patients, focusing on dosage, route of administration, and clinical outcome from clinical trials.<br><br>METHODS: PubMed and Embase databases and the grey literature were searched to identify randomised controlled trials (RCTs) that evaluated the efficacy of corticosteroids in hospitalised patients with COVID-19 between January 2020 and January 2023. This scoping review was conducted in line with the PRISMA extension for scoping reviews (PRISMA-ScR) checklist.<br><br>KEY FINDINGS: A total of 24 RCTs were eligible for inclusion. There was variation in the steroid regimens used for treatment across COVID-19 trials. Despite the heterogeneity of included RCTs, the overall results have shown the benefits of improving lung function and a lower all-cause mortality rate in hospitalised COVID-19 patients treated with systematic corticosteroids.<br><br>CONCLUSIONS: Corticosteroids have proven to be an effective treatment for COVID-19 patients in critical condition. However, comparative effectiveness studies should be conducted to assess the efficacy and safety of optimal corticosteroid treatment at the population level. Moreover, the global burden of long COVID is significant, affecting millions with persistent symptoms and long-term health complications. Thus, it is also necessary to evaluate the optimal steroid regimen for long COVID treatment.}, }
@article {pmid39195986, year = {2022}, author = {Giacca, M and Shah, AM}, title = {The pathological maelstrom of COVID-19 and cardiovascular disease.}, journal = {Nature cardiovascular research}, volume = {1}, number = {3}, pages = {200-210}, pmid = {39195986}, issn = {2731-0590}, support = {MR/V040162/1/MRC_/Medical Research Council/United Kingdom ; RE/18/2/34213//British Heart Foundation (BHF)/ ; RG/19/11/34633//British Heart Foundation (BHF)/ ; CH/1999001/11735//British Heart Foundation (BHF)/ ; 787971//EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))/ ; }, abstract = {Coronavirus disease 2019 (COVID-19) is a consequence of infection of the upper and lower respiratory tract with severe acute respiratory syndrome coronavirus 2 but often becomes a systemic disease, with important involvement of other organs. A bidirectional relationship exists between COVID-19 and cardiovascular disease. On the one hand, preexisting comorbidities, in particular high prevalence of cardiovascular risk factors such as hypertension and diabetes and chronic cardiovascular conditions predispose to severe disease. On the other hand, biomarkers of myocardial injury are frequently raised in patients with COVID-19, along with arrhythmia and heart failure. Localized thrombosis is a common finding in the lungs but can also increase the occurrence of thrombotic events systemically. Thrombosis is consequent to different pathogenic mechanisms, which include endothelial dysfunction and immunothrombosis. Thrombocytopenia is common in patients with COVID-19 and alterations in platelet function participate in the pro-thrombotic phenotype. Involvement of the cardiovascular system in COVID-19 has important consequences during recovery from infection and the development of long COVID.}, }
@article {pmid39199353, year = {2024}, author = {Yanai, H and Adachi, H and Hakoshima, M and Katsuyama, H and Sako, A}, title = {The Significance of Endothelial Dysfunction in Long COVID-19 for the Possible Future Pandemic of Chronic Kidney Disease and Cardiovascular Disease.}, journal = {Biomolecules}, volume = {14}, number = {8}, pages = {}, pmid = {39199353}, issn = {2218-273X}, mesh = {Humans ; *COVID-19/complications/epidemiology ; *Renal Insufficiency, Chronic/epidemiology/metabolism ; *Endothelium, Vascular/metabolism/physiopathology ; *Cardiovascular Diseases/epidemiology/metabolism/etiology ; *SARS-CoV-2 ; *Angiotensin-Converting Enzyme 2/metabolism ; Male ; Female ; Biomarkers/metabolism ; Middle Aged ; Aged ; Post-Acute COVID-19 Syndrome ; Risk Factors ; Pandemics ; }, abstract = {Various symptoms have been reported to persist beyond the acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which is referred to as long coronavirus disease 19 (long COVID-19). Over 65 million individuals suffer from long COVID-19. However, the causes of long COVID-19 are largely unknown. Since long COVID-19 symptoms are observed throughout the body, vascular endothelial dysfunction is a strong candidate explaining the induction of long COVID-19. The angiotensin-converting enzyme 2 (ACE2), the entry receptor for SARS-CoV-2, is ubiquitously expressed in endothelial cells. We previously found that the risk factors for atherosclerotic cardiovascular disease (ASCVD) and a history of ASCVD raise the risk of severe COVID-19, suggesting a contribution of pre-existing endothelial dysfunction to severe COVID-19. Here, we show a significant association of endothelial dysfunction with the development of long COVID-19 and show that biomarkers for endothelial dysfunction in patients with long COVID-19 are also crucial players in the development of ASCVD. We consider the influence of long COVID-19 on the development of chronic kidney disease (CKD) and ASCVD. Future assessments of the outcomes of long COVID-19 in patients resulting from therapeutic interventions that improve endothelial function may imply the significance of endothelial dysfunction in the development of long COVID-19.}, }
@article {pmid39200898, year = {2024}, author = {Finamore, P and Arena, E and Lupoi, D and Savito, L and Di Nunzio, F and Furbatto, M and Dragonieri, S and Antonelli Incalzi, R and Scarlata, S}, title = {Long COVID Syndrome: A Narrative Review on Burden of Age and Vaccination.}, journal = {Journal of clinical medicine}, volume = {13}, number = {16}, pages = {}, pmid = {39200898}, issn = {2077-0383}, abstract = {Background/Objective: The COVID-19 pandemic has led to the emergence of post-acute COVID-19 syndrome, also known as long COVID, which presents a significant challenge due to its varied symptoms and unpredictable course, particularly in older adults. Similar to COVID-19 infections, factors such as age, pre-existing health conditions, and vaccination status may influence the occurrence and severity of long COVID. The objective is to analyze the role of aging in the context of long COVID and to investigate prevalence rates and vaccination efficacy to improve prevention strategies and treatment in this age group. Methods: Four researchers independently conducted a literature search of the PubMed database to trace studies published between July 2020 and July 2024. Results: Aging influences both the likelihood of developing long COVID and the recovery process, due to age-related physiological changes, immune system alterations, and the presence of comorbidities. Vaccination plays a key role in reducing the risk of long COVID by attenuating the inflammatory responses associated with its symptoms. Conclusions: Despite the protection vaccines offer against severe infection, hospitalization, and post-infection sequelae, vaccine hesitancy remains a major obstacle, worsening the impact of long COVID. Promising treatments for this condition include antivirals although further research is needed.}, }
@article {pmid39201736, year = {2024}, author = {Ward, C and Schlichtholz, B}, title = {Post-Acute Sequelae and Mitochondrial Aberration in SARS-CoV-2 Infection.}, journal = {International journal of molecular sciences}, volume = {25}, number = {16}, pages = {}, pmid = {39201736}, issn = {1422-0067}, support = {71-01415/0004604//Gda&#x144;sk Medical University/ ; }, mesh = {Humans ; *COVID-19/virology/metabolism/pathology ; *Mitochondria/metabolism ; *SARS-CoV-2/metabolism ; *Immunity, Innate ; *Post-Acute COVID-19 Syndrome ; Proteomics/methods ; }, abstract = {This review investigates links between post-acute sequelae of SARS-CoV-2 infection (PASC), post-infection viral persistence, mitochondrial involvement and aberrant innate immune response and cellular metabolism during SARS-CoV-2 infection. Advancement of proteomic and metabolomic studies now allows deeper investigation of alterations to cellular metabolism, autophagic processes and mitochondrial dysfunction caused by SARS-CoV-2 infection, while computational biology and machine learning have advanced methodologies of predicting virus-host gene and protein interactions. Particular focus is given to the interaction between viral genes and proteins with mitochondrial function and that of the innate immune system. Finally, the authors hypothesise that viral persistence may be a function of mitochondrial involvement in the sequestration of viral genetic material. While further work is necessary to understand the mechanisms definitively, a number of studies now point to the resolution of questions regarding the pathogenesis of PASC.}, }
@article {pmid39201907, year = {2024}, author = {Rothensteiner, M and Leeb, F and Götzinger, F and Tebruegge, M and Zacharasiewicz, A}, title = {Long COVID in Children and Adolescents: A Critical Review.}, journal = {Children (Basel, Switzerland)}, volume = {11}, number = {8}, pages = {}, pmid = {39201907}, issn = {2227-9067}, abstract = {(1) Background: Data on persisting symptoms after SARS-CoV-2 infection in children and adolescents are conflicting. Due to the absence of a clear pathophysiological correlate and a definitive diagnostic test, the diagnosis of Long COVID currently rests on consensus definitions only. This review aims to summarise the evidence regarding Long COVID in children and adolescents, incorporating the latest studies on this topic. (2) Methods: We designed a comprehensive search strategy to capture all relevant publications using Medline via the PubMed interface, with the initial literature search conducted in April 2023. To be included, publications had to present original data and include >50 participants with Long COVID symptoms aged between 0 and18 years. (3) Results: A total of 51 studies met the inclusion criteria, with most studies originating from Europe (n = 34; 66.7%), followed by the Americas (n = 8; 15.7%) and Asia (n = 7; 13.7%). Various study designs were employed, including retrospective, cross-sectional, prospective, or ambispective approaches. Study sizes varied significantly, with 18/51 studies having fewer than 500 participants. Many studies had methodological limitations: 23/51 (45.1%) studies did not include a control group without prior COVID-19 infection. Additionally, a considerable number of papers (33/51; 64.7%) did not include a clear definition of Long COVID. Other limitations included the lack of PCR- or serology-based confirmation of SARS-CoV-2 infection in the study group. Across different studies, there was high variability in the reported prevalence of Long COVID symptoms, ranging from 0.3% to 66.5%, with the majority of studies included in this review reporting prevalences of approximately 10-30%. Notably, the two studies with the highest prevalences also reported very high prevalences of Long COVID symptoms in the control group. There was a relatively consistent trend for Long COVID prevalence to decline substantially over time. The prevalence of Long COVID appeared to differ across different paediatric age groups, with teenagers being more commonly affected than younger children. Furthermore, data suggest that children and adolescents are less commonly affected by Long COVID compared to adults. In children and adolescents, Long COVID is associated with a very broad range of symptoms and signs affecting almost every organ system, with the respiratory, cardiovascular, and neuropsychiatric systems being most commonly affected. (4) Conclusions: The heterogeneity and limitations of published studies on Long COVID in children and adolescents complicate the interpretation of the existing data. Future studies should be rigorously designed to address unanswered questions regarding this complex disease.}, }
@article {pmid39201991, year = {2024}, author = {Davenport, TE and Blitshteyn, S and Clague-Baker, N and Davies-Payne, D and Treisman, GJ and Tyson, SF}, title = {Long COVID Is Not a Functional Neurologic Disorder.}, journal = {Journal of personalized medicine}, volume = {14}, number = {8}, pages = {}, pmid = {39201991}, issn = {2075-4426}, abstract = {Long COVID is a common sequela of SARS-CoV-2 infection. Data from numerous scientific studies indicate that long COVID involves a complex interaction between pathophysiological processes. Long COVID may involve the development of new diagnosable health conditions and exacerbation of pre-existing health conditions. However, despite this rapidly accumulating body of evidence regarding the pathobiology of long COVID, psychogenic and functional interpretations of the illness presentation continue to be endorsed by some healthcare professionals, creating confusion and inappropriate diagnostic and therapeutic pathways for people living with long COVID. The purpose of this perspective is to present a clinical and scientific rationale for why long COVID should not be considered as a functional neurologic disorder. It will begin by discussing the parallel historical development of pathobiological and psychosomatic/sociogenic diagnostic constructs arising from a common root in neurasthenia, which has resulted in the collective understandings of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and functional neurologic disorder (FND), respectively. We will also review the case definition criteria for FND and the distinguishing clinical and neuroimaging findings in FND vs. long COVID. We conclude that considering long COVID as FND is inappropriate based on differentiating pathophysiologic mechanisms and distinguishing clinical findings.}, }
@article {pmid39202695, year = {2024}, author = {Rettew, A and Garrahy, I and Rahimian, S and Brown, R and Sangha, N}, title = {COVID-19 Coagulopathy.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {8}, pages = {}, pmid = {39202695}, issn = {2075-1729}, abstract = {Coronavirus disease of 2019 (COVID-19) is the respiratory viral infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite being a primary respiratory illness, it is commonly complicated by systemic involvement of the vasculature leading to arterial and venous thrombosis. In this review, we will focus on the association between COVID-19 and thrombosis. We will highlight the pathophysiology of COVID-19 coagulopathy. The clinical manifestations of COVID-19 vasculopathy will be discussed with a focus on venous and arterial thromboembolic events. COVID-19 vasculopathy and disseminated intravascular coagulation (DIC) are distinguished within, as well as areas of controversy, such as "long COVID". Finally, the current professional guidelines on prevention and treatment of thrombosis associated with SARS-CoV-2 infection will be discussed.}, }
@article {pmid39205230, year = {2024}, author = {da Silva, R and Vallinoto, ACR and Dos Santos, EJM}, title = {The Silent Syndrome of Long COVID and Gaps in Scientific Knowledge: A Narrative Review.}, journal = {Viruses}, volume = {16}, number = {8}, pages = {}, pmid = {39205230}, issn = {1999-4915}, mesh = {Humans ; *COVID-19/epidemiology/virology ; *SARS-CoV-2/genetics ; *Post-Acute COVID-19 Syndrome ; Risk Factors ; Prognosis ; }, abstract = {COVID-19 is still a major public health concern, mainly due to the persistence of symptoms or the appearance of new symptoms. To date, more than 200 symptoms of long COVID (LC) have been described. The present review describes and maps its relevant clinical characteristics, pathophysiology, epidemiology, and genetic and nongenetic risk factors. Given the currently available evidence on LC, we demonstrate that there are still gaps and controversies in the diagnosis, pathophysiology, epidemiology, and detection of prognostic and predictive factors, as well as the role of the viral strain and vaccination.}, }
@article {pmid39205240, year = {2024}, author = {McMillan, P and Turner, AJ and Uhal, BD}, title = {Mechanisms of Gut-Related Viral Persistence in Long COVID.}, journal = {Viruses}, volume = {16}, number = {8}, pages = {}, pmid = {39205240}, issn = {1999-4915}, mesh = {Humans ; *COVID-19/virology/immunology ; *SARS-CoV-2/physiology/pathogenicity ; *Post-Acute COVID-19 Syndrome ; Gastrointestinal Microbiome ; Gastrointestinal Tract/virology ; }, abstract = {Long COVID (post-acute sequelae of COVID-19-PASC) is a consequence of infection by SARS-CoV-2 that continues to disrupt the well-being of millions of affected individuals for many months beyond their first infection. While the exact mechanisms underlying PASC remain to be defined, hypotheses regarding the pathogenesis of long COVID are varied and include (but are not limited to) dysregulated local or systemic inflammatory responses, autoimmune mechanisms, viral-induced hormonal imbalances, skeletal muscle abnormalities, complement dysregulation, novel abzymes, and long-term persistence of virus and/or fragments of viral RNA or proteins. This review article is based on a comprehensive review of the wide range of symptoms most often observed in long COVID and an attempt to integrate that information into a plausible hypothesis for the pathogenesis of PASC. In particular, it is proposed that long-term dysregulation of the gut in response to viral persistence could lead to the myriad of symptoms observed in PASC.}, }
@article {pmid39206795, year = {2024}, author = {Jiang, Y and Neal, J and Sompol, P and Yener, G and Arakaki, X and Norris, CM and Farina, FR and Ibanez, A and Lopez, S and Al-Ezzi, A and Kavcic, V and Güntekin, B and Babiloni, C and Hajós, M}, title = {Parallel electrophysiological abnormalities due to COVID-19 infection and to Alzheimer's disease and related dementia.}, journal = {Alzheimer's &amp; dementia : the journal of the Alzheimer's Association}, volume = {20}, number = {10}, pages = {7296-7319}, pmid = {39206795}, issn = {1552-5279}, support = {I21 RX003173/RX/RRD VA/United States ; P30 AG072946/AG/NIA NIH HHS/United States ; 1220995//ANID/FONDECYT Regular/ ; 1210176//ANID/FONDECYT Regular/ ; P01 AG078116/AG/NIA NIH HHS/United States ; 101071485//Marie Sk&#x142;odowska-Curie Doctoral Networks/ ; R01AG057234//National Institute of Aging/ ; R01 AG057234/AG/NIA NIH HHS/United States ; P30AG072946//National Institute of Aging/ ; 5I21RX003173//United States Department of Veterans Affairs/ ; R21 AG046637/AG/NIA NIH HHS/United States ; 1R21AG046637//National Institute of Aging/ ; P01AG078116//National Institute of Aging/ ; R21 AG074146/AG/NIA NIH HHS/United States ; R01 AG054484/AG/NIA NIH HHS/United States ; R01AG063857//National Institute of Aging/ ; HAT-07-60437/ALZ/Alzheimer's Association/United States ; R56 AG060608/AG/NIA NIH HHS/United States ; //Tau Consortium/ ; AARF-21-848281/ALZ/Alzheimer's Association/United States ; R56AG060608//National Institute of Aging/ ; R01 AG063857/AG/NIA NIH HHS/United States ; 2010SH7H3F//Italian Ministry of University, Scientific and Technological Research/ ; //MULTI-PARTNER CONSORTIUM TO EXPAND DEMENTIA RESEARCH IN LATIN AMERICA/ ; ACT210096//ANID/PIA/ANILLOS/ ; SG-20-725707/ALZ/Alzheimer's Association/United States ; 1210195//ANID/FONDECYT Regular/ ; P50 AG005144/AG/NIA NIH HHS/United States ; PNRR-MAD-2022-12376415//Marie Sk&#x142;odowska-Curie Doctoral Networks/ ; CW2680521//Takeda/ ; 15150012//ANID/FONDAP/ ; H2021-MSCA-DN-2021//HORIZON 2021/ ; R01AG054484//National Institute of Aging/ ; ID22I10029//FONDEF/ ; //United States National Institute of Health/ ; //Global Brain Health Institute/ ; ID20I10152//FONDEF/ ; }, mesh = {Humans ; *COVID-19/complications/physiopathology ; *Alzheimer Disease/physiopathology ; *Electroencephalography ; *SARS-CoV-2 ; Dementia/physiopathology ; Cognitive Dysfunction/physiopathology/etiology ; Brain/physiopathology ; }, abstract = {Many coronavirus disease 2019 (COVID-19) positive individuals exhibit abnormal electroencephalographic (EEG) activity reflecting "brain fog" and mild cognitive impairments even months after the acute phase of infection. Resting-state EEG abnormalities include EEG slowing (reduced alpha rhythm; increased slow waves) and epileptiform activity. An expert panel conducted a systematic review to present compelling evidence that cognitive deficits due to COVID-19 and to Alzheimer's disease and related dementia (ADRD) are driven by overlapping pathologies and neurophysiological abnormalities. EEG abnormalities seen in COVID-19 patients resemble those observed in early stages of neurodegenerative diseases, particularly ADRD. It is proposed that similar EEG abnormalities in Long COVID and ADRD are due to parallel neuroinflammation, astrocyte reactivity, hypoxia, and neurovascular injury. These neurophysiological abnormalities underpinning cognitive decline in COVID-19 can be detected by routine EEG exams. Future research will explore the value of EEG monitoring of COVID-19 patients for predicting long-term outcomes and monitoring efficacy of therapeutic interventions. HIGHLIGHTS: Abnormal intrinsic electrophysiological brain activity, such as slowing of EEG, reduced alpha wave, and epileptiform are characteristic findings in COVID-19 patients. EEG abnormalities have the potential as neural biomarkers to identify neurological complications at the early stage of the disease, to assist clinical assessment, and to assess cognitive decline risk in Long COVID patients. Similar slowing of intrinsic brain activity to that of COVID-19 patients is typically seen in patients with mild cognitive impairments, ADRD. Evidence presented supports the idea that cognitive deficits in Long COVID and ADRD are driven by overlapping neurophysiological abnormalities resulting, at least in part, from neuroinflammatory mechanisms and astrocyte reactivity. Identifying common biological mechanisms in Long COVID-19 and ADRD can highlight critical pathologies underlying brain disorders and cognitive decline. It elucidates research questions regarding cognitive EEG and mild cognitive impairment in Long COVID that have not yet been adequately investigated.}, }
@article {pmid39207648, year = {2025}, author = {Gáspár, Z and Szabó, BG and Ceglédi, A and Lakatos, B}, title = {Human herpesvirus reactivation and its potential role in the pathogenesis of post-acute sequelae of SARS-CoV-2 infection.}, journal = {GeroScience}, volume = {47}, number = {1}, pages = {167-187}, pmid = {39207648}, issn = {2509-2723}, mesh = {Humans ; *COVID-19/complications/virology/immunology ; *Virus Activation ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Herpesvirus 4, Human/physiology ; Cytomegalovirus/physiology ; Epstein-Barr Virus Infections ; Cytomegalovirus Infections ; }, abstract = {The emergence of SARS-CoV-2 has precipitated a global pandemic with substantial long-term health implications, including the condition known as post-acute sequelae of SARS-CoV-2 infection (PASC), commonly referred to as Long COVID. PASC is marked by persistent symptoms such as fatigue, neurological issues, and autonomic dysfunction that persist for months beyond the acute phase of COVID-19. This review examines the potential role of herpesvirus reactivation, specifically Epstein-Barr virus (EBV) and cytomegalovirus (CMV), in the pathogenesis of PASC. Elevated antibody titers and specific T cell responses suggest recent herpesvirus reactivation in some PASC patients, although viremia is not consistently detected. SARS-CoV-2 exhibits endothelial trophism, directly affecting the vascular endothelium and contributing to microvascular pathologies. These pathologies are significant in PASC, where microvascular dysfunction may underlie various chronic symptoms. Similarly, herpesviruses like CMV also exhibit endothelial trophism, which may exacerbate endothelial damage when reactivated. Evidence suggests that EBV and CMV reactivation could indirectly contribute to the immune dysregulation, immunosenescence, and autoimmune responses observed in PASC. Additionally, EBV may play a role in the genesis of neurological symptoms through creating mitochondrial dysfunction, though direct confirmation remains elusive. The reviewed evidence suggests that while herpesviruses may not play a direct role in the pathogenesis of PASC, their potential indirect effects, especially in the context of endothelial involvement, warrant further investigation.}, }
@article {pmid39209013, year = {2024}, author = {Skare, TL and de Carvalho, JF and de Medeiros, IRT and Shoenfeld, Y}, title = {Ear abnormalities in chronic fatigue syndrome (CFS), fibromyalgia (FM), Coronavirus-19 infectious disease (COVID) and long-COVID syndrome (PCS), sick-building syndrome (SBS), post-orthostatic tachycardia syndrome (PoTS), and autoimmune/inflammatory syndrome induced by adjuvants (ASIA): A systematic review.}, journal = {Autoimmunity reviews}, volume = {23}, number = {10}, pages = {103606}, doi = {10.1016/j.autrev.2024.103606}, pmid = {39209013}, issn = {1873-0183}, mesh = {Humans ; Autoimmune Diseases/etiology ; *COVID-19/complications/prevention &amp; control ; COVID-19 Vaccines/adverse effects ; *Fatigue Syndrome, Chronic/complications ; *Fibromyalgia/complications ; Post-Acute COVID-19 Syndrome/complications ; *Postural Orthostatic Tachycardia Syndrome/complications ; SARS-CoV-2 ; }, abstract = {Chronic fatigue syndrome (CFS), fibromyalgia (FM), silicone breast implants (SBI), Coronavirus-19 infectious disease (COVID), COVID-19 vaccination (post-COVIDvac-syndrome), Long-COVID syndrome (PCS), sick-building syndrome (SBS), post-orthostatic tachycardia syndrome (PoTS), and autoimmune/ inflammatory syndrome induced by adjuvants (ASIA) are a cluster of poorly understood medical conditions that have in common a group of ill-defined symptoms and dysautonomic features. Most of the clinical findings of this group of diseases are unspecific, such as fatigue, diffuse pain, cognitive impairment, paresthesia, tachycardia, anxiety, and depression. Hearing disturbances and vertigo have also been described in this context, the underlying pathophysiologic process for these conditions might rely on autonomic autoimmune dysbalance. The authors procced a literature review regarding to hearing and labyrinthic disturbances in CSF, FM, SBI, COVID, post-COVIDvac-syndrome, PCS, SBS, POTS, and ASIA. The PRISMA guidelines were followed, and the literature reviewed encompassed papers from January 1990 to January 2024. After the initial evaluation of the articles found in the search through Pubmed, Scielo and Embase, a total of 172 articles were read and included in this review. The prevalence of hearing loss, dizziness, vertigo and tinnitus was described and correlated with the diseases investigated in this study. There are great variability in the frequencies of symptoms found, but cochlear complaints are the most frequent in most studies. Vestibular symptoms are less reported. The main pathophysiological mechanisms are discussed. Direct effects of the virus in the inner ear or nervous pathways, impaired vascular perfusion, cross-reaction or autoimmune immunoreactivity, oxidative stress, DNA methylation, epigenetic modifications and gene activation were implicated in the generation of the investigated symptoms. In clinical practice, all patients with these autoimmune conditions who have any audiological complaint an ENT consultation followed by an audiometry are needed.}, }
@article {pmid39210399, year = {2024}, author = {Fleischmann-Struzek, C and Joost, FEA and Pletz, MW and Weiß, B and Paul, N and Ely, EW and Reinhart, K and Rose, N}, title = {How are Long-Covid, Post-Sepsis-Syndrome and Post-Intensive-Care-Syndrome related? A conceptional approach based on the current research literature.}, journal = {Critical care (London, England)}, volume = {28}, number = {1}, pages = {283}, pmid = {39210399}, issn = {1466-609X}, mesh = {Humans ; *COVID-19/complications/epidemiology ; *Sepsis/complications ; Post-Acute COVID-19 Syndrome ; Critical Care/methods ; Critical Illness ; }, abstract = {Long-Covid (LC), Post-Sepsis-Syndrome (PSS) and Post-Intensive-Care-Syndrome (PICS) show remarkable overlaps in their clinical presentation. Nevertheless, it is unclear if they are distinct syndromes, which may co-occur in the same patient, or if they are three different labels to describe similar symptoms, assigned on the basis on patient history and professional perspective of the treating physician. Therefore, we reviewed the current literature on the relation between LC, PSS and PICS. To date, the three syndromes cannot reliably be distinguished due similarities in clinical presentation as they share the cognitive, psychological and physical impairments with only different probabilities of occurrence and a heterogeneity in individual expression. The diagnosis is furthermore hindered by a lack of specific diagnostic tools. It can be concluded that survivors after COVID-19 sepsis likely have more frequent and more severe consequences than patients with milder COVID-19 courses, and that are some COVID-19-specific sequelae, e.g. an increased risk for venous thromboembolism in the 30 days after the acute disease, which occur less often after sepsis of other causes. Patients may profit from leveraging synergies from PICS, PSS and LC treatment as well as from experiences gained from infection-associated chronic conditions in general. Disentangling molecular pathomechanisms may enable future targeted therapies that go beyond symptomatic treatment.}, }
@article {pmid39211746, year = {2024}, author = {Daodu, TB and Rugel, EJ and Lear, SA}, title = {Impact of Long COVID-19 on Health Outcomes Among Adults With Preexisting Cardiovascular Disease and Hypertension: A Systematic Review.}, journal = {CJC open}, volume = {6}, number = {8}, pages = {939-950}, pmid = {39211746}, issn = {2589-790X}, abstract = {BACKGROUND: This review summarizes the impact of long COVID (LC) on the health of adults with preexisting cardiovascular disease (CVD) and hypertension.<br><br>METHODS: We searched Medline, Web of Science (Core Collection), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), without language restrictions, for articles published from December 1, 2019 through October 10, 2023, to ensure all relevant studies were captured. We included studies that enrolled adults (aged &#x2265;18 years) diagnosed with CVD prior to COVID-19 infection whose infection was subsequently determined to be LC per the World Health Organization definition. We excluded studies with adults diagnosed with CVD concurrent with or subsequent to COVID-19 or with those who solely self-reported LC. We used a custom-built data extraction form to collect a range of study characteristics. Study quality was assessed using modified versions of the National Heart, Lung, and Blood Institute quality-assessment tools.<br><br>RESULTS: A total of 13,779 studies were identified; 53 were included in the final analysis. Of these, 27 were of good quality and 26 were of fair quality. Health outcomes consisted of the presence of prolonged symptoms of LC (n&#xa0;= 29), physiological health outcomes (n&#xa0;= 20), lifestyle behaviours (n&#xa0;= 19), psycho-social outcomes (n&#xa0;= 13), CVD complications (n&#xa0;= 5), and death and hospital readmission (n&#xa0;= 5). Thirty-four studies incorporated 2 or more outcomes, and 19 integrated only&#xa0;1.<br><br>CONCLUSIONS: Given the significant impact of LC among individuals with preexisting CVD, specially tailored clinical management is needed for members of this population. Additional studies on the impact of LC among those with CVD and other underlying conditions also would be beneficial.}, }
@article {pmid39218998, year = {2024}, author = {Cheng, X and Cao, M and Yeung, WF and Cheung, DST}, title = {The effectiveness of exercise in alleviating long COVID symptoms: A systematic review and meta-analysis.}, journal = {Worldviews on evidence-based nursing}, volume = {21}, number = {5}, pages = {561-574}, doi = {10.1111/wvn.12743}, pmid = {39218998}, issn = {1741-6787}, mesh = {Humans ; *COVID-19/complications/rehabilitation ; Dyspnea ; Exercise ; *Exercise Therapy/methods ; *Post-Acute COVID-19 Syndrome/therapy ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Long COVID is prevalent in the general population. Exercise is a promising component of rehabilitation for long COVID patients.<br><br>AIM: This study examined the effects of exercise interventions on managing long COVID symptoms.<br><br>METHODS: In this systematic review and meta-analysis, a systematic search was conducted through June 2023 using keywords such as "long COVID" and "post-acute COVID-19 syndrome" among major electronic databases. Randomized controlled trials that examined the effect of exercise on patients suffering from long COVID were included. Nine studies involving 672 individuals were included in this study.<br><br>RESULTS: The main outcomes for exercise interventions in patients with long COVID were fatigue, dyspnea, anxiety, depression, and cognitive impairment. The exercise interventions comprised aerobic exercise, multimodal exercise, breathing exercise, and Taichi. Most of the included studies (6/9) were at high risk of bias. According to the meta-analyses, exercise significantly improved long COVID fatigue (ES&#x2009;=&#x2009;0.89, 95% CI: 0.27 to 1.50) and dyspnea (ES&#x2009;=&#x2009;1.21, 95% CI [0.33, 2.09]), whereas no significant effect was identified on long COVID anxiety, depression, and cognitive impairment. According to subgroup analyses, multimodal exercise had the broadest spectrum of benefits on long COVID symptoms (including fatigue, dyspnea, and depression), and supervised exercise, intervention frequency &#x2264;4 times a week, the passive control group also showed a positive effect on some long COVID symptoms.}, }
@article {pmid39220224, year = {2024}, author = {Liu, X and Pan, F and Wang, Q and Wang, S and Zhang, J}, title = {Traditional Chinese Rehabilitation Exercise (TCRE) for Myofascial Pain: Current Evidence and Further Challenges.}, journal = {Journal of pain research}, volume = {17}, number = {}, pages = {2801-2810}, pmid = {39220224}, issn = {1178-7090}, abstract = {Myofascial as a holistic structure emphasizes a holistic approach to intervention and treatment of fascial-related disorders such as neck pain (NP), low back pain (LBP), and knee pain. There are currently adverse effects of medication for diseases related to myofascial. Traditional Chinese rehabilitation exercise (TCRE) is a practical approach to traditional Chinese medicine and is a valuable option for intervening in myofascial-related pain. This article found some research evidence for Baduanjin, Wuqinxi, and Yijinjing in clinical studies of myofascial chain-related pain. The article summarizes the current evidence and finds that TCRE can enhance limb movement function through breathing and slow movements, increase joint movement and flexibility, and reduce joint pathology and stress-induced pain. As for future directions, focus on TCRE in improving the health of older adults and treating long-COVID syndrome, and integrate robotic and TCRE training to frame safe and effective exercise models. Relevant studies have already been registered in the Clinical Trials Registry, and some clinical study protocols have been published. TCRE can be an alternative nonpharmacological rehabilitation therapy to alleviate chronic rheumatic pain symptoms and augment public health management.}, }
@article {pmid39220656, year = {2024}, author = {Griffin, DO}, title = {Postacute Sequelae of COVID (PASC or Long COVID): An Evidenced-Based Approach.}, journal = {Open forum infectious diseases}, volume = {11}, number = {9}, pages = {ofae462}, pmid = {39220656}, issn = {2328-8957}, abstract = {While the acute manifestations of infectious diseases are well known, in some individuals, symptoms can either persist or appear after the acute period. Postviral fatigue syndromes are recognized with other viral infections and are described after coronavirus disease 2019 (COVID-19). We have a growing number of individuals with symptoms that persist for weeks, months, and years. Here, we share the evidence regarding the abnormalities associated with postacute sequelae of COVID-19 (PASC) and therapeutics. We describe physiological and biochemical abnormalities seen in individuals reporting PASC. We describe the several evidence-based interventions to offer patients. It is expected that this growing understanding of the mechanisms driving PASC and the benefits seen with certain therapeutics may not only lead to better outcomes for those with PASC but may also have the potential for understanding and treating other postinfectious sequelae.}, }
@article {pmid39221179, year = {2024}, author = {Galgut, O and Ashford, F and Deeks, A and Ghataure, A and Islam, M and Sambhi, T and Ker, YW and Duncan, CJA and de Silva, TI and Hopkins, S and Hall, V and Klenerman, P and Dunachie, S and Richter, A}, title = {COVID-19 vaccines are effective at preventing symptomatic and severe infection among healthcare workers: A clinical review.}, journal = {Vaccine: X}, volume = {20}, number = {}, pages = {100546}, pmid = {39221179}, issn = {2590-1362}, support = {MR/X001598/1/MRC_/Medical Research Council/United Kingdom ; MR/X009297/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {INTRODUCTION: Health care workers (HCWs) have been at increased risk of infection during the SARS-CoV-2 pandemic and as essential workers have been prioritised for vaccination. Due to increased exposure HCW are considered a predictor of what might happen in the general population, particularly working age adults. This study aims to summarise effect of vaccination in this 'at risk' cohort.<br><br>METHODS: Ovid MEDLINE and Embase were searched, and 358 individual articles were identified. Of these 49 met the inclusion criteria for review and 14 were included in a meta-analysis.<br><br>RESULTS: Participants included were predominantly female and working age. Median time to infection was 51&#xa0;days. Reported vaccine effectiveness against infection, symptomatic infection, and infection requiring hospitalisation were between 5 and 100&#xa0;%, 34 and 100&#xa0;%, and 65 and 100&#xa0;% (respectively). No vaccinated HCW deaths were recorded in any study. Pooled estimates of protection against infection, symptomatic infection, and hospitalisation were, respectively, 84.7&#xa0;% (95&#xa0;% CI 72.6-91.5&#xa0;%, p&#xa0;<&#xa0;0.0001), 86.0&#xa0;% (95&#xa0;% CI 67.2&#xa0;%-94.0&#xa0;%; p&#xa0;<&#xa0;0.0001), and 96.1&#xa0;% (95&#xa0;% CI 90.4&#xa0;%-98.4&#xa0;%). Waning protection against infection was reported by four studies, although protection against hospitalisation for severe infection persists for at least 6&#xa0;months post vaccination.<br><br>CONCLUSIONS: Vaccination against SARS-CoV2 in HCWs is protective against infection, symptomatic infection, and hospitalisation. Waning protection is reported but this awaits more mature studies to understand durability more clearly. This study is limited by varying non-pharmacological responses to COVID-19 between included studies, a predominantly female and working age population, and limited information on asymptomatic transmission or long COVID protection.}, }
@article {pmid39232616, year = {2024}, author = {Abu Jawdeh, BG and Vikram, HR}, title = {Coronavirus Disease 2019 in Kidney Transplantation - A 2024 Update.}, journal = {Advances in kidney disease and health}, volume = {31}, number = {5}, pages = {458-465}, doi = {10.1053/j.akdh.2024.03.004}, pmid = {39232616}, issn = {2949-8139}, mesh = {Humans ; *Kidney Transplantation ; *COVID-19/epidemiology/prevention &amp; control/immunology ; SARS-CoV-2 ; Telemedicine ; COVID-19 Vaccines/administration &amp; dosage ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 has led to the death of about 7 million people worldwide. When infected, older individuals and those with diabetes, hypertension, cardiovascular disease, and compromised immune system are at higher risk for unfavorable outcomes. These comorbidities are prevalent in kidney transplant candidates and recipients making them inherently vulnerable to severe acute respiratory syndrome coronavirus 2 infection, hence, the significant burden the pandemic has exerted on kidney transplant programs. With the swift discovery and wide-scale availability of vaccines and therapeutics against severe acute respiratory syndrome coronavirus 2, the pandemic is currently behind us allowing transplant programs to relieve their restrictions and resume normal pre-COVID-19 operations. In the aftermath of the pandemic, we discuss the implications for immunosuppression and vaccination, COVID-19-induced kidney injury phenotypes and long COVID-19 symptoms. We also discuss some of the operational aspects the pandemic brought about - mainly the utilization of telemedicine - that are now here to stay.}, }
@article {pmid39234483, year = {2024}, author = {Wu, K and Van Name, J and Xi, L}, title = {Cardiovascular abnormalities of long-COVID syndrome: Pathogenic basis and potential strategy for treatment and rehabilitation.}, journal = {Sports medicine and health science}, volume = {6}, number = {3}, pages = {221-231}, pmid = {39234483}, issn = {2666-3376}, abstract = {Cardiac injury and sustained cardiovascular abnormalities in long-COVID syndrome, i.e. post-acute sequelae of coronavirus disease 2019 (COVID-19) have emerged as a debilitating health burden that has posed challenges for management of pre-existing cardiovascular conditions and other associated chronic comorbidities in the most vulnerable group of patients recovered from acute COVID-19. A clear and evidence-based guideline for treating cardiac issues of long-COVID syndrome is still lacking. In this review, we have summarized the common cardiac symptoms reported in the months after acute COVID-19 illness and further evaluated the possible pathogenic factors underlying the pathophysiology process of long-COVID. The mechanistic understanding of how Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) damages the heart and vasculatures is critical in developing targeted therapy and preventive measures for limiting the viral attacks. Despite the currently available therapeutic interventions, a considerable portion of patients recovered from severe COVID-19 have reported a reduced functional reserve due to deconditioning. Therefore, a rigorous and comprehensive cardiac rehabilitation program with individualized exercise protocols would be instrumental for the patients with long-COVID to regain the physical fitness levels comparable to their pre-illness baseline.}, }
@article {pmid39238359, year = {2024}, author = {Deng, J and Qin, C and Lee, M and Lee, Y and You, M and Liu, J}, title = {Effects of rehabilitation interventions for old adults with long COVID: A systematic review and meta-analysis of randomised controlled trials.}, journal = {Journal of global health}, volume = {14}, number = {}, pages = {05025}, pmid = {39238359}, issn = {2047-2986}, mesh = {Aged ; Humans ; Middle Aged ; Quality of Life ; Randomized Controlled Trials as Topic ; SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome/diagnosis/psychology/rehabilitation ; }, abstract = {BACKGROUND: There is limited evidence on the effectiveness of the existing rehabilitation interventions for old adults with long coronavirus disease (COVID), which is of particular concern among old adults.<br><br>METHODS: We systematically searched studies published in PubMed, EMBASE, Web of Science, Scopus, and Cochrane Library databases from their inception to 15 November 2023. Randomised controlled trials (RCTs) compared rehabilitation interventions with other controls in old adults (mean/median age of 60 or older) with long COVID were included. We performed a meta-analysis to compare the effects of the rehabilitation interventions with the common control group. Mean difference (MD) or standardised mean difference (SMD) with its 95% confidence intervals (CI) were used as summary statistics. Moreover, subgroup analyses based on the intervention programmes, the severity of acute infection, and the age of participants were carried out.<br><br>RESULTS: A total of 11 RCTs involving 832 participants (64.37&#x2009;&#xb1;&#x2009;7.94 years, 52.2% were men) were included in the analysis. Compared with the control groups, rehabilitation interventions significantly improved 6-minute walking test (6 MWT; MD&#x2009;=&#x2009;15.77 metres (m), 95% CI&#x2009;=&#x2009;5.40, 26.13, P&#x2009;<&#x2009;0.01), 30-second sit-to-stand test (MD&#x2009;=&#x2009;4.11 number of stands (n), 95% CI&#x2009;=&#x2009;2.46, 5.76, P&#x2009;<&#x2009;0.001), all aspects of quality of life, independence in activities of daily living (SMD&#x2009;=&#x2009;0.31, 95% CI&#x2009;=&#x2009;0.14, 0.48, P&#x2009;<&#x2009;0.001), and relieved fatigue (SMD&#x2009;=&#x2009;-0.66, 95% CI&#x2009;=&#x2009;-1.13, -0.19, P&#x2009;<&#x2009;0.01), depression (SMD&#x2009;=&#x2009;-0.89, 95% CI&#x2009;=&#x2009;-1.76, -0.02, P&#x2009;<&#x2009;0.05) and anxiety (SMD&#x2009;=&#x2009;-0.81, 95% CI&#x2009;=&#x2009;-1.58, -0.05, P&#x2009;<&#x2009;0.05). However, the improvement of hand grip strength and pulmonary function was not statistically significant (P&#x2009;>&#x2009;0.05). Subgroup analyses showed that improvements in 6 MWT, fatigue, anxiety, and depression were more pronounced in old patients who received exercise training, while those who received respiratory rehabilitation had more pronounced improvements in pulmonary function and quality of life.<br><br>CONCLUSIONS: Old adults with long COVID who underwent rehabilitation interventions experienced significant improvement in functional capacity, fatigue, quality of life, independence in activities of daily living, and mental health outcomes compared with usual/standard care. These findings suggest that screening, management, and rehabilitation interventions for long COVID in older adults should be strengthened to improve their complete health status and functional status, thereby reducing the long-term disease burden caused by long COVID and fostering healthy aging during the post-pandemic era.}, }
@article {pmid39240417, year = {2025}, author = {Haunhorst, S and Dudziak, D and Scheibenbogen, C and Seifert, M and Sotzny, F and Finke, C and Behrends, U and Aden, K and Schreiber, S and Brockmann, D and Burggraf, P and Bloch, W and Ellert, C and Ramoji, A and Popp, J and Reuken, P and Walter, M and Stallmach, A and Puta, C}, title = {Towards an understanding of physical activity-induced post-exertional malaise: Insights into microvascular alterations and immunometabolic interactions in post-COVID condition and myalgic encephalomyelitis/chronic fatigue syndrome.}, journal = {Infection}, volume = {53}, number = {1}, pages = {1-13}, pmid = {39240417}, issn = {1439-0973}, mesh = {Humans ; *Fatigue Syndrome, Chronic/immunology/physiopathology/metabolism ; *COVID-19/complications/immunology/physiopathology/metabolism ; *Exercise/physiology ; SARS-CoV-2 ; Microcirculation ; }, abstract = {BACKGROUND: A considerable number of patients who contracted SARS-CoV-2 are affected by persistent multi-systemic symptoms, referred to as Post-COVID Condition (PCC). Post-exertional malaise (PEM) has been recognized as one of the most frequent manifestations of PCC and is a diagnostic criterion of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Yet, its underlying pathomechanisms remain poorly elucidated.<br><br>PURPOSE AND METHODS: In this review, we describe current evidence indicating that key pathophysiological features of PCC and ME/CFS are involved in physical activity-induced PEM.<br><br>RESULTS: Upon physical activity, affected patients exhibit a reduced systemic oxygen extraction and oxidative phosphorylation capacity. Accumulating evidence suggests that these are mediated by dysfunctions in mitochondrial capacities and microcirculation that are maintained by latent immune activation, conjointly impairing peripheral bioenergetics. Aggravating deficits in tissue perfusion and oxygen utilization during activities cause exertional intolerance that are frequently accompanied by tachycardia, dyspnea, early cessation of activity and elicit downstream metabolic effects. The accumulation of molecules such as lactate, reactive oxygen species or prostaglandins might trigger local and systemic immune activation. Subsequent intensification of bioenergetic inflexibilities, muscular ionic disturbances and modulation of central nervous system functions can lead to an exacerbation of existing pathologies and symptoms.}, }
@article {pmid39240511, year = {2024}, author = {di Filippo, L and Franzese, V and Santoro, S and Doga, M and Giustina, A}, title = {Long COVID and pituitary dysfunctions: a bidirectional relationship?.}, journal = {Pituitary}, volume = {27}, number = {6}, pages = {955-969}, pmid = {39240511}, issn = {1573-7403}, mesh = {Humans ; *COVID-19/complications/epidemiology/physiopathology ; *SARS-CoV-2 ; *Hypothalamo-Hypophyseal System/physiopathology/metabolism ; Post-Acute COVID-19 Syndrome ; Pituitary-Adrenal System/physiopathology/metabolism ; Hypogonadism/physiopathology/epidemiology ; Pituitary Diseases/physiopathology/epidemiology/complications ; Adrenal Insufficiency/physiopathology/epidemiology ; Hypothyroidism/physiopathology/epidemiology/complications ; Pituitary Gland/physiopathology/metabolism ; }, abstract = {Long COVID is a novel emerging syndrome known to affect multiple health areas in patients previously infected by SARS-CoV-2 markedly impairing their quality of life. The pathophysiology of Long COVID is still largely poorly understood and multiple mechanisms were proposed to underlie its occurrence, including alterations in the hormonal hypothalamic-pituitary axes. Aim of this review is to present and discuss the potential negative implications of these hormonal dysfunctions in promoting and influencing the Long COVID syndrome. To date, the hypothalamic-pituitary-adrenal axis is the mostly investigated and several studies have reported a prolonged impairment leading to mild and subclinical forms of central adrenal insufficiency. Few data are also available regarding central hypogonadism, central hypothyroidism and growth hormone (GH) deficiency. A high prevalence of central hypogonadism in COVID-19 survivors several months after recovery was consistently reported in different cohorts. Conversely, very few data are available on the hypothalamic-pituitary-thyroid axis function that was mainly shown to be preserved in COVID-19 survivors. Finally, a potential impairment of the hypothalamic-GH axis in Long COVID has also been reported. These data altogether may suggest a novel possible pituitary-centred pathophysiological view of Long COVID syndrome which if confirmed by large clinical studies may have relevant implication for the diagnostic and therapeutic approach at least in a subset of patients with the syndrome.}, }
@article {pmid39252604, year = {2025}, author = {Yang, X and Shi, F and Zhang, H and Giang, WA and Kaur, A and Chen, H and Li, X}, title = {Long COVID among people with HIV: A systematic review and meta-analysis.}, journal = {HIV medicine}, volume = {26}, number = {1}, pages = {6-16}, pmid = {39252604}, issn = {1468-1293}, support = {R21 AI170159/AI/NIAID NIH HHS/United States ; R21AI170159-01A1//University of South Carolina/ ; /NH/NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/epidemiology/complications/immunology ; *HIV Infections/complications/epidemiology/immunology ; Prevalence ; Risk Factors ; }, abstract = {BACKGROUND: People with HIV might be at an increased risk of long COVID (LC) because of their immune dysfunction and chronic inflammation and alterations in immunological responses against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2; coronavirus disease 2019 [COVID-19]). This systematic review aimed to evaluate the association between HIV infection and LC and the prevalence and characteristics of and risk factors for LC among people with HIV.<br><br>METHODS: Multiple databases, including Embase, PubMed, PsycINFO, Web of Science, and Sociological Abstracts, were searched to identify articles published before June 2023. Published articles were included if they presented at least one LC outcome measure among people with HIV and used quantitative or mixed-methods study designs. For effects reported in three or more studies, meta-analyses using random-effects models were performed using R software.<br><br>RESULTS: We pooled 39&#x2009;405 people with HIV and COVID-19 in 17 eligible studies out of 6158 publications in all the databases. It was estimated that 52% of people with HIV with SARS-CoV-2 infection developed at least one LC symptom. Results from the random-effects model showed that HIV infection was associated with an increased risk of LC (odds ratio&#x2009;2.20; 95% confidence interval 1.25-3.86). The most common LC symptoms among people with HIV were cough, fatigue, and asthenia. Risk factors associated with LC among people with HIV included a history of moderate-severe COVID-19 illness, increased interferon-gamma-induced protein 10 or tumour necrosis factor-&#x3b1;, and decreased interferon-&#x3b2;, among others.<br><br>CONCLUSIONS: The COVID-19 pandemic continues to exacerbate health inequities among people with HIV because of their higher risk of developing LC. Our review is informative for public health and clinical communities to develop tailored strategies to prevent aggravated LC among people with HIV.}, }
@article {pmid39253580, year = {2024}, author = {Zhou, J and Wang, Y and Xu, R}, title = {Association of COVID-19 infection and the risk of new incident diabetes: a systematic review and meta-analysis.}, journal = {Frontiers in endocrinology}, volume = {15}, number = {}, pages = {1429848}, pmid = {39253580}, issn = {1664-2392}, mesh = {Humans ; *COVID-19/epidemiology ; *Diabetes Mellitus, Type 1/epidemiology ; *Diabetes Mellitus, Type 2/epidemiology ; Incidence ; Risk Factors ; }, abstract = {BACKGROUND: As the world population recovers from the COVID-19 infection, a series of acute sequelae emerge including new incident diabetes. However, the association between COVID-19 infection and new incident diabetes is not fully understood. We purpose to determine the risk of new incident diabetes after COVID-19 infection.<br><br>METHODS: PubMed, Embase, and Cochrane Library were used as databases to search for cohort studies published from database inception to February 4, 2024. Two reviewers independently conducted the study screening, data extraction, and risk of bias assessment. A random-effects model was adopted to pool the hazard ratio (HR) with corresponding 95% confidence intervals (CI). Subgroup analysis was conducted to explore the potential influencing factors.<br><br>RESULTS: A total of 20 cohort studies with over 60 million individuals were included. The pooling analysis illustrates the association between COVID-19 infection and an increased risk of new incident diabetes (HR = 1.46; 95% CI: 1.38-1.55). In subgroup analysis, the risk of type 1 diabetes was HR=1.44 (95% CI: 1.13-1.82), and type 2 diabetes was HR=1.47 (95% CI: 1.36-1.59). A slightly higher risk of diabetes was found in males (HR=1.37; 95% CI: 1.30-1.45) than in females (HR=1.29; 95% CI: 1.22-1.365). The risk of incident diabetes is associated with hospitalization: non-hospitalized patients have an HR of 1.16 (95% CI: 1.07-1.26), normal hospitalized patients have an HR of 2.15 (95% CI: 1.33-3.49), and patients receiving intensive care have the highest HR of 2.88 (95% CI: 1.73-4.79).<br><br>CONCLUSIONS: COVID-19 infection is associated with an elevated risk of new incident diabetes. Patients ever infected with COVID-19 should be recognized as a high-risk population with diabetes.<br><br>https://www.crd.york.ac.uk/prospero, identifier CRD42024522050.}, }
@article {pmid39254484, year = {2024}, author = {Pineros-Garcia, LN and Gonzalez-Sanchez, NI and Calvo-Henrique, C and Rojas-Lechuga, MJ and Hopkins, C and Mullol, J and Alobid, I}, title = {SNOT-22 in general population, a Spanish cohort study with an updated meta-analysis.}, journal = {Rhinology}, volume = {62}, number = {6}, pages = {700-709}, doi = {10.4193/Rhin24.233}, pmid = {39254484}, issn = {0300-0729}, mesh = {Humans ; *COVID-19/complications ; *Olfaction Disorders/physiopathology ; Female ; Prospective Studies ; Male ; Middle Aged ; *SARS-CoV-2 ; Spain ; Adult ; Aged ; Smell/physiology ; Cohort Studies ; }, abstract = {BACKGROUND: Olfactory loss (OL) has emerged as one of the most prevalent and debilitating symptoms of SARS-CoV-2 infection and long-COVID-19. The present prospective observational study aimed to evaluate the efficacy of olfactory training (OT) on orthonasal and retronasal olfactory function in a cohort of individuals with persistent post-COVID-19 OL.<br><br>METHODOLOGY: Participants with post-COVID-19 olfactory impairment underwent 4 months of OT, self-assessing their smell perception and undergoing comprehensive psychophysical evaluation of orthonasal and retronasal olfaction at baseline and after training. Orthonasal olfactory function was assessed using the extended Sniffin' Sticks test battery. Retronasal olfactory function was tested with powdered aromas.<br><br>RESULTS: Among 114 participants with post-COVID-19 olfactory loss, adherence to OT was 60%. In adherents, the average increase in composite TDI score was 6.0 points compared to 2.6 points in non-adherents. Fifty-seven percent of adherent participants achieved a clinically significant improvement in TDI score (&#x2265; 5.5 points), compared to 22% of non-adherents. In retronasal olfactory identification, 56% of adherents achieved a clinically significant improvement (&#x2265;4 points), compared to 16% of non-adherents.<br><br>CONCLUSION: Adherence to a 4-month OT regimen can yield clinically meaningful improvements in both orthonasal and retronasal olfactory function among individuals with persistent post-COVID-19 olfactory dysfunction.}, }
@article {pmid39258051, year = {2024}, author = {Mukkawar, RV and Reddy, H and Rathod, N and Kumar, S and Acharya, S}, title = {The Long-Term Cardiovascular Impact of COVID-19: Pathophysiology, Clinical Manifestations, and Management.}, journal = {Cureus}, volume = {16}, number = {8}, pages = {e66554}, pmid = {39258051}, issn = {2168-8184}, abstract = {The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has resulted in a substantial global health crisis, with effects extending far beyond the acute phase of infection. This review aims to provide a comprehensive overview of the long-term cardiovascular impact of COVID-19, focusing on the pathophysiology, clinical manifestations, diagnostic approaches, management strategies, and future research directions. SARS-CoV-2 induces cardiovascular complications through mechanisms such as inflammation, endothelial dysfunction, and direct myocardial injury, leading to conditions like myocarditis, heart failure, arrhythmias, and thromboembolic events. These long-term effects, collectively called "long COVID" or post-acute sequelae of SARS-CoV-2 infection (PASC), present significant challenges for healthcare systems and patient management. Diagnostic approaches include imaging techniques and laboratory tests to identify and monitor cardiovascular complications. Management strategies emphasize a holistic approach, incorporating pharmacological treatments and lifestyle modifications. Special attention is required for vulnerable populations, including those with pre-existing cardiovascular conditions. Ongoing research is essential to understand the full spectrum of long-term cardiovascular impacts and to develop effective treatments. This review highlights the critical need for continued vigilance, multidisciplinary care, and research to address the cardiovascular sequelae of COVID-19 and improve long-term health outcomes for survivors.}, }
@article {pmid39268246, year = {2024}, author = {Umakanthan, S and Katwaroo, AR and Bukelo, M and Bg, S and Boralingaiah, P and Ranade, AV and Rangan, P and Shashidhar, S and Kini, JR and Kini, G}, title = {Post-Acute Sequelae of Covid-19: A System-wise Approach on the Effects of Long-Covid-19.}, journal = {American journal of medicine open}, volume = {12}, number = {}, pages = {100071}, pmid = {39268246}, issn = {2667-0364}, abstract = {The SARS-CoV-2 virus responsible for the COVID-19 pandemic has profoundly impacted global health, economics, and society. This review seeks to encompass an overview of current knowledge on COVID-19, including its transmission, pathogenesis, and clinical presentation related to various systems within the human body. COVID-19 is a highly contagious illness that has rapidly spread worldwide. As of August 4, 2023, the WHO reported over 570 million confirmed cases of COVID-19 and over 6.3 million deaths. Although the virus is most common in adults, children can also be infected. Respiratory droplets that are produced when an infected person coughs or sneezes are the primary transmission mode for COVID-19. Additionally, the virus can be disseminated via contact with contaminated surfaces or objects, as it can remain viable for several hours or days. SARS-CoV-2 is a respiratory virus that enters cells by bonding with the angiotensin-converting enzyme 2 (ACE2) receptor. Once inside the cell, the virus replicates and produces new particles that can infect other cells. Interestingly, the effects of post-acute sequelae of SARS-CoV-2 infection (PASC) encompass more than just respiratory system. The findings presented in the data suggest that PASC significantly impacts multiple organs and their respective physiological processes. In light of these observations, we aim to provide a detailed discussion of the relevant findings in this paper. Through our review, we hope to provide healthcare professionals with a deeper understanding of the effects of PASC on the human body, which could ultimately lead to improved patient outcomes and treatment strategies.}, }
@article {pmid39270616, year = {2024}, author = {Burch, E and Khan, SA and Stone, J and Asgharzadeh, A and Dawe, J and Ward, Z and Brooks-Pollock, E and Christensen, H}, title = {Early mathematical models of COVID-19 vaccination in high-income countries: a systematic review.}, journal = {Public health}, volume = {236}, number = {}, pages = {207-215}, doi = {10.1016/j.puhe.2024.07.029}, pmid = {39270616}, issn = {1476-5616}, mesh = {Humans ; *COVID-19/prevention &amp; control/epidemiology ; *COVID-19 Vaccines/administration &amp; dosage ; *Developed Countries ; *Models, Theoretical ; SARS-CoV-2 ; Vaccination/statistics &amp; numerical data ; }, abstract = {OBJECTIVES: Since COVID-19 first emerged in 2019, mathematical models have been developed to predict transmission and provide insight into disease control strategies. A key research need now is for models to inform long-term vaccination policy. We aimed to review the early modelling methods utilised during the pandemic period (2019-2023) in order to identify gaps in the literature and highlight areas for future model development.<br><br>STUDY DESIGN: This study was a systematic review.<br><br>METHODS: We searched PubMed, Embase and Scopus from 1 January 2019 to 6 February 2023 for peer-reviewed, English-language articles describing age-structured, dynamic, mathematical models of COVID-19 transmission and vaccination in high-income countries that include waning immunity or reinfection. We extracted details of the structure, features and approach of each model and combined them in a narrative synthesis.<br><br>RESULTS: Of the 1109 articles screened, 47 were included. Most studies used deterministic, compartmental models set in Europe or North America that simulated a time horizon of 3.5 years or less. Common outcomes included cases, hospital utilisation and deaths. Only nine models included long COVID, costs, life years or quality of life-related measures. Two studies explored the potential impact of new variants beyond Omicron.<br><br>CONCLUSIONS: This review demonstrates a need for long-term models that focus on outcome measures such as quality-adjusted life years, the population-level effects of long COVID and the cost effectiveness of future policies - all of which are essential considerations in the planning of long-term vaccination strategies.}, }
@article {pmid39282763, year = {2024}, author = {Silva, MMD and Benites, MN and Castro, YM and Moura, PV and Zhang, L}, title = {Prevalence of symptoms of post-COVID-19 condition (long COVID) in children hospitalized with COVID-19: A systematic review of observational studies.}, journal = {Pediatric pulmonology}, volume = {59}, number = {12}, pages = {3159-3169}, doi = {10.1002/ppul.27257}, pmid = {39282763}, issn = {1099-0496}, mesh = {Humans ; *COVID-19/epidemiology/complications ; Child ; Prevalence ; *Observational Studies as Topic ; *Hospitalization/statistics &amp; numerical data ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Adolescent ; Child, Preschool ; }, abstract = {This systematic review aimed to investigate the prevalence of symptoms of post-COVID-19 condition (long COVID), in children hospitalized with COVID-19. We searched PUBMED and EMBASE on 15 March, 2023, using search strategy: "long COVID" OR "post-COVID-19" OR "postacute COVID-19" OR "long-term COVID" OR "COVID-19 sequelae" OR "persistent COVID-19" OR "chronic COVID-19". We included observational studies (case-control, cross-sectional, cohort, or case series) that investigated symptoms of post-COVID-19 condition (long COVID) in children (<18 years) admitted with COVID-19. We used the WHO case definition of post-COVID-19 condition. Long COVID was defined as persistence of otherwise unexplained symptoms for at least three months after SARS-CoV-2 infection. We used the command "metaprop" to perform random-effects meta-analysis. Eleven studies involving 2279 patients were included. In the period between ≥3 months and <12 months after acute COVID-19, the most frequent symptom was exercise intolerance with a pooled prevalence of 29% (95% CI: 7%-57%, I[2] = 95%), followed by nonspecific respiratory symptoms (12%, 95% CI: 0%-48%, I[2] = 0%), psychological disorders (10%, 95% CI: 1%-25%, I[2] = 97%), and nonspecific gastrointestinal symptoms (10%, 95% CI: 0%-37%, I[2] = 99%). In the period ≥12 months after the initial infection, the pooled prevalence of post COVID symptoms was lower, with 6% (95% CI: 2%-10%, I[2] = 83%) for exercise intolerance and 3% (95% CI: 0%-8%, I[2] = 89%) for fatigue. In conclusion, symptoms of post-COVID condition (long COVID) in hospitalized children affect multiple organ systems, with higher prevalence in the period up to 12 months after the acute phase of COVID-19.}, }
@article {pmid39283425, year = {2024}, author = {Celeghin, A and Stanziano, M and Palermo, S}, title = {Addressing Long COVID Sequelae and Neurocovid: Neuropsychological Scenarios and Neuroimaging Findings.}, journal = {Advances in experimental medicine and biology}, volume = {1457}, number = {}, pages = {143-164}, pmid = {39283425}, issn = {0065-2598}, mesh = {Humans ; *COVID-19/psychology/complications ; *Neuroimaging/methods ; *SARS-CoV-2/pathogenicity ; Post-Acute COVID-19 Syndrome ; Cognitive Dysfunction/diagnostic imaging/physiopathology/psychology ; Quality of Life ; Brain/diagnostic imaging/physiopathology ; Neuropsychological Tests ; }, abstract = {In the face of increasing reports of CNS involvement in COVID-19 cases, it is likely that the current epidemic may be accompanied by a significant increase in the prevalence of neurological sequelae, cognitive dysfunction, and long-term behavioural alterations affecting quality of life and autonomy in daily life. This is consequential to the neuroinvasion and multi-organ dysfunction, but also to the psychological distress and socioeconomic changes that occur. Long COVID and neurocovid are now an established concept worldwide. However, the clinical features of these two entities are still debated. The chapter provides information about the nosographic framing, associated pathophysiological mechanisms, alterations in the central and peripheral nervous systems, and the associated neurocognitive profile, indications about predictor and clinical evaluation according to a patient-centred multidimensional immuno-behavioural approach.}, }
@article {pmid39283441, year = {2024}, author = {Zeigler, Z and Acevedo, A}, title = {Obesity, Physical Activity, and COVID-19.}, journal = {Advances in experimental medicine and biology}, volume = {1457}, number = {}, pages = {431-446}, doi = {10.1007/978-3-031-61939-7_24}, pmid = {39283441}, issn = {0065-2598}, mesh = {*COVID-19/epidemiology/prevention &amp; control ; Humans ; *Obesity/epidemiology/physiopathology ; *Exercise ; *Sedentary Behavior ; *SARS-CoV-2 ; Risk Factors ; Comorbidity ; }, abstract = {Estimates suggest that over 80% of people with COVID-19 may experience mild to no symptoms. The Centers for Disease Control and Prevention (CDC) reported that around 7-8% of positive COVID-19 cases were hospitalized in the first year of the pandemic. A substantial body of evidence points to obesity, sedentary behavior, and low physical activity levels as risk factors for susceptibility to the virus and the severity of symptoms. Obese individuals are 46% more likely to contract the virus than those of normal weight, and those who are physically active have an 11% reduced risk of contracting the virus. Medical experts have also identified obesity, sedentary behavior, and physical inactivity as risk factors for severe COVID-19 symptoms and long COVID. Evidence from bariatric surgery suggests that weight loss decreases the susceptibility and severity of COVID-19. The mechanisms linking obesity, sedentary behavior, and physical activity to COVID-19 are somewhat similar. Obesity, sedentary behavior, and low physical activity are all linked to inflammation, immune dysfunction, and comorbidities such as diabetes and cardiovascular disease that increase COVID-19 risk. Additionally, achieving the recommended 150 min of moderate-intensity exercise seems to be the desired dose for protection from COVID-19.}, }
@article {pmid39287023, year = {2024}, author = {Scheithauer, TPM and Montijn, RC and Mieremet, A}, title = {Gut microbe-host interactions in post-COVID syndrome: a debilitating or restorative partnership?.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2402544}, pmid = {39287023}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome ; *COVID-19/microbiology/virology ; *Post-Acute COVID-19 Syndrome ; *Host Microbial Interactions ; *Probiotics/therapeutic use ; *SARS-CoV-2/physiology ; Brain-Gut Axis/physiology ; Animals ; Dysbiosis/microbiology ; Lung/microbiology/virology ; }, abstract = {Post-COVID syndrome (PCS) patients have reported a wide range of symptoms, including fatigue, shortness of breath, and diarrhea. Particularly, the presence of gastrointestinal symptoms has led to the hypothesis that the gut microbiome is involved in the development and severity of PCS. The objective of this review is to provide an overview of the role of the gut microbiome in PCS by describing the microbial composition and microbial metabolites in COVID-19 and PCS. Moreover, host-microbe interactions via the microbiota-gut-brain (MGB) and the microbiota-gut-lung (MGL) axes are described. Furthermore, we explore the potential of therapeutically targeting the gut microbiome to support the recovery of PCS by reviewing preclinical model systems and clinical studies. Overall, current studies provide evidence that the gut microbiota is affected in PCS; however, diversity in symptoms and highly individual microbiota compositions suggest the need for personalized medicine. Gut-targeted therapies, including treatments with pre- and probiotics, have the potential to improve the quality of life of affected individuals.}, }
@article {pmid39289865, year = {2024}, author = {Parums, DV}, title = {Long COVID or Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) and the Urgent Need to Identify Diagnostic Biomarkers and Risk Factors.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {30}, number = {}, pages = {e946512}, pmid = {39289865}, issn = {1643-3750}, mesh = {Humans ; *Biomarkers/blood ; Cognitive Dysfunction/blood/diagnosis/immunology/virology ; *COVID-19/complications/immunology/virology ; Dyspnea/blood/diagnosis/immunology/virology ; Fatigue/blood/diagnosis/immunology/virology ; *Post-Acute COVID-19 Syndrome/blood/diagnosis/immunology/virology ; Risk Factors ; SARS-CoV-2/immunology/pathogenicity ; }, abstract = {Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), also known as post-COVID-19 condition or post-COVID syndrome, can affect anyone infected with SARS-CoV-2, regardless of age or the severity of the initial symptoms of COVID-19. Long COVID/PASC is the continuation or development of new symptoms after three months from the initial SARS-CoV-2 infection, which lasts for at least two months and has no other identifiable cause. Long COVID/PASC occurs in 10-20% of patients infected with SARS-CoV-2. The most common symptoms include fatigue, cognitive impairment (brain fog), and shortness of breath. However, more than 200 symptoms have been reported. No phenotypic or diagnostic biomarkers have been identified for developing long COVID/PASC, which is a multisystem disorder that can present with isolated or combined respiratory, hematological, immunological, cardiovascular, and neuropsychiatric symptoms. There is no cure. Therefore, individualized patient management requires a multidisciplinary clinical approach. Because millions of people have had and continue to have COVID-19, even in the era of vaccination and antiviral therapies, long COVID/PASC is now and will increasingly become a health and economic burden that the world must prepare for. Almost five years from the beginning of the COVID-19 pandemic, this article aims to review what is currently known about long COVID/PASC, the anticipated increasing global health burden, and why there is still an urgent need to identify diagnostic biomarkers and risk factors to improve prevention and treatment.}, }
@article {pmid39291997, year = {2024}, author = {Pang, Z and Tang, A and He, Y and Fan, J and Yang, Q and Tong, Y and Fan, H}, title = {Neurological complications caused by SARS-CoV-2.}, journal = {Clinical microbiology reviews}, volume = {37}, number = {4}, pages = {e0013124}, pmid = {39291997}, issn = {1098-6618}, support = {82202492//MOST | National Natural Science Foundation of China (NSFC)/ ; 2020YFA0712102//MOST | National Key Research and Development Program of China (NKPs)/ ; QNTD2023-01//MOE | Fundamental Research Funds for the Central Universities (Fundamental Research Fund for the Central Universities)/ ; 2023BINCMCF28//Nutrition and Care of Maternal &amp; Child Research Project of Biotime Institute of Nutrition &amp; Care/ ; }, mesh = {Humans ; Central Nervous System/virology/pathology ; *COVID-19/complications/virology ; *Nervous System Diseases/pathology/virology ; *SARS-CoV-2/pathogenicity ; }, abstract = {SUMMARYSARS-CoV-2 can not only cause respiratory symptoms but also lead to neurological complications. Research has shown that more than 30% of SARS-CoV-2 patients present neurologic symptoms during COVID-19 (A. Pezzini and A. Padovani, Nat Rev Neurol 16:636-644, 2020, https://doi.org/10.1038/s41582-020-0398-3). Increasing evidence suggests that SARS-CoV-2 can invade both the central nervous system (CNS) (M.S. Xydakis, M.W. Albers, E.H. Holbrook, et al. Lancet Neurol 20: 753-761, 2021 https://doi.org/10.1016/S1474-4422(21)00182-4) and the peripheral nervous system (PNS) (M.N. Soares, M. Eggelbusch, E. Naddaf, et al. J Cachexia Sarcopenia Muscle 13:11-22, 2022, https://doi.org/10.1002/jcsm.12896), resulting in a variety of neurological disorders. This review summarized the CNS complications caused by SARS-CoV-2 infection, including encephalopathy, neurodegenerative diseases, and delirium. Additionally, some PNS disorders such as skeletal muscle damage and inflammation, anosmia, smell or taste impairment, myasthenia gravis, Guillain-Barré syndrome, ICU-acquired weakness, and post-acute sequelae of COVID-19 were described. Furthermore, the mechanisms underlying SARS-CoV-2-induced neurological disorders were also discussed, including entering the brain through retrograde neuronal or hematogenous routes, disrupting the normal function of the CNS through cytokine storms, inducing cerebral ischemia or hypoxia, thus leading to neurological complications. Moreover, an overview of long-COVID-19 symptoms is provided, along with some recommendations for care and therapeutic approaches of COVID-19 patients experiencing neurological complications.}, }
@article {pmid39299386, year = {2024}, author = {Schultz, KR and McGrath, S and Keary, TA and Meng, CK and Batchos, E and Evans, L and Fields, D and Cummings, A and Fornalski, N}, title = {A multidisciplinary approach to assessment and management of long COVID cognitive concerns.}, journal = {Life sciences}, volume = {357}, number = {}, pages = {123068}, doi = {10.1016/j.lfs.2024.123068}, pmid = {39299386}, issn = {1879-0631}, mesh = {Humans ; *COVID-19/complications/psychology/therapy ; *Cognitive Dysfunction/therapy/etiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Patient Care Team ; Practice Guidelines as Topic ; }, abstract = {Cognitive dysfunction is a commonly reported feature of Long COVID (LC). With the overlap of assessment and treatment for cognitive concerns across multiple disciplines, coupled with current guidelines supporting interdisciplinary care, the aim of this clinically focused article is to provide a review of current guidelines and research related to assessment and interventions to address LC-related cognitive concerns within clinical practice from a multidisciplinary perspective, incorporating best practices for collaboration among Clinical Neuropsychologists, Rehabilitation Psychologists, and Speech-Language Pathologists. Current guidelines for assessment and interventions for cognitive functioning are provided, with clinical suggestions for best practices offered. Additional considerations related to diversity and variable patient presentations are identified. This article provides guidance based on current research and practice standards regarding the utilization of a multidisciplinary, collaborative approach to provide comprehensive assessment and treatment for individuals with LC-related cognitive concerns.}, }
@article {pmid39310121, year = {2024}, author = {Zhai, X and Wu, W and Zeng, S and Miao, Y}, title = {Advance in the mechanism and clinical research of myalgia in long COVID.}, journal = {American journal of clinical and experimental immunology}, volume = {13}, number = {4}, pages = {142-164}, pmid = {39310121}, issn = {2164-7712}, abstract = {As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve, mortality rates of coronavirus disease 2019 (COVID-19) have significantly decreased. However, a variable proportion of patients exhibit persistent prolonged symptoms of COVID-19 infection (long COVID). This virus primarily attacks respiratory system, but numerous individuals complain persistent skeletal muscle pain or worsening pre-existing muscle pain post COVID-19, which severely affects the quality of life and recovery. Currently, there is limited research on the skeletal muscle pain in long COVID. In this brief review, we review potential pathological mechanisms of skeletal muscle pain in long COVID, and summarize the various auxiliary examinations and treatments for skeletal muscle pain in long COVID. We consider abnormal activation of inflammatory response, myopathy, and neurological damages as pivotal pathological mechanisms of skeletal muscle pain in long COVID. A comprehensive examination is significantly important in order to work out effective treatment plans and relieve skeletal muscle pain. So far, rehabilitation interventions for myalgia in long COVID contain but are not limited to drug, nutraceutical therapy, gut microbiome-targeted therapy, interventional therapy and strength training. Our study provides a potential mechanism reference for clinical researches, highlighting the importance of comprehensive approach and management of skeletal muscle pain in long COVID. The relief of skeletal muscle pain will accelerate rehabilitation process, improve activities of daily living and enhance the quality of life, promoting individuals return to society with profound significance.}, }
@article {pmid39313202, year = {2026}, author = {Bonnet, U and Juckel, G}, title = {[The Impact of Antidepressants on COVID-19 and Post-Acute COVID-19 Syndrome: A Scoping-Review Update].}, journal = {Fortschritte der Neurologie-Psychiatrie}, volume = {94}, number = {1-02}, pages = {14-33}, doi = {10.1055/a-2374-2218}, pmid = {39313202}, issn = {1439-3522}, mesh = {Humans ; *COVID-19 Drug Treatment ; *COVID-19/complications ; *Antidepressive Agents/therapeutic use ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Fluvoxamine/therapeutic use ; Selective Serotonin Reuptake Inhibitors/therapeutic use ; }, abstract = {UNLABELLED: Introduction Preclinically, fluvoxamine and other antidepressants (AD) exerted antiviral and anti-inflammatory properties also against SARS-COV-2. Therfore, It makes sense to test the clinical effect of AD against COVID-19 and Long COVID.<br><br>METHODS: On May 20, 2024, this systematic scoping review in PUBMED identified 1016 articles related to AD and COVID-19, Long COVID and SARS-COV-2. These included 10 retrospective "large scale" studies (> 20000 chart reviews), 8 prospective clinical trials (plus 4 regarding Long COVID), 11 placebo-controlled randomized (RCT) (plus 2 regarding Long COVID) and 15 meta-analyses.<br><br>RESULTS: COVID-19: Retrospective studies with cohorts taking AD primarily for psychiatric comorbidities or chronic pain conditions directly prior to SARS-COV-2 infection described that this substance class (most studied: Selective Serotonin Re-Uptake Inhibitors (SSRI) and Selective Serotonin Noradrenaline Re-Uptake Inhibitors (SSNRI)) were associated with (i) significantly fewer SARS-COV-2 infections and (ii) a milder course of COVID-19 ("COVID-19 protection"). Ten of the 11 RCTs found regarding COVID-19 tested fluvoxamine, as this old AD appeared suitable as a prophylactic agent against severe COVID-19, taking into account its in vitro potency against the progression of intracellular sepsis cascades. Therefore, most (12 out of 15) meta-analyses also referred to fluvoxamine. They found (iii) a significant (40-70% reduction) in mortality, intubation and hospitalization rates when fluvoxamine was used as an add-on to standard therapy for mild to moderate COVID-19. When this AD was used in the early stages of the disease, it was more successful than when it was given later in advanced, severe COVID-19 (e.g. severe pneumonia, final sepsis stages). A dose dependency was observed: 2x50 mg fluvoxamine over 15 days was less effective than 2x100 or even 3x100 mg with an adverse event profile still at the placebo level. Direct comparisons with drugs approved for COVID-19 do not yet exist. A first indirect meta-analytical comparison showed an advantage of paxlovid or molnupiravir versus fluvoxamine against the development of severe COVID-19: risk reduction of 95% (I2 = N/A, but only one study) or 78% (I2=0) versus 5+-5% (I2=48). However, an add-on of fluvoxamine was still significantly more efficacious than symptom-oriented standard therapy alone. Long COVID: A common Long COVID phenotype with dominant anxiety and depression symptoms, which responds to AD, relaxation therapy and/or psychotherapy, has now been identified. Casuistics report positive effects of AD on fatigue, cognitive and autonomic dysfunctions. A first large prospective open-label RCT has just shown significantly more favourable courses, less viral load and less pro-inflammatory cytokines in the treatment of mild to moderate COVID-19 with fluvoxamine versus standard treatment, also with regard to the subsequent development of neuropsychiatric and pulmonary Long COVID or fatigue.<br><br>CONCLUSION: Overall, there is promising evidence of a preventive effect of AD (especially fluvoxamine) against progression to severe COVID-19 and against the development of Long COVID. It is likely, that the entire AD substance class could be effective here. This assumption is based on the results of retrospective large scale studies, but awaits verification by better controlled studies. The potential effectiveness/efficacy (currently low and moderate confidence of the evidence for the entire substance class and specifically fluvoxamine, respectively) of fluvoxamine as an add-on against COVID-19 and possibly also directly against Long COVID could stimulate similar projects in other infectious diseases that also have the potential to pose a lasting threat to the health of those affected. We consider the evidence to date to be sufficient to be able to emphasize a possible positive effect of these substances in the psychoeducation of patients with COVID-19 or Long COVID who are already receiving AD for other conditions - especially also against the symptoms associated with the viral disease or its consequences. In regions where neither vaccines nor antiviral agents currently approved for the prevention or treatment of COVID-19 are available, AD and in particular fluvoxamine would be a cost-effective alternative to protect against a severe course, even if this AD appears to have a smaller effect against COVID-19 than the currently approved antiviral agents, but with presumably better tolerability. A direct comparative clinical trial with approved antiviral agents is still pending and should be positive to further open the door for a guideline-based recommendation of fluvoxamine (or perhaps even AD) for COVID-19 or its aftermath.}, }
@article {pmid39326415, year = {2024}, author = {Peluso, MJ and Deeks, SG}, title = {Mechanisms of long COVID and the path toward therapeutics.}, journal = {Cell}, volume = {187}, number = {20}, pages = {5500-5529}, pmid = {39326415}, issn = {1097-4172}, support = {K23 AI157875/AI/NIAID NIH HHS/United States ; R01 NS136197/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/virology/complications/therapy ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; Animals ; COVID-19 Drug Treatment ; }, abstract = {Long COVID, a type of post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PASC) defined by medically unexplained symptoms following infection with SARS-CoV-2, is a newly recognized infection-associated chronic condition that causes disability in some people. Substantial progress has been made in defining its epidemiology, biology, and pathophysiology. However, there is no cure for the tens of millions of people believed to be experiencing long COVID, and industry engagement in developing therapeutics has been limited. Here, we review the current state of knowledge regarding the biology and pathophysiology of long COVID, focusing on how the proposed mechanisms explain the physiology of the syndrome and how they provide a rationale for the implementation of a broad experimental medicine and clinical trials agenda. Progress toward preventing and curing long COVID and other infection-associated chronic conditions will require deep and sustained investment by funders and industry.}, }
@article {pmid39328154, year = {2024}, author = {Melillo, A and Perrottelli, A and Caporusso, E and Coltorti, A and Giordano, GM and Giuliani, L and Pezzella, P and Bucci, P and Mucci, A and Galderisi, S and Maj, M}, title = {Research evidence on the management of the cognitive impairment component of the post-COVID condition: a qualitative systematic review.}, journal = {European psychiatry : the journal of the Association of European Psychiatrists}, volume = {67}, number = {1}, pages = {e60}, pmid = {39328154}, issn = {1778-3585}, mesh = {Humans ; *Cognitive Dysfunction/therapy/etiology ; *Post-Acute COVID-19 Syndrome/complications/psychology/therapy ; }, abstract = {BACKGROUND: Cognitive impairment (CI) is one of the most prevalent and burdensome consequences of COVID-19 infection, which can persist up to months or even years after remission of the infection. Current guidelines on post-COVID CI are based on available knowledge on treatments used for improving CI in other conditions. The current review aims to provide an updated overview of the existing evidence on the efficacy of treatments for post-COVID CI.<br><br>METHODS: A systematic literature search was conducted for studies published up to December 2023 using three databases (PubMed-Scopus-ProQuest). Controlled and noncontrolled trials, cohort studies, case series, and reports testing interventions on subjects with CI following COVID-19 infection were included.<br><br>RESULTS: After screening 7790 articles, 29 studies were included. Multidisciplinary approaches, particularly those combining cognitive remediation interventions, physical exercise, and dietary and sleep support, may improve CI and address the different needs of individuals with post-COVID-19 condition. Cognitive remediation interventions can provide a safe, cost-effective option and may be tailored to deficits in specific cognitive domains. Noninvasive brain stimulation techniques and hyperbaric oxygen therapy showed mixed and preliminary results. Evidence for other interventions, including pharmacological ones, remains sparse. Challenges in interpreting existing evidence include heterogeneity in study designs, assessment tools, and recruitment criteria; lack of long-term follow-up; and under-characterization of samples in relation to confounding factors.<br><br>CONCLUSIONS: Further research, grounded on shared definitions of the post-COVID condition and on the accurate assessment of COVID-related CI, in well-defined study samples and with longer follow-ups, is crucial to address this significant unmet need.}, }
@article {pmid39332491, year = {2024}, author = {Herring, TE and Chopra, A and Friedly, JL and Bender, JA and Gentile, NL and Knowles, LM}, title = {Post traumatic stress and sleep disorders in long COVID: Patient management and treatment.}, journal = {Life sciences}, volume = {357}, number = {}, pages = {123081}, pmid = {39332491}, issn = {1879-0631}, support = {K23 HD111628/HD/NICHD NIH HHS/United States ; U18 HS029905/HS/AHRQ HHS/United States ; }, mesh = {Humans ; *COVID-19/complications/therapy ; *Stress Disorders, Post-Traumatic/therapy/physiopathology ; *Sleep Wake Disorders/therapy ; SARS-CoV-2 ; Risk Factors ; }, abstract = {Post traumatic stress disorder (PTSD) and sleep disorders are prevalent among patients with long COVID. The intersection of PTSD and/or sleep disorders with long COVID is complex. Thus, use of a biopsychosocial lens for assessment and treatment along with a trauma-informed approach to clinical care is recommended. This review provides an overview of the literature on PTSD and sleep disorders among patients with long COVID, including prevalence rates, risk factors, and potential pathophysiology. Pharmacological and non-pharmacological treatment options are reviewed. Also, we provide actionable steps clinicians can integrate into their practice to help effectively assess and treat PTSD and sleep disorders, including validated symptom assessments, recommended referrals, and specific components of non-pharmacological interventions.}, }
@article {pmid39334765, year = {2024}, author = {Yutani, R and Venketaraman, V and Sheren, N}, title = {Treatment of Acute and Long-COVID, Diabetes, Myocardial Infarction, and Alzheimer's Disease: The Potential Role of a Novel Nano-Compound-The Transdermal Glutathione-Cyclodextrin Complex.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {13}, number = {9}, pages = {}, pmid = {39334765}, issn = {2076-3921}, abstract = {Oxidative stress (OS) occurs from excessive reactive oxygen species or a deficiency of antioxidants-primarily endogenous glutathione (GSH). There are many illnesses, from acute and post-COVID-19, diabetes, myocardial infarction to Alzheimer's disease, that are associated with OS. These dissimilar illnesses are, in order, viral infections, metabolic disorders, ischemic events, and neurodegenerative disorders. Evidence is presented that in many illnesses, (1) OS is an early initiator and significant promotor of their progressive pathophysiologic processes, (2) early reduction of OS may prevent later serious and irreversible complications, (3) GSH deficiency is associated with OS, (4) GSH can likely reduce OS and restore adaptive physiology, (5) effective administration of GSH can be accomplished with a novel nano-product, the GSH/cyclodextrin (GC) complex. OS is an overlooked pathological process of many illnesses. Significantly, with the GSH/cyclodextrin (GC) complex, therapeutic administration of GSH is now available to reduce OS. Finally, rigorous prospective studies are needed to confirm the efficacy of this therapeutic approach.}, }
@article {pmid39334847, year = {2024}, author = {Slama Schwok, A and Henri, J}, title = {Long Neuro-COVID-19: Current Mechanistic Views and Therapeutic Perspectives.}, journal = {Biomolecules}, volume = {14}, number = {9}, pages = {}, pmid = {39334847}, issn = {2218-273X}, support = {COVNUCLEOVIR//Sorbonne Universit&#xe9;/ ; }, mesh = {Humans ; *COVID-19/therapy/virology ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Inflammation ; }, abstract = {Long-lasting COVID-19 (long COVID) diseases constitute a real life-changing burden for many patients around the globe and, overall, can be considered societal and economic issues. They include a variety of symptoms, such as fatigue, loss of smell (anosmia), and neurological-cognitive sequelae, such as memory loss, anxiety, brain fog, acute encephalitis, and stroke, collectively called long neuro-COVID-19 (long neuro-COVID). They also include cardiopulmonary sequelae, such as myocardial infarction, pulmonary damage, fibrosis, gastrointestinal dysregulation, renal failure, and vascular endothelial dysregulation, and the onset of new diabetes, with each symptom usually being treated individually. The main unmet challenge is to understand the mechanisms of the pathophysiologic sequelae, in particular the neurological symptoms. This mini-review presents the main mechanistic hypotheses considered to explain the multiple long neuro-COVID symptoms, namely immune dysregulation and prolonged inflammation, persistent viral reservoirs, vascular and endothelial dysfunction, and the disruption of the neurotransmitter signaling along various paths. We suggest that the nucleoprotein N of SARS-CoV-2 constitutes a "hub" between the virus and the host inflammation, immunity, and neurotransmission.}, }
@article {pmid39335455, year = {2024}, author = {Compeer, B and Neijzen, TR and van Lelyveld, SFL and Martina, BEE and Russell, CA and Goeijenbier, M}, title = {Uncovering the Contrasts and Connections in PASC: Viral Load and Cytokine Signatures in Acute COVID-19 versus Post-Acute Sequelae of SARS-CoV-2 (PASC).}, journal = {Biomedicines}, volume = {12}, number = {9}, pages = {}, pmid = {39335455}, issn = {2227-9059}, abstract = {The recent global COVID-19 pandemic has had a profound and enduring impact, resulting in substantial loss of life. The scientific community has responded unprecedentedly by investigating various aspects of the crisis, particularly focusing on the acute phase of COVID-19. The roles of the viral load, cytokines, and chemokines during the acute phase and in the context of patients who experienced enduring symptoms upon infection, so called Post-Acute Sequelae of COVID-19 or PASC, have been studied extensively. Here, in this review, we offer a virologist's perspective on PASC, highlighting the dynamics of SARS-CoV-2 viral loads, cytokines, and chemokines in different organs of patients across the full clinical spectrum of acute-phase disease. We underline that the probability of severe or critical disease progression correlates with increased viral load levels detected in the upper respiratory tract (URT), lower respiratory tract (LRT), and plasma. Acute-phase viremia is a clear, although not unambiguous, predictor of PASC development. Moreover, both the quantity and diversity of functions of cytokines and chemokines increase with acute-phase disease severity. Specific cytokines remain or become elevated in the PASC phase, although the driving factor of ongoing inflammation found in patients with PASC remains to be investigated. The key findings highlighted in this review contribute to a further understanding of PASC and their differences and overlap with acute disease.}, }
@article {pmid39335578, year = {2024}, author = {Lebbe, A and Aboulwafa, A and Bayraktar, N and Mushannen, B and Ayoub, S and Sarker, S and Abdalla, MN and Mohammed, I and Mushannen, M and Yagan, L and Zakaria, D}, title = {New Onset of Acute and Chronic Hepatic Diseases Post-COVID-19 Infection: A Systematic Review.}, journal = {Biomedicines}, volume = {12}, number = {9}, pages = {}, pmid = {39335578}, issn = {2227-9059}, abstract = {The SARS-CoV-2 virus caused a pandemic in the 2020s, which affected almost every aspect of life. As the world is recovering from the effect of the coronavirus, the concept of post-COVID-19 syndrome has emerged. Multiple organ systems have been implicated, including the liver. We aim to identify and analyze the reported cases of severe and long-term parenchymal liver injury post-COVID-19 infection. Several databases were used to conduct a comprehensive literature search to target studies reporting cases of severe and long-term parenchymal liver injury post-COVID-19 infection. Screening, data extraction, and cross checking were performed by two independent reviewers. Only 22 studies met our inclusion criteria. Our results revealed that liver steatosis, non-alcoholic fatty liver disease (NAFLD), and cirrhosis were the most reported liver associated complications post-COVID-19 infection. Moreover, complications like acute liver failure, hepatitis, and liver hemorrhage were also reported. The mechanism of liver injury post-COVID-19 infection is not fully understood. The leading proposed mechanisms include the involvement of the angiotensin-converting enzyme-2 (ACE-2) receptor expressed in the liver and the overall inflammatory state caused by COVID-19 infection. Future studies should incorporate longer follow-up periods, spanning several years, for better insight into the progression and management of such diseases.}, }
@article {pmid39337096, year = {2024}, author = {Boccatonda, A and D'Ardes, D and Tallarico, V and Guagnano, MT and Cipollone, F and Schiavone, C and Piscaglia, F and Serra, C}, title = {Role of Lung Ultrasound in the Detection of Lung Sequelae in Post-COVID-19 Patients: A Systematic Review and Meta-Analysis.}, journal = {Journal of clinical medicine}, volume = {13}, number = {18}, pages = {}, pmid = {39337096}, issn = {2077-0383}, abstract = {Background: During the COVID-19 pandemic, several studies demonstrated the effectiveness of lung ultrasound (LUS) as a frontline tool in diagnosing and managing acute SARS-CoV-2 pneumonia. However, its role in detecting post-COVID-19 lung sequelae remains to be fully determined. This study aims to evaluate the diagnostic accuracy of LUS in identifying lung parenchymal damage, particularly fibrotic-like changes, following COVID-19 pneumonia, comparing its performance to that of CT. Methods: Relevant studies published before July 2024 were identified through a comprehensive search of PubMed, Embase, and Cochrane library. The search terms were combinations of the relevant medical subject heading (MeSH) terms, key words and word variants for "lung", "post-COVID", "long-COVID", and "ultrasound". The pooled sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver-operating characteristic (SROC) curve were used to examine the accuracy of CEUS. The selected works used different thresholds for the detection and counting of B-lines by ultrasound. This led to dividing our analysis into two models, the first based on the lower thresholds for detection of B-lines found in the works, and the second on data obtained using a higher detection threshold. Results: In terms of the diagnostic accuracy of LUS in detecting residual fibrotic-like changes in patients post-COVID-19 infection, a low-threshold model displayed a pooled sensitivity of 0.98 [95% confidence interval (CI): 0.95-0.99] and a pooled specificity of 0.54 (95% CI: 0.49-0.59). The DOR was 44.9 (95% CI: 10.8-187.1). The area under the curve (AUC) of SROC was 0.90. In the second analysis, the model with the higher threshold to detect B-lines showed a pooled sensitivity of 0.90 (95% CI: 0.85-0.94) and a pooled specificity of 0.88 (95% CI: 0.84-0.91). The DOR was 50.4 (95% CI: 15.9-159.3). The AUC of SROC was 0.93. Conclusions: In both analyses (even using the high threshold for the detection of B-lines), excellent sensitivity (98% in model 1 and 90% in model 2) is maintained. The specificity has a significant variation between the two models from 54 (model 1) to 87% (model 2). The model with the highest threshold for the detection of B-lines displayed the best diagnostic accuracy, as confirmed by the AUC values of the SROC (0.93).}, }
@article {pmid39337465, year = {2024}, author = {Eisenreich, W and Leberfing, J and Rudel, T and Heesemann, J and Goebel, W}, title = {Interactions of SARS-CoV-2 with Human Target Cells-A Metabolic View.}, journal = {International journal of molecular sciences}, volume = {25}, number = {18}, pages = {}, pmid = {39337465}, issn = {1422-0067}, support = {EI 384/16 and RU631/17//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Humans ; *SARS-CoV-2/metabolism/physiology ; *COVID-19/metabolism/virology ; Host-Pathogen Interactions ; Glycolysis ; Virus Replication ; Pentose Phosphate Pathway ; Citric Acid Cycle ; }, abstract = {Viruses are obligate intracellular parasites, and they exploit the cellular pathways and resources of their respective host cells to survive and successfully multiply. The strategies of viruses concerning how to take advantage of the metabolic capabilities of host cells for their own replication can vary considerably. The most common metabolic alterations triggered by viruses affect the central carbon metabolism of infected host cells, in particular glycolysis, the pentose phosphate pathway, and the tricarboxylic acid cycle. The upregulation of these processes is aimed to increase the supply of nucleotides, amino acids, and lipids since these metabolic products are crucial for efficient viral proliferation. In detail, however, this manipulation may affect multiple sites and regulatory mechanisms of host-cell metabolism, depending not only on the specific viruses but also on the type of infected host cells. In this review, we report metabolic situations and reprogramming in different human host cells, tissues, and organs that are favorable for acute and persistent SARS-CoV-2 infection. This knowledge may be fundamental for the development of host-directed therapies.}, }
@article {pmid39348850, year = {2025}, author = {Kruger, A and Joffe, D and Lloyd-Jones, G and Khan, MA and Šalamon, &#x160; and Laubscher, GJ and Putrino, D and Kell, DB and Pretorius, E}, title = {Vascular Pathogenesis in Acute and Long COVID: Current Insights and Therapeutic Outlook.}, journal = {Seminars in thrombosis and hemostasis}, volume = {51}, number = {3}, pages = {256-271}, pmid = {39348850}, issn = {1098-9064}, mesh = {Humans ; *COVID-19/complications/therapy/physiopathology/pathology ; *SARS-CoV-2 ; *Endothelium, Vascular/physiopathology/pathology ; *Vascular Diseases/etiology/therapy ; }, abstract = {Long coronavirus disease 2019 (COVID-19)-a postacute consequence of severe acute respiratory syndrome coronavirus 2 infection-manifests with a broad spectrum of relapsing and remitting or persistent symptoms as well as varied levels of organ damage, which may be asymptomatic or present as acute events such as heart attacks or strokes and recurrent infections, hinting at complex underlying pathogenic mechanisms. Central to these symptoms is vascular dysfunction rooted in thrombotic endothelialitis. We review the scientific evidence that widespread endothelial dysfunction (ED) leads to chronic symptomatology. We briefly examine the molecular pathways contributing to endothelial pathology and provide a detailed analysis of how these cellular processes underpin the clinical picture. Noninvasive diagnostic techniques, such as flow-mediated dilation and peripheral arterial tonometry, are evaluated for their utility in identifying ED. We then explore mechanistic, cellular-targeted therapeutic interventions for their potential in treating ED. Overall, we emphasize the critical role of cellular health in managing Long COVID and highlight the need for early intervention to prevent long-term vascular and cellular dysfunction.}, }
@article {pmid39353473, year = {2024}, author = {Dehlia, A and Guthridge, MA}, title = {The persistence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) after SARS-CoV-2 infection: A systematic review and meta-analysis.}, journal = {The Journal of infection}, volume = {89}, number = {6}, pages = {106297}, doi = {10.1016/j.jinf.2024.106297}, pmid = {39353473}, issn = {1532-2742}, mesh = {Humans ; *COVID-19/complications/physiopathology/virology ; *Fatigue Syndrome, Chronic/diagnosis/physiopathology/virology ; *Post-Acute COVID-19 Syndrome/diagnosis/physiopathology/virology ; SARS-CoV-2 ; }, abstract = {OBJECTIVES: Long COVID-19 (LC) patients experience a number of chronic idiopathic symptoms that are highly similar to those of post-viral myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We have therefore performed a systematic review and meta-analysis to determine the proportion of LC patients that satisfy ME/CFS diagnostic criteria.<br><br>METHODS: Clinical studies published between January 2020 and May 2023 were identified using the PubMed, Web of Science, Embase and CINAHL databases. Publication inclusion/exclusion criteria were formulated using the global CoCoPop framework. Data were pooled using a random-effects model with a restricted maximum-likelihood estimator. Study quality was assessed using the Joanna Briggs Institute critical assessment tool.<br><br>RESULTS: We identified 13 eligible studies that reported a total of 1973 LC patients. Our meta-analysis indicated that 51% (95% CI, 42%-60%) of LC patients satisfied ME/CFS diagnostic criteria, with fatigue, sleep disruption, and muscle/joint pain being the most common symptoms. Importantly, LC patients also experienced the ME/CFS hallmark symptom, post-exertional malaise.<br><br>CONCLUSIONS: Our study not only demonstrates that LC patients exhibit similar symptom clusters to ME/CFS, but that approximately half of LC patients satisfy a diagnosis of ME/CFS. Our findings suggest that current ME/CFS criteria could be adapted to the identification of a subset of LC patients that may facilitate the standardised diagnosis, management and the recruitment for clinical studies in the future.}, }
@article {pmid39355045, year = {2023}, author = {Kimura, RH and Iagaru, A and Guo, HH}, title = {Mini review of first-in-human integrin αvβ6 PET tracers.}, journal = {Frontiers in nuclear medicine}, volume = {3}, number = {}, pages = {1271208}, pmid = {39355045}, issn = {2673-8880}, abstract = {This mini review of clinically-evaluated integrin αvβ6 PET-tracers reveals distinct differences in human-biodistribution patterns between linear peptides, including disulfide-stabilized formats, compared to head-to-tail cyclized peptides. All PET tracers mentioned in this mini review were able to delineate disease from normal tissues, but some αvβ6 PET tracers are better than others for particular clinical applications. Each αvβ6 PET tracer was validated for its ability to bind integrin αvβ6 with high affinity. However, all the head-to-tail cyclized peptide PET-tracers reviewed here did not accumulate in the GI-tract, in striking contrast to the linear and disulfide-bonded counterparts currently undergoing clinical evaluation in cancer, IPF and long COVID. Multiple independent investigators have reported the presence of β6 mRNA as well as αvβ6 protein in the GI-tract. Currently, there remains further need for biochemical, clinical, and structural data to satisfactorily explain the state-of-the-art in human αvβ6-imaging.}, }
@article {pmid39357795, year = {2024}, author = {King, LR}, title = {Gastrointestinal manifestations of long COVID.}, journal = {Life sciences}, volume = {357}, number = {}, pages = {123100}, doi = {10.1016/j.lfs.2024.123100}, pmid = {39357795}, issn = {1879-0631}, mesh = {Humans ; *COVID-19/complications ; *Gastrointestinal Diseases/etiology/virology/physiopathology ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome ; Gastrointestinal Microbiome ; Dysbiosis/complications ; Gastrointestinal Tract/virology/physiopathology ; Irritable Bowel Syndrome/etiology/physiopathology/virology ; }, abstract = {Long COVID is estimated to have affected 6.9 % of US adults, 17.8 million people in the US alone, as of early 2023. While SARS-CoV-2 is primarily considered a respiratory virus, gastrointestinal (GI) symptoms are also frequent in patients with coronavirus disease 2019 (COVID-19) and in patients with Long COVID. The risk of developing GI symptoms is increased with increasing severity of COVID-19, the presence of GI symptoms in the acute infection, and psychological distress both before and after COVID-19. Persistence of the virus in the GI tract, ensuing inflammation, and alteration of the microbiome are all likely mediators of the effects of SARS Co-V-2 virus on the gut. These factors may all increase intestinal permeability and systemic inflammation. GI inflammation and dysbiosis can change the absorption and metabolism of tryptophan, an important neurotransmitter. Long COVID GI symptoms resemble a Disorder of Gut Brain Interaction (DGBI) such as post infection Irritable Bowel Syndrome (IBS). Current standards of treatment for IBS can guide our treatment of Long COVID patients. Dysautonomia, a frequent Long COVID condition affecting the autonomic nervous system, can also affect the GI tract, and must be considered in Long COVID patients with GI symptoms. Long COVID symptoms fall within the broader category of Infection Associated Chronic Conditions (IACCs). Research into the GI symptoms of Long COVID may further our understanding of other post infection chronic GI conditions, and elucidate the roles of therapeutic options including antivirals, probiotics, neuromodulators, and treatments of dysautonomia.}, }
@article {pmid39360535, year = {2026}, author = {Amdani, S and Altman, CA and Chowdhury, D and Ronai, C and Soma, D and Archer, JM and Tierney, S and Renno, MS and Miller, J and Nguyen, QT and Glickstein, JS and Orr, WB}, title = {Cardiology Consult for the General Pediatrician after Cardiac Manifestations from a SARS-CoV-2 Infection.}, journal = {Current pediatric reviews}, volume = {22}, number = {1}, pages = {11-19}, pmid = {39360535}, issn = {1875-6336}, mesh = {Humans ; *COVID-19/complications ; Child ; SARS-CoV-2 ; Myocarditis/etiology/therapy/diagnosis ; Referral and Consultation ; *Heart Diseases/therapy/etiology/diagnosis ; Cardiology ; Return to Sport ; Pediatricians ; Systemic Inflammatory Response Syndrome ; }, abstract = {The novel Coronavirus Disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, created a need for evidence-based guidelines for the evaluation, management, and follow-up after infection. Data have become rapidly available, creating a challenge for medical providers to stay abreast of the ever-evolving recommendations. This article, written collaboratively by pediatric cardiovascular experts, pediatricians, and sports medicine specialists, is focused on SARS-CoV- 2-related pediatric cardiac manifestations. It aims to provide a systematic review of high-yield literature related to all cardiovascular entities as a tool for primary pediatric clinicians to utilize as they consider the cardiac consequences of acute SARS-CoV-2 infection, MIS-C, vaccine-related myocarditis, return-to-play, and long COVID-19 syndrome.}, }
@article {pmid39365220, year = {2024}, author = {Gross, M and Lansang, N and Gopaul, U and Yoney, K and Ogawa, EF and Heyn, PC and Sood, P and Omar, Z and Zanwar, PP and Schwertfeger, J and Faieta, J}, title = {What Do I Need to Know About Long COVID-related Breathing Problems?.}, journal = {Archives of physical medicine and rehabilitation}, volume = {105}, number = {12}, pages = {2401-2405}, doi = {10.1016/j.apmr.2024.06.024}, pmid = {39365220}, issn = {1532-821X}, support = {IK1 RX003636/RX/RRD VA/United States ; }, }
@article {pmid39368535, year = {2024}, author = {Raza, ML and Imam, MH and Zehra, W and Jamil, S}, title = {Neuro-inflammatory pathways in COVID-19-induced central nervous system injury: Implications for prevention and treatment strategies.}, journal = {Experimental neurology}, volume = {382}, number = {}, pages = {114984}, doi = {10.1016/j.expneurol.2024.114984}, pmid = {39368535}, issn = {1090-2430}, mesh = {Humans ; *COVID-19/complications/immunology ; *Neuroinflammatory Diseases/etiology/immunology ; *SARS-CoV-2 ; Cytokine Release Syndrome/etiology/prevention &amp; control ; Blood-Brain Barrier ; Animals ; Microglia ; }, abstract = {This review explores the neuroinflammatory pathways underlying COVID-19-induced central nervous system (CNS) injury, with a focus on mechanisms of brain damage and strategies for prevention. A comprehensive literature review was conducted to summarize current knowledge on the pathways by which SARS-CoV-2 reaches the brain, the neuroinflammatory responses triggered by viral infection, neurological symptoms and long COVID. Results: We discuss the mechanisms of neuroinflammation in COVID-19, including blood-brain barrier disruption, cytokine storm, microglial activation, and peripheral immune cell infiltration. Additionally, we highlight potential strategies for preventing CNS injury, including pharmacological interventions, immunomodulatory therapies, and lifestyle modifications. Conclusively, Understanding the neuroinflammatory pathways in COVID-19-induced CNS injury is crucial for developing effective prevention and treatment strategies to protect brain health during and after viral infection.}, }
@article {pmid39380657, year = {2024}, author = {Delpino, MV and Quarleri, J}, title = {Aging mitochondria in the context of SARS-CoV-2: exploring interactions and implications.}, journal = {Frontiers in aging}, volume = {5}, number = {}, pages = {1442323}, pmid = {39380657}, issn = {2673-6217}, abstract = {The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented global challenges with a diverse clinical spectrum, including severe respiratory complications and systemic effects. This review explores the intricate relationship between mitochondrial dysfunction, aging, and obesity in COVID-19. Mitochondria are vital for cellular energy provision and resilience against age-related macromolecule damage accumulation. They manage energy allocation in cells, activating adaptive responses and stress signals such as redox imbalance and innate immunity activation. As organisms age, mitochondrial function diminishes. Aging and obesity, linked to mitochondrial dysfunction, compromise the antiviral response, affecting the release of interferons, and worsening COVID-19 severity. Furthermore, the development of post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID has been associated with altered energy metabolism, and chronic immune dysregulation derived from mitochondrial dysfunction. Understanding the interplay between mitochondria, aging, obesity, and viral infections provides insights into COVID-19 pathogenesis. Targeting mitochondrial health may offer potential therapeutic strategies to mitigate severe outcomes and address long-term consequences in infected individuals.}, }
@article {pmid39381125, year = {2024}, author = {Eslami, Z and Joshaghani, H}, title = {Investigating the Role of Serotonin Levels in Cognitive Impairments Associated with Long COVID-19.}, journal = {Chonnam medical journal}, volume = {60}, number = {3}, pages = {141-146}, pmid = {39381125}, issn = {2233-7385}, abstract = {This study aimed to investigate the activation of the inflammation process, triggered as an immune response to combat the invasion by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a highly transmissible and pathogenic coronavirus that emerged in late 2019 and has caused a pandemic of acute respiratory disease, named 'coronavirus disease 2019' (COVID-19). Several mechanisms contribute to the reduction in serotonin levels, such as the impaired absorption of dietary tryptophan, hindered serotonin transport via platelets, and increased activity of an enzyme responsible for breaking down serotonin. Individuals seeking treatment for long COVID-19 had lower serotonin levels in their blood than those who had fully recovered from the infection. Furthermore, patients with long COVID-19 also had reduced tryptophan levels. The potential benefits of dietary supplementation with tryptophan or the use of selective serotonin reuptake inhibitors (SSRIs) to improve cognitive impairments and depressive and anxiety disorders in long-term COVID-19 patients. The findings support the immune response's pivotal role in modulating serotonin levels and further highlight the intricate connection between the immune system and neurotransmitter regulation.}, }
@article {pmid39382470, year = {2024}, author = {Sharma, SK and Mohan, A and Upadhyay, V}, title = {Long COVID syndrome: An unfolding enigma.}, journal = {The Indian journal of medical research}, volume = {159}, number = {6}, pages = {585-600}, pmid = {39382470}, issn = {0971-5916}, mesh = {Humans ; *COVID-19/epidemiology/complications/virology ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; Risk Factors ; }, abstract = {Post-acute sequelae of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) disease (COVID-19), called as long COVID syndrome, is a major global public health issue after recovery from COVID-19. The disease occurs in symptomatic patients irrespective of illness severity. The symptoms continue after four wk of recovery from acute illness and persist beyond three months. Risk factors for long COVID include older age, female gender, multiple co-morbidities including diabetes mellitus, prior chronic respiratory illnesses, hospitalized patients with severe disease, especially receiving assisted ventilation, high viral load, reactivation of Epstein Barr (EB) virus and human herpes virus 6 (HH6), circulating auto antibodies against various organs and type I interferon. The prevalence varies from 10 to 20 per cent, and most data have been reported from high-income countries. Any system can get involved in long COVID. The symptoms include fatigue, cognition impairment, cough and dyspnoea, anosmia, hair loss and diarrhoea, among others. While there are no laboratory tests for confirmation of diagnosis, reduced complement C7 complexes at six months, and a two-gene biomarker including FYN and SARS-CoV-2 antisense ribonucleic acid (RNA) are emerging as potentially useful biomarkers for long COVID. There should be no alternative disease to explain various symptoms. Vaccination against SARS-CoV-2 and early use of oral antiviral nirmatrelvir within the first five days in patients with acute mild disease having various risk factors for progression to severe disease help in preventing long COVID. Several clinical trials are underway for the treatment of long COVID and the results of these are eagerly awaited. Physical and mental rehabilitation at home, at community level or in the hospital setting as appropriate is essential in patients with long COVID.}, }
@article {pmid39384321, year = {2024}, author = {Hawke, LD and Nguyen, ATP and Wang, W and Brown, EE and Xu, D and Deuville, S and Goulding, S and Ski, CF and Rossell, SL and Thompson, DR and Rodak, T and Strudwick, G and Castle, D}, title = {Systematic review of interventions for mental health, cognition and psychological well-being in long COVID.}, journal = {BMJ mental health}, volume = {27}, number = {1}, pages = {}, pmid = {39384321}, issn = {2755-9734}, mesh = {Humans ; *COVID-19/psychology/epidemiology ; *Mental Health ; *Cognition ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Psychosocial Intervention/methods ; Psychological Well-Being ; }, abstract = {AIMS: This systematic review aims to identify and synthesise the publicly available research testing treatments for mental health, cognition and psychological well-being in long COVID.<br><br>METHODS: The following databases and repositories were searched in October-November 2023: Medline, Embase, APA PsycINFO, Cumulative Index to Nursing and Allied Health Literature, China National Knowledge Internet, WANFANG Data, Web of Science's Preprint Citation Index, The Cochrane Central Register of Controlled Trials, Clinicaltrials.gov and the WHO International Clinical Trials Registry Platform. Articles were selected if they described participants with long COVID symptoms at least 4 weeks after SAR-CoV-19 infection, reported primary outcomes on mental health, cognition and/or psychological well-being, and were available with at least an English-language summary. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for systematic reviews were followed.<br><br>RESULTS: Thirty-three documents representing 31 studies were included. Seven tested psychosocial interventions, five pharmaceutical interventions, three natural supplement interventions, nine neurocognitive interventions, two physical rehabilitation interventions and five integrated interventions. While some promising findings emerged from randomised controlled trials, many studies were uncontrolled; a high risk of bias and insufficient reporting were also frequent.<br><br>CONCLUSIONS: The published literature on treatments for mental health, cognition and psychological well-being in long COVID show that the interventions are highly heterogeneous and findings are inconclusive to date. Continued scientific effort is required to improve the evidence base. Regular literature syntheses will be required to update and educate clinicians, scientists, interventionists and the long COVID community.}, }
@article {pmid39388147, year = {2024}, author = {Menson, KE and Dowman, L}, title = {Pulmonary Rehabilitation for Diseases Other Than COPD.}, journal = {Journal of cardiopulmonary rehabilitation and prevention}, volume = {44}, number = {6}, pages = {425-431}, pmid = {39388147}, issn = {1932-751X}, support = {R01 DA059562/DA/NIDA NIH HHS/United States ; U54 DA036114/DA/NIDA NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/complications/rehabilitation ; SARS-CoV-2 ; Quality of Life ; Exercise Therapy/methods ; Asthma/rehabilitation/complications ; Exercise Tolerance/physiology ; Hypertension, Pulmonary/rehabilitation/physiopathology ; Pulmonary Disease, Chronic Obstructive/rehabilitation/physiopathology ; Bronchiectasis/rehabilitation/physiopathology ; Lung Neoplasms/rehabilitation/complications ; Lung Diseases/rehabilitation/physiopathology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Review the current literature regarding pulmonary rehabilitation (PR) for non-chronic obstructive pulmonary disease (COPD) diagnoses and what the evidence is regarding expected outcomes based on disease manifestations. Literature search was performed using PubMed database from March 2024 to June 2024. Terms included "pulmonary rehabilitation" and "exercise training" in conjunction with key words "interstitial lung disease (ILD)," "idiopathic pulmonary fibrosis," "asthma," "bronchiectasis," "post-acute sequalae of SARS-CoV-2 (PASC)," "long COVID," "pulmonary hypertension (PH)," and "lung cancer." Results were filtered for English language, randomized controlled trial, clinical trial, observational trial, meta-analysis, and guidelines. Emphasis was placed on more recent publications since prior reviews, where applicable. The abundance of literature involved ILD, where studies have demonstrated significant improvements in exercise capacity, health-related quality of life (HRQoL), and dyspnea, despite heterogeneity of diseases; benefits are similar to those seen with COPD. Those with milder disease have more sustained benefits longer term. Patients with asthma benefit in severe disease, lower exercise activity, elevated body mass index, or when comorbid conditions are present, and breathing exercises can improve symptoms of breathlessness. Patients with PASC have a multitude of symptoms and lack benefits in HRQoL measurements; PR improves performance on post-COVID-19 functional status scale, a more comprehensive measurement of symptoms. Those with bronchiectasis benefit from PR when airflow limitation or exacerbations are impacting symptoms and HRQoL. Those with stable PH can improve their exertional capacity without change in disease severity. PR reduces perioperative complications in those with lung cancer and preserve fitness during treatment.}, }
@article {pmid39389388, year = {2025}, author = {Morse, BA and Motovilov, K and Michael Brode, W and Michael Tee, F and Melamed, E}, title = {A review of intravenous immunoglobulin in the treatment of neuroimmune conditions, acute COVID-19 infection, and post-acute sequelae of COVID-19 Syndrome.}, journal = {Brain, behavior, and immunity}, volume = {123}, number = {}, pages = {725-738}, doi = {10.1016/j.bbi.2024.10.006}, pmid = {39389388}, issn = {1090-2139}, mesh = {Humans ; *Immunoglobulins, Intravenous/therapeutic use/administration &amp; dosage ; *COVID-19/immunology/complications/therapy ; *SARS-CoV-2/immunology ; *Post-Acute COVID-19 Syndrome ; Guillain-Barre Syndrome/therapy/immunology/drug therapy ; }, abstract = {Intravenous immunoglobulin (IVIG) is an immunomodulatory therapy that has been studied in several neuroimmune conditions, such as Guillain-Barré Syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and multiple sclerosis. It has also been proposed as a potential treatment option for acute COVID-19 infection and post-acute sequelae of SARS-CoV-2 infection (PASC). IVIG is thought to function by providing the recipient with a pool of antibodies, which can, in turn, modulate immune responses through multiple mechanisms including neutralization of cytokines and autoantibodies, saturation of neonatal fragment crystallizable receptors, inhibition of complement activation, and regulation of T and B cell mediated inflammation. In acute COVID-19, studies have shown that early administration of IVIG and plasmapheresis in severe cases can reduce the need for mechanical ventilation, shorten ICU and hospital stays, and lower mortality. Similarly, in PASC, while research is still in early stages, IVIG has been shown to alleviate persistent symptoms in small patient cohorts. Furthermore, IVIG has shown benefits in another condition which has symptomatic overlap with PASC, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), though studies have yielded mixed results. It is important to note that IVIG can be associated with several potential adverse effects, such as anaphylaxis, headaches, thrombosis, liver enzyme elevations and renal complications. In addition, the high cost of IVIG can be a deterrent for payers and patients. This review provides a comprehensive update on the use of IVIG in multiple neuroimmune conditions, ME/CFS, acute COVID-19, and PASC, as well as covers its history, production, pricing, and mechanisms of action. We also identify key areas of future research, including the need to optimize the use of Ig product dosing, timing, and patient selection across conditions, particularly in the context of COVID-19 and PASC.}, }
@article {pmid39391697, year = {2024}, author = {Chatatikun, M and Indo, HP and Imai, M and Kawakami, F and Kubo, M and Kitagawa, Y and Ichikawa, H and Udomwech, L and Phongphithakchai, A and Sarakul, O and Sukati, S and Somsak, V and Ichikawa, T and Klangbud, WK and Nissapatorn, V and Tangpong, J and Majima, HJ}, title = {Potential of traditional medicines in alleviating COVID-19 symptoms.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1452616}, pmid = {39391697}, issn = {1663-9812}, abstract = {This review discusses the prevention and treatment of coronavirus disease 2019 (COVID-19) caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Mutations in its spike glycoprotein have driven the emergence of variants with high transmissibility and immune escape capabilities. Some antiviral drugs are ineffective against the BA.2 subvariant at the authorized dose. Recently, 150 natural metabolites have been identified as potential candidates for development of new anti-COVID-19 drugs with higher efficacy and lower toxicity than those of existing therapeutic agents. Botanical drug-derived bioactive molecules have shown promise in dampening the COVID-19 cytokine storm and thus preventing pulmonary fibrosis, as they exert a strong binding affinity for viral proteins and inhibit their activity. The Health Ministry of Thailand has approved Andrographis paniculata (Jap. Senshinren) extracts to treat COVID-19. In China, over 85% of patients infected with SARS-CoV-2 receive treatments based on traditional Chinese medicine. A comprehensive map of the stages and pathogenetic mechanisms related to the disease and effective natural products to treat and prevent COVID-19 are presented. Approximately 10% of patients with COVID-19 are affected by long COVID, and COVID-19 infection impairs mitochondrial DNA. As the number of agents to treat COVID-19 is limited, adjuvant botanical drug treatments including vitamin C and E supplementation may reduce COVID-19 symptoms and inhibit progression to long COVID.}, }
@article {pmid39398386, year = {2024}, author = {Liu, Y and Lou, X}, title = {The Bidirectional Association Between Metabolic Syndrome and Long-COVID-19.}, journal = {Diabetes, metabolic syndrome and obesity : targets and therapy}, volume = {17}, number = {}, pages = {3697-3710}, pmid = {39398386}, issn = {1178-7007}, abstract = {BACKGROUND: The rapid global spread of a new coronavirus disease known as COVID-19 has led to a significant increase in mortality rates, resulting in an unprecedented worldwide pandemic.<br><br>METHODS: The impact of COVID-19, particularly its long-term effects, has also had a profound effect on the health and well-being of individuals.Metabolic syndrome increases the risk of heart and brain diseases, presenting a significant danger to human well-being.<br><br>PURPOSE: The prognosis of long COVID and the progression of metabolic syndrome interact with each other, but there is currently a lack of systematic reports.In this paper, the pathogenesis, related treatment and prognosis of long COVID and metabolic syndrome are systematically reviewed.}, }
@article {pmid39399934, year = {2024}, author = {Mirofsky, M and Catalano, H}, title = {Long COVID: a new disease?.}, journal = {Medicina}, volume = {84}, number = {5}, pages = {937-945}, pmid = {39399934}, issn = {1669-9106}, mesh = {*Post-Acute COVID-19 Syndrome/complications/diagnosis/therapy ; Encephalomyelitis/etiology ; Fibromyalgia/etiology ; Humans ; Terminology as Topic ; Classification ; Chronic Disease ; Post-Infectious Disorders/etiology ; }, abstract = {The definition of quaternary prevention as the set of interventions that avoids or mitigates the consequences of unnecessary or excessive activity of medical interventionism and the health system. The definition of a new disease is a complex process that involves the identification, characterization and description of a medical condition that has not been previously recognized or documented. Since mid-2020, the term chronic COVID/long COVID has been used to describe the presence of signs and symptoms after an acute SARS-CoV-2 infection, with multiple terminologies and definitions in international literature. Post-infectious syndromes, myalgia encephalomyelitis and fibromyalgia, are some of the diseases that have similarities with chronic COVID. This article presents an analysis relating the concepts of new disease and quaternary prevention with chronic COVID and other diseases described in the literature.}, }
@article {pmid39417642, year = {2024}, author = {Feuth, T}, title = {Interactions between sleep, inflammation, immunity and infections: A narrative review.}, journal = {Immunity, inflammation and disease}, volume = {12}, number = {10}, pages = {e70046}, pmid = {39417642}, issn = {2050-4527}, mesh = {Humans ; *Inflammation/immunology ; *Sleep/immunology ; *Infections/immunology ; Immunity, Innate ; Animals ; Sleep Wake Disorders/immunology ; }, abstract = {BACKGROUND: Over the past decades, it has become increasingly evident that sleep disturbance contributes to inflammation-mediated disease, including depression, mainly through activation of the innate immune system and to an increased risk of infections.<br><br>METHODS: A comprehensive literature search was performed in PubMed to identify relevant research findings in the field of immunity, inflammation and infections, with a focus on translational research findings from the past 5 years.<br><br>RESULTS: Physiological sleep is characterized by a dynamic interplay between the immune system and sleep architecture, marked by increased innate immunity and T helper 1 (Th1) -mediated inflammation in the early phase, transitioning to a T helper 2 (Th2) response dominating in late sleep. Chronic sleep disturbances are associated with enhanced inflammation and an elevated risk of infections, while other inflammatory diseases may also be affected. Conversely, inflammation in response to infection can also disrupt sleep patterns and architecture. This narrative review summarizes current data on the complex relationships between sleep, immunity, inflammation and infections, while highlighting translational aspects. The bidirectional nature of these interactions are addressed within specific conditions such as sleep apnea, HIV, and other infections. Furthermore, technical developments with the potential to accelerate our understanding of these interactions are identified, including advances in wearable devices, artificial intelligence, and omics technology. By integrating these tools, novel biomarkers and therapeutic targets for sleep-related immune dysregulation may be identified.<br><br>CONCLUSION: The review underscores the importance of understanding and addressing immune imbalance related to sleep disturbances to improve disease outcomes.}, }
@article {pmid39417730, year = {2025}, author = {Stimart, HL and Hipkins, B}, title = {The negative effects of long COVID-19 on cardiovascular health and implications for the presurgical examination.}, journal = {Journal of osteopathic medicine}, volume = {125}, number = {3}, pages = {105-117}, pmid = {39417730}, issn = {2702-3648}, mesh = {Humans ; *COVID-19/complications/epidemiology ; *Cardiovascular Diseases/diagnosis/epidemiology/etiology ; SARS-CoV-2 ; *Preoperative Care ; }, abstract = {CONTEXT: In 2019, emergence of the novel and communicable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection took scientific communities by surprise and imposed significant burden on healthcare systems globally. Although the advent of this disease piqued the interest of academic centers, healthcare systems, and the general public, there is still much yet to be elucidated regarding epidemiology, pathophysiology, and long-term impacts of coronavirus disease 2019 (COVID-19). It has been established that long COVID-19 can impact multiple organ systems, including the cardiovascular system, unfavorably. Although the pathophysiology of this damage is not well understood, adverse sequelae may range from chest pain and arrhythmias to heart failure (HF), myocardial infarction, or sudden cardiac death. For any postacute COVID-19 patient requiring a surgical procedure, the potential for cardiac injury secondary to long COVID-19 must be considered in the preoperative cardiac examination.<br><br>OBJECTIVES: This literature review serves to add to the growing body of literature exploring postacute cardiovascular outcomes of COVID-19, with a focus on presurgical cardiac clearance in the adult patient. Specifically, this review studies the prevalence of cardiovascular symptomatology including chest pain, arrhythmias, blood pressure changes, myo-/pericarditis, HF, cardiomyopathy, orthostatic intolerance, and thromboembolism. Although current evidence is scarce in both quality and quantity, it is the goal that this review will highlight the negative impacts of long COVID-19 on cardiovascular health and encourage providers to be cognizant of potential sequelae in the context of the presurgical examination.<br><br>METHODS: For this study, peer-reviewed and journal-published articles were selected based on established inclusion and exclusion criteria to address the question "How does long COVID-19 impact the presurgical cardiac examination of an adult scheduled to undergo a noncardiac procedure?" Inclusion criteria included human studies conducted in adult patients and published in peer-reviewed journals up until May 2024 examining the effects of long-COVID-19 infection on the cardiovascular system. Exclusion criteria eliminated unpublished reports, preprints, duplicate articles, literature regarding coronavirus strains other than COVID-19, studies regarding post-COVID-19 vaccination complications, animal studies, and studies conducted in people younger than 18 years of age. A total of 6,675 studies were retrieved from PubMed and Google Scholar. Following screening, 60 studies were included in final consideration.<br><br>RESULTS: Cardiovascular symptoms of postacute COVID-19 infection were encountered with the following percentages prevalence (total numbers of articles mentioning symptom/total number of articles [60]): chest pain (83.3), arrhythmias (88.3), hypertension (40.0), hypotension (16.7), myocarditis (80.0), pericarditis (51.7), HF (70.0), cardiomyopathy (55.0), orthostatic intolerance (56.7), and thromboembolic events (85.0).<br><br>CONCLUSIONS: The presence of persisting COVID symptoms may negatively impact the patient's physical examination, blood tests, electrocardiogram (ECG), imaging, and/or echocardiogram. Cardiac conditions associated with long COVID require special attention in the context of the presurgical candidate due to an increased risk of sudden cardiac death, myocarditis, stroke, and myocardial infarction&#xa0;- even in those who were healthy prior to acute COVID-19 infection. Until more specific scientific evidence comes to light, care of these patients should be viewed through the prism of the best practices already in use and clinicians should maintain a low threshold to pursue more extensive cardiac workup prior to surgery.}, }
@article {pmid39424264, year = {2024}, author = {Almulla, AF and Thipakorn, Y and Zhou, B and Vojdani, A and Paunova, R and Maes, M}, title = {The tryptophan catabolite or kynurenine pathway in long COVID disease: A systematic review and meta-analysis.}, journal = {Neuroscience}, volume = {563}, number = {}, pages = {268-277}, doi = {10.1016/j.neuroscience.2024.10.021}, pmid = {39424264}, issn = {1873-7544}, mesh = {Humans ; *Kynurenine/metabolism/analogs &amp; derivatives ; *Tryptophan/metabolism ; *COVID-19/metabolism ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Recent studies confirm the involvement of activated immune-inflammatory responses and increased oxidative and nitrosative stress in Long COVID (LC) disease. However, the influence of these pathways on the metabolism of tryptophan (TRP) through the TRP catabolite (TRYCAT) pathway and their mediating effects on LC pathophysiology, has not been fully explored.<br><br>OBJECTIVE: This meta-analysis investigates peripheral TRP and TRYCAT levels and the TRYCAT pathway in patients with LC disease.<br><br>METHOD: This review utilized systematic searches of PubMed, Google Scholar, SCOPUS and SciFinder, including 14 full-text articles and 1,167 participants, consisting of 480 patients with LC and 687 normal controls.<br><br>RESULTS: The results indicated a significant increase in the kynurenine (KYN)/TRP ratio, with a large effect size (standardized mean difference, SMD = 0.755; confidence intervals, CI: 0.119;1.392), in LC patients compared to normal controls. Additionally, LC patients exhibited a significant decrease in TRP levels (SMD = -0.520, CI: -0.793; -0.246) and an increase in KYN levels after imputing missing studies (SMD = 1.176, CI: 0.474; 1.877), suggesting activation of the indoleamine 2,3-dioxygenase (IDO) enzyme and upregulation of the TRYCAT pathway. No significant elevation in TRYCAT-related neurotoxicity, kynurenic acid (KA)/KYN and 3-hydroxykynurenine (3-HK)/KYN ratios were observed in LC patients compared to normal controls.<br><br>CONCLUSION: The current findings suggest that an activated TRYCAT pathway, characterized by decreased TRP levels and maybe elevated KYN levels, plays a significant role in the pathophysiology of LC.}, }
@article {pmid39426876, year = {2024}, author = {Gaudry, C and Dhersin, R and Dubée, V}, title = {[Mechanisms of prolonged symptoms following acute COVID-19: Some pathophysiological pathways].}, journal = {Revue des maladies respiratoires}, volume = {41}, number = {9}, pages = {660-668}, doi = {10.1016/j.rmr.2024.07.009}, pmid = {39426876}, issn = {1776-2588}, mesh = {Humans ; Dyspnea/epidemiology/immunology/physiopathology/virology ; Fatigue/epidemiology/immunology/physiopathology/virology ; France/epidemiology ; *Post-Acute COVID-19 Syndrome/epidemiology/immunology/physiopathology/virology ; *SARS-CoV-2/immunology ; }, abstract = {INTRODUCTION: Following the Omicron wave in early 2022, an estimated 60-70% of the French population was infected with the SARS-CoV-2 virus. One out of ten infected subjects could have persistent symptoms three months after infection, representing a public health challenge.<br><br>CURRENT STATE OF KNOWLEDGE: The persistent symptoms may be secondary to diverse entities with distinct mechanisms. While organic infection sequelae occur mainly after severe COVID-19, some symptoms appear to be essentially psychological in origin; in addition, many subjects present stereotyped symptoms of fluctuating intensity with no identified anatomical or psychic substratum, often in the aftermath of a benign infection. The most frequent complaints are fatigue, pain, dyspnea and difficulty concentrating.<br><br>PERSPECTIVES: The hypotheses explored to explain these symptoms include: persistent immune dysfunction, inducted autoimmunity, and microbiome disturbances. Persistent viral antigens may lie at the crossroads of these mechanisms. To date, these different etiological avenues have yet to lead to the development of diagnostic tests or specific therapeutic strategies.<br><br>CONCLUSION: Prolonged symptoms after COVID-19 correspond to heterogeneous nosological entities with poorly understood mechanisms.}, }
@article {pmid39428555, year = {2024}, author = {Park, ES and Shin, CY and Jeon, SJ and Ham, BJ}, title = {Is There such a Thing as Post-Viral Depression?: Implications for Precision Medicine.}, journal = {Biomolecules &amp; therapeutics}, volume = {32}, number = {6}, pages = {659-684}, pmid = {39428555}, issn = {1976-9148}, abstract = {Viral infections are increasingly recognized as triggers for depressive disorders, particularly following the SARS-CoV-2 pandemic and the rise of long COVID. Viruses such as Herpes Simplex Virus (HSV), Epstein-Barr Virus (EBV), Cytomegalovirus (CMV), and Human Immunodeficiency Virus (HIV) are linked to depression through complex neurobiological mechanisms. These include immune system dysregulation, chronic inflammation, and neurotransmitter imbalances that affect brain function and mood regulation. Viral activation of the immune system leads to the release of pro-inflammatory cytokines, resulting in neuroinflammation and associated depressive symptoms. Furthermore, specific viruses can disrupt neurotransmitter systems, including serotonin, dopamine, and glutamate, all of which are essential for mood stabilization. The unique interactions of different viruses with these systems underscore the need for virus-specific therapeutic approaches. Current broad-spectrum treatments often overlook the precise neurobiological pathways involved in post-viral depression, reducing their efficacy. This review emphasizes the need to understand these virus-specific interactions to create tailored interventions that directly address the neurobiological effects induced by each type of virus. These interventions may include immunomodulatory treatments that target persistent inflammation, antiviral therapies to reduce the viral load, or neuroprotective strategies that restore neurotransmitter balance. Precision medicine offers promising avenues for the effective management of virus-induced depression, providing patient-specific approaches that address the specific biological mechanisms involved. By focusing on the development of these targeted treatments, this review aims to pave the way for a new era in psychiatric care that fully addresses the root causes of depression induced by viral infections.}, }
@article {pmid39429741, year = {2024}, author = {Zhang, S and Wu, Y and Mprah, R and Wang, M}, title = {COVID-19 and persistent symptoms: implications for polycystic ovary syndrome and its management.}, journal = {Frontiers in endocrinology}, volume = {15}, number = {}, pages = {1434331}, pmid = {39429741}, issn = {1664-2392}, mesh = {Humans ; *Polycystic Ovary Syndrome/therapy/complications ; *COVID-19/complications/therapy/epidemiology ; Female ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The COVID-19 pandemic has left a profound mark on global health, leading to substantial morbidity and mortality worldwide. Beyond the immediate symptoms of infection, the emergence of "long COVID", the long-term effects of SARS-CoV-2, has become a significant public health concern. Long COVID is a multifaceted condition affecting various organs and systems, including the cardiovascular, digestive, nervous, and endocrine systems. Individuals diagnosed with polycystic ovary syndrome (PCOS) may face an increased risk of severe COVID-19 symptoms and infection. It is crucial to comprehend how long COVID affects PCOS patients to devise effective treatment and care strategies. Here, we review the detrimental effects of COVID-19 and its long-term effects on reproductive health, endocrine function, inflammation, metabolism, cardiovascular health, body composition, lifestyle, and mental health in patients with PCOS. We offer recommendations for the post-covid-19 management of PCOS, emphasizing the necessity of a comprehensive, multidisciplinary approach to patient care. Furthermore, we discuss prospective research directions, highlighting the significance of continued investigations and clinical trials to evaluate treatment approaches for long COVID and its ramifications in individuals with PCOS.}, }
@article {pmid39429966, year = {2024}, author = {Prosperini, L and Arrambide, G and Celius, EG and Goletti, D and Killestein, J and Kos, D and Lavorgna, L and Louapre, C and Sormani, MP and Stastna, D and Ziemssen, T and Di Filippo, M}, title = {COVID-19 and multiple sclerosis: challenges and lessons for patient care.}, journal = {The Lancet regional health. Europe}, volume = {44}, number = {}, pages = {100979}, pmid = {39429966}, issn = {2666-7762}, abstract = {During the COVID-19 pandemic, people with multiple sclerosis (MS) and their healthcare providers have faced unique challenges related to the interaction between SARS-CoV-2, underlying neurological disease and the use of disease-modifying treatments (DMTs). Key concerns arose, primarily related to the possibility that SARS-CoV-2 infection could trigger the initial demyelinating event or exacerbate disease activity. Another major concern was the safety and efficacy of the COVID-19 vaccines, especially for patients undergoing specific treatments that could weaken their antibody responses. In the post-infection phase, identifying long COVID in patients with MS has been complicated due to the large overlap between post-infection sequelae and MS symptoms. In addition, disruptions in health and rehabilitation services have made it difficult for MS patients to access care. This Series article explores current evidence on the interaction between MS and SARS-CoV-2, identifies the challenges posed by the COVID-19 pandemic in the care of patients with MS, and discusses the significant adoption of digital health solutions, including telemedicine and new technology-based rehabilitation approaches. Based on lessons learned, recommendations and future directions are offered for managing patients with MS, rethinking healthcare systems and improving health outcomes in the post-COVID-19 pandemic era.}, }
@article {pmid39435694, year = {2024}, author = {Shekhar Patil, M and Richter, E and Fanning, L and Hendrix, J and Wyns, A and Barrero Santiago, L and Nijs, J and Godderis, L and Polli, A}, title = {Epigenetic changes in patients with post-acute COVID-19 symptoms (PACS) and long-COVID: A systematic review.}, journal = {Expert reviews in molecular medicine}, volume = {26}, number = {}, pages = {e29}, pmid = {39435694}, issn = {1462-3994}, mesh = {Humans ; *DNA Methylation ; *Epigenesis, Genetic ; MicroRNAs/genetics ; *Post-Acute COVID-19 Syndrome/genetics ; SARS-CoV-2/pathogenicity ; }, abstract = {BACKGROUND: Up to 30% of people infected with SARS-CoV-2 report disabling symptoms 2 years after the infection. Over 100 persistent symptoms have been associated with Post-Acute COVID-19 Symptoms (PACS) and/or long-COVID, showing a significant clinical heterogeneity. To develop effective, patient-targeted treatment, a better understanding of underlying mechanisms is needed. Epigenetics has helped elucidating the pathophysiology of several health conditions and it might help unravelling inter-individual differences in patients with PACS and long-COVID. As accumulating research is exploring epigenetic mechanisms in PACS and long-COVID, we systematically summarized the available literature on the topic.<br><br>METHODS: We interrogated five databases (Medline, Embase, Web of Science, Scopus and medXriv/bioXriv) and followed PRISMA and SWiM guidelines to report our results.<br><br>RESULTS: Eight studies were included in our review. Six studies explored DNA methylation in PACS and/or long-COVID, while two studies explored miRNA expression in long-COVID associated with lung complications. Sample sizes were mostly small and study quality was low or fair. The main limitation of the included studies was a poor characterization of the patient population that made a homogeneous synthesis of the literature challenging. However, studies on DNA methylation showed that mechanisms related to the immune and the autonomic nervous system, and cell metabolism might be implicated in the pathophysiology of PACS and long-COVID.<br><br>CONCLUSION: Epigenetic changes might help elucidating PACS and long-COVID underlying mechanisms, aid subgrouping, and point towards tailored treatments. Preliminary evidence is promising but scarce. Biological and epigenetic research on long-COVID will benefit millions of people suffering from long-COVID and has the potential to be transferable and benefit other conditions as well, such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). We urge future research to employ longitudinal designs and provide a better characterization of included patients.}, }
@article {pmid39438198, year = {2025}, author = {Warrayat, A and Ali, A and Waked, J and Tocci, D and Speth, RC}, title = {Assessment of the therapeutic potential of salubrinal for ME/CFS and long-COVID.}, journal = {Trends in molecular medicine}, volume = {31}, number = {5}, pages = {466-478}, doi = {10.1016/j.molmed.2024.10.001}, pmid = {39438198}, issn = {1471-499X}, mesh = {Humans ; *Thiourea/analogs &amp; derivatives/therapeutic use/pharmacology ; *Fatigue Syndrome, Chronic/drug therapy ; *Cinnamates/therapeutic use/pharmacology ; *COVID-19/complications ; Endoplasmic Reticulum Stress/drug effects ; SARS-CoV-2 ; Quality of Life ; Animals ; }, abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic debilitating condition with no cure that shares commonality with long-COVID. This review examines current understanding of long-COVID symptoms, characteristics of the affected population, the connection with ME/CFS, and the potential for salubrinal, an agent known for its influence on cellular stress pathways, to mitigate these disorders It also describes the historical development and mechanism of action of salubrinal, to mitigate endoplasmic reticulum (ER)/cellular stress responses, that could potentially contribute to symptom improvement in both ME/CFS and long-COVID patients. Further research and clinical trials are warranted to advance our understanding of the potential role of salubrinal in improving the quality of life for individuals with long-COVID-related ME/CFS symptoms as well as ME/CFS patients.}, }
@article {pmid39444602, year = {2024}, author = {He, X and Zhang, X and Zhong, W}, title = {Emerging small-molecule antiviral agents in long COVID prevention.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1457672}, pmid = {39444602}, issn = {1663-9812}, abstract = {Long COVID, or Post-Acute Sequelae of COVID-19 (PASC), was characterized by persistent symptoms such as fatigue, shortness of breath, and cognitive impairments. These symptoms, emerging one to 2 months post-infection and persisting for several months, cannot be attributed to other diagnoses. The pathophysiology of long COVID remained elusive; however, emerging studies suggested multiple potential mechanisms, including the reactivation of Epstein-Barr virus, persistent SARS-CoV-2 reservoirs, neuroinflammation, and vascular damage, which may contribute to its development. Long COVID affected multiple organ systems, including respiratory, circulatory, and nervous systems, leading to a range of functional impairments. Additionally, it showed a profound impact on mental health, manifesting as anxiety and depression, which significantly degraded the quality of life. The absence of definitive treatments underscored the importance of prevention. Recent evidence indicated that early antiviral intervention-particularly with small-molecule drugs such as Metformin, Ensitrelvir, Molnupiravir, and Nirmatrelvir-may effectively reduce the incidence of long COVID. This underscored the promising role of small-molecule compounds in mitigating long-term COVID-19 consequences, offering a novel preventive strategy against long COVID and its extensive impacts on patients.}, }
@article {pmid39444752, year = {2024}, author = {Wang, W and Li, R and Li, C and Liang, Q and Gao, X}, title = {Advances in VNS efficiency and mechanisms of action on cognitive functions.}, journal = {Frontiers in physiology}, volume = {15}, number = {}, pages = {1452490}, pmid = {39444752}, issn = {1664-042X}, abstract = {OBJECTIVE: This systematic review aims to comprehensively analyze the efficacy and underlying mechanisms of vagus nerve stimulation (VNS) in enhancing cognitive functions and its therapeutic potential for various cognitive impairments. The review focuses on the impact of VNS on emotional processing, executive functions, learning, memory, and its clinical applications in conditions such as epilepsy, depression, Alzheimer's disease, and other neurological disorders.<br><br>METHODS: A systematic search of electronic databases (PubMed, Scopus, Web of Science) was conducted using the keywords "vagus nerve stimulation," "cognitive enhancement," "emotional processing," "executive function," "learning and memory," "epilepsy," "depression," "Alzheimer's disease," "neurological disorders," "attention-deficit/hyperactivity disorder," "sleep disorders," and "long COVID." The inclusion criteria encompassed controlled trials, longitudinal studies, and meta-analyses published in English between 2000 and July 2024.<br><br>RESULTS: A comprehensive review of 100 articles highlighted the cognitive effects of Vagus Nerve Stimulation (VNS). Studies show that VNS, especially through transcutaneous auricular VNS (taVNS), enhances emotional recognition, particularly for facial expressions, and improves selective attention under high cognitive demands. Additionally, VNS enhances learning and memory, including associative memory and spatial working memory tasks. In clinical applications, VNS exhibits promising benefits for improving cognitive functions in treatment-resistant epilepsy, depression, and Alzheimer's disease.<br><br>CONCLUSION: VNS represents a promising therapeutic approach for enhancing cognitive function across diverse patient populations. The reviewed evidence highlights its efficacy in modulating cognitive domains in healthy individuals and improving cognition in neurological conditions. However, the comparative effectiveness of different VNS modalities and the differential effects of online versus offline VNS on cognitive psychology require further investigation. Future research should focus on optimizing VNS protocols and elucidating specific cognitive domains that benefit most from VNS interventions. This ongoing exploration is essential for maximizing the therapeutic potential of VNS in clinical practice.}, }
@article {pmid39444797, year = {2024}, author = {Guo, M and Shang, S and Li, M and Cai, G and Li, P and Chen, X and Li, Q}, title = {Understanding autoimmune response after SARS-CoV-2 infection and the pathogenesis/mechanisms of long COVID.}, journal = {Medical review (2021)}, volume = {4}, number = {5}, pages = {367-383}, pmid = {39444797}, issn = {2749-9642}, abstract = {COVID-19 posed a major challenge to the healthcare system and resources worldwide. The popularization of vaccines and the adoption of numerous prevention and control measures enabled the gradual end of the COVID-19 pandemic. However, successive occurrence of autoimmune diseases in patients with COVID-19 cannot be overlooked. Long COVID has been the major focus of research due to the long duration of different symptoms and the variety of systems involved. Autoimmunity may play a crucial role in the pathogenesis of long COVID. Here, we reviewed several autoimmune disorders occurring after COVID-19 infection and the pathogenesis of long COVID.}, }
@article {pmid39445819, year = {2024}, author = {Eberhardt, J and Gibson, B and Portman, RM and Carthy, N and Rowlands, S and Batchelor, R and Kane, L and Kılınç, S}, title = {Psychosocial Aspects of the Lived Experience of Long COVID: A Systematic Review and Thematic Synthesis of Qualitative Studies.}, journal = {Health expectations : an international journal of public participation in health care and health policy}, volume = {27}, number = {5}, pages = {e70071}, pmid = {39445819}, issn = {1369-7625}, support = {//The authors received no specific funding for this work./ ; }, mesh = {Humans ; Adaptation, Psychological ; *Post-Acute COVID-19 Syndrome/psychology/rehabilitation ; Qualitative Research ; SARS-CoV-2 ; *Social Support ; Uncertainty ; }, abstract = {BACKGROUND: Despite increasing recognition of long COVID, the psychosocial impacts of the lived experience on individuals remain underexplored. This systematic review sought to fill this gap by identifying key themes that describe the psychosocial dimensions of long COVID.<br><br>OBJECTIVE: The aim of this study is to identify key themes illustrating the psychosocial aspects of individuals' lived experience of long COVID.<br><br>SEARCH STRATEGY: Searches were conducted in multiple databases and grey literature sources for qualitative studies published between November 2019 and June 2024.<br><br>INCLUSION CRITERIA: Eligible studies involved adult participants self-reporting long COVID. The studies needed to provide qualitative data that could be synthesised thematically.<br><br>DATA EXTRACTION AND SYNTHESIS: Data extraction and thematic synthesis were conducted by at least two independent reviewers at each stage. Quality appraisal was performed using the Critical Appraisal Skills Programme tool.<br><br>RESULTS: The review included 34 studies. Thematic synthesis yielded five themes: 'Debilitation', 'Uncertainty', 'Sources of Support', 'Meaning Making: Adjusting to a New Normal' and 'Experiences with Healthcare Services'. Individuals with long COVID reported experiencing physical, economic, and social challenges. Uncertainty and scepticism from others caused anxiety. Support from healthcare services, friends and online groups played an important role. Acceptance and gratitude were found to be meaningful in adjusting to the new normal. Experiences with healthcare services varied.<br><br>DISCUSSION AND CONCLUSIONS: This review provides valuable insights into the psychosocial impact of long COVID, highlighting the profound changes and challenges that individuals face. Healthcare services should adopt a holistic approach to integrate psychosocial support within their management strategies, to improve overall patient outcomes.}, }
@article {pmid39446164, year = {2024}, author = {Ramzi, A and Maya, S and Balousha, N and Amin, M and Shiha, MR}, title = {Pentoxifylline in COVID-19 and considerations for its research in long COVID.}, journal = {Inflammation research : official journal of the European Histamine Research Society ... [et al.]}, volume = {73}, number = {12}, pages = {2057-2068}, pmid = {39446164}, issn = {1420-908X}, mesh = {*Pentoxifylline/therapeutic use ; Humans ; *COVID-19 Drug Treatment ; *COVID-19 ; SARS-CoV-2/drug effects ; Length of Stay ; }, abstract = {INTRODUCTION: Pentoxifylline (PTX) affects most blood components and the blood vessels, potentially modulating various conditions. Due to its impact on markers linked to COVID-19 severity, research has explored PTX for acute COVID-19. Following the widespread administration of COVID-19 vaccinations, there has been a notable and consistently growing increase in research focusing on long COVID. Consequently, our examination of relevant acute COVID-19 data shall additionally be contextualized into long COVID research.<br><br>METHODS: Various Databases were searched until July 2024 for all primary clinical studies on Pentoxifylline (PTX) in COVID-19.<br><br>RESULTS: Studies were on acute infection with SARS-CoV-2 where PTX was an adjuvant to standard therapy for ethical and practical reasons under the circumstance. PTX generally reduced hospitalization duration and improved some inflammatory markers, but its impact on mortality was inconsistent. Adverse events were minimal. Meta-analysis revealed a significant reduction in hospitalization duration.<br><br>CONCLUSION: This systematic review and meta-analysis suggest that adding pentoxifylline (PTX) to standard COVID-19 therapy may significantly reduce hospitalization duration and improve some inflammatory markers. However, its impact on mortality rates is inconclusive. Adverse events are minimal. PTX can be favorable as an add-on in managing acute COVID-19 and could reduce the risk of long COVID, as well as assist in managing many of its most common symptoms.}, }
@article {pmid39449339, year = {2025}, author = {Qian, CY and Hu, SN and Liu, HD and Liu, JJ}, title = {Potential Mechanisms of COVID-19 Related Nervous System Damage and Effects on Female Fertility.}, journal = {Current medicinal chemistry}, volume = {32}, number = {42}, pages = {9555-9569}, pmid = {39449339}, issn = {1875-533X}, support = {JCYJ20190806153207263//Natural Science Foundation of Shenzhen Science and Technology Innovation Commission/ ; 82200315//National Natural Science Foundation/ ; 2021A1515111145//Guangdong Basic and Applied Basic Research Foundation/ ; SZSM201412012//Sanming Project of Medicine in Shenzhen/ ; SYWGSJCYJ202301//Major scientific research project of Shenzhen People's Hospital/ ; }, mesh = {Humans ; *COVID-19/complications/physiopathology/pathology ; Female ; SARS-CoV-2 ; *Infertility, Female/etiology ; *Nervous System Diseases ; *Fertility ; Autonomic Nervous System/physiopathology ; }, abstract = {Signs and symptoms that persist or worsen beyond the "acute COVID-19" stage are referred to as long-COVID. These patients are more likely to suffer from multiple organ failure, readmission, and mortality. According to a recent theory, long-lasting COVID-19 symptoms may be caused by abnormal autonomic nervous system (ANS) activity, such as hypovolemia, brain stem involvement, and autoimmune reactions. Furthermore, COVID-19 can also cause impaired fertility in women, which may also be related to inflammation and immune responses. Currently, few treatments are available for long-COVID symptoms. This article reviews the major effects of COVID-19 on the nervous system and female fertility, as well as offers potential treatment approaches.}, }
@article {pmid39451987, year = {2024}, author = {Costanza, A and Amerio, A and Aguglia, A and Rossi, M and Parise, A and Magnani, L and Serafini, G and Amore, M and Martins, D and Nguyen, KD}, title = {Reactive Astrocytosis-A Potential Contributor to Increased Suicide in Long COVID-19 Patients?.}, journal = {Brain sciences}, volume = {14}, number = {10}, pages = {}, pmid = {39451987}, issn = {2076-3425}, abstract = {BACKGROUND: Long COVID-19 is an emerging chronic illness of significant public health concern due to a myriad of neuropsychiatric sequelae, including increased suicidal ideation (SI) and behavior (SB).<br><br>METHODS: This review provides a concise synthesis of clinical evidence that points toward the dysfunction of astrocytes, the most abundant glial cell type in the central nervous system, as a potential shared pathology between SI/SB and COVID-19.<br><br>RESULTS: Depression, a suicide risk factor, and SI/SB were both associated with reduced frequencies of various astrocyte subsets and complex proteomic/transcriptional changes of astrocyte-related markers in a brain-region-specific manner. Astrocyte-related circulating markers were increased in depressed subjects and, to a less consistent extent, in COVID-19 patients. Furthermore, reactive astrocytosis was observed in subjects with SI/SB and those with COVID-19.<br><br>CONCLUSIONS: Astrocyte dysfunctions occurred in depression, SI/SB, and COVID-19. Reactive-astrocyte-mediated loss of the blood-brain barrier (BBB) integrity and subsequent neuroinflammation-a factor previously linked to SI/SB development-might contribute to increased suicide in individuals with long COVID-19. As such, the formulation of new therapeutic strategies to restore astrocyte homeostasis, enhance BBB integrity, and mitigate neuroinflammation may reduce SI/SB-associated neuropsychiatric manifestations among long COVID-19 patients.}, }
@article {pmid39454992, year = {2024}, author = {Yu, LC}, title = {Gastrointestinal pathophysiology in long COVID: Exploring roles of microbiota dysbiosis and serotonin dysregulation in post-infectious bowel symptoms.}, journal = {Life sciences}, volume = {358}, number = {}, pages = {123153}, doi = {10.1016/j.lfs.2024.123153}, pmid = {39454992}, issn = {1879-0631}, mesh = {Animals ; Humans ; *Dysbiosis/metabolism/microbiology/physiopathology/virology ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/microbiology/physiopathology/virology ; *Irritable Bowel Syndrome/physiopathology/microbiology/metabolism/virology ; *Post-Acute COVID-19 Syndrome/metabolism/microbiology/physiopathology/virology ; SARS-CoV-2 ; *Serotonin/metabolism ; }, abstract = {The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered an unprecedented public health crisis known as the coronavirus disease 2019 (COVID-19) pandemic. Gastrointestinal (GI) symptoms develop in patients during acute infection and persist after recovery from airway distress in a chronic form of the disease (long COVID). A high incidence of irritable bowel syndrome (IBS) manifested by severe abdominal pain and defecation pattern changes is reported in COVID patients. Although COVID is primarily considered a respiratory disease, fecal shedding of SARS-CoV-2 antigens positively correlates with bowel symptoms. Active viral infection in the GI tract was identified by human intestinal organoid studies showing SARS-CoV-2 replication in gut epithelial cells. In this review, we highlight the key findings in post-COVID bowel symptoms and explore possible mechanisms underlying the pathophysiology of the illness. These mechanisms include mucosal inflammation, gut barrier dysfunction, and microbiota dysbiosis during viral infection. Viral shedding through the GI route may be the primary factor causing the alteration of the microbiome ecosystem, particularly the virome. Recent evidence in experimental models suggested that microbiome dysbiosis could be further aggravated by epithelial barrier damage and immune activation. Moreover, altered microbiota composition has been associated with dysregulated serotonin pathways, resulting in intestinal nerve hypersensitivity. These mechanisms may explain the development of post-infectious IBS-like symptoms in long COVID. Understanding how coronavirus infection affects gut pathophysiology, including microbiome changes, would benefit the therapeutic advancement for managing post-infectious bowel symptoms.}, }
@article {pmid39456253, year = {2024}, author = {Gopalaswamy, R and Aravindhan, V and Subbian, S}, title = {The Ambivalence of Post COVID-19 Vaccination Responses in Humans.}, journal = {Biomolecules}, volume = {14}, number = {10}, pages = {}, pmid = {39456253}, issn = {2218-273X}, mesh = {Humans ; 2019-nCoV Vaccine mRNA-1273/immunology ; BNT162 Vaccine/immunology ; *COVID-19/prevention &amp; control ; *COVID-19 Vaccines/adverse effects/immunology ; Vaccination ; }, abstract = {The Coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has prompted a massive global vaccination campaign, leading to the rapid development and deployment of several vaccines. Various COVID-19 vaccines are under different phases of clinical trials and include the whole virus or its parts like DNA, mRNA, or protein subunits administered directly or through vectors. Beginning in 2020, a few mRNA (Pfizer-BioNTech BNT162b2 and Moderna mRNA-1273) and adenovirus-based (AstraZeneca ChAdOx1-S and the Janssen Ad26.COV2.S) vaccines were recommended by WHO for emergency use before the completion of the phase 3 and 4 trials. These vaccines were mostly administered in two or three doses at a defined frequency between the two doses. While these vaccines, mainly based on viral nucleic acids or protein conferred protection against the progression of SARS-CoV-2 infection into severe COVID-19, and prevented death due to the disease, their use has also been accompanied by a plethora of side effects. Common side effects include localized reactions such as pain at the injection site, as well as systemic reactions like fever, fatigue, and headache. These symptoms are generally mild to moderate and resolve within a few days. However, rare but more serious side effects have been reported, including allergic reactions such as anaphylaxis and, in some cases, myocarditis or pericarditis, particularly in younger males. Ongoing surveillance and research efforts continue to refine the understanding of these adverse effects, providing critical insights into the risk-benefit profile of COVID-19 vaccines. Nonetheless, the overall safety profile supports the continued use of these vaccines in combating the pandemic, with regulatory agencies and health organizations emphasizing the importance of vaccination in preventing COVID-19's severe outcomes. In this review, we describe different types of COVID-19 vaccines and summarize various adverse effects due to autoimmune and inflammatory response(s) manifesting predominantly as cardiac, hematological, neurological, and psychological dysfunctions. The incidence, clinical presentation, risk factors, diagnosis, and management of different adverse effects and possible mechanisms contributing to these effects are discussed. The review highlights the potential ambivalence of human response post-COVID-19 vaccination and necessitates the need to mitigate the adverse side effects.}, }
@article {pmid39456822, year = {2024}, author = {Papadopoulou, P and Polissidis, A and Kythreoti, G and Sagnou, M and Stefanatou, A and Theoharides, TC}, title = {Anti-Inflammatory and Neuroprotective Polyphenols Derived from the European Olive Tree, Olea europaea L., in Long COVID and Other Conditions Involving Cognitive Impairment.}, journal = {International journal of molecular sciences}, volume = {25}, number = {20}, pages = {}, pmid = {39456822}, issn = {1422-0067}, mesh = {*Olea/chemistry ; *Polyphenols/pharmacology/therapeutic use/chemistry ; Humans ; *Neuroprotective Agents/therapeutic use/pharmacology ; *Cognitive Dysfunction/drug therapy ; *Anti-Inflammatory Agents/pharmacology/therapeutic use/chemistry ; *COVID-19 ; COVID-19 Drug Treatment ; SARS-CoV-2/drug effects ; Animals ; Plant Extracts/pharmacology/therapeutic use/chemistry ; Alzheimer Disease/drug therapy ; }, abstract = {The European olive tree, Olea europaea L., and its polyphenols hold great therapeutic potential to treat neuroinflammation and cognitive impairment. This review examines the evidence for the anti-inflammatory and neuroprotective actions of olive polyphenols and their potential in the treatment of long COVID and neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). Key findings suggest that olive polyphenols exhibit antioxidant, anti-inflammatory, neuroprotective, and antiviral properties, making them promising candidates for therapeutic intervention, especially when formulated in unique combinations. Recommendations for future research directions include elucidating molecular pathways through mechanistic studies, exploring the therapeutic implications of olive polyphenol supplementation, and conducting clinical trials to assess efficacy and safety. Investigating potential synergistic effects with other agents addressing different targets is suggested for further exploration. The evidence reviewed strengthens the translational value of olive polyphenols in conditions involving cognitive dysfunction and emphasizes the novelty of new formulations.}, }
@article {pmid39457356, year = {2024}, author = {Graham, EL and D'Isabel, S and Lofrano-Porto, A and Smith, DL}, title = {Musculoskeletal, Pulmonary, and Cardiovascular COVID-19 Sequelae in the Context of Firefighter Occupational Health: A Narrative Review.}, journal = {International journal of environmental research and public health}, volume = {21}, number = {10}, pages = {}, pmid = {39457356}, issn = {1660-4601}, support = {EMW-2020-FP-00243//Federal Emergency Management Agency/ ; }, mesh = {Humans ; *COVID-19/complications ; *Firefighters ; Occupational Health ; SARS-CoV-2 ; Cardiovascular Diseases/etiology ; Musculoskeletal Diseases/etiology/virology ; Lung Diseases/etiology/physiopathology/virology ; }, abstract = {For most individuals infected with SARS-CoV-2, the acute illness resolves completely. However, for millions of people, symptoms or sequelae from COVID-19 recur or persist for months to years after infection. Post-COVID-19 sequelae are wide-ranging, often affecting the musculoskeletal, pulmonary, and cardiovascular systems. All who experience post-COVID-19 sequelae face significant challenges navigating home and work life. Occupations such as firefighting, however, are of particular concern given the strenuous nature of a job that relies on a healthy musculoskeletal, pulmonary, and cardiovascular system. Research has documented significant musculoskeletal impairment (including muscle weakness, pain, and fatigue), respiratory dysfunction (including reduced lung function, interstitial disease, and diffusion abnormalities), cardiovascular conditions (including cardiac events, ischemic disease, dysrhythmias, and infectious diseases), and diminished cardiorespiratory fitness that continues for months to years in some individuals. These persistent post-COVID-19 conditions may affect a firefighter's ability to return to work, function at full capacity while at work, and potentially compromise firefighter health and public safety. This review, therefore, explores musculoskeletal, pulmonary, and cardiovascular sequelae post-COVID-19 and the impact of these sequelae on firefighter health and occupational readiness.}, }
@article {pmid39459851, year = {2024}, author = {Mohammed, I and Podhala, S and Zamir, F and Shiyam, S and Salameh, AR and Salahuddin, Z and Salameh, H and Kim, C and Sinan, Z and Kim, J and Al-Abdulla, D and Laws, S and Mushannen, M and Zakaria, D}, title = {Gastrointestinal Sequelae of COVID-19: Investigating Post-Infection Complications-A Systematic Review.}, journal = {Viruses}, volume = {16}, number = {10}, pages = {}, pmid = {39459851}, issn = {1999-4915}, mesh = {Humans ; *COVID-19/complications ; *Gastrointestinal Diseases/etiology/virology ; *SARS-CoV-2 ; Systemic Inflammatory Response Syndrome ; Pancreatitis/complications/etiology ; Gastrointestinal Tract/virology/pathology ; Colitis, Ulcerative/complications ; }, abstract = {Gastrointestinal (GI) complications are significant manifestations of COVID-19 and are increasingly being recognized. These complications range from severe acute pancreatitis to colitis, adding complexity to diagnosis and management. A comprehensive database search was conducted using several databases. Our inclusion criteria encompassed studies reporting severe and long-term GI complications of COVID-19. Digestive disorders were categorized into infections, inflammatory conditions, vascular disorders, structural abnormalities, other diagnoses, and undiagnosed conditions. Of the 73 studies that were selected for full-text review, only 24 met our inclusion criteria. The study highlights a broad range of gastrointestinal complications following COVID-19 infection (excluding liver complications, which are examined separately), including inflammatory conditions, such as ulcerative colitis (UC), acute pancreatitis, and multisystem inflammatory syndrome in children (MIS-C). Other GI complications were reported such as vascular disorders, including diverse thrombotic events and structural abnormalities, which ranged from bowel perforations to adhesions. Additionally, undiagnosed conditions like nausea and abdominal pain were prevalent across different studies involving 561 patients. The findings emphasize the substantial impact of COVID-19 on the GI tract. Ongoing research and monitoring are crucial to understanding the long-term effects and developing effective management strategies for these complications.}, }
@article {pmid39464351, year = {2024}, author = {Sharma, A and Jakhar, RK and Kakkar, V and Singal, G}, title = {Persistent ENT Manifestations in Individuals who Recovered from COVID-19: A Systematic Review.}, journal = {International archives of otorhinolaryngology}, volume = {28}, number = {4}, pages = {e697-e701}, pmid = {39464351}, issn = {1809-9777}, abstract = {Introduction Long coronavirus disease (COVID) refers to the persistence of symptoms long after the recovery from the acute phase of the illness, and it is due to the interplay of various inflammatory mechanisms. This has led to emergence of new deficits, including otorhinolaryngological symptoms, in patients wo have recovered from COVID. The plethora of otorhinolaryngological symptoms associated with long COVID are tinnitus, sensorineural hearing loss (SNHL), vertigo, nasal congestion, sinonasal discomfort, hyposmia/anosmia, dysgeusia, sore throat, dry cough, dyspnea, dysphagia, and hoarseness of voice. Objective To evaluate the possible ENT symptoms in patients wo have recovered from COVID and to combine those findings with our experience. Data Synthesis We conducted a search on the PubMed, ENT Cochrane, Web of Science, and Google Scholar databases, and a total of 44 studies were selected for the present review. Conclusion Otorhinolaryngological complications such as tinnitus, SNHL, vertigo, nasal congestion, sinonasal discomfort, hyposmia/anosmia, dysgeusia, sore throat, dry cough, dyspnea, dysphagia, and hoarseness of voice have been widely reported among in long-COVID patients.}, }
@article {pmid39468707, year = {2024}, author = {Zhou, D and Luo, Y and Ma, Q and Xu, Y and Yao, X}, title = {The characteristics of TCR CDR3 repertoire in COVID-19 patients and SARS-CoV-2 vaccine recipients.}, journal = {Virulence}, volume = {15}, number = {1}, pages = {2421987}, pmid = {39468707}, issn = {2150-5608}, mesh = {Humans ; *COVID-19/immunology/prevention &amp; control ; *Complementarity Determining Regions/genetics/immunology ; *COVID-19 Vaccines/immunology/administration &amp; dosage ; *SARS-CoV-2/immunology/genetics ; *Receptors, Antigen, T-Cell/immunology/genetics ; T-Lymphocytes/immunology ; High-Throughput Nucleotide Sequencing ; }, abstract = {The COVID-19 pandemic and large-scale administration of multiple SARS-CoV-2 vaccines have attracted global attention to the short-term and long-term effects on the human immune system. An analysis of the "traces" left by the body's T-cell immune response is needed, especially for the prevention and treatment of breakthrough infections and long COVID-19 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant infections. T-cell receptor complementarity determining region 3 (TCR CDR3) repertoire serves as a target molecule for monitoring the effects, mechanisms, and memory of the T-cell response. Furthermore, it has been extensively applied in the elucidation of the infectious mechanism and vaccine refinement of hepatitis B virus (HBV), influenza virus, human immunodeficiency virus (HIV), and SARS-CoV. Laboratories worldwide have utilized high-throughput sequencing (HTS) and scTCR-seq to characterize, share, and apply the TCR CDR3 repertoire in COVID-19 patients and SARS-CoV-2 vaccine recipients. This article focuses on the comparative analysis of the diversity, clonality, V&amp;J gene usage and pairing, CDR3 length, shared CDR3 sequences or motifs, and other characteristics of TCR CDR3 repertoire. These findings provide molecular targets for evaluating T-cell response effects and short-term and long-term impacts on the adaptive immune system following SARS-CoV-2 infection or vaccination and establish a comparative archive of T-cell response "traces."}, }
@article {pmid39474404, year = {2024}, author = {Bistagnino, F and Pizzi, D and Mantovani, F and Antonino, JR and Tovani-Palone, MR}, title = {Long COVID and gut candidiasis: What is the existing relationship?.}, journal = {World journal of gastroenterology}, volume = {30}, number = {37}, pages = {4104-4114}, pmid = {39474404}, issn = {2219-2840}, mesh = {Humans ; *COVID-19/complications/epidemiology ; *Candidiasis/epidemiology ; *SARS-CoV-2/pathogenicity ; Post-Acute COVID-19 Syndrome ; Gastrointestinal Diseases/virology/epidemiology/microbiology/physiopathology ; }, abstract = {Since the beginning of the coronavirus disease (COVID) 2019 pandemic, thousands of articles on the topic have been published, and although there is a growing trend of research on another associated condition, long coronavirus disease, important points still remain to be clarified in this respect. Robust evidence has suggested a relevant link between new clinical discoveries and molecular mechanisms that could be associated with the manifestations of different signs and symptoms involving cases of long COVID. However, one of the existing gaps that requires further investigation concerns a possible relationship between gut candidiasis and long COVID. While recent studies also suggest an interplay between the occurrence of these two conditions, it is not yet fully clear how this may happen, as well as the specifics regarding the possible pathophysiological mechanisms involved. In this connection and with the advent of a potential strengthening of the body of evidence supporting the hypothesis of a link between gut candidiasis and long COVID, a better understanding of the clinical presentation, pathophysiology and clinical management of such a relationship should be essential and useful for both, additional advances towards more targeted research and appropriate case management. Knowing more about the signs, symptoms, and complications associated with cases of long COVID is essential in order to more effectively mitigate the related burden and provide a higher quality of care and life for the affected population. In light of this and the need for better outcomes, here we review and discuss the content on different aspects of long COVID, including its pathophysiology and the existing evidence of a potential relationship between such a condition and gut candidiasis, as well as suggest propositions for future related research.}, }
@article {pmid39475394, year = {2024}, author = {Curvelo, RD and Ribeiro, AC and da Silva André Uehara, SC}, title = {Health care for patients with long COVID: a scoping review.}, journal = {Revista da Escola de Enfermagem da U S P}, volume = {58}, number = {}, pages = {e20240056}, pmid = {39475394}, issn = {1980-220X}, mesh = {Humans ; *COVID-19/therapy ; Delivery of Health Care/organization &amp; administration ; Post-Acute COVID-19 Syndrome ; Physical Therapy Modalities ; Telerehabilitation/organization &amp; administration ; }, abstract = {OBJECTIVE: To map the scientific evidence on the care offered to health service users with Long Covid-19.<br><br>METHOD: This is a scoping review based on the methods of the Joanna Briggs Institute. Primary studies were included, in Portuguese, English and Spanish, published between December 2019 and June 2023, in the Virtual Health Library, Web of Science, Scopus, PUBMED, SciELO and LITCovid LongCovid databases.<br><br>RESULTS: Of the &#x661;&#x663; articles analyzed, it stands out that the care provided to patients with Long Covid is associated with drug prescription, indication of physical exercises, telerehabilitation and physiotherapy.<br><br>CONCLUSION: A fragmentation was identified in the care provided to users of health services with Long Covid, with care directed only at isolated symptoms, without addressing the biopsychosocial care that people with this condition need.}, }
@article {pmid39482218, year = {2025}, author = {Guedj, E and Cionca, A and Péron, JA and Ayubcha, C and Assal, F and Horowitz, T and Alavi, A}, title = {Long Coronavirus Disease and the Brain: Molecular Neuroimaging Insights into Neurologic and Psychiatric Sequelae.}, journal = {PET clinics}, volume = {20}, number = {1}, pages = {39-55}, doi = {10.1016/j.cpet.2024.09.013}, pmid = {39482218}, issn = {1879-9809}, mesh = {Humans ; *Brain/diagnostic imaging ; Magnetic Resonance Imaging/methods ; Mental Disorders/diagnostic imaging/etiology ; *Neuroimaging/methods ; Positron-Emission Tomography/methods ; *Post-Acute COVID-19 Syndrome/complications/diagnostic imaging ; SARS-CoV-2 ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic has led to a variety of health challenges, with "long COVID" emerging as a widespread and debilitating post-acute syndrome among a considerable number of infected patients. This PET review synthesizes current evidence of the neurologic and psychiatric sequelae of COVID. This review also explores the pathophysiological mechanisms of these results, including astrocyte dysfunction and glutamate dysregulation, as well as the multimodal comparison to MR imaging findings. The findings underscore the potential for long-term brain injury. Additionally, the authors discuss the role of advanced imaging multimodal techniques in diagnosing, monitoring, and guiding treatment strategies for long COVID.}, }
@article {pmid39485894, year = {2024}, author = {Borghi-Silva, A and Goulart, CDL and Silva, RN and Back, GD and Camargo, PF and Trimer, R and Teles, SN and Sampaio, LMM}, title = {Impact of COVID-19 on Exercise-Based Pulmonary Rehabilitation: What Lessons Have We Learned?.}, journal = {Journal of cardiopulmonary rehabilitation and prevention}, volume = {44}, number = {6}, pages = {409-416}, pmid = {39485894}, issn = {1932-751X}, mesh = {Humans ; *COVID-19/rehabilitation/epidemiology ; *Exercise Therapy/methods ; SARS-CoV-2 ; Pulmonary Disease, Chronic Obstructive/rehabilitation ; Telerehabilitation ; Pandemics ; }, abstract = {The Coronavirus Disease 2019 (COVID-19) pandemic had a major global impact on health care, including the delivery, modality, and importance of outcomes in pulmonary rehabilitation (PR). This review discusses the impact of the pandemic on PR and the changes that were required to maintain its delivery. This article reviews the current evidence on PR during the COVID-19 pandemic period, focusing on delivery models, modalities, outcomes, perspectives, and barriers. A search of the MEDLINE, Embase, and SciELO databases and the Cochrane Library on this topic was conducted between December 1, 2019 and August 1, 2023. Studies were reviewed and relevant topics were included in this narrative. Rehabilitation of patients with severe acute COVID-19 and symptoms of long COVID has been challenging. The number of rehabilitation programs worldwide is still low, and community-based programs are still rare. Integrated programs with a multidisciplinary approach and exercise therapy with individualized prescription based on symptoms have been an interesting strategy. Telerehabilitation and outpatient rehabilitation are both effective in the treatment of patients with chronic obstructive pulmonary disease. However, the uptake of PR remains considerably low, and technological barriers for patients and lack of technological resources in low-income countries affect the delivery of these services in much of the world.}, }
@article {pmid39489518, year = {2024}, author = {Adhikari, A and Maddumage, J and Eriksson, EM and Annesley, SJ and Lawson, VA and Bryant, VL and Gras, S}, title = {Beyond acute infection: mechanisms underlying post-acute sequelae of COVID-19 (PASC).}, journal = {The Medical journal of Australia}, volume = {221 Suppl 9}, number = {}, pages = {S40-S48}, doi = {10.5694/mja2.52456}, pmid = {39489518}, issn = {1326-5377}, support = {1159272//National Health and Medical Research Council/ ; }, mesh = {Humans ; *COVID-19/complications/immunology ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; Gastrointestinal Microbiome ; }, abstract = {Immune dysregulation is a key aspect of post-acute sequelae of coronavirus disease 2019 (PASC), also known as long COVID, with sustained activation of immune cells, T cell exhaustion, skewed B cell profiles, and disrupted immune communication thereby resulting in autoimmune-related complications. The gut is emerging as a critical link between microbiota, metabolism and overall dysfunction, potentially sharing similarities with other chronic fatigue conditions and PASC. Immunothrombosis and neurological signalling dysfunction emphasise the complex interplay between the immune system, blood clotting, and the central nervous system in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Clear research gaps in the design of PASC studies, especially in the context of longitudinal research, stand out as significant areas of concern.}, }
@article {pmid39490027, year = {2024}, author = {An, Y and Guo, Z and Fan, J and Luo, T and Xu, H and Li, H and Wu, X}, title = {Prevalence and measurement of post-exertional malaise in post-acute COVID-19 syndrome: A systematic review and meta-analysis.}, journal = {General hospital psychiatry}, volume = {91}, number = {}, pages = {130-142}, doi = {10.1016/j.genhosppsych.2024.10.011}, pmid = {39490027}, issn = {1873-7714}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Prevalence ; *COVID-19/epidemiology/diagnosis ; Fatigue/epidemiology/etiology ; }, abstract = {OBJECTIVE: Post-exertional malaise (PEM) is a common and debilitating symptom of post-acute COVID-19 syndrome (PACS), and it is also included in the core outcome set for PACS. Our aims are to determine the prevalence of PEM in patients with PACS, and to review the measurement tools utilized in studies assessing PEM among these patients.<br><br>METHODS: A systematic literature search was conducted up to 29 February 2024 across four databases: PubMed, EMBASE, Web of Science, and Cochrane Library. Studies were included if they evaluated PACS individuals who had at least one persistent symptom, with the mean or median follow-up duration of at least 3&#xa0;months after COVID-19 diagnosis or hospital discharge, and specially reported on PEM or any measurement tools utilized to assess PEM. Data extraction and quality assessment were performed independently by two authors.<br><br>RESULTS: After screening 953 articles, 12 studies comprising 2665 patients were included in the meta-analysis, and 16 studies were included in the narrative review. The pooled prevalence of PEM among PACS patients at 3&#xa0;months or more after COVID-19 diagnosis was 0.55 (95&#xa0;% CI, 0.38, 0.71). Moreover, narrative review identified seven questionnaires used to assess PEM in PACS individuals, with the DePaul Symptom Questionnaire-Post Exertional Malaise (DSQ-PEM) being the most frequently utilized instrument.<br><br>CONCLUSION: Our findings indicate that over half of the PACS individuals experience PEM, and seven questionnaires have been identified for researchers to assess PEM. It is imperative to develop effective intervention strategies to treat and alleviate the burden of PEM.}, }
@article {pmid39497009, year = {2025}, author = {Gaetano, C and Atlante, S and Gottardi Zamperla, M and Barbi, V and Gentilini, D and Illi, B and Malavolta, M and Martelli, F and Farsetti, A}, title = {The COVID-19 legacy: consequences for the human DNA methylome and therapeutic perspectives.}, journal = {GeroScience}, volume = {47}, number = {1}, pages = {483-501}, pmid = {39497009}, issn = {2509-2723}, support = {SAC.002.173//IMMUNAGE/ ; RF-2019-12368521//Ministero della Salute Ricerca Corrente 2024 1.07.128/ ; POS-T4 CAL.HUB.RIA T4-AN-09//Ministero della Salute/ ; EU-NRRP M6C2 Inv. 2.1 PNRRMAD-2022-12375790//European Commission/ ; EU PNRR/2022/C9/MCID/I8//European Commission/ ; }, mesh = {Humans ; *COVID-19/genetics ; *DNA Methylation ; SARS-CoV-2 ; *Epigenesis, Genetic ; Pandemics ; *Aging/genetics ; *Epigenome ; }, abstract = {The COVID-19 pandemic has left a lasting legacy on human health, extending beyond the acute phase of infection. This article explores the evidence suggesting that SARS-CoV-2 infection can induce persistent epigenetic modifications, particularly in DNA methylation patterns, with potential long-term consequences for individuals' health and aging trajectories. The review discusses the potential of DNA methylation-based biomarkers, such as epigenetic clocks, to identify individuals at risk for accelerated aging and tailor personalized interventions. Integrating epigenetic clock analysis into clinical management could mark a new era of personalized treatment for COVID-19, possibly helping clinicians to understand patient susceptibility to severe outcomes and establish preventive strategies. Several valuable reviews address the role of epigenetics in infectious diseases, including the Sars-CoV-2 infection. However, this article provides an original overview of the current understanding of the epigenetic dimensions of COVID-19, offering insights into the long-term health implications of the pandemic. While acknowledging the limitations of current data, we emphasize the need for future research to unravel the precise mechanisms underlying COVID-19-induced epigenetic changes and to explore potential approaches to target these modifications.}, }
@article {pmid39499751, year = {2024}, author = {Li, S and Sun, XC and Wu, ZF and Hu, L and Wang, JJ and Yin, M and Cheng, L and Wang, DH}, title = {Nasal irrigation for the prevention and treatment of upper respiratory tract infection by SARS-CoV-2: a narrative review.}, journal = {Journal of infection in developing countries}, volume = {18}, number = {9.1}, pages = {S81-S91}, doi = {10.3855/jidc.19234}, pmid = {39499751}, issn = {1972-2680}, mesh = {Humans ; *COVID-19/prevention &amp; control/therapy ; *Nasal Lavage/methods ; *SARS-CoV-2 ; *Respiratory Tract Infections/prevention &amp; control/virology/therapy ; }, abstract = {INTRODUCTION: The World Health Organization declared an end to the global emergency status of COVID-19 in May of 2023. However, the impact of COVID-19 is far from over. Individuals who have recovered from COVID-19 continue to experience physiological, psychological, or cognitive symptoms, such as fatigue, shortness of breath, dizziness, and loss of smell or taste, known as long COVID. This review aims to describe the clinical characteristics of the upper respiratory tract infection (URTI) caused by SARS-CoV-2, and provide evidence for the prevention and treatment of SARS-CoV-2 infection by using nasal irrigation. COVID-19 and nasal irrigation: Nasal irrigation presents a promising adjunct to standard COVID-19 prevention and treatment protocols. This practice is theorized to diminish viral presence in the upper respiratory tract, a region identified as a primary site for SARS-CoV-2 replication and shedding. By facilitating the removal of viral particles and enhancing mucociliary clearance, nasal irrigation could potentially lessen the severity of URTI symptoms and slow transmission rates. The review consolidates current evidence of the efficacy and safety of this approach across various populations, underscoring its practicality in both preventive and therapeutic contexts.<br><br>CONCLUSIONS: We recommend that saline nasal irrigation is an effective, safe and convenient strategy to prevent the transmission of SARS-CoV-2 and alleviate the symptoms of URTI across various age groups.}, }
@article {pmid39500417, year = {2025}, author = {Bremner, JD and Russo, SJ and Gallagher, R and Simon, NM}, title = {Acute and long-term effects of COVID-19 on brain and mental health: A narrative review.}, journal = {Brain, behavior, and immunity}, volume = {123}, number = {}, pages = {928-945}, pmid = {39500417}, issn = {1090-2139}, support = {I01 RX003418/RX/RRD VA/United States ; I01 CX002331/CX/CSRD VA/United States ; R01 MH104559/MH/NIMH NIH HHS/United States ; R01 MH120262/MH/NIMH NIH HHS/United States ; R01 MH127820/MH/NIMH NIH HHS/United States ; R01 MH114882/MH/NIMH NIH HHS/United States ; UH3 DA048502/DA/NIDA NIH HHS/United States ; UG3 DA048502/DA/NIDA NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/psychology/complications ; *Brain/diagnostic imaging ; *Mental Health ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome ; Anxiety ; Anosmia/etiology/physiopathology ; Depression/psychology ; Fatigue/etiology/psychology ; Cognitive Dysfunction/etiology/physiopathology/psychology ; Neuropsychological Tests ; }, abstract = {BACKGROUND: COVID infection has been associated with long term sequalae (Long COVID) which include neurological and behavioral effects in thousands of patients, but the etiology and scope of symptoms is not well understood. This paper reviews long term sequelae of COVID on brain and mental health in patients with the Long COVID syndrome.<br><br>METHODS: This was a literature review which queried databases for Pubmed, Psychinfo, and Medline for the following topics for January 1, 2020-July 15, 2023: Long COVID, PASC, brain, brain imaging, neurological, neurobiology, mental health, anxiety, depression.<br><br>RESULTS: Tens of thousands of patients have developed Long COVID, with the most common neurobehavioral symptoms anosmia (loss of smell) and fatigue. Anxiety and mood disorders are elevated and seen in about 25% of Long COVID patients. Neuropsychological testing studies show a correlation between symptom severity and cognitive dysfunction, while brain imaging studies show global decreases in gray matter and alterations in olfactory and other brain areas.<br><br>CONCLUSIONS: Studies to date show an increase in neurobehavioral disturbances in patients with Long COVID. Future research is needed to determine mechanisms.}, }
@article {pmid39506442, year = {2025}, author = {Barlattani, T and Celenza, G and Cavatassi, A and Minutillo, F and Socci, V and Pinci, C and Santini, R and Pacitti, F}, title = {Neuropsychiatric Manifestations of COVID-19 Disease and Post COVID Syndrome: The Role of N-acetylcysteine and Acetyl-L-carnitine.}, journal = {Current neuropharmacology}, volume = {23}, number = {6}, pages = {686-704}, pmid = {39506442}, issn = {1875-6190}, mesh = {Humans ; *COVID-19/complications/psychology ; *Acetylcysteine/therapeutic use/pharmacology ; *Acetylcarnitine/therapeutic use/pharmacology ; *Mental Disorders/drug therapy/etiology ; *COVID-19 Drug Treatment ; Animals ; SARS-CoV-2 ; }, abstract = {COVID-19 is associated with neuropsychiatric symptoms, such as anosmia, anxiety, depression, stress-related reactions, and psychoses. The illness can cause persistent cognitive impairment and "brain fog", suggesting chronic brain involvement. Clinical entities of ongoing symptomatic COVID-19 and Post COVID Syndrome (PCS) mainly present neuropsychiatric symptoms such as dysgeusia, headache, fatigue, anxiety, depression, sleep disturbances, and post-traumatic stress disorder. The pathophysiology of COVID-19-related brain damage is unclear, but it is linked to various mechanisms such as inflammation, oxidative stress, immune dysregulation, impaired glutamate homeostasis, glial and glymphatic damage, and hippocampal degeneration. Noteworthy is that the metabotropic receptor mGluR2 was discovered as a mechanism of internalisation of SARS-CoV-2 in Central Nervous System (CNS) cells. N-acetylcysteine (NAC) and acetyl-L-carnitine (ALC) are two supplements that have already been found effective in treating psychiatric conditions. Furthermore, NAC showed evidence in relieving cognitive symptomatology in PCS, and ALC was found effective in treating depressive symptomatology of PCS. The overlapping effects on the glutamatergic system of ALC and NAC could help treat COVID-19 psychiatric symptoms and PCS, acting through different mechanisms on the xc-mGluR2 network, with potentially synergistic effects on chronic pain and neuro-astrocyte protection. This paper aims to summarise the current evidence on the potential therapeutic role of NAC and ALC, providing an overview of the underlying molecular mechanisms and pathophysiology. It proposes a pathophysiological model explaining the effectiveness of NAC and ALC in treating COVID-19-related neuropsychiatric symptoms.}, }
@article {pmid39508631, year = {2024}, author = {Roshanzamir, Z and Mohammadi, F and Yadegar, A and Naeini, AM and Hojabri, K and Shirzadi, R}, title = {An Overview of Pediatric Pulmonary Complications During COVID-19 Pandemic: A Lesson for Future.}, journal = {Immunity, inflammation and disease}, volume = {12}, number = {11}, pages = {e70049}, pmid = {39508631}, issn = {2050-4527}, support = {//The authors received no specific funding for this work./ ; }, mesh = {Humans ; *COVID-19/epidemiology/complications/prevention &amp; control ; Child ; *SARS-CoV-2 ; Pandemics ; Child, Preschool ; Respiratory Distress Syndrome/etiology/epidemiology ; }, abstract = {BACKGROUND: The pediatric community is considered a suitable target for controlling the spread and mortality of viral diseases. In late December 2019, a respiratory disease due to the novel coronavirus, later COVID-19, hit the globe. The COVID-19 global disruption had direct and indirect impacts on different aspects of child health. Therefore, surveillance, preventive approaches, and treatment plans for children came into the spotlight.<br><br>OBJECTIVE: This study aims to discuss the clinical pictures as well as laboratory and radiological findings of the infected children during the COVID-19 pandemic. The focus of this study is to express the clinical manifestations of respiratory disease in pediatric SARS-CoV-2, available therapeutic options, vaccine recommendations, and long COVID sequelae in affected children. This review could serve as a hint for upcoming challenges in pediatric care during future pandemics.<br><br>RESULTS: The clinical presentation of COVID-19 in pediatrics can range from mild pulmonary disease to acute respiratory distress syndrome (ARDS). Supportive care is a crucial component of the management of pediatric COVID-19. However, the importance of specializing in how to treat patients with more severe conditions cannot be overstated. Additionally, clinicians must consider prevention strategies as well as potential complications.<br><br>CONCLUSION: Although the infected patients are dipping day by day, there is a lack of clinical guidelines for pediatric SARS-CoV-2-associated pulmonary diseases. Understanding of the physicians about all aspects of pediatric care during the COVID-19 pandemic could lead to enhanced quality of future patient care and safety, reduced costs of health policies, and surveil the risk that patients with respiratory viruses can expose to society.}, }
@article {pmid39511082, year = {2024}, author = {Diener, HC}, title = {[Not Available].}, journal = {MMW Fortschritte der Medizin}, volume = {166}, number = {19}, pages = {27}, doi = {10.1007/s15006-024-4439-5}, pmid = {39511082}, issn = {1613-3560}, }
@article {pmid39516425, year = {2025}, author = {Narayanan, SN and Padiyath, S and Chandrababu, K and Raj, L and P S, BC and Ninan, GA and Sivadasan, A and Jacobs, AR and Li, YW and Bhaskar, A}, title = {Neurological, psychological, psychosocial complications of long-COVID and their management.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {46}, number = {1}, pages = {1-23}, pmid = {39516425}, issn = {1590-3478}, mesh = {Humans ; *COVID-19/psychology/complications ; *Nervous System Diseases/etiology/psychology/therapy ; *Post-Acute COVID-19 Syndrome ; Mental Disorders/etiology/therapy/psychology ; SARS-CoV-2 ; }, abstract = {Since it first appeared, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has had a significant and lasting negative impact on the health and economies of millions of individuals all over the globe. At the level of individual health too, many patients are not recovering fully and experiencing a long-term condition now commonly termed 'long-COVID'. Long-COVID is a collection of symptoms which must last more than 12 weeks following initial COVID infection, and which cannot be adequately explained by alternate diagnoses. The neurological and psychosocial impact of long-COVID is itself now a global health crisis and therefore preventing, diagnosing, and managing these patients is of paramount importance. This review focuses primarily on: neurological functioning deficits; mental health impacts; long-term mood problems; and associated psychosocial issues, among patients suffering from long-COVID with an eye towards the neurological basis of these symptoms. A concise account of the clinical relevance of the neurological and psychosocial impacts of long-COVID, the effects on long-term morbidity, and varied approaches in managing patients with significant chronic neurological symptoms and conditions was extracted from the literature, analysed and reported. A comprehensive account of plausible pathophysiological mechanisms involved in the development of long-COVID, its management, and future research needs have been discussed.}, }
@article {pmid39518632, year = {2024}, author = {Pietranis, KA and Kostro, AM and Dzięcioł-Anikiej, Z and Moskal-Jasińska, D and Kuryliszyn-Moskal, A}, title = {Impact of COVID-19 on Diaphragmatic Function: Understanding Multiorgan Involvement and Long-Term Consequences.}, journal = {Journal of clinical medicine}, volume = {13}, number = {21}, pages = {}, pmid = {39518632}, issn = {2077-0383}, abstract = {The COVID-19 pandemic has brought significant attention to the respiratory system, with much focus on lung-related disorders. However, the diaphragm, a crucial component of respiratory physiology, has not been adequately studied, especially in the context of long COVID. This review explores the multipotential role of the diaphragm in both respiratory health and disease, emphasizing its involvement in long-term complications following SARS-CoV-2 infection. The diaphragm's fundamental role in respiratory physiology and its impact on balance and posture control, breathing patterns, and autonomic nervous system regulation are discussed. This review examines complications arising from COVID-19, highlighting the diaphragm's involvement in neurological, musculoskeletal, and inflammatory responses. Particular attention is given to the neuroinvasive impact of SARS-CoV-2, the inflammatory response, and the direct viral effects on the diaphragm. The diaphragm's role in long COVID is explored, with a focus on specific symptoms such as voice disorders, pelvic floor dysfunction, and sleep disturbances. Diagnostic challenges, current methods for assessing diaphragmatic dysfunction, and the complexities of differentiating it from other conditions are also explored. This article is the first to comprehensively address diaphragmatic dysfunction resulting from COVID-19 and long COVID across various physiological and pathological aspects, offering a new perspective on its diagnosis and treatment within a multisystem context.}, }
@article {pmid39518964, year = {2024}, author = {Paranga, TG and Mitu, I and Pavel-Tanasa, M and Rosu, MF and Miftode, IL and Constantinescu, D and Obreja, M and Plesca, CE and Miftode, E}, title = {Cytokine Storm in COVID-19: Exploring IL-6 Signaling and Cytokine-Microbiome Interactions as Emerging Therapeutic Approaches.}, journal = {International journal of molecular sciences}, volume = {25}, number = {21}, pages = {}, pmid = {39518964}, issn = {1422-0067}, support = {158/2022//Grigore T. Popa University of Medicine and Pharmacy of Iasi/ ; POC/448/1/1/127606 CENEMED project no. 367/390043/2021//Grigore T. Popa University of Medicine and Pharmacy of Iasi/ ; }, mesh = {Humans ; *COVID-19/immunology ; *Cytokine Release Syndrome/immunology/drug therapy ; *Interleukin-6/metabolism/immunology ; *Signal Transduction ; *SARS-CoV-2/immunology ; *Gastrointestinal Microbiome/immunology ; Cytokines/metabolism ; COVID-19 Drug Treatment ; }, abstract = {IL-6 remains a key molecule of the cytokine storms characterizing COVID-19, exerting both proinflammatory and anti-inflammatory effects. Emerging research underscores the significance of IL-6 trans-signaling over classical signaling pathways, which has shifted the focus of therapeutic strategies. Additionally, the synergistic action of TNF-α and IFN-γ has been found to induce inflammatory cell death through PANoptosis, further amplifying the severity of cytokine storms. Long COVID-19 patients, as well as those with cytokine storms triggered by other conditions, exhibit distinct laboratory profiles, indicating the need for targeted approaches to diagnosis and management. Growing evidence also highlights the gut microbiota's crucial role in modulating the immune response during COVID-19 by affecting cytokine production, adding further complexity to the disease's immunological landscape. Targeted intervention strategies should focus on specific cytokine cutoffs, though accurate cytokine quantification remains a clinical challenge. Current treatment strategies are increasingly focused on inhibiting IL-6 trans-signaling, which offers promise for more precise therapeutic approaches to manage hyperinflammatory responses in COVID-19. In light of recent discoveries, this review summarizes key research findings on cytokine storms, particularly their role in COVID-19 and other inflammatory conditions. It explores emerging therapeutic strategies targeting cytokines like IL-6, TNF-α, and IFN-γ, while also addressing open questions, such as the need for better biomarkers to detect and manage cytokine storms. Additionally, the review highlights ongoing challenges in developing targeted treatments that mitigate hyperinflammation without compromising immune function, emphasizing the importance of continued research in this field.}, }
@article {pmid39526116, year = {2024}, author = {Kyriakopoulos, AM and Nigh, G and McCullough, PA and Seneff, S}, title = {Clinical rationale for dietary lutein supplementation in long COVID and mRNA vaccine injury syndromes.}, journal = {F1000Research}, volume = {13}, number = {}, pages = {191}, pmid = {39526116}, issn = {2046-1402}, mesh = {Humans ; *COVID-19/prevention &amp; control ; COVID-19 Drug Treatment ; *COVID-19 Vaccines/administration &amp; dosage/adverse effects ; *Dietary Supplements ; *Lutein/administration &amp; dosage/therapeutic use ; mRNA Vaccines ; Olive Oil ; Oxidative Stress/drug effects ; Post-Acute COVID-19 Syndrome ; Spike Glycoprotein, Coronavirus/immunology ; }, abstract = {Lutein, a plant-derived xanthophyl-carotenoid, is an exceptional antioxidant and anti-inflammatory constituent found in food. High dietary intake of lutein is beneficial against eye disease, improves cardiometabolic health, protects from neurodegenerative diseases, and is beneficial for liver, kidney, and respiratory health. Lutein protects against oxidative and nitrosative stress, both of which play a major role in long COVID and mRNA vaccination injury syndromes. Lutein is an important natural agent for therapeutic use against oxidative and nitrosative stress in chronic illnesses such as cardiovascular and neurodegenerative diseases and cancer. It can also potentially inhibit spike protein-induced inflammation. Rich dietary supplementation of lutein, naturally derived in non-biodegradable Extra Virgin Olive Oil (EVOO), can most optimally be used against oxidative and nitrosative stress during post-COVID and mRNA vaccination injury syndromes. Due to its high oleic acid (OA) content, EVOO supports optimal absorption of dietary lutein. The main molecular pathways by which the SARS-CoV-2 spike protein induces pathology, nuclear factor kappa-light-chain-enhancer activated B cells (NF-κB) and activated protein (AP)-1, can be suppressed by lutein. Synergy with other natural compounds for spike protein detoxification is likely.}, }
@article {pmid39536116, year = {2024}, author = {Antar, AAR and Cox, AL}, title = {Translating insights into therapies for Long Covid.}, journal = {Science translational medicine}, volume = {16}, number = {773}, pages = {eado2106}, pmid = {39536116}, issn = {1946-6242}, support = {K08 AI143391/AI/NIAID NIH HHS/United States ; U19 AI159822/AI/NIAID NIH HHS/United States ; U54 CA260492/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/therapy/immunology/virology ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; Animals ; Translational Research, Biomedical ; }, abstract = {Long Covid is defined by a wide range of symptoms that persist after the acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Commonly reported symptoms include fatigue, weakness, postexertional malaise, and cognitive dysfunction, with many other symptoms reported. Symptom range, duration, and severity are highly variable and partially overlap with symptoms of myalgic encephalomyelitis/chronic fatigue syndrome and other post-acute infectious syndromes, highlighting opportunities to define shared mechanisms of pathogenesis. Potential mechanisms of Long Covid are diverse, including persistence of viral reservoirs, dysregulated immune responses, direct viral damage of tissues targeted by SARS-CoV-2, inflammation driven by reactivation of latent viral infections, vascular endothelium activation or dysfunction, and subsequent thromboinflammation, autoimmunity, metabolic derangements, microglial activation, and microbiota dysbiosis. The heterogeneity of symptoms and baseline characteristics of people with Long Covid, as well as the varying states of immunity and therapies given at the time of acute infection, have made etiologies of Long Covid difficult to determine. Here, we examine progress on preclinical models for Long Covid and review progress being made in clinical trials, highlighting the need for large human studies and further development of models to better understand Long Covid. Such studies will inform clinical trials that will define treatments to benefit those living with this condition.}, }
@article {pmid39536118, year = {2024}, author = {Schäfer, A and Leist, SR and Powers, JM and Baric, RS}, title = {Animal models of Long Covid: A hit-and-run disease.}, journal = {Science translational medicine}, volume = {16}, number = {773}, pages = {eado2104}, pmid = {39536118}, issn = {1946-6242}, support = {R01 AI110700/AI/NIAID NIH HHS/United States ; R01 AI157253/AI/NIAID NIH HHS/United States ; U19 AI171292/AI/NIAID NIH HHS/United States ; R01 HL171292/HL/NHLBI NIH HHS/United States ; P01 AI167966/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *COVID-19/immunology/virology ; *Disease Models, Animal ; *SARS-CoV-2 ; Humans ; *Post-Acute COVID-19 Syndrome ; }, abstract = {The severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) pandemic has caused more than 7 million deaths globally. Despite the presence of infection- and vaccine-induced immunity, SARS-CoV-2 infections remain a major global health concern because of the emergence of SARS-CoV-2 variants that can cause severe acute coronavirus disease 2019 (COVID-19) or enhance Long Covid disease phenotypes. About 5 to 10% of SARS-CoV-2-infected individuals develop Long Covid, which, similar to acute COVID 19, often affects the lung. However, Long Covid can also affect other peripheral organs, especially the brain. The causal relationships between acute disease phenotypes, long-term symptoms, and involvement of multiple organ systems remain elusive, and animal model systems mimicking both acute and post-acute phases are imperative. Here, we review the current state of Long Covid animal models, including current and possible future applications.}, }
@article {pmid39536122, year = {2024}, author = {Saydah, SH and Campbell, AP and Randolph, AG}, title = {Consequences beyond acute SARS-CoV-2 infection in children.}, journal = {Science translational medicine}, volume = {16}, number = {773}, pages = {eado2099}, pmid = {39536122}, issn = {1946-6242}, support = {CC999999/ImCDC/Intramural CDC HHS/United States ; }, mesh = {Humans ; *COVID-19/epidemiology/virology/complications ; Child ; *Systemic Inflammatory Response Syndrome ; *SARS-CoV-2/isolation &amp; purification ; Post-Acute COVID-19 Syndrome ; }, abstract = {Although most children are spared from developing complications from SARS-CoV-2 infection, some may suffer consequences including Long Covid and multisystem inflammatory syndrome in children (MIS-C). Although the occurrence of these conditions has decreased over time, they can still occur, and recognition of symptoms and prompt diagnosis is imperative for early intervention.}, }
@article {pmid39537445, year = {2024}, author = {Obraitis, D and Li, D}, title = {Blood virome research in myalgic encephalomyelitis/chronic fatigue syndrome: challenges and opportunities.}, journal = {Current opinion in virology}, volume = {68-69}, number = {}, pages = {101437}, pmid = {39537445}, issn = {1879-6265}, support = {R03 AI147084/AI/NIAID NIH HHS/United States ; R21 AI159710/AI/NIAID NIH HHS/United States ; U54 AI178855/AI/NIAID NIH HHS/United States ; }, mesh = {*Fatigue Syndrome, Chronic/virology/blood ; Humans ; *Virome ; *COVID-19/virology ; SARS-CoV-2/genetics ; }, abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease with a complex clinical presentation and an unknown etiology. Various viral infections have been proposed as potential triggers of ME/CFS onset, but no specific pathogen has been identified in all cases of postinfectious ME/CFS. The symptomatology of the postacute sequelae of SARS-CoV-2, or long COVID, mirrors that of ME/CFS, with nearly half of long COVID patients meeting ME/CFS diagnostic criteria. The influx of newly diagnosed patients has reinvigorated interest in ME/CFS pathogenesis research, with an emphasis on viral triggers. This review summarizes the current understanding of ME/CFS research on viral triggers, including blood virome screening studies. To further elucidate the molecular basis of ME/CFS, there is a need to develop innovative bioinformatics tools capable of analyzing complex virome data and integrating multiomics information.}, }
@article {pmid39545965, year = {2024}, author = {Pawlik, MT and Rinneberg, G and Koch, A and Meyringer, H and Loew, TH and Kjellberg, A}, title = {Is there a rationale for hyperbaric oxygen therapy in the patients with Post COVID syndrome? : A critical review.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {274}, number = {8}, pages = {1797-1817}, pmid = {39545965}, issn = {1433-8491}, mesh = {Humans ; *Hyperbaric Oxygenation/methods ; *COVID-19/therapy/complications ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {The SARS-CoV-2 pandemic has resulted in 762 million infections worldwide from 2020 to date, of which approximately ten percent are suffering from the effects after infection in 2019 (COVID-19) [1, 40]. In Germany, it is now assumed that at least one million people suffer from post-COVID condition with long-term consequences. These have been previously reported in diseases like Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS). Symptoms show a changing variability and recent surveys in the COVID context indicate that 10-30 % of outpatients, 50 to 70% of hospitalised patients suffer from sequelae. Recent data suggest that only 13% of all ill people were completely free of symptoms after recovery [3, 9]. Current hypotheses consider chronic inflammation, mitochondrial dysfunction, latent viral persistence, autoimmunity, changes of the human microbiome or multilocular sequelae in various organ system after infection. Hyperbaric oxygen therapy (HBOT) is applied since 1957 for heart surgery, scuba dive accidents, CO intoxication, air embolisms and infections with anaerobic pathogens. Under hyperbaric pressure, oxygen is physically dissolved in the blood in higher concentrations and reaches levels four times higher than under normobaric oxygen application. Moreover, the alternation of hyperoxia and normoxia induces a variety of processes at the cellular level, which improves oxygen supply in areas of locoregional hypoxia. Numerous target gene effects on new vessel formation, anti-inflammatory and anti-oedematous effects have been demonstrated [74]. The provision of intermittently high, local oxygen concentrations increases repair and regeneration processes and normalises the predominance of hyperinflammation. At present time only one prospective, randomized and placebo-controlled study exists with positive effects on global cognitive function, attention and executive function, psychiatric symptoms and pain interference. In conclusion, up to this date HBO is the only scientifically proven treatment in a prospective randomized controlled trial to be effective for cognitive improvement, regeneration of brain network and improvement of cardiac function. HBOT may have not only theoretical but also potential impact on targets of current pathophysiology of Post COVID condition, which warrants further scientific studies in patients.}, }
@article {pmid39547729, year = {2025}, author = {Vrettou, CS and Jolley, SE and Mantziou, V and Dimopoulou, I}, title = {Clinical Comparison of Post-intensive Care Syndrome and Long Coronavirus Disease.}, journal = {Critical care clinics}, volume = {41}, number = {1}, pages = {89-102}, doi = {10.1016/j.ccc.2024.08.009}, pmid = {39547729}, issn = {1557-8232}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Critical Care ; Post-Acute COVID-19 Syndrome ; Critical Illness ; Cognitive Dysfunction/etiology/physiopathology ; Risk Factors ; }, abstract = {Post-intensive care syndrome (PICS) encompasses persistent physical, psychological, and cognitive impairments. The coronavirus disease of 2019 (COVID-19) pandemic highlighted parallels between PICS and "long COVID". There is an overlap between the 2 in risk factors, symptoms, and pathophysiology. Physical impairments in both include weakness and fatigue. Cognitive impairments include executive dysfunction in PICS and "brain fog" in long COVID. Mental health issues consist of depression, anxiety, and posttraumatic stress disorder in both disease states. Long COVID and PICS impact families, with multifaceted effects on physical health, mental well-being, and socioeconomic stability. Understanding these syndromes is crucial for comprehensive patient care and family support.}, }
@article {pmid39550105, year = {2025}, author = {Calabrese, LH and Calabrese, C}, title = {Long COVID for the Rheumatologist: Current Understanding and Approach to Management.}, journal = {Rheumatic diseases clinics of North America}, volume = {51}, number = {1}, pages = {29-43}, doi = {10.1016/j.rdc.2024.08.004}, pmid = {39550105}, issn = {1558-3163}, mesh = {Humans ; *COVID-19/complications/therapy ; *Post-Acute COVID-19 Syndrome ; *Rheumatic Diseases/therapy ; Rheumatologists ; SARS-CoV-2 ; Rheumatology/methods ; Fibromyalgia/therapy ; }, abstract = {There are estimated tens of millions of individuals throughout the world suffering from a variety of postinfectious sequela following infection with severe acute respiratory syndrome coronavirus 2 also commonly referred to as long coronavirus disease (COVID). Long COVID is providing an opportunity for the field of rheumatology to explore the relationship between similar syndromes including fibromyalgia seen in patients with underlying inflammatory and noninflammatory rheumatic diseases, as well as other postacute infectious sequela and bring our field's traditional skill sets to bear on improving our understanding of these disorders and the care of such patients.}, }
@article {pmid39550783, year = {2024}, author = {Reyes, Z and Stovall, MC and Punyamurthula, S and Longo, M and Maraganore, D and Solch-Ottaiano, RJ}, title = {The impact of gut microbiome and diet on post-acute sequelae of SARS-CoV-2 infection.}, journal = {Journal of the neurological sciences}, volume = {467}, number = {}, pages = {123295}, doi = {10.1016/j.jns.2024.123295}, pmid = {39550783}, issn = {1878-5883}, mesh = {Humans ; Brain-Gut Axis/immunology ; *COVID-19/complications/diet therapy/immunology/virology ; *Diet, Mediterranean ; *Gastrointestinal Microbiome/immunology ; *Post-Acute COVID-19 Syndrome/immunology/microbiology/prevention &amp; control ; SARS-CoV-2/immunology/pathogenicity ; }, abstract = {Long COVID, also known as Post COVID-19 condition by the World Health Organization or Post-Acute Sequelae of SARS-CoV-2 infection (PASC), is defined as the development of symptoms such as post-exertional malaise, dysgeusia, and partial or full anosmia three months after initial SARS-CoV-2 infection. The multisystem effects of PASC make it difficult to distinguish from its mimickers. Further, a comprehensive evaluation of the gut microbiome, nutrition, and PASC has yet to be studied. The gut-brain axis describes bidirectional immune, neural, endocrine, and humoral modulatory interactions between the gut microbiome and brain function. We explore recent studies that support an association between alterations in gut microbiome diversity and the severity of acute-phase COVID-19, and how these may be affected by diets rich in antioxidants and fiber. The Mediterranean Diet (MeDi) has demonstrated promising neuroprotective effects through its anti-inflammatory processes. Further, diets rich in fiber increase gut diversity and increase the amount of short-chain fatty acids (SCFAs) within the body-both shown to protect from acute COVID-19 complications. Long-term changes to the gut microbiome persist after acute infection and may increase susceptibility to PASC. This study builds on existing knowledge of determinants of PASC and highlights a relationship between nutrition, gut microbiome, acute-phase COVID-19, and, subsequently, PASC susceptibility.}, }
@article {pmid39551439, year = {2025}, author = {Wurm, J and Ritz, N and Zimmermann, P}, title = {Coronavirus disease 2019 (COVID-19) in children: Evolving epidemiology, immunology, symptoms, diagnostics, treatment, post-COVID-19 conditions, prevention strategies, and future directions.}, journal = {The Journal of allergy and clinical immunology}, volume = {155}, number = {4}, pages = {1071-1081}, doi = {10.1016/j.jaci.2024.11.012}, pmid = {39551439}, issn = {1097-6825}, mesh = {Humans ; *COVID-19/epidemiology/diagnosis/prevention &amp; control/therapy/immunology/complications ; Child ; *SARS-CoV-2/immunology ; Adolescent ; COVID-19 Vaccines ; Antiviral Agents/therapeutic use ; Systemic Inflammatory Response Syndrome/epidemiology ; }, abstract = {The epidemiology of coronavirus disease 2019 (COVID-19) in children has evolved throughout the pandemic, with initially low infection rates rising significantly as a result of the emergence of the more transmissible Omicron variant. Adolescents, children from ethnic minorities and lower-income households, and those with obesity are at increased risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The immune response in children leads to milder symptoms compared to adults, with fever and cough being most frequent; tough symptoms vary by SARS-CoV-2 variant and age. Diagnostic methods to confirm current or past infection include reverse transcription PCR, rapid antigen tests, and serology. Treatment is mainly supportive, with antivirals and glucocorticoids reserved for severe cases. While serious conditions like multisystem inflammatory syndrome in children and other post-COVID-19 conditions are rare, they require careful management. Vaccination has proven effective in reducing severe disease and protecting against post-COVID-19 conditions. Continued surveillance, including wastewater monitoring and universal or pooled testing, remains crucial for controlling community spread. Key questions remain regarding the duration and quality of immunity after reinfection or vaccination, the impact of coinfections, and optimal treatment protocols for different pediatric populations.}, }
@article {pmid39559556, year = {2024}, author = {Chen, YH and Hsieh, YS}, title = {A Narrative Review of Impact of Incentive Spirometer Respiratory Training in Long COVID.}, journal = {International journal of general medicine}, volume = {17}, number = {}, pages = {5233-5246}, pmid = {39559556}, issn = {1178-7074}, abstract = {Long COVID refers to symptoms that appear 3 months after initial infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus of Coronavirus disease 2019 (COVID-19), and last for at least 2 months, not attributable to other diagnoses. This health issue significantly burdens patients' quality of life, the economy, and society. Improving the af-termath of COVID-19 is a crucial global health issue in the post-pandemic era. According to current results, it is evident that developing a simple, low-cost respiratory training method that can be easily used at home by themselves with long Coronavirus disease 2019 symptoms (long COVID) is an important and urgent issue. The incentive spirometer is widely used in physical, speech, and respiratory therapy, as well as in preventing postoperative pulmonary infections and improving sputum clearance. However, to date, the role of incentive spirometer respiratory training in long COVID symptoms is still limited. In this literature review is presented to explore the effectiveness of incentive spirometer respiratory training in alleviating symptoms among individuals recovering from long COVID. We also compile non-invasive assessment methods, with the aim to enable individuals to undergo training and assessments conveniently at home or in the community. In this review, a literature review approach was utilized to explore the effectiveness of incentive spirometer intervention in alleviating long-term COVID symptoms. This study is to synthesize the findings of articles published during January 2019 and December 2023 retrieved from PubMed/CINAHL/MEDLINE/ Google Scholar without re-strictions on study type. We ultimately identified seven articles and have summarized similar past studies. This review could contribute to improving symptoms related to long COVID by incentive spirometer respiratory training and serve as practical reference material for clinical medical staff and provide insights for healthcare policymakers in de-veloping guidelines for future research directions, clinical guidance, and educational strategies in the context of nursing care.}, }
@article {pmid39560821, year = {2024}, author = {Carosi, G and Cremaschi, A and Giavoli, C and Ferrante, E and Mantovani, G}, title = {Hypopituitarism and COVID-19.}, journal = {Pituitary}, volume = {27}, number = {6}, pages = {925-934}, pmid = {39560821}, issn = {1573-7403}, mesh = {Humans ; *COVID-19/epidemiology/complications ; *Hypopituitarism/etiology ; Pandemics ; Pituitary Gland ; SARS-CoV-2/physiology ; }, abstract = {PURPOSE: This review aims to collect and examine recent research findings regarding hypopituitarism and COVID-19, focusing on the virus's impact on the pituitary gland and the outcomes for infected patients with hormonal deficiencies.<br><br>METHODS: Literature review using PubMed (pubmed.ncbi.nlm.nih.gov). The search included the following terms: "COVID19" in combination with "Pituitary" and "Hypopituitarism".<br><br>RESULTS: Many studies have aimed to evaluate the function of the pituitary gland in infected patients, revealing variable degrees of deficiencies. The results are very heterogenous mostly because many different tests and hormonal cut-off have been adopted. It is unclear whether primary virus damage or the inflammatory response is responsible for these hormonal alterations. Interestingly, pituitary defects may persist long after the initial infection, possibly contributing to the "Long COVID syndrome". However, data on the recovery of pituitary function and long-term follow-up are not yet available. On the other hand, although findings are not consistent, patients with hypopituitarism may be at a higher risk for COVID-19 infection rate, complications, and mortality.<br><br>CONCLUSION: The COVID-19 pandemic presented challenges for endocrinologists. The endocrine system appears to be involved in both the acute phase of infection and the recovery period. Hypopituitarism can be a consequence of SARS-COV-2 infection, and patients with existing hypopituitarism may face higher risks of complications. It is advisable to educate these patients on how to adjust their replacement therapies. Long-term follow-up data on pituitary function after recovery from COVID-19 are needed.}, }
@article {pmid39574837, year = {2024}, author = {Kanu, JS and Vandi, MA and Bangura, B and Draper, K and Gorina, Y and Foster, MA and Harding, JD and Ikoona, EN and Jambai, A and Kamara, MAM and Kaitibi, D and Moffett, DB and Singh, T and Redd, JT}, title = {Promoting Awareness of Data Confidentiality and Security During the COVID-19 Pandemic in a Low-Income Country-Sierra Leone.}, journal = {Public health reviews}, volume = {45}, number = {}, pages = {1607540}, pmid = {39574837}, issn = {0301-0422}, abstract = {OBJECTIVES: World Health Organization issued Joint Statement on Data Protection and Privacy in the COVID-19 Response stating that collection of vast amounts of personal data may potentially lead to the infringement of fundamental human rights and freedoms. The Organization for Economic Cooperation and Development called on national governments to adhere to the international principles for data security and confidentiality. This paper describes the methods used to assist the Ministry of Health in bringing awareness of the data ownership, confidentiality and security principles to COVID-19 responders.<br><br>METHODS: The Sierra Leone Epidemiological Data (SLED) Team data managers conducted training for groups of COVID-19 responders. Training included presentations on data confidentiality, information disclosure, physical and electronic data security, and cyber-security; and interactive discussion of real-life scenarios. A game of Jeopardy was created to test the participant's knowledge.<br><br>RESULTS: This paper describes the methods used by the SLED Team to bring awareness of the DOCS principles to more than 2,500 COVID-19 responders.<br><br>CONCLUSION: Similar efforts may benefit other countries where the knowledge, resources, and governing rules for protection of personal data are limited.}, }
@article {pmid39575994, year = {2025}, author = {Somerton, A and Jeffrey, H}, title = {'It's that camaraderie': Experiences of a Long-COVID peer support group for staff working in health, social care and emergency services.}, journal = {Journal of health psychology}, volume = {30}, number = {10}, pages = {2460-2474}, doi = {10.1177/13591053241296184}, pmid = {39575994}, issn = {1461-7277}, mesh = {Humans ; *COVID-19/psychology ; *Peer Group ; Male ; United Kingdom ; *Health Personnel/psychology ; Female ; Adult ; *Self-Help Groups ; SARS-CoV-2 ; Middle Aged ; Qualitative Research ; Emergency Medical Services ; }, abstract = {Health, social care and emergency services staff, continue to feel the impact of Long-COVID. Using quantitative and qualitative methods, this study aims to evaluate the experience of UK health and social care staff who participated in a virtual Long-COVID peer support group between May 2021 and May 2023. The outcome measures (SWEMWBS and PHQ9) show an improvement in post-group scores, suggesting participation in the peer support group is linked to improved wellbeing. Thematic analysis identified five key themes: finding connectedness, reciprocity, effective facilitation, filling the gaps and virtual format. This evaluation shows how peer support groups provided space for reciprocity and the positive outcomes associated with this. This evaluation highlights the importance of co-produced, needs-based services providing Long-COVID peer support.}, }
@article {pmid39580033, year = {2024}, author = {Chow, NKN and Tsang, CYW and Chan, YH and Telaga, SA and Ng, LYA and Chung, CM and Yip, YM and Cheung, PP}, title = {The effect of pre-COVID and post-COVID vaccination on long COVID: A systematic review and meta-analysis.}, journal = {The Journal of infection}, volume = {89}, number = {6}, pages = {106358}, doi = {10.1016/j.jinf.2024.106358}, pmid = {39580033}, issn = {1532-2742}, mesh = {Humans ; *COVID-19/complications/immunology/prevention &amp; control ; *COVID-19 Vaccines/administration &amp; dosage ; *Post-Acute COVID-19 Syndrome/epidemiology/immunology/prevention &amp; control/virology ; Quality of Life ; SARS-CoV-2/immunology ; *Vaccination/statistics &amp; numerical data ; }, abstract = {BACKGROUND: Long COVID affects millions of people and results in a substantial decrease in quality of life. Previous primary studies and reviews attempted to study the effect of vaccination against long COVID, but these studies varied in the cut-off time of long COVID. We adhered to the WHO's definition of long COVID and conducted a systematic review and meta-analysis on the effect of pre-COVID and post-COVID vaccination on long COVID.<br><br>METHODS: We obtained data from 13 databases up to 18 February 2024, including peer reviewed and preprint studies. Our inclusion criteria were: (1) long COVID definition as 3 months or beyond, (2) comparing long COVID symptoms between vaccinated and unvaccinated groups, (3) subjects received vaccinations either before or after infected with COVID, (4) the number of doses received by participants was specified. We extracted study characteristics and data and computed the summary odds ratio (OR) with the DerSimonian and Laird random effects model. We then performed subgroup analyses based on the main vaccine brand and long COVID assessment method. ROBINS-I framework was used for assessment of risk of bias and the GRADE approach was used for evaluating the certainty of evidence.<br><br>FINDINGS: We included data from 25 observational studies (n&#xa0;=&#xa0;14,128,260) with no randomised controlled trials. One-dose pre-COVID vaccination did not have an effect on long COVID (number of studies = 10, summary OR = 1.01, 95% CI = 0.88-1.15, p-value = 0.896). Two-dose pre-COVID vaccination was associated with a 24% reduced odds of long COVID (number of studies = 15, summary OR = 0.76, 95% CI = 0.65-0.89, p-value = 0.001) and 4 symptoms (fatigue, headache, loss of smell, muscle pain) out of 10 symptoms analysed. The OR of three-dose pre-COVID vaccination against overall long COVID was statistically insignificant but was far away from 1 (number of studies = 3, summary OR = 0.31, 95% CI = 0.05-1.84, p-value = 0.198). One-dose post-COVID vaccination was associated with a 15% reduced odds of long COVID (number of studies = 5, summary OR = 0.85, 95% CI = 0.73-0.98, p-value = 0.024). The OR of two-dose post-COVID vaccination against long COVID was statistically insignificant but was far away from 1 (number of studies = 3, summary OR = 0.63, 95% CI = 0.38-1.03, p-value = 0.066).<br><br>INTERPRETATION: Our study suggests that 2-dose pre-COVID vaccination and 1-dose post-COVID vaccination are associated with a lower risk of long COVID. Since long COVID reduces quality of life substantially, vaccination could be a possible measure to maintain quality of life by partially protecting against long COVID.}, }
@article {pmid39587352, year = {2025}, author = {Sigal, A and Neher, RA and Lessells, RJ}, title = {The consequences of SARS-CoV-2 within-host persistence.}, journal = {Nature reviews. Microbiology}, volume = {23}, number = {5}, pages = {288-302}, pmid = {39587352}, issn = {1740-1534}, mesh = {Humans ; *SARS-CoV-2/genetics/physiology/immunology ; *COVID-19/virology/immunology ; Virus Replication ; Mutation ; Antibodies, Neutralizing/immunology ; }, abstract = {SARS-CoV-2 causes an acute respiratory tract infection that resolves in most people in less than a month. Yet some people with severely weakened immune systems fail to clear the virus, leading to persistent infections with high viral titres in the respiratory tract. In a subset of cases, persistent SARS-CoV-2 replication results in an accelerated accumulation of adaptive mutations that confer escape from neutralizing antibodies and enhance cellular infection. This may lead to the evolution of extensively mutated SARS-CoV-2 variants and introduce an element of chance into the timing of variant evolution, as variant formation may depend on evolution in a single person. Whether long COVID is also caused by persistence of replicating SARS-CoV-2 is controversial. One line of evidence is detection of SARS-CoV-2 RNA and proteins in different body compartments long after SARS-CoV-2 infection has cleared from the upper respiratory tract. However, thus far, no replication competent virus has been cultured from individuals with long COVID who are immunocompetent. In this Review, we consider mechanisms of viral persistence, intra-host evolution in persistent infections, the connection of persistent infections with SARS-CoV-2 variants and the possible role of SARS-CoV-2 persistence in long COVID. Understanding persistent infections may therefore resolve much of what is still unclear in COVID-19 pathophysiology, with possible implications for other emerging viruses.}, }
@article {pmid39589967, year = {2024}, author = {Krüger, AL and Haiduk, B and Grau, M}, title = {Identifying Factors That Might Affect Outcomes of Exercise-Based Therapies in Long-COVID.}, journal = {Diseases (Basel, Switzerland)}, volume = {12}, number = {11}, pages = {}, pmid = {39589967}, issn = {2079-9721}, abstract = {BACKGROUND: Long-COVID, which might develop after a SARS-CoV-2 infection, is a rather new disease without standardized treatment strategies. A large number of approaches that integrate physical activity have been described in the literature, and this systematic review aims to examine changes in symptom severity, physical fitness, respiratory symptoms and quality of life during training and identify factors that might influence the respective outcomes.<br><br>METHODS: A literature search was conducted using the databases Pubmed, PEDro, BioMed Central, EBSCOhost, ProQuest and the ZBSport from 13 February 2024 to 27 February 2024, and 39 studies fulfilled the search criteria.<br><br>RESULTS: The analyzed study designs varied regarding the type of intervention (isolated vs. multidisciplinary), duration and intensity of training sessions and overall length of the program. Individualized holistic concepts of physical activity paralleled by additional approaches demonstrated high effectiveness. However, many of the participants continue to suffer from Long-COVID after the intervention.<br><br>CONCLUSIONS: Long-COVID treatment should be individualized, multifactorial and not limited in time and should consider each patient's pre-existing conditions and individual course of the disease to provide the best possible support and care.}, }
@article {pmid39592027, year = {2025}, author = {Danieli, MG and Antonelli, E and Gammeri, L and Longhi, E and Cozzi, MF and Palmeri, D and Gangemi, S and Shoenfeld, Y}, title = {Intravenous immunoglobulin as a therapy for autoimmune conditions.}, journal = {Autoimmunity reviews}, volume = {24}, number = {1}, pages = {103710}, doi = {10.1016/j.autrev.2024.103710}, pmid = {39592027}, issn = {1873-0183}, mesh = {Humans ; *Autoimmune Diseases/immunology/therapy ; COVID-19/immunology/therapy ; *Immunoglobulins, Intravenous/therapeutic use ; }, abstract = {Intravenous immunoglobulin (IVIg) is a medical preparation used as replacement therapy for patients with immunodeficiencies. Over time, IVIg's anti-inflammatory and immunomodulatory effects have been recognized, which have led to the approval of this therapy in the treatment of various pathologies, such as Kawasaki disease, immune thrombocytopenia, and Guillain-Barré syndrome. There are numerous studies in the literature regarding the off-label use of IVIg in the treatment of autoimmune diseases (e.g. myositis and vasculitis), and hematological disorders. Since the role of immunoglobulins in fields other than replacement therapy is now consolidated, in this study we carried out a review of the literature to evaluate the main uses of IVIg therapy. We have focused our attention on the treatment of autoimmune, neurological, hematological, dermatological and pediatric diseases. Furthermore, our analysis of the literature also extended to the potential use of IVIg as an adjuvant treatment of long COVID-19. From our analysis, we found consistent data about IVIg's effectiveness in treating numerous clinical conditions. Treatment with IVIg represents a second-line approach or a valid adjuvant to standard therapies capable of positively influencing the clinical course of many pathologies and reducing or avoiding side effects of standard therapies, with a good safety profile.}, }
@article {pmid39596862, year = {2024}, author = {Petrella, C and Ferraguti, G and Tarani, L and Tarani, F and Messina, MP and Fiore, M}, title = {Nerve Growth Factor and Brain-Derived Neurotrophic Factor in COVID-19.}, journal = {Biology}, volume = {13}, number = {11}, pages = {}, pmid = {39596862}, issn = {2079-7737}, abstract = {Neurotrophins (NTs) constitute a family of small protein messengers that play a fundamental role in both the central and peripheral nervous systems. In particular, the nerve growth factor (NGF) and the brain-derived neurotrophic factor (BDNF) play a subtle role in the survival, differentiation, and functioning of neuronal populations, as well as in the fine regulation of immune functions. The SARS-CoV-2 infection was characterized by a sequela of symptoms (serious respiratory pathology, inflammatory storm, neurological discomfort, up to the less serious flu-like symptoms), which caused, at the end of 2023, more than 7 million deaths worldwide. Despite the official end of the pandemic, the physical and psychological consequences are currently the object of scientific research, both acute and chronic/long-lasting (Long-COVID-19). Given the multifactorial nature of the outcomes of SARS-CoV-2 infection in adults and children, several studies have investigated the potential involvement of the NGF and BDNF systems in the pathology. This narrative review aims to summarize the most recent evidence on this crucial topic.}, }
@article {pmid39597891, year = {2024}, author = {Trimble, KZ and Switzer, JN and Blitshteyn, S}, title = {Exercise in Postural Orthostatic Tachycardia Syndrome: Focus on Individualized Exercise Approach.}, journal = {Journal of clinical medicine}, volume = {13}, number = {22}, pages = {}, pmid = {39597891}, issn = {2077-0383}, abstract = {Exercise is a vital component of health and is commonly utilized as a non-pharmacologic therapy for many disorders, including postural orthostatic tachycardia syndrome (POTS). However, exercise intolerance is a key feature of POTS and other autonomic disorders and, therefore, presents a major barrier for many patients. Despite exercise being uniformly recommended as a therapeutic intervention, a majority of patients with POTS, especially those with severe orthostatic intolerance and fatigue, are unable to complete or sustain rigorous exercise programs or successfully integrate them into their daily routine. In this narrative review, we discuss the current literature on exercise and POTS and our clinical experience with a home-based exercise approach developed at the Dysautonomia Clinic. We conclude that individualized exercise programs that are delivered remotely by a certified physical therapist may be convenient, easily accessible, and safe for patients with POTS, especially those with severe symptoms who may be home- or bedbound. Future randomized controlled studies are needed to quantify and characterize the benefits of home-based exercise programs delivered remotely compared to standard therapy.}, }
@article {pmid39599809, year = {2024}, author = {Alghamdi, F and Mokbel, K and Meertens, R and Obotiba, AD and Alharbi, M and Knapp, KM and Strain, WD}, title = {Bone Mineral Density, Bone Biomarkers, and Joints in Acute, Post, and Long COVID-19: A Systematic Review.}, journal = {Viruses}, volume = {16}, number = {11}, pages = {}, pmid = {39599809}, issn = {1999-4915}, mesh = {Humans ; *COVID-19 ; *Bone Density ; *Biomarkers ; *SARS-CoV-2 ; Joints/virology ; Osteoporosis/metabolism ; Bone and Bones/metabolism/virology ; Post-Acute COVID-19 Syndrome ; }, abstract = {SARS-CoV-2 is highly transmissible and affects the respiratory system. People with COVID-19 are at higher risk of physical and mental health conditions, which could impact bone health. The aim of this review was to explore the effects of COVID-19 on BMD, BTMs, and joints. An electronic search of the PubMed, Web of Science, Scopus, and Ovid Medline databases considered studies published between 1 January 2020 and 1 November 2023. The search was limited to English, original studies in adult humans. The title and abstract of the identified papers were screened, followed by a full-text review using inclusion and exclusion criteria. The data extracted included the study and participant characteristics, BTMs, BMD, and joint abnormalities. The Newcastle-Ottawa scale quality assessment tool was used to assess the risk of bias. Five studies involving 305 out of 495 infected individuals observed a reduced BMD after COVID-19, with the most significant reduction occurring a year later. Both bone resorption and bone formation markers decreased, while regulatory markers showed higher levels in infected patients. COVID-19 may harm bone health by increasing bone regulatory markers and reducing bone formation and absorption, leading to a lower BMD. Elderly, frail, and osteopenic or osteoporotic individuals are at higher risk and should be regularly monitored for bone loss if they have long COVID.}, }
@article {pmid39599909, year = {2024}, author = {Livieratos, A and Gogos, C and Akinosoglou, K}, title = {Beyond Antivirals: Alternative Therapies for Long COVID.}, journal = {Viruses}, volume = {16}, number = {11}, pages = {}, pmid = {39599909}, issn = {1999-4915}, mesh = {Humans ; *COVID-19/therapy ; *SARS-CoV-2/drug effects ; *Antiviral Agents/therapeutic use ; Post-Acute COVID-19 Syndrome ; Metformin/therapeutic use ; COVID-19 Drug Treatment ; Anti-Inflammatory Agents/therapeutic use ; Immunoglobulins, Intravenous/therapeutic use ; Fatty Acids, Omega-3/therapeutic use ; Dexamethasone/therapeutic use ; Naltrexone/therapeutic use ; }, abstract = {Long COVID or Post-Acute Sequelae of SARS-CoV-2 infection (PASC) is a condition characterized by numerous lingering symptoms that persist for weeks to months following the viral illness. While treatment for PASC is still evolving, several therapeutic approaches beyond traditional antiviral therapies are being investigated, such as immune-modulating agents, anti-inflammatory drugs, and various supportive interventions focusing at alleviating symptoms and enhancing recovery. We aimed to summarize the breadth of available evidence, identify knowledge gaps, and highlight promising non-antiviral therapies for Long COVID/PASC. We followed the framework of a scoping methodology by mapping existing evidence from a range of studies, including randomized clinical trials, observational research, and case series. Treatments evaluated include metformin, low-dose naltrexone (LDN), dexamethasone, statins, omega-3 fatty acids, L-arginine, and emerging therapies like intravenous immunoglobulin (IVIg) and therapeutic apheresis. Early findings suggest that metformin has the strongest clinical evidence, particularly from large phase 3 trials, while LDN and dexamethasone show potential based on observational studies. However, many treatments lack robust, large-scale trials. This review emphasizes the need for further research to confirm the efficacy of these treatments and guide clinical practice for Long COVID management.}, }
@article {pmid39603665, year = {2024}, author = {Gardiner, L and Young, HML and Drover, H and Morgan-Selvaratnam, E and Natt, M and Smith, N and Daynes, E and Orme, MW and Taylor, RS and Singh, SJ and Evans, RA}, title = {Reporting of pre-existing multiple long-term conditions in physical rehabilitation for long COVID: a scoping review.}, journal = {European respiratory review : an official journal of the European Respiratory Society}, volume = {33}, number = {174}, pages = {}, pmid = {39603665}, issn = {1600-0617}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *COVID-19/rehabilitation/epidemiology ; Physical Therapy Modalities ; SARS-CoV-2 ; Time Factors ; Chronic Disease ; Treatment Outcome ; }, abstract = {BACKGROUND: Physical rehabilitation may improve health and wellbeing outcomes for some adults living with long COVID. However, individuals living with pre-existing multiple long-term conditions (MLTCs) and long COVID may have additional rehabilitation challenges. This scoping review aims to identify the available evidence describing physical rehabilitation interventions for adults living with long COVID, to systematically map the reporting of pre-existing MLTCs, and to describe the characteristics of physical rehabilitation interventions used in adults with both pre-existing long-term conditions (LTCs) and long COVID.<br><br>METHODS: MEDLINE, CINAHL, Scopus, APA PsycInfo, medRxiv, OpenGrey and MedNar were searched from January 2020 to July 2023. Eligibility criteria included adults with long COVID, rehabilitation interventions including a physical component in any setting and any study design investigating interventions or intervention content except case series/reports.<br><br>RESULTS: Of 5326 unique records, 50 articles met the inclusion criteria, of which 25 (50%) made reference to pre-existing LTCs. These articles included four protocols and one consensus statement. Four of the remaining 20 studies (20%) reported the number of pre-existing LTCs, enabling the differentiation of individuals with MLTCs. One study reported outcomes of individuals with MLTCs separately to those without. The interventions described (k=24) typically consisted of combined aerobic and strength exercises (k=17 (71%)) in an outpatient setting (k=13 (54%)).<br><br>CONCLUSIONS: There is limited and inconsistent reporting of the presence of MLTCs in studies of physical rehabilitation for adults with long COVID. Clarity and consistency of reporting of MLTCs is required to enable evaluation and adaptation of interventions to improve health and wellbeing for this population.}, }
@article {pmid39603702, year = {2024}, author = {Zeraatkar, D and Ling, M and Kirsh, S and Jassal, T and Shahab, M and Movahed, H and Talukdar, JR and Walch, A and Chakraborty, S and Turner, T and Turkstra, L and McIntyre, RS and Izcovich, A and Mbuagbaw, L and Agoritsas, T and Flottorp, SA and Garner, P and Pitre, T and Couban, RJ and Busse, JW}, title = {Interventions for the management of long covid (post-covid condition): living systematic review.}, journal = {BMJ (Clinical research ed.)}, volume = {387}, number = {}, pages = {e081318}, pmid = {39603702}, issn = {1756-1833}, mesh = {Humans ; *COVID-19/rehabilitation/therapy/complications ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Cognitive Behavioral Therapy/methods ; Randomized Controlled Trials as Topic ; Exercise ; }, abstract = {OBJECTIVE: To compare the effectiveness of interventions for the management of long covid (post-covid condition).<br><br>DESIGN: Living systematic review.<br><br>DATA SOURCES: Medline, Embase, CINAHL, PsycInfo, Allied and Complementary Medicine Database, and Cochrane Central Register of Controlled Trials from inception to December 2023.<br><br>ELIGIBILITY CRITERIA: Trials that randomised adults (&#x2265;18 years) with long covid to drug or non-drug interventions, placebo or sham, or usual care.<br><br>RESULTS: 24 trials with 3695 patients were eligible. Four trials (n=708 patients) investigated drug interventions, eight (n=985) physical activity or rehabilitation, three (n=314) behavioural, four (n=794) dietary, four (n=309) medical devices and technologies, and one (n=585) a combination of physical exercise and mental health rehabilitation. Moderate certainty evidence suggested that, compared with usual care, an online programme of cognitive behavioural therapy (CBT) probably reduces fatigue (mean difference -8.4, 95% confidence interval (CI) -13.11 to -3.69; Checklist for Individual Strength fatigue subscale; range 8-56, higher scores indicate greater impairment) and probably improves concentration (mean difference -5.2, -7.97 to -2.43; Checklist for Individual Strength concentration problems subscale; range 4-28; higher scores indicate greater impairment). Moderate certainty evidence suggested that, compared with usual care, an online, supervised, combined physical and mental health rehabilitation programme probably leads to improvement in overall health, with an estimated 161 more patients per 1000 (95% CI 61 more to 292 more) experiencing meaningful improvement or recovery, probably reduces symptoms of depression (mean difference -1.50, -2.41 to -0.59; Hospital Anxiety and Depression Scale depression subscale; range 0-21; higher scores indicate greater impairment), and probably improves quality of life (0.04, 95% CI 0.00 to 0.08; Patient-Reported Outcomes Measurement Information System 29+2 Profile; range -0.022-1; higher scores indicate less impairment). Moderate certainty evidence suggested that intermittent aerobic exercise 3-5 times weekly for 4-6 weeks probably improves physical function compared with continuous exercise (mean difference 3.8, 1.12 to 6.48; SF-36 physical component summary score; range 0-100; higher scores indicate less impairment). No compelling evidence was found to support the effectiveness of other interventions, including, among others, vortioxetine, leronlimab, combined probiotics-prebiotics, coenzyme Q10, amygdala and insula retraining, combined L-arginine and vitamin C, inspiratory muscle training, transcranial direct current stimulation, hyperbaric oxygen, a mobile application providing education on long covid.<br><br>CONCLUSION: Moderate certainty evidence suggests that CBT and physical and mental health rehabilitation probably improve symptoms of long covid.<br><br>Open Science Framework https://osf.io/9h7zm/.<br><br>READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.}, }
@article {pmid39625700, year = {2024}, author = {Blondeau, JM}, title = {Long COVID: a consequence of chronic post-infectious inflammation!.}, journal = {Expert review of respiratory medicine}, volume = {18}, number = {12}, pages = {939-945}, doi = {10.1080/17476348.2024.2438104}, pmid = {39625700}, issn = {1747-6356}, mesh = {Humans ; *COVID-19/immunology/complications ; *Inflammation/immunology/virology ; Chronic Disease ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2/immunology ; }, abstract = {INTRODUCTION: Long COVID defines persistence of symptoms in patients that recovered from acute COVID-19 infections. This manuscript is a brief update on current thinking on long COVID and potential causes and consequences.<br><br>AREAS COVERED: The extent of long COVID varies between patients with some 200 symptoms described and of different severities. Persistent inflammatory or persistent viral infections or both may be the cause of long COVID but sorting this out will take years.<br><br>EXPERT OPINION: Long COVID is an unfortunate consequence of COVID-19 infection and it remains uncertain why some people are afflicted and others not and as with other infectious diseases, it may be both a function of the virus strain, the host or both. Direct organ damage during acute infection versus inflammatory mediated damage over time are important questions to address. The disease outcome and chronic sequelae are likely related to the strains of infectious agent and/or host immunity and genetic predisposition.}, }
@article {pmid39628270, year = {2025}, author = {Duong-Quy, S and Nguyen Hai, C and Huynh-Anh, T and Nguyen-Nhu, V}, title = {Tackling pulmonary fibrosis risks in post-COVID-19: cutting-edge treatments.}, journal = {Expert opinion on pharmacotherapy}, volume = {26}, number = {1}, pages = {75-84}, doi = {10.1080/14656566.2024.2438322}, pmid = {39628270}, issn = {1744-7666}, mesh = {Humans ; *Pulmonary Fibrosis/etiology/drug therapy ; *COVID-19/complications ; Antifibrotic Agents/therapeutic use ; Tomography, X-Ray Computed ; }, abstract = {INTRODUCTION: Pulmonary fibrosis (PF) post-COVID-19 has been identified as an important complication of Long-COVID, especially in patients with severe respiratory symptoms. High-resolution computed tomography (HRCT) is the main tool for detecting fibrotic lesions in patients with PF post-COVID-19.<br><br>AREAS COVERED: We conducted a systematic review with the following objectives: (1) to summarize the incidence and disease burden of post&#x2011;COVID&#x2011;19 pulmonary fibrosis, (2) to provide information on available therapies and drugs for its management, (3) to comprehensively evaluate the initial treatment efficacy of these drugs, and (4) to identify the limitations and challenges associated with current treatment approaches.<br><br>EXPERT OPINION: Cutting-edge treatments for PF post-COVID-19 are focused on the complex and multifactorial nature of the disease progreession during Long COVID, which involves chronic inflammation, fibroblast activation, and excessive extracellular matrix deposition leading to stiffening and fibrosis of lung tissue. While traditional antifibrotic drugs with nintedanid and pirfenidone are being used, novel therapies with anti-interleukines, mesenchymal stem cells, and Rho-kinase inhibitors promise the new treatment approaches for patients with PF post-COVID-19. Further research and clinical trials are needed to determine the most effective strategies for managing this complex condition, with the goal of improving patient outcomes and quality of life.}, }
@article {pmid39628552, year = {2024}, author = {Dehghan, M and Mirzohreh, ST and Kaviani, R and Yousefi, S and Pourmehran, Y}, title = {A deeper look at long-term effects of COVID-19 on myocardial function in survivors with no prior heart diseases: a GRADE approach systematic review and meta-analysis.}, journal = {Frontiers in cardiovascular medicine}, volume = {11}, number = {}, pages = {1458389}, pmid = {39628552}, issn = {2297-055X}, abstract = {OBJECTIVES: The COVID-19 pandemic has challenged global health systems since December 2019, with the novel virus SARS-CoV-2 causing multi-systemic disease, including heart complications. While acute cardiac effects are well-known, long-term implications are understudied. This review hopes to fill a gap in the literature and provide valuable insights into the long-term cardiac consequences of the virus, which can inform future public health policies and clinical practices.<br><br>METHODS: This systematic review was prepared using PRISMA reporting guidelines. The databases searched were PubMed, Scopus, Web of Science, and Cochrane. Risk of Bias was assessed using ROBINS-I. The GRADE approach was employed to evaluate the level of certainty in the evidence for each outcome. A meta-analysis was conducted using the Comprehensive Meta-Analysis (CMA) software. In order to identify the underlying cause of high heterogeneity, a subgroup analysis was conducted. Sensitivity analysis was checked.<br><br>RESULTS: Sixty-six studies were included in this review. Thirty-two of them enrolled in meta-analysis and the rest in qualitative synthesis. Most outcomes showed a moderate certainty of evidence according to the GRADE framework. Post-COVID individuals with no prior heart diseases showed significant changes in left ventricular (LV) and right ventricular (RV) echocardiographic indices compared to controls. These significant findings were seen in both post-acute and long-COVID survivors regardless of the severity of initial infection.<br><br>CONCLUSION: This review implies that individuals recovering from post-acute and long-term effects of COVID-19 may experience changes in myocardial function as a result of the novel coronavirus. These changes, along with cardiac symptoms, have been observed in patients without prior heart diseases or comorbidities.<br><br>PROSPERO, identifier (CRD42024481337).}, }
@article {pmid39635815, year = {2024}, author = {Tényi, D and Tényi, T and Janszky, J}, title = {[Long COVID - neurological or somatoform disease?].}, journal = {Ideggyogyaszati szemle}, volume = {77}, number = {11-12}, pages = {397-405}, doi = {10.18071/isz.77.0397}, pmid = {39635815}, issn = {0019-1442}, mesh = {Humans ; *COVID-19/complications/psychology ; *Somatoform Disorders/psychology ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Nervous System Diseases/virology ; }, abstract = {BACKGROUND AND PURPOSE: Post-COVID condition (also known as long COVID) is a syndrome characterized by persistent symptoms following a suspected or confirmed SARS-CoV-2 infection, lasting for at least two months and are not attributable to other conditions. The most common symptoms include fatigue, diffuse pain, post-exertional malaise and “brain fog” (impairment of memory and concentration). The pathomechanism of long COVID is the subject of ongoing, intensive research. Our purpose was to review the literature on the pathomechanism of long COVID.<br><br>METHODS: We reviewed original and review articles in Hungarian and English on the pathomechanism of long COVID, published between January 2019 and June 2024, in the PubMed and Google Scholar databases.<br><br>RESULTS: Potential underlying causes of the symptoms are outlined in three main theories. 1) The concept of &#x201c;long COVID as a distinct neurological disease&#x201d; suggests that direct viral neuroinvasion, apoptosis, and demyelination processes are responsible for the symptoms. 2) The theory of &#x201c;long COVID as a systemic disease with neurological symptoms&#x201d; is based on the virus induced, prolonged cytokine and chemokine release, as well as the reactivation of latent viral infections. 3) According to the concept of &#x201c;long COVID as a somatoform disorder&#x201d;, the disease results from abnormal activation of the proinflammatory cytokine network leading to central nervous system sensitization, a well-known psychoneuroimmunological mechanism. Our study highlighted significant overlaps between long COVID and conditions such as chronic fatigue syndrome/myalgic encephalomyelitis, a group of symptoms not defined as a distinct mental disorder in DSM-5, but commonly referred to as Gulf War syndrome, chronic Lyme disease and somatic symptom disorder.<br><br>CONCLUSION: The pathomechanism of long COVID, which presents with a wide range of nonspecific symptoms, remains unknown, and no reproducible disease-specific biomarker has been identified to date. Clarifying the etiology of the disease is crucial for determining adequate and effective therapeutic methods.}, }
@article {pmid39639607, year = {2025}, author = {Adilović, M and Hromić-Jahjefendić, A and Mahmutović, L and Šutković, J and Rubio-Casillas, A and Redwan, EM and Uversky, VN}, title = {Intrinsic Factors Behind the Long-COVID: V. Immunometabolic Disorders.}, journal = {Journal of cellular biochemistry}, volume = {126}, number = {1}, pages = {e30683}, doi = {10.1002/jcb.30683}, pmid = {39639607}, issn = {1097-4644}, mesh = {Humans ; *COVID-19/immunology/complications/metabolism/pathology/virology ; *SARS-CoV-2/immunology ; Cytokines/metabolism/immunology ; Mitochondria/metabolism/immunology ; Inflammation/immunology/metabolism ; Cytokine Release Syndrome/immunology ; *Metabolic Diseases/immunology/metabolism ; }, abstract = {The complex link between COVID-19 and immunometabolic diseases demonstrates the important interaction between metabolic dysfunction and immunological response during viral infections. Severe COVID-19, defined by a hyperinflammatory state, is greatly impacted by underlying chronic illnesses aggravating the cytokine storm caused by increased levels of Pro-inflammatory cytokines. Metabolic reprogramming, including increased glycolysis and altered mitochondrial function, promotes viral replication and stimulates inflammatory cytokine production, contributing to illness severity. Mitochondrial metabolism abnormalities, strongly linked to various systemic illnesses, worsen metabolic dysfunction during and after the pandemic, increasing cardiovascular consequences. Long COVID-19, defined by chronic inflammation and immune dysregulation, poses continuous problems, highlighting the need for comprehensive therapy solutions that address both immunological and metabolic aspects. Understanding these relationships shows promise for effectively managing COVID-19 and its long-term repercussions, which is the focus of this review paper.}, }
@article {pmid39639960, year = {2024}, author = {Miller, CM and Borre, C and Green, A and Funaro, M and Oliveira, CR and Iwasaki, A}, title = {Postacute Sequelae of COVID-19 in Pediatric Patients Within the United States: A Scoping Review.}, journal = {American journal of medicine open}, volume = {12}, number = {}, pages = {100078}, pmid = {39639960}, issn = {2667-0364}, support = {K23 AI159518/AI/NIAID NIH HHS/United States ; TL1 TR001864/TR/NCATS NIH HHS/United States ; }, abstract = {A subset of children and adolescents experience recurrent or persistent symptoms following SARS-CoV-2 infection, known as postacute sequelae of COVID-19 (PASC), however, the clinical epidemiology within the United States (US) is not yet well understood. This scoping review aims to synthesize the clinical epidemiology of pediatric PASC in the US. A comprehensive literature search was conducted and databases were queried from inception until January 29, 2024. Studies including US children and adolescents <21 years old were considered. From 1028 studies identified, 29 met the inclusion criteria. Prevalence of PASC ranged from less than 1%-27%. Risk factors included older age, female sex, asthma, obesity, and severe initial infection. Common symptoms were dyspnea, fatigue, headaches, and chest pain. A multidisciplinary approach for diagnosis and management was common across studies. Most studies had a high risk of bias and were limited by a lack of standardized definitions and short follow-up duration. This review establishes a foundation for understanding pediatric PASC and highlights the critical need for continued research to optimize prevention and treatment strategies.}, }
@article {pmid39651728, year = {2025}, author = {Francavilla, F and Intranuovo, F and La Spada, G and Lacivita, E and Catto, M and Graps, EA and Altomare, CD}, title = {Inflammaging and Immunosenescence in the Post-COVID Era: Small Molecules, Big Challenges.}, journal = {ChemMedChem}, volume = {20}, number = {6}, pages = {e202400672}, pmid = {39651728}, issn = {1860-7187}, mesh = {Humans ; *Immunosenescence/drug effects ; *Inflammation/drug therapy/immunology ; *COVID-19/immunology ; SARS-CoV-2 ; *COVID-19 Drug Treatment ; *Anti-Inflammatory Agents/pharmacology/therapeutic use/chemistry ; Monoamine Oxidase Inhibitors/pharmacology/therapeutic use/chemistry ; *Small Molecule Libraries/pharmacology/chemistry/therapeutic use ; Aging ; Animals ; }, abstract = {Aging naturally involves a decline in biological functions, often triggering a disequilibrium of physiological processes. A common outcome is the altered response exerted by the immune system to counteract infections, known as immunosenescence, which has been recognized as a primary cause, among others, of the so-called long-COVID syndrome. Moreover, the uncontrolled immunoreaction leads to a state of subacute, chronic inflammatory state known as inflammaging, responsible in turn for the chronicization of concomitant pathologies in a self-sustaining process. Anti-inflammatory and immunosuppressant drugs are the current choice for the therapy of inflammaging in post-COVID complications, with contrasting results. The increasing knowledge of the biochemical pathways of inflammaging led to disclose new small molecules-based therapies directed toward different biological targets involved in inflammation, immunological response, and oxidative stress. Herein, paying particular attention to recent clinical data and preclinical literature, we focus on the role of endocannabinoid system in inflammaging, and the promising therapeutic option represented by the CB2R agonists, the role of novel ligands of the formyl peptide receptor 2 and ultimately the potential of newly discovered monoamine oxidase (MAO) inhibitors with neuroprotective activity in the treatment of immunosenescence.}, }
@article {pmid39653343, year = {2024}, author = {Gupte, A and Sriram, S and Gunasekaran, V and Chaudhari, K and Kamat, D}, title = {The Triad of COVID-19 in Children: Acute COVID-19, Multisystem Inflammatory Syndrome, and Long COVID-Part I.}, journal = {Pediatric annals}, volume = {53}, number = {12}, pages = {e473-e477}, doi = {10.3928/19382359-20241003-03}, pmid = {39653343}, issn = {1938-2359}, mesh = {Humans ; *COVID-19/complications/epidemiology ; *Systemic Inflammatory Response Syndrome/diagnosis/physiopathology ; Child ; Infant ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Mucocutaneous Lymph Node Syndrome/diagnosis ; }, abstract = {The coronavirus disease 2019 (COVID-19) originated in Wuhan, China, in late 2019. Within a span of a few months, it was deemed a global pandemic by the World Health Organization. It was first thought to affect the adult population, but soon after, cases of COVID-19 in children started emerging. As more and more pediatric cases started unveiling, an entity called multisystem inflammatory syndrome in children (MIS-C) that replicated Kawasaki disease was established. More recently, it has been noted that children have persistent symptoms for weeks or months after acute COVID-19 infection, and the term coined for these symptoms is "long COVID." This section of the review will summarize the respiratory, cardiovascular, dermatological, and gastroenterological manifestations noted in infants in three broad categories: acute COVID, MIS-C, and long COVID. [Pediatr Ann. 2024;53(12):e473-e477.].}, }
@article {pmid39654800, year = {2024}, author = {Li, R and Liu, W and Liu, D and Jin, X and Wang, S}, title = {The involvement of the dysfunctional insulin receptor signaling system in long COVID patients with diabetes and chronic pain and its implications for the clinical management using taVNS.}, journal = {Frontiers in pain research (Lausanne, Switzerland)}, volume = {5}, number = {}, pages = {1486851}, pmid = {39654800}, issn = {2673-561X}, abstract = {In clinical terms, chronic pain is the most prevalent sequela resulting from COVID-19, which is induced by the novel coronavirus (SARS-CoV-2), while type 2 diabetes mellitus (T2D) is the most common comorbidity. This triangular relationship can be attributed to the dysfunction of the insulin receptor signaling system (IRSS) in both central and peripheral systems. Patients with T2D are essentially more susceptible to SARS-CoV-2 infection due to the widespread expression of angiotensin converting enzyme 2 (ACE2) in their pancreatic beta cells, which serves as the cellular port for the SARS-CoV-2 to infect and enter the cell. This infection can exacerbate chronic pain and insulin resistance for various reasons. Peripherally, once infected, the virus can cause damage to peripheral nerves and pancreatic β-cells, further exacerbating pain and glucose metabolism conditions. Additionally, in the central nervous system, dysfunctional IRSS is closely linked to chronic pain. Over the past few years of the COVID-19 pandemic, an increasing body of evidence suggests that insulin and other medications currently used in clinical practice for hyperglycemia control may not be safe for treating these patients. Therefore, we need a proper approach for the treatment of chronic pain in long COVID patients, especially patients with T2D. This review presents evidence that transcutaneous auricular vagal nerve stimulation (taVNS) may provide a viable treatment option for chronic pain and metabolic dysfunction by improving the function of IRSS in both the central nervous system and peripheral tissues.}, }
@article {pmid39657574, year = {2025}, author = {Fernández-García, JM and Romero-Secin, A and Rubín-García, M}, title = {[Association between obesity and Long-Covid: A narrative review].}, journal = {Semergen}, volume = {51}, number = {3}, pages = {102390}, doi = {10.1016/j.semerg.2024.102390}, pmid = {39657574}, issn = {1578-8865}, mesh = {Humans ; *COVID-19/complications/epidemiology/physiopathology ; *Obesity/complications/epidemiology ; Risk Factors ; }, abstract = {To analyze the evidence in the scientific literature that relates Long-Covid and obesity, a narrative review of articles published in English and Spanish in Medline and Embase in the last 5years has been carried out. Infection with the SARS-CoV-2 virus causes a systemic inflammatory state increasing nutritional demand that favors sarcopenia in Long-Covid syndrome. It also causes endothelial dysfunction and a prothrombotic state that favors the formation of microthrombi and tissue hypoxia. A healthy and balanced diet is essential to treat obesity in addition to modifying the microbiota in Long-Covid and promoting physical and mental well-being. Obesity is an independent risk factor that increases the need for hospitalization, cardiovascular risk and mortality, as well as susceptibility to Long-Covid. Adipose tissue is a good reservoir of the virus, enhancing the comorbidities associated with obesity (high blood pressure, diabetes mellitus, dyslipidemia or fatty liver). There is insufficient evidence to recommend nutritional supplements to improve Long-Covid symptoms.}, }
@article {pmid39658729, year = {2025}, author = {Treadwell, JR and Wagner, J and Reston, JT and Phillips, T and Hedden-Gross, A and Tipton, KN}, title = {Treatments for Long COVID autonomic dysfunction: a scoping review.}, journal = {Clinical autonomic research : official journal of the Clinical Autonomic Research Society}, volume = {35}, number = {1}, pages = {5-29}, pmid = {39658729}, issn = {1619-1560}, support = {MSA-SOW#06-ECRI-ENG-10-02-2023/PCORI/Patient-Centered Outcomes Research Institute/United States ; }, mesh = {Humans ; *COVID-19/complications/therapy ; *Autonomic Nervous System Diseases/therapy/etiology/physiopathology ; SARS-CoV-2 ; }, abstract = {PURPOSE: For Long COVID autonomic dysfunction, we have summarized published evidence on treatment effectiveness, clinical practice guidelines, and unpublished/ongoing studies.<br><br>METHODS: We first interviewed 11 stakeholders (clinicians, clinician/researchers, payors, patient advocates) to gain clinical insights and identify key areas of focus. We searched Embase, CINAHL, Medline, PsycINFO, and PubMed databases for relevant English-language articles published between 1 January 2020 and 30 April 2024. We also searched several other resources for additional relevant guidelines (e.g., UpToDate) and unpublished/ongoing studies (e.g., the International Clinical Trials Registry Platform). All information was summarized narratively.<br><br>RESULTS: We included 11 effectiveness studies that investigated numerous treatment regimens (fexofenadine&#x2009;+&#x2009;famotidine, maraviroc&#x2009;+&#x2009;pravastatin, selective serotonin reuptake inhibitors, nutraceutical formulations, multicomponent treatments, heart rate variability biofeedback, inspiratory muscle training, or stellate ganglion block). One randomized trial reported benefits of a nutraceutical (SIM01) on fatigue and gastrointestinal upset. The 11 guidelines and position statements addressed numerous aspects of treatment, but primarily exercise/rehabilitation, fluid/salt intake, and the use of compression garments. The 15 unpublished/ongoing studies are testing nine different interventions, most prominently ivabradine and intravenous immunoglobulin.<br><br>CONCLUSION: Existing studies on the treatment of Long COVID autonomic dysfunction are often small and uncontrolled, making it unclear whether the observed pre-post changes were due solely to the administered treatments. Guidelines display some overlap, and we identified no direct contradictions. Unpublished/ongoing studies may shed light on this critical area of patient management.}, }
@article {pmid39660101, year = {2025}, author = {Toussaint, A and Weigel, A and Löwe, B and , }, title = {The overlooked burden of persistent physical symptoms: a call for action in European healthcare.}, journal = {The Lancet regional health. Europe}, volume = {48}, number = {}, pages = {101140}, pmid = {39660101}, issn = {2666-7762}, abstract = {Regardless of their cause, persistent physical symptoms are distressing somatic complaints that occur on most days for at least several months. They are common in patients with somatic diseases, functional somatic disorders, mental disorders, and undiagnosed medical conditions and are often associated with significant impairment and medical costs. Despite their prevalence and impact, persistent physical symptoms are often overlooked in medical care. This Personal View stresses the importance of recognising persistent physical symptoms as a European health issue. It advocates improvements in research, clinical management, public health, and policy. Efforts should prioritise integrating models of symptom perception and biopsychosocial perspectives into medical care and education, fostering interdisciplinary collaboration, and developing standardised guidelines to enhance patient care, reduce stigma, and improve clinical outcomes. Increased research funding can accelerate progress in understanding and effectively managing persistent physical symptoms. Addressing these priorities will support patients and healthcare professionals, ensuring adequate care and a higher quality of life for affected individuals.}, }
@article {pmid39662824, year = {2025}, author = {Górska, A and Canziani, LM and Rinaldi, E and Pana, ZD and Beale, S and Bai, F and Boxma-de Klerk, BM and de Bruijn, S and Donà, D and Ekkelenkamp, MB and Incardona, F and Mallon, P and Marchetti, GC and Puhan, M and Riva, A and Simensen, VC and Vaillant, M and van der Zalm, MM and van Kuijk, SMJ and Wingerden, SV and Judd, A and Tacconelli, E and Peñalvo, JL}, title = {Learning from post-COVID-19 condition for epidemic preparedness: a variable catalogue for future post-acute infection syndromes.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {31}, number = {3}, pages = {380-388}, doi = {10.1016/j.cmi.2024.12.001}, pmid = {39662824}, issn = {1469-0691}, mesh = {Humans ; *COVID-19/epidemiology/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Europe/epidemiology ; Pandemics ; Pandemic Preparedness ; }, abstract = {SCOPE: The emergence of post-COVID-19 condition (PCC) after SARS-CoV-2 infection underscores the critical need for preparedness in addressing future post-acute infection syndromes (PAIS), particularly those linked to epidemic outbreaks. The lack of standardized clinical and epidemiological data during the COVID-19 pandemic has significantly hindered timely diagnosis and effective treatment of PCC, highlighting the necessity of pre-emptively standardizing data collection in clinical studies to better define and manage future PAIS. In response, the Cohort Coordination Board, a consortium of European-funded COVID-19 research projects, has reviewed data from PCC studies conducted by its members. This paper leverages the Cohort Coordination Board's expertise to propose a standardized catalogue of variables, informed by the lessons learned during the pandemic, intended for immediate use in the design of future observational studies and clinical trials for emerging infections of epidemic potential.<br><br>RECOMMENDATIONS: The early implementation of standardized data collection, facilitated by the PAIS data catalogue, is essential for accelerating the identification and management of PAIS in future epidemics. This approach will enable more precise syndrome definitions, expedite diagnostic processes, and optimize treatment strategies, while also supporting long-term follow-up of affected individuals. The availability of harmonized data collection protocols will enhance preparedness across European and international cohort studies, and trials enabling a prompt and coordinated response, as well as more efficient resource allocation, in the event of emerging infections and associated PAIS.}, }
@article {pmid39663173, year = {2024}, author = {Thomas, B and Pattinson, R and Edwards, D and Dale, C and Jenkins, B and Lande, H and Bundy, C and Davies, J}, title = {Defining and measuring long COVID fatigue: a scoping review.}, journal = {BMJ open}, volume = {14}, number = {12}, pages = {e088530}, pmid = {39663173}, issn = {2044-6055}, mesh = {Humans ; *COVID-19/complications ; *Fatigue/etiology/diagnosis ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: Long COVID encompasses a range of symptoms in which fatigue is one of the most prevalents. It is clear from other conditions that the definition and measurement of fatigue can be complex, but it is not clear how fatigue is defined and measured in long COVID. To advance our understanding, this review summarises the definitions and measures of long COVID fatigue being used by researchers.<br><br>DESIGN: Scoping review following JBI methodology and reports using the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews.<br><br>DATA SOURCES: Medline, Scopus, CINAHL, PsycINFO, EMCARE, Web of Science, Epistemonikos, Cochrane Central Register of Controlled Trials, Dimensions, Overton and ProQuest Dissertation &amp; Theses Database were searched from January 2020 to May 2023.<br><br>ELIGIBILITY CRITERIA: This review included quantitative and qualitative studies that included any definition of long COVID and/or measurement tool that purported to quantify either the impact, severity or symptoms of long COVID fatigue.<br><br>DATA EXTRACTION AND SYNTHESIS: Two independent reviewers screened the title, abstracts and full texts of the selected studies based on the inclusion criteria. Data extraction was performed by two independent reviewers. The data were summarised in tabular format and a narrative summary.<br><br>RESULTS: The search retrieved 9839 studies, of which 57 met the inclusion criteria. Only 21 (37%) provided a definition of fatigue. Definitions ranged across physical, mental, cognitive, emotional, psychosocial, central, peripheral, postexertional symptom exacerbation and general dimensions of fatigue. Fifty-five (96%) used a measurement or assessment of fatigue. Twenty-six measures of fatigue were identified: 21 self-report measures (eg, Fatigue Assessment Scale) and five fatigability measures that purport to reflect changes in physiological processes that contribute to or reflect fatigue (eg, change in force generating capacity of a muscle).<br><br>CONCLUSIONS: The definitions identified demonstrate considerable diversity, each highlighting different dimensions of long COVID fatigue. Long COVID fatigue was predominantly measured through self-report methods, which were problematic. There is an urgent need to better understand long COVID fatigue and to identify the different mechanisms involved. In order to do this, we need consistency with the language around fatigue and its measurement within research and across disciplines.<br><br>REVIEW REGISTRATION: The protocol has been registered on open science framework (https://doi.org/10.17605/OSF.IO/HNF8Z).}, }
@article {pmid39665720, year = {2025}, author = {Brahimi, N and Croitoru, D and Saidoune, F and Zabihi, H and Gilliet, M and Piguet, V}, title = {From Viral Infection to Skin Affliction: Unveiling Mechanisms of Cutaneous Manifestations in COVID-19 and Post-COVID Conditions.}, journal = {The Journal of investigative dermatology}, volume = {145}, number = {2}, pages = {257-265}, doi = {10.1016/j.jid.2024.03.047}, pmid = {39665720}, issn = {1523-1747}, mesh = {Humans ; *COVID-19/complications/immunology/virology ; *SARS-CoV-2/immunology ; *Skin/pathology/immunology/virology ; *Skin Diseases/virology/immunology ; *Skin Diseases, Viral/immunology ; Interferon Type I/immunology/metabolism ; }, abstract = {COVID-19 skin manifestations are multifaceted, ranging from urticaria, morbilliform or papulovesicular rash, livedoid purpuric lesions, and to pseudochilblains (also called COVID toes). Recent insights into the mechanism of these manifestations have highlighted that morbilliform, papulovesicular, and livedoid/purpuric rashes are related to virus-induced endothelial cell damage and linked to moderate-to-severe disease, whereas pseudochilblains are related to an exaggerated IFN-1 production by plasmacytoid dendritic cells in protected individuals. In this paper, we will review the clinical and physiopathological features of cutaneous COVID-19 manifestations in relation to the direct viral cytopathic effects and dysregulated IFN-1 responses. We will also review the emerging insights into post-COVID conditions (also termed long COVID) and how they may be implicated in the persistence of COVID-19-associated skin diseases.}, }
@article {pmid39667587, year = {2025}, author = {Romanet, C and Wormser, J and Cachanado, M and Santiago, MG and Chatellier, G and Valenza, MC and Philippart, F}, title = {Effectiveness of physiotherapy modalities on persisting dyspnoea in long COVID: A systematic review and meta-analysis.}, journal = {Respiratory medicine}, volume = {236}, number = {}, pages = {107909}, doi = {10.1016/j.rmed.2024.107909}, pmid = {39667587}, issn = {1532-3064}, mesh = {Adult ; Humans ; *Dyspnea/etiology/psychology/therapy ; *Physical Therapy Modalities ; *Post-Acute COVID-19 Syndrome/complications/psychology/therapy ; Quality of Life ; Randomized Controlled Trials as Topic ; SARS-CoV-2 ; Treatment Outcome ; }, abstract = {BACKGROUND: Dyspnoea is often found months and years later in the "long-covid" syndrome, impairing quality of life and further perpetuating anxiety and post-traumatic stress disorders. Physiotherapy was recommended as a treatment in long-covid, but there is still insufficient evidence on its effectiveness.<br><br>METHODS: We conducted a systematic literature search on MEDLINE, PEDro, WOS, Scopus, VHL and the Cochrane Library until July 2023 (PROSPERO registration number: CRD42023427464). We selected comparative trials including adults with persistent breathlessness following COVID-19, regardless of the initial severity, for whom physiotherapy was implemented as a treatment for dyspnoea. We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and assessed the study quality using the PEDro Scale.<br><br>RESULTS: 19 studies that included 1292 adults fulfilled the inclusion criteria, of which 15 were randomised controlled trials and 4 non-randomised controlled trials. As for the rehabilitation modalities, 6 studies used respiratory muscle training, 6 studies used low to moderate intensity rehabilitation, 6 used high intensity rehabilitation and one used passive rehabilitation. The methods used between and within each group differed greatly, leading to an expected high heterogeneity of results. Nethertheless the random-effects model found a significant difference favouring physiotherapy (SMD -0.63, 95 CI [-1.03; -0.24], p&#xa0;<&#xa0;0.001, I[2]&#xa0;=&#xa0;88&#xa0;%). Subgroup analysis showed a significant effect in the high intensity rehabilitation group alone, with null heterogeneity.<br><br>CONCLUSION: In people suffering from dyspnoea following a SARS-CoV-2 infection, physiotherapy and especially pulmonary rehabilitation may help alleviate respiratory symptoms. Future studies will need to provide more consistent rehabilitation methods and better descriptions of them so as to reveal clear effects and avoid the confusion caused by using too many rehabilitation modalities.}, }
@article {pmid39678231, year = {2024}, author = {Khan, MWZ and Ahmad, M and Qudrat, S and Afridi, F and Khan, NA and Afridi, Z and Fahad,  and Azeem, T and Ikram, J}, title = {Vagal nerve stimulation for the management of long COVID symptoms.}, journal = {Infectious medicine}, volume = {3}, number = {4}, pages = {100149}, pmid = {39678231}, issn = {2772-431X}, abstract = {This review investigates the therapeutic potential of vagal nerve stimulation (VNS) in managing long COVID, a condition marked by persistent symptoms following acute SARS-CoV-2 infection. Long COVID manifests as ongoing fatigue, cognitive impairment, and autonomic dysfunction, hypothesized to arise from sustained inflammatory and neurological dysregulation. The vagus nerve, central to modulating systemic inflammation and autonomic homeostasis, represents a promising therapeutic target for symptom alleviation through VNS. A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science to identify studies evaluating VNS in the context of long COVID. Preliminary evidence from small-scale pilot studies suggests VNS may attenuate systemic inflammation through activation of the cholinergic anti-inflammatory pathway (CAP), thus restoring autonomic balance and ameliorating symptoms such as fatigue, cognitive dysfunction, and anxiety. In targeting the inflammatory cascade that underlies both acute COVID-19 pathophysiology and its prolonged sequelae, VNS holds potential as an innovative intervention for persistent post-viral symptoms. While these initial findings indicate promise, current data remain limited in scope and robustness, underscoring the need for larger, controlled trials to validate the efficacy and mechanisms of VNS in long COVID management. Establishing a clearer understanding of VNS's impact on inflammation and autonomic regulation in this context is crucial to inform clinical guidelines and therapeutic strategies for long COVID, potentially offering a targeted approach for mitigating this disabling condition.}, }
@article {pmid39680873, year = {2025}, author = {Díaz de León-Martínez, L and Flores-Rangel, G and Alcántara-Quintana, LE and Mizaikoff, B}, title = {A Review on Long COVID Screening: Challenges and Perspectives Focusing on Exhaled Breath Gas Sensing.}, journal = {ACS sensors}, volume = {10}, number = {3}, pages = {1564-1578}, pmid = {39680873}, issn = {2379-3694}, mesh = {Humans ; *COVID-19/diagnosis/metabolism ; Breath Tests/methods ; *Volatile Organic Compounds/analysis ; SARS-CoV-2/isolation &amp; purification ; Electronic Nose ; Exhalation ; Biomarkers/analysis ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long COVID (LC) is a great global health concern, affecting individuals recovering from SARS-CoV-2 infection. The persistent and varied symptoms across multiple organs complicate diagnosis and management, and an incomplete understanding of the condition hinders advancements in therapeutics. Current diagnostic methods face challenges related to standardization and completeness. To overcome this, new technologies such as sensor-based electronic noses are being explored for LC assessment, offering a noninvasive screening approach via volatile organic compounds (VOC) sensing in exhaled breath. Although specific LC-associated VOCs have not been fully characterized, insights from COVID-19 research suggest their potential as biomarkers. Additionally, AI-driven chemometrics are promising in identifying and predicting outcomes; despite challenges, AI-driven technologies hold the potential to enhance LC evaluation, providing rapid and accurate diagnostics for improved patient care and outcomes. This review underscores the importance of emerging and sensing technologies and comprehensive diagnostic strategies to address screening and treatment challenges in the face of LC.}, }
@article {pmid39685583, year = {2024}, author = {Serapide, F and Talarico, M and Rotundo, S and Pascale, V and Serraino, R and Trecarichi, EM and Russo, A}, title = {Lights and Shadows of Long COVID: Are Latent Infections the Real Hidden Enemy?.}, journal = {Journal of clinical medicine}, volume = {13}, number = {23}, pages = {}, pmid = {39685583}, issn = {2077-0383}, abstract = {Long COVID-19 (LC) is a poorly understood, multifactorial condition that persists for at least three months following SARS-CoV-2 infection. The underlying pathophysiological mechanisms responsible for the wide range of associated symptoms-including fatigue, brain fog, and respiratory issues-remain unclear. However, emerging evidence suggests that the reactivation of latent viral infections, such as Epstein-Barr virus, cytomegalovirus, and varicella-zoster virus, may significantly contribute to the complexity of LC. These latent viruses can be reactivated by SARS-CoV-2, contributing to a chronic inflammatory state that prolongs symptomatology. This review confirms the potential involvement of latent viral infections in LC and examines whether these infections play an independent role or act synergistically with other factors. In addition, recent studies have highlighted viral persistence and immune dysregulation as key elements in LC. Our findings suggest that preventative strategies, including vaccination and antiviral treatments during the acute phase of COVID-19, show potential in reducing LC risk by preventing viral reactivation. However, tailored diagnostic and therapeutic strategies targeting these latent infections are urgently needed. Identifying biomarkers of viral reactivation, particularly for high-risk populations, could be considered another effective strategy to mitigate LC severity. Further research is crucial to better understand the interactions between SARS-CoV-2 and latent infections, and to improve the prevention and treatment of LC.}, }
@article {pmid39693583, year = {2025}, author = {Nath, A and Kolson, DL}, title = {Reemerging Infectious Diseases and Neuroimmunologic Complications.}, journal = {Neurology(R) neuroimmunology &amp; neuroinflammation}, volume = {12}, number = {1}, pages = {e200356}, pmid = {39693583}, issn = {2332-7812}, support = {R01 NS122570/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Communicable Diseases, Emerging/complications ; COVID-19/complications ; HIV Infections/complications ; }, abstract = {During the past decade (and beyond), neurologists have become aware of the emergence, persistence, and consequences of some familiar and new infections affecting the nervous system. Even among the familiar CNS infections, such as herpes virus, polyoma virus/JC, influenza, arbovirus, and hepatitis, challenges remain in developing effective antiviral treatments and treatments of postinfection sequelae. With the changing environment and increased global travel, arthropod vectors that mediate zoonotic disease transmission have spread unfamiliar viruses such as West Nile virus, dengue, chikungunya, equine encephalitis, and Zika, among others. Although the global health impact of these diseases has not risen to that of COVID-19 and HIV, it is likely to dramatically increase with continued spread of transmission vectors and the emergence of new zoonotic animal-to-human diseases mediated by those transmission vectors. Furthermore, specific virus-targeting treatments or effective vaccines for arboviral infections are not yet available, and this represents a major challenge in limiting the morbidity of these infections. By contrast, HIV-1, a disease that originated by direct transmission from nonhuman primates to humans (as early as the 1930s), after many years of intense study, is now targeted by highly specific and effective antiviral drugs that can limit the spread of infection and extend human life and health in all populations. Even with these dramatic therapeutic effects of suppressing HIV replication, neurologic dysfunction (primarily cognitive impairment) affects significant numbers of persons living with HIV. This emphasizes not only the importance of treating the underlying infection but also developing treatments for legacy effects of the initial infection even after antiviral therapy. Notably, the rapid emergence of SARS-CoV-2 infection was met with rapid implementation of highly effective and specific antiviral therapies. This resulted in early and dramatic lowering of the morbidity and mortality of SARS-CoV-2 infection. Nonetheless, the postinfectious complications of SARS-CoV-2 infection (long COVID) are now among the more costly consequences of emerging zoonotic infections worldwide. Developing new antiviral therapies that can penetrate the CNS, vaccines, and therapies that target host immune responses and metabolic dysfunction will be necessary for management of infectious and postinfectious complications of established and emerging infections.}, }
@article {pmid39694730, year = {2025}, author = {Charlton, BT and Goulding, RP and Jaspers, RT and Appelman, B and van Vugt, M and Wüst, RCI}, title = {Skeletal muscle adaptations and post-exertional malaise in long COVID.}, journal = {Trends in endocrinology and metabolism: TEM}, volume = {36}, number = {7}, pages = {614-622}, doi = {10.1016/j.tem.2024.11.008}, pmid = {39694730}, issn = {1879-3061}, mesh = {Humans ; *COVID-19/physiopathology/complications/metabolism ; *Muscle, Skeletal/physiopathology/metabolism ; SARS-CoV-2 ; *Adaptation, Physiological/physiology ; Post-Acute COVID-19 Syndrome ; Exercise/physiology ; *Physical Exertion/physiology ; }, abstract = {When acute SARS-CoV-2 infections cause symptoms that persist longer than 3 months, this condition is termed long COVID. Symptoms experienced by patients often include myalgia, fatigue, brain fog, cognitive impairments, and post-exertional malaise (PEM), which is the worsening of symptoms following mental or physical exertion. There is little consensus on the pathophysiology of exercise-induced PEM and skeletal-muscle-related symptoms. In this opinion article we highlight intrinsic mitochondrial dysfunction, endothelial abnormalities, and a muscle fiber type shift towards a more glycolytic phenotype as main contributors to the reduced exercise capacity in long COVID. The mechanistic trigger for physical exercise to induce PEM is unknown, but rapid skeletal muscle tissue damage and intramuscular infiltration of immune cells contribute to PEM-related symptoms.}, }
@article {pmid39697632, year = {2024}, author = {Fanelli, M and Petrone, V and Chirico, R and Radu, CM and Minutolo, A and Matteucci, C}, title = {Flow cytometry for extracellular vesicle characterization in COVID-19 and post-acute sequelae of SARS-CoV-2 infection.}, journal = {Extracellular vesicles and circulating nucleic acids}, volume = {5}, number = {3}, pages = {417-437}, pmid = {39697632}, issn = {2767-6641}, abstract = {Infection with SARS-CoV-2, the virus responsible for COVID-19 diseases, can impact different tissues and induce significant cellular alterations. The production of extracellular vesicles (EVs), which are physiologically involved in cell communication, is also altered during COVID-19, along with the dysfunction of cytoplasmic organelles. Since circulating EVs reflect the state of their cells of origin, they represent valuable tools for monitoring pathological conditions. Despite challenges in detecting EVs due to their size and specific cellular compartment origin using different methodologies, flow cytometry has proven to be an effective method for assessing the role of EVs in COVID-19. This review summarizes the involvement of plasmatic EVs in COVID-19 patients and individuals with Long COVID (LC) affected by post-acute sequelae of SARS-CoV-2 infection (PASC), highlighting their dual role in exerting both pro- and antiviral effects. We also emphasize how flow cytometry, with its multiparametric approach, can be employed to characterize circulating EVs, particularly in infectious diseases such as COVID-19, and suggest their potential role in chronic impairments during post-infection.}, }
@article {pmid39701919, year = {2025}, author = {Alderman, JE and Palmer, J and Laws, E and McCradden, MD and Ordish, J and Ghassemi, M and Pfohl, SR and Rostamzadeh, N and Cole-Lewis, H and Glocker, B and Calvert, M and Pollard, TJ and Gill, J and Gath, J and Adebajo, A and Beng, J and Leung, CH and Kuku, S and Farmer, LA and Matin, RN and Mateen, BA and McKay, F and Heller, K and Karthikesalingam, A and Treanor, D and Mackintosh, M and Oakden-Rayner, L and Pearson, R and Manrai, AK and Myles, P and Kumuthini, J and Kapacee, Z and Sebire, NJ and Nazer, LH and Seah, J and Akbari, A and Berman, L and Gichoya, JW and Righetto, L and Samuel, D and Wasswa, W and Charalambides, M and Arora, A and Pujari, S and Summers, C and Sapey, E and Wilkinson, S and Thakker, V and Denniston, A and Liu, X}, title = {Tackling algorithmic bias and promoting transparency in health datasets: the STANDING Together consensus recommendations.}, journal = {The Lancet. Digital health}, volume = {7}, number = {1}, pages = {e64-e88}, pmid = {39701919}, issn = {2589-7500}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Humans ; Algorithms ; Artificial Intelligence ; Bias ; Datasets as Topic ; *Delphi Technique ; }, abstract = {Without careful dissection of the ways in which biases can be encoded into artificial intelligence (AI) health technologies, there is a risk of perpetuating existing health inequalities at scale. One major source of bias is the data that underpins such technologies. The STANDING Together recommendations aim to encourage transparency regarding limitations of health datasets and proactive evaluation of their effect across population groups. Draft recommendation items were informed by a systematic review and stakeholder survey. The recommendations were developed using a Delphi approach, supplemented by a public consultation and international interview study. Overall, more than 350 representatives from 58 countries provided input into this initiative. 194 Delphi participants from 25 countries voted and provided comments on 32 candidate items across three electronic survey rounds and one in-person consensus meeting. The 29 STANDING Together consensus recommendations are presented here in two parts. Recommendations for Documentation of Health Datasets provide guidance for dataset curators to enable transparency around data composition and limitations. Recommendations for Use of Health Datasets aim to enable identification and mitigation of algorithmic biases that might exacerbate health inequalities. These recommendations are intended to prompt proactive inquiry rather than acting as a checklist. We hope to raise awareness that no dataset is free of limitations, so transparent communication of data limitations should be perceived as valuable, and absence of this information as a limitation. We hope that adoption of the STANDING Together recommendations by stakeholders across the AI health technology lifecycle will enable everyone in society to benefit from technologies which are safe and effective.}, }
@article {pmid39703608, year = {2024}, author = {Zollner, A and Meyer, M and Jukic, A and Adolph, T and Tilg, H}, title = {The Intestine in Acute and Long COVID: Pathophysiological Insights and Key Lessons.}, journal = {The Yale journal of biology and medicine}, volume = {97}, number = {4}, pages = {447-462}, pmid = {39703608}, issn = {1551-4056}, mesh = {Humans ; *COVID-19/physiopathology/virology/immunology ; *Gastrointestinal Microbiome/physiology ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; Brain-Gut Axis/physiology ; Intestines/virology/physiopathology/microbiology ; }, abstract = {Post-Acute Sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID, represents a significant and complex health challenge with a wide range of symptoms affecting multiple organ systems. This review examines the emerging evidence suggesting a critical role of the gut and gut-brain axis in the pathophysiology of Long COVID. It explores how changes in the gut microbiome, disruption of gut barrier integrity, and the persistence of SARS-CoV-2 antigens within the gastrointestinal tract may contribute to the prolonged and varied symptoms seen in Long COVID, including chronic inflammation and neuropsychiatric disturbances. The review also summarizes key insights gained about Long COVID, highlighting its multifactorial nature, which involves immune dysregulation, microvascular damage, and autonomic nervous system dysfunction, with the gut playing a central role in these processes. While progress has been made in understanding these mechanisms, current evidence remains inconclusive. The challenges of establishing causality, standardizing research methodologies, and addressing individual variations in the microbiome are discussed, emphasizing the need for further longitudinal studies and more comprehensive approaches to enhance our understanding of these complex interactions. This review underscores the importance of personalized approaches in developing effective diagnostic and therapeutic strategies for Long COVID, while also acknowledging the significant gaps in our current understanding. Future research should aim to further unravel the complex interplay between the gut and Long COVID, ultimately improving outcomes for those affected by this condition.}, }
@article {pmid39703612, year = {2024}, author = {Mathew, J and Nugent, K}, title = {Post-Acute Sequelae of SARS-CoV-2 Infections: Exercise Limitation and Rehabilitation.}, journal = {The Yale journal of biology and medicine}, volume = {97}, number = {4}, pages = {463-472}, pmid = {39703612}, issn = {1551-4056}, mesh = {Humans ; *COVID-19/complications/physiopathology ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; Exercise/physiology ; Exercise Tolerance/physiology ; Exercise Therapy/methods ; }, abstract = {Patients with prior SARS-CoV-2 infections can develop chronic symptoms; this clinical presentation has been called post-acute sequelae of SARS-CoV-2 infection, post-COVID condition, and long COVID. It can develop in both outpatient cases and in hospital cases; the frequency depends on the severity of infection and comorbidity. Many of these patients have exercise limitation when tested using cardiopulmonary exercise tests. The potential explanations for reduced exercise capacity include cardiac limitations, respiratory limitations, skeletal muscle weakness, deconditioning, and limiting symptoms out of proportion to any measured physiological limitation, and many patients have more than one explanation for the exercise limitation. Since these patients may have required prolonged hospitalization, deconditioning has been considered a potential explanation for their post-hospitalization limitations. Patients with deconditioning have a low oxygen uptake per minute (VO2) maximum with no obvious cardiac or respiratory limitation, but some do have measurable muscle weakness. One complex study reported that these patients had a high proportion of high-fatigable glycolytic fibers, reduced mitochondrial function, atrophic fibers, and focal necrosis in skeletal muscle. Some post-COVID patients have chronic fatigue and post-exertional malaise and meet the clinical criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Most patients with post-COVID syndrome do improve with conventional cardiopulmonary rehabilitation. However, patients with post-exertional malaise need special attention to their exercise programs and careful monitoring for adverse effects. In summary, patients with long COVID can have complex presentations with a broad range of symptoms and several possible exercise limitations. Their rehabilitation program should be based on their physical capacity and their symptom profile.}, }
@article {pmid39710927, year = {2025}, author = {Heidari, F and Farahighasreaboonasr, F and Hassan, ZM and Fazeli, P and Hosseini, M and Ebtekar, M}, title = {Annual SZ: An Alternative Immunotherapy for COVID-19 and Long COVID.}, journal = {Infectious disorders drug targets}, volume = {25}, number = {5}, pages = {e18715265323116}, pmid = {39710927}, issn = {2212-3989}, mesh = {Humans ; COVID-19/immunology ; *COVID-19 Drug Treatment ; Antibodies, Monoclonal, Humanized/therapeutic use ; Adenosine Monophosphate/analogs &amp; derivatives/therapeutic use ; SARS-CoV-2/drug effects ; *Antiviral Agents/therapeutic use ; Dexamethasone/therapeutic use ; Alanine/analogs &amp; derivatives/therapeutic use ; *Immunotherapy/methods ; Cytokine Release Syndrome/drug therapy ; }, abstract = {Since the outbreak of coronavirus disease 2019 (COVID-19) in late 2019 and early 2020, the identification of drugs to control severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its symptoms has been a pressing focus of research. Cytokine storm and acute respiratory distress syndrome (ARDS) are the leading causes of mortality following infection. In this review, we discuss immune pathogenesis and four medications, including Remdesivir, Tocilizumab, Dexamethasone, and Annual SZ for COVID-19. A comparison of the effectiveness and therapeutic usage of drugs as reported in clinical trials and reports was made at different disease levels as well. Clinical studies indicate that Annual SZ with mild side effects was more affordable and might be more effective than other medications. Additionally, Annual SZ was capable of reducing the levels of pro-inflammatory cytokines as well as viral attachment and RNA replication.}, }
@article {pmid39715694, year = {2025}, author = {Cáceres, E and Divani, AA and Viñan-Garces, AE and Olivella-Gomez, J and Quintero-Altare, A and Pérez, S and Reyes, LF and Sasso, N and Biller, J}, title = {Tackling persistent neurological symptoms in patients following acute COVID-19 infection: an update of the literature.}, journal = {Expert review of neurotherapeutics}, volume = {25}, number = {1}, pages = {67-83}, doi = {10.1080/14737175.2024.2440543}, pmid = {39715694}, issn = {1744-8360}, mesh = {Humans ; *COVID-19/complications/therapy ; *Nervous System Diseases/therapy ; Post-Acute COVID-19 Syndrome ; Quality of Life ; }, abstract = {INTRODUCTION: The COVID-19 pandemic has taught myriad lessons and left several questions we are yet to comprehend. Initially, the scientific community was concerned with the management of acute disease and immunization. Once the peak of the pandemic receded, it became clear that a proportion of patients were far from fully recovered. Researchers started to recognize those persisting symptoms as a new entity termed 'Long COVID,' where neurological symptoms are evident and have a major impact on quality of life.<br><br>AREAS COVERED: The main purpose of this narrative review is to analyze and synthesize the current literature regarding Long COVID, its relation to the nervous system, and to explore the evidence on treatments for persistent neurological symptoms. The most common reported and observed neurologic manifestations include fatigue, cognitive impairment, pain, polyneuropathy, and neuropsychiatric disorders. A variety of pharmacologic and non-pharmacologic therapies have been evaluated and yielded mixed results. Many of them focused on immunomodulation and none currently have U.S. FDA approval.<br><br>EXPERT OPINION: Challenges remain in terms of clinical characterization and prognosis of Long COVID, besides understanding its pathophysiology. Standardization of biomarkers and diagnostic criteria will allow the use of common nomenclature and data elements in the design of future clinical studies.}, }
@article {pmid39720706, year = {2024}, author = {Müller, L and Di Benedetto, S}, title = {The impact of COVID-19 on accelerating of immunosenescence and brain aging.}, journal = {Frontiers in cellular neuroscience}, volume = {18}, number = {}, pages = {1471192}, pmid = {39720706}, issn = {1662-5102}, abstract = {The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has profoundly impacted global health, affecting not only the immediate morbidity and mortality rates but also long-term health outcomes across various populations. Although the acute effects of COVID-19 on the respiratory system have initially been the primary focus, it is increasingly evident that the virus can have significant impacts on multiple physiological systems, including the nervous and immune systems. The pandemic has highlighted the complex interplay between viral infection, immune aging, and brain health, that can potentially accelerate neuroimmune aging and contribute to the persistence of long COVID conditions. By inducing chronic inflammation, immunosenescence, and neuroinflammation, COVID-19 may exacerbate the processes of neuroimmune aging, leading to increased risks of cognitive decline, neurodegenerative diseases, and impaired immune function. Key factors include chronic immune dysregulation, oxidative stress, neuroinflammation, and the disruption of cellular processes. These overlapping mechanisms between aging and COVID-19 illustrate how the virus can induce and accelerate aging-related processes, leading to an increased risk of neurodegenerative diseases and other age-related conditions. This mini-review examines key features and possible mechanisms of COVID-19-induced neuroimmune aging that may contribute to the persistence and severity of long COVID. Understanding these interactions is crucial for developing effective interventions. Anti-inflammatory therapies, neuroprotective agents, immunomodulatory treatments, and lifestyle interventions all hold potential for mitigating the long-term effects of the virus. By addressing these challenges, we can improve health outcomes and quality of life for millions affected by the pandemic.}, }
@article {pmid39724975, year = {2025}, author = {Skevaki, C and Moschopoulos, CD and Fragkou, PC and Grote, K and Schieffer, E and Schieffer, B}, title = {Long COVID: Pathophysiology, current concepts, and future directions.}, journal = {The Journal of allergy and clinical immunology}, volume = {155}, number = {4}, pages = {1059-1070}, doi = {10.1016/j.jaci.2024.12.1074}, pmid = {39724975}, issn = {1097-6825}, mesh = {Humans ; *COVID-19/immunology/physiopathology/complications ; *SARS-CoV-2/immunology ; Post-Acute COVID-19 Syndrome ; Biomarkers ; Immunity, Innate ; }, abstract = {Long COVID, an umbrella term referring to a variety of symptoms and clinical presentations that emerges in a subset of patients after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has a significant effect on quality of life and places a substantial burden on health care systems worldwide, straining financial and human resources. The pathophysiology of long COVID remains incompletely understood, though several hypotheses have been proposed to explain different aspects of this complex condition. SARS-CoV-2 persistence, direct organ damage, innate and adaptive immune system perturbation, autoimmunity, latent virus reactivation, endothelial dysfunction, and microbiome disturbances are among the most relevant avenues for elucidating the evolution, complexity, and mechanisms of long COVID. Active investigation regarding potential biomarkers for long COVID and its associated disease endotypes highlights the role of inflammatory mediators, immunophenotyping, and multiomics approaches. Further advances in understanding long COVID are needed to inform current and future therapeutics.}, }
@article {pmid39727052, year = {2025}, author = {Scheibenbogen, C and Wirth, KJ}, title = {Key Pathophysiological Role of Skeletal Muscle Disturbance in Post COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Accumulated Evidence.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {16}, number = {1}, pages = {e13669}, pmid = {39727052}, issn = {2190-6009}, support = {//Weidenhammer Zoebele Foundation/ ; //Lost Voices Foundation/ ; //MECFS Research Foundation/ ; //Fatigatio e.V./ ; //German Research Foundation/ ; //German Ministry of Education and Science/ ; //German Ministry of Health (BMG)/ ; }, mesh = {Humans ; *Fatigue Syndrome, Chronic/diagnosis/physiopathology/virology ; Mitochondria/metabolism ; *Muscle, Skeletal/cytology/physiopathology ; *Post-Acute COVID-19 Syndrome/physiopathology/virology ; SARS-CoV-2/pathogenicity ; }, abstract = {BACKGROUND: Recent studies provide strong evidence for a key role of skeletal muscle pathophysiology in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In a 2021 review article on the pathophysiology of ME/CFS, we postulated that hypoperfusion and ischemia can result in excessive sodium and calcium overload in skeletal muscles of ME/CFS patients to cause mitochondrial damage. Since then, experimental evidence has been provided that supports this concept.<br><br>METHODS: We collect, summarize and discuss the current state of knowledge for the key role of skeletal muscle pathophysiology. We try to explain which risk factors and mechanisms are responsible for a subgroup of patients with post COVID syndrome (PCS) to develop ME/CFS (PC-ME/CFS).<br><br>RESULTS: Mitochondrial dysfunction is a long-held assumption to explain cardinal symptoms of ME/CFS. However, mitochondrial dysfunction could not be convincingly shown in leukocytes. By contrast, recent studies provide strong evidence for mitochondrial dysfunction in skeletal muscle tissue in ME/CFS. An electron microscopy study could directly show damage of mitochondria in skeletal muscle of ME/CFS patients with a preferential subsarcolemmal localization but not in PCS. Another study shows signs of skeletal muscle damage and regeneration in biopsies taken one day after exercise in PC-ME/CFS. The simultaneous presence of necroses and signs of regeneration supports the concept of repeated damage. Other studies correlated diminished hand grip strength (HGS) with symptom severity and prognosis. A MRI study showed that intracellular sodium in muscles of ME/CFS patients is elevated and that levels correlate inversely with HGS. This finding corroborates our concept of sodium and consecutive calcium overload as cause of muscular and mitochondrial damage caused by enhanced proton-sodium exchange due to anaerobic metabolism and diminished activity of the sodium-potassium-ATPase. The histological investigations in ME/CFS exclude ischemia by microvascular obstruction, viral presence or immune myositis. The only known exercise-induced mechanism of damage left is sodium induced calcium overload. If ionic disturbance and mitochondrial dysfunction is severe enough the patient may be captured in a vicious circle. This energy deficit is the most likely cause of exertional intolerance and post exertional malaise and is further aggravated by exertion.<br><br>CONCLUSION: Based on this pathomechanism, future treatment approaches should focus on normalizing the cause of ionic disbalance. Current treatment strategies targeting hypoperfusion have the potential to improve the dysfunction of ion transporters.}, }
@article {pmid39735263, year = {2024}, author = {Camici, M and Del Duca, G and Brita, AC and Antinori, A}, title = {Connecting dots of long COVID-19 pathogenesis: a vagus nerve- hypothalamic-pituitary- adrenal-mitochondrial axis dysfunction.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1501949}, pmid = {39735263}, issn = {2235-2988}, mesh = {Humans ; *Mitochondria/metabolism ; *Hypothalamo-Hypophyseal System/metabolism/virology ; *COVID-19/immunology/physiopathology/virology ; *Vagus Nerve/physiopathology ; *SARS-CoV-2 ; *Pituitary-Adrenal System/virology ; Post-Acute COVID-19 Syndrome ; Hydrocortisone/metabolism ; Acetylcholine/metabolism ; }, abstract = {The pathogenesis of long COVID (LC) still presents many areas of uncertainty. This leads to difficulties in finding an effective specific therapy. We hypothesize that the key to LC pathogenesis lies in the presence of chronic functional damage to the main anti-inflammatory mechanisms of our body: the three reflexes mediated by the vagus nerve, the hypothalamic-pituitary-adrenal (HPA) hormonal axis, and the mitochondrial redox status. We will illustrate that this neuro-endocrine-metabolic axis is closely interconnected and how the SARS-CoV-2 can damage it at all stages through direct, immune-inflammatory, epigenetic damage mechanisms, as well as through the reactivation of neurotropic viruses. According to our theory, the direct mitochondrial damage carried out by the virus, which replicates within these organelles, and the cellular oxidative imbalance, cannot be countered in patients who develop LC. This is because their anti-inflammatory mechanisms are inconsistent due to reduced vagal tone and direct damage to the endocrine glands of the HPA axis. We will illustrate how acetylcholine (ACh) and cortisol, with its cytoplasmatic and cellular receptors respectively, are fundamental players in the LC process. Both Ach and cortisol play multifaceted and synergistic roles in reducing inflammation. They achieve this by modulating the activity of innate and cell-mediated immunity, attenuating endothelial and platelet activation, and modulating mitochondrial function, which is crucial for cellular energy production and anti-inflammatory mechanisms. In our opinion, it is essential to study the sensitivity of the glucocorticoids receptor in people who develop LC and whether SARS-CoV-2 can cause long-term epigenetic variations in its expression and function.}, }
@article {pmid39754403, year = {2025}, author = {Nawa, H and Murakami, M}, title = {Neurobiology of COVID-19-Associated Psychosis/Schizophrenia: Implication of Epidermal Growth Factor Receptor Signaling.}, journal = {Neuropsychopharmacology reports}, volume = {45}, number = {1}, pages = {e12520}, pmid = {39754403}, issn = {2574-173X}, support = {//Grant for Joint Research Program of the Institute for Genetic Medicine, Hokkaido University/ ; 21K18242//Grant-in-Aid for Challenging Exploratory Research/ ; 22H02728//Grant-in-Aid for Scientific Research (B)/ ; JP20fk0108471//AMED/ ; JP21fk0108489//AMED/ ; JP22ek0510030h0003//AMED/ ; JP223fa627005h0001//AMED/ ; JP20ek0510030h0001//AMED/ ; JP19ek0210125h0001//AMED/ ; JP21zf0127004h0001//AMED/ ; JP20H00502//Scientific Research (A)/ ; JP21K19364//Challenging Exploratory Research/ ; JPMXS0120330644//MEXT Quantum LEAP Flagship Program/ ; JP20fk010847h0001//Research Program on Emerging and Re-emerging Infectious Diseases/ ; JP21fk0108489h0001//Research Program on Emerging and Re-emerging Infectious Diseases/ ; }, mesh = {Humans ; *COVID-19/complications/metabolism ; *ErbB Receptors/metabolism ; *Schizophrenia/metabolism/physiopathology/drug therapy ; Animals ; *Signal Transduction ; *Psychotic Disorders/metabolism/physiopathology/etiology/drug therapy ; SARS-CoV-2 ; Brain/metabolism/virology ; }, abstract = {COVID-19 exhibits not only respiratory symptoms but also neurological/psychiatric symptoms rarely including delirium/psychosis. Pathological studies on COVID-19 provide evidence that the cytokine storm, in particular (epidermal growth factor) EGF receptor (EGFR, ErbB1, Her1) activation, plays a central role in the progression of viral replication and lung fibrosis. Of note, SARS-CoV-2 virus (specifically, S1 spike domain) mimics EGF and directly transactivates EGFR, preceding the inflammatory process. In agreement, the anticancer drugs targeting EGFR such as Nimotuzumab and tyrosine kinase inhibitors are markedly effective on COVID-19. However, these data might raise a provisional caution regarding implication of psychiatric disorder such as schizophrenia. The author's group has been investigating the etiologic and neuropathologic associations of EGFR signaling with schizophrenia. There are significant molecular associations between schizophrenia and EGFR ligand levels in blood as well as in the brain. In addition, perinatal challenges of EGFR ligands and intraventricular administration of EGF to rodents and monkeys both resulted in severe behavioral and/or electroencephalographic endophenotypes relevant to this disorder. These animal models also display postpubertal abnormality in soliloquy-like self-vocalization as well as in intercortical functional connectivity. Here, we discuss neuropsychiatric implication of coronavirus infection and its interaction with the EGFR system, by searching related literatures in PubMed database as of the end of 2023.}, }
@article {pmid39760348, year = {2025}, author = {Gupte, A and Sriram, S and Gunasekaran, V and Chaudhari, K and Kamat, D}, title = {The Triad of COVID-19 in Children: Acute COVID-19, Multisystem Inflammatory Syndrome, and Long COVID-Part II.}, journal = {Pediatric annals}, volume = {54}, number = {1}, pages = {e40-e44}, doi = {10.3928/19382359-20241106-01}, pmid = {39760348}, issn = {1938-2359}, mesh = {Humans ; *COVID-19/complications ; *Systemic Inflammatory Response Syndrome/diagnosis/physiopathology ; Child ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {Coronavirus disease 2019 (COVID-19), which is now known to be caused by severe acute respiratory syndrome coronavirus 2, has been a public health threat since early 2020 and has affected millions of people worldwide. Many studies have now shown that this virus exhibits a milder infection in children compared to adults. Acute COVID-19 infection, multisystem inflammatory syndrome in children (MIS-C), and long COVID have been recently well-established in the pediatric population with a myriad of systemic manifestations. This section of the review will focus on the following systems-neurology, psychiatry, endocrinology, hematology, and oncology-under three broad lenses, such as acute COVID-19, MIS-C, and long COVID. [Pediatr Ann. 2025;54(1):e40-e44.].}, }
@article {pmid39765324, year = {2025}, author = {Chopra, A and Franko, N and Chow, EJ}, title = {Navigating neurologic post-COVID-19 conditions in adults: Management strategies for cognitive dysfunction, headaches and neuropathies.}, journal = {Life sciences}, volume = {362}, number = {}, pages = {123374}, doi = {10.1016/j.lfs.2025.123374}, pmid = {39765324}, issn = {1879-0631}, mesh = {Humans ; *COVID-19/complications ; *Cognitive Dysfunction/therapy/etiology/diagnosis ; *Headache/therapy/etiology/diagnosis ; SARS-CoV-2 ; Adult ; *Nervous System Diseases/therapy/etiology/diagnosis ; *Peripheral Nervous System Diseases/therapy/etiology/diagnosis ; Post-Acute COVID-19 Syndrome ; }, abstract = {This review aims to describe the neurologic post-COVID-19 conditions (PCC, also known as "long COVID"), a complex array of diagnoses that can occur following recovery from acute COVID-19. The review also includes clinical considerations for the recognition, diagnosis and management of neurologic manifestations of PCC. Cognitive impairment ("Brain Fog"), headaches, and neuropathies are specifically reviewed.}, }
@article {pmid39767737, year = {2024}, author = {Malioukis, A and Snead, RS and Marczika, J and Ambalavanan, R}, title = {Pathophysiological, Neuropsychological, and Psychosocial Influences on Neurological and Neuropsychiatric Symptoms of Post-Acute COVID-19 Syndrome: Impacts on Recovery and Symptom Persistence.}, journal = {Biomedicines}, volume = {12}, number = {12}, pages = {}, pmid = {39767737}, issn = {2227-9059}, abstract = {Although the impact of post-acute COVID-19 syndrome (PACS) on patients and public health is undeniably significant, its etiology remains largely unclear. Much research has been conducted on the pathophysiology, shedding light on various aspects; however, due to the multitude of symptoms and clinical conditions that directly or indirectly define PACS, it is challenging to establish definitive causations. In this exploration, through systematically reviewing the latest pathophysiological findings related to the neurological symptoms of the syndrome, we aim to examine how psychosocial and neuropsychological symptoms may overlap with neurological ones, and how they may not only serve as risk factors but also contribute to the persistence of some primary symptoms of the disorder. Findings from our synthesis suggest that psychological and psychosocial factors, such as anxiety, depression, and loneliness, may interact with neurological symptoms in a self-reinforcing feedback loop. This cycle seems to be affecting both physical and psychological distress, potentially increasing the persistence and severity of PACS symptoms. By pointing out this interaction, in this review study, we attempt to offer a new perspective on the interconnected nature of psychological, psychosocial, and neurological factors, emphasizing the importance of integrated treatment approaches to disrupt this cycle and improve outcomes when possible.}, }
@article {pmid39770368, year = {2024}, author = {Nakayama, EE and Shioda, T}, title = {Detrimental Effects of Anti-Nucleocapsid Antibodies in SARS-CoV-2 Infection, Reinfection, and the Post-Acute Sequelae of COVID-19.}, journal = {Pathogens (Basel, Switzerland)}, volume = {13}, number = {12}, pages = {}, pmid = {39770368}, issn = {2076-0817}, support = {JM00000160//Center for Infectious Disease Education and Research, CiDER/ ; }, mesh = {Humans ; *COVID-19/immunology/complications ; *SARS-CoV-2/immunology ; *Antibodies, Viral/immunology ; *Reinfection/immunology/virology ; *Antibodies, Neutralizing/immunology ; *Antibody-Dependent Enhancement/immunology ; Cytokines/immunology/metabolism ; Receptors, Fc/immunology ; Nucleocapsid/immunology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Antibody-dependent enhancement (ADE) is a phenomenon in which antibodies enhance subsequent viral infections rather than preventing them. Sub-optimal levels of neutralizing antibodies in individuals infected with dengue virus are known to be associated with severe disease upon reinfection with a different dengue virus serotype. For Severe Acute Respiratory Syndrome Coronavirus type-2 infection, three types of ADE have been proposed: (1) Fc receptor-dependent ADE of infection in cells expressing Fc receptors, such as macrophages by anti-spike antibodies, (2) Fc receptor-independent ADE of infection in epithelial cells by anti-spike antibodies, and (3) Fc receptor-dependent ADE of cytokine production in cells expressing Fc receptors, such as macrophages by anti-nucleocapsid antibodies. This review focuses on the Fc receptor-dependent ADE of cytokine production induced by anti-nucleocapsid antibodies, examining its potential role in severe COVID-19 during reinfection and its contribution to the post-acute sequelae of COVID-19, i.e., prolonged symptoms lasting at least three months after the acute phase of the disease. We also discuss the protective effects of recently identified anti-spike antibodies that neutralize Omicron variants.}, }
@article {pmid39772122, year = {2024}, author = {Pacnejer, AM and Butuca, A and Dobrea, CM and Arseniu, AM and Frum, A and Gligor, FG and Arseniu, R and Vonica, RC and Vonica-Tincu, AL and Oancea, C and Mogosan, C and Popa Ilie, IR and Morgovan, C and Dehelean, CA}, title = {Neuropsychiatric Burden of SARS-CoV-2: A Review of Its Physiopathology, Underlying Mechanisms, and Management Strategies.}, journal = {Viruses}, volume = {16}, number = {12}, pages = {}, pmid = {39772122}, issn = {1999-4915}, support = {LBUS-IRG-2023/No. 3523, 24 July 2023//Lucian Blaga University of Sibiu/ ; }, mesh = {Humans ; *COVID-19/physiopathology/psychology/virology ; *SARS-CoV-2 ; Mental Disorders/therapy/etiology ; Nervous System Diseases/virology/physiopathology ; Angiotensin-Converting Enzyme 2/metabolism ; }, abstract = {The COVID-19 outbreak, caused by the SARS-CoV-2 virus, was linked to significant neurological and psychiatric manifestations. This review examines the physiopathological mechanisms underlying these neuropsychiatric outcomes and discusses current management strategies. Primarily a respiratory disease, COVID-19 frequently leads to neurological issues, including cephalalgia and migraines, loss of sensory perception, cerebrovascular accidents, and neurological impairment such as encephalopathy. Lasting neuropsychological effects have also been recorded in individuals following SARS-CoV-2 infection. These include anxiety, depression, and cognitive dysfunction, suggesting a lasting impact on mental health. The neuroinvasive potential of the virus, inflammatory responses, and the role of angiotensin-converting enzyme 2 (ACE2) in neuroinflammation are critical factors in neuropsychiatric COVID-19 manifestations. In addition, the review highlights the importance of monitoring biomarkers to assess Central Nervous System (CNS) involvement. Management strategies for these neuropsychiatric conditions include supportive therapy, antiepileptic drugs, antithrombotic therapy, and psychotropic drugs, emphasizing the need for a multidisciplinary approach. Understanding the long-term neuropsychiatric implications of COVID-19 is essential for developing effective treatment protocols and improving patient outcomes.}, }
@article {pmid39777702, year = {2025}, author = {Fekete, M and Lehoczki, A and Szappanos, &#xc1; and Toth, A and Mahdi, M and Sótonyi, P and Benyó, Z and Yabluchanskiy, A and Tarantini, S and Ungvari, Z}, title = {Cerebromicrovascular mechanisms contributing to long COVID: implications for neurocognitive health.}, journal = {GeroScience}, volume = {47}, number = {1}, pages = {745-779}, pmid = {39777702}, issn = {2509-2723}, support = {RRF-2.3.1-21-2022-00003//Nemzeti Kutat&#xe1;si, Fejleszt&#xe9;si &#xe9;s Innovaci&#xf3;s Alap/ ; TKP2021-NKTA-47//Nemzeti Kutat&#xe1;si Fejleszt&#xe9;si &#xe9;s Innov&#xe1;ci&#xf3;s Hivatal/ ; }, mesh = {Humans ; *COVID-19/complications/physiopathology ; Blood-Brain Barrier/physiopathology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Cerebrovascular Disorders/physiopathology/etiology ; Neurovascular Coupling ; Cerebrovascular Circulation/physiology ; Endothelium, Vascular/physiopathology ; Brain/blood supply/physiopathology ; }, abstract = {Long COVID (also known as post-acute sequelae of SARS-CoV-2 infection [PASC] or post-COVID syndrome) is characterized by persistent symptoms that extend beyond the acute phase of SARS-CoV-2 infection, affecting approximately 10% to over 30% of those infected. It presents a significant clinical challenge, notably due to pronounced neurocognitive symptoms such as brain fog. The mechanisms underlying these effects are multifactorial, with mounting evidence pointing to a central role of cerebromicrovascular dysfunction. This review investigates key pathophysiological mechanisms contributing to cerebrovascular dysfunction in long COVID and their impacts on brain health. We discuss how endothelial tropism of SARS-CoV-2 and direct vascular infection trigger endothelial dysfunction, impaired neurovascular coupling, and blood-brain barrier disruption, resulting in compromised cerebral perfusion. Furthermore, the infection appears to induce mitochondrial dysfunction, enhancing oxidative stress and inflammation within cerebral endothelial cells. Autoantibody formation following infection also potentially exacerbates neurovascular injury, contributing to chronic vascular inflammation and ongoing blood-brain barrier compromise. These factors collectively contribute to the emergence of white matter hyperintensities, promote amyloid pathology, and may accelerate neurodegenerative processes, including Alzheimer's disease. This review also emphasizes the critical role of advanced imaging techniques in assessing cerebromicrovascular health and the need for targeted interventions to address these cerebrovascular complications. A deeper understanding of the cerebrovascular mechanisms of long COVID is essential to advance targeted treatments and mitigate its long-term neurocognitive consequences.}, }
@article {pmid39781525, year = {2025}, author = {Peramaiyan, R and Anthony, J and Varalakshmi, S and Sekar, AK and Ali, EM and A, AHS and Abdallah, BM}, title = {Comparison of the role of vitamin D in normal organs and those affected by COVID-19.}, journal = {International journal of medical sciences}, volume = {22}, number = {2}, pages = {240-251}, pmid = {39781525}, issn = {1449-1907}, mesh = {Humans ; *COVID-19/immunology ; *Vitamin D ; *Vitamin D Deficiency/immunology/complications ; *SARS-CoV-2/immunology ; Dietary Supplements ; }, abstract = {The outbreak of COVID-19 has opened up new avenues for exploring the importance of vitamin D in immunity, in addition to its role in calcium absorption. Recently, vitamin D supplementation has been found to enhance T regulatory lymphocytes, which are reduced in individuals with COVID-19. Increased risk of pneumonia and increases in inflammatory cytokines have been reported to be major threats associated with vitamin-D deficiency. Although vaccination reduces the threat of COVID-19 to a certain extent, herd immunity is the long-term solution to overcoming such diseases. Co-administration of vitamin D with certain inactivated vaccines has been reported to enhance the systemic immune response through stimulation of the production of antigen-specific mucosal immunity. COVID-19 was found to induce multiple organ damage, and vitamin D has a beneficial role in various organs, such as the intestines, pancreas, prostate, kidneys, liver, heart, brain, and immune cells. The consequences that occur after COVID-19 infection known as long COVID-19 are also a concern as they accumulate and target multiple organs, leading to immune dysregulation. The present review covers the overall role and impact of vitamin D and its deficiency for various organs in normal conditions and after COVID-19 infection, which is still a serious issue.}, }
@article {pmid39795908, year = {2024}, author = {Luzak, B and Golanski, J and Rozalski, M}, title = {Complex Pattern of Platelet Activation/Reactivity After SARS-CoV-2 Infection.}, journal = {International journal of molecular sciences}, volume = {26}, number = {1}, pages = {}, pmid = {39795908}, issn = {1422-0067}, support = {503/6-020-01/503-61-001//Medical University of Lodz, Poland/ ; }, mesh = {Humans ; *COVID-19/blood/complications/virology ; *Platelet Activation ; *SARS-CoV-2 ; *Blood Platelets/metabolism/virology ; Platelet Function Tests/methods ; }, abstract = {COVID-19 and post-COVID (long COVID) are associated with thromboembolic complications; however, it is still not clear whether platelets play a leading role in this phenomenon. The platelet hyperreactivity could result from the direct interaction between platelets and viral elements or the response to inflammatory and prothrombotic factors released from blood and vessel cells following infection. The existing literature does not provide clear-cut answers, as the results determining platelet status vary according to methodology. Elevated levels of soluble markers of platelet activation (P selectin, PF4), increased platelet aggregates, and platelet-derived microparticles suggest the activation of platelets circulating in the bloodstream of COVID-19 patients. Similarly, platelets isolated from COVID-19 patients demonstrate increased reactivity in response to collagen, thrombin, and ADP. By contrast, an analysis of whole blood from COVID-19 patients indicates the reduced activation of the fibrinogen receptor. Similarly, some in vitro studies report potential targets for SARS-CoV-2 in platelets, whereas others do not indicate any direct effect of the virus on platelets. The aim of this work is to review and evaluate the reliability of the methodology for testing platelet function after contact with SARS-CoV-2. Despite the diversity of methods yielding varying results and the influence of plasma components or blood cells, it can be concluded that platelets play an important role in the development of thrombotic complications after exposure to SARS-CoV-2.}, }
@article {pmid39796218, year = {2025}, author = {Yip, JMX and Chiang, GSH and Lee, ICJ and Lehming-Teo, R and Dai, K and Dongol, L and Wang, LY and Teo, D and Seah, GT and Lehming, N}, title = {Mitochondria and the Repurposing of Diabetes Drugs for Off-Label Health Benefits.}, journal = {International journal of molecular sciences}, volume = {26}, number = {1}, pages = {}, pmid = {39796218}, issn = {1422-0067}, support = {A-8000724-00-00//Ministry of Education/ ; }, mesh = {Humans ; *Drug Repositioning ; *Hypoglycemic Agents/therapeutic use/pharmacology ; *Mitochondria/metabolism/drug effects ; COVID-19/virology/metabolism ; Metformin/therapeutic use/pharmacology ; SARS-CoV-2/drug effects ; *COVID-19 Drug Treatment ; Off-Label Use ; *Diabetes Mellitus/drug therapy ; }, abstract = {This review describes our current understanding of the role of the mitochondria in the repurposing of the anti-diabetes drugs metformin, gliclazide, GLP-1 receptor agonists, and SGLT2 inhibitors for additional clinical benefits regarding unhealthy aging, long COVID, mental neurogenerative disorders, and obesity. Metformin, the most prominent of these diabetes drugs, has been called the "Drug of Miracles and Wonders," as clinical trials have found it to be beneficial for human patients suffering from these maladies. To promote viral replication in all infected human cells, SARS-CoV-2 stimulates the infected liver cells to produce glucose and to export it into the blood stream, which can cause diabetes in long COVID patients, and metformin, which reduces the levels of glucose in the blood, was shown to cut the incidence rate of long COVID in half for all patients recovering from SARS-CoV-2. Metformin leads to the phosphorylation of the AMP-activated protein kinase AMPK, which accelerates the import of glucose into cells via the glucose transporter GLUT4 and switches the cells to the starvation mode, counteracting the virus. Diabetes drugs also stimulate the unfolded protein response and thus mitophagy, which is beneficial for healthy aging and mental health. Diabetes drugs were also found to mimic exercise and help to reduce body weight.}, }
@article {pmid39800813, year = {2025}, author = {Mohd Yusoff, H and Yew, SQ and Mohammed Nawi, A and Htwe, O and Mohd Tohit, N and Mohamed, Z and Muhamad Noordin, MA and Che Mohamed, N and Mohd, FH}, title = {Prevalence and symptoms of Long Covid-19 in the workplace.}, journal = {Occupational medicine (Oxford, England)}, volume = {75}, number = {1}, pages = {33-41}, pmid = {39800813}, issn = {1471-8405}, support = {UKMP-S230424//National Institute of Occupational Safety and Health (NIOSH) Malaysia/ ; }, mesh = {Humans ; *COVID-19/epidemiology/complications ; Prevalence ; *Workplace/statistics &amp; numerical data ; SARS-CoV-2 ; Fatigue/epidemiology/etiology ; Dyspnea/epidemiology/etiology ; Post-Acute COVID-19 Syndrome ; Male ; }, abstract = {BACKGROUND: The symptoms of Long coronavirus disease 2019 (Covid-19) are heterogeneous, creating uncertainty for employers regarding the diagnosis. The prevalence of Long Covid-19 in the workforce is also unknown. Furthermore, workers affected by Long Covid-19 encounter considerable difficulties in ensuring work safety and returning to their jobs due to this condition.<br><br>AIMS: This review is aimed to identify the prevalence of Long Covid-19 in the workplace and to determine the various symptoms of Long Covid-19 experienced by the workers.<br><br>METHODS: A meta-analysis was conducted to calculate the pooled estimates for the prevalence of Long Covid-19. Heterogeneity among the estimates was evaluated using the I&#xb2; statistic.<br><br>RESULTS: The pooled prevalence of Long Covid-19 among workers across the 11 studies was 38% (95% CI 23-56). A total of 43 symptoms associated with Long Covid-19 were identified in the workplace, with the top five symptoms being dyspnoea at moderate activity (51%, 95% CI 39-62), mental symptoms (38%, 95% CI 6-87), dyspnoea at mild activity (35%, 95% CI 25-47), fatigue (26%, 95% CI 3-78) and effort intolerance (24%, 95% CI 15-35).<br><br>CONCLUSIONS: The review indicates a significant burden of long-lasting symptoms within the workforce. The top five reported symptoms of Long Covid-19 were dyspnoea during mild and moderate activities, mental symptoms, fatigue and effort intolerance.}, }
@article {pmid39806627, year = {2024}, author = {Baalmann, AK and Blome, C and Stoletzki, N and Donhauser, T and Apfelbacher, C and Piontek, K}, title = {Patient-reported outcome measures for post-COVID-19 condition: a systematic review of instruments and measurement properties.}, journal = {BMJ open}, volume = {14}, number = {12}, pages = {e084202}, pmid = {39806627}, issn = {2044-6055}, mesh = {Humans ; *Patient Reported Outcome Measures ; *COVID-19/complications/psychology ; SARS-CoV-2 ; Quality of Life ; }, abstract = {OBJECTIVES: Post-COVID-19 condition (PCC), also referred to as Long COVID, has become an emerging public health issue requiring adequate prevention, treatment and management strategies. Evaluating these strategies from the patients' perspective using patient-reported outcome measures (PROMs) is critical. In this systematic review, we aimed to critically appraise and summarise the quality of existing PROMs for PCC, and to identify PROMs that can be recommended for use in future research.<br><br>DESIGN: Systematic review using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology.<br><br>DATA SOURCES: PubMed and Web of Science were searched on 16 January 2023 and again on 23 July 2024.<br><br>ELIGIBILITY CRITERIA: We included studies reporting on the development and/or validation of any disease-specific PROMs for PCC.<br><br>DATA EXTRACTION AND SYNTHESIS: Two independent reviewers screened the results for eligibility. The methodological quality of each included study was assessed using the COSMIN Risk of Bias Checklist. We further evaluated the quality of measurement properties per PROM and study according to the criteria for good measurement properties as outlined in the COSMIN manual, and graded the evidence of the synthesised results. Based on the overall evidence, we derived recommendations for the use of the identified instruments.<br><br>RESULTS: We identified 23 studies reporting on 11 PROMs measuring functional status (COVID-19 Yorkshire Rehabilitation Scale, C19-YRS; Modified COVID-19 Yorkshire Rehabilitation Scale, C19-YRSm; Functional Impairment Checklist, FIC; Post-COVID-19 Functional Status Scale, PCFS), symptom burden and impact (Long COVID Symptom and Severity Score, LC-SSS; Long COVID Symptom Tool, LCST; Long COVID Impact Tool, LCIT; Symptom Burden Questionnaire Long COVID, SBQ-LC), quality of life (Post-acute COVID-19 Quality of Life instrument, PAC-19QoL) and stigma (Long COVID Stigma Scale, LCSS; Post-COVID-19 Condition Stigma Questionnaire, PCCSQ). Sample sizes of the included studies ranged from 29 to 1969 participants. Overall, 95 single studies on measurement properties were evaluated. Among the identified instruments, the Long Covid Stigma Scale (LCSS) showed sufficient content validity and internal consistency and can be recommended for use according to COSMIN criteria. Our assessment of measurement properties revealed significant evidence gaps for all PROMs, indicating the need for further validation studies to make an adequate decision on the recommendation for their use. Content validity is a major shortcoming of all included instruments.<br><br>CONCLUSION: The LCSS measuring stigma can be recommended for use in future research. For the assessment of PCC symptoms and impact, no instrument with sufficient measurement properties is currently available. Further validation of all identified PROMs is indicated, in particular comprehensive assessments of content validity involving experts and patients.<br><br>PROSPERO REGISTRATION NUMBER: CRD42023391238.}, }
@article {pmid39808169, year = {2024}, author = {Šerý, O and Dziedzinska, R}, title = {Risk impact of SARS-CoV-2 coronavirus and spike protein on cardiac tissue: a comprehensive review.}, journal = {Physiological research}, volume = {73}, number = {S3}, pages = {S655-S669}, pmid = {39808169}, issn = {1802-9973}, mesh = {Humans ; *Spike Glycoprotein, Coronavirus/metabolism ; *COVID-19/metabolism/complications/virology/epidemiology ; *SARS-CoV-2/pathogenicity/metabolism ; Angiotensin-Converting Enzyme 2/metabolism ; Animals ; Virus Internalization ; Myocytes, Cardiac/virology/metabolism ; *Heart Diseases/virology/metabolism ; }, abstract = {The global COVID-19 pandemic, caused by SARS-CoV-2, has led to significant morbidity and mortality, with a profound impact on cardiovascular health. This review investigates the mechanisms of SARS-CoV-2's interaction with cardiac tissue, particularly emphasizing the role of the Spike protein and ACE2 receptor in facilitating viral entry and subsequent cardiac complications. We dissect the structural features of the virus, its interactions with host cell receptors, and the resulting pathophysiological changes in the heart. Highlighting SARS-CoV-2's broad organ tropism, especially its effects on cardiomyocytes via ACE2 and TMPRSS2, the review addresses how these interactions exacerbate cardiovascular issues in patients with pre-existing conditions such as diabetes and hypertension. Additionally, we assess both direct and indirect mechanisms of virus-induced cardiac damage, including myocarditis, arrhythmias, and long-term complications such as 'long COVID'. This review underscores the complexity of SARS-CoV-2's impact on the heart, emphasizing the need for ongoing research to fully understand its long-term effects on cardiovascular health. Key words: COVID-19, Heart, ACE2, Spike protein, Cardiomyocytes, Myocarditis, Long COVID.}, }
@article {pmid39811236, year = {2024}, author = {Razzak, AN and Kaizu, Y and Starkey, J}, title = {A Comparative Review of the Terms Epipharyngitis and Nasopharyngitis in Medical Literature.}, journal = {Cureus}, volume = {16}, number = {12}, pages = {e75738}, pmid = {39811236}, issn = {2168-8184}, abstract = {This review explores the usage of the term "epipharyngitis" in medical literature, particularly in non-English-speaking contexts. The term, although rarely used in contemporary English-language medical literature, may lead to confusion due to its overlap with more commonly used terms like "nasopharyngitis." This review aims to trace the origins of the term, analyze its usage across different languages, and discuss the implications of term differences in clinical practice and medical education.}, }
@article {pmid39814621, year = {2025}, author = {Martins, RHG and de Azevedo, ES and Müller, JVC and Loli, A}, title = {Dysphonia and COVID-19: A Review.}, journal = {Journal of voice : official journal of the Voice Foundation}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jvoice.2024.11.034}, pmid = {39814621}, issn = {1873-4588}, abstract = {INTRODUCTION: Vocal symptoms are frequent in patients with coronavirus disease 2019 (COVID-19) and may occur during or after infection.<br><br>OBJECTIVE: To conduct a descriptive review on the topic "dysphonia and COVID-19" in order to alert specialists to these symptoms associated with the virus and sequelae.<br><br>METHODOLOGY: A literature review was carried out in the main databases: Web of Science, PubMed, Google Scholar, and Scopus, between April 2020 and April 2024 using descriptors that related COVID-19 or severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) to voice disorders.<br><br>RESULTS: In total, 41 studies, 13 case reports, 6 retrospective,&#xa0;and&#xa0;22 prospective, 5139 patients (2131&#xa0;M,&#xa0;2991&#xa0;F), mean age of 51 years. The&#xa0;prevalence of dysphonia ranged from 0.39% to 79%. The most prevalent vocal symptoms were&#xa0;hoarseness, cough, dry throat, sore throat, reflux, aphonia, phonasthenia, stridor, and hypersecretion. Videolaryngoscopic findings: unilateral paralysis (145), bilateral paralysis (16), erythema (84), benign lesions (56), muscle tension dysphonia (54), granulomas (33), edema (31), stenosis (22), atrophy (19), incomplete glottal closure (12), and ventricular hypertrophy (6). Auditory-perceptual analyses identified mild/moderate vocal impairment in infected patients and persistence of changes in the long-COVID period. Acoustic analyses indicated significant changes in Jitter, Shimmer, harmonic-to-noise ratio (NHR), and maximum phonation time in patients with COVID-19.<br><br>CONCLUSION: Dysphonia caused by COVID-19 infection is common, both in the acute and chronic phases of the disease. The main causes include vocal fold paralysis, inflammatory laryngitis, and muscle tension dysphonia. All patients who present vocal symptoms after COVID-19 infection should undergo videolaryngoscopy and subjective and acoustic vocal analyses to identify sequelae of the disease.}, }
@article {pmid39817917, year = {2025}, author = {Bachelet, VC and Carroza, B and Morgado, B and Silva-Ayarza, I}, title = {A systematic analysis of the literature on the post-COVID-19 condition in Latin America focusing on epidemiology, clinical characteristics, and risk of bias.}, journal = {Medwave}, volume = {25}, number = {1}, pages = {e3014}, doi = {10.5867/medwave.2025.01.3014}, pmid = {39817917}, issn = {0717-6384}, mesh = {Humans ; Latin America/epidemiology ; *COVID-19/complications/epidemiology ; Caribbean Region/epidemiology ; Bias ; Intensive Care Units ; Post-Acute COVID-19 Syndrome ; }, abstract = {This analysis article aimed to identify and analyze all articles published on the post-COVID-19 condition in Latin America and the Caribbean, focusing on epidemiology, clinical characteristics, and risk of bias. We did a systematic survey of the literature with broad inclusion criteria. The only exclusion criteria were articles referring to post-acute COVID-19 sequelae after an intensive care unit stay, which we distinguish from the post-COVID-19 condition. We searched MEDLINE/PubMed, LILACS, SciELO, Scopus, Web of Science, and Epistemonikos. We included 55 records, of which 48 were original articles (44 were observational research, 29 of which had a comparison group; and four reviews). Various definitions for long COVID were reported, or none, and few used the World Health Organization criteria. None of the included studies reported prevalence rates for the region. We extracted the reported signs and symptoms of long COVID for our region. Using the Johanna Briggs Institute critical appraisal tools for observational analytic research, we found that most included studies were prone to limitations and biases. We conclude that more research should be done on the post-COVID-19 condition in Latin America and the Caribbean, using rigorous study designs to inform public health strategies.}, }
@article {pmid39820003, year = {2025}, author = {Andrade, A and Bastos, ACRF and D'Oliveira, A and Vilarino, GT}, title = {Association between physical activity practice and sleep quality of older people in social isolation during the COVID-19 pandemic and Health Guidelines and future studies for the post-COVID period: a systematic review.}, journal = {Aging}, volume = {17}, number = {1}, pages = {51-66}, pmid = {39820003}, issn = {1945-4589}, mesh = {Humans ; *COVID-19 ; *Social Isolation/psychology ; *Exercise/physiology ; Aged ; Pandemics ; *Sleep Quality ; SARS-CoV-2 ; *Sleep ; }, abstract = {PURPOSE: Physical activity (PA) is considered an alternative to mitigate the negative impacts of the COVID-19 pandemic on the sleep of older adults. The objective was to verify the association between physical activity and the sleep quality of older people in social isolation during the COVID-19 pandemic, to analyze the Health Guidelines, and suggest future studies for the post-COVID period.<br><br>METHODS: This systematic review followed PRISMA recommendations, and the protocol was registered in PROSPERO (CRD 42023406471). The search for articles occurred in April 2024 in the databases PubMed, Web of Science, SCOPUS, and gray literature. Data were extracted and checked in a Microsoft Excel[&#xae;] spreadsheet. The quality assessment was performed using tools from the National Institutes of Health.<br><br>RESULTS: In total, 1582 studies were found in the databases, of which nine were included in the analyses. Four studies reported a negative association of reduced levels of PA during the pandemic with sleep quality, while one study showed a positive association of PA with sleep quality. Four studies demonstrated no association.<br><br>CONCLUSIONS: PA was associated with the sleep quality of older adults during the COVID-19 pandemic and reduced levels of PA during this period demonstrated a negative association with sleep quality. Practice of PA is recommended for this post-COVID scenario, as a measure to reduce social isolation and its negative effects and improve the quality of sleep in older adults.}, }
@article {pmid39826380, year = {2025}, author = {Hu, LY and Cai, AQ and Li, B and Sun, YQ and Li, Z and Liu, JP and Cao, HJ}, title = {Prevalence and risk factors for long COVID in China: A systematic review and meta-analysis of observational studies.}, journal = {Journal of infection and public health}, volume = {18}, number = {3}, pages = {102652}, doi = {10.1016/j.jiph.2025.102652}, pmid = {39826380}, issn = {1876-035X}, mesh = {Humans ; China/epidemiology ; *COVID-19/epidemiology/complications ; Prevalence ; Risk Factors ; Observational Studies as Topic ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Female ; }, abstract = {BACKGROUND: With the outbreak of COVID-19 in China, a large number of COVID-19 patients are at risk of long COVID after recovery. The purpose of our research is to systematically review the existing clinical studies to understand the current prevalence and related risk factors of long COVID in COVID-19 patients in China.<br><br>METHODS: The protocol of this systematic review was registered on PROSPERO (CRD42024519375). We searched six electronic databases from 1st January 2020-1st March 2024. Literature screening, data extraction, and risk bias assessment were independently carried out by two reviewers. Quality of the included studies was evaluated by AHRQ and NOS. The meta-analysis was performed by R software 4.2.3 to derive the prevalence of long COVID and risk factors.<br><br>RESULTS: Overall, 50 studies with 65880 participants were included. The results showed that the prevalence of long COVID (with at least one symptom) among the COVID-19 patients was approximately 50&#x202f;% (95&#x202f;%Confidence Interval (CI) 42-58&#x202f;%) in China. Although we conducted meta-regression and subgroup analysis, the heterogeneity of the study was high. But the Omicron BA.2 variant had a statistically significant effect on the prevalence of long COVID (P&#x202f;=&#x202f;0.0004). The three most common symptoms of long COVID were fatigue (0.33, 95&#x202f;%CI 0.28-0.39), cognitive decline (0.30, 95&#x202f;%CI 0.14-0.46) and shortness of breath (0.29, 95&#x202f;%CI 0.15-0.43). Patients with severe acute phase of COVID-19 (Odds Ratio (OR) 1.57, 95&#x202f;% CI 1.39-1.77), combined 2 comorbidities (OR 1.80, 95&#x202f;% CI 1.40-2.32), combined 3 comorbidities (OR 2.13, 95&#x202f;% CI 1.64-2.77), advanced age (OR 1.02, 95&#x202f;% CI 1.01-1.04), female (OR 1.58, 95&#x202f;% CI 1.44-1.73) were the risk factors for long COVID prevalence.<br><br>CONCLUSION: Current systematic review found that nearly half of COVID-19 patients may suffering from long COVID in China. Establishing a long COVID recovery-support platform and regular follow-up would help to long-term monitor and manage the patients, especially those high-risk population.}, }
@article {pmid39832090, year = {2025}, author = {Niewiadomski, P and Ortega-Ortega, M and Łyszczarz, B}, title = {Productivity Losses due to Health Problems Arising from COVID-19 Pandemic: A Systematic Review of Population-Level Studies Worldwide.}, journal = {Applied health economics and health policy}, volume = {23}, number = {2}, pages = {231-251}, pmid = {39832090}, issn = {1179-1896}, support = {2022/47/B/HS4/00081//Narodowe Centrum Nauki/ ; }, mesh = {Humans ; *COVID-19/economics/epidemiology ; *Efficiency ; *Global Health/economics ; *Pandemics/economics ; SARS-CoV-2 ; Absenteeism ; *Cost of Illness ; }, abstract = {AIM: To systematically review the evidence on productivity losses due to health problems arising from the COVID-19 pandemic based on evidence from population-level studies.<br><br>METHODS: Following PRISMA statement, we conducted a systematic review using Medline, Embase, Scopus, Web of Science, EconLit, WHO COVID-19 Research and EuropePMC databases and a grey literature search. We included population-level studies using secondary data and qualitatively assessed eligible studies. For a quantitative cross-study comparison, we calculated losses in 2020 international dollars and as a share of gross domestic product. PROSPERO registration number: CRD42023478059.<br><br>RESULTS: Thirty-eight studies were eligible for review, most of which reported losses in high-income countries and the European region. COVID-19 was a focus of 33 studies while 3 studies investigated losses from both long COVID and excess mortality. The Human Capital Approach dominated (30 studies) and no study used the Friction Cost Approach. Most studies (84%) reported on premature mortality losses and a quarter provided estimates of losses due to absenteeism. Of the 33 studies eligible for quantitative comparison, we found that the productivity losses ranged from 0 to 2.1% of gross domestic product; the greatest losses were in the high-income countries and for those aged 40-59&#xa0;years; and losses among men contributed to around 3/4 of the total burden.<br><br>CONCLUSION: The available evidence on the topic is limited, particularly considering the methodological approaches used. Thus, more research is needed to reach a more comprehensive understanding of economy-level productivity losses resulting from the recent COVID-19 pandemic.}, }
@article {pmid39835117, year = {2024}, author = {Galipeau, Y and Cooper, C and Langlois, MA}, title = {Autoantibodies in COVID-19: implications for disease severity and clinical outcomes.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1509289}, pmid = {39835117}, issn = {1664-3224}, mesh = {Humans ; *COVID-19/immunology ; *Autoantibodies/immunology ; *SARS-CoV-2/immunology ; Severity of Illness Index ; Autoimmunity ; *Autoimmune Diseases/immunology ; }, abstract = {Few pathogens have historically been subjected to as intense scientific and clinical scrutiny as SARS-CoV-2. The genetic, immunological, and environmental factors influencing disease severity and post-infection clinical outcomes, known as correlates of immunity, remain largely undefined. Clinical outcomes of SARS-CoV-2 infection vary widely, ranging from asymptomatic cases to those with life-threatening COVID-19 symptoms. While most infected individuals return to their former health and fitness within a few weeks, some develop debilitating chronic symptoms, referred to as long-COVID. Autoimmune responses have been proposed as one of the factors influencing long-COVID and the severity of SARS-CoV-2 infection. The association between viral infections and autoimmune pathologies is not new. Viruses such as Epstein-Barr virus and cytomegalovirus, among others, have been shown to induce the production of autoantibodies and the onset of autoimmune conditions. Given the extensive literature on SARS-CoV-2, here we review current evidence on SARS-CoV-2-induced autoimmune pathologies, with a focus on autoantibodies. We closely examine mechanisms driving autoantibody production, particularly their connection with disease severity and long-COVID.}, }
@article {pmid39836023, year = {2025}, author = {Baig, AM and Rosko, S and Jaeger, B and Gerlach, J}, title = {Strategic Inhibition of CHRM Autoantibodies: Molecular Insights and Therapeutic Potentials in Long COVID.}, journal = {Journal of medicinal chemistry}, volume = {68}, number = {3}, pages = {2089-2094}, doi = {10.1021/acs.jmedchem.4c00691}, pmid = {39836023}, issn = {1520-4804}, mesh = {Humans ; *Autoantibodies/immunology ; *SARS-CoV-2/immunology ; *COVID-19/immunology/virology ; *Receptors, Muscarinic/metabolism/immunology ; COVID-19 Drug Treatment ; Post-Acute COVID-19 Syndrome ; }, abstract = {In addition to the conventional symptoms reported for COVID-19, it is becoming increasingly clear that patients with long COVID are exhibiting new symptoms due to the emergence of autoantibodies against G-protein-coupled receptors, among which human muscarinic cholinergic receptors (CHRMs) have been prominently reported. With a chronic condition such as long COVID, additional symptoms caused by anti-CHRM autoantibodies (AAbs) have proven to be an added burden on these patients. The origins of these AAbs, their interactions with, and effects on the function of neural and non-neural cells within the nervous system have remained unknown. Furthermore, the specific symptom complex to which they contribute has not been clearly understood. In this context, we address these issues here and suggest methods to combat the autoantibodies that contribute to neurological symptoms in long COVID.}, }
@article {pmid39849406, year = {2025}, author = {Iqbal, NT and Khan, H and Khalid, A and Mahmood, SF and Nasir, N and Khanum, I and de Siqueira, I and Van Voorhis, W}, title = {Chronic inflammation in post-acute sequelae of COVID-19 modulates gut microbiome: a review of literature on COVID-19 sequelae and gut dysbiosis.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {31}, number = {1}, pages = {22}, pmid = {39849406}, issn = {1528-3658}, support = {U01 AI151698/AI/NIAID NIH HHS/United States ; 3U01AI151698//Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases/ ; }, mesh = {Humans ; *COVID-19/complications ; *Dysbiosis/microbiology/immunology ; *Gastrointestinal Microbiome ; SARS-CoV-2 ; *Inflammation/microbiology ; Post-Acute COVID-19 Syndrome ; Chronic Disease ; Brain-Gut Axis ; Pandemics ; }, abstract = {BACKGROUND: Long COVID or Post-acute sequelae of COVID-19 is an emerging syndrome, recognized in COVID-19 patients who suffer from mild to severe illness and do not recover completely. Most studies define Long COVID, through symptoms like fatigue, brain fog, joint pain, and headache prevailing four or more weeks post-initial infection. Global variations in Long COVID presentation and symptoms make it challenging to standardize features of Long COVID. Long COVID appears to be accompanied by an auto-immune multi-faceted syndrome where the virus or viral antigen persistence causes continuous stimulation of the immune response, resulting in multi-organ immune dysregulation.<br><br>MAIN TEXT: This review is focused on understanding the risk factors of Long COVID with a special emphasis on the dysregulation of the gut-brain axis. Two proposed mechanisms are discussed here. The first mechanism is related to the dysfunction of angiotensin-converting enzyme 2 receptor due to Severe Acute Respiratory Syndrome Corona Virus 2 infection, leading to impaired mTOR pathway activation, reduced AMP secretion, and causing dysbiotic changes in the gut. Secondly, gut-brain axis dysregulation accompanied by decreased production of short-chain fatty acids, impaired enteroendocrine cell function, and increased leakiness of the gut, which favors translocation of pathogens or lipopolysaccharide in circulation causing the release of pro-inflammatory cytokines. The altered Hypothalamic-Pituitary-Adrenal axis is accompanied by the reduced level of neurotransmitter, and decreased stimulation of the vagus nerve, which may cause neuroinflammation and dysregulation of serum cortisol levels. The dysbiotic microbiome in Long COVID patients is characterized by a decrease in beneficial short chain fatty acid-producing bacteria (Faecalibacterium, Ruminococcus, Dorea, and Bifidobacterium) and an increase in opportunistic bacteria (Corynebacterium, Streptococcus, Enterococcus). This dysbiosis is transient and may be impacted by interventions including probiotics, and dietary supplements.<br><br>CONCLUSIONS: Further studies are required to understand the geographic variation, racial and ethnic differences in phenotypes of Long COVID, the influence of viral strains on existing and emerging phenotypes, to explore long-term effects of gut dysbiosis, and gut-brain axis dysregulation, as well as the potential role of diet and probiotics in alleviating those symptoms.}, }
@article {pmid39850323, year = {2024}, author = {Stefanou, MI and Panagiotopoulos, E and Palaiodimou, L and Bakola, E and Smyrnis, N and Papadopoulou, M and Moschovos, C and Paraskevas, GP and Rizos, E and Boutati, E and Tzavellas, E and Gatzonis, S and Mengel, A and Giannopoulos, S and Tsiodras, S and Kimiskidis, VK and Tsivgoulis, G}, title = {Current update on the neurological manifestations of long COVID: more questions than answers.}, journal = {EXCLI journal}, volume = {23}, number = {}, pages = {1463-1486}, pmid = {39850323}, issn = {1611-2156}, abstract = {Since the outbreak of the COVID-19 pandemic, there has been a global surge in patients presenting with prolonged or late-onset debilitating sequelae of SARS-CoV-2 infection, colloquially termed long COVID. This narrative review provides an updated synthesis of the latest evidence on the neurological manifestations of long COVID, discussing its clinical phenotypes, underlying pathophysiology, while also presenting the current state of diagnostic and therapeutic approaches. Approximately one-third of COVID-19 survivors experience prolonged neurological sequelae that persist for at least 12-months post-infection, adversely affecting patients' quality of life. Core neurological manifestations comprise fatigue, post-exertional malaise, cognitive impairment, headache, lightheadedness ('brain fog'), sleep disturbances, taste or smell disorders, dysautonomia, anxiety, and depression. Some of these features overlap substantially with those reported in post-intensive-care syndrome, myalgic encephalomyelitis/chronic fatigue syndrome, fibromyalgia, and postural-orthostatic-tachycardia syndrome. Advances in data-driven research utilizing electronic-health-records combined with machine learning and artificial intelligence have propelled the identification of long COVID sub-phenotypes. Furthermore, the evolving definitions reflect the dynamic conceptualization of long COVID in both research and clinical contexts. Although the underlying pathophysiology remains incompletely elucidated, neuroinflammatory responses, endotheliopathy, and metabolic imbalances, rather than direct viral neuroinvasion, are implicated in neurological sequelae. Genetic susceptibility has also emerged as a potential risk factor. While major limitations remain with existing definitions, collaborative strategies to standardize diagnostic approaches are needed. Current therapeutic paradigms advocate for multimodal approaches, integrating pharmacological and non-pharmacological interventions along with comprehensive rehabilitation programs. Although preliminary evidence of therapeutic efficacy has been provided by a number of clinical trials, methodological constraints limit the generalizability of this evidence. Preventive measures, notably vaccination, have proven integral for reducing the global burden of long COVID. Considering the healthcare and socioeconomic repercussions incurred by long COVID worldwide, international collaborative initiatives are warranted to address the remaining challenges in diagnosing and managing patients presenting with neurological sequelae. See also the graphical abstract(Fig. 1).}, }
@article {pmid39854158, year = {2025}, author = {Lau, RI and Su, Q and Ng, SC}, title = {Long COVID and gut microbiome: insights into pathogenesis and therapeutics.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2457495}, pmid = {39854158}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome ; *COVID-19/complications/microbiology/therapy ; Fecal Microbiota Transplantation ; *Dysbiosis/therapy/microbiology ; Probiotics/therapeutic use ; SARS-CoV-2/physiology ; Post-Acute COVID-19 Syndrome ; Prebiotics/administration &amp; dosage ; }, abstract = {Post-acute coronavirus disease 2019 syndrome (PACS), following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 (COVID-19), is typically characterized by long-term debilitating symptoms affecting multiple organs and systems. Unfortunately, there is currently a lack of effective treatment strategies. Altered gut microbiome has been proposed as one of the plausible mechanisms involved in the pathogenesis of PACS; extensive studies have emerged to bridge the gap between the persistent symptoms and the dysbiosis of gut microbiome. Recent clinical trials have indicated that gut microbiome modulation using probiotics, prebiotics, and fecal microbiota transplantation (FMT) led to improvements in multiple symptoms related to PACS, including fatigue, memory loss, difficulty in concentration, gastrointestinal upset, and disturbances in sleep and mood. In this review, we highlight the latest evidence on the key microbial alterations observed in PACS, as well as the use of microbiome-based therapeutics in managing PACS symptoms. These novel findings altogether shed light on the treatment of PACS and other chronic conditions.}, }
@article {pmid39857114, year = {2025}, author = {Eldien, HMS and Almaeen, AH and El Fath, AA and Taha, AE and Ahmed, R and Elfadil, H and Hetta, HF}, title = {Unlocking the Potential of RNA Sequencing in COVID-19: Toward Accurate Diagnosis and Personalized Medicine.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {15}, number = {2}, pages = {}, pmid = {39857114}, issn = {2075-4418}, support = {(DSR 2020-04-2621)//Deanship of Scientific Research at Jouf University through research/ ; }, abstract = {COVID-19 has caused widespread morbidity and mortality, with its effects extending to multiple organ systems. Despite known risk factors for severe disease, including advanced age and underlying comorbidities, patient outcomes can vary significantly. This variability complicates efforts to predict disease progression and tailor treatment strategies. While diagnostic and therapeutic approaches are still under debate, RNA sequencing (RNAseq) has emerged as a promising tool to provide deeper insights into the pathophysiology of COVID-19 and guide personalized treatment. A comprehensive literature review was conducted using PubMed, Scopus, Web of Science, and Google Scholar. We employed Medical Subject Headings (MeSH) terms and relevant keywords to identify studies that explored the role of RNAseq in COVID-19 diagnostics, prognostics, and therapeutics. RNAseq has proven instrumental in identifying molecular biomarkers associated with disease severity in patients with COVID-19. It allows for the differentiation between asymptomatic and symptomatic individuals and sheds light on the immune response mechanisms that contribute to disease progression. In critically ill patients, RNAseq has been crucial for identifying key genes that may predict patient outcomes, guiding therapeutic decisions, and assessing the long-term effects of the virus. Additionally, RNAseq has helped in understanding the persistence of viral RNA after recovery, offering new insights into the management of post-acute sequelae, including long COVID. RNA sequencing significantly improves COVID-19 management, particularly for critically ill patients, by enhancing diagnostic accuracy, personalizing treatment, and predicting therapeutic responses. It refines patient stratification, improving outcomes, and holds promise for targeted interventions in both acute and long COVID.}, }
@article {pmid39857123, year = {2025}, author = {Ferrara, E and Scaramuzzino, M and Murmura, G and D'Addazio, G and Sinjari, B}, title = {Emerging Evidence on Balneotherapy and Thermal Interventions in Post-COVID-19 Syndrome: A Systematic Review.}, journal = {Healthcare (Basel, Switzerland)}, volume = {13}, number = {2}, pages = {}, pmid = {39857123}, issn = {2227-9032}, abstract = {BACKGROUND: Post-COVID-19 syndrome affects 10-60% of SARS-CoV-2 survivors. While conventional treatments show limited efficacy, emerging evidence suggests the potential benefits of balneotherapy in managing persistent symptoms. We aimed to systematically evaluate the efficacy and safety of balneotherapy and thermal treatment interventions in treating post-COVID-19 syndrome.<br><br>METHODS: We conducted a systematic review following PRISMA guidelines, searching major databases through 31 January 2024. Eligible studies included randomized controlled trials, observational studies, and pilot studies investigating thermal spa treatments for adult post-COVID-19 patients.<br><br>RESULTS: Analysis of six eligible studies (n = 617) demonstrated significant therapeutic benefits. The largest cohort (n = 159) showed 47% reduction in fatigue and 48% reduction in muscle pain (p < 0.01). Comprehensive spa therapy achieved complete symptom resolution in one-third of the participants. Combined spa-ubiquinol therapy improved metabolic function (p < 0.05). All interventions demonstrated favorable safety profiles.<br><br>CONCLUSIONS: Preliminary evidence suggests balneotherapy effectively ameliorates multiple post-COVID-19 symptoms, particularly fatigue, muscle pain, and exercise intolerance. While safety profiles appear favorable, larger randomized controlled trials with standardized protocols are needed to establish definitive therapeutic recommendations.}, }
@article {pmid39860384, year = {2025}, author = {Basaca, DG and Jugănaru, I and Belei, O and Nicoară, DM and Asproniu, R and Stoicescu, ER and Mărginean, O}, title = {Long COVID in Children and Adolescents: Mechanisms, Symptoms, and Long-Term Impact on Health-A Comprehensive Review.}, journal = {Journal of clinical medicine}, volume = {14}, number = {2}, pages = {}, pmid = {39860384}, issn = {2077-0383}, abstract = {Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), is increasingly recognized as a condition affecting not only adults but also children and adolescents. While children often experience milder acute COVID-19 symptoms compared to adults, some develop persistent physical, psychological, and neurological symptoms lasting for weeks or months after initial infection. The most commonly reported symptoms include debilitating fatigue, respiratory issues, headaches, muscle pain, gastrointestinal disturbances, and cognitive difficulties, which significantly impact daily activities, schooling, and social interactions. Additionally, many children with long COVID experience psychological symptoms, such as anxiety, depression, mood swings, and irritability, likely exacerbated by prolonged illness and lifestyle disruptions. Risk factors for long COVID in children include pre-existing health conditions such as asthma, obesity, and neurological disorders, with adolescents and females seemingly more affected. Hypothesized mechanisms underlying long COVID include chronic immune dysregulation, persistent viral particles stimulating inflammation, autonomic nervous system dysfunction, and mitochondrial impairment, which may collectively contribute to the variety of observed symptoms. Long-term outcomes remain uncertain; however, long COVID can lead to school absenteeism, social withdrawal, and psychological distress, potentially affecting cognitive development. Severe cases may develop chronic conditions such as postural orthostatic tachycardia syndrome (POTS) and reduced exercise tolerance. This review synthesizes the existing literature on long COVID in children, examining its prevalence, symptomatology, risk factors, and potential mechanisms, with an emphasis on the need for further clinical studies. While existing research largely relies on surveys and self-reported data, clinical assessments are essential to accurately characterize long COVID in pediatric populations and to guide effective management strategies.}, }
@article {pmid39860512, year = {2025}, author = {Guntinas-Lichius, O and Bitter, T and Takes, R and Lee, VHF and Saba, NF and Mäkitie, AA and Kowalski, LP and Nixon, IJ and Ferlito, A}, title = {Post COVID-19 and Long COVID Symptoms in Otorhinolaryngology-A Narrative Review.}, journal = {Journal of clinical medicine}, volume = {14}, number = {2}, pages = {}, pmid = {39860512}, issn = {2077-0383}, abstract = {Post/Long COVID (syndrome) is defined as a condition with symptoms persisting for more than 12 weeks after the onset of SARS-CoV-2 infection that cannot be explained otherwise. The prevalence of self-reported otorhinolaryngological Post/Long COVID symptoms is high. The aim of this review was to analyze the current literature regarding the actual prevalence, knowledge of the etiopathology, and evidence-based treatment recommendations of otorhinolaryngology-related Post/Long COVID symptoms. A systematic literature search of articles published since 2019 in PubMed and ScienceDirect was performed and resulted in 108 articles. These were the basis for this review and formed a comprehensive series of consented therapy statements on the most important of otorhinolaryngology-related Post/Long COVID symptoms. Otorhinolaryngological symptoms did not appear isolated but as part of a multi-organ syndrome. Self-reported otorhinolaryngology-related Post/Long COVID symptoms were often not confirmed by objective testing. The confirmed prevalence estimated for anosmia, dysgeusia, cough, facial palsy, hoarseness/dysphonia, acute hearing loss, tinnitus, and vertigo/dizziness was about 4%, 2%, 4-19%, 0%, 17-20%, 8%, 20%, and 5-26%, respectively. There are manifold theoretical concepts of the etiopathology of different symptoms, but there is no clear evidence-based proof. This certainly contributes to the fact that there is no effective specific treatment option for any of the symptoms mentioned. Healthcare pathways must be established so that otorhinolaryngological Post/Long COVID symptoms can be recognized and evaluated and otorhinolaryngologists can provide counseling. This would also help to establish and selectively include patients in clinical trials investigating specific therapeutic concepts.}, }
@article {pmid39861887, year = {2025}, author = {Vanderheiden, A and Diamond, MS}, title = {Animal Models of Non-Respiratory, Post-Acute Sequelae of COVID-19.}, journal = {Viruses}, volume = {17}, number = {1}, pages = {}, pmid = {39861887}, issn = {1999-4915}, support = {R01 AI157155/AI/NIAID NIH HHS/United States ; P01 AI168347/NH/NIH HHS/United States ; R01 AI157155/NH/NIH HHS/United States ; P01 AI168347/AI/NIAID NIH HHS/United States ; F32 NS128065/NH/NIH HHS/United States ; F32 NS128065/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *COVID-19/complications/pathology ; *Disease Models, Animal ; Mice ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Humans ; Cricetinae ; Primates ; }, abstract = {Post-acute sequelae of COVID-19 (PASC) are a diverse set of symptoms and syndromes driven by dysfunction of multiple organ systems that can persist for years and negatively impact the quality of life for millions of individuals. We currently lack specific therapeutics for patients with PASC, due in part to an incomplete understanding of its pathogenesis, especially for non-pulmonary sequelae. Here, we discuss three animal models that have been utilized to investigate PASC: non-human primates (NHPs), hamsters, and mice. We focus on neurological, gastrointestinal, and cardiovascular PASC and highlight advances in mechanistic insight that have been made using these animal models, as well as discussing the sequelae that warrant continued and intensive research.}, }
@article {pmid39862702, year = {2025}, author = {Lim, HX and Khalid, K and Abdullah, ADI and Lee, LH and Raja Ali, RA}, title = {Subphenotypes of Long COVID and the clinical applications of probiotics.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {183}, number = {}, pages = {117855}, doi = {10.1016/j.biopha.2025.117855}, pmid = {39862702}, issn = {1950-6007}, mesh = {Humans ; *Probiotics/therapeutic use ; *COVID-19/microbiology/complications ; Dysbiosis ; Gastrointestinal Microbiome ; Post-Acute COVID-19 Syndrome ; Phenotype ; SARS-CoV-2 ; }, abstract = {As the number of infections and deaths attributable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to rise, it is now becoming apparent that the health impacts of the Coronavirus disease (COVID-19) may not be limited to infection and the subsequent resolution of symptoms. Reports have shown that patients with SARS-CoV-2 infection may experience multiple symptoms across different organ systems that are associated with adverse health outcomes and develop new cardiac, renal, respiratory, musculoskeletal, and nervous conditions, a condition known as Long COVID or the post-acute sequelae of COVID-19 (PASC). This review provides insights into distinct subphenotypes of Long COVID and identifies microbiota dysbiosis as a common theme and crucial target for future therapies. Another important finding is that Long COVID is associated with prolonged and increased inflammation, potentially attributable to immune system dysfunction. A promising solution lies in the potential of probiotics to mitigate Long COVID symptoms by restoring gut microbiota balance and modulating the immune response. By evaluating the current clinical development landscape of the use of probiotics to treat Long COVID symptoms, this paper provides recommendations for future research by stressing the need to understand the modulation of bacterium strains followed by probiotic therapy to understand the association of microbiota dysbiosis with Long COVID symptoms. This will facilitate the development of effective probiotic formulations that could serve as reliable therapies against Long COVID.}, }
@article {pmid39874315, year = {2025}, author = {Bidhendi-Yarandi, R and Biglarian, A and Karlstad, JL and Moe, CF and Bakhshi, E and Khodaei-Ardakani, MR and Behboudi-Gandevani, S}, title = {Prevalence of depression, anxiety, stress, and suicide tendency among individual with long-COVID and determinants: A systematic review and meta-analysis.}, journal = {PloS one}, volume = {20}, number = {1}, pages = {e0312351}, pmid = {39874315}, issn = {1932-6203}, mesh = {Female ; Humans ; Male ; *Anxiety/epidemiology ; *Depression/epidemiology ; Prevalence ; Risk Factors ; SARS-CoV-2 ; *Stress, Psychological/epidemiology ; Suicidal Ideation ; *Suicide/psychology/statistics &amp; numerical data ; *Post-Acute COVID-19 Syndrome/complications/epidemiology/psychology ; }, abstract = {BACKGROUND: While mental health alterations during active COVID-19 infection have been documented, the prevalence of long-term mental health consequences remains unclear. This study aimed to determine the prevalence of mental health symptoms-depression, anxiety, stress, and suicidal tendencies-and to identify their trends and associated risk factors in individuals with long-COVID.<br><br>METHODS: We conducted a systematic literature search of databases including PubMed, EMBASE, Scopus, CINAHL, Cochrane Library, Web of Science, and PsycINFO up to August 2024, targeting observational studies published in English. Study quality was assessed using structured standard tools. The primary outcome was the pooled prevalence of depression, anxiety, stress, and suicidal tendencies in individuals with long-COVID. Secondary outcomes included trends in these mental health problems over time and identification of associated determinants.<br><br>RESULTS: A total of 94 eligible studies were included in the analysis. The pooled prevalence estimates, regardless of follow up times duration, were as follows: depression, 25% (95%CI:22-28%; PI:1-59%); anxiety (adjusted via trim and fill method), 23%(95%CI:21-25%;PI:2-35%); composite outcomes of depression and/or anxiety, 25% (95%CI:23-27%;PI:2-51%); stress, 26%(95%CI:13-39%;PI:1-69%); and suicidality, 19%(95%CI:15-22%;PI:13-25%). The results of meta-regression analyses revealed a statistically significant trend showing a gradual decrease in the prevalence of the composite outcome of anxiety and/or depression over time (RD = -0.004,P = 0.022). Meta-regression results indicated that being female and younger age were significantly associated with a higher prevalence of mental health symptoms. Study design and study setting did not contribute to heterogeneity.<br><br>CONCLUSION: One-fourth of individual with long-COVID experience mental health symptoms, including depression, anxiety, and stress, which remain prevalent even two years post-infection despite a slight decreasing trend. Factors such as female gender and younger age were linked to higher rates of anxiety and depression. These findings indicate the need for ongoing mental health screening and early interventions to mitigate long-term psychological distress in long-COVID patients.}, }
@article {pmid39882369, year = {2024}, author = {Pierson, BC and Apilado, K and Franzos, MA and Allard, R and Mancuso, JD and Tribble, D and Saunders, D and Koehlmoos, TP}, title = {Oral medications for the treatment of postural orthostatic tachycardia syndrome; a systematic review of studies before and during the COVID-19 pandemic.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1515486}, pmid = {39882369}, issn = {1664-2295}, abstract = {BACKGROUND: Postural Orthostatic Tachycardia Syndrome (POTS) is a complex form of dysautonomia that presents with abnormal autonomic reflexes upon standing, leading to symptoms such as lightheadedness, tachycardia, fatigue, and cognitive impairment. The COVID-19 pandemic has brought renewed attention to POTS due to its overlap with post-acute sequelae of COVID-19 (PASC). Studies have found that a substantial percentage of COVID-19 survivors exhibit symptoms resembling POTS, elevating POTS diagnoses to previously unseen levels. We systematically reviewed the literature for existing high-quality evidence on potential interventions.<br><br>METHODS: A systematic review of the literature was performed to identify studies of oral medications for the management of POTS. We searched for published manuscripts on the medical management of POTS through 6 April 2024 which met pre-specified inclusion criteria. We conducted quality appraisal and assessed risk of bias before extracting the data and performing synthesis to determine the current state of the evidence; particularly in the context of PASC.<br><br>RESULTS: The study search and selection process identified 32 studies that met inclusion criteria, comprising randomized controlled trials, observational studies, and systematic reviews. Most included studies were judged to be of moderate to high quality, with largely low risk of bias. The most frequently studied medications were beta-blockers, ivabradine, and midodrine. Ivabradine and midodrine demonstrated the highest rate of symptomatic improvement, while beta-blockers showed the largest reduction in heart rate variability. Limited evidence was available for PASC-associated POTS, but findings suggest that treatments may have similar efficacy in both PASC and non-PASC cases.<br><br>CONCLUSION: Ivabradine, midodrine, and beta-blockers currently appear to be reasonable front-line choices in pharmacologic management of POTS (PASC associated and otherwise). Further RCTs that evaluate long term outcomes of medications are needed to further establish evidence based pharmacologic treatment approaches for POTS. Particular areas of inquiry include differential efficacy of recommended therapies based on POTS subtypes, and a need for treatments directly targeting the underlying autonomic nervous system dysfunction.<br><br>PROSPERO, identifier CRD42024505967, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=505967.}, }
@article {pmid39882453, year = {2024}, author = {Xu, H and Lu, T and Liu, Y and Yang, J and Ren, S and Han, B and Lai, H and Ge, L and Liu, J}, title = {Prevalence and risk factors for long COVID among cancer patients: a systematic review and meta-analysis.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1506366}, pmid = {39882453}, issn = {2234-943X}, abstract = {OBJECTIVE: The prevalence of long COVID among cancer patients remains unknown. This study aimed to determine the prevalence of long COVID and explore potential risk factors among cancer patients.<br><br>METHODS: A systematic search was performed on PubMed, Web of Science, and Embase from database inception until 21 March 2024, to identify studies that reported long COVID in cancer patients. Two investigators independently screened the studies and extracted all information about long COVID in cancer patients for subsequent analysis. Methodological quality was assessed using the "Joannagen Briggs Institute (JBI) Critical Appraisal Checklist for Studies Reporting Prevalence Data".<br><br>RESULTS: A total of 13 studies involving 6,653 patients were included. The pooled prevalence of long COVID was 23.52% [95% confidence interval (CI), 12.14% to 40.64%] among cancer patients reported experiencing long COVID after acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The pooled prevalence of any long COVID in cancer patients was 20.51% (95% CI, 15.91% to 26.03%), 15.79% (95% CI, 11.39% to 21.47%), and 12.54% (95% CI, 6.38% to 23.18%) in 3, 6, and 12 months follow-up duration. Fatigue was the most common symptom, followed by respiratory symptoms, myalgia, and sleep disturbance. Patients with comorbidities had a significantly higher risk of experiencing long COVID [odds ratio (OR) = 1.72; 95% CI, 1.09 to 2.70; p = 0.019]. No statistically significant differences in sex, primary tumor, or tumor stage were detected.<br><br>CONCLUSION: Nearly a quarter of cancer patients will experience long COVID after surviving from SARS-CoV-2 infection, and this would even last for 1 year or longer. Fatigue, respiratory symptoms, myalgia, and sleep disturbance need to be more addressed and managed to reduce symptom burden on cancer patients and improve quality of life. Patients with comorbidities are at a high risk of developing long COVID. Further randomized controlled trials with rigorous methodological designs and large sample sizes are needed for future validation.<br><br>https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023456665.}, }
@article {pmid39884720, year = {2025}, author = {Terry, P and Heidel, RE and Wilson, AQ and Dhand, R}, title = {Risk of long covid in patients with pre-existing chronic respiratory diseases: a systematic review and meta-analysis.}, journal = {BMJ open respiratory research}, volume = {12}, number = {1}, pages = {}, pmid = {39884720}, issn = {2052-4439}, mesh = {Humans ; *COVID-19/complications/epidemiology ; *Asthma/epidemiology/complications ; *Pulmonary Disease, Chronic Obstructive/epidemiology/complications ; SARS-CoV-2 ; Risk Factors ; Chronic Disease ; }, abstract = {BACKGROUND: An estimated 10-30% of people with COVID-19 experience debilitating long-term symptoms or long covid. Underlying health conditions associated with chronic inflammation may increase the risk of long covid.<br><br>METHODS: We conducted a systematic review and meta-analysis to examine whether long covid risk was altered by pre-existing asthma or chronic obstructive pulmonary disease (COPD) in adults. We identified studies by searching the PubMed and Embase databases from inception to 13 September 2024. We excluded studies that focused on children or defined long covid only in terms of respiratory symptoms. We used random-effects, restricted maximum likelihood models to analyse data pooled from 51 studies, which included 43 analyses of asthma and 30 analyses of COPD. The risk of bias was assessed using a ROBINS-E table.<br><br>RESULTS: We found 41% increased odds of long covid with pre-existing asthma (95% CI 1.29 to 1.54); pre-existing COPD was associated with 32% increased odds (95% CI 1.16 to 1.51). Pre-existing asthma, but not COPD, was associated with increased odds of long covid-associated fatigue. We observed heterogeneity in the results of studies of asthma related to hospitalisation status. Potential confounding and inconsistent measurement of exposure and outcome variables were among the identified limitations.<br><br>CONCLUSIONS: Our findings support the hypothesis that pre-existing asthma and COPD increase the risk of long covid, including chronic fatigue outcomes in patients with asthma. Because COVID-19 targets the respiratory tract, these inflammatory conditions of the lower respiratory tract could provide mechanistic clues to a common pathway for the development of long-term sequelae in patients with long covid.}, }
@article {pmid39886482, year = {2025}, author = {Han, Y and Dai, Y and Wang, K and Zhang, X and Shao, Z and Zhu, X}, title = {Post-pandemic insights on COVID-19 and premature ovarian insufficiency.}, journal = {Open life sciences}, volume = {20}, number = {1}, pages = {20221028}, pmid = {39886482}, issn = {2391-5412}, abstract = {The COVID-19 pandemic has raised concerns regarding its potential impact on premature ovarian insufficiency (POI). This overview examines the possible interactions between COVID-19 and POI, while also suggesting preventive measures. The viral infection's inflammatory response and immune dysregulation may adversely affect ovarian tissues, leading to inflammation and damage. Additionally, alterations in vascular function could impair ovarian blood flow and hormonal imbalances may disrupt normal ovarian function. Long-term health effects, such as "long COVID," may exacerbate these issues through chronic inflammation and immune dysfunction. Public health measures, such as vaccination and home isolation, may indirectly protect ovarian health by reducing systemic inflammation. Vaccines could mitigate the severity of COVID-19's impact on ovarian function, while isolation may reduce stress and inflammation. However, further research is needed to validate these mechanisms.}, }
@article {pmid39888378, year = {2025}, author = {Braun, J}, title = {[Chronic pain syndrome in musculoskeletal diseases-how different are fibromyalgia and long Covid?-Part 1].}, journal = {Zeitschrift fur Rheumatologie}, volume = {84}, number = {4}, pages = {312-319}, pmid = {39888378}, issn = {1435-1250}, mesh = {Humans ; *Fibromyalgia/diagnosis/therapy ; *COVID-19/diagnosis/complications/therapy ; *Chronic Pain/diagnosis/therapy ; Diagnosis, Differential ; *Musculoskeletal Diseases/diagnosis ; SARS-CoV-2 ; }, abstract = {Chronic pain is a common problem in rheumatology. Nociceptive pain is distinguished from neuropathic and nociplastic pain. Mechanistically, the former is explained by persistent inflammation, for example. Included in the second category is nerve damage of various causes. In contrast, nociplastic pain is not caused by tissue damage or a lesion in the somatosensory nerve system. It is caused by an altered sensation of pain through the modulation of stimulus processing. The concept of central sensitization, together with further neurobiological and psychosocial mechanisms, best explains such pain conditions. Fibromyalgia (FM) plays a big part in rheumatology - on the one hand, as a differential diagnosis, and on the other, because the management of inflammatory rheumatic conditions is made more difficult by the simultaneous occurrence of FM. In the context of the coronavirus pandemic, persistent pain syndromes with similarities to FM have been described after COVID-19 infection. There is an increasing scientific controversy whether the so-called long Covid syndrome is an actual entity or "only" a variant of FM. This discussion and the current state of knowledge on the problem are the subject of this review.}, }
@article {pmid39888379, year = {2025}, author = {Braun, J}, title = {[Chronic pain syndrome in musculoskeletal diseases-how different are fibromyalgia and long COVID?-Part 2].}, journal = {Zeitschrift fur Rheumatologie}, volume = {84}, number = {4}, pages = {320-329}, pmid = {39888379}, issn = {1435-1250}, mesh = {Humans ; *Fibromyalgia/diagnosis/therapy ; *COVID-19/diagnosis/therapy/epidemiology ; *Chronic Pain/diagnosis/therapy ; *Musculoskeletal Diseases/diagnosis/therapy ; Pain Measurement/methods ; Diagnosis, Differential ; Pandemics ; Post-Acute COVID-19 Syndrome ; }, abstract = {Acute and chronic pain play an important part in the care of patients with musculoskeletal diseases. For rheumatologists this represents a frequent challenge. For the management of chronic pain conditions in rheumatology those that cannot be explained by objective tissue damage are particularly important-which makes patients' subjective assessment of pain a central building block of the diagnosis. For the diagnosis of fibromyalgia (FM) standardized questionnaires such as the Widespread Pain Index (WPI) and the Symptom Severity Score (SSS) are used. In connection with the recent global SARS-CoV‑2 pandemic protracted courses and health problems have been described, which have been termed long COVID syndrome and have some similarities but, as is shown in the following, also demonstrate some differences from FM. There has recently been an interesting scientific controversy that culminated in a pros and cons session at the EULAR congress 2024, following several publications. The arguments and citations exchanged have served as the basis for the overview produced here, which is intended to offer rheumatologists confronted with such clinical pictures assistance with the assessment of these diseases, even if the results of the studies presented are definitely controversial.}, }
@article {pmid39889481, year = {2025}, author = {Saha, A and Choudhary, S and Walia, P and Kumar, P and Tomar, S}, title = {Transformative approaches in SARS-CoV-2 management: Vaccines, therapeutics and future direction.}, journal = {Virology}, volume = {604}, number = {}, pages = {110394}, doi = {10.1016/j.virol.2025.110394}, pmid = {39889481}, issn = {1096-0341}, mesh = {Humans ; *COVID-19/prevention &amp; control/therapy/immunology/virology ; *COVID-19 Vaccines/immunology ; *SARS-CoV-2/immunology/drug effects/genetics ; *Antiviral Agents/therapeutic use ; *COVID-19 Drug Treatment ; Animals ; }, abstract = {The global healthcare and economic challenges caused by the pandemic of COVID-19 reinforced the urgent demand for quick and effective therapeutic and preventative interventions. While vaccines served as the frontline of defense, antivirals emerged as adjunctive countermeasures, especially for people who developed infection, were immunocompromised, or were reluctant to be vaccinated. Beyond the serious complications of SARS-CoV-2 infection, the threats of long-COVID and the potential for zoonotic spillover continue to be significant health concerns that cannot be overlooked. Moreover, the incessant viral evolution, clinical safety issues, waning immune responses, and the emergence of drug-resistant variants pinpoint towards more severe viral threats in the future and call for broad-spectrum innovative therapies as a pre-pandemic preparedness measure. The present review provides a comprehensive up-to-date overview of the strategies utilized in the development of classical and next-generation vaccines against SARS-CoV-2, the clinical and experimental data obtained from clinical trials, while addressing safety risks that may arise. Besides vaccines, the review also covers recent breakthroughs in anti-SARS-CoV-2 drug discovery, emphasizing druggable viral and host targets, virus- and host-targeting antivirals, and highlighting mechanistically representative molecules that are either approved or are under clinical investigation. In conclusion, the integration of both vaccines and antiviral therapies, along with swift innovative strategies to address viral evolution and drug resistance is crucial to strengthen our preparedness against future viral outbreaks.}, }
@article {pmid39895557, year = {2025}, author = {Khan, MS and Miller, AJ and Ejaz, A and Molinger, J and Goyal, P and MacLeod, DB and Swavely, A and Wilson, E and Pergola, M and Tandri, H and Mills, CF and Raj, SR and Fudim, M}, title = {Cerebral Blood Flow in Orthostatic Intolerance.}, journal = {Journal of the American Heart Association}, volume = {14}, number = {3}, pages = {e036752}, pmid = {39895557}, issn = {2047-9980}, mesh = {Humans ; *Cerebrovascular Circulation/physiology ; *Orthostatic Intolerance/physiopathology/diagnosis ; Ultrasonography, Doppler, Transcranial ; Spectroscopy, Near-Infrared ; }, abstract = {Cerebral blood flow (CBF) is vital for delivering oxygen and nutrients to the brain. Many forms of orthostatic intolerance (OI) involve impaired regulation of CBF in the upright posture, which results in disabling symptoms that decrease quality of life. Because CBF is not easy to measure, rises in heart rate or drops in blood pressure are used as proxies for abnormal CBF. These result in diagnoses such as postural orthostatic tachycardia syndrome and orthostatic hypotension. However, in many other OI syndromes such as myalgic encephalomyelitis/chronic fatigue syndrome and long COVID, heart rate and blood pressure are frequently normal despite significant drops in CBF. This often leads to the incorrect conclusion that there is nothing hemodynamically abnormal in these patients and thus no explanation or treatment is needed. There is a need to measure CBF, as orthostatic hypoperfusion is the shared pathophysiology for all forms of OI. In this review, we examine the literature studying CBF dysfunction in various syndromes with OI and evaluate methods of measuring CBF including transcranial Doppler ultrasound, extracranial cerebral blood flow ultrasound, near infrared spectroscopy, and wearable devices.}, }
@article {pmid39896874, year = {2025}, author = {Livieratos, A and Lockley, SW and Tsiodras, S}, title = {Post infectious fatigue and circadian rhythm disruption in long-COVID and other infections: a need for further research.}, journal = {EClinicalMedicine}, volume = {80}, number = {}, pages = {103073}, pmid = {39896874}, issn = {2589-5370}, abstract = {Chronic fatigue syndrome (CFS) remains a subject of scientific research specifically with regards to its association with infections, including the more recently described Long COVID condition. Chronic fatigue and sleep disturbances in Long COVID are intricately linked to disruptions in circadian rhythms, driven by distinct molecular and cellular mechanisms triggered by SARS-CoV-2 infection. This can be driven by various mechanisms including dysregulation of key clock genes (CLOCK, BMAL1, PER2), mitochondrial dysfunction impairing oxidative phosphorylation, and cytokine-induced neuroinflammation (e.g., interleukin-6, tumor necrosis factor-alpha). Epigenetic changes, including DNA methylation at clock-related loci, particularly in peripheral tissues, further contribute to systemic circadian dysregulation. This work underscores the multifaceted molecular and systemic disruptions to circadian regulation in relation to fatigue and sleep disturbances identified as post-infectious sequelae, focusing on the Long COVID condition.}, }
@article {pmid39902344, year = {2024}, author = {Schwendinger, F and Infanger, D and Maurer, DJ and Radtke, T and Carrard, J and Kröpfl, JM and Emmenegger, A and Hanssen, H and Hauser, C and Schwehr, U and Hirsch, HH and Ivanisevic, J and Leuzinger, K and Martinez, AE and Maurer, M and Sigrist, T and Streese, L and von Känel, R and Hinrichs, T and Schmidt-Trucksäss, A}, title = {Medium- to long-term health condition of patients post-COVID-19, exercise intolerance and potential mechanisms: A narrative review and perspective.}, journal = {SAGE open medicine}, volume = {12}, number = {}, pages = {20503121241296701}, pmid = {39902344}, issn = {2050-3121}, abstract = {BACKGROUND: Patients recovering from COVID-19 often present with impaired health and persisting symptoms such as exercise intolerance ⩾3 months post-infection. Uncertainty remains about long-term recovery. We aimed to review studies examining cardiac function, macro- or microvascular function, blood biomarkers and physical activity in adult patients post-COVID-19 and highlight current knowledge gaps.<br><br>RESULTS: Using echocardiography, persistent cardiac involvement of the left ventricle was observed in a fraction of patients both hospitalized and non-hospitalized. Ventricular dysfunction was often subclinical but may partly contribute to exercise intolerance post-COVID-19. Endothelial dysfunction was seen on micro- and macrovascular levels using retinal vessel imaging methods and brachial artery flow-mediated dilation, respectively. Studies reporting blood biomarkers of disease-specific impairment and endothelial dysfunction yielded upregulated inflammation, hypercoagulability, organ and endothelial damage up to several months after infection. Omics' scale lipid profiling studies provide preliminary evidence of alterations in several lipid subspecies, mostly during acute COVID-19, which might contribute to subsequent endothelial and cardiometabolic dysfunction. Yet, more robust evidence is warranted. Physical activity may be reduced up to 6&#x2009;months post-COVID-19. However, studies measuring physical activity more precisely using accelerometry are sparse. Overall, there is growing evidence for long-term multiple organ dysfunction.<br><br>CONCLUSION: Research combining all the above methods in the search for underlying mechanisms of post-COVID-19 symptoms is mostly missing. Moreover, studies with longer follow-ups (i.e. &#x2a7e;18&#x2009;months) and well-matched control groups are lacking. The findings may aid the development of rehabilitation regimes for post-COVID-19 syndrome.<br><br>CONDENSED ABSTRACT: This review examined cardiac function, vascular function, blood biomarkers and physical activity in patients post-COVID-19. Evidence suggests long-term dysfunction in multiple organ systems and exercise intolerance due to various factors, including endothelial damage and, in some patients, subclinical ventricular dysfunction. We highlight knowledge gaps for further research to aid post-COVID-19 rehabilitation.}, }
@article {pmid39902608, year = {2025}, author = {Tcheroyan, R and Makhoul, P and Simpson, S}, title = {An updated review of pulmonary radiological features of acute and chronic COVID-19.}, journal = {Current opinion in pulmonary medicine}, volume = {31}, number = {3}, pages = {183-195}, doi = {10.1097/MCP.0000000000001152}, pmid = {39902608}, issn = {1531-6971}, mesh = {Humans ; *COVID-19/diagnostic imaging/complications ; *Tomography, X-Ray Computed/methods ; *Lung/diagnostic imaging ; SARS-CoV-2 ; Chronic Disease ; Acute Disease ; Pulmonary Fibrosis/diagnostic imaging ; }, abstract = {PURPOSE OF REVIEW: Significant progress has been made in our understanding of the acute and chronic clinical and radiological manifestations of coronavirus-19 (COVID-19). This article provides an updated review on pulmonary COVID-19, while highlighting the key imaging features that can identify and distinguish acute COVID-19 pneumonia and its chronic sequelae from other diseases.<br><br>RECENT FINDINGS: Acute COVID-19 pneumonia typically presents with manifestations of organizing pneumonia on computed tomography (CT). In cases of severe disease, patients clinically progress to acute respiratory distress syndrome, which manifests as diffuse alveolar damage on CT. The most common chronic imaging finding is ground-glass opacities, which commonly resolves, as well as subpleural bands and reticulation. Pulmonary fibrosis is an overall rare complication of COVID-19, with characteristic features, including architectural distortion, and traction bronchiectasis.<br><br>SUMMARY: Chest CT can be a helpful adjunct tool in both diagnosing and managing acute COVID-19 pneumonia and its chronic sequelae. It can identify high-risk cases and guide decision-making, particularly in cases of severe or complicated disease. Follow-up imaging can detect persistent lung abnormalities associated with long COVID and guide appropriate management.}, }
@article {pmid39907353, year = {2025}, author = {Prediger, KM and Ribeiro, AC and Uehara, SCDSA}, title = {Prevalent symptoms and characteristics of the Long COVID-19 population: a scoping review.}, journal = {Revista latino-americana de enfermagem}, volume = {33}, number = {}, pages = {e4479}, pmid = {39907353}, issn = {1518-8345}, mesh = {Female ; Humans ; Male ; COVID-19/epidemiology ; Dyspnea/epidemiology ; *Post-Acute COVID-19 Syndrome/epidemiology ; Prevalence ; Risk Factors ; SARS-CoV-2 ; Sex Factors ; }, abstract = {UNLABELLED: to map the scientific literature on the clinical and demographic characteristics of Long COVID-19. this is a scoping review based on the principles recommended by the JBI and the PRISMA guidelines for data extraction, carried out on four databases. The PCC strategy was used for data collection, and the results were described and diagrammed. The studies were selected after removing duplicates, individual and peer review. an analysis of the 13 articles selected showed that Long COVID affects all age groups and people of both sexes, presenting a multiplicity of symptoms, such as fatigue (61.5%), dyspnea (46.1%), changes in smell and/or taste (38.6%), anxiety (15.3%) and cognitive impairment (30.7%). Females were found to be at increased risk of developing Long COVID. identifying the symptoms prevalent in Long COVID contributes to public health strategies for diagnosing and assisting people affected by the disease. Future studies are recommended on the approach to the persistence of symptoms in Long COVID and the relationship between adherence to the vaccination schedule against COVID-19, gender, race/ethnicity, degree of susceptibility in the different age groups, level of education and income, as well as the most recurrent comorbidities in the population.<br><br>BACKGROUND: (1) It was found that Long COVID affects all age groups of both sexes. (2) Most common symptoms: fatigue, dyspnea and altered sense of smell and/or taste. (3) Risk factors: female gender, COVID-19 severity and comorbidities.}, }
@article {pmid39907423, year = {2025}, author = {Araújo, FC and Amaral, ACD and Silva, HJ and Santos, JNV and Mendonça, VA and Oliveira, VC and Rocha-Vieira, E}, title = {Autoantibodies as potential prognostic factors for clinical outcomes related to COVID-19: a systematic review of inception prospective cohort studies with GRADE recommendations.}, journal = {Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas}, volume = {58}, number = {}, pages = {e13965}, pmid = {39907423}, issn = {1414-431X}, mesh = {Humans ; *COVID-19/immunology/mortality/blood ; *Autoantibodies/blood/immunology ; Prognosis ; Prospective Studies ; SARS-CoV-2/immunology ; Severity of Illness Index ; Risk Factors ; Respiration, Artificial ; }, abstract = {This systematic review of inception prospective cohort studies aimed to investigate whether autoantibodies are potential prognostic factors for short- and long-term clinical outcomes of COVID-19. Searches were conducted in MEDLINE, EMBASE, AMED, GLOBAL HEALTH, and COCHRANE databases from 2019 to 2022. When possible, meta-analysis was conducted, otherwise findings from individual studies were reported using odds ratios (OR) with 95% confidence intervals (CI). Quality of evidence was summarized using the GRADE criteria. We identified 2292 references, 18 inception prospective cohort studies (3178 patients) were included in the systematic review, and 12 studies reached criteria for meta-analysis. Studies achieved, in general, low to moderate risk of bias. Moderate quality of evidence showed that anti-interferon (IFN) was associated with increased risk of severity (OR=7.75; CI=1.79-33.61) and mechanical ventilation (OR=4.19; CI=2.06-8.53), but not with COVID-19 mortality (OR=1.68; CI=0.63-4.44). Antiphospholipids were not associated with COVID-19 mortality (OR=1.42; CI=0.85-2.37; P=0.18; I2=3.21) nor with thrombosis risk (OR=1.41; CI: 0.71-2.8; P=0.33). Antinuclear antibody level was not associated with risk of mortality or severity (risk for mortality: OR=3.8; CI=0.78-18.6; P=0.1; I2: 32.3; severity: OR=1.74; CI=0.96-3.16; P=0.07). Evidence currently available is insufficient for a quantitative analysis of autoantibodies association with long COVID-19. Anti-IFN measurement should be considered in COVID-19 follow-up. In a population-based rational, optimized vaccination strategies should be considered for individuals with anti-IFN antibodies since it could represent a risk for a worse prognosis. High-quality prospective studies for short- and long-term disease effects and autoantibody evaluation are still needed.}, }
@article {pmid39909170, year = {2025}, author = {Low, ZXB and Yong, SJ and Alrasheed, HA and Al-Subaie, MF and Al Kaabi, NA and Alfaresi, M and Albayat, H and Alotaibi, J and Al Bshabshe, A and Alwashmi, ASS and Sabour, AA and Alshiekheid, MA and Almansour, ZH and Alharthi, H and Al Ali, HA and Almoumen, AA and Alqasimi, NA and AlSaihati, H and Rodriguez-Morales, AJ and Rabaan, AA}, title = {Serotonergic psychedelics as potential therapeutics for post-COVID-19 syndrome (or Long COVID): A comprehensive review.}, journal = {Progress in neuro-psychopharmacology &amp; biological psychiatry}, volume = {137}, number = {}, pages = {111279}, doi = {10.1016/j.pnpbp.2025.111279}, pmid = {39909170}, issn = {1878-4216}, mesh = {Humans ; *COVID-19/complications ; *Hallucinogens/therapeutic use/pharmacology ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; Animals ; Serotonin ; }, abstract = {RATIONALE: In our ongoing battle against the coronavirus 2019 (COVID-19) pandemic, a major challenge is the enduring symptoms that continue after acute infection. Also known as Long COVID, post-COVID-19 syndrome (PCS) often comes with debilitating symptoms like fatigue, disordered sleep, olfactory dysfunction, and cognitive issues ("brain fog"). Currently, there are no approved treatments for PCS. Recent research has uncovered that the severity of PCS is inversely linked to circulating serotonin levels, highlighting the potential of serotonin-modulating therapeutics for PCS. Therefore, we propose that serotonergic psychedelics, acting mainly via the 5-HT2A serotonin receptor, hold promise for treating PCS.<br><br>OBJECTIVES: Our review aims to elucidate potential mechanisms by which serotonergic psychedelics may alleviate the symptoms of PCS.<br><br>RESULTS: Potential mechanisms through which serotonergic psychedelics may alleviate PCS symptoms are discussed, with emphasis on their effects on inflammation, neuroplasticity, and gastrointestinal function. Additionally, this review explores the potential of serotonergic psychedelics in mitigating endothelial dysfunction, a pivotal aspect of PCS pathophysiology implicated in organ dysfunction. This review also examines the potential role of serotonergic psychedelics in alleviating specific PCS symptoms, which include olfactory dysfunction, cognitive impairment, sleep disturbances, and mental health challenges.<br><br>CONCLUSIONS: Emerging evidence suggests that serotonergic psychedelics may alleviate PCS symptoms. However, further high-quality research is needed to thoroughly assess their safety and efficacy in treating patients with PCS.}, }
@article {pmid39910970, year = {2025}, author = {Tudorache Pantazi, MA and Gadea-Doménech, M and Espert Tortajada, R}, title = {[Cognition and Long COVID: A PRISMA Systematic Review of Longitudinal Studies].}, journal = {Revista de neurologia}, volume = {79}, number = {12}, pages = {37385}, pmid = {39910970}, issn = {1576-6578}, mesh = {Humans ; *COVID-19/complications/psychology ; Longitudinal Studies ; *Cognitive Dysfunction/etiology ; Post-Acute COVID-19 Syndrome ; Time Factors ; *Cognition ; }, abstract = {INTRODUCTION: Long COVID is defined by National Institute for Health and Care Excellence (NICE) as the set of signs and symptoms that develop during or after a SARS-CoV-2 infection and continue for more than twelve weeks without any alternative diagnosis. One of the most frequent persistent symptoms reported by patients and verified in neuroimaging studies is cognitive dysfunction, due to a generalized hypoconnectivity and a diffuse axonal lesion in white matter. Therefore, the objectives of the present review are to determine how long cognitive functions remain affected during Long COVID and to explore which cognitive functions are most affected beyond three months of follow-up in patients up to 65 years of age without previous neuropsychological or psychiatric complications.<br><br>METHODS: A systematic review was performed using PRISMA criteria and 11 articles were included through a comprehensive search of five different databases: PubMed, Medline, Scopus, WOS and ProQuest. The risk of bias of the articles was assessed using the Newcastle-Ottawa scale.<br><br>RESULTS: Cognitive problems in Long COVID persist over time and improve slowly, although studies seem to agree that most areas improved significantly after one year. The cognitive functions that remained impaired the longest were processing speed and attention.<br><br>CONCLUSIONS: These cognitive alterations cause a reduction in the quality of life of the patients and a reduction in work capacity and manifest the need for a cognitive intervention.}, }
@article {pmid39917633, year = {2025}, author = {Kumar, M and Baig, MS and Bhardwaj, K}, title = {Advancements in the development of antivirals against SARS-Coronavirus.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1520811}, pmid = {39917633}, issn = {2235-2988}, mesh = {*Antiviral Agents/pharmacology/therapeutic use ; Humans ; SARS-CoV-2/drug effects ; Animals ; COVID-19 ; *Severe Acute Respiratory Syndrome/drug therapy/virology/epidemiology ; *Severe acute respiratory syndrome-related coronavirus/drug effects ; Pandemics ; COVID-19 Drug Treatment ; *Betacoronavirus/drug effects ; *Coronavirus Infections/drug therapy ; Drug Development ; }, abstract = {Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) caused an outbreak in 2002-2003, spreading to 29 countries with a mortality rate of about 10%. Strict quarantine and infection control methods quickly stopped the spread of the disease. Later research showed that SARS-CoV came from animals (zoonosis) and stressed the possibility of a similar spread from host to human, which was clearly shown by the COVID-19 outbreak. The COVID-19 pandemic, instigated by SARS-CoV-2, has affected 776 million confirmed cases and more than seven million deaths globally as of Sept 15, 2024. The existence of animal reservoirs of coronaviruses continues to pose a risk of re-emergence with improved fitness and virulence. Given the high death rate (up to 70 percent) and the high rate of severe sickness (up to 68.7 percent in long-COVID patients), it is even more critical to identify new therapies as soon as possible. This study combines research on antivirals that target SARS coronaviruses that have been conducted over the course of more than twenty years. It is a beneficial resource that might be useful in directing future studies.}, }
@article {pmid39921187, year = {2025}, author = {Pouliopoulou, DV and Hawthorne, M and MacDermid, JC and Billias, N and Miller, E and Quinn, K and Décary, S and Razak, FA and Cheung, A and Galiatsatos, P and Pereira, TV and Bobos, P}, title = {Prevalence and Impact of Postexertional Malaise on Recovery in Adults With Post-COVID-19 Condition: A Systematic Review With Meta-analysis.}, journal = {Archives of physical medicine and rehabilitation}, volume = {106}, number = {8}, pages = {1267-1278}, doi = {10.1016/j.apmr.2025.01.471}, pmid = {39921187}, issn = {1532-821X}, mesh = {Adult ; Humans ; *COVID-19/rehabilitation/complications ; Prevalence ; SARS-CoV-2 ; Observational Studies as Topic ; }, abstract = {OBJECTIVE: To assess the prevalence of postexertional malaise (PEM) in people with post-COVID-19 condition (PCC); and the change in prevalence of PEM after rehabilitation interventions in people with PCC.<br><br>DATA SOURCES: We searched MEDLINE, Embase, CENTRAL, CINAHL, PsychINFO, and clinical trial registries from inception until February 11, 2025.<br><br>STUDY SELECTION: We included observational studies that measured the prevalence of PEM in adults with PCC and interventional studies that measured the change in prevalence of PEM after rehabilitation interventions in adults with PCC. Two independent researchers screened titles and abstracts. Any discrepancies underwent full text review. Two independent researchers screened the articles included at the full text level.<br><br>DATA EXTRACTION: Two independent researchers extracted data from eligible studies. We extracted point prevalence from the cross-sectional studies; and period prevalence from the longitudinal studies. Two independent reviewers assessed the risk of bias. Discrepancies were resolved with a senior research team member. For the prevalence studies we used the ROBINS-E tool. For randomized controlled trials we used the RoB2 tool. For non-randomized interventional studies we used the ROBINS-I tool to assess the non-randomized studies. We used the GRADE system to assess the certainty of the evidence.<br><br>DATA SYNTHESIS: We performed a single-arm proportional meta-analysis to synthesize prevalence estimates using logit transformation. We conducted a sensitivity analysis using multilevel-mixed-effects logistic regression. We used a random effects model. Results were reported as proportions with corresponding 95% confidence intervals (95% CI) or presented descriptively when statistical analysis was not applied. This study is registered with PROSPERO (CRD42024516682). The prevalence of PEM in community-dwelling adults living with PCC was 25% (95% CI: 0.17-0.36; 10 studies; 4,076 low certainty after the word participants). Five of the included studies (193 patients) found a decrease in the frequency and intensity of PEM episodes in adults with PCC after a tailored rehabilitation program centered on integrating pacing approaches. Eight studies (1080 patients) measured PEM as an adverse event following an individually tailored rehabilitation intervention with a therapeutic exercise component. Seven of these studies did not find indications of post exertional symptom exacerbation related to the exercise component of the intervention. All of the studies had high to very high risk of bias.<br><br>CONCLUSIONS: Our research confirms that there is a large burden of PEM in adults living with PCC, highlighting a critical challenge for health care systems and an urgent need for more inclusive and rigorous research, to offer safe and effective therapeutic solutions and meet the variable needs of people with PCC that experience PEM. There is a subgroup of patients with PCC who do not experience PEM; and there is limited evidence that supervised, individually tailored, symptom-titrated rehabilitation interventions with active exercise components may not trigger PEM in this subgroup of people with PCC. Our results are limited by the insufficient reporting of the percentage of PEM in the baseline before enrolling patients in the rehabilitation programs, and the large number of studies using nonvalidated, unstandardized tools to measure PEM in people with PCC; hence, there is an urgent need to strengthen the methods of future trials.}, }
@article {pmid39925756, year = {2025}, author = {Alie, MS and Tesema, GA and Abebe, GF and Girma, D}, title = {The prolonged health sequelae "of the COVID-19 pandemic" in sub-Saharan Africa: a systematic review and meta-analysis.}, journal = {Frontiers in public health}, volume = {13}, number = {}, pages = {1415427}, pmid = {39925756}, issn = {2296-2565}, mesh = {Humans ; *COVID-19/epidemiology/complications/psychology ; Africa South of the Sahara/epidemiology ; Quality of Life ; SARS-CoV-2 ; *Survivors/psychology ; Pandemics ; }, abstract = {BACKGROUND: Survivors of coronavirus disease 2019 (COVID-19) often face persistent and significant challenges that affect their physical, mental, and financial wellbeing, which can significantly diminish their overall quality of life. The emergence of new symptoms or the persistence of existing ones after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis has given rise to a complex clinical issue known as "long COVID-19" (LC). This situation has placed additional strain on global healthcare systems, underscoring the urgent need for ongoing clinical management of these patients. While numerous studies have been conducted on the long-term effects of COVID-19, our systematic review, and meta-analysis, is the first of its kind in sub-Saharan Africa, providing a comprehensive understanding of the situation in the region and highlighting the necessity for continuous clinical management.<br><br>OBJECTIVE: This study aimed to systematically synthesize evidence on the persistent sequelae of COVID-19 and their predictors in sub-Saharan Africa.<br><br>METHODS: A thorough search was conducted across multiple databases, including PubMed/MEDLINE, Web of Science, Google/Google Scholar, African online journals, and selected reference lists, from the inception of these databases until January 12, 2024. A meta-analysis of proportions was conducted using the random-effects restricted maximum-likelihood model. The association between various factors was also analyzed to determine the pooled factors that influence long COVID-19 outcomes.<br><br>RESULTS: Our comprehensive analysis of 16 research articles, involving a total of 18,104 participants revealed a pooled prevalence of COVID-19 sequelae at 42.1% (95% CI: 29.9-55.4). The long-term health sequelae identified in this review included persistent pulmonary sequelae (27.5%), sleep disturbance (22.5%), brain fog (27.4%), fatigue (17.4%), anxiety (22.3%), and chest pain (13.2%). We also found a significant association was observed between comorbidities and long COVID-19 sequelae [POR&#x202f;=&#x202f;4.34 (95% CI: 1.28-14.72)], providing a comprehensive understanding of the factors influencing long COVID-19 outcomes.<br><br>CONCLUSION: COVID-19 can have long-lasting effects on various organ systems, even after a person has recovered from the infection. These effects can include brain fog, pulmonary symptoms, sleep disturbances, anxiety, fatigue, and other neurological, psychiatric, respiratory, cardiovascular, and general symptoms. It is crucial for individuals who have recovered from COVID-19 to receive careful follow-up care to assess and reduce any potential organ damage and maintain their quality of life.<br><br>Clinicaltrial.gov, identifier CRD42024501158.}, }
@article {pmid39934846, year = {2025}, author = {Salzmann, S and de Vroege, L and Engelmann, P and Fink, P and Fischer, S and Frisch, S and Gormsen, LK and Hüfner, K and Kop, WJ and Köteles, F and Lehnen, N and Löwe, B and Pieh, C and Pitron, V and Rask, CU and Sainio, M and Schaefert, R and Shedden-Mora, M and Toussaint, A and von Känel, R and Werneke, U and Rief, W and , }, title = {Assessment of psychosocial aspects in adults in post-COVID-19 condition: the EURONET-SOMA recommendations on core outcome domains for clinical and research use.}, journal = {BMC medicine}, volume = {23}, number = {1}, pages = {81}, pmid = {39934846}, issn = {1741-7015}, mesh = {Humans ; *COVID-19/psychology/complications ; Adult ; SARS-CoV-2 ; Europe ; *Outcome Assessment, Health Care ; Consensus ; }, abstract = {BACKGROUND: Harmonizing core outcome domains allows for pooling data, comparing interventions, and streamlining research evaluation. At the same time clinicians require concise and feasible measures for routine practice. Considering the heterogeneity of post-COVID-19 condition, a biopsychosocial approach requires sufficient coverage of the psychosocial dimension with assessments. Previous recommendations for core outcome sets have serious limitations regarding the psychosocial aspects of post-COVID-19 condition. This paper specifically focuses on psychosocial outcomes for adults with post-COVID-19 condition, providing both a comprehensive set of outcome domains for research and a streamlined clinical core set tailored for routine clinical use.<br><br>METHODS: In a structured Consensus Development Approach, the European Network to improve diagnostic, treatment, and healthcare for patients with persistent somatic symptoms (EURONET-SOMA) developed psychosocial core outcome domains and assessments regarding post-COVID-19 condition. The experts identified variables and instruments which should be considered in studies on adults suffering from post-COVID-19 condition, and which are feasible in the clinical setting and relevant for research.<br><br>RESULTS: We identified three higher-order dimensions with each encompassing several domains: The first higher-order dimension, "outcomes", encompasses (1) the classification/ diagnostics of post-COVID-19 condition, (2) somatic symptoms (including fatigue), (3) the psychopathological status and mental comorbidities, (4) the physical status and somatic comorbidities, (5) neurocognitive symptoms, and (6) illness consequences. The second higher-order domain "mechanisms" encompasses (7) cognitive components, (8) affective components, (9) behavioral components, (10) social components, and (11) psychobiological bridge markers (e.g., neuroimmunological and psychoneuroendocrinological variables). The third higher-order domain, "risk factors", includes factors such as (12) socioeconomic status and sociocultural factors, (13) pre-existing mental and somatic health issues, (14) personality factors (e.g., neuroticism), (15) adverse childhood experiences, (16) ongoing disability or pension claim, and (17) social media use. For each domain, specific instruments are suggested for research purposes and clinical use.<br><br>CONCLUSIONS: The recommended core domains help to increase consistency in a biopsychosocial approach to post-COVID-19 condition across investigations, improve synergies, and facilitate decision-making when comparing different interventional approaches. It allows to better identify relevant subgroups in heterogeneous post-COVID-19 condition populations offering practical tools for routine clinical practice through the clinical core set.}, }
@article {pmid39940333, year = {2025}, author = {Dorczok, MC and Mittmann, G and Mossaheb, N and Schrank, B and Bartova, L and Neumann, M and Steiner-Hofbauer, V}, title = {Dietary Supplementation for Fatigue Symptoms in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)-A Systematic Review.}, journal = {Nutrients}, volume = {17}, number = {3}, pages = {}, pmid = {39940333}, issn = {2072-6643}, mesh = {Humans ; *Dietary Supplements ; *Fatigue/etiology ; *Fatigue Syndrome, Chronic/diet therapy ; Treatment Outcome ; }, abstract = {Background/Objectives: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex neuroimmunological disorder with limited treatment options. Despite the widespread use of Dietary Supplements (DSs) among ME/CFS patients to alleviate fatigue and associated symptoms, evidence remains inconclusive. This systematic review aims to provide an updated synthesis of the efficacy of DS interventions and explore possible mechanisms underlying their therapeutic effects. Methods: This systematic review was conducted according to PRISMA guidelines. Several databases (Ebsco Host, PubMed, Scopus, Google Scholar) were used for the systematic search, which was based on the broad search terms ME/CFS and DS with a focus on publications between 1994 and 2024. The primary outcome was fatigue, with additional considerations including psychological well-being, physical activity, and biochemical markers. Two independent researchers screened the studies for eligibility in a multi-stage process and assessed quality and bias using Cochrane's risk of bias tools (RoB-2, ROBINS-I). Results: Fourteen studies (N = 809) of heterogeneous designs were included, showing a high risk of bias, mostly due to missing data and selection bias. While some interventions (L-carnitine and guanidinoacetic acid, oxaloacetate, CoQ10-selenium combination, NADH and NADH-CoQ10 combination) showed significant reductions in fatigue, methodological limitations, like small sample sizes and missing data, prevent firm conclusions. Mixed results were reported for secondary outcomes like cognitive function and inflammatory markers. Six studies noted adverse effects, including nausea and insomnia. Conclusions: Though some DSs showed potential in reducing fatigue in ME/CFS, methodological limitations and inconsistent results hinder definitive conclusions. Future research should improve diagnostic criteria and include more diverse populations.}, }
@article {pmid39942487, year = {2025}, author = {Honorato-Cia, C and Cacho-Asenjo, E and Martinez-Simon, A and Aquerreta, I and Núñez-Córdoba, JM}, title = {Long COVID Research, 2020-2024: A PubMed-Based Bibliometric Analysis.}, journal = {Healthcare (Basel, Switzerland)}, volume = {13}, number = {3}, pages = {}, pmid = {39942487}, issn = {2227-9032}, support = {0011-3638-2020-000001 and 49-2022//Gobierno de Navarra/ ; }, abstract = {Long COVID is a SARS-CoV-2 infection-associated chronic condition with great potential to impact health and socioeconomic outcomes. The research efforts to face the challenges related to long COVID have resulted in a substantial amount of publications, which warrants the need for bibliometric profiling. This is a large-scale PubMed-based bibliometric analysis of more than 390,000 COVID-19 publications. The overall aim was to update the profile of long COVID publications in comparison with the rest of the COVID-19 scientific literature through December 2024. The estimated proportion of long COVID publications was relatively low (2.3% of all COVID-19 publications), although the cumulative frequency (n = 8928) continues to pose a challenge for proper information management. Currently, "treatment" and "mechanism" appear to be the most predominant research topics in the long COVID literature. Interestingly, this evaluation revealed a distinctive profile of the long COVID literature, with a clear preponderance of "case report" and "mechanism" research topics when compared with other COVID-19 publications. This evaluation also identified and ranked the most prolific scientific journals in the production of long COVID-related publications. This study may improve the visibility of long COVID research and contribute to the management of the growing scientific knowledge on long COVID.}, }
@article {pmid39942772, year = {2025}, author = {Kell, DB and Pretorius, E}, title = {The Proteome Content of Blood Clots Observed Under Different Conditions: Successful Role in Predicting Clot Amyloid(ogenicity).}, journal = {Molecules (Basel, Switzerland)}, volume = {30}, number = {3}, pages = {}, pmid = {39942772}, issn = {1420-3049}, mesh = {Humans ; *Proteome/metabolism/analysis ; *Amyloid/metabolism ; *Thrombosis/blood/metabolism ; *Blood Coagulation ; COVID-19/blood ; }, abstract = {A recent analysis compared the proteome of (i) blood clots seen in two diseases-sepsis and long COVID-when blood was known to have clotted into an amyloid microclot form (as judged by staining with the fluorogenic amyloid stain thioflavin T) with (ii) that of those non-amyloid clots considered to have formed normally. Such fibrinaloid microclots are also relatively resistant to fibrinolysis. The proteins that the amyloid microclots contained differed markedly both from the soluble proteome of typical plasma and that of normal clots, and also between the diseases studied (an acute syndrome in the form of sepsis in an ITU and a chronic disease represented by Long COVID). Many proteins in the amyloid microclots were low in concentration in plasma and were effectively accumulated into the fibres, whereas many other abundant plasma proteins were excluded. The proteins found in the microclots associated with the diseases also tended to be themselves amyloidogenic. We here ask effectively the inverse question. This is: can the clot proteome tell us whether the clots associated with a particular disease contained proteins that are observed uniquely (or are highly over-represented) in known amyloid clots relative to normal clots, and thus were in fact amyloid in nature? The answer is in the affirmative in a variety of major coagulopathies, viz., venous thromboembolism, pulmonary embolism, deep vein thrombosis, various cardiac issues, and ischaemic stroke. Galectin-3-binding protein and thrombospondin-1 seem to be especially widely associated with amyloid-type clots, and the latter has indeed been shown to be incorporated into growing fibrin fibres. These may consequently provide useful biomarkers with a mechanistic basis.}, }
@article {pmid39943820, year = {2025}, author = {Dieter, RS and Kempaiah, P and Dieter, EG and Alcazar, A and Tafur, A and Gerotziafas, G and Gonzalez Ochoa, A and Abdesselem, S and Biller, J and Kipshidze, N and Vandreden, P and Guerrini, M and Dieter, RA and Durvasula, R and Singh, M and Fareed, J}, title = {Cardiovascular Symposium on Perspectives in Long COVID.}, journal = {Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis}, volume = {31}, number = {}, pages = {10760296251319963}, pmid = {39943820}, issn = {1938-2723}, mesh = {Humans ; *COVID-19/complications/blood ; *SARS-CoV-2 ; *Cardiovascular Diseases/etiology ; Post-Acute COVID-19 Syndrome ; Pandemics ; }, abstract = {Significant progress has been made in treating Coronavirus disease (COVID) - an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). An ominous turn in the pandemic is the evolving public health crisis emanating from persistent SARS-CoV-2 infection and its associated long-term impact. Long COVID or post-COVID syndrome describes protean symptoms that persist at least 3 months after the onset of acute illness and last for at least 2 months in individuals with a history of confirmed SARS-CoV-2 infection. Long COVID has become a public health concern. Millions of infected individuals are now facing chronic multi-organ failures, including neuropsychiatric, cardiovascular, pulmonary, and kidney complications. In general, the cause of long COVID syndrome is unclear but factors such as prolonged activation of immune responses, and viral persistence triggering transcription dysregulation of genes associated with normal thrombotic disease may play a role in cardiovascular complications. Although inflammatory biomarkers are reported in other disorders, it remains unclear whether similar biomarkers are associated with cardiovascular manifestations following COVID. Medications such as sulodexide directed at glycocalyx and coagulation have demonstrated benefits for long COVID in smaller studies. Here, we describe the outcomes of the symposium on the underlying cardiovascular mechanisms of the long COVID.}, }
@article {pmid39944605, year = {2025}, author = {Zhang, T and Li, Z and Mei, Q and Walline, JH and Zhang, Z and Liu, Y and Zhu, H and Du, B}, title = {Cardiovascular outcomes in long COVID-19: a systematic review and meta-analysis.}, journal = {Frontiers in cardiovascular medicine}, volume = {12}, number = {}, pages = {1450470}, pmid = {39944605}, issn = {2297-055X}, abstract = {INTRODUCTION: There is growing evidence that patients with SARS-CoV-2 (The severe acute respiratory syndrome coronavirus 2) may have a variety of cardiovascular complications in the post-acute phase of COVID-19, but these manifestations have not yet been comprehensively characterized.<br><br>METHODS: We performed a systematic review and meta-analysis of primary research papers which evaluated individuals at least four weeks after confirmed COVID-19 diagnosis and reported on cardiovascular disease prevalence. Systematic search conducted without language restrictions from December 1, 2019 to June 31, 2022 on PubMed, EMBASE, Web of Science, Cochrane library, ProQuest Coronavirus Research Database, COVID-19 Living Overview of the Evidence (L-OVE) subset of Episteminokos and the World Health Organization (WHO) Covid-19 databases. Study was reported according to MOOSE-lists and the PRISMA guidelines. The risk of bias was identified using the Newcastle-Ottawa Scale (NOS) for observational studies. Random-effects meta-analyses examined the pooled risk difference in the prevalence of each symptom or symptom combination in cases with confirmed SARS-coV-2 infection compared with controls.<br><br>RESULTS: Eight cohort studies were eligible, including nearly 10 million people. Long COVID-19 was associated with a higher risk of thromboembolic disorders [HR 3.12 (1.60, 6.08)], coronary heart disease [HR 1.61 (1.13, 2.31)], stroke [HR 1.71 (1.07,2.72)], arrhythmia [HR 1.60 (1.13, 2.26)], cardiomyopathy [HR 1.71 (1.12, 2.61)], myocarditis [HR 6.11 (4.17,8.94)], hypertension [HR 1.70 (1.56, 1.85)], heart failure [HR 1.72 (1.15,2.59)] and cardiogenic shock [HR 2.09 (1.53,2.86)] compared to non-COVID-19 controls. Pooled risk differences in long COVID cases compared to controls were significantly higher for cardiomyopathy [0.15% (0.06, 0.23)], deep vein thrombosis [0.45% (0.06, 0.83)] and hypertension (0.32%, (0.06, 0.58) but not for thromboembolic disorders, coronary disease, stroke, arrhythmia, cardiomyopathy, myocarditis, hypertension, heart failure or cardiogenic shock.<br><br>CONCLUSION: The risk of cardiovascular disease increased significantly four weeks or more after recovering from acute COVID-19. Care for survivors after an acute attack of COVID-19 should include paying close attention to cardiovascular health and disease.<br><br>PROSPERO [CRD42022353965].}, }
@article {pmid39947217, year = {2025}, author = {Proal, AD and Aleman, S and Bomsel, M and Brodin, P and Buggert, M and Cherry, S and Chertow, DS and Davies, HE and Dupont, CL and Deeks, SG and Ely, EW and Fasano, A and Freire, M and Geng, LN and Griffin, DE and Henrich, TJ and Hewitt, SM and Iwasaki, A and Krumholz, HM and Locci, M and Marconi, VC and Mehandru, S and Muller-Trutwin, M and Painter, MM and Pretorius, E and Price, DA and Putrino, D and Qian, Y and Roan, NR and Salmon, D and Tan, GS and VanElzakker, MB and Wherry, EJ and Van Weyenbergh, J and Yonker, LM and Peluso, MJ}, title = {Targeting the SARS-CoV-2 reservoir in long COVID.}, journal = {The Lancet. Infectious diseases}, volume = {25}, number = {5}, pages = {e294-e306}, pmid = {39947217}, issn = {1474-4457}, support = {K23 AI157875/AI/NIAID NIH HHS/United States ; R01 HL173059/HL/NHLBI NIH HHS/United States ; R01 NS136197/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/virology/complications ; *SARS-CoV-2/physiology/drug effects ; Antiviral Agents/therapeutic use ; COVID-19 Drug Treatment ; Clinical Trials as Topic ; }, abstract = {There are no approved treatments for post-COVID-19 condition (also known as long COVID), a debilitating disease state following SARS-CoV-2 infection that is estimated to affect tens of millions of people. A growing body of evidence shows that SARS-CoV-2 can persist for months or years following COVID-19 in a subset of individuals, with this reservoir potentially driving long-COVID symptoms or sequelae. There is, therefore, an urgent need for clinical trials targeting persistent SARS-CoV-2, and several trials of antivirals or monoclonal antibodies for long COVID are underway. However, because mechanisms of SARS-CoV-2 persistence are not yet fully understood, such studies require important considerations related to the mechanism of action of candidate therapeutics, participant selection, duration of treatment, standardisation of reservoir-associated biomarkers and measurables, optimal outcome assessments, and potential combination approaches. In addition, patient subgroups might respond to some interventions or combinations of interventions, making post-hoc analyses crucial. Here, we outline these and other key considerations, with the goal of informing the design, implementation, and interpretation of trials in this rapidly growing field. Our recommendations are informed by knowledge gained from trials targeting the HIV reservoir, hepatitis C, and other RNA viruses, as well as precision oncology, which share many of the same hurdles facing long-COVID trials.}, }
@article {pmid39952011, year = {2025}, author = {Schurr, M and Graf, J and Junne, F and Giel, KE}, title = {Psychotherapy in patients with long/post-COVID - A systematic review on the feasibility, acceptability, safety, and efficacy of available and emerging interventions.}, journal = {Journal of psychosomatic research}, volume = {190}, number = {}, pages = {112048}, doi = {10.1016/j.jpsychores.2025.112048}, pmid = {39952011}, issn = {1879-1360}, mesh = {Humans ; *COVID-19/psychology/complications ; *Psychotherapy/methods ; Feasibility Studies ; SARS-CoV-2 ; *Patient Acceptance of Health Care ; }, abstract = {BACKGROUNDS: There is an urgent need for effective treatments for patients with long/post-COVID. Current recommendations for management favor a multimodal approach including psychotherapy and emphasize that interventions should also consider the mental health impact of living with long/post-COVID. This systematic review synthesizes psychotherapeutic interventions that currently target long/post-COVID complaints and summarizes data on the feasibility, acceptability, safety, and efficacy of psychotherapy for patients with long/post-COVID.<br><br>METHODS: This systematic review was conducted according to the PRISMA statement. Studies were retrieved from three databases (PubMed, PsycInfo, Web of Science) and independently assessed by two raters. Studies investigating patients of any age suffering from long/post-COVID were included if the intervention involved psychotherapeutic treatment and changes in long/post-COVID symptoms were reported. The review has been pre-registered on PROSPERO.<br><br>RESULTS: A total of 12 studies were included in the analysis. Of these, 10 were multimodal approaches with integrated psychotherapeutic interventions, and two were studies on stand-alone psychotherapy. The majority of studies were uncontrolled and demonstrate pre-post improvements in a range of long/post-COVID symptoms. Only one RCT could be identified, which supports the benefit of CBT for COVID-related fatigue. It was not possible to draw general conclusions regarding the efficacy of psychotherapy for long/post-COVID. However, data on feasibility, acceptability, and safety support the potential of psychotherapy as a treatment approach for long/post-COVID.<br><br>CONCLUSION: Future studies investigating the potential of psychotherapy approach for long/post-COVID which go beyond the pilot stage are needed to systematically assess feasibility, acceptability, safety, and efficacy in large-scale confirmatory trials.}, }
@article {pmid39954574, year = {2025}, author = {Soltsov, M and Jang, DH and Kim, JH and Keenan, A and Pain, K and Jaywant, A and Stilling, J}, title = {Understanding neural mechanisms and the use of targeted non-invasive brain stimulation for treatment of post-stroke fatigue: A scoping review.}, journal = {Journal of the neurological sciences}, volume = {470}, number = {}, pages = {123399}, doi = {10.1016/j.jns.2025.123399}, pmid = {39954574}, issn = {1878-5883}, mesh = {Humans ; *Stroke/complications/diagnostic imaging/physiopathology/therapy ; *Transcranial Magnetic Stimulation/methods ; *Transcranial Direct Current Stimulation/methods ; *Fatigue/etiology/therapy/physiopathology/diagnostic imaging ; *Brain/physiopathology/diagnostic imaging ; }, abstract = {BACKGROUND: Post-stroke fatigue (PSF) is one of the most prevalent symptoms that affects quality of life and daily function after stroke. Despite a growing body of research, its pathophysiology is poorly understood. Non-invasive brain stimulation (NIBS), such as the transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), can serve as a non-pharmacological intervention for PSF. In this review, we aim to (1) evaluate PSF neuroimaging studies to deduce potential neural mechanisms, (2) describe NIBS as a tool to probe brain structures to further understand pathophysiology of fatigue, and (3) assess NIBS as a treatment intervention for PSF.<br><br>METHODS: A systematic search was conducted for the databases PubMed, Embase, Scopus, CINAHL and Cochrane. Studies were included based on the following inclusion and exclusion criteria: >18&#xa0;years with PSF, use of neuroimaging and/or NIBS for investigation or as an intervention for PSF, English language, study types including cohort, case control, or randomized controlled trials. Data extracted included participant characteristics, concept, context, study methods, and key findings relevant to the review questions.<br><br>RESULTS: A total of 30 studies met criteria. Neuroimaging papers that investigated brain structure (MRI) found conflicting associations between lesion location and PSF. Functional methods (fMRI, TMS) revealed altered resting state functional connectivity (rsFC), cortical excitability, and a disruption in interhemispheric inhibitory balance as potential mechanisms of PSF. There were no studies using TMS as an intervention for PSF. Of the six articles that used tDCS, only two reported statistically significant reductions in the severity of PSF.<br><br>CONCLUSION: Structural characteristics of stroke lesions had conflicting findings, while functional neuroimaging studies suggested that altered rsFC, cortical excitability and interhemispheric inhibitory balance contribute to the development of PSF. There were inconsistent results on the effectiveness of tDCS as an intervention for PSF, due to varying methodologies and lack of precise targeting of underlying neural mechanisms. Further investigations are needed to determine if NIBS could be a potential treatment to alleviate the effects of PSF.}, }
@article {pmid39956089, year = {2025}, author = {Smith, DS and Postma, M and Fisman, D and Mould-Quevedo, J}, title = {Cost-effectiveness models assessing COVID-19 booster vaccines across eight countries: A review of methods and data inputs.}, journal = {Vaccine}, volume = {51}, number = {}, pages = {126879}, doi = {10.1016/j.vaccine.2025.126879}, pmid = {39956089}, issn = {1873-2518}, mesh = {Humans ; *COVID-19/prevention &amp; control/epidemiology/economics ; *COVID-19 Vaccines/economics/administration &amp; dosage/immunology ; *Cost-Benefit Analysis ; SARS-CoV-2/immunology ; *Immunization, Secondary/economics ; Vaccine Efficacy ; Europe/epidemiology ; }, abstract = {Coronavirus disease 2019 (COVID-19) continues to cause serious health consequences globally. Policy makers now assess cost effectiveness (CE) when evaluating COVID-19 vaccines. A targeted literature review was performed to examine recent CE evidence for COVID-19 vaccines, as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transitions from pandemic to endemic, to identify best practices. Data were from large EU countries (UK, Spain, Germany, France, and Italy), US, Canada, and Australia. Nine CE studies met the inclusion criteria. Studies evaluated booster vaccination, and mainly considered mRNA vaccines. CE studies reported that COVID-19 vaccines provided health benefits and were cost-effective or showed cost-savings. Benefits were more pronounced in older and high-risk populations based on higher rates of COVID-19 hospitalization and death. CE findings were most sensitive to estimates of incidence of COVID-19, SARS-CoV-2 transmissibility, vaccine effectiveness, waning/duration of vaccine protection, and hospitalization costs. Most data inputs were sourced from real-world evidence (RWE). Lack of inclusion of some parameters, such as transmission modeling, productivity losses, and the impact of long COVID may undervalue COVID-19 vaccines. As SARS-CoV-2 evolves and COVID-19 vaccines are updated, continuous generation of RWE is needed to demonstrate the CE of COVID-19 vaccines in an ongoing manner.}, }
@article {pmid39956285, year = {2025}, author = {Talwar, S and Harker, JA and Openshaw, PJM and Thwaites, RS}, title = {Autoimmunity in long COVID.}, journal = {The Journal of allergy and clinical immunology}, volume = {155}, number = {4}, pages = {1082-1094}, doi = {10.1016/j.jaci.2025.02.005}, pmid = {39956285}, issn = {1097-6825}, mesh = {Humans ; *COVID-19/immunology ; *Autoimmunity/immunology ; *SARS-CoV-2/immunology ; Autoantibodies/immunology ; *B-Lymphocytes/immunology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long COVID (also termed postacute sequelae of SARS-CoV-2, or PASC) affects up to 10% of people recovering from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diagnosis is hampered by diffuse symptomatology, lack of biomarkers, incomplete understanding of pathogenesis, and lack of validated treatments. In terms of pathogenesis, hypothesized causes include virus persistence, the legacy of endotheliitis and thrombosis, low-grade tissue-based inflammation and/or scarring, perturbation of the host virome/microbiome, or triggering of autoimmunity. Several studies show preexisting and/or de novo production of autoantibodies after infection with SARS-CoV-2, but the persistence of these antibodies and their role in causing long COVID is debated. Here, we review the mechanisms through which autoimmune responses can arise during and after viral infection, focusing on the evidence for B-cell dysregulation and autoantibody production in acute and long COVID.}, }
@article {pmid39960432, year = {2025}, author = {Syed, AM and Karius, AK and Ma, J and Wang, PY and Hwang, PM}, title = {Mitochondrial Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.}, journal = {Physiology (Bethesda, Md.)}, volume = {40}, number = {4}, pages = {0}, pmid = {39960432}, issn = {1548-9221}, support = {Z01 HL005101/ImNIH/Intramural NIH HHS/United States ; ZIA HL005101/ImNIH/Intramural NIH HHS/United States ; HL005101//HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; }, mesh = {Humans ; *Fatigue Syndrome, Chronic/metabolism/physiopathology ; *Mitochondria/metabolism/pathology ; Animals ; COVID-19/metabolism ; }, abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystem disorder of unclear etiology that affects many individuals worldwide. One of its hallmark symptoms is prolonged fatigue following exertion, a feature also observed in long COVID, suggesting an underlying dysfunction in energy production in both conditions. Here, mitochondrial dysfunction and its potential pathogenetic role in these disorders are reviewed.}, }
@article {pmid39965723, year = {2025}, author = {Foreman, L and Child, B and Saywell, I and Collins-Praino, L and Baetu, I}, title = {Cognitive reserve moderates the effect of COVID-19 on cognition: A systematic review and meta-analysis of individual participant data.}, journal = {Neuroscience and biobehavioral reviews}, volume = {171}, number = {}, pages = {106067}, doi = {10.1016/j.neubiorev.2025.106067}, pmid = {39965723}, issn = {1873-7528}, mesh = {Humans ; *COVID-19/complications/psychology ; *Cognitive Reserve/physiology ; *Cognitive Dysfunction/etiology/physiopathology/psychology ; }, abstract = {Elucidating the factors that mitigate the effects of COVID-19 on cognitive function offers important insights for public health policy and intervention. This systematic review and individual participant data (IPD) meta-analysis assesses cognitive reserve (CR) as a potential moderator of post-COVID-19 cognitive dysfunction (PCCD). Under PRISMA-IPD guidelines, data searches were conducted via PubMed, PsycINFO, Scopus, and Embase, up to January 2023. Eligible studies included at least one cognitive assessment, CR proxy, and disease severity indicator. Of 5604 studies, 87 were eligible (10,950 COVID-19 cases; 78,305 controls), and IPD was obtained for 29 datasets (3919 COVID-19 cases; 8267 controls). Three-level random-effects meta-analyses indicated that CR had a moderate positive association (rsp =.29), and COVID-19 severity had a small negative association (rsp = -.07) with cognitive outcomes. These effects were moderated by a significant within-study interaction. Cognitive deficits following COVID-19 were 33 % smaller among high CR individuals, and 33 % greater among low CR individuals, relative to those with average CR. Population-based initiatives promoting reserve-building behaviors may alleviate the PCCD-related public health burden. REVIEW REGISTRATION: PROSPERO registration number: CRD42022360670.}, }
@article {pmid39967803, year = {2025}, author = {Smadja, DM and Abreu, MM}, title = {Hyperthermia and targeting heat shock proteins: innovative approaches for neurodegenerative disorders and Long COVID.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1475376}, pmid = {39967803}, issn = {1662-4548}, abstract = {Neurodegenerative diseases (NDs) and Long COVID represent critical and growing global health challenges, characterized by complex pathophysiological mechanisms including neuronal deterioration, protein misfolding, and persistent neuroinflammation. The emergence of innovative therapeutic approaches, such as whole-body hyperthermia (WBH), offers promising potential to modulate underlying pathophysiological mechanisms in NDs and related conditions like Long COVID. WBH, particularly in fever-range, enhances mitochondrial function, induces heat shock proteins (HSPs), and modulates neuroinflammation-benefits that pharmacological treatments often struggle to replicate. HSPs such as HSP70 and HSP90 play pivotal roles in protein folding, aggregation prevention, and cellular protection, directly targeting pathological processes seen in NDs like Alzheimer's, Parkinson's, and Huntington's disease. Preliminary findings also suggest WBH's potential to alleviate neurological symptoms in Long COVID, where persistent neuroinflammation and serotonin dysregulation are prominent. Despite the absence of robust clinical trials, the therapeutic implications of WBH extend to immune modulation and the restoration of disrupted physiological pathways. However, the dual nature of hyperthermia's effects-balancing pro-inflammatory and anti-inflammatory responses-emphasizes the need for dose-controlled applications and stringent patient monitoring to minimize risks in vulnerable populations. While WBH shows potential interest, significant challenges remain. These include individual variability in response, limited accessibility to advanced hyperthermia technologies, and the need for standardized clinical protocols. Future research must focus on targeted clinical trials, biomarker identification, and personalized treatment strategies to optimize WBH's efficacy in NDs and Long COVID. The integration of WBH into therapeutic paradigms could mark a transformative step in addressing these complex conditions.}, }
@article {pmid39967901, year = {2024}, author = {Panesar, A and Gharanei, P and Khovanova, N and Young, L and Grammatopoulos, D}, title = {Thyroid function during COVID-19 and post-COVID complications in adults: a systematic review.}, journal = {Frontiers in endocrinology}, volume = {15}, number = {}, pages = {1477389}, pmid = {39967901}, issn = {1664-2392}, mesh = {Humans ; *COVID-19/complications/physiopathology ; *Thyroid Gland/physiopathology/virology ; *SARS-CoV-2 ; Adult ; *Thyroid Diseases/etiology/virology/physiopathology ; Thyroid Hormones ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, has presented multifaceted health challenges. COVID-19 primarily targets the respiratory system but also affects multiple organ systems, including the endocrine system. Emerging evidence suggests interactions between thyroid function, the acute phase of COVID-19, and the prolonged symptoms known as post-COVID sequalae or long COVID. Several studies have reported that COVID-19 can induce thyroid dysfunction, leading to conditions such as thyroiditis and alterations in thyroid hormone levels. The mechanisms through which SARS-CoV-2 affects the thyroid include direct viral infection of thyroid cells, leading to viral thyroiditis, which causes inflammation and transient or sustained thyroid dysfunction, as well as an excessive systemic immune response (cytokine storm). This is associated with elevated levels of cytokines, such as IL-6, that disrupt thyroid function and lead to nonthyroidal illness syndrome (NTIS). Medications administered during the acute illness phase, such as corticosteroids and antiviral drugs, can also impact thyroid hormone actions. The involvement of the thyroid gland in long COVID, or postacute sequelae of SARS-CoV-2 infection, is an area not well defined, with potential implications for understanding and managing this condition. Persistent low-grade inflammation affecting thyroid function over time can lead to ongoing thyroiditis or exacerbate pre-existing thyroid conditions. Viral infections, including SARS-CoV-2, can trigger or worsen autoimmune thyroid diseases, such as Hashimoto's thyroiditis and Graves' disease. Long COVID may disrupt the hypothalamic-pituitary-adrenal (HPA) axis, which can, in turn, affect the hypothalamic-pituitary-thyroid (HPT) axis, leading to abnormal thyroid function. This review was designed to systematically capture recent literature on COVID-19-related thyroid dysfunction in the adult population, the prognostic consequences of thyroid dysfunction during COVID-19, and the effects of thyroid dysfunction on patients with long COVID. A comprehensive search of PubMed and EMBASE databases was conducted. The systematic review was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Study quality was assessed using the Critical Appraisal Skills Programme (CASP). A total of 53 studies met the inclusion criteria. The review summarises recent findings and provides an update of the current understanding of thyroid dysfunction in COVID-19-related spectrum of disorders, underscoring the complex nature of SARS-CoV-2 infection and its far-reaching impacts on human health.}, }
@article {pmid39971694, year = {2025}, author = {Tsang, MS and Zhou, IW and Zhang, AL and Xue, CC}, title = {Chinese herbal medicine for dyspnea and persistent symptoms of long COVID: A systematic review and meta-analysis of randomized controlled trials.}, journal = {Journal of integrative medicine}, volume = {23}, number = {2}, pages = {126-137}, doi = {10.1016/j.joim.2025.01.001}, pmid = {39971694}, issn = {2095-4964}, mesh = {Humans ; *Dyspnea/drug therapy/etiology ; *Drugs, Chinese Herbal/therapeutic use ; Randomized Controlled Trials as Topic ; *COVID-19/complications ; Fatigue/drug therapy ; SARS-CoV-2 ; Anxiety/drug therapy ; Depression/drug therapy ; Sleep Initiation and Maintenance Disorders/drug therapy ; Betacoronavirus ; }, abstract = {BACKGROUND: Over 65 million people have long COVID. Evidence for using Chinese herbal medicine (CHM) to treat long COVID is growing. A systematic review of evidence for guiding clinical decision is warranted.<br><br>OBJECTIVE: To examine the effects and safety of CHM in alleviating the severity of dyspnea, fatigue, exercise intolerance, depression, anxiety and insomnia in long COVID adults based on registered randomized clinical trials (RCT).<br><br>SEARCH STRATEGY: World Health Organization International Clinical Trials Registry Platform and Chinese Clinical Trial Registry were searched for registered trial protocols from database inception to February 10, 2023. English (PubMed, Embase, AMED and CINAHL) and Chinese databases (CNKI, Wanfang Data and CQVIP) were then searched to identify relevant publications from December 2019 through April 6, 2023.<br><br>INCLUSION CRITERIA: Registered RCTs that compared the effects of Chinese herbal medicines or Chinese herbal formulas against a control treatment (i.e., the placebo or usual care) in adults with persistent symptoms of long COVID. The primary outcome of dyspnea, and secondary outcomes of fatigue, exercise intolerance, depression, anxiety and insomnia were measured using validated tools at the end of the treatment.<br><br>DATA EXTRACTION AND ANALYSIS: Data were extracted, and eligible RCTs were evaluated using version 2 of the Cochrane risk-of-bias tool for randomized trials and Grading of Recommendations, Assessment, Development and Evaluations independently by two researchers. Effect sizes were estimated by random-effects modelling and mean difference (MD). Heterogeneity between trials was quantified by I[2].<br><br>RESULTS: Among the 38 registered clinical trials we identified, seven RCTs (1,519 patients) were included in the systematic review. One RCT had a low overall risk of bias. Compared to the control, CHM reduces dyspnea on the Borg Dyspnea Scale score (MD&#xa0;=&#xa0;-0.2, 95% confidence interval [CI]&#xa0;=&#xa0;-0.65 to 0.25) with moderate certainty, and reduces fatigue on the Borg Scale (MD&#xa0;=&#xa0;-0.48, 95% CI&#xa0;=&#xa0;-0.74 to -0.22) with low certainty. CHM clinically reduces depression on Hamilton Depression Rating Scale score (MD&#xa0;=&#xa0;-6.00, 95% CI&#xa0;=&#xa0;-7.56 to -4.44) and anxiety on Hamilton Anxiety Rating Scale score (MD&#xa0;=&#xa0;-6.10, 95% CI&#xa0;=&#xa0;-7.67 to -4.53), and reduces insomnia on the Insomnia Severity Index (MD&#xa0;=&#xa0;-4.86, 95% CI&#xa0;=&#xa0;-12.50 to 2.79) with moderate certainty. Meta-analysis of two RCTs (517 patients) showed that CHM clinically improves exercise intolerance by increasing 6-minute walking distance (MD&#xa0;=&#xa0;-15.92, 95% CI&#xa0;=&#xa0;-10.20 to 42.05) with substantial heterogeneity (I[2]&#xa0;=&#xa0;68%) and low certainty.<br><br>CONCLUSION: CHM is associated with a post-treatment clinical reduction in depression and anxiety in long COVID adults, compared to the control, but it does not have a strong treatment effect on dyspnea and insomnia. Effects of CHM on exercise intolerance and fatigue are uncertain, and the safety of using CHM remains questionable. Please cite this article as: Tsang MS, Zhou IW, Zhang AL, Xue CC. Chinese herbal medicine for dyspnea and persistent symptoms of long COVID: A systematic review and meta-analysis of randomized controlled trials. J Integr Med. 2025; 23(2): 126-137.}, }
@article {pmid39974559, year = {2025}, author = {Ewing, AG and Salamon, S and Pretorius, E and Joffe, D and Fox, G and Bilodeau, S and Bar-Yam, Y}, title = {Review of organ damage from COVID and Long COVID: a disease with a spectrum of pathology.}, journal = {Medical review (2021)}, volume = {5}, number = {1}, pages = {66-75}, pmid = {39974559}, issn = {2749-9642}, abstract = {Long COVID, as currently defined by the World Health Organization (WHO) and other authorities, is a symptomatic condition that has been shown to affect an estimated 10 %-30 % of non-hospitalized patients after one infection. However, COVID-19 can also cause organ damage in individuals without symptoms, who would not fall under the current definition of Long COVID. This organ damage, whether symptomatic or not, can lead to various health impacts such as heart attacks and strokes. Given these observations, it is necessary to either expand the definition of Long COVID to include organ damage or recognize COVID-19-induced organ damage as a distinct condition affecting many symptomatic and asymptomatic individuals after COVID-19 infections. It is important to consider that many known adverse health outcomes, including heart conditions and cancers, can be asymptomatic until harm thresholds are reached. Many more medical conditions can be identified by testing than those that are recognized through reported symptoms. It is therefore important to similarly recognize that while Long COVID symptoms are associated with organ damage, there are many individuals that have organ damage without displaying recognized symptoms and to include this harm in the characterization of COVID-19 and in the monitoring of individuals after COVID-19 infections.}, }
@article {pmid39981885, year = {2025}, author = {Zhang, Y and Chen, H and Li, Y and Luo, C and Zhu, Y and Zhou, X and Wang, R and He, J and Guo, H and Xu, X and Qiu, M and Li, J}, title = {Animal Models for Long COVID: Current Advances, Limitations, and Future Directions.}, journal = {Journal of medical virology}, volume = {97}, number = {2}, pages = {e70237}, doi = {10.1002/jmv.70237}, pmid = {39981885}, issn = {1096-9071}, mesh = {Animals ; *Disease Models, Animal ; *COVID-19/pathology/virology/epidemiology ; Humans ; Mice ; SARS-CoV-2/pathogenicity ; Mesocricetus ; Cricetinae ; Primates ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long COVID (LC) represents a chronic, systemic, and often disabling condition that poses a significant ongoing threat to public health. Foundational scientific studies are needed to unravel the underlying mechanisms, with the ultimate goal of developing effective preventative and therapeutic strategies. Therefore, there is an urgent demand for animal models that can accurately replicate the clinical features of LC. This review integrates clinical epidemiological data to summarize the pathological changes in extrapulmonary systems involved in LC. Additionally, it critically examines the capacity of existing animal models, including nonhuman primates, genetically modified mice, and Syrian hamsters, to exhibit enduring postinfection symptoms that align with human clinical manifestations, and identifies key areas requiring further development. The objective is to offer insights that will aid in the development of next-generation animal models, thereby accelerating our understanding of how acute respiratory viral infections transition into chronic conditions, and ensuring preparedness for future pandemics.}, }
@article {pmid39984803, year = {2025}, author = {Ivlev, I and Wagner, J and Phillips, T and Treadwell, JR}, title = {Interventions for Long COVID: A Narrative Review.}, journal = {Journal of general internal medicine}, volume = {40}, number = {9}, pages = {2005-2023}, pmid = {39984803}, issn = {1525-1497}, support = {MSA-SOW#05-ECRI-ENG-11-07-2022/PCORI/Patient-Centered Outcomes Research Institute/United States ; }, mesh = {Humans ; *COVID-19/therapy/complications/psychology/epidemiology ; *Survivors/psychology ; Post-Acute COVID-19 Syndrome ; Randomized Controlled Trials as Topic/methods ; SARS-CoV-2 ; }, abstract = {Long COVID continues to impose a significant burden on COVID-19 survivors, presenting with diverse symptoms and clinical uncertainty. This review synthesized evidence from 97 studies, including 26 randomized controlled trials and 15 non-randomized comparative studies, which explored the effectiveness, comparative effectiveness, and potential risks of proposed interventions for managing common long COVID symptoms: fatigue, neurocognitive symptoms, anxiety, depression, and sleep issues. Our comprehensive analysis, encompassing English-language articles, gray literature, and feedback from 14 Key Informants (i.e., patients, caregivers, clinicians, payors, and researchers), reveals a persistently weak body of evidence, characterized by high imprecision and considerable uncertainty regarding the benefits and harms of the interventions. The studies examined a wide array of treatment categories, including multi-component rehabilitation, supplements, complementary treatments, prescription medications, and the COVID-19 vaccine. Key informants emphasized the critical need for establishing robust diagnostic criteria and utilizing functional outcomes while also highlighting significant barriers to care, including dismissive attitudes from healthcare providers, inadequate insurance coverage, and restricted access to specialty care. Given the evolving definitions of long COVID and the variable mechanisms of its management, our findings underscore the pressing need for further rigorous research to refine and validate effective treatment protocols. Until more definitive evidence is available, both clinicians and patients face substantial uncertainty in treatment decisions, with many resorting to self-treatment using costly and potentially ineffective options.}, }
@article {pmid39990183, year = {2025}, author = {Łukomska, E and Kloc, K and Kowalska, M and Matjaszek, A and Joshi, K and Scholz, S and Van de Velde, N and Beck, E}, title = {Healthcare Resource Utilization (HCRU) and Direct Medical Costs Associated with Long COVID or Post-COVID-19 Conditions: Findings from a Literature Review.}, journal = {Journal of market access &amp; health policy}, volume = {13}, number = {1}, pages = {7}, pmid = {39990183}, issn = {2001-6689}, abstract = {Approximately 10-20% of individuals suffering from COVID-19 develop prolonged symptoms known as long COVID or post-COVID condition (LC). This review aimed to assess healthcare resource use (HCRU) and healthcare costs associated with LC. Because LC is not clearly defined and often remains undiagnosed, studies reporting on long-term follow-up of individuals with a COVID-19 diagnosis were also included. Among the 41 publications included, 36 reported on HCRU and 16 on costs. Individuals with LC had significantly elevated HCRU and healthcare costs vs. controls without a COVID-19 diagnosis over ≥15 months, with a 7.6-13.1% increase in total healthcare costs per person per month as assessed by difference-in-difference analysis. Among studies that did not specifically refer to LC, having a COVID-19 diagnosis was associated with a significant 4-10% increase in long-term total HCRU over 6-8 months and a 1.3- to 2.9-fold relative increase in total healthcare costs over 6 months. Due to the heterogeneity of the included studies, high-quality evidence is needed to better understand the economic burden of LC. In the absence of effective treatments, prioritizing the prevention of acute COVID-19, e.g., through vaccination, may be crucial for preventing LC and the associated long-term HCRU and medical spending.}, }
@article {pmid39993991, year = {2025}, author = {Mink, S and Wilhelm, F and Cadamuro, J and Reimann, P and Fraunberger, P}, title = {Anti-SARS-CoV-2 Antibodies in Long-COVID-Markers of Protection or Elevated Risk? A Systematic Review.}, journal = {Reviews in medical virology}, volume = {35}, number = {2}, pages = {e70027}, doi = {10.1002/rmv.70027}, pmid = {39993991}, issn = {1099-1654}, mesh = {Humans ; *COVID-19/immunology/virology/blood ; *Antibodies, Viral/blood/immunology ; *SARS-CoV-2/immunology ; Biomarkers/blood ; Risk Factors ; }, abstract = {Long-COVID affects a significant number of COVID-19 survivors, profoundly impacting daily life and work. Although research suggests a potential link between antibody levels and long-COVID risk, findings remain inconclusive. Understanding antibody dynamics could support the identification of patients at risk, improve long-COVID diagnosis, and guide protective strategies such as vaccination. Despite growing evidence, no systematic review has yet evaluated the current literature on this topic. We therefore aimed to synthesise and evaluate existing evidence on the association between anti-SARS-CoV-2 antibody titres and long-COVID, with the goal of clarifying their potential role in predicting long-COVID risk, guiding patient management, and informing future research directions. Studies published in PubMed/Medline databases between January 2020 and October 2024 were included without language restrictions. Studies on body fluids other than serum/blood were excluded. Study selection and quality assessment was conducted independently by two researchers. After screening 949 studies, 58 studies encompassing 53,739 individuals, and 7812 long-COVID patients, were included. Evidence was highly heterogenous but most studies reported an association between anti-SARS-CoV-2-spike antibodies and long-COVID, although the nature of the association appeared to be dependent on time from acute infection. Low anti-SARS-CoV-2-spike antibodies during acute COVID-19 were associated with increased risk of long-COVID. The association between low anti-SARS-CoV-2-spike antibodies during acute COVID-19 and long-COVID suggests that maintaining sufficiently high antibody levels may be protective. However, the current evidence level is low and further studies with sufficient power are required to confirm this association and to potentially determine protective cutoffs.}, }
@article {pmid39997467, year = {2025}, author = {Ayyoub, S and Dhillon, NK and Tura-Ceide, O}, title = {Genetics of Long COVID: Exploring the Molecular Drivers of Persistent Pulmonary Vascular Disease Symptoms.}, journal = {Infectious disease reports}, volume = {17}, number = {1}, pages = {}, pmid = {39997467}, issn = {2036-7430}, support = {PI21/01212//Catalan Pneumology Foundation (FUCAP) and from the Institute of Health Carlos III/ ; 2024 FI-3 00065//AGAUR-FI ajuts Joan Or&#xf3;, backed by the Secretariat of Universities and Research of the Department of Research and Universities of the Generalitat of Catalonia, and the European Social Plus Fund/ ; R01HL1528322//NIH Funding/ ; CP17/00114, CPII22/00006)//Miguel Servet type grants from the Institute of Health Carlos III/ ; R01 HL152832/HL/NHLBI NIH HHS/United States ; }, abstract = {Background/ Objectives: Long COVID or post-acute sequelae of SARS-CoV-2 infection (PASC) are symptoms that manifest despite passing the acute infection phase. These manifestations encompass a wide range of symptoms, the most common being fatigue, shortness of breath, and cognitive dysfunction. Genetic predisposition is clearly involved in the susceptibility of individuals to developing these persistent symptoms and the variation in the severity and forms. This review summarizes the role of genetic factors and gene polymorphisms in the development of major pulmonary vascular disorders associated with long COVID. Methods: A comprehensive review of current literature was conducted to examine the genetic contributions to pulmonary complications following SARS-CoV-2 infection. Studies investigating genetic polymorphisms linked to pulmonary hypertension, pulmonary thromboembolism, and pulmonary vascular endothelialitis were reviewed and summarized. Results: Findings show that specific genetic variants contribute to increased susceptibility to pulmonary vascular complications in long COVID patients. Variants associated with endothelial dysfunction, coagulation pathways, and inflammatory responses have been implicated in the development of pulmonary hypertension and thromboembolic events. Genetic predispositions influencing vascular integrity and immune responses appear to influence disease severity and progression. Conclusions: Understanding these mechanisms and genetic predispositions could pave the way for targeted therapeutic interventions to alleviate the burden on patients experiencing long COVID.}, }
@article {pmid40002834, year = {2025}, author = {Whitaker-Hardin, B and McGregor, KM and Uswatte, G and Lokken, K}, title = {A Narrative Review of the Efficacy of Long COVID Interventions on Brain Fog, Processing Speed, and Other Related Cognitive Outcomes.}, journal = {Biomedicines}, volume = {13}, number = {2}, pages = {}, pmid = {40002834}, issn = {2227-9059}, abstract = {In the years following the global emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or COVID-19, researchers have become acutely aware of long-term symptomology associated with this disease, often termed long COVID. Long COVID is associated with pervasive symptoms affecting multiple organ systems. Neurocognitive symptoms are reported by up to 40% of long COVID patients, with resultant effects of loss of daily functioning, employment issues, and enormous economic impact and high healthcare utilization. The literature on effective, safe, and non-invasive interventions for the remediation of the cognitive consequences of long COVID is scarce and poorly described. Of specific interest to this narrative review is the identification of potential interventions for long COVID-associated neurocognitive deficits. Articles were sourced from PubMed, EBSCO, Scopus, and Embase following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles published between the dates of January 2020 and 30 June 2024 were included in the search. Twelve studies were included in the narrative review, including a feasibility study, a pilot study, a case series, a case study, and an observational study, in addition to three randomized clinical trials and four interventional studies. Overall, treatment interventions such as cognitive training, non-invasive brain stimulation therapy, exercise rehabilitation, targeted pharmacological intervention, and other related treatment paradigms show promise in reducing long COVID cognitive issues. This narrative review highlights the need for more rigorous experimental designs and future studies are needed to fully evaluate treatment interventions for persistent cognitive deficits associated with long COVID.}, }
@article {pmid40003500, year = {2025}, author = {Smyth, NJ and Blitshteyn, S}, title = {Language Matters: What Not to Say to Patients with Long COVID, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, and Other Complex Chronic Disorders.}, journal = {International journal of environmental research and public health}, volume = {22}, number = {2}, pages = {}, pmid = {40003500}, issn = {1660-4601}, mesh = {Humans ; *Fatigue Syndrome, Chronic/psychology/therapy ; *COVID-19/psychology/therapy ; *Language ; Chronic Disease/psychology ; SARS-CoV-2 ; *Physician-Patient Relations ; }, abstract = {People with Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and other complex chronic disorders consistently report having difficulty obtaining effective and compassionate medical care and being disbelieved, judged, gaslighted, and even dismissed by healthcare professionals. We believe that these adversarial interactions and language are more likely to arise when healthcare professionals are confronting complex chronic illnesses without proper training, diagnostic biomarkers, or FDA-approved therapies. These problematic conversations between practitioners and patients often involve specific words and phrases-termed the "never-words"-can leave patients in significant emotional distress and negatively impact the clinician-patient relationship and recovery. Seeking to prevent these destructive interactions, we review key literature on best practices for difficult clinical conversations and discuss the application of these practices for people with Long COVID, ME/CFS, dysautonomia, and other complex chronic disorders. We provide recommendations for alternative, preferred phrasing to the never-words, which can enhance therapeutic relationship and chronic illness patient care via compassionate, encouraging, and non-judgmental language.}, }
@article {pmid40004799, year = {2025}, author = {Aliberti, A and Gasparro, R and Mignogna, M and Canfora, F and Spagnuolo, G and Sammartino, G and Coppola, N}, title = {Unveiling the Oral Lesions, Dysgeusia and Osteonecrosis Related to COVID-19: A Comprehensive Systematic Review.}, journal = {Journal of clinical medicine}, volume = {14}, number = {4}, pages = {}, pmid = {40004799}, issn = {2077-0383}, abstract = {Background/Objectives: The oral cavity has garnered increasing attention as a site for viral infection and related pathological manifestations in coronavirus disease-19. This article aims to provide a comprehensive overview of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2)-related oral manifestations, including taste disturbances, oral lesions and osteonecrosis. Methods: A search was conducted up to September 2024 according to PRISMA (Preferred Reporting Items for Systematic Reviews) guidelines using the databases PubMed and Scopus. All the observational, case-series, case-report and cross-sectional studies written in English on oral manifestations related to COVID-19 disease and long-COVID disease were included. All other types of studies and studies based on oral manifestation after COVID-19 vaccination and oral impairment due to lockdown were excluded. The risk of bias of included studies was assessed using the Joanna Briggs Appraisal checklist. Results: A total of 104 articles including 23 case-report, 15 case-series, 8 case-control, 18 cohort and 40 cross-sectional studies were selected. The results showed that patients with COVID-19 were found to have a significantly higher prevalence of xerostomia (45-74%) and dysgeusia (32-59%) compared to non-infected individuals. Regarding oral mucosal lesions, ulcers, candidiasis and herpes simplex infections were frequently observed. As for osteonecrosis, a significant number of patients with COVID-19-associated rhinomaxillary mucormycosis presented with maxillary osteonecrosis due to fungal infection, primarily mucormycosis. The methodological quality of most of the studies was moderate/high. Conclusions: COVID-19 has been associated with a range of oral manifestations. The complex interplay of viral infection, immune response, medication use and stress likely contributes to these oral complications. Early recognition and management of these oral manifestations are crucial for improving patient outcomes and developing targeted preventive and therapeutic strategies for COVID-19-related oral health issues.}, }
@article {pmid40011942, year = {2025}, author = {Leitzke, M and Roach, DT and Hesse, S and Schönknecht, P and Becker, GA and Rullmann, M and Sattler, B and Sabri, O}, title = {Long COVID - a critical disruption of cholinergic neurotransmission?.}, journal = {Bioelectronic medicine}, volume = {11}, number = {1}, pages = {5}, pmid = {40011942}, issn = {2332-8886}, abstract = {BACKGROUND: Following the COVID-19 pandemic, there are many chronically ill Long COVID (LC) patients with different symptoms of varying degrees of severity. The pathological pathways of LC remain unclear until recently and make identification of path mechanisms and exploration of therapeutic options an urgent challenge. There is an apparent relationship between LC symptoms and impaired cholinergic neurotransmission.<br><br>METHODS: This paper reviews the current literature on the effects of blocked nicotinic acetylcholine receptors (nAChRs) on the main affected organ and cell systems and contrasts this with the unblocking effects of the alkaloid nicotine. In addition, mechanisms are presented that could explain the previously unexplained phenomenon of post-vaccination syndrome&#xa0;(PVS). The fact that not only SARS-CoV-2 but numerous other viruses can bind to nAChRs is discussed under the assumption that numerous other post-viral diseases and autoimmune diseases (ADs) may also be due to impaired cholinergic transmission. We also present a case report that demonstrates changes in cholinergic transmission, specifically, the availability of &#x3b1;4&#x3b2;2 nAChRs by using (-)-[[18]F]Flubatine whole-body positron emission tomography (PET) imaging of cholinergic dysfunction in a LC patient along with a significant neurological improvement before and after low-dose transcutaneous nicotine (LDTN) administration. Lastly, a descriptive analysis and evaluation were conducted on the results of a survey involving 231 users of LDTN.<br><br>RESULTS: A substantial body of research has emerged that offers a compelling explanation for the phenomenon of LC, suggesting that it can be plausibly explained because of impaired nAChR function in the human body. Following a ten-day course of transcutaneous nicotine administration, no enduring neuropathological manifestations were observed in the patient. This observation was accompanied by a significant increase in the number of free ligand binding sites (LBS) of nAChRs, as determined by (-)-[[18]F]Flubatine PET imaging. The analysis of the survey shows that the majority of patients (73.5%) report a significant improvement in the symptoms of their LC/MEF/CFS disease as a result of LDTN.<br><br>CONCLUSIONS: In conclusion, based on current knowledge, LDTN appears to be a promising and safe procedure to relieve LC symptoms with no expected long-term harm.}, }
@article {pmid40012912, year = {2024}, author = {Naiditch, H and Betts, MR and Larman, HB and Levi, M and Rosenberg, AZ}, title = {Immunologic and inflammatory consequences of SARS-CoV-2 infection and its implications in renal disease.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1376654}, pmid = {40012912}, issn = {1664-3224}, support = {F32 MD019534/MD/NIMHD NIH HHS/United States ; R01 DK127830/DK/NIDDK NIH HHS/United States ; T32 HL007563/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/immunology/complications ; *SARS-CoV-2/immunology ; Inflammation/immunology ; Cytokines/immunology/metabolism ; *Kidney Diseases/immunology ; }, abstract = {The emergence of the COVID-19 pandemic made it critical to understand the immune and inflammatory responses to the SARS-CoV-2 virus. It became increasingly recognized that the immune response was a key mediator of illness severity and that its mechanisms needed to be better understood. Early infection of both tissue and immune cells, such as macrophages, leading to pyroptosis-mediated inflammasome production in an organ system critical for systemic oxygenation likely plays a central role in the morbidity wrought by SARS-CoV-2. Delayed transcription of Type I and Type III interferons by SARS-CoV-2 may lead to early disinhibition of viral replication. Cytokines such as interleukin-1 (IL-1), IL-6, IL-12, and tumor necrosis factor α (TNFα), some of which may be produced through mechanisms involving nuclear factor kappa B (NF-κB), likely contribute to the hyperinflammatory state in patients with severe COVID-19. Lymphopenia, more apparent among natural killer (NK) cells, CD8+ T-cells, and B-cells, can contribute to disease severity and may reflect direct cytopathic effects of SARS-CoV-2 or end-organ sequestration. Direct infection and immune activation of endothelial cells by SARS-CoV-2 may be a critical mechanism through which end-organ systems are impacted. In this context, endovascular neutrophil extracellular trap (NET) formation and microthrombi development can be seen in the lungs and other critical organs throughout the body, such as the heart, gut, and brain. The kidney may be among the most impacted extrapulmonary organ by SARS-CoV-2 infection owing to a high concentration of ACE2 and exposure to systemic SARS-CoV-2. In the kidney, acute tubular injury, early myofibroblast activation, and collapsing glomerulopathy in select populations likely account for COVID-19-related AKI and CKD development. The development of COVID-19-associated nephropathy (COVAN), in particular, may be mediated through IL-6 and signal transducer and activator of transcription 3 (STAT3) signaling, suggesting a direct connection between the COVID-19-related immune response and the development of chronic disease. Chronic manifestations of COVID-19 also include systemic conditions like Multisystem Inflammatory Syndrome in Children (MIS-C) and Adults (MIS-A) and post-acute sequelae of COVID-19 (PASC), which may reflect a spectrum of clinical presentations of persistent immune dysregulation. The lessons learned and those undergoing continued study likely have broad implications for understanding viral infections' immunologic and inflammatory consequences beyond coronaviruses.}, }
@article {pmid40029778, year = {2025}, author = {Wang, J and Xiong, Y and Song, Z and Li, Y and Zhang, L and Qin, C}, title = {Progress in research on osteoporosis secondary to SARS-CoV-2 infection.}, journal = {Animal models and experimental medicine}, volume = {8}, number = {5}, pages = {829-841}, pmid = {40029778}, issn = {2576-2095}, support = {2060204//State Key Laboratory Special Fund/ ; 2022B1111020005//Key-Area Research and Development Program of Guangdong Province/ ; 2021-I2M-1-034,2023-I2M-2-001//Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences/ ; 82221004//The Foundation for Innovative Research Groups of the National Natural Science Foundation of China/ ; }, mesh = {*COVID-19/complications ; *Osteoporosis/etiology/virology ; Humans ; Animals ; *SARS-CoV-2 ; Bone Density ; }, abstract = {The World Health Organization has declared that COVID-19 no longer constitutes a "public health emergency of international concern," yet the long-term impact of SARS-CoV-2 infection on bone health continues to pose new challenges for global public health. In recent years, numerous animal model and clinical studies have revealed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to secondary osteoporosis. The mechanisms involved are related to the virus's direct effects on bone tissue, dysregulation of the body's inflammatory response, hypoxia, noncoding RNA imbalance, and metabolic abnormalities. Although these studies have unveiled the connection between SARS-CoV-2 infection and osteoporosis, current research is not comprehensive and in depth. Future studies are needed to evaluate the long-term effects of SARS-CoV-2 on bone density and metabolism, elucidate the specific mechanisms of pathogenesis, and explore potential interventions. This review aims to collate existing research literature on SARS-CoV-2 infection-induced secondary osteoporosis, summarize the underlying mechanisms, and provide direction for future research.}, }
@article {pmid40042223, year = {2025}, author = {Monte, AL and Karla Tavares do Nascimento Faustino da Silva, J and Duarte de Oliveira, M and Quintella Farah, B and Kanegusuku, H and Almeida Correia, M and Mendes Ritti-Dias, R}, title = {Dropouts in Exercise Rehabilitation Program in Patients With Long COVID: A Systematic Review.}, journal = {American journal of physical medicine &amp; rehabilitation}, volume = {104}, number = {10}, pages = {883-889}, pmid = {40042223}, issn = {1537-7385}, mesh = {Humans ; *COVID-19/rehabilitation ; *Patient Dropouts/statistics &amp; numerical data ; *Exercise Therapy ; Male ; Female ; Middle Aged ; SARS-CoV-2 ; }, abstract = {OBJECTIVE: The aim of the study was to describe dropout rates, reasons, and factors associated with dropout during rehabilitation programs for patients with long COVID.<br><br>DESIGN: A search was conducted in PubMed, Embase, and Web of Science. Clinical trials were included that involved exercise programs lasting at least 4 weeks and focused on long-COVID patients aged 18 or older of both sexes, reporting on dropouts and their reasons. The TESTEX scale assessed study quality. Data on patients, interventions, and dropout rates were extracted and presented as frequencies.<br><br>RESULTS: Twenty-three studies with 1523 patients (mean age 53.0 &#xb1; 6.4 yrs, 51% female) were included. Overall, 14% (n = 216) of long-COVID patients dropped out. Reasons included health problems (23%), incomplete assessments (19%), loss of interest (16%), lack of adherence (7%), adherence to other interventions (4%), and 31% unreported. The dropout rate was significantly higher in 2020 compared to 2021 (P = 0.039), while no significant associations were observed between the dropout rate and other variables.<br><br>CONCLUSIONS: Exercise rehabilitation studies for long-COVID patients show a 14% dropout rate, with the most common reasons being health-related issues and incomplete assessments.}, }
@article {pmid40046430, year = {2024}, author = {Talkington, GM and Kolluru, P and Gressett, TE and Ismael, S and Meenakshi, U and Acquarone, M and Solch-Ottaiano, RJ and White, A and Ouvrier, B and Paré, K and Parker, N and Watters, A and Siddeeque, N and Sullivan, B and Ganguli, N and Calero-Hernandez, V and Hall, G and Longo, M and Bix, GJ}, title = {Neurological sequelae of long COVID: a comprehensive review of diagnostic imaging, underlying mechanisms, and potential therapeutics.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1465787}, pmid = {40046430}, issn = {1664-2295}, support = {TL1 TR003106/TR/NCATS NIH HHS/United States ; }, abstract = {One lingering effect of the COVID-19 pandemic created by SARS-CoV-2 is the emergence of Long COVID (LC), characterized by enduring neurological sequelae affecting a significant portion of survivors. This review provides a thorough analysis of these neurological disruptions with respect to cognitive dysfunction, which broadly manifest as chronic insomnia, fatigue, mood dysregulation, and cognitive impairments with respect to cognitive dysfunction. Furthermore, we characterize how diagnostic tools such as PET, MRI, EEG, and ultrasonography provide critical insight into subtle neurological anomalies that may mechanistically explain the Long COVID disease phenotype. In this review, we explore the mechanistic hypotheses of these neurological changes, which describe CNS invasion, neuroinflammation, blood-brain barrier disruption, and gut-brain axis dysregulation, along with the novel vascular disruption hypothesis that highlights endothelial dysfunction and hypoperfusion as a core underlying mechanism. We lastly evaluate the clinical treatment landscape, scrutinizing the efficacy of various therapeutic strategies ranging from antivirals to anti-inflammatory agents in mitigating the multifaceted symptoms of LC.}, }
@article {pmid40051665, year = {2025}, author = {Sakellaropoulos, SG and Sakellaropoulos, PG and Steinberg, BS and Rogers, C and Ismael, O and Scholl, EW and Mohammed, M and Mitsis, A and Patrinou, NG}, title = {Five Years of Long COVID Syndrome: An Updated Review on Cardiometabolic and Psychiatric Aspects.}, journal = {Cardiology research}, volume = {16}, number = {2}, pages = {81-85}, pmid = {40051665}, issn = {1923-2829}, abstract = {Five years after the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, there is still a significant number of people who have survived COVID-19 but never fully recovered from the disease. They go through an odyssey of doctor visits and a multitude of diagnostic tests, which ultimately do not provide concrete correlations and answers to the question of how exactly long COVID (LC) affects both physical and mental health, and performance. Often, not even highly technical and highly specialized methods, such as cardiac magnetic resonance imaging (MRI), can provide further explanation. Various research efforts continue to investigate the causes, effects and possible treatments of LC, particularly its impact on cognition and mental health. Patients with LC may experience persistent symptoms, but new symptoms also occur. Based on available studies, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) does not only affect the pulmonary system, but nearly every major system and organ, from the brain and heart to the kidneys and immune system. What mechanisms could explain the persistent symptoms of LC and the inadequate recovery? How valuable is an early internal and neurological examination, particularly in the context of psychotherapy? In this review, we examined which factors could contribute to the persistence of LC symptoms and to what extent mitochondrial impairment by LC can explain the symptoms of LC.}, }
@article {pmid40062991, year = {2025}, author = {Cavarelli, M}, title = {[Ghosts of the virus : unmasking the persistent threat of SARS-CoV-2 in Long COVID].}, journal = {Virologie (Montrouge, France)}, volume = {29}, number = {1}, pages = {41-53}, doi = {10.1684/vir.2025.1073}, pmid = {40062991}, issn = {1267-8694}, mesh = {Humans ; *COVID-19/virology/immunology/complications ; *SARS-CoV-2/physiology/immunology ; Post-Acute COVID-19 Syndrome ; Inflammation/virology ; }, abstract = {Long COVID has emerged as a debilitating condition, severely impacting the daily functioning and quality of life of affected individuals. The pathogenesis of Long COVID is complex and multifactorial, involving immune dysregulation, persistent inflammation, and potential reactivation of other pathogens. A key driver of Long COVID is the potential persistence of SARS-CoV-2 in various tissues beyond the respiratory tract, leading to the formation of viral reservoirs that contribute to ongoing symptoms, several months after initial infection. These reservoirs have been suggested in the gastrointestinal tract, central nervous system, cardiovascular system, and other tissues, often persisting months after the initial infection. Additionally, viral RNA and proteins in these tissues are associated with chronic inflammation and immune system disruptions, which are primary contributors to Long COVID symptoms. This article explores the mechanisms and consequences of SARS-CoV-2 persistence in respiratory and non-respiratory tissues, highlighting its impact on the immune system and underscoring critical areas for future research to improve outcomes for individuals suffering from Long COVID.}, }
@article {pmid40062993, year = {2025}, author = {Cavarelli, M}, title = {Ghosts of the virus : unmasking the persistent threat of SARS-CoV-2 in Long COVID.}, journal = {Virologie (Montrouge, France)}, volume = {29}, number = {1}, pages = {57-68}, doi = {10.1684/vir.2025.1074}, pmid = {40062993}, issn = {1267-8694}, mesh = {Humans ; *COVID-19/virology/immunology/complications ; *SARS-CoV-2/physiology/immunology ; Post-Acute COVID-19 Syndrome ; Inflammation/virology ; }, abstract = {Long COVID has emerged as a debilitating condition, severely impacting the daily functioning and quality of life of affected individuals. The pathogenesis of Long COVID is complex and multifactorial, involving immune dysregulation, persistent inflammation, and potential reactivation of other pathogens. A key driver of Long COVID is the potential persistence of SARS-CoV-2 in various tissues beyond the respiratory tract, leading to the formation of viral reservoirs that contribute to ongoing symptoms, several months after initial infection. These reservoirs have been suggested in the gastrointestinal tract, central nervous system, cardiovascular system, and other tissues, often persisting months after the initial infection. Additionally, viral RNA and proteins in these tissues are associated with chronic inflammation and immune system disruptions, which are primary contributors to Long COVID symptoms. This article explores the mechanisms and consequences of SARS-CoV-2 persistence in respiratory and non-respiratory tissues, highlighting its impact on the immune system and underscoring critical areas for future research to improve outcomes for individuals suffering from Long COVID.}, }
@article {pmid40068974, year = {2025}, author = {Emery, I and Rosen, C}, title = {Adult Long Coronavirus Disease 2019: Definition, Prevalence Pathophysiology, and Clinical Manifestations.}, journal = {Infectious disease clinics of North America}, volume = {39}, number = {2}, pages = {345-360}, doi = {10.1016/j.idc.2025.02.007}, pmid = {40068974}, issn = {1557-9824}, mesh = {Humans ; *COVID-19/physiopathology/epidemiology/complications ; SARS-CoV-2 ; Prevalence ; Risk Factors ; Post-Acute COVID-19 Syndrome ; Adult ; Female ; Male ; }, abstract = {Long coronavirus disease 2019 (COVID-19) is a multisystem disorder with variable manifestations and duration. One in 10 people with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection will develop some manifestation of long COVID-19. Currently, there is no one single etiologic factor for the symptoms and signs of long COVID-19 beyond exposure to the SARS-CoV-2 virus. There are multiple theories about the pathophysiology ranging from viral persistence, reactivation, autoimmunity, and immune depletion. Certain risk factors have been identified including female sex, severe acute/hospitalized COVID-19, previous infections with SARS-CoV-2, and absence of vaccinations.}, }
@article {pmid40071133, year = {2025}, author = {Monsalve, DM and Acosta-Ampudia, Y and Acosta, NG and Celis-Andrade, M and Şahin, A and Yilmaz, AM and Shoenfeld, Y and Ramírez-Santana, C}, title = {NETosis: A key player in autoimmunity, COVID-19, and long COVID.}, journal = {Journal of translational autoimmunity}, volume = {10}, number = {}, pages = {100280}, pmid = {40071133}, issn = {2589-9090}, abstract = {NETosis, the process through which neutrophils release neutrophil extracellular traps (NETs), has emerged as a crucial mechanism in host defense and the pathogenesis of autoimmune responses. During the SARS-CoV-2 pandemic, this process received significant attention due to the central role of neutrophil recruitment and activation in infection control. However, elevated neutrophil levels and dysregulated NET formation have been linked to coagulopathy and endothelial damage, correlating with disease severity and poor prognosis in COVID-19. Moreover, it is known that SARS-CoV-2 can induce persistent low-grade systemic inflammation, known as long COVID, although the underlying causes remain unclear. It has been increasingly acknowledged that excessive NETosis and NET generation contribute to further pathophysiological abnormalities following SARS-CoV-2 infection. This review provides an updated overview of the role of NETosis in autoimmune diseases, but also the relationship between COVID-19 and long COVID with autoimmunity (e.g., latent and overt autoimmunity, molecular mimicry, epitope spreading) and NETosis (e.g., immune responses, NET markers). Finally, we discuss potential therapeutic strategies targeting dysregulated NETosis to mitigate the severe complications of COVID-19 and long COVID.}, }
@article {pmid40071259, year = {2025}, author = {Velati, D and Puoti, M}, title = {Real-world experience with therapies for SARS-CoV-2: Lessons from the Italian COVID-19 studies.}, journal = {Le infezioni in medicina}, volume = {33}, number = {1}, pages = {64-75}, pmid = {40071259}, issn = {2532-8689}, abstract = {The therapeutic armamentarium that has been made available from the beginning of the emergency phase of the COVID-19 pandemic to date is briefly reviewed, and an overview of the real-world clinical evidence published by the Italian medical and scientific community during the last three years is presented herein. Prior to the introduction of a vaccine for SARS-CoV-2, several treatment options were implemented from the onset given the evidence that a "cytokine storm" was present during infection with SARS-CoV-2. However, with the exception of tocilizumab, baricitinib and perhaps anakinra, most studies with anti-cytokine biological agents in patients with severe COVID-19 did not show any significant clinical improvement or decrease in mortality at day 28. The same is true of several repurposed drugs including ivermectin, lactoferrin, interferon ß-1a, lopinavir/ritonavir alone or combined with hydroxychloroquine, and darunavir/ cobicistat, which did not show any benefits in clinical status or mortality. Treatment with neutralizing monoclonal antibodies (mAbs) for COVID-19 is changing continually with the evolution of new viral variants. In Italy, current indications for treatment of COVID-19 outpatients underline that the use of specific mAbs may vary over time depending on the prevalent SARS-CoV-2 variant and the sensitivity to the different mAbs available. Three antiviral drugs against SARS-CoV-2 were studied extensively and initially available in Italy: remdesivir, molnupiravir, and nirmaltrelvir/ritonavir, but at present the latter is the only oral antiviral for SARS-CoV-2 available in Italy. Several real-world studies for the use of nirmatrelvir/ ritonavir in the Italian population have been published. Among the current unmet needs, a clear and universal definition for long COVID along with treatments and prevention are still lacking as is clarity of the pathogenetic mechanisms responsible for it.}, }
@article {pmid40073162, year = {2025}, author = {Taher, MK and Salzman, T and Banal, A and Morissette, K and Domingo, FR and Cheung, AM and Cooper, CL and Boland, L and Zuckermann, AM and Mullah, MA and Laprise, C and Colonna, R and Hashi, A and Rahman, P and Collins, E and Corrin, T and Waddell, LA and Pagaduan, JE and Ahmad, R and Jaramillo Garcia, AP}, title = {Global prevalence of post-COVID-19 condition: a systematic review and meta-analysis of prospective evidence.}, journal = {Health promotion and chronic disease prevention in Canada : research, policy and practice}, volume = {45}, number = {3}, pages = {112-138}, pmid = {40073162}, issn = {2368-738X}, mesh = {Humans ; *COVID-19/epidemiology/complications ; Prevalence ; Prospective Studies ; SARS-CoV-2 ; Global Health ; Female ; *Survivors/statistics &amp; numerical data ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: We investigated the prevalence of new or persistent manifestations experienced by COVID-19 survivors at 3 or more months after their initial infection, collectively known as post-COVID-19 condition (PCC).<br><br>METHODS: We searched four electronic databases and major grey literature resources for prospective studies, systematic reviews, authoritative reports and population surveys. A random-effects meta-analysis pooled the prevalence data of 22 symptoms and outcomes. The GRADE approach was used to assess the certainty of evidence. PROSPERO CRD42021231476.<br><br>RESULTS: Of 20 731 identified references, 194 met our inclusion criteria. These studies followed 483 531 individuals with confirmed COVID-19 diagnosis over periods of up to 2 years. Most focused on adults, nearly two-thirds were conducted in Europe and 63% were of high or moderate quality. The supplementary search identified 17 systematic reviews, five authoritative reports and four population surveys that reported on PCC prevalence. Our analysis revealed that more than half of COVID-19 survivors experienced one or more symptoms more than a year after their initial infection. The most common symptoms were fatiguedyspneamemory, sleep or concentration disturbances; depressionand pain. Limitation in returning to work was the most common outcome. Prevalence tended to be higher among females, individuals hospitalized during their initial infection and those who experienced severe COVID-19 illness.<br><br>CONCLUSION: PCC presents a significant health burden, affecting some groups more than others. This information will help inform health care system policies and services for people living with PCC and those caring for them.}, }
@article {pmid40074704, year = {2025}, author = {Schwartz, J and Capistrano, K and Hussein, H and Hafedi, A and Shukla, D and Naqvi, A}, title = {Oral SARS-CoV-2 Infection and Risk for Long Covid.}, journal = {Reviews in medical virology}, volume = {35}, number = {2}, pages = {e70029}, pmid = {40074704}, issn = {1099-1654}, support = {R56DE033249//NIDCR/NIH/ ; R01EY033622//NEI/NIH/ ; R01DE027980//NIDCR/NIH/ ; R01 DE027980/DE/NIDCR NIH HHS/United States ; R56 DE033249/DE/NIDCR NIH HHS/United States ; /NH/NIH HHS/United States ; R01 EY033622/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/virology/complications/pathology/immunology ; *SARS-CoV-2/pathogenicity ; Dysbiosis/virology/microbiology ; Mouth Mucosa/virology/microbiology/immunology/pathology ; *Mouth Diseases/virology/microbiology ; Angiotensin-Converting Enzyme 2/genetics/metabolism ; Microbiota ; Post-Acute COVID-19 Syndrome ; Serine Endopeptidases ; }, abstract = {SARS-CoV-2 is an oral pathogen that infects and replicates in mucosal and salivary epithelial cells, contributing to oral post-acute sequelae COVID-19 (PASC) and other oral and non-oral pathologies. While pre-existing inflammatory oral diseases provides a conducive environment for the virus, acute infection and persistence of SARS-CoV-2 can also results in oral microbiome dysbiosis that further worsens poor oral mucosal health. Indeed, oral PASC includes periodontal diseases, dysgeusia, xerostomia, pharyngitis, oral keratoses, and pulpitis suggesting significant bacterial contributions to SARS-CoV-2 and oral tissue tropism. Dysbiotic microbiome-induced inflammation can promote viral entry via angiotensin-converting enzyme receptor-2 (ACE2), serine transmembrane TMPRSS2 and possibly other non-canonical pathways. Additionally, metabolites derived from a dysbiotic microbiome can alter the physiological and biochemical pathways related to the metabolism of lipids, carbohydrates, and amino acids. This may promote a pro-inflammatory microenvironment, leading to immune exhaustion, loss of tolerance, and susceptibility to a variety of oral pathogens, causing acute and later chronic inflammation. Microbial release of mimics of host metallopeptidases related to furin, ADAM17 (A disintegrin and metalloproteinase 17), and glycoprotein metabolites can further aid viral attachment to T cell immunoglobulin-like (TIMs), enhancing viral entry while simultaneously depressing oral mucosal immune resistance and clearance. Membrane reorganization characterised by neuroproteins, such as neuropilins, also functionally assists with SARS-CoV-2 entry and extends the pathogenesis of PASC from the oral cavity to the brain, gut, or other non-oral tissues. Thus, poor oral health, characterised by disrupted oral microbiomes can promote viral tropism, weaken antiviral resistance, and heightens susceptibility to SARS-CoV-2 infection. This immune dysfunction also increases the risk of additional viral infections, exacerbating oral conditions like periodontal and endodontic diseases. These persistent oral health issues can contribute to systemic inflammation, creating bidirectional effects between oral and non-oral tissues, potentially leading to Post-Acute Sequelae of COVID-19 (PASC).}, }
@article {pmid40075382, year = {2025}, author = {Weigel, B and Inderyas, M and Eaton-Fitch, N and Thapaliya, K and Marshall-Gradisnik, S}, title = {Health-related quality of life in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post COVID-19 Condition: a systematic review.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {318}, pmid = {40075382}, issn = {1479-5876}, support = {489798//Stafford Fox Medical Research Foundation/ ; 1199502//National Health and Medical Research Council/ ; 47107//Mason Foundation/ ; 49979//McCusker Charitable Foundation/ ; 4676//Buxton Foundation/ ; 4879//Henty Community/ ; 4579//Blake Beckett Trust Foundation/ ; 4570//Alison Hunter Memorial Foundation/ ; 4575//Change for ME Charity/ ; }, mesh = {Humans ; *Fatigue Syndrome, Chronic/psychology ; *Quality of Life ; *COVID-19/complications/psychology ; SARS-CoV-2 ; }, abstract = {PURPOSE: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Post COVID-19 Condition (PCC) are debilitating, chronic multi-systemic illnesses that require multidisciplinary care. However, people with ME/CFS (pwME/CFS) and people with PCC (pwPCC) are often precluded from accessing necessary disability and social support services. These unmet care needs exacerbate the existing illness burdens experienced by pwME/CFS and pwPCC. To deliver appropriate care and optimise health outcomes for pwME/CFS and pwPCC, the development of evidence-based healthcare policies that recognise the disabling impacts of these illnesses must be prioritised. This systematic review summarises the health-related quality of life (HRQoL) of pwME/CFS and pwPCC when compared with healthy controls (HCs) to elucidate the impacts of these illnesses and guide healthcare policy reform.<br><br>METHODS: CINAHL, Embase, MEDLINE, PubMed, PsycINFO and the Web of Science Core Collection were systematically searched from 1st January 2003 to 23rd July 2024. Eligible publications included observational studies capturing quantitative HRQoL data among pwME/CFS or pwPCC when compared with HCs. The use of validated patient-reported outcome measures (PROMs) was mandatory. Eligible studies were also required to employ the most stringent diagnostic criteria currently available, including the Canadian Consensus Criteria or International Consensus Criteria for ME/CFS and the World Health Organization case definition for PCC (PROSPERO ID: CRD42024501309).<br><br>RESULTS: This review captured 16 studies, including eight studies among pwME/CFS, seven studies among pwPCC and one study among both illness cohorts. Most participants were female and middle-aged. All pwPCC had experienced prolonged COVID-19 symptoms for at least three months. When compared with HCs, all HRQoL domains were significantly impaired among pwME/CFS and pwPCC. Both illnesses had a salient impact on physical health, including pain and ability to perform daily and work activities. While direct comparisons between pwME/CFS and pwPCC were limited by inconsistencies in the PROMs employed, comparable impact trends across HRQoL domain scores were observed.<br><br>CONCLUSION: ME/CFS and PCC have similar, profound impacts on HRQoL that warrant access to multidisciplinary disability and social support services. Future research must harmonise HRQoL data collection and prioritise longitudinal investigations among pwME/CFS and pwPCC to characterise PCC subgroups (including those fulfilling ME/CFS criteria) and predictors of prognosis.}, }
@article {pmid40076527, year = {2025}, author = {Sun, DS and Lien, TS and Chang, HH}, title = {Virus-Induced Pathogenic Antibodies: Lessons from Long COVID and Dengue Hemorrhage Fever.}, journal = {International journal of molecular sciences}, volume = {26}, number = {5}, pages = {}, pmid = {40076527}, issn = {1422-0067}, support = {104-2320-B-320 -009 -MY3, 107-2311-B-320-002-MY3, 111-2320-B320-006-MY3, 112-2320-B-320-007//National Science and Technology Council, Taiwan/ ; TCMMP104-06, TCMMP108-04, TCMMP 111-01, TCAS111-02, TCAS-112-02, TCAS113-04, TCRD112-033, TCRD113-041//Tzu-Chi Medical Foundation/ ; }, mesh = {Humans ; *COVID-19/immunology/virology ; *Severe Dengue/immunology/virology ; *Antibodies, Viral/immunology ; *Dengue Virus/immunology ; Antibody-Dependent Enhancement/immunology ; *SARS-CoV-2/immunology ; Autoantibodies/immunology ; Animals ; Antibodies, Neutralizing/immunology ; }, abstract = {Virus-induced antibodies represent a dual-edged sword in the immune response to viral infections. While antibodies are critical for neutralizing pathogens, some can paradoxically exacerbate disease severity through mechanisms such as antibody-dependent enhancement (ADE), autoantibody, and prolonged inflammation. Long coronavirus disease (COVID) and dengue hemorrhagic fever (DHF) exemplify conditions where pathogenic antibodies play a pivotal role in disease progression. Long COVID is associated with persistent immune dysregulation and autoantibody production, leading to chronic symptoms and tissue damage. In DHF, pre-existing antibodies against dengue virus contribute to ADE, amplifying viral replication, immune activation, and vascular permeability. This review explores the mechanisms underlying these pathogenic antibody responses, highlighting the shared pathways of immune dysregulation and comparing the distinct features of both conditions. By examining these studies, we identify key lessons for therapeutic strategies, vaccine design, and future research aimed at mitigating the severe outcomes of viral infections.}, }
@article {pmid40079963, year = {2025}, author = {Rudolph, AE and Al Akoury, N and Bogdanenko, N and Markus, K and Whittle, I and Wright, O and Haridy, H and Spinardi, JR and McLaughlin, JM and Kyaw, MH}, title = {Factors affecting the impact of COVID-19 vaccination on post COVID-19 conditions among adults: A systematic literature review.}, journal = {Human vaccines &amp; immunotherapeutics}, volume = {21}, number = {1}, pages = {2474772}, pmid = {40079963}, issn = {2164-554X}, mesh = {Humans ; *COVID-19 Vaccines/administration &amp; dosage/immunology ; *COVID-19/prevention &amp; control/immunology ; *Vaccination ; Adult ; *Vaccine Efficacy ; SARS-CoV-2/immunology ; }, abstract = {This systematic literature review summarizes the evidence across 56 publications and pre-prints (January 2020-July 2023) with low-risk of bias based on JBI critical appraisal, that report adjusted estimates for the relationship between COVID-19 vaccination and Post-COVID-19 Condition (PCC) by timing of vaccination relative to infection or PCC-onset. Comparisons of adjusted vaccine effectiveness (aVE) against ≥1 PCC (vs. unvaccinated) across study characteristics known to impact PCC burden or VE against other COVID-19 endpoints were possible for 31 studies where vaccination preceded infection. Seventy-seven percent of pre-infection aVE estimates were statistically significant (range: 7%-95%). Statistically significant pre-infection aVE estimates were slightly higher for mRNA (range: 14%-84%) than non-mRNA vaccines (range: 16%-38%) and aVE ranges before and during Omicron overlapped. Our findings suggest that COVID-19 vaccination before SARS-CoV-2 infection reduces the risk of PCC regardless of vaccine type, number of doses received, PCC definition, predominant variant, and severity of acute infections included.}, }
@article {pmid40080079, year = {2025}, author = {Li, D and Long, F and Zhang, S and Yu, B}, title = {Mechanisms and treatment progress of neurological diseases of COVID and L-C19 in children.}, journal = {Physiology international}, volume = {112}, number = {1}, pages = {12-32}, doi = {10.1556/2060.2025.00484}, pmid = {40080079}, issn = {2498-602X}, mesh = {Humans ; *COVID-19/complications/therapy ; Child ; *Immunoglobulins, Intravenous/therapeutic use/adverse effects ; *Nervous System Diseases/therapy/virology ; SARS-CoV-2 ; *COVID-19 Drug Treatment ; }, abstract = {OBJECTIVE: Although SARS-CoV-2 primarily targets the respiratory system, there is evidence that it can also infect the central nervous system, especially in children, leading to neurological symptoms and long-term consequences. It is imperative to summarize the possible mechanisms, main symptoms, and treatments of neurological symptoms of COVID-19 in children.<br><br>METHODS: We performed a literature search using the PubMed online database to find studies investigating the mechanisms of COVID-19 infection of the central nervous system and therapies for COVID-19 neurological symptoms in children.<br><br>RESULTS: The main mechanisms of action of SARS-CoV-2 virus on the nervous system are direct invasion, systemic inflammation and molecular mimicry. Although the incidence of adverse reactions to intravenous IgG therapy (IVIG) varies greatly and the contraindications are not yet clear, IVIG has been shown to be clearly effective for the neurological symptoms of COVID-19 in children.<br><br>CONCLUSION: However, due to insufficient data, more clinical studies are still needed to confirm its safety and efficacy, further improve the treatment plan, and determine the appropriate dosage to better serve clinical practice.<br><br>SIGNIFICANCE: The specific regimen of IVIG treatment for COVID-19 in children was explored, which further improved the understanding of COVID-19 and L-C19 neurological diseases in children.}, }
@article {pmid40083165, year = {2025}, author = {Li, S and Dai, B and Hou, Y and Zhang, L and Liu, J and Hou, H and Song, D and Wang, S and Li, X and Zhao, H and Wang, W and Kang, J and Tan, W}, title = {Effect of pulmonary rehabilitation for patients with long COVID-19: a systematic review and meta-analysis of randomized controlled trials.}, journal = {Therapeutic advances in respiratory disease}, volume = {19}, number = {}, pages = {17534666251323482}, pmid = {40083165}, issn = {1753-4666}, mesh = {Humans ; *COVID-19/complications/physiopathology/rehabilitation ; Exercise Tolerance ; *Lung/physiopathology ; Quality of Life ; Randomized Controlled Trials as Topic ; Recovery of Function ; Respiratory Function Tests ; Time Factors ; Treatment Outcome ; Walk Test ; *Post-Acute COVID-19 Syndrome/rehabilitation ; }, abstract = {BACKGROUND: Pulmonary rehabilitation (PR) has demonstrated efficacy in managing long COVID-19, underscoring the need to refine and tailor PR strategies for optimal patient outcomes.<br><br>OBJECTIVES: To evaluate the impact of PR on patients with long COVID-19 and to compare the efficacy of different types and durations of PR interventions.<br><br>DESIGN: Systematic review and meta-analysis.<br><br>DATA SOURCES AND METHODS: We systematically searched randomized controlled trials (RCTs) of the effectiveness of PR in long COVID-19 patients published before April 2024. The primary outcomes were physical capacity assessed by the 6-minute walking test (6MWT), lung function measured by forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC), health-related quality of life (HRQoL), and fatigue. Secondary outcomes were thirty-second sit-to-stand test (30STST), handgrip strength tests, maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), dyspnea, depression, anxiety, perceived effort, and adverse events.<br><br>RESULTS: A total of 37 studies with 3363 patients were included. Compared to controls, PR improved physical capacity (6MWT, 30STST, handgrip), lung function (FEV1, FVC, MIP, MEP), HRQoL, fatigue, dyspnea, and anxiety but did not reach statistical significance for depression. Subgroup analyses of PR duration indicated that programs of &#x2a7d;4 weeks improved 6MWT; those between 4 and 8 weeks significantly improved 6MWT, lung function (FEV1, FVC), HRQoL, and reduced fatigue; and programs over 8 weeks improved HRQoL and reduced fatigue. Exercise type analysis revealed that breathing exercises improved 6MWT, lung function (FEV1, FVC), and HRQoL; multicomponent exercises enhanced 6MWT performance and reduced fatigue; the combination of both types improved 6MWT, FEV1 (L), FVC (%pred), HRQoL, and reduced fatigue.<br><br>CONCLUSION: PR improves physical capacity, lung function, and quality of life and alleviates dyspnea, fatigue, and anxiety in long COVID-19 patients. A 4- to 8-week PR program and a combination of both breath exercises and multicomponent training is most effective for managing long-term COVID-19 syndromes.<br><br>TRIAL REGISTRATION: PROSPERO ID: CRD42024455008.}, }
@article {pmid40084919, year = {2025}, author = {Baalbaki, N and Slob, EMA and Kazer, SW and I Abdel-Aziz, M and Bogaard, HJ and Golebski, K and Maitland-van der Zee, AH}, title = {The Omics Landscape of Long COVID-A Comprehensive Systematic Review to Advance Biomarker, Target and Drug Discovery.}, journal = {Allergy}, volume = {80}, number = {4}, pages = {932-948}, pmid = {40084919}, issn = {1398-9995}, support = {//Health~Holland/ ; }, mesh = {Humans ; *COVID-19/metabolism/genetics ; Biomarkers/metabolism ; SARS-CoV-2 ; Metabolomics ; *Drug Discovery ; Genomics ; Proteomics ; Post-Acute COVID-19 Syndrome ; }, abstract = {An estimated 10% of coronavirus disease (COVID-19) survivors suffer from persisting symptoms referred to as long COVID (LC), a condition for which approved treatment options are still lacking. This systematic review (PROSPERO: CRD42024499281) aimed to explore the pathophysiological mechanisms underlying LC and potential treatable traits across symptom-based phenotypes. We included studies with primary data, written in English, focusing on omics analyses of human samples from LC patients with persistent symptoms of at least 3 months. Our search in PubMed and Embase, conducted on January 8, 2024, identified 642 studies, of which 29 met the inclusion criteria after full-text assessment. The risk of bias was evaluated using the Joanna Briggs Institute appraisal tool. The synthesis of omics data, including genomics, transcriptomics, proteomics, metabolomics, and metagenomics, revealed common findings associated with fatigue, cardiovascular, pulmonary, neurological, and gastrointestinal phenotypes. Key findings included mitochondrial dysfunction, dysregulated microRNAs associated with pulmonary dysfunction, tissue impairment, blood-brain barrier disruption, coagulopathy, vascular dysfunction, microbiome disturbances, microbial-derived metabolite production and persistent inflammation. Limitations include cross-study heterogeneity and variability in sampling methods. Our review emphasizes the complexity of LC and the need for further longitudinal omics-integrated studies to advance the development of biomarkers and targeted treatments.}, }
@article {pmid40093756, year = {2025}, author = {Sanger, BD and Alarachi, A and McNeely, HE and McKinnon, MC and McCabe, RE}, title = {Brain Fog and Cognitive Dysfunction in Posttraumatic Stress Disorder: An Evidence-Based Review.}, journal = {Psychology research and behavior management}, volume = {18}, number = {}, pages = {589-606}, pmid = {40093756}, issn = {1179-1578}, abstract = {The term "brain fog" has long been used both colloquially and in research literature in reference to various neurocognitive phenomenon that detract from cognitive efficiency. We define "brain fog" as the subjective experience of cognitive difficulties, in keeping with the most common colloquial and research use of the term. While a recent increase in use of this term has largely been in the context of the post-coronavirus-19 condition known as long COVID, "brain fog" has also been discussed in relation to several other conditions including mental health conditions such as post-traumatic stress disorder (PTSD). PTSD is associated with both subjective cognitive complaints and relative deficits on cognitive testing, but the phenomenology and mechanisms contributing to "brain fog" in this population are poorly understood. PTSD psychopathology across cognitive, affective and physiological symptom domains have been tied to "brain fog". Furthermore, dissociative symptoms common in PTSD also contribute to the experience of "brain fog". Comorbid physical and mental health conditions may also increase the risk of experiencing "brain fog" among individuals with PTSD. Considerations for the assessment of "brain fog" in PTSD as part of psychodiagnostic assessment are discussed. While standard psychological intervention for PTSD is associated with a reduction in subjective cognitive deficits, other cognitive interventions may be valuable when "brain fog" persists following PTSD remission or when "brain fog" interferes with treatment. Limitations of current research on "brain fog" in PTSD include a lack of consistent definition and operationalization of "brain fog" in the literature, as well as limited tools for measurement. Future research should address these limitations, as well as further evaluate the use of cognitive remediation as an intervention for "brain fog".}, }
@article {pmid40094893, year = {2025}, author = {Mara, G and Nini, G and Cotoraci, C}, title = {Impact of Pulmonary Comorbidities on COVID-19: Acute and Long-Term Evaluations.}, journal = {Journal of clinical medicine}, volume = {14}, number = {5}, pages = {}, pmid = {40094893}, issn = {2077-0383}, abstract = {Background/Objectives: Pulmonary comorbidities, such as chronic obstructive pulmonary disease (COPD), asthma, and interstitial lung diseases (ILDs), have emerged as critical factors influencing the severity and outcomes of COVID-19. This review aims to evaluate the interplay between these comorbidities and COVID-19, both during the acute phase and in long-term recovery, focusing on their impact on clinical management and outcomes. Methods: This systematic review examined studies sourced from major medical databases, including PubMed and Scopus, using keywords such as "COVID-19", "pulmonary comorbidities", "long COVID", and "respiratory sequelae". Peer-reviewed articles published from January 2020 to the present were included, with data extracted to evaluate both the acute and long-term effects of these comorbidities on COVID-19 patients. Results: Patients with COPD demonstrated significantly higher risks of severe COVID-19, including increased hospitalization and mortality. Asthma, while less consistently associated with severe outcomes, showed a variable risk based on disease control. ILDs were strongly correlated with poor outcomes, including higher rates of respiratory failure and mortality. Long-term complications, such as persistent dyspnea, impaired lung function, and structural changes like fibrosis, were prevalent in patients recovering from moderate to severe COVID-19. These complications adversely affected quality of life and increased healthcare dependency. Conclusions: Pulmonary comorbidities amplify both the acute severity and long-term respiratory consequences of COVID-19. Effective management necessitates tailored strategies addressing both phases, integrating rehabilitation and continuous monitoring to mitigate chronic impairments. Future research should prioritize understanding the mechanisms behind these interactions to inform public health interventions and improve patient outcomes.}, }
@article {pmid40094929, year = {2025}, author = {Patrascu, R and Dumitru, CS}, title = {Advances in Understanding Inflammation and Tissue Damage: Markers of Persistent Sequelae in COVID-19 Patients.}, journal = {Journal of clinical medicine}, volume = {14}, number = {5}, pages = {}, pmid = {40094929}, issn = {2077-0383}, abstract = {This review explores the crucial role of established and emerging biomarkers in the diagnosis, management, and understanding of post-COVID-19 conditions. With COVID-19 affecting multiple organ systems, biomarkers have been instrumental in identifying ongoing inflammation and tissue damage, facilitating early diagnosis and prognostication. Specifically, markers like C-reactive protein (CRP), interleukin-6 (IL-6), and novel entities such as soluble urokinase plasminogen activator receptor (suPAR) and neutrophil extracellular traps (NETs) provide insights into the pathophysiological mechanisms and predict long-term outcomes. This review highlights the integration of these biomarkers into clinical workflows and their implications for personalized medicine, emphasizing their potential in guiding therapeutic interventions and monitoring recovery. Future directions suggest a focus on longitudinal studies to explore biomarker trajectories and their interaction with therapeutic outcomes, aiming to enhance the management of post-COVID-19 conditions and refine public health strategies.}, }
@article {pmid40105889, year = {2025}, author = {Mueller, MR and Ganesh, R and Beckman, TJ and Hurt, RT}, title = {Long COVID: emerging pathophysiological mechanisms.}, journal = {Minerva medica}, volume = {116}, number = {2}, pages = {156-165}, doi = {10.23736/S0026-4806.25.09539-4}, pmid = {40105889}, issn = {1827-1669}, mesh = {Humans ; *COVID-19/physiopathology/complications ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Fatigue/physiopathology/etiology ; }, abstract = {Post-COVID conditions, also termed "long COVID," are a heterogeneous set of conditions persisting greater than 28 days after initial infection. These conditions, which include fatigue, brain fog, orthostatic intolerance, and pain, are a significant source of morbidity and limited function worldwide. Nonetheless, both the pathophysiology and treatment of long COVID remain poorly understood. Several pathophysiologic mechanisms have been proposed including neuroinflammatory drivers, endothelial dysfunction, neurotransmitter dysregulation, mitochondrial dysfunction, autonomic dysfunction, and central sensitization. In this article, we present a conceptual framework for evaluation of long COVID symptoms, as well as the evidence behind their proposed pathophysiologic mechanisms. Patients may struggle with one or more of the proposed mechanisms listed above, and the contributions from each process may vary depending on the patient. Although no FDA-approved therapies exist for long COVID, we review several potential promising and mechanistically plausible therapies.}, }
@article {pmid40117126, year = {2026}, author = {Bast, E and Jester, DJ and Palacio, A and Krengel, M and Reinhard, M and Ashford, JW}, title = {Gulf War Illness: A Historical Review and Considerations of a Post-Viral Syndrome.}, journal = {Military medicine}, volume = {191}, number = {1-2}, pages = {e7-e11}, doi = {10.1093/milmed/usaf092}, pmid = {40117126}, issn = {1930-613X}, mesh = {Humans ; *Persian Gulf Syndrome/history/epidemiology/physiopathology/etiology/diagnosis ; COVID-19/complications ; Gulf War ; History, 20th Century ; Fatigue Syndrome, Chronic ; Veterans ; }, abstract = {Gulf War Illness (GWI) is a condition that affects 30-40% of nearly 700,000 Veterans who were deployed to Operations Desert Shield/Storm/Sabre (ODS/S/S) between August 1990 and June 1991 and is characterized by a constellation of symptoms, including fatigue, mood/cognition, chronic pain, gastrointestinal (most frequently referred to as "irritable bowel syndrome"), respiratory, and skin issues. We review the development of various case definitions for GWI, as well as exposure theories. Despite heavy investment in research, both the pathophysiology and underlying cause of GWI remain areas of active inquiry. Similarities have previously been noted in symptomatology between GWI and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and more recently, long COVID (LC), a late effect of infection with the Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2). These conditions are discussed with respect to the similarities of their symptomatology and pathophysiology. Long COVID is a post-viral syndrome, and ME/CFS is widely considered to be likely post-infectious as well. This comparison leads to the proposal of the hypothesis that GWI may also be post-viral. Given the similarity of GWI and LC, it is possible that Veterans with GWI had an antecedent infection with a virus related to SARS-CoV-2, potentially the Middle East Respiratory Syndrome Coronavirus (MERS) or an ancestor of this virus. The MERS antibodies have been found in dromedary camels in Saudi Arabia since 1983 to the present, including the time of ODS/S/S. There is abundant evidence to support further investigation into this topic.}, }
@article {pmid40120171, year = {2025}, author = {Das Sarma, J}, title = {Murine β-coronavirus spike protein: A major determinant of neuropathogenic properties.}, journal = {Virology}, volume = {606}, number = {}, pages = {110499}, doi = {10.1016/j.virol.2025.110499}, pmid = {40120171}, issn = {1096-0341}, mesh = {*Spike Glycoprotein, Coronavirus/metabolism/genetics/chemistry ; Animals ; Mice ; *Murine hepatitis virus/pathogenicity/genetics/metabolism ; Humans ; SARS-CoV-2 ; Disease Models, Animal ; COVID-19 ; *Coronavirus Infections/virology ; }, abstract = {Coronaviruses have emerged as a significant challenge to human health. While earlier outbreaks of coronaviruses such as SARS-CoV and MERS-CoV posed serious threats, the recent SARS-CoV-2 pandemic has heightened interest in coronavirus research due to its pulmonary pathology, in addition to its neurological manifestations. In addition, the patients who have recovered from SARS-CoV-2 infection show long-term symptoms such as anosmia, brain fog and long COVID. A major hurdle in studying these viruses is the limited availability of specialized research facilities, emphasizing the need for prototype virus-based models to investigate the pathophysiology. The mouse hepatitis virus (MHV), a member of the β-coronavirus family, serves as an excellent model to unravel the mechanisms underlying virus-induced pathogenesis. This review highlights two decades of research efforts aimed at understanding the pathophysiological mechanism of coronavirus-induced diseases, focusing on the development of targeted recombinant strains to identify the minimal essential motif of the spike protein responsible for fusogenicity and neuropathogenicity. By synthesizing findings from these studies, the review identifies the most promising therapeutic targets against coronaviruses, paving the way for the development of pan-coronavirus antivirals.}, }
@article {pmid40122540, year = {2025}, author = {McDowell, CP and Tyner, B and Shrestha, S and McManus, L and Comaskey, F and Harrington, P and Walsh, KA and O'Neill, M and Ryan, M}, title = {Effectiveness and tolerance of exercise interventions for long COVID: a systematic review of randomised controlled trials.}, journal = {BMJ open}, volume = {15}, number = {3}, pages = {e082441}, pmid = {40122540}, issn = {2044-6055}, mesh = {Humans ; *COVID-19/complications/therapy/physiopathology ; Randomized Controlled Trials as Topic ; *Exercise Therapy/methods ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Quality of Life ; Treatment Outcome ; }, abstract = {OBJECTIVES: To examine the effectiveness of exercise interventions to improve long COVID symptoms and the tolerance of exercise interventions among people with long COVID.<br><br>DESIGN: Systematic review.<br><br>DATA SOURCES: Medline via EBSCOhost, Embase via OVID and CENTRAL via the Cochrane Library up to 28 February 2023.<br><br>Inclusion criteria were: (1) participants with long COVID, as defined by study authors; (2) random assignment to either an exercise intervention or a comparison group and (3) a quantitative measure of at least 1 of the 12 core long COVID outcomes. Exclusion criteria were: (1) signs or symptoms not reasonably attributable to prior SARS-CoV-2 infection; (2) pre-exposure or postexposure prophylaxis for COVID-19 or the prevention of long COVID symptoms and (3) interventions where the primary exercise component is breathing or respiratory muscle training.<br><br>DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data, and studies were narratively synthesised.<br><br>RESULTS: Eight studies were included. Follow-up periods ranged from 2 to 28 weeks (mean=8.5 weeks). Sample sizes ranged from 39 to 119 (mean=56). All studies were in adults (mean age=49.9 years) and both sexes (mean female proportion=53.9%). Four studies were at low risk of bias, two were unclear and two were high. The evidence suggests that exercise interventions lead to short-term improvements in dyspnoea, fatigue, physical function and the physical domain of quality of life among people with long COVID. Of the five studies that reported adverse events, rates were low and, when reported, mild. Of the seven studies that reported sufficient relevant information, 1 of 252 participants who received exercise discontinued the intervention due to tolerance-related issues.<br><br>CONCLUSION: Available evidence suggests that exercise interventions may be beneficial and tolerable among some people with long COVID. However, the evidence base consists of a limited number of studies with small sample sizes and short follow-up periods.}, }
@article {pmid40126325, year = {2025}, author = {Nyasulu, PS and Tamuzi, JL and Oliveira, RKF and Oliveira, SD and Petrosillo, N and de Jesus Perez, V and Dhillon, N and Butrous, G}, title = {COVID-19 and Parasitic Co-Infection: A Hypothetical Link to Pulmonary Vascular Disease.}, journal = {Infectious disease reports}, volume = {17}, number = {2}, pages = {}, pmid = {40126325}, issn = {2036-7430}, abstract = {Background/Objectives: Before the Coronavirus disease 2019 (COVID-19) era, the global prevalence of pulmonary arterial hypertension (PAH) was between 0.4 and 1.4 per 100,000 people. The long-term effects of protracted COVID-19 associated with pulmonary vascular disease (PVD) risk factors may increase this prevalence. According to preliminary data, the exact prevalence of early estimates places the prevalence of PVD in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at 22%, although its predictive value remains unknown. PVD caused by COVID-19 co-infections is understudied and underreported, and its future impact is unclear. However, due to COVID-19/co-infection pathophysiological effects on pulmonary vascularization, PVD mortality and morbidity may impose a genuine concern-both now and in the near future. Based on reported studies, this literature review focused on the potential link between COVID-19, parasitic co-infection, and PVD. This review article also highlights hypothetical pathophysiological mechanisms between COVID-19 and parasitic co-infection that could trigger PVD. Methods: We conducted a systematic literature review (SLR) searching peer-reviewed articles, including link between COVID-19, parasitic co-infection, and PVD. Results: This review hypothesized that multiple pathways associated with pathogens such as underlying schistosomiasis, human immunodeficiency virus (HIV), pulmonary tuberculosis (PTB), pulmonary aspergillosis, Wuchereria bancrofti, Clonorchis sinensis, paracoccidioidomycosis, human herpesvirus 8, and scrub typhus coupled with acute or long COVID-19, may increase the burden of PVD and worsen its mortality in the future. Conclusions: Further experimental studies are also needed to determine pathophysiological pathways between PVD and a history of COVID-19/co-infections.}, }
@article {pmid40137051, year = {2025}, author = {Kukreti, S and Lu, MT and Yeh, CY and Ko, NY}, title = {Physiological Sensors Equipped in Wearable Devices for Management of Long COVID Persisting Symptoms: Scoping Review.}, journal = {Journal of medical Internet research}, volume = {27}, number = {}, pages = {e69506}, pmid = {40137051}, issn = {1438-8871}, mesh = {Humans ; *COVID-19/physiopathology/therapy/diagnosis ; Monitoring, Physiologic/instrumentation ; *Wearable Electronic Devices ; }, abstract = {BACKGROUND: Wearable technology has evolved in managing COVID-19, offering early monitoring of key physiological parameters. However, the role of wearables in tracking and managing long COVID is less understood and requires further exploration of their potential.<br><br>OBJECTIVE: This review assessed the application and effectiveness of wearable devices in managing long COVID symptoms, focusing on commonly used sensors and their potential for improving long-term patient care.<br><br>METHODS: A literature search was conducted across databases including PubMed, Embase, Web of Science, and Cochrane Central, adhering to PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) reporting guidelines. The search was updated regularly throughout 2024. Abstract and full-text screening and selection were facilitated using Rayyan software developed by&#xa0;Qatar Computing Research Institute. Quality appraisal was conducted using the Joanna Briggs Institute (JBI) critical appraisal tool to ensure the methodological rigor of the included studies. Data were extracted on study characteristics, wearable devices, sensors used, and monitored physiological parameters, and the results were synthesized in a narrative format.<br><br>RESULTS: A total of 1186 articles were identified, and after duplicate removal and screening, 15 studies were initially included, with 11 studies meeting the criteria for final data synthesis. The included studies varied in design, ranging from observational to interventional trials, and involved sample sizes from 3 to 17,667 participants across different countries. In total, 10 different wearable devices were used to monitor long COVID symptoms, capturing key metrics such as heart rate variability, body temperature, sleep, and physical activity. Smartwatches were the most used wearable devices and fitness trackers with electrocardiography and photoplethysmography sensors were used to monitor heart rate, oxygen saturation, and respiratory rate. Of the 10 devices, 4 were Food and Drug Administration-approved, emphasizing the reliability and validation of the physiological data collected. Studies were primarily conducted in the United States and Europe, reflecting significant regional research interest in wearable technology for long COVID management.<br><br>CONCLUSIONS: This review highlights the potential of wearable technology in providing continuous and personalized monitoring for long COVID patients. Although wearables show promise in tracking persistent symptoms, further research is needed to improve usability, validate long-term efficacy, and enhance patient engagement.}, }
@article {pmid40140333, year = {2025}, author = {Wei, C and Jiang, W and Luo, M and Shao, F}, title = {BBB breakdown caused by plasma membrane pore formation.}, journal = {Trends in cell biology}, volume = {35}, number = {11}, pages = {933-943}, doi = {10.1016/j.tcb.2025.02.012}, pmid = {40140333}, issn = {1879-3088}, mesh = {Humans ; *Blood-Brain Barrier/metabolism/pathology ; *Cell Membrane/metabolism ; Animals ; Endothelial Cells/metabolism/pathology ; COVID-19/pathology ; Lipopolysaccharides ; Phosphate-Binding Proteins/metabolism ; Brain/metabolism ; Gasdermins ; }, abstract = {The blood-brain barrier, recently reintroduced as the blood-brain border (BBB), is a dynamic interface between the central nervous system (CNS) and the bloodstream. Disruption of the BBB exposes the CNS to peripheral pathogens and harmful substances, causing or worsening various CNS diseases. While traditional views attribute BBB failure to tight junction disruption or increased transcytosis, recent studies highlight the critical role of gasdermin D (GSDMD) pore formation in brain endothelial cells (bECs) during BBB disruption by lipopolysaccharide (LPS) or bacterial infections. This mechanism may also be involved in neurological complications like the 'brain fog' seen in long COVID. Pore formation in bECs may represent a prevalent mechanism causing BBB leakage. Investigating membrane-permeabilizing pores or channels and their effects on BBB integrity is a growing area of research. Further exploration of molecular processes that maintain, disrupt, and restore bEC membrane integrity will advance our understanding of brain vasculature and aid in developing new therapies for BBB-related diseases.}, }
@article {pmid40141748, year = {2025}, author = {Stasi, C}, title = {Post-COVID-19 Pandemic Sequelae in Liver Diseases.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {3}, pages = {}, pmid = {40141748}, issn = {2075-1729}, abstract = {During the coronavirus disease 2019 (COVID-19) pandemic, several studies highlighted a worse prognosis for patients with alterations in liver function tests, especially those with pre-existing liver diseases. However, further studies are needed to define the long-term impact of the COVID-19 pandemic on liver diseases. Long COVID-19 encompasses a wide range of signs and symptoms, including exacerbations of pre-existing chronic conditions or new onset conditions developed after the COVID-19 acute phase. Therefore, the long-term effects of COVID-19 extensively include hepatic manifestations. The co-expression of angiotensin-converting receptor 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) has been demonstrated also in enterocytes, cholangiocytes, and hepatocytes. Studies on the post-COVID-19 sequelae have shown the presence of steatosis and necroinflammation in the liver, concomitantly with an alteration of inflammation, cytolysis and cholestasis indices. Some studies also demonstrated an increased risk for hepatobiliary pathologies, including secondary biliary cholangitis and worsening of the severity of metabolic-associated fatty liver disease (MASLD). Based on these premises, this review aims to provide an overview of the pathophysiological mechanisms contributing to COVID-19-related liver and hepatobiliary damage; explore its implications for liver inflammation and fibrosis, with a particular focus on MASLD and metabolic dysfunction-associated steatohepatitis (MASH); and analyze the short- and long-term COVID-19 sequelae. A literature search was conducted using the PubMed database for relevant studies published in English.}, }
@article {pmid40141784, year = {2025}, author = {Caliman-Sturdza, OA and Gheorghita, R and Lobiuc, A}, title = {Neuropsychiatric Manifestations of Long COVID-19: A Narrative Review of Clinical Aspects and Therapeutic Approaches.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {3}, pages = {}, pmid = {40141784}, issn = {2075-1729}, abstract = {The COVID-19 (C-19) pandemic has highlighted the significance of understanding the long-term effects of this disease on the quality of life of those infected. Long COVID-19 (L-C19) presents as persistent symptoms that continue beyond the main illness period, usually lasting weeks to years. One of the lesser-known but significant aspects of L-C19 is its impact on neuropsychiatric manifestations, which can have a profound effect on an individual's quality of life. Research shows that L-C19 creates neuropsychiatric issues such as mental fog, emotional problems, and brain disease symptoms, along with sleep changes, extreme fatigue, severe head pain, tremors with seizures, and pain in nerves. People with cognitive problems plus fatigue and mood disorders experience great difficulty handling everyday activities, personal hygiene, and social interactions. Neuropsychiatric symptoms make people withdraw from social activity and hurt relationships, thus causing feelings of loneliness. The unpredictable state of L-C19 generates heavy psychological pressure through emotional suffering, including depression and anxiety. Neuropsychiatric changes such as cognitive impairment, fatigue, and mood swings make it hard for people to work or study effectively, which decreases their output at school or work and lowers their job contentment. The purpose of this narrative review is to summarize the clinical data present in the literature regarding the neuropsychiatric manifestations of L-C19, to identify current methods of diagnosis and treatment that lead to correct management of the condition, and to highlight the impact of these manifestations on patients' quality of life.}, }
@article {pmid40152069, year = {2025}, author = {Chen, YH and Jan, JS and Yang, CH and Yen, TL and Linh, TTD and Annavajjula, S and Satapathy, MK and Tsao, SY and Hsieh, CY}, title = {Cognitive Sequelae of COVID-19: Mechanistic Insights and Therapeutic Approaches.}, journal = {CNS neuroscience &amp; therapeutics}, volume = {31}, number = {3}, pages = {e70348}, pmid = {40152069}, issn = {1755-5949}, support = {R113-020//Ditmanson Medical Foundation Chia-Yi Christian Hospital/ ; CGH-A10610//Cathay General Hospital/ ; }, mesh = {Humans ; *COVID-19/complications/psychology/therapy ; *Cognitive Dysfunction/therapy/etiology/physiopathology ; Animals ; }, abstract = {BACKGROUND: The COVID-19 pandemic has left an indelible mark on the world, with mounting evidence suggesting that it not only posed acute challenges to global healthcare systems but has also unveiled a complex array of long-term consequences, particularly cognitive impairment (CI). As the persistence of post-COVID-19 neurological syndrome could evolve into the next public health crisis, it is imperative to gain a better understanding of the intricate pathophysiology of CI in COVID-19 patients and viable treatment strategies.<br><br>METHODS: This comprehensive review explores the pathophysiology and management of cognitive impairment across the phases of COVID-19, from acute infection to Long-COVID, by synthesizing findings from clinical, preclinical, and mechanistic studies to identify key contributors to CI, as well as current therapeutic approaches.<br><br>RESULTS: Key mechanisms contributing to CI include persistent neuroinflammation, cerebrovascular complications, direct neuronal injury, activation of the kynurenine pathway, and psychological distress. Both pharmacological interventions, such as anti-inflammatory therapies and agents targeting neuroinflammatory pathways, and non-pharmacological strategies, including cognitive rehabilitation, show promise in addressing these challenges. Although much of the current evidence is derived from preclinical and animal studies, these findings provide foundational insights into potential treatment approaches.<br><br>CONCLUSION: By synthesizing current knowledge, this review highlights the importance of addressing COVID-19-related cognitive impairment and offers actionable insights for mitigation and recovery as the global community continues to grapple with the pandemic's long-term impact.}, }
@article {pmid40159916, year = {2025}, author = {Sterian, M and Naganathan, T and Corrin, T and Waddell, L}, title = {Evidence on the associations and safety of COVID-19 vaccination and post COVID-19 condition: an updated living systematic review.}, journal = {Epidemiology and infection}, volume = {153}, number = {}, pages = {e62}, pmid = {40159916}, issn = {1469-4409}, mesh = {Humans ; *COVID-19 Vaccines/adverse effects/administration &amp; dosage ; *COVID-19/prevention &amp; control/complications ; *Vaccination/adverse effects ; Child ; SARS-CoV-2 ; Adolescent ; }, abstract = {Post COVID-19 condition (PCC) refers to persistent symptoms occurring ≥12 weeks after COVID-19. This living systematic review (SR) assessed the impact of vaccination on PCC and vaccine safety among those with PCC, and was previously published with data up to December 2022. Searches were updated to 31 January 2024 and standard SR methodology was followed. Seventy-eight observational studies were included (47 new). There is moderate confidence that two doses pre-infection reduces the odds of PCC (pooled OR (pOR) 0.69, 95% CI 0.64-0.74, I[2] = 35.16%). There is low confidence for remaining outcomes of one dose and three or more doses. A booster dose may further reduce the odds of PCC compared to only a primary series (pOR 0.85, 95% CI 0.74-0.98, I[2] = 16.85%). Among children ≤18 years old, vaccination may not reduce the odds (pOR 0.79, 95% CI 0.56-1.11, I[2] = 37.2%) of PCC. One study suggests that vaccination within 12 weeks post-infection may reduce the odds of PCC. For those with PCC, vaccination appears safe (four studies) and may reduce the odds of PCC persistence (pOR 0.73, 95% CI 0.57-0.92, I[2] = 15.5%).}, }
@article {pmid40167111, year = {2025}, author = {Ocampo, FF and Holroyd, KB}, title = {Updates on the neurological manifestations of SARS-CoV-2 infection.}, journal = {Current opinion in infectious diseases}, volume = {38}, number = {3}, pages = {234-241}, doi = {10.1097/QCO.0000000000001110}, pmid = {40167111}, issn = {1473-6527}, mesh = {Humans ; *COVID-19/complications ; *Nervous System Diseases/virology/etiology/therapy ; *SARS-CoV-2 ; }, abstract = {PURPOSE OF REVIEW: Since its emergence in 2020, the COVID-19 pandemic has created a global surge of survivors experiencing neurologic effects from SARS-CoV-2 infection. This review aims to provide an updated synthesis of the acute and chronic neurological manifestations of COVID-19, and to outline the current therapeutic strategies for these conditions.<br><br>RECENT FINDINGS: Epidemiological studies have shown that COVID-19 patients with neurological symptoms during acute infection tend to have poorer hospital and functional outcomes. While the risk of adverse neurologic symptoms including cognitive dysfunction, headache, autonomic dysfunction, and chronic fatigue are thought to be greatest following infection with the original SARS-CoV-2 strain and its alpha variant, they remain prevalent after infection with subsequent less virulent strains as well. Some recent work has also found a link between SARS-CoV-2 and structural brain changes. However, ongoing trials show promising results for pharmacologic and nonpharmacologic treatments targeting the postacute neurological sequelae of COVID-19.<br><br>SUMMARY: Lingering neurological manifestations after COVID-19 still pose considerable individual, healthcare system, and socioeconomic repercussions. Both preventive and multimodal treatment approaches are necessary to address these conditions. Further research is required to assess the lasting impacts of SARS-CoV-2 on the nervous system, particularly its potential contribution to the development of neurodegenerative diseases.}, }
@article {pmid40170623, year = {2025}, author = {Iqbal, MM and Iqbal, A and Evans, RA}, title = {Long COVID update: respiratory sequelae and symptoms.}, journal = {Current opinion in supportive and palliative care}, volume = {19}, number = {2}, pages = {95-102}, doi = {10.1097/SPC.0000000000000755}, pmid = {40170623}, issn = {1751-4266}, mesh = {Humans ; *COVID-19/complications/physiopathology/therapy ; *Dyspnea/etiology/virology ; Cough/etiology/virology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Lung Diseases, Interstitial/etiology/therapy/virology/physiopathology ; }, abstract = {PURPOSE OF REVIEW: Long COVID affects approximately 6% of the population after SARS-CoV-2 infection commonly involving persistent respiratory symptoms such as breathlessness and cough. This review provides an update on the latest evidence regarding post-COVID condition/Long COVID and respiratory sequelae, focusing on persistent symptoms, respiratory complications, and therapeutic approaches to date.<br><br>RECENT FINDINGS: Post-COVID interstitial lung abnormalities are estimated to persist in approximately 11% of patients hospitalized with acute COVID-19. However, breathlessness is common in adults (non-hospitalized) with Long COVID, suggesting aetiologies beyond pneumonitis. The risk of venous thromboembolic disease in Long COVID remains uncertain and trial results of anti-coagulation in Long COVID are awaited.<br><br>SUMMARY: Long COVID presents complex respiratory challenges, and careful assessment is crucial to differentiate Long COVID symptoms from exacerbations of pre-existing respiratory conditions. Current management includes a symptom-based multidisciplinary approach, with ongoing research into effective treatments including immune modulating agents.}, }
@article {pmid40175252, year = {2025}, author = {Tarasco, MC and Iacomino, N and Mantegazza, R and Cavalcante, P}, title = {COVID-19, Epstein-Barr virus reactivation and autoimmunity: Casual or causal liaisons?.}, journal = {Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi}, volume = {58}, number = {5}, pages = {508-516}, doi = {10.1016/j.jmii.2025.03.014}, pmid = {40175252}, issn = {1995-9133}, mesh = {Humans ; *COVID-19/immunology/virology/complications ; *Herpesvirus 4, Human/physiology/immunology ; *Epstein-Barr Virus Infections/immunology/virology/complications ; *Virus Activation/immunology ; *Autoimmunity/immunology ; SARS-CoV-2/immunology ; *Autoimmune Diseases/immunology/virology ; }, abstract = {The coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 virus infection, has been associated with a substantial risk of autoimmune disease development or exacerbation. The postulated pathophysiological mechanisms linking COVID-19 with autoimmunity include reactivation of latent Epstein-Barr virus (EBV), whose dysregulated infection in the host can trigger or promote an autoimmune response. This review summarizes recent studies highlighting a potential immunopathogenetic link between SARS-CoV-2 infection and EBV reactivation, which could underlie autoimmunity onset or worsening, as well as immune-related long COVID manifestations in COVID-19 patients. We offer our perspective on the direction that research should take to disentangle the nature (whether causal or casual) of the "COVID-19-EBV-autoimmunity" liaisons. Further advances in this research area may be crucial for designing strategies to prevent or treat EBV reactivation-related autoimmune conditions in COVID-19 patients, or patients with inflammatory co-infectious diseases, at the same time promising to improve our knowledge on the viral contribution to autoimmune phenomena.}, }
@article {pmid40180332, year = {2025}, author = {Yang, OO}, title = {The immunopathogenesis of SARS-CoV-2 infection: Overview of lessons learned in the first 5 years.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {214}, number = {6}, pages = {1095-1104}, doi = {10.1093/jimmun/vkaf033}, pmid = {40180332}, issn = {1550-6606}, mesh = {Humans ; *COVID-19/immunology/pathology ; *SARS-CoV-2/immunology ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; CD8-Positive T-Lymphocytes/immunology ; Immunity, Cellular ; Immunity, Humoral ; }, abstract = {This review provides a broad overview of lessons learned in the five years since COVID-19 was identified. It is a bimodal disease, starting with an initially virus-driven phase, followed by resolution or ensuing inappropriate immune activation causing severe inflammation that is no longer strictly virus dependent. Humoral immunity is beneficial for preventing or attenuating the early stage, without benefit once the later stage begins. Neutralizing antibodies elicited by natural infection or vaccination are short-lived and highly vulnerable to viral sequence variation. By contrast, cellular immunity, particularly the CD8+ T cell arm, has a role in preventing or attenuating severe disease, is far less susceptible to viral variation, and is longer-lived than antibodies. Finally, an ill-defined phenomenon of prolonged symptoms after acute infection, termed "long COVID," is poorly understood but may involve various immunologic defects that are hyperactivating or immunosuppressive. Remaining issues include needing to better understand the immune dysregulation of severe disease to allow more tailored therapeutic interventions, developing antibody strategies that cope with the viral spike sequence variability, prolonging vaccine efficacy, and unraveling the mechanisms of long COVID to design therapeutic approaches.}, }
@article {pmid40180726, year = {2025}, author = {Diener, HC}, title = {[Not Available].}, journal = {MMW Fortschritte der Medizin}, volume = {167}, number = {6}, pages = {30}, doi = {10.1007/s15006-025-4871-1}, pmid = {40180726}, issn = {1613-3560}, }
@article {pmid40193038, year = {2025}, author = {Sadowski, J and Ostrowska, SA and Klaudel, T and Zaborska, M and Chruszcz, M and Sztangreciak-Lehun, A and Bułdak, RJ}, title = {Neuropsychiatric disorders in the course to SARS-CoV-2 virus infection, including biological pathomechanisms, psychosocial factors and long COVID-19 associated with "brain fog".}, journal = {Journal of neurovirology}, volume = {31}, number = {2}, pages = {116-130}, pmid = {40193038}, issn = {1538-2443}, mesh = {Humans ; *COVID-19/psychology/complications/virology/immunology/pathology ; SARS-CoV-2/pathogenicity ; *Mental Disorders/virology/psychology ; *Brain/virology/pathology/physiopathology ; Post-Acute COVID-19 Syndrome ; Cytokine Release Syndrome/virology/psychology ; }, abstract = {During the COVID-19 pandemic, neuropsychiatric disorders began to be observed in a significant proportion of patients, occurring at different times after infection and characterised by varying degrees of severity. This article discusses neurological and psychiatric disorders associated with SARS-CoV-2 virus infection, taking into account biological pathomechanisms and psychosocial factors. The long COVID-19 along with the "brain fog" phenomenon were considered in the study. The purpose of the study is to analyse and discuss the available information from the scientific literature on the possible association between SARS-CoV-2 virus infection and the occurrence of neuropsychiatric disorders with different degrees of severity and temporal correlation. To discuss the correlation of COVID-19 with the occurrence of neuropsychiatric disorders, a systematic literature review was conducted using the following databases: PubMed, Elsevier and Google Scholar. The following keywords were used when searching the materials used: "neuropsychiatric disorders", "COVID-19", "SARS-CoV-2", "NeuroCOVID", "cytokine storm" and "long COVID-19". Focusing on the characteristics of the materials and methods used, as well as the results obtained and conclusions reached in each article, 164 publications of research, meta-analysis, review and case reports were included in the study. Neuropsychiatric disorders resulting from SARS-CoV-2 virus infection are multifactorial in nature. The main elements responsible for the varied pattern of symptoms include direct and indirect central nervous system effects of the disease, individual patient conditions, psychosocial factors, severity of immune responses and severity of infection. The neuropsychiatric effects of SARS-CoV-2 infection can be divided into symptoms directly related to the neurological and psychiatric zones and mixed disorders.}, }
@article {pmid40195851, year = {2025}, author = {Chung, J and Pierce, J and Franklin, C and Olson, RM and Morrison, AR and Amos-Landgraf, J}, title = {Translating animal models of SARS-CoV-2 infection to vascular, neurological and gastrointestinal manifestations of COVID-19.}, journal = {Disease models &amp; mechanisms}, volume = {18}, number = {9}, pages = {}, pmid = {40195851}, issn = {1754-8411}, support = {IK2BX002527//U.S. Department of Veterans Affairs/ ; I01 CX002231/CX/CSRD VA/United States ; R01 HL163005/HL/NHLBI NIH HHS/United States ; T32 OD011126/OD/NIH HHS/United States ; P20 GM103652/GM/NIGMS NIH HHS/United States ; R01 HL139795/HL/NHLBI NIH HHS/United States ; U42 OD010918/OD/NIH HHS/United States ; IK2 BX002527/BX/BLRD VA/United States ; U42OD010918//Institutes of Health (NIH)/ ; T32OD011126//NIH Office of the Director/ ; P30 GM149398/GM/NIGMS NIH HHS/United States ; }, mesh = {*COVID-19/complications/pathology/virology ; Animals ; *Disease Models, Animal ; *SARS-CoV-2/physiology ; *Gastrointestinal Diseases/virology/etiology/pathology ; Humans ; *Nervous System Diseases/virology/etiology/pathology ; *Vascular Diseases/virology/etiology ; Gastrointestinal Tract/pathology/virology ; *Translational Research, Biomedical ; }, abstract = {Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) initiated a global pandemic resulting in an estimated 775 million infections with over 7 million deaths, it has become evident that COVID-19 is not solely a pulmonary disease. Emerging evidence has shown that, in a subset of patients, certain symptoms - including chest pain, stroke, anosmia, dysgeusia, diarrhea and abdominal pain - all indicate a role of vascular, neurological and gastrointestinal (GI) pathology in the disease process. Many of these disease processes persist long after the acute disease has been resolved, resulting in 'long COVID' or post-acute sequelae of COVID-19 (PASC). The molecular mechanisms underlying the acute and systemic conditions associated with COVID-19 remain incompletely defined. Appropriate animal models provide a method of understanding underlying disease mechanisms at the system level through the study of disease progression, tissue pathology, immune system response to the pathogen and behavioral responses. However, very few studies have addressed PASC and whether existing models hold promise for studying this challenging problem. Here, we review the current literature on cardiovascular, neurological and GI pathobiology caused by COVID-19 in patients, along with established animal models of the acute disease manifestations and their prospects for use in PASC studies. Our aim is to provide guidance for the selection of appropriate models in order to recapitulate certain aspects of the disease to enhance the translatability of mechanistic studies.}, }
@article {pmid40199308, year = {2024}, author = {Bona, JP}, title = {Knowledge Representation and Management in the Age of Long Covid and Large Language Models: a 2022-2023 Survey.}, journal = {Yearbook of medical informatics}, volume = {33}, number = {1}, pages = {216-222}, pmid = {40199308}, issn = {2364-0502}, mesh = {Humans ; *Artificial Intelligence ; COVID-19 ; *Large Language Models ; Surveys and Questionnaires ; *Post-Acute COVID-19 Syndrome/epidemiology ; }, abstract = {OBJECTIVES: To select, present, and summarize cutting edge work in the field of Knowledge Representation and Management (KRM) published in 2022 and 2023.<br><br>METHODS: A comprehensive set of KRM-relevant articles published in 2022 and 2023 was retrieved by querying PubMed. Topic modeling with Latent Dirichlet Allocation was used to further refine this query and suggest areas of focus. Selected articles were chosen based on a review of their title and abstract.<br><br>RESULTS: An initial set of 8,706 publications were retrieved from PubMed. From these, fifteen papers were ultimately selected matching one of two main themes: KRM for long COVID, and KRM approaches used in combination with generative large language models.<br><br>CONCLUSIONS: This survey shows the ongoing development and versatility of KRM approaches, both to improve our understanding of a global health crisis and to augment and evaluate cutting edge technologies from other areas of artificial intelligence.}, }
@article {pmid40210368, year = {2025}, author = {Verduzco-Gutierrez, M and Fleming, TK and Azola, AM}, title = {Considerations for Long COVID Rehabilitation in Women.}, journal = {Physical medicine and rehabilitation clinics of North America}, volume = {36}, number = {2}, pages = {371-387}, doi = {10.1016/j.pmr.2024.11.009}, pmid = {40210368}, issn = {1558-1381}, mesh = {Humans ; *COVID-19/rehabilitation/epidemiology ; Female ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Sex Factors ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic has given rise to long COVID, a prolonged manifestation of severe acute respiratory syndrome coronavirus 2 infection, which presents with varied symptoms and conditions lasting beyond expected acute illness. Despite efforts, diagnostic and treatment approaches remain insufficient, particularly for women who experience higher prevalence rates. Rehabilitation professionals have played a crucial role during the pandemic. Individualized rehabilitation plans, encompassing various therapies and interdisciplinary collaborations, are essential. Addressing disparities and biological sex differences is paramount, requiring increased research, understanding, and advocacy for effective rehabilitative care tailored to all individuals affected by long COVID.}, }
@article {pmid40211768, year = {2025}, author = {Gao, J and Zhao, D and Nouri, HR and Chu, HW and Huang, H}, title = {Transcriptional Regulation of Mouse Mast Cell Differentiation and the Role of Human Lung Mast Cells in Airway Inflammation.}, journal = {Immunological reviews}, volume = {331}, number = {1}, pages = {e70026}, pmid = {40211768}, issn = {1600-065X}, support = {R01 AI083986/AI/NIAID NIH HHS/United States ; R01AI152504/NH/NIH HHS/United States ; U19 AI125357/AI/NIAID NIH HHS/United States ; R01AI107022/NH/NIH HHS/United States ; R01 AI107022/AI/NIAID NIH HHS/United States ; R01 AI150082/AI/NIAID NIH HHS/United States ; R01AI150082/NH/NIH HHS/United States ; R01 AI152504/AI/NIAID NIH HHS/United States ; R56 AI180204/AI/NIAID NIH HHS/United States ; R01 AI161296/AI/NIAID NIH HHS/United States ; R01AI161296/NH/NIH HHS/United States ; R01AI083986/NH/NIH HHS/United States ; R01 AI182277/AI/NIAID NIH HHS/United States ; U19AI125357/NH/NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Mast Cells/immunology/metabolism ; Cell Differentiation/genetics ; Mice ; *Lung/immunology ; Gene Expression Regulation ; Inflammation/immunology ; *COVID-19/immunology ; Transcription Factors/metabolism ; *SARS-CoV-2/immunology ; }, abstract = {Mast cells (MCs) play a critical role in allergic inflammation, anaphylaxis, and chronic inflammatory diseases such as asthma, COPD, and osteoarthritis. Dysregulated MC activation can lead to MC activation syndrome (MACS), which is observed in patients with long COVID. MCs express the high-affinity receptor for IgE and, upon activation, release mediators and cytokines that trigger anaphylactic shock and promote allergic inflammation. They also interact with epithelial and nerve cells, which are crucial in forming a complex network of cell-cell and gene-gene interactions driving chronic inflammation that can confer resistance to treatment. In this review, in the context of the literature, we focus on experiments conducted in our laboratory investigating how transcription factors and enhancers regulate genes critical in mouse MC differentiation and function related to human lung inflammation.}, }
@article {pmid40212158, year = {2025}, author = {Abbas, AH and Haji, MR and Shimal, AA and Kurmasha, YH and Al-Janabi, AAH and Azeez, ZT and Al-Ali, ARS and Al-Najati, HMH and Al-Waeli, ARA and Abdulhadi, NASA and Al-Tuaama, AZH and Al-Ashtary, MM and Hussin, OA}, title = {A multidisciplinary review of long COVID to address the challenges in diagnosis and updated management guidelines.}, journal = {Annals of medicine and surgery (2012)}, volume = {87}, number = {4}, pages = {2105-2117}, pmid = {40212158}, issn = {2049-0801}, abstract = {Long COVID has emerged as a significant challenge since the COVID-19 pandemic, which was declared as an outbreak in March 2020, marked by diverse symptoms and prolonged duration of disease. Defined by the WHO as symptoms persisting or emerging for at least two months post-SARS-CoV-2 infection without an alternative cause, its prevalence varies globally, with estimates of 10-20% in Europe, 7.3% in the USA, and 3.0% in the UK. The condition's etiology remains unclear, involving factors, such as renin-angiotensin system overactivation, persistent viral reservoirs, immune dysregulation, and autoantibodies. Reactivated viruses, like EBV and HSV-6, alongside epigenetic alterations, exacerbate mitochondrial dysfunction and energy imbalance. Emerging evidence links SARS-CoV-2 to chromatin and gut microbiome changes, further influencing long-term health impacts. Diagnosis of long COVID requires detailed systemic evaluation through medical history and physical examination. Management is highly individualized, focusing mainly on the patient's symptoms and affected systems. A multidisciplinary approach is essential, integrating diverse perspectives to address systemic manifestations, underlying mechanisms, and therapeutic strategies. Enhanced understanding of long COVID's pathophysiology and clinical features is critical to improving patient outcomes and quality of life. With a growing number of cases expected globally, advancing research and disseminating knowledge on long COVID remain vital for developing effective diagnostic and management frameworks, ultimately supporting better care for affected individuals.}, }
@article {pmid40219044, year = {2025}, author = {Marchesi, N and Allegri, M and Bruno, GM and Pascale, A and Govoni, S}, title = {Exploring the Potential of Dietary Supplements to Alleviate Pain Due to Long COVID.}, journal = {Nutrients}, volume = {17}, number = {7}, pages = {}, pmid = {40219044}, issn = {2072-6643}, mesh = {Humans ; *Dietary Supplements ; *COVID-19/complications ; SARS-CoV-2 ; *Chronic Pain/etiology ; Analgesics/therapeutic use ; *Pain Management/methods ; Post-Acute COVID-19 Syndrome ; *Pain/etiology/drug therapy ; }, abstract = {Long COVID, characterized by persistent symptoms following COVID-19 infection, significantly impacts individuals' health and daily functioning due to fatigue and pain. Focusing on pain, this review addresses nociplastic and chronic pain conditions. Interventions designed to reduce inflammation, oxidative stress, and enhance vagal activity may offer a promising approach to managing post-pandemic pain. This review presents individual components of food supplements with demonstrated efficacy in one or more pain conditions, focusing on their proposed mechanisms and clinical activity in pain, including their use in post-COVID-19 pain when available. Many of these substances have a long history of safe use and may offer an alternative to long-term analgesic drug treatment, which is often associated with potential side effects. This review also explores the potential for synergistic effects when combining these substances with each other or with conventional analgesics, considering the advantages for both patients and the healthcare system in using these substances as adjunctive or primary therapies for pain symptoms related to long COVID. While preclinical scientific literature provides a mechanistic basis for the action of several food supplements on pain control mechanisms and signaling pathways, clinical experience, particularly in the field of long COVID-associated pain, is still limited. However, the reviewed literature strongly suggests that the use of food supplements in long COVID-associated pain is an attainable goal, provided that rigorous clinical trials are conducted.}, }
@article {pmid40231214, year = {2025}, author = {Serafini, RA and Frere, JJ and Giosan, IM and Nwaneshiudu, CA}, title = {SARS-CoV-2-induced sensory perturbations: A narrative review of clinical phenotypes, molecular pathologies, and possible interventions.}, journal = {Brain, behavior, &amp; immunity - health}, volume = {45}, number = {}, pages = {100983}, pmid = {40231214}, issn = {2666-3546}, abstract = {BACKGROUND: The acute and post-acute sequelae of SARS-CoV-2 infection have been of great clinical interest since the inception of the COVID-19 pandemic. Despite a high prevalence of individuals with persistent symptoms, a wholistic view of the effects of SARS-CoV-2 on special sensory systems is lacking. Considering the significant impact of normal sensory function on quality of life, the goal of this review is to highlight unresolved issues related to SARS-CoV-2-associated insults to the sensory nervous system.<br><br>MAJOR FINDINGS: In this narrative review, we discuss the epidemiology of SARS-CoV-2-induced sensory perturbations, underlying pathological mechanisms, and possible therapeutic strategies across the olfactory, gustatory, somatosensory, visual, and auditory systems. Examined literature included studies with human biospecimens, human-derived cell lines, and naturally susceptible animal models, which highlighted evidence of persistent functional disruption in all sensory systems. SARS-CoV-2 infection was associated with persistent inflammation in the olfactory epithelium/bulb, somatosensory ganglia, and gustatory systems, long-term transcriptional perturbations in the sensory central nervous system and peripheral nervous system, and detectable degeneration/apoptosis in the gustatory and visual systems. Few studies have proposed evidence-based therapeutic strategies for attenuating specific sensory abnormalities after SARS-CoV-2 infection.<br><br>CONCLUSION: While the olfactory system, and to some extent the visual and somatosensory systems, have been more thoroughly investigated from symptomatology, behavioral and molecular perspectives, there is still an unmet need for the development of therapeutics to treat COVID-induced impairment of these systems. Further, additional attention must be placed on COVID-associated impairment of the gustatory, visual, and auditory systems, which lack detailed mechanistic investigations into their pathogenesis.}, }
@article {pmid40241147, year = {2025}, author = {Morello, R and De Rose, C and Martino, L and Raffaelli, F and Zampino, G and Valentini, P and Buonsenso, D}, title = {Role of nutrient supplements in children with post-COVID condition: a retrospective preliminary observation and narrative review.}, journal = {Italian journal of pediatrics}, volume = {51}, number = {1}, pages = {119}, pmid = {40241147}, issn = {1824-7288}, mesh = {Humans ; *Dietary Supplements ; Retrospective Studies ; *COVID-19/complications ; Child ; Male ; Female ; Child, Preschool ; Adolescent ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Post-COVID Condition (PCC), emerging as a significant long-term consequence of SARS-CoV-2 infection, affects not only adults but also the pediatric population. Despite ongoing research, the precise pathophysiology of PCC remains elusive. However, several putative mechanisms have been identified, leading to the exploration of various therapeutic strategies. Notably, in the adult population, there has been substantial interest in the potential efficacy of nutritional supplements. Regrettably, information regarding the use of such supplements in the pediatric population is currently lacking.<br><br>METHODS: The present study was conducted to assess the impact of nutritional supplements on alleviating long COVID symptoms in children. To achieve this, we conducted a retrospective analysis of nutrient supplements administered by parents to children with Post-COVID Condition (PCC) between February 2020 and October 2022. Statistical analyses were employed to determine associations between categorical variables.<br><br>RESULTS: A total of 1243 children were enrolled following documented SARS-CoV-2 infection, with 940 (76.2%) diagnosed as recovered and 294 (23.8%) diagnosed with Long COVID. Among Long COVID patients experiencing disabling symptoms, treatment with oral lactoferrin and/or a Multi-Element Product (MEP) with antioxidant and anti-inflammatory properties was initiated. The correlation analysis between the use of supplements and persistence of long COVID at the next follow-up showed that the use of MEP alone (OR 5.7, 95% CI 3.8-8.5), or the combination of MEP and lactoferrin (OR 5.06, 95% CI 3.3-7.6) three months after the initial infection and for the following three months, were associated with a lower risk having long covid at six months following initial infection, when compared with the use of lactoferrin alone (OR 7.6 95% CI 5.1-11.4).<br><br>CONCLUSIONS: This proof-of-concept study revealed that MEP and lactoferrin, when administered three months after initial infection in patients with a new diagnosis of long covid, may have a positive impact on improving Long COVID symptoms in children during follow-up evaluations. This positive trend toward reducing Post-COVID Condition (PCC) exhibited by MEP and lactoferrin suggested a potential benefit worthy of exploration in future randomized controlled trials.}, }
@article {pmid40246346, year = {2025}, author = {Adilović, M}, title = {COVID-19 related complications.}, journal = {Progress in molecular biology and translational science}, volume = {213}, number = {}, pages = {259-314}, doi = {10.1016/bs.pmbts.2025.02.002}, pmid = {40246346}, issn = {1878-0814}, mesh = {Humans ; *COVID-19/complications ; *SARS-CoV-2 ; Pregnancy ; Pandemics ; Female ; }, abstract = {The COVID-19 pandemic has significantly impacted global healthcare systems, revealed vulnerabilities and prompted a re-evaluation of medical practices. Acute complications from the virus, including cardiovascular and neurological issues, have underscored the necessity for timely medical interventions. Advances in diagnostic methods and personalized therapies have been pivotal in mitigating severe outcomes. Additionally, Long COVID has emerged as a complex challenge, affecting various body systems and leading to respiratory, cardiovascular, neurological, psychological, and musculoskeletal problems. This broad spectrum of complications highlights the importance of multidisciplinary management approaches that prioritize therapy, rehabilitation, and patient-centered care. Vulnerable populations such as paediatric patients, pregnant women, and immunocompromised individuals face unique risks and complications, necessitating continuous monitoring and tailored management strategies to reduce morbidity and mortality associated with COVID-19.}, }
@article {pmid40246350, year = {2025}, author = {Rubio-Casillas, A and Rodríguez-Quintero, CM and Hromić-Jahjefendić, A and Uversky, VN and Redwan, EM and Brogna, C}, title = {The essential role of prebiotics in restoring gut health in long COVID.}, journal = {Progress in molecular biology and translational science}, volume = {213}, number = {}, pages = {385-411}, doi = {10.1016/bs.pmbts.2025.01.004}, pmid = {40246350}, issn = {1878-0814}, mesh = {Humans ; *Prebiotics/administration &amp; dosage ; *COVID-19/microbiology/immunology ; *Gastrointestinal Microbiome/drug effects ; SARS-CoV-2 ; Dysbiosis/microbiology ; Probiotics ; Pandemics ; }, abstract = {The gut microbiota (GM) plays an essential role in human health, influencing not only digestive processes but also the immune system´s functionality. The COVID-19 pandemic has highlighted the complex interaction between viral infections and the GM. Emerging evidence has demonstrated that SARS-CoV-2 can disrupt microbial homeostasis, leading to dysbiosis and compromised immune responses. The severity of COVID-19 has been associated with a reduction in the abundance of several beneficial bacteria in the gut. It has been proposed that consuming probiotics may help to re-colonize the GM. Although probiotics are important, prebiotics are essential for their metabolism, growth, and re-colonization capabilities. This chapter delves into the critical role of prebiotics in restoring GM after COVID-19 disease. The mechanisms by which prebiotics enhance the metabolism of beneficial bacteria will be described, and how prebiotics mediate the re-colonization of the gut with beneficial bacteria, thereby restoring microbial diversity and promoting the resilience of the gut-associated immune system. The benefits of consuming prebiotics from natural sources are superior to those from chemically purified commercial products.}, }
@article {pmid40252805, year = {2025}, author = {Gentilotti, E and Canziani, LM and Caponcello, MG and Azzini, AM and Savoldi, A and De Nardo, P and Palacios-Baena, ZR and Tazza, B and Caroccia, N and Marchetti, GC and Antinori, A and Giannella, M and Rodríguez-Baño, J and Tacconelli, E and , }, title = {ORCHESTRA Delphi consensus: diagnostic and therapeutic management of post-COVID-19 condition in vulnerable populations.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {31}, number = {8S}, pages = {S44-S54}, doi = {10.1016/j.cmi.2025.04.009}, pmid = {40252805}, issn = {1469-0691}, mesh = {Humans ; *COVID-19/complications/therapy ; Delphi Technique ; *Vulnerable Populations ; Risk Factors ; SARS-CoV-2 ; *Rheumatic Diseases/complications/therapy ; HIV Infections/complications ; Hematologic Neoplasms/complications ; Female ; Male ; }, abstract = {OBJECTIVES: Post-COVID-19 condition (PCC) remains poorly understood, especially in clinically vulnerable groups. We applied the Delphi approach to drive recommendations for the diagnosis, management, and prevention of PCC in people living with HIV (PWH) and patients affected by rheumatological diseases (RD) and haematological malignancies.<br><br>METHODS: On the basis of literature review, three areas of interest in PCC in PWH, haematological malignancies, and RD were identified: (a) features and risk factors; (b) diagnosis and management; and (c) prevention. A three-round Delphi anonymous survey consisting of 15 questions was conducted including 69 experts. Consensus was measured by the six-point Likert scale categorized into four tiers: strong disagreement, moderate disagreement, moderate agreement, and strong agreement. Statements were generated on questions achieving consensus.<br><br>RESULTS: Eleven statements were generated: six on features and risk factors of PCC in clinically vulnerable populations, two on diagnosis and management, and three on prevention. Chronic fatigue was identified as the most frequent presentation of PCC in PWH and RD populations. A different case definition of PCC is required for RD population, as symptoms of PCC and autoimmune disorders may overlap. Risk factors for PCC include age >65, severity of COVID-19, and female sex; the latter is also associated with increased smell/taste impairment. A clinical assessment or a routine laboratory test performed 3 months after acute infection is not suggested to diagnose PCC in PWH. PWH and RD should be screened to exclude additional autoimmune disorders in case of chronic fatigue/arthralgia of new onset. Full-course vaccination and early treatment for COVID-19 should be promoted to prevent PCC, whereas corticosteroids during acute infection are not recommended.<br><br>DISCUSSION: Diagnosis, management, and prevention of PCC are still under discussion. This Delphi offers valuable insights on PCC in selected clinically vulnerable populations and suggests a tailored approach in vulnerable populations.}, }
@article {pmid40254579, year = {2025}, author = {Ewing, AG and Joffe, D and Blitshteyn, S and Brooks, AES and Wist, J and Bar-Yam, Y and Bilodeau, S and Curtin, J and Duncan, R and Faghy, M and Galland, L and Pretorius, E and Salamon, S and Buonsenso, D and Hastie, C and Kane, B and Khan, MA and Lal, A and Lau, D and MacIntyre, R and McFarland, S and Munblit, D and Nicholson, J and Ollila, HM and Putrino, D and Rosario, A and Tan, T and , }, title = {Long COVID clinical evaluation, research and impact on society: a global expert consensus.}, journal = {Annals of clinical microbiology and antimicrobials}, volume = {24}, number = {1}, pages = {27}, pmid = {40254579}, issn = {1476-0711}, mesh = {Humans ; *COVID-19/diagnosis/therapy/complications/epidemiology ; SARS-CoV-2 ; Delphi Technique ; Post-Acute COVID-19 Syndrome ; Global Health ; Child ; }, abstract = {BACKGROUND: Long COVID is a complex, heterogeneous syndrome affecting over four hundred million people globally. There are few recommendations, and no formal training exists for medical professionals to assist with clinical evaluation and management of patients with Long COVID. More research into the pathology, cellular, and molecular mechanisms of Long COVID, and treatments is needed. The goal of this work is to disseminate essential information about Long COVID and recommendations about definition, diagnosis, treatment, research and social issues to physicians, researchers, and policy makers to address this escalating global health crisis.<br><br>METHODS: A 3-round modified Delphi consensus methodology was distributed internationally to 179 healthcare professionals, researchers, and persons with lived experience of Long COVID in 28 countries. Statements were combined into specific areas: definition, diagnosis, treatment, research, and society.<br><br>RESULTS: The survey resulted in 187 comprehensive statements reaching consensus with the strongest areas being diagnosis and clinical assessment, and general research. We establish conditions for diagnosis of different subgroups within the Long COVID umbrella. Clear consensus was reached that the impacts of COVID-19 infection on children should be a research priority, and additionally on the need to determine the effects of Long COVID on societies and economies. The consensus on COVID and Long COVID is that it affects the nervous system and other organs and is not likely to be observed with initial symptoms. We note, biomarkers are critically needed to address these issues.<br><br>CONCLUSIONS: This work forms initial guidance to address the spectrum of Long COVID as a disease and reinforces the need for translational research and large-scale treatment trials for treatment protocols.}, }
@article {pmid40259563, year = {2025}, author = {Cornish, F and Sabaine, B and Soares, L and Caldas, B and Portela, MC and Bousquat, A and Aveling, EL}, title = {The erasure of infection-associated chronic conditions: Critical interpretive synthesis of literature on healthcare for long COVID and related conditions in Brazil.}, journal = {Global public health}, volume = {20}, number = {1}, pages = {2490720}, doi = {10.1080/17441692.2025.2490720}, pmid = {40259563}, issn = {1744-1706}, mesh = {Humans ; Brazil/epidemiology ; *COVID-19/epidemiology/therapy/complications ; Chronic Disease/epidemiology/therapy ; SARS-CoV-2 ; *Delivery of Health Care ; Post-Acute COVID-19 Syndrome ; }, abstract = {Evidence is emerging that long COVID is at least as prevalent in the Global South as the Global North, but literature on long COVID healthcare in the Global South is in its infancy. Brazil is seeing significant levels of debility due to long COVID but a limited national evidence-base. long COVID shares symptomatology and appropriate care with a wider category of infection-associated chronic conditions (IACCs). This article reviews literature published between 2000 and 2023 addressing healthcare for long COVID and IACCs in Brazil, in the interest of exploring challenges and opportunities for the SUS (Brazil's universal health system) to offer appropriate long COVID healthcare. We find that long COVID and IACCs collectively are subject to erasure from Brazilian healthcare knowledge, through lack of expertise, a resource-limited health system prioritising urgent care, and the concentration of poor health in marginalised populations with limited decision-making power. A nascent intellectual will to address long COVID, and a tradition of social participation in healthcare governance present potential opportunities. We call for ignition of a global step-change in tackling healthcare for long COVID and IACCs. Global equity in long COVID healthcare requires the development and sharing of expertise regarding its universal and context-specific features.}, }
@article {pmid40259865, year = {2025}, author = {Bjorvatn, B and Merikanto, I and Chung, F and Holzinger, B and Morin, CM and Penzel, T and De Gennaro, L and Dauvilliers, Y and Wing, YK and Benedict, C and Xue, P and Reis, C and Korman, M and Landtblom, AM and Matsui, K and Hrubos-Strøm, H and Mota-Rolim, S and Nadorff, MR and Berezin, L and Sarkanen, T and Liu, Y and Scarpelli, S and Brandao, LEM and Cedernaes, J and Fränkl, EC and Partinen, E and Bolstad, CJ and Plazzi, G and Partinen, M and Espie, CA}, title = {Sleep During Pandemic Times: Summary of Findings and Future Outlook Through the Lens of the International COVID Sleep Study (ICOSS).}, journal = {Journal of sleep research}, volume = {34}, number = {5}, pages = {e70076}, doi = {10.1111/jsr.70076}, pmid = {40259865}, issn = {1365-2869}, mesh = {Humans ; *COVID-19/epidemiology ; *Sleep Wake Disorders/epidemiology ; *Sleep/physiology ; Pandemics ; Circadian Rhythm/physiology ; Surveys and Questionnaires ; SARS-CoV-2 ; }, abstract = {To study the impact of the COVID-19 pandemic on sleep and circadian rhythms-two fundamental pillars for health-the collaboration International COVID-19 Sleep Study (ICOSS) was established. The present overview comprehensively discusses the findings from this collaboration. Involving sleep researchers across the globe, ICOSS used a harmonised questionnaire to cover changes in sleep and sleep disorders, as well as physical and mental health. Two survey waves were conducted, one in 2020 and another one in 2021. In ICOSS-1, a total of 26,539 people from 14 countries across four continents (Europe, Asia, North and South America) participated. In ICOSS-2, two more countries joined ICOSS, and 15,813 people participated. The focus in ICOSS-2 was on Long COVID. Participants accessed the widely disseminated online surveys in their native language. In the 20 papers published so far, the surveys have uncovered several novel findings, including how the pandemic impacted sleep patterns, the prevalence of sleep disorders, chronotype-based differences and sleep-immune system interactions. To the best of our knowledge, there is no other large-scale multinational study targeting the general population investigating the role of sleep and sleep disorders alongside a variety of psychological, biological, social and economic factors during the recent COVID-19 pandemic.}, }
@article {pmid40278579, year = {2025}, author = {Lan, L and Wang, Y and Chen, Y and Wang, T and Zhang, J and Tan, B}, title = {A Review on the Prevalence and Treatment of Antibiotic Resistance Genes in Hospital Wastewater.}, journal = {Toxics}, volume = {13}, number = {4}, pages = {}, pmid = {40278579}, issn = {2305-6304}, abstract = {Antibiotic resistance is a global environmental and health threat. Approximately 4.95 million deaths were associated with antibiotic resistance in 2019, including 1.27 million deaths that were directly attributable to bacterial antimicrobial resistance. Hospital wastewater is one of the key sources for the spread of clinically relevant antibiotic resistance genes (ARGs) into the environment. Understanding the current situation of ARGs in hospital wastewater is of great significance. Here, we review the prevalence of ARGs and antibiotic-resistant bacteria (ARB) in hospital wastewater and wastewater from other places and the treatment methods used. We further discuss the intersection between ARGs and COVID-19 during the pandemic. This review highlights the issues associated with the dissemination of critical ARGs from hospital wastewater into the environment. It is imperative to implement more effective processes for hospital wastewater treatment to eliminate ARGs, particularly during the current long COVID-19 period.}, }
@article {pmid40283075, year = {2025}, author = {Loboda, D and Golba, KS and Gurowiec, P and Bredelytė, A and Razbadauskas, A and Sarecka-Hujar, B}, title = {Variability in Arterial Stiffness and Vascular Endothelial Function After COVID-19 During 1.5 Years of Follow-Up-Systematic Review and Meta-Analysis.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {4}, pages = {}, pmid = {40283075}, issn = {2075-1729}, support = {BNW-2-016/N/4/K//Medical University of Silesia/ ; }, abstract = {Increasing long-term observations suggest that coronavirus disease 2019 (COVID-19) vasculopathy may persist even 1.5 years after the acute phase, potentially accelerating the development of atherosclerotic cardiovascular diseases. This study systematically reviewed the variability of brachial flow-mediated dilation (FMD) and carotid-femoral pulse wave velocity (cfPWV) from the acute phase of COVID-19 through 16 months of follow-up (F/U). Databases including PubMed, Web of Science, MEDLINE, and Embase were screened for a meta-analysis without language or date restrictions (PROSPERO reference CRD42025642888, last search conducted on 1 February 2025). The quality of the included studies was assessed using the Newcastle-Ottawa Quality Scale. We considered all studies (interventional pre-post studies, prospective observational studies, prospective randomized, and non-randomized trials) that assessed FMD or cfPWV in adults (aged ≥ 18 years) with or after laboratory-confirmed COVID-19 compared with non-COVID-19 controls or that assessed changes in these parameters during the F/U. Twenty-one studies reported differences in FMD, and 18 studies examined cfPWV between COVID-19 patients and control groups during various stages: acute/subacute COVID-19 (≤30 days from disease onset), early (>30-90 days), mid-term (>90-180 days), late (>180-270 days), and very late (>270 days) post-COVID-19 recovery. Six studies assessed variability in FMD, while nine did so for cfPWV during the F/U. Data from 14 FMD studies (627 cases and 694 controls) and 15 cfPWV studies (578 cases and 703 controls) were included in our meta-analysis. FMD showed a significant decrease compared to controls during the acute/subacute phase (standardized mean difference [SMD]= -2.02, p < 0.001), with partial improvements noted from the acute/subacute phase to early recovery (SMD = 0.95, p < 0.001) and from early to mid-term recovery (SMD = 0.92, p = 0.006). Normalization compared to controls was observed in late recovery (SMD = 0.12, p = 0.69). In contrast, cfPWV values, which were higher than controls in the acute/subacute phase (SMD = 1.27, p < 0.001), remained elevated throughout the F/U, with no significant changes except for a decrease from mid-term to very late recovery (SMD= -0.39, p < 0.001). In the very late recovery, cfPWV values remained higher than those of controls (SMD = 0.45, p = 0.010). In the manuscript, we discuss how various factors, including the severity of acute COVID-19, the persistence of long-term COVID-19 syndrome, and the patient's initial vascular age, depending on metrics age and cardiovascular risk factors, influenced the time and degree of FMD and cfPWV improvement.}, }
@article {pmid40284540, year = {2025}, author = {Jason, LA and Katz, BZ}, title = {Predisposing and Precipitating Factors in Epstein-Barr Virus-Caused Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.}, journal = {Microorganisms}, volume = {13}, number = {4}, pages = {}, pmid = {40284540}, issn = {2076-2607}, abstract = {Long COVID following SARS-CoV-2 and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) following infectious mononucleosis (IM) are two examples of post-viral syndromes. The identification of risk factors predisposing patients to developing and maintaining post-infectious syndromes may help uncover their underlying mechanisms. The majority of patients with ME/CFS report infectious illnesses before the onset of ME/CFS, with 30% of cases of ME/CFS due to IM caused by the Epstein-Barr virus. After developing IM, one study found 11% of adults had ME/CFS at 6 months and 9% had ME/CFS at 1 year. Another study of adolescents found 13% and 7% with ME/CFS at 6 and 12 months following IM, respectively. However, it is unclear which variables are potential risk factors contributing to the development and maintenance of ME/CFS following IM, because few prospective studies have collected baseline data before the onset of the triggering illness. The current article provides an overview of a study that included pre-illness predictors of ME/CFS development following IM in a diverse group of college students who were enrolled before the onset of IM. Our data set included an ethnically and sociodemographically diverse group of young adult students, and we were able to longitudinally follow these youths over time to better understand the risk factors associated with the pathophysiology of ME/CFS. General screens of health and psychological well-being, as well as blood samples, were obtained at three stages of the study (Stage 1-Baseline-when the students were well, at least 6 weeks before the student developed IM; Stage 2-within 6 weeks following the diagnosis of IM, and Stage 3-six months after IM, when they had either developed ME/CFS or recovered). We focused on the risk factors for new cases of ME/CFS following IM and found factors both at baseline (Stage 1) and at the time of IM (Stage 2) that predicted nonrecovery. We are now collecting seven-year follow-up data on this sample, as well as including cases of long COVID. The lessons learned in this prospective study are reviewed.}, }
@article {pmid40294910, year = {2025}, author = {Sessford, JD and Dodwell, A and Elms, K and Gill, M and Premnazeer, M and Scali, O and Roque, M and Cameron, JI}, title = {Factors associated with mental health outcomes among family caregivers to adults with COVID: a scoping review.}, journal = {Disability and rehabilitation}, volume = {47}, number = {23}, pages = {5983-6000}, doi = {10.1080/09638288.2025.2494223}, pmid = {40294910}, issn = {1464-5165}, mesh = {Humans ; *Caregivers/psychology ; *COVID-19/psychology ; *Mental Health ; Adaptation, Psychological ; Adult ; Risk Factors ; SARS-CoV-2 ; Social Support ; }, abstract = {PURPOSE: Family caregivers (FCGs) are essential to the health and wellbeing of people affected by COVID. Protecting mental health of FCGs is essential to sustaining their caregiving role. The objective of this scoping review was to synthesise identified risks factors and protective factors for mental health of FCGs to adults with COVID.<br><br>MATERIALS AND METHODS: Using the Joanna Briggs Institute (JBI) methodology, the search was conducted across Medline, CINAHL, and PsycINFO. Original studies conducted since the pandemic began were included. The population was adult FCGs to adults with COVID, and studies reported mental health outcomes and related factors.<br><br>RESULTS: Of 3474 identified articles, 22 met inclusion criteria (14 quantitative, seven qualitative, one mixed-methods, 18/22 conducted in Iran). Across all study designs, risk factors included limited support, financial burden, family challenges, unpredictable nature of COVID, inexperience, isolation, and unpleasant experiences. Protective factors included accessing support services, self-reinforcement, coping strategies, professional help, and online intervention.<br><br>CONCLUSIONS: Quantitative and qualitative research identified common mental health risk factors and protective factors for FCGs to adults with COVID. These factors may inform development of supports and services for FCGs to people with COVID, such as online interventions. Studies did not distinguish acute versus long COVID.}, }
@article {pmid40300093, year = {2025}, author = {Rane Levendovszky, S and Patel, P and Zhu, C and Rutman, AM and Basha, MM}, title = {Neuroimaging biomarkers of post-acute sequelae of Coronavirus Disease 2019.}, journal = {The British journal of radiology}, volume = {98}, number = {1172}, pages = {1165-1175}, doi = {10.1093/bjr/tqaf090}, pmid = {40300093}, issn = {1748-880X}, support = {R01 HL162743/HL/NHLBI NIH HHS/United States ; //Chronic Post COVID-19 Infection Neuroimaging and Cerebrovascular Imaging/ ; //Bayer Healthcare LLC/ ; //Long terms effects of COVID-19/ ; }, mesh = {Humans ; *COVID-19/complications/diagnostic imaging ; *Neuroimaging/methods ; *Brain/diagnostic imaging/pathology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Biomarkers ; Magnetic Resonance Imaging/methods ; Diffusion Tensor Imaging ; }, abstract = {COVID-19, caused by SARS-CoV-2, has led to the condition known as Long COVID or post-acute sequelae of COVID-19 (PASC), where individuals experience persistent debilitating symptoms long after the initial infection. We provide here a comprehensive review of findings in the central nervous system associated with PASC. Neuroimaging has been instrumental in identifying brain changes associated with PASC. Structural MRI studies consistently reveal grey matter volume reductions in the frontal and temporal lobes and white matter hyperintensities, particularly in the periventricular regions. Studies especially found these changes to correlate strongly with cognitive deficits. Diffusion tensor imaging has shown increased tissue damage and oedema in the brain's white matter tracts, particularly in the sagittal stratum and thalamic radiation. Resting-state functional MRI studies indicate altered brain connectivity in PASC patients, especially in those with post-traumatic stress symptoms. Reduced connectivity within and between critical networks, such as the default mode network and the executive control network, has been observed. These changes correlate with cognitive impairments, such as attention and memory deficits. Dynamic functional connectivity analyses further reveal that PASC patients spend less time in states with rich inter-regional connectivity, and transitions between connectivity states were linked to post-traumatic stress disorder symptoms. Positron emission tomography scans have shown hypometabolism in the frontal and temporal lobes, particularly in regions associated with memory and executive functions. Hypometabolism in the hippocampus and thalamus is linked to symptoms like anosmia and fatigue. Despite the heterogeneity in clinical presentations and diagnostic criteria, these neuroimaging findings underscore the significant impact of COVID-19 on brain structure and function. Continued research using advanced imaging techniques is essential for a deeper understanding of PASC's neurological effects. This will aid in developing targeted interventions and improving outcomes for those affected by Long COVID and inform studies investigating downstream effects of viral infections on the brain.}, }
@article {pmid40304923, year = {2025}, author = {Millhouse, PW and Bloom, RW and Beckstrand, JN and McClure, ML and Eckmann, MS and Feeko, KJ and Mojica, JJ}, title = {The Ganglia of the Head and Neck: Clinical Relevance for the Interventional Pain Physician.}, journal = {Current pain and headache reports}, volume = {29}, number = {1}, pages = {80}, pmid = {40304923}, issn = {1534-3081}, mesh = {Humans ; *Facial Pain/therapy/physiopathology ; *Pain Management/methods ; Nerve Block/methods ; *Headache/therapy ; *Headache Disorders/therapy ; Clinical Relevance ; }, abstract = {PURPOSE OF REVIEW: The purpose of this article is to provide a comprehensive review of the ganglia of the head and neck and their role in the interventional management of chronic headaches and facial pain disorders.<br><br>RECENT FINDINGS: Interventions targeting the sphenopalatine, stellate and gasserian ganglia are well described in the literature for headaches and facial pain disorders. There is a growing body of evidence supporting use of these techniques for clinical conditions outside of pain such as post-traumatic stress disorder and Long COVID symptoms. These findings increase the potential applications of such procedures, making them more relevant to the interventional physician tasked with managing symptoms in difficult to treat medical conditions. Nerve blocks of the head and neck are used for diagnostic and therapeutic purposes in the management of headaches and facial pain disorders. Headaches, whether acute or chronic, are common pain conditions with a wide-range of etiologies and are often difficult to treat. Chronic facial pain can have a variety of underlying causes, including direct or indirect nerve damage, infection, inflammation, and muscle dysfunction. Traditional pain management strategies such as medications and physical therapy often fail or are associated with significant adverse effects. Interventions such as nerve blocks and neuroablative procedures have shown promise in managing headaches and facial pain by directly targeting the underlying causes. This review article summarizes the most recent evidence regarding the efficacy, safety, applications and limitations of these interventional pain management techniques.}, }
@article {pmid40305533, year = {2025}, author = {Wang, R and Lin, M and Yu, S and Xue, X and Hu, X and Wang, Z}, title = {Predictors of post-COVID-19 syndrome: a meta-analysis.}, journal = {Journal of infection in developing countries}, volume = {19}, number = {4}, pages = {490-497}, doi = {10.3855/jidc.18574}, pmid = {40305533}, issn = {1972-2680}, mesh = {Female ; Humans ; Male ; Comorbidity ; *COVID-19/complications/diagnosis/epidemiology/virology ; Dyspnea/diagnosis/epidemiology/virology ; *Post-Acute COVID-19 Syndrome/diagnosis/epidemiology/virology ; Prognosis ; Risk Factors ; SARS-CoV-2 ; Severity of Illness Index ; Sex Factors ; }, abstract = {INTRODUCTION: Post Coronavirus Disease 2019 (COVID-19) Syndrome also known as long COVID-19 would affect survivors of various patients. At present, the evidence for predicting a poor prognosis of COVID-19 remains insufficient. This study aims to explore potential predictors of post-COVID-19 syndrome.<br><br>METHODOLOGY: A systematic review process and meta-analysis method are applied to identify the predictors. Systematic searches were conducted without language restrictions from December 1, 2019, to February 28, 2022, on PubMed, Embase, Google Scholar, Web of Science, and Cochrane Library using specific keywords relevant to our targets. The Newcastle Ottawa Scale observational research tool was used to assess study quality and the R (4.1.1) package meta was used for statistical analysis.<br><br>RESULTS: Our meta-analysis of 14 studies showed that females (OR = 1.42, 95% CI: 1.19-1.70), the severity of patients (OR = 2.43, 95% CI: 1.26-4.68), comorbidity (OR = 2.08, 95% CI: 1.29-3.35), dyspnea (OR = 2.02, 95% CI: 1.34-3.04) associated with a higher risk of post-COVID-19 syndrome.<br><br>CONCLUSIONS: Our study showed that females, the severity of COVID-19, comorbidity, and dyspnea were associated with a higher risk of post-COVID-19 syndrome. More attention should be paid to these factors to prevent and treat post-COVID-19 syndrome.}, }
@article {pmid40310228, year = {2025}, author = {Bontempo, AC and Bontempo, JM and Duberstein, PR}, title = {Ignored, dismissed, and minimized: Understanding the harmful consequences of invalidation in health care-A systematic meta-synthesis of qualitative research.}, journal = {Psychological bulletin}, volume = {151}, number = {4}, pages = {399-427}, doi = {10.1037/bul0000473}, pmid = {40310228}, issn = {1939-1455}, support = {//U.S. Department of Health and Human Services; Health Resources and Services Administration/ ; }, mesh = {Humans ; Qualitative Research ; *Disease/psychology ; *Delivery of Health Care ; }, abstract = {The upsurge in the prevalence of contested, ambiguous, and difficult-to-diagnose illnesses presents challenges for clinicians who too often respond by invalidating patients' symptoms. Although numerous qualitative studies have reported the effects of invalidation on patients' psychological and behavioral outcomes, this body of research has not been systematically reviewed. Informed by Linehan's (1993) conceptualization of invalidation, this systematic review elucidated the negative consequences, of symptom invalidation, or the dismissal or minimization of a person's experiences with illness. We reviewed 151 qualitative reports representing 11,307 individuals with Ehlers-Danlos syndrome, endometriosis, fibromyalgia syndrome, Gulf War syndrome, irritable bowel syndrome, long COVID, multiple chemical sensitivity, myalgic encephalomyelitis/chronic fatigue syndrome, postural orthostatic tachycardia syndrome, systemic lupus erythematosus, and vulvodynia. Consistent with Linehan's theorizing, thematic analysis identified four broad classes of consequences: induced emotional states and beliefs (e.g., shame, suicidality), induced health care emotional states and beliefs (e.g., health care-related anxiety and trauma), induced health care behavior (e.g., health care system avoidance), and diagnostic delay. Informed by these findings, we developed a novel conceptual model explaining how symptom invalidation leads to these consequences and thereby undermines health outcomes. Future work should explore the proposed conceptual model and identify theoretically informed interventions and policies aimed at preventing symptom invalidation to improve psychological, behavioral, and health outcomes. (PsycInfo Database Record (c) 2025 APA, all rights reserved).}, }
@article {pmid40322881, year = {2025}, author = {Vieira Junior, JCA and Sander, MRL and Matos, JAO and Medeiros, AM and Silva, FSD and Aires, CAM}, title = {Neurological Post-Acute Sequelae of COVID-19 in Non-Hospitalized Patients: An Integrative Review.}, journal = {Biological research for nursing}, volume = {27}, number = {4}, pages = {652-665}, doi = {10.1177/10998004251335968}, pmid = {40322881}, issn = {1552-4175}, mesh = {Humans ; *COVID-19/complications ; *Nervous System Diseases/etiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {The COVID-19 pandemic has had a significant impact on the global population. The infection, caused by SARS-CoV-2, presents with a variety of clinical manifestations, from asymptomatic cases to more severe forms, including a variety of neurological symptoms, such as fatigue, weakness, brain fog, paresthesias, dysautonomia, anosmia, and dysgeusia. Additionally, the disease is associated with the long COVID syndrome, in which there is persistence of the effects and symptoms of the acute phase. In recent years the literature has shown relevant data on long COVID, but there is still a need to deepen the knowledge about these long term manifestations. Thus, the present study aimed to describe the main neurological sequelae resulting from SARS-CoV-2 infection in non-hospitalized population during the long phase of the disease, gathering scientific evidence through an integrative review of the prevalence of symptoms, patient profile, duration and severity of sequelae, risk factors, comorbidities, and possible nervous system structural damage. The PubMed/Medline database was used with descriptors and, at the end of the screening process with predefined inclusion and exclusion criteria, 22 studies were included. A group of neurological symptoms associated with long COVID was identified: myalgia, dysgeusia, memory alterations, olfactory dysfunction, dizziness, and pain. Most patients presented multiple symptoms that lasted for more than one year with a significant impact on quality of life. The main risk factors were dyslipidemia, age, ethnicity, muscle/ joint pain, and sex. This review highlights the importance of further studies on the syndrome, its etiology, diagnosis, follow-up, and treatments.}, }
@article {pmid40326310, year = {2025}, author = {El-Naas, A and Hamad, O and Nair, S and Alfakhri, B and Mahmoud, S and Haji, A and Ahmed, L and Lebbe, A and Aboulwafa, A and Shaikh, F and Bouhali, I and Zakaria, D}, title = {New onset of type 1 and type 2 diabetes post-COVID-19 infection: a systematic review.}, journal = {Emerging microbes &amp; infections}, volume = {14}, number = {1}, pages = {2492211}, pmid = {40326310}, issn = {2222-1751}, mesh = {Humans ; *COVID-19/complications/epidemiology ; *Diabetes Mellitus, Type 1/epidemiology/etiology ; *Diabetes Mellitus, Type 2/epidemiology/etiology ; Prevalence ; Risk Factors ; SARS-CoV-2 ; }, abstract = {COVID-19 may primarily cause respiratory symptoms but can lead to long-term effects known as long COVID. COVID-19-induced diabetes mellitus was reported in many patients which shares characteristics of types 1 and 2 (T1DM and T2DM). This study aims to identify and analyse the reported cases of new onset diabetes post-COVID-19 infection. Several databases were used to conduct a comprehensive literature search to target studies reporting cases of T1DM or T2DM post-COVID-19 infection. Screening, data extraction, and cross-checking were performed by two independent reviewers. Only 43 studies met our inclusion criteria. Our results revealed that the overall prevalence of new onset diabetes post-COVID-19 was 1.37% with higher prevalence for T2DM (0.84%) as compared to T1DM (0.017%) while the type of diabetes was not reported in 0.51% of the cases. Several risk factors for developing diabetes post-COVID-19 infection were identified including the type of SARS-CoV-2 variant, age, comorbidities, and the vaccination status. The direct viral attack of the pancreatic beta cells as well as inflammation and the anti-inflammatory corticosteroids were proposed as possible mechanisms of the COVID-19 induced diabetes. A multidisciplinary approach involving endocrinologists, primary care physicians, and infectious disease specialists should be implemented in the management of post-COVID patients to address both the acute and long-term complications, including metabolic changes and risk of diabetes.}, }
@article {pmid40329717, year = {2025}, author = {Parwani, S and Upreti, S and Mishra, CK and Tripathi, A and Chakraborty, S and Tiwari, S}, title = {Navigating the COVID-19 Treatment Landscape: Efficacy and Side-Effects of Current Therapies against SARS-CoV-2.}, journal = {Current HIV research}, volume = {23}, number = {3}, pages = {145-160}, doi = {10.2174/011570162X338375250414114957}, pmid = {40329717}, issn = {1873-4251}, mesh = {Humans ; COVID-19/immunology ; *SARS-CoV-2/drug effects ; *Antiviral Agents/therapeutic use/adverse effects ; *COVID-19 Drug Treatment ; COVID-19 Vaccines/immunology ; *HIV Infections/complications/immunology/drug therapy ; Drug Repositioning ; }, abstract = {Coronavirus Disease 2019 (COVID-19), caused by the highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 in Wuhan, China. Designated as an epidemic by the World Health Organization (WHO) on January 30, 2020, the virus quickly escalated to a global emergency, officially declared a pandemic in March 2020. With over 6 million recorded deaths and more than 200 identified symptoms in diverse individuals, the impact of COVID-19 is substantial. COVID-19 poses a greater risk to individuals with advanced HIV, while those with well-managed HIV are not at increased risk. Although COVID-19 vaccines are generally effective for people with HIV, some may experience reduced vaccine effectiveness and breakthrough infections due to suboptimal immune responses. Long COVID, affecting at least 65 million individuals, adds a layer of complexity. The virus's rapid mutation has led to diverse symptomatology, prompting adjustments in treatment guidelines. This review comprehensively examines repurposed antiviral drug candidates against COVID-19, explores immune responses across different age groups, delves into the mechanisms of COVID-19 vaccines, and discusses potential immunosuppressants. Additionally, the focus extends to Intravenous Immunoglobulin (IVIG), steroids, and anti-cytokine therapy as promising avenues to address cytokine release syndrome (CRS), a critical condition in COVID-19 patients.}, }
@article {pmid40330025, year = {2025}, author = {Smail, SW and Albarzinji, N and Salih, RH and Taha, KO and Hirmiz, SM and Ismael, HM and Noori, MF and Azeez, SS and Janson, C}, title = {Microbiome dysbiosis in SARS-CoV-2 infection: implication for pathophysiology and management strategies of COVID-19.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1537456}, pmid = {40330025}, issn = {2235-2988}, mesh = {Humans ; *Dysbiosis/microbiology/therapy ; *COVID-19/microbiology/physiopathology/therapy/complications ; *SARS-CoV-2 ; *Gastrointestinal Microbiome ; }, abstract = {The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), in late 2019 initiated a global health crisis marked by widespread infection, significant mortality, and long-term health implications. While SARS-CoV-2 primarily targets the respiratory system, recent findings indicate that it also significantly disrupts the human microbiome, particularly the gut microbiota, contributing to disease severity, systemic inflammation, immune dysregulation, and increased susceptibility to secondary infections and chronic conditions. Dysbiosis, or microbial imbalance, exacerbates the clinical outcomes of COVID-19 and has been linked to long-COVID, a condition affecting a significant proportion of survivors and manifesting with over 200 symptoms across multiple organ systems. Despite the growing recognition of microbiome alterations in COVID-19, the precise mechanisms by which SARS-CoV-2 interacts with the microbiome and influences disease progression remain poorly understood. This narrative review investigates the impact of SARS-CoV-2 on host-microbiota dynamics and evaluates its implications in disease severity and for developing personalized therapeutic strategies for COVID-19. Furthermore, it highlights the dual role of the microbiome in modulating disease progression, and as a promising target for advancing diagnostic, prognostic, and therapeutic approaches in managing COVID-19.}, }
@article {pmid40335476, year = {2025}, author = {O'Mahoney, LL and Routen, A and Gillies, C and Jenkins, SA and Almaqhawi, A and Ayoubkhani, D and Banerjee, A and Brightling, C and Calvert, M and Cassambai, S and Ekezie, W and Funnell, MP and Welford, A and Peace, A and Evans, RA and Jeffers, S and Kingsnorth, AP and Pareek, M and Seidu, S and Wilkinson, TJ and Willis, A and Shafran, R and Stephenson, T and Sterne, J and Ward, H and Ward, T and Khunti, K}, title = {The risk of Long Covid symptoms: a systematic review and meta-analysis of controlled studies.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {4249}, pmid = {40335476}, issn = {2041-1723}, mesh = {Humans ; *COVID-19/epidemiology/complications/physiopathology/virology ; *Post-Acute COVID-19 Syndrome/epidemiology/physiopathology/virology ; Risk Factors ; SARS-CoV-2/pathogenicity ; }, abstract = {The global evidence on the risk of symptoms of Long Covid in general populations infected with SARS-CoV-2 compared to uninfected comparator/control populations remains unknown. We conducted a systematic literature search using multiple electronic databases from January 1, 2022, to August 1, 2024. Included studies had ≥100 people with confirmed or self-reported COVID-19 at ≥28 days following infection onset, and an uninfected comparator/control group. Results were summarised descriptively and meta-analyses were conducted to derive pooled risk ratio estimates. 50 studies totaling 14,661,595 people were included. In all populations combined, there was an increased risk of a wide range of 39 out of 40 symptoms in those infected with SARS‑CoV‑2 compared to uninfected controls. The symptoms with the highest pooled relative risks were loss of smell (RR 4.31; 95% CI 2.66, 6.99), loss of taste (RR 3.71; 95% CI 2.22, 7.26), poor concentration (RR 2.68; 95% CI 1.66, 4.33), impaired memory (RR 2.53; 95% CI 1.82, 3.52), and hair loss/alopecia (RR 2.38; 95% CI 1.69, 3.33). This evidence synthesis, of 50 controlled studies with a cumulative participant count exceeding 14 million people, highlights a significant risk of diverse long-term symptoms in individuals infected with SARS-CoV-2, especially among those who were hospitalised.}, }
@article {pmid40354786, year = {2025}, author = {Kardos, P and Becker, S and Heidenreich, KR and Klimek, L and Köhnlein, T and Labenz, J and Mülleneisen, N and Pfeiffer-Kascha, D and Pink, I and Sitter, H and Trinkmann, F and Worth, H and Winterholler, C and ,  and ,  and ,  and ,  and ,  and ,  and ,  and ,  and , }, title = {[Specialist Guidelines of The German Respiratory Society for Diagnosis and Treatment of adult Patients Suffering from Cough].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {79}, number = {5}, pages = {329-357}, doi = {10.1055/a-2550-3738}, pmid = {40354786}, issn = {1438-8790}, mesh = {Humans ; *Cough/diagnosis/therapy/etiology ; Germany ; Adult ; Societies, Medical ; *Pulmonary Medicine/standards ; Chronic Disease ; }, abstract = {This is the 4[th] edition of the Cough Guidelines of the German Respiratory Society written by respiratory, gastroenterology, ear-nose-throat specialists, including respiratory physiotherapists and speech pathology specialists; importantly, a patient representative was also involved.Compared with earlier versions we used a new methodology: after discussion in the guidelines group, we asked and answered the 12 most important and most frequent "key" questions regarding the clinical practice. The extent of the guideline could thus be significantly reduced.We added a short scientific background to each of the answers including the most recent references. The recommendations and statements were created in consensus and graded as strong, or weak. If sufficient literature was not available, we suggested discussing joint decisions with the patient.The 12 key questions are as follows:- Key question 1: The classification of cough (acute, i. e. up to three weeks duration; chronic, i. e. after 8 weeks duration and subacute in between) did not change, but we added "cough with or without expectoration as an additional classification aspect with therapeutic consequences.- Key question 2: Acute and subacute cough are mostly (but not exclusively) due to the common cold. They are the first or second most frequent symptom prompting patients to seek medical (or pharmacist's) care. Antibiotic therapy is strongly discouraged for common cold- Key question 3: We defined "Red flags" for mandatory immediate diagnostic for acute cough, which usually does not require such diagnostic procedures- Key question 4: Chronic cough overview of the most common causes for- Key question 5: Cough in acute SARS-CoV-2 infection and in long COVID - Key question 6: Refractory chronic cough and idiopathic chronic cough, two recently established entities were explained more in detail- Key question 7: To upper airway cough syndrome - Key question 8: Gastro-oesophageal-reflux-related cough - Key question 9: Cough-variant asthma and non-asthmatic eosinophilic bronchitis - Key question 10: Overview of drugs causing cough - Key question 11: Basic and personalized (due to the individual history) diagnostic procedures for patients with cough- Key question 12: Physiotherapy, speech therapy and pharmacotherapy for cough.}, }
@article {pmid40364089, year = {2025}, author = {Moustakli, E and Stavros, S and Michaelidis, TM and Potiris, A and Christodoulaki, C and Zachariou, A and Drakakis, P and Zikopoulos, K and Domali, E and Zikopoulos, A}, title = {Long-Term Effects of COVID-19 on Women's Reproductive Health and Its Association with Autoimmune Diseases, Including Multiple Sclerosis.}, journal = {Journal of clinical medicine}, volume = {14}, number = {9}, pages = {}, pmid = {40364089}, issn = {2077-0383}, abstract = {Concern over COVID-19's long-term influence on women's reproductive health is growing, with emerging research suggesting potential links to ovarian dysfunction, menstrual irregularities, fertility challenges, and adverse pregnancy outcomes. Post-viral immune dysregulation is linked to both the development and exacerbation of autoimmune diseases, including multiple sclerosis (MS). Long COVID has been associated with immunological dysfunction, hormonal imbalances, and chronic inflammation, all of which may worsen autoimmune disorders and reproductive health issues. Long COVID is characterized by symptoms persisting for weeks or months beyond the acute infection phase. There are indications that prolonged COVID may contribute to autoimmune disease development through mechanisms such as immune hyperactivation, molecular mimicry, and dysregulated cytokine responses. Although this research field is still emerging, growing evidence suggests that SARS-CoV-2 infection may have lasting effects on women's health, highlighting the need for further studies into its underlying mechanisms and long-term clinical outcomes. This review compiles recent findings on the long-term impact of COVID-19 on women's reproductive health and its potential association with autoimmune disorders, particularly MS.}, }
@article {pmid40364149, year = {2025}, author = {Brewer, KD and Santo, NV and Samanta, A and Nag, R and Trotsyuk, AA and Rajadas, J}, title = {Advances in Therapeutics for Chronic Lung Diseases: From Standard Therapies to Emerging Breakthroughs.}, journal = {Journal of clinical medicine}, volume = {14}, number = {9}, pages = {}, pmid = {40364149}, issn = {2077-0383}, abstract = {Background: The global health burden of chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), asthma, idiopathic pulmonary fibrosis (IPF), and acute respiratory distress syndrome (ARDS) affects billions of people and is associated with high levels of healthcare expenditure. Conventional therapies (bronchodilators and corticosteroids) provide symptomatic benefit but take no effect on disease progression, demonstrating the need to develop new therapies. Emerging therapies treat the underlying mechanisms of these chronic diseases, which provide symptomatic relief and benefit the underlying disease. Methods: This review assesses the evolution of therapeutic interventions for chronic lung diseases from a series of established inhaled combination therapies to biologics, gene therapy, and even AI-based stratification of therapies for patients. In addressing these issues, we review the mechanisms of action, evidence of efficacy, and clinical trial evidence, while discussing access issues affecting the implementation of these therapies and ethical issues in relation to their use. Results: The review highlights recent developments in treatment approaches, such as gene therapies aimed at cystic fibrosis mutations, advanced drug delivery pathways for more accurate targeting, and stem cell-based therapies designed to replace damaged lung tissue. These developments have the potential to improve outcomes for chronic lung diseases, but the challenges, including a lack of access, adequate patient selection, and long-term safety, need to be addressed. Conclusions: New therapies offer tremendous potential, but their transition from laboratory to clinic still face numerous barriers including access, regulation, and a need for personalized therapy approaches. The review indicates that future research should develop strategies to reduce barriers to access, improve distribution, and improve clinical guidelines to successfully implement these new therapies.}, }
@article {pmid40366711, year = {2025}, author = {Vu, PD and Abdi, S}, title = {Post-acute sequelae SARS-CoV-2 infection and neuropathic pain: a narrative review of the literature and future directions.}, journal = {Pain management}, volume = {15}, number = {6}, pages = {333-343}, pmid = {40366711}, issn = {1758-1877}, mesh = {Humans ; *Neuralgia/etiology/therapy/epidemiology/physiopathology ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {PURPOSE OF REVIEW: Neuropathic pain is a recognized and debilitating symptom of SARS-CoV-2 infection across acute, post-acute, and long-COVID phases. Initially emerging as acute or subacute symptoms, these neuropathic manifestations can evolve into chronic conditions, with approximately 10% of all SARS-CoV-2 cases (estimated 65 million individuals globally) developing post-acute SARS-CoV-2 (PASC) neuropathic sequalae. Given the limited literature specifically addressing neuropathic pain related to PASC, a deeper understanding is needed to improve management and reduce patient burden.<br><br>RECENT FINDINGS: PASC symptoms are associated with disease severity, elevated body mass indexes, preexisting psychological conditions, and addiction history. Sex differences appear to influence prevalence, and the multisystem nature of PASC complicates symptom presentation, with mood disorders, fatigue, and cognitive dysfunction contributing to altered pain perception. Proposed mechanisms include immune dysregulation, persistent viral protein effects, and neuroanatomical changes. Management typically involves a multimodal approach.<br><br>SUMMARY: This review examines SARS-CoV-2 neuropathic pain across the illness trajectory, examining its pathophysiology, prevalence, and treatment. It highlights the potential for subacute neuropathic symptoms to become chronic and calls for future research to refine long-term management strategies and assess broader healthcare implications.}, }
@article {pmid40375203, year = {2025}, author = {Vallée, A and Arutkin, M and Ceccaldi, PF and Feki, A and Ayoubi, JM}, title = {Long COVID and endometriosis: a systematic review and meta-analysis.}, journal = {BMC women's health}, volume = {25}, number = {1}, pages = {229}, pmid = {40375203}, issn = {1472-6874}, mesh = {Humans ; *Endometriosis/epidemiology/complications ; Female ; *COVID-19/epidemiology/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Prevalence ; }, abstract = {Long COVID conditions entail the persistence of COVID-19-related symptoms for at least eight weeks following SARS-CoV-2 infection. The prevalence of long COVID is estimated to range from 10 to 30% among individuals infected with SARS-CoV-2. Despite its growing impact on healthcare systems, long COVID remains poorly understood. In parallel, endometriosis, a chronic inflammatory condition affecting around 10% of reproductive-age women, is marked by symptoms such as pelvic pain and infertility. The aim of this study was to assess the association between endometriosis and long COVID. We performed a systematic review of long COVID among endometriosis patients in Pubmed/Medline, Cochran Library and Science Direct databases from inception to August 2023. We independently selected studies, extracted data, assessed risk of bias, and compared endometriosis versus non endometriosis patients for long. Pooled analyses were based on random-effect models, and the I[2] statistic was used to quantify heterogeneity across studies. A total of 2 cross-sectional studies (N = 216,095 participants) were included. The pooled analysis comparing endometriosis to non-endometriosis patients significantly showed association for long COVID (pooled RR = 1.41 [1.31-1.52], I[2] = 29%, p < 0.001). Women, who are disproportionately affected by long COVID, particularly those with endometriosis, may face compounded health challenges. While our findings suggest a possible association between endometriosis and long COVID, the evidence is currently limited to two observational studies. Further research involving diverse populations and robust study designs is needed to confirm this relationship and clarify underlying mechanisms.}, }
@article {pmid40384184, year = {2025}, author = {Rejinold N, S and Choi, G and Jin, GW and Choy, JH}, title = {Transforming Niclosamide through Nanotechnology: A Promising Approach for Long COVID Management.}, journal = {Small (Weinheim an der Bergstrasse, Germany)}, volume = {21}, number = {27}, pages = {e2410345}, pmid = {40384184}, issn = {1613-6829}, support = {//National Academy of Sciences, Republic of Korea/ ; }, mesh = {*Niclosamide/therapeutic use/chemistry ; Humans ; COVID-19/complications ; *Nanotechnology/methods ; SARS-CoV-2 ; Pandemics ; COVID-19 Drug Treatment ; Post-Acute COVID-19 Syndrome ; Betacoronavirus ; *Coronavirus Infections/drug therapy ; }, abstract = {Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected over 770 million people worldwide. The long-term effects of COVID-19 and their management have become important issues. Accumulating evidence indicates that post-COVID-19 syndrome, also known as long COVID, is not limited to respiratory symptoms but affects a wide range of systems, including neurological, cardiovascular, gastrointestinal, musculoskeletal, and reproductive systems etc. The social and economic losses associated with these effects are estimated to reach 3·7 trillion dollars in the United States alone. However, no treatment for long COVID has been developed. Herein, the literature on long COVID is comprehensively reviewed to examine the underlying causes. Additionally, evidence supporting the efficacy of nanoengineered niclosamide is presented, given its ability to counteract the underlying causes. Niclosamide is already Food and Drug Administration (FDA)-approved, and the nanoengineered one is a viable candidate for clinical trials for long COVID.}, }
@article {pmid40385588, year = {2025}, author = {Ranque, B and Cogan, E}, title = {Internal medicine at the crossroads of long COVID diagnosis and management.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1521472}, pmid = {40385588}, issn = {2296-858X}, abstract = {The lack of specificity in its definition is a major obstacle to both explanatory and therapeutic research in long COVID. It brings together, on the one hand, patients with severe COVID-19 who suffer the classic complications of prolonged hospitalization and decompensation of comorbidities and, on the other hand, patients with non-severe acute COVID-19 who report multiple symptoms that cannot be fully explained by a biomechanical model. Indeed, despite numerous studies, it remains unclear how persistent viral infection, immunological or coagulation disturbances may contribute mechanistically to long COVID. Nevertheless, internal medicine should be in good place to manage these patients. Indeed, the diversity of symptoms may evoke a broad spectrum of differential diagnoses that are familiar to internists. Their experience in the exploration of unexplained symptoms is also valuable. It can reduce the need for multiple consultations with specialists and unnecessary laboratory or imaging tests. However, long COVID diagnosis cannot be limited to the exclusion of all other conditions one by one. An open and non-dualistic approach is required to identify other mechanisms that may explain the symptoms. Based on their clinical experience, most French internists who responded to an opinion survey consider that long COVID corresponds most closely to a functional somatic disorder (FSD) and seek the help of specialists in mental health care to assist in the management of the patients in a multi-disciplinary approach. However, as with other FSDs, patients with long COVID are usually reluctant to be managed by mental health care specialists, given the very physical nature of their presentation. Unfortunately, most physicians are in turn reluctant to take care of them, due to poor knowledge about FSD, leading to management failure. Alternatively, a comprehensive multidisciplinary care orchestrated by an experienced internist is generally well-accepted. It includes providing rational cognitive explanations for the symptoms and support for behavioral changes tailored to the patient. While waiting for hypothetical randomized controlled trials assessing drugs with positive results, such a holistic approach has been successfully applied in many individuals with severe long COVID. However, its generalization would require a much broader training for FSD of all health care providers.}, }
@article {pmid40387694, year = {2026}, author = {Weix, NM and Shake, HM and Duran Saavedra, AF and Clingan, HE and Hernandez, VC and Johnson, GM and Hansen, AD and Collins, DM and Pryor, LE and Kitchens, R and Armstead, A and Hilton, C}, title = {Cognitive Interventions and Rehabilitation to Address Long-COVID Symptoms: A Systematic Review.}, journal = {OTJR : occupation, participation and health}, volume = {46}, number = {1}, pages = {74-95}, pmid = {40387694}, issn = {1938-2383}, mesh = {Humans ; *COVID-19/rehabilitation/complications/psychology ; *Cognitive Behavioral Therapy/methods ; *Occupational Therapy/methods ; SARS-CoV-2 ; *Cognitive Dysfunction/rehabilitation ; Quality of Life ; }, abstract = {Long COVID symptoms include cognitive and physical deficits impacting one's functional performance and quality of life. Limited evidence examines the use of cognitive interventions provided by occupational therapists in treating long COVID symptoms among adults. This systematic review summarizes existing studies on cognitive interventions and rehabilitation to treat long COVID symptoms and discusses their potential use within the scope of occupational therapy practice. We identified literature from 2021 to 2023 through searches of MEDLINE, CINAHL, PsycINFO, Cochrane Trials, and Scopus databases. Nineteen articles met inclusion criteria and were categorized into five types of intervention: (a) cognitive training, (b) cognitive behavioral therapy, (c) neurostimulation, (d) neurostimulation combined with cognitive training, and (e) multi-component rehabilitation programs. Strong evidence supports cognitive training, moderate supports cognitive behavioral training and low-level evidence supports other interventions provided by occupational therapists to target long COVID cognitive symptoms in adults.}, }
@article {pmid40389117, year = {2025}, author = {Rudroff, T}, title = {Climate crossroads: How global warming drives coronavirus emergence, the long COVID crisis of tomorrow, and AI's role in navigating our future.}, journal = {Infectious diseases now}, volume = {55}, number = {6}, pages = {105091}, doi = {10.1016/j.idnow.2025.105091}, pmid = {40389117}, issn = {2666-9919}, mesh = {Humans ; *COVID-19/epidemiology/transmission/virology ; *Global Warming ; SARS-CoV-2 ; Animals ; *Artificial Intelligence ; Climate Change ; Pandemics ; *Coronavirus Infections/epidemiology/transmission ; }, abstract = {This narrative review examines the critical nexus between climate change, coronavirus emergence, and Long COVID-a triad that may shape public health outcomes for generations. Climate change disrupts ecological balances that have historically limited viral spillover events, creating novel interfaces between wildlife reservoirs and human populations. The coronavirus family presents particular concern due to its diversity, adaptability, and demonstrated capacity for cross-species transmission. With over 200 coronaviruses identified in bat populations alone, this vast reservoir of genetic diversity, combined with the family's propensity for recombination, creates substantial pandemic potential that climate disruption may further amplify. Long COVID has revealed another dimension of the coronavirus threat: the potential for significant chronic disease burden following acute infection. This complex multisystem condition affects a substantial portion of SARS-CoV-2 infected individuals, with mechanisms including viral persistence, autoimmunity, microclot formation, and mitochondrial dysfunction. Future projections suggest that climate change could increase global viral spillover risk by 30-45% by 2070, particularly in Southeast Asia, Central Africa, and parts of South America. Artificial intelligence offers promising tools for addressing these interconnected challenges through enhanced surveillance, accelerated therapeutic development, and optimized healthcare delivery. Understanding the climate-coronavirus-chronic illness nexus has become essential to the development of resilient health systems and effective planetary health policies face to an uncertain future.}, }
@article {pmid40391044, year = {2025}, author = {Duenas, K and Chwa, WJ and Hoque, F}, title = {Overview of Long COVID: Navigating the Aftermath.}, journal = {Journal of Brown hospital medicine}, volume = {4}, number = {2}, pages = {133879}, pmid = {40391044}, issn = {2994-5593}, abstract = {The coronavirus disease (COVID-19) pandemic was a global health crisis with far-reaching consequences. Among these were physical and mental health complications that emerged weeks or even months after the initial COVID-19 infection, collectively termed "long COVID" or "post-COVID syndrome." Identifying the epidemiology, risk factors, clinical manifestations, and management strategies for long COVID is crucial for both clinicians and patients, which is the focus of this review. The prevalence of long COVID varies across studies, generally ranging from 5% to 20%. Prominent risk factors include female sex, older age, a high number of acute symptoms, lower socioeconomic status, and underlying comorbidities such as diabetes, asthma, or chronic obstructive pulmonary disease. The clinical manifestations of long COVID are diverse; beyond the commonly reported symptoms of fatigue, malaise, ageusia, and anosmia, neuropsychiatric complications such as headache, cognitive deficits, and depression are also potential outcomes. Although there is currently no consensus on the management of long COVID, multidisciplinary care teams with appropriate referrals and follow-up diagnostic studies are essential in evaluating the clinical course of long COVID patients.}, }
@article {pmid40393269, year = {2025}, author = {Struhal, W and Almamoori, D}, title = {A review of the sequelae of post Covid-19 with neurological implications (post-viral syndrome).}, journal = {Journal of the neurological sciences}, volume = {474}, number = {}, pages = {123532}, doi = {10.1016/j.jns.2025.123532}, pmid = {40393269}, issn = {1878-5883}, mesh = {Humans ; *COVID-19/complications ; *Nervous System Diseases/etiology/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {Post Covid-19 conditions represent a medical challenge; a unified definition is not achieved after 5 years of the Pandemic. The incidence of Post Covid-19 conditions varies, nevertheless the neurological complications represent an important aspect in the spectrums of fields involved. The current perception is that varied manifestations and long-term complications of COVID-19 reflect underlying pathophysiological processes, including inflammatory, immune-mediated, and vascular mechanisms. These mechanisms underscore the complexity of COVID-19's impact including the nervous system and its potential for lasting effects. A number of symptoms are extremely severe and may also need neurologic attention including fatigue, cognitive disturbances, autonomic symptoms, headache, and sleep disorders. Post Covid-19 conditions are often of chronic nature. Management as in other chronic conditions should rely on the conventional diagnostic measures and management of symptoms irrespective of the temporal relation to the viral infection. To date Post Covid-19 conditions is only accepted as an additional or explanatory diagnosis.}, }
@article {pmid40400892, year = {2025}, author = {Ferrer, G and Valerio-Pascua, F and Alas-Pineda, C and Gaitán-Zambrano, K and Pavón-Varela, DJ}, title = {Intranasal Chlorpheniramine for Early Symptomatic Treatment of COVID-19 and the Impact on Long-COVID.}, journal = {Cureus}, volume = {17}, number = {4}, pages = {e82736}, pmid = {40400892}, issn = {2168-8184}, abstract = {This review explores the therapeutic potential of intranasal chlorpheniramine maleate (iCPM) in managing both acute COVID-19 and Long COVID by integrating histamine H1 receptor antagonism and bitter taste receptor (T2R) activation. Current literature on histamine-mediated inflammation, T2R activation, and the dual-action mechanisms of iCPM were analyzed. Emphasis was placed on its antiviral, anti-inflammatory, and mucosal immunity-enhancing properties. iCPM demonstrates significant efficacy in addressing acute COVID-19 symptoms by inhibiting histamine-mediated inflammatory pathways and reducing cytokine storms. As a T2R agonist, it enhances mucosal immunity through nitric oxide production, mucociliary clearance, and antimicrobial peptide synthesis, reducing viral replication and supporting respiratory health. Additionally, iCPM shows promise in mitigating persistent symptoms of long COVID, including fatigue, brain fog, and respiratory dysfunction, by addressing chronic inflammation and residual viral activity. The integration of H1 receptor antagonism and T2R activation positions iCPM as a novel dual-target therapy for respiratory infections. Its localized delivery and broad mechanism of action make it a promising candidate for managing both the acute and chronic phases of COVID-19. Future research should focus on large-scale clinical trials and personalized approaches based on genetic variations in T2R pathways.}, }
@article {pmid40402473, year = {2025}, author = {de Andrade, ML and do Monte, AL and Gerage, AM and Galliano, LM and Costa, EC and Ritti Dias, RM and Corrêa, FI}, title = {Effects of Physical Exercise on Functional Physical Performance in Individuals With Long COVID: A Systematic Review.}, journal = {Journal of cardiopulmonary rehabilitation and prevention}, volume = {45}, number = {4}, pages = {239-246}, pmid = {40402473}, issn = {1932-751X}, mesh = {Humans ; *COVID-19/rehabilitation/physiopathology/complications/psychology ; *Physical Functional Performance ; Quality of Life ; *Exercise Therapy/methods ; *Exercise/physiology ; SARS-CoV-2 ; Cardiorespiratory Fitness ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE: To analyze the effect of physical exercise on functional parameters in individuals with long coronavirus disease-2019 (COVID-19).<br><br>REVIEW METHODS: A search in MEDLINE, EMBASE, Web of Science, Scielo, and EBSCO was carried out in October 2022, and it was updated in June 2024. For inclusion, studies should have involved physical training without pulmonary rehabilitation, have involved individuals who had long COVID-19, and were prospective trials, clinical trials, or controlled trials. Two reviewers independently performed data extraction and assessed the risk of bias. Seven studies were reviewed, three of high methodological quality. Participants with long COVID-19 were hospitalized in two studies. Interventions lasted 2 to 16&#xa0;weeks, with frequencies of 2 to 7&#xa0;days per week, often involving resistance exercise. Strength improved in 67% of studies, cardiorespiratory fitness in 50%, and agility/mobility in 60%. Anxiety improved in 25% of studies, while depression improved in 75%. Quality of life improved across all studies, with dyspnea and fatigue improving in 40% and 80%, respectively.<br><br>SUMMARY: Results suggest potential benefits of exercise training for subjects with long COVID-19 in several outcomes, mainly in functional capacity, depression symptoms, quality of life, and fatigue.}, }
@article {pmid40405092, year = {2025}, author = {Seo, YB and Choi, YJ and Seo, JW and Kim, EJ and Lee, J and Song, JY}, title = {Therapeutic options for the treatment of post-acute sequelae of COVID-19: a scoping review.}, journal = {BMC infectious diseases}, volume = {25}, number = {1}, pages = {731}, pmid = {40405092}, issn = {1471-2334}, support = {HD22C2045//Korea Health Industry Development Institute/Republic of Korea ; }, mesh = {Humans ; Antiviral Agents/therapeutic use ; *COVID-19/complications/therapy ; *COVID-19 Drug Treatment ; Hyperbaric Oxygenation ; *Post-Acute COVID-19 Syndrome/therapy ; }, abstract = {OBJECTIVES: This scoping review aimed to summarize the available studies to address the question of which therapeutic agents can be utilized for patients with post-acute sequelae of COVID-19 (PASC).<br><br>METHODS: We conducted a systematic search in medical databases, including PubMed and Embase, for studies aligned with our objectives published between January 1, 2020, and July 22, 2024. For each study, we summarized the main symptoms targeted, study design, therapeutic regimens, evaluation tools, and clinical outcomes.<br><br>RESULTS: A total of 413 studies were identified, and 39 studies were included in this review based on relevance to the research objectives. We primarily focused on high-level evidence studies, such as meta-analyses and randomized controlled trials, but observational studies were included when evidence was scarce. Therapeutic agents evaluated included hyperbaric oxygen, ivermectin, metformin, naltrexone, micronutrient supplements, antifibrotic agents, antiviral agents, and selective serotonin reuptake inhibitors (SSRIs). Among these, hyperbaric oxygen, antifibrotic agents, antiviral agents, and SSRIs demonstrated promising results. However, the heterogeneity of PASC symptoms posed challenges in synthesizing findings for specific symptom-based outcomes.<br><br>CONCLUSION: Given the heterogeneity of symptoms, this review highlights the need for standardized and targeted research to better address the diverse therapeutic needs of patients with PASC.<br><br>CLINICAL TRIAL: Not applicable.}, }
@article {pmid40407658, year = {2025}, author = {Park, SO and Nanda, N}, title = {Long COVID: A Systematic Review of Preventive Strategies.}, journal = {Infectious disease reports}, volume = {17}, number = {3}, pages = {}, pmid = {40407658}, issn = {2036-7430}, abstract = {Background: Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, long COVID (LC) has become a significant global health burden. While knowledge about LC is accumulating, studies on its prevention are still lacking. Methods: We conducted a systematic review following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to investigate prevention options for LC. We identified fifteen articles on vaccines, seven on antivirals, and six on other interventions after searching for articles in the PubMed/MEDLINE database using the MeSH terms. Results: Most vaccine-related studies demonstrated a protective effect of COVID-19 vaccines against developing LC. Our review found an equivocal effect of antivirals, while metformin had a protective effect in outpatients and corticosteroids were protective in hospitalized patients against LC. Conversely, COVID-19 convalescent plasma and multiple micronutrient supplement did not confer any protection against LC. Conclusions: COVID-19 vaccination is vital as it not only prevents COVID-19 but also reduces the severity of illness and may help prevent LC. Further studies are warranted to shed light on preventive strategies for long COVID.}, }
@article {pmid40412913, year = {2025}, author = {DeMasi, M and Bujold, L}, title = {Effect of the Covid Pandemic on Women's Health.}, journal = {Primary care}, volume = {52}, number = {2}, pages = {371-382}, doi = {10.1016/j.pop.2025.01.009}, pmid = {40412913}, issn = {1558-299X}, mesh = {Humans ; *COVID-19/epidemiology ; Female ; *Women's Health ; United States/epidemiology ; SARS-CoV-2 ; Pandemics ; }, abstract = {The corona virus disease 2019 (COVID-19) pandemic impacted all spheres of the lives of women. This article focuses on the impact on the health, careers, and family lives of women in the United States. There is a lasting impact from COVID-19 on the lives and health of women. Preventative care and chronic care were disrupted. Long covid seems to impact premenopausal women at much higher rates than men. Time spent between work and home changed for many during the pandemic. Women shifted to more time spent on home duties. The long-term outcome of career advancement and economic success is unknown.}, }
@article {pmid40415285, year = {2025}, author = {Eltayeb, A and Rubio-Casillas, A and Uversky, VN and Redwan, EM}, title = {Intrinsic Factors Behind Long COVID: VI. Combined Impact of G3BPs and SARS-CoV-2 Nucleocapsid Protein on the Viral Persistence and Long COVID.}, journal = {Journal of cellular biochemistry}, volume = {126}, number = {5}, pages = {e70038}, doi = {10.1002/jcb.70038}, pmid = {40415285}, issn = {1097-4644}, support = {//The authors received no specific funding for this work./ ; }, mesh = {Humans ; *COVID-19/virology/metabolism/immunology/pathology ; *SARS-CoV-2/metabolism/physiology ; *Coronavirus Nucleocapsid Proteins/metabolism ; *RNA Recognition Motif Proteins/metabolism/immunology ; *Poly-ADP-Ribose Binding Proteins/metabolism/immunology ; *DNA Helicases/metabolism ; *Phosphoproteins/metabolism ; *RNA Helicases/metabolism ; Virus Replication ; Stress Granules/metabolism/virology ; Host-Pathogen Interactions ; }, abstract = {The efficient transmission of SARS-CoV-2 caused the COVID-19 pandemic, which affected millions of people around the globe. Despite extensive efforts, specific therapeutic interventions and preventive measures against COVID-19 and its consequences, such as long COVID, have not yet been identified due to the lack of a comprehensive knowledge of the SARS-CoV-2 biology. Therefore, a deeper understanding of the sophisticated strategies employed by SARS-CoV-2 to bypass the host antiviral defense systems is needed. One of these strategies is the inhibition of the Ras GTPase-activating protein-binding protein (GAP SH3-binding protein or G3BP)-dependent host immune response by the SARS-CoV-2 nucleocapsid (N) protein. This inhibition disrupts the formation of stress granules (SGs), which are crucial for antiviral defense. By preventing SG formation, the virus enhances its replication and evades the host's immune response, leading to increased disease severity. Given the involvement of G3BP1 in SG formation and its ability to interact with viral proteins, along with the crucial role of the N protein in the replication of the virus, we hypothesize that these proteins may have a potential role in the pathogenesis of long COVID. Despite the current lack of direct evidence linking these proteins to long COVID, their interactions and functions suggest a possible connection that warrants further investigation.}, }
@article {pmid40416015, year = {2025}, author = {Harabuchi, Y and Kumai, T and Nishi, K and Tanaka, A and Hotta, O and Hagino, H and Kusuyama, T and Mogitate, M and Ohno, Y and Sakakibara, A and Araki, S and Nishida, Y and Shintani, T and Takezawa, H and Ito, H and Komazawa, D and Nishiwaki, N and Toritani, R and Hirahata, K and Marumo, S}, title = {Retracted: Chronic Epipharyngitis Treated with Epipharyngeal Abrasion Therapy: Symptoms, Diagnosis, Pathogenesis, and Treatment Outcomes.}, journal = {JMA journal}, volume = {8}, number = {2}, pages = {371-384}, pmid = {40416015}, issn = {2433-3298}, abstract = {Chronic epipharyngitis is associated with a wide variety of symptoms, including local symptoms such as postnasal drip, sore throat, lump sensation of the pharynx, headache, chronic cough, nasal obstruction, tinnitus/ear fullness, chronic phlegm and dysphonia due to inflammation of the epipharynx, functional somatic symptoms such as chronic fatigue, dizziness, insomnia, brain fog, abdominal discomfort, and depression caused by dysfunction of the hypothalamus-limbic system via disturbances of vagal response and cerebrospinal fluid outflow, and distant organ symptoms such as immunoglobulin A nephropathy and palmoplantar pustulosis caused by the epipharyngeal lymphoid tissue as an etiologic organ. In the past, chronic inflammation in the epipharynx was difficult to prove by gross findings, now, direct observation of the epipharyngeal inflammation by endoscopy has become easier for the diagnosis. For the treatment of chronic epipharyngitis, epipharyngeal abrasive therapy (EAT), epipharyngeal application of a 1% zinc chloride solution intranasally or orally was popular since the 1960s, recently, endoscopic EAT (E-EAT), in which epipharynx is safely and accurately observed and abraded under clear vision using an endoscope, has been developed. The mechanisms of EAT effects can be classified into anti-inflammatory/antiviral effect, bloodletting effect, and vagus nerve stimulation effect. Recently, the effectiveness of EAT for post-acute sequelae of coronavirus disease 2019 (COVID-19), known as long COVID, has come into the limelight, and the number of patients for whom EAT is expected to increase. In 2019, the Japan Society of Stomato-pharyngology established the EAT Review Committee to accumulate evidence on the efficacy of EAT and to establish indications and techniques for its use. In this article, the EAT Review Committee outlines its symptoms, pathogenesis, and diagnosis of chronic epipharyngitis, technique of E-EAT, mechanisms of EAT effects, past reports for the efficacy of EAT, and a multicenter prospective study.}, }
@article {pmid40416618, year = {2025}, author = {Eltayeb, A and Adilović, M and Golzardi, M and Hromić-Jahjefendić, A and Rubio-Casillas, A and Uversky, VN and Redwan, EM}, title = {Intrinsic factors behind long COVID: exploring the role of nucleocapsid protein in thrombosis.}, journal = {PeerJ}, volume = {13}, number = {}, pages = {e19429}, pmid = {40416618}, issn = {2167-8359}, mesh = {Humans ; *COVID-19/complications ; *Thrombosis/virology/metabolism/etiology ; *SARS-CoV-2 ; *Coronavirus Nucleocapsid Proteins/metabolism ; }, abstract = {COVID-19, caused by the SARS-CoV-2, poses significant global health challenges. A key player in its pathogenesis is the nucleocapsid protein (NP), which is crucial for viral replication and assembly. While NPs from other coronaviruses, such as SARS-CoV and MERS-CoV, are known to increase inflammation and cause acute lung injury, the specific effects of the SARS-CoV-2 NP on host cells remain largely unexplored. Recent findings suggest that the NP acts as a pathogen-associated molecular pattern (PAMP) that binds to Toll-like receptor 2 (TLR2), activating NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and MAPK (mitogen-activated protein kinase) signaling pathways. This activation is particularly pronounced in severe COVID-19 cases, leading to elevated levels of soluble ICAM-1 (intercellular adhesion molecule 1) and VCAM-1 (vascular cell adhesion molecule 1), which contribute to endothelial dysfunction and multiorgan damage. Furthermore, the NP is implicated in hyperinflammation and thrombosis-key factors in COVID-19 severity and long COVID. Its potential to bind with MASP-2 (mannan-binding lectin serine protease 2) may also be linked to persistent symptoms in long COVID patients. Understanding these mechanisms, particularly the role of the NP in thrombosis, is essential for developing targeted therapies to manage both acute and chronic effects of COVID-19 effectively. This comprehensive review aims to elucidate the multifaceted roles of the NP, highlighting its contributions to viral pathogenesis, immune evasion, and the exacerbation of thrombotic events, thereby providing insights into potential therapeutic targets for mitigating the severe and long-term impacts of COVID-19.}, }
@article {pmid40430160, year = {2025}, author = {Caliman-Sturdza, OA and Gheorghita, RE and Soldanescu, I}, title = {Vitamin D and COVID-19: Clinical Evidence and Immunological Insights.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {5}, pages = {}, pmid = {40430160}, issn = {2075-1729}, abstract = {Vitamin D has emerged as a potential modulator of immune responses, sparking interest in its role in COVID-19 susceptibility and clinical outcomes. This review synthesizes current clinical evidence and explores immunological insights into the relationship between vitamin D levels and COVID-19 infection severity. Epidemiological studies indicate an inverse correlation between vitamin D deficiency and an increased risk of severe disease, hospitalization, and mortality in COVID-19 patients. Immunologically, vitamin D exerts regulatory effects on both innate and adaptive immunity, enhancing antimicrobial defense mechanisms, reducing excessive inflammatory responses, and potentially mitigating cytokine storm events observed in severe COVID-19 cases. Despite promising observational data, clinical trials evaluating vitamin D supplementation have shown mixed results, underscoring the need for standardized dosing regimens and patient stratification. Future research should focus on large-scale randomized controlled trials to conclusively determine the therapeutic potential and optimal supplementation strategies for vitamin D in managing COVID-19.}, }
@article {pmid40430532, year = {2025}, author = {Kell, DB and Pretorius, E and Zhao, H}, title = {A Direct Relationship Between 'Blood Stasis' and Fibrinaloid Microclots in Chronic, Inflammatory, and Vascular Diseases, and Some Traditional Natural Products Approaches to Treatment.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {18}, number = {5}, pages = {}, pmid = {40430532}, issn = {1424-8247}, abstract = {'Blood stasis' (syndrome) (BSS) is a fundamental concept in Traditional Chinese Medicine (TCM), where it is known as Xue Yu (). Similar concepts exist in Traditional Korean Medicine ('Eohyul') and in Japanese Kampo medicine (Oketsu). Blood stasis is considered to underpin a large variety of inflammatory diseases, though an exact equivalent in Western systems medicine is yet to be described. Some time ago we discovered that blood can clot into an anomalous amyloid form, creating what we have referred to as fibrinaloid microclots. These microclots occur in a great many chronic, inflammatory diseases are comparatively resistant to fibrinolysis, and thus have the ability to block microcapillaries and hence lower oxygen transfer to tissues, with multiple pathological consequences. We here develop the idea that it is precisely the fibrinaloid microclots that relate to, and are largely mechanistically responsible for, the traditional concept of blood stasis (a term also used by Virchow). First, the diseases known to be associated with microclots are all associated with blood stasis. Secondly, by blocking red blood cell transport, fibrinaloid microclots provide a simple mechanistic explanation for the physical slowing down ('stasis') of blood flow. Thirdly, Chinese herbal medicine formulae proposed to treat these diseases, especially Xue Fu Zhu Yu and its derivatives, are known mechanistically to be anticoagulatory and anti-inflammatory, consistent with the idea that they are actually helping to lower the levels of fibrinaloid microclots, plausibly in part by blocking catalysis of the polymerization of fibrinogen into an amyloid form. We rehearse some of the known actions of the constituent herbs of Xue Fu Zhu Yu and specific bioactive molecules that they contain. Consequently, such herbal formulations (and some of their components), which are comparatively little known to Western science and medicine, would seem to offer the opportunity to provide novel, safe, and useful treatments for chronic inflammatory diseases that display fibrinaloid microclots, including Myalgic Encephalopathy/Chronic Fatigue Syndrome, long COVID, and even ischemic stroke.}, }
@article {pmid40431629, year = {2025}, author = {de Melo, BP and da Silva, JAM and Rodrigues, MA and Palmeira, JDF and Saldanha-Araujo, F and Argañaraz, GA and Argañaraz, ER}, title = {SARS-CoV-2 Spike Protein and Long COVID-Part 1: Impact of Spike Protein in Pathophysiological Mechanisms of Long COVID Syndrome.}, journal = {Viruses}, volume = {17}, number = {5}, pages = {}, pmid = {40431629}, issn = {1999-4915}, mesh = {Humans ; *Spike Glycoprotein, Coronavirus/metabolism ; *COVID-19/complications/virology/physiopathology/pathology ; *SARS-CoV-2/pathogenicity ; Post-Acute COVID-19 Syndrome ; }, abstract = {SARS-CoV-2 infection has resulted in more than 700 million cases and nearly 7 million deaths worldwide. Although vaccination efforts have effectively reduced mortality and transmission rates, a significant proportion of recovered patients-up to 40%-develop long COVID syndrome (LC) or post-acute sequelae of COVID-19 infection (PASC). LC is characterized by the persistence or emergence of new symptoms following initial SARS-CoV-2 infection, affecting the cardiovascular, neurological, respiratory, gastrointestinal, reproductive, and immune systems. Despite the broad range of clinical symptoms that have been described, the risk factors and pathogenic mechanisms behind LC remain unclear. This review, the first of a two-part series, is distinguished by the discussion of the role of the SARS-CoV-2 spike protein in the primary mechanisms underlying the pathophysiology of LC.}, }
@article {pmid40431631, year = {2025}, author = {de Melo, BP and da Silva, JAM and Rodrigues, MA and Palmeira, JDF and Amato, AA and Argañaraz, GA and Argañaraz, ER}, title = {SARS-CoV-2 Spike Protein and Long COVID-Part 2: Understanding the Impact of Spike Protein and Cellular Receptor Interactions on the Pathophysiology of Long COVID Syndrome.}, journal = {Viruses}, volume = {17}, number = {5}, pages = {}, pmid = {40431631}, issn = {1999-4915}, mesh = {*Spike Glycoprotein, Coronavirus/metabolism/genetics ; Humans ; *COVID-19/virology/physiopathology/complications/metabolism ; *SARS-CoV-2/metabolism/genetics/physiology ; *Receptors, Virus/metabolism ; Protein Binding ; Post-Acute COVID-19 Syndrome ; }, abstract = {SARS-CoV-2 infection has had a significant impact on global health through both acute illness, referred to as coronavirus disease 2019 (COVID-19), and chronic conditions (long COVID or post-acute sequelae of COVID-19, PASC). Despite substantial advancements in preventing severe COVID-19 cases through vaccination, the rise in the prevalence of long COVID syndrome and a notable degree of genomic mutation, primarily in the S protein, underscores the necessity for a deeper understanding of the underlying pathophysiological mechanisms related to the S protein of SARS-CoV-2. In this review, the latest part of this series, we investigate the potential pathophysiological molecular mechanisms triggered by the interaction between the spike protein and cellular receptors. Therefore, this review aims to provide a differential and focused view on the mechanisms potentially activated by the binding of the spike protein to canonical and non-canonical receptors for SARS-CoV-2, together with their possible interactions and effects on the pathogenesis of long COVID.}, }
@article {pmid40431734, year = {2025}, author = {Kim, DH and Kim, JH and Jeon, MT and Kim, KS and Kim, DG and Choi, IS}, title = {The Role of TDP-43 in SARS-CoV-2-Related Neurodegenerative Changes.}, journal = {Viruses}, volume = {17}, number = {5}, pages = {}, pmid = {40431734}, issn = {1999-4915}, support = {25-BR-02-03//Korea Brain Research Institute/ ; }, mesh = {Humans ; *DNA-Binding Proteins/metabolism/genetics ; *COVID-19/complications/metabolism/virology/pathology ; *SARS-CoV-2/physiology ; *Neurodegenerative Diseases/metabolism/virology/pathology/etiology ; Virus Replication ; Animals ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic has been linked to long-term neurological effects with multifaceted complications of neurodegenerative diseases. Several studies have found that pathological changes in transactive response DNA-binding protein of 43 kDa (TDP-43) are involved in these cases. This review explores the causal interactions between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and TDP-43 from multiple perspectives. Some viral proteins of SARS-CoV-2 have been shown to induce pathological changes in TDP-43 through its cleavage, aggregation, and mislocalization. SARS-CoV-2 infection can cause liquid-liquid phase separation and stress granule formation, which accelerate the condensation of TDP-43, resulting in host RNA metabolism disruption. TDP-43 has been proposed to interact with SARS-CoV-2 RNA, though its role in viral replication remains to be fully elucidated. This interaction potentially facilitates viral replication, while viral-induced oxidative stress and protease activity accelerate TDP-43 pathology. Evidence from both clinical and experimental studies indicates that SARS-CoV-2 infection may contribute to long-term neurological sequelae, including amyotrophic lateral sclerosis-like and frontotemporal dementia-like features, as well as increased phosphorylated TDP-43 deposition in the central nervous system. Biomarker studies further support the link between TDP-43 dysregulation and neurological complications of long-term effects of COVID-19 (long COVID). In this review, we presented a novel integrative framework of TDP-43 pathology, bridging a gap between SARS-CoV-2 infection and mechanisms of neurodegeneration. These findings underscore the need for further research to clarify the TDP-43-related neurodegeneration underlying SARS-CoV-2 infection and to develop therapeutic strategies aimed at mitigating long-term neurological effects in patients with long COVID.}, }
@article {pmid40435383, year = {2025}, author = {Nairn, B and Tsakanikas, V and Gordon, B and Karapintzou, E and Kaski, D and Fotiadis, DI and Bamiou, DE}, title = {Smart Wearable Technologies for Balance Rehabilitation in Older Adults at Risk of Falls: Scoping Review and Comparative Analysis.}, journal = {JMIR rehabilitation and assistive technologies}, volume = {12}, number = {}, pages = {e69589}, pmid = {40435383}, issn = {2369-2529}, abstract = {BACKGROUND: Falls among older adults are a significant public health concern, often leading to severe injuries, decreased quality of life, and substantial health care costs. Smart wearable technologies for balance rehabilitation present a promising avenue for addressing the falls epidemic, capable of providing detailed objective movement data, engaging visuals, and real-time feedback. With the recent and rapid evolution of innovative technologies, including artificial intelligence (AI), augmented reality (AR) or virtual reality (VR), and motion tracking, there is a need to evaluate the market to identify the most effective and accessible smart balance systems currently available.<br><br>OBJECTIVE: This study aims to evaluate the current landscape of smart wearable technology systems for balance rehabilitation in older adults at risk of falls. In addition, it aims to compare market-available systems to the telerehabilitation of balance clinical and economic decision support system (TeleRehab DSS), a recently developed smart balance system.<br><br>METHODS: A scoping review and strengths, weaknesses, opportunities, and threats (SWOT) analysis was completed, exploring the landscape of smart balance systems in older adults at risk of falls. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines, electronic databases PubMed, MEDLINE, and Cochrane were systematically searched for articles in English from July 1, 2014, to July 1, 2024. Gray literature searches of relevant institutions and web pages were also conducted. The database search and commercial systems were then compared against the TeleRehab DSS in a SWOT analysis.<br><br>RESULTS: The scoping review yielded 17 systems that met the inclusion criteria; 10 investigational systems and 7 commercially available systems. Out of 10 studies, only 1 reported the use of intelligent learning or AI, 8 studies reported the use of motion tracking, and 9 studies used virtual reality. Of the studies incorporating motion tracking, 3 provided feedback as either visual or auditory. All but 2 studies reported the use of gamification, and 7 studies incorporated balance exercises. In total, 2 studies reported remote delivery, with 5 being clinician-supervised and 4 providing a clinician report. The SWOT analysis of TeleRehab DSS against the 7 market-available smart balance systems revealed several unique advantages, including personalized therapy with AI-DSS, AR for real-world interaction, enhanced clinician involvement, and comprehensive data analytics.<br><br>CONCLUSIONS: The findings from this scoping review highlight the rapid evolution of smart balance systems, yet significant gaps remain in AI integration, remote accessibility, and clinician-driven data analytics. Despite limitations such as cost, accessibility, and user training requirements, TeleRehab DSS emerges as a significant innovation, addressing many of these gaps through AI-driven personalization, AR for real-world interaction, and real-time clinician monitoring. These features position it as a next-generation solution that aligns closely with the evolving needs of patients and clinicians. The results of this review provide valuable insights for future research, supporting the need for further validation studies and the development of more intelligent and accessible balance rehabilitation technologies.}, }
@article {pmid40436612, year = {2025}, author = {Daynes, E and Barker, RE and Jones, AV and Walsh, JA and Nolan, CM and Man, WD and Singh, SJ and Greening, NJ and Houchen-Wolloff, L and Evans, RA}, title = {Determining the minimum important differences for field walking tests in adults with long-term conditions: a systematic review and meta-analysis.}, journal = {European respiratory review : an official journal of the European Respiratory Society}, volume = {34}, number = {176}, pages = {}, pmid = {40436612}, issn = {1600-0617}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *Walk Test ; *Exercise Tolerance ; Time Factors ; Predictive Value of Tests ; Male ; Female ; *Minimal Clinically Important Difference ; Reproducibility of Results ; Adult ; Middle Aged ; *Lung/physiopathology ; *Walking ; Aged ; *Respiratory Tract Diseases/diagnosis/physiopathology/therapy ; *Heart Diseases/diagnosis/physiopathology ; Prognosis ; *Exercise Test ; *Nervous System Diseases/diagnosis/physiopathology ; Chronic Disease ; }, abstract = {IMPORTANCE: The minimum important difference (MID) for field walking tests aims to improve interpretation of outcomes, but the volume and heterogeneity of MIDs for these tests is challenging. We aimed to determine the MID for the 6-min walk distance (6MWD), incremental shuttle walk test (ISWT) and endurance shuttle walk test (ESWT) in adults with long-term conditions.<br><br>METHODS: This systematic review included studies that generated a MID using an anchor-based approach in patients with long-term conditions for the 6MWD, ISWT or ESWT field walking tests. Studies were screened and data extracted by independent reviewers. Meta-analyses were performed using RevMan.<br><br>RESULTS: 42 studies were included in the analyses, involving n=13&#x2009;949 participants. Of these, 12 studies involving exercise as an intervention were included in the meta-analyses to produce MIDs, presented as mean (95% confidence interval). The MID for the 6MWD was 25&#x2005;m (24-26&#x2005;m) for respiratory conditions, 23&#x2005;m (8-37&#x2005;m) for cardiac conditions and 37&#x2005;m (26-49&#x2005;m) for neurological/musculoskeletal conditions. The MID for the ISWT was 48&#x2005;m (39-57&#x2005;m) for respiratory conditions and 70&#x2005;m (55-85&#x2005;m) for cardiac conditions. The MID for ESWT in COPD was 159&#x2005;s (94-224&#x2005;s). The pooled MID across conditions within exercise interventions was 26&#x2005;m (22-40&#x2005;m) for the 6MWD and 53&#x2005;m (44-62&#x2005;m) for the ISWT, with reasonable heterogeneity (I[2]=48% and I[2]=47%, respectively).<br><br>CONCLUSION: We propose new MIDs for exercise interventions using anchor-based methodology in long&#x2011;term conditions for the 6MWD, ISWT and ESWT. These can be used internationally for meta&#x2011;analyses where studies have used different field walking tests, to optimise trial sample size calculations, and for clinical service benchmarking.}, }
@article {pmid40438846, year = {2025}, author = {Idris Fadul, AA and Osman Mohamed, AA and Mohammed Ahmed, AAS and Elmobark, S and Merghani Hammour, AS and Elgaleel Khir Elsiad, NMN and Mohammed Elhaj, EA}, title = {Post-coronavirus Disease 2019 (COVID-19) Cardiovascular Manifestations: A Systematic Review of Long-Term Risks and Outcomes.}, journal = {Cureus}, volume = {17}, number = {4}, pages = {e83083}, pmid = {40438846}, issn = {2168-8184}, abstract = {Emerging evidence suggests that coronavirus disease 2019 (COVID-19) survivors face increased risks of cardiovascular complications, but the long-term risks, underlying mechanisms, and clinical implications remain incompletely characterized. This systematic review synthesizes current evidence on post-COVID-19 cardiovascular manifestations, evaluating their incidence, pathophysiology, and outcomes. A comprehensive literature search was conducted across PubMed/MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Fifteen observational studies (cohort, case-control, cross-sectional) meeting predefined eligibility criteria, confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, cardiovascular outcomes assessed ≥4 weeks post-infection, sample sizes >10, and peer-reviewed publication, were included. The risk of bias was assessed using the Newcastle-Ottawa Scale. The multinational studies (United States, Europe, Asia, South America) involved diverse populations (n=80-8,126,462), with follow-up durations ranging from three to 24 months. Mechanisms such as endothelial dysfunction, myocardial inflammation, and autonomic dysregulation were consistently supported across studies via imaging (e.g., cardiac MRI) and biomarkers (e.g., troponin, C-reactive protein (CRP)). Persistent arrhythmias and subclinical myocardial injury were directly demonstrated in 40-60% of patients. Worse outcomes were associated with hospitalization during acute infection, preexisting cardiovascular disease, and metabolic syndrome. Heterogeneity in follow-up durations may limit the detection of very-late-onset complications, though risks remained elevated across all intervals. Individualized management strategies should include cardiovascular imaging (echocardiography, MRI), biomarker profiling, and tailored pharmacotherapy (anti-inflammatory agents, anticoagulants). The ethical rationale for randomized trials is now strengthened by the clear evidence of long-term risks; ongoing trials are testing targeted anti-inflammatory and anticoagulant regimens. These findings underscore the necessity of systematic cardiovascular surveillance and risk-stratified care for COVID-19 survivors. Future research should prioritize extended follow-up studies and randomized controlled trials (RCTs) to optimize interventions for this growing population.}, }
@article {pmid40447142, year = {2025}, author = {Vreeman, ECA and Pillay, J and Burgess, JK}, title = {Post-COVID pulmonary sequelae: Mechanisms and potential targets to reduce persistent fibrosis.}, journal = {Pharmacology &amp; therapeutics}, volume = {272}, number = {}, pages = {108891}, doi = {10.1016/j.pharmthera.2025.108891}, pmid = {40447142}, issn = {1879-016X}, mesh = {Humans ; *COVID-19/complications ; *Pulmonary Fibrosis/etiology/drug therapy/virology ; SARS-CoV-2 ; Lung/pathology ; }, abstract = {After the severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) pandemic, the emergence of long-term sequelae post-infection poses a new healthcare challenge. Following initial infection with SARS-CoV-2, approximately 1 in 10 people experience post-acute sequelae of COVID-19 (PASC), also known as long COVID. PASC can affect the entire body, with the airways and lungs being a primary target of the initial viral infection. Many post-COVID symptoms have been associated with fibrotic lung lesions and diminished respiratory function. The reversibility, persistence, or progression of post-COVID-19 pulmonary fibrosis is still a topic of debate. We aimed to compare current findings and examined similar viral infections from the past, to increase understanding of prevalence, persistence and possible pharmacological targets of post-COVID-19 pulmonary fibrosis. Recent studies have documented PASC symptoms persisting up to 3 years post-recovery, and lung impairments present after 15 years after infection with the similar SARS-CoV virus in 2003. These findings suggest the potential for long-term pulmonary fibrosis following SARS-CoV-2 infection, highlighting the need for new anti-fibrotic treatments capable of reversing pulmonary fibrosis. Besides the approved anti-fibrotics, pirfenidone and nintedanib, other promising treatments include histone deacetylase inhibitors, angiotensin receptor blockers and mesenchymal stem cells. The pathophysiological mechanisms underlying post-COVID-19 pulmonary fibrosis are still incompletely understood, necessitating future research to clarify the development of persistent post-COVID-19 pulmonary fibrosis following SARS-CoV-2 infection. Given the widespread transmission of SARS-CoV-2, even a low prevalence of persistent post-COVID-19 pulmonary fibrosis would represent a significant public health concern for which therapeutic strategies are essential to identify.}, }
@article {pmid40453253, year = {2025}, author = {Boorle, NVLD and Kurra, NC and Gandrakota, N and Modi, K and Sudireddy, K and Irfan, SA and Jain, A and Parikh, PA and Jillella, D}, title = {Central Nervous System Manifestations of Long COVID: A Systematic Review.}, journal = {Cureus}, volume = {17}, number = {4}, pages = {e83247}, pmid = {40453253}, issn = {2168-8184}, abstract = {Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been one of the most widespread and devastating global pandemics, impacting hundreds of millions of people worldwide. After the cessation of active infection, the disease continues to have a disabling impact due to the persistence of fatigue, brain fog, anxiety, and depression - among the most common symptoms. This study explores the progression of neurological symptoms over 12 months and beyond following an initial diagnosis of COVID-19. Through an electronic search of eligible studies from PubMed, the Cochrane Trial Register, and Google Scholar, 10 studies were included for qualitative analysis. The systematic review highlights the similarities and differences in findings across the included studies. Olfactory dysfunction was prevalent in 0.9%-51% of individuals, and taste impairment was observed in 1.1%-21.3%. At 12 months, anxiety was more prevalent (3.5%-29%) than depression (3.5%-26%). Fatigue was the predominant neurocognitive complaint in 56% of individuals with severe COVID-19. Nearly half of individuals reported sleep difficulties. Memory impairment, followed by headaches and dizziness, also constitutes neurocognitive symptoms reported at 12 months. Our study found that there is a significant neurological burden one year following the diagnosis of COVID-19. Further studies exploring the pathological mechanisms of long-term COVID-19 are necessary to better delineate the mechanisms behind several long-term neurological manifestations of COVID-19.}, }
@article {pmid40464778, year = {2025}, author = {Leite Barbosa, N and Rangel Agra Oliveira, T and Nóbrega, LD and Araújo, TTF and Dos Santos Bezerra, SR and Oliveira, GM and Do Nascimento, RM and de Miranda Silva Nogueira, PA and Tomaz, AF and Do Nascimento Sales Figueiredo Fernandes, AT}, title = {Prevalence and characteristics of respiratory and cardiovascular sequelae in post-COVID-19 syndromes: a scoping review.}, journal = {Expert review of respiratory medicine}, volume = {19}, number = {9}, pages = {935-953}, doi = {10.1080/17476348.2025.2515992}, pmid = {40464778}, issn = {1747-6356}, mesh = {Humans ; *COVID-19/complications/epidemiology/therapy ; Prevalence ; *Cardiovascular Diseases/epidemiology/etiology ; *Dyspnea/epidemiology/etiology ; Risk Factors ; Post-Acute COVID-19 Syndrome ; Cough/epidemiology ; SARS-CoV-2 ; }, abstract = {INTRODUCTION: Post acute and Long COVID-19 are public health issues, marked by persistent respiratory and cardiovascular symptoms such as dyspnea and palpitations. These complications often extend beyond the acute phase, affecting even individuals with mild or moderate COVID-19. This article reviews the clinical impact of long COVID-19 and emphasizes the need for a multidisciplinary approach to management.<br><br>AREAS COVERED: A comprehensive literature search was conducted through PubMed, Medline, CINAHL, SciELO, and LILACS to identify studies published up to 28 October 2024, reporting on respiratory and cardiovascular sequelae in long COVID-19. This review examines the prevalence and characteristics of persistent symptoms such as dyspnea, cough, and palpitations, as well as the associated risk factors and assessment methods.<br><br>EXPERT OPINION: Long COVID-19 represents a significant healthcare challenge, underscoring the need for standardized protocols for diagnosis and treatment. A multidisciplinary approach is crucial to address the diverse symptoms of affected patients. Future research should focus on understanding the underlying pathophysiology, and developing targeted therapeutic strategies to improve patient outcomes.}, }
@article {pmid40465774, year = {2025}, author = {Salmam, I and Dubé, MO and Zahouani, I and Ramos, A and Desmeules, F and Best, KL and Roy, JS}, title = {The impact of long COVID on physical and cardiorespiratory parameters: A systematic review.}, journal = {PloS one}, volume = {20}, number = {6}, pages = {e0318707}, pmid = {40465774}, issn = {1932-6203}, mesh = {Humans ; *COVID-19/physiopathology/complications ; SARS-CoV-2 ; Respiratory Function Tests ; Adult ; Exercise Tolerance ; }, abstract = {BACKGROUND: Since the emergence of COVID-19, millions worldwide have continued to experience persistent symptoms months after infection. Among these, physical and cardiorespiratory impairments are frequently reported, but remain poorly understood. This systematic review aimed to identify and synthesize evidence regarding physical and cardiorespiratory impairments in individuals with long COVID, defined as symptoms persisting for at least three months post-infection.<br><br>METHODS AND FINDINGS: A structured search was conducted across the MEDLINE, Embase, CINAHL, and Web of Science databases to identify cross-sectional and longitudinal cohort studies on physical and cardiorespiratory deficits in adults with long COVID. Twenty-two studies involving 3,041 adults with long COVID were included. Critical appraisal using the JBI-APT indicated that most studies had clear inclusion criteria (17/22), well-defined study populations (17/22), and valid exposure measurements (16/22), though confounding factors were often unaddressed (9/22 unclear or not reported). Findings indicate that while adults with long COVID displayed normal pulmonary function at rest, including Forced Vital Capacity (FVC), Forced Expiratory Volume (FEV1), Total Lung Capacity (TLC), and resting Arterial oxygen saturation (SpO2), significant impairments in exercise capacity were identified. Notably, all studies assessing the 6-minute walk test (6MWT) reported reduced distances, consistently falling below the 50th percentile of normative values. Additionally, VO&#x2082;peak was decreased in most studies (7/10), falling below 80% of the predicted value, indicating impaired aerobic capacity. Lower Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) values were observed in three out of six studies, with values below 75% of predicted, suggesting impaired gas exchange efficiency during exertion.<br><br>CONCLUSION: Despite preserved resting lung function, these findings highlight significant physical deconditioning in Long COVID adults, with substantial reduction in exercise capacity. Routine assessments should include more sensitive measures, such as the 6MWT and VO&#x2082;peak, to detect subtle exercise limitations, even in patients with normal resting SpO&#x2082;, to better inform rehabilitation interventions.}, }
@article {pmid40470564, year = {2025}, author = {Iannuccelli, C and Favretti, M and Dolcini, G and Di Carlo, M and Pellegrino, G and Bazzichi, L and Atzeni, F and Lucini, D and Varassi, G and Leoni, MLG and Fornasari, DMM and Conti, F and Salaffi, F and Sarzi-Puttini, P and Di Franco, M}, title = {Fibromyalgia: one year in review 2025.}, journal = {Clinical and experimental rheumatology}, volume = {43}, number = {6}, pages = {957-969}, doi = {10.55563/clinexprheumatol/buhd2z}, pmid = {40470564}, issn = {0392-856X}, mesh = {Humans ; *Fibromyalgia/therapy/physiopathology/diagnosis/epidemiology/psychology ; Quality of Life ; COVID-19/epidemiology ; }, abstract = {Fibromyalgia (FM) is a chronic syndrome characterised by widespread pain, high prevalence, and a significant impact on quality of life. Despite extensive research, its pathogenesis and treatment remain only partially understood, driving continued investigation throughout 2024. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system has been linked to chronic stress responses and neuroinflammation, with neuroimaging and preclinical studies confirming altered pain and stress processing. Low-grade inflammation and metabolic disturbances, including cytokine imbalance and increased adipose tissue infiltration, further exacerbate symptoms. Alterations in the gut microbiota contribute to immune and emotional dysregulation. MRI studies continue to reveal brain changes that differentiate FM from other chronic pain disorders. Multi-omics approaches, including transcriptomic and metabolomic analyses, show promise as diagnostic biomarkers. Mitochondrial dysfunction also emerges as a key factor, since impaired energy metabolism seems to correlate with symptom severity. From a clinical perspective, recent studies have explored under-recognised aspects of FM, such as sexual and cognitive dysfunction, the role of gender, environmental exposures, and the disease's impact on relationships and family life. The differential diagnosis of FM and long COVID has ignited discussion about potential shared mechanisms. Conversely, residual pain in inflammatory diseases remains insufficiently addressed. Therapeutically, non-pharmacological strategies, particularly physical activity and psychosocial interventions, remain fundamental. Emerging areas such as non-invasive neuromodulation, psychedelic therapies, and the integration of technologies like virtual reality and artificial intelligence are opening new frontiers in treatment, patient care, and research. These advances underscore the multifactorial nature of FM and the need for personalised, interdisciplinary approaches.}, }
@article {pmid40474772, year = {2025}, author = {Gupta, G and Buonsenso, D and Wood, J and Mohandas, S and Warburton, D}, title = {Mechanistic Insights Into Long Covid: Viral Persistence, Immune Dysregulation, and Multi-Organ Dysfunction.}, journal = {Comprehensive Physiology}, volume = {15}, number = {3}, pages = {e70019}, doi = {10.1002/cph4.70019}, pmid = {40474772}, issn = {2040-4603}, mesh = {Humans ; *COVID-19/immunology/complications/virology/physiopathology ; *SARS-CoV-2/physiology ; *Multiple Organ Failure/immunology/virology/etiology ; Post-Acute COVID-19 Syndrome ; Animals ; }, abstract = {Long Covid is a post-viral syndrome characterized by persistent symptoms targeting multiple organ systems after initial SARS-CoV-2 infection. Current literature suggests that the mechanisms causing Long Covid involve viral persistence, immune dysregulation, systemic inflammation, endothelial dysfunction, and metabolic disturbances. By forming reservoirs in the tissues of various organs, SARS-CoV-2 may evade immunological clearances while triggering immune responses and contributing to chronic symptoms through cytokine imbalances, T-cell exhaustion, and systemic inflammation. These symptoms parallel other post-viral syndromes such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), suggesting similar mechanisms of pathology. The coronavirus has also been linked to neuroinflammation and endothelial dysfunction causing cognitive symptoms and cardiovascular complications. Furthermore, its ability to lower energy production links it to post-exertion malaise (PEM) and muscle pain. These symptoms may result from iron dysregulation and persistent oxidative stress due to Covid-impaired mitochondrial function. This review synthesizes current data on the mechanisms that drive Long Covid pathogenesis and explores potential therapeutic strategies to mitigate viral persistence, immune dysfunction, and metabolic disturbances. It is critical to understand these interactions to develop targeted interventions that address the long-term sequelae of SARS-CoV-2 infection and improve patient outcomes.}, }
@article {pmid40476637, year = {2025}, author = {Rahmati, M and Udeh, R and Kang, J and Dolja-Gore, X and McEvoy, M and Kazemi, A and Soysal, P and Smith, L and Kenna, T and Fond, G and Boussat, B and Nguyen, DC and Do, H and Tran, BX and Veronese, N and Yon, DK and Boyer, L}, title = {Long-Term Sequelae of COVID-19: A Systematic Review and Meta-Analysis of Symptoms 3 Years Post-SARS-CoV-2 Infection.}, journal = {Journal of medical virology}, volume = {97}, number = {6}, pages = {e70429}, pmid = {40476637}, issn = {1096-9071}, support = {//The authors received no specific funding for this work./ ; }, mesh = {Humans ; *COVID-19/complications/epidemiology/physiopathology ; Fatigue/epidemiology ; Dyspnea/epidemiology ; SARS-CoV-2 ; Prevalence ; Sleep Wake Disorders/epidemiology ; Post-Acute COVID-19 Syndrome ; Survivors ; }, abstract = {The symptoms of long COVID are well-documented. However, the long-term effects beyond 2 years remain poorly understood due to a lack of data. This systematic review and meta-analysis examined the prevalence of persistent symptoms in COVID-19 survivors 3 years following initial SARS-CoV-2 infection. PubMed, MEDLINE (Ovid), CENTRAL, Web of Science, Scopus, and Embase were searched from inception of the databases up to July 20, 2024, by two independent researchers for articles reporting on the prevalence of persistent symptoms 3 years' post-infection of people who survived COVID-19 infection. We employed a random-effect model for the pooled analysis, and the meta-analytical effect size was prevalence for the applicable end-points, I[2] statistics, and quality assessment of included studies using the Newcastle-Ottawa Scale. Eleven articles were included after the literature search yielded 223 potentially relevant articles. We found that among patients with long COVID, fatigue, sleep disturbances, and dyspnea were the most common symptoms. Pooled analysis showed that the proportion of individuals experiencing at least one persistent symptom 3 years post-COVID-19 is 20% (95% confidence interval [CI]: 8-43). The prevalence of persistent symptoms was dyspnea (12%; 95% CI: 10-15), fatigue (11%; 95% CI: 6-20), insomnia (11%; 95% CI: 2-37), loss of smell (7%; 95% CI: 5-8), loss of taste (7%; 95% CI: 3-16), and anxiety (6%; 95% CI: 1-32). Prevalence of other findings include impaired diffusion capacity (42%; 95% CI: 34-50) and impaired forced expiratory volume in 1 s (10%; 95% CI: 8-12). Our findings confirm the persistence of unresolved symptoms 3 years post-COVID-19 infection, with implications for future research, healthcare policy, and patient care.}, }
@article {pmid40478033, year = {2022}, author = {Barroso, E and Tuta-Quintero, E and Olivella, J and Aragón, C and Vásquez, L and Acosta, L and Pinzón, O and Pantoja, CA and Collazos, E and Ascanio, YP and Morales, VDCDR and Kuan, JC and Velásquez, LA and Díaz, YN and Pimentel, J}, title = {[Guillain Barré syndrome in the paediatric population. Consequence of active infection or long Covid?].}, journal = {Revista colombiana de reumatologia}, volume = {29}, number = {4}, pages = {335-346}, pmid = {40478033}, issn = {2027-9000}, abstract = {BACKGROUND: Guillain-Barré syndrome is a polyradiculoneuropathy that has been associated with infectious diseases as triggers. There is currently little medical evidence exploring the relationship between the development of Guillain-Barré syndrome caused by SARS-CoV-2 infection and long Covid.<br><br>OBJECTIVE: To synthesize the medical evidence that describes the relationship between post Covid syndrome and Guillain-Barr&#xe9; syndrome in the paediatric population.<br><br>METHODOLOGY: A scoping review was developed using Scopus and PubMed databases, including analytical and/or descriptive experimental and observational studies.<br><br>RESULTS: The main clinical manifestations presented by paediatric patients were distal and ascending weakness in the lower limbs and myalgia. The diagnostic approach was based on clinical findings, imaging findings on spinal magnetic resonance and electromyography. The therapeutic strategy is based on the use of intravenous human immunoglobulins.<br><br>CONCLUSION: Guillain-Barr&#xe9; syndrome is a frequent disease in the paediatric population with active SARS-CoV-2 infection or in survivors, however, it is necessary to encourage further clinical studies that increase the medical literature that describes this association.}, }
@article {pmid40479330, year = {2022}, author = {Tuta Quintero, E and Mosquera Pongutá, AC and Barroso da Silva, EA and Olivella, J and Silvera, AA and Aragón, C and Vásquez, L and Collazos, E and Olivares Vigles, K and Martínez, K and León Machicado, M and Díaz Pérez, YN and Pimentel, J}, title = {[SARS-CoV-2 and post-COVID-19 syndrome in paediatric rheumatology: A scoping review].}, journal = {Revista colombiana de reumatologia}, volume = {}, number = {}, pages = {}, pmid = {40479330}, issn = {2027-9000}, abstract = {INTRODUCTION: An increasing number of musculoskeletal clinical manifestations, the onset of diseases and rheumatological manifestations have been seen in the paediatric population surviving COVID-19, however, the medical literature on the subject is limited.<br><br>OBJECTIVE: To explore the available evidence on musculoskeletal symptoms and autoimmune diseases in the paediatric population with post-COVID syndrome.<br><br>METHODOLOGY: Scoping systematic review in PubMed and Scopus through search strategies. Observational and experimental studies are included in populations under 21&#xa0;years of age with and without autoimmune diseases, without time limit in English and Spanish.<br><br>RESULTS: The 28 documents included: case reports (n&#xa0;=&#xa0;6), cross-sectional studies (n&#xa0;=&#xa0;5), prospective cohort studies (n&#xa0;=&#xa0;5), retrospective cohort (n&#xa0;=&#xa0;6), case series (n&#xa0;=&#xa0;6), ambidirectional section (n&#xa0;=&#xa0;1), randomized controlled trial (n&#xa0;=&#xa0;1), and longitudinal section study (n&#xa0;=&#xa0;1). The total study population was 56,738 patients. The most frequent symptoms presented in long COVID-19 are myalgias and arthralgias. The evidence showing a relationship between SARS-CoV-2 infection in the development of musculoskeletal symptoms and autoimmune diseases in the convalescent period is limited.<br><br>CONCLUSIONS: Myalgias and arthralgias are the most frequent symptoms in long COVID. patients with SARS-CoV-2 infection and a history of rheumatic disease who are undergoing immunomodulatory treatment do not have a dangerous risk of developing severe presentations and/or complications of the disease.}, }
@article {pmid40481619, year = {2025}, author = {Linton, J and Carmichael, J and Newlands, F and Puri, A and Fox-Smith, L and Pinto Pereira, SM and Coughtrey, A and Shafran, R and Stephenson, T}, title = {Pre-Pandemic Prevalence of Post COVID-19 Condition Symptoms in Adolescents.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {114}, number = {9}, pages = {2116-2123}, pmid = {40481619}, issn = {1651-2227}, support = {COV-LT-0022//UK Research and Innovation/ ; 183885//Beryl Alexander Charity PhD Studentship/ ; MR/Y009398/1//UK Medical Research Council Senior Non-clinical Fellowship/ ; //NIHR Great Ormond Street Hospital Biomedical Research Centre/ ; }, mesh = {Humans ; Adolescent ; *COVID-19/complications/epidemiology ; Prevalence ; Child ; Young Adult ; *Adolescent Health ; }, abstract = {AIM: The emergence of post COVID-19 condition (PCC) within adolescents has been characterised by a wide range of symptoms, raising concerns for young people's health and quality of life. However, many symptoms are non-specific and there is considerable variation in symptom reporting. It is essential to understand how rates of these symptoms compare to the pre-pandemic health of adolescents.<br><br>METHODS: A systematic search of academic literature and websites, using traditional and automated search systems, was undertaken to identify symptoms described in adolescents aged 10-19&#x2009;years in the 30&#x2009;years up to and including 2019. Studies were reviewed and symptom prevalence data extracted.<br><br>RESULTS: Twenty-five sources (n&#x2009;=&#x2009;483&#x2009;097 participants) met the inclusion criteria, including longitudinal and cross-sectional study designs. The description and prevalence of symptoms varied widely, but there was a high pre-pandemic median prevalence of cough (13.6%), headache (30.0%), and fatigue (20.5%). These high prevalences highlight a gap in understanding of pre-pandemic adolescent health and the need for comprehensive, serial symptom profiling.<br><br>CONCLUSION: These findings provide a baseline of adolescent symptomatology prior to the emergence of PCC and provide important context for interpreting ongoing COVID symptoms. Data on PCC in adolescents should consider pre-pandemic symptom prevalence.}, }
@article {pmid40492581, year = {2025}, author = {Vlaming-van Eijk, LE and Tang, G and Bourgonje, AR and den Dunnen, WFA and Hillebrands, JL and van Goor, H}, title = {Post-COVID-19 condition: clinical phenotypes, pathophysiological mechanisms, pathology, and management strategies.}, journal = {The Journal of pathology}, volume = {266}, number = {4-5}, pages = {369-389}, pmid = {40492581}, issn = {1096-9896}, mesh = {Humans ; *COVID-19/complications/therapy/physiopathology/pathology ; Phenotype ; SARS-CoV-2 ; Risk Factors ; Post-Acute COVID-19 Syndrome ; }, abstract = {Post-COVID-19 condition (PCC), also known as long COVID, is a complex multiple organ system condition that can develop and persist for months after acute COVID-19. PCC encompasses a wide range of symptoms, resulting in heterogeneous clinical manifestations. These manifestations likely arise from diverse underlying pathophysiological mechanisms, which, in turn, are influenced by risk factors such as age, sex, and comorbidities. To this end, characterising clinical phenotypes of PCC is essential for deepening our understanding of its (potentially) distinct pathophysiological mechanisms and for advancing diagnostic and patient-tailored management strategies. PCC is thought to result from a complex interaction of various pathophysiological mechanisms, leading to functional and structural pathological alterations across multiple organ systems. Investigating these alterations is critical to improving our currently incomplete understanding of PCC's complex pathophysiology. This review provides an overview of the main clinical phenotypes of PCC, characterises these phenotypes by examining symptoms and signs, as well as the associated risk factors. The main hypothesised pathophysiological mechanisms are discussed by outlining the current knowledge on PCC pathology, focussing on the most commonly affected organ systems. Current PCC management includes supportive care such as physiotherapy and the repurposing of existing drugs primarily targeting persistence of SARS-CoV-2 (e.g. antivirals, monoclonal antibodies) and immune dysfunction (e.g. antiinflammatory drugs, immunomodulators). To date, prevention of SARS-CoV-2 infection remains critical, which can be achieved through effective public health measures and vaccination strategies. Finally, this review highlights current knowledge gaps and proposes future research directions to advance the understanding and treatment of PCC. © 2025 The Author(s). The Journal of Pathology published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.}, }
@article {pmid40496528, year = {2024}, author = {Akbari, B and Wang, JM and Baghaei-Yazdi, N and Lahooti, H and Sherman, JH}, title = {Systems Thinking, Causal Loop Diagram, and Systems Dynamic in Public Health Challenges: Navigating Long COVID Syndrome and Sense of Smell in LGBTQIA+ Communities.}, journal = {Public health challenges}, volume = {3}, number = {3}, pages = {e70004}, pmid = {40496528}, issn = {2769-2450}, abstract = {BACKGROUND: The coronavirus pandemic has profoundly affected global health, economic stability, and environmental sustainability. Despite these challenges, significant gaps in data remain, particularly in effectively assessing and engaging diverse communities such as color, LGBTQIA+ individuals, and low-income groups. This shortage of comprehensive research limits our capacity to undertake sensitive studies, specifically in dealing with the complexities of long COVID, which some individuals continue to suffer from after their initial recovery.<br><br>OBJECTIVE: This review delves into the ongoing repercussions of long-term COVID-19, a postinfectious syndrome marked by neurological symptoms such as cognitive deficits and sensory impairments, which may last well beyond the acute phase of the illness. These symptoms frequently overlap with mental health issues (e.g., anxiety and depression), which can aggravate the socioeconomic challenges faced by vulnerable populations, especially within the LGBTQA+ communities.<br><br>METHODS: To tackle these complex interactions, we have introduced a novel public health framework: model-based systems thinking (MBST), which incorporates System Dynamics and causal loop diagrams (CLD).<br><br>RESULTS AND DISCUSSION: The articles were selected on the basis of their discussion of COVID-19-associated anosmia, exploration of olfactory dysfunction alongside neurocognitive disorders, and the challenges experienced in LGBQA+ communities. This approach offers a robust framework for dissecting the intricate ties between socioeconomic factors, health outcomes, and the extended recovery trajectories associated with long-term COVID-19, with a particular focus on olfactory dysfunction. We also explore strategies to make our models more accessible to healthcare providers and the LGBTQA+ communities, encouraging its broader adoption.<br><br>CONCLUSION: Long COVID's impact on public health and marginalized communities highlights the urgent need for adopting systems thinking models. Additionally, this article calls for a concerted effort from all experts to foster multidisciplinary, team-based research and implement effective support measures for COVID-19 survivors across all communities, mainly focusing on the scientific, social, and behavioral challenges LGBTQIA+ and low-income individuals face.}, }
@article {pmid40507071, year = {2025}, author = {Bigman, G and Rusu, ME and Shelawala, N and Sorkin, JD and Beamer, BA and Ryan, AS}, title = {A Comprehensive Scoping Review on Diet and Nutrition in Relation to Long COVID-19 Symptoms and Recovery.}, journal = {Nutrients}, volume = {17}, number = {11}, pages = {}, pmid = {40507071}, issn = {2072-6643}, support = {IK6 RX003977/RX/RRD VA/United States ; K01 AG078545/AG/NIA NIH HHS/United States ; P30 AG028747/AG/NIA NIH HHS/United States ; R01 AG051752/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/complications/physiopathology/diet therapy ; *Nutritional Status ; *Diet ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Adult ; }, abstract = {Background/Objectives: Long COVID-19 is characterized by persistent symptoms lasting three months or more following SARS-CoV-2 infection. Nutrition has emerged as a modifiable factor influencing recovery trajectories and symptom burden; however, existing evidence remains fragmented across diverse study designs and populations. This scoping review synthesized global evidence on the role of diet and nutrition in managing long COVID-19 symptoms and supporting recovery. Methods: Following PRISMA-ScR and Joanna Briggs Institute guidelines for scoping reviews, we searched major biomedical databases for studies published between 2020 and 2025. Eligible studies examined dietary intake, nutritional status, or nutrition-related interventions in adults with long COVID-19. Results: After duplicates were removed, 1808 records were screened, resulting in 50 studies that met the inclusion criteria-27 intervention studies and 23 observational studies. Nutritional exposures included micronutrients (e.g., vitamins D, K2), amino acids (e.g., L-arginine), multinutrient formulations, microbiota-targeted therapies (e.g., probiotics, synbiotics), nutritional status, diet quality, and whole-diet patterns (e.g., the Mediterranean diet). Approximately 76% of studies reported improvements in long COVID-19-related symptoms such as fatigue, mood disturbances, physical function, and markers of inflammation. Conclusions: Diet and nutrition may support long COVID-19 recovery by targeting inflammation and the gut microbiome to alleviate symptoms and improve functional outcomes. Well-powered trials of whole-diet approaches, combined with targeted supplementation, are needed to confirm their potential as scalable, accessible tools for post-COVID-19 recovery and management.}, }
@article {pmid40507911, year = {2025}, author = {Popa, E and Popa, AE and Poroch, M and Poroch, V and Ungureanu, MI and Slanina, AM and Bacusca, A and Coman, EA}, title = {The Molecular Mechanisms of Cognitive Dysfunction in Long COVID: A Narrative Review.}, journal = {International journal of molecular sciences}, volume = {26}, number = {11}, pages = {}, pmid = {40507911}, issn = {1422-0067}, mesh = {Humans ; *COVID-19/complications/metabolism ; *Cognitive Dysfunction/etiology/metabolism/virology ; SARS-CoV-2 ; Biomarkers/metabolism ; Blood-Brain Barrier/metabolism ; }, abstract = {Cognitive dysfunction represents one of the most persistent and disabling features of Long COVID, yet its molecular underpinnings remain incompletely understood. This narrative review synthesizes current evidence on the pathophysiological mechanisms linking SARS-CoV-2 infection to long-term neurocognitive sequelae. Key processes include persistent neuroinflammation, blood-brain barrier (BBB) disruption, endothelial dysfunction, immune dysregulation, and neuroendocrine imbalance. Microglial activation and cytokine release (e.g., IL-6, TNF-α) promote synaptic dysfunction and neuronal injury, while activation of inflammasomes such as NLRP3 amplifies CNS inflammation. Vascular abnormalities, including microthrombosis and BBB leakage, facilitate the infiltration of peripheral immune cells and neurotoxic mediators. Hypothalamic-pituitary-adrenal axis dysfunction and reduced vagal tone further exacerbate systemic inflammation and autonomic imbalance. Biomarkers such as GFAP, NFL, IL-6, and S100B have been associated with both neuroinflammation and cognitive symptoms. Notably, transcriptomic signatures in Long COVID overlap with those observed in Alzheimer's disease, highlighting shared pathways involving tau dysregulation, oxidative stress, and glial reactivity. Understanding these mechanisms is critical for identifying at-risk individuals and developing targeted therapeutic strategies. This review underscores the need for longitudinal research and integrative biomarker analysis to elucidate the molecular trajectory of cognitive impairment in Long COVID.}, }
@article {pmid40512228, year = {2025}, author = {Goldenberg, DL}, title = {The pivotal role of central sensitization in long COVID, fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome.}, journal = {Expert review of neurotherapeutics}, volume = {25}, number = {8}, pages = {973-989}, doi = {10.1080/14737175.2025.2516097}, pmid = {40512228}, issn = {1744-8360}, mesh = {Humans ; *Fatigue Syndrome, Chronic/physiopathology/therapy ; *Fibromyalgia/physiopathology/therapy ; *COVID-19/physiopathology/complications/therapy ; *Central Nervous System Sensitization/physiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {INTRODUCTION: Long COVID is a condition characterized by persistent unexplained symptoms following COVID-19 infection. These symptoms are not related to another disease or organ damage and are similar to those in fibromyalgia and myslgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).<br><br>AREAS COVERED: The similar clinical and pathophysiological features and management of long COVID, fibromyalgia and ME/CFS are explored from the unifying framework of central sensitivity syndromes. The article is based on a literature search utilizing PubMed for content published between 2021 and 1 May 2025, using search terms: long COVID, long COVID syndrome, post-COVID-19, post-acute SARS-CoV-2, fibromyalgia, ME/CFS, post-exertional malaise and central sensitization.<br><br>EXPERT OPINION: Once long COVID is redefined to exclude patients with well-defined organ disease, it fits best as a model of central sensitization. Long COVID is a single syndrome, rather than many distinct diseases. Optimal management of long COVID and similar central sensitivity syndromes should include personalized care with a primary care led-multidisciplinary team.}, }
@article {pmid40514644, year = {2025}, author = {Elboraay, T and Ebada, MA and Elsayed, M and Aboeldahab, HA and Salamah, HM and Rageh, O and Elmallahy, M and AboElfarh, HE and Mansour, LS and Nabil, Y and Eltawab, AKA and Atwan, H and Alkanj, S}, title = {Long-term neurological and cognitive impact of COVID-19: a systematic review and meta-analysis in over 4 million patients.}, journal = {BMC neurology}, volume = {25}, number = {1}, pages = {250}, pmid = {40514644}, issn = {1471-2377}, mesh = {Humans ; *COVID-19/complications/psychology/epidemiology ; *Nervous System Diseases/epidemiology/etiology ; *Cognitive Dysfunction/epidemiology/etiology ; Prevalence ; Fatigue/epidemiology ; }, abstract = {BACKGROUND: Neuropsychiatric symptoms emerged early in the COVID-19 pandemic as a key feature of the virus, with research confirming a range of neuropsychiatric manifestations linked to acute SARS-CoV-2 infection. However, the persistence of neurological symptoms in the post-acute and chronic phases remains unclear. This meta-analysis assesses the long-term neurological effects of COVID-19 in recovered patients, providing insights for mental health service planning.<br><br>METHODS: A comprehensive literature search was conducted across five electronic databases: PubMed, Scopus, Web of Science, EBSCO, and CENTRAL, up to March 22, 2024. Studies evaluating the prevalence of long-term neurological symptoms in COVID-19 survivors with at least six months of follow-up were included. Pooled prevalence estimates, subgroup analyses, and meta-regression were performed, and publication bias was assessed.<br><br>RESULTS: The prevalence rates for the different symptoms were as follows: fatigue 43.3% (95% CI [36.1-50.9%]), memory disorders 27.8% (95% CI [20.1-37.1%]), cognitive impairment 27.1% (95% CI [20.4-34.9%]), sleep disorders 24.4% (95% CI [18.1-32.1%]), concentration impairment 23.8% (95% CI [17.2-31.9%]), headache 20.3% (95% CI [15-26.9%]), dizziness 16% (95% CI [9.5-25.7%]), stress 15.9% (95% CI [10.2-24%]), depression 14.0% (95% CI [10.1-19.2%]), anxiety 13.2% (95% CI [9.6-17.9%]), and migraine 13% (95% CI [2.2-49.8%]). Significant heterogeneity was observed across all symptoms. Meta-regression analysis showed higher stress, fatigue, and headache in females, and increased stress and concentration impairment with higher BMI.<br><br>CONCLUSIONS: Neurological symptoms are common and persistent in COVID-19 survivors. This meta-analysis highlights the significant burden these symptoms place on individuals, emphasizing the need for well-resourced multidisciplinary healthcare services to support post-COVID recovery.<br><br>REGISTRATION AND PROTOCOL: This meta-analysis was registered in PROSPERO with registration number CRD42024576237.}, }
@article {pmid40529374, year = {2025}, author = {Trautmann, A}, title = {Core features and inherent diversity of post-acute infection syndromes.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1509131}, pmid = {40529374}, issn = {1664-3224}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; Animals ; Fatigue/etiology ; *Infections/immunology/complications ; Critical Illness ; }, abstract = {Post-acute infection syndromes (PAIS), i.e., long-lasting pathologies subsequent to infections that do not properly resolve, have both a common core and a broad diversity of manifestations. PAIS include a group of core symptoms (pathological fatigue, cognitive problems, sleep disorders and pain) accompanied by a large set of diverse symptoms. Core and diverse additional symptoms, which can persist for years, exhibiting periods of relapses and remissions, usually start suddenly after an apparently common infection. PAIS display highly variable clinical features depending on the nature of the initial pathogen, and to an even larger extent, on the diversity of preexisting individual terrains in which PAIS are rooted. In a first part, I discuss biological issues related to the persistence of microbial antigens, dysregulated immune responses, reactivation of latent viruses, different potential self-sustained inflammatory loops, mitochondrial dysfunction, metabolic disorders in the tryptophan- kynurenin pathway (TKP) with impact on serotonin, and consequences of a dysfunctional bidirectional microbiota-gut-brain axis. The second part deals with the nervous system dependence of PAIS. I rely on the concept of interoception, the process by which the brain senses, integrates and interprets signals originating from within the body, and sends feebacks aimed at maintaining homeostasis. Interoception is central for understanding the origin of fatigue, dysautonomia, dysfunctioning of the hypothalamus-pituitary-adrenal (HPA) axis, and its relation with stress, inflammation or depression. I propose that all individual predispositions leading to self-sustained vicious circles constitute building blocks that can self-assemble in many possible ways, to give rise to both core and diverse features of PAIS. A useful discrimination between different PAIS subtypes should be obtained with a composite profiling including biomarkers, questionnaires and functional tests so as to take into account PAIS multidimensionality.}, }
@article {pmid40531392, year = {2025}, author = {da Silva, MD and da Silva, TS and Mendes, CG and Valbão, MCM and Badu-Tawiah, AK and Laurindo, LF and Barbalho, SM and Direito, R and Miglino, MA}, title = {Advances in Understanding Long COVID: Pathophysiological Mechanisms and the Role of Omics Technologies in Biomarker Identification.}, journal = {Molecular diagnosis &amp; therapy}, volume = {29}, number = {5}, pages = {617-636}, pmid = {40531392}, issn = {1179-2000}, support = {200177/2022-2//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; }, mesh = {Humans ; *COVID-19/metabolism/virology/complications/physiopathology ; *Biomarkers/metabolism/analysis ; Metabolomics/methods ; *SARS-CoV-2 ; Proteomics/methods ; Lipidomics ; Post-Acute COVID-19 Syndrome ; Risk Factors ; }, abstract = {Long coronavirus disease (COVID) is a multisystem condition that affects a significant proportion of individuals following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with persistent symptoms ranging from fatigue and cognitive dysfunction to cardiovascular disorders. It is estimated that 30-60% of infected individuals experience symptoms lasting more than 12 weeks. Despite advances in understanding acute infection, the pathophysiological mechanisms underlying long COVID remain unclear. Current hypotheses suggest that viral persistence, immune dysfunction, and metabolic alterations play central roles. Omics approaches, including metabolomics, proteomics, and lipidomics, have played a crucial role in investigating molecular changes, identifying biomarkers, and refining therapeutic strategies. This review discusses recent advances in understanding long COVID, addressing its mechanisms, risk factors, the impact of viral variants, and the role of vaccination, with an emphasis on the importance of omics technologies in elucidating this condition.}, }
@article {pmid40534826, year = {2025}, author = {Souissi, A and Prieto-González, P and Ben Saad, H}, title = {Widespread pain syndrome in long COVID-19: melatonin as an adjuvant treatment.}, journal = {Frontiers in pain research (Lausanne, Switzerland)}, volume = {6}, number = {}, pages = {1609095}, pmid = {40534826}, issn = {2673-561X}, abstract = {Long coronavirus disease 2019 (LC19) represents a complex global health challenge. Survivors frequently report persistent problems like widespread pain syndrome (WPS), cognitive dysfunction, cardiovascular complications, and sleep disturbances. These health problems, which are worsened by oxidative stress and inflammaging, open the prospect of treatment strategies targeting these mechanisms. Melatonin is a potential option for treating LC19 problems because of its anti-inflammatory, antioxidant, and pain-modulating properties. Melatonin targets shared pathological pathways, offering a promising approach to reducing inflammation, oxidative stress, and neuroendocrine dysfunction. The present mini-review explores the therapeutic potential of melatonin in the treatment of LC19, focusing on its effects on WPS and inflammation.}, }
@article {pmid40536011, year = {2025}, author = {Moen, JK and Baker, CA and Iwasaki, A}, title = {Neuroimmune pathophysiology of long COVID.}, journal = {Psychiatry and clinical neurosciences}, volume = {79}, number = {9}, pages = {514-530}, pmid = {40536011}, issn = {1440-1819}, support = {/HHMI/Howard Hughes Medical Institute/United States ; R01 AI157488/AI/NIAID NIH HHS/United States ; R01AI157488//National Institute of Allergy and Infectious Diseases/ ; N/A/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Humans ; *COVID-19/immunology/complications/physiopathology ; Post-Acute COVID-19 Syndrome ; *Neuroimmunomodulation/physiology ; *Nervous System Diseases/immunology/physiopathology/etiology ; SARS-CoV-2 ; Animals ; *Peripheral Nervous System Diseases/immunology/physiopathology/etiology ; Fatigue/physiopathology/immunology ; }, abstract = {Although COVID-19 was originally considered a respiratory illness, it is now well established that SARS-CoV-2 infection can have far-reaching impacts on the nervous system. Neurological symptoms such as chemosensory dysfunction are frequently observed during acute infection and approximately 10% of COVID-19 cases will go on to develop new or persistent long-term symptoms, a condition known in the literature as post-acute symptoms of COVID-19 (PASC) or by the patient-coined term Long COVID. Common neurological symptoms in Long COVID include new onset cognitive difficulties, dysautonomia, fatigue, and peripheral neuropathy. The emergence of Long COVID has prompted renewed interest in the study of post-acute infection syndromes (PAIS), particularly in the area of neuroimmune interactions. In this review we provide a comprehensive overview of the current body of literature on neurological manifestations of SARS-CoV-2 infection and Long COVID, with an emphasis on neuroimmune mechanisms drawn largely from autopsy studies and animal models. A more complete understanding of neuroimmune crosstalk in Long COVID will not only guide the development of therapies for this highly disabling condition but will also contribute to our general understanding of neuroimmune interactions in health and disease.}, }
@article {pmid40540167, year = {2025}, author = {Lang, SM and Schiffl, H}, title = {Long-term renal consequences of COVID-19. Emerging evidence and unanswered questions.}, journal = {International urology and nephrology}, volume = {57}, number = {12}, pages = {4169-4176}, pmid = {40540167}, issn = {1573-2584}, mesh = {Humans ; *COVID-19/complications/epidemiology ; *Renal Insufficiency, Chronic/epidemiology/etiology ; *Acute Kidney Injury/epidemiology ; SARS-CoV-2 ; }, abstract = {PURPOSE: COVID-19 infection is associated with a high burden of acute or acute on chronic kidney injury (AKI), particularly in critically ill patients. Given the large numbers of COVID-19 survivors, characterization of long-term adverse kidney effects of COVID-19 have important implications for post-COVID-19 care.<br><br>METHODS: This narrative review provides a summary of epidemiologic evidence for post-COVID kidney disorders.<br><br>RESULTS: Precise post-COVID renal data are scarce. The true burden of long-COVID chronic kidney disease (CKD) remains unknown owing to under-recognition, under-diagnosis, clinical heterogeneity of patients, incomplete follow-up, and temporal trends in critical COVID-19 disease across waves of the pandemic. Collectively, the few well-designed studies assessing the impact of long-COVID on kidney health found that the overwhelming majority of patients with normal renal function at admission and without AKI during acute COVID-19 disease preserved kidney function. Post-infection kidney function trajectories of patients who experience a loss of renal function vary. Kidney function may decline gradually even in non-hospitalized patients, hospitalized patients may experience a rapid loss of kidney function 6-12&#xa0;months after COVID-19 diagnosis or hospital discharge resulting from AKI during the acute phase of the disease. End-stage renal disease may occur after non-recovery from AKI and rapid progression of pre-existing CKD. Multiple mechanisms may trigger post-COVID CKD including maladaptive repair after AKI, or progression of renal lesions of systemic co-morbidities, persistence of the virus and dysregulation of inflammatory cytokines.<br><br>CONCLUSIONS: The COVID-19 pandemic has significantly impacted and may continue to have an impact on kidney health. Patients at risk have a higher propensity to develop critical COVID-19 disease. Post-COVID-19 care must pay close attention to renal function in patients discharged from hospital.}, }
@article {pmid40543387, year = {2025}, author = {Beuren, T and Ferrari, F and Franzoni, LT and Goulart, CDL and Val, F and Cipriano, G and Stein, R}, title = {Exploring the interplay between host genetics and acute and long COVID: A narrative review.}, journal = {Clinics (Sao Paulo, Brazil)}, volume = {80}, number = {}, pages = {100708}, pmid = {40543387}, issn = {1980-5322}, mesh = {Humans ; *COVID-19/genetics/immunology ; *Genetic Predisposition to Disease/genetics ; SARS-CoV-2 ; }, abstract = {Over the past four years, pivotal discoveries have deepened the understanding of the relationship between genetic factors and SARS-CoV-2 infection. Numerous genes associated with severe COVID-19 suggest a potential genetic predisposition, which may help explain why some individuals develop more serious illnesses. Emerging evidence highlights the role of genes involved in pulmonary immunity, such as Forkhead box Protein P4 (FOXP4), whose increased expression in lung tissue has been linked to more severe disease. Other genes - Transmembrane Protease Serine-2 (TMPRSS2), Leucine Zipper Transcription Factor Like-1 (LZTFL1), Solute Carrier family 6 member 20 (SLC6A20), Tyrosine Kinase-2 (TYK2), Angiotensin-Converting Enzyme (ACE), and FYVE and Coiled-Coil Domain-Containing-1 (FYCO1) - have also been implicated in COVID-19 severity. In contrast, certain genetic variants - such as the T-allele of rs12329760 in the TMPRSS2 gene and rs35705950-T in the Mucin-5B (MUC5B) gene - may confer protection against severe disease. Overall, the evidence suggests that genetic factors can influence both susceptibility to and protection from severe COVID-19, although these associations are likely shaped by complex interactions with environmental, behavioral, and other biological factors. This review summarizes current knowledge on genetic determinants linked to COVID-19 outcomes.}, }
@article {pmid40549427, year = {2025}, author = {Luo, X and Li, Y and Xu, J and Zheng, Z and Ying, F and Huang, G}, title = {AI in Medical Questionnaires: Scoping Review.}, journal = {Journal of medical Internet research}, volume = {27}, number = {}, pages = {e72398}, pmid = {40549427}, issn = {1438-8871}, mesh = {Humans ; *Artificial Intelligence ; Surveys and Questionnaires ; COVID-19/epidemiology ; *Mental Disorders/diagnosis ; SARS-CoV-2 ; }, abstract = {UNLABELLED: This systematic review aimed to explore the current applications, potential benefits, and issues of artificial intelligence (AI) in medical questionnaires, focusing on its role in 3 main functions: assessment, development, and prediction. The global mental health burden remains severe. The World Health Organization reports that >1 billion people worldwide experience mental disorders, with the prevalence of depression and anxiety among children and adolescents at 2.6% and 6.5%, respectively. However, commonly used clinical questionnaires such as the Hamilton Depression Rating Scale and the Beck Depression Inventory suffer from several problems, including the high degree of overlap of symptoms of depression with those of other psychiatric disorders and a lack of professional supervision during administration of the questionnaires, which often lead to inaccurate diagnoses. In the wake of the COVID-19 pandemic, the health care system is facing the dual challenges of a surge in patient numbers and the complexity of mental health issues. AI technology has now been shown to have great promise in improving diagnostic accuracy, assisting clinical decision-making, and simplifying questionnaire development and data analysis. To systematically assess the value of AI in medical questionnaires, this study searched 5 databases (PubMed, Embase, Cochrane Library, Web of Science, and China National Knowledge Infrastructure) for the period from database inception to September 2024. Of 49,091 publications, a total of 14 (0.03%) studies met the inclusion criteria. AI technologies showed significant advantages in assessment, such as distinguishing myalgic encephalomyelitis or chronic fatigue syndrome from long COVID-19 with 92.18% accuracy. In questionnaire development, natural language processing using generative models such as ChatGPT was used to construct culturally competent scales. In terms of disease prediction, one study had an area under the curve of 0.790 for cataract surgery risk prediction. Overall, 24 AI technologies were identified, covering traditional algorithms such as random forest, support vector machine, and k-nearest neighbor, as well as deep learning models such as convolutional neural networks, Bidirectional Encoder Representations From Transformers, and ChatGPT. Despite the positive findings, only 21% (3/14) of the studies had entered the clinical validation phase, whereas the remaining 79% (11/14) were still in the exploratory phase of research. Most of the studies (10/14, 71%) were rated as being of moderate methodological quality, with major limitations including lack of a control group, incomplete follow-up data, and inadequate validation systems. In summary, the integrated application of AI in medical questionnaires has significant potential to improve diagnostic efficiency, accelerate scale development, and promote early intervention. Future research should pay more attention to model interpretability, system compatibility, validation standardization, and ethical governance to effectively address key challenges such as data privacy, clinical integration, and transparency.<br><br>BACKGROUND: The World Health Organization reports that >1 billion people worldwide experience mental disorders, with the prevalence of depression and anxiety among children and adolescents at 2.6% and 6.5%, respectively. However, commonly used clinical questionnaires such as the Hamilton Depression Rating Scale and the Beck Depression Inventory suffer from several problems, including the high degree of overlap of symptoms of depression with those of other psychiatric disorders and a lack of professional supervision during administration of the questionnaires, which often lead to inaccurate diagnoses. In the wake of the COVID-19 pandemic, the health care system is facing the dual challenges of a surge in patient numbers and the complexity of mental health issues. Artificial Intelligence (AI) technology has now been shown to have great promise in improving diagnostic accuracy, assisting clinical decision-making, and simplifying questionnaire development and data analysis.<br><br>OBJECTIVE: This review aimed to explore the current applications, potential benefits, and issues of AI in medical questionnaires, focusing on its role in 3 main functions: assessment, development, and prediction. The global mental health burden remains severe.<br><br>METHODS: The review included peer-reviewed studies that applied AI technologies to medical, psychological, or physiological questionnaires and reported measurable outcomes; non&#x2013;peer-reviewed, non-English/Chinese, ethically noncompliant, or AI-unrelated studies were excluded. Five databases (PubMed, Embase, Cochrane Library, Web of Science, and CNKI) were searched from inception through September 2024. Three independent reviewers conducted data extraction, quality appraisal using the Joanna Briggs Institute tools, and narrative synthesis of AI applications across questionnaire assessment, development, and prediction tasks.<br><br>RESULTS: Of 49,091 publications, a total of 14 (0.03%) studies met the inclusion criteria. AI technologies showed advantages in assessment, such as distinguishing myalgic encephalomyelitis or chronic fatigue syndrome from long COVID-19 with 92.18% accuracy. In questionnaire development, natural language processing using generative models such as ChatGPT was used to construct culturally competent scales. In terms of disease prediction, one study had an area under the curve of 0.790 for cataract surgery risk prediction. Overall, 24 AI technologies were identified, covering traditional algorithms such as random forest, support vector machine, and k-nearest neighbor, as well as deep learning models such as convolutional neural networks, Bidirectional Encoder Representations From Transformers, and ChatGPT. Despite the positive findings, only 21% (3/14) of the studies had entered the clinical validation phase, whereas the remaining 79% (11/14) were still in the exploratory phase of research. Most of the studies (10/14, 71%) were rated as being of moderate methodological quality, with major limitations including lack of a control group, incomplete follow-up data, and inadequate validation systems.<br><br>CONCLUSIONS: In summary, the integrated application of AI in medical questionnaires has significant potential to improve diagnostic efficiency, accelerate scale development, and promote early intervention. Future research should pay more attention to model interpretability, system compatibility, validation standardization, and ethical governance to effectively address key challenges such as data privacy, clinical integration, and transparency.}, }
@article {pmid40552782, year = {2025}, author = {Xu, Y and Xu, JW and Wu, Y and Rong, LJ and Ye, L and Franco, OH and Chien, CW and Feng, XR and Chen, JY and Tung, TH}, title = {Prevalence and prognosis of sarcopenia in acute COVID-19 and long COVID: a systematic review and meta-analysis.}, journal = {Annals of medicine}, volume = {57}, number = {1}, pages = {2519678}, pmid = {40552782}, issn = {1365-2060}, mesh = {Humans ; *Sarcopenia/epidemiology ; *COVID-19/complications/epidemiology/mortality ; Prevalence ; Prognosis ; SARS-CoV-2 ; Length of Stay/statistics &amp; numerical data ; Hospitalization/statistics &amp; numerical data ; }, abstract = {BACKGROUND: A comprehensive investigation delineating the prevalence of sarcopenia across different infection phases, from acute COVID-19 to long COVID, is lacking. Meanwhile, the relationship between sarcopenia and adverse outcomes among COVID-19 patients remains inconsistent.<br><br>MATERIALS AND METHODS: A systematic search of MEDLINE/PubMed, Embase, Cochrane Library, Web of Science, and Scopus, before 22nd February 2025, was conducted to identify studies assessing sarcopenia prevalence in acute COVID-19 and long COVID. Random effects meta-analyses were performed to estimate the pooled prevalence of sarcopenia for acute COVID-19 and long COVID patients. Subgroup analyses stratified by assessment tool, region, income, hospitalization status, and age were performed. The associations between sarcopenia and COVID-19-related clinical outcomes were further quantified.<br><br>RESULTS: A total of 39 studies with 6,982 individuals were included. The pooled prevalence of sarcopenia was 48.7% (95% confidence interval (CI): 39.6-57.9%) in acute COVID-19 and 23.5% (95% CI: 12.7-39.4%) in long COVID. In acute COVID-19 patients, sarcopenia was not significantly associated with length of stay (mean difference = 2.215, 95% CI: -0.004 to 4.433), mechanical ventilation (Odds ratio (OR) = 1.80, 95% CI: 0.84-3.85), admission to the intensive care unit (OR = 1.05, 95% CI: 0.63-1.77), or mortality (OR = 1.41, 95% CI: 0.86-2.32), but was significantly associated with tracheostomy (OR = 2.48, 95% CI: 1.28-4.82).<br><br>CONCLUSION: In conclusion, our findings indicate that sarcopenia is highly prevalent in acute COVID-19 and persists in a substantial proportion of long COVID patients, suggesting prolonged muscle loss beyond the acute phase. Future well-designed studies are needed to further investigate the association between sarcopenia and short-term and long-term prognostic outcomes in both acute and long COVID patients.}, }
@article {pmid40563736, year = {2025}, author = {Doskas, T and Vavougios, GD and Kormas, C and Kokkotis, C and Tsiptsios, D and Spiliopoulos, KC and Tsiakiri, A and Christidi, F and Aravidou, T and Dekavallas, L and Kazis, D and Dardiotis, E and Vadikolias, K}, title = {Neurocognitive Impairment After COVID-19: Mechanisms, Phenotypes, and Links to Alzheimer's Disease.}, journal = {Brain sciences}, volume = {15}, number = {6}, pages = {}, pmid = {40563736}, issn = {2076-3425}, abstract = {BACKGROUND/OBJECTIVES: SARS-CoV-2 can affect the central nervous system directly or indirectly. AD shares several similarities with long COVID cognitive impairment on a molecular and imaging level, as well as common risk factors. The objective of this review is to evaluate the incidence of post-acute COVID-19 cognitive impairment. Secondarily, we aim to determine if neuroinflammation in COVID-19 survivors may be associated with the onset of neurological disease, with a focus on Alzheimer's disease (AD).<br><br>METHODS: literature search up to March 2025 on the prevalence of cognitive deficits in COVID-19 survivors, underlying pathophysiology and associations with neurological disorders.<br><br>RESULTS: a wide array of neuropsychiatric manifestations is associated with COVID-19; executive function, memory, and attention are the most frequently reported neurocognitive deficits, regardless of COVID-19 severity. There are associations between the risks for cognitive deficits post-infection with the age of the patients and the severity of the disease. Increasing evidence suggests that neurocognitive deficits are associated with the onset of neurological and neuropsychiatric disease in COVID-19 survivors.<br><br>CONCLUSIONS: clinicians caring for COVID-19 survivors should actively investigate neurocognitive sequelae, particularly for patients with increased risk for cognitive deficits.}, }
@article {pmid40564201, year = {2025}, author = {Hemat Jouy, S and Tonchev, H and Mostafa, SM and Mahmoud, AM}, title = {Post-COVID Metabolic Fallout: A Growing Threat of New-Onset and Exacerbated Diabetes.}, journal = {Biomedicines}, volume = {13}, number = {6}, pages = {}, pmid = {40564201}, issn = {2227-9059}, support = {1R00HL140049-03/NH/NIH HHS/United States ; R00 HL140049/HL/NHLBI NIH HHS/United States ; P30 ES027792/ES/NIEHS NIH HHS/United States ; R01 HL161386/HL/NHLBI NIH HHS/United States ; 1R01HL161386-04/NH/NIH HHS/United States ; }, abstract = {Emerging evidence highlights the profound and lasting impact of severe illnesses such as COVID-19, particularly among individuals with underlying comorbidities. Patients with pre-existing conditions like diabetes mellitus (DM) are disproportionately affected, facing heightened risks of both disease exacerbation and the onset of new complications. Notably, the convergence of advanced age and DM has been consistently associated with poor COVID-19 outcomes. However, the long-term metabolic consequences of SARS-CoV-2 infection, especially its role in disrupting glucose homeostasis and potentially triggering or worsening DM, remain incompletely understood. This review synthesizes current clinical and experimental findings to clarify the bidirectional relationship between COVID-19 and diabetes. We critically examine literature reporting deterioration of glycemic control, onset of hyperglycemia in previously non-diabetic individuals, and worsening of metabolic parameters in diabetic patients after infection. Furthermore, we explore proposed mechanistic pathways, including pancreatic β-cell dysfunction, systemic inflammation, and immune-mediated damage, that may underpin the development or progression of DM in the post-COVID setting. Collectively, this work underscores the urgent need for continued research and clinical vigilance in managing metabolic health in COVID-19 survivors.}, }
@article {pmid40566294, year = {2025}, author = {Rocha, DM and Pedroso, AO and Menegueti, MG and Silveira, RCCP and Sousa, LRM and Gir, E and Reis, RK}, title = {Predictors of Anxiety, Depression, and Stress in Long COVID: Systematic Review of Prevalence.}, journal = {International journal of environmental research and public health}, volume = {22}, number = {6}, pages = {}, pmid = {40566294}, issn = {1660-4601}, support = {88881.657963/2021-01//Coordena&#xe7;&#xe3;o de Aperfeicoamento de Pessoal de N&#xed;vel Superior/ ; }, mesh = {Humans ; *COVID-19/psychology/epidemiology/complications ; *Anxiety/epidemiology/etiology ; *Depression/epidemiology/etiology ; Prevalence ; *Stress, Psychological/epidemiology/etiology ; Aged ; SARS-CoV-2 ; Adult ; }, abstract = {Anxiety, depression, and stress are prevalent psychosocial manifestations in Long COVID, and understanding their global impact can guide safe, effective, and evidence-based interventions. This study reviewed the literature to analyze the prevalence indicators and predictors of anxiety, depression, or stress experienced by adults and older adults with Long COVID. This systematic prevalence review was conducted using the databases MEDLINE via PubMed[®], CINAHL-EBSCO, Web of Science, Scopus, EMBASE, LILACS, and BDENF. Observational studies that assessed anxiety, depression, or perceived stress in adults and older adults with Long COVID were included, with no restrictions on time or language. Two reviewers independently conducted the selection process. Full texts were analyzed for their eligibility potential. Methodological quality was assessed using the JBI Critical Appraisal Checklist for Studies. Ten observational studies with moderate methodological quality were included. Anxiety and depression were the most prevalent psychosocial symptoms in Long COVID, reported in mild, moderate, and severe cases of COVID-19 infection. Prevalence rates reached up to 47.8% for anxiety, 37.3% for depression, and 23% for stress. The combined analysis revealed a pooled prevalence of 15.3% (95% CI: 10.8% to 20.2%). Being female, having pre-existing mental disorders or associated clinical comorbidities, experiencing severe infection in the acute phase, and receiving intensive care were predictors of greater mental burden. The experience of anxiety, depression, and stress in prolonged COVID-19 was reported in countries with different income levels and was disproportionately experienced, especially by women and individuals with associated clinical conditions or psychopathological comorbidities.}, }
@article {pmid40566540, year = {2025}, author = {Koutsiaris, AG and Karakousis, K}, title = {Long COVID Mechanisms, Microvascular Effects, and Evaluation Based on Incidence.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {6}, pages = {}, pmid = {40566540}, issn = {2075-1729}, abstract = {Since the initial reports of Long COVID symptoms, numerous pathophysiological mechanisms have been proposed to explain them; nevertheless, no consensus has been reached. Some of these mechanisms are directly linked to microcirculation, while others are related indirectly. Those with a direct connection involve the respiratory system (such as pulmonary embolism), the cardiovascular system (including cardiac arrest, heart failure, myocardial inflammation, stroke, endothelial dysfunction, and microangiopathy), hematological conditions (like coagulopathy, deep vein thrombosis, microclots, and endothelial irregularities), and brain function. However, few of these mechanisms are grounded in quantitative data and fundamental physiological principles. Furthermore, diagnostic and therapeutic methods remain inadequate. This report provides a brief overview of these processes, focusing primarily on quantitative data, recently proposed mechanisms, and advances in microcirculation, with a special emphasis on the tissue blood supply reduction (TBSR or SR in short) mechanism. Then, the SR pathophysiological mechanism is assessed based on the total incidence rate of the Long COVID symptoms that can be directly attributed to this mechanism. The proposed SR mechanism can account for seven principal Long COVID symptoms with a total normalized incidence of 76%.}, }
@article {pmid40575972, year = {2025}, author = {Zhu, T and Li, X and Gao, S and Cui, R and Wang, J and Deng, Q}, title = {Successful salvage therapy of ruxolitinib on interstitial pneumonia after long COVID or post-COVID-19 syndrome with follicular lymphoma: two case reports and literature review.}, journal = {Chinese clinical oncology}, volume = {14}, number = {3}, pages = {35}, doi = {10.21037/cco-24-106}, pmid = {40575972}, issn = {2304-3873}, mesh = {Humans ; Nitriles ; *Pyrazoles/therapeutic use ; *COVID-19/complications ; Pyrimidines ; *Lymphoma, Follicular/complications/drug therapy ; *Salvage Therapy/methods ; Male ; SARS-CoV-2 ; Middle Aged ; Female ; *Lung Diseases, Interstitial/drug therapy/etiology ; COVID-19 Drug Treatment ; Aged ; Methylprednisolone/therapeutic use ; }, abstract = {BACKGROUND: Immunocompromised patients with B lymphocyte deficiency and hypogammaglobulinemia after anti-CD19 chimeric antigen receptor (CAR) T cell therapy for relapsed/refractory follicular lymphoma (FL) are at high risk of severe coronavirus disease 2019 (COVID-19) infection.<br><br>CASE DESCRIPTION: In our study, two patients with refractory FL had persistent COVID-19 infection after their anti-CD19 CAR T cell therapy. The patients were diagnosed with post-COVID-19 syndrome or COVID-19 with interstitial inflammation and persistent hypoxemia. The patients received molnupiravir and Paxlovid, along with methylprednisolone therapy when their interleukin (IL)-6 levels were high. No response was observed in interstitial inflammation, persistent hypoxemia, or persistent positive expression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, the level of IL-6 decreased after these therapies. These two patients subsequently received low-dose ruxolitinib (5 mg, twice daily) as salvage therapy in combination with a gradually reduced dosage of methylprednisolone. After 1-2 months of ruxolitinib therapy, persistent hypoxemia was relieved, and interstitial inflammation was significantly absorbed. At the same time, the SARS-CoV-2 detection was found to be negative.<br><br>CONCLUSIONS: Ruxolitinib might be a safe and effective alternative salvage therapy for patients with COVID-19 having interstitial inflammation and persistent hypoxemia without high cytokine levels and no response to corticosteroids.}, }
@article {pmid40582622, year = {2025}, author = {Xu, K and He, W and Yu, B and Wang, JJ and Wu, J and Wang, DW}, title = {Unveiling the silent threat: COVID-19 and myocardial injury.}, journal = {Pharmacology &amp; therapeutics}, volume = {273}, number = {}, pages = {108904}, doi = {10.1016/j.pharmthera.2025.108904}, pmid = {40582622}, issn = {1879-016X}, mesh = {Humans ; *COVID-19/complications ; *Myocarditis/etiology/virology/diagnosis ; COVID-19 Vaccines/adverse effects ; SARS-CoV-2 ; COVID-19 Drug Treatment ; }, abstract = {Since COVID-19 firstly appeared in 2019 December, it has been defined as an infectious disease mainly performing lung symptoms, which contracted more attention. However, more and more findings indicate myocardial injury appears in considerable proportion of COVID-19 patients (30 % - 50 %) not only but also major cause leading to the death in patients, many of whom may be even without severe respiratory symptoms. Meanwhile myocarditis after injecting vaccines has been paid more attention to globally which always performs uncontrollable inflammation and lead to death. Now myocardial injury has been a main complication in patients with long COVID-19, which is worthy of attention. Furthermore, myocardial injury or myocarditis is detectable and treatable. In order to abstract attention to myocardial injury associated with COVID-19 and provide more evidence and experience for patients who still suffer myocardial injury from COVID-19 vaccines or long COVID-19, the review comprehensively summarized previous researches from pathogenesis, clinical symptoms, diagnosis and treatment and emphasized the crucial role of RASS inhibitors especially ARBs.}, }
@article {pmid40583757, year = {2025}, author = {Cornwell, WK and Levine, BD and Baptiste, D and Bhave, N and Desai, S and Dineen, E and Durstenfeld, M and Edward, J and Huang, M and Jacobsen, R and Kim, JH and Spatz, E and , }, title = {Exercise Intolerance and Response to Training in Patients With Postacute Sequelae of SARS-CoV2 (Long COVID): A Scientific Statement From the American Heart Association.}, journal = {Circulation}, volume = {152}, number = {5}, pages = {e50-e62}, doi = {10.1161/CIR.0000000000001348}, pmid = {40583757}, issn = {1524-4539}, mesh = {Humans ; *COVID-19/physiopathology/complications/therapy ; *Exercise Tolerance ; American Heart Association ; United States ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Exercise Therapy/methods ; Cardiovascular Deconditioning ; Quality of Life ; Exercise ; }, abstract = {The postacute sequelae of SARS-CoV-2, also known as Long COVID, may affect 10% to 25% of individuals diagnosed with SARS-CoV-2. More than 100 symptoms have been reported among patients with Long COVID, but almost all patients report severe fatigue, orthostatic intolerance, shortness of breath, and reductions in exercise tolerance. Emerging data suggest that cardiovascular deconditioning plays a major role in the development of this syndrome and that reductions in functional capacity among patients with Long COVID are comparable to reductions seen among individuals with cardiovascular deconditioning resulting from bed rest. Concern has been raised about the use of exercise training as part of the management strategy for patients with Long COVID. However, exercise training appropriately tailored to the patient with cardiovascular deconditioning may be an effective strategy to facilitate improvement in symptoms. This American Heart Association scientific statement provides a concise yet comprehensive overview of mechanisms contributing to development of Long COVID and methods by which exercise training may be applied to this unique patient population to alleviate symptoms and improve quality of life. In addition, methods of reintroducing exercise and return to play among athletes affected by COVID-19 are discussed.}, }
@article {pmid40589858, year = {2025}, author = {Saikarthik, J and Saraswathi, I and Padhi, BK and Shamim, MA and Alzerwi, N and Alarifi, A and Gandhi, AP}, title = {Structural and functional neuroimaging of hippocampus to study adult neurogenesis in long COVID-19 patients with neuropsychiatric symptoms: a scoping review.}, journal = {PeerJ}, volume = {13}, number = {}, pages = {e19575}, pmid = {40589858}, issn = {2167-8359}, mesh = {Humans ; *COVID-19/complications/diagnostic imaging/physiopathology ; *Hippocampus/diagnostic imaging/physiopathology/pathology ; *Neurogenesis/physiology ; SARS-CoV-2 ; Adult ; *Functional Neuroimaging ; *Mental Disorders/diagnostic imaging/physiopathology ; Neuroimaging ; Magnetic Resonance Imaging ; }, abstract = {BACKGROUND: Worsening of neuropsychiatric and neurodegenerative disorders occurs in COVID-19. Impaired adult neurogenesis is linked to most of the neuropsychiatric symptoms and disorders.<br><br>AIM: The current scoping review identified and mapped the available evidence on adult neurogenesis in long COVID-19, at a global level following the JBI methodology for scoping reviews and followed the framework by Arksey and O'Malley.<br><br>METHOD: Original studies focusing on structural and functional neuroimaging of the hippocampus to study adult neurogenesis in long COVID-19 were included in the review. Studies published in English language with no restriction on the time of publication were searched using the specified search strategy in PubMed, Web of Science, Embase, and SCOPUS. Articles obtained from the database search were collated and uploaded into the Nested Knowledge AutoLit semi-automated systematic review platform for data extraction.<br><br>RESULTS: The current review provides evidence of the potential alterations in adult neurogenesis in long COVID-19 and its potential link to neuropsychiatric sequelae of long COVID-19, with further research required to validate this assertion.<br><br>CONCLUSION: This review proposes conceptual and methodological approaches for future investigations to address existing limitations and elucidate the precise role of adult neurogenesis in the pathophysiology and treatment of long COVID-19.}, }
@article {pmid40590080, year = {2025}, author = {Goh, DY and Lam, WC and Zhong, LLD}, title = {Effect of interventions for the management of sleep disturbances in patients with long COVID: a systematic review and meta-analysis of randomized controlled trials.}, journal = {Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine}, volume = {21}, number = {11}, pages = {1993-2005}, pmid = {40590080}, issn = {1550-9397}, mesh = {Humans ; *COVID-19/complications ; *Sleep Wake Disorders/therapy/etiology ; Randomized Controlled Trials as Topic ; Quality of Life ; SARS-CoV-2 ; }, abstract = {STUDY OBJECTIVES: Long COVID presents with symptoms that persist for weeks or months postinfection, with sleep disturbances that significantly affect quality of life. The diverse approaches to managing sleep disturbances highlight the need for comparing treatment effectiveness to improve patient outcomes. This study systematically reviews and conducts a meta-analysis of randomized controlled trials to assess the effectiveness of current interventions for sleep disturbances in patients with long COVID and explores the underlying mechanisms and promising treatments.<br><br>METHODS: Relevant studies were identified through a comprehensive literature search across Embase, Web of Science, PubMed, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Data databases. The included studies focused on interventions aimed at managing patients with long COVID with sleep disturbances. Data extraction and analysis were performed, followed by a meta-analysis of comparable studies. The quality of evidence was assessed using the Cochrane Risk of Bias Tool (RoB 2.0) and the Grading of Recommendations, Assessment, Development, and Evaluation system.<br><br>RESULTS: Out of 3,352 retrieved studies, 14 were included in the systematic review and 2 in the meta-analysis. Interventions were categorized as pharmacological and nonpharmacological. Whereas most studies indicated improved sleep quality measured by standardized scales, some did not demonstrate significant benefits. The quality of evidence varied from low to moderate.<br><br>CONCLUSIONS: The results suggest that sleep disturbances in patients with long COVID result from a complex interplay of physiological, psychological, and neurological factors. Both pharmacological and nonpharmacological interventions show potential in managing these disturbances, with nonpharmacological approaches showing particular promise. To establish more robust evidence, more high-quality, large-scale randomized controlled trials are necessary in future research.<br><br>CITATION: Goh DY, Lam WC, Zhong LLD. Effect of interventions for the management of sleep disturbances in patients with long COVID: a systematic review and meta-analysis of randomized controlled trials. J Clin Sleep Med. 2025;21(11):1993-2005.}, }
@article {pmid40597822, year = {2025}, author = {Münte, C and Glattacker, M and Müller, S and Zülke, AE and Heinze, M and Riedel-Heller, SG and Pieper, D and Jacke, C and Deckert, S and Neumann, A}, title = {Long COVID in people with mental health disorders: a scoping review.}, journal = {BMC psychiatry}, volume = {25}, number = {1}, pages = {669}, pmid = {40597822}, issn = {1471-244X}, mesh = {Humans ; *COVID-19/complications/psychology ; *Mental Disorders/psychology/epidemiology/complications/therapy ; *Post-Acute COVID-19 Syndrome/complications/epidemiology/psychology ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Long COVID, Post COVID Syndrome or PASC (post-acute sequelae of COVID-19), according to the World Health Organization (WHO), is defined as the continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation. The term Long COVID will be used throughout this review. Little is known about individuals with pre-existing mental health conditions experiencing Long COVID. This scoping review aims to provide an overview of these individuals, focusing on: 1) the course of mental disorders, 2) care needs, 3) utilization of healthcare services, and 4) psychosocial aspects, as outlined by the International Classification of Functioning (ICF).<br><br>METHODS: This review followed the JBI (Joanna Briggs Institute) methodology for scoping reviews and the PRISMA extension for scoping reviews. We included reports focusing on individuals with at least one pre-existing mental health diagnosis and Long COVID. Full-text reports in English or German were included, with no geographical limitations. Literature searches were conducted in PubMed, Embase, and PsycINFO on November 1, 2023, for records published between January 2020 and October 2023. Six reviewers participated in the screening process in pairs, independently conducting study selection and data extraction. Conflicts were resolved by consensus. Citation tracking was performed, and data were summarized narratively in tables.<br><br>RESULTS: From 4256 initial hits and citation tracking, 8 reports were included. The studies were heterogeneous, including chart reviews, case reports, cross-sectional, and longitudinal studies. Evidence on the impact of Long COVID on pre-existing mental health conditions was inconsistent. Most findings focused on the course of mental health disorders, ranging from symptom worsening to new symptoms of anxiety, depression, or insomnia. Evidence on mental health care needs, service utilization, and psychosocial aspects was limited.<br><br>CONCLUSION: Limited evidence suggests that individuals with pre-existing mental health disorders who experience Long COVID may be at an increased risk of worsening mental health. However, critical aspects such as care needs, service utilization, and psychosocial factors remain under-researched, highlighting the need for further studies on mental health care for Long COVID.<br><br>REVIEW REGISTRATION: Open Science Framework https://osf.io/tqexa .<br><br>CLINICAL TRIAL NUMBER: Not applicable.}, }
@article {pmid40622467, year = {2025}, author = {Chatterjee, D and Maparu, K}, title = {Long COVID syndrome: exploring therapies for managing and overcoming persistent symptoms.}, journal = {Inflammopharmacology}, volume = {33}, number = {7}, pages = {4097-4113}, pmid = {40622467}, issn = {1568-5608}, mesh = {Humans ; *COVID-19/therapy/complications/epidemiology/physiopathology ; Post-Acute COVID-19 Syndrome ; COVID-19 Drug Treatment ; SARS-CoV-2 ; Risk Factors ; }, abstract = {Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), is a growing global health concern, affecting 10-35% of COVID-19 survivors. Characterized by persistent multisystem symptoms lasting beyond 12 weeks, common manifestations include fatigue, dyspnea, chest pain, cognitive impairment, depression, and anxiety. The underlying pathophysiology remains unclear but is likely to involve immune dysregulation, persistent inflammation, endothelial dysfunction, gut dysbiosis, and viral persistence. This review examines the epidemiology, risk factors, and clinical manifestations of long COVID, with a focus on its impact on cardiopulmonary, neurological, and mental health. Therapeutic approaches include pharmacological interventions such as anti-inflammatory agents, antioxidants, neuroprotective drugs, and repurposed medications. Non-pharmacological strategies, such as physical rehabilitation, cognitive therapy, dietary modification, and emerging therapies like stem cell therapy, as well as immunomodulatory approaches, offer promising avenues for recovery. We also highlight ongoing clinical trials evaluating targeted therapies for long-term COVID syndrome. Future research should focus on elucidating the pathophysiological mechanisms, identifying biomarkers, and optimizing personalized treatment strategies for long-term COVID-19 management.}, }
@article {pmid40640033, year = {2025}, author = {Giunta, S and Giuliani, A and Sabbatinelli, J and Olivieri, F}, title = {A multidimensional immunological perspective on long COVID.}, journal = {Cytokine &amp; growth factor reviews}, volume = {84}, number = {}, pages = {1-11}, doi = {10.1016/j.cytogfr.2025.07.001}, pmid = {40640033}, issn = {1879-0305}, mesh = {Humans ; *COVID-19/immunology/complications ; *SARS-CoV-2/immunology ; Inflammation/immunology ; Cytokines/immunology ; Post-Acute COVID-19 Syndrome ; Autoantibodies/immunology/blood ; }, abstract = {Long COVID is a chronic condition that arises after SARS-CoV-2 infection and is characterized by persistent and often debilitating symptoms, such as fatigue, cognitive dysfunction ("brain fog"), dyspnea, and autonomic disturbances. Increasing evidence suggests that Long COVID shares key immunopathological mechanisms with autoimmune diseases, primarily sustained immune dysregulation. In individuals with genetic or immunological susceptibility, SARS-CoV-2 infection can trigger the production of autoantibodies targeting cytokines, membrane receptors, and components of the autonomic nervous system (ANS), thereby disrupting neuroimmune homeostasis. This immune imbalance may impair anti-inflammatory regulatory pathways, such as the cholinergic anti-inflammatory pathway (CAP), and may contribute to a chronic state of inflammation and autoimmunity. One proposed contributor to this process is inflammaging - a chronic, low-grade inflammation associated with aging - which may not only predispose individuals to Long COVID but may also be amplified by the persistent immune activation seen in this condition. In this perspective, we propose a conceptual framework in which inflammaging, immune-tolerance breakdown, and autonomic dysfunctions interact to sustain the pathophysiology of Long COVID. We discuss emerging biomarkers across these axes, including inflammatory cytokines, circulating autoantibodies, immune cell phenotypes, epigenetic modifications, and heart rate variability. Advances in inflammaging-related biomarkers and biological clocks may support early identification of individuals at higher risk for persistent immune and autonomic dysregulation, ultimately informing more precise diagnostic and therapeutic strategies for Long COVID.}, }
@article {pmid40643301, year = {2025}, author = {Beka, SG and Griffiths, RF and Myers, JA and Skirrow, PM}, title = {Appropriate Screening Tests to Assess Post-COVID-19 Cognitive Dysfunction in Aeromedical Settings.}, journal = {Aerospace medicine and human performance}, volume = {96}, number = {5}, pages = {414-424}, doi = {10.3357/AMHP.6500.2025}, pmid = {40643301}, issn = {2375-6322}, mesh = {Humans ; *COVID-19/complications/psychology ; *Cognitive Dysfunction/diagnosis/etiology ; *Pilots/psychology ; *Aerospace Medicine ; *Neuropsychological Tests ; SARS-CoV-2 ; Mass Screening ; }, abstract = {INTRODUCTION: Post-COVID-19, 10-20% of individuals may experience long-term symptoms (some having cognitive deficits), even after mild or nonsymptomatic infection. A sufficiently sensitive screening test of cognitive function, based on the typical cognitive effects of COVID-19 and skills considered most relevant to pilot performance, would be highly beneficial to be used alongside other performance checks. This study aimed to identify appropriate screening tests for post-COVID-19 cognitive dysfunction.<br><br>METHODS: Initially, a systematic search and narrative review identified 13 screening tools that are likely to be effective in screening pilots for post-COVID-19 neurocognitive impairment. Following a more in-depth evaluation of the identified tools, five tests including the Trail Making Test, Symbol Digit Modalities Test, Stroop Color Word Test, Psychomotor Vigilance Test, and Paced Auditory Serial Addition Test were chosen for a Delphi evaluation exercise. A two-round modified Delphi process was undertaken with international aviation medicine and psychology experts to obtain a consensus on which of the identified tests would be appropriate to screen for cognitive dysfunction in pilots.<br><br>RESULTS: Based on evaluation of literature review findings and Delphi consultation with subject matter experts, the Trail Making Test and Symbol Digit Modalities Test were identified as quick and suitable screening tests likely to detect post-COVID-19 cognitive dysfunction.<br><br>DISCUSSION: These tools are objective, have good utility, are available in multiple versions, and assess cognitive abilities relevant to pilot performance. Their use for screening in aeromedical examinations would be further supported by confirming their ability to reliably detect neurocognitive impacts associated with COVID-19. Beka SG, Griffiths RF, Myers JA, Skirrow PM. Appropriate screening tests to assess post-COVID-19 cognitive dysfunction in aeromedical settings. Aerosp Med Hum Perform. 2025; 96(5):414-424.}, }
@article {pmid40649991, year = {2025}, author = {Hein, ZM and Thazin,  and Kumar, S and Che Ramli, MD and Che Mohd Nassir, CMN}, title = {Immunomodulatory Mechanisms Underlying Neurological Manifestations in Long COVID: Implications for Immune-Mediated Neurodegeneration.}, journal = {International journal of molecular sciences}, volume = {26}, number = {13}, pages = {}, pmid = {40649991}, issn = {1422-0067}, mesh = {Humans ; *COVID-19/immunology/complications ; SARS-CoV-2/immunology ; *Neurodegenerative Diseases/immunology/etiology ; Blood-Brain Barrier/immunology ; Biomarkers ; Post-Acute COVID-19 Syndrome ; *Immunomodulation ; }, abstract = {The COVID-19 pandemic has revealed the profound and lasting impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the nervous system. Beyond acute infection, SARS-CoV-2 acts as a potent immunomodulatory agent, disrupting immune homeostasis and contributing to persistent inflammation, autoimmunity, and neurodegeneration. Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by a spectrum of neurological symptoms, including cognitive dysfunction, fatigue, neuropathy, and mood disturbances. These are linked to immune dysregulation involving cytokine imbalance, blood-brain barrier (BBB) disruption, glial activation, and T-cell exhaustion. Key biomarkers such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NFL) correlate with disease severity and chronicity. This narrative review examines the immunopathological mechanisms underpinning the neurological sequelae of long COVID, focusing on neuroinflammation, endothelial dysfunction, and molecular mimicry. We also assess the role of viral variants in shaping neuroimmune outcomes and explore emerging diagnostic and therapeutic strategies, including biomarker-guided and immune-targeted interventions. By delineating how SARS-CoV-2 reshapes neuroimmune interactions, this review aims to support the development of precision-based diagnostics and targeted therapies for long COVID-related neurological dysfunction. Emerging approaches include immune-modulatory agents (e.g., anti-IL-6), neuroprotective drugs, and strategies for repurposing antiviral or anti-inflammatory compounds in neuro-COVID. Given the high prevalence of comorbidities, personalized therapies guided by biomarkers and patient-specific immune profiles may be essential. Advancements in vaccine technologies and targeted biologics may also hold promise for prevention and disease modification. Finally, continued interdisciplinary research is needed to clarify the complex virus-immune-brain axis in long COVID and inform effective clinical management.}, }
@article {pmid40656089, year = {2024}, author = {Burkauskas, J and Branchi, I and Pallanti, S and Domschke, K}, title = {Anxiety in post-covid-19 syndrome - prevalence, mechanisms and treatment.}, journal = {Neuroscience applied}, volume = {3}, number = {}, pages = {103932}, pmid = {40656089}, issn = {2772-4085}, abstract = {In addition to the general impact of the COVID-19 pandemic on anxiety-related mental state, anxiety and anxiety disorders have also been implicated within 'post-COVID-19 syndrome', i.e. following a SARS-CoV-2 infection. The present narrative review provides an update on the current state of knowledge on anxiety and anxiety disorders in the context of post-COVID-19 syndrome, on epidemiological, psychological, and biological factors that may contribute to anxiety following a SARS-CoV-2 infection, as well as on therapy options available for anxiety in the context of post-COVID-19 syndrome. A multi-step systematic literature search of PubMed and Web of Science databases was performed applying the following broad search terms: ("anxiety" OR "anxiety disorder") AND ("COVID" OR "COVID-19" OR "corona" OR "pandemic" OR "Post-COVID" OR "Long-COVID"). Eligible articles published until November 15, 2022 were included. Meta-analyses identified anxiety prevalence rates ranging from 16.6% to 29.6% after a SARS-CoV-2 infection. Premorbid anxiety has not reliably been shown to be associated with post-COVID-19 syndrome. Female sex, older age, severity of COVID-19 infection, hospitalization, reduced mobility, uncertainty, loneliness and low social support, anxiety sensitivity and cognitive inflexibility as well as biological factors such as immune dysregulation, alterations in the angiotensin system and hypothalamus-pituitary-adrenal axis activation have been identified as potential anxiety risk factors in the context of post-COVID-19 syndrome. Treatment options comprise pharmacotherapy with selective serotonin/noradrenaline reuptake inhibitors and (internet-/computer-based) cognitive behavioral psychotherapy, possibly augmented by mindfulness-based techniques, physical exercise and non-invasive brain stimulation. Provided corroboration of the currently suggested increased risk of anxiety in the context of post-COVID-19 syndrome by future large-scale, prospective studies, a standardized screening for anxiety in patients with a SARS-CoV-2 infection - particularly in individuals with risk factors - and a psychiatric consultation and liaison service should be established to provide preventive and therapeutic interventions as early as possible.}, }
@article {pmid40660830, year = {2025}, author = {Pagliano, P and Salzano, F and D'Amore, C and Spera, A and Conti, V and Folliero, V and Franci, G and Ascione, T}, title = {How do drug discovery scientists address the unmet need of long COVID syndrome therapeutics and what more can be done?.}, journal = {Expert opinion on drug discovery}, volume = {20}, number = {10}, pages = {1251-1265}, doi = {10.1080/17460441.2025.2534056}, pmid = {40660830}, issn = {1746-045X}, mesh = {Humans ; *COVID-19/complications/physiopathology ; Post-Acute COVID-19 Syndrome ; *Drug Discovery/methods ; *COVID-19 Drug Treatment ; *Antiviral Agents/pharmacology/therapeutic use/administration &amp; dosage ; COVID-19 Vaccines/administration &amp; dosage ; SARS-CoV-2 ; }, abstract = {INTRODUCTION: Long COVID (LC), also known as post-acute COVID-19 syndrome (PASC), has emerged as a significant public health concern characterized by persistent symptoms following SARS-CoV-2 infection. This condition affects regardless of initial illness severity and can significantly impair daily functioning. Understanding the implications of LC is crucial, given that approximately 6.9 % of adults reported related symptoms in 2022, with increased prevalence among women and individuals of Hispanic descent. The pathogenesis of LC is multifactorial, involving mechanisms such as endothelial dysfunction, chronic inflammation, immune dysregulation, and potential viral persistence. The clinical manifestations include fatigue, cognitive impairment, musculoskeletal pain, and sleep disturbances. Current research emphasizes the importance of early antiviral interventions and vaccines to mitigate the risk of developing LC. Despite promising therapies like anti-inflammatory agents and metabolic enhancers, the lack of established biomarkers complicates diagnosis and treatment.<br><br>AREAS COVERED: The authors provide an overview of the pathogenesis of LC and briefly review the currently available therapy. The authors then give their perspectives on how best future drug discovery efforts can be utilized to address the current demand for novel LC therapeutics to reduce the burden of this public health problem.<br><br>EXPERT OPINION: Progress has been made in understanding the pathophysiology and potential treatment options, as well as in establishing reliable biomarkers for potential tailored strategies. Future research should prioritize both pharmacological and non-pharmacological interventions to enhance patient outcomes and quality of life. Addressing these challenges is essential for developing comprehensive care protocols for individuals affected by LC.}, }
@article {pmid40663038, year = {2025}, author = {Avais, LS and Pacheco, EC and Gomes, LPOZ and Baldani, MH and Martins, CM and Waldman, EA and Gonzalez, JPJ and Steen, TY and Borges, PKO}, title = {Oral Manifestations in the Post COVID-19 Condition: A Systematic Review With Meta-Analysis.}, journal = {Reviews in medical virology}, volume = {35}, number = {4}, pages = {e70057}, pmid = {40663038}, issn = {1099-1654}, support = {//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; //Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; }, mesh = {Humans ; *COVID-19/complications/virology ; *Mouth Diseases/epidemiology/etiology/virology ; SARS-CoV-2/pathogenicity ; *Taste Disorders/epidemiology/virology ; Prevalence ; Xerostomia ; }, abstract = {Post-COVID-19 condition, or Long COVID, is characterised by symptoms persisting or emerging beyond 12 weeks after acute infection. Among over 200 reported symptoms, oral manifestations such as taste loss and dry mouth have been identified. This systematic review reports the frequency and characteristics of these symptoms. Registered in PROSPERO and following PRISMA guidelines, the review included observational studies on COVID-19-positive adults presenting oral symptoms in the post-COVID-19 condition. A search in six databases (Medline/PubMed, Embase, Web of Science, Cochrane, SCOPUS, and LILACS) was conducted in January 2024. Risk of bias was assessed using Joanna Briggs Institute's critical appraisal tools, and certainty of evidence via GRADE. A meta-analysis using the inverse variance method estimated oral symptom prevalence. Of 4552 articles, 107 were included. Taste dysfunction persisted in 8% (95% CI 6%-10%) of patients beyond 12 weeks. Combined taste and smell alterations had a prevalence of 17% (95% CI 13%-21%). Less frequent symptoms included hyposalivation, periodontitis, mouth ulcers, tongue mucosal changes, facial tingling, sensitivity in the trigeminal nerve, difficulty swallowing, and lesions in the hard palate. Taste alterations were the most commonly reported symptom, underscoring the need for clinical recognition and appropriate management by oral health professionals. Additionally, the wide range of other oral manifestations highlights the necessity for further research to better understand their prevalence, underlying mechanisms, and clinical implications in post-COVID-19 patients.}, }
@article {pmid40670058, year = {2025}, author = {Aretouli, E and Malik, M and Widmann, C and Parker, AM and Oh, ES and Vannorsdall, TD}, title = {Cognitive and mental health outcomes in long covid.}, journal = {BMJ (Clinical research ed.)}, volume = {390}, number = {}, pages = {e081349}, doi = {10.1136/bmj-2024-081349}, pmid = {40670058}, issn = {1756-1833}, mesh = {Humans ; *COVID-19/psychology/complications ; SARS-CoV-2 ; Mental Health ; *Cognitive Dysfunction/etiology ; Post-Acute COVID-19 Syndrome ; *Anxiety/etiology ; Risk Factors ; *Depression/etiology ; }, abstract = {Roughly one in five adults who meet criteria for long covid present with objective or subjective cognitive dysfunction or elevated symptoms of depression or anxiety lasting ≥12 weeks from an acute covid illness. These neuropsychiatric sequelae have considerable functional consequences at the level of the individual, society, and the broader economy. Neuropsychiatric long covid symptoms are thought to be causally diverse, and a range of risk factors as well as biological, psychological, and environmental mechanisms have been hypothesized to contribute to symptom development and persistence. When present, objective cognitive deficits tend to be modest for most individuals, with some evidence suggesting increased risk of dysfunction and decline specifically for older adults with a history of severe acute illness. Longitudinal data suggest a delayed emergence of psychiatric symptoms may occur in the weeks and months after an acute covid illness. Emerging research points to the early recovery period as a potential window of opportunity for intervention to alter patient trajectories, though evidence based treatment remains lacking.}, }
@article {pmid40671020, year = {2025}, author = {Wang, Y and Li, X and Hui, H and Yang, D}, title = {Efficacy and safety of traditional Chinese medicine for post-COVID-19 syndrome: a systematic review and meta-analysis.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {801}, pmid = {40671020}, issn = {1479-5876}, mesh = {Humans ; *Medicine, Chinese Traditional/methods/adverse effects ; *COVID-19/complications ; *Drugs, Chinese Herbal/therapeutic use/adverse effects ; Randomized Controlled Trials as Topic ; Treatment Outcome ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Fatigue/drug therapy ; Cough/drug therapy ; *COVID-19 Drug Treatment ; }, abstract = {BACKGROUND: Post-COVID-19 syndrome, characterized by persistent symptoms such as fatigue, dyspnea, cough, insomnia, and exercise intolerance, poses a significant challenge to global healthcare systems. Traditional Chinese Medicine (TCM) has been used to manage post-viral syndromes, but high-quality evidence for its effectiveness in post-COVID-19 recovery is limited. This study aimed to evaluate the clinical efficacy and safety of Chinese herbal medicine (CHM) in treating post-COVID-19 syndrome through a systematic review and meta-analysis of randomized controlled trials (RCTs).<br><br>METHODS: Five electronic databases (PubMed, Embase, Web of Science, Cochrane Library and CNKI) were systematically searched up to March 15, 2025. RCTs comparing CHM with placebo or usual care in patients with confirmed post-COVID-19 syndrome were included. Primary outcomes were symptom severity measured by the Visual Analogue Scale (VAS); secondary outcomes included relief rates of cough, fatigue, chest tightness, dyspnea, insomnia, and exercise intolerance. Data were pooled using a random-effects model, and heterogeneity was assessed using I[2] statistics.<br><br>RESULTS: Ten RCTs involving 2401 patients were included. CHM showed a greater reduction in VAS scores compared to controls (MD&#x2009;=&#x2009;-1.03; 95% CI -2.10 to 0.03; P&#x2009;=&#x2009;0.0577), with higher heterogeneity (I[2]&#x2009;=&#x2009;92%). Although this result did not reach conventional statistical significance, it suggests a potentially meaningful clinical trend favoring CHM. Subgroup analysis indicated both short-term and long-term CHM treatments improved VAS scores, with a stronger effect in long-term treatment. CHM significantly improved chest tightness (RR&#x2009;=&#x2009;1.40; 95% CI 1.21-1.61; P&#x2009;<&#x2009;0.0001; I[2]&#x2009;=&#x2009;0%) and insomnia (RR&#x2009;=&#x2009;1.23; 95% CI 1.03-1.47; P&#x2009;=&#x2009;0.0216; I[2]&#x2009;=&#x2009;0%). A trend toward improvement was observed in fatigue (RR&#x2009;=&#x2009;1.58, 95% CI 0.95-2.64; P&#x2009;=&#x2009;0.0781) and dyspnea (RR&#x2009;=&#x2009;1.39, 95% CI 0.99-1.95; P&#x2009;=&#x2009;0.0554), although these results did not reach statistical significance. No significant difference was observed in terms of 6-min walking distance (MD&#x2009;=&#x2009;13.95&#xa0;m, 95% CI -11.64 to 39.55; P&#x2009;=&#x2009;0.2853). Adverse event rates were comparable between the herbal and control groups (RR&#x2009;=&#x2009;0.72, 95% CI 0.49-1.07; P&#x2009;=&#x2009;0.1052).<br><br>CONCLUSIONS: This meta-analysis indicates that Traditional Chinese Medicine (TCM) may help relieve certain post-COVID-19 symptoms, especially chest tightness and insomnia. Trends toward benefit were also noted for fatigue and dyspnea, though without statistical significance. Given the non-significant VAS results and high heterogeneity, these findings should be interpreted cautiously. Further large-scale, high-quality trials are needed to validate these outcomes and optimize treatment strategies.<br><br>https://www.crd.york.ac.uk/PROSPERO/home , CRD420251016442.}, }
@article {pmid40676931, year = {2025}, author = {Abdul-Azees, PA and Marinkovic, M and Singh, BB and Dean, DD and Chen, XD and Goldberg, MP and Restrepo, MI and Loomer, PM and Yeh, CK}, title = {The Impact of Aging Oral Health on Long COVID-19.}, journal = {Journal of dental research}, volume = {104}, number = {12}, pages = {1294-1303}, doi = {10.1177/00220345251349805}, pmid = {40676931}, issn = {1544-0591}, mesh = {*Oral Health ; Humans ; SARS-CoV-2 ; *COVID-19/complications/immunology ; *Post-Acute COVID-19 Syndrome ; Mouth Diseases/virology ; *Aging/immunology/physiology ; Hospitalization/statistics &amp; numerical data ; }, abstract = {At least 10% of individuals infected with SARS-CoV-2 develop a variety of multisystem symptoms lasting more than 12 wk known as postacute sequelae of COVID-19 (PASC) or "long COVID." While the precise pathogenesis of PASC remains unclear, immune dysregulation is widely recognized as a key factor. Moreover, PASC disproportionately affects older individuals who are prone to age-related immune system decline, which further exacerbates the risk and severity of PASC. The oral cavity, a primary site for initial SARS-CoV-2 infection, may contribute to the development and persistence of PASC. Emerging evidence suggests that changes in age-related oral health, such as periodontitis, salivary gland (SG) dysfunction, and gustatory and olfactory impairments, may create an environment conducive to forming an oral reservoir of intact virus or viral antigens, which may contribute to the chronicity of PASC. Alternatively, the pathogenesis of PASC may increase the risk of a wide range of oral health issues, such as dental diseases, dry mouth, and sensory dysfunction (e.g., taste and smell) that are frequently reported by patients with PASC. This review highlights how aging facilitates oral SARS-CoV-2 infection, co-infection with other viruses may drive PASC in aging patients, aging and PASC dysregulate the oral microbiome, SARS-CoV-2 infection promotes molecular mechanisms involved in oral tissue aging, aging oral health affects susceptibility to developing PASC, and inflammation associated with PASC exacerbates dysregulation of metabolic/enzymatic pathways of aging oral mucosa and diseases of the periodontal apparatus, SGs, and taste. It underscores the urgent need to comprehensively address the interplay between aging oral health and PASC, which will help mitigate long-term complications and improve overall health outcomes for affected individuals.}, }
@article {pmid40677535, year = {2024}, author = {Mundra, P and Kailani, Z and Yaghoobi, M and Matthews, P and Tobis, M and Sadeghian, S and Albashir, S}, title = {Liver injury in post-acute COVID-19 syndrome: A systematic review and meta-analysis of early observational studies.}, journal = {Canadian liver journal}, volume = {7}, number = {4}, pages = {470-489}, pmid = {40677535}, issn = {2561-4444}, abstract = {BACKGROUND: Post-acute COVID-19 syndrome (PACS; long COVID) is characterized by persistent or delayed symptoms at least 4 weeks from acute COVID-19 infection. Given the well-documented incidence of liver injury in acute COVID-19, this systematic review aims to assess the odds of liver injury in earlier experiencers of PACS.<br><br>METHODS: Observational studies published prior to March 2022 were screened for data describing liver injury (defined per primary study) in patients with PACS.<br><br>RESULTS: A total of 2,117 abstracts and 35 full texts were screened, of which 26 met the inclusion criteria. The mean time since acute COVID infection across all studies was 195.5 days. Seven studies included COVID-negative control groups. Twenty-three studies measured lab findings, and nine studies measured imaging or elastography. Five studies were eligible for meta-analysis of odds ratios, which did not demonstrate a statistically significant difference in odds for liver injury in patients with PACS compared with COVID-negative patients (OR 2.22 [95% CI 0.51-9.61; p = 0.28]). Newcastle-Ottawa Scale assessments for all studies found 24 of 26 studies with high to very high risk of bias. ROBINS-E assessments for studies included in the meta-analysis found five of five studies with high to very high risk of bias.<br><br>CONCLUSIONS: Overall, our findings demonstrate no statistical difference in odds ratios of liver injury in patients with PACS compared with COVID-negative controls. As such, routine assessment and monitoring of liver injury in patients with PACS may not be required; however, higher quality data with lower risk of bias are required to make recommendations of higher certainty.}, }
@article {pmid40680383, year = {2025}, author = {Chen, TH and Jeng, TH and Lee, MY and Wang, HC and Tsai, KF and Chou, CK}, title = {Viral mitochondriopathy in COVID-19.}, journal = {Redox biology}, volume = {85}, number = {}, pages = {103766}, pmid = {40680383}, issn = {2213-2317}, mesh = {Humans ; *COVID-19/virology/metabolism/pathology/immunology/complications ; *SARS-CoV-2/pathogenicity ; *Mitochondria/metabolism/virology/pathology ; Mitochondrial Dynamics ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), disrupts cellular mitochondria, leading to widespread chronic inflammation and multi-organ dysfunction. Viral proteins cause mitochondrial bioenergetic collapse, disrupt mitochondrial dynamics, and impair ionic homeostasis, while avoiding antiviral defenses, including mitochondrial antiviral signaling. These changes drive both acute COVID-19 and its longer-term effects, known as "long COVID". This review examines new findings on the mechanisms by which SARS-CoV-2 affects mitochondria and for the impact on chronic immunity, long-term health risks, and potential treatments.}, }
@article {pmid40683613, year = {2025}, author = {Chen, K and Wang, Z and Li, J and Xu, Y and Gu, S and Li, H and Li, J and Zhang, Y and Mao, N}, title = {Chronic inflammation in Long COVID relationship to autoimmune diseases.}, journal = {Autoimmunity reviews}, volume = {24}, number = {10}, pages = {103882}, doi = {10.1016/j.autrev.2025.103882}, pmid = {40683613}, issn = {1873-0183}, mesh = {Humans ; *COVID-19/immunology/complications ; *Autoimmune Diseases/immunology/therapy/complications ; *SARS-CoV-2/immunology ; *Inflammation/immunology ; Chronic Disease ; Gastrointestinal Microbiome/immunology ; Post-Acute COVID-19 Syndrome ; }, abstract = {The new coronavirus pandemic has been ongoing for nearly five years. In addition to the severe symptoms in the acute phase, it is accompanied by long-term complications and sequelae involving the respiratory, neurological, immune, circulatory, and gastrointestinal systems for several months or even years, which is called the Long COVID. Many studies have suggested that systemic chronic inflammation caused by residual viral components may be one of the pathophysiologic mechanisms of Long COVID. In this paper, we will review the autoimmune diseases caused by chronic inflammation. In particular, cytokine storminess, pro-inflammatory responses of inflammatory vesicles, mast cell activation syndrome, changes in the gut microbiota, molecular mimicry, reactivation of latent viruses, and coagulation abnormalities are among the pathways that contribute to autoimmune diseases, including Systemic Lupus Erythematosus, Guillain-Barré syndrome, rheumatoid arthritis. We intervene in the treatment of the disease with probiotics, immunoglobulins, the RECOVER clinical trial model, and immunomodulatory drugs. The aim is to enhance understanding of the pathophysiological mechanism of Long COVID and to provide a reference for the immunotherapy of patients.}, }
@article {pmid40684905, year = {2025}, author = {Gershon, AS and Fung, D and Lam, GY}, title = {Diagnosing Respiratory Long COVID: A Practical Approach.}, journal = {Chest}, volume = {168}, number = {4}, pages = {874-879}, pmid = {40684905}, issn = {1931-3543}, mesh = {Humans ; *COVID-19/complications/diagnosis/physiopathology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Dyspnea/etiology ; Cough/etiology ; Male ; Fatigue/etiology ; Middle Aged ; Female ; }, abstract = {Long COVID or a post-COVID condition, defined as the persistence of symptoms at least 3 months after acute COVID-19 infection, is a novel condition in which a definitive diagnostic marker and treatment have yet to be found. This condition, which has been estimated to impact > 65 million individuals worldwide, manifests with multisystem involvement, most commonly presenting with fatigue, brain fog, dyspnea, cough, or a combination thereof. The burden of these symptoms can range from mild to severe, with many patients reporting an inability to return to usual activities. Herein, we present several hypothetical but clinically representative case reports to allow discussion around how we approach the diagnosis of respiratory symptoms of long COVID in those with and without chronic lung disease.}, }
@article {pmid40685660, year = {2025}, author = {Davis, S and Mon-Yee, M and Sutton, A and Leaviss, J and Forsyth, JE and Burton, C}, title = {Cost effectiveness of non-pharmacological interventions for fatigue in patients with long-term conditions: a systematic literature review.}, journal = {Expert review of pharmacoeconomics &amp; outcomes research}, volume = {25}, number = {8}, pages = {1159-1166}, doi = {10.1080/14737167.2025.2537194}, pmid = {40685660}, issn = {1744-8379}, mesh = {Humans ; Cost-Benefit Analysis ; *Cognitive Behavioral Therapy/economics/methods ; *Fatigue/therapy/economics/etiology ; Chronic Disease ; *Exercise Therapy/economics/methods ; United Kingdom ; Cost-Effectiveness Analysis ; }, abstract = {INTRODUCTION: We aimed to assess the cost-effectiveness of non-pharmacological interventions for fatigue in patients with chronic conditions in the UK.<br><br>METHODS: This systematic review of cost-effectiveness studies aligns with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 statement. Data sources: Electronic databases and citation searches. Inclusion criteria: Studies including adults with one or more long-term health condition, either physical or mental. Exclusion criteria: Studies associated with cancer, long-COVID, post-viral fatigue, medically unexplained conditions, developmental disorders and injuries. Assessment: A single reviewer completed a two-stage sifting process.<br><br>RESULTS: Four studies met the inclusion criteria. They included patients with either multiple sclerosis or inflammatory rheumatic conditions, and assessed either cognitive behavioral therapy (CBT) or a personalized exercise program (PEP). CBT was either dominated by usual care or had an incremental cost-effectiveness ratio (ICER) over &#xa3;30,000. PEP dominated CBT, with the ICER for PEP versus usual care ranging from &#xa3;13,159 to &#xa3;35,424.<br><br>CONCLUSIONS: The economic literature on this topic is much more limited than the clinical effectiveness literature, both in terms of interventions and populations covered. Future research should focus on a de novo economic evaluation to identify interventions with a high potential to be cost-effective across multiple conditions.<br><br>REGISTRATION: PROSPERO (CRD42023440141).}, }
@article {pmid40696830, year = {2025}, author = {Paulose, M and Adams, NN and Martin, KR and Grant, A}, title = {Lived Experiences of New-Onset Long Covid Pain and Its Impact on Health-Related Quality of Life. A Scoping Review of Current Evidence.}, journal = {Health expectations : an international journal of public participation in health care and health policy}, volume = {28}, number = {4}, pages = {e70352}, pmid = {40696830}, issn = {1369-7625}, support = {//The authors received no specific funding for this work./ ; }, mesh = {Humans ; *Quality of Life/psychology ; *COVID-19/complications/psychology ; *Chronic Pain/psychology/etiology ; SARS-CoV-2 ; }, abstract = {INTRODUCTION: Long Covid (LC) is a multisystem condition that can cause persistent symptoms such as breathlessness, fatigue, cognitive problems and pain, with major effects on individuals and healthcare systems. Globally, nearly 400 million people have been affected. New-onset pain is among the most commonly reported symptoms and may develop into chronic pain, contributing to reduced health-related quality of life (HRQoL) and highlighting the need for appropriate care. Given its global prevalence, exploring how people experience new-onset LC pain and how it impacts their lives can help improve pain management and support services.<br><br>METHODS: A mixed-methods scoping review was conducted following the Joanna Briggs Institute (JBI) guidance and the Preferred Reporting Items for Systematic Reviews Extension for Scoping Reviews (PRISMA-ScR). The review mapped and synthesised evidence from eligible primary research articles (quantitative, qualitative and mixed-methods) published in English between December 2019 and June 2024. Seven studies using cross-sectional, case-control and observational designs (n&#x2009;=&#x2009;30 to 2507 participants) were included, with data collected from Europe and Asia.<br><br>RESULTS: While qualitative data on lived experience were limited, 69.5% of LC patients reported new-onset pain, most commonly musculoskeletal (MSK) pain (73.2%). Psychological symptoms such as post-traumatic stress disorder (PTSD) were also reported (38%). Pain medications were widely used. Findings suggest that new-onset LC pain affects physical, psychological and social well-being. No studies involving children or adolescents were identified, indicating a gap in the evidence on paediatric experiences of new-onset LC pain.<br><br>CONCLUSION: This review highlights major gaps in the literature, especially the lack of qualitative research on how people experience new-onset LC pain. Future research should explore these experiences in depth, with involvement from patients and the public, to inform the development of appropriate treatment and support strategies.<br><br>During the review process, opportunities to involve PPI were not fully explored due to limited awareness of how to support meaningful involvement in a scoping review, alongside time and resource constraints. Such involvement could have helped shape the review question, refine the search terms and interpret the findings in ways that better reflect lived experience. This is acknowledged as both a limitation and a learning point. PPI will be actively embedded in the next phases of the research.}, }
@article {pmid40707035, year = {2025}, author = {Meagher, T}, title = {Long Covid in Year 5: Some Progress, Still Many Questions.}, journal = {Journal of insurance medicine (New York, N.Y.)}, volume = {52}, number = {2}, pages = {61-65}, doi = {10.17849/insm-52-2-1-5.2}, pmid = {40707035}, issn = {0743-6661}, mesh = {Humans ; *COVID-19/complications/epidemiology/physiopathology ; Fatigue Syndrome, Chronic ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {Long Covid was first described in 2020. Five years later, progress in disease characterization has been considerable, and definitions continue to evolve. Several disease mechanisms are under study, and evidence for multiple endotypes is accumulating. No clinical biomarker has been identified, nor has an effective therapy been developed. Overlap with other post-infectious syndromes, particularly myalgic encephalomyelitis/chronic fatigue syndrome, is now more evident. For most individuals, symptoms of long Covid progressively disappear over time. Recurrent Covid-19 infections are now an important contributor to the pool of affected individuals. While symptoms limit activity in as many as 20%, inability to work is less common. The anticipated surge of disability claims from insured individuals has not materialized.}, }
@article {pmid40708204, year = {2025}, author = {Malerba, M and Purghè, B and Ragnoli, B and Manfredi, M and Baldanzi, G}, title = {Molecular profiling of exhaled breath condensate in respiratory diseases.}, journal = {Annals of medicine}, volume = {57}, number = {1}, pages = {2537910}, pmid = {40708204}, issn = {1365-2060}, mesh = {Humans ; Breath Tests/methods ; *COVID-19/metabolism/diagnosis ; Metabolomics/methods ; Proteomics/methods ; SARS-CoV-2 ; Exhalation ; Pulmonary Disease, Chronic Obstructive/diagnosis/metabolism ; Asthma/diagnosis/metabolism ; Mass Spectrometry/methods ; Biomarkers/analysis ; *Respiratory Tract Diseases/diagnosis/metabolism ; }, abstract = {BACKGROUND: Respiratory disorders, , continue to pose a major global health burden. Their complexity and heterogeneity challenge accurate diagnosis, effective monitoring, and therapeutic decision-making. Exhaled breath condensate (EBC) provides a reliable, non-invasive means of sampling the molecular environment of the airways.<br><br>AIM: This review presents the state-of-the-art in EBC-based omics approaches-particularly metabolomics and proteomics-to characterize molecular signatures associated with chronic respiratory (e.g. asthma, chronic obstructive pulmonary disease, and rhinitis) and infectious diseases (e.g. COVID-19).<br><br>RESULTS: We critically examine findings from studies applying nuclear magnetic resonance (NMR), mass spectrometry (MS), and sensor-based technologies to analyze EBC across various respiratory conditions. NMR, valued for its reproducibility and minimal sample preparation, consistently discriminates among disease phenotypes, identifies distinct metabotypes, and monitors treatment response over time. MS-based approaches afford enhanced sensitivity and specificity, enabling detailed profiling of inflammatory mediators, such as lipid-derived eicosanoids and amino acid derivatives. Proteomic studies reveal protein-level alterations associated with inflammation and tissue remodeling. In COVID-19 and long COVID, metabolomic and volatile compound profiling distinguishes affected individuals from healthy controls suggesting clinical potential. However, inconsistent sample processing and lack of analytical standardization remain limiting factors.<br><br>CONCLUSIONS: EBC profiling shows clear promise for improving diagnosis, monitoring, and stratification in respiratory medicine. Yet, translation into clinical practice is hindered by limited standardization and validation. Broader, longitudinal studies will be essential to establish robust molecular signatures across disease states. This review underscores the timely need to implement breathomics investigations to gain mechanistic insight into the underlying biology of respiratory diseases.}, }
@article {pmid40717478, year = {2025}, author = {Bajić, D and Todorović, N and Popović, ML and Plazačić, M and Mihajlović, A}, title = {Immunity's core reset: Synbiotics and gut microbiota in the COVID-19 era.}, journal = {Innate immunity}, volume = {31}, number = {}, pages = {17534259251362023}, pmid = {40717478}, issn = {1753-4267}, mesh = {Humans ; *COVID-19/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; *Synbiotics/administration &amp; dosage ; *SARS-CoV-2/immunology ; *Dysbiosis/immunology/microbiology ; Probiotics/therapeutic use ; Prebiotics/administration &amp; dosage ; Inflammation/immunology ; }, abstract = {The gut microbiome plays a crucial role in shaping immune responses, and its connection to immunity has never been more relevant than in the COVID-19 era. The interaction between gut microbes and the immune system, known as microbiome-immunity crosstalk, influences both how the body responds to infections and how well it recovers. COVID-19, whether in its acute phase or lingering as long COVID, has been linked to disturbances in the gut microbiome. During infection, many patients experience dysbiosis-an imbalance in gut bacteria-that can contribute to immune dysfunction and excessive inflammation. This imbalance may not only worsen the severity of the disease but also prolong recovery, leading to persistent symptoms like fatigue, brain fog, and digestive issues. Long COVID, in particular, has been associated with ongoing immune dysregulation, where the body's defense system remains in a state of heightened activation, causing chronic inflammation. Given the strong link between gut health and immunity, there is growing interest in strategies to restore microbial balance. Synbiotics-combinations of probiotics (beneficial bacteria) and prebiotics (nutrients that support them)-are being explored as a potential therapeutic approach. By replenishing beneficial gut microbes, synbiotics may help regulate immune responses, reduce inflammation, and support overall recovery from COVID-19. Emerging research suggests that improving gut health could enhance the body's ability to fight infections and recover more efficiently. As we continue to understand the long-term impact of COVID-19, focusing on the gut microbiome offers a promising path forward. Supporting a balanced and diverse microbiome through diet, lifestyle, and targeted interventions like synbiotics may provide a natural way to strengthen immunity and improve health outcomes in both acute and long COVID cases.}, }
@article {pmid40721817, year = {2025}, author = {Yogendra, R and Perlowski, A and Johng, B and Dahshan, H and Orr, C and Jeffers, D and Husain, K and Patterson, BK}, title = {Perioperative and anesthetic considerations for post-acute sequelae of COVID (PASC)/long COVID.}, journal = {Perioperative medicine (London, England)}, volume = {14}, number = {1}, pages = {80}, pmid = {40721817}, issn = {2047-0525}, abstract = {Post-acute sequelae of COVID (PASC), commonly known as long COVID, presents with a broad spectrum of medical conditions and symptoms persisting beyond 3 months post-SARS-CoV-2 infection, affecting over 18 million Americans and 65 million people worldwide. Despite its prevalence, to date, there are no specific clinical guidelines for the perioperative management of PASC patients. PASC is a complex, multisystemic condition leading to neurological, respiratory, and endocrine sequelae, potentially resulting from persistent viral presence, immune dysregulation, and/or end-organ damage. This manuscript discusses the implications of these sequelae on anesthesia practice, emphasizing the need for vigilance in pre-operative assessments to identify PASC and associated conditions through detailed patient history, understanding of off-label medication use, and familiarity with medical terminologies like POTS, MCAS, and brain fog. Key perioperative considerations include cautious use of anesthetics, especially in patients with neurological and cardiovascular complications. Pulmonary management strategies for PASC patients, such as lung-protective ventilation and non-invasive post-operative support, could mitigate any perioperative respiratory complications. Finally, we underscore the importance of a multidisciplinary approach to manage PASC patients effectively during surgery, advocating for personalized anesthetic plans and calling for more evidence-driven guidelines for this emerging patient group as research progresses.}, }
@article {pmid40723876, year = {2025}, author = {Richardson, E and Mo, CC and Calabretta, E and Corrado, F and Kocoglu, MH and Baron, RM and Connors, JM and Iacobelli, M and Wei, LJ and Benjamin, EJ and Rapoport, AP and Díaz-Ricart, M and Martínez-Mellado, AJ and Carlo-Stella, C and Richardson, PG and Moraleda, JM}, title = {Defibrotide for Protecting Against and Managing Endothelial Injury in Hematologic Malignancies and COVID-19.}, journal = {Biomolecules}, volume = {15}, number = {7}, pages = {}, pmid = {40723876}, issn = {2218-273X}, mesh = {Humans ; *Hematologic Neoplasms/drug therapy/complications/pathology ; *Polydeoxyribonucleotides/therapeutic use/pharmacology ; *COVID-19/complications/pathology/virology ; SARS-CoV-2 ; Hepatic Veno-Occlusive Disease/drug therapy ; *COVID-19 Drug Treatment ; Graft vs Host Disease/drug therapy ; Cytokine Release Syndrome/drug therapy ; *Fibrinolytic Agents/therapeutic use/pharmacology ; }, abstract = {Defibrotide, which is approved for treating hepatic veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS), exhibits pleiotropic anti-inflammatory, anti-thrombotic, and fibrinolytic properties, conferring broad endothelial protective effects. Given these mechanisms, defibrotide has potential utility in various conditions involving endothelial injury or activation. In this review we outline the endothelial-protective mechanisms of defibrotide and comprehensively summarize current evidence supporting its applications in hematologic malignancies, including the prevention and treatment of hepatic VOD/SOS, graft-versus-host disease, and transplant-associated thrombotic microangiopathy. Additionally, we discuss its role in mitigating key toxicities linked to chimeric antigen receptor (CAR) T-cell therapies and bispecific antibodies, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). We also explore emerging evidence on defibrotide's potential in SARS-CoV-2 infection-associated endotheliopathies, including acute COVID-19 and post-acute sequelae of SARS-CoV-2 infection ("long-COVID"), and the endothelial protective activity of defibrotide in these settings. Finally, we highlight potential future applications of defibrotide in hematologic malignancies and viral infections, emphasizing its multimodal mechanism of action.}, }
@article {pmid40729821, year = {2025}, author = {Kell, DB and Kell, L and Kenny, LC and Merriel, A and Moore, JB and Pretorius, E}, title = {The roles of placental senescence, autophagy and senotherapeutics in the development and prevention of pre-eclampsia: A focus on ergothioneine.}, journal = {Journal of reproductive immunology}, volume = {171}, number = {}, pages = {104621}, doi = {10.1016/j.jri.2025.104621}, pmid = {40729821}, issn = {1872-7603}, mesh = {Humans ; *Ergothioneine/metabolism/therapeutic use ; Pregnancy ; Female ; *Pre-Eclampsia/prevention &amp; control/immunology ; *Autophagy/drug effects ; *Placenta/pathology ; NF-E2-Related Factor 2/metabolism ; Cellular Senescence ; Oxidative Stress ; Animals ; Antioxidants/metabolism/therapeutic use ; }, abstract = {Cellular senescence is a well-established biological phenomenon in eukaryotes. It involves DNA damage, telomere shortening, a senescence-associated secretory phenotype (SASP), and the inability of cells to replicate. It is associated with ageing, and also with oxidative stress. Given the importance of oxidative stress in pre-eclampsia, there is considerable evidence, that we review, that senescence plays an important role in both normal placental development and in the development of both early- and late-term pre-eclampsia. Autophagy is capable of delaying or even reversing the development of senescence, and certain small molecules such as sulforaphane and spermidine can stimulate autophagy, including via the redox-sensitive transcription factor Nrf2. Ergothioneine is a thiohistidine antioxidant that is protective against a variety of cardiovascular and other diseases. Ergothioneine also interacts with Nrf2, and pre-eclampsia occurs far less frequently in individuals with higher plasma ergothioneine levels. Together, these elements provide a self-consistent, molecular and systems biology explanation for at least one mechanism by which ergothioneine may be protective against pre-eclampsia.}, }
@article {pmid40733521, year = {2025}, author = {Mahajan, S and Mahajan, S and Patgiri, S}, title = {Association and Interaction of Epstein-Barr Virus with SARS-CoV-2 Infection-A Review.}, journal = {Viruses}, volume = {17}, number = {7}, pages = {}, pmid = {40733521}, issn = {1999-4915}, mesh = {Humans ; *COVID-19/virology/complications/immunology ; *Herpesvirus 4, Human/physiology ; *Epstein-Barr Virus Infections/virology/complications/drug therapy ; *SARS-CoV-2/physiology ; Virus Activation ; }, abstract = {Despite the significant decrease in SARS-CoV-2-related mortality, COVID-19 continues to impose a high public health burden due to the high rate of post-COVID-19 pathological conditions, broadly termed Long COVID, that continue for any period of time and are generally multisystemic. However, recent studies have strengthened the evidence that the reactivation of the Epstein-Barr virus (EBV) in the post-COVID-19 era has significantly contributed to the exacerbation and prolongation of Long COVID symptoms. The mechanism and pathophysiology of EBV reactivation in Long COVID patients still need further exploration due to limited studies. This review summarises the various studies linking EBV reactivation in Long COVID along with its pathophysiology and novel therapeutics for EBV in a post-COVID-19 era.}, }
@article {pmid40736492, year = {2025}, author = {Grad, R and Ebell, MH}, title = {Top 20 Research Studies of 2024 for Primary Care Physicians.}, journal = {American family physician}, volume = {112}, number = {1}, pages = {34-41}, pmid = {40736492}, issn = {1532-0650}, mesh = {Humans ; Anti-Bacterial Agents/therapeutic use ; *Physicians, Primary Care ; COVID-19 ; *Primary Health Care ; SARS-CoV-2 ; }, abstract = {This article summarizes the top 20 research studies of 2024 identified as POEMs (patient-oriented evidence that matters). Based on a network meta-analysis, the oral antibiotics most likely to be effective for community-acquired pneumonia are telithromycin (not available in the United States), azithromycin, amoxicillin-clavulanate, and the quinolones levofloxacin and nemonoxacin (not available in the United States). The oral antivirals molnupiravir and nirmatrelvir-ritonavir reduce hospitalizations in immunocompromised patients with COVID-19. In average-risk infants, a single dose of nirsevimab reduces hospitalizations due to respiratory syncytial virus. Amoxicillin with or without clavulanate is more effective than placebo for children with symptoms of acute sinusitis. Benzyl benzoate 25% is highly effective for scabies in adolescents and adults. Lactobacillus-containing probiotics reduce the incidence of recurrent urinary tract infections (UTIs) in premenopausal women with frequent UTIs. Low-dose amitriptyline is effective as second-line therapy for irritable bowel syndrome. For patients with uncomplicated gallstones, conservative management is a reasonable option. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists are better than older drugs at improving patient-oriented outcomes for type 2 diabetes. Continuous or intermittent glucose monitoring is minimally effective for control of type 2 diabetes and can be harmful. Phentermine-topiramate and GLP-1 receptor agonists are the most effective drugs for promoting weight loss. Semaglutide is effective for secondary prevention of cardiovascular disease in people with obesity and no diabetes. SGLT-2 inhibitors and GLP-1 receptor agonists decrease cardiovascular death in older adults with type 2 diabetes and heart failure. Beta blockers do not prevent subsequent events after myocardial infarction in patients with preserved ejection fraction. For patients who do not quit smoking after a trial of varenicline or combined nicotine replacement therapy, a higher dose of either drug can increase quit rates. e-Cigarettes increase abstinence from smoking, but long-term vaping is a consequence for some. Oral naltrexone and acamprosate are safe and effective treatments for alcohol use disorder. Cognitive behavior therapy can reduce fatigue attributed to long COVID. New monoclonal antibodies for Alzheimer disease are harmful, expensive, and minimally effective. Clinicians may choose to deliver bad news in person or by telephone, using their judgment or patient preference to decide which is best for the patient.}, }
@article {pmid40738238, year = {2025}, author = {Maison, DP and Khadka, VS and Mohd-Ibrahim, I and Peluso, MJ and Henrich, TJ and Deng, Y and Gerschenson, M}, title = {Peripheral immune progression to long COVID is associated with mitochondrial gene transcription: A meta-analysis.}, journal = {Mitochondrion}, volume = {85}, number = {}, pages = {102072}, pmid = {40738238}, issn = {1872-8278}, support = {P20 GM103466/GM/NIGMS NIH HHS/United States ; U54 MD007601/MD/NIMHD NIH HHS/United States ; U54 HG013243/HG/NHGRI NIH HHS/United States ; U54 GM138062/GM/NIGMS NIH HHS/United States ; P20 GM113134/GM/NIGMS NIH HHS/United States ; T32 DK137523/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/immunology/genetics ; Disease Progression ; *Genes, Mitochondrial ; Leukocytes, Mononuclear/immunology ; *Mitochondria/genetics ; *Transcription, Genetic ; *Post-Acute COVID-19 Syndrome/genetics/immunology ; }, abstract = {SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has led to millions of cases of Long COVID worldwide. Long COVID is a phenomenon characterized by persistent and debilitating mental and physical symptoms following acute infection. Despite ongoing research, trials, and considerable progress in understanding Long COVID, its exact causes remain only partially understood, with current hypotheses addressing specific aspects of the condition. We conducted one of the most comprehensive meta-analyses to date of all quality bulk RNA-seq studies worldwide from the COVID-19 pandemic and show significant mitochondrial transcript changes in the peripheral immune system of people with Long COVID, with unexpectedly low levels of intracellular viral RNA in Long COVID. This extensive analysis, which includes 26 studies and 1,272 individuals, shows that mononuclear cells, PBMC, and granulocytes from Long COVID patients exhibit significant alterations in mitochondrial genes and related processes. These findings likely represent the true transcriptomic landscape of Long COVID across diverse datasets, highlighting the long-lasting impacts of SARS-CoV-2 on peripheral immune function. In combination with other ex vivo and proteomics studies showing mitochondrial dysfunction, our results suggest critical new directions, such as the potential role of clonal hematopoiesis and infected seed cells. This work highlights the need for further investigation into the mechanisms underlying these immune changes and persistent symptoms in people with Long COVID. These findings will serve as a foundation for defining the paradigm underlying the biological mechanisms of Long COVID, driving research into the peripheral immune system, bone marrow, and mitochondria.}, }
@article {pmid40744021, year = {2025}, author = {Komaroff, AL and Dantzer, R}, title = {Causes of symptoms and symptom persistence in long COVID and myalgic encephalomyelitis/chronic fatigue syndrome.}, journal = {Cell reports. Medicine}, volume = {6}, number = {8}, pages = {102259}, pmid = {40744021}, issn = {2666-3791}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; R21 NS130712/NS/NINDS NIH HHS/United States ; R01 CA193522/CA/NCI NIH HHS/United States ; U54 AI138370/AI/NIAID NIH HHS/United States ; R01 NS073939/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Fatigue Syndrome, Chronic/pathology/etiology/physiopathology ; *COVID-19/complications/pathology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Gastrointestinal Microbiome ; }, abstract = {Debilitating symptoms for many years can follow acute COVID-19 ("long COVID"), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and various post-acute infection syndromes (PAISs). Together, long COVID and ME/CFS affect 60-400 million individuals, globally. Many similar underlying biological abnormalities have been identified in both conditions including autoantibodies against neural targets, endothelial dysfunction, acquired mitochondrial dysfunction, and a pro-inflammatory gut microbiome. Each of these abnormalities may directly cause some of the symptoms. In addition, the symptoms also may be caused by ancient, evolutionarily conserved symptomatic and metabolic responses to vital threats-sickness behavior and torpor-responses mediated by specific, recently discovered neural circuits. These neural circuits constitute a symptom-generating pathway, activated by neuroinflammation, which may be targeted by therapeutics to quell neuroinflammation. Many factors cause the symptoms to become chronic, including persistent infectious agents (and/or their nucleic acids and antigens) and the fact that many of the underlying biological abnormalities reinforce each other, creating ongoing physiological vicious cycles.}, }
@article {pmid40748012, year = {2025}, author = {Waxse, BJ and Rao, S}, title = {Data science for pediatric infectious disease: utilizing COVID-19 as a model.}, journal = {Current opinion in infectious diseases}, volume = {38}, number = {5}, pages = {493-498}, pmid = {40748012}, issn = {1473-6527}, support = {ZIA HG200417/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/epidemiology/prevention &amp; control ; Child ; *Data Science/methods ; SARS-CoV-2 ; Pediatrics ; Pandemics ; Public Health ; }, abstract = {PURPOSE OF REVIEW: During the COVID-19 pandemic, governments and public health agencies used data science tools and data sources in real time to evaluate pathogen transmissibility, disease burden, healthcare capacity, and evaluate treatment and preventive measures. The purpose of the review is to highlight the application of these data sources and methods during the COVID-19 response.<br><br>RECENT FINDINGS: Advances in the development of common data models enabled multisite data networks to overcome healthcare data fragmentation, enabling national surveillance platforms, and offering unprecedented statistical power to conduct national surveillance and detect emerging clinical entities like MIS-C and long COVID in diverse pediatric populations. These integrated networks were also used in evaluating the effectiveness of vaccines and therapies. New surveillance approaches combining traditional clinical data with novel data sources including wastewater detection, web-based search engines, and mobility patterns yielded comprehensive ensemble approaches that informed public health policy.<br><br>SUMMARY: The COVID-19 pandemic highlighted the importance of timely evidence for decision-making during outbreak responses and the benefits of using data science tools to help provide real time, actionable insights, which can help guide our public health response to infectious diseases threats in the future.}, }
@article {pmid40748784, year = {2026}, author = {Pollett, S and Agan, BK and Letizia, AG and Richard, SA and Porter, C and Epsi, NJ and Haigney, M and Saunders, D and Colombo, R and Burgess, TH and Morris, M and Tribble, DR and La Croix, C and Jones, M and O'Connell, RJ}, title = {Long COVID and the Military: A Current Research Landscape, Knowledge Gaps, and Future Directions.}, journal = {Military medicine}, volume = {191}, number = {1-2}, pages = {e102-e110}, doi = {10.1093/milmed/usaf343}, pmid = {40748784}, issn = {1930-613X}, support = {HU00012120103//Defense Health Program/ ; //Disease Clinical Research Program/ ; //Department of Defense/ ; //Uniformed Services University of the Health Sciences/ ; //Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc./ ; }, mesh = {Humans ; *COVID-19/complications/epidemiology ; *Military Personnel/statistics &amp; numerical data ; Post-Acute COVID-19 Syndrome ; United States/epidemiology ; SARS-CoV-2 ; }, abstract = {INTRODUCTION: This narrative review highlights the impact and epidemiology of post-COVID conditions (PCC, 'Long COVID') in military service members and beneficiaries, characterizing the threat of Long COVID to military readiness. We leveraged this review to propose a Long COVID research road map for Military Health System (MHS)-based studies, identifying key questions and knowledge gaps that the Department of Defense research enterprise is well-positioned to address.<br><br>MATERIALS AND METHODS: We searched MEDLINE (PubMed) in addition to MHS conference abstracts and websites, bibliographies of relevant published articles and https://clinicaltrials.gov/.<br><br>RESULTS: Multiple studies in U.S., U.K., and European military service members have noted medically attended and patient reported post-acute sequelae and symptoms across the domains of cardiorespiratory, neurocognitive, and mental health. Studies have also noted an association with SARS-CoV-2 infection and fitness in young adult service members, but the ongoing prevalence, morbidity, and functional impact of Long COVID in military populations in the current era remains unclear. All identified studies have limitations.<br><br>CONCLUSIONS: Considerable research has been conducted to understand the risk of and risk factors associated with Long COVID in active duty, much in the earlier pandemic period. Future research priorities include establishing Long COVID definitions most relevant to active duty personnel and conducting studies to delineate, treat, and prevent Long COVID's impact on cognitive, cardiorespiratory, and overall health and fitness for duty. Many considerations in this review article may also apply to post-acute sequelae from other infectious diseases, which pose risks to military health and readiness, including future respiratory virus pandemics.}, }
@article {pmid40754067, year = {2025}, author = {Peine, C and Stoliaroff-Pepin, A and Reinacher, U and Heldt, K and Sarganas, G and Piechotta, V and Mikolajewska, A and Pilic, A and Barkowski, N and Bleve, D and Giebeler, MH and Poser, S and Searle, L and Kißner, E and Nitsche, L and Bayram, F and Siemens, W and Ziegler, A and Meerpohl, JJ and Sandmann, F and Wichmann, O and Harder, T}, title = {Effectiveness of COVID-19 vaccines against post-COVID-19 condition/long COVID: systematic review and meta-analysis.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {31}, number = {12}, pages = {1961-1971}, doi = {10.1016/j.cmi.2025.07.026}, pmid = {40754067}, issn = {1469-0691}, mesh = {Humans ; *COVID-19/prevention &amp; control/complications ; *COVID-19 Vaccines/immunology/administration &amp; dosage ; *Vaccine Efficacy ; SARS-CoV-2/immunology ; Vaccination ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Persons infected with SARS-CoV-2 can develop long-term symptoms known as postCOVID-19 condition (PCC; symptoms ≥3 months after infection) or long COVID (LC; symptoms ≥1 month after infection). Vaccination against COVID-19 might prevent PCC/LC, but the extent of protection is unclear.<br><br>OBJECTIVES: The aim of this systematic review was to evaluate the vaccine efficacy/effectiveness (VE) of COVID-19 vaccines given prior to SARS-CoV-2 infection in preventing PCC or LC.<br><br>METHODS DATA SOURCES: Studies were identified in Embase, MEDLINE, PreView, COVID-19 L.OVE repository, and Cochrane Library up to August 1, 2024.<br><br>Randomized controlled trials and nonrandomized studies of interventions (NRSI) that investigated immunization with a COVID-19 vaccine before SARS-CoV-2 infection were eligible, irrespective of participant age and sex.<br><br>ASSESSMENT OF RISK OF BIAS: Risk of bias was assessed using the ''Risk Of Bias In Nonrandomized Studies-of Interventions'' tool.<br><br>METHODS OF DATA SYNTHESIS: Primary outcome was PCC, secondary outcomes were LC, time until reconvalescence, limitations in everyday activity, and quality of life. Meta-analyses were primarily conducted using the random-effects model.<br><br>RESULTS: A total of 6423 records were screened, and 65 NRSI reporting adjusted estimates were included, comprising >5.7 mio.<br><br>PARTICIPANTS: VE for &#x2265;1 vaccine dose against PCC was 41.0% (95% CI 27.8%; 51.7%; 22 NRSI, certainty of evidence: low). VE after 1, 2, or 3 doses versus unvaccinated was 19.1% (-119.4%; 70.2%, 3 NRSI), 43.2% (4.5%; 66.2%; 4 NRSI), and 70.0% (30.0%; 87.0%; 1 NRSI), respectively. In <18 years old, VE against PCC was 26% for &#x2265;1 dose (-4%; 48%, 1 NRSI) and in >60 years old 41% (17%; 59%, 1 NRSI). VE after pre-Omicron-SARS-CoV-2 infection was 32.1% (-54.3%; 70.1%, 3 NRSI) and 20.9% (-10.1%; 43.3%, 2 NRSI) after Omicron infection. Sensitivity analyses indicated no influence of risk of bias and effect measure.<br><br>CONCLUSIONS: COVID-19 vaccines may be moderately effective in preventing PCC/LC. VE may increase with the number of vaccine doses administered.}, }
@article {pmid40762988, year = {2025}, author = {Gusmão, ACS and Scaléa, ACR and Uehara, SCDSA}, title = {Symptoms of long COVID in children and adolescents: a scoping review.}, journal = {Revista da Escola de Enfermagem da U S P}, volume = {59}, number = {}, pages = {e20240435}, pmid = {40762988}, issn = {1980-220X}, mesh = {Humans ; Adolescent ; Child ; *COVID-19/complications/diagnosis/epidemiology/physiopathology ; Age Factors ; }, abstract = {OBJECTIVE: To map the symptoms of Long Covid (LC) presented by children and adolescents.<br><br>METHOD: This is a scoping review, using the search engines Web of Science, Scopus, Virtual Health Library, and PUBMED, following the principles of the Joanna Briggs Institute.<br><br>RESULTS: Sixteen studies were selected, which showed that fatigue, headache, dyspnea, and cough were the most frequent symptoms of LC. There is a tendency for the development of child-adolescent LC related to the increase in age range, and the correlation between LC and predominant sex proved to be inconclusive. The presence of comorbidities, such as obesity, respiratory, neurological and renal diseases, was the most reported and a study showed an association between Covid-19 vaccine protection and LC.<br><br>CONCLUSION: This review points to a plurality of symptomatic manifestations of LC in children and adolescents, changing according to age group and health history.}, }
@article {pmid40769733, year = {2025}, author = {Wilson, CM and Boright, LE and Henshaw, AM and Naccarato, A}, title = {Role of rehabilitation in palliative care after the COVID-19 pandemic: a narrative review.}, journal = {Annals of palliative medicine}, volume = {14}, number = {4}, pages = {379-392}, doi = {10.21037/apm-25-6}, pmid = {40769733}, issn = {2224-5839}, mesh = {Humans ; *COVID-19/rehabilitation/epidemiology ; *Palliative Care/organization &amp; administration ; Pandemics ; SARS-CoV-2 ; }, abstract = {BACKGROUND AND OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic resulted in an historic disruption and transformation of the healthcare system, including the management of individuals with serious illness. Rehabilitation for patients facing serious or life-threatening illness is underutilized and poorly understood, resulting in unwarranted suffering, disability, and poorly coordinated care. This narrative review aims to describe the impact of the COVID-19 pandemic on the role and scope of rehabilitation within the context of serious illness and palliative care.<br><br>METHODS: A focused review of the literature included selected articles identified from three databases published from January 2020 to January 2025. Findings were synthesized narratively, with a focus on identifying themes and gaps in the literature related to two main topics: (I) the evidence related to rehabilitation for those with serious or life-threatening COVID-19 during the pandemic and (II) how rehabilitation for patients with serious illness has been transformed after emerging from the pandemic (including non-COVID diagnoses such as cancer, neurologic conditions, etc.).<br><br>KEY CONTENT AND FINDINGS: The key themes identified during the COVID-19 pandemic emphasized the need for early rehabilitation, interdisciplinary care, and an emphasis on cardiopulmonary principles for rehabilitation. Themes identified during the pandemic also included the emerging role of telerehabilitation, and need for evidence and clinical guidelines for serious illnesses (including long COVID). Themes related to the transformative effect on palliative rehabilitation after the pandemic included an increased importance and focus on coordination of care and interdisciplinary care for those with serious illness and increased focus on mental health and social determinants of health (SDOH). Additionally, there appears to be increased infrastructure and activity related to research, advocacy, and awareness for palliative rehabilitation.<br><br>CONCLUSIONS: The COVID-19 global pandemic highlighted the need for high quality, coordinated palliative care, including rehabilitation services, for patients facing a serious or life-threatening illness. Due to the benefits to a person's quality of life (QoL), dignity, and comfort, there is increasing evidence of the importance of seamless, ongoing access to rehabilitation services for patients with serious illness.}, }
@article {pmid40772993, year = {2025}, author = {Siqueira, IFB and Figueiredo, LA and Fernandes, CEM and Cintra, LP and de Oliveira, GF and Rios, MA and Maciel, R and Ferretjans, R and Guimarães, NS and Magno, LAV}, title = {Metabolic brain changes in post-acute COVID-19: systematic review and meta-analysis of [18F]-FDG-PET findings.}, journal = {Brain structure &amp; function}, volume = {230}, number = {7}, pages = {128}, pmid = {40772993}, issn = {1863-2661}, mesh = {Humans ; *COVID-19/metabolism/diagnostic imaging/complications ; Positron-Emission Tomography/methods ; Fluorodeoxyglucose F18 ; *Brain/metabolism/diagnostic imaging ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Radiopharmaceuticals ; Glucose/metabolism ; }, abstract = {Individuals with long COVID exhibit neurological and psychiatric symptoms that often persist well beyond the initial SARS-CoV-2 infection. Studies using [18F]-FDG positron emission tomography (FDG-PET) have revealed diverse abnormalities in brain glucose metabolism during the post-acute phase of COVID-19. We conducted a systematic review and meta-analysis to assess the spatial distribution and heterogeneity of brain metabolic changes in patients in the post-acute phase of COVID-19 relative to controls. We searched the MEDLINE, EMBASE, and CENTRAL databases in June 2025 for studies reporting FDG-PET data in patients with post-acute COVID-19 who have persistent neurological symptoms. Of the 14 eligible studies (584 scans), 13 reported glucose hypometabolism across frontoparietal regions, with the frontal cortex being the most consistently affected. This finding was confirmed by meta-analysis, which revealed a large and significant effect in the frontal cortex (Hedges' g = 1.34; 95% CI: 0.79-1.88; p < 0.001), despite high heterogeneity (I[2] = 93.6%). The systematic review indicates that brain metabolism generally improves over time, with widely varying recovery timelines, and consistently correlates hypometabolism with neurological symptom burden. These findings underscore the clinical relevance of frontoparietal hypometabolism in post-acute COVID-19 and its association with neurocognitive deficits, highlighting the need for longitudinal, quantitative PET studies to elucidate temporal dynamics and inform therapeutic development.}, }
@article {pmid40799952, year = {2025}, author = {Di Micco, P and Siniscalchi, C and Imbalzano, E and Russo, V and Camporese, G and Lodigiani, C and Meschi, T and Perrella, A}, title = {COVID-19: A Disease Driven by Protease/Antiprotease Imbalance? A Specific Review Five Years into the Pandemic.}, journal = {Infection and drug resistance}, volume = {18}, number = {}, pages = {3967-3975}, pmid = {40799952}, issn = {1178-6973}, abstract = {COVID-19, caused by SARS-CoV-2, has profoundly impacted global health since late 2019. Beyond respiratory complications, the disease involves systemic manifestations driven by immune dysregulation, inflammation, and coagulopathy. Among the many mechanisms implicated in severe disease, a growing body of evidence suggests a central role for the imbalance between proteases and antiproteases. This review examines how dysregulated protease activity contributes to viral entry, cytokine activation, vascular injury, and thrombosis. We focus on the integration of proteolytic systems such as the renin-angiotensin system, coagulation cascade, and neutrophil extracellular traps with established pathways like endothelial dysfunction and immune hyperactivation. Furthermore, we highlight therapeutic strategies aimed at restoring proteolytic balance and discuss the potential relevance of this paradigm in the management of long COVID.}, }
@article {pmid40801304, year = {2025}, author = {Ellen, A}, title = {From Stagnation to Strategy: Challenges in Advancing Long COVID Research.}, journal = {Journal of evaluation in clinical practice}, volume = {31}, number = {5}, pages = {e70180}, pmid = {40801304}, issn = {1365-2753}, mesh = {Humans ; *COVID-19/physiopathology/complications/epidemiology/therapy ; *Biomedical Research/organization &amp; administration ; SARS-CoV-2 ; Comorbidity ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long COVID is a debilitating multisystemic condition and is a major public health burden, yet the pathophysiology remains poorly understood and there are no effective treatments. Despite the urgent need for better management strategies, research into long COVID is losing momentum.<br><br>OBJECTIVES: To help tackle this loss of momentum, this article analyses the major challenges impeding progress and proposes innovative strategies to navigate them and to reinvigorate this research field.<br><br>METHOD: The analysis of the long COVID research domain drew on a broad range of scientific literature to identify major barriers to research and potential pathways forward.<br><br>RESULTS: The research highlighted critical obstacles, including the lack of reliable biomarkers which has necessitated a reliance on symptom reporting that is inherently heterogenous, temporally complex and often confounded by symptoms arising from pre-existing comorbidities. The absence of pre-infection baseline data further complicates the distinction between long COVID-specific pathophysiology and the effects of pre-existing co-morbidities. Additionally, the long COVID patient population has heterogenous multiorgan pathology, and this diversity makes it difficult to identify and interpret clinical findings.<br><br>CONCLUSION: Addressing these methodological and conceptual challenges is essential to accelerate the understanding of long COVID pathophysiology and guide the development of effective interventions.}, }
@article {pmid40801614, year = {2025}, author = {Sonkodi, B}, title = {Underlying Piezo2 Channelopathy-Induced Neural Switch of COVID-19 Infection.}, journal = {Cells}, volume = {14}, number = {15}, pages = {}, pmid = {40801614}, issn = {2073-4409}, mesh = {Animals ; Humans ; *Channelopathies/metabolism ; *COVID-19/metabolism ; *Ion Channels/metabolism ; Neurons/metabolism/pathology ; Pandemics ; SARS-CoV-2 ; }, abstract = {The focal "hot spot" neuropathologies in COVID-19 infection are revealing footprints of a hidden underlying collapse of a novel ultrafast ultradian Piezo2 signaling system within the nervous system. Paradoxically, the same initiating pathophysiology may underpin the systemic findings in COVID-19 infection, namely the multiorgan SARS-CoV-2 infection-induced vascular pathologies and brain-body-wide systemic pro-inflammatory signaling, depending on the concentration and exposure to infecting SARS-CoV-2 viruses. This common initiating microdamage is suggested to be the primary damage or the acquired channelopathy of the Piezo2 ion channel, leading to a principal gateway to pathophysiology. This Piezo2 channelopathy-induced neural switch could not only explain the initiation of disrupted cell-cell interactions, metabolic failure, microglial dysfunction, mitochondrial injury, glutamatergic synapse loss, inflammation and neurological states with the central involvement of the hippocampus and the medulla, but also the initiating pathophysiology without SARS-CoV-2 viral intracellular entry into neurons as well. Therefore, the impairment of the proposed Piezo2-induced quantum mechanical free-energy-stimulated ultrafast proton-coupled tunneling seems to be the principal and critical underlying COVID-19 infection-induced primary damage along the brain axes, depending on the loci of SARS-CoV-2 viral infection and intracellular entry. Moreover, this initiating Piezo2 channelopathy may also explain resultant autonomic dysregulation involving the medulla, hippocampus and heart rate regulation, not to mention sleep disturbance with altered rapid eye movement sleep and cognitive deficit in the short term, and even as a consequence of long COVID. The current opinion piece aims to promote future angles of science and research in order to further elucidate the not entirely known initiating pathophysiology of SARS-CoV-2 infection.}, }
@article {pmid40802287, year = {2025}, author = {Coughtrey, A and Pereira, SMP and Ladhani, S and Shafran, R and Stephenson, T}, title = {Long COVID in children and young people: then and now.}, journal = {Current opinion in infectious diseases}, volume = {38}, number = {5}, pages = {487-492}, pmid = {40802287}, issn = {1473-6527}, mesh = {Humans ; *COVID-19/complications/epidemiology/physiopathology ; Child ; Adolescent ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Fatigue ; Young Adult ; }, abstract = {PURPOSE OF REVIEW: On 11 March 2020, the WHO characterized COVID-19 as a pandemic. A clinical case definition for post-COVID-19 condition in children and adolescents by expert consensus was agreed by the WHO in 2023. It is now 5 years since the WHO declared a pandemic, and this review aims to summarize key advances in our understanding of long COVID over those 5 years.<br><br>RECENT FINDINGS: That symptoms could persist in adults and CYP for months after initial infection was first reported in Autumn 2020. Long COVID in adults is frequently characterized by symptoms of fatigue and breathlessness but brain-fog, joint and muscle pain have been reported much more commonly in adult follow-up than CYP. The most common persisting symptoms experienced by CYP after COVID-19 infection in initial studies, often with less than a year of follow-up, were fatigue, headache, shortness of breath and persisting loss of smell and taste. With longer follow-up, up to 2&#x200a;years, the commonest symptoms still include not only fatigue, headache and shortness of breath but also sleep difficulties, whereas loss of smell and taste persisted only in a minority. However, many symptoms were almost as common in test-negative controls, raising questions about the causal role of SARS-CoV-2 virus. Predictors of long COVID, as defined, were female sex, history of asthma, allergy problems, learning difficulties at school and family history of ongoing COVID-19 problems.<br><br>SUMMARY: The implications of the findings for clinical practice and research are that long COVID is not the same in CYP as adults; both their physical and mental health should be studied; and intervention trials are needed.}, }
@article {pmid40804645, year = {2025}, author = {Paval, NE and Căliman-Sturdza, OA and Lobiuc, A and Dimian, M and Sirbu, IO and Covasa, M}, title = {MicroRNAs in long COVID: roles, diagnostic biomarker potential and detection.}, journal = {Human genomics}, volume = {19}, number = {1}, pages = {90}, pmid = {40804645}, issn = {1479-7364}, support = {285/30.11.2022//Ministerul Cercet&#x103;rii, Inov&#x103;rii &#x15f;i Digitaliz&#x103;rii/ ; }, mesh = {Humans ; *COVID-19/genetics/diagnosis/virology ; *MicroRNAs/genetics ; Biomarkers/metabolism ; SARS-CoV-2 ; Sequence Analysis, RNA/methods ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long COVID or Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), marked by persistent symptoms lasting weeks to months after acute SARS-CoV-2 infection, affects multiple organ systems including the respiratory, cardiovascular, neurological, gastrointestinal, and renal systems. These prolonged effects stem from chronic inflammation, immune dysregulation, and direct viral injury. MicroRNAs (miRNAs)-small non-coding RNAs involved in gene regulation-play a pivotal role in this process by modulating immune responses, inflammation, and cellular stress. Altered miRNA expression patterns during and after infection contribute to the pathogenesis of Long COVID. While conventional miRNA detection techniques have been valuable, they face limitations in sensitivity, throughput, and detecting RNA modifications. This review highlights Oxford Nanopore Sequencing (ONS) as a promising alternative, offering real-time, long-read, amplification-free RNA sequencing that preserves native modifications. ONS enables direct sequencing of full-length miRNAs and their precursors, providing novel insights into miRNA processing and regulatory roles. Despite current challenges with short-read accuracy, ongoing technical advances are improving ONS performance. Its integration in miRNA profiling holds significant potential for uncovering novel regulatory interactions and advancing clinical biomarker discovery in Long COVID and other conditions.}, }
@article {pmid40805931, year = {2025}, author = {Mazzonetto, LF and Cordeiro, JFC and Correia, IM and Oliveira, AS and Moraes, C and Brilhadori, J and Gomide, EBG and Kudlacek, M and Machado, DRL and Anjos, JRCD and Santos, APD}, title = {Physical Training Protocols for Improving Dyspnea and Fatigue in Long COVID: A Systematic Review with Meta-Analysis.}, journal = {Healthcare (Basel, Switzerland)}, volume = {13}, number = {15}, pages = {}, pmid = {40805931}, issn = {2227-9032}, abstract = {Objective: This study aimed to evaluate physical training protocols for alleviating long COVID symptoms, especially dyspnea and fatigue, through a systematic review with meta-analysis. Method: Data were collected from EMBASE, LILACS, PubMed, Scopus, CINAHL, Web of Science, and grey literature (Google Scholar, medRxiv). Studies evaluating dyspnea and/or fatigue before and after physical rehabilitation, using validated questionnaires, were included. Studies lacking pre- and post-assessments or physical training were excluded. Two reviewers independently extracted data on intervention type, duration, frequency, intensity, and assessment methods for dyspnea and fatigue. Bias risk was evaluated using the Cochrane tool. Results: Combined methods, such as respiratory muscle training with strength and aerobic exercise, were common for long COVID symptoms. Aerobic exercise notably improved dyspnea and/or fatigue. Among 25 studies, four had a low risk of bias. Meta-analysis of two studies found no significant reduction in fatigue. Conclusion: Combined training methods, particularly aerobic exercise, alleviate dyspnea and fatigue in long COVID. More high-quality studies are needed to confirm these findings.}, }
@article {pmid40809128, year = {2024}, author = {Sun, J and Aikawa, M and Ashktorab, H and Beckmann, ND and Enger, ML and Espinosa, JM and Gai, X and Horne, BD and Keim, P and Lasky-Su, J and Letts, R and Maier, CL and Mandal, M and Nichols, L and Roan, NR and Russell, MW and Rutter, J and Saade, GR and Sharma, K and Shiau, S and Thibodeau, SN and Yang, S and Miele, L and , }, title = {A multi-omics strategy to understand PASC through the RECOVER cohorts: a paradigm for a systems biology approach to the study of chronic conditions.}, journal = {Frontiers in systems biology}, volume = {4}, number = {}, pages = {1422384}, pmid = {40809128}, issn = {2674-0702}, abstract = {Post-Acute Sequelae of SARS-CoV-2 infection (PASC or "Long COVID"), includes numerous chronic conditions associated with widespread morbidity and rising healthcare costs. PASC has highly variable clinical presentations, and likely includes multiple molecular subtypes, but it remains poorly understood from a molecular and mechanistic standpoint. This hampers the development of rationally targeted therapeutic strategies. The NIH-sponsored "Researching COVID to Enhance Recovery" (RECOVER) initiative includes several retrospective/prospective observational cohort studies enrolling adult, pregnant adult and pediatric patients respectively. RECOVER formed an "OMICS" multidisciplinary task force, including clinicians, pathologists, laboratory scientists and data scientists, charged with developing recommendations to apply cutting-edge system biology technologies to achieve the goals of RECOVER. The task force met biweekly over 14 months, to evaluate published evidence, examine the possible contribution of each "omics" technique to the study of PASC and develop study design recommendations. The OMICS task force recommended an integrated, longitudinal, simultaneous systems biology study of participant biospecimens on the entire RECOVER cohorts through centralized laboratories, as opposed to multiple smaller studies using one or few analytical techniques. The resulting multi-dimensional molecular dataset should be correlated with the deep clinical phenotyping performed through RECOVER, as well as with information on demographics, comorbidities, social determinants of health, the exposome and lifestyle factors that may contribute to the clinical presentations of PASC. This approach will minimize lab-to-lab technical variability, maximize sample size for class discovery, and enable the incorporation of as many relevant variables as possible into statistical models. Many of our recommendations have already been considered by the NIH through the peer-review process, resulting in the creation of a systems biology panel that is currently designing the studies we proposed. This system biology strategy, coupled with modern data science approaches, will dramatically improve our prospects for accurate disease subtype identification, biomarker discovery and therapeutic target identification for precision treatment. The resulting dataset should be made available to the scientific community for secondary analyses. Analogous system biology approaches should be built into the study designs of large observational studies whenever possible.}, }
@article {pmid40819231, year = {2025}, author = {Levin, J and Bradshaw, M}, title = {The Challenge of Long COVID: Is the Pandemic Really Over?.}, journal = {Public health reports (Washington, D.C. : 1974)}, volume = {140}, number = {5-6}, pages = {506-513}, pmid = {40819231}, issn = {1468-2877}, mesh = {Humans ; *COVID-19/epidemiology/complications ; United States/epidemiology ; SARS-CoV-2 ; Prevalence ; Public Health ; Pandemics ; Post-Acute COVID-19 Syndrome ; Incidence ; }, abstract = {Sequelae of SARS-CoV-2 infection began appearing among patients who had COVID-19 within months of the first wave of the COVID-19 pandemic in 2020. This phenomenon, termed post-COVID-19 condition and also known as long COVID, has been a source of controversy among physicians, as presentation of long COVID has been a somewhat mysterious constellation of signs and symptoms that seem mostly impervious to efficacious treatment. Although a considerable amount has been learned about the pathophysiology and other biomedical features of long COVID, the epidemiologic parameters of long COVID, including incidence and prevalence, are uncertain in the United States and globally. The best estimates are that millions of people have long COVID. Despite the declining incidence of COVID-19, the low case fatality of long COVID suggests that its prevalence is poised to continue to grow. This increasing prevalence of long COVID presents a challenge for the public health sector. Here, we examine the public health implications of long COVID. We offer policy recommendations, including ending congratulatory talk that the pandemic is over, encouraging more focused attention from the United States and global nongovernmental organizations, and establishing a multinational research initiative to better understand and respond to long COVID and other postviral and postinfectious chronic conditions. Although COVID-19 may not be as widespread and disruptive as in the early months of the pandemic, it would be a mistake to presume that, because the acute crisis is behind us, the pandemic is past. Long COVID is an ongoing public health threat and merits our concern.}, }
@article {pmid40857408, year = {2025}, author = {Bayarri-Olmos, R and Bain, W and Iwasaki, A}, title = {The role of complement in long COVID pathogenesis.}, journal = {JCI insight}, volume = {10}, number = {16}, pages = {}, pmid = {40857408}, issn = {2379-3708}, mesh = {Humans ; *COVID-19/immunology/complications ; *Complement System Proteins/immunology ; SARS-CoV-2/immunology ; Immunity, Innate/immunology ; Inflammation/immunology ; Complement Activation ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long COVID is a debilitating condition that can develop after a SARS-CoV-2 infection and is characterized by a wide range of chronic symptoms, including weakness, neurocognitive impairment, malaise, fatigue, and many others, that affect multiple organ systems. At least 10% of individuals with a previous infection may develop long COVID, which affects their ability to perform daily functions and work. Despite its severity and widespread impact, this multisystemic condition remains poorly understood. Recent studies suggest that dysregulation of the complement system, a key component of the innate immune response, may contribute to the pathogenesis of long COVID, particularly in connection with coagulation, inflammation, and vascular injury. In this Review, we examine the evidence linking complement system dysregulation to long COVID and explore its potential role in driving disease pathology.}, }
@article {pmid40866305, year = {2025}, author = {Bombardieri, AM and Denoue, CF}, title = {Cervical sympathetic block to treat Long COVID: a scoping review.}, journal = {Regional anesthesia and pain medicine}, volume = {}, number = {}, pages = {}, doi = {10.1136/rapm-2025-106879}, pmid = {40866305}, issn = {1532-8651}, abstract = {BACKGROUND: Long COVID is a complex and poorly understood condition characterized by persistent symptoms such as autonomic dysfunction, fatigue, neurocognitive impairment, and olfactory disturbances. Current treatments offer limited and inconsistent benefits. Dysregulation of the sympathetic nervous system is increasingly recognized as a contributor to Long COVID pathophysiology. Cervical sympathetic block (CSB), a procedure that modulates sympathetic tone, has emerged as a potential therapeutic approach.<br><br>OBJECTIVE: To review the existing literature on CSB, for Long COVID, focusing on symptom outcomes, proposed mechanisms, and procedural considerations.<br><br>EVIDENCE REVIEW: A structured literature search across PubMed, Embase, Scopus, and Web of Science identified studies published between 2022 and March 2025 reporting on CSB in adults with Long COVID. Eligible articles included case reports, case series, observational studies, and one randomized controlled trial evaluating symptom outcomes after the procedure.<br><br>FINDINGS: Sixteen studies involving 224 patients were included. Most reported improvement in fatigue, brain fog, and autonomic symptoms, including reduced heart rate and enhanced orthostatic tolerance. Cognitive and psychiatric symptoms such as memory impairment, anxiety, and depression showed variable improvement. Olfactory recovery was inconsistent and appeared to depend on symptom severity. Symptom relief was observed after both unilateral and bilateral blocks, with some responses lasting up to 1 year. No serious complications were reported.<br><br>CONCLUSIONS: CSB may offer symptom relief in Long COVID, particularly for fatigue, brain fog, and dysautonomia. However, the evidence remains preliminary and limited by small sample sizes and methodological heterogeneity. Controlled trials are needed to establish efficacy and patient selection criteria.}, }
@article {pmid40867811, year = {2025}, author = {Villegas Sánchez, V and Chávez Pacheco, JL and Palacios Arreola, MI and Sierra-Vargas, MP and Colín Godinez, LA and Ahumada Topete, VH and Fernández Plata, R and Higuera-Iglesias, A and Lara-Lemus, R and Aquino-Gálvez, A and Torres-Espíndola, LM and Castillejos-López, M}, title = {A Systematic Review of Genetic Variants in Glutathione S-Transferase Genes and Their Dual Role in SARS-CoV-2 Pathogenesis: From Acute Respiratory Complications to Long COVID.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {8}, pages = {}, pmid = {40867811}, issn = {2076-3921}, abstract = {Oxidative stress (OS) occurs when there is an imbalance between oxidants and antioxidants, leading to disruptions in cellular signaling and causing damage to molecules. Glutathione S-transferase (GST) enzymes are crucial for maintaining redox balance by facilitating glutathione conjugation. Increased oxidative damage has been noted during the COVID-19 pandemic, and its persistence may be linked to the onset of long COVID. This systematic review aimed to assess the relationship between GST gene polymorphisms and the prognosis of COVID-19, including long COVID. Adhering to the PRISMA guidelines, a thorough search was carried out in MEDLINE, CENTRAL, PubMed, and EMBASE for studies published from September 2020 to February 2025. Out of an initial selection of 462 articles, ten studies (four concerning COVID-19 severity and six related to long COVID) satisfied the inclusion criteria. The findings regarding GST polymorphisms were not consistent, especially concerning the GSTM1 and GSTT1 isoforms. Nevertheless, evidence indicates a sustained state of oxidative stress in patients with long COVID. The majority of research has focused on cytosolic GSTs, while the functions of microsomal and mitochondrial GST families remain largely unexplored. These findings suggest that further research into the various GST subfamilies and their genetic variants is necessary to enhance our understanding of their impact on COVID-19 severity and the pathophysiology of long COVID.}, }
@article {pmid40868058, year = {2025}, author = {Gonzaga, A and Martinez-Navarrete, G and Macia, L and Anton-Bonete, M and Cahuana, G and Tejedo, JR and Zorrilla-Muñoz, V and Fernandez-Jover, E and Andreu, E and Eguizabal, C and Pérez-Martínez, A and Solano, C and Hernández-Blasco, LM and Soria, B}, title = {Non-Viral Therapy in COVID-19: Where Are We Standing? How Our Experience with COVID May Help Us Develop Cell Therapies for Long COVID Patients.}, journal = {Biomedicines}, volume = {13}, number = {8}, pages = {}, pmid = {40868058}, issn = {2227-9059}, support = {ICI21/00016//Instituto de Salud Carlos III/ ; AVI-GVA-COVID19-068//Valencian Agency of Innovation(AVI)/ ; GVA-COVID19/2021-047//Valencian Agency of Innovation(AVI)/ ; NA//Al-Andalus Biopharma SL/ ; }, abstract = {Objectives: COVID-19, caused by the SARS-CoV-2 virus, has infected over 777 million individuals and led to approximately 7 million deaths worldwide. Despite significant efforts to develop effective therapies, treatment remains largely supportive, especially for severe complications like acute respiratory distress syndrome (ARDS). Numerous compounds from diverse pharmacological classes are currently undergoing preclinical and clinical evaluation, targeting both the virus and the host immune response. Methods: Despite the large number of articles published and after a preliminary attempt was published, we discarded the option of a systematic review. Instead, we have done a description of therapies with these results and a tentative mechanism of action. Results: Preliminary studies and early-phase clinical trials have demonstrated the potential of Mesenchymal Stem Cells (MSCs) in mitigating severe lung damage in COVID-19 patients. Previous research has shown MSCs to be effective in treating various pulmonary conditions, including acute lung injury, idiopathic pulmonary fibrosis, ARDS, asthma, chronic obstructive pulmonary disease, and lung cancer. Their ability to reduce inflammation and promote tissue repair supports their potential role in managing COVID-19-related complications. This review demonstrates the utility of MSCs in the acute phase of COVID-19 and postulates the etiopathogenic role of mitochondria in Long-COVID. Even more, their combination with other therapies is also analyzed. Conclusions: While the therapeutic application of MSCs in COVID-19 is still in early stages, emerging evidence suggests promising outcomes. As research advances, MSCs may become an integral part of treatment strategies for severe COVID-19, particularly in addressing immune-related lung injury and promoting recovery. However, a full pathogenic mechanism may explain or unify the complexity of signs and symptoms of Long COVID and Post-Acute Sequelae (PASC).}, }
@article {pmid40868961, year = {2025}, author = {Florea, CE and Bălaș-Maftei, B and Rotaru, A and Abudanii, PL and Vieru, ST and Grigoriu, M and Stoian, A and Manciuc, C}, title = {Multiorgan Involvement and Particularly Liver Injury in Long COVID: A Narrative Review.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {8}, pages = {}, pmid = {40868961}, issn = {2075-1729}, abstract = {Since the start of the COVID-19 pandemic, increasing evidence has shown that SARS-CoV-2 infection can cause long-term symptoms, collectively known as long COVID, and that patients with mild COVID-19 can also be affected by persistent fatigue, cognitive impairment, dyspnea, muscle pain, etc. Recent research has also found multiple organ systems, including the liver, to be significant sites of ongoing injury. This narrative review summarizes current knowledge on organ involvement during and after COVID-19, with particular focus on early and delayed hepatic manifestations and associated risk factors. Pathogenesis appears to be multifactorial, involving direct virus action, the body's immune-mediated inflammatory response, microvascular damage, drug-induced hepatotoxicity, and, in some cases, reactivation or exacerbation of pre-existing liver conditions. The hepatic clinical manifestations range from asymptomatic elevations of transaminases to cholangiopathy and even fibrosis. These can persist or progress for months after the initial infection with SARS-CoV-2 is resolved, requiring prolonged monitoring and interdisciplinary care, especially in the presence of metabolic disorders, obesity, or hepatitis. Neurological, cardiovascular, and other sequelae are discussed in parallel, with attention paid to common inflammatory and thrombotic pathways. This review concludes that liver dysfunction is of particular interest in long-COVID due to the liver's central role in metabolism and inflammation. While further research is being conducted into organ-specific and systemic interactions, the available evidence makes a compelling case for extended monitoring and integrated management strategies post infection.}, }
@article {pmid40868989, year = {2025}, author = {Cimmino, G and D'Elia, S and Morello, M and Titolo, G and Luisi, E and Solimene, A and Serpico, C and Conte, S and Natale, F and Loffredo, FS and Bianco, A and Golino, P}, title = {Cardio-Pulmonary Features of Long COVID: From Molecular and Histopathological Characteristics to Clinical Implications.}, journal = {International journal of molecular sciences}, volume = {26}, number = {16}, pages = {}, pmid = {40868989}, issn = {1422-0067}, mesh = {Humans ; *COVID-19/complications/pathology ; SARS-CoV-2 ; *Cardiovascular Diseases/etiology/pathology ; Lung/pathology/virology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long COVID is a persistent post-viral syndrome with the significant involvement of both the cardiovascular and pulmonary systems, often extending well beyond the acute phase of SARS-CoV-2 infection. Emerging evidence has highlighted a spectrum of chronic alterations, including endothelial dysfunction, microvascular inflammation, perivascular fibrosis, and in some cases, the persistence of viral components in the cardiac and pulmonary tissues. At the molecular level, a sustained inflammatory milieu-characterized by elevated pro-inflammatory cytokines such as interleukin 6 (IL-6)-and chronic platelet hyperreactivity contribute to a prothrombotic state. These mechanisms are implicated in microvascular damage, cardiac strain, and impaired gas exchange, correlating with clinical manifestations such as fatigue, dyspnea, chest discomfort, and reduced exercise capacity. In certain patients, especially those who were not hospitalized during the acute phase, cardiac MRI and myocardial biopsy may reveal signs of myocardial inflammation and autonomic dysregulation. These often subclinical cardiovascular alterations underscore the need for improved diagnostic strategies, integrating molecular and histopathological markers during post-COVID evaluations. Recognizing persistent inflammatory and thrombotic activity may inform risk stratification and individualized therapeutic approaches. The interdependence between pulmonary fibrosis and cardiac dysfunction highlights the importance of multidisciplinary care. In this context, molecular and tissue-based diagnostics play a pivotal role in elucidating the long-term cardio-pulmonary sequelae of long COVID and guiding targeted interventions. Early identification and structured follow-up are essential to mitigate the burden of chronic complications in affected individuals.}, }
@article {pmid40869200, year = {2025}, author = {Lesgards, JF and Cerdan, D and Perronne, C}, title = {Do Long COVID and COVID Vaccine Side Effects Share Pathophysiological Picture and Biochemical Pathways?.}, journal = {International journal of molecular sciences}, volume = {26}, number = {16}, pages = {}, pmid = {40869200}, issn = {1422-0067}, mesh = {Humans ; *COVID-19/immunology/prevention &amp; control/physiopathology ; *COVID-19 Vaccines/adverse effects/immunology ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus/immunology/metabolism ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID affects around 400 million individuals today with a strong economic impact on the global economy. The list of long COVID symptoms is extremely broad because it is derived from neurological, cardiovascular, respiratory, immune, and renal dysfunctions and damages. We review here these pathophysiological manifestations and the predictors of this multi-organ pathology like the persistence of the virus, altered endothelial function, unrepaired tissue damage, immune dysregulation, and gut dysbiosis. We also discuss the similarities between long COVID and vaccine side effects together with possible common immuno-inflammatory pathways. Since the spike protein is present in SARS-CoV-2 (and its variants) but also produced by the COVID vaccines, its toxicity may also apply to all mRNA or adenoviral DNA vaccines as they are based on the production of a very similar spike protein to the virus. After COVID infection or vaccination, the spike protein can last for months in the body and may interact with ACE2 receptors and mannan-binding lectin (MBL)/mannan-binding lectin serine protease 2 (MASP-2), which are present almost everywhere in the organism. As a result, the spike protein may be able to trigger inflammation in a lot of organs and systems similar to COVID infection. We suggest that three immuno-inflammatory pathways are particularly key and responsible for long COVID and COVID vaccine side effects, as it has been shown for COVID, which may explain in large part their strong similarities: the renin-angiotensin-aldosterone system (RAAS), the kininogen-kinin-kallikrein system (KKS), and the lectin complement pathway. We propose that therapeutic studies should focus on these pathways to propose better cures for both long COVID as well as for COVID vaccine side effects.}, }
@article {pmid40872762, year = {2025}, author = {Cao, Y and Wang, Y and Huang, D and Tan, YJ}, title = {The Role of SARS-CoV-2 Nucleocapsid Protein in Host Inflammation.}, journal = {Viruses}, volume = {17}, number = {8}, pages = {}, pmid = {40872762}, issn = {1999-4915}, support = {T2EP30121-0012//Ministry of Education/ ; }, mesh = {Humans ; *Coronavirus Nucleocapsid Proteins/immunology/metabolism ; *COVID-19/immunology/virology ; *SARS-CoV-2/immunology ; *Inflammation/immunology/virology ; *Phosphoproteins/immunology/metabolism ; Host-Pathogen Interactions ; Animals ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has posed substantial health threats and triggered widespread global economic disruption. The nucleocapsid (N) protein of SARS-CoV-2 is not only a key structural protein but also instrumental in mediating the host immune response, contributing significantly to inflammation and viral pathogenesis. Due to its immunogenic properties, SARS-CoV-2 N protein also interacts with host factors associated with various pre-existing inflammatory conditions and may possibly contribute to the long-term symptoms suffered by some COVID-19 patients after recovery-known as long COVID. This review provides a comprehensive overview of recent advances in elucidating the biological functions of the N protein. In particular, it highlights the mechanisms by which the N protein contributes to host inflammatory responses and elaborates on its association with long COVID and pre-existing inflammatory disorders.}, }
@article {pmid40872813, year = {2025}, author = {Muthiah, D and Vaddadi, K and Liu, L}, title = {Breathless Aftermath: Post-COVID-19 Pulmonary Fibrosis.}, journal = {Viruses}, volume = {17}, number = {8}, pages = {}, pmid = {40872813}, issn = {1999-4915}, support = {P30 GM149368/GM/NIGMS NIH HHS/United States ; R01 HL157450/HL/NHLBI NIH HHS/United States ; R21 AI189861/AI/NIAID NIH HHS/United States ; R01HL157450, R21AI189861 and P30GM149368//National Institutes of Health grants, Oklahoma Center for Adult Stem Cell Research and the Lundberg-Kienlen Endowment fund (to LL)/ ; }, mesh = {Humans ; *COVID-19/complications ; *Pulmonary Fibrosis/etiology/epidemiology/diagnosis/therapy/pathology/virology ; SARS-CoV-2 ; Lung/pathology/virology ; Post-Acute COVID-19 Syndrome ; Quality of Life ; }, abstract = {A significant number of individuals recovering from COVID-19 continue to experience persistent symptoms, collectively referred to as Post-Acute Sequelae of SARS-CoV-2 infection (PASC), or long COVID. Among these complications, post-COVID-19 pulmonary fibrosis (PC19-PF) is one of the most severe long-term outcomes, characterized by progressive lung scarring, chronic respiratory impairment, and reduced quality of life. Despite the increasing prevalence of PC19-PF, its underlying mechanisms remain poorly understood. In this review, we provide a comprehensive overview of PC19-PF, including its epidemiology, clinical manifestations, diagnostic strategies, and mechanistic insights. Additionally, we highlight the shared pathways between PC19-PF and other fibrotic lung diseases and discuss emerging therapeutic strategies. This review consolidates emerging insights from both clinical and experimental studies to advance our understanding of PC19-PF pathogenesis and guide the development of mechanism-based therapeutic approaches.}, }
@article {pmid40872911, year = {2025}, author = {Zambrano-Sánchez, G and Rivadeneira, J and Manterola, C and Otzen, T and Fuenmayor-González, L}, title = {Immunization as Protection Against Long COVID in the Americas: A Scoping Review.}, journal = {Vaccines}, volume = {13}, number = {8}, pages = {}, pmid = {40872911}, issn = {2076-393X}, support = {Folio (85220114).//ANID + SUBVENCI&#xd3;N A INSTALACI&#xd3;N EN LA ACADEMIA CONVOCATORIA A&#xd1;O 2022/ ; }, abstract = {INTRODUCTION: Long COVID syndrome is defined as persistent or new symptoms that appear after an acute SARS-CoV-2 infection and last at least three months without explanation. It is estimated that between 10% and 20% of those infected develop long COVID; however, data is not precise in Latin America. Although high immunization rates have reduced acute symptoms and the pandemic's impact, there is a lack of evidence of its efficacy in preventing long COVID in the region.<br><br>METHODS: This scoping review followed PRISMA-ScR guidelines. Studies on vaccinated adults with long COVID from Central and South America and the Caribbean were included (Mexico was also considered). A comprehensive search across multiple databases was conducted. Data included study design, participant characteristics, vaccine type, and efficacy outcomes. Results are presented narratively and in tables.<br><br>RESULTS: Out of 3466 initial records, 8 studies met the inclusion criteria after rigorous selection processes. These studies encompassed populations from Brazil, Mexico, Latin America, and Bonaire, with 11,333 participants, 69.3% of whom were female. Vaccination, particularly with three or more doses, substantially reduces the risk and duration of long COVID. Variability was noted in the definitions and outcomes assessed across studies.<br><br>CONCLUSIONS: This scoping review highlights that SARS-CoV-2 vaccination exhibits potential in reducing the burden of long COVID in the Americas. However, discrepancies in vaccine efficacy were observed depending on the study design, the population studied, and the vaccine regimen employed. Further robust, region-specific investigations are warranted to delineate the effects of vaccination on long COVID outcomes.}, }
@article {pmid40875678, year = {2025}, author = {Schapowal, A}, title = {[Long COVID, Post-COVID-Syndrom: Langzeitfolgen von SARS-CoV-2-Infektionen und Nutzen von standardisierten Ginkgo-biloba Extrakten].}, journal = {Complementary medicine research}, volume = {32}, number = {5}, pages = {432-437}, doi = {10.1159/000548075}, pmid = {40875678}, issn = {2504-2106}, mesh = {Humans ; *Ginkgo biloba/chemistry ; *Plant Extracts/therapeutic use ; *COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Pandemics ; COVID-19 Drug Treatment ; Phytotherapy ; Ginkgo Extract ; }, abstract = {Hintergrund: Long COVID und das Post-COVID-Syndrom sind langfristige Folgen einer SARS-CoV-2-Infektion, die eine Vielzahl physischer, kognitiver und psychischer Symptome hervorrufen können. Dazu gehören Erschöpfung, Atemnot, Gedächtnisstörungen und Schlafprobleme. Die zugrunde liegenden Mechanismen sind noch nicht vollständig geklärt, umfassen jedoch persistierende Viruspartikel, mikrovaskuläre Dysfunktionen, Autoimmunreaktionen und eine Dysregulation des autonomen Nervensystems. Fragestellung: Welchen Nutzen könnten standardisierte Ginkgo-biloba-Extrakte aufgrund ihrer pharmakologischen Wirkungen und ihrer klinischen Wirksamkeit bei Long COVID und Post-COVID-Syndrom bringen? Zusammenfassung: Die Diagnose von Long COVID bleibt aufgrund fehlender standardisierter Tests eine Herausforderung. Therapeutisch wird ein multimodaler Ansatz empfohlen, der symptomatische Medikation, Physiotherapie, Psychotherapie sowie Ernährungs- und Bewegungstherapie umfasst. Ein vielversprechender ergänzender Therapieansatz ist die Verwendung von standardisierten Ginkgo-biloba-Extrakten. Dank ihrer antioxidativen, entzündungshemmenden und neuroprotektiven Eigenschaften könnten sie zur Verbesserung kognitiver Beeinträchtigungen, Fatigue und kardiovaskulärer Symptome beitragen. Erste Studien und Fallberichte deuten auf positive Effekte hin, jedoch sind weitere klinische Untersuchungen erforderlich, um die Wirksamkeit zu bestätigen. Kernaussagen: Long COVID und das Post-COVID-Syndrom betreffen zahlreiche Organsysteme und beeinträchtigen die Lebensqualität erheblich. Die Diagnose bleibt schwierig, da es keine spezifischen Tests gibt. Eine multimodale Therapie ist derzeit der vielversprechendste Behandlungsansatz. Standardisierte Ginkgo-biloba-Extrakte zeigen in ersten Studien positive Effekte auf neurokognitive und kardiovaskuläre Symptome.}, }
@article {pmid40883647, year = {2025}, author = {Fayyad-Kazan, M}, title = {MicroRNAs in SARS-CoV-2 infection: emerging modulators of inflammation, pathogenesis, and therapeutic potential.}, journal = {Inflammopharmacology}, volume = {33}, number = {9}, pages = {4895-4910}, pmid = {40883647}, issn = {1568-5608}, mesh = {Humans ; *MicroRNAs/genetics/metabolism ; *COVID-19/genetics/therapy ; *Inflammation/genetics ; *SARS-CoV-2 ; Animals ; }, abstract = {Since the onset of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), elucidating the molecular regulators of viral pathogenesis and host response has been a critical international research objective. Among these, microRNAs (miRNAs), small non-coding RNAs, that modulate gene expression post-transcriptionally-have emerged as central orchestrators of host-virus interactions. This review exhaustively examines the roles of host-derived miRNAs in SARS-CoV-2 infection, including their roles in viral entry, replication, immune evasion, inflammation, and tissue injury. Dysregulation of certain miRNAs, such as miR-155, miR-146a, and miR-21, has been implicated in disease severity, comorbidities (such as diabetes, obesity), neurological complications, and pregnancy complications. In long COVID (PASC), chronic miRNA changes are linked to persistent inflammation, fibrosis, and cardiometabolic impairment. We emphasize current breakthroughs in miRNA research, including machine learning algorithms for miRNA-based disease stratification, CRISPR-engineered miRNA modulation, exosomal miRNA delivery platforms, and miRNA-adjuvanted vaccines. These advances highlight the potential of miRNAs as diagnostic biomarkers and therapeutic targets. Nevertheless, shortcomings persist in clinical validation, delivery optimization, and tissue-specific miRNA function elucidation. These gaps must be addressed to involve miRNAs in controlling current and future viral infections. This review consolidated differentially expressed miRNAs across disease stages, comorbidities, and clinical settings, providing a valuable resource for translational research and therapeutic innovation.}, }
@article {pmid40904575, year = {2025}, author = {Shen, S and Zhao, X and Pei, J and Wang, B and Hou, J and Chai, R and Guo, Y and Li, F and Hao, J and Wu, Z}, title = {Exploring the psychological impact of long COVID: symptoms, mechanisms, and treatments.}, journal = {Frontiers in psychiatry}, volume = {16}, number = {}, pages = {1555370}, pmid = {40904575}, issn = {1664-0640}, abstract = {Long COVID (LC) refers to a multisystem condition that persists after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). In addition to physical symptoms, the psychological impact is particularly pronounced. This review summarizes the manifestations, potential mechanisms, epidemiological characteristics, and current interventions related to psychological disorders in LC. Drawing on domestic and international literature, it highlights anxiety, depression, cognitive dysfunction, and post-traumatic stress disorder (PTSD) as the primary psychological symptoms. These symptoms may be associated with neuroinflammation, immune abnormalities, vascular dysfunction, and psychosocial stress. Although research in this area is still developing, psychotherapy, pharmacotherapy, neuromodulation, and lifestyle interventions show promise as treatment approaches. This review aims to provide insights that can inform future research on clinical treatments and psychological care for individuals with LC.}, }
@article {pmid40908304, year = {2025}, author = {Ivković, V and Anandh, U and Bell, S and Kronbichler, A and Soler, MJ and Bruchfeld, A}, title = {Long COVID and the kidney.}, journal = {Nature reviews. Nephrology}, volume = {21}, number = {12}, pages = {833-845}, pmid = {40908304}, issn = {1759-507X}, mesh = {Humans ; *COVID-19/complications/epidemiology ; *Renal Insufficiency, Chronic/epidemiology/etiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; COVID-19 Vaccines ; }, abstract = {Long coronavirus disease (COVID) - commonly defined as symptoms and/or long-term effects that persist for at least 3 months after acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and cannot be explained by an alternative diagnosis - is a complex, multifaceted and heterogeneous disease that affects many organ systems, including the kidney. COVID-19 can cause acute kidney injury, and several studies have reported an increased risk of chronic kidney disease (CKD) following COVID-19, suggesting that CKD can be a manifestation of long COVID. Furthermore, patients with CKD are at an increased risk of severe COVID-19 and of long COVID. COVID-19 has also been associated with the development of COVID-19-associated nephropathy, which is a collapsing form of focal segmental glomerulosclerosis, and an increased incidence of new-onset vasculitis. Some early reports described associations of COVID-19 and/or SARS-CoV-2 vaccines with relapse or new-onset of other glomerular diseases, but this link was not confirmed in large population-based studies. SARS-CoV-2 vaccination reduces the risk of COVID-19 and long COVID and is particularly important for protecting vulnerable populations such as patients with CKD. Structured long-term follow-up of patients with COVID-19 and post-infectious sequelae is needed to provide further insight into the trajectory of long COVID and enable identification of those at risk of CKD.}, }
@article {pmid40910058, year = {2025}, author = {Mazzali, C and Magnoni, P and Zucchi, A and Maifredi, G and Cavalieri d'Oro, L and Gambino, ML and Fanetti, AC and Perotti, PG and Villa, M and Valsecchi, MG and Vigani, D and Lucifora, C and Russo, AG}, title = {Strategies for population-level identification of post-acute sequelae of COVID-19 through health administrative data.}, journal = {Frontiers in public health}, volume = {13}, number = {}, pages = {1637112}, pmid = {40910058}, issn = {2296-2565}, mesh = {Humans ; *COVID-19/complications/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {INTRODUCTION: Post-acute sequelae of COVID-19 (PASC) encompass several clinical outcomes, from new-onset symptoms to both acute and chronic diagnoses, including pulmonary and extrapulmonary manifestations. Health administrative data (HAD) from health information systems allow population-level analyses of such outcomes. Our primary aim was to identify clinical conditions potentially attributable to SARS-CoV-2 infection, and the types of HAD and "diagnostic criteria" used for their detection.<br><br>METHODS: We performed a literature review to identify HAD-based cohort studies assessing the association between SARS-CoV-2 infection and medium-/long-term outcomes in the general population. From each included study, we extracted data on design, algorithms used for outcome identification (sources, coding systems, codes, time criteria/thresholds), and whether significant associations with SARS-CoV-2 infection were reported.<br><br>RESULTS: We identified six studies investigating acute and chronic conditions grouped by clinical domain (cardiovascular, respiratory, neurologic, mental health, endocrine/metabolic, pediatric, miscellaneous). Two studies also addressed the onset of specific symptoms. Cardio/cerebrovascular conditions were most studied, with significant associations reported for deep vein thrombosis, heart failure, atrial fibrillation, and coronary artery disease. Conditions in other domains were less investigated, with inconsistent findings. Only three studies were designed as test-positive vs. test-negative comparisons.<br><br>DISCUSSION: Heterogeneity in data sources, study design, and outcome definitions hinder the comparability of studies and explain the inconsistencies in findings about associations with SARS-CoV-2 infection. Rigorously designed studies on large populations with wide availability of data from health information systems are needed for population-level analyses on PASC, and especially on its impact on chronic diseases and their future burden on healthcare systems.}, }
@article {pmid40922860, year = {2025}, author = {Potluri, S and Chittiprol, N and Varaganti, V and Avr, V and Vadakedath, S and Arvapally, D and Vemulapalli, C and Begum, GS and Madamsetti, N and Kandi, V}, title = {The Association of SARS-CoV-2 Infection and COVID-19 Vaccination With Sudden Death: An Explorative Review.}, journal = {Cureus}, volume = {17}, number = {8}, pages = {e89527}, pmid = {40922860}, issn = {2168-8184}, abstract = {Since its discovery, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has become the epicenter of public health concern. This was mainly attributed to the complexity of COVID-19 that resulted in variable disease progression with some developing asymptomatic infections, some suffering mild to moderate infections that resolved without the need for hospitalizations, and a few infected persons developing severe infections that required intensive care unit (ICU) admission and mechanical ventilation. The COVID-19 pandemic spread globally, affecting billions of people and killing millions. Most of the consequences were related to the novelty of the virus, poor understanding of its pathogenesis, and the lack of a specific antiviral drug and vaccine. The vaccines, although manufactured and made available to the public, were approved for emergency use before the completion of human clinical trials. Moreover, the continuous emergence of viruses following mutations resulted in the emergence of viral variants. This has led to doubts over the efficacy of vaccines. Vaccine inequity, represented by the disproportionate availability and distribution of vaccines among the rich and poor, concerns over long-term safety, and hesitancy, affected COVID-19 vaccination, thereby increasing the spread of SARS-CoV-2. Although the COVID-19 pandemic is no longer considered a public health emergency of international concern (PHEIC), the repercussions of the pandemic are still evident in the form of long COVID and post-COVID functional health status (PCFHS), wherein individuals who were previously infected continue to suffer organ dysfunction, primarily affecting the lungs and other organs of the body. During and after the pandemic, COVID-19 and probably vaccination were attributed to the death of many individuals, which were categorized as sudden death (SD) and sudden unnatural death (SUD). It is unclear if these deaths were a result of previous SARS-CoV-2 infection and prior COVID-19 vaccination or both. There are several instances of infected and recovered individuals who were healthy but suddenly developed complications and died. Through this explorative review, we aim to comprehend the role that SARS-CoV-2 infection and/or COVID-19 vaccination play in predisposing people to cardiovascular system (CVS) and central nervous system (CNS) disorders that can result in SD and SUD.}, }
@article {pmid40930270, year = {2025}, author = {Walker, TA and Kohler, JZ and Haddad, MM}, title = {Long COVID: Current landscape of neurocognitive sequalae and opportunities to improve care management.}, journal = {Brain, behavior, and immunity}, volume = {130}, number = {}, pages = {106108}, doi = {10.1016/j.bbi.2025.106108}, pmid = {40930270}, issn = {1090-2139}, }
@article {pmid40934937, year = {2026}, author = {Wilhelm, F and Cadamuro, J and Mink, S}, title = {Autoantibodies in long COVID: a systematic review.}, journal = {The Lancet. Infectious diseases}, volume = {26}, number = {4}, pages = {e220-e230}, doi = {10.1016/S1473-3099(25)00411-6}, pmid = {40934937}, issn = {1474-4457}, mesh = {Humans ; *COVID-19/immunology/complications/diagnosis ; *Autoantibodies/blood/immunology ; SARS-CoV-2/immunology ; Biomarkers/blood ; Prognosis ; Antibodies, Antinuclear/blood/immunology ; }, abstract = {Post-COVID-19 condition (also known as long COVID) affects a substantial proportion of individuals who have been infected with SARS-CoV-2, profoundly affecting their daily lives and work. Diagnosis and prognosis of long COVID are complex and hindered by heterogeneous symptoms and the absence of validated biomarkers. This systematic review synthesises current evidence on the association between autoantibodies and long COVID, with the goal of evaluating their prognostic and diagnostic utility. Studies published in the PubMed and MEDLINE databases between Jan 1, 2020, and June 10, 2025, were considered. Study selection and quality assessment were done independently by two researchers. Of the 1113 publications screened, 44 studies met the inclusion criteria, with a total of 7571 participants, including 3372 individuals with long COVID. 31 (71%) studies reported an association between autoantibodies and long COVID; however, there was substantial heterogeneity in study design, type and timing of antibody measurements, and long COVID definitions. Several autoantibodies have been associated with long COVID occurrence, symptoms, and severity. Antinuclear antibodies, and autoantibodies targeting G protein-coupled receptors and chemokines, have emerged as potential biomarkers for aiding in the diagnosis, prognosis, and assessment of disease severity in long COVID. However, larger studies are needed to confirm the diagnostic and prognostic utility of these autoantibodies in the context of long COVID.}, }
@article {pmid40943770, year = {2025}, author = {Var, SR and Maeser, N and Blake, J and Zahs, E and Deep, N and Vasilakos, Z and McKay, J and Johnson, S and Strell, P and Chang, A and Korthas, H and Krishna, V and Narayanan, M and Arju, T and Natera-Rodriguez, DE and Roman, A and Schulz, SJ and Shetty, A and Vernekar, M and Waldron, MA and Person, K and Cheeran, M and Li, L and Low, WC}, title = {Pulmonary and Immune Dysfunction in Pediatric Long COVID: A Case Study Evaluating the Utility of ChatGPT-4 for Analyzing Scientific Articles.}, journal = {Journal of clinical medicine}, volume = {14}, number = {17}, pages = {}, pmid = {40943770}, issn = {2077-0383}, support = {R01 AG077772/AG/NIA NIH HHS/United States ; RF1 AG077772/AG/NIA NIH HHS/United States ; AG077772/NH/NIH HHS/United States ; }, abstract = {Coronavirus disease 2019 (COVID-19) in adults is well characterized and associated with multisystem dysfunction. A subset of patients develop post-acute sequelae of SARS-CoV-2 infection (PASC, or long COVID), marked by persistent and fluctuating organ system abnormalities. In children, distinct clinical and pathophysiological features of COVID-19 and long COVID are increasingly recognized, though knowledge remains limited relative to adults. The exponential expansion of the COVID-19 literature has made comprehensive appraisal by individual researchers increasingly unfeasible, highlighting the need for new approaches to evidence synthesis. Large language models (LLMs) such as the Generative Pre-trained Transformer (GPT) can process vast amounts of text, offering potential utility in this domain. Earlier versions of GPT, however, have been prone to generating fabricated references or misrepresentations of primary data. To evaluate the potential of more advanced models, we systematically applied GPT-4 to summarize studies on pediatric long COVID published between January 2022 and January 2025. Articles were identified in PubMed, and full-text PDFs were retrieved from publishers. GPT-4-generated summaries were cross-checked against the results sections of the original reports to ensure accuracy before incorporation into a structured review framework. This methodology demonstrates how LLMs may augment traditional literature review by improving efficiency and coverage in rapidly evolving fields, provided that outputs are subjected to rigorous human verification.}, }
@article {pmid40944962, year = {2025}, author = {Yong, SJ and Kenny, TA and Halim, A and Munipalli, B and Alhashem, YN and AlSaihati, H and Al-Subaie, MF and Al Kaabi, NA and Al Fares, MA and Garout, M and Sabour, AA and Alshiekheid, MA and Almansour, ZH and Alotaibi, J and Alrasheed, HA and Alamri, AA and Albayat, H and Alamodi, AS and Tombuloglu, H and Mohapatra, RK and Hazazi, A and Rabaan, AA}, title = {Post-COVID-19 Vaccination (or Long Vax) Syndrome: Putative Manifestation, Pathophysiology, and Therapeutic Options.}, journal = {Reviews in medical virology}, volume = {35}, number = {5}, pages = {e70070}, doi = {10.1002/rmv.70070}, pmid = {40944962}, issn = {1099-1654}, mesh = {Humans ; *COVID-19 Vaccines/adverse effects ; *COVID-19/prevention &amp; control/immunology ; *Vaccination/adverse effects ; SARS-CoV-2/immunology ; Fatigue Syndrome, Chronic ; Syndrome ; }, abstract = {With the global rollout of COVID-19 vaccines, vaccine safety remains a priority. Emerging concerns have raised the potential risk of a long COVID-like syndrome following vaccination, informally called long Vax and provisionally termed post-COVID-19 vaccination syndrome (PCVS). Our narrative review describes the putative manifestation, pathophysiology, and therapeutic approaches of PCVS based on the available evidence, mostly from case reports/series and observational studies. Our review noted that PCVS typically manifests within days to weeks post-vaccination, with symptoms lasting months to years. PCVS may present as recognized diagnoses such as postural orthostatic tachycardia syndrome (POTS), small-fibre neuropathy (SFN), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), or as long-term sequelae of myocarditis, vaccine-induced thrombotic thrombocytopaenia (VITT), or immune thrombocytopaenia purpura (ITP). Symptomatically, PCVS overlaps with long COVID, such as fatigue and brain fog, but PCVS may involve more frequent paraesthesia and less dyspnoea. We also review pathophysiological hypotheses of PCVS, focussing on the vaccine-derived spike protein and related immune responses. Finally, we discuss potential therapies used to treat patients with PCVS or related conditions, primarily documented in case reports/series, which could guide future clinical research. Overall, PCVS remains a poorly understood condition that requires more research to elucidate its prevalence, prognosis, risk factors, and treatments.}, }
@article {pmid40954187, year = {2025}, author = {van der Bie, J and Coleon, A and Visser, D and Bogers, WM and den Dunnen, J and Spronk, HMH and Langermans, JAM and Willemen, HLDM and De Melo, GD and Middeldorp, J and Stammes, MA}, title = {Post Pandemic Problem, is there an animal model suitable to investigate PASC.}, journal = {Npj imaging}, volume = {3}, number = {1}, pages = {41}, pmid = {40954187}, issn = {2948-197X}, support = {11080012310002/ZONMW_/ZonMw/Netherlands ; }, abstract = {Although the COVID-19 pandemic is no longer a global health emergency, many patients still suffer from long-term effects, known as post-acute sequelae of COVID-19 (PASC) or long COVID. Understanding its complex pathophysiology requires animal models replicating the post-acute phase, which may aid in developing, the urgently needed, therapeutics. Our review assessed and summarized 81 studies from 1979 manuscripts. In addition, a second table summarizing the imaging findings of 26 studies related to this topic was added, based on a separate literature search of 797 manuscripts. In humans a SARS-CoV-2 infection, the sequelae and possible development of PASC is heterogenic. The same holds true for experimental animal models. While several models are suitable to address different research questions, no single model can fully replicate all aspects of PASC. Imaging plays a crucial role in visualizing these aspects, especially since questionnaires, the primary diagnostic tool in humans, cannot be used in animals. Thus, imaging allows the investigation of pathophysiology in a controlled setting, offering valuable insights. This review summarizes the available animal models and imaging modalities used in PASC research. Our aim is to provide researchers with guidance on selecting the most appropriate model and imaging technique to address their specific research questions.}, }
@article {pmid40956349, year = {2025}, author = {Corrêa-Dias, LC and Lopes-Ribeiro, &#xc1; and Mendes, GER and Marques-Ferreira, G and Wilker-Teixeira, C and Clarindo, FA and de Melo Rocha, V and Martuchele-Félix, ME and Retes, HM and Santos, TAP and Azevedo, GLA and Pereira, VEV and de Fátima Silva Moraes, T and de Sousa Reis, EV and Gomes-de-Pontes, L and Rabelo, LF and Dos Santos, EAS and Pereira, CLD and Coelho, FDS and Coelho, RP and Santos, RA and Coelho, GP and da Fonseca, FG and Coelho-Dos-Reis, JGA}, title = {A pain from the nose to the head: neurological commitment during long COVID.}, journal = {Inflammation research : official journal of the European Histamine Research Society ... [et al.]}, volume = {74}, number = {1}, pages = {127}, pmid = {40956349}, issn = {1420-908X}, mesh = {Humans ; *COVID-19/complications/immunology ; *Neuroinflammatory Diseases/immunology/etiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long COVID is a debilitating illness with multi-systemic symptoms that affects at least 10% of individuals who have had COVID-19. Symptoms include respiratory, dermatological, gastrointestinal, cardiovascular, and most frequently reported, neurological sequelae. The most common neurological manifestations include fatigue, brain fog, memory issues, attention disorder, and headaches.<br><br>METHODS: In this review, we explore the current literature and highlight key findings regarding not only the clinical presentations of neurological commitment during long COVID but mainly the mechanisms that culminate in neuroinflammation, such as autoimmunity, viral reservoirs, and lack of surveillance of T-cells.<br><br>RESULTS: Neuroinflammation is a complex multicellular response that directly impacts microglial cells and includes inflammasome activation, trafficking of immune cells, and increased circulating autoantibodies, cytokines, and chemokines in the central nervous system, directly impacting the tissue homeostasis. This review provides important information beyond the clinical manifestations of long COVID. Here, we highlight multifactorial neuroinflammation as the main mechanism involved in long COVID, bringing together several studies that address the different mechanisms that culminate in inflammation of the central nervous system, and highlight possible biomarkers involved in this syndrome and potential therapeutic approaches that have been studied.<br><br>CONCLUSION: Thus, this review strengthens research into long COVID and provides new possibilities for future studies.}, }
@article {pmid40956375, year = {2025}, author = {Naushad, Z and Malik, J and Mishra, AK and Singh, S and Shrivastav, D and Sharma, CK and Verma, VV and Pal, RK and Roy, B and Sharma, VK}, title = {Artificial Intelligence in Cardiovascular Health: Insights into Post-COVID Public Health Challenges.}, journal = {High blood pressure &amp; cardiovascular prevention : the official journal of the Italian Society of Hypertension}, volume = {32}, number = {5}, pages = {475-494}, pmid = {40956375}, issn = {1179-1985}, mesh = {Humans ; *COVID-19/epidemiology ; *Cardiovascular Diseases/diagnosis/epidemiology/therapy ; *Artificial Intelligence ; *Public Health ; Risk Assessment ; SARS-CoV-2/pathogenicity ; Risk Factors ; }, abstract = {Cardiovascular diseases (CVDs) continue to be the topmost cause of the worldwide morbidity and mortality. Risk factors such as diabetes, hypertension, obesity and smoking are significantly worsening the situation. The COVID-19 pandemic has powerfully highlighted the undeniable connection between viral infections and cardiovascular health. Current literature highlights that SARS-CoV-2 contributes to myocardial injury, endothelial dysfunction, thrombosis, and systemic inflammation, increasing the severity of CVD outcomes. Long COVID has also been associated with persistent cardiovascular complications, including myocarditis, arrhythmias, thromboembolic events, and accelerated atherosclerosis. Addressing these challenges requires continued research and public health strategies to mitigate long-term risks. Artificial intelligence (AI) is changing cardiovascular medicine and community health through progressive machine learning (ML) and deep learning (DL) applications. AI enhances risk prediction, facilitates biomarker discovery, and improves imaging techniques such as echocardiography, CT, and MRI for detecting coronary artery disease and myocardial injury on time. Remote monitoring and wearable devices powered by AI enable real-time cardiovascular assessment and personalized treatment. In public health, AI optimizes disease surveillance, epidemiological modeling, and healthcare resource allocation. AI-driven clinical decision support systems improve diagnostic accuracy and health equity by enabling targeted interventions. The integration of AI into cardiovascular medicine and public health offers data-driven, efficient, and patient-centered solutions to mitigate post-COVID cardiovascular complications.}, }
@article {pmid40958852, year = {2025}, author = {Zhu, Y and Quan, P and Yamazaki, T and Norweg, A and Natelson, B and Xu, X}, title = {Metabolic neuroimaging of myalgic encephalomyelitis/chronic fatigue syndrome and Long-COVID.}, journal = {Immunometabolism (Cobham, Surrey)}, volume = {7}, number = {4}, pages = {e00068}, pmid = {40958852}, issn = {2633-0407}, support = {R01 NS136806/NS/NINDS NIH HHS/United States ; R21 NS129120/NS/NINDS NIH HHS/United States ; }, abstract = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long-COVID are complex, disabling conditions that have emerged as significant public health challenges, affecting millions worldwide. Despite their growing prevalence, effective diagnostics and treatments remain limited, largely due to an incomplete understanding of their underlying pathophysiology. Both conditions share hallmark symptoms of chronic fatigue, cognitive dysfunction, and postexertional malaise, but their biological underpinnings remain to be elucidated. Neuroimaging offers a promising, noninvasive window into the brain's metabolic landscape and has the potential to uncover objective biomarkers for these conditions. In this mini review, we highlight recent advancements in metabolic neuroimaging, particularly positron emission tomography and magnetic resonance imaging/magnetic resonance spectroscopy, that reveal alterations in glucose and oxygen metabolism, neurotransmitter balance, and oxidative stress. These insights point toward shared disruptions in brain energy metabolism and neuroinflammatory processes, which may underlie the persistent symptoms in both ME/CFS and Long-COVID. Importantly, while some findings overlap, inconsistencies in metabolite profiles between ME/CFS and Long-COVID underscore the need for further stratification and longitudinal research. Standardizing definitions, such as identifying Long-COVID patients who meet ME/CFS diagnostic criteria, could help improve study comparability. By summarizing current imaging evidence, this review underscores the potential of neuroimaging to identify imaging biomarkers to advance the clinical diagnosis of Long-COVID and identify therapeutic targets for treatment development. As we continue to face the growing burden of Long-COVID and ME/CFS, metabolic imaging may serve as a powerful tool to bridge gaps in knowledge and accelerate progress toward effective care.}, }
@article {pmid40975587, year = {2025}, author = {Sinha, SS and Bari, S and Tripathi, P and Kant, S and Tripathi, SM}, title = {Neuropsychiatric manifestations of long COVID.}, journal = {The Indian journal of tuberculosis}, volume = {72}, number = {4}, pages = {532-536}, doi = {10.1016/j.ijtb.2025.02.020}, pmid = {40975587}, issn = {0019-5707}, mesh = {Humans ; *COVID-19/psychology/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Mental Disorders/etiology ; *Nervous System Diseases/etiology ; }, abstract = {In 2019 after the COVID-19 outbreak, a subset of patients was observed to be experiencing unusual symptoms and prolonged illness following SARS-CoV-2 infection and were labeled as "Long-haulers". Various terms like Long COVID, and Post-COVID-19 Conditions (PCC) were used to describe symptoms extending four weeks or more. Long COVID encompasses a range of persistent symptoms with a multisystemic nature, exhibiting a relapsing-remitting pattern. Various theories explaining Long COVID such as direct neuro-invasion, systemic effects of the virus, and neuroimmune dysregulation have been suggested. Clinical manifestations of Long COVID include diverse symptoms with fatigue, dyspnea, and cognitive impairment being common symptoms reported. Neurological manifestations are more prevalent in severe COVID-19 cases. Non-specific neurological manifestations include loss of taste and smell while specific neurological manifestations include hemiplegia and large artery ischemic stroke. COVID-19 medications may also cause neurological symptoms. Psychiatric manifestations include depression, anxiety, panic disorders, post-traumatic stress disorder (PTSD), psychosis, and cognitive symptoms such as attention and executive function deficits. Psychological symptoms vary among different social groups like frontline health workers, young individuals, and the elderly. Social isolation exerts a substantial impact on the psychological presentations of Long COVID through mechanisms such as Hypothalamic-Pituitary-Adrenal axis (HPA) hyperactivation, epigenetic modifications, increased steroid concentrations, immune system suppression, and reactivation of latent infections. Conclusively, neuroimmune dysregulation, social isolation and associated factors serve as the link between SARS-CoV-2 virus, long COVID and its neuropsychiatric manifestations.}, }
@article {pmid40980513, year = {2025}, author = {Pettemeridou, E and Loizidou, M and Trajkovic, J and Constantinou, M and De Smet, S and Baeken, C and Sack, AT and Williams, SCR and Constantinidou, F}, title = {Cognitive and Psychological Symptoms in Post-COVID-19 Condition: A Systematic Review of Structural and Functional Neuroimaging, Neurophysiology, and Intervention Studies.}, journal = {Archives of rehabilitation research and clinical translation}, volume = {7}, number = {3}, pages = {100461}, pmid = {40980513}, issn = {2590-1095}, abstract = {OBJECTIVE: To investigate the structural, functional, and neurophysiological brain changes associated with post-COVID-19 condition (PCC)-related cognitive and psychological issues and evaluate the efficacy of noninvasive brain stimulation (NIBS) and cognitive rehabilitation interventions.<br><br>DATA SOURCES: Electronic databases, including Web of Science, PubMed, and Embase, were systematically searched for articles published before February 1, 2025, using terms such as "post-COVID-19 condition," "cognitive dysfunction," "brain changes," "noninvasive brain stimulation," and "cognitive rehabilitation." Language was restricted to English, and only studies involving human participants were included.<br><br>STUDY SELECTION: Studies with human participants aged &#x2265;18 years diagnosed with PCC, employing magnetic resonance imaging, functional magnetic resonance imaging, positron emission tomography, and electroencephalography, and interventions such as NIBS and cognitive rehabilitation were included. Articles were selected through independent review by multiple authors, with consensus resolving discrepancies. Of the 123 studies initially identified, 78 met the inclusion criteria.<br><br>DATA EXTRACTION: Data on participant demographics, methodologies, neurophysiological changes, and intervention outcomes were extracted by 2 independent reviewers using predefined guidelines. Study quality was assessed using the Newcastle-Ottawa Scale and Critical Appraisal Skills Program tools.<br><br>DATA SYNTHESIS: Seventy-eight studies with over 5900 participants met the inclusion criteria. Significant cognitive impairments were observed in attention, executive function, and memory (N=78). Key findings included mixed evidence of gray matter (N=16) and white matter volume changes (N=20), cortical thickness alterations (N=9), variations in functional connectivity (N=14), electrophysiology (N=9), and blood flow (N=8). NIBS, including transcranial magnetic stimulation (N=8) and transcranial direct current stimulation (N=2), showed potential benefits for managing depression and cognitive impairments. Although cognitive rehabilitation (N=3) showed promise, it requires further investigation.<br><br>CONCLUSIONS: This review highlights the complex neurologic underpinnings of PCC and the potential of NIBS and cognitive rehabilitation as interventions. Further research is essential to refine these interventions and establish evidence-based strategies for addressing long-term cognitive and psychological effects of PCC.}, }
@article {pmid40981264, year = {2025}, author = {Pomroy, HJ and Mote, A and Mathew, S and Chanasseril, S and Lu, V and Cheema, AK}, title = {From Fork to Brain: The Role of AGE-RAGE Signaling and the Western Diet in Neurodegenerative Disease.}, journal = {NeuroSci}, volume = {6}, number = {3}, pages = {}, pmid = {40981264}, issn = {2673-4087}, abstract = {Advanced glycation end products (AGEs) are reactive compounds formed through non-enzymatic glycation in a process known as the Maillard reaction. While humans produce AGEs endogenously, these compounds can also enter the body through dietary sources, food preparation methods, and exposure to agricultural and food-related chemicals. AGEs can accumulate within cells and impair cellular function. In addition, when AGEs bind to receptors for advanced glycation end products (RAGE), they activate intracellular signaling pathways that promote the generation of reactive oxygen species (ROS), mitochondrial dysfunction, and inflammation. Sustained AGE-RAGE signaling drives chronic inflammation contributing to the development of various ailments, including neurodegenerative diseases. This review examines AGE formation, metabolism, and accumulation, with an emphasis on dietary sources as modifiable contributors to AGE-RAGE mediated pathology. We highlight the need for further research on dietary AGE restriction as a potential strategy to prevent or slow the progression of neurodegenerative and neuroinflammatory disorders.}, }
@article {pmid40989546, year = {2025}, author = {Cruz Neto, J and Fiuza Olivindo, CV and Guimarães Dos Santos, JA and Araujo da Silva, MA and de Oliveira Sales Junior, R}, title = {Cardiometabolic factors related to post-COVID-19 conditions: a scoping review.}, journal = {Revista Cuidarte}, volume = {16}, number = {2}, pages = {e4290}, pmid = {40989546}, issn = {2346-3414}, abstract = {INTRODUCTION: Post-COVID syndrome is a pathology that involves multiple sequelae. It is important to identify cardiometabolic risk factors as a way of preventing complications.<br><br>OBJECTIVE: To map the scientific evidence related to cardiometabolic factors in long post-COVID-19 conditions.<br><br>MATERIALS AND METHODS: Scoping review with the guiding question: What scientific evidence relates cardiometabolic factors to patients with long post-Covid-19 syndrome? The sources of information used were six databases via the CAPES journal portal. For the gray literature, we used the CAPES catalog of theses and dissertations, the Brazilian Digital Library of Theses and Dissertations, the Who Library Database and the medRxiv and OpenGrey repositories. The following descriptors were used: Adult, heart disease risk factors, Syndrome, SARS-CoV-2 and Covid 19 crossed using the Boolean operators AND and OR.<br><br>RESULTS: 14 studies were included. The cardiometabolic factors found were: abnormal levels of triglycerides, glycated hemoglobin, ferritin, inflammatory processes, decreased platelets, phospholipids and endothelial cells, oxidative stress, higher concentrations of monosaccharides and reduced polysaccharides, increased LDL, ALT, AST and bilirubin, with reduced GFR.<br><br>DISCUSSION: Patients with long-term COVID report persistent and debilitating symptoms that affect recovery, quality of life, economic and social activities. In addition to increased resting heart rate, tachycardia, palpitations, hypotension, syncope, orthostatic tachycardia, angina and heart attack.<br><br>CONCLUSION: Cardiometabolic factors expose the vulnerability of individuals affected by long Covid-19, so strategies are needed to reduce the systemic inflammatory impact of the disease and its clinical consequences.}, }
@article {pmid40995517, year = {2025}, author = {Guo, X and Li, X}, title = {Advances in home-based respiratory muscle training for improving physical function in older adults with long COVID.}, journal = {Frontiers in physiology}, volume = {16}, number = {}, pages = {1662537}, pmid = {40995517}, issn = {1664-042X}, abstract = {Long COVID imposes a substantial burden on older adults, manifesting as respiratory muscle dysfunction that severely compromises physical function. This narrative review synthesizes current evidence on home-based respiratory muscle training (RMT)-a non-pharmacological intervention targeting this impairment in older patients with long COVID-while critically evaluating its physiological mechanisms, therapeutic efficacy, implementation feasibility, and persistent challenges. Respiratory muscle dysfunction, caused by multifaceted neurophysiological and structural impairments, is a core mechanism of exertional dyspnea and fatigue in older adults, further aggravated by age-related decline. RMT mitigates these effects through improvements in respiratory strength, endurance, ventilatory efficiency, metaboreflex and autonomic regulation, and psychological wellbeing. Home-based RMT demonstrates non-inferior efficacy to conventional programs while providing critical accessibility for mobility-limited older adults. Nevertheless, implementation barriers include challenges in individualizing geriatric-adapted exercise prescriptions, technological access limitations, variable adherence, insufficient clinician training in remote assessment, and regulatory/policy gaps in telerehabilitation frameworks. Despite these challenges, home-based RMT represents a promising strategy for managing debilitating respiratory sequelae in this vulnerable population. This review consolidates RMT's physiological rationale and clinical evidence, underscores its integration potential within collaborative care models, and outlines key translational priorities-including hybrid delivery systems and refined geriatric-specific protocols-to accelerate clinical adoption.}, }
@article {pmid41003635, year = {2025}, author = {Presta, V and Guarnieri, A and Laurenti, F and Mazzei, S and di Martino, O and Vitale, M and Condello, G}, title = {Post-Acute COVID-19 Syndrome (PACS) and Exercise Interventions: A Systematic Review of Randomized Controlled Trials.}, journal = {Sports (Basel, Switzerland)}, volume = {13}, number = {9}, pages = {}, pmid = {41003635}, issn = {2075-4663}, support = {MUR_DM737_2022_FIL_PROGETTI_B_CONDELLO_COFIN//Bando di Ateneo per la Ricerca 2022 - Azione B/ ; }, abstract = {The aim of this systematic review (PROSPERO registration number CRD42024517069) was to investigate the effectiveness of exercise interventions in Post-Acute COVID-19 Syndrome (PACS). We searched on several databases and followed the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). We included randomized controlled trials that evaluate exercise interventions in adults (40-60 years old) diagnosed with PACS. The outcomes of interest were health-related quality of life (HRQoL) and functional fitness. Twenty studies were included after screening. Thirteen and fourteen studies were rated as "low" risk for HRQoL and functional fitness outcomes, respectively. Based on the evidence, an 8-week exercise protocol of aerobic training in combination with strength-based and breathing exercises was found to be safe and feasible while improving quality of life and functional fitness in people with PACS. Telerehabilitation can also be an option to avoid contagion and physical contact with the same beneficial effects. Future research should expand the knowledge about other types of exercise (i.e., water-based exercises) with high-quality trials and consider whether findings could be potentially transferable to recovery from a wider spectrum of viral infections.}, }
@article {pmid41007506, year = {2025}, author = {Kachroo, P and Boivin, G and Cowling, BJ and Shannon, W and Mallefet, P and Kalita, P and Georgescu, AM}, title = {Long COVID Symptom Management Through Self-Care and Nonprescription Treatment Options: A Narrative Review.}, journal = {International journal of environmental research and public health}, volume = {22}, number = {9}, pages = {}, pmid = {41007506}, issn = {1660-4601}, mesh = {Humans ; *COVID-19/therapy/complications ; *Self Care ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {Many patients experience unique or persistent symptoms several months following the onset of infection with severe acute respiratory syndrome coronavirus 2, the causative agent of COVID-19. While this condition is commonly referred to as long COVID, no universally accepted definition exists; therefore, many patients go underrecognized and underreported. Long COVID can involve almost any major organ system and is characterized by widely heterogeneous persistent or recurrent symptoms including fatigue, headache, cough, dyspnea, chest pain, cognitive dysfunction, anxiety, and depression. In line with the wide array of symptoms, numerous potential underlying pathophysiologic pathways, including viral persistence, prolonged inflammation, autoimmune reactions, endothelial dysfunction, and dysbiosis of the microbiome of the gut, may contribute to the symptomology of long COVID. Therapy is directed at symptomatic control; however, no pharmacologic treatments are specifically approved for the management of symptoms associated with long COVID. Several common symptoms of long COVID may be managed with nonprescription treatments (pharmacologic and nonpharmacologic). The goal of this review is to provide clinicians with a better understanding of long COVID and review the latest recommendations for managing common mild-to-moderate symptoms with nonprescription treatment options.}, }
@article {pmid41008646, year = {2025}, author = {Lee, E and Ozigbo, AA and Varon, J and Halma, M and Laezzo, M and Ang, SP and Iglesias, J}, title = {Mitochondrial Reactive Oxygen Species: A Unifying Mechanism in Long COVID and Spike Protein-Associated Injury: A Narrative Review.}, journal = {Biomolecules}, volume = {15}, number = {9}, pages = {}, pmid = {41008646}, issn = {2218-273X}, mesh = {Humans ; *COVID-19/metabolism/complications/pathology ; *Mitochondria/metabolism/pathology ; *Reactive Oxygen Species/metabolism ; SARS-CoV-2/metabolism ; *Spike Glycoprotein, Coronavirus/metabolism ; Post-Acute COVID-19 Syndrome ; Oxidative Stress ; }, abstract = {Post-acute sequelae of SARS-CoV-2 infection (long COVID) present with persistent fatigue, cognitive impairment, and autonomic and multisystem dysfunctions that often go unnoticed by standard diagnostic tests. Increasing evidence suggests that mitochondrial dysfunction and oxidative stress are central drivers of these post-viral sequelae. Viral infections, particularly SARS-CoV-2, disrupt mitochondrial bioenergetics by altering membrane integrity, increasing mitochondrial reactive oxygen species (mtROS), and impairing mitophagy, leading to sustained immune activation and metabolic imbalance. This review synthesizes an understanding of how mitochondrial redox signaling and impaired clearance of damaged mitochondria contribute to chronic inflammation and multisystem organ symptoms in both long COVID and post-vaccine injury. We discuss translational biomarkers and non-invasive techniques, exploring therapeutic strategies that include pharmacological, non-pharmacological, and nutritional approaches, as well as imaging modalities aimed at assessing and restoring mitochondrial health. Recognizing long COVID as a mitochondrial disorder that stems from redox imbalance will open new options for personalized treatment and management guided by biomarkers. Future clinical trials are essential to validate these approaches and translate mitochondrial resuscitation into effective care for patients suffering from long COVID and related post-viral syndromes.}, }
@article {pmid41009608, year = {2025}, author = {Mantle, D and Domingo, JC and Golomb, BA and Castro-Marrero, J}, title = {Gulf War Illness, Fibromyalgia, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID Overlap in Common Symptoms and Underlying Biological Mechanisms: Implications for Future Therapeutic Strategies.}, journal = {International journal of molecular sciences}, volume = {26}, number = {18}, pages = {}, pmid = {41009608}, issn = {1422-0067}, mesh = {Humans ; *Fatigue Syndrome, Chronic/therapy/metabolism/pathology/drug therapy ; *Persian Gulf Syndrome/therapy/pathology/metabolism ; Ubiquinone/analogs &amp; derivatives/therapeutic use ; *Fibromyalgia/therapy/metabolism/pathology/drug therapy ; *COVID-19/complications/metabolism/therapy ; Oxidative Stress ; SARS-CoV-2 ; }, abstract = {Although Gulf War Illness (GWI), fibromyalgia (FM), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID have distinct origins, in this article we have reviewed evidence that these disorders comprise a group of so-called low-energy associated disorders with overlapping common symptoms underlying pathology. In particular, evidence for mitochondrial dysfunction, oxidative stress, inflammation, immune dysregulation, neuroendocrine dysfunction, disrupted brain-gut-microbiome axis, apoptosis/ferroptosis and telomere shortening as common features in the pathogenesis of these disorders has been identified. Given the role of coenzyme Q10 (CoQ10) in promoting normal mitochondrial function, as an antioxidant, antiinflammatory and antiapoptotic and antiferroptotic agent, there is a rationale for supplementary CoQ10 in the management of these disorders. The reported benefits of supplementary CoQ10 administration in GWI, FM, ME/CFS and long COVID have been reviewed; the potential benefit of supplementary CoQ10 in reducing telomere shortening and improving the efficiency of stem cell transfer relevant has also been identified as promising therapeutic strategies in these disorders. This review advances beyond previous systematic reviews and consensus statements on overlapping similar symptoms and underlying biological pathomechanisms in these complex disorders.}, }
@article {pmid41011507, year = {2025}, author = {Maddaloni, L and Bugani, G and Fracella, M and Bitossi, C and D'Auria, A and Aloisi, F and Azri, A and Santinelli, L and Ben M'Hadheb, M and Pierangeli, A and Frasca, F and Scagnolari, C}, title = {Pattern Recognition Receptors (PRRs) Expression and Activation in COVID-19 and Long COVID: From SARS-CoV-2 Escape Mechanisms to Emerging PRR-Targeted Immunotherapies.}, journal = {Microorganisms}, volume = {13}, number = {9}, pages = {}, pmid = {41011507}, issn = {2076-2607}, support = {RM124190A260C1F0//Sapienza University of Rome/ ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is recognized by pattern recognition receptors (PRRs), which play a vital role in triggering innate immune responses such as the production of type I and III interferons (IFNs). While modest PRR activation helps to defend against SARS-CoV-2, excessive or sustained activation can cause harmful inflammation and contribute to severe Coronavirus Disease 2019 (COVID-19). Altered expression of Toll-like receptors (TLRs), which are among the most important members of the PRR family members, particularly TLRs 2, 3, 4, 7, 8 and 9, has been strongly linked to COVID-19 severity. Furthermore, retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5), collectively known as RLRs (RIG-I-like receptors), act as sensors that detect SARS-CoV-2 RNA. The expression of these receptors, as well as that of different DNA sensors, varies in patients infected with SARS-CoV-2. Changes in PRR expression, particularly that of TLRs, cyclic GMP-AMP synthase (cGAS), and the stimulator of interferon genes (STING), have also been shown to play a role in the development and persistence of long COVID (LC). However, SARS-CoV-2 has evolved strategies to evade PRR recognition and subsequent signaling pathway activation, contributing to the IFN response dysregulation observed in SARS-CoV-2-infected patients. Nevertheless, PRR agonists and antagonists remain promising therapeutic targets for SARS-CoV-2 infection. This review aims to describe the PRRs involved in recognizing SARS-CoV-2, explore their expression during SARS-CoV-2 infection, and examine their role in determining the severity of both COVID-19 and long-term manifestations of the disease. It also describes the strategies developed by SARS-CoV-2 to evade PRR recognition and activation. Moreover, given the considerable interest in modulating PRR activity as a novel immunotherapy approach, this review will provide a description of PRR agonists and antagonists that have been investigated as antiviral strategies against SARS-CoV-2. This review aims to explore the complex interplay between PRRs and SARS-CoV-2 in depth, considering its implications for prognostic biomarkers, targeted therapeutic strategies and the mechanistic understanding of long LC. Additionally, it outlines future perspectives that could help to address knowledge gaps in PRR-mediated responses during SARS-CoV-2 infection.}, }
@article {pmid41030634, year = {2025}, author = {Johnson, BL}, title = {"In-Flu-Enza and Out-Flew Hair:" Post-Epidemic Health and the Importance of the History of Epidemics.}, journal = {The Yale journal of biology and medicine}, volume = {98}, number = {3}, pages = {341-348}, pmid = {41030634}, issn = {1551-4056}, mesh = {Humans ; *COVID-19/epidemiology/history ; History, 20th Century ; *Influenza, Human/epidemiology/history ; SARS-CoV-2 ; *Epidemics/history ; Pandemics/history ; History, 21st Century ; Influenza Pandemic, 1918-1919/history ; }, abstract = {When COVID-19 survivors reported ongoing symptoms or new health concerns following their infections in 2020 and early 2021, many medical practitioners and health agencies questioned the connection between novel viruses and long-term health impacts. Medical historians studying epidemics understand the connection between viral infection and health complications emerging immediately or years or decades later. In this essay, I explore the similarities between the medical fallout of the 1918 influenza and COVID-19 pandemics. Despite the differences between the viruses, these novel strains produced similar medium- and long-term health difficulties, including cardiovascular dysfunction and crushing fatigue. As I demonstrate, a significant difference between these two pandemics is in the response by medical practitioners. Following influenza, practitioners expected new and worsening health issues and took their patients' complaints seriously, offering support through food delivery, convalescent care, specialist oversight, and in-home nursing. Early in the COVID-19 pandemic, many practitioners characterized ongoing or new symptoms as anxiety. Patients led efforts to recognize Long COVID as an authentic medical condition, and today, physicians around the country refer their patients to Long COVID clinics. The value of medical history is apparent in this comparison-if practitioners understand how historical epidemics impacted various populations, they expect that in the epidemic aftermath or the period following an acute epidemic crisis, not all patients get well. Including the history of epidemics in public health education, continuing education programming, and even medical school curricula can resist epidemic erasure and empower medical practitioners to expect the unexpected.}, }
@article {pmid41038267, year = {2025}, author = {Thomas, D and Yang, PC and Wu, JC and Sayed, N}, title = {Decoding long COVID-associated cardiovascular dysfunction: Mechanisms, models, and new approach methodologies.}, journal = {Journal of molecular and cellular cardiology}, volume = {209}, number = {}, pages = {37-50}, pmid = {41038267}, issn = {1095-8584}, support = {R01 HL161002/HL/NHLBI NIH HHS/United States ; 869015/AHA/American Heart Association-American Stroke Association/United States ; R01 HL130020/HL/NHLBI NIH HHS/United States ; R01 HL176822/HL/NHLBI NIH HHS/United States ; R01 HL146690/HL/NHLBI NIH HHS/United States ; K01 HL135455/HL/NHLBI NIH HHS/United States ; R35 HL150698/HL/NHLBI NIH HHS/United States ; K99 HL163443/HL/NHLBI NIH HHS/United States ; R01 HL145676/HL/NHLBI NIH HHS/United States ; R01 HL158641/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/complications/virology/pathology ; *Cardiovascular Diseases/etiology/virology/physiopathology/pathology ; *SARS-CoV-2 ; Animals ; Induced Pluripotent Stem Cells ; Post-Acute COVID-19 Syndrome ; }, abstract = {The COVID-19 pandemic has revealed that the impact of SARS-CoV-2 infection extends well beyond the acute phase, with long-term sequelae affecting multiple organ systems, most notably, the cardiovascular system. Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by persistent symptoms such as fatigue, dyspnea, chest pain, and palpitations, which can last for months or even years after initial recovery. Increasing evidence implicates immune dysregulation, endothelial dysfunction, persistent viral antigens, and coagulopathy as central drivers of cardiovascular complications. Mechanistic studies demonstrate that direct viral infection of cardiac and vascular cells, along with autoantibody formation and cytokine-mediated injury, contribute to myocardial inflammation, fibrosis, and arrhythmias. Sex-based immunological differences and underlying comorbidities further influence individual susceptibility and disease trajectory. Large-scale epidemiological studies have confirmed significantly increased risks of pericarditis, cardiomyopathy, dysrhythmias, and heart failure among COVID-19 survivors. In parallel, the emergence of advanced preclinical platforms, including patient-derived induced pluripotent stem cell (iPSC)-based cardiac organoids, engineered heart tissues, and organ-on-a-chip systems has enabled mechanistic dissection of Long COVID pathophysiology. These human-relevant models, when integrated with clinical datasets and artificial intelligence (AI)-driven analytics, offer powerful tools for biomarker discovery, risk stratification, and precision therapeutic development. This review synthesizes the current understanding of cardiovascular involvement in Long COVID, highlights key mechanistic insights from both clinical and preclinical studies, and outlines future directions for diagnostic and therapeutic innovation.}, }
@article {pmid41048263, year = {2025}, author = {Verma, A and Naidu, SV and Sulthana, H and Ullah, A and Shabil, M and Sah, R and Mehta, R and Jan, A and Ain, NU and Rahim, A and Abu Nahla, U}, title = {Musculoskeletal manifestations in post-acute sequelae of SARS-CoV-2 infection: a systematic review and meta-analysis.}, journal = {Frontiers in public health}, volume = {13}, number = {}, pages = {1662953}, pmid = {41048263}, issn = {2296-2565}, mesh = {Humans ; *COVID-19/complications/epidemiology ; *Musculoskeletal Diseases/epidemiology/etiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Prevalence ; Incidence ; Myalgia/epidemiology ; }, abstract = {BACKGROUND: The COVID-19 pandemic has highlighted a spectrum of long-term sequelae, with musculoskeletal symptoms being a substantial component of Post-Acute Sequelae of SARS-CoV-2 infection (PASC). This systematic review and meta-analysis aimed to evaluate the incidence and nature of musculoskeletal manifestations in individuals recovering from COVID-19.<br><br>METHODS: A systematic search across PubMed, Embase, and Web of Science was performed up to February 15, 2024, to identify studies reporting on musculoskeletal symptoms post-COVID-19. Observational studies which reported any musculoskeletal symptoms of PASC were included. Data were pooled using a random-effects model to calculate the incidence of symptoms, with subgroup analyses based on time since infection. Statistical analysis were conducted in R software (V 4.3).<br><br>RESULTS: Sixty-four studies were included, demonstrating a pooled prevalence of muscle pain at 28% (95% CI: 22%-35%), which increased to 25.9% (95% CI: 20.7%-31.7%) at 12 months post-infection. Joint pain showed a pooled prevalence of 14.8% (95% CI: 10.6%-20.2%), with no significant temporal change. Muscle weakness was observed in 12.9% (95% CI: 4.2%-32.9%) of patients. Notable heterogeneity was observed across studies (I [2] > 89% for all symptoms).<br><br>CONCLUSION: Musculoskeletal symptoms are prevalent in individuals with PASC, with muscle pain being the most common. The findings highlight the need for comprehensive clinical management and continuous research to create targeted treatments and revise care protocols as the pandemic evolves.}, }
@article {pmid41049897, year = {2025}, author = {Castellano, B and Castellano, C and Sobczak, A and Khanna, D}, title = {Long-Term Manifestations of COVID-19: A Review.}, journal = {Cureus}, volume = {17}, number = {9}, pages = {e91492}, pmid = {41049897}, issn = {2168-8184}, abstract = {Although most coronavirus disease 2019 (COVID-19) cases resolve within a few weeks after the onset of infection, a considerable number of patients still suffer from prolonged or recurrent symptoms evident after weeks or months post-COVID-19 recovery. This paper analyzed the current literature related to long-term manifestations of COVID-19 and aimed to identify the common symptoms reported four weeks or more after the initial onset of the disease. COVID-19 has been shown to have lasting systemic effects on an array of organ systems, such as the lungs, heart, brain, and gastrointestinal systems. Common symptoms include, but are not limited to, fatigue, brain fog, respiratory difficulties, and loss of taste and smell. The impact of COVID-19 on multiple organ systems is thought to be associated with its ability to bind angiotensin-converting enzyme 2 (ACE2) receptors throughout the body and promote cytokine release. This study provides insight into common long-term manifestations of COVID-19. Future studies should look at how long COVID-19 syndrome affects various subpopulations differently.}, }
@article {pmid41049923, year = {2025}, author = {Pedraza, A and Bonnice, S and Won, MN and Kesselman, MM and Demory Beckler, M}, title = {Impact of COVID-19 on the Gut Microbiome: A Review.}, journal = {Cureus}, volume = {17}, number = {9}, pages = {e91470}, pmid = {41049923}, issn = {2168-8184}, abstract = {Coronavirus Disease 2019 (COVID-19) has resulted in over 6 million deaths worldwide in fewer than four years and is a result of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The protein that mediates SARS-CoV-2 host cell entry is the angiotensin-converting enzyme 2 (ACE2), which is highly expressed on the membrane of gastrointestinal (GI) cells. Consequently, infection can lead to direct damage to the GI tract and gut dysbiosis, which is associated with an imbalance of microbiota, inflammation, and other systemic infections and diseases. In this review, we will focus on the impact of COVID-19 on the GI system. We will examine the pathophysiology of gut dysbiosis in COVID-19 patients, as well as emphasize the significance of probiotics in addressing this condition. Additionally, we will identify key areas of interest that warrant further investigation.}, }
@article {pmid41056092, year = {2025}, author = {Newby, MJ and Haracz, K and Lane, SJ and Tona, J}, title = {Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and Occupational Performance: A Scoping Review.}, journal = {The American journal of occupational therapy : official publication of the American Occupational Therapy Association}, volume = {79}, number = {6}, pages = {}, doi = {10.5014/ajot.2025.051238}, pmid = {41056092}, issn = {0272-9490}, mesh = {Humans ; *Occupational Therapy/methods ; Child ; *Obsessive-Compulsive Disorder/rehabilitation ; *Activities of Daily Living ; Social Participation ; Autoimmune Diseases ; }, abstract = {IMPORTANCE: Pediatric acute-onset neuropsychiatric syndrome (PANS) is a neuroimmune condition that significantly affects children's occupational performance across multiple domains. However, occupational performance is often overlooked in current PANS clinical frameworks, despite its critical role in daily functioning and well-being.<br><br>OBJECTIVE: To synthesize evidence on the occupational performance challenges experienced by children with PANS, the tools used to assess these challenges, and occupational therapy interventions used with these children.<br><br>DATA SOURCES: MEDLINE, CINAHL, Cochrane Library, PsycINFO, SCOPUS, ERIC, and EMBASE were searched from their inception through May 17, 2024.<br><br>Peer-reviewed studies addressing PANS and occupational performance were included, with data categorized using the Occupational Therapy Practice Framework, 4th Edition.<br><br>FINDINGS: Of 3,431 records, 40 studies met inclusion criteria. Occupational performance challenges centered on communication, nutrition, education, rest/sleep, social participation, and toileting, with limited data on bathing, dressing, personal hygiene, and play and leisure. Assessments emphasized client factors, rarely using occupation-based tools. Only 2 studies mentioned occupational therapy interventions.<br><br>CONCLUSIONS AND RELEVANCE: PANS has a pervasive impact on children's occupational performance, highlighting the urgent need to prioritize it within clinical frameworks. Future research should focus on occupation-based intervention studies and assessments to enhance outcomes for children with PANS. Plain-Language Summary: Pediatric acute-onset neuropsychiatric syndrome (PANS) causes sudden, severe symptoms, such as obsessive-compulsive behaviors, eating difficulties, sensory and motor changes, and developmental regression, which significantly disrupt children's ability to perform daily activities. This study included 40 research articles addressing what is known about the impact of PANS on children's daily functioning and the role of occupational therapy in managing challenges. Results showed that most studies focused on communication, nutrition, education, sleep, social, and toileting challenges, but few addressed other daily tasks like bathing, dressing, personal hygiene, and play or leisure. Despite identified challenges, only two studies mentioned occupational therapy interventions, highlighting a major gap in the evidence. Assessments focused mainly on a child's skills and challenges, rather than looking at how the child participates in everyday activities. The findings highlight the need to better understand the challenges children with PANS face in their everyday activities and to provide practical strategies to help them succeed. Positionality Statement: Newby is a pediatric occupational therapist and researcher with both professional and personal experience of PANS. Her clinical work with children diagnosed with PANS, along with personal experience supporting a family member with this condition, has deepened her interest in the episodic fluctuations in occupational performance that occur during periods of exacerbation and remission. Haracz is an occupational therapist, academic, and researcher with a focus on mental health and the intersection between physical and psychological well-being. Lane is an occupational therapist, academic, and researcher who specializes in the neuroscience of developmental conditions and how sensory processing differences affect children's engagement in daily occupations. Tona is an occupational therapist and educational psychologist whose interest in neuroinflammatory disorders emerged following a family member's diagnosis with PANS. Her research explores the characteristics of PANS, treatment access, caregiver burden, and the role of occupational therapy in improving participation in both PANS and long-COVID populations.}, }
@article {pmid41057797, year = {2025}, author = {Bessaguet, C and Bonilla, A and Polin, C and Lacroix, A and Cartz-Piver, L}, title = {A systematic review to find link between past psychiatric history and development of long covid.}, journal = {BMC psychiatry}, volume = {25}, number = {1}, pages = {942}, pmid = {41057797}, issn = {1471-244X}, mesh = {Humans ; *COVID-19/psychology/complications/epidemiology ; *Mental Disorders/epidemiology/psychology/complications ; Risk Factors ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Anxiety/epidemiology/psychology ; *Depression/epidemiology ; }, abstract = {BACKGROUND: Covid-19 is a pandemic acute infectious disease that emerged in 2019. It is estimated that 10-20% will develop persistent symptoms, known as long Covid or post-Covid syndrome. The risk factors for the development of this syndrome are still being studied. Psychosocial factors are known to increase the duration and severity of respiratory infections.<br><br>AIMS: (i) to review current knowledge of the link between past psychiatric history and the development of long Covid; (ii) to obtain information on the psychological experience of the initial infection; (iii) to establish a link between the presence of psychiatric symptoms during the acute phase and the development of long Covid.<br><br>METHOD: We conducted a systematic review according to PRISMA standards using the Pubmed, Science Direct and Scopus databases. We included observational studies of adult subjects with long Covid whose psychiatric and/or addictive histories were searched.<br><br>RESULTS: A total of 36 articles were included in our review. Depression and anxiety appear to be risk factors for the development of long Covid. There is no consensus on the contribution of smoking to the onset of the syndrome. The negative psychological experience of the acute infection favours the persistence of symptoms. Psychological symptoms during the acute phase, studied in only one of our articles, seem to contribute to the persistence of concentration and attention problems.<br><br>CONCLUSION: Psychological comorbidities pre-existing COVID-19 infection, in particular depression and anxiety, as well as a poor psychological experience of the acute phase, may favour the development of long Covid.<br><br>TRIAL REGISTRATION NUMBER: PROSPERO registration number CRD42023391720.}, }
@article {pmid41057923, year = {2025}, author = {Gidey, K and Niriayo, YL and Asgedom, SW and Lubetkin, E}, title = {Health-related quality of life in COVID-19 patients: a systematic review and meta-analysis of EQ-5D studies.}, journal = {Health and quality of life outcomes}, volume = {23}, number = {1}, pages = {97}, pmid = {41057923}, issn = {1477-7525}, support = {U54 MD017979/MD/NIMHD NIH HHS/United States ; 1627-RA//EuroQol Research Foundation/ ; }, mesh = {Humans ; *Quality of Life/psychology ; *COVID-19/psychology ; SARS-CoV-2 ; Female ; Male ; Health Status ; }, abstract = {BACKGROUND: COVID-19 has affected millions globally, with a significant proportion experiencing long-COVID and impaired health-related quality of life (HRQoL). This systematic review and meta-analysis aimed to synthesize the existing literature on HRQoL in COVID-19 patients.<br><br>METHODS: We conducted a systematic search of PubMed, Embase, Web of Science, Scopus, and the Cochrane Library for studies published between December 2019 and March 2025. Eligible studies were peer-reviewed and assessed HRQoL in COVID-19 patients using the EQ-5D instrument. Study quality and risk of bias were evaluated using the Newcastle-Ottawa Scale. Pooled health utility values were estimated using a random-effects model, and heterogeneity was assessed via I[2] statistics. Predictors of poor HRQoL were qualitatively narrated.<br><br>RESULTS: Out of 3539 references, 187 studies with 116,525 participants were analyzed. The majority (80.2%) used the EQ-5D-5&#xa0;L version. The pooled mean EQ-5D utility score was 0.76 (95% CI 0.74-0.79, I[2] = 99.9%) while the mean EQ-5D Visual Analogue Scale (VAS) score was 70.76 (95% CI 68.48-73.04; I[2] = 99.7%). Pain/discomfort and anxiety/depression were the most affected domains, reported by 51% and 46% of patients, respectively. Subgroup analysis showed significant differences in HRQoL based on national income status (p&#x2009;=&#x2009;0.038) and geographic region (p&#x2009;<&#x2009;0.001). Common predictors of lower HRQoL included older age, female gender, disease severity, comorbidities, and post-COVID-19 symptoms.<br><br>CONCLUSION: This systematic review demonstrates a substantial reduction in HRQoL among COVID-19 patients compared to the general population. The pooled utility values of COVID-19 contribute to understanding patients' HRQoL and can assist in calculating Quality-Adjusted Life Years. This provides essential data for future economic evaluations and informs health policy decisions.}, }
@article {pmid41062137, year = {2025}, author = {Daniels, S and Wei, H and McElvenny, DM and van Tongeren, M and Bramwell, D and Coleman, A and Forde, D and Wiggans, R}, title = {Return to work with long COVID: a rapid review of support and challenges.}, journal = {BMJ open}, volume = {15}, number = {10}, pages = {e101698}, pmid = {41062137}, issn = {2044-6055}, mesh = {Humans ; *Return to Work ; Workplace ; *Post-Acute COVID-19 Syndrome/rehabilitation ; }, abstract = {OBJECTIVES: To explore existing evidence for the provision of support for return to work (RTW) in long COVID (LC) patients and the barriers and facilitators to taking up this support.<br><br>DESIGN: A rapid review reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The study was preregistered in PROSPERO (ID: CRD42023478126).<br><br>DATA SOURCES: Searches were completed in June 2024 across major databases including MEDLINE, Embase, PsycINFO, evidence-based medicine reviews, Web of Science and Google Scholar.<br><br>ELIGIBILITY CRITERIA: Included studies focused on people with LC (PwLC) symptoms lasting over 12 weeks and addressed either: (1) non-workplace- or workplace-based support for RTW and/or (2) barriers and facilitators to RTW in this population.<br><br>DATA EXTRACTION AND SYNTHESIS: A quality assessment was conducted using the JBI Systematic Reviews critical appraisal tool. The data were summarised in tabular format and a narrative synthesis.<br><br>RESULTS: Twenty-five studies were included. While many studies demonstrated rigorous methodologies and low risk of bias levels, some had high and medium risk levels. Non-workplace-based support was mostly measured quantitatively and included interdisciplinary healthcare programmes, clinical interventions and rehabilitation programmes focusing on pacing and breathing strategies. Compensation and insurance schemes were important funders of these interventions.Workplace-based support was mostly measured qualitatively. Barriers to the provision of support at organisational level included lack of understanding of LC symptoms, insufficient workplace guidance and educational gaps among managers. Individual barriers included threat of income loss, remote working and disconnection from the workplace. Facilitators for support included recognition and validation of LC and its symptoms, and eligibility for disability benefits associated with work.<br><br>CONCLUSIONS: RTW is an important outcome of health-related absence and should be systematically recorded in studies of PwLC. The heterogeneity and unpredictability of LC symptoms create challenges for supporting working age populations. Further research is crucial to better understand the specific RTW needs for PwLC and address potential barriers and facilitators to workplace-based support, particularly through interventions, organisational practices and employ-led policies that enable sustained RTW. Consistent guidelines on LC's definition and disability status may facilitate the provision of support and the development of interventions.<br><br>PROSPERO REGISTRATION NUMBER: CRD42023478126.}, }
@article {pmid41062170, year = {2025}, author = {Houweling, L and Rots, I and Bloemsma, LD and van Vorstenbosch, R and Del Motto, S and Vermeulen, RCH and Maitland-Van der Zee, AH and Golebski, K and Downward, GS}, title = {Impact of air pollution on COVID-19 severity: a systematic review of underlying biological mechanisms.}, journal = {European respiratory review : an official journal of the European Respiratory Society}, volume = {34}, number = {178}, pages = {}, pmid = {41062170}, issn = {1600-0617}, mesh = {Humans ; *Air Pollutants/adverse effects ; *Air Pollution/adverse effects ; *COVID-19/diagnosis/epidemiology/immunology/virology ; Particulate Matter/adverse effects ; SARS-CoV-2 ; Severity of Illness Index ; }, abstract = {BACKGROUND: Our recent systematic review highlighted key associations between ambient air pollution (AAP) exposure and COVID-19 severity. This systematic review aims to summarise toxicological studies on the biological mechanisms underlying these associations.<br><br>METHODS: On 17 July 2025, PubMed, Embase, Scopus and Web of Science were searched for in vitro, in vivo and in silico studies that examined the biological mechanisms of AAP exposure on COVID-19 health outcomes. Two independent reviewers engaged in the selection and data extraction process. The methodological quality of the included studies was assessed with the Toxicological Data Reliability Assessment Tool. The Integrated Network and Dynamical Reasoning Assembler (INDRA) was used to provide visual biomechanistic summaries of the included studies by creating knowledge graphs of the described mechanisms.<br><br>RESULTS: A total of 18 studies were included in this review. Findings consistently indicated that AAP exposure can worsen COVID-19 severity through two key mechanisms 1) increased expression of viral entry factors (e.g. angiotensin-converting enzyme 2 and transmembrane serine protease 2), facilitating infection, and 2) immune dysregulation, resulting in increased inflammation and oxidative stress. These key mechanisms were also identified in the INDRA networks. While studies commonly focused on particulate matter (n=15), similar effects were seen with ultrafine particles and ozone.<br><br>CONCLUSION: These findings highlight the impact of AAP exposure on COVID-19 health outcomes on the molecular level. The findings of this review illustrate the urgent need for air quality improvements to help shape public health strategies to reduce and prevent future health impacts caused by AAP exposure.}, }
@article {pmid41065846, year = {2025}, author = {Chang, CC and Li, YH and Chen, HH and Sun, SF}, title = {Clinical applications and molecular mechanisms for intravenous laser blood irradiation: a systematic review.}, journal = {Lasers in medical science}, volume = {40}, number = {1}, pages = {416}, pmid = {41065846}, issn = {1435-604X}, support = {TSGH-D-110120//Tri-Service General Hospital/ ; VTA114-V3-1-2//Taipei, Taichung, Kaohsiung Veterans General Hospital, Tri-Service General Hospital, Academia Sinica Joint Research Program/ ; VTA114-V3-1-1//Taipei, Taichung, Kaohsiung Veterans General Hospital, Tri-Service General Hospital, Academia Sinica Joint Research Program/ ; KAFGH-ZY-A-113016//Zuoying Armed Forces General Hospital/ ; KSVGH-114-102//Kaohsiung Veterans General Hospital/ ; }, mesh = {Humans ; *Blood/radiation effects ; Cardiovascular Diseases/radiotherapy ; COVID-19 ; *Low-Level Light Therapy/methods ; Musculoskeletal Diseases/radiotherapy ; Nervous System Diseases/radiotherapy ; }, abstract = {Intravenous Laser Irradiation of Blood (ILIB) is a therapeutic approach that utilizes low-level laser energy to irradiate blood, showing potential clinical value in treating various diseases in recent years. This systematic review aims to comprehensively examine the basic principles, technological developments, biological effects, and clinical applications of ILIB, while analyzing the level of evidence and limitations of existing research. Through searching relevant literature in databases such as PubMed, this study collected research on ILIB applications in musculoskeletal diseases, respiratory diseases, cardiovascular diseases, and neurological disorders. Results indicate that ILIB exhibits multiple biological effects, including improved blood rheological properties, enhanced erythrocyte oxygen-carrying capacity, immune regulation, and reduction of inflammatory responses and oxidative stress. Clinical studies suggest that ILIB has positive therapeutic effects on musculoskeletal pain, sleep disorders, pulmonary diseases, and long COVID-related cognitive impairments. However, existing research still has limitations such as small sample sizes, lack of large-scale randomized controlled trials, and non-standardized dosage parameters. Future research should focus on developing standardized treatment protocols, exploring mechanisms of action in depth, and strategies for combining with conventional therapies to further establish ILIB's position in clinical practice.}, }
@article {pmid41073313, year = {2025}, author = {Wang, MC and Liu, X and Hu, K}, title = {[Intermittent hypoxia exposure in the rehabilitation of long COVID patients].}, journal = {Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases}, volume = {48}, number = {10}, pages = {961-964}, doi = {10.3760/cma.j.cn112147-20250601-00295}, pmid = {41073313}, issn = {1001-0939}, support = {JCRCYG-2022-012//Interdisciplinary Innovative Talents Foundation from Renmin Hospital of Wuhan University/ ; }, mesh = {Humans ; *COVID-19/rehabilitation ; *Hypoxia/rehabilitation ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Fatigue ; }, abstract = {Patients recovering from COVID-19 infection often experience "Long COVID", which is characterized by symptoms such as fatigue, reduced exercise capacity or dyspnea, and cognitive dysfunction. These symptoms negatively impact their quality of life. Currently, there is a lack of widely recognized therapeutic approaches or specific pharmacological interventions for managing these conditions. During intermittent hypoxic exposure (IHE), participants are alternated to hypoxic and normoxic exposure, which induced beneficial adaptive responses in the body. Emerging evidence suggests that IHE can alleviate symptoms of Long COVID through mechanisms such as improving ventilatory function, enhancing cardiopulmonary endurance, modulating immune responses, and reducing inflammation. These effects contribute to an improved quality of life and more holistic recovery, highlighting the promising potential of IHE in managing long COVID.}, }
@article {pmid41073921, year = {2025}, author = {Takamatsu, N and Kuga, H}, title = {Applicability and adaptation of cognitive behavior therapy for long COVID neuropsychiatric symptoms: a review with insights from ME/CFS.}, journal = {BMC infectious diseases}, volume = {25}, number = {1}, pages = {1275}, pmid = {41073921}, issn = {1471-2334}, support = {JP23K02953//Japan Society for the Promotion of Science/ ; }, abstract = {BACKGROUND: Long COVID presents a spectrum of persistent symptoms that substantially overlap with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), including debilitating fatigue, post-exertional malaise, cognitive dysfunction, and neuropsychiatric manifestations. Despite growing evidence of shared pathophysiological mechanisms, neither condition has established diagnostic biomarkers or disease-modifying treatments. Cognitive behavior therapy (CBT), when appropriately implemented, may serve as one component of comprehensive care. This review examines the neuropsychiatric manifestations, management principles, and implementation considerations for CBT in long COVID, drawing insights from ME/CFS experience.<br><br>MAIN BODY: Our analyses revealed substantial overlap between patients with long COVID and ME/CFS including immune dysregulation, neuroinflammation, and metabolic dysfunction while identifying distinct features in disease trajectories. Evidence suggests ME/CFS may represent a severe phenotype in a subset of patients with long COVID. Management principles applicable to both conditions include patient validation, comprehensive needs assessment, individualized energy management, symptom-specific interventions, and comorbidity management. Current clinical trials demonstrate methodological evolution in CBT implementation, from traditional protocols to digital platforms. Moderate-certainty evidence indicates CBT may reduce fatigue and improve cognitive function in long COVID. However, substantial heterogeneity exists in both intervention characteristics and condition definitions. Implementation success requires provider competency, terminological precision, and individualized approaches that respect energy limitations. Careful monitoring for post-exertional symptom exacerbation is essential. We emphasize that these approaches do not imply these conditions are primarily psychological.<br><br>CONCLUSION: Our review synthesizes current evidence on CBT in long COVID management, considering lessons from ME/CFS. Substantial challenges remain in standardizing terminology, strengthening trial methodology, and determining optimal implementation strategies. Future research should incorporate objective outcome measures alongside subjective reports, while clinical practice should consider how cognitive-behavioral approaches might contribute to comprehensive care plans tailored to individual patient needs. This approach recognizes that addressing both physical and psychological dimensions of these conditions may enhance treatment outcomes, while acknowledging the individualized nature of patient responses to different therapeutic elements.}, }
@article {pmid41076807, year = {2025}, author = {Domingo, JL}, title = {Differentiating COVID-19 vaccine-related adverse events from long COVID: A comprehensive review of clinical manifestations, pathophysiology, and diagnostic approaches.}, journal = {Vaccine}, volume = {66}, number = {}, pages = {127842}, doi = {10.1016/j.vaccine.2025.127842}, pmid = {41076807}, issn = {1873-2518}, mesh = {Humans ; *COVID-19 Vaccines/adverse effects/administration &amp; dosage ; *COVID-19/prevention &amp; control/diagnosis/immunology ; SARS-CoV-2/immunology ; Post-Acute COVID-19 Syndrome ; Vaccination/adverse effects ; }, abstract = {The global deployment of COVID-19 vaccines has introduced diagnostic challenges due to overlapping symptoms with long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), prompting a comprehensive review of vaccine safety profiles, long COVID manifestations, and evidence-based differentiation strategies. Through a literature search (PubMed, Scopus, Web of Science) from December 2020 to June 2025, including peer-reviewed studies, clinical trials, and cohort studies, the present review reports that COVID-19 vaccines maintain robust safety, with rare adverse events like myocarditis and thrombosis with thrombocytopenia syndrome, while long COVID affects 10-40 % of SARS-CoV-2 survivors, presenting symptoms such as fatigue, cognitive dysfunction, and dyspnea. Differentiation between these conditions relies on careful analysis of the timing of symptom onset, detailed symptom characterization, and the use of advanced diagnostic tools. Systematic clinical assessment is essential for accurate diagnosis, which is critical for appropriate patient management, maintaining public confidence in vaccination, and guiding future research. Further studies are needed to validate diagnostic biomarkers, develop targeted therapies, and monitor long-term outcomes, with standardized global registries and interdisciplinary collaboration identified as key priorities for improving care and advancing the field.}, }
@article {pmid41082082, year = {2025}, author = {Wasim, R}, title = {From infection to intervention: post-acute sequelae of SARS-CoV-2 infection and cardiovascular risk.}, journal = {Inflammopharmacology}, volume = {33}, number = {11}, pages = {6577-6588}, pmid = {41082082}, issn = {1568-5608}, mesh = {Humans ; *COVID-19/complications ; *Cardiovascular Diseases/etiology/epidemiology/virology ; Post-Acute COVID-19 Syndrome ; Risk Factors ; SARS-CoV-2 ; Biomarkers ; }, abstract = {COVID is now a worldwide epidemic of non-communicable diseases. The symptoms, which impact several organs, might last for hours, weeks, or even months after the SARS-CoV-2 infection has ended. Electrocardiogram abnormalities (ECG), postural orthostatic tachycardia, and supraventricular or ventricular arrhythmias are among the common signs of long COVID-19. According to data, certain patient groups have persistent, post-infectious perimyocarditis, which may lead to left or right ventricular failure, arterial wall inflammation, or microthrombosis. This information has been made available by cardiac and vasculature imaging, and it may be used to develop efficient treatment plans for the cardiovascular symptoms of long COVID. Long COVID requires a greater understanding of the cellular and molecular processes. There are a variety of approaches that have been put forward, some of which include direct impacts on the heart and others that involve microthrombotic damage to the arteries or heart. When evaluated 3 months after SARS-CoV-2 infection, the currently employed circulating biomarkers, such as coagulation and inflammatory markers, do not serve as a highly predictive predictor for the existence or outcome of long COVID. However, further study is required to better understand the underlying processes and particular biomarkers for future COVID preventive methods.}, }
@article {pmid41087378, year = {2025}, author = {Yonker, LM and Dredge, D and Munro, A and Di Chiara, C and Cotugno, N and Buonsenso, D}, title = {The second-order effects that the COVID-19 pandemic has had on pediatric populations.}, journal = {Expert review of anti-infective therapy}, volume = {23}, number = {10}, pages = {997-1009}, doi = {10.1080/14787210.2025.2575044}, pmid = {41087378}, issn = {1744-8336}, support = {R01 HL173059/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/epidemiology/complications/immunology/therapy ; Child ; Adolescent ; Systemic Inflammatory Response Syndrome/epidemiology ; Public Health ; Pandemics ; SARS-CoV-2 ; Autoimmune Diseases/epidemiology ; }, abstract = {INTRODUCTION: SARS-CoV-2 can have long-term health consequences that persist beyond acute infection. While this is evident in adults and the elderly, the impact on children and adolescents remains under recognized. Here we navigate the second-order post-acute effects that the COVID-19 has had on the pediatric populations, with the exception of the mental health implication of social restrictions.<br><br>AREAS COVERED: We outline common scenarios related with SARS-CoV-2 infection encountered in pediatric clinical practice, such as in the Multisystem inflammatory syndrome (MIS-C), Long Covid, neurological and autoimmune complications of Covid-19, immunological impact of the viral infection, as well as epidemiological and public health consequences associated with the implementation of non-pharmacological interventions.<br><br>EXPERT OPINION: SARS-CoV-2 has had several second-order effects on child health, from a biological, epidemiological, and public health perspective, highlighting the complexity of dealing with new infections and the urgent need to implement multidisciplinary interventions that support the health of people at single person and societal level. Funding on modern surveillance system, preventing strategies and research to better understand and cure post-acute complications of viral infections should be a priority of every funding agency.}, }
@article {pmid41089328, year = {2025}, author = {Blitshteyn, S and Funez-dePagnier, G and Szombathy, A and Hutchinson, M}, title = {Immunotherapies for postural orthostatic tachycardia syndrome, other common autonomic disorders, and Long COVID: current state and future direction.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1647203}, pmid = {41089328}, issn = {2235-2988}, mesh = {Humans ; *Postural Orthostatic Tachycardia Syndrome/therapy/immunology ; *COVID-19/therapy/immunology/complications ; *Immunotherapy/methods/trends ; *Autonomic Nervous System Diseases/therapy/immunology ; Immunoglobulins, Intravenous/therapeutic use ; SARS-CoV-2 ; Plasmapheresis ; Adrenal Cortex Hormones/therapeutic use ; Post-Acute COVID-19 Syndrome ; }, abstract = {Postural orthostatic tachycardia syndrome (POTS), neurocardiogenic syncope, and orthostatic hypotension are the most common autonomic disorders encountered in clinical practice. The autoimmune etiology and association of these conditions with systemic autoimmune and inflammatory disorders, autonomic neuropathy, and post-acute infectious syndromes, including Long COVID, suggest that immunotherapies should be considered as a therapeutic option, at least in a subset of patients. However, the treatment of common autonomic disorders has traditionally included pharmacologic and non-pharmacologic symptomatic therapies as the standard approach. Unfortunately, these symptomatic therapies have been of limited or insufficient efficacy to meaningfully improve functional status or result in recovery, especially in patients with severe symptoms. Case reports, case series, and clinical experience suggest that intravenous and subcutaneous immunoglobulin, as well as other immunologic therapies (such as plasmapheresis, corticosteroids, and rituximab), may be effective in some patients with severe POTS and other common autonomic disorders who are refractory to standard therapies. In this narrative review, we summarize the literature available on the topic of immunotherapies for POTS, other common autonomic disorders, and Long COVID. We also highlight the need for large, multicenter, placebo-controlled trials of immunoglobulin, plasmapheresis, intermittent corticosteroids, and other repurposed immunotherapies in patients with common autonomic disorders who have significant functional impairment.}, }
@article {pmid41089587, year = {2025}, author = {Albazee, E and Alajmi, SA and Alkandari, AM and Aladwani, AN and Alenezi, YY and Alsaeed, MA and Uqlah, B and Abu-Zaid, A}, title = {Platelet-Rich Plasma for COVID-19-Related Olfactory Dysfunction: A Systematic Review and Meta-analysis of Randomized Controlled Trials.}, journal = {Cureus}, volume = {17}, number = {10}, pages = {e94386}, pmid = {41089587}, issn = {2168-8184}, abstract = {A notable rise in olfactory dysfunction (OD) prevalence has been observed since the COVID-19 pandemic. COVID-19-related OD is associated with several consequences, especially deteriorated quality of life. Hence, several treatment options have been investigated, with platelet-rich plasma (PRP) showing promising results. A systematic review and meta-analysis summarizing randomized controlled trial (RCT) evidence were retrieved from PubMed, Google Scholar, Scopus, and Web of Science up to June 2025. The risk of bias was assessed using the Cochrane Risk of Bias 2 assessment tool. Data were analyzed using Stata MP version 18 (StataCorp LLC, College Station, TX), pooling dichotomous outcomes as relative risks (RRs) and continuous outcomes as standardized mean differences (SMDs), each with 95% confidence intervals (CIs). Four RCTs, including 198 participants, were included in our meta-analysis. PRP significantly improved objective olfactory scores (SMD = 1.86, 95% CI (0.14, 3.57), p = 0.03) and subjective olfactory scores (SMD = 0.92, 95% CI (0.32, 1.51), p < 0.001). Additionally, PRP significantly increased the response rate (RR = 1.79, 95% CI (1.14, 2.81), p = 0.01). PRP was generally well-tolerated across the included trials, with no major adverse events reported. Two RCTs showed an overall low risk of bias, one trial showed some concerns, and another showed a high risk of bias. With uncertain evidence, PRP may improve both objective and subjective smell function and clinical outcomes in people with long COVID-related OD. PRP treatment was reported to be safe, with minor, temporary side effects primarily related to the procedure. Although initial results are promising, the small number of RCTs requires a cautious approach to interpretation.}, }
@article {pmid41091675, year = {2025}, author = {Nagra, G and Ezeugwu, VE and Bostick, GP and Branton, E and Dennett, L and Drake, K and Durand-Moreau, Q and Guptill, C and Hall, M and Ho, C and Hung, P and Khan, A and Lam, GY and Nowrouzi-Kia, B and Gross, DP}, title = {Return-to-work for people living with long COVID: A scoping review of interventions and recommendations.}, journal = {PloS one}, volume = {20}, number = {10}, pages = {e0321891}, pmid = {41091675}, issn = {1932-6203}, mesh = {Humans ; *Return to Work ; *Post-Acute COVID-19 Syndrome/complications/rehabilitation ; }, abstract = {INTRODUCTION: Long COVID is characterized by the presence of new onset or persistent symptoms 3 months after a suspected or confirmed history of SARS-CoV-2 infection. It is a complex and multi-faceted condition that affects people in different ways. Long COVID affects individuals' labour market participation. While some cannot work, others may return to work (RTW) in a limited capacity. Determining what rehabilitation or related strategies are safe and effective for facilitating RTW is necessary.<br><br>OBJECTIVES: To synthesize evidence on RTW interventions for people living with Long COVID and to identify 'promising' interventions for enhancing work ability and RTW.<br><br>METHODS: We followed Arksey &amp; O'Malley's methodology and the PRISMA extension for scoping reviews. Five electronic bibliographic databases and grey literature were searched. The literature search included various study designs, such as randomized controlled trials (RCT), quasi-experimental designs, and observational studies as well as clinical practice guidelines (CPGs). Two reviewers conducted screening and data extraction, with disagreements resolved through consensus. Intervention studies were categorized as promising (statistically significant RTW outcomes or &#x2265; 50% RTW), somewhat promising (20% to < 50% RTW), not promising (non-statistically significant RTW outcomes or < 20% RTW), or uncertain (did not specify proportion of RTW).<br><br>RESULTS: Twelve CPGs and nineteen intervention studies were identified. Of the intervention studies, 5 were cohort studies, 3 quasi-experimental studies, 4 observational, 2 interventional, 3 RCTs, and 2 case reports. Promising interventions included multimodal and interdisciplinary work-focused rehabilitation, multidisciplinary inpatient and outpatient rehabilitation, psychoeducation, pacing, and breathing strategies, shifting focus from symptom monitoring to optimizing functional outcomes, enhanced external counterpulsation inflatable pressure to improve blood flow, and constraint-induced cognitive therapy.<br><br>CONCLUSION: Many uncertainties remain regarding which RTW interventions are effective or the optimal characteristics of these interventions.}, }
@article {pmid41094377, year = {2025}, author = {Arab, Z and Shayanfar, N and Mojaver, MR and Khormali, M and Boskabady, MH and Niazmand, S}, title = {Cardiopulmonary crosstalk in Long COVID: a systematic review of emerging evidence.}, journal = {BMC cardiovascular disorders}, volume = {25}, number = {1}, pages = {742}, pmid = {41094377}, issn = {1471-2261}, mesh = {Humans ; *COVID-19/physiopathology/complications ; Renin-Angiotensin System ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Endothelium, Vascular/physiopathology ; *Pulmonary Fibrosis/physiopathology ; }, abstract = {BACKGROUND: Long COVID is a complex, multisystem syndrome with significant cardiopulmonary implications. Persistent inflammation, endothelial dysfunction, and microvascular injury contribute to prolonged symptoms such as dyspnea, chest pain, and exercise intolerance. Despite growing recognition of these complications, the underlying mechanisms of cardiopulmonary interactions remain poorly understood.<br><br>METHODS: A comprehensive literature search was conducted on PubMed, Scopus, Google Scholar, and Web of Science covering studies from 2019 to 2025. Keywords included "Long COVID", "cardiopulmonary interaction", "pulmonary fibrosis", "myocardial inflammation", and "endothelial dysfunction". A total of 102 articles were included, comprising 65 original research studies and 37 review articles.<br><br>RESULTS: Pulmonary sequelae, such as fibrotic remodeling, persistent hypoxia, and microthrombosis, impose significant strain on the cardiovascular system, exacerbating myocardial inflammation, arrhythmias, and endothelial dysfunction. Shared mechanisms, such as oxidative stress, immune dysregulation, and neurohumoral activation, create a vicious cycle of sustained cardiopulmonary impairment. The disruption of the renin-angiotensin-aldosterone system (RAAS) further contributes to systemic vascular dysregulation.<br><br>CONCLUSION: A deeper understanding of cardiopulmonary interactions in Long COVID is essential for developing effective management strategies. Targeting inflammatory pathways, restoring endothelial function, and addressing autonomic instability may provide therapeutic benefits. As the long-term impact of this syndrome continues to evolve, further research is needed to refine treatment approaches and mitigate its burden on global health.}, }
@article {pmid41104805, year = {2025}, author = {Luo, S and Lai, LY and Zhu, R and Gao, Y and Zhao, Z}, title = {Prevalence and duration of common symptoms in people with long COVID: a systematic review and meta-analysis.}, journal = {Journal of global health}, volume = {15}, number = {}, pages = {04282}, pmid = {41104805}, issn = {2047-2986}, mesh = {Humans ; *COVID-19/epidemiology/complications ; Prevalence ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Time Factors ; Fatigue/epidemiology ; }, abstract = {BACKGROUND: During the COVID-19 pandemic, an increasing number of patients have reported persistent symptoms after recovery, a phenomenon known as long COVID. These symptoms may persist for weeks or months, affecting the patient's daily life and health. To systematically understand the long-term impact of long COVID, this study conducted a systematic review and meta-analysis. This study aims to determine the long-term effects of long COVID by identifying, evaluating and summarising the incidence and duration of persistent symptoms after the acute phase of COVID-19.<br><br>METHOD: We searched PubMed, Embase, and medRxiv up to August 2021 for articles and preprints presenting original research on the symptoms of long COVID. Following title/abstract and full-text screening, based on the PICOS framework, we excluded articles that did not clearly report on diagnoses, reported on symptoms lasting less than four weeks, lacked epidemiological data, or did not provide complete data. We assessed the bias of included studies using the Newcastle-Ottawa Scale. For effects reported in more than two studies, we performed meta-analysis of prevalence, and also counted the duration of each symptom.<br><br>RESULTS: We included 19 observational studies in the meta-analysis, through which we determined the incidence and duration of five common long COVID symptoms, including cognitive/memory/attention disorders (36%, unreported duration), fatigue (34%, 5.5 months), mental health problems (including anxiety and depression, 31%, 3.5-3.8 months), and dyspnoea (24%, 6.52 months) and chest pain (23%, 2 months).<br><br>CONCLUSIONS: The symptoms of long COVID usually persist after the acute phase of COVID-19. The clustering of long COVID symptoms provides a direction for studying the aetiology, diagnosis, and management of post-COVID conditions. Our findings provide important baseline data for the prevention and treatment of long COVID.}, }
@article {pmid41108594, year = {2026}, author = {Akbar, N and Phadke, S and Mehelay, S and Pullattayil, AK and Fakolade, A and Busse, M}, title = {Considerations of race and ethnicity within rehabilitation studies for post COVID-19 condition: A scoping review.}, journal = {PM &amp; R : the journal of injury, function, and rehabilitation}, volume = {18}, number = {4}, pages = {476-491}, pmid = {41108594}, issn = {1934-1563}, mesh = {Humans ; *COVID-19/rehabilitation/ethnology/epidemiology ; *Ethnicity ; *Racial Groups ; SARS-CoV-2 ; *Rehabilitation Research ; Minority Groups ; Patient Selection ; Pandemics ; }, abstract = {Post COVID-19 condition (PCC) or long COVID disproportionately affects racial and ethnic minority communities. There are a growing number of rehabilitation studies for PCC, however, it has yet to be determined whether existing studies take race and ethnicity into account in their study designs and whether existing rehabilitative approaches are equally effective across diverse racial and ethnic groups. The objective of this study was to describe the extent to which rehabilitation studies of PCC consider race and ethnicity in defining eligibility criteria, planning recruitment strategies, designing intervention delivery and adherence promoting approaches, selecting outcome measures, and reporting results. Of the 4845 studies screened, 23 met eligibility criteria and were included in this review. The most common reason for exclusion was a lack of mention of race or ethnicity anywhere within the article. Among the 23 studies included, 13 studies provided data on the race and/or ethnicity characteristics of their sample, with 88% of participants across all of these studies being White. Less than 25% of studies described the incorporation of race and/or ethnicity in their recruitment strategies (n = 3, 13%) or data analysis (n = 5, 22%). Greater racial and ethnic diversity is needed within rehabilitation studies for PCC as there is currently a significant underrepresentation of racial and ethnic minorities in existing studies. Overall, more PCC rehabilitation studies need to incorporate race and ethnicity into their study designs as it is not well understood whether existing rehabilitation strategies are equally effective across different racial and ethnic groups.}, }
@article {pmid41117273, year = {2026}, author = {Oba, S and Hosoya, T and Iwai, H and Yasuda, S}, title = {Long COVID: mechanisms of disease, multisystem sequelae, and prospects for treatment.}, journal = {Immunological medicine}, volume = {49}, number = {1}, pages = {35-58}, doi = {10.1080/25785826.2025.2570902}, pmid = {41117273}, issn = {2578-5826}, mesh = {Humans ; *COVID-19/therapy/epidemiology/complications/immunology/physiopathology ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Antiviral Agents/therapeutic use ; }, abstract = {Long COVID has emerged as a significant global health issue, affecting individuals across a wide spectrum of initial disease severity. While its definition and prevalence vary across studies, persistent symptoms such as fatigue, cognitive dysfunction, respiratory difficulties, and cardiovascular complications have been widely reported. Multiple pathophysiological mechanisms have been proposed, including incomplete viral clearance, reactivation of latent viruses, immune dysregulation, autoimmunity, endothelial dysfunction, microbiome alterations, and mitochondrial impairment. These interconnected processes are thought to contribute to chronic inflammation and multi-organ disease. To date, there are no established therapies for Long COVID, and management primarily focuses on symptomatic relief and rehabilitation. Vaccination has been shown to reduce the incidence of Long COVID, and emerging strategies, including antiviral agents, immune-modulating therapies, microbiome restoration, and mitochondria-targeted interventions, are under investigation. This review summarizes the current understanding of the epidemiology, pathophysiology, organ-specific manifestations, and potential therapeutic approaches for Long COVID, aiming to provide insights into future research directions and clinical management strategies.}, }
@article {pmid41145456, year = {2025}, author = {Sujith, S and Gatzke, N}, title = {An overview of clinical presentation and management of long COVID.}, journal = {The Nurse practitioner}, volume = {50}, number = {11}, pages = {38-42}, doi = {10.1097/01.NPR.0000000000000374}, pmid = {41145456}, issn = {1538-8662}, mesh = {Humans ; *COVID-19/complications/diagnosis/nursing/physiopathology ; Nurse Practitioners ; Vaccination ; COVID-19 Vaccines/immunology ; SARS-CoV-2/immunology ; }, abstract = {The COVID-19 pandemic has been the 21st century's most significant public health emergency. In addition to the acute symptoms of COVID-19, many individuals are facing long-term health issues related to the infection. The terms "long COVID," "postacute sequelae of SARS-CoV-2 infection," "postacute COVID syndrome," and "long-haul COVID-19" refer to long-term consequences of SARS-CoV-2 infection. Symptoms may persist for weeks or months, reducing quality of life. Health practitioners must stay updated and take proactive measures to manage long COVID effectively. This manuscript provides an overview of risk factors, diagnostic tools, and management strategies, which serve as a resource for understanding and managing long COVID.}, }
@article {pmid41146789, year = {2025}, author = {Dudek, A and Bursy, M and Szkudlarek, W and Linkiewicz, J and Fabiszewski, Z and Starosta, P}, title = {Chronic Cardiovascular Disorders Associated With COVID-19: A Literature Review.}, journal = {Cureus}, volume = {17}, number = {9}, pages = {e93271}, pmid = {41146789}, issn = {2168-8184}, abstract = {The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, is now widely recognized for causing several long-term effects known as post-COVID-19 syndrome (PCS) or long COVID (LC). This presents a growing challenge for healthcare systems worldwide. This narrative review summarizes original peer-reviewed studies indexed in PubMed and published between January 2020 and August 2025. It focuses on adult populations unless stated otherwise. We included studies that provided primary clinical or imaging data on chronic cardiovascular outcomes after confirmed SARS-CoV-2 infection. We excluded case reports, pediatric-only cohorts, and non-peer-reviewed sources. Among the various cardiovascular issues related to LC, we focused on heart fibrosis (HF), postural orthostatic tachycardia syndrome (POTS), new-onset hypertension (HT), and coagulopathy. These conditions consistently show up in the reports and are significant in terms of illness, potential long-term disability, and public health impact. Although these issues are distinct in their underlying causes, they share common mechanisms. These include ongoing inflammation of the endothelium, disruption of the renin-angiotensin-aldosterone system (RAAS), immune-related tissue damage, and an ongoing state that promotes blood clots. These processes can lead to measurable myocardial fibrosis that cardiac magnetic resonance imaging can detect, autonomic dysfunction often seen as POTS, a greater risk of developing hypertension shortly after infection, and a long-term rise in thromboembolic events due to increased clotting and resistant microclots. Current management is mostly focused on relief of symptoms and involves a team approach. It uses repurposed medications and tailored physical rehabilitation since no specific cure is available yet. Promising but still experimental methods, such as endothelial-protective agents like sulodexide and targeting inflammatory pathways, need thorough testing. There are significant gaps in our understanding of the long-term risk of hypertension, the natural progression of fibrosis, and the best treatment for POTS. This highlights urgent needs for future research. Beyond caring for individual patients, these ongoing cardiovascular problems raise important public health concerns. They include higher healthcare use, long-term disability, and economic costs. This situation requires increased clinical attention and proactive cardiovascular monitoring for those recovering from COVID-19.}, }
@article {pmid41151241, year = {2025}, author = {Raijmakers, RPH and Lund Berven, L and Keijmel, SP and Rodrigo, C and Wyller, VBB and Katz, BZ and Buchwald, D and Evans, RA and Gérardin, P and Knoop, H and Prins, M and Stavem, K and Stiansen-Sonerud, T and Taylor, R and Valencia Arroyo, BM and Wensaas, KA and Selvakumar, JP and van den Wijngaard, C and Lloyd, AR and Sandler, CX}, title = {Immunological associations in post-infective fatigue syndromes including Long COVID-a systematic review and meta-analysis.}, journal = {EBioMedicine}, volume = {121}, number = {}, pages = {105970}, pmid = {41151241}, issn = {2352-3964}, support = {R01 AI105781/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/complications/immunology ; SARS-CoV-2 ; Biomarkers ; *Fatigue/immunology/etiology ; }, abstract = {BACKGROUND: The pathophysiology of post-infective fatigue syndromes (PIFS), including Long COVID, is unknown. This systematic review and meta-analysis aimed to investigate if PIFS is associated with persistent immune activation.<br><br>METHODS: PubMed, EMBASE, and Web of Science were searched for terms related to infection, fatigue, persistent symptoms, and immunological markers.<br><br>POPULATION: adults and adolescents; Exposure: documented acute infection; Comparator: those who developed PIFS vs. recovered controls from the same exposure; and Outcomes: immunological biomarkers. Studies which documented acute infection, applied diagnostic criteria for PIFS, and assayed circulating immunologic markers were eligible.<br><br>FINDINGS: From 14,985 studies screened, 30 articles were included (n = 5102 participants; 833 PIFS/PIFS-like cases, n = 4269 recovered control participants) with many studies excluded by inadequate quality in eligibility criteria. The meta-analysis (11 studies; n = 413 PIFS cases, analysed with random-effects models) showed PIFS cases had increased: white cell counts at 3-6 months (Cohen's d: 0.41, 95% CI 0.09-0.74); and circulating levels of RANTES and TNF&#x3b1; at 6-12 months (Cohen's d: 0.45 [95% CI 0.16-0.73] and 0.30 [95% CI 0.04-0.57], respectively) compared to controls recovered from the same exposure.<br><br>INTERPRETATION: These findings provide cautious support for persistent immune activation in PIFS, but warrant further replication. Future studies should include better documentation of acute infection and PIFS case characterisation.<br><br>FUNDING: ARL is supported by a National Health and Medical Research Council Practitioner Fellowship (Grant 1041897). CXS is supported by a Cancer Institute New South Wales Early Career Fellowship (2021/ECF1310). BZK is supported by the National Institute of Allergy and Infectious Diseases (AI 105781). RAE is supported by the National Institute for Health and Care.}, }
@article {pmid41155179, year = {2025}, author = {Refrigeri, M and Tola, A and Mogavero, R and Pietracupa, MM and Gionta, G and Scatena, R}, title = {Mechanisms of Mitochondrial Impairment by SARS-CoV-2 Proteins: A Nexus of Pathogenesis with Significant Biochemical and Clinical Implications.}, journal = {International journal of molecular sciences}, volume = {26}, number = {20}, pages = {}, pmid = {41155179}, issn = {1422-0067}, mesh = {Humans ; *Mitochondria/metabolism/virology/pathology ; *COVID-19/metabolism/virology/pathology ; *SARS-CoV-2/metabolism/pathogenicity ; Reactive Oxygen Species/metabolism ; Host-Pathogen Interactions ; Immunity, Innate ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) closely interacts with host cellular mechanisms, with mitochondria playing a crucial role in this process. As essential organelles that control cellular energy production, apoptosis, reactive oxygen species (ROS) metabolism, and innate immune responses, mitochondria are vital to the development of COVID-19. However, the exact molecular interactions between mitochondria and SARS-CoV-2 remain under active investigation. Gaining a comprehensive understanding of mitochondrial involvement in SARS-CoV-2 infection is therefore essential for uncovering complex disease mechanisms, identifying prognostic biomarkers, and developing effective treatments. Ultimately, exploring these virus-host interactions may provide new insights into the fundamental and complex aspects of mitochondrial physiology and pathophysiology.}, }
@article {pmid41155411, year = {2025}, author = {Caliman-Sturdza, OA and Hamamah, S and Iatcu, OC and Lobiuc, A and Bosancu, A and Covasa, M}, title = {Microbiome and Long COVID-19: Current Evidence and Insights.}, journal = {International journal of molecular sciences}, volume = {26}, number = {20}, pages = {}, pmid = {41155411}, issn = {1422-0067}, support = {760073/23.05.2023, code 285/30.11.2022, within Pillar III, Component C9, Investment 8.//Romania's National Recovery and Resilience Plan/ ; 760073/23.05.2023, code 285/30.11.2022, within Pillar III, Component C9, Investment 8.//Romania's National Recovery and Resilience Plan/ ; }, mesh = {Humans ; *COVID-19/microbiology/complications ; *Gastrointestinal Microbiome ; SARS-CoV-2 ; Dysbiosis/microbiology ; Post-Acute COVID-19 Syndrome ; Probiotics/therapeutic use ; *Microbiota ; }, abstract = {Long COVID, also referred to as post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by persistent multi-systemic symptoms such as fatigue, cognitive impairment, and respiratory dysfunction. Accumulating evidence indicates that gut and oral microbiota play an important role in its pathogenesis. Patients with long COVID consistently exhibit reduced microbial diversity, depletion of beneficial short-chain fatty acid (SCFA)-producing species such as Faecalibacterium prausnitzii and Bifidobacterium spp. and enrichment of proinflammatory taxa including Ruminococcus gnavus, Bacteroides vulgatus, and Veillonella. These alterations may disrupt intestinal barrier integrity, sustain low-grade systemic inflammation, and influence host immune and neuroendocrine pathways through the gut-brain and gut-lung axes. Distinct microbial signatures have also been associated with symptom clusters, including neuropsychiatric, respiratory, and gastrointestinal manifestations. Proposed mechanisms linking dysbiosis to long COVID include impaired SCFA metabolism, tryptophan depletion, microbial translocation, and interactions with host immune and inflammatory responses, including autoantibody formation and viral antigen persistence. Preliminary interventional studies using probiotics, synbiotics, and fecal microbiota transplantation suggest that microbiome-targeted therapies may alleviate symptoms, although evidence remains limited and heterogeneous. This review synthesizes current literature on the role of gut and oral microbiota in long COVID, highlights emerging microbial biomarkers, and discusses therapeutic implications. While causality remains to be firmly established, restoring microbial balance represents a promising avenue for diagnosis, prevention, and management of long COVID.}, }
@article {pmid41156656, year = {2025}, author = {Delpino, MV and Quarleri, J}, title = {Mitochondrial Dysfunction in Aging, HIV, and Long COVID: Mechanisms and Therapeutic Opportunities.}, journal = {Pathogens (Basel, Switzerland)}, volume = {14}, number = {10}, pages = {}, pmid = {41156656}, issn = {2076-0817}, mesh = {Humans ; *Aging/metabolism ; *HIV Infections/metabolism/therapy/pathology ; *Mitochondria/metabolism/pathology ; *COVID-19/metabolism/therapy/pathology ; DNA, Mitochondrial/genetics ; *Mitochondrial Diseases/therapy ; Oxidative Stress ; SARS-CoV-2 ; Mitophagy ; }, abstract = {We hypothesize that a unified mitochondrial perspective on aging, HIV, and long COVID reveals shared pathogenic mechanisms and specific therapeutic vulnerabilities that are overlooked when these conditions are treated independently. Mitochondrial dysfunction is increasingly recognized as a common factor driving aging, HIV, and long COVID. Shared mechanisms-including oxidative stress, impaired mitophagy and dynamics, mtDNA damage, and metabolic reprogramming-contribute to ongoing energy failure and chronic inflammation. Recent advancements highlight new therapeutic strategies such as mitochondrial transfer, transplantation, and genome-level correction of mtDNA variants, with early preclinical and clinical studies providing proof-of-concept. This review summarizes current evidence on mitochondrial changes across aging and post-viral syndromes, examines emerging organelle-based therapies, and discusses key challenges related to safety, durability, and translation.}, }
@article {pmid41157147, year = {2025}, author = {Jach, ME and Sajnaga, E and Bumbul, M and Serefko, A and Borowicz, KK and Golczyk, H and Kieliszek, M and Wiater, A}, title = {The Role of Probiotics and Their Postbiotic Metabolites in Post-COVID-19 Syndrome.}, journal = {Molecules (Basel, Switzerland)}, volume = {30}, number = {20}, pages = {}, pmid = {41157147}, issn = {1420-3049}, mesh = {*Probiotics/pharmacology/therapeutic use ; *Post-Acute COVID-19 Syndrome/complications/metabolism/therapy ; Humans ; Fatty Acids, Volatile/metabolism ; *SARS-CoV-2/drug effects/physiology ; Virus Replication/drug effects ; *Gastrointestinal Microbiome/drug effects/physiology ; Brain-Gut Axis/drug effects/physiology ; Neuropsychological Tests ; }, abstract = {Post-COVID-19 syndrome, also known as long-COVID, is characterized by a wide spectrum of persistent symptoms involving multiple body organs and systems, including fatigue, gastrointestinal disorders, and neurocognitive dysfunction. Emerging evidence suggests that gut microbiota dysbiosis and disruption of the gut-brain axis play a central role in the pathophysiology of this condition. Probiotics and their metabolites (postbiotics) have gained increasing attention as potential therapeutic agents given their immunomodulatory, anti-inflammatory, and antiviral properties. In this review, we discuss the current understanding of the antiviral mechanisms of probiotics, including reinforcement of intestinal epithelial barrier function, direct virus inhibition, receptor competition, and immune system modulation. Special emphasis is placed on short-chain fatty acids (SCFAs), lactic acid, hydrogen peroxide, and bacteriocins as key factors that contribute to these effects. SCFAs appear to be essential postbiotic compounds during post-COVID recovery. We also highlight recent clinical trials involving specific probiotic species, such as Lactiplantibacillus plantarum, Lacticaseibacillus rhamnosus, and Bifidobacterium longum, and their potential role in alleviating long-term COVID symptoms. Although the current results are promising, further research is needed to clarify the most effective strains, dosages, and mechanisms of action in post-COVID therapeutic strategies.}, }
@article {pmid41157582, year = {2025}, author = {Prakash, S and Karan, S and Lekbach, Y and Tifrea, DF and Figueroa, CJ and Ulmer, JB and Young, JF and Glenn, G and Gil, D and Jones, TM and Redfield, RR and BenMohamed, L}, title = {Insights into Persistent SARS-CoV-2 Reservoirs in Chronic Long COVID.}, journal = {Viruses}, volume = {17}, number = {10}, pages = {}, pmid = {41157582}, issn = {1999-4915}, support = {R01 AI158060/AI/NIAID NIH HHS/United States ; AI158060//National Institute of Allergy and Infectious Diseases/ ; }, mesh = {Humans ; *COVID-19/virology/immunology/complications ; *SARS-CoV-2/physiology/genetics ; Animals ; Chronic Disease ; Post-Acute COVID-19 Syndrome ; RNA, Viral ; Disease Reservoirs/virology ; *Persistent Infection/virology ; }, abstract = {Long COVID (LC), also known as post-acute sequelae of COVID-19 infection (PASC), is a heterogeneous and debilitating chronic disease that currently affects 10 to 20 million people in the U.S. and over 420 million people globally. With no approved treatments, the long-term global health and economic impact of chronic LC remains high and growing. LC affects children, adolescents, and healthy adults and is characterized by over 200 diverse symptoms that persist for months to years after the acute COVID-19 infection is resolved. These symptoms target twelve major organ systems, causing dyspnea, vascular damage, cognitive impairments ("brain fog"), physical and mental fatigue, anxiety, and depression. This heterogeneity of LC symptoms, along with the lack of specific biomarkers and diagnostic tests, presents a significant challenge to the development of LC treatments. While several biological abnormalities have emerged as potential drivers of LC, a causative factor in a large subset of patients with LC, involves reservoirs of virus and/or viral RNA (vRNA) that persist months to years in multiple organs driving chronic inflammation, respiratory, muscular, cognitive, and cardiovascular damages, and provide continuous viral antigenic stimuli that overstimulate and exhaust CD4[+] and CD8[+] T cells. In this review, we (i) shed light on persisting virus and vRNA reservoirs detected, either directly (from biopsy, blood, stool, and autopsy samples) or indirectly through virus-specific B and T cell responses, in patients with LC and their association with the chronic symptomatology of LC; (ii) explore potential mechanisms of inflammation, immune evasion, and immune overstimulation in LC; (iii) review animal models of virus reservoirs in LC; (iv) discuss potential T cell immunotherapeutic strategies to reduce or eliminate persistent virus reservoirs, which would mitigate chronic inflammation and alleviate symptom severity in patients with LC.}, }
@article {pmid41157587, year = {2025}, author = {Heath, AM and Li, D}, title = {Symptomatology of Long COVID Associated with Inherited and Acquired Thrombophilic Conditions: A Systematic Review.}, journal = {Viruses}, volume = {17}, number = {10}, pages = {}, pmid = {41157587}, issn = {1999-4915}, mesh = {Humans ; *COVID-19/complications ; *Thrombophilia/complications ; SARS-CoV-2 ; }, abstract = {Thrombophilic conditions, conditions where blood has a tendency to form thrombi due to abnormal coagulatory processes, can affect the trajectory of diseases such as Post-Acute Sequelae of SARS-CoV-2 Infection, better known as Long COVID (LC), by worsening symptoms and complicating outlooks. As a comorbidity in pro-coagulatory diseases such as COVID-19 and LC, patients with thrombophilic conditions may experience worse symptoms than their peers, due to this elevated level of hypercoagulation. A 15-week literature review through the public PubMed database was conducted to investigate the severity, mechanisms, and symptom profiles of thrombophilic patients with LC. Papers were only included if samples included participants with pre-existing tendencies for hypercoagulable states, and confirmation of SARS-CoV-2 infection via a Polymerase Chain Reaction test. Each paper included in this review was analyzed by topic and assessed for eligibility against the Joanna Briggs Institute's Critical Appraisal tool. Each paper was also assessed for biases. Results from the 6 papers included in this review showed that LC could be predicted following COVID-19 illness by a hypercoagulable blood profile, indicating that LC may be linked to chronic hypercoagulation and inflammation post-infection. Additionally, symptoms linked to microthrombi formation, such as hair loss, arrhythmia, and dizziness, were exhibited more frequently in patients with thrombophilia and/or thrombophilic conditions, indicating that those with thrombophilic conditions may exhibit unique LC symptom profiles compared to healthy controls. This paper's research is preliminary and thus is limited in the strength of its findings; However, further research into LC and its interactions with co-morbidities like thrombophilic conditions would aid in the development of better treatment plans for patients, such as the usage of anticoagulants or screening for hypercoagulable blood profiles post-COVID-19 to assess patient risk.}, }
@article {pmid41158347, year = {2025}, author = {Xie, K and Zhang, P and Li, Y and Xia, L}, title = {The post-COVID-19 pulmonary sequelae: manifestations, mechanisms and treatment strategies.}, journal = {Journal of thoracic disease}, volume = {17}, number = {9}, pages = {7414-7429}, pmid = {41158347}, issn = {2072-1439}, abstract = {Recent studies have increasingly demonstrated that coronavirus disease 2019 (COVID-19) patients may develop long-term sequelae of varying severity, collectively referred to as long COVID or post-COVID-19 condition. Pulmonary sequelae are particularly common, which significantly impair patients' quality of life. The mechanisms underlying post-COVID-19 pulmonary sequelae are complex and multifactorial, and their management is still at an exploratory stage. This review explores the manifestations, underlying mechanisms, and potential treatment approaches for post-COVID-19 pulmonary sequelae. Fatigue, dyspnea, myalgia, and sleep disturbances are the most commonly reported symptoms following COVID-19 infection, while anxiety and depression are also prevalent. Respiratory symptoms include dyspnoea, persistent cough, hypoxia, and reduced exercise capacity. Impaired lung diffusion capacity is the most frequently observed pulmonary function abnormality, and residual abnormalities on chest computed tomography (CT) commonly include ground-glass opacities (GGO) and fibrotic-like changes. Air trapping is also an important CT finding and has been reported to associated with impaired lung diffusion function. The potential mechanisms may include pulmonary fibrosis, chronic inflammation, immune dysregulation, coagulation abnormalities and thrombosis, and persistent viral infection. Current treatment strategies encompass vaccination, pulmonary rehabilitation, and pharmacological interventions such as antifibrotic, anti-inflammatory, and anticoagulant therapies. A comprehensive understanding of the recovery trajectory and the mechanisms underlying post-COVID-19 pulmonary sequelae is crucial for improving patient outcomes.}, }
@article {pmid41160239, year = {2026}, author = {Krassnig, K and Bauer, R and Glasl, S and Haubenberger, P and Evanzin, HJ and Schneider, K and Margotti, D}, title = {[Herbal treatment options for post-viral symptoms and long COVID].}, journal = {Wiener medizinische Wochenschrift (1946)}, volume = {176}, number = {5-6}, pages = {130-148}, pmid = {41160239}, issn = {1563-258X}, mesh = {Humans ; *Phytotherapy/methods ; *COVID-19/complications ; *COVID-19 Drug Treatment ; Post-Acute COVID-19 Syndrome ; Fatigue Syndrome, Chronic/drug therapy ; *Plant Preparations/therapeutic use ; }, abstract = {BACKGROUND: Long COVID and post-viral symptom complexes have become a significant focus in medical practice. There is an urgent need to provide evidence-based treatment options to those patients. The aim of the literature review was to summarize herbal medicinal products as a treatment option for post-viral conditions, particularly long COVID.<br><br>METHODS: A&#xa0;working group of the Austrian Society for Phytotherapy conducted a&#xa0;narrative review between 2022 and 2024, based on external literature from the PubMed, PubPharm and Scopus databases and clinical experience from practice. The review identified the most relevant medicinal plants and their preparations for the most common symptom complexes of long COVID.<br><br>RESULTS: A&#xa0;total of 98&#xa0;publications and 24 monographs were included in the literature review. The symptom complexes (+ relevant phytopharmaceuticals) include neurological complaints, such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) (Ginseng radix, Panax quinquefolii radix, Eleutherocci radix, Rhodiolae rhizoma et radix, Schisandrae fructus), nootropics (Ginkgo folium, Lavandulae flos), irritations of the respiratory tract (Liquiritiae radix, Nigellae semen, Eucalypti folium), gastrointestinal complaints (Gentianae radix, Centauri herba, Artemisii herba, Galangae rhizoma, Zingiberis rhizoma, Boswellia serrata, Curcuma longae rhizoma), circulatory weakness (Crataegi folium cum flore, Rosmarini folium, Salviae officinalis folium) and loss of smell (Rosae flos, Citri pericarpium, Caryophylli flos, Eucalypti folium). External evidence and clinical experience in medical practice show that many important symptoms of post-viral conditions can be successfully treated with herbal preparations.<br><br>CONCLUSION: Phytopharmaceuticals can provide evidence-based support for the therapeutic portfolio for viral diseases and their consequences in current and future viral epidemics.}, }
@article {pmid41161981, year = {2025}, author = {Vishnu, P and Aboulafia, DM}, title = {Hemostatic Disorders Following Severe Acute Respiratory Syndrome Coronavirus 2 Infection, COVID-19 Vaccination, and Long-COVID Syndrome: Current Evidence and Controversies in Clinical Practice.}, journal = {Clinics in laboratory medicine}, volume = {45}, number = {4}, pages = {643-655}, doi = {10.1016/j.cll.2025.07.008}, pmid = {41161981}, issn = {1557-9832}, mesh = {Humans ; *COVID-19/complications/prevention &amp; control ; *COVID-19 Vaccines/adverse effects ; *Hemostatic Disorders/etiology ; SARS-CoV-2 ; *Vaccination/adverse effects ; }, abstract = {The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented profound global health challenges. Beyond acute illness, a substantial proportion of individuals experience persistent symptoms including fatigue, brain fog, and post-exertional malaise, collectively known as Long-COVID. Among the complications associated with SARS-CoV-2 infection and vaccination, hemostatic disorders ranging from mild platelet dysfunction to severe thromboembolic events, and rare but serious coagulation-related adverse effects, such as vaccine-induced immune thrombotic thrombocytopenia, have emerged as a significant concern. Herein we provide an overview of current information and controversies surrounding hemostatic complications in SARS-CoV-2 infection and COVID-19 vaccination.}, }
@article {pmid41164170, year = {2025}, author = {Raveendran, VV and AlQattan, S and AlMutairy, E}, title = {A review on clinical implications of S100 proteins in lung diseases.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1618772}, pmid = {41164170}, issn = {2296-858X}, abstract = {The S100 family of proteins plays a pivotal role in the pathogenesis of lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, pulmonary arterial hypertension (PAH), pulmonary fibrosis, lung cancers, acute lung injury, acute respiratory distress syndrome, COVID-19, and lung transplantation. This review comprehensively examines the contributions of S100 proteins to the progression of these disorders, focusing on their potential as diagnostic and prognostic biomarkers, as well as therapeutic targets. S100A protein-mediated key molecular mechanisms that influence inflammation, airway remodeling, fibrosis, and tumorigenesis in the lungs are discussed. The importance of their normal function is evident from the observation that simultaneous mutations in S100A3 and S100A13 predispose individuals to early-onset pulmonary fibrosis, underscoring their critical role in lung health. Furthermore, sustained S100 protein elevation is explored in the context of long COVID, shedding light on its role in chronic inflammation. These proteins act as damage-associated molecular patterns (DAMPs), activating immune pathways via receptors like TLR4 and RAGE, thereby driving inflammation and immune cell recruitment. Notably, in lung transplantation, elevated levels of S100A8, S100A9, and S100A12 serve as early biomarkers of graft rejection and complications such as graft-vs.-host disease, which indicates their role in mediating immune responses and transplant outcomes. While promising, the clinical application of S100 proteins faces challenges, including disease-specific variability and the need for robust validation across diverse populations. This narrative review underscores the dual potential of S100 proteins as biomarkers and therapeutic targets in respiratory medicine while emphasizing the importance of overcoming current limitations through targeted research and clinical trials.}, }
@article {pmid41168795, year = {2025}, author = {Gartmann, J and Sturm, C and Bökel, A}, title = {Physiotherapy interventions in post- and long-COVID-19: a scoping review of the literature up to February 2023.}, journal = {BMC health services research}, volume = {25}, number = {1}, pages = {1425}, pmid = {41168795}, issn = {1472-6963}, abstract = {BACKGROUND: Physiotherapy is an accepted and recommended treatment for post- and long-COVID-19 condition. It is assumed that physiotherapists reported a lack of information on physiotherapy interventions and treatment parameters. This scoping review provides an overview of the evidence on physiotherapy interventions published in the scientific literature.<br><br>METHODS: The scoping review includes studies analysing physiotherapy treatment parameters and interventions in post- and long-COVID patients. Studies focusing on telemedicine or exclusively home-based workouts are excluded. A systematic literature search was conducted by two independent researchers in the databases PubMed, EBSCO, SCOPUS, Web of Science, EMBASE, PEDro, Cochrane, and WISO. Following the abstract screening process, data extraction and critical assessment were performed.<br><br>RESULTS: In this scoping review, 6 studies were included, providing information physiotherapy management of post- and long-COVID-19. The research identified respiratory therapy, aerobic training or strength training as key areas of focus.<br><br>CONCLUSION: This scoping review highlights the need for further studies on physiotherapy treatment in post- and long-COVID condition.<br><br>TRIAL REGISTRATION: Open Science Framework (Registry number osf.io/5k3tA).<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12913-025-13631-7.}, }
@article {pmid41171518, year = {2026}, author = {Mallouli, SZ and Munblit, D and Iakovleva, E and Winkler, AS and Fornari, A and Helbok, R and Struhal, W and Beretta, S and De Groote, W and Curatoli, C and Lanza, M and Ericka, F and Crivelli, L and Giussani, G and Wasay, M and Chakroun Walha, O and Safi, F and Leonardi, M and Allegri, R and Guekht, A and Triki, CC}, title = {Persistent neurological sequelae in children and adolescents after SARS-CoV-2: a scoping review.}, journal = {Infection}, volume = {54}, number = {1}, pages = {57-74}, pmid = {41171518}, issn = {1439-0973}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Humans ; Adolescent ; *COVID-19/complications/epidemiology ; Child ; *Nervous System Diseases/epidemiology/etiology/virology ; SARS-CoV-2 ; }, abstract = {OBJECTIVES: For the past five years, COVID-19 has not only been a priority for health planning but also a hotspot for clinical research. Yet, the weight of the worldwide COVID-19 pandemic arises from the critical phase consequences due to the onset of acute disease, associated containment measures, and documented ongoing disabling symptoms. Investigating the global longitudinal effects on children and adolescents will inform future health directives tailored to this population's needs. This review aimed to report the spectrum of persistent neurological sequelae in children and adolescents following SARS-CoV-2 infection.<br><br>METHODS: Hence, we conducted a scoping review following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). We included the peer-reviewed articles from PubMed, Google Scholar, Web of Science, Cochrane Library, and WHO COVID database to identify relevant literature on long-COVID-19 neurological signs/symptoms among children and adolescents. The search covered the period between September 2020 and September 2024.<br><br>RESULTS: The results of our analysis of 33 studies found long-COVID-19-related neurological signs/symptoms were predominantly: pain and sensory problems (N&#x2009;=&#x2009;74,612/91,543; 81.5%), followed by sleep disturbances (N&#x2009;=&#x2009;14,630/91,543; 15.9%), and cognitive difficulties (N&#x2009;=&#x2009;2274/91,543; 2.4%). The global prevalence of long COVID-19 neurological signs/symptoms was estimated between 0.4% (20/5032; 95% CI&#x2009;=&#x2009;2.1-3%) and 34% (27/79) based on data obtained through online questionnaire; while it varied between 1.8% (4/215) and 83.14% (74/89; 95%CI&#x2009;=&#x2009;&#x2009;&#x2009;-&#x2009;&#x2009;0.12; 0.30) based on patient assessment. Long-COVID-19-related neurological signs/symptoms were more common in the 11-16 age group. Children with immunocompetent profiles were at higher risk of developing long-COVID-19-related neurological signs/symptoms.<br><br>CONCLUSION: Our results demonstrate a considerable burden of COVID-19-related persistent neurological signs/symptoms in children and adolescents, which should be taken into consideration in healthcare decision-making.}, }
@article {pmid41178423, year = {2025}, author = {Limami, Y and Wahnou, H and Ndayambaje, M and Hba, S and Chgari, O and Ammara, M and El Kebbaj, R and Naya, A and Oudghiri, M and Duval, RE}, title = {SARS-CoV-2: A Liver Brief.}, journal = {WIREs mechanisms of disease}, volume = {17}, number = {6}, pages = {e70005}, doi = {10.1002/wsbm.70005}, pmid = {41178423}, issn = {2692-9368}, mesh = {Humans ; *COVID-19/complications/virology/pathology/immunology ; *SARS-CoV-2/pathogenicity ; *Liver Diseases/virology/pathology ; *Liver/virology/pathology/immunology/metabolism ; Angiotensin-Converting Enzyme 2/metabolism ; Virus Internalization ; }, abstract = {The Coronavirus Disease 2019 (COVID-19) pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has revealed the virus's ability to induce multi-organ damage, including significant liver injury. The molecular mechanisms of liver dysfunction in COVID-19 patients are explored, focusing on direct viral infection, immune-mediated damage, and the gut-liver axis. SARS-CoV-2 enters liver cells through the Angiotensin-Converting Enzyme 2 (ACE2) and Transmembrane Serine Protease 2 (TMPRSS2) receptors, but alternative pathways, such as CD209/Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN) and AXL receptors, can also contribute to viral entry. Additionally, immune responses, particularly the cytokine storm, exacerbate liver inflammation, leading to hepatocyte damage. Pre-existing liver conditions, such as metabolic-associated fatty liver disease (MAFLD), alcohol-related liver disease (ALD), and liver fibrosis, heighten the risk of severe outcomes in COVID-19 patients. Post-COVID-19 liver complications, including fibrosis progression and persistent liver damage, have been reported, with emerging evidence suggesting chronic inflammation, viral persistence, and autoimmune reactions as potential contributors. Furthermore, Drug-Induced Liver Injury (DILI) from COVID-19 treatments remains a concern, highlighting the need for careful management. Consequently, understanding the interplay between SARS-CoV-2 and the liver is critical for improving patient outcomes and developing targeted therapies to mitigate liver-related complications in both acute and Long COVID-19 phases. This article is categorized under: Infectious Diseases > Molecular and Cellular Physiology.}, }
@article {pmid41189723, year = {2025}, author = {Fineberg, D and Moreau, A and Schneider-Futschik, EK and Armstrong, CW}, title = {A Perspective on the Role of Metformin in Treating Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID.}, journal = {ACS pharmacology &amp; translational science}, volume = {8}, number = {10}, pages = {3411-3431}, pmid = {41189723}, issn = {2575-9108}, abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID (LC) are increasingly recognized as debilitating postinfectious conditions that impact both individuals and society. Recent research highlights the potential of metformin, an antidiabetic agent, as a treatment for these syndromes by targeting their underlying mechanisms. This review assesses the effectiveness of metformin in ME/CFS and LC, which involve complex dysfunctions related to cytokines, glycolysis, ATP generation, oxidative stress, gastrointestinal microbiomes, and vascular endothelial function. Metformin, traditionally known for its antihyperglycemic properties may offer broader therapeutic benefits by influencing these pathological pathways. It works by inhibiting complexes I and IV of the electron transport chain, which reduces the strain on malfunctioning complex V and decreases the production of harmful free radicals. Additionally, metformin's impact on mTOR signaling could improve energy metabolism in ME/CFS and LC by downregulating an overactive but underperforming protein, thereby alleviating symptoms. Beyond the impact on cellular metabolism, metformin has shown to have anti-inflammatory, vascular, gastrointestinal, neuroprotective and epigenetic effects. We explore this impact of metformin and the potential role it could play to help people with ME/CFS. While metformin shows promise, it is unlikely to be a stand-alone solution. Instead, it may be part of a broader treatment strategy that includes other therapies targeting neurocognitive and autonomic impairments.}, }
@article {pmid41194817, year = {2025}, author = {Dimitrakopoulou, A and Sarantaki, A and Nanou, CI and Georgakopoulou, VE and Taskou, C and Chouli, M and Diamanti, A}, title = {Long COVID-Related Fatigue During Pregnancy: A Systematic Review.}, journal = {Cureus}, volume = {17}, number = {10}, pages = {e93877}, pmid = {41194817}, issn = {2168-8184}, abstract = {Long sequelae of COVID-19 (Long COVID), or post-acute sequelae of SARS-CoV-2 infection, encompasses a wide range of persistent symptoms, with fatigue emerging as one of the most prevalent and disabling. Pregnant individuals may be uniquely susceptible to post-viral fatigue due to immunological and physiological adaptations during gestation. This review consolidates existing data regarding the prevalence, risk factors, and clinical implications of Long COVID-associated fatigue in pregnant individuals. A narrative review was conducted of studies examining fatigue among pregnant individuals with confirmed SARS-CoV-2 infection. Key outcomes included fatigue prevalence, symptom persistence, associated risk or protective factors, and comparisons with non-pregnant populations. Across both the acute and post-acute stages of COVID-19, fatigue emerged as a consistently common symptom. Its prevalence and persistence varied significantly across studies, partly due to heterogeneity in assessment tools and follow-up durations. Severe acute illness, hospitalization, obesity, and smoking during pregnancy were linked to a higher risk of prolonged fatigue, whereas anosmia appeared to act as a potential protective factor. In contrast, comorbidities such as hypertension, diabetes, and lung disease were not significantly linked to fatigue risk. No consistent associations were found with maternal age or alcohol use. Long COVID-related fatigue presents a substantial burden in pregnancy, with implications for maternal health, quality of life, and postpartum recovery. Early recognition, individualized care strategies, and public health interventions targeting modifiable risk factors are essential to support this vulnerable population. Ongoing research is essential to uncover underlying mechanisms and guide evidence-based clinical management.}, }
@article {pmid41212631, year = {2025}, author = {Goodfellow, H and Blandford, A and Bradbury, K and Gomes, M and Hamilton, F and Henley, W and Stevenson, F and Fernandez-Reyes, D and Hurst, J and Heightman, M and Pfeffer, P and Ricketts, W and Singh, R and Hylton, H and Linke, S and Bindman, J and Robson, C and Walker, S and Ismaila, H}, title = {Development and implementation of a digital health intervention in routine care for long COVID patients: a comprehensive synopsis.}, journal = {Health and social care delivery research}, volume = {13}, number = {39}, pages = {1-27}, doi = {10.3310/GJHG0331}, pmid = {41212631}, issn = {2755-0079}, mesh = {Humans ; *COVID-19/rehabilitation ; Male ; Female ; Telemedicine/organization &amp; administration ; Middle Aged ; SARS-CoV-2 ; Adult ; Patient Reported Outcome Measures ; United Kingdom ; Aged ; State Medicine ; Digital Health ; }, abstract = {BACKGROUND: By July 2020, large numbers of post-COVID patients were experiencing symptoms for weeks or months, but traditional National Health Service models of rehabilitation service delivery could not meet demand.<br><br>OBJECTIVES: Design and deploy a digital health intervention to provide digitally delivered, remotely supported rehabilitation to long COVID patients on complicated and evolving pathways.<br><br>METHODS: The multidisciplinary team combined established research methods based on engineering and computer science (considering safety, stability and user requirements) with those based on biomedical and health service research (considering effectiveness and population impact). Qualitative data comprised recordings of meetings between study team members and clinicians and semistructured interviews with clinician and patient users. Quantitative data comprised referral, registration and usage rates; demographic and clinical characteristics of patients; and patient-reported outcome measures.<br><br>RESULTS: We created a modifiable digital health intervention, 'Living With COVID Recovery[TM] developed by Living With Ltd', London, UK, that continues to be used by National Health Service trusts. The digital health intervention included integration into a clinical pathway, a clinician-facing dashboard, two-way messaging and a patient-facing app with information and evidence-based treatments. We aimed to register 1000 users. By study completion on 20 December 2022, there were 9781 patients invited, of whom 7679 (78.5%) had registered, at 33 National Health Service clinics.<br><br>LIMITATIONS: Data came from patients at long COVID clinics, however data were unlikely to be representative of people with long COVID. We could not observe clinics under lockdown and had limited access to patient digital health intervention users or to people not engaging with the digital health intervention. Patient user data were incomplete, with inconsistent patient-reported outcome measure and other questionnaire data completion and no data on initial severity of disease, vaccination status, comorbidities or other individual circumstances.<br><br>CONCLUSIONS: Long COVID can be extremely debilitating, comparable to stage IV lung cancer in relation to fatigue and health-related quality of life. Care and rehabilitation should address the management of fatigue and reflect the impact of social disadvantage on symptom severity. With sufficient resources, a digital health intervention can be developed quickly and effectively using agile methodology and bringing together a genuinely multidisciplinary team, including, importantly, an industry partner. Digital health intervention product design and deployment are both important in getting National Health Service trusts, healthcare professionals and patients to engage with a digital health intervention. Projects should work closely with all user groups. Lockdown and the unmet need of a new patient group encouraged those who might otherwise have been reluctant to try a digital health intervention. Many patients and clinics accepted this digital remote support, which helped patients feel cared for while reducing strain on health services. This may encourage acceptance of other digital health intervention, although medical record integration remains a deterrent to clinics.<br><br>FUTURE WORK: This research focused on the development, deployment and evaluation of a digitally enabled rehabilitation programme for long COVID. Clinical effectiveness will be assessed within the Symptoms, Trajectory, Inequalities and Management: Understanding Long-COVID to Address and Transform Existing Integrated Care Pathways (UCL, London, UK) study.<br><br>FUNDING: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme as award number NIHR132243.}, }
@article {pmid41218870, year = {2025}, author = {He, XY and Li, XH and Tong, ZH}, title = {[Cognitive impairment in long COVID: advances in pathological mechanisms and exercise rehabilitation interventions].}, journal = {Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases}, volume = {48}, number = {11}, pages = {1087-1095}, doi = {10.3760/cma.j.cn112147-20250610-00315}, pmid = {41218870}, issn = {1001-0939}, support = {2023YFC0872500//National Key Research and Development Program/ ; Ggyfz202503//Reform and Development Program of Beijing Institute of Respiratory Medicine/ ; }, mesh = {Humans ; *Cognitive Dysfunction/rehabilitation/etiology ; *COVID-19/complications/psychology ; *Exercise Therapy ; *Post-Acute COVID-19 Syndrome ; Quality of Life ; }, abstract = {Since the outbreak of the novel coronavirus (COVID-19) pandemic, long-term effects of the virus, known as long-COVID, has emerged. It is a chronic syndrome following infection. It is estimated that around 20% of COVID-19 survivors worldwide experience cognitive dysfunction. This is characterized by impairments in executive function, attention, memory, and other cognitive domains, and can have a significant impact on quality of life and social functioning. This article systematically reviewed recent studies and summarized the potential pathological mechanisms underlying cognitive dysfunction in long COVID, including neuroinflammation, glial cell dysregulation, involvement of the olfactory pathway and limbic system, autoimmunity and viral reactivation, cerebrovascular and blood-brain barrier damage, as well as abnormalities in neurotrophic factors and synaptic plasticity. Additionally, it explored the effects of exercise rehabilitation and multidimensional comprehensive rehabilitation strategies. The aim was to provide theoretical and scientific foundations for optimizing intervention programs for cognitive dysfunction in long COVID and for formulating clinical guidelines and public health policies.}, }
@article {pmid41223394, year = {2025}, author = {Zamora, FV and Santos, ACFF and Zamora, AV and Galvao, LKCS and Pimenta, NDS and Salles, JPCEA and Carneiro, VB and Starling, CEF}, title = {Hyperbaric Oxygen Treatment for Long-COVID syndrome: A Systematic Review of Current Evidence on Cognitive Decline.}, journal = {Undersea &amp; hyperbaric medicine : journal of the Undersea and Hyperbaric Medical Society, Inc}, volume = {52}, number = {3}, pages = {327-335}, pmid = {41223394}, issn = {1066-2936}, mesh = {Humans ; *Hyperbaric Oxygenation/methods ; *Cognitive Dysfunction/therapy/etiology ; *COVID-19/complications ; Executive Function ; Post-Acute COVID-19 Syndrome ; Attention ; Randomized Controlled Trials as Topic ; Fatigue/therapy ; }, abstract = {INTRODUCTION: There is no established specific treatment for long-COVID syndrome (LCS), yet hyperbaric oxygen (HBO2) treatment has been studied as a potential option. Therefore, we conducted a systematic review to evaluate the benefits of HBO2 treatment in LCS patients.<br><br>METHODS: We systematically searched PubMed, Embase, and Cochrane databases until April 2024. Risk of bias and GRADE quality assessment were evaluated. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) with ID CRD42024530421.<br><br>RESULTS: Seven studies from seven countries, divided into RCTs and observational studies, included 199 participants. HBO&#x2082; treatment protocols included breathing 100% oxygen at 2.0 ATA until 2.5 ATA; the number of sessions varied from ten to 60 depending on the patient's comorbidities and symptoms. Memory, executive function, attention, fatigue, and pain level improved with HBO2 treatment. The intervention had minimal side effects, and none were serious.<br><br>CONCLUSION: HBO&#x2082; treatment might be a potential option and safe treatment in LCS patients. However, further research should be focused on evaluating its efficacy in a larger number of patients through randomized studies.}, }
@article {pmid41223978, year = {2026}, author = {Spanoghe, M and Antonacci, T and Schneider, N and Molmans, THJ}, title = {Viewpoint | linking long Covid and AD(H)D through neuroimmune dysfunction: A translational framework proposal for precision medicine.}, journal = {Brain, behavior, and immunity}, volume = {131}, number = {}, pages = {106181}, doi = {10.1016/j.bbi.2025.106181}, pmid = {41223978}, issn = {1090-2139}, }
@article {pmid41226415, year = {2025}, author = {Zolotarenko, AD and Poghosyan, HM and Sheptiy, VV and Bruskin, SA}, title = {COVID-19 Hijacking of the Host Epigenome: Mechanisms, Biomarkers and Long-Term Consequences.}, journal = {International journal of molecular sciences}, volume = {26}, number = {21}, pages = {}, pmid = {41226415}, issn = {1422-0067}, support = {123120500032-9//Ministry of Science and Higher Education of the Russian Federation/ ; }, mesh = {Humans ; *COVID-19/genetics/virology/immunology/pathology ; *SARS-CoV-2/physiology ; *Epigenesis, Genetic ; *Epigenome ; Biomarkers/metabolism ; Immunity, Innate ; *Host-Pathogen Interactions/genetics ; MicroRNAs/genetics ; DNA Methylation ; }, abstract = {The epigenetics of COVID-19 is a rapidly expanding field that reveals how the SARS-CoV-2 virus initiates alterations in the host's genome, influencing the susceptibility to infection, the disease severity, and long-term consequences, known as "long COVID." In this review, we describe the mechanisms utilized by the virus to manipulate the host epigenome, suppressing antiviral responses and creating a favorable environment for viral replication. We also highlight virus-induced epigenetic changes across diverse cell populations that contribute to COVID-19 pathogenesis. Notably, the virus reprograms hematopoietic stem and progenitor cells, leading to long-lasting alterations in innate immunity, a phenomenon known as "trained immunity." These epigenetic modifications are maintained in differentiated daughter cells and may explain the persistent inflammation and other symptoms of long COVID. Furthermore, we discuss emerging epigenetic biomarkers of disease severity, including methylation signatures in genes such as AIM2, HLA-C, and PARP9, as well as dysregulated miRNA profiles. Understanding this complex interplay between the virus and the host's epigenetic landscape is crucial for developing new therapeutic approaches that target specific epigenetic modifications to suppress pathological processes and improve clinical outcomes for COVID-19 patients.}, }
@article {pmid41226731, year = {2025}, author = {Varghese, S and Al-Hassani, I and Al-Aani, U and Rob, NJ and Al-Mannai, S and Jaguri, A and Yousif, RA and Al-Mulla, A and Palayangal, FF and Laws, S and Al-Ali, D and Zakaria, D}, title = {Long-Term Complications of Multisystem Inflammatory Syndrome in Children and Adults Post-COVID-19: A Systematic Review.}, journal = {International journal of molecular sciences}, volume = {26}, number = {21}, pages = {}, pmid = {41226731}, issn = {1422-0067}, mesh = {Adult ; Child ; Humans ; *COVID-19/complications ; SARS-CoV-2 ; *Systemic Inflammatory Response Syndrome/complications/therapy/etiology ; }, abstract = {The SARS-CoV-2 pandemic has posed global medical challenges due to its ability to affect multiple organ systems. Among the post-COVID-19 complications, multisystem inflammatory syndrome has emerged as a severe condition affecting both children (MIS-C) and adults (MIS-A). This review aims to compile and analyze published data to investigate clinical characteristics, laboratory findings, and outcomes of MIS post-COVID-19. A comprehensive search of various databases was conducted to identify studies reporting MIS-related complications in pediatric and adult populations post-COVID-19 infection. Screening, data extraction, and cross-checking were performed by two independent reviewers. Only 64 studies met our inclusion criteria, and compiled results revealed that cardiac complications were the predominant manifestation followed by gastrointestinal, hematologic, neurological, and mucocutaneous involvement. Laboratory findings consistently demonstrated elevated inflammatory markers including CRP, ferritin, D-dimer, and IL-6. Most patients required hospitalization, and many needed intensive care; treatment typically involved IVIG, corticosteroids, and biologic therapies. While most patients recovered, a subset experienced persistent complications. These findings highlight the importance of early recognition, multidisciplinary management, and structured follow-up for MIS. Future research is warranted to clarify the underlying mechanisms, risk factors, and long-term outcomes associated with MIS in post-COVID-19 patients.}, }
@article {pmid41235244, year = {2025}, author = {Wang, D and Zhang, F}, title = {CKD-related impairment in humoral and cellular immune response and potential correlation with long COVID-19: a systematic review.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1690298}, pmid = {41235244}, issn = {1664-3224}, mesh = {Humans ; *COVID-19/immunology/prevention &amp; control ; *Immunity, Humoral ; *Renal Insufficiency, Chronic/immunology/therapy ; *Immunity, Cellular ; *SARS-CoV-2/immunology ; *COVID-19 Vaccines/immunology ; Antibodies, Viral/blood/immunology ; Vaccination ; }, abstract = {INTRODUCTION: Patients with chronic kidney disease (CKD) are at high risk of morbidity and mortality from SARS-CoV-2 infection (COVID-19). However, their immune response to vaccination may vary among individuals. The purpose of this review was to identify characteristics of alterations in humoral and cellular immune responses to the vaccination, and to provide insights into their immune dysfunctions for a better care of acute COVID-19 and prevention of long COVID-19.<br><br>METHODS: PubMed, Embase, Scopus, Web of science and Cochrane Central were systematically searched. Eligible publications included clinical studies reporting immune response to COVID-19 vaccination in CKD patients without dialysis or KT, CKD patients undergoing dialysis, as well as CKD patients with KT. Demographics, measurements and results of their humoral and cellular response were evaluated, and the quality of studies were assessed using the Joanna Briggs Institute (JBI) critical appraisal tool and the Newcastle-Ottawa quality assessment scale (NOS).<br><br>RESULTS: A total of 31 eligible studies were identified. A decreased proportion of patients with KT showed anti-S IgG positivity after the 2[nd] (67%) and 3[rd] (56.6%) dose of vaccination. Similarly, a decreased proportion of these patients presented S-specific T-cell response after the 2[nd] (17.7%) and 3[rd] (12.9%) dose. Though lower anti-S IgG titers in patients with CKD or on dialysis, as well as T-cell response in patients on dialysis were reported to be lower after the 2[nd] or 3[rd] dose of vaccination, conflicting results were reported by other studies. Limited studies on correlated change between humoral and cellular immune response revealed a low rate of co-presence of the two in patients with dialysis, though antibody level was correlated with rate of cellular response, while no such correlation was revealed in patients with KT.<br><br>CONCLUSION: The study provides crucial information on features of humoral and cellular immune responses to COVID-19 vaccinations in CKD patients, and suggests possible directions for strategy of management such as antibody monitoring, additional booster dose or immunomodulatory therapies not only for acute COVID-19 but also for long COVID-19.}, }
@article {pmid41235245, year = {2025}, author = {Chen-Camaño, R and DeAntonio, R and López-Vergès, S}, title = {T-cell exhaustion in COVID-19: what do we know?.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1678149}, pmid = {41235245}, issn = {1664-3224}, mesh = {Humans ; *COVID-19/immunology ; *SARS-CoV-2/immunology ; *T-Lymphocytes/immunology ; T-Cell Exhaustion ; }, abstract = {T-cell exhaustion is a terminal state of immune dysfunction characterized by impaired proliferation and effector functions, diminished cytokine secretion, and sustained expression of inhibitory receptors. In coronavirus disease 2019 (COVID-19), increasing evidence links exhausted T-cell phenotypes with poor clinical outcomes, including severe disease, delayed viral clearance, and persistent symptoms associated with Long COVID. Exhaustion results from prolonged antigenic stimulation and inflammatory signals and is marked by transcriptional reprogramming, metabolic and epigenetic dysregulation, and co-expression of inhibitory receptors such as programmed cell death protein-1 (PD-1), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Notably, exhausted phenotypes in COVID-19 frequently coexist with hyperactivation, raising the unresolved question of whether inhibitory receptor expression reflects transient activation or irreversible dysfunction. Emerging therapeutic strategies to reverse these dysfunctional states include immune checkpoint inhibitors, cytokine modulation, metabolic interventions, and epigenetic therapies, although their clinical translation remains at an early stage. Critical research gaps include the scarcity of longitudinal data, incomplete profiling of T-cell subsets across disease stages during COVID-19 and Long COVID-19, and contradictory evidence of vaccine-induced exhaustion with limited understanding of its consequences. This non-systematic literature review synthesizes current advances in COVID-19 immunopathology and therapeutic strategies, underscoring that understanding T-cell exhaustion is crucial to improving outcomes and shaping next-generation immunotherapies and vaccines.}, }
@article {pmid41241149, year = {2025}, author = {Park, WH}, title = {The mitochondrial nexus: Dysfunction, inhibition, and therapeutic frontiers in lung disease.}, journal = {Respiratory medicine}, volume = {250}, number = {}, pages = {108506}, doi = {10.1016/j.rmed.2025.108506}, pmid = {41241149}, issn = {1532-3064}, mesh = {Humans ; *Mitochondria/metabolism/physiology ; *Lung Diseases/metabolism/physiopathology/therapy ; COVID-19/metabolism ; Reactive Oxygen Species/metabolism ; SARS-CoV-2 ; Mitophagy/physiology ; Pulmonary Disease, Chronic Obstructive ; Energy Metabolism ; Antioxidants/therapeutic use ; }, abstract = {Mitochondria are increasingly recognized as central arbiters of cellular fate, placing them at the nexus of pulmonary health and disease. Beyond their canonical role in adenosine triphosphate (ATP) synthesis, these organelles are critical hubs for redox signaling, metabolic homeostasis, and programmed cell death. Mitochondrial dysfunction-a multifaceted condition characterized by impaired bioenergetics, excessive reactive oxygen species (ROS) production, aberrant dynamics, and defective quality control via mitophagy-is a unifying pathogenic feature in chronic lung diseases, including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and pulmonary arterial hypertension (PAH). This dysfunction is also a critical determinant of severity in acute conditions like acute lung injury (ALI) and COVID-19 and is a key mechanistic driver of Long COVID. This review synthesizes the core mechanisms of mitochondrial impairment, delineates their specific contributions to this spectrum of pulmonary pathologies, and discusses the burgeoning field of mitochondria-targeted therapeutics. Strategies ranging from targeted antioxidants and metabolic modulators to novel regenerative approaches like mitochondrial transplantation are highlighted, with an expanded discussion on their limitations, challenges, and clinical implications. By framing mitochondrial integrity as a critical determinant of pulmonary disease, we underscore a pivotal axis for future diagnostic and therapeutic innovation.}, }
@article {pmid41244103, year = {2025}, author = {Yue, Y and Han, X and Chen, Q and Dai, L and Ai, Q and Zhang, Z and Ma, F and Gao, J}, title = {The effect of pulmonary rehabilitation for post-acute sequelae of SARS-CoV-2 infection in patients: a systematic review and meta-analysis.}, journal = {Frontiers in rehabilitation sciences}, volume = {6}, number = {}, pages = {1634351}, pmid = {41244103}, issn = {2673-6861}, abstract = {BACKGROUND: Post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID, are characterized by persistent symptoms such as fatigue, dyspnea, and reduced functional capacity. Pulmonary rehabilitation (PR) is recommended for chronic respiratory conditions, but its effectiveness in PASC, particularly across different delivery modes, remains uncertain.<br><br>OBJECTIVE: To assess the impact of PR, including telerehabilitation and in-person modalities, on physical function, dyspnea, pulmonary function, fatigue, and quality of life in patients with PASC.<br><br>METHODS: We conducted a systematic search of PubMed, Embase, the Cochrane Library, and Web of Science from inception to March 25 for controlled clinical trials assessing the effects of PR in PASC patients. Two independent reviewers performed study selection and data extraction. The risk of bias was assessed using the Cochrane Risk of Bias Tool, and data were analyzed using Review Manager (RevMan) 5.4.1. Effect sizes were reported as mean differences (MD) or standardized mean differences (SMD) with 95% confidence intervals (CI).<br><br>RESULTS: Ten randomized controlled trials involving 673 participants were included. Most studies were judged to have a moderate risk of bias. Compared with usual care, PR significantly improved six-minute walk distance (MD: 76.85 meters; 95% CI: 57.35-96.36; p&#x2009;<&#x2009;0.001), maximal inspiratory pressure (MD: 17.63&#x2005;cmH&#x2082;O; 95% CI: 4.50-30.76; p&#x2009;=&#x2009;0.009), fatigue (SMD: -1.15; 95% CI: -1.83 to -0.48; p&#x2009;<&#x2009;0.001), and quality of life (SMD: 1.73; 95% CI: 0.56-2.91; p&#x2009;=&#x2009;0.004). No statistically significant improvement was found for dyspnea (MD: -0.41; 95% CI: -1.51 to -0.68; p&#x2009;=&#x2009;0.46). Subgroup analyses showed no significant differences between telerehabilitation and in-person PR across all outcomes, including exercise capacity (p&#x2009;=&#x2009;0.84), dyspnea (p&#x2009;=&#x2009;0.86), fatigue (p&#x2009;=&#x2009;0.93), and quality of life (p&#x2009;=&#x2009;0.44).<br><br>CONCLUSIONS: PR improves physical and functional outcomes in patients with PASC. Telerehabilitation offers a clinically equivalent alternative to in-person PR, supporting its broader implementation.}, }
@article {pmid41247781, year = {2025}, author = {Henrich, TJ and Montgomery, CP and Graf, J and Ismail, N and Mohandas, S and Suthar, MS and Brim, H and Coffin, JM and Pagaria, A and Guzmán Rivera, J and Vudali, U and Keim, P and Zhong, G and McGrath, R and Edwards, B and García-Sastre, A and Gennaro, ML}, title = {The role of co-infection in the pathogenesis of acute SARS-CoV-2 infection and development of post-acute sequelae: A perspective.}, journal = {eLife}, volume = {14}, number = {}, pages = {}, pmid = {41247781}, issn = {2050-084X}, mesh = {Humans ; *COVID-19/complications/pathology/virology ; *Coinfection/virology ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Bacterial Infections/complications ; }, abstract = {A major health challenge resulting from the COVID-19 pandemic is the manifestation of post-acute sequelae of SARS-CoV-2 (PASC). PASC (or long COVID) is a collective term used for clinical symptoms, various pathologies, and life-quality-changing functional impairment that persist for months to years after the initial SARS-CoV-2 infection. The mechanisms underlying PASC are not understood, although advances have been made in identifying factors that may contribute to long-term pathology. Recent data have emerged, showing an association between SARS-CoV-2 viral persistence and non-SARS-CoV-2 infections (pre-existing, viral reactivation, or new infections) in facilitating or mediating PASC. However, the heterogeneous nature and timing of co-infections have made it challenging to understand, interpret, and contextualize their contribution to PASC. Here, we summarize the impact of potential viral, bacterial, and fungal infections on SARS-CoV-2 pathogenesis, with a focus on their possible roles in the development of PASC. We also provide a framework to understand the mechanisms of PASC and inform basic, translational, and clinical research initiatives, including RECOVER, a large and ongoing research initiative to understand, treat, and prevent long COVID.}, }
@article {pmid41262872, year = {2025}, author = {Lv, X and Ji, L and Cao, W and Xue, Y and Dai, H and Zhang, S}, title = {Revisiting lung cancer immunotherapy in the era of long COVID: mechanistic insights and therapeutic implications.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1657691}, pmid = {41262872}, issn = {2235-2988}, mesh = {Humans ; *COVID-19/immunology/complications ; *Immunotherapy/methods ; *Lung Neoplasms/therapy/immunology ; SARS-CoV-2/immunology ; Tumor Microenvironment/immunology ; Immune Checkpoint Inhibitors/therapeutic use ; }, abstract = {In the post-COVID-19 era, understanding the long-term impact of Long COVID on the immune system is essential for deciphering its influence on lung cancer pathogenesis and immunotherapeutic efficacy. This review comprehensively examines how persistent COVID-19 sequelae-manifested as chronic inflammation, pulmonary fibrosis, cytokine dysregulation, and T-cell exhaustion can reshape the lung cancer microenvironment. In addition, the emerging roles of memory B cells and altered neutrophil function in promoting tumorigenesis are discussed. Importantly, we analyze recent clinical evidence suggesting that COVID-19 vaccination may enhance the efficacy of immune checkpoint inhibitors, potentially by modulating host immunity. By integrating mechanistic insights with clinical observations, this review aims to illuminate the challenges and opportunities at the intersection of Long COVID and lung cancer treatment, thereby fostering the development of personalized therapeutic strategies in the post-pandemic era.}, }
@article {pmid41268373, year = {2025}, author = {Calleja-Conde, J and Echeverry-Alzate, V and Sánchez-Diez, S and Giné, E and Bühler, KM}, title = {Severe alcohol use and COVID-19: implications for physical and mental health.}, journal = {Frontiers in psychiatry}, volume = {16}, number = {}, pages = {1640207}, pmid = {41268373}, issn = {1664-0640}, abstract = {The COVID-19 pandemic has revealed and intensified the vulnerability of individuals with pre-existing medical and behavioral conditions, notably those related to substance use. Among these, chronic alcohol consumption represents a clinically significant, yet often under-addressed, vulnerability factor that may exacerbate both the acute severity and long-term consequences of SARS-CoV-2 infection. This narrative review examines the biological and clinical intersections between alcohol use and COVID-19, focusing on shared mechanisms of immune dysfunction, neuroinflammation, and disruption of the gut-brain axis. We synthesize current findings showing that both conditions compromise innate and adaptive immune responses, alter cytokine signaling, and weaken mucosal and blood-brain barriers. These changes contribute to cognitive and emotional dysregulation and may increase the risk of persistent neuropsychiatric symptoms, including those observed in Long COVID. In addition, we discuss how chronic alcohol use may alter host susceptibility to infection and affect the immune response to vaccination, with implications for treatment outcomes and recovery. Our findings highlight the need to integrate alcohol use disorder into COVID-19 risk assessments, clinical management, and long-term mental health care planning. A multidisciplinary approach is essential to address the overlapping biological pathways that link alcohol-related vulnerability to COVID-19 outcomes.}, }
@article {pmid41271803, year = {2025}, author = {Bansal, A}, title = {Economic burden of long COVID: macroeconomic, cost-of-illness and microeconomic impacts.}, journal = {NPJ primary care respiratory medicine}, volume = {35}, number = {1}, pages = {53}, pmid = {41271803}, issn = {2055-1010}, mesh = {Humans ; *COVID-19/economics/epidemiology ; *Cost of Illness ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Global Health ; Unemployment ; }, abstract = {Long COVID, defined by symptoms persisting three months post-SARS-CoV-2 infection, presents a significant global health and economic challenge, with global prevalence estimated at 36% (ranging from 1-92%). This brief communication consolidates current knowledge on its economic impacts, including macroeconomic, cost-of-illness, and microeconomic impacts, which are estimated at an average annual burden of $1 trillion globally and $9000 per patient in the USA, with some individuals covering substantial out-of-pocket expenses. Annual lost earnings in the USA alone are estimated at approximately $170 billion. Long COVID was associated with increased unemployment, financial distress, and work impairment for up to three years post-infection. This paper highlights discrepancies in impact estimation methodologies and calls for standardised metrics especially in emerging economies. Key research gaps include the absence of comprehensive longitudinal studies on individual and aggregated economic burden, specific long COVID phenotypes and biomarkers, and cost-effectiveness evaluations of interventions.}, }
@article {pmid41272382, year = {2026}, author = {Dornas, W and Reis, JP and Belilo, TE and Vaz, LG and Nasser, HH and de Souza Maia, ML and Figueiredo, A and Tcherniacovski, AG and Montenegro, LCC and Yang, X and C Santiago, H}, title = {Persistent inflammatory cytokine signature in long Covid-19 patients: a meta-analysis.}, journal = {Inflammopharmacology}, volume = {34}, number = {1}, pages = {1-16}, pmid = {41272382}, issn = {1568-5608}, mesh = {Humans ; *COVID-19/immunology/blood/complications ; *Cytokines/blood/metabolism ; *Inflammation/immunology ; }, abstract = {Post-acute sequelae of Covid-19 (PASC) refer to persistent symptoms lasting weeks to months after acute SARS-CoV-2 infection. However, identifying biological mechanisms, potential therapeutic targets, and modifiable environmental risk factors remains necessary. Here, we analyzed cytokine levels in patients with PASC through a systematic literature search of the PubMed/MEDLINE, Web of Science, and Scopus databases, including articles published up to December 2024. A total of 33 studies (comprising 3294 patients) were included, addressing the long-term sequelae following acute Covid-19 infection. Levels of IL-6, IL-2, MCP-1/CCL2, TNF-α, IFN-γ, and IP-10/CXCL10 were higher in Covid-19 patients with PASC compared to those without PASC, suggesting an inflammatory basis for the persistence of symptoms. Conversely, little or no difference was observed for IL-1β, IL-7, IL-10, IL-4, IL-17A, IL-8, and IL-1α. To assess the duration of the sustained inflammatory response post-infection, cytokine measurements were categorized as < 6 months or ≥ 6 months after diagnosis. IL-6, MCP-1/CCL2, TNF-α, and IFN-γ remained elevated in both time windows, while IL-1β, IL-8, IP-10/CXCL10, IL-2, and IL-10 showed increased levels beyond 6 months post-Covid-19 diagnosis. Our findings indicate that persistent elevation of inflammatory cytokine is associated with PASC, contributing to a better understanding of the immune pathology underlying chronic dysfunction related to Covid-19.}, }
@article {pmid41285857, year = {2025}, author = {Green, R and Marjenberg, Z and Lip, GYH and Banerjee, A and Wisnivesky, J and Delaney, BC and Peluso, MJ and Wynberg, E and Abduljawad, S}, title = {A systematic review and meta-analysis of the impact of vaccination on prevention of long COVID.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {10326}, pmid = {41285857}, issn = {2041-1723}, mesh = {Humans ; *COVID-19/prevention &amp; control/immunology/virology/epidemiology ; *COVID-19 Vaccines/administration &amp; dosage/immunology ; Immunization, Secondary ; *SARS-CoV-2/immunology ; *Vaccination ; Odds Ratio ; }, abstract = {Long COVID affects millions worldwide and its prevention is a critical public health strategy. While prior analyses show primary vaccination prevents long COVID in subsequent infections, the effect of booster vaccination on long COVID after Omicron infections is unclear. This systematic review identifies 31 observational studies, of which 11 are suitable for pairwise meta-analyses. The pooled odds ratio (OR) of long COVID in those vaccinated (any dose) versus unvaccinated is 0.77 (95% confidence interval [CI] 0.70-0.85; p < 0.0001; 10 studies). ORs were also lower for primary course vaccination versus unvaccinated (OR 0.81; 95% CI 0.79-0.83; p < 0.0001; 3 studies), booster vaccination versus unvaccinated (OR 0.74; 95% CI 0.63-0.86; p = 0.0001; 4 studies), and booster vaccination versus primary course vaccination (OR 77; 95% CI 0.65-0.92; p = 0.0044; 3 studies). These findings indicate that booster vaccination can provide additional protection against long COVID, highlighting the importance of seasonal vaccination against new SARS-CoV-2 variants. They should, however, be interpreted cautiously, given the small number of studies and the low quality of evidence.}, }
@article {pmid41301889, year = {2025}, author = {Ivanovska, M and Homadi, MS and Angelova, G and Taskov, H and Murdjeva, M}, title = {Differential Characteristics and Comparison Between Long-COVID Syndrome and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).}, journal = {Biomedicines}, volume = {13}, number = {11}, pages = {}, pmid = {41301889}, issn = {2227-9059}, abstract = {Long-COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome are disabling diseases characterised by ongoing fatigue, post-exertional malaise, cognitive impairment, and autonomic dysfunction. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome typically follows viral infections, whereas Long-COVID exclusively follows SARS-CoV-2 infection, with overlapping but distinct features. This review uses comprehensive searches of online databases to compare their clinical presentations, pathophysiologies, and treatments. Both Long-COVID and ME/CFS appear to involve multifactorial mechanisms, including viral persistence, immune dysregulation, endothelial dysfunction, and autoimmunity, though their relative contributions remain uncertain. Symptom management strategies are consistent, however. Cognitive behaviour therapy has been successful, and there are minimal drug treatments. Graded exercise therapy occupies a contested place, recommending individualised pacing and multidisciplinary rehabilitation. Common and exclusive mechanisms must be identified to formulate valuable therapies. A more significant body of research focusing on immune dysfunction as a pathogenic mechanism for advancing the disease and enabling more effective therapies and diagnostics is needed.}, }
@article {pmid41302566, year = {2025}, author = {Sui, SX and Yu, L}, title = {Patient and Professional Perspectives on Long COVID: A Systematic Literature Review and Meta-Synthesis.}, journal = {International journal of environmental research and public health}, volume = {22}, number = {11}, pages = {}, pmid = {41302566}, issn = {1660-4601}, mesh = {Humans ; *COVID-19/psychology ; *Health Personnel/psychology ; SARS-CoV-2 ; Qualitative Research ; }, abstract = {BACKGROUND: Post-COVID-19 condition ('long COVID') involves fluctuating symptoms across multiple organ systems and disability or functional loss, which may be episodic, continuous, or permanent. Qualitative research is essential to capture lived experiences and explain how social and health system contexts may influence improvement, recovery, and service use. We synthesised perspectives from people living with long COVID and healthcare professionals to inform service design and policy.<br><br>METHODS: We conducted a systematic review and qualitative meta-synthesis. MEDLINE, Embase, PsycINFO, CINAHL, Scopus, and Web of Science were searched for studies published between 1 January 2020 and 19 August 2025. Eligible studies reported qualitative data from adults with long COVID (&#x2265;12 weeks after acute infection) and/or healthcare professionals in any setting. We excluded non-qualitative, non-primary, or non-English reports. Two reviewers independently screened, extracted, and appraised studies using the Critical Appraisal Skills Programme checklist. Data were synthesised thematically. The protocol was registered with the Open Science Framework.<br><br>FINDINGS: Of 1544 records screened, 49 studies met the inclusion criteria: 41 involving patients, two involving professionals, and six involving both. Eight patient themes (including symptom burden, identity disruption and stigma) and four professional themes (including recognition, care coordination and holistic care models) were identified. Recognition emerged as a cross-cutting mechanism: validation and consistent pacing guidance facilitated engagement and safer activity, whereas invalidation and inconsistent advice were associated with distress, avoidance, and disengagement. Trajectories showed gradual expansion of multidisciplinary care models, but major capacity and equity gaps persisted. Most studies had low methodological concerns, although heterogeneity in populations and settings was substantial.<br><br>INTERPRETATION: Long COVID is a chronic, biological condition that also intersects with social and psychological dimensions, and may present with episodic, continuous, or progressive trajectories. Healthcare services must prioritise early validation, provide consistent pacing and relapse prevention guidance, expand access to multidisciplinary and peer-supported rehabilitation, integrate mental healthcare, strengthen coordinated pathways, and support graded return to work. Explicit attention to equity is required to avoid widening disparities.}, }
@article {pmid41303176, year = {2025}, author = {Olarinde, F and Nunes-Silva, A and Sanchez-Ramirez, DC and Molgat-Seon, Y and Villar, R}, title = {Using Active Standing Orthostatic Stress Test to Assess Physiological Responses in Individuals with Long COVID: A Systematic Review.}, journal = {Journal of clinical medicine}, volume = {14}, number = {22}, pages = {}, pmid = {41303176}, issn = {2077-0383}, abstract = {Background/Objectives: Individuals experiencing long COVID (LC) frequently report orthostatic intolerance symptoms, which may be linked to autonomic and cardiovascular dysfunction. The active standing test provides a simple, clinically relevant means to assess these impairments. This systematic review aims to determine the use of the active standing orthostatic stress test in evaluating cardiovascular, autonomic, and respiratory responses in people experiencing LC. Methods: A systematic search, according to PRISMA guidelines, was conducted in PubMed, MEDLINE, EMBASE, CINAHL, and Scopus for articles published between 2020 and 2025. This study was registered in PROSPERO CRD-42024615872. Studies were included if they used the active standing test, enrolled adults (≥18 years), included both long COVID and healthy control groups, used continuous beat-to-beat measurements, and reported physiological outcomes. Risk of bias was assessed using the nine-point Newcastle-Ottawa Scale. Results: Three studies (216 participants experiencing LC and 186 controls) met the inclusion criteria. Across studies, LC individuals consistently exhibited elevated heart rate in both supine and standing positions. However, blood pressure findings were more variable: only one study reported 13% of participants met orthostatic hypotension criteria, while another found significant increases in diastolic blood pressure during standing. Long COVID groups also showed reduced heart rate variability compared to controls. Conclusions: Individuals experiencing LC show elevated heart rate and impaired autonomic function during active standing, with subgroup-specific blood pressure changes. These alterations may contribute to dizziness, fatigue, and reduced activity tolerance. Incorporating active standing into clinical assessment could aid early identification of autonomic dysfunction and inform rehabilitation strategies, though more research is urgently needed.}, }
@article {pmid41304215, year = {2025}, author = {Arruda, ISA and Cavalcante, CDS and Rubens, RS and Castro, LNPF and Nóbrega, YKM and Dalmolin, TV}, title = {Changes in the Gut Microbiota of Patients After SARS-CoV-2 Infection: What Do We Know?.}, journal = {Microorganisms}, volume = {13}, number = {11}, pages = {}, pmid = {41304215}, issn = {2076-2607}, support = {DPI/BCE n&#xba; 01/2025//University of Brasilia/ ; FAPDF n&#xba; 09/2023//Funda&#xe7;&#xe3;o de Apoio &#xe0; Pesquisa do Distrito Federal/ ; }, abstract = {COVID-19 can cause long-term symptoms, such as a post-infection syndrome, known as Long-COVID. Among the symptoms present during this period, the most reported are gastrointestinal symptoms. This study discusses the effects of changes in the gut microbiota of post-COVID-19 patients. SARS-CoV-2 infection is associated with significant alterations in gut microbial composition, disturbing its homeostasis and promoting a reduction in the abundance of beneficial symbiotic bacteria and an increase in the abundance of opportunistic pathogens. Furthermore, the composition of the gut microbiota may play a role in the prognosis of patients with post-COVID-19 infection. The microbiota of the intestinal tract and the respiratory tract influence each other; therefore, the gut-lung axis has attracted increasing interest in understanding COVID-19. Moreover, the brain-gut axis has been studied, since there have been reports of anxiety and depression along with post-COVID-19 gastrointestinal symptoms. Treatments options for intestinal dysbiosis in Long-COVID patients include probiotics, prebiotics, and fecal microbiota transplantation. These treatments may serve as an approach to improve gastrointestinal symptoms during Long-COVID, increasing microbiome diversity, strengthening the integrity of intestinal barrier functions, and consequently influencing the treatment of COVID-19.}, }
@article {pmid41304256, year = {2025}, author = {Mateescu, DM and Ilie, AC and Cotet, I and Guse, C and Muresan, CO and Pah, AM and Badalica-Petrescu, M and Iurciuc, S and Craciun, ML and Avram, A and Margan, MM and Enache, A}, title = {Gut Microbiome Dysbiosis in COVID-19: A Systematic Review and Meta-Analysis of Diversity Indices, Taxa Alterations, and Mortality Risk.}, journal = {Microorganisms}, volume = {13}, number = {11}, pages = {}, pmid = {41304256}, issn = {2076-2607}, support = {"Victor Babes" University of Medicine and Pharmacy Timisoara//"Victor Babes" University of Medicine and Pharmacy Timisoara/ ; }, abstract = {COVID-19 is associated with gut microbiome alterations that may influence disease outcomes through immune and inflammatory pathways. This systematic review and meta-analysis evaluated global evidence on gut dysbiosis in COVID-19. We searched PubMed/MEDLINE, Embase, Web of Science, Scopus, and Cochrane Library up to 5 October 2025 (PROSPERO CRD420251160970). Alpha-diversity indices and microbial taxa log-fold changes (logFC) were analyzed using random-effects models. The pooled standardized mean difference (SMD) for the Shannon index was -0.69 (95% CI -0.84 to -0.54; I[2] = 42%), confirming reduced microbial diversity. Faecalibacterium prausnitzii showed a significant pooled depletion (logFC = -1.24; 95% CI -1.68 to -0.80; k = 10; I[2] = 74%), while Enterococcus spp. was increased (logFC = 1.45; 95% CI 1.12-1.78). Egger's test did not suggest publication bias (p = 0.32). Gut dysbiosis was consistently associated with reduced microbial diversity and enrichment of pathogenic taxa, correlating with increased disease severity and mortality (HR = 1.67). These findings highlight the potential of microbiome profiling as a prognostic tool in COVID-19, although clinical translation requires further validation.}, }
@article {pmid41305428, year = {2025}, author = {Chiang, KC and Chiu, CEN and Altaf, M and Cheng, MTK and Gupta, RK}, title = {Mechanisms of Cell-Cell Fusion in SARS-CoV-2: An Evolving Strategy for Transmission and Immune Evasion.}, journal = {Viruses}, volume = {17}, number = {11}, pages = {}, pmid = {41305428}, issn = {1999-4915}, mesh = {Humans ; *SARS-CoV-2/immunology/physiology/pathogenicity/genetics ; *COVID-19/transmission/immunology/virology ; *Immune Evasion ; Cell Fusion ; *Virus Internalization ; Giant Cells/virology ; Animals ; Antibodies, Neutralizing/immunology ; }, abstract = {Early studies on the evolution of SARS-CoV-2 revealed mutations that favored host transmission of the virus and more efficient viral entry. However, cell-free virus spread is vulnerable to host-neutralizing antibodies. As population immunity developed, mutations that confer escape from neutralization were selected. Notably, cell syncytia formation wherein an infected cell fuses with a noninfected cell is a more efficient route of transmission that bypasses humoral immunity. Cell syncytia formation has been implicated in the pathogenicity of SARS-CoV-2 infection whilst compromising host transmission due to impaired whole virion release. Therefore, understanding the mechanisms of virus-mediated cell-cell fusion will aid in identifying and targeting more pathogenic strains of SARS-CoV-2. Whilst the general kinetics of cell-cell fusion have been known for decades, the specific mechanisms by which SARS-CoV-2 induces fusion are beginning to be elucidated. This is partially due to emergence of more reliable, high throughput methods of quantifying and comparing fusion efficiency in experimental models. Moreover, the ongoing inflammatory response and emerging health burden of long COVID may point to cell-cell fusion in the pathogenesis. In this review, we synthesize current understanding of SARS-CoV-2-mediated cell-cell fusion and its consequences on immune escape, viral persistence, and the innate immune response.}, }
@article {pmid41305454, year = {2025}, author = {Miftahof, J and Bernauer, B and Tan, CS}, title = {Neurological Manifestations of SARS-CoV-2.}, journal = {Viruses}, volume = {17}, number = {11}, pages = {}, pmid = {41305454}, issn = {1999-4915}, mesh = {Humans ; *COVID-19/complications/pathology/virology ; Animals ; *SARS-CoV-2/pathogenicity ; Disease Models, Animal ; Brain/virology/pathology ; *Nervous System Diseases/virology/pathology/etiology ; Central Nervous System/virology/pathology ; }, abstract = {Neurocognitive symptoms have emerged as notable sequelae of SARS-CoV-2 infection (COVID-19). Although primarily a respiratory virus, SARS-CoV-2 has been associated with central nervous system (CNS) changes observed in both clinical and experimental settings. To better understand these effects and their pathological mechanisms, we conducted a systematic literature search of published studies and employed a qualitative, analytical approach to identify and synthesize key findings from peer-reviewed studies, including large-scale retrospective clinical cohorts, human autopsy reports, animal models (murine, non-human primate), and in vitro brain organoid systems. While viral components were detected in post mortem central nervous system tissues, COVID-19 neuropathology appears to stem primarily from immune-mediated inflammation and vascular injury rather than direct CNS infection. Persistent glial activation and BBB disruption may underlie the long-term neurological symptoms reported in long COVID-19. Although animal models offer mechanistic insight, species-specific differences necessitate cautious extrapolation to human pathology. Further investigation into the chronic effects of SARS-CoV-2 on the brain is essential to guide long-term clinical management and therapeutic development.}, }
@article {pmid41308689, year = {2025}, author = {Amdal, CD and Falk, RS and Alanya, A and Schlichting, M and Roychoudhury, S and Bhatnagar, V and Wintner, LM and Regnault, A and Ingelgård, A and Coens, C and le Cessie, S and Holzner, B and Chang, J and Taphoorn, M and Cislo, P and Giesinger, JM and Cappelleri, JC and Pawar, V and Ten Seldam, S and Papadopoulos, EJ and Calvert, MJ and Joseph, KL and Bottomley, A and Griebsch, I and Arraras, JI and Astrup, GL and Basch, E and Belančić, A and Brundage, M and Campbell, A and Rerhou Rantell, K and Cocks, K and Cherny, N and Eremenco, S and Ferrer, M and Fiero, MH and Gerlinger, C and Goetghebeur, E and Grouven, U and Lauer, A and Aiyegbusi, OL and Machingura, A and Mizusawa, J and Molenberghs, G and Aa Petersen, M and Reijneveld, JC and Ringash, J and Rumpold, G and Rutherford, C and Quinten, C and Sail, K and Sasseville, M and Sauerbrei, W and Schiel, A and Smith, AW and Snyder, C and Velikova, G and Wang, XS and Bjordal, K and Pe, M and , }, title = {SISAQOL-IMI consensus-based guidelines to design, analyse, interpret, and present patient-reported outcomes in cancer clinical trials.}, journal = {The Lancet. Oncology}, volume = {26}, number = {12}, pages = {e683-e693}, doi = {10.1016/S1470-2045(25)00520-0}, pmid = {41308689}, issn = {1474-5488}, mesh = {Humans ; *Patient Reported Outcome Measures ; *Neoplasms/therapy/drug therapy ; Consensus ; Quality of Life ; *Research Design/standards ; *Clinical Trials as Topic/standards ; Randomized Controlled Trials as Topic/standards ; }, abstract = {Standardising the implementation of patient-reported outcomes (PROs) in clinical trials is crucial for evaluating the benefits and risks of cancer treatments. The Setting International Standards in Analysing Patient-Reported Outcomes and Quality of Life Endpoints in Cancer Clinical Trials-Innovative Medicines Initiative (SISAQOL-IMI) has developed 146 consensus-based recommendations for designing, analysing, interpreting, and presenting PROs in cancer clinical trials. This initiative, undertaken from 2021 to 2025, involved experts, including statisticians, PRO measurement experts, clinicians, and patient representatives from 41 organisations representing regulatory agencies, academia, the pharmaceutical industry, health-technology assessment bodies, and patient advocates. SISAQOL-IMI provides guidance on the implementation of PROs in randomised controlled trials and single-arm trials, terminology, definitions and the selection of PRO score interpretation thresholds, and for visualising PRO results for different audiences. To facilitate the implementation of these standards, in addition to this Policy Review, four key outputs are available: an interactive table, a guidebook, plain language materials, and a glossary.}, }
@article {pmid41318861, year = {2026}, author = {Yadav, JP and Yadav, S and Dubey, NK and Yadav, IP and Pathak, P and Verma, A}, title = {Lingering echoes of SARS-CoV-2: mechanistic insights and management of long COVID syndrome.}, journal = {Inflammopharmacology}, volume = {34}, number = {1}, pages = {17-46}, pmid = {41318861}, issn = {1568-5608}, mesh = {Humans ; *COVID-19/therapy/complications/physiopathology/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Antiviral Agents/therapeutic use ; }, abstract = {Throughout the world-wide COVID-19 pandemic, there has arisen a significant and a sustained public-health issue, whereby a significant proportion of individuals report persistent symptoms, well beyond the acute period of infection. The non-united array of chronic, multisystemic events, such as fatigue, cognitive deficit, respiratory dysfunction, cardiovascular abnormalities, and neuropsychiatric disorders characterize this sequela, which is referred to as LCS. LCS is much more than the starting viral insult, as it causes long-term complications that impact various organ systems. The current review questions the pathophysiological mechanisms of LCS, including scrutinizing the importance of the dysregulation of immunity, the persistence of viral reservoirs, endothelial dysfunction, autonomic imbalance, and mitochondrial injury. We highlight the heterogeneity of the syndrome and the associated diagnostic and treatment difficulties. In addition, we stress the urgency of powerful biomarkers that will be used to diagnose LCS as early as possible and monitor it over time. Present treatment strategies, including pharmacologic therapy (immunomodulators, anticoagulants, antiviral medications, etc.) and non-pharmacologic treatment (rehabilitative programs, etc.) are discussed against the backdrop of recent clinical findings. This review incorporates the recent literature and presents a review of potential treatment options that alleviate symptoms and improve the quality of life of LCS patients. Finally, this integrated synthesis can be used by both clinicians and researchers to gain practical information on the diagnosis, treatment, and future treatment directions of LCS.}, }
@article {pmid41346576, year = {2025}, author = {Guimarães, GN and Brunetti, NS and De Lima, DG and Proenca-Modena, JL and Farias, AS}, title = {Vaccination and COVID-19: impact on long-COVID.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1686572}, pmid = {41346576}, issn = {1664-3224}, mesh = {Humans ; *COVID-19/immunology/prevention &amp; control ; *COVID-19 Vaccines/immunology/administration &amp; dosage ; *SARS-CoV-2/immunology ; *Vaccination ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long- and post-COVID-19 syndromes have emerged as a significant global health challenge, with millions of individuals experiencing persistent or the development of new symptoms after a long period of an initial SARS-CoV-2 infection. These symptoms are multisystemic and may indicate changes in the respiratory, neurological, cardiovascular and gastrointestinal systems, in addition to prolonged fatigue. Vaccination has played a crucial role in reducing severe disease and mortality, but the impact of the different vaccine combinations on the development and resolution of Long COVID remains a topic of debate. This review synthesizes current evidence on how different vaccine platforms, dosing strategies and booster doses influence the immunological response, protection, incidence, severity, and persistence of Long COVID symptoms. We discuss key immunological mechanisms by which vaccination may modulate and protect post-COVID syndrome outcomes, including its effects on viral clearance, immune response reprogramming, inflammation, and autoimmunity, seeking to combat misinformation and concepts spread by fake news. The review also highlights controversies and research gaps, such as variability in vaccine response among different populations and the role in the selection of more transmissible and virulent SARS-CoV-2 variants, as well as the potential differences between vaccine-induced and infection-induced immunity, and the role of pre-existing immune conditions in this scenario.}, }
@article {pmid41349247, year = {2025}, author = {Halma, M and Varon, J}, title = {Metabolic modulation as a therapeutic strategy for post-acute vaccination syndrome (PACVS): A review of pathomechanisms and existing therapeutic components.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {193}, number = {}, pages = {118864}, doi = {10.1016/j.biopha.2025.118864}, pmid = {41349247}, issn = {1950-6007}, mesh = {Humans ; *Vaccination/adverse effects ; Oxidative Stress/drug effects ; Mitochondria/metabolism/drug effects ; Animals ; *Energy Metabolism/drug effects ; }, abstract = {Post-Acute Vaccination Syndrome (PACVS) is a post-vaccination disorder marked by persistent fatigue, cognitive impairment, and exercise intolerance. Current research identifies interconnected pathophysiological processes, including persisting spike protein, mitochondrial dysfunction, decreased tissue oxygenation, and impaired metabolism. Emerging treatments rely on metabolic regulation and therapeutic agents promoting mitochondrial and vascular function. These therapies stimulate cellular energy generation, reduce oxidative stress, and regulate inflammatory pathways. This review examines metabolic and mitochondrial mechanisms underlying PACVS, evaluates existing therapeutic strategies targeting these pathways, and synthesizes current evidence for future research and clinical management.}, }
@article {pmid41349462, year = {2026}, author = {Eksteen, C and Asja, LC and Rass, A and Riedemann, J and Engelbrecht, AM}, title = {Post COVID-19 pandemic Inflammatory Insights into Cancer: Consequences for immunotherapy.}, journal = {Cytokine &amp; growth factor reviews}, volume = {87}, number = {}, pages = {10-18}, doi = {10.1016/j.cytogfr.2025.12.002}, pmid = {41349462}, issn = {1879-0305}, mesh = {Humans ; *COVID-19/immunology/complications ; *Neoplasms/immunology/therapy/pathology ; *Immunotherapy/methods ; SARS-CoV-2/immunology ; Tumor Microenvironment/immunology ; *Inflammation/immunology ; Cytokine Release Syndrome/immunology ; Spike Glycoprotein, Coronavirus/immunology ; Cytokines/immunology ; Pandemics ; }, abstract = {The COVID-19 pandemic has reshaped the landscape of global health, revealing novel interactions between infectious diseases and chronic conditions such as cancer. Beyond acute infection, growing evidence suggests that persistent exposure to SARS-CoV-2 spike protein, whether through infection or vaccination, may sustain inflammatory pathways that contribute to tumour progression and immune modulation. This review explores the overlap between post-COVID inflammation, particularly in Long-COVID syndromes and the tumour microenvironment (TME), focusing on key mediators such as IL-6, TNF-α, IL-1β, and NF-κB. We revisit the concept of the cytokine storm in the context of persistent inflammation, spike protein immunogenicity and immune exhaustion, proposing a model in which chronic inflammatory signalling may disrupt tumour immune surveillance, reawaken dormant cancer cells and compromise the efficacy of immunotherapies. Comparative analysis with other cancer types highlights shared pathways of oncogenic inflammation. Lastly, we outline emerging therapeutic strategies to mitigate these effects, including cytokine-targeted interventions and immunomodulatory screening in post-COVID cancer patients. These post-pandemic insights call for urgent translational research to ensure effective and safe cancer immunotherapy in the evolving inflammatory landscape.}, }
@article {pmid41350176, year = {2026}, author = {Miller, CM and Moen, JK and Iwasaki, A}, title = {The lingering shadow of epidemics: post-acute sequelae across history.}, journal = {Trends in immunology}, volume = {47}, number = {1}, pages = {9-18}, doi = {10.1016/j.it.2025.10.010}, pmid = {41350176}, issn = {1471-4981}, mesh = {Humans ; *COVID-19/epidemiology/complications/immunology ; Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; Epidemics ; *Fatigue Syndrome, Chronic/epidemiology/etiology ; Host-Pathogen Interactions/immunology ; Chronic Disease ; Lyme Disease ; }, abstract = {The SARS-CoV-2 pandemic has drawn global attention to post-acute infection syndromes (PAIS), with millions affected by post-acute sequelae of COVID-19 (PASC, or Long COVID). While Long COVID is newly defined, PAIS have been described for over a century following epidemic infections. Multiple pathogens - including influenza, Epstein-Barr virus, and Borrelia burgdorferi, among others - can precipitate persistent, poorly understood symptoms. Chronic illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have long been linked to infectious triggers. This recurring association highlights critical knowledge gaps and underscores the need for systematic investigation. Unlike prior pandemics, the current era offers advanced technologies and analytic tools to address these gaps. Defining the biology of Long COVID may yield broader insights into host-pathogen interactions and mechanisms of chronic illness.}, }
@article {pmid41368891, year = {2026}, author = {Pinero, S and Li, X and Zhang, J and Winter, M and Lee, SH and Nguyen, T and Liu, L and Li, J and Le, TD}, title = {Omics-based computational approaches for biomarker identification, prediction, and treatment of Long COVID.}, journal = {Critical reviews in clinical laboratory sciences}, volume = {63}, number = {4}, pages = {332-358}, doi = {10.1080/10408363.2025.2583083}, pmid = {41368891}, issn = {1549-781X}, mesh = {Humans ; *COVID-19/therapy/diagnosis/metabolism/genetics ; *Biomarkers/analysis/metabolism ; Post-Acute COVID-19 Syndrome ; Multiomics ; Proteomics ; Genomics/methods ; *Computational Biology/methods ; Metabolomics ; SARS-CoV-2 ; Epigenomics ; }, abstract = {Long COVID, or post-acute sequelae of COVID-19 (PASC), is a major global health problem, with cumulative estimates suggesting that around 400 million people worldwide have been affected. It is characterized by persistent or new symptoms such as fatigue, cognitive impairment, and breathlessness lasting beyond four weeks after acute infection. Diverse clinical manifestations, chronic course, and incompletely understood pathophysiology-including hypotheses involving viral persistence, immune dysregulation, autoimmunity, endothelial dysfunction, and metabolic reprogramming-impede the development of diagnostic criteria, biomarkers, and targeted therapies. We conducted a critical review of 101 Long COVID omics studies, focusing on the computational methods used and their methodological quality. Using standardized criteria, we evaluated study design, statistical rigor, reproducibility, and clinical relevance across genomics, epigenomics, transcriptomics, proteomics, metabolomics, and multiomics integration, and mapped these findings onto regulatory and translational frameworks. Despite substantial methodological heterogeneity, convergent biological signals emerged. Genomic studies implicate risk loci in immune and cardiopulmonary pathways. Epigenomic analyses identify differentially methylated regions in immune and circadian genes. Transcriptomic studies reveal persistent dysregulation of innate immune and coagulation pathways, as well as reproducible molecular endotypes. Proteomic studies consistently show abnormalities in the complement cascade and coagulation, with a small panel of complement proteins showing highly reproducible changes across independent cohorts. Metabolomic studies demonstrate sustained mitochondrial dysfunction and altered cellular bioenergetics for up to two years after infection. Multiomics integration supports at least two major endotypes, characterized by predominant inflammatory versus metabolic dysregulation, and provides a basis for patient stratification and computational treatment discovery. Machine learning models frequently achieve high classification performance, but are rarely externally validated. Critical limitations restrict clinical translation. Most studies are underpowered relative to analytical complexity, use heterogeneous case definitions and controls, and report platform-specific signatures with limited overlap. External validation, preregistered analysis plans, and regulatory-aligned assay development are uncommon. To date, no regulatory-approved diagnostic assay or evidence-based therapeutic intervention has directly emerged from these computational findings. Future progress requires harmonized phenotyping protocols, adequately powered longitudinal cohorts with external validation, integration of spatial omics and explainable artificial intelligence, and early engagement with regulatory and health-technology assessment pathways. This review provides a critical assessment and a translational roadmap, outlining how methodologically robust computational omics can be advanced toward clinically actionable tools for Long COVID.}, }
@article {pmid41379191, year = {2025}, author = {La Scaléa, ACR and Uehara, SCDSA}, title = {Pain in Long COVID: A scoping review of clinical characteristics and patterns of manifestation.}, journal = {Revista latino-americana de enfermagem}, volume = {33}, number = {}, pages = {e4777}, pmid = {41379191}, issn = {1518-8345}, mesh = {Humans ; *COVID-19/complications ; Female ; *Pain/etiology/diagnosis/epidemiology ; Male ; Pain Measurement ; SARS-CoV-2 ; }, abstract = {to map the available scientific evidence on the clinical characteristics and patterns of pain manifestation (location, frequency, duration, intensity, and quality) in individuals with Long COVID. a scoping review of publications from March 2020 to June 2024, indexed across four databases. Study selection was conducted by two independent, blinded reviewers. Data were extracted using a standardized instrument and analyzed descriptively. nineteen studies were included, indicating that pain affects individuals across all age groups, with higher prevalence among women, primarily involving the head, neck, shoulder, lower back, and hip. Pain frequency ranged from daily to monthly episodes, with duration exceeding one year in some cases. Intensity varied from mild to severe, and pain characteristics were diverse, with descriptors including burning, pressure, colicky, and throbbing pain. the clinical characteristics and patterns of pain manifestation in Long COVID are diverse. However, there is a paucity of studies providing detailed analyses of pain features and the influence of individual variables. These findings should guide future research and clinical practice toward a more comprehensive and contextualized assessment of pain in Long COVID.}, }
@article {pmid41384659, year = {2025}, author = {Bessalah, S and Sinha, D and Yuan, X and Paul, S and Longet, S}, title = {[Long COVID: therapeutic challenges and opportunities in the face of persistent sequelae].}, journal = {Medecine sciences : M/S}, volume = {41}, number = {11}, pages = {869-876}, doi = {10.1051/medsci/2025185}, pmid = {41384659}, issn = {1958-5381}, mesh = {Humans ; *COVID-19/complications/therapy/epidemiology ; *SARS-CoV-2/physiology ; Post-Acute COVID-19 Syndrome ; Pandemics ; COVID-19 Drug Treatment ; Antiviral Agents/therapeutic use ; Chronic Disease ; }, abstract = {The COVID-19 pandemic, caused by SARS-CoV-2, has not only led to a global health and economic crisis but also renewed attention to a clinical phenomenon of persistent symptoms after viral infection. This phenomenon is defined as long COVID or post-COVID-19 syndrome. Approximately one in eight patients experience persistent symptoms of varying intensity after the acute phase of the infection. This phenomenon, combined with the virus's high transmissibility and rapid mutation rate, poses a major public health challenge. This review examines various therapeutic approaches currently under consideration for treating long COVID, and explores future prospects in this field.}, }
@article {pmid41394849, year = {2025}, author = {Gabig-Cimińska, M}, title = {Dysregulated TFEB-autophagy-lysosome pathway links acute COVID-19 immunopathology to Long COVID sequelae.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1708364}, pmid = {41394849}, issn = {1664-3224}, mesh = {Humans ; *COVID-19/immunology/pathology/complications ; *Lysosomes/immunology/metabolism ; *Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism/immunology ; *Autophagy/immunology ; *SARS-CoV-2/immunology ; Animals ; Signal Transduction/immunology ; Immunity, Innate ; }, abstract = {SARS-CoV-2 disrupts cellular homeostasis, including the autophagy-lysosome pathway (ALP), a critical component of innate immunity and viral clearance. By subverting autophagy, SARS-CoV-2 proteins such as ORF3a, ORF7a, and NSP6 inhibit autophagosome-lysosome (APG-L) fusion, generating "incomplete autophagy" that permits viral persistence and drives hyperinflammation. Transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy, has emerged as a central player in the host response to coronavirus infection. TFEB orchestrates the expression of genes required for lysosomal function and autophagic flux while also shaping immune processes, including cytokine production, interferon-stimulated gene expression, and inflammasome clearance. This mini review synthesizes current knowledge on the TFEB-ALP axis in COVID-19 pathogenesis, highlighting its influence on acute immunopathology and its potential contribution to post-acute sequelae (Long COVID). Restoring TFEB activity and autophagic flux may counteract SARS-CoV-2 evasion strategies and restrain aberrant inflammatory responses. Harnessing the TFEB-autophagy pathway as a host-directed therapeutic strategy could help rebalance immune homeostasis, limit tissue damage during acute infection, and mitigate persistent inflammatory sequelae in Long COVID.}, }
@article {pmid41394882, year = {2025}, author = {Padilla-Blanco, M and García-García, T and Grigas, J and López-Ayllón, BD and Garrido, JJ and Oliva, MA and Montoya, M}, title = {Hidden players of COVID-19: the evolving roles of SARS-CoV-2 accessory proteins.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1726698}, pmid = {41394882}, issn = {1664-3224}, mesh = {Humans ; *SARS-CoV-2/immunology/genetics ; *COVID-19/immunology/virology ; Host-Pathogen Interactions/immunology ; Interferon Type I/immunology/metabolism ; Animals ; *Viral Regulatory and Accessory Proteins/immunology/genetics/metabolism ; Viral Proteins/immunology ; }, abstract = {SARS-CoV-2 accessory proteins (APs), particularly ORF3a and ORF9b, have emerged as key modulators of host-pathogen interaction and potential contributors to long COVID. Of the 13 predicted APs, only nine are expressed during infection - termed Infection-related APs - while the remaining are classified as Putative APs. Despite this distinction, extensive gene overlap among APs underscores the remarkable adaptability of SARS-CoV-2 viral genome. This review delves into the diverse roles of the original Wuhan APs and their Omicron counterparts in shaping host immunity, with an emphasis on their ability to suppress type I interferon (IFN-I) signalling, modulate cellular metabolism, and trigger inflammatory/apoptotic pathways. By integrating immunopathological insights with evolutionary dynamics and structural perspectives, this review provides a comprehensive understanding of the mechanism underlying Omicron's reduced pathogenicity and highlights promising, yet unexplored, therapeutic targets within the SARS-CoV-2 accessory proteome.}, }
@article {pmid41404772, year = {2025}, author = {Van Patten, R and Keatley, E}, title = {Cognitive rehabilitation for functional neurological disorder.}, journal = {CNS spectrums}, volume = {31}, number = {1}, pages = {e1}, pmid = {41404772}, issn = {2165-6509}, mesh = {Humans ; *Nervous System Diseases/rehabilitation/psychology/complications ; *Conversion Disorder/rehabilitation/psychology ; Cognitive Dysfunction/rehabilitation ; *Cognitive Behavioral Therapy/methods ; Cognitive Training ; }, abstract = {Cognitive problems represent one of the most common symptom dimensions in functional neurological disorder (FND; >80% of patients) and are frequently associated with distress, disability, and difficulties engaging in evidence-based treatments such as psychotherapy. Cognitive difficulties occur across the FND subtypes (eg, seizures, movement disorders, dizziness) but are largely underrecognized and undertreated by healthcare providers. That is, although a variety of interventions are available for primary functional symptoms and mental health comorbidities, there have not been any systematic efforts to date to specifically target cognitive functioning in FND, leaving an important gap in the literature.Cognitive rehabilitation is a flexible approach utilizing diverse techniques aimed at improving cognition and enhancing functional independence in people with neuropsychiatric disorders. Cognitive rehabilitation can have positive impacts (moderate effect sizes) on cognition and everyday functioning across a variety of conditions, including traumatic brain injury, mild cognitive impairment, long COVID, PTSD, and others. Given the transdiagnostic clinical utility of cognitive rehabilitation, it has potential for benefit in many patients with FND if adapted and applied appropriately.In this review, we highlight the utility of cognitive rehabilitation for FND, with a focus on clinically actionable advice and guidance. We describe fundamental principles of cognitive rehabilitation, evidence for its efficacy and effectiveness across neuropsychiatric disorders, and methods for avoiding potential pitfalls when applying it in FND. We then discuss a Case Vignette in order to emphasize the application of cognitive rehabilitation principles in an individual patient. We conclude with future directions for research and clinical care.}, }
@article {pmid41407484, year = {2025}, author = {Wilson, JC and Liu, KY and Mittelman, E and Bareke, P and Shleifer, E and Howard, R}, title = {Brain fog with long covid and chemotherapy: systematic review and meta-analysis.}, journal = {BMJ mental health}, volume = {28}, number = {1}, pages = {}, pmid = {41407484}, issn = {2755-9734}, mesh = {Humans ; *COVID-19/complications/psychology ; *Antineoplastic Agents/adverse effects ; *Neoplasms/drug therapy ; SARS-CoV-2 ; *Cognitive Dysfunction/etiology ; }, abstract = {QUESTION: What are the cognitive, functional and affective characteristics of brain fog in individuals with long covid and following chemotherapy, and how are these features assessed across studies?<br><br>STUDY SELECTION AND ANALYSIS: In March 2024, we conducted a systematic review and meta-analysis of peer-reviewed studies assessing cognition, function or mood in adults (&#x2265;18 years) with brain fog after COVID-19 or chemotherapy. PubMed, Embase and Web of Science were searched systematically according to eligibility criteria to March 2024, with an update in May 2025. Random-effects meta-analyses using the 'dmetar' package (V.0.0.9000) in R V.4.3.1 were performed for studies comparing individuals with and without brain fog. Bias was assessed using the National Institutes of Health Study Quality Assessment Tools.<br><br>FINDINGS: Of 3077 records screened, 65 studies met inclusion criteria: 40 investigated brain fog in long covid and 25 in chemotherapy populations. Considerable variation in assessment tools was observed. Montreal Cognitive Assessment was the most common cognitive test in long covid studies; Functional Assessment of Cancer Therapy-Cognitive Function was most used in chemotherapy studies. Nine long covid studies were eligible for meta-analysis. Compared with controls, individuals with brain fog had significantly lower cognitive performance (Hedge's g=-0.63, 95%&#x2009;CI -1.15 to -0.12), higher fatigue (Hedge's g=2.64, 95%&#x2009;CI 0.41 to 4.86) and more depressive symptoms (Hedge's g=1.48, 95%&#x2009;CI 0.40 to 2.55). Heterogeneity was high (I[2]>70%). No chemotherapy studies were appropriate for meta-analysis, preventing direct comparison of brain fog features between long covid and chemotherapy groups.<br><br>CONCLUSIONS: Brain fog in long covid and chemotherapy populations is associated with cognitive complaints, fatigue and mood disturbance, though assessment methods differ widely. To improve comparability and clinical understanding, we propose adoption of consistent tools and definitions in future studies. This will be a crucial step in generating findings that can be meaningfully compared across populations.<br><br>PROSPERO REGISTRATION NUMBER: CRD42024520549.}, }
@article {pmid41407606, year = {2026}, author = {Ouksel, H}, title = {[Long covid pulmonary rehabilitation].}, journal = {Revue des maladies respiratoires}, volume = {43}, number = {1}, pages = {49-56}, doi = {10.1016/j.rmr.2025.12.001}, pmid = {41407606}, issn = {1776-2588}, mesh = {Humans ; *COVID-19/rehabilitation/complications/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Patient Education as Topic ; Respiratory Therapy/methods ; Pandemics ; Exercise Therapy/methods ; }, abstract = {While the SARS-CoV-2 pandemic has left a lasting impression, the long-term effects of this virus, such as persistent symptoms or long COVID, remain unclear. However, recommendations from learned societies for improving these symptoms exist and are being applied by a number of respiratory rehabilitation centers. In this paper, we provide a summary of the specificities of long COVID care in the context of respiratory rehabilitation, particularly as regards respiratory symptoms, fatigue, cognitive disorders, and cardiovascular symptoms and, more specifically, vegetative dysautonomia. The key elements of support are Therapeutic Patient Education (TPE) and activity management and fractionated exercise (PACING). While the effects of respiratory rehabilitation are highly promising, with potential improvement in symptoms and exercise capacity, the level of evidence remains low to moderate. Structured and coordinated multidisciplinary work is of paramount importance as a means of providing for these individuals the best possible support on their road to recovery. Further studies are needed to improve the level of evidence on the effectiveness of rehabilitation in cases of long COVID.}, }
@article {pmid41415584, year = {2025}, author = {Kvandova, M and Balis, P and Kalocayova, B and Vlkovicova, J and Dobrodenkova, S and Puzserova, A}, title = {Cardiovascular damage and comorbidities related to long COVID: pathomechanisms, prevention, and therapy.}, journal = {Frontiers in cardiovascular medicine}, volume = {12}, number = {}, pages = {1671951}, pmid = {41415584}, issn = {2297-055X}, abstract = {Long COVID (LC) is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-associated chronic condition and is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems, including cardiovascular. Extensive literature supports an association between SARS-CoV-2 infection and cardiovascular complications and increased cardiovascular risk after infection. The cardiovascular sequelae after SARS-CoV-2 infection have not yet been comprehensively characterized. A growing body of evidence suggests that endothelial dysfunction is a central mechanism in COVID-19 and has also been identified as a key pathogenic mechanism in LC. Although considerable progress has been made in characterizing the epidemiology, clinical course, and biology of LC, many questions remain unanswered. The incomplete understanding of the pathomechanisms of LC has hampered the development of targeted therapies to date. Further research and data are needed to develop effective therapeutic and preventive tools. Based on current literature this review aims to provide an up-to-date overview of the pathomechanisms affecting the cardiovascular system and the potential role of selected micronutrients, vitamins and minerals, and flavonoids as preventive and therapeutic strategies in LC.}, }
@article {pmid41421320, year = {2026}, author = {Soares, L and Davis, H and Spier, E and Walker, T and Davenport, T and Putrino, D and Peluso, M and Vogel, JM}, title = {Recommended long COVID outcome measures and their implications for clinical trial design, with a focus on post-exertional malaise.}, journal = {EBioMedicine}, volume = {123}, number = {}, pages = {106083}, pmid = {41421320}, issn = {2352-3964}, mesh = {Humans ; *COVID-19/complications/therapy ; *Clinical Trials as Topic ; SARS-CoV-2 ; *Research Design ; COVID-19 Drug Treatment ; Treatment Outcome ; Outcome Assessment, Health Care ; }, abstract = {Long COVID has created a worldwide public health crisis and has no approved treatments or validated biomarkers. We summarize the current challenges and considerations of outcome selection in Long COVID trials, along with recommendations for current trial design and future endpoint validation, with a focus on post-exertional malaise (PEM). We make five overarching recommendations for Long COVID clinical trials: 1) thorough characterisation of baseline disease; 2) collection of longitudinal data; 3) design of a placebo arm to enable comparison of treatment effect relative to the disease natural history; 4) accounting for, and when feasible, measuring PEM; 5) balancing severity, duration, and relevant phenotypes across trial arms and within subgroups to be analysed. We present a list of outcomes that may be considered for Long COVID clinical trials, with a focus on PEM. Crucially, the field of Long COVID clinical trials urgently needs funding and research effort investment to develop and validate outcomes concomitantly with clinical trial research.}, }
@article {pmid41425584, year = {2025}, author = {Ruiz-Pablos, M and Paiva, B and Zabaleta, A}, title = {The origin of autoimmune diseases: is there a role for ancestral HLA-II haplotypes in immune hyperactivity.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1710571}, pmid = {41425584}, issn = {1664-3224}, mesh = {Humans ; *Autoimmune Diseases/immunology/genetics/etiology ; *Haplotypes ; Genetic Predisposition to Disease ; Autoimmunity ; *Histocompatibility Antigens Class II/genetics/immunology ; Animals ; }, abstract = {The prevalence of autoimmune diseases in contemporary human populations poses a challenge for both medicine and evolutionary biology. This review explores how the ancestral human leukocyte antigen class II (HLA-II) haplotypes DR2-DQ6, DR4-DQ8 and DR3-DQ2 could play a central role in susceptibility to these diseases. We propose that these haplotypes, selected in historical contexts of high infectious pressure, may have been maintained because of their ability to elicit strong T-cell responses against pathogens; however, that antigenic promiscuity may be associated with an increased tendency toward immune hyperreactivity in modern environments. This hyperreactivity, involving proinflammatory cytokines including interferon-gamma (IFN-γ), could contribute to the breakdown of tolerance and the emergence of autoimmunity and related clinical phenomena (e.g., Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome and post-vaccination syndromes), although the evidence for the latter remains limited. Finally, we discuss how chronic infections, immunotherapies, vaccination, obesity and chronic physical stressors may exacerbate this susceptibility and consider the therapeutic implications of integrating HLA-II profiling into clinical practice.}, }
@article {pmid41428252, year = {2026}, author = {Yet, M and Teo, HS and Kwa, H and Yeo, J and Wang, SSY}, title = {Long COVID: a review of mechanisms and treatment modalities.}, journal = {Inflammopharmacology}, volume = {34}, number = {2}, pages = {1111-1121}, pmid = {41428252}, issn = {1568-5608}, mesh = {Humans ; *COVID-19/therapy/complications/immunology/physiopathology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; COVID-19 Drug Treatment ; }, abstract = {Long COVID is defined by the World Health Organisation (WHO) as a condition arising within 3 months of an acute COVID infection with symptoms lasting for a minimum of 2 weeks. However, this syndrome is poorly understood and has been recorded to include many systemic manifestations, including neurological, respiratory, cardiovascular, gastrointestinal, dermatological, psychosocial, and metabolic systems. Constitutional symptoms also include fatigue, insomnia, body weight changes, poor attention span, hair loss, sexual dysfunction, myalgia, and joint pain, with fatigue being the most common. Given the various proposed mechanisms published in the literature, the postulated mechanisms and pathways are discussed in this paper to contribute to the understanding of defining this syndrome. In this review article, the authors first explored how endothelial damage from COVID infection can lead to a hypercoagulable state. In addition, the effects of an insufficient initial immune response can lead to viral persistence alongside a potentially prolonged hyperactive immune response that includes a cytokine storm and mast cell activation syndrome. Furthermore, the viral persistence can be exacerbated by antibody-dependent enhancement or complicated by molecular mimicry. Current pharmacological therapies are explored and evaluated to investigate their efficacy in addressing this complex and chronic presentation. This review article has been written after an extensive literature review to increase the understanding and awareness regarding Long COVID, as a sincere effort to direct further research for an effective diagnosis and management.}, }
@article {pmid41438927, year = {2025}, author = {Cheng, AL and Barker, R and von Nordheim, D and McQueen, A}, title = {Long COVID: What is it? Who has it? What Are Treatment Resources in Missouri?.}, journal = {Missouri medicine}, volume = {122}, number = {6}, pages = {488-494}, pmid = {41438927}, issn = {0026-6620}, mesh = {Humans ; Missouri/epidemiology ; *COVID-19/epidemiology/complications/therapy ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {As we pass the five-year mark since the COVID-19 pandemic hit, the prevalence of persistent (and often disabling) symptoms from the SARS-CoV-2 virus is estimated to be on par with the prevalence of heart disease. Yet, these Long COVID symptoms can masquerade as other conditions and/or normal aging, so it is believed that Long COVID is under-diagnosed and, as a result, under-treated. Although there is not yet a true cure for Long COVID, many patients benefit substantially from rehabilitation strategies, medications, and social support resources that are available in Missouri. The purpose of this article is to review the definition and epidemiology of Long COVID, provide practical guidance for Long COVID assessment and management especially in the primary care setting, and increase awareness of regional resources for people in Missouri who are living with Long COVID and for the clinicians who are caring for them.}, }
@article {pmid41439932, year = {2025}, author = {Zuñiga-Jimenez, CT and Rojas-Esguerra, DF and Muñoz-Martinez, AP and Mendoza-Guzman, DC and Daza-Arana, JE}, title = {Musculoskeletal Sequelae of Post-COVID-19 Syndrome: A Systematic Review.}, journal = {Diseases (Basel, Switzerland)}, volume = {13}, number = {12}, pages = {}, pmid = {41439932}, issn = {2079-9721}, abstract = {Background/Objectives: COVID-19 infection is a respiratory illness that affects multiple body systems, including the musculoskeletal system. In August 2024, Colombia reported 6 million infections and a 2.2% mortality rate related to COVID-19. Post-COVID-19 syndrome (PCS) is a chronic condition occurring after the acute infection, typically characterized by fatigue, weakness, pain, and sarcopenia, impacting the patient's quality of life (QoL). This systematic review aimed to identify musculoskeletal sequelae, including peripheral muscle strength, fatigue, and QoL, in patients with PCS. Methods: We searched the PubMed, Scopus, and Web of Science databases for cross-sectional, case-control, and cohort studies focusing on musculoskeletal sequelae in patients with COVID-19 infection published between 2020 and 2025. Study quality and risk of bias were assessed using the MINORS and the ROBINS-E scales, respectively. Results: Thirteen studies (n = 5657 patients) met the eligibility criteria. Seventy-six percent of studies indicated muscle weakness as the most common sequela, primarily in older adults and individuals with comorbidities (obesity, diabetes, and chronic obstructive pulmonary disease). General fatigue (reported in 76% of the studies) significantly influenced patients' daily lives, whereas 90% of patients reported some level of deterioration in their QoL, primarily regarding mental health, bodily pain, and physical performance. Conclusions: Patients with PCS who required mechanical ventilation showed reduced muscle strength and poor physical performance, especially older adults. Inactive individuals had worse musculoskeletal sequelae, while physical activity was associated with better strength levels. Although QoL improved after 12 months, the combination of aerobic exercise with adequate nutrition is essential to promote muscle recovery, reduce fatigue, and improve overall functional capacity in post-COVID-19 patients.}, }
@article {pmid41440526, year = {2025}, author = {László, SA and Ianoși, ES and Văsieșiu, AM and Szathmáry, M and Ianoși, MB and Rachiș, DL and Nistor, G and Jimborean, G}, title = {COVID-19 and Lung Cancer Interactions: A Literature Review.}, journal = {Medical sciences (Basel, Switzerland)}, volume = {13}, number = {4}, pages = {}, pmid = {41440526}, issn = {2076-3271}, mesh = {Humans ; *COVID-19/epidemiology/complications/virology ; *Lung Neoplasms/epidemiology/diagnosis/virology ; SARS-CoV-2 ; Incidence ; Pandemics ; }, abstract = {This review aims to discuss the apparent reduction in pulmonary cancer incidence in the general population during and shortly after the COVID-19 pandemic from a biological and pathophysiological mechanistic point of view. While the epidemiological evidence points to a disruption in the early- and mid-stage diagnostic process, which causes a shift to late-stage lung cancer discovery with no impact on its actual prevalence, an alternative hypothesis based on the intersection of viral and cancer biology could have a real effect on lung carcinogenesis as an independent phenomenon. By weaving together population-level trends, mechanistic insights, and translational oncology, we discuss whether the pandemic-associated decline in lung cancer diagnoses reflects primarily a temporary diagnostic artifact or whether it also reveals biologically relevant intersections between SARS-CoV-2 and pulmonary oncogenesis. The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has exerted profound and multifaceted effects on global healthcare systems, altering patterns of disease detection, management, and outcomes across nearly all medical disciplines. These disruptions generated what has been termed a "diagnostic deficit", producing a backlog of undetected cancers that have only partially been recovered in subsequent years. This phenomenon, sometimes described as a "COVID-19 debt" in oncology, is thought to contribute to excess late-stage diagnoses and potentially worse medium-term survival outcomes. Beyond the disruption of medical systems, the pandemic also raised a more speculative but biologically intriguing question: could SARS-CoV-2 infection itself, through direct or indirect mechanisms, influence lung cancer biology? Our review aims to critically synthesize the evidence across seven domains to address this dual hypothesis. (1) We examine the observed effects of the pandemic on cancer incidence, highlighting global registry and health-system data; (2) we review SARS-CoV-2 infection biology, including viral entry, replication, protein functions, and treatment implications; (3) we summarize the pathogenesis of lung cancer; (4) we explore the role of immune checkpoints in tumor immune evasion, followed by (5) analyses of immune dysregulation in acute infection and (6) in long COVID; and (7) finally, we evaluate proposed oncogenic mechanisms of SARS-CoV-2, integrating molecular virology with cancer immunology. We conclude that the "diagnostic deficit" phenomenon was a reality during and immediately post-pandemic. However, a definitive answer to the questions related to the impact of the infection as an independent phenomenon would require advanced research information covering the biology of the viral infection and lung cancer oncogenesis: processes that are not currently implemented in routine clinical laboratory investigations.}, }
@article {pmid41444262, year = {2025}, author = {Wilson, JE and Gurdasani, D and Helbok, R and Ozturk, S and Fraser, DD and Filipović, SR and Peluso, MJ and Iwasaki, A and Yasuda, CL and Bocci, T and Priori, A and Altmann, D and Alwan, NA and Wesley Ely, E}, title = {COVID-19-associated neurological and psychological manifestations.}, journal = {Nature reviews. Disease primers}, volume = {11}, number = {1}, pages = {91}, pmid = {41444262}, issn = {2056-676X}, mesh = {Humans ; *COVID-19/complications/psychology/physiopathology/epidemiology ; *Nervous System Diseases/etiology/virology ; *Mental Disorders/etiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Anxiety/etiology ; Depression/etiology ; }, abstract = {Long COVID is an infection-associated chronic condition that typically occurs within 3 months of acute COVID-19 infection in which symptoms are intermittently or continuously present for at least 3 months. Long COVID is estimated to affect between 80 and 400 million people globally, with an incidence of 5-20% in the community and up to 50% among hospitalized patients following acute SARS-CoV-2 infection. Common neuropsychiatric and mental health symptoms of long COVID include memory deficits, executive dysfunction, anxiety, depression, recurring headaches, sleep disturbances, neuropathies, problems with taste and smell, and dizziness that accompanies erratic heart rates and severe post-exertional malaise. Underlying pathophysiological mechanisms includes SARS-CoV-2 viral persistence, herpesvirus reactivation, microbiota dysbiosis, autoimmunity, clotting and endothelial abnormalities, and chronic immune activation. Owing to the variability in the clinical presentation, management must be tailored based on a patient's presenting symptoms.}, }
@article {pmid41462476, year = {2025}, author = {Tamim El Jarkass, T and Nandakumar, S and Skidmore, B and Pinto, AD and Hosseini, B}, title = {Understanding how social determinants of health shape Long COVID outcomes: a rapid review of evidence.}, journal = {Archives of public health = Archives belges de sante publique}, volume = {83}, number = {1}, pages = {308}, pmid = {41462476}, issn = {0778-7367}, support = {Grant #FRN 183092 and PPE 190332/CAPMC/CIHR/Canada ; }, abstract = {BACKGROUND: Long COVID affects over 65 million people worldwide, yet the impact of social determinants of health (SDoH), such as socioeconomic status, race/ethnicity, education, occupation, and geography, remains poorly understood. To evaluate the association between SDoH and the risk and severity of Long COVID.<br><br>METHODS: A rapid review of observational studies was conducted using MEDLINE, Embase, and Web of Science (up to September 29, 2024). Studies reporting original data on SDoH and Long COVID outcomes were included. Data were extracted on study characteristics, population demographics, Long COVID definitions, and SDoH-related findings. Study quality was assessed using the Newcastle-Ottawa Scale.<br><br>RESULTS: Seventy-one studies (43 cohort, 28 cross-sectional) were included. Definitions of Long COVID varied. Commonly studied SDoH included age, sex, race/ethnicity, education, financial security, employment, and geography. Female sex and older age were consistently associated with increased risk and severity of Long COVID. Black and Hispanic individuals were more likely to experience Long COVID. Lower education and financial insecurity were also linked to greater prevalence and symptom burden. Frontline and essential workers were found to be at increased risk. Geographic disparities were evident but varied across rural and urban residence.<br><br>CONCLUSIONS: SDoH play a key role in shaping Long COVID outcomes. Addressing these disparities requires targeted public health efforts and standardized case definitions.}, }
@article {pmid41462744, year = {2025}, author = {Fronticelli Baldelli, G and Buonsenso, D}, title = {Proposed Mechanistic Axis of Infections and mTOR Hyperactivation: A Multidisciplinary Review of Immune, Rheumatologic, and Psychiatric Links.}, journal = {Children (Basel, Switzerland)}, volume = {12}, number = {12}, pages = {}, pmid = {41462744}, issn = {2227-9067}, abstract = {Early-life infections can produce durable changes in immune function and behavior. We propose a mechanistic hypothesis positioning the mechanistic target of rapamycin (mTOR) as the link between peripheral inflammation and central nervous system dysfunction in pediatric post-infectious syndromes. Based on clinical, translational, and experimental literature, we outline a stepwise pathway. First, sustained mTOR activation skews T-cell and macrophage differentiation toward pro-inflammatory and autoimmune states. Second, endothelial mTOR signaling weakens tight junctions and increases vesicular transport, compromising blood-brain barrier integrity. Third, cytokines and sometimes autoreactive cells enter the brain and engage mTOR in microglia and neurons, driving neuroinflammation, impaired synaptic maintenance and plasticity, and neurotransmitter disruption. This framework accounts for features observed in Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and pediatric acute neuropsychiatry syndrome (PANS/PANDAS) and yields testable predictions on pathway activity and barrier permeability. It also motivates targeted interventions that modulate mTOR-related processes in immune and endothelial compartments and within neural circuits in children. So, this article aims to outline a mechanistic framework linking infection-driven mTOR activation to post-infectious neuropsychiatric syndromes.}, }
@article {pmid41462874, year = {2025}, author = {Halas, RG and Berceanu Vaduva, DM and Radulescu, M and Bredicean, AC and Mateescu, DM and Toma, AO and Cotet, IG and Guse, CE and Marginean, A and Margan, MM and Lazureanu, VE}, title = {Long COVID Prevalence and Risk Factors: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.}, journal = {Biomedicines}, volume = {13}, number = {12}, pages = {}, pmid = {41462874}, issn = {2227-9059}, abstract = {Background: Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), affects millions globally, with persistent symptoms impacting quality of life. This meta-analysis synthesizes prospective cohort studies to estimate the prevalence of Long COVID symptoms and identify risk factors. Methods: We systematically searched PubMed for prospective cohort studies (2020-2025) on Long COVID, focusing on prevalence and risk factors. Studies with ≥100 participants and follow-up ≥3 months were included. Data were extracted on symptom prevalence (e.g., fatigue, dyspnoea) and risk factors (e.g., sex, hospitalization). Random-effects models were used to pool prevalence and odds ratios (OR). Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). Results: Fourteen prospective studies (n = 168,679) were included. Pooled prevalence of Long COVID was 18.0% (95% CI: 12.5-23.5%, I[2] = 9.8%) among survivors followed for ≥6 months. Fatigue (41.0%, 95% CI: 33.2-49.4%) and dyspnoea (22.5%, 95% CI: 15.6-29.8%) were the most common symptoms. Female sex (OR = 1.52, 95% CI: 1.25-1.92) and prior hospitalization (OR = 2.35, 95% CI: 1.98-2.90) were significant risk factors. High heterogeneity (I[2] > 90%) was noted. Conclusions: Long COVID affects over one-fifth of SARS-CoV-2 survivors, with fatigue and dyspnoea persisting in many. Female sex and severe acute infection increase risk. Standardized definitions and longer follow-up are needed.}, }
@article {pmid41463036, year = {2025}, author = {Andriankaja, OM and Whiteheart, S and Mattos, MBA}, title = {Biological Plausibility Between Long-COVID and Periodontal Disease Development or Progression.}, journal = {Biomedicines}, volume = {13}, number = {12}, pages = {}, pmid = {41463036}, issn = {2227-9059}, abstract = {Background: Long COVID (LC) is a multi-system disorder with persistent symptoms following SARS-CoV-2 infection. The presence of SARS-CoV-2 in the oral cavity and periodontium raises questions about its potential impact on periodontal health. Methods: A comprehensive literature search was conducted in PubMed using terms related to LC (e.g., "long-COVID," "post-acute sequelae of SARS-CoV-2 infection," "PASC," "post-COVID-19," "long-haul COVID") and oral/periodontal diseases (e.g., "periodontal disease," "periodontitis," "gingiva," "oral disease," "dental"), filtered for English-language full-text articles published from 2019 to 2024. The search yielded 260 articles, which were supplemented with targeted searches on pathogenesis, immune mechanisms, microbiome alterations, and clinical outcomes, resulting in approximately 248 studies included in this review. Results: LC exhibits systemic immunoinflammatory dysregulation, including neutrophil activation, elevated pro-inflammatory cytokines, and complement activation, overlapping with mechanisms implicated in periodontitis. LC also leads to gastrointestinal and pulmonary dysbiosis, with potential effects on oral microbial communities. Gingival epithelium and periodontal ligament cells express ACE2, which is increased in periodontitis, facilitating viral entry. LC has been associated with reactivation of herpesviruses, such as Epstein-Barr virus, which are linked to autoimmune disorders and periodontitis. Conclusions: LC may act as a systemic risk factor for periodontitis. This review provides the theoretical foundation for the interactions between LC and oral health and highlights priorities for future epidemiologic and mechanistic research to better understand these relationships.}, }
@article {pmid41464319, year = {2025}, author = {Raycheva, R and Kostadinov, K and Rangelova, V and Kevorkyan, A}, title = {Economic Analyses of COVID-19 Interventions: A Narrative Review of Global Evidence.}, journal = {Healthcare (Basel, Switzerland)}, volume = {13}, number = {24}, pages = {}, pmid = {41464319}, issn = {2227-9032}, abstract = {Background/Objectives: The coronavirus disease 2019 (COVID-19) pandemic imposed an unprecedented global health and economic burden, prompting rapid implementation of diverse public health interventions. This review aimed to synthesize global evidence on the cost-effectiveness of key COVID-19 control strategies, including vaccination, testing, and social distancing and to identify methodological, contextual, and equity-related determinants of their economic value. Methods: A narrative literature review was conducted using peer-reviewed studies published between January 2020 and September 2025 and indexed in PubMed, Scopus, and Web of Science. Eligible studies included economic evaluations and modeling analyses addressing COVID-19 interventions in healthcare, community, or educational settings. Data on costs, outcomes, and methodological features were extracted and synthesized descriptively. Results: Across 74 included studies, vaccination-particularly with messenger RNA (mRNA) platforms-emerged as the most cost-effective intervention across all settings, often cost-saving among high-risk populations. Combined or layered strategies integrating vaccination, testing, and selective social distancing consistently outperformed single interventions in both health and economic outcomes. Early and targeted implementation yielded the highest cost-effectiveness by preventing exponential transmission and healthcare overload. However, heterogeneity in modeling assumptions, analytic perspectives, and outcome measures limited comparability. Few studies applied extended or distributional cost-effectiveness frameworks to address equity, while indirect and long-term effects such as productivity losses and "long COVID" were frequently omitted. Conclusions: COVID-19 interventions are most efficient when early, targeted, and adaptive to local epidemiologic conditions. Integrating equity, methodological consistency, and broader societal impacts into future evaluations will strengthen evidence-based, economically sustainable pandemic preparedness and response strategies.}, }
@article {pmid41480252, year = {2025}, author = {Salas, RL and la Asunción, M and Vásquez-Soto, C and Orta-Visbal, K and Serrano, V and Villarreal, E and Sepúlveda, S and Montalvo, MJ and Nuñez, JA and Borja, J}, title = {Scoping review of the emerging definition of long COVID: implications for future research and clinical practice.}, journal = {Revista de salud publica (Bogota, Colombia)}, volume = {27}, number = {6}, pages = {122127}, pmid = {41480252}, issn = {2539-3596}, mesh = {Humans ; *COVID-19/complications/diagnosis ; *Terminology as Topic ; Biomedical Research ; SARS-CoV-2 ; }, abstract = {INTRODUCTION: Long COVID, Post-COVID19 syndrome and prolonged COVID-19, are concepts classified as the set of signs and symptoms that persist after an acute episode of COVID-19 disease.<br><br>OBJECTIVE: To describe what definitions have been published for the term "long COVID".<br><br>METHODS: The PRISMA ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) was used as a base for a scoping review, as suggested by Joanna Briggs Institute. A search of databases, Medline via PubMed, Embase, SciELO and The Cochrane Library was undertaken. The data registry and synthesis of the results was carried out independently by two reviewers.<br><br>RESULTS: Following removal of duplicates, 896 articles were retrieved of which 91 met the eligibility principles and 51 of which included a definition. At least four characteristics of the definitions were identified: time or term, organs affected, symptoms and clinical manifestations.<br><br>CONCLUSIONS: The review identified many concepts and definitions of "long COVID". These findings show that there is lack of consensus on the definition of long COVID-19.}, }
@article {pmid41486438, year = {2025}, author = {Seo, JW and Seo, YB and Kim, SE and Kim, Y and Kim, EJ and Kim, T and Kim, T and Lee, SH and Lee, E and Lee, J and Jeong, YH and Jung, YH and Choi, YJ and Song, JY}, title = {Clinical Practice Guideline Recommendations for Post-Acute Sequelae of COVID-19.}, journal = {Infection &amp; chemotherapy}, volume = {57}, number = {4}, pages = {478-521}, pmid = {41486438}, issn = {2093-2340}, support = {HD22C2045//Korea Health Industry Development Institute/Republic of Korea ; }, abstract = {The guidelines presented herewith are based on the "Clinical Practice Guideline Recommendations for Post-Acute Sequelae of COVID-19 (PASC)" published in Infection &amp; Chemotherapy in March 2024; these guidelines have been refined by incorporating the most recent Korean and international research findings and clinical evidence published since then. In the context of patients experiencing various physical and mental symptoms that persist long after the acute phase of coronavirus disease 2019 (COVID-19) infection, the diagnosis and management of PASC has emerged as a novel public health challenge. These guidelines are intended to provide standardized diagnostic and management recommendations applicable to the Korean healthcare setting and were developed through a comprehensive review of existing guidelines from organizations such as the World Health Organization, the United States National Institutes of Health, the United Kingdom National Institute for Health and Care Excellence, and the European Society of Clinical Microbiology and Infectious Diseases, along with the latest meta-analyses and Korean cohort studies. PASC is defined as the persistent presence of symptoms and signs lasting more than 3 months after COVID-19 diagnosis for which the symptoms cannot be explained by alternative diagnoses. The revised guidelines emphasize the importance of integrated management for patients with PASC, including a multidisciplinary approach considering risk groups, symptom-specific assessment, and rehabilitation and psychological interventions, based on a total of 32 key questions. This revision reflects rapidly evolving research trends regarding the long-term effects of COVID-19 and is expected to serve as an evidence-based standard guideline for future patient care, clinical research, and health policy development in Korea.}, }
@article {pmid41488148, year = {2025}, author = {Shitaye, G and Getie, M and Mekonnen, Z and D'Abrosca, G and Fattorusso, R and Isernia, C and Amuamuta, A and Malgieri, G}, title = {Molecular analysis of long COVID and new-onset diabetes mellitus: pathobiological relationships and current mechanistic views.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1737894}, pmid = {41488148}, issn = {1664-2392}, mesh = {Humans ; *COVID-19/complications/metabolism/pathology/epidemiology ; *SARS-CoV-2 ; *Diabetes Mellitus, Type 2/epidemiology/etiology/virology/metabolism/pathology ; *Diabetes Mellitus, Type 1/epidemiology/metabolism/etiology/virology ; Renin-Angiotensin System ; Post-Acute COVID-19 Syndrome ; Insulin Resistance ; }, abstract = {Long COVID, or post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC), refers to a range of persistent health effects associated with SARS-CoV-2 infection. Long COVID is a complex, multisystem disorder that can affect nearly every organ system and is strongly linked with the incidence of diabetes and other chronic conditions. Increasing evidence also connects persistent SARS-CoV-2 infection with the development of new-onset diabetes and other metabolic disorders. In this review, we assess the current evidence and discuss the incidence of new-onset diabetes, along with the pathobiological mechanisms by which SARS-CoV-2 may contribute to the progression of both new-onset type 1 and type 2 diabetes mellitus (T1DM and T2DM). We summarize the latest understanding of the molecular and cellular mechanisms underlying SARS-CoV-2-associated new-onset diabetes. Potential mechanisms include direct damage to pancreatic β-cells, inflammation, insulin resistance, and autoimmune responses. Dysregulation of the ACE2/renin-angiotensin system (RAS) pathway has been linked to multiple inter-organ pathologies, and increased inflammatory cytokines together with dysregulation of interferon regulatory factors (IRFs)-such as overexpression of IRF1-appear to represent key mechanistic links to widespread tissue damage and metabolic alterations. Moreover, the presence of viral RNA or viral RNA fragments may directly damage pancreatic islets, contributing to insulin resistance and β-cell dysfunction that, in turn, may promote the development of new-onset diabetes. In light of these findings, this review further examines evidence supporting the persistence of SARS-CoV-2 RNA in PASC reservoir tissues, including the pancreas, and its potential association with the development of new-onset diabetes mellitus.}, }
@article {pmid41494490, year = {2026}, author = {Messina, A and Bella, F and Maccarone, G and Avincola, G and Signorelli, MS}, title = {Astrocyte-mediated hippocampal damage in the pathogenesis of dysexecutive syndrome following COVID-19: A narrative review.}, journal = {Journal of psychiatric research}, volume = {194}, number = {}, pages = {164-173}, doi = {10.1016/j.jpsychires.2026.01.007}, pmid = {41494490}, issn = {1879-1379}, mesh = {Humans ; *COVID-19/complications/immunology/pathology ; *Astrocytes/pathology/immunology/metabolism ; *Hippocampus/pathology/physiopathology/metabolism/virology/immunology ; SARS-CoV-2 ; *Neuroinflammatory Diseases ; *Cognitive Dysfunction/etiology ; *Executive Function/physiology ; }, abstract = {SARS-CoV-2 infection has been implicated in hippocampal damage, contributing to the pathogenesis of dysexecutive syndrome observed in post-COVID-19 patients. Given the growing prevalence of long-COVID worldwide, understanding how SARS-CoV-2 affects hippocampal structure and function has become an urgent scientific and clinical priority. The hippocampus-crucial for memory, emotional regulation, and executive functioning-is especially susceptible to viral-driven neuroinflammatory cascades. SARS-CoV-2 triggers astrocyte and microglia activation, disrupts blood-brain barrier integrity, and induces cytokine-mediated neurotoxicity, ultimately impairing neuroplasticity and neurogenesis. These mechanisms converge to produce cognitive and affective disturbances-most notably fatigue, apathy, low mood, and executive dysfunction-that typify dysexecutive syndrome in long-COVID. This review synthesizes current evidence from clinical and experimental studies, integrating findings on viral neurotropism, hippocampal hypometabolism, and astrocyte-mediated neurodegeneration. Distinctions between depressive symptoms driven by neuroinflammation and classical depressive disorders are clarified to improve diagnostic accuracy and guide personalized treatment. Emerging data on the neuroprotective role of COVID-19 vaccination-particularly its capacity to modulate microglial activation and support hippocampal neurogenesis-are also examined. Overall, the findings underscore the need for targeted therapeutic strategies aimed at modulating neuroinflammation and supporting hippocampal plasticity, including cognitive rehabilitation approaches. Longitudinal studies are essential to elucidate the enduring impact of SARS-CoV-2 on hippocampal function and to inform effective clinical interventions.}, }
@article {pmid41496808, year = {2025}, author = {Woods, JA and Hutchinson, NT and Powers, SK and Gomez-Cabrera, MC and Radak, Z and Leeuwenburgh, C and Cacciatore, S and Marzetti, E and Zhang, T and Garza, R and Sidebottom, C and Anderson, E and Durstine, JL and Sun, J and Ji, LL}, title = {Physical activity during COVID-19 pandemic: A 5-year retrospect.}, journal = {Sports medicine and health science}, volume = {7}, number = {6}, pages = {405-418}, pmid = {41496808}, issn = {2666-3376}, abstract = {The purpose of this article is to provide a follow-up review of the impact of the SARS-CoV-2 Disease or Coronavirus Disease 2019 (COVID-19) pandemic on human health and the role of physical activity (PA) during the 5-year pandemic. We aim to cover the immune system, the cardiopulmonary system, the musculoskeletal system, and the central nervous system (brain function), particularly among older adults, college students, and individuals with post-acute sequelae of COVID-19 (Long-COVID). The COVID-19 pandemic has given us many lessons, learned from the death of six million lives and tremendous disturbance to human life. First, we need to continue to investigate cellular and molecular mechanisms that mediate various organistic failures resulting from the viral infection. Such investigations are the only way to completely understand the etiology of the diseases and to develop new drugs and vaccines. The molecular pathways that transmit the signals of viral infection to each organ system are different requiring both basic and clinical research. Available evidence suggests that mitochondrial dysfunction, reduced microcirculation and latent immune activation play a major role, eventually impairing cardiovascular tolerance and peripheral bioenergetics. Second, the COVID-19 pandemic has manifested major disturbances to human lifestyles with reduced PA and exercise standing out as a major factor. Conversely, physical inactivity due to social confinement and mental/psychological stresses has been clearly linked to intensified pathogenic symptoms and amplification of adverse effects on multiple physiological systems. If not intervened, this interaction can lead to Long-COVID, a dangerous futile circle to cause systemic failure. Finally, the COVID-19 pandemic has exerted differential impacts on different populations. Thus, the strategy to develop and conduct to cope with the negativity of pandemic needs to be specific, flexible and tailored to fit different patient populations.}, }
@article {pmid41497070, year = {2026}, author = {Obeagu, EI}, title = {Immunomodulatory strategies for managing cytokine storms in chronic COVID: mechanisms, therapeutic targets, and clinical advances.}, journal = {Annals of medicine and surgery (2012)}, volume = {88}, number = {1}, pages = {653-659}, pmid = {41497070}, issn = {2049-0801}, abstract = {Chronic COVID, characterized by persistent symptoms following acute SARS-CoV-2 infection, is increasingly linked to sustained immune dysregulation, particularly cytokine storms that drive chronic inflammation and multi-organ complications. Understanding the mechanisms underlying cytokine dysregulation in chronic COVID is essential for developing effective therapeutic strategies aimed at restoring immune balance and mitigating long-term morbidity. This review critically examines current immunomodulatory strategies for managing cytokine storms in chronic COVID, including corticosteroids, cytokine-specific biologics, Janus kinase inhibitors, and emerging cell-based therapies. Additionally, the role of biomarker-guided precision medicine in personalizing treatment to optimize efficacy and safety is discussed. Challenges such as patient heterogeneity, timing and duration of therapy, and potential adverse effects are also addressed. Future research directions emphasize the need for robust clinical trials, novel therapeutic development, and integrated multidisciplinary care to improve patient outcomes. By tailoring immunomodulatory approaches based on individual immune profiles, it is possible to enhance the management of cytokine-driven inflammation in chronic COVID and advance the field toward more effective, personalized treatments.}, }
@article {pmid41513611, year = {2026}, author = {Nunes, M and Kell, L and Slaghekke, A and Wüst, RC and Fielding, BC and Kell, DB and Pretorius, E}, title = {Virus-induced endothelial senescence as a cause and driving factor for ME/CFS and long COVID: mediated by a dysfunctional immune system.}, journal = {Cell death &amp; disease}, volume = {17}, number = {1}, pages = {16}, pmid = {41513611}, issn = {2041-4889}, support = {NNF20CC0035580//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; }, mesh = {Humans ; *COVID-19/immunology ; *Cellular Senescence ; SARS-CoV-2 ; *Fatigue Syndrome, Chronic/immunology/virology/pathology ; Post-Acute COVID-19 Syndrome ; *Coronavirus Infections/immunology/virology/pathology ; Animals ; *Endothelial Cells/pathology/virology/immunology ; *Betacoronavirus ; *Endothelium, Vascular/immunology/pathology/virology ; *Immune System ; }, abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID are two post-viral diseases, which share many common symptoms and pathophysiological alterations. Yet a mechanistic explanation of disease induction and maintenance is lacking. This hinders the discovery and implementation of biomarkers and treatment options, and ultimately the establishment of effective clinical resolution. Here, we propose that acute viral infection results in (in)direct endothelial dysfunction and senescence, which at the blood-brain barrier, cerebral arteries, gastrointestinal tract, and skeletal muscle can explain symptoms. The endothelial senescence-associated secretory phenotype (SASP) is proinflammatory, pro-oxidative, procoagulant, primed for vasoconstriction, and characterized by impaired regulation of tissue repair, but also leads to dysregulated inflammatory processes. Immune abnormalities in ME/CFS and long COVID can account for the persistence of endothelial senescence long past the acute infection by preventing their clearance, thereby providing a mechanism for the chronic nature of ME/CFS and long COVID. The systemic and tissue-specific effects of endothelial senescence can thus explain the multisystem involvement in and subtypes of ME/CFS and long COVID, including dysregulated blood flow and perfusion deficits. This can occur in all tissues, but especially the brain as evidenced by findings of reduced cerebral blood flow and impaired perfusion of various brain regions, post-exertional malaise (PEM), gastrointestinal disturbances, and fatigue. Paramount to this theory is the affected endothelium, and the bidirectional sustainment of immune abnormalities and endothelial senescence. The recognition of endothelial cell dysfunction and senescence as a core element in the aetiology of both ME/CFS and Long COVID should aid in the establishment of effective biomarkers and treatment regimens.}, }
@article {pmid41516190, year = {2025}, author = {Mcmillan, P and Turner, AJ and Uhal, BD}, title = {The Central Role of Macrophages in Long COVID Pathophysiology.}, journal = {International journal of molecular sciences}, volume = {27}, number = {1}, pages = {}, pmid = {41516190}, issn = {1422-0067}, mesh = {Humans ; *Macrophages/immunology/pathology ; *COVID-19/immunology/physiopathology/pathology/virology ; Post-Acute COVID-19 Syndrome ; Macrophage Activation ; Immunity, Innate ; SARS-CoV-2/immunology ; Epigenesis, Genetic ; Animals ; Spike Glycoprotein, Coronavirus/metabolism ; }, abstract = {This review article attempts to provide a unifying hypothesis to explain the myriad of symptoms and predispositions underlying the development of PASC (Postacute Sequelae of COVID), often referred to as Long COVID. The hypothesis described here proposes that Long COVID is best understood as a disorder of persistent immune dysregulation, with chronic macrophage activation representing the fundamental underlying pathophysiology. Unlike transient post-viral syndromes, Long COVID involves a sustained innate immune response, particularly within monocyte-derived macrophages, driven by persistent spike protein (peripherally in MAIT cells and centrally in Microglial cells), epigenetic imprinting, and gut-related viral reservoirs. These macrophages are not merely activated temporarily but also become epigenetically "trained" into a prolonged inflammatory state, as demonstrated by enduring histone acetylation markers such as H3K27acDNA Reprogramming. It is proposed that recognizing macrophage activation as the central axis of Long COVID pathology offers a framework for personalized risk assessment, targeted intervention, and therapeutic recalibration.}, }
@article {pmid41516301, year = {2025}, author = {Stojanovic, M and Djuric, M and Nenadic, I and Bojic, S and Andrijevic, A and Popovic, A and Pesic, S}, title = {Vascular Complications of Long COVID-From Endothelial Dysfunction to Systemic Thrombosis: A Systematic Review.}, journal = {International journal of molecular sciences}, volume = {27}, number = {1}, pages = {}, pmid = {41516301}, issn = {1422-0067}, mesh = {Humans ; *COVID-19/complications/pathology ; *Thrombosis/etiology/pathology ; *Endothelium, Vascular/physiopathology/pathology ; SARS-CoV-2 ; }, abstract = {Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated not only with respiratory illness but also with profound vascular and coagulation disturbances. Long COVID (LC) is characterized by persistent symptoms such as fatigue, dyspnea, cognitive impairment, and palpitations. Mechanistically, SARS-CoV-2 induces direct endothelial injury, promotes a pro-inflammatory cytokine milieu, and activates platelets, leading to immunothrombosis and impaired fibrinolysis. Consequently, patients exhibit microthrombosis, elevated plasma D-dimer, fibrinogen dysregulation, and persistent hypercoagulability. Clinically, this translates into an increased risk of venous thromboembolism, including deep vein thrombosis and pulmonary embolism, as well as arterial thrombotic events such as myocardial infarction and stroke, which may persist months after acute infection. Understanding the interplay between endothelial injury, inflammation, and coagulation is crucial for risk stratification and the development of preventive and therapeutic strategies. We conducted a systematic narrative review of the literature, including human clinical and mechanistic studies identified through PubMed, Scopus and Web of Science up to 30 September 2025. This review synthesizes current evidence on vascular complications in LC, highlighting endothelial dysfunction as a central pathophysiological nexus linking the acute phase of SARS-CoV-2 infection with chronic LC manifestations.}, }
@article {pmid41519610, year = {2026}, author = {Lau, DH and Fedorowski, A and Raj, SR and Schild, C and Pace, LA and Blitshteyn, S and Raj, V and Boris, JR and Kavi, L and Seeley, MC and Gallagher, C}, title = {Postural Orthostatic Tachycardia Syndrome: A State-of-the-Art Review.}, journal = {Heart, lung &amp; circulation}, volume = {35}, number = {2}, pages = {171-185}, doi = {10.1016/j.hlc.2025.09.004}, pmid = {41519610}, issn = {1444-2892}, mesh = {Humans ; *Postural Orthostatic Tachycardia Syndrome/diagnosis/therapy/physiopathology ; }, abstract = {Postural orthostatic tachycardia syndrome (POTS) is a complex disorder mainly of orthostatic intolerance, often accompanied by a spectrum of symptoms related to autonomic nervous system dysfunction. Although the diagnostic criteria require an orthostatic challenge test, the associated symptom burden can be broad and is often missed by treating healthcare professionals, resulting in significant diagnostic delay. Treatment of this highly heterogenous condition is nuanced and consists of non-pharmacologic and pharmacologic approaches. Availability of POTS care is limited, with a dearth of medical specialists or general practitioners specialising in autonomic medicine. The complexity of care for those with POTS necessitates a multidisciplinary approach due to the need for extended appointment times and frequent follow-ups to monitor therapeutic response and progress. This should include a primary team consisting of a general practitioner and trained autonomic physicians with specialist nurses, allied health professionals, and any other specialists required to manage the affected systems. This state-of-the-art review aims to cover the key aspects of diagnosing and managing POTS, including special neurological, gastroenterological, psychological, and paediatric considerations. There is an urgent need to provide services that meet the needs of the growing POTS population.}, }
@article {pmid41532066, year = {2026}, author = {Feng, X and Wang, Y and Li, Y and Long, J and Liu, F and Yang, H}, title = {Application of the humanized mouse model in research into SARS-CoV-2 infection (Review).}, journal = {Medicine international}, volume = {6}, number = {1}, pages = {9}, pmid = {41532066}, issn = {2754-1304}, abstract = {The coronavirus disease 2019 (COVID-19) pandemic triggered by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a profound impact on global public health. The complexity of its pathogenic mechanisms and host interactions urgently requires high-fidelity animal models to support research. Humanized mouse models break the species barrier through gene editing and immune reconstitution technologies, providing a key tool to simulate human infection characteristics and pathological processes. A number of studies have reported the application of humanized mouse models in the fields of COVID-19 research, such as SARS-CoV-2 pathogenesis, anti-SARS-CoV-2 drug discovery and vaccine development, etc. The present review aimed to systematically document the latest advances in the application of humanized mouse models based on different construction strategies, such as receptor humanization, immune system humanization and composite humanization. These models have not only elucidated the pathogenicity differences and immune escape mechanisms of SARS-CoV-2 variants, but have also validated the efficacy of broad-spectrum anti-SARS-CoV-2 strategies, including angiotensin-converting enzyme 2-targeted therapies, antibody cocktail regimens and mucosal vaccines. Additionally, humanized mouse models have played a pivotal role in investigating the mechanisms underlying long COVID. By revealing the multi-system pathogenic mechanisms of pulmonary fibrosis, neurodegeneration and intestinal microbiota dysregulation, these models provide a theoretical foundation for the development of targeted intervention strategies.}, }
@article {pmid41543809, year = {2026}, author = {Bozkir, C and Kartal, T and Hokelek, B}, title = {Obesity and Nutritional Vulnerability in long COVID: A Neuroinflammatory and Cognitive Perspective.}, journal = {Current nutrition reports}, volume = {15}, number = {1}, pages = {5}, pmid = {41543809}, issn = {2161-3311}, mesh = {Humans ; *Obesity/complications/physiopathology ; *COVID-19/complications/physiopathology ; *Neuroinflammatory Diseases/etiology ; Post-Acute COVID-19 Syndrome ; *Nutritional Status ; *Cognition Disorders/etiology ; *Cognition ; SARS-CoV-2 ; *Malnutrition/complications ; Inflammation ; }, abstract = {PURPOSE OF REVIEW: To examine the interplay between obesity, nutritional vulnerability, and long COVID, with a particular focus on neuroinflammatory and cognitive outcomes. This review synthesizes emerging evidence on shared pathophysiological pathways and evaluates the therapeutic potential of dietary and weight management strategies.<br><br>RECENT FINDINGS: Cognitive symptoms such as brain fog and memory deficits are among the most persistent and disabling features of long COVID. Obesity is associated with more severe manifestations through pathways involving chronic systemic inflammation, compromised blood-brain barrier integrity, and neuroimmune dysregulation. Concurrently, malnutrition and poor diet quality including low intake of antioxidants, omega-3 fatty acids, and micronutrients may impair neuroplasticity and delay recovery. Interventions such as Mediterranean and ketogenic dietary patterns, as well as structured weight loss programs, show promise in reducing inflammation and improving cognitive outcomes. Obesity and suboptimal nutritional status amplify the neurocognitive burden of long COVID through shared pathophysiological mechanisms. Integrated care models that incorporate metabolic screening, nutritional assessment, and individualized dietary interventions may improve recovery trajectories. Public health strategies that address food quality, obesity prevention, and equitable access to nutrition care are essential for long-term resilience in the post-COVID era.}, }
@article {pmid41559316, year = {2026}, author = {Shi, Y and Li, B and Zheng, Y and Xue, C and Zhu, J}, title = {Therapeutic effect of anti-neuroinflammatory supplement combined with olfactory training on post-covid olfactory dysfunction: a systematic review and meta-analysis.}, journal = {European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery}, volume = {}, number = {}, pages = {}, pmid = {41559316}, issn = {1434-4726}, abstract = {BACKGROUND: There is no established specific treatment for post-COVID olfactory dysfunction (PCOD) currently. Olfactory training (OT) is the only effective intervention supported by clinical evidence. The anti-neuroinflammatory supplement palmitoylethanolamide and luteolin (PEA-LUT) has shown potential in alleviating the symptoms of post-COVID, but its therapeutic effect on olfactory dysfunction and the gain effect when combined with OT remain to be evaluated.<br><br>METHODS: We comprehensively searched the online databases EMBASE, PubMed, ScienceDirect, Web of Science, Cochrane Library, Google Scholar, and ClinicalTrials.govfor the literature related to the treatment of PCOD, identified studies reporting the efficacy of PEA-LUT combined with OT, extracted the treatment outcome data, and performed data synthesis.<br><br>RESULTS: A total of 7 eligible RCTs published between 2021 and 2024 were included, comprising 525 patients with PCOD. Of the seven studies, five (71.4%) used the full Threshold-Discrimination-Identification (TDI) scoresystem to assess olfactory function, while two (28.6%) used only the Identification ("I") subscale; 332 patients (63.2%) received PEA-LUT&#x2009;+&#x2009;OT therapy and 203 (38.8%) received OT alone. Meta-analysis of these studies showed that patients receiving PEA-LUT combined with OT had significantly higher TDI scores compared to those receiving OT alone (Standard mean difference (SMD)&#x2009;=&#x2009;0.90; 95% CI: 0.24-1.58; P&#x2009;<&#x2009;0.01). The overall response rate was also significantly higher in the combination group (Risk difference (RD)&#x2009;=&#x2009;0.33; 95% CI: 0.01-0.64; P&#x2009;=&#x2009;0.04).<br><br>CONCLUSION: The neuroprotective properties of PEA-LUT appear to enhance recovery from post-COVID olfactory dysfunction. When combined with olfactory training, this treatment shows promising potential as a novel therapeutic approach.}, }
@article {pmid41577420, year = {2026}, author = {Schuster, AM and Alwan, NA and Callard, F and Chen, EYH and Gilbody, S and Graham, BM and Hatch, SL and Jones, E and Jordan, A and Knapp, M and López-Jaramillo, C and Nakimuli-Mpungu, E and Pathare, S and Ressler, KJ and Wessely, S and White, LA and ,  and Jones, PB}, title = {The implications of the COVID-19 pandemic for clinical mental health care.}, journal = {The lancet. Psychiatry}, volume = {13}, number = {2}, pages = {140-161}, doi = {10.1016/S2215-0366(25)00247-0}, pmid = {41577420}, issn = {2215-0374}, mesh = {Humans ; *COVID-19/psychology/epidemiology ; *Mental Health Services/organization &amp; administration ; *Mental Disorders/therapy/epidemiology ; Pandemics ; SARS-CoV-2 ; Mental Health ; }, abstract = {A Position Paper published in The Lancet Psychiatry in 2020 suggested an agenda for research about the effects of the COVID-19 pandemic on mental health, following which an interdisciplinary Lancet Psychiatry standing commission was established in 2022 to examine the emerging evidence and refine recommendations for more research. In this first Series paper from the standing commission, we focus on changes in the delivery of clinical mental health care during the COVID-19 pandemic. The second paper in the Series focuses on public mental health and policy perspectives, and the third will address neuropsychiatric consequences of infection by SARS-CoV-2. Evidence from high-quality longitudinal studies with pre-pandemic baseline data, controlled intervention trials, or systematic reviews took time to accrue. During the early months of the COVID-19 pandemic, symptoms of anxiety and depression became more prevalent, and many mental health services were compromised by pandemic-related factors; however, whether the COVID-19 pandemic accelerated pre-existing long-term trends of increasing incidence of mental health disorders, especially in children and adolescents, is unclear. Little research has been done in low-income and middle-income countries, or regarding post-COVID-19 condition (also known as long COVID), which emerged as a multisystem condition with mental health implications. Vulnerable populations, including socioeconomically disadvantaged and minoritised groups, faced disproportionate mental health impacts and limited access to care during the COVID-19 pandemic, reflecting systemic, pre-pandemic inequalities. Bold implementation of existing evidence-based mental health support for vulnerable communities, ambitious trials of novel interventions, and systematic pooling of rapidly accumulating evidence about best healh care should be priorities in future pandemics.}, }
@article {pmid41580734, year = {2026}, author = {Fang, H and Wang, Q}, title = {The silent epidemic within the pandemic: pathophysiology and prediction of post-COVID-19 diabetes.}, journal = {Journal of translational medicine}, volume = {24}, number = {1}, pages = {266}, pmid = {41580734}, issn = {1479-5876}, abstract = {BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has presented extraordinary challenges to global public health, with impacts reaching beyond acute respiratory manifestations to include long-term metabolic disturbances. Emerging evidence indicates a significant link between SARS-CoV-2 infection and the onset of diabetes mellitus, establishing this condition as a major element of the post-acute sequelae of COVID-19, often referred to as Long COVID.<br><br>MAIN BODY: This review synthesizes epidemiological findings that demonstrate a elevated incidence of new-onset diabetes following COVID-19, particularly among certain high-risk demographic groups. We examine the molecular mechanisms underpinning this association, such as viral entry into pancreatic &#x3b2;-cells via ACE2 receptors, systemic inflammation leading to insulin resistance, and the potential diabetogenic effects of glucocorticoids used in COVID-19 treatment. Furthermore, this review outlines biomarker profiles that distinguish COVID-19-associated diabetes from traditional type 2 diabetes, underscoring important pathophysiological differences. Additionally, we evaluate advances and ongoing challenges in developing predictive risk models that combine clinical and molecular data to identify individuals at elevated risk for post-COVID diabetes.<br><br>CONCLUSIONS: By integrating multidisciplinary evidence, this comprehensive narrative review aims to guide future research and shape clinical approaches for early detection, prevention, and management of diabetes following COVID-19, thereby confronting a latent health crisis emerging within the broader pandemic context.}, }
@article {pmid41588096, year = {2026}, author = {Sharpe, H and Lam, GY}, title = {The evolving understanding of cystic fibrosis-related diabetes in the highly effective modulator therapy era: a scoping review.}, journal = {Diabetologia}, volume = {69}, number = {4}, pages = {855-871}, pmid = {41588096}, issn = {1432-0428}, mesh = {Humans ; *Cystic Fibrosis/complications/drug therapy/metabolism ; *Diabetes Mellitus/etiology/drug therapy ; Insulin/therapeutic use/metabolism ; Blood Glucose/metabolism/drug effects ; Hypoglycemic Agents/therapeutic use ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics/metabolism ; Hyperglycemia/drug therapy ; }, abstract = {Cystic fibrosis-related diabetes (CFRD) is a unique form of diabetes that shares features with both type 1 and type 2 diabetes and is most often characterised by transient postprandial hyperglycaemia as a consequence of delayed first-phase insulin release. In the last decade, new developments in the form of highly effective modulators have transformed the landscape of cystic fibrosis (CF) care and life expectancy. As CFRD is one of the most common complications of CF, there is a growing and urgent need to better understand how to optimise CFRD diagnosis and management across the continuum. In this review, we examine recent advancements in the understanding of CF dysglycaemia and CFRD monitoring and treatment, and synthesise the growing body of literature on post-market findings on how glycaemic management changes in response to modulator therapy.}, }
@article {pmid41594661, year = {2026}, author = {Förster, CY and Shityakov, S}, title = {A Possible Role for the Vagus Nerve in Physical and Mental Health.}, journal = {Biomolecules}, volume = {16}, number = {1}, pages = {}, pmid = {41594661}, issn = {2218-273X}, support = {Fo-315/5-1//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Humans ; *Vagus Nerve/physiology/physiopathology ; *Vagus Nerve Stimulation/methods ; *Mental Health ; COVID-19/therapy ; Animals ; SARS-CoV-2 ; Depression/therapy ; }, abstract = {For decades, researchers have explored the therapeutic potential of the vagus nerve through vagus nerve stimulation (VNS). Initially developed for epilepsy, VNS has since been applied to treat resistant depression, stroke recovery, and inflammatory conditions. Transcutaneous VNS (tVNS) now offers a noninvasive alternative, fueling clinical trials in disorders ranging from rheumatoid arthritis and migraines to long COVID-19. Mechanistic studies suggest that afferent and efferent vagal fibers modulate immune responses, mood regulation, and neurotransmitter systems. The SPARC initiative has accelerated mapping of vagal circuits, enabling more precise approaches to stimulation. Despite progress, the results remain mixed: while some patients experience lasting symptom relief, others respond no better than to placebo. Depression studies, in particular, highlight both the promise and the complexity of VNS, as inflammation, motivation circuits, and gut-brain signaling emerge as key modulators. Next-generation closed-loop devices and circuit-specific targeting may improve efficacy and reduce adverse effects. VNS research thus lies at the intersection of neuromodulation, psychiatry, and immunology-offering hope for hard-to-treat conditions, yet demanding rigorous trials to separate myths from medicine. In this article, we review the current clinical and experimental applications of tVNS, analyze its mixed efficacy across psychiatric, immunological, and neurological disorders, and highlight the mechanistic insights, stimulation parameters, and emerging technologies that may shape next-generation therapies.}, }
@article {pmid41597249, year = {2026}, author = {Stigliano, E and Tocci, A and Florio, R and Arena, V and Amadoro, G}, title = {Olfactory Dysfunction and Cognitive Deterioration in Long COVID: Pathomechanisms and Clinical Implications in Development of Alzheimer's Disease.}, journal = {Cells}, volume = {15}, number = {2}, pages = {}, pmid = {41597249}, issn = {2073-4409}, support = {RF-2021-12374//Italian Ministry of Health/ ; 971925//Alzheimer's Association Research Grant/ ; FOE D.M865/2019//Fondo Ordinario Enti/ ; }, mesh = {Humans ; *COVID-19/complications/pathology ; *Alzheimer Disease/etiology/pathology ; *Olfaction Disorders/etiology ; SARS-CoV-2 ; *Cognitive Dysfunction/etiology ; Anosmia ; }, abstract = {Complete or partial loss of smell (anosmia), sometimes in association with distorted olfactory perceptions (parosmia), is a common neurological symptom affecting nearly 60% of patients suffering from post-acute neurological sequelae of COronaVIrus Disease of 2019 (COVID-19) syndrome, called long COVID. Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) may gain access from the nasal cavity to the brain (neurotropism), and the olfactory route has been proposed as a peripheral site of virus entry. COVID-19 is a risk factor for developing Alzheimer's Disease (AD), an age-dependent and progressive neurodegenerative disorder characterized in affected patients by early olfaction dysfunction that precedes signs of cognitive decline associated with neurodegeneration in vulnerable brain regions of their limbic system. Here, we summarize the recent literature data supporting the causal correlation between the persistent olfactory deterioration following SARS-CoV-2 infection and the long-delayed manifestation of AD-like memory impairment. SARS-CoV-2 infection of the olfactory neuroepithelium is likely to trigger a pattern of detrimental events that, directly and/or indirectly, affect the anatomically interconnected hippocampal and cortical areas, thus resulting in tardive clinical dementia. We also delineate future advancement on pharmacological and rehabilitative treatments to improve the olfactory dysfunction in patients recovering even from the acute/mild phase of COVID-19. Collectively, the present review aims at highlighting the physiopathological nexus between COVID-19 anosmia and post-pandemic mental health to favor the development of best-targeted and more effective therapeutic strategies in the fight against the long-term neurological complications associated with SARS-CoV-2 infection.}, }
@article {pmid41599072, year = {2026}, author = {Dave, RS and Fox, HS}, title = {Synergy of SARS-CoV-2 and HIV-1 Infections in the Human Brain.}, journal = {Pathogens (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {}, pmid = {41599072}, issn = {2076-0817}, mesh = {Humans ; *COVID-19/virology/pathology/complications/epidemiology ; *HIV Infections/virology/pathology/complications ; *SARS-CoV-2 ; *HIV-1 ; *Brain/virology/pathology ; Microglia/virology/pathology ; Coinfection/virology ; Cytokines/metabolism ; }, abstract = {This review explores the interplay between SARS-CoV-2 and HIV-1 infections within the human brain, highlighting the significant neurological implications of these viral infections. SARS-CoV-2 can infect the central nervous system (CNS), with evidence of the virus detected in various brain regions, including the hypothalamus, cerebellum, and olfactory bulb. This infection is linked to microglial activation and neuroinflammation, which can lead to severe neurological outcomes in affected individuals. Autopsy studies revealed microglial changes, including downregulation of the P2RY12 receptor, indicating a shift from homeostatic to inflammatory phenotype. Similar changes in microglia are found in the brains of people with HIV-1 (PWH). In SARS-CoV-2, the correlation between inflammatory cytokines, such as IL-1, IL-6, and MCP-1, found in cerebrospinal fluid and brain tissues, indicates significant neurovascular inflammation. Astrogliosis and microglial nodules were observed, further emphasizing the inflammatory response triggered by the viral infections, again in parallel to those found in the brains of PWH. Epidemiologic data indicate that although SARS-CoV-2 infection rates in PWH mirror those in People without HIV (PWoH) populations, Long-COVID prevalence is markedly higher among PWH. Evidence of overlapping cognitive impairment, mental health burden, and persistent neuroinflammation highlights diagnostic complexity and therapeutic gaps. Despite plausible mechanistic synergy, direct neuropathological confirmation remains scarce, warranting longitudinal, biomarker-driven studies. Understanding these interactions is critical for developing targeted interventions to mitigate CNS injury and improve outcomes.}, }
@article {pmid41607640, year = {2026}, author = {Al-Hindawi, Y and Akkerman, OW and Byrne, A and Duarte, R and Jaramillo, E and Konstantynovska, O and Premuda, C and Vilaplana, C and Migliori, GB and Günther, G and Viney, K and Falzon, D}, title = {Post-tuberculosis lung disease.}, journal = {Breathe (Sheffield, England)}, volume = {22}, number = {1}, pages = {250243}, pmid = {41607640}, issn = {1810-6838}, abstract = {Tuberculosis (TB) burden concentrates in low-income settings and remains the leading global cause of death from a single infectious agent, despite that it is preventable and treatable. TB-associated lung diseases (TBALD), a broad range of respiratory abnormalities which can start before or during a TB episode, may increase morbidity. TBALD may persist after successful completion of TB treatment as post-TB lung disease (PTLD). PTLD varies in severity and is characterised by persistent respiratory symptoms and lung impairment that can significantly impact social activities, health-related quality of life, and long-term survival. Risk factors for PTLD include increasing age, smoking, HIV infection, delayed diagnosis, and poor socioeconomic conditions. Action to limit PTLD may be taken before TB develops through TB screening, early diagnosis and TB preventive treatment, during treatment of TB, and upon its completion. Early detection, clinical assessment, and tailored management (including smoking cessation, immunisation, addressing respiratory comorbidities, pulmonary rehabilitation and social protection) can mitigate impairment and disability. Healthcare providers and national programmes play a vital role through clinical follow-up, patient education, and integration of TBALD care into broader health and social protection services. Sustained funding and research are crucial for this and to develop new tools to enhance care.}, }
@article {pmid41623576, year = {2026}, author = {Birla, S and Angural, A and Madathumchalil, A and Shende, RV and Shastry, SV and Shekar, PK and Mahadevappa, M and Vishwanath, P and Prashant, A}, title = {"Bridging the clinical, molecular and genetic perspectives on myocarditis in post-COVID-19 era".}, journal = {International journal of cardiology. Cardiovascular risk and prevention}, volume = {28}, number = {}, pages = {200576}, pmid = {41623576}, issn = {2772-4875}, abstract = {Myocarditis is a non-familial inflammatory manifestation of the myocardium, primarily induced by viral infections, but it may also stem from bacterial pathogens, autoimmune disorders, or adverse drug reactions. Its diagnosis remains challenging due to heterogeneous and often non-specific clinical presentations. Recent epidemiological studies have indicated a markedly increased incidence of myocarditis following SARS-CoV-2 infection and mRNA COVID-19 vaccinations (to a lesser extent) compared to pre-pandemic statistics. While a significant number of cases follow a mild and self-limiting disease course, severe manifestations can lead to arrhythmias, heart failure, or even sudden cardiac death. Importantly, accumulating evidence indicates that even mild myocarditis confers an elevated long-term risk of adverse cardiovascular outcomes. Beyond clinical and imaging-based observations, recent advances highlight a critical role for host genetic susceptibility in modulating immune responses, myocardial injury, and disease severity. This review provides a comprehensive synthesis of the etiology, pathophysiological mechanisms, clinical spectrum, diagnostic approaches, and evidence-based management of COVID-19-associated myocarditis, while critically integrating emerging genetic and transcriptomic insights that may explain disease heterogeneity, variable inter-individual susceptibility, and long-term prognosis. By bridging clinical aspects with molecular and genetic frameworks, this review underscores the importance of personalized risk stratification, vigilant post-recovery surveillance, and targeted preventive strategies in the post-pandemic era.}, }
@article {pmid41639776, year = {2026}, author = {Aboulwafa, A and Lebbe, A and Khalil, A and Bayraktar, N and Mushannen, B and Ayoub, S and Sarker, S and Abdalla, MN and Laws, S and Mohammed, I and Yagan, L and Mushannen, M and Zakaria, D}, title = {New onset of severe and long-term hepatobiliary diseases post-COVID-19 infection: a systematic review.}, journal = {BMC infectious diseases}, volume = {26}, number = {1}, pages = {253}, pmid = {41639776}, issn = {1471-2334}, abstract = {BACKGROUND: The COVID-19 pandemic has resulted in a surge of reports linking the virus to various systemic complications, including hepatobiliary disorders. Understanding the spectrum and severity of hepatobiliary diseases following COVID-19 infection is crucial for comprehensive patient management and long-term health outcomes.<br><br>METHODS: A systematic review was conducted to identify studies reporting on hepatobiliary manifestations post-COVID-19 infection. PubMed, Medline, Embase, Scopus, Web of Science, Science Direct and Cochrane Library databases were searched in October 2023, with set inclusion and exclusion criteria in place to select papers documenting new onset hepatobiliary diseases following COVID-19 infection.<br><br>RESULTS: A total of 23 studies met the inclusion criteria, covering a diverse range of hepatobiliary conditions such as acute hepatitis, cholestasis, autoimmune liver diseases, and gallbladder pathology.<br><br>CONCLUSION: This systematic review underscores the emerging evidence of severe and long-term hepatobiliary diseases following COVID-19 infection. Healthcare providers should maintain a high index of suspicion for hepatobiliary complications in patients recovering from COVID-19, emphasizing the need for prolonged monitoring and specialized management strategies to mitigate long-term morbidity and mortality."<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-025-11840-3.}, }
@article {pmid41641003, year = {2025}, author = {Leclerc, L and Poudrier, J and Power, C and Lam, GY and Falcone, EL}, title = {Intestinal barrier compromise, viral persistence, and immune dysregulation converge on neurological sequelae in Long COVID.}, journal = {Frontiers in aging neuroscience}, volume = {17}, number = {}, pages = {1744415}, pmid = {41641003}, issn = {1663-4365}, abstract = {Long COVID (LC) is a multisystem, post-infectious conditions diagnosed ≥3 months after acute SARS-CoV-2 infection and marked by relapsing, persistent, or progressive symptoms, especially fatigue, post-exertional symptom exacerbation and neuropsychiatric syndromes. We synthesized evidence suggesting that LC arises from intersecting pathways including viral persistence, intestinal dysbiosis and barrier compromise with microbial translocation, innate immune activation with neutrophil extracellular traps (NET) and thromboinflammation, and immune dysregulation with features of exhaustion and autoimmunity. These processes adversely impact blood-brain barrier (BBB) function and lead to neuroinflammation. We propose a mechanistic model in which viral antigens and translocated microbial products amplify pro-inflammatory networks promoting immunothrombosis and tissue hypoperfusion. Hematogenous and gut-brain pathways may then deliver inflammatory mediators to the central nervous system (CNS), resulting in BBB disruption and glial activation that underpin nervous system disorders in LC. Treatment regimens aimed at lowering antigen load, restoring mucosal barrier integrity and modulating myeloid/coagulation pathways may warrant investigation as novel therapeutic strategies to treat LC.}, }
@article {pmid41646510, year = {2026}, author = {Melo-Oliveira, MES and Lourenço, RA and Louzada, EB and Moutinho, M and Barbosa, AF and Moreira, VG and Porto, LC}, title = {Systematic Review of Dyspnea and Chronic Fatigue in Patients With Long COVID: Clinical Characteristics and Associated Laboratory Parameters.}, journal = {Pulmonary medicine}, volume = {2026}, number = {}, pages = {5426125}, pmid = {41646510}, issn = {2090-1844}, mesh = {Humans ; *Dyspnea/etiology/physiopathology/virology/epidemiology ; *COVID-19/complications/physiopathology ; Quality of Life ; *Fatigue/etiology/physiopathology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Fatigue Syndrome, Chronic/etiology ; }, abstract = {ABSTRACT: Dyspnea and chronic fatigue stand out as prevalent manifestations in the postacute phase of COVID, resulting in substantial adverse effects on patients' quality of life and functional capacity. Although these symptoms have been widely documented, there is no clear consensus on the pathophysiological mechanisms that underlie them. The available literature reveals a dispersion of clinical and laboratory data, and the variability in the methods of assessment of fatigue and dyspnea, as well as in the laboratory variables examined, limits the standardized understanding of this complex condition.<br><br>OBJECTIVE: This study was aimed at identifying and synthesizing the evidence on the main clinical and laboratory characteristics related to dyspnea and fatigue in patients during long COVID from 2021 onwards.<br><br>METHODS: The main databases used to select the studies were PubMed and Medline, also using LitCovid and Embase.<br><br>RESULTS: A total of 42 articles that met the inclusion criteria were included, covering a total population of 30,682 patients diagnosed with COVID-19. The findings underscore the significant impact of long COVID on patients' quality of life, with persistent symptoms such as fatigue and dyspnea affecting a considerable proportion of individuals for durations ranging from 1 to 24 months.<br><br>CONCLUSION: The heterogeneity in research approaches highlights the urgent need for collaborative initiatives to elucidate the determinants of long COVID symptomatology and create more consistent evaluation protocols.}, }
@article {pmid41650532, year = {2026}, author = {Labied, S and Atifi, F and Wahnou, H and Mabrouk, M and Jeddoub, O and Allaoui, A and Jalali, F and Zaid, Y}, title = {Megakaryocytes and afucosylated IgG in post-acute COVID-19: Bridging immune dysregulation and vascular pathology - A narrative review.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {196}, number = {}, pages = {119049}, doi = {10.1016/j.biopha.2026.119049}, pmid = {41650532}, issn = {1950-6007}, mesh = {Humans ; *COVID-19/immunology/pathology/complications ; *Immunoglobulin G/immunology/metabolism ; *Megakaryocytes/immunology/pathology/metabolism ; SARS-CoV-2/immunology ; Post-Acute COVID-19 Syndrome ; Glycosylation ; Glycoproteins ; }, abstract = {Post-acute sequelae of SARS-CoV-2 infection (PASC), also referred to as long COVID, encompasses a constellation of persistent symptoms lasting for at least three months after acute SARS-CoV-2 infection and not explained by alternative diagnoses. The multifactorial pathophysiology underlying PASC remains incompletely understood, limiting the development of effective management strategies. Increasing evidence suggests that both immune dysregulation and hemostatic imbalance play central roles in post-COVID-19 complications. Megakaryocytes, key regulators of platelet production and coagulation, have emerged as potential contributors to sustained thrombo-inflammatory processes following SARS-CoV-2 infection. In parallel, afucosylated IgG antibodies have been strongly implicated in exaggerated immune activation and hyperinflammatory responses during acute COVID-19. The persistence of such antibody glycosylation patterns beyond the acute phase raises the possibility that they may also contribute to chronic immune and vascular alterations observed in PASC. This narrative review explores the potential interplay between megakaryocyte dysfunction and afucosylated IgG antibodies in the pathogenesis of PASC. By examining mechanisms identified during acute SARS-CoV-2 infection, we discuss how prolonged immune-hemostatic crosstalk may promote persistent inflammation, endothelial dysfunction, and microvascular abnormalities. Understanding these interconnected pathways may provide mechanistic insight into the heterogeneity of PASC manifestations and help identify novel therapeutic targets for long-term post-COVID-19 sequelae.}, }
@article {pmid41668172, year = {2026}, author = {Kim, DY and Youn, J and Kang, N and Cho, SI and Ha, IH}, title = {Potential application of brain-gut axis-based treatments in Long COVID and ME/CFS: a case-based systematic review.}, journal = {Journal of translational medicine}, volume = {24}, number = {1}, pages = {}, pmid = {41668172}, issn = {1479-5876}, mesh = {Humans ; *COVID-19/complications/therapy/physiopathology ; *Fatigue Syndrome, Chronic/therapy/physiopathology ; Electroacupuncture ; SARS-CoV-2 ; *Brain-Gut Axis/physiology ; Male ; *Brain/physiopathology ; Adult ; Female ; Middle Aged ; }, abstract = {BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID share clinical features including persistent fatigue, post-exertional malaise (PEM), and gastrointestinal (GI) dysfunction. Growing evidence implicates brain-gut axis dysregulation, characterized by dysbiosis, neuroinflammation within the central nervous system (CNS), increased intestinal permeability, and microbial translocation in their pathophysiology. However, therapeutic strategies targeting these pathways remain poorly defined.<br><br>METHODS: We report a case of post-COVID ME/CFS successfully treated with electroacupuncture (EA)-based deep peroneal nerve stimulation which was employed to potentiate the vagal reflex. Fatigue trajectories were assessed using the Multidimensional Fatigue Inventory over 12&#x2009;weeks. Based on the case, a systematic review of randomized controlled trials (RCTs) evaluating brain-gut axis-modulating interventions in ME/CFS or Long COVID was conducted.<br><br>RESULTS: The patient exhibited a significant reduction in total fatigue, with early improvements in motivation and mental fatigue, and delayed improvement in physical fatigue following transient systemic symptom flares. Across included RCTs (n&#x2009;=&#x2009;8, 790 participants), four investigated gut microbiome-modulating therapies and four employed nerve stimulation. Synbiotic and herbal interventions demonstrated benefits for fatigue or PEM, accompanied by alterations in specific bacterial populations or CNS metabolisms. Regarding nerve stimulation, transcranial direct current stimulation (tDCS) combined with exercise program improved fatigue, whereas standalone tDCS, auricular or peripheral TENS showed limited efficacy.<br><br>CONCLUSION: Brain-gut axis-based interventions may alleviate fatigue in ME/CFS and Long COVID by potentially modulating neuroinflammation, restoring microbiome balance, and improving epithelial barrier function. EA-based vagal stimulation represents a feasible option for patients with severe or treatment-resistant symptoms. Larger mechanistic studies and rigorously designed RCTs are needed to establish therapeutic targets and optimize intervention strategies.}, }
@article {pmid41674460, year = {2026}, author = {McTiernan, K and Hughes, C and Gilheaney, &#xd3;}, title = {Cognitive Communication, Voice and Swallowing Difficulties Experienced by Adults With Long-COVID: A Scoping Review.}, journal = {Health expectations : an international journal of public participation in health care and health policy}, volume = {29}, number = {1}, pages = {e70595}, pmid = {41674460}, issn = {1369-7625}, mesh = {Humans ; *COVID-19/complications ; *Deglutition Disorders/etiology ; *Voice Disorders/etiology ; *Communication ; Adult ; SARS-CoV-2 ; *Communication Disorders/etiology ; }, abstract = {BACKGROUND: Adults with Long-COVID frequently experience impairments in cognitive-communication, voice and swallowing, however, few comprehensive reviews of the existing literature has yet to be conducted to map the current research landscape. To go some way toward addressing this gap, this scoping review collected and analysed relevant published studies to identify reported symptoms related to cognitive communication, voice and swallowing in post COVID-19 patients and the assessments used to identify these difficulties.<br><br>OBJECTIVE: This study aimed to systematically map the existing literature on cognitive-communication, voice and swallowing difficulties in individuals living with Long-COVID and the assessments used to identify these difficulties.<br><br>METHODS: Four databases were searched to identify original research articles aligned with the study's objectives. Studies meeting the inclusion criteria were selected, and the findings were analysed with a specific focus on three key symptom domains: cognitive-communication, voice and swallowing.<br><br>RESULTS: Nineteen studies met the inclusion criteria. A broad range of assessments were used, and a broad range of symptoms were identified related to cognitive-communication, voice and swallowing difficulties in patients with Long-COVID-19. The symptoms reported most frequently in the selected studies included memory deficits, incomplete or inefficient glottic closure, paradoxical vocal fold motion during inspiration, episodes of choking, globus sensation, premature spillage and pyriform sinus residue.<br><br>CONCLUSION: Despite limited prior research in this area, the findings underscore the significant impact that COVID-19 infection may have on cognitive communication, voice and swallowing functions. Post-COVID-19 patients report a wide array of challenges in these domains. As a result, further clinical research is essential to develop patient-centred care strategies and to equip healthcare professionals with the expertise required for effective management of this group of patients.}, }
@article {pmid41683839, year = {2026}, author = {Chen, JJ and Hsu, CW and Wang, HY and Stubbs, B and Chen, TY and Liang, CS and Chen, YW and Zeng, BS and Tseng, PT}, title = {Audiovestibular Dysfunction Related to Long COVID-19 Syndrome: A Systematic Review of Characteristics, Pathophysiology, Diagnosis, and Management.}, journal = {International journal of molecular sciences}, volume = {27}, number = {3}, pages = {}, pmid = {41683839}, issn = {1422-0067}, mesh = {Humans ; *COVID-19/complications/physiopathology/diagnosis ; SARS-CoV-2 ; *Vestibular Diseases/diagnosis/therapy/physiopathology/etiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long COVID-19 syndrome (or so-called post-COVID-19) is indicated by miscellaneous symptoms, usually starting 3 months from the COVID-19 infection and lasting for at least 2 months, which cannot be explained by an alternative diagnosis. There has been more and more reports addressing the audiovestibular dysfunction related to long COVID-19 syndrome. Emerging evidence suggests that the linkage between audiovestibular dysfunction and long COVID-19 syndrome might rely on (a) direct inner ear system damage related to viral invasion and consequent inflammation, (b) micro thromboembolic events, which might result from the COVID-19-induced autoimmune reaction against endothelial cells, and consequent transient-ischemia and hypoxia of the auditory pathways, (c) the disturbed nerve conduction in vestibulocochlear nerves due to viral invasion, and finally (d) altered auditory cortex function, either imbalanced central gain or neurotransmitter disturbance. However, most of the aforementioned mechanism remained hypothetic and still needed further studies to approve or refute. This systematic review synthesizes current evidence on the characteristics, pathophysiology, diagnostic approaches, and management of audiovestibular dysfunction related to long COVID-19 syndrome. Literature searches across PubMed, Embase, ClinicalKey, Web of Science, and ScienceDirect (up to 15 December 2025) were conducted in accordance with PRISMA guidelines. Through this systematic review, we provided a schematic diagram of the physiopathology of long COVID-19 syndrome-related audiovestibular dysfunction. Further, we summarized the currently available diagnostic tools to explore the audiovestibular function in such patients. The currently available treatment, either pharmacotherapy or nonpharmacotherapy, mainly tackles idiopathic audiovestibular dysfunction but not specifically long COVID-19 syndrome-related audiovestibular dysfunction. Timely recognition and intervention may prevent progression to permanent hearing loss or vestibular disability, improving quality of life. Trial registration: PROSPERO CRD420251265741.}, }
@article {pmid41697443, year = {2026}, author = {Camara, B and Buonsenso, D}, title = {Biomarkers of long COVID in children and young adults: a scoping review.}, journal = {European journal of pediatrics}, volume = {185}, number = {3}, pages = {132}, pmid = {41697443}, issn = {1432-1076}, mesh = {Humans ; *COVID-19/complications/diagnosis ; Child ; *Biomarkers/blood ; Adolescent ; Young Adult ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {UNLABELLED: Following the SARS-CoV-2 pandemic, a significant percentage of people are now experiencing long-term symptoms, despite a continuing lack of concrete documentation of physiological and risk profiles that hinders diagnosis and treatment, particularly in pediatric contexts. This review aims to highlight the existing evidence for measurable physiological markers for post-acute sequelae of SARS-CoV-2 infection (long COVID) in children, adolescents, and young adults. Titles providing data related to measurable biomarkers distinguishing young long COVID patients from controls were compiled and analyzed. Results were displayed in table and diagram form for optimal qualitative evaluation of the relationship between markers and symptomatology within the context of each organ system. Only human studies published in English, Italian, Portuguese, German, and Spanish between the 5th of February 2025 and the 31st of December 2025 were considered, and no other time constraints were applied. Following search and criteria evaluation, nine studies were included, totaling 41 occurrences identified in diseased patients with statistically significant variation from healthy controls. Markers suggest the presence of organic manifestations based on published literature, although more data and future studies will be necessary to establish clear connections.<br><br>CONCLUSION: The data compiled for this review adds to the body of evidence indicating a physiological manifestation of long COVID and its consequences. Further investigation into potential risk factors, pre- and post-pubescent manifestations, and specific inflammatory and immune pathways will be necessary for a more concrete understanding of long COVID and its effects on children, adolescents, and young adults.<br><br>WHAT IS KNOWN: &#x2022; Long COVID is estimated to affect a significant population of patients, despite the lack of concrete physiological diagnostic and prognostic measures. &#x2022; Pediatric incidence of the disease is still largely debated, and published data are scarce.<br><br>WHAT IS NEW: &#x2022; A total of 41 biomarker occurrences were identified by selected studies, which were consistent with expected physiology behind reported symptoms. &#x2022; The body of data discussed suggests the presence of physiological phenomena behind the long-term symptoms experienced by pediatric long- COVID patients.}, }
@article {pmid41712028, year = {2026}, author = {Chakraborty, C and Bhattacharya, M and Chatterjee, S and Lee, SS}, title = {Long COVID-associated neurological symptoms and brain fog: Understanding the mechanism of neuroinflammation, BBB disruption, diagnostics, and therapeutics.}, journal = {Molecular biology reports}, volume = {53}, number = {1}, pages = {401}, pmid = {41712028}, issn = {1573-4978}, mesh = {Humans ; *Blood-Brain Barrier/pathology/metabolism/virology ; *COVID-19/complications/diagnosis/therapy ; *Neuroinflammatory Diseases/diagnosis/therapy/virology ; SARS-CoV-2 ; Animals ; Brain/pathology/virology ; *Nervous System Diseases/diagnosis/therapy/etiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long COVID affects at least 10% of those with severe disease, and many experience neurological symptoms and brain fog. More than 200 symptoms are reported, yet a detailed understanding remains limited. This article summarizes current knowledge of neurological symptoms, brain fog, molecular mechanisms, neuroinflammation, blood-brain barrier disruption, diagnostics, and available therapeutics. Our review highlights the lack of diagnostics and treatments for these patients. We catalog the ongoing clinical trials, identify the urgent need for further therapeutics, and stress that advances in understanding pathophysiology will drive new treatments. We urge prioritizing animal model studies and improving diagnostics to accelerate the discovery and delivery of effective treatments for long COVID neurological symptoms.}, }
@article {pmid41717886, year = {2026}, author = {Cucunawangsih, C and Ansori, ANM and Vatvani, AD and Hariyanto, TI}, title = {Impact of nirmatrelvir/ritonavir on the risk of long COVID in outpatients: a systematic review and meta-analysis.}, journal = {Expert review of anti-infective therapy}, volume = {24}, number = {2}, pages = {271-284}, doi = {10.1080/14787210.2026.2636175}, pmid = {41717886}, issn = {1744-8336}, mesh = {Humans ; *Ritonavir/administration &amp; dosage ; *COVID-19 Drug Treatment ; *COVID-19/prevention &amp; control/epidemiology ; Outpatients ; *Antiviral Agents/administration &amp; dosage ; Drug Combinations ; }, abstract = {BACKGROUND: This study systematically synthesized existing evidence to evaluate whether outpatient treatment with nirmatrelvir/ritonavir during the acute phase reduces the incidence of long COVID.<br><br>METHODS: We conducted a systematic search of Europe PMC, Medline, Scopus, and the Cochrane Library from inception to 15 September 2025. Eligible studies compared COVID-19 outpatients prescribed nirmatrelvir/ritonavir during the acute phase with those who did not receive the drug. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model.<br><br>RESULTS: Nineteen studies met inclusion criteria. Overall, nirmatrelvir/ritonavir use during acute infection was associated with a significant reduction in the likelihood of developing post-COVID-19 condition (OR 0.85; 95% CI: 0.80-0.91; p&#x2009;<&#x2009;0.00001; I[2]&#x2009;=&#x2009;99%). Protective effects were consistently observed across multiple clinical domains, including cardiovascular (arrhythmia, ischemic disease, heart failure), pulmonary (dyspnea, COPD), thromboembolic (DVT, PE), neurological (stroke, cognitive impairment, headache), psychiatric (depression), gastrointestinal, metabolic (new-onset diabetes), renal (AKI), and general symptoms (malaise and fatigue). Conversely, no significant differences were noted for cough, asthma, dysautonomia, anxiety, PTSD, sleep disturbances, musculoskeletal pain, or olfactory/gustatory dysfunction.<br><br>CONCLUSIONS: Early outpatient treatment with nirmatrelvir/ritonavir may mitigate the risk of developing several domains of long COVID, though its benefits are not uniform across all symptom categories.}, }
@article {pmid41718988, year = {2026}, author = {Wang, Y and Gandy, S}, title = {Golgi Fragmentation as a Potential Link Between SARS-CoV-2 Infection and Alzheimer's Disease: Mechanisms and Implications for Neurodegeneration in Long COVID.}, journal = {Sub-cellular biochemistry}, volume = {111}, number = {}, pages = {463-482}, pmid = {41718988}, issn = {0306-0225}, mesh = {Humans ; *Alzheimer Disease/pathology/metabolism/virology ; *COVID-19/pathology/complications/metabolism/virology ; *Golgi Apparatus/pathology/metabolism/virology ; *SARS-CoV-2/metabolism ; Animals ; }, abstract = {The COVID-19 pandemic has impacted millions of people worldwide, and recent studies have shown that SARS-CoV-2 infection can lead to an Alzheimer's-like neuropathological and biomarker phenotype, as well as clinical symptoms of "brain fog". This raises an intriguing question: "How and where might the molecular pathways underlying SARS-CoV-2 infection and Alzheimer's disease (AD) converge?" One common feature of both SARS-CoV-2 infection and AD is the alteration of the endomembrane system, particularly the fragmentation of the Golgi apparatus. In this review article, we summarize the existing literature on SARS-CoV-2 infection biology and speculate about the potential mechanisms linking Golgi defects, SARS-CoV-2 infection, and neurodegeneration.}, }
@article {pmid41729280, year = {2026}, author = {Kaya, G and Kroehn-Liedtke, F and Kalinowski, O and Moran, JK and Neal, R and Pirmorady-Sehouli, A and Dini, L and Schouler-Ocak, M}, title = {[Psychiatric and psychotherapeutic recommendations for long/post-COVID and ME/CFS: a narrative review of international guidelines].}, journal = {Der Nervenarzt}, volume = {}, number = {}, pages = {}, pmid = {41729280}, issn = {1433-0407}, abstract = {BACKGROUND: Long/post-COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are often accompanied by fatigue, cognitive impairments and psychological symptoms. Psychiatric and psychotherapeutic care is challenged by unclear evidence, symptomatic overlaps, and controversial treatment recommendations.<br><br>OBJECTIVE: Presentation and comparison of psychiatric and psychotherapeutic recommendations in relevant international and national guidelines on long/post-COVID and ME/CFS, focusing on psychotherapy and psychopharmacotherapy.<br><br>METHODS: A&#xa0;narrative review was conducted. National and international guidelines focusing on ME/CFS and long/post-COVID published between 2020 and 2025, particularly by the WHO, AWMF, NICE, CDC and IQWiG, were included. The selected guidelines were analyzed in terms of key aspects.<br><br>RESULTS: Psychiatric pharmacotherapy is recommended only for comorbid disorders. Psychotherapeutic interventions are mostly recommended as supportive in the guidelines. Activating treatment approaches, such as graded exercise therapy (GET) are generally viewed critically in connection with postexertional malaise (PEM), whereas for patients without PEM, several guidelines explicitly endorse moderate, individually adapted activation. Pacing strategies are highlighted across guidelines as a&#xa0;central concept of activity management.<br><br>DISCUSSION: Psychiatric and psychotherapeutic interventions in long/post-COVID and ME/CFS are supportive but not causal treatments. Guidelines recommend symptom-oriented, individualized therapeutic approaches as well as an integrative consideration of somatic, social and psychological factors in the sense of the biopsychosocial model. There is a&#xa0;high need for specific research on psychotherapeutic intervention forms in these patient groups.}, }
@article {pmid41732619, year = {2026}, author = {Manoukian, G and Kundukulam, S and Asatorian, G and Johnson, DM and Masood, MH and Venugopal, A and Manoukian, M and Aswathappa, S}, title = {Post-COVID Syndrome in Patients With Comorbid Hypertension or Diabetes: A Narrative Review of Long-Term Outcomes.}, journal = {Cureus}, volume = {18}, number = {1}, pages = {e102117}, pmid = {41732619}, issn = {2168-8184}, abstract = {Post-COVID syndrome (PCS), or long COVID, refers to a cluster of enduring symptoms that extend beyond the acute phase of the initial SARS-CoV-2 infection. Acute infection predominantly impacts the respiratory tract, but there is growing evidence for the multisystem involvement, such as cardiovascular, metabolic, and neurological, to be responsible for the prolonged presentation in PCS. Underlying cardiometabolic vulnerability may contribute to a high degree of susceptibility in patients with comorbidities like hypertension (HTN) and diabetes mellitus (DM). This narrative review summarizes current literature regarding PCS in patients with HTN and/or DM, focusing on proposed pathophysiological mechanisms, clinical manifestations, and reported long-term outcomes. In these populations, PCS has been linked across studies to processes including endothelial dysfunction, chronic low-grade inflammation, autonomic imbalance, and potential dysregulation of the renin-angiotensin-aldosterone system (RAAS). Persistent cardiovascular, metabolic, and neurocognitive symptoms are reported, but the magnitude and patterns of risk vary across studies, while comparative findings across HTN and DM remain heterogeneous. Symptoms reported frequently include fatigue, cognitive impairment ("brain fog"), and psychological distress, supporting the multisystem complexity of PCS. Although, previous work has indicated that cardiometabolic comorbidities could interact and moderate PCS severity and persistence, there is an important shortfall of both causality and prognosis, as well as the management of PCS. Longitudinal studies are needed for future research regarding risk stratification, disease course, and targeted interventions in individuals with PCS with comorbid high blood pressure and diabetes.}, }
@article {pmid41737593, year = {2026}, author = {Thangaleela, S and Wang, CK}, title = {Impact of nutrition on long COVID.}, journal = {Sports medicine and health science}, volume = {8}, number = {2}, pages = {128-144}, pmid = {41737593}, issn = {2666-3376}, abstract = {Long COVID is characterized by a group of persistent symptoms following the acute SARS-COV2 infection, which presented a multifaceted challenge to the healthcare systems all over the globe. The long COVID symptoms span various organ systems including the respiratory, cardiovascular, gastrointestinal, and neurological manifestations. Mitochondrial dysfunction and immune dysregulation play crucial roles in the long COVID pathophysiology. Recently nutritional intervention gained much attention in managing post-viral syndromes. Effective interventions like supplementation of omega-3 fatty acid, macro and micro nutrients, and vitamins help to reduce systemic inflammation and counteract muscle wasting. Other approaches like nutritional recovery, dietetic interventions, continuous nutritional care post-hospital discharge, nutritional rehabilitation programs, whole-diet approaches like Mediterranean diet, plant-based diet, and caloric optimization, improve overall functional recovery. Physical activity and exercise regimes have been shown to improve fatigue, dyspnea, and cognitive function. Tailored exercise regimes may promote safe rehabilitation. Certain ineffective interventions, such as non-personalized approaches, high dose of antioxidants, use of herbal products that are not clinically validated need to be addressed. Dietary interventions such as personalized nutritional counseling have been demonstrated to improve physical performance in long COVID patients. Further research is needed to refine protocols and identify optimal combinations of dietary and movement-based therapies to support the recovery of long-COVID patients. This narrative review focuses on the ongoing researches that reveals the intricate relationship between nutrition and long COVID recovery and also establishes effective protocols for nutritional care.}, }
@article {pmid41740316, year = {2026}, author = {Spedding, M and Aerts, J and Alexander, S and Bellozzi Woestelandt, AG and Chiricozzi, E and Henriques, A and Lledo, PM and Loeffler, JP and Perera, R and Platt, FM and Pradat, PF and Rene, F and Schapira, A and St Clair, L and Talbot, K and Taquet, M and Toborek, M and Turner, B and Zandi, M and Gressens, P}, title = {Links between COVID-19, long COVID, and neurodegeneration: The role of glycosphingolipids.}, journal = {Pharmacological reviews}, volume = {78}, number = {2}, pages = {100113}, doi = {10.1016/j.pharmr.2026.100113}, pmid = {41740316}, issn = {1521-0081}, support = {T32AI007417-28//NIH/National Institute of Health NIAID/ ; F32AI186453-01//NIH/National Institute of Health NIAID/ ; L70AG084124-01//NIH National Institute of Health /NIA/ ; }, mesh = {Humans ; *COVID-19/metabolism/complications ; *Glycosphingolipids/metabolism ; SARS-CoV-2 ; *Neurodegenerative Diseases/metabolism/virology/etiology ; Animals ; Pandemics ; }, abstract = {Glycosphingolipids (GSLs) play major roles in viral infections by mediating viral entry and egress from cells in lipid rafts; however, GSLs are also important in neurodegenerative diseases. The role of GSLs in acute COVID-19 infection is critical but remains less-studied in the sequelae of long COVID (post-COVID condition); because the same enzymes that regulate GSL metabolism are critical for viral entry and exit, neuromuscular junctions, neurological function, and cellular metabolism, it is important to determine whether long COVID may increase the risk of subsequent neurodegeneration. SARS-CoV-2 infection alters lipid metabolism and oxygen use and can bind to and modify the expression of neurotrophic GSLs such as GM1 ganglioside. GM1 (N-acetylneuraminic acid) is human-specific and probably evolved as a result of a pandemic 3-2.5 million years ago that drove its selection. GM1 functions as a coreceptor with angiotensin-converting enzyme 2 for SARS-CoV-2 while also being a neurotrophin. Viral multiplication takes place in the endoplasmic reticulum/Golgi apparatus, where GSLs are synthesized. This review defines the complex interaction between viruses, GSLs, and neurodegeneration, which provides new perspectives on the interlinked metabolic changes. A European working group has been set up to assess the risks of neurodegeneration with long COVID, based on potential GSL-mediated mechanisms. SIGNIFICANCE STATEMENT: The SARS-CoV-2 pandemic has resulted in a large number of subjects living with long-term consequences (long COVID). Glycosphingolipids and gangliosides are involved in both viral infections and neurodegeneration; hence, it is important to evaluate whether long COVID may increase the risk of neurodegeneration via this route. This study is the result of a European consortium formed to evaluate this possibility.}, }
@article {pmid41742356, year = {2026}, author = {Ogbu-Nwobodo, L and Hwong, AR and Murphy, K and Goldman, ML and Dilley, JW}, title = {Long COVID in Populations With Serious Mental Illness: Clinical and Policy Implications.}, journal = {Psychiatric services (Washington, D.C.)}, volume = {77}, number = {5}, pages = {449-456}, doi = {10.1176/appi.ps.20240457}, pmid = {41742356}, issn = {1557-9700}, mesh = {Humans ; *COVID-19/complications/psychology/epidemiology ; *Mental Disorders/epidemiology/therapy ; Post-Acute COVID-19 Syndrome ; Health Policy ; Comorbidity ; }, abstract = {As the world recovers from the height of the COVID-19 pandemic with ongoing plans for a strengthened behavioral health infrastructure-from crisis services to long-term care-one of the health conditions that has emerged is long COVID. This multisystem condition is characterized by persistent symptoms that develop after the acute phase of COVID-19 infection. Although the full clinical and scientific understanding of long COVID's neuropsychiatric impact is still evolving, a sizable cohort of patients has emerged with various long-term and often confusing symptoms, which can include cognitive impairment, mood dysregulation (e.g., anxiety or depression), sleep disturbances, posttraumatic symptoms, and chronic fatigue. Recognizing long COVID's debilitating impact on quality of life and wide-ranging societal consequences, the authors sought to summarize current knowledge about long COVID among individuals with a preexisting serious mental illness and to propose care and treatment recommendations for clinicians and public policy makers.}, }
@article {pmid41745098, year = {2026}, author = {Zoccali, F and Fratini, C and Pennacchia, F and Cascone, F and de Vincentiis, M and Petrella, C and Barbato, C and Minni, A}, title = {Hyperbaric Oxygen Therapy on Long COVID Symptoms: A Breath of Fresh Air.}, journal = {Diseases (Basel, Switzerland)}, volume = {14}, number = {2}, pages = {}, pmid = {41745098}, issn = {2079-9721}, abstract = {Long COVID is defined as "the continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanations", as reported by the World Health Organization. A growing number of people are dealing with a variety of lingering symptoms even after recovering from an acute infection. These can include fatigue, muscle pain, shortness of breath, headaches, cognitive issues, neurodegenerative symptoms, anxiety, depression, and a feeling of hopelessness, and therapeutic options for long COVID are investigated. The potential of hyperbaric oxygen therapy (HBOT) to improve chronic fatigue, cognitive impairments, and neurological disorders has been established; therefore, the use of HBOT to treat long COVID has also been studied. The aim of this literature search is to analyze the state of the art of a potential role of HBOT to improve chronic fatigue, cognitive impairments and neurological disorders. A literature analysis was performed, focusing on the clinical efficacy of HBOT for treating long COVID symptoms. The results from January 2021 to October 2025, using a standard registry database, showed 21 studies, including one case report, ten randomized controlled trial, eight systematic reviews and three studies regarding the molecular mechanism and markers changing after HBOT. They suggested that HBOT can improve quality of life, fatigue, cognition, neuropsychiatric symptoms and cardiopulmonary functions. HBOT is a safe treatment and has shown some benefits for long COVID symptoms. To precisely define indications, protocols, and post-treatment evaluations, we need to conduct more in-depth, large-scale studies.}, }
@article {pmid41750353, year = {2026}, author = {Makki, R and Kassem-Moussa, S and Al Nemer, F and El Majzoub, R and Fayyad-Kazan, H and Rachidi, W and Badran, B and Fayyad-Kazan, M}, title = {MicroRNAs in Long COVID: Key Regulators, Biomarkers, and Therapeutic Targets of Post-SARS-CoV-2 Sequelae.}, journal = {Biomolecules}, volume = {16}, number = {2}, pages = {}, pmid = {41750353}, issn = {2218-273X}, mesh = {Humans ; *COVID-19/genetics/complications/virology/metabolism ; *MicroRNAs/genetics/metabolism/blood ; Biomarkers/metabolism/blood ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), is clinically defined by persistent symptoms that endure beyond acute infection and affect multiple organ systems, including the immune, cardiopulmonary, neurological, and metabolic axes. The underlying mechanisms remain poorly resolved, limiting the development of targeted diagnostics and therapeutics. MicroRNAs (miRNAs), as key post-transcriptional regulators of gene expression, control inflammatory networks, antiviral responses, mitochondrial bioenergetics, and fibrotic pathways, all of which are implicated in long COVID pathogenesis. Recent studies show durable changes in circulating miRNA signatures months after recovery from the acute phase, suggesting a role in maintaining chronic immune activation and metabolic dysfunction. Importantly, circulating miRNAs are stable, quantifiable in biofluids, and reflect systems-level dysregulation, positioning them as promising biomarker candidates for patient stratification, symptom clustering, and disease monitoring. Moreover, miRNA-directed interventions, such as mimics and antagomiRs, represent an emerging precision-medicine strategy to correct sustained molecular disturbances. This review summarizes current evidence linking miRNAs to long COVID, highlights their biomarker potential, and discusses therapeutic avenues that may help advance mechanism-based interventions for this globally emerging chronic condition.}, }
@article {pmid41751338, year = {2026}, author = {Notarte, KI and Catahay, JA and Velasco, JV and Ver, AT and Lee, J and Rizk, JG and Lippi, G and Fernández-de-Las-Peñas, C}, title = {Complement System Dysregulation in the Immunopathogenesis of Long COVID: Systematic Evidence Synthesis.}, journal = {Biomedicines}, volume = {14}, number = {2}, pages = {}, pmid = {41751338}, issn = {2227-9059}, abstract = {Background/Objective: Long COVID is an important cause of disability following SARS-CoV-2 infection; yet, its underlying mechanisms are not completely understood. One proposed mechanism is the long-lasting dysregulation of the immune complement system. This systematic review is the first to summarize the current evidence and evaluate the potential role of long-lasting complement activation in people with long COVID. Methods: A systematic electronic search on PubMed, MEDLINE, CINAHL, and Embase was conducted up to 15 October 2025, to identify studies investigating complement activation in people with the post-COVID-19 condition. The Newcastle-Ottawa Scale was used to evaluate the risk of bias and methodological quality. Results: Among the 247 studies initially identified, eleven met the inclusion criteria, comprising 1435 individuals (age: 48.5 years, 70% females) with long COVID and 1124 controls (age: 43.6 years, 60% females). All studies were of a high quality, with scores ranging from 7 to 8 stars (mean: 7.6 ± 0.5). The activation of the classical complement pathway was investigated in nine studies, whereas the lectin, alternative, and terminal complement pathways were each assessed in three studies. Multiple studies investigated several complement pathways. The results were heterogeneous since several markers of complement activation spanning the classical (C2, C4a, C4b, and C1s-C1INH), alternative (Ba, iC3b, and Factor D), and terminal (C5bC6, C5a, C9, and TCC) pathways were elevated, whereas other markers were not significantly different (C3, C4, and C4d) between patients with/without long COVID. In addition, markers spanning the lectin complement pathway (MBL, and MASP1-C1INH) were not significantly different between individuals with and without long COVID. Conclusions: The current evidence suggests potential long-lasting complement system dysregulation in individuals with long COVID, although the clinical significance remains controversial, due to heterogenous findings. Specific post-COVID symptom clusters, such as fatigue, dyspnea, or brain fog, have been linked to a distinct pattern of complement dysregulation. Substantial methodological heterogeneity, including differences in follow-up periods, complement markers, assessment methods, and control groups, along with the small number of available studies, underscores the need for further research to clarify the mechanisms linking complement dysregulation to long COVID.}, }
@article {pmid41754151, year = {2026}, author = {Caliman-Sturdza, OA and Gheorghita, RE and Soldanescu, I and Dimian, M and Mangul, S}, title = {Vitamin D in Infectious Diseases: A Narrative Review Focusing on COVID-19, Long COVID, and Influenza.}, journal = {Nutrients}, volume = {18}, number = {4}, pages = {}, pmid = {41754151}, issn = {2072-6643}, mesh = {Humans ; *Vitamin D/therapeutic use/blood/administration &amp; dosage/analogs &amp; derivatives ; *COVID-19/immunology/complications ; *Influenza, Human/immunology/drug therapy ; *Vitamin D Deficiency/immunology/complications/drug therapy ; Dietary Supplements ; SARS-CoV-2 ; Immunity, Innate/drug effects ; Vitamins ; }, abstract = {Vitamin D is a secosteroid hormone traditionally recognized for its role in bone and mineral metabolism, but it is increasingly understood to also function as an important immunomodulator influencing susceptibility to and outcomes of infectious diseases. This narrative review summarizes current evidence on the immunological, clinical, and preventive effects of vitamin D in the context of novel coronavirus disease (COVID-19), post-acute sequelae of SARS-CoV-2 infection (long COVID), and influenza. Mechanistically, vitamin D enhances innate immune defenses through the induction of antimicrobial peptides, including cathelicidin and defensins, and modulates adaptive immunity by suppressing maladaptive Th1/Th17 responses while promoting regulatory T-cell activity. Observational studies have frequently associated vitamin D deficiency with more severe COVID-19 outcomes; however, these associations may be influenced by confounding factors and reverse causality. Some meta-analyses suggest that vitamin D supplementation reduced rates of intensive care unit admission and ventilatory support, particularly among older adults and individuals with low baseline serum 25-hydroxyvitamin D concentrations. Emerging evidence also indicates that inadequate vitamin D status may be associated with an increased risk and symptom burden of long COVID, although causality has not been established. In the case of influenza, a limited number of randomized controlled trials (RCTs) and meta-analyses report a modest but statistically significant reduction in infection risk, especially with daily or weekly vitamin D supplementation in populations with low baseline vitamin D levels. Clinical guidelines consistently recommend maintaining adequate vitamin D status for general health but do not endorse high-dose vitamin D as a treatment for COVID-19 due to inconsistent trial findings. Overall, vitamin D should not be considered a standalone therapeutic agent; rather, maintaining sufficient vitamin D levels represents a low-risk, potentially beneficial strategy to support immune resilience against respiratory viral infections.}, }
@article {pmid41754590, year = {2026}, author = {De Stefanis, S and Colavita, F and Maggi, F and Antonioli, M}, title = {SARS-CoV-2 Persistence and the Gut Microbiota: New Insights into Long COVID Pathogenesis.}, journal = {Viruses}, volume = {18}, number = {2}, pages = {}, pmid = {41754590}, issn = {1999-4915}, support = {Ricerca Corrente Linea 1 - Progetto 1 to IRCCS INMI L. Spallanzani//Ministero della Salute/ ; Ricerca di Ateneo 2024- Dipartimento di Biologia (AutoCuRC)//University of Rome Tor Vergata/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *COVID-19/complications/microbiology/virology/immunology/pathology ; *SARS-CoV-2/physiology/pathogenicity ; Dysbiosis/microbiology ; Inflammation ; Gastrointestinal Tract/virology/microbiology ; Inflammatory Bowel Diseases/microbiology ; }, abstract = {In December 2019, the world experienced the emergence of a new virus, SARS-CoV-2, which caused the 2020 pandemic. SARS-CoV-2 causes COVID-19, primarily affecting the respiratory system, as well as the gastrointestinal tract. Remarkably, one in eight COVID-19 patients develops Long COVID, which is linked to SARS-CoV-2 persistence in the gastrointestinal tract, resulting in chronic inflammation and microbiota dysregulation. Given that gut microbiota dysbiosis plays a pivotal role in antiviral defense and gastrointestinal conditions, here we examine emerging evidence on how persistent SARS-CoV-2 infection may contribute to the aetiology of enteric disorders. In particular, we emphasise the intricate connection between chronic inflammation caused by persistent SARS-CoV-2 infection (e.g., irritable bowel syndrome and inflammatory bowel disease) and the possible development of diseases such as Crohn's disease and ulcerative colitis.}, }
@article {pmid41768410, year = {2026}, author = {Hung, TS}, title = {Rehabilitation strategies for long COVID: integrating human factors engineering.}, journal = {Frontiers in rehabilitation sciences}, volume = {7}, number = {}, pages = {1708460}, pmid = {41768410}, issn = {2673-6861}, abstract = {Long COVID presents unique challenges that extend beyond conventional biomedical rehabilitation, necessitating strategies that are adaptive, multidisciplinary, and patient-centered. This mini-review synthesizes current evidence on physical, cognitive, and occupational rehabilitation, and introduces human factors engineering as a framework to optimize the design, delivery, and usability of interventions. Emerging approaches such as telerehabilitation, cognitive ergonomics, and structured return-to-work programs illustrate the value of integrating clinical rehabilitation with user-centered design. Yet critical gaps remain, including the limited number of randomized controlled trials, the heterogeneity of outcome measures, and the lack of systematic integration between rehabilitation and human factors research. Addressing these challenges will be essential to develop effective, scalable, and sustainable interventions. By aligning rehabilitation protocols with the principles of human factors engineering, future practice can better enhance efficacy, promote sustained patient engagement, and ultimately improve the quality of life for individuals living with long COVID.}, }
@article {pmid41782085, year = {2026}, author = {Heugno, VJN and Kamdem, OL and Same, EGE and Lele, ECB and Biloa, YM and Ayina, CA and Guyot, J and Bongue, B and Mandengue, SH and Moukoko, CEE}, title = {Factors associated with long COVID in sub-Saharan Africa: a scoping review.}, journal = {BMC infectious diseases}, volume = {26}, number = {1}, pages = {}, pmid = {41782085}, issn = {1471-2334}, support = {ANRS283//ANRS - Agence Nationale de la Recherche / Emerging Infectious Diseases/ ; }, mesh = {Humans ; *COVID-19/epidemiology/complications ; Africa South of the Sahara/epidemiology ; Risk Factors ; SARS-CoV-2 ; Female ; Male ; Comorbidity ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long COVID is a condition characterized by persistent symptoms of COVID-19 that continue to occur in patients after apparent recovery. Given that, these symptoms may vary from person to person due to clinical, demographic, and genetic factors as well as comorbidities, our review aims to identify and analyze risk factors associated with persistent symptoms of COVID-19 (long COVID) in the specific context of sub-Saharan Africa.<br><br>METHODS: Article searches were conducted in the PubMed, Scopus, African Journals Online (AJOL), Science Direct and Google Scholar databases using the keywords "long COVID" or "long-term COVID-19" or "post-COVID condition" or "post-acute sequelae of COVID-19" and "sub-Saharan Africa" or "sub-Saharan Africans". The obtained data were entered into software for duplication checking. Two reviewers selected and extracted the data. Due to substantial heterogeneity in definitions and study designs, a narrative synthesis approach was adopted. Fifteen studies were included in this review, totaling 8,233 participants previously infected with SARS-CoV-2, with approximately 2,011 patients with long COVID from six countries. Six studies were cross-sectional, three were retrospective, three were cohort studies, two were case-control, and one was a case report.<br><br>RESULTS: The review found that the prevalence of long COVID in sub-Saharan Africa ranged from 2% in Ghana to 66.7% in South Africa. The persistent COVID-19 symptoms most commonly experienced by people living in sub-Saharan Africa were fatigue (reported in 12 studies, 25-66% of patients), cough (7 studies, 9-86%), chest pain (9 studies, 9%-29%), dyspnea (10 studies, 15-45%), palpitations (4 studies, 10-30%), headache (9 studies, 12-38%), and cognitive impairment (6 studies, 8-20%). The main risk factors for the occurrence of persistent COVID-19 symptoms were older age (&#x2c3; 60 years), female sex, low education level, hypertension, type 2 diabetes, cardiovascular disease, length of hospitalization during the acute episode, number of initial COVID-19 symptoms, and initial disease severity.<br><br>CONCLUSION: Long COVID is a reality in sub-Saharan Africa. Fatigue and hypertension have proven to be the most common symptom and risk factor, respectively. The heterogeneity of long COVID definitions across studies limits direct prevalence comparisons. Given the socio-economic challenges, pre-existing comorbidities and differences in health systems in the sub-Saharan region, it is therefore necessary to develop new strategies for care, rehabilitation and treatment (specific to the realities of the sub-Saharan region) targeted at each persistent symptom of COVID-19 in order to resolve this emerging problem and allow patients to have a good quality of life.<br><br>CLINICAL TRIAL NUMBER: Not applicable.}, }
@article {pmid41790576, year = {2026}, author = {Morcos, ZL and Theoharides, TC}, title = {Long COVID neuropathy: The role of mast cells.}, journal = {Journal of neuropathology and experimental neurology}, volume = {85}, number = {5}, pages = {413-424}, doi = {10.1093/jnen/nlag016}, pmid = {41790576}, issn = {1554-6578}, mesh = {Humans ; *Mast Cells/immunology ; *COVID-19/complications/immunology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Peripheral Nervous System Diseases/immunology/etiology ; Animals ; }, abstract = {Postacute sequelae of SARS-CoV-2 infection (PASC), or Long COVID, is estimated to affect over 60 million individuals globally, with almost half of COVID-19 survivors experiencing persistent symptoms such as neuropathic pain, fatigue, and autonomic dysfunction. Despite its prevalence, the pathophysiology of PASC remains poorly understood. This narrative review highlights activation of mast cells (MCs), the unique tissue immune cells as a central contributor to neuropathic manifestations in PASC. Mast cell locations near nerves and vessels allows them to regulate neuroimmune and neurovascular processes. Mast cell activation mirrors patterns seen in small-fiber neuropathy and myalgic encephalomyelitis/chronic fatigue syndrome, suggesting a shared immune-mediated etiology. The SARS-CoV-2 spike protein has been shown to activate MCs via angiotensin-converting enzyme 2 and toll-like receptor 4, triggering release of pro-inflammatory and neurotoxic mediators, including interleukin-1β, interleukin-6, tumor necrosis factor alpha, histamine, and tryptase. Such mediators sensitize peripheral nerves, disrupt the blood-brain barrier, and recruit microglia, ultimately contributing to small-fiber injury, neuroinflammation, and dysautonomia. Emerging reports suggest benefit from MC-directed treatments although responses remain variable. Understanding the role of MCs in PASC may offer a plausible mechanism of pathogenesis and guide targeted therapies. Future studies are needed to validate these findings and improve PASC patient outcomes.}, }
@article {pmid41795913, year = {2026}, author = {Thorpe, DW and Jones, LA and Martin, AM and Coleman, RA and Allman, C and Peterson, RA and Keating, DJ}, title = {The role of peripheral serotonin in SARS-CoV-2 infectivity, COVID-19 treatment and long COVID.}, journal = {Immunology and cell biology}, volume = {104}, number = {4}, pages = {368-376}, pmid = {41795913}, issn = {1440-1711}, mesh = {Humans ; *Serotonin/metabolism ; *COVID-19/virology/metabolism/complications ; *SARS-CoV-2/physiology/pathogenicity ; Selective Serotonin Reuptake Inhibitors/therapeutic use ; *COVID-19 Drug Treatment ; Virus Internalization ; Gastrointestinal Tract/virology/metabolism ; Animals ; }, abstract = {Gastrointestinal symptoms have emerged as a common, but underappreciated, cause of morbidity in relation to SARS-CoV-2 infection and the COVID-19 pandemic. This manifests as a range of indications including diarrhea, anorexia, nausea, vomiting and abdominal pain. In addition, the gastrointestinal tract may represent a route of viral entry via the epithelial cell layer lining the gut wall. This route of entry could be a significant component of disease pathogenesis, including effects on the nervous system via the gut-brain axis. In this review, we provide an assessment of the effects of COVID-19 on the gastrointestinal system, its involvement in disease severity and potential pathways for viral entry and infection in the gastrointestinal tract. We also examine evidence that gut-derived serotonin is affected by SARS-CoV-2 infection, how this may link to symptoms and disease pathogenesis and the potential link to the efficacy of selective serotonin reuptake inhibitors in reducing COVID-19 severity.}, }
@article {pmid41796425, year = {2026}, author = {Peñaherrera-Vásquez, D and Reina, A and Merlo, F and Fajardo-Loaiza, T and Zambrano-Sánchez, G and Rivadeneira, J and Fuenmayor-González, L}, title = {Unveiling the genitourinary phenotype of long COVID: a systematic review and meta-analysis.}, journal = {International urology and nephrology}, volume = {}, number = {}, pages = {}, pmid = {41796425}, issn = {1573-2584}, abstract = {IMPORTANCE: Long COVID has been associated with persistent multisystemic manifestations. However, genitourinary alterations have not been formally recognized as a distinct phenotype despite growing reports suggesting their relevance for long-term morbidity and quality of life.<br><br>OBJECTIVES: To determine the frequency and characteristics of genitourinary manifestations in patients with long COVID and to evaluate the evidence supporting the possible emergence of a genitourinary phenotype within long COVID.<br><br>DATA SOURCES: For this Systematic review and meta-analysis, a comprehensive search was conducted in PubMed (MEDLINE), Scopus, Web of Science, Embase, SciELO, and Bireme-BvS from inception to October 2025, without language or publication date restrictions. Observational studies (cross-sectional, cohort, or case-control) assessing individuals with one or more genitourinary symptoms-such as menstrual alterations, erectile dysfunction, urinary tract symptoms, or renal function decline-persisting&#x2009;&#x2265;&#x2009;12&#xa0;weeks after SARS-CoV-2 infection were included. Studies addressing only acute-phase manifestations, vaccine-related effects, or pre-existing genitourinary conditions were excluded.<br><br>DATA EXTRACTION AND SYNTHESIS: Data extraction was performed independently by two reviewers following PRISMA guidelines. Risk of bias (RoB) was assessed using the Joanna Briggs Institute checklist for prevalence studies. A random-effects meta-analysis using the Freeman-Tukey double arcsine transformation was applied to estimate pooled proportions, and heterogeneity was quantified using the I[2] statistic, Cochran's Q test, and the between-study variance (&#x3c4;[2]).<br><br>MAIN OUTCOMES AND MEASURES: The primary outcomes were the pooled frequencies of genitourinary manifestations in long COVID, including menstrual disorders, erectile dysfunction, and renal function decline.<br><br>RESULTS: Nine primary studies encompassing 2332 participants from eight countries were included. Most studies (88.9%) presented a low RoB. The pooled frequency of menstrual disorders was 49% (95% CI 24-74), erectile dysfunction 21% (95% CI 16-28), and renal function decline 29% (95% CI 20-39).<br><br>CONCLUSIONS AND RELEVANCE: This systematic review and meta-analysis provide evidence supporting the possible emergence of a genitourinary phenotype of long COVID, encompassing menstrual irregularities, erectile dysfunction, cystitis-like symptoms, and renal impairment. Recognition of this potential phenotype is crucial for improving diagnostic accuracy, patient follow-up, and multidisciplinary management. Further high-quality studies are warranted to elucidate the underlying mechanisms and long-term clinical implications.}, }
@article {pmid41809272, year = {2026}, author = {Zarkadi, A and Katotomichelakis, M and Chaidas, K}, title = {Long-Term Olfactory Dysfunction in COVID-19 Patients: A Systematic Review.}, journal = {Cureus}, volume = {18}, number = {2}, pages = {e103143}, pmid = {41809272}, issn = {2168-8184}, abstract = {Olfactory dysfunction (OD) emerged early in the COVID-19 pandemic as a prevalent and often persistent symptom. While most individuals recover within weeks, a significant proportion continue to suffer from long-term impairments, including both quantitative and qualitative sensory deficits. Our review aimed to summarize current evidence on long-term post-COVID-19 OD with a duration of at least three months, including prevalence, recovery trajectory, and prognostic factors. The PubMed and Scopus databases were searched for relevant studies up to August 2024 following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Twenty-one studies were ultimately included, involving over 4,000 individuals. A remarkable proportion of patients continue to experience persistent dysfunction post-infection for a period ranging from several months to over two years. Qualitative disorders, such as parosmia and phantosmia, frequently appeared during recovery. Prognosis seemed to be related to age, initial severity, duration of OD, co-existing symptoms, and potentially sex. A consistent discrepancy between subjective reports and objective psychophysical test results was observed. Methodological heterogeneity limited comparability across studies. Olfactory dysfunction is a significant and often overlooked long-term complication of COVID-19. Standardized diagnostic criteria, validated outcome measures, and prospective longitudinal research are urgently needed to guide evidence-based management and improve patient outcomes.}, }
@article {pmid41814585, year = {2026}, author = {Caliman-Sturdza, OA and Gheorghita, R and Lobiuc, A and Filip, R and Soldanescu, I and Mangul, S and Dimian, M}, title = {Management of long COVID-19 in children and adolescents: from diagnosis to therapeutically approaches.}, journal = {Annals of medicine}, volume = {58}, number = {1}, pages = {2642510}, pmid = {41814585}, issn = {1365-2060}, mesh = {Humans ; *COVID-19/therapy/complications/diagnosis ; Child ; Adolescent ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Long Coronavirus disease 2019 (COVID-19), also termed post-acute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC), has emerged as a complex multisystem condition in children and adolescents worldwide. It can occur even after mild or asymptomatic acute infections, with symptoms that may persist, fluctuate, or relapse over time. This review aims to comprehensively explore the characteristic manifestations, management and current therapeutic possibilities of pediatric Long COVID-19 (L-C19).<br><br>METHODS: A systematic search was conducted in multiple databases such as PubMed, Scopus, Web of Science, and Google Scholar, for literature published between January 2020 and October 2025.<br><br>RESULTS: Diagnosing pediatric L-C19 is challenging due to the heterogeneity of symptoms and lack of specific diagnostic biomarkers. Most young patients experience gradual improvement over months, but a significant subset remains symptomatic for >1&#x2009;year with substantial disability, underscoring the need for timely diagnosis and intervention. Current clinical consensus emphasizes an individualized, multidisciplinary management approach focused on symptom relief and functional rehabilitation. No definitive cure exists for L-C19; thus, care is tailored to each patient's predominant issues. Therapeutic strategies combine supportive self-management (e.g. energy conservation and pacing) with both non-pharmacological and pharmacological interventions. Multimodal rehabilitation programs - including graded exercise therapy and cognitive behavioral therapy - have shown promise in improving fatigue, mental health, and overall quality of life. Targeted treatments for specific sequelae (such as autonomic dysfunction or chronic pain) are applied on a case-by-case basis, although high-quality evidence for medications remains limited. Globally, interdisciplinary collaborations have been established to provide harmonized diagnostic and treatment protocols, and major research initiatives are underway to evaluate novel therapies and include children in L-C19 clinical trials.<br><br>CONCLUSION: Ongoing international efforts to develop standardized diagnostic tools, outcome measures, and evidence-based interventions are crucial to optimize care and long-term outcomes for children and adolescents affected by L-C19.}, }
@article {pmid41816409, year = {2026}, author = {Chai, X and Qi, H and Liu, X and Zhou, F and Jiang, Y and Wu, M and Lian, S and Wang, L and Bao, Y}, title = {A narrative review of SARS-CoV-2 variants and long COVID.}, journal = {Journal of thoracic disease}, volume = {18}, number = {2}, pages = {164}, pmid = {41816409}, issn = {2072-1439}, abstract = {BACKGROUND AND OBJECTIVE: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the onset of the pandemic, there has been a continuous rise in cases of both COVID-19 and long COVID. It is acknowledged that long COVID is a multisystem disorder with a wide range of symptoms; its primary symptoms and indicators include fatigue, dyspnea, anosmia, myalgia, cough, and hyposmia. SARS-CoV-2 has continuously evolved since the wild strain first appeared, resulting in numerous genetic variants. These strains exhibit significant differences in terms of pathogenicity and immune evasion. Key scientific questions remain regarding whether and how these variations influence the development and clinical course of long COVID. This review aims to examine associations between SARS-CoV-2 strains and long COVID, synthesize current evidence, identify research gaps, and provide recommendations for subsequent rehabilitation treatments.<br><br>METHODS: Literature searches were conducted using PubMed, focusing on publications from January 2020 to August 2025. Relevant literature on long COVID and SARS-CoV-2 variants was systematically reviewed and summarized, and included in this review.<br><br>KEY CONTENT AND FINDINGS: This review highlights the ongoing genetic evolution of SARS-CoV-2 as a key temporal dynamic during the pandemic. Different SARS-CoV-2 variants result in varying severity of long COVID. Anti-inflammatory treatments demonstrate significant efficacy for long COVID patients. COVID-19 vaccination prior to SARS-CoV-2 infection reduces the risk of long COVID, and another successful treatment option for persistent COVID symptoms is physical therapy.<br><br>CONCLUSIONS: Long COVID remains a significant public health challenge. The relationship between SARS-CoV-2 variants and long COVID requires further elucidation. This condition may cause significant economic and medical burdens in the future. To completely protect the physical and mental health of long COVID patients, it is essential to broaden therapeutic options and create individualized therapy programs. Therefore, understanding the connection between long COVID and SARS-CoV-2 variants is crucial. Based on this knowledge, effective strategies must be designed to empower individuals in proactively addressing and managing long COVID.}, }
@article {pmid41824149, year = {2026}, author = {van der Feltz-Cornelis, CM}, title = {Cognition and Long COVID: a Review.}, journal = {Current neurology and neuroscience reports}, volume = {26}, number = {1}, pages = {}, pmid = {41824149}, issn = {1534-6293}, }
@article {pmid41835098, year = {2026}, author = {Dos Santos, LPM and Leão, JV and Silva, KYBM and Dos Santos, DL and Batista, CN and Barros, JA and Paranhos, ACM and Dias, &#xc1;RN and Falcão, LFM}, title = {Transcranial stimulation as a possible therapeutic proposal in long COVID.}, journal = {Frontiers in rehabilitation sciences}, volume = {7}, number = {}, pages = {1766757}, pmid = {41835098}, issn = {2673-6861}, abstract = {The COVID-19 pandemic triggered an unprecedented global health crisis, with significant repercussions on the mental and neurological health of millions of individuals. Long COVID, characterized by persistent and debilitating symptoms, including chronic fatigue, pain, cognitive impairment, and mood swings, represents a substantial therapeutic challenge. In this context, neuromodulation emerges as a promising therapeutic strategy, offering new perspectives for the management of refractory neurological symptoms. This article aims to critically review the current evidence on the use of neuromodulation in patients with long COVID.}, }
@article {pmid41836927, year = {2026}, author = {Baptista, SN and Atkins, T and Chakraborty, S and Bakhit, M and Glasziou, P and Byambasuren, O}, title = {Candidate treatments for long COVID: a narrative review of expert and patient-driven priorities.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1734600}, pmid = {41836927}, issn = {2296-858X}, abstract = {OBJECTIVE: To map the existing evidence for candidate treatments for long COVID that were prioritised by clinicians and people with lived experience, and to characterise their feasibility, acceptability and safety.<br><br>STUDY DESIGN: The study was conducted as a narrative review using pragmatic methods including iterative stakeholder-informed decision-making a monthly-updated evidence search, rapid lay evidence summaries and a structured research prioritisation process.<br><br>DATA SOURCES: Potential candidate treatments were identified via a combination of database and trial registry searches. These were then ranked by clinicians and people with lived experience using surveys. Evidence summaries for the top 14 interventions (low-dose naltrexone, antivirals, metformin, nicotine, vagus nerve stimulation, antihistamines, guanfacine, colchicine, nattokinase, intravenous immunoglobulins, monoclonal antibodies, coenzyme Q10, multicomponent rehabilitation packages, and exercise training) were created. Prioritised treatments were collated first by searching a collaborative living evidence database (updated monthly) of relevant systematic reviews and randomised controlled trials and then by conducting supplementary searches of other study designs.<br><br>DATA SYNTHESIS: Six of 14 interventions had long-COVID-specific randomised controlled trial (RCT) evidence (exercise [16 RCTs], multicomponent packages [5 RCTs], coenzyme Q10 [2 RCTs], antivirals [1 RCT], vagus nerve stimulation [1 pilot RCT], monoclonal antibodies [1 small RCT]); the remainder relied on indirect or very low-certainty data (e.g., uncontrolled studies or mechanistic rationale). Across interventions, evidence certainty was mostly low to very low, and safety/feasibility varied.<br><br>CONCLUSION: This review prioritises and maps candidate treatments for long COVID. There was insufficient direct evidence to inform clinical recommendations. Rather, the treatments presented in this review represent those that could be rigorously tested in clinical trials as they show biological plausibility and/or are feasible and acceptable to people with lived experience and clinicians.<br><br>REGISTRATION: A review protocol was not prospectively registered because the review adopted an iterative approach to support priority setting rather than clinical guidance.}, }
@article {pmid41847505, year = {2026}, author = {Chagay, N and Tamadon, A and Kim, S and Dossimov, A and Issanguzhina, Z and Tulegenova, G and Kuldeeva, G and Puxovikova, N and Kim, I and Mussin, NM and Sharoffidin, RS}, title = {Pediatric-related post-COVID condition (long COVID) research and its foundational influences: a bibliometric analysis (2020-2025).}, journal = {Frontiers in pediatrics}, volume = {14}, number = {}, pages = {1677983}, pmid = {41847505}, issn = {2296-2360}, abstract = {BACKGROUND: The COVID-19 pandemic significantly influenced healthcare systems worldwide. The long-term consequences of the infection in children, the phenomenon of post-COVID-19 syndrome, have been attracting increasing attention of the scientific community. The present study is a bibliometric analysis of publications addressing post-COVID (long COVID) complications in pediatric population over the period 2020-2025.<br><br>METHODS AND MATERIALS: The analysis covers 1,292 records retrieved from Scopus and Web of Science (search date: June 2025). Records were retrieved using post-COVID condition/long COVID terminology combined with pediatric-related keywords; therefore, the corpus includes pediatric-focused studies as well as influential general PCC publications indexed with pediatric terms and frequently cited in pediatric research. The search strategy combined post-COVID condition/long COVID terminology with pediatric terms (child/infant/adolescent), applying filters for English language, publication years 2020-2025, and document type (articles and reviews). Data were merged and analyzed in R using bibliometrix/Biblioshiny to describe productivity, collaboration, citations, and thematic structure.<br><br>RESULTS: The retrieved corpus included 1,292 publications from 84 countries/regions. The United States led productivity with 270 publications (20.9%), followed by the United Kingdom (114; 8.8%) and China (90; 7.0%). The most frequent author keywords included "COVID-19" (n&#x2009;=&#x2009;900) and "long COVID" (n&#x2009;=&#x2009;818). Highly cited items predominantly consisted of general or mixed-age PCC frameworks, indicating that foundational long COVID literature substantially shapes citation patterns within pediatric-tagged publications. Thematic mapping showed symptom-focused clusters as dominant, while MIS-C and cognitive impairment were less prominent in author-keyword frequency and thematic clustering within the retrieved dataset.<br><br>CONCLUSION: The findings describe the pediatric-term-indexed PCC research landscape and highlight substantial gaps in pediatric-specific evidence, definitions, and longitudinal data.}, }
@article {pmid41848128, year = {2025}, author = {Hajji, H and Kalai, A and Chaabeni, A and Migaou, H and Jebali, B and Ben Salah Frih, Z and Ben Saad, H and Jellad, A}, title = {Beyond the basics: exploring non-conventional treatment for fatigue in post-acute COVID-19 syndrome.}, journal = {La Tunisie medicale}, volume = {103}, number = {9}, pages = {1265-1271}, doi = {10.62438/tunismed.v103i9.5926}, pmid = {41848128}, issn = {2724-7031}, mesh = {Humans ; *COVID-19/complications/therapy ; Post-Acute COVID-19 Syndrome ; *Fatigue/therapy/etiology ; SARS-CoV-2 ; Dietary Supplements ; Acupuncture Therapy/methods ; }, abstract = {INTRODUCTION: Post-acute 2019 coronavirus disease syndrome (PACS) is a multifaceted, multisystem disorder affecting an estimated 75 million individuals globally (in May 2024). Defined by symptoms persisting beyond four weeks post-infection, PACS manifests in subacute (4-12 weeks) and chronic (>12 weeks) phases, with fatigue being a prominent and debilitating feature. Comprehensive management of PACS-associated fatigue needs diverse therapeutic strategies extending beyond conventional rehabilitation.<br><br>AIM: This narrative review explored non-conventional interventions for PACS-related fatigue, focusing on treatments involving nutritional rehabilitation, physical modalities, and other innovative therapies.<br><br>METHODS: Narrative review.<br><br>RESULTS: Treatments reported in the literature include melatonin, QingjinYiqi, nutritional supplements, aromatherapy, antioxidants, Tai Chi, acupuncture, yoga, singing, hyperbaric oxygen therapy (HBOT), pulsed electromagnetic field therapy, and whole-body vibration. Melatonin and QingjinYiqi have shown notable improvements in fatigue and overall health. Nutritional supplements such as vitamin-minerals combinations have demonstrated enhancements in muscle strength, physical performance, and quality of life. Tai Chi, acupuncture, and yoga have shown positive effects on fatigue, muscle strength, and overall well-being. Aromatherapy, singing, HBOT, pulsed electromagnetic field therapy, and whole-body vibration effectively reduce fatigue while enhancing physical and cognitive functions.<br><br>CONCLUSION: These non-conventional treatments offer promising supplementary benefits to conventional rehabilitation.}, }
@article {pmid41859298, year = {2026}, author = {Blitshteyn, S and Doherty, TA and Steinman, L}, title = {Postural Orthostatic Tachycardia Syndrome, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID as Neuroimmune Disorders.}, journal = {ImmunoTargets and therapy}, volume = {15}, number = {}, pages = {581262}, pmid = {41859298}, issn = {2253-1556}, abstract = {Postural orthostatic tachycardia syndrome (POTS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID are heterogeneous disorders with overlapping complex, multi-factorial and multi-systemic pathophysiology. POTS and ME/CFS are the most common phenotypes of Long COVID that can lead to significant disability and functional impairment. The exact pathophysiologic mechanisms of these disorders alone or in combination are still being investigated, but important mechanistic factors have been identified, such as autonomic dysfunction, immune dysregulation, autoimmunity, mitochondrial dysfunction, cerebral hypoperfusion, and neuroinflammation. To this end, we believe that these conditions should be viewed as neuroimmune disorders and should be included in the field of neuroimmunology, with its educational curriculum, training, and clinical care pathways. Including these disorders as part of neuroimmunology subspecialty is the key to advancing the science and clinical care of this underserved patient population with these complex and disabling conditions.}, }
@article {pmid41861833, year = {2026}, author = {Alger, E and Regnault, A and Dueck, AC and Pe, M and Grayling, MJ and Calvert, MJ and Hansen, AR and Kholmanskikh, O and Lai-Kwon, J and Lee, JJ and Minchom, A and Qiao, Y and Rantell, KR and Roydhouse, J and Snyder, C and Symeonides, SN and Wages, NA and Wilson, R and Yap, C}, title = {A practical toolkit with recommendations for analysing and visualising patient-reported outcomes in early phase dose-finding oncology trials (OPTIMISE-AR).}, journal = {The Lancet. Oncology}, volume = {27}, number = {4}, pages = {e218-e230}, doi = {10.1016/S1470-2045(26)00018-5}, pmid = {41861833}, issn = {1474-5488}, mesh = {Humans ; *Patient Reported Outcome Measures ; *Neoplasms/drug therapy ; *Antineoplastic Agents/administration &amp; dosage/adverse effects ; Dose-Response Relationship, Drug ; Maximum Tolerated Dose ; *Clinical Trials as Topic/methods ; Research Design ; }, abstract = {Patient-reported outcomes (PROs) are increasingly recognised for their role in assessing tolerability in dose-finding oncology trials (DFOTs). However, analysis and reporting of PRO data within DFOTs are often unclear and inconsistent. OPTIMISE-AR (Incorporating Patient-Reported Outcomes in Dose-Finding Trials-Analysis Recommendations) establishes a practical toolkit supporting the statistical analysis, visualisation, and reporting of PRO data within DFOT publications. International, multidisciplinary, cross-sector statistical analysis and data visualisation working groups identified analytical and visualisation approaches for PROs data, addressing key DFOT PRO research objectives. Informed by existing literature, case studies and recommendations are provided in this Policy Review for analysing binary, ordinal, and continuous PRO data to assess tolerability across doses and timepoints, and to integrate PROs into interim and final dose-decision processes. The OPTIMISE-AR toolkit is structured around four methodological domains aligned with key DFOT PRO research objectives, providing statistical analysis and data visualisation recommendations for (1) PRO endpoints across timepoints, (2) PRO endpoints between timepoints, (3) time-to-event PRO endpoints, and (4) PRO endpoints for formal dose-decision making in model-based dose-finding designs. As PROs have an increasing role in tolerability assessment, this Policy Review promotes analysis and data visualisation of PRO data, facilitating robust, patient-centred tolerability conclusions and supporting the broader development of tolerable and effective treatments.}, }
@article {pmid41862909, year = {2026}, author = {Khalid, K and Abdullah, ADI and Lim, HX and Ali, RAR}, title = {Pharmacological and non-pharmacological management of long COVID.}, journal = {Virology journal}, volume = {23}, number = {1}, pages = {}, pmid = {41862909}, issn = {1743-422X}, mesh = {Humans ; *COVID-19/complications/therapy ; Probiotics/therapeutic use ; SARS-CoV-2 ; Dysbiosis/therapy ; *COVID-19 Drug Treatment ; Gastrointestinal Microbiome ; Post-Acute COVID-19 Syndrome ; }, abstract = {Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a major global health burden in terms of acute infection and long-term consequences. Approximately 10% of infected experience autonomic dysfunction, cardiovascular complications, and neurological impairments. While immune dysregulation, persistent viral reservoirs, chronic inflammation, gut dysbiosis, and vascular dysfunction are implicated, the exact pathophysiological mechanisms of Long COVID remain unclear. Additionally, treatment options are limited and challenging to prescribe due to symptom heterogeneity. Non-pharmacological interventions such as increased salt intake, elimination diets for gastrointestinal symptoms, and cognitive pacing for fatigue may not be sufficient for severe symptoms. Moreover, pharmacological interventions such as β-blockers, calcium channel blockers, pyridostigmine, antihistamines, and low-dose naltrexone can improve tachycardia, fatigue, and brain fog but there are no standardized guidelines. In light of evidence supporting a strong association of Long COVID with gut dysbiosis, probiotics have emerged as a promising intervention. Clinical studies have shown that Bacillus coagulans, Bacillus subtilis, Lactobacillus acidophilus, and Bifidobacterium species can improve fatigue, gastrointestinal health, and overall physical and mental well-being in Long COVID patients. Large-scale randomized controlled trials are warranted to validate probiotic efficacy in Long COVID and reduce burden on individual health and healthcare institutions.}, }
@article {pmid41862917, year = {2026}, author = {Luo, S and Zheng, Z and Karimi, L and Plebanski, M and Lankatillake, C and Sheahan, J and Anderson, K and Jovanovski, N and Seal, EL and Cockshaw, W and Wollersheim, D and Cleary, S and El-Ansary, D and Flanagan, KL and Jessup, R and Abrahamson, S and Whyler, N and Fineberg, D and Scoullar, MJL and Seeley, MC and Tippett, E and Xenos, S and Itsiopoulos, C}, title = {Between silence and solutions: a global guideline review of long COVID care and services in Australia.}, journal = {BMC health services research}, volume = {26}, number = {1}, pages = {}, pmid = {41862917}, issn = {1472-6963}, abstract = {BACKGROUND: As the acute response to the COVID-19 pandemic shifts to long-term management, the lasting effects of infection are becoming increasingly evident. Long COVID continues to challenge healthcare systems, with many healthcare professionals reporting uncertainty about assessment and referral pathways. This updated review examines recent international guidelines alongside Australian services to identify gaps between guidelines and practice.<br><br>METHODS: Between April and October 2025, we searched for guidelines on Long COVID published in English and assessed their quality by applying the AGREE II appraisal tool. We also conducted a grey literature search to profile active Australian services providing Long COVID care.<br><br>RESULTS: Three new or updated guidelines were published in the United States, Canada, and New South Wales, Australia. Together with the World Health Organisation, United Kingdom and New Zealand guidelines identified in the previous review, all emphasise integrated, primary care-led approaches. Notably, Australian service delivery remains fragmented, with a growing number of primary health practitioner-led private services operating largely under a fee-for-service model, leading to variations in access and affordability. Many hospital-based outpatient clinics have been absorbed into existing chronic-disease services. The most fundamental challenge is statistical invisibility: without an activated diagnostic code, services cannot reliably identify or follow people living with Long COVID. This invisibility limits both surveillance and service planning.<br><br>DISCUSSION AND CONCLUSIONS: Australia is currently developing national clinical best-practice guidelines for ME/CFS, which may also benefit Long COVID; however, Australia remains behind comparable nations such as Canada, the United Kingdom, and the United States in developing and implementing the integrated, multidisciplinary care models recommended internationally. This has significant implications, namely that the rapid transition from hospital-based Long COVID clinics to primary care-led services has resulted in fragmented and uncoordinated care. Strengthening Australia&#x2019;s response will require national leadership and investment in workforce training, sustainable funding for care coordination, improved public and professional awareness, the establishment of primary care-led multidisciplinary pathways, and the activation of a dedicated diagnostic code. Also importantly, shifting to a patient-centred approach and patient-practitioner collaborative model of care is essential to prepare the health system for managing Long COVID and future complex, multi-system conditions.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12913-026-14268-w.}, }
@article {pmid41864480, year = {2026}, author = {Rauf, M and Naveed, A and Asghar, MU}, title = {Post-acute sequelae of COVID-19: A disorder of impaired innate immune resolution - A narrative review.}, journal = {Clinical immunology (Orlando, Fla.)}, volume = {285}, number = {}, pages = {110701}, doi = {10.1016/j.clim.2026.110701}, pmid = {41864480}, issn = {1521-7035}, mesh = {Humans ; *COVID-19/immunology/complications ; *Immunity, Innate/immunology ; *SARS-CoV-2/immunology ; Post-Acute COVID-19 Syndrome ; Alarmins/immunology ; Inflammation/immunology ; }, abstract = {Post-acute sequelae of COVID-19 (PASC) affect millions of people worldwide and are increasingly recognized as a disorder of failed innate immune resolution rather than a persistent viral infection. Emerging evidence shows that residual SARS-CoV-2 antigens, host-derived alarmins, reactivated latent viruses, and mucosal microbiome-derived products from oral-nasopharyngeal and gut reservoirs sustain the chronic activation of pattern-recognition receptors, inflammasomes, and complement pathways. In parallel, deficits in specialized pro-resolving mediators, impaired efferocytosis, and persistent tissue injury prevent physiological termination of inflammation. These unresolved cues drive long-lasting epigenetic and metabolic reprogramming of hematopoietic stem cells and myeloid lineages, creating maladaptive trained immunity states characterized by hyper-responsiveness or exhaustion of these cells. Thromboinflammatory processes, including aberrant NETosis and sustained interface signalingling, further reinforce self-perpetuating inflammatory circuits. Together, these pathways give rise to reproducible molecular endotypes, including thromboinflammatory, interferon-driven, and neuroinflammatory phenotypes, which explain clinical heterogeneity. Framing PASC as a disorder of impaired immune resolution within a mucosal microbial viral context provides a unifying mechanistic scaffold for biomarker identification and host-directed therapies. This review proposes that restoring active resolution programs, rebalancing metabolic-epigenetic networks, and dismantling pathogenic innate feedback loops are promising strategies for reversing the chronic immune imprint of PASC.}, }
@article {pmid41873998, year = {2026}, author = {Goh, GK and Foster, JA and Uversky, VN}, title = {Clues to Long COVID Linked to Virulence and Infectivity Found in Shell Proteins.}, journal = {Advances in respiratory medicine}, volume = {94}, number = {2}, pages = {}, pmid = {41873998}, issn = {2543-6031}, mesh = {Humans ; *COVID-19/virology ; *SARS-CoV-2/pathogenicity ; Virulence ; Animals ; }, abstract = {Clinical, experimental, and computational evidence of COVID-19 virulence and infectivity has been linked to SARS-CoV-2 shell disorder. A strong link was first discovered using an AI disorder-predicting tool, which detected an unusually hard (low disorder) outer shell among all SARS-CoV-2-related viruses but not in the 2003 SARS-CoV-1. This could account for the high infectivity found in SARS-CoV-2-but not in SARS-CoV-1-as it is believed that hard shells protect viral particles from the onslaught of the antimicrobial enzymes present in the respiratory system and saliva. As a result, much larger quantities of particles are shed by COVID-19 patients. Abnormally hard outer shells (M) are associated with burrowing animals, e.g., pangolins, and SARS-CoV-2 likely acquired these shells due to its long-term evolutionary interactions with pangolins. As for virulence, the inner shell of SARS-CoV-2 (N) has been found to exhibit lower disorder than that of SARS-CoV-1. This lower disorder is consistent with the fact that SARS-CoV-2 is less virulent than SARS-CoV-1, as higher disorder in the inner shell is associated with more efficient protein-protein binding during replication. The link between N/M disorder and virulence or infectivity falls under the umbrella of shell disorder models (SDMs), which can connect virulence, infectivity, and long COVID under one coherent concept. Evidence of the reliability and reproducibility of SDMs as applied to COVID-19 is examined. The hard M that is resisting the antimicrobial enzymes in the respiratory system can be extended to immunological enzymes, especially those found in phagocytes such as macrophages, which can therefore become a reservoir for the virus.}, }
@article {pmid41878230, year = {2026}, author = {Choi, S and Huda, MN and John, JR and Eapen, V}, title = {The Effectiveness of Non-Pharmacological Interventions in Treating Adolescents and Young Adults with Neuropsychiatric Symptoms of Long COVID: A Systematic Review and Meta-Analysis.}, journal = {Neuropsychiatric disease and treatment}, volume = {22}, number = {}, pages = {570223}, pmid = {41878230}, issn = {1176-6328}, abstract = {BACKGROUND: The management of persistent symptoms for long COVID (eg, fatigue, concentration difficulties, sleep difficulties, loss of appetite and taste, depression, and anxiety) has not been widely studied among adolescents and young adults (AYA). This systematic review and meta-analysis aimed to synthesise and review evidence on the effectiveness of non-pharmacological interventions for AYA aged 13-25 years, presenting with long COVID symptoms.<br><br>METHODS: A systematic literature search was conducted in four electronic databases (PubMed, EMBASE, PsycInfo, and ProQuest) in addition to manual searches for studies from January 2020 to May 2025 (PROSPERO: CRD42024516016). The studies were screened for eligibility, and methodological quality was assessed using the Joanne Briggs Institute Critical Appraisal tool by two independent reviewers. Findings were summarised using a narrative synthesis approach, and where possible, a meta-analysis was conducted using a random effects model with standardised mean differences (SMD) and a 95% confidence interval (CI).<br><br>RESULTS: Of the 325 screened articles, seven studies were included, which discussed six interventions. Three studies reported on the effectiveness of three multidisciplinary rehabilitation programs (eg, neuropsychological rehabilitation program, multidisciplinary post-COVID rehabilitation program, micro-choice-based concentrated group rehabilitation), three on alternative medicine practices (eg, forest bathing, traditional Thai Medicine), and one on mechanical therapy (eg, enhanced external counterpulsation). Findings suggested that interventions, although varied in duration and follow-up, were effective in improving mental health (SMD: 0.64, 95%, p<0.0497). There were also non-statistical improvements in fatigue (SMD: 1.74, 95%, p = 0.1307), quality of life (SMD: -1.34, 95%, p = 0.2787), and cognitive function (SMD: 1.05, p = 0.2989).<br><br>CONCLUSION: This review's findings suggest that non-pharmacological interventions may effectively treat neuropsychiatric symptoms of long COVID in AYA, ensuring better outcomes. Nevertheless, further research must be conducted with longer-term follow-up and robust methodology to explore sustained benefits, which may better inform treatment decisions.<br><br>TRIAL REGISTRATION: This systematic review is registered in Prospero (CRD42024516016).}, }
@article {pmid41880671, year = {2026}, author = {Garriga-Salvó, C and Navarro, E and Lidón-Moyano, C and Arévalo, A and Roca, R and Morera, M and Llistosella, M}, title = {Psychological interventions for individuals with long COVID: a systematic review and meta-analysis.}, journal = {Health psychology review}, volume = {}, number = {}, pages = {1-22}, doi = {10.1080/17437199.2026.2646179}, pmid = {41880671}, issn = {1743-7202}, abstract = {Introduction: Long COVID involves a variety of persistent symptoms after initial SARS-CoV-2 infection, affects multiple functional areas and requires multidisciplinary treatment. Objective: This study aimed to explore the available evidence about psychological interventions for individuals with long COVID and their effectiveness in reducing some prevalent symptoms, such as fatigue, anxiety or depression, among others, and improving patient quality of life. Methodology: A systematic review and meta-analysis were conducted following the PRISMA 2020 guidelines. Two independent reviewers performed study selection and data extraction using Web of Science, Scopus, and PubMed databases prior to March 2024. Data synthesis was performed via random-effects meta-analysis, with heterogeneity assessed using the I2 statistic. Results: Of the 1041 articles obtained, 19 were included in the systematic review and 14 in the meta-analysis. Results showed significant reductions in symptoms of anxiety [SMD = -0.64 (95% CI: -1.18 to -0.10)], depression [SMD = -0.41 (95% CI: -0.73 to -0.10)] and fatigue [SMD = -1.37 (95% CI: -2.48 to -0.26)]. Significant improvements were only registered in self-perceived health-related quality of life [SMD = 7.59 (95% CI: 3.70-11.48)]. Conclusion: Results showed improvements in anxiety, depression or fatigue, highlighting the potential role of psychological interventions in patient recovery.}, }
@article {pmid41883910, year = {2026}, author = {Montoya, S and Alvarez Ramirez, D and Chavarría, R and Zamora, EL and Soto Cordero, CA}, title = {Anesthesia in Patients With Long COVID or Post-infectious Respiratory Sequelae Undergoing Emergency Surgery: Clinical Challenges and Perioperative Strategies.}, journal = {Cureus}, volume = {18}, number = {2}, pages = {e104067}, pmid = {41883910}, issn = {2168-8184}, abstract = {The COVID-19 pandemic has left lasting health consequences that extend beyond the acute infection phase, with long COVID emerging as a complex multisystem condition that poses significant challenges in the perioperative setting. Patients with post-infectious respiratory or cardiovascular sequelae present an increased anesthetic risk due to persistent inflammation, pulmonary fibrosis, reduced lung compliance, and myocardial dysfunction. These alterations predispose to hypoxemia, arrhythmias, and hemodynamic instability during surgery, making preoperative assessment and individualized anesthetic planning essential. Comprehensive evaluation, including functional tests, cardiac and pulmonary imaging, and laboratory analysis, allows early identification of residual organ dysfunction that can compromise perioperative safety. Anesthetic management must be adapted to the patient's physiological condition, emphasizing lung-protective ventilation, cautious fluid therapy, and close hemodynamic monitoring. Regional anesthesia is preferred when feasible to minimize airway manipulation and reduce respiratory complications, while total intravenous anesthesia represents a safer option when general anesthesia is required. Postoperative care focuses on extended respiratory monitoring, multimodal analgesia to limit opioid use, and the implementation of pulmonary physiotherapy and antithrombotic prophylaxis to prevent complications. Psychological support is also recommended to address post-COVID anxiety and fatigue, contributing to holistic recovery. Although clinical guidelines provide useful recommendations, current evidence remains limited and heterogeneous. Further research is required to clarify the pathophysiological mechanisms of long COVID, evaluate anesthetic drug interactions, and develop validated risk stratification tools. Establishing standardized, evidence-based perioperative protocols is essential to improve outcomes and ensure patient safety in individuals with long COVID undergoing emergency surgery.}, }
@article {pmid41884491, year = {2026}, author = {Ayoubkhani, D and Atchison, CJ and Banerjee, A and Brightling, C and Calvert, M and Diamond, I and Eggo, RM and Elliott, P and Evans, RA and Haroon, S and Herrett, E and Nafilyan, V and O'Mahoney, LL and Pinto Pereira, SM and Routen, A and Shafran, R and Stephenson, T and Sterne, J and Ward, H and Zaccardi, F and Khunti, K}, title = {Considerations for epidemiological studies investigating emerging post-acute infection syndromes: Long Covid as a case study.}, journal = {EClinicalMedicine}, volume = {94}, number = {}, pages = {103833}, pmid = {41884491}, issn = {2589-5370}, abstract = {Epidemiological research studies into Long Covid, currently defined by prolonged symptoms after SARS-CoV-2 infection, have reported widely varying prevalence estimates. As well as rapidly evolving scientific knowledge of Long Covid, these differences are partly driven by substantial methodological heterogeneity between studies, including the outcome definition of Long Covid; duration of follow-up; study design, period and population; sampling frame; data source; and the statistical techniques employed. Having a robust understanding of the prevalence of and risk factors for Long Covid is essential for informing treatment pathways, service provision and policy decisions. In preparation for the public health response to future epidemics and pandemics, this review outlines key epidemiological and statistical considerations and recommendations when designing studies of emerging post-acute infection syndromes, focussing on Long Covid as a case study.}, }
@article {pmid41890193, year = {2026}, author = {Zhu, B and Qu, S and Li, J and Deng, W and Shen, WJ and Chen, J}, title = {The mechanisms underlying COVID-19 induced insulin resistance: a narrative review.}, journal = {Frontiers in endocrinology}, volume = {17}, number = {}, pages = {1781679}, pmid = {41890193}, issn = {1664-2392}, mesh = {Humans ; *Insulin Resistance/physiology ; *COVID-19/complications/metabolism ; SARS-CoV-2 ; Gastrointestinal Microbiome ; Diabetes Mellitus/etiology/metabolism ; }, abstract = {The COVID-19 pandemic, caused by SARS-CoV-2, has resulted in a significant increase in insulin resistance and new-onset diabetes among recovered individuals. This review examines the multifactorial mechanisms underlying these metabolic complications, including activation of the immune system and inflammatory cascades, lifestyle changes, nutritional deficiencies, imbalances in amino acid metabolism, alterations in ketogenesis, disruptions in the gut microbiome, psychological impacts, and COVID-19 vaccines. We discuss how these factors collectively contribute to insulin resistance, particularly in the context of COVID-19, and highlight potential therapeutic strategies, such as dietary interventions and ACE2 activators, that may mitigate these effects. Our analysis underscores the need for targeted approaches to prevent and treat insulin resistance in post-COVID-19 patients, emphasizing the importance of understanding the pandemic's long-term metabolic consequences.}, }
@article {pmid41895458, year = {2026}, author = {Fehrer, A and Windzio, L and Schoening, S and Steiner, S and Aschenbrenner, AC and Babel, N and Behrends, U and Bellmann-Strobl, J and Cammà, G and Cash, A and Doehner, W and den Dunnen, J and Fluge, &#xd8; and Franke, C and Hoffmann, K and Kedor, C and Kim, L and Löhden, W and Mella, O and Mihatsch, LL and Peluso, MJ and Puta, C and Putrino, D and Ramoji, A and Sato, W and Sawitzki, B and Schlieper, G and Schoenfeld, Y and Seifert, M and Sigurdsson, F and Slaghekke, A and Sommerfelt, K and Sotzny, F and Stein, E and Steinacker, JM and Stingl, M and Systrom, DM and Tronstad, KJ and Wirth, K and Wörmann, B and Wüst, RCI and Yamamura, T and Scheibenbogen, C}, title = {Expert perspectives on Myalgic encephalomyelitis/chronic fatigue syndrome - Insights from the 3[rd] International Conference of the Charité Fatigue Center.}, journal = {Autoimmunity reviews}, volume = {25}, number = {5}, pages = {104043}, doi = {10.1016/j.autrev.2026.104043}, pmid = {41895458}, issn = {1873-0183}, mesh = {Humans ; *Fatigue Syndrome, Chronic/therapy/diagnosis/epidemiology/immunology ; *COVID-19/complications/epidemiology/immunology ; *SARS-CoV-2 ; Quality of Life ; Congresses as Topic ; }, abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multisystemic disorder mostly triggered by viral infections, with core symptoms including post-exertional malaise (PEM), fatigue, pain, and cognitive dysfunction. Its prevalence has increased significantly in the context of the coronavirus disease 2019 (COVID-19) pandemic. Despite its severity and impact on patients' quality of life, ME/CFS remains poorly understood. On May 12 and 13, 2025, the 3[rd] International Conference hosted by the Charité Fatigue Center brought together nearly 200 researchers from various disciplines on-site, and around 3,700 participants online to discuss recent advances in ME/CFS research, diagnostics, clinical care, and therapeutic trials. The program featured 33 lectures by international experts on key topics such as post-COVID syndrome (PCS), care structures, and pathophysiological mechanisms including cardiovascular dysregulation, immune dysregulation, autoimmune mechanisms, and metabolic dysfunction. In addition, results from clinical trials addressing disease mechanisms, including those specifically targeting autoantibodies, were presented. While public awareness and funding opportunities have increased in the wake of the pandemic and the emergence of PCS, ME/CFS remains severely underresearched. Sustained and adequately funded research efforts are urgently required to advance understanding, identify diagnostic markers, and develop targeted therapeutic interventions.}, }
@article {pmid41900303, year = {2026}, author = {Hommos, L and Gohil, H and Rob, M and Manyama, J and Ramy, H and Naseem, N and Nishan, H and Ibrahim, RS and Ibrahim, SS and Njoku, VCE and Al-Mutawa, I and Khan, AF and Holroyd, S and Zakaria, D}, title = {Long-Term Thyroid Complications Post-COVID-19: A Systematic Review.}, journal = {Microorganisms}, volume = {14}, number = {3}, pages = {}, pmid = {41900303}, issn = {2076-2607}, abstract = {Coronavirus disease 2019 (COVID-19) is increasingly shown to be a multisystem disorder with long-term complications, including endocrine system complications. The thyroid gland is also susceptible, as it contains ACE2 receptors, making it exposed to both direct viral damage and autoimmune-mediated dysfunction. Recent reports document the various thyroid complications that persist well after the acute infection phase. This systematic review investigates the long-term thyroid complications in individuals with a history of SARS-CoV-2 infection. A comprehensive literature search across several databases was conducted. Eligible studies reported new onset long-term thyroid complications occurring post-COVID-19 infection. Abstract and full-text screening as well as data extraction and quality assessment was performed by two independent reviewers. Only 28 studies met our inclusion criteria, reporting 419 patients from 18 countries. These studies included case reports, case series, cohort, and cross-sectional studies. Reported thyroid disorders included subacute thyroiditis, thyrotoxicosis, hyperthyroidism (including Graves' disease), isolated high T3/T4, hypothyroidism, central hypothyroidism, and non-thyroidal illness syndrome (NTIS). While many of these eventually resolved, a significant portion persisted or recurred, especially autoimmune thyroiditis. COVID-19 is associated with a range of long-term thyroid complications. Although some cases are temporary, others last, especially autoimmune thyroid disorders. Proposed mechanisms include direct viral cytotoxicity, cytokine-mediated Hypothalamic-Pituitary-Thyroid (HPT) axis suppression, post-viral autoimmunity, vascular injury, and neuroendocrine disruption. Routine thyroid function monitoring in COVID-19 survivors, particularly those with severe disease or persistent symptoms is recommended, and larger prospective studies are needed to better understand incidence and outcomes.}, }
@article {pmid41914684, year = {2026}, author = {Brüssow, H}, title = {Antivirals Targeting Coronavirus RNA-Dependent RNA Polymerase and Main Protease: From Mechanisms of Action to Outcomes in COVID-19 Clinical Trials.}, journal = {Microbial biotechnology}, volume = {19}, number = {4}, pages = {e70342}, pmid = {41914684}, issn = {1751-7915}, mesh = {Humans ; *Antiviral Agents/therapeutic use/pharmacology ; *COVID-19 Drug Treatment ; *SARS-CoV-2/drug effects/enzymology ; Clinical Trials as Topic ; COVID-19/virology ; Hydroxylamines/therapeutic use/pharmacology ; *Coronavirus RNA-Dependent RNA Polymerase/antagonists &amp; inhibitors ; Cytidine/analogs &amp; derivatives/therapeutic use ; Alanine/analogs &amp; derivatives/therapeutic use ; Animals ; Adenosine Monophosphate/analogs &amp; derivatives/therapeutic use ; Coronavirus 3C Proteases/antagonists &amp; inhibitors ; }, abstract = {The rapid global spread of SARS-CoV-2 triggered an unprecedented effort to develop effective antivirals. Among the first approved agents was remdesivir, an injectable nucleoside analogue developed by Gilead Sciences, that led to chain termination of viral RNA synthesis and showed broad antiviral activity against RNA viruses. Early clinical results were mixed: The US ACTT-1 trial reported an accelerated recovery and reduced mortality in treated patients, while the WHO Solidarity and a European trial revealed no impact of remdesivir on mortality. In contrast, a US trial in outpatients demonstrated a clear clinical benefit when treatment was administered early. Molnupiravir, an orally applicable nucleoside analogue developed by Merck, induces lethal mutations in the viral genome rather than chain termination. Molnupiravir showed in vivo antiviral activity against coronaviruses in different animals. In MOVe-OUT trials, molnupiravir reduced the rate of hospitalisation in treated outpatients. In the PANORAMIC trial, molnupiravir reduced the time to recovery in outpatients but not their rate of hospitalisation. No drug effect of molnupiravir was seen in the RECOVERY trial with hospitalised COVID-19 patients. Using structural biology and medicinal chemistry approaches, Pfizer developed nirmatrelvir, an oral inhibitor of the major coronavirus protease. In high-risk but not in standard-risk COVID-19 patients, the combination nirmatrelvir/ritonavir reduced the rate of hospitalisation (EPIC HR and SR trials). Retrospective cohort studies showed treatment effects in defined patient groups. This review compares the efficacy and clinical performance of different antivirals, including emerging drugs such as obeldesivir and alternative protease inhibitors (lopinavir, simnotrelvir). It further examines their roles in prophylaxis, treatment of long covid symptoms, pharmacological considerations and antiviral resistance. Particular attention is given to factors underlying variable outcome of the trials, including viral variant evolution, population immunity increases, disease severity changes and timing of therapy initiation.}, }
@article {pmid41918727, year = {2026}, author = {Stallmach, A and Layer, P and Katzer, K and Reuken, PA}, title = {Lessons from irritable bowel syndrome: potential for understanding and managing post-COVID.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1717324}, pmid = {41918727}, issn = {1664-3224}, mesh = {Humans ; *Irritable Bowel Syndrome/therapy/diagnosis/etiology ; *COVID-19/complications ; *SARS-CoV-2 ; }, abstract = {Post-COVID presents a complex medical challenge characterized by persistent symptoms following SARS-CoV-2 infection. Similarities between post-COVID and post-infectious Irritable Bowel Syndrome (PI-IBS) suggest that the latter can serve as a useful model for understanding pathophysiological mechanisms and developing therapeutic approaches. Both conditions are functional disorders triggered by an acute infection, with multifactorial etiology and limited biomarker-based diagnostics. The variability of symptoms and the high frequency of comorbidities make these disorders particularly difficult to diagnose. Diagnostic efforts may be further hindered by the stigmatization of such disorders among healthcare providers, the health insurance industry, and the general public. This article explores the parallels between PI-IBS and post-COVID, highlighting, on the one hand, what can be learned from the management of IBS to better address the needs of patients with post-COVID long-term sequelae, and, on the other hand, raising doubts-based on decades of research into drug therapy development for IBS-about the likelihood of a rapidly available treatment for post-COVID.}, }
@article {pmid41930109, year = {2026}, author = {Friedberg, F and LeBaron, TW}, title = {Molecular hydrogen as a treatment for ME/CFS: a mini-review of clinical evidence and mechanistic rationale.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1760210}, pmid = {41930109}, issn = {2296-858X}, abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystem illness characterized by profound fatigue, post-exertional malaise, cognitive impairment, and autonomic dysfunction, yet it currently lacks FDA-approved treatments. Molecular hydrogen (H2), administered primarily as hydrogen-rich water (HRW), has emerged as a potential therapeutic candidate due to its selective antioxidant effects, anti-inflammatory activity, and support of mitochondrial and cellular homeostasis. These mechanisms align with several biological abnormalities implicated in ME/CFS, including oxidative stress, chronic inflammation, and impaired energy metabolism. This narrative mini-review summarizes mechanistic evidence relevant to ME/CFS and evaluates three developmental clinical studies of HRW in this population. Although early trials are small and methodologically limited, moderate-dose HRW consumed over extended durations has demonstrated feasibility and preliminary benefits in reducing fatigue and improving physical function, with generally mild side effects. Overlapping findings in Long COVID further suggest potential applicability across related post-viral fatigue conditions. Key limitations include small sample sizes, reliance on self-report outcomes, and the absence of objective biomarkers. Future research should prioritize larger, rigorously controlled trials incorporating remote biometric and biochemical assessments to clarify mechanisms of action and identify responsive subgroups. Overall, molecular hydrogen represents a promising, low-burden adjunctive therapy warranting further investigation in ME/CFS.}, }
@article {pmid41932347, year = {2026}, author = {Camici, M and Piano Mortari, E and Del Duca, G and Cimini, E and Mazzotta, V and De Ponte, C and Mastrorosa, I and Mazzotta, S and Pinnetti, C and Notari, S and Bordoni, V and Gili, S and Prencipe, G and Maggi, F and Carsetti, R and Girardi, E and Antinori, A and Agrati, C}, title = {Intravenous immunoglobulin treatment for long COVID: a case report of clinical and immunological findings.}, journal = {The Lancet. Infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1016/S1473-3099(26)00063-0}, pmid = {41932347}, issn = {1474-4457}, abstract = {A previously healthy 39-year-old man developed highly symptomatic post-COVID-19 condition (also known as long COVID) marked by cognitive dysfunction, disabling fatigue, and autonomic symptoms unresponsive to multiple multidisciplinary interventions. Given the presence of markedly elevated serum autoantibodies against G protein-coupled receptors, high-dose intravenous immunoglobulin therapy was initiated at 400 mg/kg per day for 5 consecutive days. After 4 weeks, a maintenance dose of 500 mg/kg was administered for 1 day, followed by two further maintenance cycles consisting of 500 mg/kg per day for 3 consecutive days, each given at 4-week intervals. In parallel, the patient underwent a cognitive stimulation intervention. Neurological symptoms were assessed with the Fatigue Assessment Scale and the WHO Disability Assessment Schedule 2.0, and the immunological profile was longitudinally analysed during intravenous immunoglobulin treatment. Fatigue scores normalised, neurocognitive performance returned to normal value, and quality of life improved after the first infusion and fully recovered within 1 year. Immunological profiling revealed the presence of an inverted CD4 to CD8 T-cell ratio that persisted during the whole follow-up. We also identified a CD8[+] T cell-monocyte complex and spontaneous IFNγ release. Intravenous immunoglobulin therapy was associated with a significant reduction of these complexes, spontaneous IFNγ and TNF production, markers of endothelial inflammation, and circulating autoantibody titres. This patient provides exploratory evidence that high-dose intravenous immunoglobulin was associated with sustained clinical recovery from long COVID over 1 year of follow-up, accompanied by immunological changes consistent with modulation of post-viral immune dysregulation, including a reduction in pathogenic T cell-monocyte synapses. Although causal inference cannot be established from a single patient, these findings suggest that this cellular interaction can contribute to long COVID and that immunomodulation could represent a rational therapeutic approach to be evaluated in selected patients.}, }
@article {pmid41934421, year = {2026}, author = {Shakeel, A and Sircar, K and Popli, DB}, title = {Xerostomia after COVID-19 recovery: A preliminary investigation.}, journal = {The Indian journal of medical research}, volume = {163}, number = {1}, pages = {122-125}, pmid = {41934421}, issn = {0971-5916}, mesh = {Humans ; *Xerostomia/epidemiology/virology/etiology/physiopathology ; *COVID-19/complications/epidemiology/virology/physiopathology ; Male ; Female ; Middle Aged ; SARS-CoV-2 ; Adult ; Aged ; Surveys and Questionnaires ; }, abstract = {Background and objectives Xerostomia, or dry mouth, was frequently reported during COVID-19 infection, but its persistence after recovery remains underexplored. This study aimed to assess the prevalence and duration of xerostomia following recovery from COVID-19 infection. Methods This observational study included 50 participants who had recovered from COVID-19. They were surveyed using a xerostomia assessment questionnaire and underwent the modified Schirmer test (MST) to measure their salivary flow rate. Results Overall, n=31(62%) of participants reported one or more xerostomia-related symptoms after recovery. "Feeling of dry mouth" (n=22, 44%) was the most common, followed by nocturnal water intake (n=18, 36%), difficulty swallowing dry food (n=7, 14%), and reliance on liquids during swallowing (n=6, 12%). Hyposalivation (MST <15 mm at 3 min) was observed in 10% (n=5) of participants, all of whom were infected during the second wave (Delta variant). A significant association was noted between self-reported dry mouth and MST findings (P=0.029). Symptoms persisted up to 15 months post-recovery. Interpretation and conclusions Xerostomia may persist after COVID-19 recovery, with potential implications for oral health. Early recognition and management are warranted.}, }
@article {pmid41940032, year = {2026}, author = {Cazzola, M and Rogliani, P and Calzetta, L and van Haren, FMP and Page, C and Matera, MG}, title = {Redox signaling in chronic airway diseases: pathogenic mechanisms and therapeutic implications.}, journal = {Frontiers in physiology}, volume = {17}, number = {}, pages = {1734890}, pmid = {41940032}, issn = {1664-042X}, abstract = {Chronic airway diseases, including asthma, chronic obstructive pulmonary disease (COPD), and bronchiectasis, impose a significant global health burden. A central unifying feature of these diseases is redox imbalance, which is characterized by an excess of reactive oxygen and nitrogen species (ROS/RNS) that overwhelms the body's antioxidant defenses, causing cellular dysfunction, inflammation, and tissue damage. Physiological ROS/RNS are essential for immune regulation and transcriptional control, but chronic oxidative stress disrupts these processes, driving disease progression. In asthma, eosinophil- and epithelial-derived ROS worsen airway hyperresponsiveness, induce mucus overproduction, and reduce steroid effects. COPD involves neutrophil-dominated inflammation, mitochondrial dysfunction, protease- and oxidant-mediated extracellular matrix degradation, and accelerated senescence. Bronchiectasis features persistent neutrophilic oxidative injury, microbial colonization, impaired mucociliary clearance, and progressive airway destruction. Exogenous oxidants, cigarette smoke, biomass fuels, pollutants, and pathogens further burden antioxidant systems, including superoxide dismutases, catalase, glutathione peroxidase, and Nrf2-regulated pathways. Redox dysregulation also contributes to post-COVID sequelae, promoting ongoing airway inflammation, fibrosis, and systemic complications. Therapeutic strategies targeting redox imbalance, mainly thiol-based antioxidants, Nrf2 activators, NADPH oxidase inhibitors, and mitochondria-targeted antioxidants, show mechanistic promise but face challenges in specificity, bioavailability, and clinical translation. Advancing precision redox medicine requires biomarker-guided patient stratification, high-resolution redox proteomics, single-cell and organoid models, and spatial imaging to identify disease-specific redox endotypes. Modulating pathological oxidative stress while preserving physiological signaling offers a novel avenue to improve outcomes. Understanding redox biology in airway disease highlights the potential of precision antioxidant strategies as adjuncts to conventional therapies, representing a paradigm shift in managing chronic airway disorders.}, }
@article {pmid41947042, year = {2026}, author = {Sahu, D and Van Nynatten, LR and Tweddell, D and Daley, M and Fraser, DD}, title = {Computational proteomics to enhance personalized treatment of COVID-19 and Long COVID.}, journal = {Clinical proteomics}, volume = {23}, number = {1}, pages = {}, pmid = {41947042}, issn = {1542-6416}, abstract = {UNLABELLED: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to significant global health burden, including both acute infections and persistent post-acute sequelae, also known as Long COVID (LC) in survivors. While clinical management has reduced case-fatality rates, a substantial proportion of patients develop LC, a heterogeneous syndrome with long-term symptoms. This complex continuum requires therapeutic strategies for both the acute and chronic phases. Plasma proteomics has emerged as a powerful tool in precision medicine, offering insights into systemic molecular changes and disease trajectories. Using targeted and untargeted proteomic analyses, researchers can identify disease-relevant pathways, perform cellular deconvolution to assess tissue-specific contributions, and pinpoint therapeutic targets for both acute infection and persistent symptoms. Combined with bioinformatics and machine learning, these proteomic insights support biomarker discovery and drug repurposing strategies.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12014-026-09601-8.}, }
@article {pmid41951954, year = {2026}, author = {King, R and Ford, T and Coleman, Z and Hammond, E and Henley, D and Hirschtick, JL}, title = {Racial Disparities in Long COVID: Why Black Americans are Likely Underrepresented in Long COVID Estimates.}, journal = {Journal of racial and ethnic health disparities}, volume = {}, number = {}, pages = {}, pmid = {41951954}, issn = {2196-8837}, }
@article {pmid41953516, year = {2026}, author = {Qu, HQ and Kao, C and Hakonarson, H}, title = {Redefining the role of the thiol-based agent N-acetylcysteine in human health and disease and elucidating potential advantages of its amide derivative.}, journal = {RSC medicinal chemistry}, volume = {17}, number = {5}, pages = {2183-2196}, pmid = {41953516}, issn = {2632-8682}, abstract = {N-Acetylcysteine (NAC) is the established antidote for acetaminophen toxicity and an approved mucolytic agent. Beyond these traditional uses, increasing evidence highlights its broader role as a modulator of thiol-redox biology. Rather than functioning as a nonspecific antioxidant, NAC modulates glutathione metabolism, redox-sensitive signaling, immune checkpoints, thiol-based post-translational modifications, ferroptosis susceptibility, and glutamatergic neurotransmission. This review synthesizes mechanistic, preclinical, and clinical evidence across pulmonary, hepatic, neuropsychiatric, metabolic, cardiovascular, and oncologic disorders, emphasizing how variability in baseline redox state, pharmacogenetics, and delivery contributes to heterogeneous outcomes. Strategies to improve pharmacokinetics and tissue targeting include structural derivatives such as N-acetylcysteine amide (NACA), and combination regimens such as NAC with probenecid or GlyNAC. Emerging applications span long COVID, neurodegeneration, psychiatric disorders, microbiome-redox interactions, environmental toxicology, and cancer immunotherapy. NAC and NACA exemplify the evolution of redox-targeted therapeutics. NAC is well established for safety and clinical utility, but its pharmacokinetic and tissue distribution properties constrain broader efficacy. NACA, a lipophilic amide derivative, enhances membrane permeability and cellular uptake, suggesting it may achieve higher tissue exposure at lower doses. Future progress will rely on biomarker-guided, precision approaches that optimize dosing, formulation, and delivery while exploring rational combinations across disease contexts defined by redox biology.}, }
@article {pmid41955274, year = {2026}, author = {Wu, D and Dasgupta, A and Hora, JS and Chen, KH and Banerjee, A and Archer, SL}, title = {SARS-CoV-2 targets mitochondria, exacerbating COVID-19 pneumonia.}, journal = {The Journal of physiology}, volume = {}, number = {}, pages = {}, doi = {10.1113/JP290297}, pmid = {41955274}, issn = {1469-7793}, support = {SEA-20-015//Southeastern Ontario Academic Medical Organization/ ; MM1181122/CAPMC/CIHR/Canada ; }, abstract = {Mitochondrial damage is a conserved feature of coronavirus infection, occurring with human (SARS-CoV-2, HCoV-OC43) and murine (MHV-1) coronaviruses. Coronaviruses damage mitochondria in airway epithelial cells (AEC), pulmonary artery smooth muscle cells (PASMC), pulmonary artery endothelial cells, immune cells and cardiomyocytes by causing rapid transcriptomic changes in nuclear-encoded genes regulating mitochondria and by viral proteins interacting with host mitochondrial proteins. Coronavirus infection causes mitochondrial depolarization, mitochondrial transition pore (MTP) opening, inhibition of the electron transport chain (ETC) and ATP synthetic apparatus, increased mitochondrial fission, apoptosis, and impaired mitochondrial oxygen sensing. Within hours of infection, SARS-CoV-2 induces transcriptional reprogramming of genes relevant to the mitochondrial matrix in AECs, downregulating mRNA encoding ETC complex I components and the ATP synthesis complex. These bioenergetic consequences of SARS-CoV-2 mitochondriopathy may contribute to long COVID. Infection also upregulates dynamin-related protein 1 (DRP1), activating mitochondrial fission while promoting apoptosis by activating apoptosis inducing factor (AIF) and caspase 7. Even without infection, transfection with specific coronaviral proteins opens the MTP and depolarizes the mitochondria, or activates DRP1 and AIF, promoting AEC damage or apoptosis, thereby contributing to diffuse alveolar damage. In human PASMCs, coronaviral M and Nsp9 proteins suppress hypoxic pulmonary vasoconstriction (HPV), a homeostatic mechanism in PASMCs that uses a mitochondrial oxygen sensor to redistribute blood flow to well-ventilated lung regions during pneumonia. Impairment of HPV, seen as intrapulmonary shunting, contributes to the profound hypoxaemia in COVID-19 pneumonia. Coronavirus-induced mitochondriopathy may have therapeutic relevance as blocking AIF-induced apoptosis or enhancing HPV appears beneficial in a MHV-1 model of COVID-19 pneumonia.}, }
@article {pmid41972671, year = {2026}, author = {Asaba, CN and Gwanyama, BN and Ayuk, HS and Odo, TI and Bitazar, R and Noumi, T and Labonté, P and Bukong, TN}, title = {Neutrophil Extracellular Traps in Viral Infections: Regulation, Immune Consequences, and Pathogenic Outcomes.}, journal = {Cells}, volume = {15}, number = {7}, pages = {}, pmid = {41972671}, issn = {2073-4409}, support = {Relance 2024//The INRS-Armand-Frappier Sant&#xe9; Biotechnologie Research Centre/ ; 363424//A doctoral scholarship from the Fonds de Recherche du Qu&#xe9;bec./ ; }, mesh = {*Extracellular Traps/immunology ; Humans ; *Neutrophils/immunology ; *Virus Diseases/immunology/pathology ; Animals ; COVID-19/immunology ; SARS-CoV-2/immunology ; Immunity, Innate ; Signal Transduction ; }, abstract = {Neutrophils are among the early responders of the innate immune system and play a key role in host defense against viral infections. Beyond their classical antimicrobial functions, neutrophils can engage in a specialized defense mechanism by releasing web-like extracellular DNA known as neutrophil extracellular traps (NETs). These extracellular traps are a mesh-like network of chromatin DNA decorated with cellular components, including histones, proteases, and antimicrobial enzymes, that function to contain and limit the spread of pathogens. While NET formation contributes to antiviral immunity, accumulating evidence indicates that excessive or dysregulated NET formation can significantly contribute to immunopathology during viral infections. Thus, depending on the context and outcome, NET formation may be viewed as a double-edged sword. Therefore, understanding the regulatory mechanisms governing NET formation and its harmful effects is critical for developing therapeutic strategies that enhance antiviral defense while minimizing tissue damage. In this review, we provide a comprehensive overview of the molecular mechanisms that drive NET formation and clearance, with a particular focus on how viruses modulate these processes to influence disease outcome. We also discuss the pathways underlying NET formation and subsequent neutrophil cell death (NETosis), including canonical and non-canonical pathways, and highlight key signaling axes involving SYK, MAPKs, and NF-κB. Using SARS-CoV-2 and hepatitis B virus as representative models, we examine how different viral components trigger, exploit, or evade NET targeting and how persistent accumulation of NETs can contribute to hyperinflammation, progressive tissue injury, and post-viral syndromes. We further explore emerging evidence linking impaired NET clearance and neutrophil heterogeneity, particularly low-density neutrophils (LDNs), to chronic inflammation and post-viral sequelae such as long COVID and autoimmune hepatitis. Finally, we summarize current and emerging therapeutic strategies aimed at modulating NET formation or enhancing NET clearance. Altogether, this review underscores the dual nature of NETs in viral infections, highlighting their potential roles in antiviral defense and tissue injury, and provides a framework for the development of targeted interventions to limit virus-induced immunopathology.}, }
@article {pmid41973314, year = {2026}, author = {Peddireddy, S and VanWingerden, N and Patel, P and Howard, G and Berger, J}, title = {Stellate Ganglion Block in the Treatment of Long COVID: A Systematic Review.}, journal = {Current pain and headache reports}, volume = {30}, number = {1}, pages = {}, pmid = {41973314}, issn = {1534-3081}, mesh = {Humans ; *Stellate Ganglion ; *COVID-19/complications/therapy ; *Autonomic Nerve Block/methods ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: This review evaluates stellate ganglion block as a treatment for long COVID, seeking to evaluate the treatment's efficacy by various symptoms and the limitations of the current literature.<br><br>STUDY DESIGN: Systematic Review.<br><br>SETTING: Ambulatory or Outpatient Setting.<br><br>METHODS, SUBJECTS: A systematic review of the current literature regarding use of stellate ganglion block in patients with long COVID was conducted. 2 databases were searched on August 28th, 2025. Search terms were "long COVID" and "stellate ganglion block", yielding 45 results. Studies examining patient outcomes after stellate ganglion block were included. Case reports, case series, basic science studies and previous reviews were excluded. Seven studies met inclusion criteria.<br><br>RESULTS: Patients received a single stellate ganglion block in some studies and multiple stellate ganglion blocks in others. All studies reported symptomatic improvement without control groups. Response rates ranged from 55.8% to 100%. The most robust improvements (>&#x2009;80% patients reporting relief) were seen in cough, dyspnea, headache, joint pain, pain interference/intensity, pins/needles, subjective relief.<br><br>CONCLUSION: Stellate ganglion block is a promising treatment that appears to generate substantive benefit for many of the symptoms seen in long COVID. However, the current literature has small, uncontrolled studies with heterogenous study designs and follow-up periods. Standardized research with larger sample sizes, control groups, and longer-term follow up is necessary to elucidate the degree of benefit. IRB approval and clinical trial registration not required.}, }
@article {pmid41975034, year = {2026}, author = {Matthews, R and Alam, A and Bullmore, E and Michael, BD}, title = {Understanding the long-term neurological effects of SARS-CoV-2 infection.}, journal = {Nature reviews. Neurology}, volume = {22}, number = {6}, pages = {351-365}, pmid = {41975034}, issn = {1759-4766}, abstract = {Post-COVID-19 condition (PCC), also known as long COVID, is a heterogeneous condition marked by persistent symptoms following acute SARS-CoV-2 infection. As approximately 6% of people who have experienced acute COVID-19 are estimated to develop PCC, the potential population is vast. Many of the key symptoms of PCC reflect involvement of the nervous system, ranging from cognitive impairment ('brain fog'), headaches and fatigue to anxiety and depression. This Review summarizes the spectrum of neurological and psychological symptoms that occur following acute SARS-CoV-2 infection, with a particular focus on the international consensus-based core outcome set for PCC. We also explore the proposed underlying mechanisms, including evidence for immune system dysregulation, microvascular dysfunction and volumetric changes on neuroimaging. In addition, we review ongoing and completed large-scale treatment trials. Growing evidence suggests a bidirectional interaction between symptoms traditionally considered neurobiological in origin, such as cognitive deficits and headache, and those within the purview of psychiatry, such as anxiety and depression. PCC represents an opportunity to better understand the long-term consequences of acute infection and improve management strategies and outcomes, not only for people with the condition but also for those with other post-viral syndromes that affect brain health.}, }
@article {pmid41975732, year = {2026}, author = {Fanò-Illic, G and Coscia, F and Gigliotti, PV and Checcaglini, F and Carraro, U and Fulle, S and Mancinelli, R}, title = {Pathophysiological, Translational, and Diagnostic Aspects of ME/CFS: A Focus on Skeletal Muscle Involvement.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {16}, number = {7}, pages = {}, pmid = {41975732}, issn = {2075-4418}, abstract = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic, multisystemic disorder characterized by severe, persistent fatigue not alleviated by rest and worsened by minimal exertion, often accompanied by post-exertional malaise (PEM), unrefreshing sleep, cognitive dysfunction, and autonomic disturbances. Despite decades of research, its pathophysiology remains incompletely understood, and skeletal muscle involvement has only recently gained attention. This review aims to provide a historical and pathophysiological synthesis of ME/CFS, emphasizing the pivotal role of skeletal muscle in the onset and persistence of symptoms, and to integrate molecular, cellular, and pathophysiological evidence into a coherent explanatory framework. This is a narrative review of published literature (1990-2025) with critical integration of clinical, biochemical, and experimental data on oxidative stress, mitochondrial dysfunction, Excitation-Contraction (E-C coupling) dysregulation, and muscle secretome alterations in ME/CFS also in relation to post-viral syndromes (e.g., Long COVID). Evidence consistently points to mitochondrial oxidative stress, redox imbalance, impaired Ca[2+] handling, and altered signaling pathways in skeletal muscle of patients with ME/CFS. Historical milestones show an evolution from psychogenic interpretations toward recognition of ME/CFS as a biological disorder with neuromuscular and metabolic underpinnings. ME/CFS can be interpreted as a skeletal muscle-metabolic disorder characterized by oxidative distress, mitochondrial dysfunction, and impaired energy regulation, leading to the clinical picture of exercise intolerance and post-exertional malaise. Integrating basic and clinical research through a translational approach provides the foundation for new diagnostic tools, targeted therapies, and biomarkers.}, }
@article {pmid41976966, year = {2026}, author = {Mihai, AM and Marc, M and Lucaciu, F and Sima, A}, title = {Incident Heart Failure Risk Following COVID-19 Recovery: A Systematic Review and Meta-Analysis.}, journal = {Journal of clinical medicine}, volume = {15}, number = {7}, pages = {}, pmid = {41976966}, issn = {2077-0383}, support = {We would like to acknowledge the Victor Babes University of Medicine and Pharmacy, Timisoara, for paying the APC. The funder had no role in study design, data collection/analysis, decision to publish, or manuscript preparation//Victor Babe&#x219; University of Medicine and Pharmacy Timi&#x219;oara/ ; }, abstract = {Background/Objectives: While acute cardiac injury during COVID-19 is well-documented, the long-term risk of new-onset heart failure (HF) in survivors remains a critical clinical concern. This study aims to quantify the risk of new-onset heart failure during a 25 months prognostic follow-up period following recovery from SARS-CoV-2. Methods: We conducted a systematic review and meta-analysis of nine high-quality studies (n > 400,000 survivors) in accordance with PRISMA 2020 guidelines. Databases including PubMed/MEDLINE and Scopus were searched through January 2026. A quantitative meta-analysis was performed on six studies using a random-effects model to pool adjusted hazard ratios (aHR). Results: The pooled analysis revealed a significant 35% increased risk of new-onset heart failure following COVID-19 recovery (aHR 1.35; 95% CI: 1.14-1.60; p = 0.001). Significant heterogeneity was observed (I[2] = 92.62%), reflecting diverse risk profiles among survivors. The risk was most pronounced in immunocompromised kidney transplant recipients (aHR 2.32) and younger adults under the age of 65 (aHR 1.53). Subclinical myocardial damage, characterized by reduced left ventricular longitudinal strain, was identified even in survivors who experienced mild initial infections. Conclusions: COVID-19 recovery serves as a significant independent risk factor for chronic heart failure, emphasizing that cardiovascular impact extends far beyond the acute phase. These findings necessitate the implementation of structured cardiovascular monitoring and biomarker screening for at least one year post-infection to address this emerging chronic disease burden.}, }
@article {pmid41979291, year = {2026}, author = {Abid, S and Jannath, H}, title = {Cardiac Effects in Post-COVID-19 Heart Failure: A Systematic Review of Longitudinal Imaging- and Biomarker-Based Structural and Functional Remodeling.}, journal = {Annals of cardiac anaesthesia}, volume = {29}, number = {2}, pages = {157-168}, pmid = {41979291}, issn = {0974-5181}, mesh = {Humans ; *COVID-19/complications/diagnostic imaging/physiopathology ; Biomarkers/blood ; *Heart Failure/diagnostic imaging/physiopathology/etiology ; *Ventricular Remodeling/physiology ; Echocardiography ; Longitudinal Studies ; Magnetic Resonance Imaging ; }, abstract = {COVID-19 has been linked to persistent cardiovascular sequelae, yet the trajectory of structural and functional cardiac changes beyond the acute phase remains unclear. This systematic review synthesizes longitudinal evidence on post-COVID cardiac remodeling assessed by imaging and biomarkers. Following PRISMA guidelines, we searched PubMed and Cochrane Library (January 2020-April 2025) for peer-reviewed studies enrolling adults (≥18 years) with polymerase chain reaction (PCR)/antigen-confirmed SARS-CoV-2 infection and reporting cardiac outcomes ≥ 12 weeks post-infection. Eligible outcomes included imaging-based abnormalities (cardiac magnetic resonance [CMR]: T1/T2 mapping, late gadolinium enhancement [LGE]; echocardiography: left ventricular ejection fraction [LVEF], LV/RV strain). Longitudinal trends of biomarkers (troponin, NT-proBNP, C-reactive protein [CRP]) were also studied. Risk of bias was assessed using joanna briggs institute (JBI) tools; synthesis followed synthesis without metaanalysis (SWiM) principles. Fifteen studies (n ≈ 166,000; 14 cohorts, 1 case report) were included. Across CMR cohorts, global systolic function was largely preserved, but tissue abnormalities were frequent early and improved over time: edema indices normalized by ~ 12 months, while LGE prevalence declined (e.g. 50%→19% in paired scans). However, residual non-ischemic scars and elevated T1/T2 persisted in symptomatic subgroups. Echocardiography showed normal LVEF, but subtle left ventricular global longitudinal strain (LV-GLS) impairment versus controls (e.g. -18.5% vs - 19.3%). Biomarker trends were heterogeneous: natriuretic peptide positivity persisted in patients with prior cardiovascular disease (CVD), while troponin and CRP generally normalized. Large population-based cohorts demonstrated sustained 12-month risk for heart failure, myocarditis, and major cardiovascular events, graded by acute severity. Most patients recover gross systolic function, yet subclinical myocardial changes and elevated population-level cardiovascular risk persist up to 1 year. These findings support risk-stratified follow-up, judicious use of advanced imaging, and preventive cardiology strategies.}, }
@article {pmid41991875, year = {2026}, author = {Hensel, O and Pfrommer, L and Furch, P and Strutz, N and Wohlgemuth, WA and Posa, A}, title = {[Post-COVID: An inventory focusing on the key complaints PEM and POTS].}, journal = {MMW Fortschritte der Medizin}, volume = {168}, number = {Suppl 3}, pages = {3-10}, doi = {10.1007/s15006-026-5691-7}, pmid = {41991875}, issn = {1613-3560}, mesh = {Humans ; *COVID-19/complications ; *Postural Orthostatic Tachycardia Syndrome/therapy/etiology/diagnosis ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {BACKGROUND: More than five years after the start of the COVID-19 pandemic, its long-term effects are increasingly coming into focus. Post-COVID disease poses a significant challenge, - not only for the individuals affected, but also for healthcare providers and society as a whole. In order to improve care for post-COVID patients, the current state of research should be reviewed and the frequent and characteristic complaints post-exertional malaise and postural tachycardia syndrome should be presented.<br><br>METHOD: The literature search for this narrative review was conducted in the PubMed and Semantic Scholar databases.<br><br>RESULTS: Post-COVID symptoms are often nonspecific, diverse, and fluctuating. However, post-exertional malaise and postural tachycardia syndrome are characteristic of post-COVID when they occur newly after COVID-19 disease. Post-exertional malaise is an intensification of symptoms after exertion that occurs in about 86% of post-COVID patients. Pacing is a promising treatment approach here. Postural tachycardia syndrome manifests as autonomic, tachycardic, orthostatic dysregulation and affects up to 82% of post-COVID patients. Symptomatic therapy includes pharmacological and non-pharmacological measures.<br><br>CONCLUSIONS: Post-exertional malaise and postural tachycardia syndrome are typical and characteristic post-COVID symptoms. Current scientific findings underscore the SARS-CoV-2-related organic origin of post-COVID symptoms.}, }
@article {pmid41995128, year = {2026}, author = {Gonah, L and Ginindza, TG and Hlongwana, KW}, title = {Mapping global evidence on compassion fatigue among healthcare workers during COVID-19: insights and implications for future preparedness - a scoping review.}, journal = {Journal of global health}, volume = {16}, number = {}, pages = {04130}, pmid = {41995128}, issn = {2047-2986}, mesh = {Humans ; *COVID-19/epidemiology/psychology ; *Health Personnel/psychology ; *Compassion Fatigue/epidemiology ; Risk Factors ; SARS-CoV-2 ; Prevalence ; Global Health ; Burnout, Professional/epidemiology ; Female ; }, abstract = {BACKGROUND: Compassion fatigue (CF) is a critical occupational hazard for healthcare workers (HCWs), intensified by the COVID-19 pandemic, with implications for well-being, retention, and quality of care. We aimed to map the global evidence on CF prevalence, risk factors, effects, interventions, and research gaps among HCWs during the COVID-19 pandemic.<br><br>METHODS: A scoping review of 56 studies from 21 countries (2020-2025) was conducted following PRISMA-ScR guidelines. Seven databases were searched, and findings were synthesised narratively with attention to occupational, demographic, and systemic determinants of CF.<br><br>RESULTS: Compassion fatigue prevalence ranged from 20 to 87%. It was most pronounced among nurses, women, frontline staff, early-career professionals, and those in under-resourced or rural settings. Key risk factors included high workload, long shifts, repeated exposure to death, moral distress, and limited organisational support. Symptoms encompassed emotional exhaustion, depersonalisation, diminished empathy, and co-occurring anxiety, depression, or secondary traumatic stress. Interventions (resilience and peer-support programmes, self-compassion training, motivational messaging, and mobile psychoeducation) showed small-to-moderate benefits but were limited by methodological heterogeneity and scarce robust evaluation. Temporally, CF peaked during early pandemic surges and persisted among frontline staff and in resource-constrained or long-COVID contexts.<br><br>CONCLUSIONS: Compassion fatigue is a multifactorial, context-dependent hazard disproportionately affecting vulnerable HCWs. Effective mitigation requires longitudinal research, inclusive global representation, and multi-level strategies linking individual resilience with organisational reform and policy action to safeguard HCW well-being in current and future crises.}, }
@article {pmid42011141, year = {2026}, author = {Lloyd-Jones, G and Santamarina, MG and Alcock, R and Oudkerk, M}, title = {Acute COVID-19 lung disease and long COVID vascular pathophysiology modelling: the relevance of medical imaging in building multidisciplinary understanding.}, journal = {The British journal of radiology}, volume = {99}, number = {1182}, pages = {1009-1023}, doi = {10.1093/bjr/tqag056}, pmid = {42011141}, issn = {1748-880X}, mesh = {*COVID-19/diagnostic imaging/epidemiology/physiopathology ; *Post-Acute COVID-19 Syndrome/diagnostic imaging/epidemiology/physiopathology ; *Diagnostic Imaging/methods ; *Lung/blood supply/diagnostic imaging ; SARS-CoV-2 ; Acute Disease ; Models, Theoretical ; Interdisciplinary Research/methods ; Guidelines as Topic ; Humans ; }, abstract = {Radiologists have a central role in building understanding of many diseases. In multidisciplinary settings, medical imaging has a role in diagnosing, assessing severity, monitoring progress and delineating anatomical structures involved in diseases. Imaging also helps to elucidate models of disease pathogenesis. In this review, imaging features of COVID-19 lung disease are analysed in the context of pathophysiological processes in different phases of the disease. Radiological evidence is presented for the central role of vasculopathic phenomena in both the acute and post-acute phases of COVID-19. From the outset of the COVID-19 pandemic, a lack of formal collaborative interdisciplinary systems to build models of pathophysiology led to widespread misunderstanding of the lung disease. Specifically, the lack of a systematic multidisciplinary approach to share concepts relating to radiological evidence with collaborators from other medical and scientific fields led to the use of terminology which was, and remains, potentially inappropriate or misleading. In conclusion, imaging is essential to multidisciplinary understanding of COVID-19 vascular pathophysiology. Current evidence should lead to adapted diagnostic guidelines for long COVID. Formation of collaborative systems to build interdisciplinary understanding of disease pathogenesis across all medical and scientific specialties should be a priority at the outset of any future pandemic.}, }
@article {pmid42019647, year = {2026}, author = {Nieuwland, JM and Scaramuzza, A and Bugiani, M and van de Berg, WDJ and Middeldorp, J}, title = {Human brain matters: Navigating the neuropathology of COVID-19.}, journal = {Brain pathology (Zurich, Switzerland)}, volume = {}, number = {}, pages = {e70101}, doi = {10.1111/bpa.70101}, pmid = {42019647}, issn = {1750-3639}, support = {//European research project NEUROCOV, funded by Horizon Europe (EU)/ ; }, abstract = {Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of deaths worldwide. Although the incidence of severe acute cases has declined, the prevalence of long COVID, also known as post-acute sequelae of COVID-19 (PASC), is rising. The pathological mechanisms underlying severe COVID-19, along with the relationship to neurological disorders and potential risk for neurodegeneration, remain poorly understood. The aim of this narrative review is to summarize neuropathological features described in postmortem human COVID-19 brains (n = 352). Furthermore, analysis of biofluids and neuroimaging from PASC patients underline long-term changes in the proteome and CNS response following the infection. Postmortem brain studies from severe COVID-19 patients highlight disruption of the fluid-brain barriers and vascular dysregulation defined by endothelial inflammation and disruption, hemorrhages, and hypoxic-ischemic damage. Neuroinflammation, including astrogliosis, microglia nodules and infiltration of adaptive immune cells, has been reported in the olfactory bulb, medulla oblongata, midbrain and cerebellum. Neuronal damage was demonstrated in the hippocampus, midbrain and cerebellum in severe COVID-19 and protein aggregation was observed in the midbrain and entorhinal cortex. Neuropathological burden and elevated blood and/or cerebrospinal fluid (CSF) levels of proinflammatory cytokines (e.g. IL-6) and neuro-axonal proteins (e.g. NfL) correlated with severity of anosmia, memory deficits, and cerebellar ataxia. Elderly patients and/or patients with underlying neurological diseases were more susceptible and had worsened symptoms. Potential disease mechanisms underlying neurological symptoms observed in severe COVID-19 are vascular and fluid-brain barrier abnormalities, chronic neuroinflammation, persistent axonal damage and protein aggregation. In PASC patients, an altered biofluid proteome with increased neuronal proteins and pro-inflammatory cytokines was observed. The pathological burden in affected brain regions may contribute to manifestations such as anosmia, memory deficits, and cerebellar ataxia.}, }
@article {pmid42028925, year = {2026}, author = {Silva, LI and Gonzalez-Zambrano, CM and Ferreira, VCMP and Corrêa, FC and Dias-Melicio, LA}, title = {MicroRNAs in Acute COVID-19 and Long COVID: Dysregulation, Pathogenic Roles, and Clinical Implications.}, journal = {Journal of immunology research}, volume = {2026}, number = {1}, pages = {e5862241}, pmid = {42028925}, issn = {2314-7156}, support = {001//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; }, mesh = {Humans ; *COVID-19/genetics/immunology/virology/pathology ; *MicroRNAs/genetics ; *SARS-CoV-2/physiology/immunology ; Post-Acute COVID-19 Syndrome ; Extracellular Vesicles ; Gene Expression Regulation ; Biomarkers ; Inflammation ; }, abstract = {MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression with central roles in immune responses, inflammation, and viral pathogenesis. Increasing evidence indicates that severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection induces marked dysregulation of host and viral miRNAs (v-miRNAs), contributing to disease severity during acute COVID-19 and to the persistent manifestations observed in long COVID (LC). This narrative review critically synthesizes current evidence on miRNA dysregulation across the acute and post-acute phases of COVID-19, highlighting their pathogenic roles, clinical relevance, and existing knowledge gaps. During acute infection, altered miRNA profiles-including those associated with immune activation, endothelial dysfunction, and immunothrombosis-reflect both host responses and viral strategies of immune modulation, including miRNAs carried by extracellular vesicles (EVs) and SARS-CoV-2-derived v-miRNAs. In LC, emerging data suggest that persistent miRNA alterations are associated with unresolved inflammation, pulmonary dysfunction, neurological symptoms, and vascular injury, although available studies remain limited and heterogeneous. Overall, miRNAs represent promising biomarkers and potential therapeutic targets in COVID-19; however, robust longitudinal and mechanistic studies are urgently needed to clarify their causal roles and translational utility in post-acute disease.}, }
@article {pmid42035205, year = {2026}, author = {Yuan, MQ and Pan, YF and Zhang, ZY and Wu, YX and Zhu, KD and Wang, ZR and Zhang, ZY and Xiong, JQ and Xu, Z and Huang, L and Wang, FS and Shi, L}, title = {Therapeutic potential of mesenchymal stromal cells in COVID-19: a meta-analysis of clinical trials conducted since the pandemic onset.}, journal = {Stem cell research &amp; therapy}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13287-026-05020-6}, pmid = {42035205}, issn = {1757-6512}, support = {No. 2022YFA1105604//National Key Research and Development Program of China/ ; }, abstract = {BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can induce immune dysregulation and multi-organ injury; mesenchymal stromal cell (MSC) therapy has shown promise in clinical trials for COVID-19 and may have broader applicability to pneumonia induced by respiratory viruses (e.g., the influenza virus). This meta-analysis synthesized the available comparative clinical evidence on the safety and efficacy of MSCs in patients with moderate to critical COVID-19 and examined the reported outcomes relevant to Long-COVID.<br><br>METHODS: We searched the PubMed, Embase, and CNKI databases for original, comparative studies in moderate, severe, or critical COVID-19 published up to September 2, 2024. Twenty-four eligible studies (13 RCTs and 11 non-randomized controlled trials; n&#x2009;=&#x2009;1080) were included in the mortality meta-analysis. Patients were assigned to either the intervention group (MSC therapy plus standard care) or the control group (standard care with or without placebo). The primary efficacy outcome was all-cause mortality, while the primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs). Secondary outcomes included clinical recovery, hospitalization metrics, chest imaging, and inflammatory biomarkers. We performed a pooled meta-analysis on mortality with subgroup analyses (by disease severity, administration route, dosing frequency, and study design), assessment of publication bias (using funnel plots and Egger's test), and evaluation of the quality of evidence via the GRADE approach. AEs/SAEs were analyzed using meta-analysis and descriptive statistics, while other secondary outcomes were summarized descriptively.<br><br>RESULTS: MSC therapy significantly reduced all-cause mortality (MSC: 26.4% vs control: 31.9%; fixed-effect OR&#x2009;=&#x2009;0.74, 95% CI 0.55-0.99), with low heterogeneity (I[2]&#x2009;=&#x2009;2.8%, P&#x2009;=0.422[Q-test]) and no publication bias. The quality of evidence was moderate (according to the GRADE assessment). The subgroup analysis revealed a significant survival benefit in severe/critical patients (OR&#x2009;=&#x2009;0.73, 95% CI 0.54-0.98) but not in studies that included moderate cases (OR&#x2009;=&#x2009;0.91, 95% CI 0.23-3.65). No significant heterogeneity was found across study designs, administration routes, or dosing frequencies, which confirmed the robustness of the primary findings while indicating insufficient evidence to determine the optimal regimen. The secondary outcomes suggested improvements in clinical recovery, pulmonary function, and pro-/anti-inflammatory cytokine balance in patients that received MSC therapy. Limited studies with long-term follow-up indicated potential benefits for Long-COVID outcomes (e.g., fatigue, quality of life, residual CT abnormalities, and exercise tolerance). No significant differences were observed in AEs or SAEs post-MSC infusion, which suggested that MSC therapy was well tolerated.<br><br>CONCLUSION: This meta-analysis indicated that MSC therapy may reduce mortality in patients with severe or critical COVID-19, demonstrating a favorable safety profile and potential benefits for Long-COVID and other viral pneumonias. Further large-scale, rigorous RCTs and mechanistic studies are warranted to strengthen the evidence base and standardize MSC administration regimens (source, dosing, frequency, and intervals) for managing COVID-19, Long-COVID, and other viral pneumonias.}, }
@article {pmid42041273, year = {2026}, author = {Silveira, JM and Nakaishi, APM and da Silva, MG and Dos Santos, DO and Gastaldi, AC}, title = {Effects of Exercise-Based Pulmonary Rehabilitation in Patients with Long COVID: A Systematic Review and Meta-Analysis.}, journal = {Advances in respiratory medicine}, volume = {94}, number = {2}, pages = {}, pmid = {42041273}, issn = {2543-6031}, mesh = {Humans ; *COVID-19/rehabilitation/complications/physiopathology ; *Exercise Therapy/methods ; Quality of Life ; Exercise Tolerance ; SARS-CoV-2 ; Randomized Controlled Trials as Topic ; }, abstract = {Background/Objective: A substantial proportion of infected individuals develop persistent symptoms after the acute phase of COVID-19, regardless of initial disease severity. Long COVID (LC) remains a public health challenge characterized by impaired functional exercise capacity (FEC) and quality of life (QoL). We systematically synthesized evidence on the effects of in-person outpatient pulmonary rehabilitation (OPR) with individualized and supervised exercise in adults with LC. Methods: Following PROSPERO (CRD42023389365), this study reviewed randomized controlled trials (RCTs) and observational cohort studies (OCSs) published between November 2019 and January 2026 in MEDLINE/PubMed, Web of Science, PEDro, and EMBASE. Results: Fifteen studies (n = 803) were included. OPR improved FEC (6MWT; MD: 53.72 m, 95% CI 43.69-63.75) and 30″SST (MD: 4.68, 95% CI 3.59-5.77) and reduced exertional dyspnea. RCTs showed benefits in physical (MD: 8.04, 95% CI 3.02-13.05) and mental QoL (MD: 6.60, 95% CI 2.01-11.18) and dyspnea impact, with inconsistent PF findings. Fatigue showed a trend toward improvement but was measured using heterogeneous patient-reported tools in RCTs and OCSs. Conclusions: Supervised PR improves FEC, QoL, and dyspnea in individuals with LC. In patients with fatigue/PEM, systematic assessment and continuous symptom monitoring are essential. High-quality controlled studies are needed to strengthen evidence and clinical guide.}, }
@article {pmid42043247, year = {2026}, author = {Mahajan, S and Mahajan, S and Kaushik, N}, title = {Integrative Insights into the Immunopathogenesis and Organ-Specific Immunological Mechanisms of Long COVID: A Narrative Review.}, journal = {Viruses}, volume = {18}, number = {4}, pages = {}, pmid = {42043247}, issn = {1999-4915}, mesh = {Humans ; *COVID-19/immunology/pathology/complications/virology ; *SARS-CoV-2/immunology ; Post-Acute COVID-19 Syndrome ; Immunity, Innate ; Adaptive Immunity ; Organ Specificity ; Autoimmunity ; }, abstract = {Long COVID (LC), also referred to as post-acute sequelae of SARS-CoV-2 infection, is characterized by persistent symptoms originating 3 months following acute COVID-19, lasting for at least two months and frequently affecting individuals who initially experienced mild to moderate disease. The clinical spectrum is heterogeneous, involving respiratory, cardiovascular, neurological, renal, gastrointestinal, and endocrine systems, thereby posing substantial diagnostic and therapeutic challenges. Despite extensive investigation, the precise immunopathogenic mechanisms underlying LC remain incompletely defined. Accumulating evidence suggests that LC is driven by a multifactorial interplay of persistent viral antigen reservoirs, chronic immune activation, dysregulated innate and adaptive immune responses, autoimmunity, endothelial dysfunction, microvascular injury, and aberrant tissue repair. These systemic immune perturbations manifest variably across different organs, contributing to the diverse clinical phenotypes observed. However, mechanistic clarity is hindered by heterogeneity in study designs, limited longitudinal data, and the absence of standardized immunological profiling. This narrative review provides integrative insights into the immunopathogenesis of LC, synthesizing current evidence on systemic immune dysregulation and organ-specific immunological mechanisms. A conceptual framework is proposed to facilitate a structured understanding of this complex syndrome and to guide future research toward targeted immunomodulatory strategies.}, }
@article {pmid42051540, year = {2026}, author = {Jin, H and An, Y and Huang, J and Luo, T and Wu, X}, title = {Pathophysiological mechanisms of post-exertional malaise: an integrative analysis based on the metabolism-immune-neuro interaction model.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1774310}, pmid = {42051540}, issn = {1664-3224}, mesh = {Humans ; *COVID-19/immunology/complications/metabolism/physiopathology ; *SARS-CoV-2 ; *Fatigue Syndrome, Chronic/immunology/physiopathology/metabolism ; Exercise/physiology ; Mitochondria/metabolism ; Neuroimmunomodulation ; Post-Acute COVID-19 Syndrome ; Reactive Oxygen Species/metabolism ; }, abstract = {Post-exertional malaise (PEM) is a common core symptom in various chronic debilitating conditions, such as Post COVID-19 Condition (PCC, also known as Long COVID) and Chronic Fatigue Syndrome (CFS). It is characterized by the delayed and persistent exacerbation of symptoms following even mild physical or cognitive activities. This review presents a systematic review of the pathophysiological mechanisms involved in PEM, proposing a dynamic framework of multi-system interactions that may lead to homeostatic imbalance. The etiology of PEM is multifactorial, potentially involving factors such as the persistent presence of pathogens, exposure to environmental toxins, and genetic predisposition. Collectively, these factors may establish a vulnerable baseline that heightens the body's physiological response to stressors, such as exercise, potentially triggering a pathological reaction. First, mitochondrial dysfunction and metabolic abnormalities may act as potential initiating factors in PEM, manifesting as impaired ATP synthesis, overproduction of reactive oxygen species (ROS), and the accumulation of metabolic byproducts. It is crucial to emphasize that exercise itself induces a 'toxic excitatory effect,' whereby healthy individuals enhance mitochondrial function and antioxidant defenses through physical activity. However, in individuals predisposed to PEM, due to underlying pathological conditions (e.g., sequelae of viral infections), this adaptive process is disrupted, preventing effective restoration of mitochondrial homeostasis and may initiate a potential vicious cycle of dysfunction. Second, ROS and mitochondrial DNA (mtDNA), as damage-associated molecular patterns (DAMPs), along with pathogen-associated molecular patterns (PAMPs), may activate the NLRP3 inflammasome and induce the release of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α, potentially transforming localized metabolic stress into a systemic inflammatory response. Subsequently, peripheral inflammation may be transmitted to the central nervous system through disruption of the blood-brain barrier and vagal nerve pathways, activating glial cells and initiating neuroinflammation. This process may ultimately affect the brain's interoceptive network, particularly the insular cortex, resulting in altered perception and processing of signals related to fatigue and pain. Furthermore, mitochondrial dysfunction in neurons may contribute to central energy depletion, which may impair synaptic plasticity and induce cognitive deficits and brain fatigue. Ultimately, this review proposes that PEM may arise from a complex interplay among mitochondrial dysfunction, immune activation, and neuroinflammation, which together form a self-perpetuating loop of "energy exhaustion - inflammation amplification," potentially contributing to the chronic and multi-system nature of PEM symptoms. The integrated "metabolism-immune-neuro" interaction model presented in this article may provide a potential comprehensive framework for understanding PEM and highlights the need for a multi-target, collaborative intervention approach that may help disrupt the pathological cycle.}, }
@article {pmid42055593, year = {2026}, author = {Syam, S and Aboelhassan, A and Althobiani, MA and Uysal, &#xd6;F and Sulaiman, N and Shah, AJ and Mandal, S and Mani, AR and Porter, JC and Hurst, JR}, title = {Differentiating the start of an exacerbation from day-to-day variation in people with COPD: a systematic review.}, journal = {European respiratory review : an official journal of the European Respiratory Society}, volume = {35}, number = {180}, pages = {}, pmid = {42055593}, issn = {1600-0617}, mesh = {Humans ; *Pulmonary Disease, Chronic Obstructive/physiopathology/diagnosis/therapy ; Disease Progression ; *Lung/physiopathology ; Time Factors ; Predictive Value of Tests ; Prognosis ; Male ; Female ; Aged ; Middle Aged ; }, abstract = {INTRODUCTION: COPD symptoms occur with day-to-day variation. An exacerbation of COPD is a symptom worsening that exceeds these fluctuations and requires systemic treatment. Differentiating the start of an exacerbation from day-to-day disease variation is an unmet research need. We sought to examine the evidence that monitoring daily variation in COPD can differentiate this from the onset of an exacerbation.<br><br>METHODS: A systematic review was conducted across MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature, Institute of Electrical and Electronics Engineers and Cochrane databases, as well as a citation search, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eligible studies focused on monitoring daily symptoms and/or physiological parameters in stable COPD. Quality assessments were conducted using the Newcastle-Ottawa Scale and the Cochrane Risk of Bias tool. Findings were qualitatively synthesised, considering essential components.<br><br>RESULTS: 22 studies were included in the review. The definitions of exacerbation were diverse across studies. 14 (64%) of the included studies demonstrated that day-to-day variation in symptoms (e.g. Chronic Airways Assessment Test score), vital signs (heart rate, respiratory rate and peripheral oxygen saturation) and lung function (peak expiratory flow, forced oscillatory technique), alone and in combination, showed promise in differentiating the onset of exacerbations. Daily monitoring provided earlier detection of exacerbation, up to 7 days before the day of onset. Baseline and threshold settings were identified as crucial factors. Continuous monitoring was more effective than once-daily assessments.<br><br>CONCLUSION: This review summarises evidence on how day-to-day variation differs from the start of an exacerbation in COPD. The combination of continuous monitoring, reliable measurement tools and a refined algorithm, with personalised baseline and threshold values, yields promising results.}, }
@article {pmid42056917, year = {2026}, author = {Bergqvist, E and Valerio-Shewmaker, M and Swartz, M and Patel, J and Padilla, L and Amavisca, XF and Gandhi, H and Messiah, SE}, title = {Association of race, ethnicity, and pediatric long COVID and MIS-C: a systematic review and meta-analysis.}, journal = {BMC infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12879-026-12848-z}, pmid = {42056917}, issn = {1471-2334}, }
@article {pmid42074690, year = {2026}, author = {Lucaciu, FC and Wellmann, N and Mihai, AM and Sima, A and Rosca, O and Suba, MI and Tarau, A and Bosoanca, A and Marc, M}, title = {Post-COVID Respiratory Sequelae in COPD: Mucus Plugging, Infectious Complications, and Risk-Stratified Follow-Up.}, journal = {Journal of clinical medicine}, volume = {15}, number = {8}, pages = {}, pmid = {42074690}, issn = {2077-0383}, abstract = {Context/Objectives: In patients with COPD (chronic obstructive pulmonary disease), SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection represents an overlap of viral injury on a lung already affected by pathological mucus, altered mucociliary clearance, chronic inflammation, and impaired antiviral immunity. Methods: A focused narrative review (2020-2025) was conducted using clinical, experimental, and consensus evidence. The evidence was synthesized qualitatively, with priority given to cohort studies, meta-analyses, and mechanism-focused studies with clinical relevance. Results: Mucus obstruction ("mucus plugs") is frequent in COPD (41-67%) and is associated with unfavorable outcomes. COPD also increases the risk of post-COVID respiratory sequelae. Bacterial coinfection at presentation is uncommon (3-5%), whereas secondary bacterial infections are more frequent (14-18%), especially in severe disease requiring intensive care, where VA-LRTI/VAP (ventilator-associated lower respiratory tract infection/ventilator-associated pneumonia) become predominant. Sepsis, whether viral or mixed, reflects disease severity and may contribute to functional decline and susceptibility to reinfections; however, the concept of a post-acute "sepsis legacy" in COPD after COVID-19 should currently be regarded as a clinically plausible but still emerging hypothesis rather than an established COPD-specific outcome. During recovery, acute exacerbation risk rises to 5.6% versus 3.9%, peaking in the first 30 days after severe disease (aHR ≈ 8.14). Persistent dyspnea and reduced DLCO (diffusing capacity for carbon monoxide) suggest ARDS-related injury, tissue remodeling, and microvascular dysfunction. Conclusions: In COPD, post-COVID respiratory sequelae result from the interaction of mucus, immunity, and infectious/sepsis-related complications. The first post-discharge month is a critical period requiring careful risk stratification and targeted follow-up.}, }
@article {pmid42088258, year = {2026}, author = {Huang, H and Chen, S and Fang, Z and Ma, Y and Xu, Y and Dong, G}, title = {The "two-hit" storm: a hyper-inflammatory endotype in pediatric long COVID and its role in the severity of secondary bacterial pneumonia-a mechanistic review and clinical implications.}, journal = {Frontiers in public health}, volume = {14}, number = {}, pages = {1782871}, pmid = {42088258}, issn = {2296-2565}, mesh = {Humans ; *COVID-19/immunology/complications ; Child ; SARS-CoV-2 ; *Pneumonia, Bacterial/immunology ; *Inflammation/immunology ; Severity of Illness Index ; Pneumonia, Mycoplasma/immunology ; }, abstract = {Following the COVID-19 pandemic, the clinical patterns of pediatric respiratory infections have undergone significant changes, with increasing attention on the immunological imprint left by Post-Acute Sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID. A perplexing clinical phenomenon has been observed: some children with a history of Long COVID exhibit a disproportionately severe inflammatory response and extensive lung injury when encountering common community-acquired pneumonia, such as that caused by Mycoplasma pneumoniae or Streptococcus pneumoniae, inconsistent with their pathogen load. This review aims to dissect this phenomenon and proposes the "Immune Priming and Two-Hit" model as its core pathophysiological framework. This model posits that the Long COVID state constitutes the "first hit," establishing a "primed" or "hyper-reactive" immune baseline through viral persistence, trained immunity-induced monocyte reprogramming, and sustained endothelial dysfunction. Upon the "second hit" of a bacterial infection, this primed immune system triggers a dysregulated, synergistically amplified inflammatory cascade. The mechanisms involve the exponential release of cytokines such as Interleukin-6 (IL-6), IL-1β, and Tumor Necrosis Factor-α (TNF-α), inflammation-mediated immunothrombosis, and excessive activation of Neutrophil Extracellular Trap formation (NETosis), ultimately leading to severe outcomes like Acute Respiratory Distress Syndrome (ARDS) and necrotizing pneumonia. Consequently, identifying and defining this "Hyper-inflammatory endotype" is of critical clinical importance. We define it as an "endotype" to emphasize the distinct, host-determined pathophysiological mechanisms underlying it, rather than merely a collection of clinical manifestations. By monitoring biomarkers such as ferritin, D-dimer, lactate dehydrogenase (LDH), and lymphocyte counts, clinicians may be able to perform early risk stratification of these children. This approach not only facilitates a shift in therapeutic strategy from purely antimicrobial therapy to "host-directed therapy"-emphasizing the necessity of early, adequate corticosteroid use and consideration of anticoagulation-but also provides a new theoretical basis and intervention window for preventing long-term sequelae such as pulmonary fibrosis.}, }
@article {pmid42101066, year = {2026}, author = {Boufleuer, E and Vieira, TW and Sakamoto, VTM and Anschau, F and Tavares, JP and Filho, FFD and Pai, DD}, title = {Psychological and Cognitive Sequelae of COVID-19: Systematic Review and Meta-Analysis.}, journal = {Journal of psychiatric and mental health nursing}, volume = {}, number = {}, pages = {}, doi = {10.1111/jpm.70139}, pmid = {42101066}, issn = {1365-2850}, support = {312850/2025-5//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; }, abstract = {INTRODUCTION: COVID-19 pandemic has exacerbated global mental health problems with the development of persistent symptoms.<br><br>AIM: To conduct a prevalence meta-analysis of persistent psychological and cognitive sequelae of COVID-19 based on cohort studies.<br><br>METHOD: This study followed PRISMA. Cohort studies that followed individuals for at least 12&#x2009;weeks post-COVID-19 were included and pediatric studies were excluded. The databases Embase, Lilacs/BVS, PubMed, SciELO and Scopus were searched in November 2023. Meta-analyses were performed with subgroup analyses conducted. Results were presented with forest plot graphs and tables. Risk of bias and methodological quality were assessed using Eggers's Test and the Newcastle-Ottawa Scale.<br><br>RESULTS: 2,456 studies were identified and screened. Forty-seven articles were included in the systematic review, and 46 in the meta-analysis (192,158 participants). The most prevalent psychological outcome was anxiety (0.17; 95% CI 0.11-0.27, 19 studies), followed by cognitive impairments (0.15; 95% CI 0.11-0.20, 35 studies), sleep disturbances (0.14; 95% CI 0.09-0.19, 33 studies) and depression (0.11; 95% CI 0.06-0.19, 16 studies).<br><br>DISCUSSION: The mental health consequences of COVID-19 highlight the need for long-term monitoring and represent a significant public health challenge. The limitation is the heterogeneity among the studies.<br><br>These findings represent a public health issue emphasizing the need for public policies and support strategies to mitigate consequences.<br><br>CONCLUSION: Although high prevalence rates were identified, the prediction intervals were wide and heterogeneity remained high-common characteristics of studies conducted during the pandemic.<br><br>REGISTRATION: Registered in the international Prospective Register of Ongoing Systematic Reviews (PROSPERO) under number CRD42023460632, on&#xa0;September 5, 2023.}, }
@article {pmid42121889, year = {2026}, author = {Kopańska, M and Trojniak, J and Góral-Półrola, J and Pąchalska, M}, title = {Alterations in Cortical Oscillatory Dynamics Following SARS-CoV-2 Infection: QEEG Biomarkers of Vulnerability to Attention and Seizure-Related Symptoms.}, journal = {Cells}, volume = {15}, number = {9}, pages = {}, pmid = {42121889}, issn = {2073-4409}, mesh = {Humans ; *COVID-19/complications/physiopathology ; *Electroencephalography/methods ; *Seizures/physiopathology/etiology ; Biomarkers/metabolism ; SARS-CoV-2 ; *Attention/physiology ; *Cerebral Cortex/physiopathology ; }, abstract = {SARS-CoV-2 infection is associated with not only acute respiratory symptoms but is also characterized by strong neurotropism which may contribute to the development of the multisystem post-COVID syndrome (PASC). Patients frequently report chronic neurocognitive disorders such as brain fog, significant attention deficits and increased susceptibility to epileptiform discharges. The aim of this review is to systematize the knowledge regarding deviations in quantitative electroencephalography (QEEG) recordings in convalescents and to evaluate the utility of this method as an objective biomarker. This work constitutes a comprehensive literature review integrating the latest data on neuroinflammation, blood-brain barrier damage and changes in cortical oscillatory dynamics induced by the infection. The literature analysis indicates that the virus may induce a pathological excitation and inhibition imbalance (E/I imbalance) in neuronal networks. In QEEG studies this manifests as excessive activity of slow bands (Theta, Delta), a deficit of rhythms responsible for attention and sensorimotor integration (SMR) and a pathologically elevated Theta to Beta ratio (TBR). In conclusion, QEEG can serve as an objective and highly sensitive tool supporting the diagnosis and stratification of patients with neurocognitive complications of Long COVID. The integration of precise electrophysiological phenotyping with targeted behavioral neuromodulation (e.g., EEG-Biofeedback) fits into the paradigm of personalized medicine and offers a prospective strategy for mitigating long-term neurological burdens.}, }
@article {pmid42123618, year = {2026}, author = {Wirth, KJ and Scheibenbogen, C}, title = {Imbalance of Excitatory and Inhibitory Neurotransmitter Systems in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.}, journal = {International journal of molecular sciences}, volume = {27}, number = {9}, pages = {}, pmid = {42123618}, issn = {1422-0067}, mesh = {Humans ; *Fatigue Syndrome, Chronic/metabolism/physiopathology ; *Neurotransmitter Agents/metabolism ; *COVID-19/metabolism/complications ; SARS-CoV-2 ; Synaptic Transmission ; Animals ; }, abstract = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and post-COVID-19 syndrome share a symptom profile, including severe fatigue, cognitive dysfunction, exertional intolerance, sleep disturbances, hypervigilance, and the paradoxical state of being "wired but tired." A well-established finding is sympathetic hyperactivity with reduced vagal tone, typically interpreted as autonomic nervous system dysfunction. Emerging evidence, however, suggests a broader disturbance across multiple neurotransmitter systems. This paper reviews current knowledge on neurotransmitter systems implicated in ME/CFS and Long COVID, focusing on potential mechanisms of dysregulation and their roles in disease pathology and symptom generation, as well as implications for treatment. In addition to abnormalities of the noradrenergic system, disturbances in serotonergic, GABAergic, and glutamatergic signaling have been reported. Contributing factors may include autoimmunity, neuroinflammation, gut dysbiosis, epigenetic influences, and stressors such as orthostatic intolerance, metabolic strain, and pain. A shift favoring excitatory over inhibitory neurotransmission can lead to excessive neural activation, autonomic dysfunction, sensory hypersensitivities, sleep disturbances, and cognitive impairment. Reduced GABAergic tone combined with increased glutamatergic and noradrenergic activity may elevate skeletal muscle tone, contributing to calcium overload, mitochondrial dysfunction, exertional intolerance, and post-exertional malaise. Various pharmacological treatments may partially rebalance these neurotransmitter systems, but limited efficacy highlights the need for systematic investigation and individualized strategies.}, }
@article {pmid42129072, year = {2026}, author = {Veenstra, TD}, title = {Viral Prognosis Using Proteomics.}, journal = {Advances in experimental medicine and biology}, volume = {1511}, number = {}, pages = {75-102}, pmid = {42129072}, issn = {0065-2598}, mesh = {Humans ; *COVID-19/virology/diagnosis/metabolism/epidemiology ; *Proteomics/methods ; *SARS-CoV-2/genetics/metabolism/pathogenicity ; Prognosis ; Pandemics ; }, abstract = {So much was learned during the COVID-19 pandemic of 2020-2023. Some of the things that were learned were obvious. Many people in the public learned about social distancing, personal hygiene, and how to conduct a COVID-19 diagnostic test. Pharmaceutical companies and government organizations learned to efficiently work together to produce and distribute vaccines in record time. Although it may have generated controversy, the value in getting vaccinated was revalidated. There were other things that the world learned, although it was not as obvious. The effect of vaccination rate on preventing virus mutation became evident during the pandemic. The original SARS-CoV-2 virus that started the pandemic mutated several times over the course of the pandemic. One thing that became clear during the pandemic was the lack of knowledge on how SARS-CoV-2 infection would affect individuals during the course of the disease. This inability to accurately prognose the disease made it difficult to personalize treatments for specific individuals and the distribution of resources to protect the most vulnerable populations challenging. What is required to increase the accuracy of prognosis is more knowledge about how dynamic changes occur within the host cell during viral infection. Since many proteins become dysregulated during infection, proteomics is a prime technology for gaining this knowledge to increase prognostic capabilities and enable personalized treatments that alleviate the suffering viruses cause on humanity.}, }
@article {pmid42130374, year = {2026}, author = {Kell, DB and Pretorius, E}, title = {Assessing the Health and Functionality of the Microcirculation Using Thermal Imaging.}, journal = {Journal of biophotonics}, volume = {19}, number = {5}, pages = {e70270}, pmid = {42130374}, issn = {1864-0648}, support = {18//Balvi/ ; //Polybio/ ; //Kanro/ ; }, mesh = {*Microcirculation ; Humans ; *Thermography/methods ; Animals ; }, abstract = {The microcirculation, composed of vessels below 100 μm in diameter, sustains tissue perfusion and metabolic exchange. Its dysfunction is increasingly implicated in chronic, inflammatory, and thrombotic disorders such as diabetes, sepsis, cardiovascular disease, and Long COVID. Accurate, noninvasive assessment of microvascular health is therefore clinically significant. Infrared thermal imaging provides a rapid, contact-free, and physiologically coherent means of visualizing temperature distributions that reflect underlying blood flow. Because thermal gradients directly correspond to perfusion heterogeneity, this approach offers an interpretable surrogate for assessing microvascular function. Here, we review the physical principles of thermal imaging, summarize its application to the peripheral circulation, and compare it with established modalities including nailfold capillaroscopy and laser-based techniques. We also outline its utility across diverse pathologies associated with fibrinaloid microclot complexes and endothelial injury. Thermal imaging thus emerges as an inexpensive/scalable tool for evaluating microcirculatory dysfunction in both research and (where approved) in clinical settings.}, }
@article {pmid42135534, year = {2026}, author = {Rosa, GD and Raffo, M and Tammaro, S and Morelli, M and Arcaniolo, D and Pandolfo, SD and Sciorio, C and Romano, L and Manfredi, C and Cindolo, L and De Sio, M and Spirito, L}, title = {The impact of COVID-19 on sexual behavior, male sexual function, and reproductive health: an interdisciplinary narrative review from a urological perspective.}, journal = {International urology and nephrology}, volume = {}, number = {}, pages = {}, pmid = {42135534}, issn = {1573-2584}, abstract = {The COVID-19 pandemic profoundly modified daily life and interpersonal relationships, with relevant consequences on sexual health, which integrates biological, psychological, and social components. This narrative review summarizes current evidence regarding the impact of the pandemic on sexual behavior, sexual function, and male reproductive health. A comprehensive literature search of recent studies and clinical reports was performed focusing on psychosexual wellbeing, erectile function, fertility, and healthcare access during and after infection or lockdown periods. Current evidence indicates that lockdown-related stress, anxiety, and depression were consistently associated with reduced sexual desire and frequency of sexual activity, as reported in predominantly cross-sectional, questionnaire-based studies conducted during lockdown periods, particularly among couples with children and non-cohabiting partners, whereas alternative sexual practices increased. Sexual activity generally recovered after restrictions were lifted. Emerging data suggest a possible association between COVID-19 and erectile dysfunction mediated by endothelial damage, hypogonadism, and psychological distress, while long-COVID symptoms may further worsen sexual function. Male fertility alterations related to inflammatory and oxidative stress pathways have also been reported. Overall, the pandemic primarily affected sexuality through psychosocial mechanisms, although potential organic effects of SARS-CoV-2 infection on erectile function and fertility cannot be excluded. This review provides an interdisciplinary synthesis of current evidence with a specific focus on clinically relevant urological implications, including erectile dysfunction and male reproductive health, which remain incompletely addressed in the existing literature.}, }
@article {pmid42140539, year = {2026}, author = {Tamariz, L and Shehadeh, LA and Bast, E and Klimas, N and Palacio, A}, title = {The role of the endothelium in long COVID.}, journal = {Vascular pharmacology}, volume = {163}, number = {}, pages = {107654}, doi = {10.1016/j.vph.2026.107654}, pmid = {42140539}, issn = {1879-3649}, abstract = {SARS-CoV2 infection significantly increases the risk of cardiovascular events through multiple interconnected mechanisms including systemic inflammation, dysautonomia, endothelial dysfunction, and prothrombotic states. The endothelium plays a critical role in this increase in risk together with dysautonomia and mast cell activation. SARS-CoV2 activates endothelial cells creating a pro-inflammatory, and pro-thrombotic phenotype. This phenotype could lead to microcirculatory changes that decrease oxygen delivery to tissues because of loss of laminar flow, lack of nitric oxide dependent vasodilation, increased viscosity and abnormal constriction of vascular smooth muscle cells due to neuropathy. There are several ways of identifying patients with endothelial dysfunction and the most used is flow mediated dilation. Many randomized trials have already found significant treatments for endothelial dysfunction and include antihypertensives, statins, beta-blockers, supplements and lifestyle interventions. Only two studies using vitamin C and L-arginine demonstrated improvements in flow mediated dilation in patients with long COVID.}, }
@article {pmid42163969, year = {2026}, author = {Hendriks, S and Grady, C and Fitzgerald, ML and Gross, RS and Maughan, C and Peluso, MJ and Varma, S and Nath, A and Rid, A}, title = {The next phase in Long COVID research: addressing the ethical challenges in trials of disease-modifying treatments.}, journal = {EClinicalMedicine}, volume = {95}, number = {}, pages = {103918}, pmid = {42163969}, issn = {2589-5370}, abstract = {Almost five years after COVID-19 emerged, multiple scientific uncertainties remain about why some people experience ongoing symptoms long after being infected with SARS-CoV-2 (Long COVID). The pathophysiology underlying Long COVID and its potential to represent several endotypes are still under investigation. These scientific uncertainties around Long COVID have been cited as a reason to delay treatment trials until the disease is better understood. In this paper, a group of bioethicists, clinician-scientists and people with lived experience with Long COVID argue that it is ethically imperative to conduct trials of disease-modifying treatments for Long COVID now. Furthermore, we argue that although conducting such trials can pose ethical challenges, these challenges can be overcome through careful research priority-setting, rigorous trial design, fair participant selection, and ensuring that the risk-benefit profile is favorable.}, }
@article {pmid42168400, year = {2026}, author = {Si, Y and Zhu, X and Zhang, Y and Zhou, Z and Liu, Y and Ma, H}, title = {PANoptosis as a Therapeutic Target for COVID-19.}, journal = {Current microbiology}, volume = {83}, number = {7}, pages = {}, pmid = {42168400}, issn = {1432-0991}, support = {No.2023-CX-TD-66//the Innovation Capability Support Program of Shaanxi/ ; 82202367//the National Natural Science Foundation of China/ ; }, mesh = {Humans ; *SARS-CoV-2/drug effects ; *COVID-19/immunology/virology/pathology ; *COVID-19 Drug Treatment ; Apoptosis/drug effects ; *Necroptosis/drug effects ; Pyroptosis/drug effects ; Antiviral Agents/therapeutic use/pharmacology ; Cytokine Release Syndrome ; Animals ; }, abstract = {Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has sparked a global pandemic with extensive spread, posing a severe threat to public health due to its high mortality rate in severe cases. The continuous emergence of variants with enhanced immune evasion capabilities, coupled with the prolonged and debilitating symptoms of Long Coronavirus Disease (Long COVID) such as intermittent dyspnea, persistent fatigue, and cognitive impairment (brain fog), has become a major global concern. The pathogenesis of COVID-19 is a complex interplay of direct viral cytotoxicity and an overwhelming secondary inflammatory response in the host, with the latter being a key driver of immune homeostasis disruption. Accumulating evidence indicates that PANoptosis, an integrated programmed cell death process involving the crosstalk and coordinated activation of apoptosis, pyroptosis, and necroptosis, is closely linked to the cytokine storm syndrome triggered by SARS-CoV-2 infection. As a critical mediator of various infectious diseases, PANoptosis plays a pivotal role in regulating the balance between viral clearance and pathological inflammation. This review specifically targets SARS-CoV-2, adopting a "basic mechanism-molecular regulation-therapeutic target-clinical translation" framework. We elaborate on SARS-CoV-2-induced PANoptosis mechanisms, including its constituent cell death pathways and contributions to cytokine storms. By dissecting the intricate regulatory networks between PANoptosis and interferon (IFN) signaling during viral infection, this work aims to identify potential therapeutic targets and provide novel insights for the development of effective strategies to mitigate severe COVID-19 and its long-term sequelae.}, }
@article {pmid42173633, year = {2026}, author = {Agrawal, P}, title = {AI in multi-omics analysis of COVID-19 patient data.}, journal = {Progress in molecular biology and translational science}, volume = {222}, number = {}, pages = {261-293}, doi = {10.1016/bs.pmbts.2026.01.017}, pmid = {42173633}, issn = {1878-0814}, mesh = {*COVID-19/genetics/metabolism/virology ; Humans ; *Artificial Intelligence ; *Genomics/methods ; *SARS-CoV-2 ; Metabolomics ; Proteomics ; Machine Learning ; Epigenomics ; Neural Networks, Computer ; Multiomics ; }, abstract = {The COVID-19 pandemic has led to an unprecedented increase in the volume of biological data generation, demonstrating the importance of developing an integrative and intelligent analytical framework. In the last few years, advancements in the artificial intelligence (AI) approaches have completely transformed the biological research landscape. Researchers have integrated the AI approaches with the multi-omics data generated from the COVID-19 patients to have a systems-level understanding of underlying disease mechanisms, predicting new variants and their spread rate, disease severity, immune response, and therapeutic opportunities. In this chapter, we have explored the utility of AI on multi-omics data. We started with an introduction to different kinds of omics data, such as genomics, epigenomics, transcriptomics, proteomics, and metabolomics. Next, we elaborated on what AI is and discussed its types, which include conventional machine learning methods (supervised and unsupervised), deep learning methods (autoencoders and convolutional neural networks), and network-based methods (graph neural networks, network propagation, and knowledge graphs). Next, we discussed different types of integration methods (early, intermediate, and late) used for integrating AI and multi-omics data. Moving ahead, we mentioned several applications of AI, such as biomarker discovery, host-pathogen interaction, drug repurposing, and predicting long COVID. Lastly, we mentioned several important projects and consortia and discussed several important case studies highlighting the usefulness of integrating AI with multi-omics data for personalized medicine.}, }
@article {pmid42174604, year = {2026}, author = {Watton, P and Prusty, BK}, title = {Reframing ME/CFS: toward a unified mechanistic model of chronic post-infectious diseases.}, journal = {Journal of translational medicine}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12967-026-08319-3}, pmid = {42174604}, issn = {1479-5876}, abstract = {BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe multisystem illness marked by post-exertional malaise (PEM), cognitive dysfunction, autonomic disturbance, and impaired physiological resilience. Historically, the absence of validated biomarkers, heterogeneous definitions, and limited investigative capacity have complicated mechanistic interpretation and contributed to the use of psychosocial and rehabilitative frameworks in clinical practice and in parts of the literature.<br><br>MAIN BODY: Advances in systems biology, accelerated by Long-COVID research, have transformed our understanding of post-infectious syndromes, implicating persistent immune dysregulation, mitochondrial and metabolic reprogramming, endothelial and microvascular dysfunction, abnormal coagulation, lipid-mediated signalling, extracellular vesicle communication, and viral protein-associated immune activation. This review charts the shift from early post-infectious observations through psychosocial dominance to contemporary biological frameworks, emphasising that pathology is state-dependent and revealed under physiological stress.<br><br>CONCLUSION: ME/CFS is thus reframed here as a disorder of impaired adaptive capacity within post-infectious disease biology.}, }
@article {pmid42174645, year = {2026}, author = {Plaut, S}, title = {A systematic scoping review and conceptual analysis of new-onset fibromyalgia manifestations after non-hospitalized COVID-19: empirics, definitions, methodologies, pathophysiology, mapping of literature, and knowledge gaps.}, journal = {Journal of translational medicine}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12967-026-08145-7}, pmid = {42174645}, issn = {1479-5876}, abstract = {BACKGROUND: The global coronavirus pandemic has led to a quiet wave of a chronic illness referred to as 'Long/Post Covid-19 syndrome' (LC) which bears a notable resemblance to functional-somatic or 'fibromyalgia-type' syndromes, and whose pathophysiology is undetermined. The lack of effective therapies for LC is straining healthcare systems worldwide and causing widespread public health and socioeconomic concerns. "Fibromyalgia" is a controversial chronic pain condition of unknown etiology largely attributed to generalized sensory hypersensitivity due to dysregulated central pain processing pathways (i.e. neuroplasting central sensitization). Despite intense research and growing attention in the scientific community, the clinical overlap of fibromyalgia, somatic symptom disorder, and post-viral chronic fatigue, is a medical puzzle yet to be solved, especially when occurring in non-severe infections and previously healthy individuals.<br><br>METHODS: This systematic scoping review covers the empirical findings on new-onset fibromyalgia manifestations after non-hospitalized covid-19. MEDLINE, Web of Science, and APA PsycINFO were searched in a systematic scoping approach for empirical studies on new-onset fibromyalgia after non-severe non-hospitalized covid-19, charting study characteristics and outcome data. A total of 228 records were included.<br><br>FINDINGS: Various types of methods, tools, and study designs are being used for LC research, with inconsistency in key concepts and definitions. This leads to a fragmented understanding of the relationship between SARS-CoV-2 infection and LC. Prevalence studies of post-Covid fibromyalgia are ongoing and susceptible to bias. The empirical evidence supports an overlap between LC, chronic fatigue syndrome, and fibromyalgia but the molecular mechanisms still remain unclear. There are conflicting findings regarding presence of viral particles, central sensitization, autoantibodies, and more.<br><br>DISCUSSION: This review highlights the need for standardized definitions and rigorous methodologies in research on LC. Future research should focus on epidemiological population-based studies with representative sampling and improving methodology, refining evolving definitions, harmonization of research, elucidating neurological mechanisms in hypothesis driven studies, and developing effective therapeutic strategies. The discussion synthesizes findings and offers an integrative mechanism for the pathophysiology of fibromyalgia and multisystem medically unexplained manifestations of LC as a non-autoimmune connective tissue disease. It helps explain neuropsychiatric and psychosomatic manifestations and is used to make testable theory-based predictions for future hypothesis-driven investigations.}, }
@article {pmid42181627, year = {2026}, author = {Maurya, N and Le, A and Melbourne, G and Chow, JSF}, title = {Long-term cardiovascular impact of COVID-19 among hospitalised and non-hospitalised populations: a narrative synthesis review.}, journal = {Frontiers in cardiovascular medicine}, volume = {13}, number = {}, pages = {1741293}, pmid = {42181627}, issn = {2297-055X}, abstract = {INTRODUCTION: COVID-19, initially recognised as a respiratory illness, affects multiple organ systems, including the cardiovascular system. Both hospitalised and non-hospitalised patients may experience persistent cardiac complications; however, the long-term impact across different levels of disease severity remains unclear. This review aims to summarise the existing evidence on the long-term cardiovascular impact of COVID-19, with a particular focus on differences between hospitalised and non-hospitalised patients.<br><br>METHOD: PubMed, MEDLINE, CINAHL, and Embase databases were searched for studies published between December 2019 and January 2024 that investigated cardiovascular outcomes in long COVID. Studies were screened for eligibility, and data were extracted using a standardised form. Due to heterogeneity across the included studies, a narrative synthesis was performed.<br><br>RESULTS: Seventy-one studies were included, most of which were observational and conducted in Europe and Asia, with follow-up periods ranging from <1 to >24 months. Hospitalised patients reported more frequent cardiovascular symptoms; however, echocardiographic abnormalities were observed across all groups. Reporting of symptom severity was inconsistent. Common cardiovascular manifestations included palpitations, chest pain, fatigue, and arrhythmias. Persistent cardiac dysfunction and dysautonomia were observed regardless of hospitalisation status.<br><br>CONCLUSION: Hospitalised patients are at higher risk of long-term cardiovascular complications, including myocardial injury, arrhythmias, and heart failure, while non-hospitalised individuals may experience subclinical cardiac changes. Vaccination appears to have a protective effect. Standardised, prospective studies are needed to clarify long-term cardiovascular risks and to guide follow-up care.}, }
@article {pmid42183165, year = {2026}, author = {Uddin, AS and Bulusu, S and Oderinde, OM and Zheng, QH}, title = {Positron emission tomography imaging of T-cell activity in cardiovascular disease and its emerging role in imaging adaptive immunity.}, journal = {American journal of nuclear medicine and molecular imaging}, volume = {16}, number = {2}, pages = {77-89}, pmid = {42183165}, issn = {2160-8407}, abstract = {T lymphocytes are central mediators of cardiovascular disease, driving myocardial injury in myocarditis, transplant rejection, post-infarct remodeling, atherosclerosis, and post-viral syndromes. Yet current imaging tools ([[18]F]FDG PET, somatostatin receptor tracers, CXCR4 PET, and cardiac MRI) offer only indirect or nonspecific measures of immune activity. The ability to noninvasively visualize and quantify T-cell infiltration and activation could transform diagnosis and management in cardio-immunology. Advances in immuno-PET have produced a growing arsenal of T-cell specific tracers. CD8-targeted agents ([89]Zr-Df-IAB22M2C) and small-molecule probes such as [[18]F]F-AraG have entered early clinical trials, demonstrating feasibility and safety in humans. Other tracers, including CD4- and CD3-directed antibodies, IL-2R and OX40 probes, checkpoint tracers (PD-1, CTLA-4), and granzyme B ligands, remain largely preclinical but show strong potential for cardiovascular translation. Applications span acute myocarditis, noninvasive transplant rejection surveillance, assessment of post-MI immune remodeling, plaque vulnerability in atherosclerosis, and systemic immune activation in long COVID. Compared with existing imaging modalities, T-cell PET offers cell-type specificity, quantitative longitudinal monitoring, and the capacity for whole-body immune mapping, particularly when integrated with total-body PET or hybrid PET/MR. Challenges include low T-cell density in the myocardium, tracer specificity, radiation burden, and the need for histopathologic validation. Future directions involve repurposing oncology tracers for cardiology, engineering antibody fragments with improved kinetics, and establishing T-cell PET as a mechanistic biomarker in cardiovascular clinical trials. With further innovation and validation, T-cell PET has the potential to evolve from an experimental tool into a clinically actionable modality, reshaping the management of immune-mediated heart disease.}, }
@article {pmid42205482, year = {2026}, author = {Albelasi, A}, title = {Symptoms, mechanisms, and management of long COVID: understanding its prevalence, characteristics, and healthcare challenges in Saudi Arabia.}, journal = {Frontiers in cellular and infection microbiology}, volume = {16}, number = {}, pages = {1747443}, pmid = {42205482}, issn = {2235-2988}, mesh = {Humans ; *COVID-19/epidemiology/therapy ; Saudi Arabia/epidemiology ; Post-Acute COVID-19 Syndrome ; Prevalence ; SARS-CoV-2 ; Pandemics ; }, abstract = {Long COVID is a prolonged health condition wherein patients continue to experience symptoms long after recovering from infection, so it presents a significant global health challenge with multi-organ involvement. This review provides evidence from several studies to elucidate the prevalence, symptom clusters, and underlying mechanisms of Long COVID. Key findings highlight fatigue (25-73%), cognitive dysfunction, respiratory symptoms (dyspnea: 6.9-47%), cardiovascular symptoms (49.37/1,000), and reproductive symptoms (menstrual irregularities, erectile dysfunction) as predominant manifestations. Mechanistic insights include viral persistence, immune dysregulation, and endothelial dysfunction. The review gives detailed information about prevalence and immunological studies carried out in Saudi Arabia on Long COVID and underscores the importance of longitudinal immune studies, multidisciplinary approaches, biobanks, and global collaborations to improve patient outcomes. Recommendations emphasize tailored therapies, psychological support, and large-scale cohort studies to address heterogeneity and optimize care for Long COVID patients in Saudi Arabia.}, }
@article {pmid42215147, year = {2026}, author = {Petropoulou, D and Karampela, I and Christodoulatos, GS and Kounatidis, D and Vallianou, NG and Dalamaga, M}, title = {Hormonal, metabolic and metabolomic biomarkers in long COVID.}, journal = {Advances in clinical chemistry}, volume = {133}, number = {}, pages = {217-283}, doi = {10.1016/bs.acc.2026.01.002}, pmid = {42215147}, issn = {2162-9471}, mesh = {Humans ; Biomarkers/metabolism/blood ; Post-Acute COVID-19 Syndrome ; *COVID-19/metabolism/complications ; *Hormones/metabolism ; Metabolomics ; SARS-CoV-2 ; }, abstract = {Long COVID (LC), a complex syndrome affecting approximately 6-12 % of individuals post infection, is characterized by persistent, fluctuating, or progressive symptoms lasting at least three months. Its pathogenic mechanisms involve viral persistence, chronic inflammation, immune dysregulation, endothelial dysfunction, and endocrine/metabolic abnormalities. Currently, no specific diagnostic tests exist for LC, highlighting the need for reliable biomarkers. This review synthesizes current evidence on hormonal, metabolic, and metabolite biomarkers in LC. While vitamin D deficiency is prevalent in LC, being associated with neurocognitive symptoms, delayed recovery and poor physical performance, particularly in older adults, its lack of specificity reduces diagnostic utility. Insulin resistance markers consistently correlate with fatigue, mood disturbances, and myalgia, suggesting a distinct metabolic LC phenotype. Lower cortisol frequently correlates with fatigue, sensory disturbances, and neurocognitive symptoms. Alterations in cortisol/adrenocorticotropic hormone, growth hormone, prolactin, and gonadotropins suggest a potential hypothalamic-pituitary axis involvement; however, these abnormalities are often transient, dynamic or nonsignificant. While some patients may exhibit low free triiodothyronine associated with fatigue, no significant incidence of thyroid dysfunction and autoimmunity was associated with LC. Despite the absence of a distinct and consistent metabolomic signature, LC is characterized by the activation of the kynurenine pathway, including increased kynurenine and quinolinic acid, being associated with fatigue, neurocognitive and depressive symptoms. Emerging metabolites of mitochondrial dysfunction and lipid metabolism alterations require further validation. Despite promising findings, evidence remains scattered, hindered by small sample sizes and methodological limitations. Future research should prioritize standardization of biomarker assessment, validation in diverse populations, and exploration of targeted therapeutic interventions.}, }
@article {pmid42216347, year = {2026}, author = {Faseeh, A and Rida, M and Karim, NE and Zafar, A and Shah, A and Perveen, A}, title = {Prevalence and long-term outcomes of brain fog and cognitive impairment in individuals with long COVID: A systematic review.}, journal = {Medicine}, volume = {105}, number = {22}, pages = {e49022}, pmid = {42216347}, issn = {1536-5964}, mesh = {Humans ; *Cognitive Dysfunction/epidemiology/etiology ; Prevalence ; *COVID-19/complications/epidemiology ; Post-Acute COVID-19 Syndrome ; Female ; Male ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Long COVID is increasingly recognized as a complex multisystem condition, with brain fog and cognitive impairment emerging as some of its manifestations. Despite growing literature, the pooled prevalence, subgroup differences, and underlying mechanisms remain incompletely understood.<br><br>METHODS: We systematically reviewed 47 studies (2000-2025) encompassing over 25,000 patients to evaluate the prevalence of brain fog and cognitive impairment among long COVID populations. Data were extracted on study design, patient demographics, follow-up duration, and subgroup variables including gender, hospitalization, vaccination, and geographic region. Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS v9.0) and JBI checklists. Quantitative synthesis was performed with subgroup and temporal analyses, presented in forest plots and summary figures.<br><br>RESULTS: The pooled prevalence of brain fog was 30% (95% CI: 28-32), while cognitive impairment was 25% (95% CI: 23-27). Female patients consistently showed higher rates compared to males (34% vs 23% for brain fog; 29% vs 21% for cognitive impairment). Community-managed patients demonstrated higher prevalence compared to hospitalized cohorts, and unvaccinated individuals had a greater burden than vaccinated ones. Temporal analyses indicated that prevalence increased with longer follow-up, suggesting symptom persistence or late manifestation. Pathophysiological explanations include neuroinflammation, microvascular injury, immune dysregulation, and psychosocial stressors.<br><br>CONCLUSION: Brain fog and cognitive impairment are common, persistent, and clinically significant features of long COVID. Gender differences, vaccination status, and follow-up duration influence prevalence. Future studies should focus on mechanisms, preventive strategies, and targeted interventions to mitigate long-term cognitive sequelae.}, }
@article {pmid32967479, year = {2020}, author = {Zoltie, T and Owen, K and Devigus, A and Kelly, S}, title = {COVID-19 decontamination procedures for photographic equipment in a secondary care setting.}, journal = {Journal of visual communication in medicine}, volume = {43}, number = {4}, pages = {184-189}, doi = {10.1080/17453054.2020.1796478}, pmid = {32967479}, issn = {1745-3062}, mesh = {Betacoronavirus/*isolation &amp; purification ; *Built Environment ; COVID-19 ; Coronavirus Infections/*prevention &amp; control ; Decontamination/*methods ; Humans ; Pandemics/*prevention &amp; control ; Photography/*instrumentation ; Pneumonia, Viral/*prevention &amp; control ; SARS-CoV-2 ; }, abstract = {This article provides an overview of how long COVID-19 (SARS-CoV-2) survives on the built environment, and reviews currently available resources to provide recommendations on effective decontamination of photographic equipment based within a secondary care setting.}, }
@article {pmid33205450, year = {2021}, author = {Ludvigsson, JF}, title = {Case report and systematic review suggest that children may experience similar long-term effects to adults after clinical COVID-19.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {110}, number = {3}, pages = {914-921}, pmid = {33205450}, issn = {1651-2227}, mesh = {Adolescent ; Age Factors ; COVID-19/*complications/diagnosis/epidemiology ; Child ; Female ; Humans ; Male ; Symptom Assessment ; Time Factors ; }, abstract = {AIM: Persistent symptoms in adults after COVID-19 are emerging and the term long COVID is increasingly appearing in the literature. However, paediatric data are scarce.<br><br>METHODS: This paper contains a case report of five Swedish children and the long-term symptoms reported by their parents. It also includes a systematic literature review of the MEDLINE, EMBASE and Web of Science databases and the medRxiv/bioRxiv pre-print servers up to 2 November 2020.<br><br>RESULTS: The five children with potential long COVID had a median age of 12&#xa0;years (range 9-15) and four were girls. They had symptoms for 6-8&#xa0;months after their clinical diagnoses of COVID-19. None were hospitalised at diagnosis, but one was later admitted for peri-myocarditis. All five children had fatigue, dyspnoea, heart palpitations or chest pain, and four had headaches, difficulties concentrating, muscle weakness, dizziness and sore throats. Some had improved after 6-8&#xa0;months, but they all suffered from fatigue and none had fully returned to school. The systematic review identified 179 publications and 19 of these were deemed relevant and read in detail. None contained any information on long COVID in children.<br><br>CONCLUSION: Children may experience similar long COVID symptoms to adults and females may be more affected.}, }
@article {pmid33243837, year = {2021}, author = {Dani, M and Dirksen, A and Taraborrelli, P and Torocastro, M and Panagopoulos, D and Sutton, R and Lim, PB}, title = {Autonomic dysfunction in 'long COVID': rationale, physiology and management strategies.}, journal = {Clinical medicine (London, England)}, volume = {21}, number = {1}, pages = {e63-e67}, pmid = {33243837}, issn = {1473-4893}, mesh = {COVID-19/*epidemiology/therapy ; *Disease Management ; Global Health ; Humans ; Morbidity/trends ; *Pandemics ; *SARS-CoV-2 ; Survival Rate/trends ; }, abstract = {The SARS-CoV-2 (COVID-19) pandemic has caused unprecedented morbidity, mortality and global disruption. Following the initial surge of infections, focus shifted to managing the longer-term sequelae of illness in survivors. 'Post-acute COVID' (known colloquially as 'long COVID') is emerging as a prevalent syndrome. It encompasses a plethora of debilitating symptoms (including breathlessness, chest pain, palpitations and orthostatic intolerance) which can last for weeks or more following mild illness. We describe a series of individuals with symptoms of 'long COVID', and we posit that this condition may be related to a virus- or immune-mediated disruption of the autonomic nervous system resulting in orthostatic intolerance syndromes. We suggest that all physicians should be equipped to recognise such cases, appreciate the symptom burden and provide supportive management. We present our rationale for an underlying impaired autonomic physiology post-COVID-19 and suggest means of management.}, }
@article {pmid33322316, year = {2020}, author = {Vink, M and Vink-Niese, A}, title = {Could Cognitive Behavioural Therapy Be an Effective Treatment for Long COVID and Post COVID-19 Fatigue Syndrome? Lessons from the Qure Study for Q-Fever Fatigue Syndrome.}, journal = {Healthcare (Basel, Switzerland)}, volume = {8}, number = {4}, pages = {}, pmid = {33322316}, issn = {2227-9032}, abstract = {An increasing number of young and previously fit and healthy people who did not require hospitalisation continue to have symptoms months after mild cases of COVID-19. Rehabilitation clinics are already offering cognitive behavioural therapy (CBT) as an effective treatment for long COVID and post-COVID-19 fatigue syndrome based on the claims that it is effective for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)-the most common post-infectious syndrome-as no study into the efficacy of CBT for post-COVID-19 fatigue syndrome has been published. Re-analyses of these studies, however, showed that CBT did not lead to objective improvements in heterogeneous groups of ME/CFS patients, nor did it restore the ability to work. The group of patients with long COVID and post-COVID-19 fatigue syndrome, on the other hand, is homogeneous. We therefore analysed the Dutch Qure study, as it studied the efficacy of CBT in a homogeneous group of patients who developed Q-fever fatigue syndrome-which affects up to 30% of patients-after the largest reported outbreak of Q-fever, to see if CBT might potentially be an effective treatment for long-haulers after COVID-19 infection. Our reanalysis found that the Qure study suffered from many serious methodological problems, which included relying on one subjective primary outcome in a study without a control group for the non-blinded CBT treatment group, using a post hoc definition of improvement, waiting 2 years before publishing their objective actometer results and ignoring the null effect of said results. Moreover, only 10% of participants achieved a clinically meaningful subjective improvement in fatigue as a result of CBT according to the study's own figures. Consequently, CBT has no subjective clinically meaningful effect in nine out of every ten patients that are treated with it. Additionally, the subjective improvement in fatigue was not matched by an improvement in disability, even though the disability was fatigue related according to the researchers. On top of this, CBT did not lead to an objective improvement in physical performance. Therefore, it cannot be said that CBT is an effective treatment for Q-fever fatigue syndrome either. It seems therefore unlikely that CBT will reduce disability or lead to objective improvement in long COVID or in post-COVID-19 fatigue syndrome.}, }
@article {pmid33347790, year = {2021}, author = {Higgins, V and Sohaei, D and Diamandis, EP and Prassas, I}, title = {COVID-19: from an acute to chronic disease? Potential long-term health consequences.}, journal = {Critical reviews in clinical laboratory sciences}, volume = {58}, number = {5}, pages = {297-310}, doi = {10.1080/10408363.2020.1860895}, pmid = {33347790}, issn = {1549-781X}, mesh = {Betacoronavirus ; COVID-19/*complications ; *Chronic Disease ; Coronavirus Infections ; Critical Illness ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite pulmonary impairments being the most prevalent, extra-pulmonary manifestations of COVID-19 are abundant. Confirmed COVID-19 cases have now surpassed 57.8 million worldwide as of 22 November 2020. With estimated case fatality rates (number of deaths from COVID-19 divided by number of confirmed COVID-19 cases) varying between 1 and 7%, there will be a large population of recovered COVID-19 patients that may acquire a multitude of long-term health consequences. While the multi-organ manifestations of COVID-19 are now well-documented, the potential long-term implications of these manifestations remain to be uncovered. In this review, we turn to previous similar coronaviruses (i.e. SARS-CoV-1 and Middle East respiratory syndrome coronavirus [MERS-CoV]) in combination with known health implications of SARS-CoV-2 infection to predict potential long-term effects of COVID-19, including pulmonary, cardiovascular, hematologic, renal, central nervous system, gastrointestinal, and psychosocial manifestations, in addition to the well-known post-intensive care syndrome. It is necessary to monitor COVID-19 patients after discharge to understand the breadth and severity of long-term effects. This can be accomplished by repurposing or initiating large cohort studies to not only focus on the long-term consequences of SARS-CoV-2 infection, but also on acquired immune function as well as ethno-racial group and household income disparities in COVID-19 cases and hospitalizations. The future for COVID-19 survivors remains uncertain, and if this virus circulates among us for years to come, long-term effects may accumulate exponentially.}, }
@article {pmid33403218, year = {2020}, author = {Amenta, EM and Spallone, A and Rodriguez-Barradas, MC and El Sahly, HM and Atmar, RL and Kulkarni, PA}, title = {Postacute COVID-19: An Overview and Approach to Classification.}, journal = {Open forum infectious diseases}, volume = {7}, number = {12}, pages = {ofaa509}, pmid = {33403218}, issn = {2328-8957}, support = {T32 AI055413/AI/NIAID NIH HHS/United States ; }, abstract = {As the coronavirus disease 2019 (COVID-19) pandemic has progressed, a large volume of literature has developed delineating the clinical manifestations of acute infection. Recent reports have also started to describe persistent symptoms extending beyond the period of initial illness or hospitalization. Anecdotes of different signs and symptoms occurring after acute infection have also arisen in the lay press. Here we describe the current existing medical literature on the emerging concept of postacute COVID-19 and suggest an approach to classifying different manifestations of the syndrome. We also review long-term clinical manifestations observed in patients who recovered from infection due to other epidemic coronaviruses and briefly discuss potential mechanisms driving the phenomenon of postacute COVID-19.}, }
@article {pmid33458558, year = {2021}, author = {McFarland, AJ and Yousuf, MS and Shiers, S and Price, TJ}, title = {Neurobiology of SARS-CoV-2 interactions with the peripheral nervous system: implications for COVID-19 and pain.}, journal = {Pain reports}, volume = {6}, number = {1}, pages = {e885}, pmid = {33458558}, issn = {2471-2531}, abstract = {SARS-CoV-2 is a novel coronavirus that infects cells through the angiotensin-converting enzyme 2 receptor, aided by proteases that prime the spike protein of the virus to enhance cellular entry. Neuropilin 1 and 2 (NRP1 and NRP2) act as additional viral entry factors. SARS-CoV-2 infection causes COVID-19 disease. There is now strong evidence for neurological impacts of COVID-19, with pain as an important symptom, both in the acute phase of the disease and at later stages that are colloquially referred to as "long COVID." In this narrative review, we discuss how COVID-19 may interact with the peripheral nervous system to cause pain in the early and late stages of the disease. We begin with a review of the state of the science on how viruses cause pain through direct and indirect interactions with nociceptors. We then cover what we currently know about how the unique cytokine profiles of moderate and severe COVID-19 may drive plasticity in nociceptors to promote pain and worsen existing pain states. Finally, we review evidence for direct infection of nociceptors by SARS-CoV-2 and the implications of this potential neurotropism. The state of the science points to multiple potential mechanisms through which COVID-19 could induce changes in nociceptor excitability that would be expected to promote pain, induce neuropathies, and worsen existing pain states.}, }
@article {pmid33519972, year = {2021}, author = {Lucas, S}, title = {Pandemics and pathology: a reflection on influenza, HIV/AIDS and SARS (COVID-19) pandemic infections.}, journal = {Diagnostic histopathology (Oxford, England)}, volume = {27}, number = {3}, pages = {128-133}, pmid = {33519972}, issn = {1756-2317}, abstract = {The COVID-19 pandemic has reminded pathologists of our significant roles in the management and understanding of rapidly spreading and dangerous pathogens, from identifying the agent to characterizing the clinical pathology to managing the dead. Cellular pathology - through autopsy - has depicted the main features: viral pneumonitis, acute lung injury, organising pneumonia, secondary bacterial pneumonia, thrombophilia and infarction, and systemic inflammatory response syndrome with multi-organ failure. These are similar to another viral pandemic of the 20th century, H1N1 influenza; but contrast with the second major more complicated pandemic, that of HIV/AIDS. The outcomes of these infections are compared, along with seasonal influenza and SARS-1-CoV disease. Work to be done on COVID-19 includes characterisation of the emerging 'long COVID' syndrome, and monitoring the complications of therapies and vaccination programs.}, }
@article {pmid33538586, year = {2021}, author = {Yong, SJ}, title = {Persistent Brainstem Dysfunction in Long-COVID: A Hypothesis.}, journal = {ACS chemical neuroscience}, volume = {12}, number = {4}, pages = {573-580}, doi = {10.1021/acschemneuro.0c00793}, pmid = {33538586}, issn = {1948-7193}, mesh = {Angiotensin-Converting Enzyme 2/metabolism ; Brain Diseases/metabolism/*physiopathology/virology ; Brain Stem/blood supply/metabolism/*physiopathology/virology ; COVID-19/*complications/metabolism/physiopathology ; Humans ; Inflammation/metabolism/*physiopathology/virology ; Neuropilin-1/metabolism ; RNA, Viral/isolation &amp; purification/metabolism ; Receptors, Coronavirus/metabolism ; SARS-CoV-2/genetics/pathogenicity ; Thrombosis/metabolism/*physiopathology/virology ; Viral Tropism ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long-COVID is a postviral illness that can affect survivors of COVID-19, regardless of initial disease severity or age. Symptoms of long-COVID include fatigue, dyspnea, gastrointestinal and cardiac problems, cognitive impairments, myalgia, and others. While the possible causes of long-COVID include long-term tissue damage, viral persistence, and chronic inflammation, the review proposes, perhaps for the first time, that persistent brainstem dysfunction may also be involved. This hypothesis can be split into two parts. The first is the brainstem tropism and damage in COVID-19. As the brainstem has a relatively high expression of ACE2 receptor compared with other brain regions, SARS-CoV-2 may exhibit tropism therein. Evidence also exists that neuropilin-1, a co-receptor of SARS-CoV-2, may be expressed in the brainstem. Indeed, autopsy studies have found SARS-CoV-2 RNA and proteins in the brainstem. The brainstem is also highly prone to damage from pathological immune or vascular activation, which has also been observed in autopsy of COVID-19 cases. The second part concerns functions of the brainstem that overlap with symptoms of long-COVID. The brainstem contains numerous distinct nuclei and subparts that regulate the respiratory, cardiovascular, gastrointestinal, and neurological processes, which can be linked to long-COVID. As neurons do not readily regenerate, brainstem dysfunction may be long-lasting and, thus, is long-COVID. Indeed, brainstem dysfunction has been implicated in other similar disorders, such as chronic pain and migraine and myalgic encephalomyelitis or chronic fatigue syndrome.}, }
@article {pmid33609255, year = {2023}, author = {Oronsky, B and Larson, C and Hammond, TC and Oronsky, A and Kesari, S and Lybeck, M and Reid, TR}, title = {A Review of Persistent Post-COVID Syndrome (PPCS).}, journal = {Clinical reviews in allergy &amp; immunology}, volume = {64}, number = {1}, pages = {66-74}, pmid = {33609255}, issn = {1559-0267}, mesh = {Humans ; *COVID-19 ; Disease Progression ; Immunosuppression Therapy ; *Post-Acute COVID-19 Syndrome ; Quality of Life ; }, abstract = {Persistent post-COVID syndrome, also referred to as long COVID, is a pathologic entity, which involves persistent physical, medical, and cognitive sequelae following COVID-19, including persistent immunosuppression as well as pulmonary, cardiac, and vascular fibrosis. Pathologic fibrosis of organs and vasculature leads to increased mortality and severely worsened quality of life. Inhibiting transforming growth factor beta (TGF-β), an immuno- and a fibrosis modulator, may attenuate these post-COVID sequelae. Current preclinical and clinical efforts are centered on the mechanisms and manifestations of COVID-19 and its presymptomatic and prodromal periods; by comparison, the postdrome, which occurs in the aftermath of COVID-19, which we refer to as persistent post-COVID-syndrome, has received little attention. Potential long-term effects from post-COVID syndrome will assume increasing importance as a surge of treated patients are discharged from the hospital, placing a burden on healthcare systems, patients' families, and society in general to care for these medically devastated COVID-19 survivors. This review explores underlying mechanisms and possible manifestations of persistent post-COVID syndrome, and presents a framework of strategies for the diagnosis and management of patients with suspected or confirmed persistent post-COVID syndrome.}, }
@article {pmid33633106, year = {2021}, author = {Stefano, GB}, title = {Historical Insight into Infections and Disorders Associated with Neurological and Psychiatric Sequelae Similar to Long COVID.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {27}, number = {}, pages = {e931447}, pmid = {33633106}, issn = {1643-3750}, mesh = {Brain/virology ; COVID-19/*complications/epidemiology/metabolism/*physiopathology/*psychology ; Cognitive Dysfunction/physiopathology/virology ; History, 21st Century ; Humans ; Influenza Pandemic, 1918-1919 ; Pandemics ; SARS-CoV-2/enzymology/isolation &amp; purification/metabolism ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long-term sequelae of coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are now recognized. However, there is still a lack of consensus regarding the terminology for this emerging chronic clinical syndrome, which includes long COVID, chronic COVID syndrome, post-COVID-19 syndrome, post-acute COVID-19, and long-hauler COVID-19. In this review, I will use the term "long COVID". A review of the medical history and epidemiology of past pandemics and epidemics in modern literature review identifies common long-term post-infectious disorders, with the common finding of altered cognition. In the brain, the cerebral hypoxia induced by SARS-CoV-2 infection may be caused by mitochondrial dysfunction, resulting in "brain fog". Historically, the common symptom of altered cognition has been reported during earlier pandemics, which include the influenza pandemics of 1889 and 1892 (Russian flu), the Spanish flu pandemic (1918-1919), encephalitis lethargica, diphtheria, and myalgic encephalomyelitis (chronic fatigue syndrome or post-viral fatigue syndrome). There are similarities between chronic fatigue syndrome and the "brain fog" described in long COVID. During past viral epidemics and pandemics, a commonality of neural targets may have increased viral survival by conformational matching. The neurological and psychiatric sequelae of SARS-CoV-2 infection, or long COVID, may have emerged from neural effects that have emerged from an invertebrate and vertebrate virosphere. This review aims to present a historical overview of infections and disorders associated with neurological and psychiatric sequelae that have shown similarities with long COVID.}, }
@article {pmid33634830, year = {2021}, author = {Burgess, LC and Venugopalan, L and Badger, J and Street, T and Alon, G and Jarvis, JC and Wainwright, TW and Everington, T and Taylor, P and Swain, ID}, title = {Effect of neuromuscular electrical stimulation on the recovery of people with COVID-19 admitted to the intensive care unit: A narrative review.}, journal = {Journal of rehabilitation medicine}, volume = {53}, number = {3}, pages = {jrm00164}, pmid = {33634830}, issn = {1651-2081}, mesh = {COVID-19/rehabilitation/*therapy/virology ; Clinical Trials as Topic ; Electric Stimulation Therapy/*methods ; Hospitalization ; Humans ; Intensive Care Units ; Randomized Controlled Trials as Topic ; SARS-CoV-2/isolation &amp; purification ; }, abstract = {The rehabilitation of patients with COVID-19 after prolonged treatment in the intensive care unit is often complex and challenging. Patients may develop a myriad of long-term multiorgan impairments, affecting the respiratory, cardiac, neurological, digestive and musculoskeletal systems. Skeletal muscle dysfunction of respiratory and limb muscles, commonly referred to as intensive care unit acquired weakness, occurs in approximately 40% of all patients admitted to intensive care. The impact on mobility and return to activities of daily living is severe. Furthermore, many patients experience ongoing symptoms of fatigue, weakness and shortness of breath, in what is being described as "long COVID". Neuromuscular electrical stimulation is a technique in which small electrical impulses are applied to skeletal muscle to cause contractions when voluntary muscle contraction is difficult or impossible. Neuromuscular electrical stimulation can prevent muscle atrophy, improve muscle strength and function, maintain blood flow and reduce oedema. This review examines the evidence, current guidelines, and proposed benefits of using neuromuscular electrical stimulation with patients admitted to the intensive care unit. Practical recommendations for using electrical muscle stimulation in patients with COVID-19 are provided, and suggestions for further research are proposed. Evidence suggests NMES may play a role in the weaning of patients from ventilators and can be continued in the post-acute and longer-term phases of recovery. As such, NMES may be a suitable treatment modality to implement within rehabilitation pathways for COVID-19, with consideration of the practical and safety issues highlighted within this review.}, }
@article {pmid33740207, year = {2021}, author = {Raj, SR and Arnold, AC and Barboi, A and Claydon, VE and Limberg, JK and Lucci, VM and Numan, M and Peltier, A and Snapper, H and Vernino, S and , }, title = {Long-COVID postural tachycardia syndrome: an American Autonomic Society statement.}, journal = {Clinical autonomic research : official journal of the Clinical Autonomic Research Society}, volume = {31}, number = {3}, pages = {365-368}, pmid = {33740207}, issn = {1619-1560}, support = {UL1 TR000445/TR/NCATS NIH HHS/United States ; K99 HL122507/HL/NHLBI NIH HHS/United States ; }, mesh = {COVID-19/*complications ; Humans ; Postural Orthostatic Tachycardia Syndrome/*etiology/therapy ; Societies, Medical ; United States ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19 is a global pandemic that has had a devastating effect on the health and economy of much of human civilization. While the acute impacts of COVID-19 were the initial focus of concern, it is becoming clear that in the wake of COVID-19, many patients are developing chronic symptoms that have been called Long-COVID. Some of the symptoms and signs include those of postural tachycardia syndrome (POTS). Understanding and managing long-COVID POTS will require a significant infusion of health care resources and a significant additional research investment. In this document from the American Autonomic Society, we outline the scope of the problem, and the resources and research needed to properly address the impact of Long-COVID POTS.}, }
@article {pmid33796241, year = {2021}, author = {Wildwing, T and Holt, N}, title = {The neurological symptoms of COVID-19: a systematic overview of systematic reviews, comparison with other neurological conditions and implications for healthcare services.}, journal = {Therapeutic advances in chronic disease}, volume = {12}, number = {}, pages = {2040622320976979}, pmid = {33796241}, issn = {2040-6223}, abstract = {AIMS: In response to the rapid spread of COVID-19, this paper provides health professionals with better accessibility to available evidence, summarising findings from a systematic overview of systematic reviews of the neurological symptoms seen in patients with COVID-19. Implications of so-called 'Long Covid' on neurological services and primary care and similarities with other neurological disorders are discussed.<br><br>METHODS: Firstly, a systematic overview of current reviews of neurological symptoms of COVID-19 was conducted. Secondly, the implications of these findings are discussed in relation to the potential effect on neurological services and the similarities in the experience of patients with COVID-19 and those with other neurological disorders. A total of 45 systematic reviews were identified within seven databases, published between 11 April 2020 and 15 October 2020, following a search in June 2020, updated on 20 October 2020.<br><br>RESULTS: The results indicated that COVID-19 exhibits two types of neurological symptoms; life-threatening symptoms such as Guillain-Barre Syndrome (GBS) and encephalitis, and less devastating symptoms such as fatigue and myalgia. Many of these so-called lesser symptoms appear to be emerging as longer-term for some sufferers and have been recently labelled Long Covid. When compared, these less devastating symptoms are very similar to other neurological conditions such as chronic fatigue syndrome (CFS) and functional neurological disorder (FND).<br><br>CONCLUSION: Implications for neurological healthcare services in the United Kingdom (UK) may include longer waiting times and a need for more resources (including more qualified health professionals). There is also a possible change-effect on health professionals' perceptions of other neurological conditions such as CFS and FND. Future research is recommended to explore changes in health professionals' perceptions of neurological symptoms because of COVID-19.}, }
@article {pmid33807280, year = {2021}, author = {Vollbracht, C and Kraft, K}, title = {Feasibility of Vitamin C in the Treatment of Post Viral Fatigue with Focus on Long COVID, Based on a Systematic Review of IV Vitamin C on Fatigue.}, journal = {Nutrients}, volume = {13}, number = {4}, pages = {}, pmid = {33807280}, issn = {2072-6643}, mesh = {Ascorbic Acid/administration &amp; dosage/*therapeutic use ; COVID-19/*complications/pathology ; Fatigue/*drug therapy/*etiology ; Feasibility Studies ; Humans ; Injections, Intravenous ; *SARS-CoV-2 ; }, abstract = {Fatigue is common not only in cancer patients but also after viral and other infections. Effective treatment options are still very rare. Therefore, the present knowledge on the pathophysiology of fatigue and the potential positive impact of treatment with vitamin C is illustrated. Additionally, the effectiveness of high-dose IV vitamin C in fatigue resulting from various diseases was assessed by a systematic literature review in order to assess the feasibility of vitamin C in post-viral, especially in long COVID, fatigue. Nine clinical studies with 720 participants were identified. Three of the four controlled trials observed a significant decrease in fatigue scores in the vitamin C group compared to the control group. Four of the five observational or before-and-after studies observed a significant reduction in pre-post levels of fatigue. Attendant symptoms of fatigue such as sleep disturbances, lack of concentration, depression, and pain were also frequently alleviated. Oxidative stress, inflammation, and circulatory disorders, which are important contributors to fatigue, are also discussed in long COVID fatigue. Thus, the antioxidant, anti-inflammatory, endothelial-restoring, and immunomodulatory effects of high-dose IV vitamin C might be a suitable treatment option.}, }
@article {pmid33811910, year = {2021}, author = {Santhosh, L and Block, B and Kim, SY and Raju, S and Shah, RJ and Thakur, N and Brigham, EP and Parker, AM}, title = {Rapid Design and Implementation of Post-COVID-19 Clinics.}, journal = {Chest}, volume = {160}, number = {2}, pages = {671-677}, pmid = {33811910}, issn = {1931-3543}, support = {P30 AI094189/AI/NIAID NIH HHS/United States ; }, mesh = {Aftercare/*organization &amp; administration ; *COVID-19/therapy ; Hospital Design and Construction ; Humans ; Outpatient Clinics, Hospital/*organization &amp; administration ; *Survivors ; Time Factors ; }, abstract = {Survivors of COVID-19 are a vulnerable population, with complex needs because of lingering symptoms and complications across multiple organ systems. Those who required hospitalization or intensive care are also at risk for post-hospital syndrome and post-ICU syndromes, with attendant cognitive, psychological, and physical impairments, and high levels of health care utilization. Effective ambulatory care for COVID-19 survivors requires coordination across multiple subspecialties, which can be burdensome if not well coordinated. With growing recognition of these needs, post-COVID-19 clinics are being created across the country. We describe the design and implementation of multidisciplinary post-COVID-19 clinics at two academic health systems, Johns Hopkins and the University of California-San Francisco. We highlight components of the model which should be replicated across sites, while acknowledging opportunities to tailor offerings to the local institutional context. Our goal is to provide a replicable framework for others to create these much-needed care delivery models for survivors of COVID-19.}, }
@article {pmid33847020, year = {2021}, author = {Theoharides, TC and Cholevas, C and Polyzoidis, K and Politis, A}, title = {Long-COVID syndrome-associated brain fog and chemofog: Luteolin to the rescue.}, journal = {BioFactors (Oxford, England)}, volume = {47}, number = {2}, pages = {232-241}, pmid = {33847020}, issn = {1872-8081}, mesh = {Brain/drug effects/physiopathology/virology ; COVID-19/complications/physiopathology/virology ; Cognitive Dysfunction/complications/*drug therapy/physiopathology/virology ; Cytokines/genetics ; Fatigue/complications/*drug therapy/physiopathology/virology ; Humans ; Luteolin/*therapeutic use ; Mast Cells/drug effects/virology ; SARS-CoV-2/pathogenicity ; *COVID-19 Drug Treatment ; }, abstract = {COVID-19 leads to severe respiratory problems, but also to long-COVID syndrome associated primarily with cognitive dysfunction and fatigue. Long-COVID syndrome symptoms, especially brain fog, are similar to those experienced by patients undertaking or following chemotherapy for cancer (chemofog or chemobrain), as well in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or mast cell activation syndrome (MCAS). The pathogenesis of brain fog in these illnesses is presently unknown but may involve neuroinflammation via mast cells stimulated by pathogenic and stress stimuli to release mediators that activate microglia and lead to inflammation in the hypothalamus. These processes could be mitigated by phytosomal formulation (in olive pomace oil) of the natural flavonoid luteolin.}, }
@article {pmid33857435, year = {2021}, author = {Song, WJ and Hui, CKM and Hull, JH and Birring, SS and McGarvey, L and Mazzone, SB and Chung, KF}, title = {Confronting COVID-19-associated cough and the post-COVID syndrome: role of viral neurotropism, neuroinflammation, and neuroimmune responses.}, journal = {The Lancet. Respiratory medicine}, volume = {9}, number = {5}, pages = {533-544}, pmid = {33857435}, issn = {2213-2619}, mesh = {COVID-19/*complications/*physiopathology ; Cough/*etiology/physiopathology ; Humans ; Inflammation/*etiology/physiopathology ; Nervous System Diseases/*etiology/physiopathology ; *Neuroimmunomodulation ; SARS-CoV-2 ; Syndrome ; }, abstract = {Cough is one of the most common presenting symptoms of COVID-19, along with fever and loss of taste and smell. Cough can persist for weeks or months after SARS-CoV-2 infection, often accompanied by chronic fatigue, cognitive impairment, dyspnoea, or pain-a collection of long-term effects referred to as the post-COVID syndrome or long COVID. We hypothesise that the pathways of neurotropism, neuroinflammation, and neuroimmunomodulation through the vagal sensory nerves, which are implicated in SARS-CoV-2 infection, lead to a cough hypersensitivity state. The post-COVID syndrome might also result from neuroinflammatory events in the brain. We highlight gaps in understanding of the mechanisms of acute and chronic COVID-19-associated cough and post-COVID syndrome, consider potential ways to reduce the effect of COVID-19 by controlling cough, and suggest future directions for research and clinical practice. Although neuromodulators such as gabapentin or opioids might be considered for acute and chronic COVID-19 cough, we discuss the possible mechanisms of COVID-19-associated cough and the promise of new anti-inflammatories or neuromodulators that might successfully target both the cough of COVID-19 and the post-COVID syndrome.}, }
@article {pmid33889231, year = {2021}, author = {Iwu, CJ and Iwu, CD and Wiysonge, CS}, title = {The occurrence of long COVID: a rapid review.}, journal = {The Pan African medical journal}, volume = {38}, number = {}, pages = {65}, pmid = {33889231}, issn = {1937-8688}, mesh = {COVID-19/*complications ; Hospitalization ; Humans ; Randomized Controlled Trials as Topic ; *Survivors ; Time Factors ; }, abstract = {The long-term effects of the severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) are not well understood. This rapid review was aimed at synthesizing evidence on the long-term effects of the SARS-CoV-2 infection among survivors. We considered both randomised controlled trials and non-randomised studies eligible for inclusion in this review. The following databases were searched: PubMed, Scopus, Cochrane library, Google Scholar, and the World Health Organization (WHO) COVID-19 database. The reference lists of all the included studies were also searched. Two authors independently screened the search outputs and reviewed full texts of potentially eligible articles. Data extraction was done by one author and checked by a second author. A meta-analysis was not conducted due to heterogeneity among the included studies. Results are presented narratively. Eleven studies met our inclusion criteria. All these studies were conducted in high-income countries. Study findings demonstrate that COVID-19 survivors can experience persistent symptoms after recovering from their initial illness, especially among previously hospitalized persons. The majority of symptoms reported were fatigue, shortness of breath, cough, and sleep disorders. Mental conditions, such as depression and anxiety disorders, were also reported. In conclusion, this study showed that COVID-19 survivors can experience persistent symptoms after recovering from their initial illness. Therefore, there is a need for a long-term follow-up of COVID-19 patients and rehabilitation services for survivors. More research is needed in this area, especially in Africa.}, }
@article {pmid33892403, year = {2021}, author = {Raveendran, AV and Jayadevan, R and Sashidharan, S}, title = {Long COVID: An overview.}, journal = {Diabetes &amp; metabolic syndrome}, volume = {15}, number = {3}, pages = {869-875}, pmid = {33892403}, issn = {1878-0334}, mesh = {COVID-19/*complications/epidemiology/etiology/pathology/therapy ; Cough/epidemiology/etiology/therapy ; Fatigue/epidemiology/etiology/therapy ; Humans ; SARS-CoV-2/physiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND AND AIMS: Long COVID is the collective term to denote persistence of symptoms in those who have recovered from SARS-CoV-2 infection.<br><br>METHODS: WE searched the pubmed and scopus databases for original articles and reviews. Based on the search result, in this review article we are analyzing various aspects of Long COVID.<br><br>RESULTS: Fatigue, cough, chest tightness, breathlessness, palpitations, myalgia and difficulty to focus are symptoms reported in long COVID. It could be related to organ damage, post viral syndrome, post-critical care syndrome and others. Clinical evaluation should focus on identifying the pathophysiology, followed by appropriate remedial measures. In people with symptoms suggestive of long COVID but without known history of previous SARS-CoV-2 infection, serology may help confirm the diagnosis.<br><br>CONCLUSIONS: This review will helps the clinicians to manage various aspects of Long COVID.}, }
@article {pmid33919537, year = {2021}, author = {Silva Andrade, B and Siqueira, S and de Assis Soares, WR and de Souza Rangel, F and Santos, NO and Dos Santos Freitas, A and Ribeiro da Silveira, P and Tiwari, S and Alzahrani, KJ and Góes-Neto, A and Azevedo, V and Ghosh, P and Barh, D}, title = {Long-COVID and Post-COVID Health Complications: An Up-to-Date Review on Clinical Conditions and Their Possible Molecular Mechanisms.}, journal = {Viruses}, volume = {13}, number = {4}, pages = {}, pmid = {33919537}, issn = {1999-4915}, mesh = {COVID-19/*complications/*physiopathology ; Cardiovascular System ; Diarrhea ; Guillain-Barre Syndrome ; Hemostasis ; Humans ; Immune System ; Inflammation ; Mental Health ; Nervous System ; Pandemics ; SARS-CoV-2 ; Severe Acute Respiratory Syndrome ; Systemic Inflammatory Response Syndrome/*complications/*physiopathology ; Thrombosis ; }, abstract = {The COVID-19 pandemic has infected millions worldwide, leaving a global burden for long-term care of COVID-19 survivors. It is thus imperative to study post-COVID (i.e., short-term) and long-COVID (i.e., long-term) effects, specifically as local and systemic pathophysiological outcomes of other coronavirus-related diseases (such as Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS)) were well-cataloged. We conducted a comprehensive review of adverse post-COVID health outcomes and potential long-COVID effects. We observed that such adverse outcomes were not localized. Rather, they affected different human systems, including: (i) immune system (e.g., Guillain-Barré syndrome, rheumatoid arthritis, pediatric inflammatory multisystem syndromes such as Kawasaki disease), (ii) hematological system (vascular hemostasis, blood coagulation), (iii) pulmonary system (respiratory failure, pulmonary thromboembolism, pulmonary embolism, pneumonia, pulmonary vascular damage, pulmonary fibrosis), (iv) cardiovascular system (myocardial hypertrophy, coronary artery atherosclerosis, focal myocardial fibrosis, acute myocardial infarction, cardiac hypertrophy), (v) gastrointestinal, hepatic, and renal systems (diarrhea, nausea/vomiting, abdominal pain, anorexia, acid reflux, gastrointestinal hemorrhage, lack of appetite/constipation), (vi) skeletomuscular system (immune-mediated skin diseases, psoriasis, lupus), (vii) nervous system (loss of taste/smell/hearing, headaches, spasms, convulsions, confusion, visual impairment, nerve pain, dizziness, impaired consciousness, nausea/vomiting, hemiplegia, ataxia, stroke, cerebral hemorrhage), (viii) mental health (stress, depression and anxiety). We additionally hypothesized mechanisms of action by investigating possible molecular mechanisms associated with these disease outcomes/symptoms. Overall, the COVID-19 pathology is still characterized by cytokine storm that results to endothelial inflammation, microvascular thrombosis, and multiple organ failures.}, }
@article {pmid33923972, year = {2021}, author = {Sisó-Almirall, A and Brito-Zerón, P and Conangla Ferrín, L and Kostov, B and Moragas Moreno, A and Mestres, J and Sellarès, J and Galindo, G and Morera, R and Basora, J and Trilla, A and Ramos-Casals, M and On Behalf Of The CAMFiC Long Covid-Study Group, }, title = {Long Covid-19: Proposed Primary Care Clinical Guidelines for Diagnosis and Disease Management.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {8}, pages = {}, pmid = {33923972}, issn = {1660-4601}, mesh = {*COVID-19 ; Disease Management ; Humans ; Primary Health Care ; SARS-CoV-2 ; }, abstract = {Long COVID-19 may be defined as patients who, four weeks after the diagnosis of SARS-Cov-2 infection, continue to have signs and symptoms not explainable by other causes. The estimated frequency is around 10% and signs and symptoms may last for months. The main long-term manifestations observed in other coronaviruses (Severe Acute Respiratory Syndrome (SARS), Middle East respiratory syndrome (MERS)) are very similar to and have clear clinical parallels with SARS-CoV-2: mainly respiratory, musculoskeletal, and neuropsychiatric. The growing number of patients worldwide will have an impact on health systems. Therefore, the main objective of these clinical practice guidelines is to identify patients with signs and symptoms of long COVID-19 in primary care through a protocolized diagnostic process that studies possible etiologies and establishes an accurate differential diagnosis. The guidelines have been developed pragmatically by compiling the few studies published so far on long COVID-19, editorials and expert opinions, press releases, and the authors' clinical experience. Patients with long COVID-19 should be managed using structured primary care visits based on the time from diagnosis of SARS-CoV-2 infection. Based on the current limited evidence, disease management of long COVID-19 signs and symptoms will require a holistic, longitudinal follow up in primary care, multidisciplinary rehabilitation services, and the empowerment of affected patient groups.}, }
@article {pmid33925784, year = {2021}, author = {Wong, TL and Weitzer, DJ}, title = {Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)-A Systemic Review and Comparison of Clinical Presentation and Symptomatology.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {57}, number = {5}, pages = {}, pmid = {33925784}, issn = {1648-9144}, mesh = {Humans ; *COVID-19 ; *Fatigue Syndrome, Chronic/diagnosis ; Research Design ; SARS-CoV-2 ; }, abstract = {Background and Objectives: Long COVID defines a series of chronic symptoms that patients may experience after resolution of acute COVID-19. Early reports from studies with patients with long COVID suggests a constellation of symptoms with similarities to another chronic medical illness-myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). A review study comparing and contrasting ME/CFS with reported symptoms of long COVID may yield mutualistic insight into the characterization and management of both conditions. Materials and Methods: A systemic literature search was conducted in MEDLINE and PsycInfo through to 31 January 2021 for studies related to long COVID symptomatology. The literature search was conducted in accordance with PRISMA methodology. Results: Twenty-one studies were included in the qualitative analysis. Long COVID symptoms reported by the included studies were compared to a list of ME/CFS symptoms compiled from multiple case definitions. Twenty-five out of 29 known ME/CFS symptoms were reported by at least one selected long COVID study. Conclusions: Early studies into long COVID symptomatology suggest many overlaps with clinical presentation of ME/CFS. The need for monitoring and treatment for patients post-COVID is evident. Advancements and standardization of long COVID research methodologies would improve the quality of future research, and may allow further investigations into the similarities and differences between long COVID and ME/CFS.}, }
@article {pmid33961259, year = {2021}, author = {Jebrini, T and Reinhard, MA and Ortmann, M and Strupf, M and Rüb, M and Padberg, F and Adorjan, K}, title = {[Psychiatric complications of COVID-19: The unknown disease (Long Covid)].}, journal = {MMW Fortschritte der Medizin}, volume = {163}, number = {9}, pages = {48-50}, doi = {10.1007/s15006-021-9888-5}, pmid = {33961259}, issn = {1613-3560}, mesh = {*COVID-19 ; Humans ; SARS-CoV-2 ; }, }
@article {pmid33962805, year = {2021}, author = {Pavli, A and Theodoridou, M and Maltezou, HC}, title = {Post-COVID Syndrome: Incidence, Clinical Spectrum, and Challenges for Primary Healthcare Professionals.}, journal = {Archives of medical research}, volume = {52}, number = {6}, pages = {575-581}, pmid = {33962805}, issn = {1873-5487}, mesh = {*COVID-19/complications/diagnosis ; Humans ; Incidence ; Primary Health Care ; Post-Acute COVID-19 Syndrome ; }, abstract = {Post-COVID syndrome also known as long COVID refers to symptoms persisting for more than three weeks after the diagnosis of COVID-19. We reviewed the current evidence on post-COVID syndrome, focusing on its clinical manifestations and addressing the challenges for its management in primary healthcare. The incidence of post-COVID syndrome is estimated at 10-35%, while for hospitalized patients it may reach 85%. Fatigue is the most common symptom reported in 17.5-72% of post-COVID cases, followed by residual dyspnea with an incidence ranging from 10-40%. Mental problems, chest pain, and olfactory and gustatory dysfunction may affect up to 26, 22 and 11% of patients, respectively. More than one third of patients with post-COVID syndrome have pre-existing comorbidities, hypertension and diabetes mellitus being the most common. Beyond the prolonged duration of symptoms, the scarce published data indicate that most patients with post-COVID syndrome have a good prognosis with no further complications or fatal outcomes reported. Given the clinical spectrum of patients with post-COVID syndrome, most of them will be managed by primary healthcare professionals, in conjunction with pre-existing or new co-morbidities, which, in turn, may increase the burden of COVID-19 on primary healthcare. In conclusion approximately 10% of patients with COVID-19 may have symptoms persisting beyond three weeks, fulfilling the criteria of post-COVID syndrome. Primary healthcare professionals have a key role in the management of patients with post-COVID syndrome. Research is needed to elucidate the pathogenesis, clinical spectrum, and prognosis of post-COVID syndrome.}, }
@article {pmid33977626, year = {2021}, author = {Cabrera Martimbianco, AL and Pacheco, RL and Bagattini, &#xc2;M and Riera, R}, title = {Frequency, signs and symptoms, and criteria adopted for long COVID-19: A systematic review.}, journal = {International journal of clinical practice}, volume = {75}, number = {10}, pages = {e14357}, pmid = {33977626}, issn = {1742-1241}, support = {//Sociedade Beneficente de Senhoras Hospital S&#xed;rio-Liban&#xea;s/ ; }, mesh = {*COVID-19/complications ; Cross-Sectional Studies ; Dyspnea/diagnosis/epidemiology/etiology ; Female ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {AIMS: To identify, systematically evaluate and summarise the best available evidence on the frequency of long COVID-19 (post-acute COVID-19 syndrome), its clinical manifestations, and the criteria used for diagnosis.<br><br>METHODS: Systematic review conducted with a comprehensive search including formal databases, COVID-19 or SARS-CoV-2 data sources, grey literature, and manual search. We considered for inclusion clinical trials, observational longitudinal comparative and non-comparative studies, cross-sectional, before-and-after, and case series. We assessed the methodological quality by specific tools based on the study designs. We presented the results as a narrative synthesis regarding the frequency and duration of long COVID-19, signs and symptoms, criteria used for diagnosis, and potential risk factors.<br><br>RESULTS: We included 25 observational studies with moderate to high methodological quality, considering 5440 participants. The frequency of long COVID-19 ranged from 4.7% to 80%, and the most prevalent signs/symptoms were chest pain (up to 89%), fatigue (up to 65%), dyspnea (up to 61%), and cough and sputum production (up to 59%). Temporal criteria used to define long COVID-19 varied from 3 to 24&#xa0;weeks after acute phase or hospital discharge. Potentially associated risk factors were old age, female sex, severe clinical status, a high number of comorbidities, hospital admission, and oxygen supplementation at the acute phase. However, limitations related to study designs added uncertainty to this finding. None of the studies assessed the duration of signs/symptoms.<br><br>CONCLUSION: The frequency of long COVID-19 reached up to 80% over the studies included and occurred between 3 and 24&#xa0;weeks after acute phase or hospital discharge. Chest pain, fatigue, dyspnea, and cough were the most reported clinical manifestations attributed to the condition. Based on these systematic review findings, there is an urgent need to understand this emerging, complex and challenging medical condition. Proposals for diagnostic criteria and standard terminology are welcome.}, }
@article {pmid33983522, year = {2021}, author = {Chilazi, M and Duffy, EY and Thakkar, A and Michos, ED}, title = {COVID and Cardiovascular Disease: What We Know in 2021.}, journal = {Current atherosclerosis reports}, volume = {23}, number = {7}, pages = {37}, pmid = {33983522}, issn = {1534-6242}, support = {Amato Fund in Women's Cardiovascular Health//Johns Hopkins University/ ; }, mesh = {Athletes ; COVID-19/blood/*complications/rehabilitation/virology ; Cardiovascular Diseases/*diagnostic imaging/*etiology/virology ; Humans ; Magnetic Resonance Imaging/methods ; Prognosis ; *Return to Sport ; *SARS-CoV-2 ; Severity of Illness Index ; Troponin/blood ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19) has been the cause of significant global morbidity and mortality. Here, we review the literature to date of the short-term and long-term consequences of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection on the heart.<br><br>RECENT FINDINGS: Early case reports described a spectrum of cardiovascular manifestations of COVID-19, including myocarditis, stress cardiomyopathy, myocardial infarction, and arrhythmia. However, in most cases, myocardial injury in COVID-19 appears to be predominantly mediated by the severity of critical illness rather than direct injury to myocardium from viral particles. While cardiac magnetic resonance imaging remains a powerful tool for diagnosing acute myocarditis, it should be used judiciously in light of low baseline prevalence of myocarditis. Guiding an athletic patient through return to play (RTP) after COVID-19 infection is a challenging process. More recent data show RTP has been a safe endeavor using a screening protocol. "Long COVID" or post-acute sequelae of SARS-CoV-2 infection has also been described. The reported symptoms span a large breadth of cardiopulmonary and neurologic complaints including fatigue, palpitations, chest pain, breathlessness, brain fog, and dysautonomia including postural tachycardia syndrome (POTS). Management of POTS/dysautonomia primarily centers on education, exercise, and salt and fluid repletion. Our understanding of the impact of COVID-19 on the cardiovascular system is constantly evolving. As we enter a new age of survivorship, additional research is needed to catalogue the burden of persistent cardiopulmonary symptoms. Research is also needed to learn how acute management may alter the likelihood and prevalence of this chronic syndrome.}, }
@article {pmid33985343, year = {2021}, author = {Cumpstey, AF and Clark, AD and Santolini, J and Jackson, AA and Feelisch, M}, title = {COVID-19: A Redox Disease-What a Stress Pandemic Can Teach Us About Resilience and What We May Learn from the Reactive Species Interactome About Its Treatment.}, journal = {Antioxidants &amp; redox signaling}, volume = {35}, number = {14}, pages = {1226-1268}, doi = {10.1089/ars.2021.0017}, pmid = {33985343}, issn = {1557-7716}, mesh = {COVID-19/diagnosis/*immunology ; Humans ; Oxidation-Reduction ; *Pandemics ; *COVID-19 Drug Treatment ; }, abstract = {Significance: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 2019 (COVID-19), affects every aspect of human life by challenging bodily, socioeconomic, and political systems at unprecedented levels. As vaccines become available, their distribution, safety, and efficacy against emerging variants remain uncertain, and specific treatments are lacking. Recent Advances: Initially affecting the lungs, COVID-19 is a complex multisystems disease that disturbs the whole-body redox balance and can be long-lasting (Long-COVID). Numerous risk factors have been identified, but the reasons for variations in susceptibility to infection, disease severity, and outcome are poorly understood. The reactive species interactome (RSI) was recently introduced as a framework to conceptualize how cells and whole organisms sense, integrate, and accommodate stress. Critical Issues: We here consider COVID-19 as a redox disease, offering a holistic perspective of its effects on the human body, considering the vulnerability of complex interconnected systems with multiorgan/multilevel interdependencies. Host/viral glycan interactions underpin SARS-CoV-2's extraordinary efficiency in gaining cellular access, crossing the epithelial/endothelial barrier to spread along the vascular/lymphatic endothelium, and evading antiviral/antioxidant defences. An inflammation-driven "oxidative storm" alters the redox landscape, eliciting epithelial, endothelial, mitochondrial, metabolic, and immune dysfunction, and coagulopathy. Concomitantly reduced nitric oxide availability renders the sulfur-based redox circuitry vulnerable to oxidation, with eventual catastrophic failure in redox communication/regulation. Host nutrient limitations are crucial determinants of resilience at the individual and population level. Future Directions: While inflicting considerable damage to health and well-being, COVID-19 may provide the ultimate testing ground to improve the diagnosis and treatment of redox-related stress diseases. "Redox phenotyping" of patients to characterize whole-body RSI status as the disease progresses may inform new therapeutic approaches to regain redox balance, reduce mortality in COVID-19 and other redox diseases, and provide opportunities to tackle Long-COVID. Antioxid. Redox Signal. 35, 1226-1268.}, }
@article {pmid33987484, year = {2021}, author = {McCorkell, L and S Assaf, G and E Davis, H and Wei, H and Akrami, A}, title = {Patient-Led Research Collaborative: embedding patients in the Long COVID narrative.}, journal = {Pain reports}, volume = {6}, number = {1}, pages = {e913}, pmid = {33987484}, issn = {2471-2531}, abstract = {A large subset of patients with coronavirus disease 2019 (COVID-19) are experiencing symptoms well beyond the claimed 2-week recovery period for mild cases. These long-term sequelae have come to be known as Long COVID. Originating out of a dedicated online support group, a team of patients formed the Patient-Led Research Collaborative and conducted the first research on Long COVID experience and symptoms. This article discusses the history and value of patient-centric and patient-led research; the formation of Patient-Led Research Collaborative as well as key findings to date; and calls for the following: the acknowledgement of Long COVID as an illness, an accurate estimate of the prevalence of Long COVID, publicly available basic symptom management, care, and research to not be limited to those with positive polymerase chain reaction and antibody tests, and aggressive research and investigation into the pathophysiology of symptoms.}, }
@article {pmid33992686, year = {2021}, author = {Korompoki, E and Gavriatopoulou, M and Hicklen, RS and Ntanasis-Stathopoulos, I and Kastritis, E and Fotiou, D and Stamatelopoulos, K and Terpos, E and Kotanidou, A and Hagberg, CA and Dimopoulos, MA and Kontoyiannis, DP}, title = {Epidemiology and organ specific sequelae of post-acute COVID19: A narrative review.}, journal = {The Journal of infection}, volume = {83}, number = {1}, pages = {1-16}, pmid = {33992686}, issn = {1532-2742}, mesh = {*COVID-19/complications ; Humans ; Pandemics ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: "Long COVID", a term coined by COVID-19 survivors, describes persistent or new symptoms in a subset of patients who have recovered from acute illness. Globally, the population of people infected with SARS-CoV-2 continues to expand rapidly, necessitating the need for a more thorough understanding of the array of potential sequelae of COVID-19. The multisystemic aspects of acute COVID-19 have been the subject of intense investigation, but the long-term complications remain poorly understood. Emerging data from lay press, social media, commentaries, and emerging scientific reports suggest that some COVID-19 survivors experience organ impairment and/or debilitating chronic symptoms, at times protean in nature, which impact their quality of life.<br><br>METHODS/RESULTS: In this review, by addressing separately each body system, we describe the pleiotropic manifestations reported post COVID-19, their putative pathophysiology and risk factors, and attempt to offer guidance regarding work-up, follow-up and management strategies. Long term sequelae involve all systems with a negative impact on mental health, well-being and quality of life, while a subset of patients, report debilitating chronic fatigue, with or without other fluctuating or persistent symptoms, such as pain or cognitive dysfunction. Although the pathogenesis is unclear, residual damage from acute infection, persistent immune activation, mental factors, or unmasking of underlying co-morbidities are considered as drivers. Comparing long COVID with other post viral chronic syndromes may help to contextualize the complex somatic and emotional sequalae of acute COVID-19. The pace of recovery of different aspects of the syndrome remains unclear as the pandemic began only a year ago.<br><br>CONCLUSIONS: Early recognition of long-term effects and thorough follow-up through dedicated multidisciplinary outpatient clinics with a carefully integrated research agenda are essential for treating COVID-19 survivors holistically.}, }
@article {pmid33992951, year = {2021}, author = {Llach, CD and Vieta, E}, title = {Mind long COVID: Psychiatric sequelae of SARS-CoV-2 infection.}, journal = {European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology}, volume = {49}, number = {}, pages = {119-121}, pmid = {33992951}, issn = {1873-7862}, mesh = {Brain/pathology ; COVID-19/*complications/diagnosis/etiology/psychology ; *Disease Progression ; Humans ; Mental Disorders/*diagnosis/etiology/psychology ; Nervous System Diseases/*diagnosis/etiology/psychology ; Post-Acute COVID-19 Syndrome ; }, }
@article {pmid33998773, year = {2022}, author = {Rasile, M and Lauranzano, E and Mirabella, F and Matteoli, M}, title = {Neurological consequences of neurovascular unit and brain vasculature damages: potential risks for pregnancy infections and COVID-19-babies.}, journal = {The FEBS journal}, volume = {289}, number = {12}, pages = {3374-3392}, pmid = {33998773}, issn = {1742-4658}, mesh = {Animals ; Brain ; *COVID-19 ; Female ; Humans ; *Mental Disorders ; Pregnancy ; *Pregnancy Complications, Infectious ; *Prenatal Exposure Delayed Effects ; }, abstract = {Intragravidic and perinatal infections, acting through either direct viral effect or immune-mediated responses, are recognized causes of liability for neurodevelopmental disorders in the progeny. The large amounts of epidemiological data and the wealth of information deriving from animal models of gestational infections have contributed to delineate, in the last years, possible underpinning mechanisms for this phenomenon, including defects in neuronal migration, impaired spine and synaptic development, and altered activation of microglia. Recently, dysfunctions of the neurovascular unit and anomalies of the brain vasculature have unexpectedly emerged as potential causes at the origin of behavioral abnormalities and psychiatric disorders consequent to prenatal and perinatal infections. This review aims to discuss the up-to-date literature evidence pointing to the neurovascular unit and brain vasculature damages as the etiological mechanisms in neurodevelopmental syndromes. We focus on the inflammatory events consequent to intragravidic viral infections as well as on the direct viral effects as the potential primary triggers. These authors hope that a timely review of the literature will help to envision promising research directions, also relevant for the present and future COVID-19 longitudinal studies.}, }
@article {pmid34016708, year = {2021}, author = {Lever, J and Altman, RB}, title = {Analyzing the vast coronavirus literature with CoronaCentral.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {23}, pages = {}, pmid = {34016708}, issn = {1091-6490}, support = {LM05652/NH/NIH HHS/United States ; }, mesh = {Animals ; *COVID-19/epidemiology/metabolism/therapy/transmission ; Humans ; *Machine Learning ; Middle East Respiratory Syndrome Coronavirus/*metabolism/pathogenicity ; *Pandemics ; SARS-CoV-2/*metabolism/pathogenicity ; *Severe Acute Respiratory Syndrome/epidemiology/metabolism/therapy/transmission ; }, abstract = {The SARS-CoV-2 pandemic has caused a surge in research exploring all aspects of the virus and its effects on human health. The overwhelming publication rate means that researchers are unable to keep abreast of the literature. To ameliorate this, we present the CoronaCentral resource that uses machine learning to process the research literature on SARS-CoV-2 together with SARS-CoV and MERS-CoV. We categorize the literature into useful topics and article types and enable analysis of the contents, pace, and emphasis of research during the crisis with integration of Altmetric data. These topics include therapeutics, disease forecasting, as well as growing areas such as "long COVID" and studies of inequality. This resource, available at https://coronacentral.ai, is updated daily.}, }
@article {pmid34019446, year = {2021}, author = {Funke-Chambour, M and Feldmeyer, L and Hoepner, R and Huynh-Do, U and Maurer, B and Rexhaj, E and Geiser, T}, title = {[The Long-COVID Syndrome - a New Clinical Picture after COVID-19 Infection].}, journal = {Praxis}, volume = {110}, number = {7}, pages = {377-382}, doi = {10.1024/1661-8157/a003678}, pmid = {34019446}, issn = {1661-8157}, mesh = {*COVID-19 ; Humans ; Lung ; SARS-CoV-2 ; Syndrome ; }, abstract = {The Long-COVID Syndrome - a New Clinical Picture after COVID-19 Infection Abstract. Long-term consequences are increasingly reported in the current literature after COVID-19 infections. Some patients suffer from persistent pulmonary and extrapulmonary symptoms even months after the acute infection. Pulmonary impairment, but also dysregulation and effects on immune system, cardiovascular system, neurological system, skin and kidney are described or anticipated. This mini review gives a short update to the practitioner about the current knowledge about Long COVID.}, }
@article {pmid34024217, year = {2021}, author = {Yong, SJ}, title = {Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments.}, journal = {Infectious diseases (London, England)}, volume = {53}, number = {10}, pages = {737-754}, pmid = {34024217}, issn = {2374-4243}, mesh = {*COVID-19/complications ; Female ; Humans ; *Mental Disorders ; Risk Factors ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long COVID or post-COVID-19 syndrome first gained widespread recognition among social support groups and later in scientific and medical communities. This illness is poorly understood as it affects COVID-19 survivors at all levels of disease severity, even younger adults, children, and those not hospitalized. While the precise definition of long COVID may be lacking, the most common symptoms reported in many studies are fatigue and dyspnoea that last for months after acute COVID-19. Other persistent symptoms may include cognitive and mental impairments, chest and joint pains, palpitations, myalgia, smell and taste dysfunctions, cough, headache, and gastrointestinal and cardiac issues. Presently, there is limited literature discussing the possible pathophysiology, risk factors, and treatments in long COVID, which the current review aims to address. In brief, long COVID may be driven by long-term tissue damage (e.g. lung, brain, and heart) and pathological inflammation (e.g. from viral persistence, immune dysregulation, and autoimmunity). The associated risk factors may include female sex, more than five early symptoms, early dyspnoea, prior psychiatric disorders, and specific biomarkers (e.g. D-dimer, CRP, and lymphocyte count), although more research is required to substantiate such risk factors. While preliminary evidence suggests that personalized rehabilitation training may help certain long COVID cases, therapeutic drugs repurposed from other similar conditions, such as myalgic encephalomyelitis or chronic fatigue syndrome, postural orthostatic tachycardia syndrome, and mast cell activation syndrome, also hold potential. In sum, this review hopes to provide the current understanding of what is known about long COVID.}, }
@article {pmid34050501, year = {2021}, author = {Roe, K}, title = {The Symptoms and Clinical Manifestations Observed in COVID-19 Patients/Long COVID-19 Symptoms that Parallel Toxoplasma gondii Infections.}, journal = {Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology}, volume = {16}, number = {3}, pages = {513-516}, pmid = {34050501}, issn = {1557-1904}, mesh = {Brain/parasitology/pathology ; COVID-19/*complications/diagnosis/etiology/mortality/physiopathology ; Humans ; Toxoplasma/isolation &amp; purification ; Toxoplasmosis/*diagnosis/*mortality/physiopathology ; Post-Acute COVID-19 Syndrome ; }, }
@article {pmid34066174, year = {2021}, author = {Chakraborty, T and Jamal, RF and Battineni, G and Teja, KV and Marto, CM and Spagnuolo, G}, title = {A Review of Prolonged Post-COVID-19 Symptoms and Their Implications on Dental Management.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {10}, pages = {}, pmid = {34066174}, issn = {1660-4601}, mesh = {*COVID-19 ; Cohort Studies ; Cross-Sectional Studies ; Dental Care ; Humans ; SARS-CoV-2 ; }, abstract = {The available data regarding the short and long-term consequences of COVID-19 is still insufficient. This narrative review aims to provide information on the prolonged COVID-19 symptoms in recovered patients and their implications during dental management. Additionally, this manuscript highlights the oral manifestations of COVID-19 and its management. A systematic search was conducted in PubMed, Embase, Cochrane Library and Web of Science databases, WHO and CDC websites, and grey literature was searched through Google Scholar. Clinical articles (clinical trials, case-reports, cohort, and cross-sectional studies) were included, reporting prolonged post-COVID-19 symptoms. Although COVID-19 is an infectious disease primarily affecting the lungs, its multi-organ involvement is responsible for several prolonged symptoms, including oral implications. In recovered patients with prolonged COVID-19 symptoms, considerations for providing dental treatment has to be made as they can present with assortment of symptoms. These prolonged post-COVID-19 symptoms can affect the delivery of the required dental treatment. Hence, the recommendations proposed in this narrative review can be a useful starting point to aid dental teams providing adequate care for such recovered patients.}, }
@article {pmid34067776, year = {2021}, author = {Jimeno-Almazán, A and Pallarés, JG and Buendía-Romero, &#xc1; and Martínez-Cava, A and Franco-López, F and Sánchez-Alcaraz Martínez, BJ and Bernal-Morel, E and Courel-Ibáñez, J}, title = {Post-COVID-19 Syndrome and the Potential Benefits of Exercise.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {10}, pages = {}, pmid = {34067776}, issn = {1660-4601}, mesh = {*COVID-19 ; Exercise ; Humans ; Pandemics ; *SARS-CoV-2 ; }, abstract = {The coronavirus disease (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, is leading to unknown and unusual health conditions that are challenging to manage. Post-COVID-19 syndrome is one of those challenges, having become increasingly common as the pandemic evolves. The latest estimates suggest that 10 to 20% of the SARS-CoV-2 patients who undergo an acute symptomatic phase are experiencing effects of the disease beyond 12 weeks after diagnosis. Although research is beginning to examine this new condition, there are still serious concerns about the diagnostic identification, which limits the best therapeutic approach. Exercise programs and physical activity levels are well-known modulators of the clinical manifestations and prognosis in many chronic diseases. This narrative review summarizes the up-to-date evidence on post-COVID-19 syndrome to contribute to a better knowledge of the disease and explains how regular exercise may improve many of these symptoms and could reduce the long-term effects of COVID-19.}, }
@article {pmid34072390, year = {2021}, author = {Desimmie, BA and Raru, YY and Awadh, HM and He, P and Teka, S and Willenburg, KS}, title = {Insights into SARS-CoV-2 Persistence and Its Relevance.}, journal = {Viruses}, volume = {13}, number = {6}, pages = {}, pmid = {34072390}, issn = {1999-4915}, mesh = {COVID-19/immunology/physiopathology/prevention &amp; control/*virology ; Humans ; Reinfection ; SARS-CoV-2/immunology/*physiology ; Viral Tropism ; Virus Shedding ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), continues to wreak havoc, threatening the public health services and imposing economic collapse worldwide. Tailoring public health responses to the SARS-CoV-2 pandemic depends on understanding the mechanism of viral replication, disease pathogenesis, accurately identifying acute infections, and mapping the spreading risk of hotspots across the globe. However, effective identification and isolation of persons with asymptomatic and mild SARS-CoV-2 infections remain the major obstacles to efforts in controlling the SARS-CoV-2 spread and hence the pandemic. Understanding the mechanism of persistent viral shedding, reinfection, and the post-acute sequalae of SARS-CoV-2 infection (PASC) is crucial in our efforts to combat the pandemic and provide better care and rehabilitation to survivors. Here, we present a living literature review (January 2020 through 15 March 2021) on SARS-CoV-2 viral persistence, reinfection, and PASC. We also highlight potential areas of research to uncover putative links between viral persistence, intra-host evolution, host immune status, and protective immunity to guide and direct future basic science and clinical research priorities.}, }
@article {pmid34090980, year = {2021}, author = {Paterson, I and Ramanathan, K and Aurora, R and Bewick, D and Chow, CM and Clarke, B and Cowan, S and Ducharme, A and Gin, K and Graham, M and Gupta, A and Jassal, DS and Kazmi, M and Krahn, A and Lamarche, Y and Marelli, A and Roifman, I and Ruel, M and Singh, G and Sterns, L and Turgeon, R and Virani, S and Wong, KK and Zieroth, S}, title = {Long COVID-19: A Primer for Cardiovascular Health Professionals, on Behalf of the CCS Rapid Response Team.}, journal = {The Canadian journal of cardiology}, volume = {37}, number = {8}, pages = {1260-1262}, pmid = {34090980}, issn = {1916-7075}, mesh = {COVID-19/*complications/epidemiology/physiopathology/therapy ; Canada ; *Cardiology/methods/trends ; Humans ; Hypoxia/etiology/*therapy ; Myocardial Ischemia/etiology/physiopathology/therapy ; Myocarditis/etiology/physiopathology/*therapy/virology ; *Patient Care Management/methods/organization &amp; administration ; Patient Care Team/organization &amp; administration ; Post-Acute COVID-19 Syndrome ; }, abstract = {It is now widely recognized that COVID-19 illness can be associated with significant intermediate and potentially longer-term physical limitations. The term, "long COVID-19" is used to define any patient with persistent symptoms after acute COVID-19 infection (ie, after 4 weeks). It is postulated that cardiac injury might be linked to symptoms that persist after resolution of acute infection, as part of this syndrome. The Canadian Cardiovascular Society Rapid Response Team has generated this document to provide guidance to health care providers on the optimal management of patients with suspected cardiac complications of long COVID-19.}, }
@article {pmid34091456, year = {2021}, author = {Funke-Chambour, M and Bridevaux, PO and Clarenbach, CF and Soccal, PM and Nicod, LP and von Garnier, C and , }, title = {Swiss Recommendations for the Follow-Up and Treatment of Pulmonary Long COVID.}, journal = {Respiration; international review of thoracic diseases}, volume = {100}, number = {8}, pages = {826-841}, pmid = {34091456}, issn = {1423-0356}, mesh = {Aftercare/*standards ; COVID-19/*complications/diagnostic imaging ; Humans ; Pulmonary Medicine/*standards ; Radiography, Thoracic ; *COVID-19 Drug Treatment ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Emerging evidence suggests that long-term pulmonary symptoms and functional impairment occurs in a proportion of individuals following SARS-CoV-2 infection. Although the proportion of affected patients remains to be determined, physicians are increasingly being confronted with patients reporting respiratory symptoms and impairment beyond the acute phase of COVID-19. In face of limited evidence, the Swiss Society for Pulmonology established a working group to address this area of unmet need and formulated diagnostic and treatment recommendations for the care of patients with pulmonary long COVID (LC).<br><br>METHOD: The Swiss COVID Lung Study group and Swiss Society for Pulmonology (SSP) formulated 13 questions addressing the diagnosis and treatment of pulmonary LC. A survey within the SSP special interest groups involved in care of LC patients was conducted in Switzerland. A CORE process/Delphi-like process was used to formulate recommendations. Forty experienced pulmonologists replied to the first survey and 22 completed the second follow-up survey. Agreement of &#x2265;70% consensus led to formulation of a recommendation.<br><br>RESULTS: The participants in the survey reached consensus and formulated a strong recommendation for regarding the following points. Patients hospitalized for COVID-19 should have a pulmonary assessment including pulmonary function tests. Symptomatic subjects affected by COVID-19, including those with mild disease, should benefit from a pulmonary follow-up. Persistent respiratory symptoms after COVID-19 should be investigated by a pulmonary follow-up including plethysmography, diffusion capacity measurement, and blood gases analysis. Individuals having suffered from COVID-19 and who present with persistent respiratory symptoms should be offered a rehabilitation. Additional questions were given moderateor weak recommendations for. The panel did not reach sufficient consensus for pharmacological therapy (e.g., therapy specifically targeting lung fibrosis) to formulate recommendations for LC drug treatment.<br><br>CONCLUSION: The formulated recommendations should serve as an interim guidance to facilitate diagnosis and treatment of patients with pulmonary LC. As new evidence emerges, these recommendations may need to be adapted.}, }
@article {pmid34096390, year = {2021}, author = {Sarfraz, Z and Sarfraz, A and Barrios, A and Garimella, R and Dominari, A and Kc, M and Pandav, K and Pantoja, JC and Retnakumar, V and Cherrez-Ojeda, I}, title = {Cardio-Pulmonary Sequelae in Recovered COVID-19 Patients: Considerations for Primary Care.}, journal = {Journal of primary care &amp; community health}, volume = {12}, number = {}, pages = {21501327211023726}, pmid = {34096390}, issn = {2150-1327}, mesh = {*COVID-19/complications ; Cross-Sectional Studies ; Humans ; Middle Aged ; Primary Health Care ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Current literature lacks characterization of the post-recovery sequelae among COVID-19 patients. This review characterizes the course of clinical, laboratory, radiological findings during the primary infection period, and the complications post-recovery. Primary care findings are presented for long-COVID care.<br><br>METHODS: Adhering to PRISMA guidelines, 4 databases were searched (PubMed, Embase, CINAHL Plus, Scopus) through December 5, 2020, using the keywords "COVID-19 and/or recovered and/or cardiovascular and/or long-term and/or sequelae and/or sub-acute and/or complication." We included published peer-reviewed case reports, case series, and cross-sectional studies providing the clinical course of COVID-19 infection, and cardiopulmonary complications of patients who recovered from COVID-19, while making healthcare considerations for primary care workers.<br><br>RESULTS: We identified 29 studies across 9 countries including 37.9% Chinese and 24.1% U.S. studies, comprising 655 patients (Mean Age&#x2009;=&#x2009;45) with various ethnical backgrounds including Asian and European. Based on the WHO COVID-19 severity classification scale, initial disease severity was mild for 377 patients and severe for 52 patients. Treatments during primary infection included corticosteroids, oxygen support, and antivirals. The mean value (in days) for complication onset after acute recovery was 28&#x2009;days. Complete blood counts and RT-PCR tests were the most common laboratory results described. In 22 of the studies, patients showed signs of clinical improvement and were prescribed medications such as anticoagulants or corticosteroids.<br><br>CONCLUSION: Post-recovery infectious complications are common in long-COVID-19 patients ranging from mild infections to life-threatening conditions. International thoracic and cardiovascular societies need to develop guidelines for patients recovering from COVID-19 pneumonia, while focused patient care by the primary care physician is crucial to curb preventable adverse events. Recommendations for real-time and lab-quality diagnostic tests are warranted to establish point-of-care testing, detect early complications, and provide timely treatment.}, }
@article {pmid34103194, year = {2022}, author = {Arena, R and Myers, J and Ozemek, C and Hall, G and Severin, R and Laddu, D and Kaminsky, LA and Stoner, L and Conners, RT and Faghy, MA and , }, title = {An Evolving Approach to Assessing Cardiorespiratory Fitness, Muscle Function and Bone and Joint Health in the COVID-19 Era.}, journal = {Current problems in cardiology}, volume = {47}, number = {1}, pages = {100879}, pmid = {34103194}, issn = {1535-6280}, mesh = {Activities of Daily Living ; *COVID-19/complications ; *Cardiorespiratory Fitness ; Humans ; Muscles ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Cardiorespiratory fitness (CRF) is now an established vital sign. CRF, along with muscle function and bone and joint health is related to functional independence and a higher quality of life. Wasserman and colleagues proposed a gear model illustrating the integrated role of the respiratory, cardiovascular, and skeletal muscle systems during aerobic exercise; in 2015, a revision to the original model was proposed. Our understanding of the effects and challenges associated with the coronavirus disease 2019 (COVID-19) are rapidly evolving. Initial evidence indicates higher levels of CRF, and muscle function protect individuals infected with COVID-19 from a complicated medical course. Moreover, for those individuals infected with COVID-19, there are initial signs of a reduction in CRF following the initial phase of recovery. We are also gaining an understanding of long COVID syndrome, where individuals who have recovered from the acute phase of viral infection present with lasting symptoms, which include but are not limited to reduced CRF, shortness of breath, and fatigue. Clearly, these individuals will require rehabilitation to restore and/or improve CRF, muscle function, bone and joint health, functional capacity (ie, the ability to perform activities of daily living), and quality of life. The importance of assessing the synergistic function of systems essential to performing activities that require physical exertion is a health care imperative. This graphical narrative provides an update to the gear model initially proposed by Wasserman and updated to a gear and circuit in 2015. External CRF, muscle function, and bone and joint health influencers and an approach to clinical assessment are also introduced.}, }
@article {pmid34110078, year = {2021}, author = {Brüssow, H and Timmis, K}, title = {COVID-19: long covid and its societal consequences.}, journal = {Environmental microbiology}, volume = {23}, number = {8}, pages = {4077-4091}, doi = {10.1111/1462-2920.15634}, pmid = {34110078}, issn = {1462-2920}, mesh = {COVID-19/*complications ; Humans ; Lung ; SARS-CoV-2 ; Social Conditions ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19 is an acute, highly transmissible respiratory infection that is potentially lethal, but often mild, sometimes asymptomatic, especially in the young. However, it has become clear that, in some patients, there may be sequelae involving tissues other than the lung, resulting in other types of morbidity, and sometimes longer term consequences that are often termed 'long covid'. In this Lilliput, we summarize recent findings about COVID-19 sequelae, with a particular focus on long covid. We also discuss some of the long scars that COVID-19 and long covid will collectively leave on society that we term Societal Long Covid.}, }
@article {pmid34140635, year = {2022}, author = {Bornstein, SR and Voit-Bak, K and Donate, T and Rodionov, RN and Gainetdinov, RR and Tselmin, S and Kanczkowski, W and Müller, GM and Achleitner, M and Wang, J and Licinio, J and Bauer, M and Young, AH and Thuret, S and Bechmann, N and Straube, R}, title = {Chronic post-COVID-19 syndrome and chronic fatigue syndrome: Is there a role for extracorporeal apheresis?.}, journal = {Molecular psychiatry}, volume = {27}, number = {1}, pages = {34-37}, pmid = {34140635}, issn = {1476-5578}, mesh = {*Blood Component Removal ; *COVID-19/complications ; *Fatigue Syndrome, Chronic/diagnosis/drug therapy ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {As millions of patients have been infected by SARS-CoV-2 virus a vast number of individuals complain about continuing breathlessness and fatigue even months after the onset of the disease. This overwhelming phenomenon has not been well defined and has been called "post-COVID syndrome" or "long-COVID" [1]. There are striking similarities to myalgic encephalomyelitis also called chronic fatigue syndrome linked to a viral and autoimmune pathogenesis. In both disorders neurotransmitter receptor antibodies against ß-adrenergic and muscarinic receptors may play a key role. We found similar elevation of these autoantibodies in both patient groups. Extracorporeal apheresis using a special filter seems to be effective in reducing these antibodies in a significant way clearly improving the debilitating symptoms of patients with chronic fatigue syndrome. Therefore, such a form of neuropheresis may provide a promising therapeutic option for patients with post-COVID-19 syndrome. This method will also be effective when other hitherto unknown antibodies and inflammatory mediators are involved.}, }
@article {pmid34151246, year = {2021}, author = {Touyz, RM and Boyd, MOE and Guzik, T and Padmanabhan, S and McCallum, L and Delles, C and Mark, PB and Petrie, JR and Rios, F and Montezano, AC and Sykes, R and Berry, C}, title = {Cardiovascular and Renal Risk Factors and Complications Associated With COVID-19.}, journal = {CJC open}, volume = {3}, number = {10}, pages = {1257-1272}, pmid = {34151246}, issn = {2589-790X}, support = {CH/12/4/29762/BHF_/British Heart Foundation/United Kingdom ; MR/M016560/1/MRC_/Medical Research Council/United Kingdom ; MR/N003403/1/MRC_/Medical Research Council/United Kingdom ; PG/17/25/32884/BHF_/British Heart Foundation/United Kingdom ; }, abstract = {The current COVID-19 pandemic, caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) virus, represents the largest medical challenge in decades. It has exposed unexpected cardiovascular vulnerabilities at all stages of the disease (pre-infection, acute phase, and subsequent chronic phase). The major cardiometabolic drivers identified as having epidemiologic and mechanistic associations with COVID-19 are abnormal adiposity, dysglycemia, dyslipidemia, and hypertension. Hypertension is of particular interest, because components of the renin-angiotensin system (RAS), which are critically involved in the pathophysiology of hypertension, are also implicated in COVID-19. Specifically, angiotensin-converting enzyme-2 (ACE2), a multifunctional protein of the RAS, which is part of the protective axis of the RAS, is also the receptor through which SARS-CoV-2 enters host cells, causing viral infection. Cardiovascular and cardiometabolic comorbidities not only predispose people to COVID-19, but also are complications of SARS-CoV-2 infection. In addition, increasing evidence indicates that acute kidney injury is common in COVID-19, occurs early and in temporal association with respiratory failure, and is associated with poor prognosis, especially in the presence of cardiovascular risk factors. Here, we discuss cardiovascular and kidney disease in the context of COVID-19 and provide recent advances on putative pathophysiological mechanisms linking cardiovascular disease and COVID-19, focusing on the RAS and ACE2, as well as the immune system and inflammation. We provide up-to-date information on the relationships among hypertension, diabetes, and COVID-19 and emphasize the major cardiovascular diseases associated with COVID-19. We also briefly discuss emerging cardiovascular complications associated with long COVID-19, notably postural tachycardia syndrome (POTS).}, }
@article {pmid34163217, year = {2021}, author = {Garg, M and Maralakunte, M and Garg, S and Dhooria, S and Sehgal, I and Bhalla, AS and Vijayvergiya, R and Grover, S and Bhatia, V and Jagia, P and Bhalla, A and Suri, V and Goyal, M and Agarwal, R and Puri, GD and Sandhu, MS}, title = {The Conundrum of 'Long-COVID-19': A Narrative Review.}, journal = {International journal of general medicine}, volume = {14}, number = {}, pages = {2491-2506}, pmid = {34163217}, issn = {1178-7074}, abstract = {COVID-19 is an ongoing pandemic with many challenges that are now extending to its intriguing long-term sequel. 'Long-COVID-19' is a term given to the lingering or protracted illness that patients of COVID-19 continue to experience even in their post-recovery phase. It is also being called 'post-acute COVID-19', 'ongoing symptomatic COVID-19', 'chronic COVID-19', 'post COVID-19 syndrome', and 'long-haul COVID-19'. Fatigue, dyspnea, cough, headache, brain fog, anosmia, and dysgeusia are common symptoms seen in Long-COVID-19, but more varied and debilitating injuries involving pulmonary, cardiovascular, cutaneous, musculoskeletal and neuropsychiatric systems are also being reported. With the data on Long-COVID-19 still emerging, the present review aims to highlight its epidemiology, protean clinical manifestations, risk predictors, and management strategies. With the re-emergence of new waves of SARS-CoV-2 infection, Long-COVID-19 is expected to produce another public health crisis on the heels of current pandemic. Thus, it becomes imperative to emphasize this condition and disseminate its awareness to medical professionals, patients, the public, and policymakers alike to prepare and augment health care facilities for continued surveillance of these patients. Further research comprising cataloging of symptoms, longer-ranging observational studies, and clinical trials are necessary to evaluate long-term consequences of COVID-19, and it warrants setting-up of dedicated, post-COVID care, multi-disciplinary clinics, and rehabilitation centers.}, }
@article {pmid34170086, year = {2021}, author = {Richter, D and Guasti, L and Koehler, F and Squizzato, A and Nistri, S and Christodorescu, R and Dievart, F and Gaudio, G and Asteggiano, R and Ferrini, M}, title = {Late phase of COVID-19 pandemic in General Cardiology. A position paper of the ESC Council for Cardiology Practice.}, journal = {ESC heart failure}, volume = {8}, number = {5}, pages = {3483-3494}, pmid = {34170086}, issn = {2055-5822}, mesh = {*COVID-19/complications ; *Cardiology ; Humans ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Cardiovascular (CV) engagement in coronavirus disease 2019 (COVID-19) is a huge determinant of prognosis during the acute phase of the disease. However, little is known about the potential chronic implications of the late phase of COVID-19 and about the appropriate approach to these patients. Heart failure, type 1 and type 2 myocardial infarction, arrhythmias, myocarditis, pulmonary fibrosis, and thrombosis have been shown to be related to severe acute respiratory syndrome coronavirus 2 infection, and a 'long COVID-19' illness has been recognized with fatigue, chest pain, and dyspnoea among the most frequent symptoms reported after discharge from hospital. This paper focuses on some open questions that cardiologists are going to face during the next months in a general cardiology outpatient clinic, in particular how to evaluate a 'post-COVID' patient during follow-up of CV complications of the acute phase and how to manage new CV symptoms that could be the consequence, at least in part, of heart/vessels and/or lung involvement of the previous virus infection. Present symptoms and signs, history of previous CV disease (both preceding COVID-19 and occurring during viral infection), and specific laboratory and imaging measurements during the acute phase may be of interest in focusing on how to approach the clinical evaluation of a post-COVID patient and how to integrate in our standard of care the new information on COVID-19, possibly in a multidisciplinary view. Dealing with the increased COVID-associated CV risk burden and becoming acquainted with potential new e-cardiology approaches aimed at integrating the cardiology practice are relevant new challenges brought by severe acute respiratory syndrome coronavirus 2 infection and its sequelae.}, }
@article {pmid34171458, year = {2021}, author = {Ramadan, MS and Bertolino, L and Zampino, R and Durante-Mangoni, E and , }, title = {Cardiac sequelae after coronavirus disease 2019 recovery: a systematic review.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {27}, number = {9}, pages = {1250-1261}, pmid = {34171458}, issn = {1469-0691}, mesh = {Adult ; COVID-19/complications/*diagnosis ; COVID-19 Nucleic Acid Testing ; Echocardiography ; Electrocardiography ; Heart Diseases/*epidemiology/etiology ; Humans ; Magnetic Resonance Imaging, Cine ; SARS-CoV-2/genetics/*isolation &amp; purification ; }, abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19) has been implicated in a wide spectrum of cardiac manifestations following the acute phase of the disease.<br><br>OBJECTIVES: To assess the range of cardiac sequelae after COVID-19 recovery.<br><br>DATA SOURCES: PubMed, Embase, Scopus (inception through 17 February 2021) and Google scholar (2019 through 17 February 2021).<br><br>STUDY ELIGIBILITY CRITERIA: Prospective and retrospective studies, case reports and case series.<br><br>PARTICIPANTS: Adult patients assessed for cardiac manifestations after COVID-19 recovery.<br><br>EXPOSURE: Severe acute respiratory syndrome coronavirus 2 infection diagnosed by PCR.<br><br>METHODS: Systematic review.<br><br>RESULTS: Thirty-five studies (fifteen prospective cohort, seven case reports, five cross-sectional, four case series, three retrospective cohort and one ambidirectional cohort) evaluating cardiac sequelae in 52&#xa0;609 patients were included. Twenty-nine studies used objective cardiac assessments, mostly cardiac magnetic resonance imaging (CMR) in 16 studies, echocardiography in 15, electrocardiography (ECG) in 16 and cardiac biomarkers in 18. Most studies had a fair risk of bias. The median time from diagnosis/recovery to cardiac assessment was 48&#xa0;days (1-180&#xa0;days). Common short-term cardiac abnormalities (<3&#xa0;months) included increased T1 (proportion: 30%), T2 (16%), pericardial effusion (15%) and late gadolinium enhancement (11%) on CMR, with symptoms such as chest pain (25%) and dyspnoea (36%). In the medium term (3-6&#xa0;months), common changes included reduced left ventricular global longitudinal strain (30%) and late gadolinium enhancement (10%) on CMR, diastolic dysfunction (40%) on echocardiography and elevated N-terminal proB-type natriuretic peptide (18%). In addition, COVID-19 survivors had higher risk (risk ratio 3; 95% CI 2.7-3.2) of developing heart failure, arrythmias and myocardial infarction.<br><br>CONCLUSIONS: COVID-19 appears to be associated with persistent/de novo cardiac injury after recovery, particularly subclinical myocardial injury in the earlier phase and diastolic dysfunction later. Larger well-designed and controlled studies with baseline assessments are needed to better measure the extent of cardiac injury and its clinical impact.}, }
@article {pmid34175230, year = {2021}, author = {Komaroff, AL and Lipkin, WI}, title = {Insights from myalgic encephalomyelitis/chronic fatigue syndrome may help unravel the pathogenesis of postacute COVID-19 syndrome.}, journal = {Trends in molecular medicine}, volume = {27}, number = {9}, pages = {895-906}, pmid = {34175230}, issn = {1471-499X}, support = {U54 AI138370/AI/NIAID NIH HHS/United States ; }, mesh = {COVID-19/*complications/etiology/physiopathology ; Energy Metabolism ; Fatigue Syndrome, Chronic/*etiology/physiopathology ; Gastrointestinal Microbiome ; Humans ; Nervous System/physiopathology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause chronic and acute disease. Postacute sequelae of SARS-CoV-2 infection (PASC) include injury to the lungs, heart, kidneys, and brain that may produce a variety of symptoms. PASC also includes a post-coronavirus disease 2019 (COVID-19) syndrome ('long COVID') with features that can follow other acute infectious diseases and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Here we summarize what is known about the pathogenesis of ME/CFS and of 'acute' COVID-19, and we speculate that the pathogenesis of post-COVID-19 syndrome in some people may be similar to that of ME/CFS. We propose molecular mechanisms that might explain the fatigue and related symptoms in both illnesses, and we suggest a research agenda for both ME/CFS and post-COVID-19 syndrome.}, }
@article {pmid34181102, year = {2021}, author = {Moghimi, N and Di Napoli, M and Biller, J and Siegler, JE and Shekhar, R and McCullough, LD and Harkins, MS and Hong, E and Alaouieh, DA and Mansueto, G and Divani, AA}, title = {The Neurological Manifestations of Post-Acute Sequelae of SARS-CoV-2 infection.}, journal = {Current neurology and neuroscience reports}, volume = {21}, number = {9}, pages = {44}, pmid = {34181102}, issn = {1534-6293}, mesh = {Brain ; *COVID-19/complications ; Humans ; *SARS-CoV-2 ; United States ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health challenge. This review aims to summarize the incidence, risk factors, possible pathophysiology, and proposed management of neurological manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC) or neuro-PASC based on the published literature.<br><br>RECENT FINDINGS: The National Institutes of Health has noted that PASC is a multi-organ disorder ranging from mild symptoms to an incapacitating state that can last for weeks or longer following recovery from initial infection with SARS-CoV-2. Various pathophysiological mechanisms have been proposed as the culprit for the development of PASC. These include, but are not limited to, direct or indirect invasion of the virus into the brain, immune dysregulation, hormonal disturbances, elevated cytokine levels due to immune reaction leading to chronic inflammation, direct tissue damage to other organs, and persistent low-grade infection. A multidisciplinary approach for the treatment of neuro-PASC will be required to diagnose and address these symptoms. Tailored rehabilitation and novel cognitive therapy protocols are as important as pharmacological treatments to treat neuro-PASC effectively. With recognizing the growing numbers of COVID-19 patients suffering from neuro-PASC, there is an urgent need to identify affected individuals early to provide the most appropriate and efficient treatments. Awareness among the general population and health care professionals about PASC is rising, and more efforts are needed to understand and treat this new emerging challenge. In this review, we summarize the relevant scientific literature about neuro-PASC.}, }
@article {pmid34192289, year = {2021}, author = {Dixit, NM and Churchill, A and Nsair, A and Hsu, JJ}, title = {Post-Acute COVID-19 Syndrome and the cardiovascular system: What is known?.}, journal = {American heart journal plus : cardiology research and practice}, volume = {5}, number = {}, pages = {100025}, pmid = {34192289}, issn = {2666-6022}, abstract = {Post-Acute COVID-19 Syndrome (PACS) is defined by persistent symptoms >3-4 weeks after onset of COVID-19. The mechanism of these persistent symptoms is distinct from acute COVID-19 although not completely understood despite the high incidence of PACS. Cardiovascular symptoms such as chest pain and palpitations commonly occur in PACS, but the underlying cause of symptoms is infrequently known. While autopsy studies have shown that the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) rarely causes direct myocardial injury, several syndromes such as myocarditis, pericarditis, and Postural Orthostatic Tachycardia Syndrome have been implicated in PACS. Additionally, patients hospitalized with acute COVID-19 who display biomarker evidence of myocardial injury may have underlying coronary artery disease revealed by the physiological stress of SARS-CoV-2 infection and may benefit from medical optimization. We review what is known about PACS and the cardiovascular system and propose a framework for evaluation and management of related symptoms.}, }
@article {pmid34209705, year = {2021}, author = {Lee, CCE and Ali, K and Connell, D and Mordi, IR and George, J and Lang, EM and Lang, CC}, title = {COVID-19-Associated Cardiovascular Complications.}, journal = {Diseases (Basel, Switzerland)}, volume = {9}, number = {3}, pages = {}, pmid = {34209705}, issn = {2079-9721}, abstract = {Coronavirus disease 2019 (COVID-19) has been reported to cause cardiovascular complications such as myocardial injury, thromboembolic events, arrhythmia, and heart failure. Multiple mechanisms-some overlapping, notably the role of inflammation and IL-6-potentially underlie these complications. The reported cardiac injury may be a result of direct viral invasion of cardiomyocytes with consequent unopposed effects of angiotensin II, increased metabolic demand, immune activation, or microvascular dysfunction. Thromboembolic events have been widely reported in both the venous and arterial systems that have attracted intense interest in the underlying mechanisms. These could potentially be due to endothelial dysfunction secondary to direct viral invasion or inflammation. Additionally, thromboembolic events may also be a consequence of an attempt by the immune system to contain the infection through immunothrombosis and neutrophil extracellular traps. Cardiac arrhythmias have also been reported with a wide range of implicated contributory factors, ranging from direct viral myocardial injury, as well as other factors, including at-risk individuals with underlying inherited arrhythmia syndromes. Heart failure may also occur as a progression from cardiac injury, precipitation secondary to the initiation or withdrawal of certain drugs, or the accumulation of des-Arg[9]-bradykinin (DABK) with excessive induction of pro-inflammatory G protein coupled receptor B1 (BK1). The presenting cardiovascular symptoms include chest pain, dyspnoea, and palpitations. There is currently intense interest in vaccine-induced thrombosis and in the treatment of Long COVID since many patients who have survived COVID-19 describe persisting health problems. This review will summarise the proposed physiological mechanisms of COVID-19-associated cardiovascular complications.}, }
@article {pmid34236922, year = {2021}, author = {Brimson, JM and Prasanth, MI and Malar, DS and Brimson, S and Thitilertdecha, P and Tencomnao, T}, title = {Drugs that offer the potential to reduce hospitalization and mortality from SARS-CoV-2 infection: The possible role of the sigma-1 receptor and autophagy.}, journal = {Expert opinion on therapeutic targets}, volume = {25}, number = {6}, pages = {435-449}, pmid = {34236922}, issn = {1744-7631}, mesh = {Antiviral Agents/*therapeutic use ; *Autophagy ; COVID-19/mortality/virology ; Hospitalization/*statistics &amp; numerical data ; Humans ; Receptors, sigma/*physiology ; SARS-CoV-2/isolation &amp; purification ; *COVID-19 Drug Treatment ; Sigma-1 Receptor ; }, abstract = {Introduction: Despite the availability of new vaccines for SARS-CoV-2, there has been slow uptake and problems with supply in some parts of the world. Hence, there is still a necessity for drugs that can prevent hospitalization of patients and reduce the strain on health care systems. Drugs with sigma affinity potentially provide protection against the most severe symptoms of SARS-COV-2 and could prevent mortality via interactions with the sigma-1 receptor.Areas covered: This review examines the role of the sigma-1 receptor and autophagy in SARS-CoV-2 infections and how they may be linked. The authors reveal how sigma ligands may reduce the symptoms, complications, and deaths resulting from SARS-CoV-2 and offer insights on those patient cohorts that may benefit most from these drugs.Expert opinion: Drugs with sigma affinity potentially offer protection against the most severe symptoms of SARS-CoV-2 via interactions with the sigma-1 receptor. Agonists of the sigma-1 receptor may provide protection of the mitochondria, activate mitophagy to remove damaged and leaking mitochondria, prevent ER stress, manage calcium ion transport, and induce autophagy to prevent cell death in response to infection.}, }
@article {pmid34237419, year = {2021}, author = {Zacharias, H and Dubey, S and Koduri, G and D'Cruz, D}, title = {Rheumatological complications of Covid 19.}, journal = {Autoimmunity reviews}, volume = {20}, number = {9}, pages = {102883}, pmid = {34237419}, issn = {1873-0183}, mesh = {Autoimmunity ; *COVID-19/complications ; Humans ; *Rheumatic Diseases ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: COVID-19 has caused unprecedented hardships in the 21st century with more than 150 million infections. Various immunological phenomena have been described during the course of the infection, and this infection has also triggered autoimmunity. Rheumatological illnesses have been described following resolution of the acute infection; hence we sought to conduct a review of the rheumatological complications of COVID-19.<br><br>METHODS: We conducted a literature search for articles relating to sequelae of COVID-19 from Jan 2020 to 30th April 2021.<br><br>RESULTS: We found a number of reports of inflammatory arthritis after SARS-CoV-2 infection. SLE and renal disease have been described, and vasculitis also appears to be a common complication. Rhabdomyolysis and myositis has also been reported in a number of patients. We also found some evidence of large vessel vasculitis in 'long COVID' patients.<br><br>CONCLUSIONS: This review highlights a number of important complications such as inflammatory arthritis, lupus-like disease, myostis and vasculitis following SARS-CoV-2 infection.}, }
@article {pmid34240374, year = {2021}, author = {Zeile, T}, title = {[Treating elderly geriatric patients right - some special aspects regarding sequential acute medical treatment and rehabilitation, rehabilitation and the new IPReG and long-Covid- rehabilitation].}, journal = {MMW Fortschritte der Medizin}, volume = {163}, number = {13}, pages = {48-50}, doi = {10.1007/s15006-021-0017-2}, pmid = {34240374}, issn = {1613-3560}, mesh = {Aged ; *COVID-19/complications ; Geriatric Assessment ; *Health Services for the Aged ; Humans ; Patient Rights ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, }
@article {pmid34241639, year = {2022}, author = {Frank, U and Frank, K}, title = {[COVID-19-New challenges in dysphagia and respiratory therapy].}, journal = {Der Nervenarzt}, volume = {93}, number = {2}, pages = {167-174}, pmid = {34241639}, issn = {1433-0407}, mesh = {*COVID-19/complications ; *Deglutition Disorders/diagnosis/therapy ; Humans ; Respiration, Artificial/*adverse effects ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Coronavirus disease 2019 (COVID-19) can lead to severe disease courses with multiple organ involvement, respiratory and neurological functional impairments. Swallowing disorders (dysphagia) in this patient group can result from primary damage to the central and peripheral neuronal swallowing network but also from the frequently prolonged intensive care treatment and mechanical ventilation. Clinical observations indicate persistence of dysphagia in post-acute COVID-19 syndrome (long COVID), so that these patients probably also need long-term interventions for rehabilitation of safe and sufficient oral feeding. Therefore, structured disease-specific monitoring of dysphagia symptoms should be integrated into the treatment of COVID-19 patients and respiratory therapy should be an essential part of dysphagia management to re-establish cough effectiveness and breathing-swallowing coordination. Challenges arise from necessary adjustments to established treatment standards to prevent infections. Furthermore, the selection and intensity of therapeutic measures have to be adapted to the capacities and the specific pathophysiology of COVID-19 and long COVID patients to prevent further functional deterioration.}, }
@article {pmid34248921, year = {2021}, author = {Proal, AD and VanElzakker, MB}, title = {Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {698169}, pmid = {34248921}, issn = {1664-302X}, abstract = {The novel virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic of coronavirus disease 2019 (COVID-19). Across the globe, a subset of patients who sustain an acute SARS-CoV-2 infection are developing a wide range of persistent symptoms that do not resolve over the course of many months. These patients are being given the diagnosis Long COVID or Post-acute sequelae of COVID-19 (PASC). It is likely that individual patients with a PASC diagnosis have different underlying biological factors driving their symptoms, none of which are mutually exclusive. This paper details mechanisms by which RNA viruses beyond just SARS-CoV-2 have be connected to long-term health consequences. It also reviews literature on acute COVID-19 and other virus-initiated chronic syndromes such as post-Ebola syndrome or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) to discuss different scenarios for PASC symptom development. Potential contributors to PASC symptoms include consequences from acute SARS-CoV-2 injury to one or multiple organs, persistent reservoirs of SARS-CoV-2 in certain tissues, re-activation of neurotrophic pathogens such as herpesviruses under conditions of COVID-19 immune dysregulation, SARS-CoV-2 interactions with host microbiome/virome communities, clotting/coagulation issues, dysfunctional brainstem/vagus nerve signaling, ongoing activity of primed immune cells, and autoimmunity due to molecular mimicry between pathogen and host proteins. The individualized nature of PASC symptoms suggests that different therapeutic approaches may be required to best manage care for specific patients with the diagnosis.}, }
@article {pmid34249236, year = {2021}, author = {Alqahtani, JS and Alghamdi, SM and Aldhahir, AM and Althobiani, M and Raya, RP and Oyelade, T}, title = {Thoracic imaging outcomes in COVID-19 survivors.}, journal = {World journal of radiology}, volume = {13}, number = {6}, pages = {149-156}, pmid = {34249236}, issn = {1949-8470}, abstract = {The coronavirus disease 2019 (COVID-19) pandemic presents a significant global public health challenge. One in five individuals with COVID-19 presents with symptoms that last for weeks after hospital discharge, a condition termed "long COVID". Thus, efficient follow-up of patients is needed to assess the resolution of lung pathologies and systemic involvement. Thoracic imaging is multimodal and involves using different forms of waves to produce images of the organs within the thorax. In general, it includes chest X-ray, computed tomography, lung ultrasound and magnetic resonance imaging techniques. Such modalities have been useful in the diagnosis and prognosis of COVID-19. These tools have also allowed for the follow-up and assessment of long COVID. This review provides insights on the effectiveness of thoracic imaging techniques in the follow-up of COVID-19 survivors who had long COVID.}, }
@article {pmid34256409, year = {2021}, author = {Simon, OJ and Menzler, K and Timmermann, L}, title = {[Update 2021: COVID-19 from the perspective of neurology].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {146}, number = {13-14}, pages = {918-923}, doi = {10.1055/a-1449-5098}, pmid = {34256409}, issn = {1439-4413}, mesh = {COVID-19/*complications ; Humans ; Nervous System Diseases/*complications/etiology ; *Neurology ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Neurological complications, direct affection of neuronal structures in the course of infections with SARS-CoV-2 and long-term effects ("long COVID") are evident. This article aims to summarize and evaluate the current literature on this topic.}, }
@article {pmid34257762, year = {2021}, author = {Okada, Y and Yoshimura, K and Toya, S and Tsuchimochi, M}, title = {Pathogenesis of taste impairment and salivary dysfunction in COVID-19 patients.}, journal = {The Japanese dental science review}, volume = {57}, number = {}, pages = {111-122}, pmid = {34257762}, issn = {1882-7616}, abstract = {Coronavirus disease 2019 (COVID-19) is a highly transmissible pandemic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The characteristics of the disease include a broad range of symptoms from mild to serious to death, with mild pneumonia to acute respiratory distress syndrome and complications in extrapulmonary organs. Taste impairment and salivary dysfunction are common early symptoms in COVID-19 patients. The mouth is a significant entry route for SARS-COV-2, similar to the nose and eyes. The cells of the oral epithelium, taste buds, and minor and major salivary glands express cell entry factors for SARS-COV-2, such as ACE2, TMPRSS2, and Furin. We describe the occurrence of taste impairment and salivary dysfunction in COVID-19 patients and show immunohistochemical findings regarding the cell entry factors in the oral tissue. We review and describe the pathogeneses of taste impairment and salivary dysfunction. Treatment for the oral disease is also described. Recently, it was reported that some people experience persistent and prolonged taste impairment and salivary dysfunction, described as post-COVID-19 syndrome or long COVID-19, after the acute illness of the infection has healed. To resolve these problems, it is important to understand the pathogenesis of oral complications. Recently, important advances have been reported in the understanding of gustatory impairment and salivary dysfunction. Although some progress has been made, considerable effort is still required for in-depth elucidation of the pathogenesis.}, }
@article {pmid34265229, year = {2021}, author = {Aiyegbusi, OL and Hughes, SE and Turner, G and Rivera, SC and McMullan, C and Chandan, JS and Haroon, S and Price, G and Davies, EH and Nirantharakumar, K and Sapey, E and Calvert, MJ and , }, title = {Symptoms, complications and management of long COVID: a review.}, journal = {Journal of the Royal Society of Medicine}, volume = {114}, number = {9}, pages = {428-442}, pmid = {34265229}, issn = {1758-1095}, support = {/WT_/Wellcome Trust/United Kingdom ; MC_PC_20050/MRC_/Medical Research Council/United Kingdom ; MC_PC_21015/MRC_/Medical Research Council/United Kingdom ; MR/L008335/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {COVID-19/*complications/therapy ; Delivery of Health Care ; Diarrhea/etiology ; Employment ; Fatigue/etiology ; Headache/etiology ; Humans ; Mental Disorders/etiology ; Mental Health ; Pain/etiology ; *Quality of Life ; Respiratory Tract Diseases/etiology ; SARS-CoV-2 ; Sensation Disorders/etiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Globally, there are now over 160 million confirmed cases of COVID-19 and more than 3 million deaths. While the majority of infected individuals recover, a significant proportion continue to experience symptoms and complications after their acute illness. Patients with 'long COVID' experience a wide range of physical and mental/psychological symptoms. Pooled prevalence data showed the 10 most prevalent reported symptoms were fatigue, shortness of breath, muscle pain, joint pain, headache, cough, chest pain, altered smell, altered taste and diarrhoea. Other common symptoms were cognitive impairment, memory loss, anxiety and sleep disorders. Beyond symptoms and complications, people with long COVID often reported impaired quality of life, mental health and employment issues. These individuals may require multidisciplinary care involving the long-term monitoring of symptoms, to identify potential complications, physical rehabilitation, mental health and social services support. Resilient healthcare systems are needed to ensure efficient and effective responses to future health challenges.}, }
@article {pmid34268454, year = {2021}, author = {Yuen, KCJ and Mortensen, MJ and Azadi, A and Fonkem, E and Findling, JW}, title = {Rethinking the management of immune checkpoint inhibitor-related adrenal insufficiency in cancer patients during the COVID-19 pandemic.}, journal = {Endocrinology, diabetes &amp; metabolism}, volume = {4}, number = {3}, pages = {e00246}, pmid = {34268454}, issn = {2398-9238}, mesh = {Adrenal Insufficiency/chemically induced/*drug therapy ; *COVID-19 ; Humans ; Immune Checkpoint Inhibitors/*adverse effects/therapeutic use ; Neoplasms/*drug therapy ; Pandemics ; }, abstract = {INTRODUCTION: The coronavirus disease 2019 (COVID-19) is currently a major pandemic challenge, and cancer patients are at a heightened risk of severity and mortality from this infection. In recent years, immune checkpoint inhibitor (ICI) use to treat multiple cancers has increased in oncology, but equally has raised the question of whether ICI therapy and its side-effects is harmful or beneficial during this pandemic.<br><br>METHODS: A combination of published literature in PubMed between January 2010 and December 2020, recommended guidelines in non-cancer patients, and clinical experience was utilized to outline recommendations on glucocorticoid timing and dosing regimens in ICI-treated patients presenting with AI during this COVID-19 pandemic.<br><br>RESULTS: The potential immune interaction between ICIs and COVID-19 require major consideration because these agents act at the intersection between effective cancer immunotherapy and increasing patient susceptibility, severity and complications from the SARS-CoV-2 sepsis. Furthermore, ICI use can induce autoimmune adrenal insufficiency (AI) that further increases infection susceptibility. Thus, ICI-treated cancer patients with AI may be at greater risk of COVID-19 infection. Glucocorticoids are the cornerstone for replacement therapy, and for treatment and mitigation of adrenal crisis and relief of mass effects in ICI-related hypophysitis. High-dose glucocorticoids have also been used with cytotoxic chemotherapy as part of cancer treatment, and iatrogenic AI may arise after glucocorticoid discontinuation that increases the risk of adrenal crisis. Furthermore, in patients who develop the "long COVID-19" syndrome, when to discontinue glucocorticoid therapy becomes crucial to avoid unnecessary prolongation of therapy and the development of iatrogenic hypercortisolemia.<br><br>CONCLUSION: During the COVID-19 pandemic, much of cancer care have been impacted and an important clinical question is how to optimally manage ICI-related AI during these unprecedented times. Herein, we suggest practical recommendations on the timing and dosing regimens of glucocorticoids in different clinical scenarios of ICI-treated cancer patients presenting with AI during this COVID-19 pandemic.}, }
@article {pmid34268556, year = {2022}, author = {van Kessel, SAM and Olde Hartman, TC and Lucassen, PLBJ and van Jaarsveld, CHM}, title = {Post-acute and long-COVID-19 symptoms in patients with mild diseases: a systematic review.}, journal = {Family practice}, volume = {39}, number = {1}, pages = {159-167}, pmid = {34268556}, issn = {1460-2229}, mesh = {*COVID-19/complications ; Cough/etiology ; Fatigue/etiology ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: It is expected that GPs are increasingly confronted with a large group of patients with symptoms persisting three weeks after initial symptoms of a mild (managed in the outpatient setting) COVID-19 infection. Currently, research on these persistent symptoms mainly focuses on patients with severe infections (managed in an inpatient setting) whereas patients with mild disease are rarely studied.<br><br>OBJECTIVE: The main objective of this systematic review was to create an overview of the nature and frequency of persistent symptoms experienced by patients after mild COVID-19 infection.<br><br>METHODS: Systematic literature searches were performed in Pubmed, Embase and PsychINFO on 2 February 2021. Quantitative studies, qualitative studies, clinical lessons and case reports were considered eligible designs.<br><br>RESULTS: In total, nine articles were included in this literature review. The frequency of persistent symptoms in patients after mild COVID-19 infection ranged between 10% and 35%. Symptoms persisting after a mild COVID-19 infection can be distinguished into physical, mental and social symptoms. Fatigue was the most frequently described persistent symptom. Other frequently occurring persistent symptoms were dyspnoea, cough, chest pain, headache, decreased mental and cognitive status and olfactory dysfunction. In addition, it was found that persisting symptoms after a mild COVID-19 infection can have major consequences for work and daily functioning.<br><br>CONCLUSION: There is already some evidence that symptoms of mild COVID-19 persist after 3 weeks in a third of patients. However, there is a lack of data about symptoms persisting after 3 months (long-COVID). More research is needed to help GPs in managing long-COVID.}, }
@article {pmid34275164, year = {2022}, author = {Johnson, AS and Winlow, W}, title = {COVID-19 vulnerabilities are intensified by declining human serum albumin levels.}, journal = {Experimental physiology}, volume = {107}, number = {7}, pages = {674-682}, pmid = {34275164}, issn = {1469-445X}, mesh = {*COVID-19/complications ; Humans ; Ligands ; Protein Binding ; SARS-CoV-2 ; Serum Albumin/metabolism/therapeutic use ; Serum Albumin, Human/metabolism ; Post-Acute COVID-19 Syndrome ; }, abstract = {What is the topic of this review? Human serum albumin (HSA) a common factor in COVID-19 vulnerabilities. What advances does it highlight? Understanding of HSA capacity, and systemic vulnerabilities to COVID-19. Raising HSA in COVID-19 patients may alleviate systemic injury caused by diminished native HSA binding. A change in fluid therapy administration into the portal system of the liver is proposed to safely raise HSA levels. ABSTRACT: The specific nature of the vulnerabilities to COVID-19 are an intrinsic part of COVID-19 infection in many patients. This paper proposes that vulnerabilities to COVID-19 may be intensified by a decrease in human serum albumin (HSA) as a ligand carrier for nutrients. A mechanism for COVID-19 vulnerabilities is evident from consideration of ligand carriers such as HSA as intermediaries. We hypothesise that low levels of pool HSA binding, caused for whatever reason, affect the performance of albumin as a carrier protein reducing the availability of nutrients. Hypoalbuminaemia (low HSA) has been implicated as an indicator of COVID-19 and long-COVID-19. The levels of HSA directly affect the immune system and vulnerabilities to age, diabetes and obesity in COVID-19. Any slight reduction in available HSA has profound effects on ligand concentrations in the small capillaries where damage occurs in COVID-19. The clinical implication is that attempts should be made to return HSA to clinical levels to compensate for the additional ligands caused by infection (SARS-CoV-2 virions, antibodies and cellular breakdown products). Therapeutic albumin is usually given peripherally, and usual preparations are unbound to ligands, but we suggest that a clinical trial of HSA therapy via the hepatic portal vein should be considered.}, }
@article {pmid34276671, year = {2021}, author = {Ramakrishnan, RK and Kashour, T and Hamid, Q and Halwani, R and Tleyjeh, IM}, title = {Unraveling the Mystery Surrounding Post-Acute Sequelae of COVID-19.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {686029}, pmid = {34276671}, issn = {1664-3224}, mesh = {Anxiety/etiology ; Arthralgia/etiology ; Autoimmunity ; COVID-19/*complications/epidemiology/immunology/virology ; Depression/etiology ; Dyspnea/etiology ; Fatigue/etiology ; Gastrointestinal Microbiome/immunology ; Humans ; Immunocompromised Host ; Incidence ; Prevalence ; Renin-Angiotensin System/immunology ; SARS-CoV-2/*immunology ; Post-Acute COVID-19 Syndrome ; }, abstract = {More than one year since its emergence, corona virus disease 2019 (COVID-19) is still looming large with a paucity of treatment options. To add to this burden, a sizeable subset of patients who have recovered from acute COVID-19 infection have reported lingering symptoms, leading to significant disability and impairment of their daily life activities. These patients are considered to suffer from what has been termed as "chronic" or "long" COVID-19 or a form of post-acute sequelae of COVID-19, and patients experiencing this syndrome have been termed COVID-19 long-haulers. Despite recovery from infection, the persistence of atypical chronic symptoms, including extreme fatigue, shortness of breath, joint pains, brain fogs, anxiety and depression, that could last for months implies an underlying disease pathology that persist beyond the acute presentation of the disease. As opposed to the direct effects of the virus itself, the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is believed to be largely responsible for the appearance of these lasting symptoms, possibly through facilitating an ongoing inflammatory process. In this review, we hypothesize potential immunological mechanisms underlying these persistent and prolonged effects, and describe the multi-organ long-term manifestations of COVID-19.}, }
@article {pmid34284531, year = {2021}, author = {Petersen, E and Gökengin, D and Al Balushi, A and Zumla, A}, title = {One and a half years into the COVID-19 pandemic - exit strategies and efficacy of SARS-CoV-2 vaccines for holistic management and achieving global control.}, journal = {Turkish journal of medical sciences}, volume = {51}, number = {SI-1}, pages = {3157-3161}, pmid = {34284531}, issn = {1303-6165}, mesh = {Aged ; COVID-19/complications/epidemiology/genetics/*prevention &amp; control/transmission ; COVID-19 Vaccines/immunology ; Child ; Communicable Disease Control ; Humans ; Pandemics/*prevention &amp; control ; Population Surveillance/*methods ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {One and a half years into the pandemic, SARS-CoV-2 is still here to stay. Whilst rapid several effective COVID-19 vaccines have been developed and are being rolled out, the critical questions remain whether vaccines provide widespread protection against infection and reinfection, and what the duration of protection is. Community wide control cannot be obtained until almost everyone is immune. Vaccine production must be ramped up to cover the world population. The price of herd immunity through natural infection is high mortality in the elderly and morbidity in other age groups including children and Long-COVID. We must expect a new wave in the coming winter. The severity will depend on the proportion of the population with immunity from natural infections or immunisation. Therefore, control rests on a population wide immunisation including children, which may or may not need to be repeated if new SARS-CoV-2 variants evolve that can escape immunity from either previous infections or immunisations. Preventing long term sequelae of COVID-19 also remains a priority.}, }
@article {pmid34286502, year = {2021}, author = {Lagadinou, M and Kostopoulou, E and Karatza, A and Marangos, M and Gkentzi, D}, title = {The prolonged effects of COVID-19. A new "threat"?.}, journal = {European review for medical and pharmacological sciences}, volume = {25}, number = {13}, pages = {4611-4615}, doi = {10.26355/eurrev_202107_26253}, pmid = {34286502}, issn = {2284-0729}, mesh = {COVID-19/*diagnosis/epidemiology ; Humans ; Pandemics ; Quality of Life ; Risk Factors ; SARS-CoV-2/isolation &amp; purification ; }, abstract = {Coronavirus 'long-haulers" currently represent a significant public health concern. Recent reports suggest that persistent effects of COVID-19, such as fatigue, dyspnea, chest pain, anxiety, depression, arthralgia, may last for months and lead to a decline in quality of life. Risk factors for long COVID are still not very well understood. Survivors suffer from ongoing symptoms. This new entity highlights the need for a multidisciplinary approach that would enable closer monitoring of affected patients and implementation of measures that could reduce the impact of the pandemic on the overall patient wellbeing after the resolution of acute symptoms.}, }
@article {pmid34288064, year = {2021}, author = {Roe, K}, title = {A role for T-cell exhaustion in Long COVID-19 and severe outcomes for several categories of COVID-19 patients.}, journal = {Journal of neuroscience research}, volume = {99}, number = {10}, pages = {2367-2376}, pmid = {34288064}, issn = {1097-4547}, mesh = {COVID-19/*complications/*immunology/mortality/therapy ; Humans ; T-Lymphocytes/*immunology ; Toxoplasmosis/*complications/mortality ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; }, abstract = {Unusual mortality rate differences and symptoms have been experienced by COVID-19 patients, and the postinfection symptoms called Long COVID-19 have also been widely experienced. A substantial percentage of COVID-19-infected individuals in specific health categories have been virtually asymptomatic, several other individuals in the same health categories have exhibited several unusual symptoms, and yet other individuals in the same health categories have fatal outcomes. It is now hypothesized that these differences in mortality rates and symptoms could be caused by a SARS-CoV-2 virus infection acting together with one or more latent pathogen infections in certain patients, through mutually beneficial induced immune cell dysfunctions, including T-cell exhaustion. A latent pathogen infection likely to be involved is the protozoan parasite Toxoplasma gondii, which infects approximately one third of the global human population. Furthermore, certain infections and cancers that cause T-cell exhaustion can also explain the more severe outcomes of other COVID-19 patients having several disease and cancer comorbidities.}, }
@article {pmid34302866, year = {2021}, author = {Ladhani, SN}, title = {Crossing the Rubicon: A fine line between waiting and vaccinating adolescents against COVID-19.}, journal = {The Journal of infection}, volume = {83}, number = {3}, pages = {294-297}, pmid = {34302866}, issn = {1532-2742}, mesh = {Adolescent ; *COVID-19/complications ; *COVID-19 Vaccines ; Child ; Humans ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome ; Post-Acute COVID-19 Syndrome ; }, abstract = {Several countries with advanced adult COVID-19 immunisation programmes have already started vaccinating adolescents with an mRNA vaccine that recently received emergency use authorisation for 12-15 year-olds. The decision to vaccinate adolescents remains highly divisive among parents, clinicians, politicians and policy makers. There are very few downsides to immunising adolescents with a safe and effective COVID-19 vaccine because that would significantly reduce their risk of COVID-19 and all its complications. Based on current evidence, however, adolescents have a very low risk of severe or fatal COVID-19, even among those with comorbidities, or rare complications such as long COVID or Paediatric Multisystem Inflammatory Syndrome (PIMS-TS), a hyperinflammatory syndrome temporally associated with SARS-CoV-2. Additionally, currently authorised vaccines are very reactogenic and have limited post-marketing population-level safety data in adolescents and young adults, but these are emerging from countries that have forged ahead with vaccinating adolescents. Countries that have yet to make a recommendation can afford to wait until there is sufficient information to make informed decisions on the risk-benefits of vaccinating adolescents with current and future COVID-19 vaccines. Alternatives to two-dose vaccination in adolescents may include a single dose or a reduced dose schedule as is currently being trialled in younger children.}, }
@article {pmid34312178, year = {2021}, author = {Crook, H and Raza, S and Nowell, J and Young, M and Edison, P}, title = {Long covid-mechanisms, risk factors, and management.}, journal = {BMJ (Clinical research ed.)}, volume = {374}, number = {}, pages = {n1648}, doi = {10.1136/bmj.n1648}, pmid = {34312178}, issn = {1756-1833}, mesh = {COVID-19/*complications/diagnosis/epidemiology/etiology/therapy ; Clinical Trials as Topic ; Combined Modality Therapy/methods/standards ; Drug Repositioning ; Global Burden of Disease ; Humans ; Incidence ; Practice Guidelines as Topic ; Risk Factors ; Severity of Illness Index ; Post-Acute COVID-19 Syndrome ; }, abstract = {Since its emergence in Wuhan, China, covid-19 has spread and had a profound effect on the lives and health of people around the globe. As of 4 July 2021, more than 183 million confirmed cases of covid-19 had been recorded worldwide, and 3.97 million deaths. Recent evidence has shown that a range of persistent symptoms can remain long after the acute SARS-CoV-2 infection, and this condition is now coined long covid by recognized research institutes. Studies have shown that long covid can affect the whole spectrum of people with covid-19, from those with very mild acute disease to the most severe forms. Like acute covid-19, long covid can involve multiple organs and can affect many systems including, but not limited to, the respiratory, cardiovascular, neurological, gastrointestinal, and musculoskeletal systems. The symptoms of long covid include fatigue, dyspnea, cardiac abnormalities, cognitive impairment, sleep disturbances, symptoms of post-traumatic stress disorder, muscle pain, concentration problems, and headache. This review summarizes studies of the long term effects of covid-19 in hospitalized and non-hospitalized patients and describes the persistent symptoms they endure. Risk factors for acute covid-19 and long covid and possible therapeutic options are also discussed.}, }
@article {pmid34319569, year = {2021}, author = {Akbarialiabad, H and Taghrir, MH and Abdollahi, A and Ghahramani, N and Kumar, M and Paydar, S and Razani, B and Mwangi, J and Asadi-Pooya, AA and Malekmakan, L and Bastani, B}, title = {Long COVID, a comprehensive systematic scoping review.}, journal = {Infection}, volume = {49}, number = {6}, pages = {1163-1186}, pmid = {34319569}, issn = {1439-0973}, support = {K43 TW010716/TW/FIC NIH HHS/United States ; }, mesh = {*COVID-19/complications ; Fatigue ; Humans ; Randomized Controlled Trials as Topic ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE: To find out what is known from literature about Long COVID until January 30, 2021.<br><br>METHODS: We undertook a four-step search with no language restriction. A preliminary search was made to identify the keywords. A search strategy of all electronic databases resulted in 66 eligible studies. A forward and backward search of the references and citations resulted in additional 54 publications. Non-English language articles were translated using Google Translate. We conducted our scoping review based on the PRISMA-ScR Checklist.<br><br>RESULTS: Of 120 papers, we found only one randomized clinical trial. Of the 67 original studies, 22 were cohort, and 28 were cross-sectional studies. Of the total 120 publications, 49.1% focused on signs and symptoms, 23.3% on management, and 10.8% on pathophysiology. Ten publications focused on imaging studies. The results are also presented extensively in a narrative synthesis in separated sections (nomenclature, diagnosis, pathophysiology, risk factors, signs/symptoms, management).<br><br>CONCLUSIONS: The controversies in its definition have impaired proper recognition and management. The predominant symptoms were: fatigue, breathlessness, arthralgia, sleep difficulties, and chest pain. Recent reports also point to the risk of long-term sequela with cutaneous, respiratory, cardiovascular, musculoskeletal, mental health, neurologic, and renal involvement in those who survive the acute phase of the illness.}, }
@article {pmid34328636, year = {2021}, author = {Piotrowicz, K and Gąsowski, J and Michel, JP and Veronese, N}, title = {Post-COVID-19 acute sarcopenia: physiopathology and management.}, journal = {Aging clinical and experimental research}, volume = {33}, number = {10}, pages = {2887-2898}, pmid = {34328636}, issn = {1720-8319}, mesh = {Aged ; *COVID-19/complications ; Communicable Disease Control ; Humans ; SARS-CoV-2 ; *Sarcopenia/therapy ; Post-Acute COVID-19 Syndrome ; }, abstract = {In this review, we discuss the pathophysiologic and management aspects of acute sarcopenia in relation to SARS-CoV-2 infection. COVID-19 is as a multi-organ infectious disease characterized by a severe inflammatory and highly catabolic status, influencing the deep changes in the body build, especially the amount, structure, and function of skeletal muscles which would amount to acutely developed sarcopenia. Acute sarcopenia may largely impact patients' in-hospital prognosis as well as the vulnerability to the post-COVID-19 functional and physical deterioration. The individual outcome of the COVID-19 and the degree of muscle mass and functional loss may be influenced by multiple factors, including the patient's general pre-infection medical and functional condition, especially in older adults. This paper gathers the information about how the SARS-CoV-2 hyper-inflammatory involvement exacerbates the immunosenescence process, enhances the endothelial damage, and due to mitochondrial dysfunction and autophagy, induces myofibrillar breakdown and muscle degradation. The aftermath of these acute and complex immunological SARS-CoV-2-related phenomena, augmented by anosmia, ageusia and altered microbiota may lead to decreased food intake and exacerbated catabolism. Moreover, the imposed physical inactivity, lock-down, quarantine or acute hospitalization with bedrest would intensify the acute sarcopenia process. All these deleterious mechanisms must be swiftly put to a check by a multidisciplinary approach including nutritional support, early physical as well cardio-pulmonary rehabilitation, and psychological support and cognitive training. The proposed holistic and early management of COVID-19 patients appears essential to minimize the disastrous functional outcomes of this disease and allow avoiding the long COVID-19 syndrome.}, }
@article {pmid34333907, year = {2021}, author = {Halaçlı, B and Topeli, A}, title = {Implementation of post-intensive care outpatient clinic (I-POINT) for critically ill COVID-19 survivors.}, journal = {Turkish journal of medical sciences}, volume = {51}, number = {SI-1}, pages = {3350-3358}, pmid = {34333907}, issn = {1303-6165}, mesh = {Ambulatory Care Facilities ; COVID-19/*complications/diagnosis/therapy ; Critical Care/*methods ; Critical Illness ; Humans ; Intensive Care Units ; Pandemics ; Respiratory Distress Syndrome/*therapy ; SARS-CoV-2 ; Survivors ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; }, abstract = {Although we have enough and cumulative information about acute effects of COVID-19, our knowledge is extremely limited about long-term consequences of COVID-19, in terms of its impacts and burdens on patients, families, and the health system. Considering the underlying pathophysiological mechanisms affecting all of the organ systems in critically ill COVID-19 patients who are admitted to intensive care units, the development of post-intensive care syndrome is inevitable. This situation brings along the development of long-COVID. These patients should be followed regarding cognitive, physical, and psychiatric aspects and necessary specialist referrals should be carried out. In this article, we are presenting the experience and recommendations of our center, as a guide for the establishment process of post-intensive care outpatient clinics for the critically ill patients who required intensive care admission due to COVID-19 and could be discharged.}, }
@article {pmid34339806, year = {2021}, author = {Schou, TM and Joca, S and Wegener, G and Bay-Richter, C}, title = {Psychiatric and neuropsychiatric sequelae of COVID-19 - A systematic review.}, journal = {Brain, behavior, and immunity}, volume = {97}, number = {}, pages = {328-348}, pmid = {34339806}, issn = {1090-2139}, mesh = {Anxiety ; Anxiety Disorders ; *COVID-19 ; Female ; Humans ; SARS-CoV-2 ; *Stress Disorders, Post-Traumatic ; }, abstract = {It has become evident that coronavirus disease 2019 (COVID-19) has a multi-organ pathology that includes the brain and nervous system. Several studies have also reported acute psychiatric symptoms in COVID-19 patients. An increasing number of studies are suggesting that psychiatric deficits may persist after recovery from the primary infection. In the current systematic review, we provide an overview of the available evidence and supply information on potential risk factors and underlying biological mechanisms behind such psychiatric sequelae. We performed a systematic search for psychiatric sequelae in COVID-19 patients using the databases PubMed and Embase. Included primary studies all contained information on the follow-up period and provided quantitative measures of mental health. The search was performed on June 4th 2021. 1725 unique studies were identified. Of these, 66 met the inclusion criteria and were included. Time to follow-up ranged from immediately after hospital discharge up to 7 months after discharge, and the number of participants spanned 3 to 266,586 participants. Forty studies reported anxiety and/or depression, 20 studies reported symptoms- or diagnoses of post-traumatic stress disorder (PTSD), 27 studies reported cognitive deficits, 32 articles found fatigue at follow-up, and sleep disturbances were found in 23 studies. Highlighted risk factors were disease severity, duration of symptoms, and female sex. One study showed brain abnormalities correlating with cognitive deficits, and several studies reported inflammatory markers to correlate with symptoms. Overall, the results from this review suggest that survivors of COVID-19 are at risk of psychiatric sequelae but that symptoms generally improve over time.}, }
@article {pmid34340958, year = {2021}, author = {Rodríguez-Alfonso, B and Ruiz Solís, S and Silva-Hernández, L and Pintos Pascual, I and Aguado Ibáñez, S and Salas Antón, C}, title = {[18]F-FDG-PET/CT in SARS-CoV-2 infection and its sequelae.}, journal = {Revista espanola de medicina nuclear e imagen molecular}, volume = {40}, number = {5}, pages = {299-309}, pmid = {34340958}, issn = {2253-8089}, mesh = {COVID-19/*complications/*diagnostic imaging ; *Fluorodeoxyglucose F18 ; Humans ; *Positron Emission Tomography Computed Tomography/methods ; *Radiopharmaceuticals ; }, abstract = {In recent months, much of the scientific efforts have focused on research on SARSCoV-2 infection and its consequences in humans. Still, many aspects remain unknown. It is known that the damage caused by SARS-CoV-2 is multifactorial and that its extension goes beyond lung inflammation and the acute phase, with the appearance of numerous complications and sequelae. To date, knowledge about the usefulness of [18]F-FDG-PET/CT in the acute phase has been limited to the incidental detection of SARS-CoV-2 unsuspected pneumonia. Recent studies have been appearing collecting the findings of [18]F-FDG-PET/CT in long COVID-19 or persistent COVID-19 state as well as the alterations caused after mass vaccination of the population in the metabolic studies. This work aims to review the existing literature focusing on these three issues and to briefly present our own preliminary experience.}, }
@article {pmid34361021, year = {2021}, author = {Cooper, SL and Boyle, E and Jefferson, SR and Heslop, CRA and Mohan, P and Mohanraj, GGJ and Sidow, HA and Tan, RCP and Hill, SJ and Woolard, J}, title = {Role of the Renin-Angiotensin-Aldosterone and Kinin-Kallikrein Systems in the Cardiovascular Complications of COVID-19 and Long COVID.}, journal = {International journal of molecular sciences}, volume = {22}, number = {15}, pages = {}, pmid = {34361021}, issn = {1422-0067}, support = {MR/N020081/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Angiotensin-Converting Enzyme 2/metabolism ; Bradykinin/metabolism ; COVID-19/*complications ; Cardiovascular Diseases/drug therapy/*etiology ; Cytokine Release Syndrome/etiology/metabolism ; Humans ; *Kallikrein-Kinin System ; *Renin-Angiotensin System ; Post-Acute COVID-19 Syndrome ; COVID-19 Drug Treatment ; }, abstract = {Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the virus responsible for the COVID-19 pandemic. Patients may present as asymptomatic or demonstrate mild to severe and life-threatening symptoms. Although COVID-19 has a respiratory focus, there are major cardiovascular complications (CVCs) associated with infection. The reported CVCs include myocarditis, heart failure, arrhythmias, thromboembolism and blood pressure abnormalities. These occur, in part, because of dysregulation of the Renin-Angiotensin-Aldosterone System (RAAS) and Kinin-Kallikrein System (KKS). A major route by which SARS-CoV-2 gains cellular entry is via the docking of the viral spike (S) protein to the membrane-bound angiotensin converting enzyme 2 (ACE2). The roles of ACE2 within the cardiovascular and immune systems are vital to ensure homeostasis. The key routes for the development of CVCs and the recently described long COVID have been hypothesised as the direct consequences of the viral S protein/ACE2 axis, downregulation of ACE2 and the resulting damage inflicted by the immune response. Here, we review the impact of COVID-19 on the cardiovascular system, the mechanisms by which dysregulation of the RAAS and KKS can occur following virus infection and the future implications for pharmacological therapies.}, }
@article {pmid34373540, year = {2021}, author = {Lopez-Leon, S and Wegman-Ostrosky, T and Perelman, C and Sepulveda, R and Rebolledo, PA and Cuapio, A and Villapol, S}, title = {More than 50 long-term effects of COVID-19: a systematic review and meta-analysis.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {16144}, pmid = {34373540}, issn = {2045-2322}, support = {R21 NS106640/NS/NINDS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alopecia/complications/*diagnosis ; Attention Deficit Disorder with Hyperactivity/complications/*diagnosis ; COVID-19/*complications/virology ; Dyspnea/complications/*diagnosis ; Fatigue/complications/*diagnosis ; Headache/complications/*diagnosis ; Humans ; Middle Aged ; SARS-CoV-2/physiology ; Young Adult ; }, abstract = {COVID-19 can involve persistence, sequelae, and other medical complications that last weeks to months after initial recovery. This systematic review and meta-analysis aims to identify studies assessing the long-term effects of COVID-19. LitCOVID and Embase were searched to identify articles with original data published before the 1st of January 2021, with a minimum of 100 patients. For effects reported in two or more studies, meta-analyses using a random-effects model were performed using the MetaXL software to estimate the pooled prevalence with 95% CI. PRISMA guidelines were followed. A total of 18,251 publications were identified, of which 15 met the inclusion criteria. The prevalence of 55 long-term effects was estimated, 21 meta-analyses were performed, and 47,910 patients were included (age 17-87 years). The included studies defined long-COVID as ranging from 14 to 110 days post-viral infection. It was estimated that 80% of the infected patients with SARS-CoV-2 developed one or more long-term symptoms. The five most common symptoms were fatigue (58%), headache (44%), attention disorder (27%), hair loss (25%), and dyspnea (24%). Multi-disciplinary teams are crucial to developing preventive measures, rehabilitation techniques, and clinical management strategies with whole-patient perspectives designed to address long COVID-19 care.}, }
@article {pmid34384972, year = {2021}, author = {Raveendran, AV and Misra, A}, title = {Post COVID-19 Syndrome ("Long COVID") and Diabetes: Challenges in Diagnosis and Management.}, journal = {Diabetes &amp; metabolic syndrome}, volume = {15}, number = {5}, pages = {102235}, pmid = {34384972}, issn = {1878-0334}, mesh = {COVID-19/*complications/diagnosis/epidemiology/etiology/therapy ; Comorbidity ; Diabetes Mellitus, Type 2/complications/diagnosis/epidemiology/therapy ; Fatigue/diagnosis/epidemiology/etiology/therapy ; Humans ; SARS-CoV-2/physiology ; Sarcopenia/diagnosis/epidemiology/etiology/therapy ; Tachycardia/diagnosis/epidemiology/etiology/therapy ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND AND AIMS: Post Covid-19 syndrome (PCS) is a major cause of morbidity. In this article we intend to review the association and consequences of PCS and diabetes.<br><br>METHODS: We reviewed all studies on "Long Covid", "Post COVID-19 Syndrome" and diabetes in PubMed and Google Scholar.<br><br>RESULTS: The symptoms of PCS can be due to organ dysfunction, effects of hospitalisation and drugs, or unrelated to these. Type 2 diabetes mellitus has a bidirectional relationship with COVID-19. Presence of diabetes also influences PCS via various pathophysiological mechanisms. COVID-19 can add to or exacerbate tachycardia, sarcopenia (and muscle fatigue), and microvascular dysfunction (and organ damage) in patients with diabetes.<br><br>CONCLUSION: PCS in patients with diabetes could be detrimental in multiple ways. Strict control of diabetes and other comorbidities, supervised rehabilitation and physical exercise, and optimal nutrition could help in reducing and managing PCS.}, }
@article {pmid34391037, year = {2021}, author = {Jesuthasan, A and Massey, F and Manji, H and Zandi, MS and Wiethoff, S}, title = {Emerging potential mechanisms and predispositions to the neurological manifestations of COVID-19.}, journal = {Journal of the neurological sciences}, volume = {428}, number = {}, pages = {117608}, pmid = {34391037}, issn = {1878-5883}, mesh = {*COVID-19/complications ; Cytokine Release Syndrome ; Humans ; *Nervous System Diseases/etiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {A spectrum of neurological disease associated with COVID-19 is becoming increasingly apparent. However, the mechanisms behind these manifestations remain poorly understood, significantly hindering their management. The present review subsequently attempts to address the evolving molecular, cellular and systemic mechanisms of NeuroCOVID, which we have classified as the acute and long-term neurological effects of COVID-19. We place particular emphasis on cerebrovascular, demyelinating and encephalitic presentations, which have been reported. Several mechanisms are presented, especially the involvement of a "cytokine storm". We explore the genetic and demographic factors that may predispose individuals to NeuroCOVID. The increasingly evident long-term neurological effects are also presented, including the impact of the virus on cognition, autonomic function and mental wellbeing, which represent an impending burden on already stretched healthcare services. We subsequently reinforce the need for cautious surveillance, especially for those with predisposing factors, with effective clinical phenotyping, appropriate investigation and, if possible, prompt treatment. This will be imperative to prevent downstream neurological sequelae, including those related to the long COVID phenotypes that are being increasingly recognised.}, }
@article {pmid34396514, year = {2021}, author = {Wagner, C and Griesel, M and Mikolajewska, A and Mueller, A and Nothacker, M and Kley, K and Metzendorf, MI and Fischer, AL and Kopp, M and Stegemann, M and Skoetz, N and Fichtner, F}, title = {Systemic corticosteroids for the treatment of COVID-19.}, journal = {The Cochrane database of systematic reviews}, volume = {8}, number = {8}, pages = {CD014963}, pmid = {34396514}, issn = {1469-493X}, mesh = {Adrenal Cortex Hormones/*therapeutic use ; COVID-19/diagnosis ; Humans ; Immunization, Passive ; Randomized Controlled Trials as Topic ; Respiration, Artificial ; SARS-CoV-2 ; *COVID-19 Drug Treatment ; }, abstract = {BACKGROUND: Systemic corticosteroids are used to treat people with COVID-19 because they counter hyper-inflammation. Existing evidence syntheses suggest a slight benefit on mortality. So far, systemic corticosteroids are one of the few treatment options for COVID-19. Nonetheless, size of effect, certainty of the evidence, optimal therapy regimen, and selection of patients who are likely to benefit most are factors that remain to be evaluated.<br><br>OBJECTIVES: To assess whether systemic corticosteroids are&#xa0;effective and safe in the treatment of people with COVID-19,&#xa0;and to&#xa0;keep up to date with the evolving evidence base using a living systematic review approach.<br><br>SEARCH METHODS: We searched the Cochrane COVID-19 Study Register (which includes PubMed, Embase, CENTRAL, ClinicalTrials.gov, WHO ICTRP, and medRxiv), Web of Science (Science Citation Index, Emerging Citation Index), and the WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies to 16 April 2021.<br><br>SELECTION CRITERIA: We included randomised controlled trials (RCTs) that evaluated systemic corticosteroids for&#xa0;people with COVID-19, irrespective of disease severity, participant age, gender or ethnicity.&#xa0; We included any type or dose of systemic corticosteroids. We included the following comparisons: systemic corticosteroids plus standard care versus standard care (plus/minus placebo), dose comparisons, timing&#xa0;comparisons (early versus late), different types of corticosteroids and systemic corticosteroids versus other active substances.&#xa0; We excluded studies that included populations with other coronavirus diseases (severe acute respiratory syndrome or Middle East respiratory syndrome), corticosteroids in combination with other active substances&#xa0;versus standard care, topical or inhaled corticosteroids, and corticosteroids for long-COVID treatment.<br><br>DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. To assess the risk of bias in included studies, we used the Cochrane 'Risk of bias' 2 tool for RCTs.&#xa0;We rated the certainty of evidence using the GRADE approach&#xa0;for the following outcomes: all-cause mortality, ventilator-free days, new need for invasive mechanical ventilation,&#xa0;quality of life,&#xa0;serious adverse events, adverse events, and hospital-acquired infections.<br><br>MAIN RESULTS: We included 11&#xa0;RCTs in 8075 participants, of whom 7041 (87%) originated from high-income countries. A total of 3072&#xa0;participants were randomised to corticosteroid arms and the majority received dexamethasone (n = 2322). We also identified 42 ongoing studies and 16 studies reported as being completed or terminated in a study registry, but without results yet.&#xa0; Hospitalised&#xa0;individuals with&#xa0;a confirmed or suspected diagnosis of symptomatic COVID-19 Systemic corticosteroids plus standard care versus standard care plus/minus placebo&#xa0; We included 10 RCTs (7989 participants), one of which did not report any of our pre-specified outcomes and thus our analysis included outcome data from nine studies.&#xa0; All-cause mortality (at longest follow-up available): systemic corticosteroids plus standard care probably reduce all-cause mortality slightly in people with COVID-19 compared to standard care alone (median 28 days: risk difference of 30 in 1000 participants fewer than the control group rate of 275 in 1000 participants; risk ratio (RR) 0.89, 95% confidence interval (CI) 0.80 to 1.00; 9 RCTs, 7930 participants; moderate-certainty evidence).&#xa0; Ventilator-free days: corticosteroids may increase ventilator-free days (MD 2.6 days more than control group rate of 4 days, 95% CI 0.67 to 4.53; 1 RCT, 299 participants; low-certainty evidence). Ventilator-free days have inherent limitations as a composite endpoint and should be interpreted with caution.&#xa0; New need for invasive&#xa0;ventilation:&#xa0;the evidence is of very low certainty. Because of high risk of&#xa0;bias arising from deaths that occurred before ventilation we are uncertain about the size and direction of the effects. Consequently, we did not perform analysis beyond the presentation of descriptive statistics.&#xa0; Quality of life/neurological outcome:&#xa0;no data were available. Serious adverse events: we included data on two RCTs (678 participants)&#xa0;that evaluated systemic corticosteroids compared to standard care (plus/minus placebo); for adverse events and hospital-acquired infections, we included data on five RCTs (660 participants).&#xa0;Because of high risk of&#xa0;bias, heterogeneous definitions, and underreporting we are uncertain about the size and direction of the effects. Consequently, we did not perform analysis beyond the presentation of descriptive statistics (very low-certainty evidence). &#xa0;&#xa0; Different types, dosages or timing of systemic corticosteroids&#xa0; We identified one study that compared methylprednisolone with dexamethasone. The evidence for mortality and new need for invasive mechanical ventilation is very low certainty due to the small number of participants (n = 86). No data were available for the other outcomes. We did not identify comparisons of different dosages or timing. Outpatients with asymptomatic or mild disease Currently, there are no studies published in populations with asymptomatic infection or mild disease.<br><br>AUTHORS' CONCLUSIONS: Moderate-certainty evidence shows that systemic corticosteroids probably slightly reduce all-cause mortality in people hospitalised because of symptomatic COVID-19. Low-certainty evidence suggests that there may also be a reduction in ventilator-free days. Since we are unable to &#xa0;adjust for the impact of early death on subsequent endpoints, the findings for ventilation outcomes and harms have limited applicability to inform treatment decisions. Currently, there is no evidence for asymptomatic or mild disease (non-hospitalised participants).&#xa0; There is an urgent need for good-quality evidence for specific subgroups of disease severity, for which we propose level of respiratory support at randomisation. This applies to the comparison or subgroups of different types and doses of corticosteroids, too. Outcomes apart from mortality should be measured and analysed appropriately taking into account confounding through death if applicable.&#xa0; We identified&#xa0;42 ongoing and 16 completed but not published RCTs in trials registries suggesting possible changes of effect estimates and certainty of the evidence in the future. Most ongoing studies target people who need respiratory support at baseline. With the living approach of this review, we will continue to update our search and include eligible trials and published data.}, }
@article {pmid34400495, year = {2021}, author = {Paul, BD and Lemle, MD and Komaroff, AL and Snyder, SH}, title = {Redox imbalance links COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {34}, pages = {}, pmid = {34400495}, issn = {1091-6490}, support = {R01 AG071512/AG/NIA NIH HHS/United States ; 5U54 AI138370/NH/NIH HHS/United States ; DA044123/NH/NIH HHS/United States ; U54 AI138370/AI/NIAID NIH HHS/United States ; R21 AG073684/AG/NIA NIH HHS/United States ; /AHA/American Heart Association-American Stroke Association/United States ; P50 DA044123/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; COVID-19/complications/etiology/immunology/*metabolism ; Encephalomyelitis/immunology/*metabolism ; Fatigue Syndrome, Chronic/immunology/*metabolism ; Humans ; Oxidation-Reduction ; Post-Acute COVID-19 Syndrome ; }, abstract = {Although most patients recover from acute COVID-19, some experience postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC). One subgroup of PASC is a syndrome called "long COVID-19," reminiscent of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS is a debilitating condition, often triggered by viral and bacterial infections, leading to years-long debilitating symptoms including profound fatigue, postexertional malaise, unrefreshing sleep, cognitive deficits, and orthostatic intolerance. Some are skeptical that either ME/CFS or long COVID-19 involves underlying biological abnormalities. However, in this review, we summarize the evidence that people with acute COVID-19 and with ME/CFS have biological abnormalities including redox imbalance, systemic inflammation and neuroinflammation, an impaired ability to generate adenosine triphosphate, and a general hypometabolic state. These phenomena have not yet been well studied in people with long COVID-19, and each of them has been reported in other diseases as well, particularly neurological diseases. We also examine the bidirectional relationship between redox imbalance, inflammation, energy metabolic deficits, and a hypometabolic state. We speculate as to what may be causing these abnormalities. Thus, understanding the molecular underpinnings of both PASC and ME/CFS may lead to the development of novel therapeutics.}, }
@article {pmid34416191, year = {2021}, author = {Adeloye, D and Elneima, O and Daines, L and Poinasamy, K and Quint, JK and Walker, S and Brightling, CE and Siddiqui, S and Hurst, JR and Chalmers, JD and Pfeffer, PE and Novotny, P and Drake, TM and Heaney, LG and Rudan, I and Sheikh, A and De Soyza, A and , }, title = {The long-term sequelae of COVID-19: an international consensus on research priorities for patients with pre-existing and new-onset airways disease.}, journal = {The Lancet. Respiratory medicine}, volume = {9}, number = {12}, pages = {1467-1478}, pmid = {34416191}, issn = {2213-2619}, support = {MC_PC_19004/MRC_/Medical Research Council/United Kingdom ; MC_PC_19075/MRC_/Medical Research Council/United Kingdom ; MR/V027859/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {COVID-19/*complications ; Humans ; Research ; *Respiration Disorders ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Persistent ill health after acute COVID-19-referred to as long COVID, the post-acute COVID-19 syndrome, or the post-COVID-19 condition-has emerged as a major concern. We undertook an international consensus exercise to identify research priorities with the aim of understanding the long-term effects of acute COVID-19, with a focus on people with pre-existing airways disease and the occurrence of new-onset airways disease and associated symptoms. 202 international experts were invited to submit a minimum of three research ideas. After a two-phase internal review process, a final list of 98 research topics was scored by 48 experts. Patients with pre-existing or post-COVID-19 airways disease contributed to the exercise by weighting selected criteria. The highest-ranked research idea focused on investigation of the relationship between prognostic scores at hospital admission and morbidity at 3 months and 12 months after hospital discharge in patients with and without pre-existing airways disease. High priority was also assigned to comparisons of the prevalence and severity of post-COVID-19 fatigue, sarcopenia, anxiety, depression, and risk of future cardiovascular complications in patients with and without pre-existing airways disease. Our approach has enabled development of a set of priorities that could inform future research studies and funding decisions. This prioritisation process could also be adapted to other, non-respiratory aspects of long COVID.}, }
@article {pmid34419773, year = {2021}, author = {Montanari, M and Canonico, B and Nordi, E and Vandini, D and Barocci, S and Benedetti, S and Carlotti, E and Zamai, L}, title = {Which ones, when and why should renin-angiotensin system inhibitors work against COVID-19?.}, journal = {Advances in biological regulation}, volume = {81}, number = {}, pages = {100820}, pmid = {34419773}, issn = {2212-4934}, mesh = {ADAM17 Protein/antagonists &amp; inhibitors/*biosynthesis ; Angiotensin I/metabolism ; Angiotensin-Converting Enzyme 2/antagonists &amp; inhibitors/*biosynthesis ; COVID-19/*metabolism ; Gene Expression Regulation, Enzymologic ; Humans ; Peptide Fragments/metabolism ; *Renin-Angiotensin System ; SARS-CoV-2/*metabolism ; Spike Glycoprotein, Coronavirus/antagonists &amp; inhibitors/*metabolism ; Up-Regulation ; COVID-19 Drug Treatment ; }, abstract = {The article describes the possible pathophysiological origin of COVID-19 and the crucial role of renin-angiotensin system (RAS), providing several "converging" evidence in support of this hypothesis. SARS-CoV-2 has been shown to initially upregulate ACE2 systemic activity (early phase), which can subsequently induce compensatory responses leading to upregulation of both arms of the RAS (late phase) and consequently to critical, advanced and untreatable stages of COVID-19 disease. The main and initial actors of the process are ACE2 and ADAM17 zinc-metalloproteases, which, initially triggered by SARS-CoV-2 spike proteins, work together in increasing circulating Ang 1-7 and Ang 1-9 peptides and downstream (Mas and Angiotensin type 2 receptors) pathways with anti-inflammatory, hypotensive and antithrombotic activities. During the late phase of severe COVID-19, compensatory secretion of renin and ACE enzymes are subsequently upregulated, leading to inflammation, hypertension and thrombosis, which further sustain ACE2 and ADAM17 upregulation. Based on this hypothesis, COVID-19-phase-specific inhibition of different RAS enzymes is proposed as a pharmacological strategy against COVID-19 and vaccine-induced adverse effects. The aim is to prevent the establishment of positive feedback-loops, which can sustain hyperactivity of both arms of the RAS independently of viral trigger and, in some cases, may lead to Long-COVID syndrome.}, }
@article {pmid34440170, year = {2021}, author = {Yan, Z and Yang, M and Lai, CL}, title = {Long COVID-19 Syndrome: A Comprehensive Review of Its Effect on Various Organ Systems and Recommendation on Rehabilitation Plans.}, journal = {Biomedicines}, volume = {9}, number = {8}, pages = {}, pmid = {34440170}, issn = {2227-9059}, abstract = {The majority of people infected with SARS-CoV-2 fully recovered within a few weeks. However, a considerable number of patients of different ages still suffer from long-lasting problems similar to the multi-organ damage in its acute phase of infection, or experience symptoms continuously for a longer term after the recovery. The severity of the primary infection seems not to be associated with the possibility and severity of long-term symptoms. Various unresolved symptoms have been reported in COVID-19 survivors months after hospital discharge. Long COVID-19 Syndrome refers to survivors 4 months after initial symptoms onset. It is important to understand the systemic effects of Long COVID-19 Syndrome, its presentations, and the need for rehabilitations to restore functional recovery in survivors. Government, healthcare workers, and survivor groups should collaborate to establish a self-sustaining system to facilitate follow-up and rehabilitations, with prioritization of resources to more severely Long COVID-19 Syndrome survivors. This review looks into the systemic effects of Long COVID-19 Syndrome in various aspects: respiratory, cardiovascular, hematological, renal, gastrointestinal, neurological, and metabolic effects of Long COVID-19 Syndromes. Recommendations for follow-up and rehabilitations details have been explored to cope with the tremendous Long COVID-19 Syndrome patients.}, }
@article {pmid34440903, year = {2021}, author = {Hirschenberger, M and Hunszinger, V and Sparrer, KMJ}, title = {Implications of Innate Immunity in Post-Acute Sequelae of Non-Persistent Viral Infections.}, journal = {Cells}, volume = {10}, number = {8}, pages = {}, pmid = {34440903}, issn = {2073-4409}, support = {IMMUNOMOD//Bundesministerium f&#xfc;r Bildung und Forschung/ ; SP1600/4-1//Deutsche Forschungsgemeinschaft/ ; SPP1923//Deutsche Forschungsgemeinschaft/ ; CRC1279//Deutsche Forschungsgemeinschaft/ ; }, mesh = {COVID-19/*immunology/physiopathology ; Cytokines ; Disease Progression ; Humans ; Immunity, Innate/*immunology ; Inflammation ; }, abstract = {Non-persistent viruses classically cause transient, acute infections triggering immune responses aimed at the elimination of the pathogen. Successful viruses evolved strategies to manipulate and evade these anti-viral defenses. Symptoms during the acute phase are often linked to dysregulated immune responses that disappear once the patient recovers. In some patients, however, symptoms persist or new symptoms emerge beyond the acute phase. Conditions resulting from previous transient infection are termed post-acute sequelae (PAS) and were reported for a wide range of non-persistent viruses such as rota-, influenza- or polioviruses. Here we provide an overview of non-persistent viral pathogens reported to be associated with diverse PAS, among them chronic fatigue, auto-immune disorders, or neurological complications and highlight known mechanistic details. Recently, the emergence of post-acute sequelae of COVID-19 (PASC) or long COVID highlighted the impact of PAS. Notably, PAS of non-persistent infections often resemble symptoms of persistent viral infections, defined by chronic inflammation. Inflammation maintained after the acute phase may be a key driver of PAS of non-persistent viruses. Therefore, we explore current insights into aberrant activation of innate immune signaling pathways in the post-acute phase of non-persistent viruses. Finally, conclusions are drawn and future perspectives for treatment and prevention of PAS are discussed.}, }
@article {pmid34445238, year = {2021}, author = {Schomburg, L}, title = {Selenium Deficiency Due to Diet, Pregnancy, Severe Illness, or COVID-19-A Preventable Trigger for Autoimmune Disease.}, journal = {International journal of molecular sciences}, volume = {22}, number = {16}, pages = {}, pmid = {34445238}, issn = {1422-0067}, support = {Research Unit FOR-2558 "TraceAge" (Scho 849/6-2)//Deutsche Forschungsgemeinschaft/ ; CRC/TR 296 "Local control of TH action" (LocoTact, P17)//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Autoimmune Diseases/*drug therapy ; Dietary Supplements ; Female ; Humans ; Immune System/*drug effects ; Pregnancy ; Selenium/*pharmacology ; Trace Elements/*pharmacology ; *COVID-19 Drug Treatment ; }, abstract = {The trace element selenium (Se) is an essential part of the human diet; moreover, increased health risks have been observed with Se deficiency. A sufficiently high Se status is a prerequisite for adequate immune response, and preventable endemic diseases are known from areas with Se deficiency. Biomarkers of Se status decline strongly in pregnancy, severe illness, or COVID-19, reaching critically low concentrations. Notably, these conditions are associated with an increased risk for autoimmune disease (AID). Positive effects on the immune system are observed with Se supplementation in pregnancy, autoimmune thyroid disease, and recovery from severe illness. However, some studies reported null results; the database is small, and randomized trials are sparse. The current need for research on the link between AID and Se deficiency is particularly obvious for rheumatoid arthritis and type 1 diabetes mellitus. Despite these gaps in knowledge, it seems timely to realize that severe Se deficiency may trigger AID in susceptible subjects. Improved dietary choices or supplemental Se are efficient ways to avoid severe Se deficiency, thereby decreasing AID risk and improving disease course. A personalized approach is needed in clinics and during therapy, while population-wide measures should be considered for areas with habitual low Se intake. Finland has been adding Se to its food chain for more than 35 years-a wise and commendable decision, according to today's knowledge. It is unfortunate that the health risks of Se deficiency are often neglected, while possible side effects of Se supplementation are exaggerated, leading to disregard for this safe and promising preventive and adjuvant treatment options. This is especially true in the follow-up situations of pregnancy, severe illness, or COVID-19, where massive Se deficiencies have developed and are associated with AID risk, long-lasting health impairments, and slow recovery.}, }
@article {pmid34456621, year = {2021}, author = {Richter, K and Kellner, S}, title = {["Coronasomnia"-promoting resilience through insomnia treatment].}, journal = {Somnologie : Schlafforschung und Schlafmedizin = Somnology : sleep research and sleep medicine}, volume = {25}, number = {3}, pages = {170-175}, pmid = {34456621}, issn = {1432-9123}, abstract = {BACKGROUND: The term "coronasomnia" is used in popular science to describe sleep disorders associated with the COVID-19 pandemic. These disorders may also affect part of the population in the aftermath of the pandemic. Early scientific evidence suggests that COVID-19-associated insomnia and insomniac symptoms can become chronic and will continue to preoccupy the sleep medicine community even after the pandemic has ended.<br><br>METHODS: A&#xa0;literature review was conducted in Medline and Google Scholar using the following combination of keywords: "insomnia and COVID-19", "insomnia and long COVID", "insomnia, PTSD and COVID-19", and "fatigue and insomnia in long COVID". In addition, the authors reviewed several recent articles published by members of the European Insomnia Network.<br><br>RESULTS: Studies on insomnia and COVID-19 show significant associations between acute infection and insomnia in affected individuals. The prevalence of insomnia symptoms in COVID-19-affected individuals was 36 to 88%, which is significantly higher than the estimated 10 to 40% prevalence of insomnia in the general population.<br><br>CONCLUSION: Digital therapy as a&#xa0;current treatment option for insomnia can be offered to patients regardless of physical distance. Accordingly, not only early approval of therapy apps, but also person-led, digital therapy options for insomnia would be recommended. The inclusion of personalised and sleep-coaching measures in the area of occupational health management is encouraged.}, }
@article {pmid34463956, year = {2022}, author = {Malik, P and Patel, K and Pinto, C and Jaiswal, R and Tirupathi, R and Pillai, S and Patel, U}, title = {Post-acute COVID-19 syndrome (PCS) and health-related quality of life (HRQoL)-A systematic review and meta-analysis.}, journal = {Journal of medical virology}, volume = {94}, number = {1}, pages = {253-262}, pmid = {34463956}, issn = {1096-9071}, mesh = {Adult ; Age Factors ; COVID-19/*complications ; Female ; Humans ; Intensive Care Units ; Male ; Middle Aged ; *Quality of Life ; Post-Acute COVID-19 Syndrome ; }, abstract = {There is an established literature on the symptoms and complications of COVID-19 but the after-effects of COVID-19 are not well understood with few studies reporting persistent symptoms and quality of life. We aim to evaluate the pooled prevalence of poor quality of life in post-acute COVID-19 syndrome (PCS) and conducted meta-regression to evaluate the effects of persistent symptoms and intensive care unit (ICU) admission on the poor quality of life. We extracted data from observational studies describing persistent symptoms and quality of life in post-COVID-19 patients from March 10, 2020, to March 10, 2021, following PRISMA guidelines with a consensus of two independent reviewers. We calculated the pooled prevalence with 95% confidence interval (CI) and created forest plots using random-effects models. A total of 12 studies with 4828 PCS patients were included. We found that amongst PCS patients, the pooled prevalence of poor quality of life (EQ-VAS) was (59%; 95% CI: 42%-75%). Based on individual factors in the EQ-5D-5L questionnaire, the prevalence of mobility was (36, 10-67), personal care (8, 1-21), usual quality (28, 2-65), pain/discomfort (42, 28-55), and anxiety/depression (38, 19-58). The prevalence of persistent symptoms was fatigue (64, 54-73), dyspnea (39.5, 20-60), anosmia (20, 15-24), arthralgia (24.3, 14-36), headache (21, 3-47), sleep disturbances (47, 7-89), and mental health (14.5, 4-29). Meta-regression analysis showed the poor quality of life was significantly higher among post-COVID-19 patients with ICU admission (p = 0.004) and fatigue (p = 0.0015). Our study concludes that PCS is associated with poor quality of life, persistent symptoms including fatigue, dyspnea, anosmia, sleep disturbances, and worse mental health. This suggests that we need more research on PCS patients to understand the risk factors causing it and eventually leading to poor quality of life.}, }
@article {pmid34473556, year = {2021}, author = {Robinson, P}, title = {Long COVID and breathlessness: an overview.}, journal = {British journal of community nursing}, volume = {26}, number = {9}, pages = {438-443}, doi = {10.12968/bjcn.2021.26.9.438}, pmid = {34473556}, issn = {1462-4753}, mesh = {COVID-19/*complications/nursing/physiopathology ; *Community Health Nursing ; *Dyspnea/etiology/nursing ; Humans ; Palliative Care ; Post-Acute COVID-19 Syndrome ; }, abstract = {This article offers a review of what is known so far about post-acute covid-19 and the underlying pathophysiology related to this condition. The main focus will be on the respiratory symptoms. It will then explore how community nurses can monitor and support patients with symptoms of breathlessness with a supporting discussion of the current recommendations for the management and treatment of patients presenting with symptoms of breathlessness. Palliation of symptoms will be highlighted but managing the supportive care needs for patients affected by COVID-19 and nearing the end of life is outside the scope of this article.}, }
@article {pmid34474488, year = {2021}, author = {Koczulla, AR and Ankermann, T and Behrends, U and Berlit, P and Böing, S and Brinkmann, F and Franke, C and Glöckl, R and Gogoll, C and Hummel, T and Kronsbein, J and Maibaum, T and Peters, EMJ and Pfeifer, M and Platz, T and Pletz, M and Pongratz, G and Powitz, F and Rabe, KF and Scheibenbogen, C and Stallmach, A and Stegbauer, M and Wagner, HO and Waller, C and Wirtz, H and Zeiher, A and Zwick, RH}, title = {[S1 Guideline Post-COVID/Long-COVID].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {75}, number = {11}, pages = {869-900}, doi = {10.1055/a-1551-9734}, pmid = {34474488}, issn = {1438-8790}, mesh = {*COVID-19/complications ; Consensus ; Humans ; *Pulmonary Medicine ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The German Society of Pneumology initiated the AWMFS1 guideline Post-COVID/Long-COVID. In a broad interdisciplinary approach, this S1 guideline was designed based on the current state of knowledge.The clinical recommendation describes current post-COVID/long-COVID symptoms, diagnostic approaches, and therapies.In addition to the general and consensus introduction, a subject-specific approach was taken to summarize the current state of knowledge.The guideline has an expilcit practical claim and will be continuously developed and adapted by the author team based on the current increase in knowledge.}, }
@article {pmid34506003, year = {2021}, author = {Storz, MA}, title = {Lifestyle Adjustments in Long-COVID Management: Potential Benefits of Plant-Based Diets.}, journal = {Current nutrition reports}, volume = {10}, number = {4}, pages = {352-363}, pmid = {34506003}, issn = {2161-3311}, mesh = {*COVID-19/complications ; Diet, Vegetarian ; Humans ; Life Style ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE OF REVIEW: The SARS-CoV-2-pandemic has caused mortality and morbidity at an unprecedented global scale. Many patients infected with SARS-CoV-2 continue to experience symptoms after the acute phase of infection and report fatigue, sleep difficulties, anxiety, and depression as well as arthralgia and muscle weakness. Summarized under the umbrella term "long-COVID," these symptoms may last weeks to months and impose a substantial burden on affected individuals. Dietary approaches to tackle these complications have received comparably little attention. Although plant-based diets in particular were shown to exert benefits on underlying conditions linked to poor COVID-19 outcomes, their role with regard to COVID-19 sequelae is yet largely unknown. Thus, this review sought to investigate whether a plant-based diet could reduce the burden of long-COVID.<br><br>RECENT FINDINGS: The number of clinical trials investigating the role of plant-based nutrition in COVID-19 prevention and management is currently limited. Yet, there is evidence from pre-pandemic observational and clinical studies that a plant-based diet may be of general benefit with regard to several clinical conditions that can also be found in individuals with COVID-19. These include anxiety, depression, sleep disorders, and musculoskeletal pain. Adoption of a plant-based diet leads to a reduced intake in pro-inflammatory mediators and could be one accessible strategy to tackle long-COVID associated prolonged systemic inflammation. Plant-based diets may be of general benefit with regard to some of the most commonly found COVID-19 sequelae. Additional trials investigating which plant-based eating patterns confer the greatest benefit in the battle against long-COVID are urgently warranted.}, }
@article {pmid34509649, year = {2021}, author = {Anaya, JM and Rojas, M and Salinas, ML and Rodríguez, Y and Roa, G and Lozano, M and Rodríguez-Jiménez, M and Montoya, N and Zapata, E and ,  and Monsalve, DM and Acosta-Ampudia, Y and Ramírez-Santana, C}, title = {Post-COVID syndrome. A case series and comprehensive review.}, journal = {Autoimmunity reviews}, volume = {20}, number = {11}, pages = {102947}, pmid = {34509649}, issn = {1873-0183}, mesh = {Adult ; *Antibodies, Viral ; *COVID-19 ; Female ; Humans ; Immunoglobulin G ; Lung ; Middle Aged ; SARS-CoV-2 ; }, abstract = {The existence of a variety of symptoms with a duration beyond the acute phase of COVID-19, is referred to as post-COVID syndrome (PCS). We aimed to report a series of patients with PCS attending a Post-COVID Unit and offer a comprehensive review on the topic. Adult patients with previously confirmed SARS-CoV-2 infection and PCS were systematically assessed through a semi-structured and validated survey. Total IgG, IgA and IgM serum antibodies to SARS-CoV-2 were evaluated by an electrochemiluminescence immunoassay. A systematic review of the literature and meta-analysis were conducted, following PRISMA guidelines. Univariate and multivariate methods were used to analyze data. Out of a total of 100 consecutive patients, 53 were women, the median of age was 49 years (IQR: 37.8-55.3), the median of post-COVID time after the first symptoms was 219 days (IQR: 143-258), and 65 patients were hospitalized during acute COVID-19. Musculoskeletal, digestive (i.e., diarrhea) and neurological symptoms including depression (by Zung scale) were the most frequent observed in PCS patients. A previous hospitalization was not associated with PCS manifestation. Arthralgia and diarrhea persisted in more than 40% of PCS patients. The median of anti-SARS-CoV-2 antibodies was 866.2 U/mL (IQR: 238.2-1681). Despite this variability, 98 patients were seropositive. Based on autonomic symptoms (by COMPASS 31) two clusters were obtained with different clinical characteristics. Levels of anti-SARS-CoV-2 antibodies were not different between clusters. A total of 40 articles (11,196 patients) were included in the meta-analysis. Fatigue/muscle weakness, dyspnea, pain and discomfort, anxiety/depression and impaired concentration were presented in more than 20% of patients reported. In conclusion, PCS is mainly characterized by musculoskeletal, pulmonary, digestive and neurological involvement including depression. PCS is independent of severity of acute illness and humoral response. Long-term antibody responses to SARS-CoV-2 infection and a high inter-individual variability were confirmed. Future studies should evaluate the mechanisms by which SARS-CoV-2 may cause PCS and the best therapeutic options.}, }
@article {pmid34511734, year = {2021}, author = {Bär, C and Derda, AA and Thum, T}, title = {[Not Available].}, journal = {Biospektrum : Zeitschrift der Gesellschaft fur Biologishe Chemie (GBCH) und der Vereinigung fur Allgemeine und Angewandte Mikrobiologie (VAAM)}, volume = {27}, number = {5}, pages = {485-487}, pmid = {34511734}, issn = {0947-0867}, abstract = {COVID-19 still remains a severe global health threat. Despite the high-speed development of vaccines that efficiently prevent COVID-19, there are still no effective treatments of the disease once people are infected. MicroRNAs are powerful regulators of gene expression. They are intensely investigated as therapeutic targets up to the clinical stage. In addition, microRNAs can be detected in the circulation, and thus, represent promising diagnostic and prognostic biomarkers for (long)-COVID-19.}, }
@article {pmid34512810, year = {2021}, author = {Mrusek, M}, title = {[Not Available].}, journal = {Pneumo news}, volume = {13}, number = {4}, pages = {53}, doi = {10.1007/s15033-021-2752-6}, pmid = {34512810}, issn = {2199-3866}, }
@article {pmid34529126, year = {2021}, author = {Milos, RI and Kifjak, D and Heidinger, BH and Prayer, F and Beer, L and Röhrich, S and Wassipaul, C and Gompelmann, D and Prosch, H}, title = {[Morphological and functional sequelae after COVID-19 pneumonia].}, journal = {Der Radiologe}, volume = {61}, number = {10}, pages = {888-895}, pmid = {34529126}, issn = {1432-2102}, mesh = {*COVID-19 ; Humans ; Lung/diagnostic imaging ; *Pneumonia ; Respiratory Function Tests ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Following coronavirus disease 2019 (COVID-19), a proportion of patients report prolonged or worsening symptoms and impairments. These symptoms are increasingly referred to as "long COVID" syndrome. They may be associated with radiological changes on computed tomography (CT) and pulmonary function impairment.<br><br>OBJECTIVES: To discuss the role of long-term assessment of COVID-19&#xa0;patients to determine which patients may benefit from follow-up.<br><br>MATERIALS AND METHODS: This article presents the current results of clinical, radiological, and pulmonary function follow-up tests after COVID-19 pneumonia.<br><br>RESULTS: Chronic fatigue and dyspnea are the most common persistent symptoms after COVID-19. Patients also present impaired exercise capacity. On CT, ground-glass opacities and parenchymal bands are the most common residual changes after COVID-19 pneumonia, histologically corresponding to organizing pneumonia. A&#xa0;proportion of patients who had severe COVID-19 pneumonia may show fibrotic-like changes during follow-up. Patients with severe acute infection may present with a&#xa0;restrictive syndrome with lower diffusing capacity for carbon monoxide (DLCO) and total lung capacity (TLC) values. Overall, significant and continuous improvement in all symptoms as well as radiomorphological and functional changes were observed over time.<br><br>CONCLUSIONS: Patients with persistent symptoms after COVID-19 should be evaluated and treated in specialized post-COVID-19 clinics in a&#xa0;multidisciplinary manner.}, }
@article {pmid34531126, year = {2022}, author = {Espinosa Rodríguez, P and Martínez Aguilar, A and Ripoll Muñoz, MP and Rodríguez Navarro, M&#xc1;}, title = {[Long COVID: Is it really myalgic encephalomyelitis? Bibliographic review and considerations].}, journal = {Semergen}, volume = {48}, number = {1}, pages = {63-69}, pmid = {34531126}, issn = {1578-8865}, mesh = {*COVID-19/complications ; Consensus ; *Fatigue Syndrome, Chronic/diagnosis/epidemiology/etiology ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Clinical sequelae of a disease as widespread as COVID-19 can be of great importance for primary care due to their prevalence and the morbidity they entail. The definition of long COVID and the establishment of its temporality are various, but some authors consider possible that this syndrome is actually myalgic encephalomyelitis. Similarities are observed when comparing the International Consensus Criteria for the diagnosis of myalgic encephalomyelitis with the symptoms described for long COVID. Blood tests, pulse oximetry, chest radiography, and thoracic ultrasound are recommended in patients with persistent symptoms after acute infection. Management in both conditions consists of treating the main symptoms. The possibility that COVID-19 can lead to a chronic condition such as myalgic encephalomyelitis makes long-term follow-up of patients who have suffered from this infection essential.}, }
@article {pmid34533807, year = {2021}, author = {Ahmad, MS and Shaik, RA and Ahmad, RK and Yusuf, M and Khan, M and Almutairi, AB and Alghuyaythat, WKZ and Almutairi, SB}, title = {"LONG COVID": an insight.}, journal = {European review for medical and pharmacological sciences}, volume = {25}, number = {17}, pages = {5561-5577}, doi = {10.26355/eurrev_202109_26669}, pmid = {34533807}, issn = {2284-0729}, mesh = {COVID-19/*complications/epidemiology ; Humans ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {We aimed this systematic review to analyze and review the currently available published literature related to long COVID, understanding its pattern, and predicting the long-term effects on survivors. We thoroughly searched the databases for relevant articles till May 2021. The research articles that met our inclusion and exclusion criteria were assessed and reviewed by two independent researchers. After preliminary screening of the identified articles through title and abstract, 249 were selected. Consequently, 167 full-text articles were assessed and reviewed based on our inclusion criteria and thus 20 articles were regarded as eligible and analyzed in the present analysis. All the studies included adult population aged between 18 and above 60 years. The median length of hospital stay of the COVID-19 patients during the acute infection phase ranged from 8 days to 17 days. The most common prevalent long-term symptoms in COVID-19 patients included persistent fatigue and dyspnea in almost all of the studies. Other reported common symptoms included: shortness of breath, cough, joint pain, chest pain or tightness, headache, loss of smell/taste, sore throat, diarrhea, loss of memory, depression, anxiety. Associated cardiovascular events included arrhythmias, palpitations and hypotension, increased HR, venous thromboembolic diseases, myocarditis, and acute/decompensated heart failure as well. Among neurological manifestations headache, peripheral neuropathy symptoms, memory issues, concentration, and sleep disorders were most commonly observed with varying frequencies. Mental health issues affecting mental abilities, mood fluctuations namely anxiety and depression, and sleep disorders were commonly seen. Further, diarrhea, vomiting, digestive disorders, and Loss of appetite or weight loss are common gastrointestinal manifestations. Therefore, appropriate clinical evaluation is required in long COVID cases which in turn may help us to identify the risk factors, etiology, and to my help, we treat them early with appropriate management strategies.}, }
@article {pmid34541421, year = {2021}, author = {Jiang, DH and Roy, DJ and Gu, BJ and Hassett, LC and McCoy, RG}, title = {Postacute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A State-of-the-Art Review.}, journal = {JACC. Basic to translational science}, volume = {6}, number = {9}, pages = {796-811}, pmid = {34541421}, issn = {2452-302X}, abstract = {The vast majority of patients (>99%) with severe acute respiratory syndrome coronavirus 2 survive immediate infection but remain at risk for persistent and/or delayed multisystem. This review of published reports through May 31, 2021, found that manifestations of postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC) affect between 33% and 98% of coronavirus disease 2019 survivors and comprise a wide range of symptoms and complications in the pulmonary, cardiovascular, neurologic, psychiatric, gastrointestinal, renal, endocrine, and musculoskeletal systems in both adult and pediatric populations. Additional complications are likely to emerge and be identified over time. Although data on PASC risk factors and vulnerable populations are scarce, evidence points to a disproportionate impact on racial/ethnic minorities, older patients, patients with preexisting conditions, and rural residents. Concerted efforts by researchers, health systems, public health agencies, payers, and governments are urgently needed to better understand and mitigate the long-term effects of PASC on individual and population health.}, }
@article {pmid34554270, year = {2021}, author = {Thurnher, MM and Reith, W and Thurnher, AP and Rommer, P}, title = {[Long COVID: long-term symptoms and morphological/radiological correlates].}, journal = {Der Radiologe}, volume = {61}, number = {10}, pages = {915-922}, pmid = {34554270}, issn = {1432-2102}, mesh = {Adult ; *COVID-19/complications ; Disease Progression ; Humans ; SARS-CoV-2 ; Syndrome ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Neurologic, pulmonary, cardiac and gastrointestinal functional disorders can persist in the post-acute phase and constitute a long COVID syndrome, also known as post-acute sequelae of SARS-CoV‑2 infection (PASC). Some patients develop persistent and debilitating symptoms despite a relatively mild illness at onset and they are known as COVID-19 long haulers.<br><br>OBJECTIVE: Presentation of symptoms, signs and biomarkers present in patients previously affected by COVID-19 and discussion of possible underlying mechanisms and consequences.<br><br>METHODS: Existing literature and reported cases as well as expert opinions are analyzed and discussed.<br><br>RESULTS: Long COVID affects survivors of COVID-19&#x202f;at all levels of disease severity, even in mild to moderate cases and younger adults who did not require respiratory support, hospitalization or intensive care. A challenging aspect is that many long haulers never had laboratory confirmation of COVID-19, raising skepticism that the persistent symptoms have a&#xa0;physiological basis. On the other hand, some symptoms seen in post-acute COVID-19 may occur as a&#xa0;consequence of critical illness or as a&#xa0;side effect of treatment.<br><br>CONCLUSION: Given that COVID-19 is a&#xa0;new disease, it is not possible to determine how long these effects will last. Long-term monitoring of post-acute COVID-19 symptoms and screening for frequent comorbid conditions are essential.}, }
@article {pmid34560321, year = {2021}, author = {Zuo, T and Wu, X and Wen, W and Lan, P}, title = {Gut Microbiome Alterations in COVID-19.}, journal = {Genomics, proteomics &amp; bioinformatics}, volume = {19}, number = {5}, pages = {679-688}, pmid = {34560321}, issn = {2210-3244}, mesh = {Bacteria ; *COVID-19/complications ; Fungi ; *Gastrointestinal Microbiome ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Since the outset of the coronavirus disease 2019 (COVID-19) pandemic, the gut microbiome in COVID-19 has garnered substantial interest, given its significant roles in human health and pathophysiology. Accumulating evidence is unveiling that the gut microbiome is broadly altered in COVID-19, including the bacterial microbiome, mycobiome, and virome. Overall, the gut microbial ecological network is significantly weakened and becomes sparse in patients with COVID-19, together with a decrease in gut microbiome diversity. Beyond the existence of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the gut microbiome of patients with COVID-19 is also characterized by enrichment of opportunistic bacteria, fungi, and eukaryotic viruses, which are also associated with disease severity and presentation. Meanwhile, a multitude of symbiotic bacteria and bacteriophages are decreased in abundance in patients with COVID-19. Such gut microbiome features persist in a significant subset of patients with COVID-19 even after disease resolution, coinciding with 'long COVID' (also known as post-acute sequelae of COVID-19). The broadly-altered gut microbiome is largely a consequence of SARS-CoV-2infection and its downstream detrimental effects on the systemic host immunity and the gut milieu. The impaired host immunity and distorted gut microbial ecology, particularly loss of low-abundance beneficial bacteria and blooms of opportunistic fungi including Candida, may hinder the reassembly of the gut microbiome post COVID-19. Future investigation is necessary to fully understand the role of the gut microbiome in host immunity against SARS-CoV-2 infection, as well as the long-term effect of COVID-19 on the gut microbiome in relation to the host health after the pandemic.}, }
@article {pmid34563621, year = {2022}, author = {Byrne, EA}, title = {Understanding Long Covid: Nosology, social attitudes and stigma.}, journal = {Brain, behavior, and immunity}, volume = {99}, number = {}, pages = {17-24}, doi = {10.1016/j.bbi.2021.09.012}, pmid = {34563621}, issn = {1090-2139}, mesh = {Attitude ; *COVID-19/complications ; Humans ; SARS-CoV-2 ; Social Stigma ; Post-Acute COVID-19 Syndrome ; }, abstract = {The debate around Long Covid has so far shown resistance to accept parallels between Long Covid and a set of existing conditions which have historically been subject to stigma. This resistance risks endorsing the stigma associated with such existing conditions, and as such, these dynamics of stigma ought to be dismantled in order to facilitate the development of effective clinical resources for all such implicated conditions. As well as affecting proceedings at the structural level, I discuss how the aforementioned problems also risk affecting patients at the personal level by motivating the reconfiguration and restriction of patient illness narratives. The problems I identify therefore risk affecting both collective and individual understanding of Long Covid.}, }
@article {pmid34565332, year = {2021}, author = {Begemann, M and Gross, O and Wincewicz, D and Hardeland, R and Daguano Gastaldi, V and Vieta, E and Weissenborn, K and Miskowiak, KW and Moerer, O and Ehrenreich, H}, title = {Addressing the 'hypoxia paradox' in severe COVID-19: literature review and report of four cases treated with erythropoietin analogues.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {27}, number = {1}, pages = {120}, pmid = {34565332}, issn = {1528-3658}, support = {TRR 274/1 2020 - 408885537//dfg/ ; R215-2015-4121//lundbeckfonden/ ; }, mesh = {COVID-19/*complications/genetics/pathology/virology ; Erythropoietin/analogs &amp; derivatives/*genetics/therapeutic use ; Humans ; Hypoxia/*drug therapy/genetics/pathology/virology ; Lung/*drug effects/pathology/virology ; Pandemics ; Recombinant Proteins/genetics/therapeutic use ; SARS-CoV-2/drug effects ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {BACKGROUND: Since fall 2019, SARS-CoV-2 spread world-wide, causing a major pandemic with estimated ~ 220 million subjects affected as of September 2021. Severe COVID-19 is associated with multiple organ failure, particularly of lung and kidney, but also grave neuropsychiatric manifestations. Overall mortality reaches > 2%. Vaccine development has thrived in thus far unreached dimensions and will be one prerequisite to terminate the pandemic. Despite intensive research, however, few treatment options for modifying COVID-19 course/outcome have emerged since the pandemic outbreak. Additionally, the substantial threat of serious downstream sequelae, called 'long COVID' and 'neuroCOVID', becomes increasingly evident. Among candidates that were suggested but did not yet receive appropriate funding for clinical trials is recombinant human erythropoietin. Based on accumulating experimental and clinical evidence, erythropoietin is expected to (1) improve respiration/organ function, (2) counteract overshooting inflammation, (3) act sustainably neuroprotective/neuroregenerative. Recent counterintuitive findings of decreased serum erythropoietin levels in severe COVID-19 not only support a relative deficiency of erythropoietin in this condition, which can be therapeutically addressed, but also made us coin the term 'hypoxia paradox'. As we review here, this paradox is likely due to uncoupling of physiological hypoxia signaling circuits, mediated by detrimental gene products of SARS-CoV-2 or unfavorable host responses, including microRNAs or dysfunctional mitochondria. Substitution of erythropoietin might overcome this 'hypoxia paradox' caused by deranged signaling and improve survival/functional status of COVID-19 patients and their long-term outcome. As supporting hints, embedded in this review, we present 4 male patients with severe COVID-19 and unfavorable prognosis, including predicted high lethality, who all profoundly improved upon treatment which included erythropoietin analogues.<br><br>SHORT CONCLUSION: Substitution of EPO may-among other beneficial EPO effects in severe COVID-19-circumvent downstream consequences of the 'hypoxia paradox'. A double-blind, placebo-controlled, randomized clinical trial for proof-of-concept is warranted.}, }
@article {pmid34575615, year = {2021}, author = {Boutou, AK and Asimakos, A and Kortianou, E and Vogiatzis, I and Tzouvelekis, A}, title = {Long COVID-19 Pulmonary Sequelae and Management Considerations.}, journal = {Journal of personalized medicine}, volume = {11}, number = {9}, pages = {}, pmid = {34575615}, issn = {2075-4426}, abstract = {The human coronavirus 2019 disease (COVID-19) and the associated acute respiratory distress syndrome (ARDS) are responsible for the worst global health crisis of the last century. Similarly, to previous coronaviruses leading to past pandemics, including severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS), a growing body of evidence support that a substantial minority of patients surviving the acute phase of the disease present with long-term sequelae lasting for up to 6 months following acute infection. The clinical spectrum of these manifestations is widespread across multiple organs and consists of the long-COVID-19 syndrome. The aim of the current review is to summarize the current state of knowledge on the pulmonary manifestations of the long COVID-19 syndrome including clinical symptoms, parenchymal, and functional abnormalities, as well as highlight epidemiology, risk factors, and follow-up strategies for early identification and timely therapeutic interventions. The literature data on management considerations including the role of corticosteroids and antifibrotic treatment, as well as the therapeutic potential of a structured and personalized pulmonary rehabilitation program are detailed and discussed.}, }
@article {pmid34579171, year = {2021}, author = {Cereda, E and Clavé, P and Collins, PF and Holdoway, A and Wischmeyer, PE}, title = {Recovery Focused Nutritional Therapy across the Continuum of Care: Learning from COVID-19.}, journal = {Nutrients}, volume = {13}, number = {9}, pages = {}, pmid = {34579171}, issn = {2072-6643}, mesh = {COVID-19/complications/*therapy ; Continuity of Patient Care ; Health Personnel ; Humans ; Malnutrition/prevention &amp; control ; *Nutrition Therapy ; Post-Acute COVID-19 Syndrome ; }, abstract = {Targeted nutritional therapy should be started early in severe illness and sustained through to recovery if clinical and patient-centred outcomes are to be optimised. The coronavirus disease 2019 (COVID-19) pandemic has shone a light on this need. The literature on nutrition and COVID-19 mainly focuses on the importance of nutrition to preserve life and prevent clinical deterioration during the acute phase of illness. However, there is a lack of information guiding practice across the whole patient journey (e.g., hospital to home) with a focus on targeting recovery (e.g., long COVID). This review paper is of relevance to doctors and other healthcare professionals in acute care and primary care worldwide, since it addresses early, multi-modal individualised nutrition interventions across the continuum of care to improve COVID-19 patient outcomes. It is of relevance to nutrition experts and non-nutrition experts and can be used to promote inter-professional and inter-organisational knowledge transfer on the topic. The primary goal is to prevent complications and support recovery to enable COVID-19 patients to achieve the best possible nutritional, physical, functional and mental health status and to apply the learning to date from the COVID-19 pandemic to other patient groups experiencing acute severe illness.}, }
@article {pmid34580069, year = {2021}, author = {Michelen, M and Manoharan, L and Elkheir, N and Cheng, V and Dagens, A and Hastie, C and O'Hara, M and Suett, J and Dahmash, D and Bugaeva, P and Rigby, I and Munblit, D and Harriss, E and Burls, A and Foote, C and Scott, J and Carson, G and Olliaro, P and Sigfrid, L and Stavropoulou, C}, title = {Characterising long COVID: a living systematic review.}, journal = {BMJ global health}, volume = {6}, number = {9}, pages = {}, pmid = {34580069}, issn = {2059-7908}, support = {MC_PC_19026/MRC_/Medical Research Council/United Kingdom ; MC_UU_12014/8/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*COVID-19/complications ; Child ; Cross-Sectional Studies ; Female ; Humans ; Male ; Prospective Studies ; *Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: While it is now apparent clinical sequelae (long COVID) may persist after acute COVID-19, their nature, frequency and aetiology are poorly characterised. This study aims to regularly synthesise evidence on long COVID characteristics, to help inform clinical management, rehabilitation strategies and interventional studies to improve long-term outcomes.<br><br>METHODS: A living systematic review. Medline, CINAHL (EBSCO), Global Health (Ovid), WHO Global Research on COVID-19 database, LitCovid and Google Scholar were searched till 17 March 2021. Studies including at least 100 people with confirmed or clinically suspected COVID-19 at 12 weeks or more post onset were included. Risk of bias was assessed using the tool produced by Hoy et al. Results were analysed using descriptive statistics and meta-analyses to estimate prevalence.<br><br>RESULTS: A total of 39 studies were included: 32 cohort, 6 cross-sectional and 1 case-control. Most showed high or moderate risk of bias. None were set in low-income countries and few included children. Studies reported on 10&#x2009;951 people (48% female) in 12 countries. Most included previously hospitalised people (78%, 8520/10 951). The longest mean follow-up time was 221.7 (SD: 10.9) days post COVID-19 onset. Over 60 physical and psychological signs and symptoms with wide prevalence were reported, most commonly weakness (41%; 95%&#x2009;CI 25% to 59%), general malaise (33%; 95%&#x2009;CI 15% to 57%), fatigue (31%; 95%&#x2009;CI 24% to 39%), concentration impairment (26%; 95%&#x2009;CI 21% to 32%) and breathlessness (25%; 95%&#x2009;CI 18% to 34%). 37% (95% CI 18% to 60%) of patients reported reduced quality of life; 26% (10/39) of studies presented evidence of reduced pulmonary function.<br><br>CONCLUSION: Long COVID is a complex condition with prolonged heterogeneous symptoms. The nature of studies precludes a precise case definition or risk evaluation. There is an urgent need for prospective, robust, standardised, controlled studies into aetiology, risk factors and biomarkers to characterise long COVID in different at-risk populations and settings.<br><br>PROSPERO REGISTRATION NUMBER: CRD42020211131.}, }
@article {pmid34601116, year = {2022}, author = {Doyle, MF}, title = {Central nervous system outcomes of COVID-19.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {241}, number = {}, pages = {41-51}, pmid = {34601116}, issn = {1878-1810}, support = {R01 AG067457/AG/NIA NIH HHS/United States ; }, mesh = {COVID-19/*complications/virology ; Central Nervous System/*physiopathology ; Humans ; SARS-CoV-2/isolation &amp; purification ; Post-Acute COVID-19 Syndrome ; }, abstract = {The worldwide pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected an estimated 200 million people with over 4 million deaths. Although COVID-19, the disease caused by the SARS-CoV-2 virus, is primarily a respiratory disease, an increasing number of neurologic symptoms have been reported. Some of these symptoms, such as loss of smell or taste, are mild and non-life threatening, while others, such as stroke or seizure, are more critical. Many of these symptoms remain long after the acute illness has passed, a phenomenon known as "long COVID" or postacute sequelae of SARS-CoV-2 infection (PASC). Neurological symptoms can be difficult to study due to the complexity of the central and peripheral nervous system. These neurologic symptoms can be difficult to identify and quantitate. This narrative review will describe approaches for assessing neurologic manifestations of COVID-19, with examples of the data they provide, as well as some directions for future research to aid in understanding the pathophysiology of COVID-19-related neurological implications.}, }
@article {pmid34609841, year = {2021}, author = {Najafloo, R and Majidi, J and Asghari, A and Aleemardani, M and Kamrava, SK and Simorgh, S and Seifalian, A and Bagher, Z and Seifalian, AM}, title = {Mechanism of Anosmia Caused by Symptoms of COVID-19 and Emerging Treatments.}, journal = {ACS chemical neuroscience}, volume = {12}, number = {20}, pages = {3795-3805}, doi = {10.1021/acschemneuro.1c00477}, pmid = {34609841}, issn = {1948-7193}, mesh = {Anosmia ; *COVID-19/complications ; Humans ; *Olfaction Disorders ; SARS-CoV-2 ; Smell ; Post-Acute COVID-19 Syndrome ; }, abstract = {The occurrence of anosmia, the loss or change in sense of smell, is one of the most common symptoms of COVID-19 experienced by almost 53% of those affected. Several hypotheses explain the mechanism of anosmia in patients suffering from COVID-19. This study aims to review the related mechanisms and answer the questions regarding COVID-19-related anosmia as well as propose a new strategy for treatment of long-term anosmia as a result of COVID-19 infection. This paper covers all of the studies investigating olfactory disorders following COVID-19 infection and explains the possible reasons for the correlated anosmia, including olfactory cleft syndrome, local inflammation in the nasal epithelium, early apoptosis of olfactory cells, changes in olfactory cilia and odor transmission, damage to microglial cells, effect on olfactory bulbs, epithelial olfactory injury, and impairment of olfactory neurons and stem cells. The key questions that arise in this field have been discussed, such as why prevalent anosmia is varied among the age categories and among sexes and the correlation of anosmia with mild or severe COVID-19 infection. The angiotensin-converting enzyme 2 receptor is a significant player in the mechanism of anosmia in COVID-19 patients. Based on current studies, a novel approach to treat long-COVID-19 with ongoing anosmia has been proposed. The fields of smart drug delivery, tissue engineering, and cell therapy provide a hypothesized strategy that can minimize the side effects of current treatments and support efficient recovery of the olfactory system.}, }
@article {pmid34611512, year = {2021}, author = {Arentz, S and Hunter, J and Khamba, B and Mravunac, M and Lee, Z and Alexander, K and Lauche, R and Goldenberg, J and Myers, SP}, title = {Honeybee products for the treatment and recovery from viral respiratory infections including SARS-COV-2: A rapid systematic review.}, journal = {Integrative medicine research}, volume = {10}, number = {Suppl}, pages = {100779}, pmid = {34611512}, issn = {2213-4220}, abstract = {BACKGROUND: This rapid review systematically evaluated the effects of honeybee products compared to controls for the prevention, duration, severity, and recovery of acute viral respiratory tract infections (RTIs), including SARS-CoV-2, in adults and children.<br><br>METHODS: Cochrane rapid review methods were applied. Four English databases plus preprint servers and trial registries were searched for randomized controlled trials (RCTs). The evidence was appraised and synthesized using RoB 2.0 and GRADE.<br><br>RESULTS: 27 results were derived from 9&#xa0;RCTs that included 674 adults and 781 children. In hospitalized adults with SARS-CoV-2, propolis plus usual-care compared to usual-care alone reduced the risk of shock, respiratory failure and kidney injury and duration of hospital admission. Honey was less effective than Guaifenesin for&#xa0;reducing cough severity at 60-minutes in adults with non-specific acute viral RTIs. Compared to coffee, honey plus coffee, and honey alone reduced the severity of post-infectious cough in adults. Honey reduced the duration of cough in children compared to placebo and salbutamol; and the global impact&#xa0;of nocturnal cough after one night compared to usual-care alone and pharmaceutical cough medicines.<br><br>CONCLUSION: More studies are needed to robustly assess honeybee's role in SARS-CoV-2 and non-specific viral respiratory infections.<br><br>PROTOCOL REGISTRATION: PROSPERO: CRD42020193847.}, }
@article {pmid34619336, year = {2022}, author = {Bucciarelli, V and Nasi, M and Bianco, F and Seferovic, J and Ivkovic, V and Gallina, S and Mattioli, AV}, title = {Depression pandemic and cardiovascular risk in the COVID-19 era and long COVID syndrome: Gender makes a difference.}, journal = {Trends in cardiovascular medicine}, volume = {32}, number = {1}, pages = {12-17}, pmid = {34619336}, issn = {1873-2615}, mesh = {*COVID-19/complications/psychology ; *Cardiovascular Diseases/diagnosis/epidemiology ; *Depression/diagnosis/epidemiology ; Female ; Heart Disease Risk Factors ; Humans ; Male ; Pandemics ; Risk Factors ; *Sex Factors ; Post-Acute COVID-19 Syndrome ; }, abstract = {The ongoing COVID-19 pandemic highlighted a significant interplay between cardiovascular disease (CVD), COVID-19 related inflammatory status, and depression. Cardiovascular (CV) injury is responsible for a substantial percentage of COVID-19 deaths while COVID-19 social restrictions emerged as a non-negligible risk factor for CVD as well as a variety of mental health issues, and in particular, depression. Inflammation seems to be a shared condition between these two disorders. Gender represents a potential modifying factor both in CVD and depression, as well as in COVID-19 short- and long-term outcomes, particularly in cases involving long-term COVID complications. Results from emerging studies indicate that COVID-19 pandemic affected male and female populations in different ways. Women seem to experience less severe short-term complications but suffer worse long-term COVID complications, including depression, reduced physical activity, and deteriorating lifestyle habits, all of which may impact CV risk. Here, we summarize the current state of knowledge about the interplay between COVID-19, depression, and CV risk in women.}, }
@article {pmid34631916, year = {2021}, author = {Sandler, CX and Wyller, VBB and Moss-Morris, R and Buchwald, D and Crawley, E and Hautvast, J and Katz, BZ and Knoop, H and Little, P and Taylor, R and Wensaas, KA and Lloyd, AR}, title = {Long COVID and Post-infective Fatigue Syndrome: A Review.}, journal = {Open forum infectious diseases}, volume = {8}, number = {10}, pages = {ofab440}, pmid = {34631916}, issn = {2328-8957}, abstract = {Fatigue is a dominant feature of both acute and convalescent coronavirus disease 2019 (COVID-19) (sometimes termed "long-COVID"), with up to 46% of patients reporting fatigue that lasts from weeks to months. The investigators of the international Collaborative on Fatigue Following Infection (COFFI) conducted a systematic review of post-COVID fatigue and a narrative review on fatigue after other infections, and made recommendations for clinical and research approaches to assessing fatigue after COVID-19. In the majority of COVID-19 cohort studies, persistent fatigue was reported by a significant minority of patients, ranging from 13% to 33% at 16-20 weeks post-symptom onset. Data from the prospective cohort studies in COFFI and others indicate that fatigue is also a prevalent outcome from many acute systemic infections, notably infectious mononucleosis, with a case rate for clinically significant Post-infective fatigue after exclusion of recognized medical and psychiatric causes, ranging from 10%-35% at 6 months. To better characterize post-COVID fatigue, the COFFI investigators recommend the following: application of validated screening questionnaires for case detection; standardized interviews encompassing fatigue, mood, and other symptoms; and investigative approaches to identify end-organ damage and mental health conditions.}, }
@article {pmid34646278, year = {2021}, author = {Bellucci, G and Rinaldi, V and Buscarinu, MC and Reniè, R and Bigi, R and Pellicciari, G and Morena, E and Romano, C and Marrone, A and Mechelli, R and Salvetti, M and Ristori, G}, title = {Multiple Sclerosis and SARS-CoV-2: Has the Interplay Started?.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {755333}, pmid = {34646278}, issn = {1664-3224}, mesh = {Animals ; COVID-19/epidemiology/*immunology/prevention &amp; control/virology ; COVID-19 Vaccines/administration &amp; dosage ; Host-Pathogen Interactions ; Humans ; Multiple Sclerosis/epidemiology/*immunology/virology ; Prognosis ; Risk Factors ; SARS-CoV-2/*immunology/pathogenicity ; Vaccination ; }, abstract = {Current knowledge on Multiple Sclerosis (MS) etiopathogenesis encompasses complex interactions between the host's genetic background and several environmental factors that result in dysimmunity against the central nervous system. An old-aged association exists between MS and viral infections, capable of triggering and sustaining neuroinflammation through direct and indirect mechanisms. The novel Coronavirus, SARS-CoV-2, has a remarkable, and still not fully understood, impact on the immune system: the occurrence and severity of both acute COVID-19 and post-infectious chronic illness (long COVID-19) largely depends on the host's response to the infection, that echoes several aspects of MS pathobiology. Furthermore, other MS-associated viruses, such as the Epstein-Barr Virus (EBV) and Human Endogenous Retroviruses (HERVs), may enhance a mechanistic interplay with the novel Coronavirus, with the potential to interfere in MS natural history. Studies on COVID-19 in people with MS have helped clinicians in adjusting therapeutic strategies during the pandemic; similar efforts are being made for SARS-CoV-2 vaccination campaigns. In this Review, we look over 18 months of SARS-CoV-2 pandemic from the perspective of MS: we dissect neuroinflammatory and demyelinating mechanisms associated with COVID-19, summarize pathophysiological crossroads between MS and SARS-CoV-2 infection, and discuss present evidence on COVID-19 and its vaccination in people with MS.}, }
@article {pmid34648081, year = {2021}, author = {Tizenberg, BN and Brenner, LA and Lowry, CA and Okusaga, OO and Benavides, DR and Hoisington, AJ and Benros, ME and Stiller, JW and Kessler, RC and Postolache, TT}, title = {Biological and Psychological Factors Determining Neuropsychiatric Outcomes in COVID-19.}, journal = {Current psychiatry reports}, volume = {23}, number = {10}, pages = {68}, pmid = {34648081}, issn = {1535-1645}, mesh = {Brain ; *COVID-19 ; Central Nervous System ; Humans ; SARS-CoV-2 ; *Stress Disorders, Post-Traumatic ; }, abstract = {PURPOSE OF REVIEW: We present biological and psychological factors implicated in psychiatric manifestations of SARS-CoV-2, as well as its neuroinvasive capability and immune pathophysiology.<br><br>RECENT FINDINGS: Preexisting mental illness leads to worse clinical outcomes in COVID-19. The presence of the virus was reported in the cerebrospinal fluid (CSF) and brain tissue post-mortem. Most common psychiatric manifestations include delirium, mood disorders, anxiety disorders, and posttraumatic stress disorder. "Long-COVID" non-syndromal presentations include "brain-fogginess," autonomic instability, fatigue, and insomnia. SARS-CoV-2 infection can trigger prior vulnerabilities based on the priming of microglia and other cells, induced or perpetuated by aging and mental and physical illnesses. COVID-19 could further induce priming of neuroimmunological substrates leading to exacerbated immune response and autoimmunity targeting structures in the central nervous system (CNS), in response to minor immune activating environmental exposures, including stress, minor infections, allergens, pollutants, and traumatic brain injury.}, }
@article {pmid34651183, year = {2023}, author = {Pye, A and Roberts, SR and Blennerhassett, A and Iqbal, H and Beenstock, J and Iqbal, Z}, title = {A public health approach to estimating the need for long COVID services.}, journal = {Journal of public health (Oxford, England)}, volume = {45}, number = {1}, pages = {169-175}, doi = {10.1093/pubmed/fdab365}, pmid = {34651183}, issn = {1741-3850}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Public Health ; Pandemics ; }, abstract = {BACKGROUND: The term 'long COVID' describes ongoing symptoms and conditions experienced by people infected with SARS-CoV-2. This paper illustrates how a public health approach was used to influence and inform the development of post-COVID services across two Integrated Care Systems (ICSs).<br><br>METHODS: A literature review was conducted between October and December 2020 to identify prevalence estimates for long COVID. The prevalence estimates were applied to locally available data on the susceptible population to estimate the number of people with long COVID. They were also used to develop a dashboard to predict fluctuations in the number of people experiencing persistent symptoms over time.<br><br>RESULTS: A substantial number of people in each ICS may have experienced persistent symptoms or complications as a result of COVID-19. In Lancashire and South Cumbria, it is estimated that 33&#xa0;000 people may have experienced post-COVID-19 syndrome since the beginning of the pandemic, which will include respiratory or cardiovascular complications.<br><br>CONCLUSIONS: The findings have been valuable in informing early service developments, engaging with managers and clinicians, and supporting applications for funding at a local level. Continued attention to emergent evidence on this topic will be vital in refining estimates and supporting service planning in the longer term.}, }
@article {pmid34653099, year = {2022}, author = {Pierce, JD and Shen, Q and Cintron, SA and Hiebert, JB}, title = {Post-COVID-19 Syndrome.}, journal = {Nursing research}, volume = {71}, number = {2}, pages = {164-174}, pmid = {34653099}, issn = {1538-9847}, mesh = {*COVID-19/complications ; Humans ; Mass Screening ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, many individuals have reported persistent symptoms and/or complications lasting beyond 4 weeks, which is now called post-COVID-19 syndrome. SARS-CoV-2 is a respiratory coronavirus that causes COVID-19, and injury to the lungs is expected; however, there is often damage to numerous other cells and organs, leading to an array of symptoms. These long-term symptoms occur in patients with mild to severe COVID-19; currently, there is limited literature on the potential pathophysiological mechanisms of this syndrome.<br><br>OBJECTIVES: The purpose of this integrative review is to summarize and evaluate post-COVID-19 syndrome from a biological perspective.<br><br>METHODS: An integrative review was conducted using Whittemore and Knafl's methodology for literature published through August 30, 2021. The PubMed, CINAHL, and Web of Science databases were searched for articles published as of August 30, 2021, using combinations of the following key words: post-COVID-19 syndrome, post-SARS-CoV-2, long COVID-19, long COVID-19 syndrome, and pathophysiology of post-COVID-19. Data were analyzed using the constant comparison method.<br><br>RESULTS: The search generated 27,929 articles. After removing duplicates and screening abstracts and full-text reviews, we retained 68 articles and examined 54 specific articles related to the pathophysiology of post-COVID-19 syndrome. The findings from our review indicated that there were four pathophysiological categories involved: virus-specific pathophysiological variations, oxidative stress, immunologic abnormalities, and inflammatory damage.<br><br>DISCUSSION: Although studies examining the pathophysiology of post-COVID-19 syndrome are still relatively few, there is growing evidence that this is a complex and multifactorial syndrome involving virus-specific pathophysiological variations that affect many mechanisms but specifically oxidative stress, immune function, and inflammation. Further research is needed to elucidate the pathophysiology, pathogenesis, and longer term consequences involved in post-COVID-19 syndrome.}, }
@article {pmid34659259, year = {2021}, author = {Kumar, S and Çalışkan, DM and Janowski, J and Faist, A and Conrad, BCG and Lange, J and Ludwig, S and Brunotte, L}, title = {Beyond Vaccines: Clinical Status of Prospective COVID-19 Therapeutics.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {752227}, pmid = {34659259}, issn = {1664-3224}, mesh = {Antibodies, Monoclonal/therapeutic use ; Antiviral Agents/*therapeutic use ; COVID-19/pathology/prevention &amp; control ; COVID-19 Vaccines/*immunology ; Humans ; SARS-CoV-2/*drug effects/immunology ; Vaccination ; *COVID-19 Drug Treatment ; }, abstract = {Since November 2019 the SARS-CoV-2 pandemic has caused nearly 200 million infection and more than 4 million deaths globally (Updated information from the World Health Organization, as on 2[nd] Aug 2021). Within only one year into the pandemic, several vaccines were designed and reached approval for the immunization of the world population. The remarkable protective effects of the manufactured vaccines are demonstrated in countries with high vaccination rates, such as Israel and UK. However, limited production capacities, poor distribution infrastructures and political hesitations still hamper the availability of vaccines in many countries. In addition, due to the emergency of SARS-CoV-2 variants with immune escape properties towards the vaccines the global numbers of new infections as well as patients developing severe COVID-19, remains high. New studies reported that about 8% of infected individuals develop long term symptoms with strong personal restrictions on private as well as professional level, which contributes to the long socioeconomic problems caused by this pandemic. Until today, emergency use-approved treatment options for COVID-19 are limited to the antiviral Remdesivir, a nucleoside analogue targeting the viral polymerase, the glucocorticosteroide Dexamethasone as well as neutralizing antibodies. The therapeutic benefits of these treatments are under ongoing debate and clinical studies assessing the efficiency of these treatments are still underway. To identify new therapeutic treatments for COVID-19, now and by the post-pandemic era, diverse experimental approaches are under scientific evaluation in companies and scientific research teams all over the world. To accelerate clinical translation of promising candidates, repurposing approaches of known approved drugs are specifically fostered but also novel technologies are being developed and are under investigation. This review summarizes the recent developments from the lab bench as well as the clinical status of emerging therapeutic candidates and discusses possible therapeutic entry points for the treatment strategies with regard to the biology of SARS-CoV-2 and the clinical course of COVID-19.}, }
@article {pmid34665645, year = {2022}, author = {Muller, AE and Berg, RC and Jardim, PSJ and Johansen, TB and Ormstad, SS}, title = {Can Remote Patient Monitoring Be the New Standard in Primary Care of Chronic Diseases, Post-COVID-19?.}, journal = {Telemedicine journal and e-health : the official journal of the American Telemedicine Association}, volume = {28}, number = {7}, pages = {942-969}, doi = {10.1089/tmj.2021.0399}, pmid = {34665645}, issn = {1556-3669}, mesh = {Adult ; *COVID-19/epidemiology ; Chronic Disease ; *Diabetes Mellitus/therapy ; Humans ; *Hypertension/therapy ; Monitoring, Physiologic/methods ; Pandemics ; Primary Health Care ; Quality of Life ; }, abstract = {Background: One lesson from the current COVID-19 pandemic is the need to optimize health care provision outside of traditional settings, and potentially over longer periods of time. An important strategy is remote patient monitoring (RPM), allowing patients to remain at home, while they transmit health data and receive follow-up services. Materials and Methods: We conducted an overview of the latest systematic reviews that had included randomized controlled trials with adult patients with chronic diseases. We summarized results and displayed these in forest plots, and used GRADE (Grading of Recommendations Assessment, Development, and Evaluation) to assess our certainty of the evidence. Results: We included 4 systematic reviews that together reported on 11 trials that met our definition of RPM, each including patients with diabetes and/or hypertension. RPM probably makes little to no difference on HbA1c levels. RPM probably leads to a slight reduction in systolic blood pressure, with questionable clinical meaningfulness. RPM probably has a small negative effect on the physical component of health-related quality of life, but the clinical significance of this reduction is uncertain. We have low confidence in the finding that RPM makes no difference to the remaining five primary outcomes. Conclusion: Most of our findings are consistent with reviews of other, broader definitions of RPM. The type of RPM examined in this review is as effective as standard treatment for patients with diabetes/hypertension. If this or other types of RPM are to be used for "long covid" patients or for other chronic disease groups post-pandemic, we need to understand why RPM may negatively affect quality of life.}, }
@article {pmid34667307, year = {2021}, author = {Boyton, RJ and Altmann, DM}, title = {The immunology of asymptomatic SARS-CoV-2 infection: what are the key questions?.}, journal = {Nature reviews. Immunology}, volume = {21}, number = {12}, pages = {762-768}, pmid = {34667307}, issn = {1474-1741}, support = {MC_PC_20031/MRC_/Medical Research Council/United Kingdom ; MR/S019553/1/MRC_/Medical Research Council/United Kingdom ; MR/W020610/1/MRC_/Medical Research Council/United Kingdom ; MC_PC_20060/MRC_/Medical Research Council/United Kingdom ; MR/V036939/1/MRC_/Medical Research Council/United Kingdom ; MR/R02622X/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; *Asymptomatic Infections/epidemiology ; COVID-19/complications/epidemiology/*immunology/*transmission ; Humans ; *Immunologic Memory ; SARS-CoV-2/immunology ; Post-Acute COVID-19 Syndrome ; }, abstract = {An important challenge during the COVID-19 pandemic has been to understand asymptomatic disease and the extent to which this may be a source of transmission. As asymptomatic disease is by definition hard to screen for, there is a lack of clarity about this aspect of the COVID-19 spectrum. Studies have considered whether the prevalence of asymptomatic disease is determined by differences in age, demographics, viral load, duration of shedding, and magnitude or durability of immunity. It is clear that adaptive immunity is strongly activated during asymptomatic infection, but some features of the T cell and antibody response may differ from those in symptomatic disease. Areas that need greater clarity include the extent to which asymptomatic disease leads to persistent symptoms (long COVID), and the quality, quantity and durability of immune priming required to confer subsequent protection.}, }
@article {pmid34670282, year = {2021}, author = {Gogoll, C and Leo, F and Schueller, PO and Grohé, C}, title = {[Post-COVID sequela of the lung - follow up and treatment].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {146}, number = {21}, pages = {1399-1404}, doi = {10.1055/a-1492-8808}, pmid = {34670282}, issn = {1439-4413}, mesh = {COVID-19/*complications/epidemiology/physiopathology/therapy ; Europe ; Humans ; Incidence ; Practice Guidelines as Topic ; Post-Acute COVID-19 Syndrome ; }, abstract = {Most people recover completely after an acute infection with the novel corona virus SARS-CoV2. But some people continue to experience symptoms after their recovery. This phenomenon is called post-acute or long-COVID (from week 4 after the infection up to week 12) and persistent post-COVID (symptoms for effects that persist 12 or more weeks after onset). The exact processes that cause long COVID remain unknown.Most of those patients suffer from long-term symptoms of lung damage, including breathlessness, coughing, fatigue and limited ability to exercise. Today, 18 months after the first infections in Europe we have access to the first practical guidelines for the long-/post-COVID syndrome. Further on first prospective studies analysing the incidence of post-COVID are now available.In this review we will discuss some questions about treatment and follow up of patients suffering from pulmonary sequelae after their COVID-19 infection, based on the actual literature.}, }
@article {pmid34674005, year = {2022}, author = {Beghi, E and Giussani, G and Westenberg, E and Allegri, R and Garcia-Azorin, D and Guekht, A and Frontera, J and Kivipelto, M and Mangialasche, F and Mukaetova-Ladinska, EB and Prasad, K and Chowdhary, N and Winkler, AS}, title = {Acute and post-acute neurological manifestations of COVID-19: present findings, critical appraisal, and future directions.}, journal = {Journal of neurology}, volume = {269}, number = {5}, pages = {2265-2274}, pmid = {34674005}, issn = {1432-1459}, support = {001/WHO_/World Health Organization/International ; }, mesh = {*COVID-19/complications ; Hospital Mortality ; Humans ; *Nervous System Diseases/epidemiology/etiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Acute and post-acute neurological symptoms, signs and diagnoses have been documented in an increasing number of patients infected by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which causes Coronavirus Disease 2019 (COVID-19). In this review, we aimed to summarize the current literature addressing neurological events following SARS-CoV-2 infection, discuss limitations in the existing literature and suggest future directions that would strengthen our understanding of the neurological sequelae of COVID-19. The presence of neurological manifestations (symptoms, signs or diagnoses) both at the onset or during SARS-CoV-2 infection is associated with a more severe disease, as demonstrated by a longer hospital stay, higher in-hospital death rate or the continued presence of sequelae at discharge. Although biological mechanisms have been postulated for these findings, evidence-based data are still lacking to clearly define the incidence, range of characteristics and outcomes of these manifestations, particularly in non-hospitalized patients. In addition, data from low- and middle-income countries are scarce, leading to uncertainties in the measure of neurological findings of COVID-19, with reference to geography, ethnicity, socio-cultural settings, and health care arrangements. As a consequence, at present a specific phenotype that would specify a post-COVID (or long-COVID) neurological syndrome has not yet been identified.}, }
@article {pmid34680460, year = {2021}, author = {Mangge, H and Kneihsl, M and Schnedl, W and Sendlhofer, G and Curcio, F and Domenis, R}, title = {Immune Responses against SARS-CoV-2-Questions and Experiences.}, journal = {Biomedicines}, volume = {9}, number = {10}, pages = {}, pmid = {34680460}, issn = {2227-9059}, abstract = {Understanding immune reactivity against SARS-CoV-2 is essential for coping with the COVID-19 pandemic. Herein, we discuss experiences and open questions about the complex immune responses to SARS-CoV-2. Some people react excellently without experiencing any clinical symptoms, they do not get sick, and they do not pass the virus on to anyone else ("sterilizing" immunity). Others produce antibodies and do not get COVID-19 but transmit the virus to others ("protective" immunity). Some people get sick but recover. A varying percentage develops respiratory failure, systemic symptoms, clotting disorders, cytokine storms, or multi-organ failure; they subsequently decease. Some develop long COVID, a new pathologic entity similar to fatigue syndrome or autoimmunity. In reality, COVID-19 is considered more of a systemic immune-vascular disease than a pulmonic disease, involving many tissues and the central nervous system. To fully comprehend the complex clinical manifestations, a profound understanding of the immune responses to SARS-CoV-2 is a good way to improve clinical management of COVID-19. Although neutralizing antibodies are an established approach to recognize an immune status, cellular immunity plays at least an equivalent or an even more important role. However, reliable methods to estimate the SARS-CoV-2-specific T cell capacity are not available for clinical routines. This deficit is important because an unknown percentage of people may exist with good memory T cell responsibility but a low number of or completely lacking peripheral antibodies against SARS-CoV-2. Apart from natural immune responses, vaccination against SARS-CoV-2 turned out to be very effective and much safer than naturally acquired immunity. Nevertheless, besides unwanted side effects of the currently available vector and mRNA preparations, concerns remain whether these vaccines will be strong enough to defeat the pandemic. Altogether, herein we discuss important questions, and try to give answers based on the current knowledge and preliminary data from our laboratories.}, }
@article {pmid34687321, year = {2022}, author = {Trapani, V and Rosanoff, A and Baniasadi, S and Barbagallo, M and Castiglioni, S and Guerrero-Romero, F and Iotti, S and Mazur, A and Micke, O and Pourdowlat, G and Scarpati, G and Wolf, FI and Maier, JA}, title = {The relevance of magnesium homeostasis in COVID-19.}, journal = {European journal of nutrition}, volume = {61}, number = {2}, pages = {625-636}, pmid = {34687321}, issn = {1436-6215}, mesh = {*COVID-19 ; Homeostasis ; Humans ; Magnesium ; Pandemics ; SARS-CoV-2 ; }, abstract = {PURPOSE: In less than one and a half year, the COVID-19 pandemic has nearly brought to a collapse our health care and economic systems. The scientific research community has concentrated all possible efforts to understand the pathogenesis of this complex disease, and several groups have recently emphasized recommendations for nutritional support in COVID-19 patients. In this scoping review, we aim at encouraging a deeper appreciation of magnesium in clinical nutrition, in view of the vital role of magnesium and the numerous links between the pathophysiology of SARS-CoV-2 infection and magnesium-dependent functions.<br><br>METHODS: By searching PubMed and Google Scholar from 1990 to date, we review existing evidence from experimental and clinical studies on the role of magnesium in chronic non-communicable diseases and infectious diseases, and we focus on recent reports of alterations of magnesium homeostasis in COVID-19 patients and their association with disease outcomes. Importantly, we conduct a census on ongoing clinical trials specifically dedicated to disclosing the role of magnesium in COVID-19.<br><br>RESULTS: Despite many methodological limitations, existing data seem to corroborate an association between deranged magnesium homeostasis and COVID-19, and call for further and better studies to explore the prophylactic or therapeutic potential of magnesium supplementation.<br><br>CONCLUSION: We propose to reconsider the relevance of magnesium, frequently overlooked in clinical practice. Therefore, magnesemia should be monitored and, in case of imbalanced magnesium homeostasis, an appropriate nutritional regimen or supplementation might contribute to protect against SARS-CoV-2 infection, reduce severity of COVID-19 symptoms and facilitate the recovery after the acute phase.}, }
@article {pmid34687462, year = {2022}, author = {Korompoki, E and Gavriatopoulou, M and Fotiou, D and Ntanasis-Stathopoulos, I and Dimopoulos, MA and Terpos, E}, title = {Late-onset hematological complications post COVID-19: An emerging medical problem for the hematologist.}, journal = {American journal of hematology}, volume = {97}, number = {1}, pages = {119-128}, pmid = {34687462}, issn = {1096-8652}, mesh = {Animals ; COVID-19/*complications/etiology/therapy ; Disease Management ; Hematologic Diseases/*etiology/therapy ; Hemorrhagic Disorders/etiology/therapy ; Humans ; SARS-CoV-2/isolation &amp; purification ; Thrombocytopenia/etiology/therapy ; Thromboembolism/etiology/therapy ; Thrombosis/etiology/therapy ; Post-Acute COVID-19 Syndrome ; }, abstract = {Coronavirus disease 19 (COVID-19) is considered a multisystemic disease. Several studies have reported persistent symptoms or late-onset complications after acute COVID-19, including post-COVID-19 hematological disorders. COVID-19-induced coagulopathy, an immunothrombotic state, has been linked to thromboembolic and hemorrhagic events. Late-onset thrombocytopenia related to immune system dysregulation has also been reported as a rare manifestation post COVID-19. Close monitoring of laboratory dynamics is considered essential to identify timely abnormal values that need further investigation, providing supportive care whenever indicated. The role of hematologists is essential in terms of the multidisciplinary approach of long COVID-19. This review summarizes all the available evidence on post-acute COVID-19 hematological complications.}, }
@article {pmid34688543, year = {2022}, author = {Kopanczyk, R and Kumar, N and Papadimos, T}, title = {Post-Acute COVID-19 Syndrome for Anesthesiologists: A Narrative Review and a Pragmatic Approach to Clinical Care.}, journal = {Journal of cardiothoracic and vascular anesthesia}, volume = {36}, number = {8 Pt A}, pages = {2727-2737}, pmid = {34688543}, issn = {1532-8422}, mesh = {Anesthesiologists ; *COVID-19/complications ; Humans ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Post-acute coronavirus disease 2019 (COVID-19) syndrome is a novel, poorly understood clinical entity with life-impacting ramifications. Patients with this syndrome, also known as "COVID-19 long-haulers," often present with nonspecific ailments involving more than one body system. The most common complaints include dyspnea, fatigue, brain fog, and chest pain. There currently is no single agreed-upon definition for post-acute COVID-19 syndrome, but most agree that criterion for this syndrome is the persistence of mental and physical health consequences after initial infection. Given the millions of acute infections in the United States over the course of the pandemic, perioperative providers will encounter these patients in clinical practice in growing numbers. Symptoms of the COVID-19 long-haulers should not be minimized, as these patients are at higher risk for postoperative respiratory complications and perioperative mortality for up to seven weeks after initial illness. Instead, a cautious multidisciplinary preoperative evaluation should be performed. Perioperative care should be viewed through the prism of best practices already in use, such as avoidance of benzodiazepines in patients with cognitive impairment and use of lung-protective ventilation. Recommendations especially relevant to the COVID-19 long-haulers include assessment of critical care myopathies and neuropathies to determine suitable neuromuscular blocking agents and reversal, preoperative workup of insidious cardiac or pulmonary pathologies in previously healthy patients, and, thorough medication review, particularly of anticoagulation regimens and chronic steroid use. In this article, the authors define the syndrome, synthesize the available scientific evidence, and make pragmatic suggestions regarding the perioperative clinical care of COVID-19 long-haulers.}, }
@article {pmid34690357, year = {2022}, author = {Martín-Garrido, I and Medrano-Ortega, FJ}, title = {[Beyond acute SARS-CoV-2 infection: A new challenge for Internal Medicine].}, journal = {Revista clinica espanola}, volume = {222}, number = {3}, pages = {176-179}, pmid = {34690357}, issn = {1578-1860}, abstract = {Infection with the new SARS-CoV-2 coronavirus has reached pandemic proportions, with a very high death toll worldwide. Despite the scientific community's strenuous efforts to address this disease in its acute phase, as well as in prevention through the development of vaccines in record time, there remains another important workhorse: understanding and treating the persistence of symptoms beyond the acute phase, the so-called protracted COVID-19 syndrome or persistent COVID. These persistent manifestations affect several organs and systems and may depend on both the pathogenic mechanisms of the virus and the pathophysiological response of the patient. One year after the onset of this pandemic, there is an urgent need to address this situation from a comprehensive approach.}, }
@article {pmid34694037, year = {2022}, author = {Howard-Jones, AR and Burgner, DP and Crawford, NW and Goeman, E and Gray, PE and Hsu, P and Kuek, S and McMullan, BJ and Tosif, S and Wurzel, D and Bowen, AC and Danchin, M and Koirala, A and Sharma, K and Yeoh, DK and Britton, PN}, title = {COVID-19 in children. II: Pathogenesis, disease spectrum and management.}, journal = {Journal of paediatrics and child health}, volume = {58}, number = {1}, pages = {46-53}, pmid = {34694037}, issn = {1440-1754}, mesh = {*COVID-19/complications ; Child ; Humans ; Pandemics ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome ; Post-Acute COVID-19 Syndrome ; }, abstract = {The global disruption of the COVID-19 pandemic has impacted the life of every child either directly or indirectly. This review explores the pathophysiology, immune response, clinical presentation and treatment of COVID-19 in children, summarising the most up-to-date data including recent developments regarding variants of concern. The acute infection with SARS-CoV-2 is generally mild in children, whilst the post-infectious manifestations, including paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) and 'long COVID' in children, are more complex. Given that most research on COVID-19 has focused on adult cohorts and that clinical manifestations, treatment availability and impacts differ markedly in children, research that specifically examines COVID-19 in children needs to be prioritised.}, }
@article {pmid34696160, year = {2021}, author = {Günl, F and Mecate-Zambrano, A and Rehländer, S and Hinse, S and Ludwig, S and Brunotte, L}, title = {Shooting at a Moving Target-Effectiveness and Emerging Challenges for SARS-CoV-2 Vaccine Development.}, journal = {Vaccines}, volume = {9}, number = {10}, pages = {}, pmid = {34696160}, issn = {2076-393X}, support = {BR 5189/1-1//Deutsche Forschungsgemeinschaft/ ; CRU342//Clinical Research Unit/ ; 01KI20218//Bundesministerium f&#xfc;r Bildung und Forschung/ ; 01KX2021//Network University Medicine/ ; Bru2/015/19//Interdisciplinary Centre for Clinical Research (IZKF)/ ; }, abstract = {Since late 2019 the newly emerged pandemic SARS-CoV-2, the causative agent of COVID-19, has hit the world with recurring waves of infections necessitating the global implementation of non-pharmaceutical interventions, including strict social distancing rules, the wearing of masks and the isolation of infected individuals in order to restrict virus transmissions and prevent the breakdown of our healthcare systems. These measures are not only challenging on an economic level but also have a strong impact on social lifestyles. Using traditional and novel technologies, highly efficient vaccines against SARS-CoV-2 were developed and underwent rapid clinical evaluation and approval to accelerate the immunization of the world population, aiming to end the pandemic and return to normality. However, the emergence of virus variants with improved transmission, enhanced fitness and partial immune escape from the first generation of vaccines poses new challenges, which are currently being addressed by scientists and pharmaceutical companies all over the world. In this ongoing pandemic, the evaluation of SARS-CoV-2 vaccines underlies diverse unpredictable dynamics, posed by the first broad application of the mRNA vaccine technology and their compliance, the occurrence of unexpected side effects and the rapid emergence of variations in the viral antigen. However, despite these hurdles, we conclude that the available SARS-CoV-2 vaccines are very safe and efficiently protect from severe COVID-19 and are thereby the most powerful tools to prevent further harm to our healthcare systems, economics and individual lives. This review summarizes the unprecedented pathways of vaccine development and approval during the ongoing SARS-CoV-2 pandemic. We focus on the real-world effectiveness and unexpected positive and negative side effects of the available vaccines and summarize the timeline of the applied adaptations to the recommended vaccination strategies in the light of emerging virus variants. Finally, we highlight upcoming strategies to improve the next generations of SARS-CoV-2 vaccines.}, }
@article {pmid34704045, year = {2021}, author = {Kalyanaraman, B}, title = {Reactive oxygen species, proinflammatory and immunosuppressive mediators induced in COVID-19: overlapping biology with cancer.}, journal = {RSC chemical biology}, volume = {2}, number = {5}, pages = {1402-1414}, pmid = {34704045}, issn = {2633-0679}, abstract = {This review analyzes the published literature linking the different mechanisms focused on oxidative stress and inflammation that contribute to COVID-19 disease severity. The objective is to bring together potential proinflammatory mechanisms of COVID-19 pathogenesis and address mitigation strategies using naturally occurring compounds and FDA-approved drugs. Outstanding questions addressed include the following: What is the mechanistic basis for linking enhanced vulnerability in COVID-19 to increased oxidative damage and proinflammatory mediators (e.g., cytokines), especially in high-risk people? Can we repurpose anti-inflammatory and immunomodulatory agents to mitigate inflammation in COVID-19 patients? How does 2-deoxy-d-glucose function as an anti-COVID drug? COVID-19, cancer biology, and immunotherapy share many mechanistic similarities. Repurposing drugs that already have been FDA-approved for mitigating inflammation and immunosuppression in cancer may be a way to counteract disease severity, progression, and chronic inflammation in COVID-19. What are the long-term effects of reactive oxygen species-inducing immune cells and sustained inflammation in so-called long-haulers (long COVID) after recovery from COVID-19? Can we use mitochondria-targeted agents prophylactically to prevent inflammation and boost immunity in long-haulers? Addressing the oxidative chemical biology of COVID-19 and the mechanistic commonalities with cancer may provide new insights potentially leading to appropriate clinical trials and new treatments.}, }
@article {pmid34710173, year = {2021}, author = {Poudel, AN and Zhu, S and Cooper, N and Roderick, P and Alwan, N and Tarrant, C and Ziauddeen, N and Yao, GL}, title = {Impact of Covid-19 on health-related quality of life of patients: A structured review.}, journal = {PloS one}, volume = {16}, number = {10}, pages = {e0259164}, pmid = {34710173}, issn = {1932-6203}, mesh = {Adult ; Aged ; Aged, 80 and over ; COVID-19/complications/*psychology ; Female ; Humans ; Male ; Middle Aged ; Pandemics/prevention &amp; control ; Quality of Life/*psychology ; SARS-CoV-2/pathogenicity ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Coronavirus disease (Covid-19) has led to a global pandemic since its emergence in December 2019. The majority of research into Covid-19 has focused on transmission, and mortality and morbidity associated with the virus. However, less attention has been given to its impact on health-related quality of life (HRQoL) of patients with Covid-19.<br><br>METHODS: We searched for original studies published between December 2019 and Jan 2021 in PubMed, Scopus and Medline databases using a specific search strategy. We also explored literature on websites of distinguished public health organisations and hand-searched reference lists of eligible studies. The studies were screened by two reviewers according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) flowchart using pre-determined eligibility criteria. Data were synthesised, analysed descriptively and reported in line with PRISMA guidelines.<br><br>RESULTS: In total, 1276 studies were identified through the search strategy. Of these, 77 studies were selected for full-text reading after screening the studies. After reading full-text, 12 eligible studies were included in this review. The majority of the studies used a generic HRQoL assessment tool; five studies used SF-36, five studies used EQ-5D-5L, and three used pulmonary disease-specific HRQoL tools (two studies used two tools each). The impact of Covid-19 on HRQoL was found to be considerable in both Acute Covid and Long Covid patients. Higher impact on HRQoL was reported in Acute Covid, females, older ages, patients with more severe disease and patients from low-income countries.<br><br>CONCLUSION: The impact of Covid-19 on HRQoL of Acute and Long Covid patients is substantial. There was disproportional impact on patients by gender, age, severity of illness and study country. The long-term impact of Covid-19 is still in its initial stage. The findings of the review may be useful to researchers, policymakers, and clinicians caring for people following Covid-19 infection.}, }
@article {pmid34720198, year = {2021}, author = {Zepp, F and Knuf, M}, title = {[Coronavirus disease 2019 in childhood and adolescence].}, journal = {Monatsschrift Kinderheilkunde : Organ der Deutschen Gesellschaft fur Kinderheilkunde}, volume = {169}, number = {11}, pages = {1010-1033}, pmid = {34720198}, issn = {0026-9298}, abstract = {The coronavirus disease 2019 (COVID‑19) mostly occurs in children and adolescents as an asymptomatic infection. The course of the disease is usually mild or moderate. The estimated seroprevalence in Germany before the start of the vaccination program in children and adolescents was > 10%. Individual risk factors for a severe course are known. The COVID‑19-associated pediatric inflammatory multisystem syndrome (PIMS) is a very rare and severe disease with a favorable prognosis if diagnosed early and treated appropriately. The data situation on long-COVID syndrome in children and adolescents is still insufficiently defined and the incidence is not known. The primary source of infections in children and adolescents are household contacts. Transmission in school settings and other day care facilities play a subordinate role, at least in Germany.Two mRNA vaccines are currently approved in Europe for the prevention of COVID‑19 in children and adolescents above the age of 12 years. Except for the very rare occurrence of pericarditis/myocarditis in temporal association with the vaccination, especially in young men, the COVID‑19 vaccines are considered effective and safe in the age group 12-17 years. The Standing Vaccination Commission (STIKO) issued a vaccination recommendation for all 12-17-year-olds on 19 August 2021.}, }
@article {pmid34721055, year = {2021}, author = {Hebbard, C and Lee, B and Katare, R and Garikipati, VNS}, title = {Diabetes, Heart Failure, and COVID-19: An Update.}, journal = {Frontiers in physiology}, volume = {12}, number = {}, pages = {706185}, pmid = {34721055}, issn = {1664-042X}, abstract = {The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared a pandemic by the WHO in March 2020. As of August 2021, more than 220 countries have been affected, accounting for 211,844,613 confirmed cases and 4,432,802 deaths worldwide. A new delta variant wave is sweeping through the globe. While previous reports consistently have demonstrated worse prognoses for patients with existing cardiovascular disease than for those without, new studies are showing a possible link between SARS-CoV-2 infection and an increased incidence of new-onset heart disease and diabetes, regardless of disease severity. If this trend is true, with hundreds of millions infected, the disease burden could portend a potentially troubling increase in heart disease and diabetes in the future. Focusing on heart failure in this review, we discuss the current data at the intersection of COVID, heart failure, and diabetes, from clinical findings to potential mechanisms of how SARS-CoV-2 infection could increase the incidence of those pathologies. Additionally, we posit questions for future research areas regarding the significance for patient care.}, }
@article {pmid34726085, year = {2021}, author = {Lindsay, RK and Wilson, JJ and Trott, M and Olanrewaju, O and Tully, MA and López-Sánchez, GF and Shin, JI and Pizzol, D and Allen, P and Butler, LT and Barnett, Y and Smith, L}, title = {What are the recommendations for returning athletes who have experienced long term COVID-19 symptoms?.}, journal = {Annals of medicine}, volume = {53}, number = {1}, pages = {1935-1944}, pmid = {34726085}, issn = {1365-2060}, mesh = {*Athletes ; Athletic Performance/*physiology ; COVID-19/*complications/physiopathology/rehabilitation ; Humans ; Post-Acute COVID-19 Syndrome ; }, abstract = {Currently, there is limited research reporting the symptoms of long COVID among athletes, and the recommendations for athletes returning to competition/training who have experienced long COVID symptoms. Therefore, the aim of this systematic review is to synthesise the recommendations for returning athletes who have experienced long COVID symptoms. The protocol was registered in PROSPERO under CRD42021265939. Two authors searched the electronic databases PubMed, Embase, Scopus, the Cochrane Library, Web of Science, CINAHL, PsycINFO, and SPORTDiscus from August 2019-July 2021. Search terms included words related to "long COVID", "athlete" and "return". Data extraction was completed for each study by two independent investigators for: (1) first author name; (2) year of publication; (3) journal; (4) Definition of athlete (i.e. elite or non-elite) (5) Recommendations reported. A total of 220 records were found. Following title and abstract screening, 61 studies were eligible for full text screening. Overall, no studies, commentaries, editorials or reviews provided specific recommendations for "long COVID" defined as COVID-19 signs and symptoms lasting for over 4 weeks as a result of COVID-19 infection. In addition, we found no studies which reported symptoms of athletes suffering from long COVID. Despite the lack of evidence, we did find eight separate professional recommendations for managing "long-term effects" and "ongoing" or "prolonged" symptoms and COVID-19 complications among athletes. Practitioners should be aware of both mental and physical symptoms of long COVID, and additional considerations may be required for athletes who have undergone intensive care. The present review provides a list of recommendations based on existing literature that may be followed and implemented for returning athletes.Key MessagesFurther research, including longitudinal research of athletes who have tested positive for COVID-19, is required to develop evidenced-based guidelines for athletes with ongoing COVID-19 symptoms.Prior to returning to play after COVID-19 infection, a thorough medical history, physical and psychological examination should be conducted by a medical professional.Athletes should continue to monitor and record their own physical and psychological markers of health.}, }
@article {pmid34747740, year = {2021}, author = {Rajkumar Tripathi, AK and Pinto, LM}, title = {Long COVID: "And the fire rages on".}, journal = {Lung India : official organ of Indian Chest Society}, volume = {38}, number = {6}, pages = {564-570}, pmid = {34747740}, issn = {0970-2113}, abstract = {With the increasing cohort of COVID-19 survivors worldwide, we now realize the proportionate rise in post-COVID-19 syndrome. In this review article, we try to define, summarize, and classify this syndrome systematically. This would help clinicians to identify and manage this condition more efficiently. We propose a tool kit that might be useful in recording follow-up data of COVID-19 survivors.}, }
@article {pmid34750595, year = {2022}, author = {García-Saugar, M and Jaén-Jover, C and Hernández-Sánchez, S and Poveda-Pagán, EJ and Lozano-Quijada, C}, title = {[Recommendations for outpatient respiratory rehabilitation of long COVID patients].}, journal = {Anales del sistema sanitario de Navarra}, volume = {45}, number = {1}, pages = {}, pmid = {34750595}, issn = {2340-3527}, mesh = {*COVID-19/complications ; Humans ; Outpatients ; Physical Therapy Modalities ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The appearance of COVID-19 has been a problem for public health on a global scale, putting pressure on health care systems. The after-effects of this illness have highlighted the importance of rehabilitation in long COVID patients involv-ing different health professionals. The treatment of the respiratory after-effects of this disease in an outpatient setting is a specialized field. It is appropriate to offer a series of practical recommendations of cardio-respiratory rehabilitation that are helpful to the professionals involved in the after-effects when ending hospitalisation. This review of the literature includes ten key aspects of respiratory physiotherapy that range from assessment, parameters to monitor, signs of alarm and respiratory rehabilitation techniques and other exercises for this population.}, }
@article {pmid34752489, year = {2021}, author = {Fowler-Davis, S and Platts, K and Thelwell, M and Woodward, A and Harrop, D}, title = {A mixed-methods systematic review of post-viral fatigue interventions: Are there lessons for long Covid?.}, journal = {PloS one}, volume = {16}, number = {11}, pages = {e0259533}, pmid = {34752489}, issn = {1932-6203}, mesh = {Humans ; *COVID-19/complications/epidemiology ; *Fatigue/therapy/etiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: Fatigue syndromes have been widely observed following post-viral infection and are being recognised because of Covid19. Interventions used to treat and manage fatigue have been widely researched and this study aims to synthesise the literature associated with fatigue interventions to investigate the outcomes that may be applicable to 'long Covid'.<br><br>METHOD: The study was registered with PROSPERO (CRD42020214209) in October 2020 and five electronic databases were searched. Papers were screened, critically appraised and data extracted from studies that reported outcomes of fatigue interventions for post-viral syndromes. The narrative synthesis includes statistical analysis associated with effectiveness and then identifies the characteristics of the interventions, including identification of transferable learning for the treatment of fatigue in long Covid. An expert panel supported critical appraisal and data synthesis.<br><br>RESULTS: Over 7,000 research papers revealed a diverse range of interventions and fatigue outcome measures. Forty papers were selected for data extraction after final screening. The effectiveness of all interventions was assessed according to mean differences (MD) in measured fatigue severity between each experimental group and a control following the intervention, as well as standardised mean differences as an overall measure of effect size. Analyses identified a range of effects-from most effective MD -39.0 [95% CI -51.8 to -26.2] to least effective MD 42.28 [95% CI 33.23 to 51.34]-across a range of interventions implemented with people suffering varying levels of fatigue severity. Interventions were multimodal with a range of supportive therapeutic methods and varied in intensity and requirements of the participants. Those in western medical systems tended to be based on self- management and education principles (i.e., group cognitive behavioural therapy (CBT).<br><br>CONCLUSION: Findings suggest that the research is highly focussed on a narrow participant demographic and relatively few methods are effective in managing fatigue symptoms. Selected literature reported complex interventions using self-rating fatigue scales that report effect. Synthesis suggests that long Covid fatigue management may be beneficial when a) physical and psychological support, is delivered in groups where people can plan their functional response to fatigue; and b) where strengthening rather than endurance is used to prevent deconditioning; and c) where fatigue is regarded in the context of an individual's lifestyle and home-based activities are used.}, }
@article {pmid34756590, year = {2022}, author = {France, K and Glick, M}, title = {Long COVID and oral health care considerations.}, journal = {Journal of the American Dental Association (1939)}, volume = {153}, number = {2}, pages = {167-174}, pmid = {34756590}, issn = {1943-4723}, mesh = {*COVID-19/complications ; Delivery of Health Care ; Humans ; Oral Health ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: People who have recovered from the initial severe acute respiratory syndrome coronavirus 2 infection are at risk of developing long COVID, a prolonged suite of signs and symptoms that may interfere with daily life and the ability to undergo routine oral health care.<br><br>METHODS: The available literature on long COVID was reviewed and compiled to produce a review of the syndrome as currently understood. Articles were evaluated with a focus on how long COVID may affect the provision of oral health care and on ways in which treatment may need to be modified to best care for this vulnerable patient population.<br><br>RESULTS: Long COVID includes a wide variety of symptoms, such as fatigue, shortness of breath, chest pain, risk of developing thromboembolism, and neurologic and psychiatric complications. These symptoms may arise at various times and in a wide range of patients, and they may necessitate modification of routine oral health care interventions.<br><br>CONCLUSIONS: Recommendations for the treatment of affected people in an oral health care setting are presented, including a thorough evaluation of the patient history and current status, understanding of how related symptoms may affect oral health care interventions, and which modifications to treatment are needed to provide safe and appropriate care.<br><br>PRACTICAL IMPLICATIONS: Oral health care professionals must be aware of long COVID, an increasingly prevalent condition with a widely variable presentation and impact. Oral health care professionals should be prepared to treat these patients safely in an outpatient oral health setting.}, }
@article {pmid34765889, year = {2021}, author = {, }, title = {The microvascular hypothesis underlying neurologic manifestations of long COVID-19 and possible therapeutic strategies.}, journal = {Cardiovascular endocrinology &amp; metabolism}, volume = {10}, number = {4}, pages = {193-203}, pmid = {34765889}, issn = {2574-0954}, abstract = {With the ongoing distribution of the coronavirus disease (COVID) vaccines, the pandemic of our age is ending, leaving the world to deal with its well-documented aftereffects. Long COVID comprises a variety of symptoms, of which the neurological component prevails. The most permeating theory on the genesis of these symptoms builds upon the development of microvascular dysfunction similar to that seen in numerous vascular diseases such as diabetes. This can occur through the peripheral activation of angiotensin-converting enzyme 2 receptors, or through exacerbations of pro-inflammatory cytokines that can remain in circulation even after the infection diminishes. Several drugs have been identified to act on the neurovascular unit to promote repair, such as gliptins, and others. They also succeeded in improving neurologic outcome in diabetic patients. The repurposing of such drugs for treatment of long COVID-19 can possibly shorten the time to recovery of long COVID-19 syndrome.}, }
@article {pmid34772779, year = {2021}, author = {Vance, H and Maslach, A and Stoneman, E and Harmes, K and Ransom, A and Seagly, K and Furst, W}, title = {Addressing Post-COVID Symptoms: A Guide for Primary Care Physicians.}, journal = {Journal of the American Board of Family Medicine : JABFM}, volume = {34}, number = {6}, pages = {1229-1242}, doi = {10.3122/jabfm.2021.06.210254}, pmid = {34772779}, issn = {1558-7118}, mesh = {*COVID-19 ; Humans ; *Physicians, Primary Care ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Post-COVID symptoms, defined as symptoms lasting >4 weeks postinfection, have been identified not only among those patients who were hospitalized with severe symptoms but also among those who were asymptomatic or with only mild symptoms. Primary care providers (PCPs) will often be the first point of contact for patients experiencing potential complications of post-COVID symptoms. The aim of this article is to present a post-COVID management tool for PCPs to use as a quick reference and guide to the initial workup and management of the most common post-COVID symptoms.<br><br>METHODS: Published guidance, recent literature, and expert specialist opinion were used to create the structure outlining the outpatient evaluation and treatment for post-COVID symptoms.<br><br>RESULTS: A quick-reference guide for management of post-COVID symptoms was created for PCPs. Educational materials were created for clinicians to share with patients. Our article reviews several common complaints including respiratory, cognitive, and neurological symptoms, chronic fatigue, dysautonomia, and anosmia and presents recommendations for management.<br><br>CONCLUSIONS: Data on long-term effects of COVID-19 are still emerging, and rapid dissemination of this data to front-line PCPs is crucial. This table was our effort to make the currently available evidence accessible for our PCPs in a simple, easy-to-use format.}, }
@article {pmid34790680, year = {2021}, author = {Hayes, LD and Ingram, J and Sculthorpe, NF}, title = {More Than 100 Persistent Symptoms of SARS-CoV-2 (Long COVID): A Scoping Review.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {750378}, pmid = {34790680}, issn = {2296-858X}, support = {COV/LTE/20/08/CSO_/Chief Scientist Office/United Kingdom ; }, abstract = {Background: Persistent coronavirus disease 2019 (COVID-19) symptoms are increasingly well-reported in cohort studies and case series. Given the spread of the pandemic, number of individuals suffering from persistent symptoms, termed 'long COVID', are significant. However, type and prevalence of symptoms are not well reported using systematic literature reviews. Objectives: In this scoping review of the literature, we aggregated type and prevalence of symptoms in people with long COVID. Eligibility Criteria: Original investigations concerning the name and prevalence of symptoms were considered in participants ≥4-weeks post-infection. Sources of Evidence: Four electronic databases [Medline, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL)] were searched. Methods: A scoping review was conducted using the Arksey and O'Malley framework. Review selection and characterisation was performed by three independent reviewers using pretested forms. Results: Authors reviewed 2,711 titles and abstracts for inclusion with 152 selected for full-text review. 102 articles were subsequently removed as this did not meet inclusion criteria. Thus, fifty studies were analysed, 34 of which were described as cohort studies or prospective cohort studies, 14 were described as cross-sectional studies, one was described as a case control study, and one was described as a retrospective observational study. In total, >100 symptoms were identified and there was considerable heterogeneity in symptom prevalence and setting of study. Ten studies reported cardiovascular symptoms, four examined pulmonary symptoms, 25 reported respiratory symptoms, 24 reported pain-related symptoms, 21 reported fatigue, 16 reported general infection symptoms, 10 reported symptoms of psychological disorders, nine reported cognitive impairment, 31 reported a sensory impairment, seven reported a dermatological complaint, 11 reported a functional impairment, and 18 reported a symptom which did not fit into any of the above categories. Conclusion: Most studies report symptoms analogous to those apparent in acute COVID-19 infection (i.e., sensory impairment and respiratory symptoms). Yet, our data suggest a larger spectrum of symptoms, evidenced by >100 reported symptoms. Symptom prevalence varied significantly and was not explained by data collection approaches, study design or other methodological approaches, and may be related to unknown cohort-specific factors.}, }
@article {pmid34803180, year = {2022}, author = {López-Sampalo, A and Bernal-López, MR and Gómez-Huelgas, R}, title = {[Persistent COVID-19 syndrome. A narrative review].}, journal = {Revista clinica espanola}, volume = {222}, number = {4}, pages = {241-250}, pmid = {34803180}, issn = {1578-1860}, abstract = {As the coronavirus-2019 disease (COVID-19) pandemic, caused by the infection with severe acute respiratory syndrome (SARS-CoV-2) coronavirus type 2, has progressed, persistent COVID-19 syndrome is an increasingly recognized problem on which a significant volume of medical literature is developing. Symptoms may be persistent or appear, after an asymptomatic period, weeks or months after the initial infection. The clinical picture is as markedly heterogeneous and multisystemic as in the acute phase, so multidisciplinary management is required. In addition, their appearance is not related to the severity of the initial infection, so they can affect both mild patients, even asymptomatic, and seriously ill patients who have required hospitalization. Although it can affect people of any age, it is more common in middle-aged women. The sequelae can generate a high impact on the quality of life, and in the work and social environment. The objective of this paper is to review persistent COVID-19 syndrome, to know its clinical manifestations and the strategies for the management and follow-up of these patients.}, }
@article {pmid34813820, year = {2022}, author = {Behnood, SA and Shafran, R and Bennett, SD and Zhang, AXD and O'Mahoney, LL and Stephenson, TJ and Ladhani, SN and De Stavola, BL and Viner, RM and Swann, OV}, title = {Persistent symptoms following SARS-CoV-2 infection amongst children and young people: A meta-analysis of controlled and uncontrolled studies.}, journal = {The Journal of infection}, volume = {84}, number = {2}, pages = {158-170}, pmid = {34813820}, issn = {1532-2742}, mesh = {Adolescent ; *COVID-19 ; Child ; Fatigue ; Fever/etiology ; Headache/complications/etiology ; Humans ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Data on the long-term impact of SARS-CoV-2 infection in children and young people (CYP) are conflicting. We assessed evidence on long-term post-COVID symptoms in CYP examining prevalence, risk factors, type and duration.<br><br>METHODS: Systematic search of published and unpublished literature using 13 online databases between 01/12/2019 and 31/07/2021. Eligible studies reported CYP &#x2264;19 years with confirmed or probable SARS-CoV-2 with any symptoms persisting beyond acute illness. Random effects meta-analyses estimated pooled risk difference in symptom prevalence (controlled studies only) and pooled prevalence (uncontrolled studies also included). Meta-regression examined study characteristics hypothesised to be associated with symptom prevalence. Prospectively registered: CRD42021233153.<br><br>FINDINGS: Twenty two of 3357 unique studies were eligible, including 23,141 CYP. Median duration of follow-up was 125 days (IQR 99-231). Pooled risk difference in post-COVID cases compared to controls (5 studies) were significantly higher for cognitive difficulties (3% (95% CI 1, 4)), headache (5% (1, 8)), loss of smell (8%, (2, 15)), sore throat (2% (1, 2)) and sore eyes (2% (1, 3)) but not abdominal pain, cough, fatigue, myalgia, insomnia, diarrhoea, fever, dizziness or dyspnoea. Pooled prevalence of symptoms in post-COVID participants in 17 studies ranged from 15% (diarrhoea) to 47% (fatigue). Age was associated with higher prevalence of all symptoms except cough. Higher study quality was associated with lower prevalence of all symptoms, except loss of smell and cognitive symptoms.<br><br>INTERPRETATION: The frequency of the majority of reported persistent symptoms was similar in SARS-CoV-2 positive cases and controls. This systematic review and meta-analysis highlights the critical importance of a control group in studies on CYP post SARS-CoV-2 infection.}, }
@article {pmid34816207, year = {2021}, author = {Newson, L and Manyonda, I and Lewis, R and Preissner, R and Preissner, S and Seeland, U}, title = {Sensitive to Infection but Strong in Defense-Female Sex and the Power of Oestradiol in the COVID-19 Pandemic.}, journal = {Frontiers in global women's health}, volume = {2}, number = {}, pages = {651752}, pmid = {34816207}, issn = {2673-5059}, abstract = {The incidence of SARS-CoV2 infections is around 15% higher in premenopausal women compared to age matched men, yet the fatality rate from COVID-19 is significantly higher in men than women for all age strata. Sex differences have also been observed in recent epidemics including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), with SARS-CoV 2 virus infection sex differences appear more dramatic. The regulation and expression of the angiotensin converting enzyme 2 (ACE2) is the key for this special coronavirus SARS-CoV-2 to enter the cell. 17β-oestradiol increases expression level and activity of angiotensin converting enzyme-2 (ACE2) and the alternative signaling pathway of Ang II via the angiotensin II receptor type II (AT2R) and the Mas receptor is more dominant in female sex than in male sex. Maybe a hint to explain the higher infection risk in women. The same hormonal milieu plays a major role in protecting women where morbidity and mortality are concerned, since the dominant female hormone, oestradiol, has immune-modulatory properties that are likely to be protective against virus infections. It is also known that the X chromosome contains the largest number of immune-related genes, potentially conferring an advantage to women in efficient immune responsiveness. Lifestyle factors are also likely to be contributory. Premenopausal women could possibly face higher exposure to infection (hence higher infection rates) because economic conditions are often less favorable for them with less opportunity for home office work because of jobs requiring mandatory attendance. Due to the additional task of childcare, it is likely that contact times with other people will be longer. Women generally make healthier lifestyle choices, thus reducing the disease burden that confers high risk of mortality in COVID-19 infected men. This narrative review aims to present key concepts and knowledge gaps on the effects of oestrogen associated with SARS-CoV2 infection and COVID-19 disease.}, }
@article {pmid34817268, year = {2022}, author = {Desai, AD and Lavelle, M and Boursiquot, BC and Wan, EY}, title = {Long-term complications of COVID-19.}, journal = {American journal of physiology. Cell physiology}, volume = {322}, number = {1}, pages = {C1-C11}, pmid = {34817268}, issn = {1522-1563}, support = {R01 HL152236/HL/NHLBI NIH HHS/United States ; }, mesh = {Algorithms ; COVID-19/*complications/etiology/*physiopathology ; Cardiovascular Diseases/etiology ; Central Nervous System Diseases/etiology ; Disease Progression ; Hematologic Diseases/etiology ; Humans ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {SARS-CoV-2 has rapidly spread across the globe and infected hundreds of millions of people worldwide. As our experience with this virus continues to grow, our understanding of both short-term and long-term complications of infection with SARS-CoV-2 continues to grow as well. Just as there is heterogeneity in the acute infectious phase, there is heterogeneity in the long-term complications seen following COVID-19 illness. The purpose of this review article is to present the current literature with regards to the epidemiology, pathophysiology, and proposed management algorithms for the various long-term sequelae that have been observed in each organ system following infection with SARS-CoV-2. We will also consider future directions, with regards to newer variants of the virus and their potential impact on the long-term complications observed.}, }
@article {pmid34821709, year = {2021}, author = {Bisaccia, G and Ricci, F and Recce, V and Serio, A and Iannetti, G and Chahal, AA and Ståhlberg, M and Khanji, MY and Fedorowski, A and Gallina, S}, title = {Post-Acute Sequelae of COVID-19 and Cardiovascular Autonomic Dysfunction: What Do We Know?.}, journal = {Journal of cardiovascular development and disease}, volume = {8}, number = {11}, pages = {}, pmid = {34821709}, issn = {2308-3425}, abstract = {Post-acute sequelae of SARS-CoV-2 (PASC), or long COVID syndrome, is emerging as a major health issue in patients with previous SARS-CoV-2 infection. Symptoms commonly experienced by patients include fatigue, palpitations, chest pain, dyspnea, reduced exercise tolerance, and "brain fog". Additionally, symptoms of orthostatic intolerance and syncope suggest the involvement of the autonomic nervous system. Signs of cardiovascular autonomic dysfunction appear to be common in PASC and are similar to those observed in postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia. In this review, we report on the epidemiology of PASC, discuss current evidence and possible mechanisms underpinning the dysregulation of the autonomic nervous system, and suggest nonpharmacological and pharmacological interventions to treat and relieve symptoms of PASC-associated dysautonomia.}, }
@article {pmid34828592, year = {2021}, author = {Brownlie, H and Speight, N}, title = {Back to the Future? Immunoglobulin Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.}, journal = {Healthcare (Basel, Switzerland)}, volume = {9}, number = {11}, pages = {}, pmid = {34828592}, issn = {2227-9032}, abstract = {The findings of controlled trials on use of intravenous immunoglobulin G (IV IgG) to treat myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are generally viewed as representing mixed results. On detailed review, a clearer picture emerges, which suggests that the potential therapeutic value of this intervention has been underestimated. Our analysis is consistent with the propositions that: (1) IgG is highly effective for a proportion of patients with severe and well-characterised ME/CFS; (2) responders can be predicted with a high degree of accuracy based on markers of immune dysfunction. Rigorous steps were taken in the research trials to record adverse events, with transient symptom exacerbation commonly experienced in both intervention and placebo control groups, suggesting that this reflected the impact of participation on people with an illness characterised by post-exertional symptom exacerbation. Worsening of certain specific symptoms, notably headache, did occur more commonly with IgG and may have been concomitant to effective treatment, being associated with clinical improvement. The findings emerging from this review are supported by clinical observations relating to treatment of patients with severe and very severe ME/CFS, for whom intramuscular and subcutaneous administration provide alternative options. We conclude that: (1) there is a strong case for this area of research to be revived; (2) pending further research, clinicians would be justified in offering a course of IgG to selected ME/CFS patients at the more severe end of the spectrum. As the majority of trial participants had experienced an acute viral or viral-like onset, we further suggest that IgG treatment may be pertinent to the care of some patients who remain ill following infection with SARS-CoV-2 virus.}, }
@article {pmid34830303, year = {2021}, author = {Loke, XY and Imran, SAM and Tye, GJ and Wan Kamarul Zaman, WS and Nordin, F}, title = {Immunomodulation and Regenerative Capacity of MSCs for Long-COVID.}, journal = {International journal of molecular sciences}, volume = {22}, number = {22}, pages = {}, pmid = {34830303}, issn = {1422-0067}, support = {FF-2021-378//National University of Malaysia/ ; FPR-1//National University of Malaysia/ ; }, mesh = {COVID-19/*complications/pathology/therapy/virology ; Humans ; Immunomodulation/*physiology ; Lung/pathology/physiology ; *Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/cytology/metabolism ; Regeneration/*physiology ; Respiratory Distress Syndrome/pathology/therapy ; SARS-CoV-2/isolation &amp; purification ; Post-Acute COVID-19 Syndrome ; }, abstract = {The rapid mutation of the SARS-CoV-2 virus is now a major concern with no effective drugs and treatments. The severity of the disease is linked to the induction of a cytokine storm that promotes extensive inflammation in the lung, leading to many acute lung injuries, pulmonary edema, and eventually death. Mesenchymal stem cells (MSCs) might prove to be a treatment option as they have immunomodulation and regenerative properties. Clinical trials utilizing MSCs in treating acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) have provided a basis in treating post-COVID-19 patients. In this review, we discussed the effects of MSCs as an immunomodulator to reduce the severity and death in patients with COVID-19, including the usage of MSCs as an alternative regenerative therapy in post-COVID-19 patients. This review also includes the current clinical trials in utilizing MSCs and their potential future utilization for long-COVID treatments.}, }
@article {pmid34839263, year = {2021}, author = {Deer, RR and Rock, MA and Vasilevsky, N and Carmody, L and Rando, H and Anzalone, AJ and Basson, MD and Bennett, TD and Bergquist, T and Boudreau, EA and Bramante, CT and Byrd, JB and Callahan, TJ and Chan, LE and Chu, H and Chute, CG and Coleman, BD and Davis, HE and Gagnier, J and Greene, CS and Hillegass, WB and Kavuluru, R and Kimble, WD and Koraishy, FM and Köhler, S and Liang, C and Liu, F and Liu, H and Madhira, V and Madlock-Brown, CR and Matentzoglu, N and Mazzotti, DR and McMurry, JA and McNair, DS and Moffitt, RA and Monteith, TS and Parker, AM and Perry, MA and Pfaff, E and Reese, JT and Saltz, J and Schuff, RA and Solomonides, AE and Solway, J and Spratt, H and Stein, GS and Sule, AA and Topaloglu, U and Vavougios, GD and Wang, L and Haendel, MA and Robinson, PN}, title = {Characterizing Long COVID: Deep Phenotype of a Complex Condition.}, journal = {EBioMedicine}, volume = {74}, number = {}, pages = {103722}, pmid = {34839263}, issn = {2352-3964}, support = {K23 DK124654/DK/NIDDK NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; R01 HG010067/HG/NHGRI NIH HHS/United States ; K23 HL128909/HL/NHLBI NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; K99 GM145411/GM/NIGMS NIH HHS/United States ; P30 AG024832/AG/NIA NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; }, mesh = {COVID-19/*complications/diagnosis/*pathology ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Numerous publications describe the clinical manifestations of post-acute sequelae of SARS-CoV-2 (PASC or "long COVID"), but they are difficult to integrate because of heterogeneous methods and the lack of a standard for denoting the many phenotypic manifestations. Patient-led studies are of particular importance for understanding the natural history of COVID-19, but integration is hampered because they often use different terms to describe the same symptom or condition. This significant disparity in patient versus clinical characterization motivated the proposed ontological approach to specifying manifestations, which will improve capture and integration of future long COVID studies.<br><br>METHODS: The Human Phenotype Ontology (HPO) is a widely used standard for exchange and analysis of phenotypic abnormalities in human disease but has not yet been applied to the analysis of COVID-19.<br><br>FUNDING: We identified 303 articles published before April 29, 2021, curated 59 relevant manuscripts that described clinical manifestations in 81 cohorts three weeks or more following acute COVID-19, and mapped 287 unique clinical findings to HPO terms. We present layperson synonyms and definitions that can be used to link patient self-report questionnaires to standard medical terminology. Long COVID clinical manifestations are not assessed consistently across studies, and most manifestations have been reported with a wide range of synonyms by different authors. Across at least 10 cohorts, authors reported 31 unique clinical features corresponding to HPO terms; the most commonly reported feature was Fatigue (median 45.1%) and the least commonly reported was Nausea (median 3.9%), but the reported percentages varied widely between studies.<br><br>INTERPRETATION: Translating long COVID manifestations into computable HPO terms will improve analysis, data capture, and classification of long COVID patients. If researchers, clinicians, and patients share a common language, then studies can be compared/pooled more effectively. Furthermore, mapping lay terminology to HPO will help patients assist clinicians and researchers in creating phenotypic characterizations that are computationally accessible, thereby improving the stratification, diagnosis, and treatment of long COVID.<br><br>FUNDING: U24TR002306; UL1TR001439; P30AG024832; GBMF4552; R01HG010067; UL1TR002535; K23HL128909; UL1TR002389; K99GM145411.}, }
@article {pmid34845562, year = {2022}, author = {Sapkota, HR and Nune, A}, title = {Long COVID from rheumatology perspective - a narrative review.}, journal = {Clinical rheumatology}, volume = {41}, number = {2}, pages = {337-348}, pmid = {34845562}, issn = {1434-9949}, mesh = {*COVID-19/complications ; Humans ; *Rheumatic Diseases/complications/diagnosis ; *Rheumatology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long-term sequel of acute COVID-19, commonly referred to as long COVID, has affected millions of patients worldwide. Long COVID patients display persistent or relapsing and remitting symptoms that include fatigue, breathlessness, cough, myalgia, arthralgia, sleep disturbance, cognitive impairment and skin rashes. Due to the shared clinical features, laboratory and imaging findings, long COVID could mimic rheumatic disease posing a diagnostic challenge. Our comprehensive literature review will help rheumatologist to be aware of long COVID manifestations and differentiating features from rheumatic diseases to ensure a timely and correct diagnosis is reached.}, }
@article {pmid34850268, year = {2021}, author = {Steinestel, K and Czech, A and Hackenbroch, C and Bloch, W and Gagiannis, D}, title = {[Clinical, radiological, and histopathological features of pulmonary post-COVID syndrome : A form of autoimmune-mediated interstitial lung disease?].}, journal = {Der Pathologe}, volume = {42}, number = {Suppl 2}, pages = {160-164}, pmid = {34850268}, issn = {1432-1963}, mesh = {Adult ; *COVID-19 ; Humans ; Lung/diagnostic imaging ; *Lung Diseases, Interstitial ; Pilot Projects ; SARS-CoV-2 ; }, abstract = {BACKGROUND: About 10% of patients develop persistent symptoms after mild/moderate COVID-19. We have previously reported detection of antinuclear autoantibodies/extractable nuclear antigens (ANA/ENA) in patients with severe COVID-19.<br><br>OBJECTIVES: The aim of this small pilot study was to characterize long-/post-COVID and to evaluate possible similarities between lung involvement in long-/post-COVID and connective tissue disease (CTD).<br><br>METHODS: We prospectively enrolled 33&#xa0;previously healthy patients with persistent pulmonal symptoms after mild/moderate COVID-19 without hospitalization (median age, 39&#x202f;years). We performed clinical evaluation including pulmonary function tests, computed tomography (CT), and serology for ANA/ENA. In 29 of 33&#xa0;patients, transbronchial biopsies (TBBs) were taken for histopathological assessment.<br><br>RESULTS: Most patients presented with disturbed oxygen pulse in spiroergometry and slight lymphocytosis in bronchoalveolar lavage (BAL) fluid. The CT pattern showed bronchial wall thickening and increased low-attenuation volume. Autoantibodies were detected in 13 of 33&#xa0;patients (39.4%). Histopathological assessment showed interstitial lymphocytosis with alveolar fibrin and organizing pneumonia. Ultrastructural analyses revealed interstitial collagen deposition.<br><br>CONCLUSION: While histopathology of pulmonary long-/post-COVID alone is unspecific, the combination with clinical and radiological features together with detection of autoantibodies would allow for a&#xa0;diagnosis of interstitial pneumonia with autoimmune features (IPAF). Since we observe interstitial collagen deposition and since IPAF/CTD-ILD might progress to fibrosis, the persistence of autoantibodies and possible fibrotic change should be closely monitored in autoantibody-positive long-/post-COVID patients.}, }
@article {pmid34850782, year = {2021}, author = {Marciniak, E and Górniak, A and Hanke, W}, title = {[Long lasting symptoms of dyspnea, cough and fatigue after COVID-19 - narrative review of epidemiological studies].}, journal = {Medycyna pracy}, volume = {72}, number = {6}, pages = {711-720}, doi = {10.13075/mp.5893.01190}, pmid = {34850782}, issn = {2353-1339}, mesh = {*COVID-19/complications ; Cough/epidemiology/etiology ; Dyspnea/epidemiology ; Epidemiologic Studies ; Humans ; Middle Aged ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {"Long-COVID" is described as long-term effects of SARS‑ CoV‑2 infection that last >4 weeks after the acutephase of infection. The aim of this narrative reviews to evaluate the frequency of occurrence of 3 symptoms often observed in Long-COVID, i.e., chronic fatigue, shortness of breath and cough, and whether comorbidities such as diabetes and arterial hypertension increase the risk of complications after a history of SARS‑ CoV‑2 infection. The method of narrative review was used in this paper. PubMed (May 31, 2021) search was performed to retrieve articles concerning the occurrence of long COVID-19 chronic fatigue, dyspnoea and chronic cough. Studies in which the observation period was <30 days and the average age of subjects exceeded 60 years, as well as studies with no information on the methodology used, in particular without the method of recruiting people for the study, were excluded. Populations with a high frequency of diabetes were defined as the prevalence >10%, and in the case of arterial hypertension >40%. The average frequency of diabetes <10%, hypertension 40%. It can be concluded that in the period of >30 days after discharge from the hospital, in populations with a high incidence of diabetes and hypertension, the incidence of chronic fatigue and cough was higher than in the other analyzed groups. Symptoms of dyspnea were most frequently reported in populations with high rates of diabetes, but at the same time in the average percentage of people with arterial hypertension. Persistent symptoms specific to "Long-COVID" can significantly reduce the ability to perform work. In this situation, check-ups performed before returning to work after long-term leave tape on a new dimension. Med Pr. 2021;72(6):711-20.}, }
@article {pmid34851455, year = {2021}, author = {Rabady, S and Altenberger, J and Brose, M and Denk-Linnert, DM and Fertl, E and Götzinger, F and de la Cruz Gomez Pellin, M and Hofbaur, B and Hoffmann, K and Hoffmann-Dorninger, R and Koczulla, R and Lammel, O and Lamprecht, B and Löffler-Ragg, J and Müller, CA and Poggenburg, S and Rittmannsberger, H and Sator, P and Strenger, V and Vonbank, K and Wancata, J and Weber, T and Weber, J and Weiss, G and Wendler, M and Zwick, RH}, title = {[Guideline S1: Long COVID: Diagnostics and treatment strategies].}, journal = {Wiener klinische Wochenschrift}, volume = {133}, number = {Suppl 7}, pages = {237-278}, pmid = {34851455}, issn = {1613-7671}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {This guideline comprises the state of science at the time of the editorial deadline. In view of the high turnover of knowledge the guideline is designed as a living guideline. The main objective was to provide a tool for the use in primary care, being considered well suited as a first point of entry and for the provision of care. The guideline gives recommendations on the differential diagnosis of symptoms following SARS-CoV‑2 infection, on their therapeutic options, as well as for guidance and care of the patients concerned. It also offers advice concerning return to daily life and rehabilitation. Long COVID being a very variable condition, we chose an interdisciplinary approach.}, }
@article {pmid34853527, year = {2021}, author = {Murugan, AK and Alzahrani, AS}, title = {SARS-CoV-2: Emerging Role in the Pathogenesis of Various Thyroid Diseases.}, journal = {Journal of inflammation research}, volume = {14}, number = {}, pages = {6191-6221}, pmid = {34853527}, issn = {1178-7031}, abstract = {Coronavirus disease-2019 (COVID-19) is asymptomatic in most cases, but it is impartible and fatal in fragile and elderly people. Heretofore, more than four million people succumbed to COVID-19, while it spreads to every part of the globe. Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) induces various dysfunctions in many vital organs including the thyroid by utilizing ACE2 as a receptor for cellular entry. Emerging reports clearly show the involvement of SARS-CoV-2 in diverse thyroid disorders. Thus, this review article aims to review comprehensively all the recent developments in SARS-CoV-2-induced pathogenesis of thyroid diseases. The review briefly summarizes the recent key findings on the mechanism of SARS-CoV-2 infection, the role of ACE2 receptor in viral entry, SARS-CoV-2-activated molecular signaling in host cells, ACE2 expression in the thyroid, cytokine storm, and its vital role in thyroid dysfunction and long-COVID in relation to thyroid and autoimmunity. Further, it extensively discusses rapidly evolving knowledge on the potential part of SARS-CoV-2 in emerging various thyroid dysfunctions during and post-COVID-19 conditions which include subacute thyroiditis, Graves' diseases, Hashimoto's thyroiditis, thyrotoxicosis, and other recent advances in further discerning the implications of this virus within thyroid dysfunction. Unraveling the pathophysiology of SARS-CoV-2-triggered thyroid dysfunctions may aid pertinent therapeutic options and management of these patients in both during and post-COVID-19 scenarios.}, }
@article {pmid34853850, year = {2021}, author = {Ladani, AP and Loganathan, M and Kolikonda, MK and Lippmann, S}, title = {COVID-19 Legacy.}, journal = {Southern medical journal}, volume = {114}, number = {12}, pages = {751-759}, pmid = {34853850}, issn = {1541-8243}, mesh = {COVID-19/*complications/*epidemiology ; Comorbidity ; Humans ; Incidence ; Pandemics ; Prognosis ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Coronavirus disease 2019 (COVID-19) is an infection caused by the severe acute respiratory syndrome-coronavirus-2 virus that led to a pandemic. Acute manifestations of COVID-19 include fever, cough, dyspnea, respiratory failure, pneumonitis, anosmia, thromboembolic events, cardiogenic shock, renal injury, ischemic strokes, encephalitis, and cutaneous eruptions, especially of hands or feet. Prolonged symptoms, unpredictable recoveries, and chronic sequelae (long COVID) sometimes emerge even for some people who survive the initial illness. Sequelae such as fatigue occasionally persist even for those with only mild to moderate cases. There is much to learn about postacute COVID-19 dyspnea, anosmia, psychosis, thyroiditis, cardiac arrhythmia, and/or multisystem inflammatory response syndrome in children. Determining prognoses is imprecise. Examining patient databases about those who have survived COVID-19 is warranted. Multidisciplinary teams are assessing such disease databases to better understand longer-term complications and guide treatment.}, }
@article {pmid34870392, year = {2021}, author = {Zimmermann, P and Pittet, LF and Curtis, N}, title = {How Common is Long COVID in Children and Adolescents?.}, journal = {The Pediatric infectious disease journal}, volume = {40}, number = {12}, pages = {e482-e487}, pmid = {34870392}, issn = {1532-0987}, mesh = {Adolescent ; COVID-19/*complications/epidemiology/ethnology/*pathology ; Child ; Humans ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {In children, the risk of coronavirus disease (COVID) being severe is low. However, the risk of persistent symptoms following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is uncertain in this age group, and the features of "long COVID" are poorly characterized. We reviewed the 14 studies to date that have reported persistent symptoms following COVID in children and adolescents. Almost all the studies have major limitations, including the lack of a clear case definition, variable follow-up times, inclusion of children without confirmation of SARS-CoV-2 infection, reliance on self- or parent-reported symptoms without clinical assessment, nonresponse and other biases, and the absence of a control group. Of the 5 studies which included children and adolescents without SARS-CoV-2 infection as controls, 2 did not find persistent symptoms to be more prevalent in children and adolescents with evidence of SARS-CoV-2 infection. This highlights that long-term SARS-CoV-2 infection-associated symptoms are difficult to distinguish from pandemic-associated symptoms.}, }
@article {pmid34881263, year = {2021}, author = {Wu, L and Wu, Y and Xiong, H and Mei, B and You, T}, title = {Persistence of Symptoms After Discharge of Patients Hospitalized Due to COVID-19.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {761314}, pmid = {34881263}, issn = {2296-858X}, abstract = {Many patients who had coronavirus disease 2019 (COVID-19) had at least one symptom that persisted after recovery from the acute phase. Our purpose was to review the empirical evidence on symptom prevalence, complications, and management of patients with long COVID. We systematically reviewed the literature on the clinical manifestations of long COVID-19, defined by the persistence of symptoms beyond the acute phase of infection. Bibliographic searches in PubMed and Google Scholar were conducted to retrieve relevant studies on confirmed patients with long COVID that were published prior to August 30, 2021. The most common persistent symptoms were fatigue, cough, dyspnea, chest pains, chest tightness, joint pain, muscle pain, loss of taste or smell, hair loss, sleep difficulties, anxiety, and depression. Some of the less common persistent symptoms were skin rash, decreased appetite, sweating, inability to concentrate, and memory lapses. In addition to these general symptoms, some patients experienced dysfunctions of specific organs, mainly the lungs, heart, kidneys, and nervous system. A comprehensive understanding of the persistent clinical manifestations of COVID-19 can improve and facilitate patient management and referrals. Prompt rehabilitative care and targeted interventions of these patients may improve their recovery from physical, immune, and mental health symptoms.}, }
@article {pmid34884216, year = {2021}, author = {Vallée, A}, title = {Dysautonomia and Implications for Anosmia in Long COVID-19 Disease.}, journal = {Journal of clinical medicine}, volume = {10}, number = {23}, pages = {}, pmid = {34884216}, issn = {2077-0383}, abstract = {Long COVID-19 patients often reported anosmia as one of the predominant persisting symptoms. Recent findings have shown that anosmia is associated with neurological dysregulations. However, the involvement of the autonomic nervous system (ANS), which can aggregate all the long COVID-19 neurological symptoms, including anosmia, has not received much attention in the literature. Dysautonomia is characterized by the failure of the activities of components in the ANS. Long COVID-19 anosmia fatigue could result from damage to olfactory sensory neurons, leading to an augmentation in the resistance to cerebrospinal fluid outflow by the cribriform plate, and further causing congestion of the glymphatic system with subsequent toxic build-up in the brain. Studies have shown that anosmia was an important neurologic symptom described in long COVID-19 in association with potential COVID-19 neurotropism. SARS-CoV-2 can either travel via peripheral blood vessels causing endothelial dysfunction, triggering coagulation cascade and multiple organ dysfunction, or reach the systemic circulation and take a different route to the blood-brain barrier, damaging the blood-brain barrier and leading to neuroinflammation and neuronal excitotoxicity. SARS-CoV-2 entry via the olfactory epithelium and the increase in the expression of TMPRSS2 with ACE2 facilitates SARS-CoV-2 neurotropism and then dysautonomia in long COVID-19 patients. Due to this effect, patients with anosmia persisting 3 months after COVID-19 diagnosis showed extensive destruction of the olfactory epithelium. Persistent anosmia observed among long COVID-19 patients may be involved by a cascade of effects generated by dysautonomia leading to ACE2 antibodies enhancing a persistent immune activation.}, }
@article {pmid34888989, year = {2022}, author = {Yong, SJ and Liu, S}, title = {Proposed subtypes of post-COVID-19 syndrome (or long-COVID) and their respective potential therapies.}, journal = {Reviews in medical virology}, volume = {32}, number = {4}, pages = {e2315}, doi = {10.1002/rmv.2315}, pmid = {34888989}, issn = {1099-1654}, mesh = {*COVID-19/complications ; *Fatigue Syndrome, Chronic/diagnosis/epidemiology/etiology ; Humans ; Pandemics ; *Postural Orthostatic Tachycardia Syndrome/diagnosis/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {The effects of coronavirus disease 2019 (COVID-19), a highly transmissible infectious respiratory disease that has initiated an ongoing pandemic since early 2020, do not always end in the acute phase. Depending on the study referred, about 10%-30% (or more) of COVID-19 survivors may develop long-COVID or post-COVID-19 syndrome (PCS), characterised by persistent symptoms (most commonly fatigue, dyspnoea, and cognitive impairments) lasting for 3 months or more after acute COVID-19. While the pathophysiological mechanisms of PCS have been extensively described elsewhere, the subtypes of PCS have not. Owing to its highly multifaceted nature, this review proposes and characterises six subtypes of PCS based on the existing literature. The subtypes are non-severe COVID-19 multi-organ sequelae (NSC-MOS), pulmonary fibrosis sequelae (PFS), myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), postural orthostatic tachycardia syndrome (POTS), post-intensive care syndrome (PICS) and medical or clinical sequelae (MCS). Original studies supporting each of these subtypes are documented in this review, as well as their respective symptoms and potential interventions. Ultimately, the subtyping proposed herein aims to provide better clarity on the current understanding of PCS.}, }
@article {pmid34899999, year = {2022}, author = {Shimohata, T}, title = {Neuro-COVID-19.}, journal = {Clinical &amp; experimental neuroimmunology}, volume = {13}, number = {1}, pages = {17-23}, pmid = {34899999}, issn = {1759-1961}, abstract = {Neuromuscular manifestations of new coronavirus disease 2019 (COVID-19) infection are frequent, and include dizziness, headache, myopathy, and olfactory and gustatory disturbances. Patients with acute central nervous system disorders, such as delirium, impaired consciousness, stroke and convulsive seizures, have a high mortality rate. The encephalitis/encephalopathy that causes consciousness disturbance and seizures can be classified into three conditions, including direct infection with the SARS-CoV-2 virus, encephalopathy caused by central nervous system damage secondary to systemic hypercytokinemia (cytokine storm) and autoimmune-mediated encephalitis that occurs after infection. The sequelae, called post-acute COVID-19 syndrome or long COVID, include neuromuscular manifestations, such as anxiety, depression, sleep disturbance, muscle weakness, brain fog and cognitive impairment. It is desirable to establish diagnostic criteria and treatment for these symptoms. Vaccine-induced thrombotic thrombocytopenia, Guillain-Barré syndrome, bilateral facial paralysis, encephalitis and opsoclonus-myoclonus syndrome have been reported as adverse reactions after the COVID-19 vaccine, although these are rare.}, }
@article {pmid34905407, year = {2022}, author = {Miller, L and Berber, E and Sumbria, D and Rouse, BT}, title = {Controlling the Burden of COVID-19 by Manipulating Host Metabolism.}, journal = {Viral immunology}, volume = {35}, number = {1}, pages = {24-32}, pmid = {34905407}, issn = {1557-8976}, support = {R21 AI142862/AI/NIAID NIH HHS/United States ; R01 EY005093/EY/NEI NIH HHS/United States ; }, mesh = {*COVID-19/metabolism/therapy ; *Cost of Illness ; Humans ; Pandemics ; SARS-CoV-2 ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic caused by the coronavirus-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to cause global health problems, but its impact would be minimized if the many effective vaccines that have been developed were available and in widespread use by all societies. This ideal situation is not occurring so other means of controlling COVID-19 are needed. In this short review, we make the case that manipulating host metabolic pathways could be a therapeutic approach worth exploring. The rationale for such an approach comes from the fact that viruses cause metabolic changes in cells they infect, effective host defense mechanisms against viruses requires the activity of one or more metabolic pathways, and that hosts with metabolic defects such as diabetes are more susceptible to severe consequences after COVID-19. We describe the types of approaches that could be used to redirect various aspects of host metabolism and the success that some of these maneuvers have had at controlling other virus infections. Manipulating metabolic activities to control the outcome of COVID-19 has to date received minimal attention. Manipulating host metabolism will never replace vaccines to control COVID-19 but could be used as an adjunct therapy to the extent of ongoing infection.}, }
@article {pmid34912345, year = {2021}, author = {Emadi-Baygi, M and Ehsanifard, M and Afrashtehpour, N and Norouzi, M and Joz-Abbasalian, Z}, title = {Corona Virus Disease 2019 (COVID-19) as a System-Level Infectious Disease With Distinct Sex Disparities.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {778913}, pmid = {34912345}, issn = {1664-3224}, mesh = {Biomarkers ; Blood Coagulation ; Blood Coagulation Disorders/diagnosis/etiology ; COVID-19/complications/diagnosis/*epidemiology/*virology ; Cytokines/metabolism ; Disease Susceptibility ; Endothelium/metabolism ; Female ; Host-Pathogen Interactions/immunology ; Humans ; Inflammation Mediators ; Male ; Renin-Angiotensin System ; *SARS-CoV-2 ; Severity of Illness Index ; Sex Factors ; }, abstract = {The current global pandemic of the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) causing COVID-19, has infected millions of people and continues to pose a threat to many more. Angiotensin-Converting Enzyme 2 (ACE2) is an important player of the Renin-Angiotensin System (RAS) expressed on the surface of the lung, heart, kidney, neurons, and endothelial cells, which mediates SARS-CoV-2 entry into the host cells. The cytokine storms of COVID-19 arise from the large recruitment of immune cells because of the dis-synchronized hyperactive immune system, lead to many abnormalities including hyper-inflammation, endotheliopathy, and hypercoagulability that produce multi-organ dysfunction and increased the risk of arterial and venous thrombosis resulting in more severe illness and mortality. We discuss the aberrated interconnectedness and forthcoming crosstalks between immunity, the endothelium, and coagulation, as well as how sex disparities affect the severity and outcome of COVID-19 and harm men especially. Further, our conceptual framework may help to explain why persistent symptoms, such as reduced physical fitness and fatigue during long COVID, may be rooted in the clotting system.}, }
@article {pmid34913540, year = {2024}, author = {Cha, C and Baek, G}, title = {Symptoms and management of long COVID: A scoping review.}, journal = {Journal of clinical nursing}, volume = {33}, number = {1}, pages = {11-28}, doi = {10.1111/jocn.16150}, pmid = {34913540}, issn = {1365-2702}, mesh = {Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Pandemics ; COVID-19 Drug Treatment ; Fatigue ; Cough ; }, abstract = {AIM: This scoping review aims to describe published work on the symptoms and management of long COVID conditions.<br><br>BACKGROUND: Symptoms and management of COVID-19 have focused on the acute stage. However, long-term consequences have also been observed.<br><br>METHODS: A scoping review was performed based on the framework suggested by Arksey and O'Malley. We conducted a literature search to retrieve articles published from May 2020 to March 2021 in CINHAL, Cochrane library, Embase, PubMed and Web of science, including backward and forward citation tracking from the included articles. Among the 1880 articles retrieved, 34 articles met our criteria for review: 21 were related to symptom presentation and 13 to the management of long COVID.<br><br>RESULTS: Long COVID symptoms were described in 21 articles. Following COVID-19 treatment, hospitalised patients most frequently reported dyspnoea, followed by anosmia/ageusia, fatigue and cough, while non-hospitalised patients commonly reported cough, followed by fever and myalgia/arthralgia. Thirteen studies described management for long COVID: Focused on a multidisciplinary approach in seven articles, pulmonary rehabilitation in three articles, fatigue management in two articles and psychological therapy in one study.<br><br>CONCLUSION: People experience varied COVID-19 symptoms after treatment. However, guidelines on evidence-based, multidisciplinary management for long COVID conditions are limited in the literature. The COVID-19 pandemic may extend due to virus mutations; therefore, it is crucial to develop and disseminate evidence-based, multidisciplinary management guidelines.<br><br>A rehabilitation care plan and community healthcare plans are necessary for COVID-19 patients before discharge. Remote programmes could facilitate the monitoring and screening of people with long COVID.}, }
@article {pmid34918437, year = {2022}, author = {Schneider, SA and Hennig, A and Martino, D}, title = {Relationship between COVID-19 and movement disorders: A narrative review.}, journal = {European journal of neurology}, volume = {29}, number = {4}, pages = {1243-1253}, doi = {10.1111/ene.15217}, pmid = {34918437}, issn = {1468-1331}, mesh = {*COVID-19/complications ; COVID-19 Vaccines ; Humans ; *Movement Disorders/epidemiology/etiology ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND AND PURPOSE: The scientific literature on COVID-19 is increasingly growing.<br><br>METHODS: In this paper, we review the literature on movement disorders in the context of the COVID-19 pandemic.<br><br>RESULTS: First, there are a variety of transient movement disorders that may manifest in the acute phase of COVID-19, most often myoclonus, with more than 50 patients described in the literature. New onset parkinsonism, chorea, and tic-like behaviours have also been reported. Movement disorders as a side effect after COVID-19 vaccination are rare, occurring with a frequency of 0.00002-0.0002 depending on the product used, mostly manifesting with tremor. Current evidence for potential long-term manifestations, for example, long COVID parkinsonism, is separately discussed. Second, the pandemic has also had an impact on patients with pre-existing movement disorder syndromes, with negative effects on clinical status and overall well-being, and reduced access to medication and health care. In many parts, the pandemic has led to reorganization of the medical system, including the development of new digital solutions. The movement disorder-related evidence for this is reviewed and discussed.<br><br>CONCLUSIONS: The pandemic and the associated preventive measures have had a negative impact on the clinical status, access to health care, and overall well-being of patients with pre-existing movement disorders.}, }
@article {pmid34919045, year = {2021}, author = {Chowdhury, F and Grigoriadou, S and Bombardieri, M}, title = {Severity of COVID-19 infection in primary Sjögren's syndrome and the emerging evidence of COVID-19-induced xerostomia.}, journal = {Clinical and experimental rheumatology}, volume = {39 Suppl 133}, number = {6}, pages = {215-222}, doi = {10.55563/clinexprheumatol/k7x3ta}, pmid = {34919045}, issn = {0392-856X}, support = {21268/VAC_/Versus Arthritis/United Kingdom ; MR/N003063/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*Autoimmune Diseases ; *COVID-19 ; Humans ; SARS-CoV-2 ; *Sjogren's Syndrome/diagnosis/drug therapy/epidemiology ; *Xerostomia ; }, abstract = {Since the beginning of the COVID-19 disease pandemic caused by the new coronavirus SARS-CoV-2, the disease has claimed over 205M cases (205,338,159) and 4,333,094 deaths (WHO dashboard - accessed 15/08/2021). In addition to the overwhelming impact on healthcare systems treating acutely ill patients, the pandemic has had an impact on all other aspects of health care delivery, including the management of chronic diseases, the risk that is posed in patients with chronic conditions and the risk of the infection itself in those with chronic conditions. Autoimmune rheumatic diseases (ARDs), including primary Sjögren's syndrome (pSS), characterised by immune dysregulation affecting several organs in variable severity, have been of particular interest given the accelerated phase of the immune response in the course of SARS-CoV-2 infection leading to the acute inflammatory response and respiratory distress syndrome or multi-organ failure. On the other hand, the effect of immunosuppressive drug therapies can represent a double edge sword on the course of the disease, either by increased susceptibility to and severity of the infection, or by preventing the accelerated inflammatory response induced by the infection. Additionally, the long-term impact of SARS-CoV-2 infection on the host immune system has led to the onset of novel complex clinical manifestations, comprised under the large umbrella of "long-COVID", which we are only starting to understand. In this review we focus on two interrelated aspects: i) the impact of COVID-19 on patients with pSS and ii) the emerging evidence of long-term xerostomia after SARS-CoV-2 infection.}, }
@article {pmid34927603, year = {2022}, author = {Kasi, SG and Dhir, SK and Shah, A and Shivananda, S and Verma, S and Marathe, S and Chatterjee, K and Agarwalla, S and Srirampur, S and Kalyani, S and Pemde, HK and Balasubramanian, S and Basavaraja, GV and Parekh, BJ and Kumar, R and Gupta, P and , }, title = {Coronavirus Disease 2019 (COVID-19) Vaccination for Children: Position Statement of Indian Academy of Pediatrics Advisory Committee on Vaccination and Immunization Practices.}, journal = {Indian pediatrics}, volume = {59}, number = {1}, pages = {51-57}, pmid = {34927603}, issn = {0974-7559}, mesh = {Adolescent ; Advisory Committees ; *COVID-19/complications ; COVID-19 Vaccines ; Child ; Child, Preschool ; Humans ; Immunization ; Immunization Schedule ; *Pediatrics ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome ; Vaccination ; Post-Acute COVID-19 Syndrome ; }, abstract = {JUSTIFICATION: Data generated after the first wave has revealed that some children with coronavirus 19 (COVID-19) can become seriously ill. Multi-inflammatory syndrome in children (MIS-C) and long COVID cause significant morbidity in children. Prolonged school closures and quarantine have played havoc with the psychosocial health of children. Many countries in the world have issued emergency use authorisation (EUA) of selected Covid-19 vaccines for use in children. In India, a Subject Expert Committee (SEC) has recommended the use of Covaxin (Bharat Biotech) for children from the ages of 2-18 years. The recommendation has been given to the Drugs Controller General of India (DCGI) for final approval.<br><br>OBJECTIVE: To provide an evidence-based document to guide the pediatricians on the recommendation to administer COVID vaccines to children, as and when they are available for use.<br><br>PROCESS: Formulation of key questions was done by the committee, followed by review of literature on epidemiology and burden of Covid-19 in children, review of the studies on COVID vaccines in children, and the IAP stand on Covid-19 vaccination in children. The available data was discussed in the ACVIP focused WhatsApp group followed by an online meeting on 24 October, 2021, wherein the document was discussed in detail and finalized.<br><br>RECOMMENDATIONS: The IAP supports the Government of India's decision to extend the COVID-19 vaccination program to children between 2-18 years of age. Children with high-risk conditions may be immunized on a priority basis. The IAP and its members should be a partner with the Government of India, in the implementation of this program and the surveillance that is necessary following the roll-out.}, }
@article {pmid34930107, year = {2021}, author = {Chen, C and Amelia, A and Ashdown, GW and Mueller, I and Coussens, AK and Eriksson, EM}, title = {Risk surveillance and mitigation: autoantibodies as triggers and inhibitors of severe reactions to SARS-CoV-2 infection.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {27}, number = {1}, pages = {160}, pmid = {34930107}, issn = {1528-3658}, support = {GNT1161627//National Health and Medical Research Council/ ; GNT1043345//National Health and Medical Research Council/ ; }, mesh = {Animals ; Autoantibodies/*immunology/*metabolism ; Autoimmunity/physiology ; COVID-19/*complications/*immunology/metabolism ; Humans ; SARS-CoV-2/*immunology/metabolism ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19 clinical presentation differs considerably between individuals, ranging from asymptomatic, mild/moderate and severe disease which in some cases are fatal or result in long-term effects. Identifying immune mechanisms behind severe disease development informs screening strategies to predict who are at greater risk of developing life-threatening complications. However, to date clear prognostic indicators of individual risk of severe or long COVID remain elusive. Autoantibodies recognize a range of self-antigens and upon antigen recognition and binding, important processes involved in inflammation, pathogen defence and coagulation are modified. Recent studies report a significantly higher prevalence of autoantibodies that target immunomodulatory proteins including cytokines, chemokines, complement components, and cell surface proteins in COVID-19 patients experiencing severe disease compared to those who experience mild or asymptomatic infections. Here we discuss the diverse impacts of autoantibodies on immune processes and associations with severe COVID-19 disease.}, }
@article {pmid34933829, year = {2022}, author = {Sansone, A and Mollaioli, D and Limoncin, E and Ciocca, G and Bắc, NH and Cao, TN and Hou, G and Yuan, J and Zitzmann, M and Giraldi, A and Jannini, EA}, title = {The Sexual Long COVID (SLC): Erectile Dysfunction as a Biomarker of Systemic Complications for COVID-19 Long Haulers.}, journal = {Sexual medicine reviews}, volume = {10}, number = {2}, pages = {271-285}, pmid = {34933829}, issn = {2050-0521}, mesh = {Biomarkers ; *COVID-19/complications ; *Erectile Dysfunction/epidemiology ; Humans ; Male ; Quality of Life/psychology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Long term complications of COVID-19, the disease caused by the SARS-CoV-2, involve many organ systems, dramatically worsening the quality of life, and finally contributing to impaired physical functioning. Despite the presence of well-identified pathogenetic mechanisms, the effect of "Long COVID" on sexual health has been only marginally addressed.<br><br>OBJECTIVES: To provide coverage of the current literature on long COVID, its epidemiology, pathophysiology, and relevance for erectile function.<br><br>METHODS: Comprehensive review of literature pertaining to the epidemiology and pathophysiology of long COVID, and its relevance for erectile function.<br><br>RESULTS: Symptoms of long COVID are highly prevalent and involve almost all systems of the human body, with a plethora of clinical manifestations which range from minor nuisances to life-threatening conditions. "Brain fog" and fatigue are the most common complaints, although other neuropsychiatric complications, including sensory dysfunctions, anxiety, depression, and cerebrovascular events have also been reported. The respiratory and cardiovascular systems are also affected, with dyspnea, pulmonary fibrosis, endothelial dysfunction, and myocarditis occurring in some COVID long haulers. A subset of patients might develop endocrine manifestations, including onset of diabetes, thyroid dysfunction, and hypogonadism. Overall, long COVID features many complications which can impair erectile function by multiple pathogenetic mechanisms, and which could require tailored treatment: (i) careful investigation and management from the sexual medicine expert are therefore much needed, (ii) and future research on this topic is warranted.<br><br>CONCLUSION: in COVID-19 long haulers, several complications can adversely affect erectile function which, upon future tailored studies, could be used as biomarker for the severity of the long COVID disease and for its follow-up. Sansone A, Mollaioli D, Limoncin E et&#xa0;al. The Sexual Long COVID (SLC): Erectile Dysfunction as a Biomarker of Systemic Complications for COVID-19 Long Haulers. Sex Med Rev 2022;10:271-285.}, }
@article {pmid34940980, year = {2021}, author = {Danieli, MG and Piga, MA and Paladini, A and Longhi, E and Mezzanotte, C and Moroncini, G and Shoenfeld, Y}, title = {Intravenous immunoglobulin as an important adjunct in the prevention and therapy of coronavirus 2019 disease.}, journal = {Scandinavian journal of immunology}, volume = {94}, number = {5}, pages = {e13101}, pmid = {34940980}, issn = {1365-3083}, mesh = {Adult ; Antiviral Agents/*therapeutic use ; Autoimmune Diseases/etiology/immunology/*prevention &amp; control ; COVID-19/*complications/etiology/immunology/prevention &amp; control ; COVID-19 Vaccines/adverse effects/*immunology ; Chemotherapy, Adjuvant ; Critical Illness ; Humans ; Immunoglobulins, Intravenous/*therapeutic use ; Italy ; Length of Stay ; Respiration, Artificial ; SARS-CoV-2/*physiology ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {The coronavirus disease-19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenged globally with its morbidity and mortality. A small percentage of affected patients (20%) progress into the second stage of the disease clinically presenting with severe or fatal involvement of lung, heart and vascular system, all contributing to multiple-organ failure. The so-called 'cytokines storm' is considered the pathogenic basis of severe disease and it is a target for treatment with corticosteroids, immunotherapies and intravenous immunoglobulin (IVIg). We provide an overview of the role of IVIg in the therapy of adult patients with COVID-19 disease. After discussing the possible underlying mechanisms of IVIg immunomodulation in COVID-19 disease, we review the studies in which IVIg was employed. Considering the latest evidence that show a link between new coronavirus and autoimmunity, we also discuss the use of IVIg in COVID-19 and anti-SARS-CoV-2 vaccination related autoimmune diseases and the post-COVID-19 syndrome. The benefit of high-dose IVIg is evident in almost all studies with a rapid response, a reduction in mortality and improved pulmonary function in critically ill COVID-19 patients. It seems that an early administration of IVIg is crucial for a successful outcome. Studies' limitations are represented by the small number of patients, the lack of control groups in some and the heterogeneity of included patients. IVIg treatment can reduce the stay in ICU and the demand for mechanical ventilation, thus contributing to attenuate the burden of the disease.}, }
@article {pmid34943875, year = {2021}, author = {Lynch, SM and Guo, G and Gibson, DS and Bjourson, AJ and Rai, TS}, title = {Role of Senescence and Aging in SARS-CoV-2 Infection and COVID-19 Disease.}, journal = {Cells}, volume = {10}, number = {12}, pages = {}, pmid = {34943875}, issn = {2073-4409}, support = {COM/5618/20//Public Health Agency/ ; }, mesh = {Aging/*pathology ; Animals ; Biomarkers/metabolism ; COVID-19/*pathology ; Cellular Senescence ; Humans ; SARS-CoV-2/*physiology ; Translational Research, Biomedical ; }, abstract = {Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global pandemic associated with substantial morbidity and mortality worldwide, with particular risk for severe disease and mortality in the elderly population. SARS-CoV-2 infection is driven by a pathological hyperinflammatory response which results in a dysregulated immune response. Current advancements in aging research indicates that aging pathways have fundamental roles in dictating healthspan in addition to lifespan. Our review discusses the aging immune system and highlights that senescence and aging together, play a central role in COVID-19 pathogenesis. In our review, we primarily focus on the immune system response to SARS-CoV-2 infection, the interconnection between severe COVID-19, immunosenescence, aging, vaccination, and the emerging problem of Long-COVID. We hope to highlight the importance of identifying specific senescent endotypes (or "sendotypes"), which can used as determinants of COVID-19 severity and mortality. Indeed, identified sendotypes could be therapeutically exploited for therapeutic intervention. We highlight that senolytics, which eliminate senescent cells, can target aging-associated pathways and therefore are proving attractive as potential therapeutic options to alleviate symptoms, prevent severe infection, and reduce mortality burden in COVID-19 and thus ultimately enhance healthspan.}, }
@article {pmid34945095, year = {2021}, author = {Fernández-Lázaro, D and Sánchez-Serrano, N and Mielgo-Ayuso, J and García-Hernández, JL and González-Bernal, JJ and Seco-Calvo, J}, title = {Long COVID a New Derivative in the Chaos of SARS-CoV-2 Infection: The Emergent Pandemic?.}, journal = {Journal of clinical medicine}, volume = {10}, number = {24}, pages = {}, pmid = {34945095}, issn = {2077-0383}, support = {07.04.467804.74011.0//Instituto de Salud Carlos III/ ; &#xb0; 07.04.467804.74011.0//Consejer&#xed;a de Educaci&#xf3;n Junta of Castilla-Leon/ ; }, abstract = {Coronavirus disease 2019 (COVID-19) is a multisystem illness caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which can manifest with a multitude of symptoms in the setting of end-organ damage, though it is predominantly respiratory. However, various symptoms may remain after acute SARS-CoV-2 infection, and this condition is referred to as "Long COVID" (LC). Patients with LC may develop multi-organ symptom complex that remains 4-12 weeks after the acute phase of illness, with symptoms intermittently persisting over time. The main symptoms are fatigue, post-exertional malaise, cognitive dysfunction, and limitation of functional capacity. Pediatric patients developed the main symptoms of LC like those described in adults, although there may be variable presentations of LC in children. The underlying mechanisms of LC are not clearly known, although they may involve pathophysiological changes generated by virus persistence, immunological alterations secondary to virus-host interaction, tissue damage of inflammatory origin and hyperactivation of coagulation. Risk factors for developing LC would be female sex, more than five early symptoms, early dyspnea, previous psychiatric disorders, and alterations in immunological, inflammatory and coagulation parameters. There is currently no specific treatment for LC, but it could include pharmacological treatments to treat symptoms, supplements to restore nutritional, metabolic, and gut flora balance, and functional treatments for the most disabling symptoms. In summary, this study aims to show the scientific community the current knowledge of LC.}, }
@article {pmid34945213, year = {2021}, author = {Jennings, G and Monaghan, A and Xue, F and Mockler, D and Romero-Ortuño, R}, title = {A Systematic Review of Persistent Symptoms and Residual Abnormal Functioning following Acute COVID-19: Ongoing Symptomatic Phase vs. Post-COVID-19 Syndrome.}, journal = {Journal of clinical medicine}, volume = {10}, number = {24}, pages = {}, pmid = {34945213}, issn = {2077-0383}, support = {SFI COVID-19 Programme - 20/COV/8493/SFI_/Science Foundation Ireland/Ireland ; }, abstract = {OBJECTIVE: To compare the two phases of long COVID, namely ongoing symptomatic COVID-19 (OSC; signs and symptoms from 4 to 12 weeks from initial infection) and post-COVID-19 syndrome (PCS; signs and symptoms beyond 12 weeks) with respect to symptomatology, abnormal functioning, psychological burden, and quality of life.<br><br>DESIGN: Systematic review.<br><br>DATA SOURCES: Electronic search of EMBASE, MEDLINE, ProQuest Coronavirus Research Database, LitCOVID, and Google Scholar between January and April 2021, and manual search for relevant citations from review articles. Eligibility Criteria: Cross-sectional studies, cohort studies, randomised control trials, and case-control studies with participant data concerning long COVID symptomatology or abnormal functioning.<br><br>DATA EXTRACTION: Studies were screened and assessed for risk of bias by two independent reviewers, with conflicts resolved with a third reviewer. The AXIS tool was utilised to appraise the quality of the evidence. Data were extracted and collated using a data extraction tool in Microsoft Excel.<br><br>RESULTS: Of the 1145 studies screened, 39 were included, all describing adult cohorts with long COVID and sample sizes ranging from 32 to 1733. Studies included data pertaining to symptomatology, pulmonary functioning, chest imaging, cognitive functioning, psychological disorder, and/or quality of life. Fatigue presented as the most prevalent symptom during both OSC and PCS at 43% and 44%, respectively. Sleep disorder (36%; 33%), dyspnoea (31%; 40%), and cough (26%; 22%) followed in prevalence. Abnormal spirometry (FEV1 < 80% predicted) was observed in 15% and 11%, and abnormal chest imaging was observed in 34% and 28%, respectively. Cognitive impairments were also evident (20%; 15%), as well as anxiety (28%; 34%) and depression (25%; 32%). Decreased quality of life was reported by 40% in those with OSC and 57% with PCS.<br><br>CONCLUSIONS: The prevalence of OSC and PCS were highly variable. Reported symptoms covered a wide range of body systems, with a general overlap in frequencies between the two phases. However, abnormalities in lung function and imaging seemed to be more common in OSC, whilst anxiety, depression, and poor quality of life seemed more frequent in PCS. In general, the quality of the evidence was moderate and further research is needed to understand longitudinal symptomatology trajectories in long COVID. Systematic Review Registration: Registered with PROSPERO with ID #CRD42021247846.}, }
@article {pmid34951953, year = {2022}, author = {Soriano, JB and Murthy, S and Marshall, JC and Relan, P and Diaz, JV and , }, title = {A clinical case definition of post-COVID-19 condition by a Delphi consensus.}, journal = {The Lancet. Infectious diseases}, volume = {22}, number = {4}, pages = {e102-e107}, pmid = {34951953}, issn = {1474-4457}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Adult ; Child ; Humans ; Consensus ; *COVID-19/complications ; Delphi Technique ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Consensus Statements as Topic ; }, abstract = {People with COVID-19 might have sustained postinfection sequelae. Known by a variety of names, including long COVID or long-haul COVID, and listed in the ICD-10 classification as post-COVID-19 condition since September, 2020, this occurrence is variable in its expression and its impact. The absence of a globally standardised and agreed-upon definition hampers progress in characterisation of its epidemiology and the development of candidate treatments. In a WHO-led Delphi process, we engaged with an international panel of 265 patients, clinicians, researchers, and WHO staff to develop a consensus definition for this condition. 14 domains and 45 items were evaluated in two rounds of the Delphi process to create a final consensus definition for adults: post-COVID-19 condition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset, with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include, but are not limited to, fatigue, shortness of breath, and cognitive dysfunction, and generally have an impact on everyday functioning. Symptoms might be new onset following initial recovery from an acute COVID-19 episode or persist from the initial illness. Symptoms might also fluctuate or relapse over time. A separate definition might be applicable for children. Although the consensus definition is likely to change as knowledge increases, this common framework provides a foundation for ongoing and future studies of epidemiology, risk factors, clinical characteristics, and therapy.}, }
@article {pmid34973396, year = {2022}, author = {Ceban, F and Ling, S and Lui, LMW and Lee, Y and Gill, H and Teopiz, KM and Rodrigues, NB and Subramaniapillai, M and Di Vincenzo, JD and Cao, B and Lin, K and Mansur, RB and Ho, RC and Rosenblat, JD and Miskowiak, KW and Vinberg, M and Maletic, V and McIntyre, RS}, title = {Fatigue and cognitive impairment in Post-COVID-19 Syndrome: A systematic review and meta-analysis.}, journal = {Brain, behavior, and immunity}, volume = {101}, number = {}, pages = {93-135}, pmid = {34973396}, issn = {1090-2139}, mesh = {*COVID-19/complications ; COVID-19 Testing ; *Cognitive Dysfunction ; Fatigue/etiology ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {IMPORTANCE: COVID-19 is associated with clinically significant symptoms despite resolution of the acute infection (i.e., post-COVID-19 syndrome). Fatigue and cognitive impairment are amongst the most common and debilitating symptoms of post-COVID-19 syndrome.<br><br>OBJECTIVE: To quantify the proportion of individuals experiencing fatigue and cognitive impairment 12 or more weeks following COVID-19 diagnosis, and to characterize the inflammatory correlates and functional consequences of post-COVID-19 syndrome.<br><br>DATA SOURCES: Systematic searches were conducted without language restrictions from database inception to June 8, 2021 on PubMed/MEDLINE, The Cochrane Library, PsycInfo, Embase, Web of Science, Google/Google Scholar, and select reference lists.<br><br>STUDY SELECTION: Primary research articles which evaluated individuals at least 12&#xa0;weeks after confirmed COVID-19 diagnosis and specifically reported on fatigue, cognitive impairment, inflammatory parameters, and/or functional outcomes were selected.<br><br>Two reviewers independently extracted published summary data and assessed methodological quality and risk of bias. A meta-analysis of proportions was conducted to pool Freeman-Tukey double arcsine transformed proportions using the random-effects restricted maximum-likelihood model.<br><br>MAIN OUTCOMES &amp; MEASURES: The co-primary outcomes were the proportions of individuals reporting fatigue and cognitive impairment, respectively, 12 or more weeks following COVID-19 infection. The secondary outcomes were inflammatory correlates and functional consequences associated with post-COVID-19 syndrome.<br><br>RESULTS: The literature search yielded 10,979 studies, and 81 studies were selected for inclusion. The fatigue meta-analysis comprised 68 studies, the cognitive impairment meta-analysis comprised 43 studies, and 48 studies were included in the narrative synthesis. Meta-analysis revealed that the proportion of individuals experiencing fatigue 12 or more weeks following COVID-19 diagnosis was 0.32 (95% CI, 0.27, 0.37; p&#xa0;<&#xa0;0.001; n&#xa0;=&#xa0;25,268; I[2]&#xa0;=&#xa0;99.1%). The proportion of individuals exhibiting cognitive impairment was 0.22 (95% CI, 0.17, 0.28; p&#xa0;<&#xa0;0.001; n&#xa0;=&#xa0;13,232; I[2]&#xa0;=&#xa0;98.0). Moreover, narrative synthesis revealed elevations in proinflammatory markers and considerable functional impairment in a subset of individuals.<br><br>CONCLUSIONS &amp; RELEVANCE: A significant proportion of individuals experience persistent fatigue and/or cognitive impairment following resolution of acute COVID-19. The frequency and debilitating nature of the foregoing symptoms provides the impetus to characterize the underlying neurobiological substrates and how to best treat these phenomena.<br><br>STUDY REGISTRATION: PROSPERO (CRD42021256965).}, }
@article {pmid35017239, year = {2022}, author = {Macpherson, K and Cooper, K and Harbour, J and Mahal, D and Miller, C and Nairn, M}, title = {Experiences of living with long COVID and of accessing healthcare services: a qualitative systematic review.}, journal = {BMJ open}, volume = {12}, number = {1}, pages = {e050979}, pmid = {35017239}, issn = {2044-6055}, mesh = {*COVID-19/complications ; Delivery of Health Care ; Female ; Health Services ; Humans ; Qualitative Research ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: To explore the experiences of people living with long COVID and how they perceive the healthcare services available to them.<br><br>DESIGN: Qualitative systematic review.<br><br>DATA SOURCES: Electronic literature searches of websites, bibliographic databases and discussion forums, including PubMed LitCovid, Proquest COVID, EPPI Centre living systematic map of evidence, medRxiv, bioRxiv, Medline, Psychinfo and Web of Science Core Collection were conducted to identify qualitative literature published in English up to 13 January 2021.<br><br>INCLUSION CRITERIA: Papers reporting qualitative or mixed-methods studies that focused on the experiences of long COVID and/or perceptions of accessing healthcare by people with long COVID. Title/abstract and full-text screening were conducted by two reviewers independently, with conflicts resolved by discussion or a third reviewer.<br><br>QUALITY APPRAISAL: Two reviewers independently appraised included studies using the qualitative CASP (Critical Appraisal Skills Programme) checklist. Conflicts were resolved by discussion or a third reviewer.<br><br>DATA EXTRACTION AND SYNTHESIS: Thematic synthesis, involving line-by-line reading, generation of concepts, descriptive and analytical themes, was conducted by the review team with regular discussion.<br><br>RESULTS: Five studies published in 2020 met the inclusion criteria, two international surveys and three qualitative studies from the UK. Sample sizes varied from 24 (interview study) to 3762 (survey). Participants were predominantly young white females recruited from social media or online support groups. Three analytical themes were generated: (1) symptoms and self-directed management of long COVID; (2) emotional aspects of living with long COVID and (3) healthcare experiences associated with long COVID.<br><br>CONCLUSIONS: People experience long COVID as a heterogeneous condition, with a variety of physical and emotional consequences. It appears that greater knowledge of long COVID is required by a number of stakeholders and that the design of emerging long COVID services or adaptation of existing services for long COVID patients should take account of patients' experiences in their design.}, }
@article {pmid35028901, year = {2022}, author = {Theoharides, TC}, title = {Could SARS-CoV-2 Spike Protein Be Responsible for Long-COVID Syndrome?.}, journal = {Molecular neurobiology}, volume = {59}, number = {3}, pages = {1850-1861}, pmid = {35028901}, issn = {1559-1182}, mesh = {COVID-19/*complications/etiology/virology ; Humans ; Prospective Studies ; Spike Glycoprotein, Coronavirus/*physiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {SARS-CoV-2 infects cells via its spike protein binding to its surface receptor on target cells and results in acute symptoms involving especially the lungs known as COVID-19. However, increasing evidence indicates that many patients develop a chronic condition characterized by fatigue and neuropsychiatric symptoms, termed long-COVID. Most of the vaccines produced so far for COVID-19 direct mammalian cells via either mRNA or an adenovirus vector to express the spike protein, or administer recombinant spike protein, which is recognized by the immune system leading to the production of neutralizing antibodies. Recent publications provide new findings that may help decipher the pathogenesis of long-COVID. One paper reported perivascular inflammation in brains of deceased patients with COVID-19, while others showed that the spike protein could damage the endothelium in an animal model, that it could disrupt an in vitro model of the blood-brain barrier (BBB), and that it can cross the BBB resulting in perivascular inflammation. Moreover, the spike protein appears to share antigenic epitopes with human molecular chaperons resulting in autoimmunity and can activate toll-like receptors (TLRs), leading to release of inflammatory cytokines. Moreover, some antibodies produced against the spike protein may not be neutralizing, but may change its conformation rendering it more likely to bind to its receptor. As a result, one wonders whether the spike protein entering the brain or being expressed by brain cells could activate microglia, alone or together with inflammatory cytokines, since protective antibodies could not cross the BBB, leading to neuro-inflammation and contributing to long-COVID. Hence, there is urgent need to better understand the neurotoxic effects of the spike protein and to consider possible interventions to mitigate spike protein-related detrimental effects to the brain, possibly via use of small natural molecules, especially the flavonoids luteolin and quercetin.}, }
@article {pmid35029046, year = {2022}, author = {Jarrott, B and Head, R and Pringle, KG and Lumbers, ER and Martin, JH}, title = {"LONG COVID"-A hypothesis for understanding the biological basis and pharmacological treatment strategy.}, journal = {Pharmacology research &amp; perspectives}, volume = {10}, number = {1}, pages = {e00911}, pmid = {35029046}, issn = {2052-1707}, mesh = {Antiviral Agents/*therapeutic use ; Biomarkers/metabolism ; COVID-19/*complications/physiopathology/virology ; Endothelium, Vascular/virology ; Humans ; SARS-CoV-2/isolation &amp; purification/physiology ; Virus Replication ; Post-Acute COVID-19 Syndrome ; COVID-19 Drug Treatment ; }, abstract = {Infection of humans with SARS-CoV-2 virus causes a disease known colloquially as "COVID-19" with symptoms ranging from asymptomatic to severe pneumonia. Initial pathology is due to the virus binding to the ACE-2 protein on endothelial cells lining blood vessels and entering these cells in order to replicate. Viral replication causes oxidative stress due to elevated levels of reactive oxygen species. Many (~60%) of the infected people appear to have eliminated the virus from their body after 28 days and resume normal activity. However, a significant proportion (~40%) experience a variety of symptoms (loss of smell and/or taste, fatigue, cough, aching pain, "brain fog," insomnia, shortness of breath, and tachycardia) after 12 weeks and are diagnosed with a syndrome named "LONG COVID." Longitudinal clinical studies in a group of subjects who were infected with SARS-CoV-2 have been compared to a non-infected matched group of subjects. A cohort of infected subjects can be identified by a battery of cytokine markers to have persistent, low level grade of inflammation and often self-report two or more troubling symptoms. There is no drug that will relieve their symptoms effectively. It is hypothesized that drugs that activate the intracellular transcription factor, nuclear factor erythroid-derived 2-like 2 (NRF2) may increase the expression of enzymes to synthesize the intracellular antioxidant, glutathione that will quench free radicals causing oxidative stress. The hormone melatonin has been identified as an activator of NRF2 and a relatively safe chemical for most people to ingest chronically. Thus, it is an option for consideration of re-purposing studies in "LONG COVID" subjects experiencing insomnia, depression, fatigue, and "brain fog" but not tachycardia. Appropriately designed clinical trials are required to evaluate melatonin.}, }
@article {pmid35043333, year = {2022}, author = {Bisenius, S and Kersting, A}, title = {[Psychosomatic aspects of Long COVID].}, journal = {MMW Fortschritte der Medizin}, volume = {164}, number = {1}, pages = {40-41}, doi = {10.1007/s15006-021-0540-1}, pmid = {35043333}, issn = {1613-3560}, mesh = {*COVID-19/complications/psychology ; Humans ; *Psychophysiologic Disorders/diagnosis ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, }
@article {pmid35043334, year = {2022}, author = {Grund, S and Bauer, J}, title = {[Long COVID Syndrome in frail older persons - complex to diagnose and treat].}, journal = {MMW Fortschritte der Medizin}, volume = {164}, number = {1}, pages = {42-47}, doi = {10.1007/s15006-021-0575-3}, pmid = {35043334}, issn = {1613-3560}, mesh = {Aged ; Aged, 80 and over ; *COVID-19/complications ; Frail Elderly ; Geriatric Assessment ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, }
@article {pmid35052628, year = {2022}, author = {Satoh, T and Trudler, D and Oh, CK and Lipton, SA}, title = {Potential Therapeutic Use of the Rosemary Diterpene Carnosic Acid for Alzheimer's Disease, Parkinson's Disease, and Long-COVID through NRF2 Activation to Counteract the NLRP3 Inflammasome.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {11}, number = {1}, pages = {}, pmid = {35052628}, issn = {2076-3921}, support = {R35 AG071734/AG/NIA NIH HHS/United States ; R01 AG078756/AG/NIA NIH HHS/United States ; R01 AG056259/AG/NIA NIH HHS/United States ; RF1 AG057409, R01 AG056259, R01 DA048882, R01 NS086890 and DP1 DA041722//NIH grants/ ; DISC2 COVID19-11811, and a COVID-19 award from Fast Grants//California Institute for Regenerative Medicine (CIRM) grant/ ; R01 DA048882/DA/NIDA NIH HHS/United States ; RF1 AG057409/AG/NIA NIH HHS/United States ; }, abstract = {Rosemary (Rosmarinus officinalis [family Lamiaceae]), an herb of economic and gustatory repute, is employed in traditional medicines in many countries. Rosemary contains carnosic acid (CA) and carnosol (CS), abietane-type phenolic diterpenes, which account for most of its biological and pharmacological actions, although claims have also been made for contributions of another constituent, rosmarinic acid. This review focuses on the potential applications of CA and CS for Alzheimer's disease (AD), Parkinson's disease (PD), and coronavirus disease 2019 (COVID-19), in part via inhibition of the NLRP3 inflammasome. CA exerts antioxidant, anti-inflammatory, and neuroprotective effects via phase 2 enzyme induction initiated by activation of the KEAP1/NRF2 transcriptional pathway, which in turn attenuates NLRP3 activation. In addition, we propose that CA-related compounds may serve as therapeutics against the brain-related after-effects of SARS-CoV-2 infection, termed "long-COVID." One factor that contributes to COVID-19 is cytokine storm emanating from macrophages as a result of unregulated inflammation in and around lung epithelial and endovascular cells. Additionally, neurological aftereffects such as anxiety and "brain fog" are becoming a major issue for both the pandemic and post-pandemic period. Many reports hold that unregulated NLRP3 inflammasome activation may potentially contribute to the severity of COVID-19 and its aftermath. It is therefore possible that suppression of NLRP3 inflammasome activity may prove efficacious against both acute lung disease and chronic neurological after-effects. Because CA has been shown to not only act systemically but also to penetrate the blood-brain barrier and reach the brain parenchyma to exert neuroprotective effects, we discuss the evidence that CA or rosemary extracts containing CA may represent an effective countermeasure against both acute and chronic pathological events initiated by SARS-CoV-2 infection as well as other chronic neurodegenerative diseases including AD and PD.}, }
@article {pmid35053059, year = {2022}, author = {Thye, AY and Law, JW and Tan, LT and Pusparajah, P and Ser, HL and Thurairajasingam, S and Letchumanan, V and Lee, LH}, title = {Psychological Symptoms in COVID-19 Patients: Insights into Pathophysiology and Risk Factors of Long COVID-19.}, journal = {Biology}, volume = {11}, number = {1}, pages = {}, pmid = {35053059}, issn = {2079-7737}, support = {FRGS/1/2019/SKK08/MUSM/02/7//Fundamental Research Grant Scheme/ ; MBRS/JCSMHS/02/2020//SEED Funding from Microbiome and Bioresource Research Strength (MBRS), Jeffrey Cheah School of Medicine and Health Sciences/ ; }, abstract = {There is growing evidence of studies associating COVID-19 survivors with increased mental health consequences. Mental health implications related to a COVID-19 infection include both acute and long-term consequences. Here we discuss COVID-19-associated psychiatric sequelae, particularly anxiety, depression, and post-traumatic stress disorder (PTSD), drawing parallels to past coronavirus outbreaks. A literature search was completed across three databases, using keywords to search for relevant articles. The cause may directly correlate to the infection through both direct and indirect mechanisms, but the underlying etiology appears more complex and multifactorial, involving environmental, psychological, and biological factors. Although most risk factors and prevalence rates vary across various studies, being of the female gender and having a history of psychiatric disorders seem consistent. Several studies will be presented, demonstrating COVID-19 survivors presenting higher rates of mental health consequences than the general population. The possible mechanisms by which the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the brain, affecting the central nervous system (CNS) and causing these psychiatric sequelae, will be discussed, particularly concerning the SARS-CoV-2 entry via the angiotensin-converting enzyme 2 (ACE-2) receptors and the implications of the immune inflammatory signaling on neuropsychiatric disorders. Some possible therapeutic options will also be considered.}, }
@article {pmid35054906, year = {2022}, author = {Lauwers, M and Au, M and Yuan, S and Wen, C}, title = {COVID-19 in Joint Ageing and Osteoarthritis: Current Status and Perspectives.}, journal = {International journal of molecular sciences}, volume = {23}, number = {2}, pages = {}, pmid = {35054906}, issn = {1422-0067}, mesh = {Adipose Tissue/metabolism/physiopathology ; *Aging ; Angiotensin-Converting Enzyme 2/metabolism ; COVID-19/complications/*pathology/virology ; Humans ; Musculoskeletal System/metabolism/physiopathology ; Osteoarthritis/complications/*pathology ; Pain/etiology ; Renin-Angiotensin System ; SARS-CoV-2/isolation &amp; purification ; }, abstract = {COVID-19 is a trending topic worldwide due to its immense impact on society. Recent trends have shifted from acute effects towards the long-term morbidity of COVID-19. In this review, we hypothesize that SARS-CoV-2 contributes to age-related perturbations in endothelial and adipose tissue, which are known to characterize the early aging process. This would explain the long-lasting symptoms of SARS-CoV-2 as the result of an accelerated aging process. Connective tissues such as adipose tissue and musculoskeletal tissue are the primary sites of aging. Therefore, current literature was analyzed focusing on the musculoskeletal symptoms in COVID-19 patients. Hypovitaminosis D, increased fragility, and calcium deficiency point towards bone aging, while joint and muscle pain are typical for joint and muscle aging, respectively. These characteristics could be classified as early osteoarthritis-like phenotype. Exploration of the impact of SARS-CoV-2 and osteoarthritis on endothelial and adipose tissue, as well as neuronal function, showed similar perturbations. At a molecular level, this could be attributed to the angiotensin-converting enzyme 2 expression, renin-angiotensin system dysfunction, and inflammation. Finally, the influence of the nicotinic cholinergic system is being evaluated as a new treatment strategy. This is combined with the current knowledge of musculoskeletal aging to pave the road towards the treatment of long-term COVID-19.}, }
@article {pmid35056324, year = {2021}, author = {Hayden, MR and Tyagi, SC}, title = {Impaired Folate-Mediated One-Carbon Metabolism in Type 2 Diabetes, Late-Onset Alzheimer's Disease and Long COVID.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {58}, number = {1}, pages = {}, pmid = {35056324}, issn = {1648-9144}, mesh = {*Alzheimer Disease ; *COVID-19/complications ; Carbon ; *Diabetes Mellitus, Type 2 ; Folic Acid ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Impaired folate-mediated one-carbon metabolism (FOCM) is associated with many pathologies and developmental abnormalities. FOCM is a metabolic network of interdependent biosynthetic pathways that is known to be compartmentalized in the cytoplasm, mitochondria and nucleus. Currently, the biochemical mechanisms and causal metabolic pathways responsible for the initiation and/or progression of folate-associated pathologies have yet to be fully established. This review specifically examines the role of impaired FOCM in type 2 diabetes mellitus, Alzheimer's disease and the emerging Long COVID/post-acute sequelae of SARS-CoV-2 (PASC). Importantly, elevated homocysteine may be considered a biomarker for impaired FOCM, which is known to result in increased oxidative-redox stress. Therefore, the incorporation of hyperhomocysteinemia will be discussed in relation to impaired FOCM in each of the previously listed clinical diseases. This review is intended to fill gaps in knowledge associated with these clinical diseases and impaired FOCM. Additionally, some of the therapeutics will be discussed at this early time point in studying impaired FOCM in each of the above clinical disease states. It is hoped that this review will allow the reader to better understand the role of FOCM in the development and treatment of clinical disease states that may be associated with impaired FOCM and how to restore a more normal functional role for FOCM through improved nutrition and/or restoring the essential water-soluble B vitamins through oral supplementation.}, }
@article {pmid35086782, year = {2022}, author = {Martín-Garrido, I and Medrano-Ortega, FJ}, title = {Beyond acute SARS-CoV-2 infection: A new challenge for Internal Medicine.}, journal = {Revista clinica espanola}, volume = {222}, number = {3}, pages = {176-179}, pmid = {35086782}, issn = {2254-8874}, mesh = {*COVID-19 ; Humans ; SARS-CoV-2 ; }, abstract = {Infection with the new SARS-CoV-2 coronavirus has reached pandemic proportions, with a very high death toll worldwide. Despite the scientific community's strenuous efforts to address this disease in its acute phase, as well as in prevention through the development of vaccines in record time, there remains another important workhorse: understanding and treating the persistence of symptoms beyond the acute phase, the so-called protracted COVID-19 syndrome or persistent COVID. These persistent manifestations affect several organs and systems and may depend on both the pathogenic mechanisms of the virus and the pathophysiological response of the patient. One year after the onset of this pandemic, there is an urgent need to address this situation from a comprehensive approach.}, }
@article {pmid35114136, year = {2022}, author = {Bechmann, N and Barthel, A and Schedl, A and Herzig, S and Varga, Z and Gebhard, C and Mayr, M and Hantel, C and Beuschlein, F and Wolfrum, C and Perakakis, N and Poston, L and Andoniadou, CL and Siow, R and Gainetdinov, RR and Dotan, A and Shoenfeld, Y and Mingrone, G and Bornstein, SR}, title = {Sexual dimorphism in COVID-19: potential clinical and public health implications.}, journal = {The lancet. Diabetes &amp; endocrinology}, volume = {10}, number = {3}, pages = {221-230}, pmid = {35114136}, issn = {2213-8595}, support = {CH/16/3/32406/BHF_/British Heart Foundation/United Kingdom ; RG/16/14/32397/BHF_/British Heart Foundation/United Kingdom ; }, mesh = {*COVID-19/complications/epidemiology/physiopathology ; Female ; *Health Status Disparities ; Humans ; Hypothalamo-Hypophyseal System ; Male ; Pituitary-Adrenal System ; Public Health ; *Sex Characteristics ; Post-Acute COVID-19 Syndrome ; }, abstract = {Current evidence suggests that severity and mortality of COVID-19 is higher in men than in women, whereas women might be at increased risk of COVID-19 reinfection and development of long COVID. Differences between sexes have been observed in other infectious diseases and in the response to vaccines. Sex-specific expression patterns of proteins mediating virus binding and entry, and divergent reactions of the immune and endocrine system, in particular the hypothalamic-pituitary-adrenal axis, in response to acute stress might explain the higher severity of COVID-19 in men. In this Personal View, we discuss how sex hormones, comorbidities, and the sex chromosome complement influence these mechanisms in the context of COVID-19. Due to its role in the severity and progression of SARS-CoV-2 infections, we argue that sexual dimorphism has potential implications for disease treatment, public health measures, and follow-up of patients predisposed to the development of long COVID. We suggest that sex differences could be considered in future pandemic surveillance and treatment of patients with COVID-19 to help to achieve better disease stratification and improved outcomes.}, }
@article {pmid35114535, year = {2022}, author = {Cau, R and Faa, G and Nardi, V and Balestrieri, A and Puig, J and Suri, JS and SanFilippo, R and Saba, L}, title = {Long-COVID diagnosis: From diagnostic to advanced AI-driven models.}, journal = {European journal of radiology}, volume = {148}, number = {}, pages = {110164}, pmid = {35114535}, issn = {1872-7727}, mesh = {Artificial Intelligence ; *COVID-19/complications ; Humans ; RNA, Viral ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {SARS-COV 2 is recognized to be responsible for a multi-organ syndrome. In most patients, symptoms are mild. However, in certain subjects, COVID-19 tends to progress more severely. Most of the patients infected with SARS-COV2 fully recovered within some weeks. In a considerable number of patients, like many other viral infections, various long-lasting symptoms have been described, now defined as "long COVID-19 syndrome". Given the high number of contagious over the world, it is necessary to understand and comprehend this emerging pathology to enable early diagnosis and improve patents outcomes. In this scenario, AI-based models can be applied in long-COVID-19 patients to assist clinicians and at the same time, to reduce the considerable impact on the care and rehabilitation unit. The purpose of this manuscript is to review different aspects of long-COVID-19 syndrome from clinical presentation to diagnosis, highlighting the considerable impact that AI can have.}, }
@article {pmid35118594, year = {2022}, author = {Borel, M and Xie, L and Kapera, O and Mihalcea, A and Kahn, J and Messiah, SE}, title = {Long-term physical, mental and social health effects of COVID-19 in the pediatric population: a scoping review.}, journal = {World journal of pediatrics : WJP}, volume = {18}, number = {3}, pages = {149-159}, pmid = {35118594}, issn = {1867-0687}, mesh = {Adolescent ; Adult ; *COVID-19 ; Child ; Fatigue/diagnosis/epidemiology/etiology ; Humans ; Pandemics ; Physical Examination ; SARS-CoV-2 ; }, abstract = {BACKGROUND: The majority of coronavirus disease 2019 (COVID-19) symptom presentations in adults and children appear to run their course within a couple of weeks. However, a subgroup of adults has started to emerge with effects lasting several months or more after initial infection, which raises questions about the long-term physical, mental and social health effects of COVID-19 in the pediatric population. The purpose of this review was to determine these impacts well into the second year of the pandemic.<br><br>METHODS: A search was conducted using PubMed, Web of Science, Science Direct, and Cochrane between 11/1/2019 and 9/1/2021. Search inclusion criteria were as follows: (1) COVID-19 illness and symptoms in children; (2) severe acute respiratory syndrome coronavirus 2 in children; (3) English language; and (4) human studies only.<br><br>RESULTS: The few studies that have documented long-term physical symptoms in children show that fatigue, difficulty in concentrating (brain fog), sleep disturbances, and sensory problems are the most reported outcomes. Most studies examining the impact of COVID-19 in pediatric populations have focused on initial clinical presentation, and symptoms, which are similar to those in adult populations. In addition, COVID-19 has had a moderate impact on children and adolescents' social environment, which may exacerbate current and future physiological, psychological, behavioral, and academic outcomes.<br><br>CONCLUSIONS: There are limited studies reporting long physical symptoms of COVID-19 in the pediatric population. However, pediatric COVID-19 cases are underreported due to low rates of testing and symptomatic infection, which calls for more longitudinal studies. Children who have experienced COVID-19 illness should be monitored for long physiological, psychological, behavioral, and academic outcomes.}, }
@article {pmid35121209, year = {2022}, author = {Premraj, L and Kannapadi, NV and Briggs, J and Seal, SM and Battaglini, D and Fanning, J and Suen, J and Robba, C and Fraser, J and Cho, SM}, title = {Mid and long-term neurological and neuropsychiatric manifestations of post-COVID-19 syndrome: A meta-analysis.}, journal = {Journal of the neurological sciences}, volume = {434}, number = {}, pages = {120162}, pmid = {35121209}, issn = {1878-5883}, support = {K23 HL157610/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Anxiety/epidemiology/etiology/psychology ; *COVID-19/complications/epidemiology ; Fatigue/diagnosis ; Headache/epidemiology ; Humans ; Post-Acute COVID-19 Syndrome ; }, abstract = {IMPORTANCE: Neurological and neuropsychiatric symptoms that persist or develop three months after the onset of COVID-19 pose a significant threat to the global healthcare system. These symptoms are yet to be synthesized and quantified via meta-analysis.<br><br>OBJECTIVE: To determine the prevalence of neurological and neuropsychiatric symptoms reported 12&#xa0;weeks (3&#xa0;months) or more after acute COVID-19 onset in adults.<br><br>DATA SOURCES: A systematic search of PubMed, EMBASE, Web of Science, Google Scholar and Scopus was conducted for studies published between January 1st, 2020 and August 1st, 2021. The systematic review was guided by Preferred Reporting Items for Systematic Review and Meta-Analyses.<br><br>STUDY SELECTION: Studies were included if the length of follow-up satisfied the National Institute for Healthcare Excellence (NICE) definition of post-COVID-19 syndrome (symptoms that develop or persist &#x2265;3&#xa0;months after the onset of COVID-19). Additional criteria included the reporting of neurological or neuropsychiatric symptoms in individuals with COVID-19.<br><br>DATA EXTRACTION AND SYNTHESIS: Two authors independently extracted data on patient characteristics, hospital and/or ICU admission, acute-phase COVID-19 symptoms, length of follow-up, and neurological and neuropsychiatric symptoms.<br><br>The primary outcome was the prevalence of neurological and neuropsychiatric symptoms reported &#x2265;3&#xa0;months post onset of COVID-19. We also compared post-COVID-19 syndrome in hospitalised vs. non-hospitalised patients, with vs. without ICU admission during the acute phase of infection, and with mid-term (3 to 6&#xa0;months) and long-term (>6&#xa0;months) follow-up.<br><br>RESULTS: Of 1458 articles, 19 studies, encompassing a total of 11,324 patients, were analysed. Overall prevalence for neurological post-COVID-19 symptoms were: fatigue (37%, 95% CI: 24%-50%), brain fog (32%, 9%-55%), memory issues (27%, 18%-36%), attention disorder (22%, 10%-34%), myalgia (18%, 4%-32%), anosmia (12%, 7%-17%), dysgeusia (11%, 4%-17%) and headache (10%, 1%-21%). Neuropsychiatric conditions included sleep disturbances (31%, 18%-43%), anxiety (23%, 13%-33%) and depression (12%, 7%-21%). Neuropsychiatric symptoms substantially increased in prevalence between mid- and long-term follow-up. Compared to non-hospitalised patients, patients hospitalised for acute COVID-19 had reduced frequency of anosmia, anxiety, depression, dysgeusia, fatigue, headache, myalgia, and sleep disturbance at three (or more) months post-infection. Conversely, hospital admission was associated with higher frequency of memory issues (OR: 1.9, 95% CI: 1.4-2.3). Cohorts with >20% of patients admitted to the ICU during acute COVID-19 experienced higher prevalence of fatigue, anxiety, depression, and sleep disturbances than cohorts with <20% of ICU admission.<br><br>CONCLUSIONS AND RELEVANCE: Fatigue, cognitive dysfunction (brain fog, memory issues, attention disorder) and sleep disturbances appear to be key features of post-COVID-19 syndrome. Psychiatric manifestations (sleep disturbances, anxiety, and depression) are common and increase significantly in prevalence over time. Randomised controlled trials are necessary to develop intervention strategy to reduce disease burden.}, }
@article {pmid35127274, year = {2022}, author = {Thallapureddy, K and Thallapureddy, K and Zerda, E and Suresh, N and Kamat, D and Rajasekaran, K and Moreira, A}, title = {Long-Term Complications of COVID-19 Infection in Adolescents and Children.}, journal = {Current pediatrics reports}, volume = {10}, number = {1}, pages = {11-17}, pmid = {35127274}, issn = {2167-4841}, abstract = {PURPOSE OF REVIEW: Compared to adults, post-COVID-19 symptoms are uncommon and have not been thoroughly evaluated in children. This review summarizes the literature in terms of persistent symptoms in children and adolescents after SARS-CoV-2 infection.<br><br>RECENT FINDINGS: Children were less likely to develop long COVID when compared to adults. Older children (e.g., adolescents) and those who had symptomatic COVID-19 had a higher probability for long COVID.<br><br>SUMMARY: Families and health care providers need to be aware of a new constellation of long COVID symptoms in the pediatric population. More evidence and time are needed to better understand the potential effects of long COVID-19 in children and adolescents. In comparison to adults, children are less likely to have persistent COVID-19 symptoms.}, }
@article {pmid35131989, year = {2022}, author = {Daines, L and Zheng, B and Pfeffer, P and Hurst, JR and Sheikh, A}, title = {A clinical review of long-COVID with a focus on the respiratory system.}, journal = {Current opinion in pulmonary medicine}, volume = {28}, number = {3}, pages = {174-179}, pmid = {35131989}, issn = {1531-6971}, support = {COV/LTE/20/15/CSO_/Chief Scientist Office/United Kingdom ; /MRC_/Medical Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; }, mesh = {*COVID-19/complications/epidemiology ; Cough ; Humans ; Respiratory System ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE OF REVIEW: Persistence of symptoms after acute coronavirus disease 2019 (COVID-19), often described as long- COVID, is common and debilitating. In this article, we review the epidemiology, clinical features, and research priorities for long-COVID focusing on the respiratory system.<br><br>RECENT FINDINGS: Breathlessness, cough and chest pain were the most commonly reported respiratory symptoms associated with long-COVID. In hospitalised patients, abnormalities on lung function testing or chest imaging were observed less commonly at 12&#x200a;months compared to six months since discharge. Clinical assessment of patients with persisting symptoms after acute COVID-19 requires a comprehensive evaluation to exclude other possible causes for symptoms. With no robust current evidence for interventions to treat long-COVID respiratory symptoms, symptomatic treatment, supported self-management and pulmonary rehabilitation should be considered to help individuals with respiratory symptoms associated with long-COVID.<br><br>SUMMARY: Long-COVID is a debilitating syndrome that often includes persisting respiratory symptoms and to a lesser degree, abnormalities in lung physiology or imaging. Respiratory features of long-COVID may reduce over time, yet resolution is not seen in all cases. Future research is needed to understand the natural history of long-COVID, identify factors associated with spontaneous improvement/persistence, investigate mechanisms for persisting symptoms, and test interventions to prevent and treat long-COVID.}, }
@article {pmid35134812, year = {2022}, author = {Yelin, D and Margalit, I}, title = {Challenges and Management of Long COVID in Individuals with Hematological Illnesses.}, journal = {Acta haematologica}, volume = {145}, number = {3}, pages = {275-281}, pmid = {35134812}, issn = {1421-9662}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19 has impacted hundreds of millions of people globally, a relatively large proportion of whom continue to suffer from ongoing, sometime debilitating symptoms. This phenomenon, termed "long COVID," is difficult to diagnose and manage because of a paucity of objective findings and despite the abundance of descriptive data published so far. In this review, we aimed to describe the common manifestations of long COVID, diagnostic and management challenges, and address specific aspects in hematologic patients.}, }
@article {pmid35137496, year = {2022}, author = {Taga, A and Lauria, G}, title = {COVID-19 and the peripheral nervous system. A 2-year review from the pandemic to the vaccine era.}, journal = {Journal of the peripheral nervous system : JPNS}, volume = {27}, number = {1}, pages = {4-30}, pmid = {35137496}, issn = {1529-8027}, mesh = {*COVID-19/complications/epidemiology/prevention &amp; control ; COVID-19 Vaccines/adverse effects ; *Guillain-Barre Syndrome/epidemiology/etiology ; Humans ; Pandemics ; Peripheral Nervous System ; }, abstract = {Increasing literature has linked COVID-19 to peripheral nervous system (PNS) diseases. In addition, as we move from the pandemic to the vaccination era, literature interest is shifting towards the potential association between COVID-19 vaccines and PNS manifestations. We reviewed published literature on COVID-19, COVID-19 vaccines and PNS manifestations between 1 January 2020 and 1 December 2021. For Guillain-Barré syndrome (GBS), isolated cranial neuropathy (ICN) and myositis associated with COVID-19, the demographic, clinical, laboratory, electrophysiological and imaging features were included in a narrative synthesis. We identified 169 studies on COVID-19-associated complications, including 63 papers (92 patients) on GBS, 29 papers (37 patients) on ICN and 11 papers (18 patients) on myositis. Additional clinical phenotypes included chronic inflammatory demyelinating polyneuropathy, vasculitic neuropathies, neuralgic amyotrophy, critical care-related complications, and myasthenia gravis. PNS complications secondary to COVID-19 vaccines have been reported during randomized clinical trials, in real-world case reports, and during large-scale surveillance programs. These mainly include cases of GBS, Bell's palsy, and cases of neuralgic amyotrophy. Based on our extensive review of the literature, any conclusion about a pathophysiological correlation between COVID-19 and PNS disorders remains premature, and solely supported by their temporal association, while epidemiological and pathological data are insufficient. The occurrence of PNS complications after COVID-19 vaccines seems limited to a possible higher risk of facial nerve palsy and GBS, to a degree that widespread access to the ongoing vaccination campaign should not be discouraged, while awaiting for more definitive data from large-scale surveillance studies.}, }
@article {pmid35142947, year = {2022}, author = {Nguyen, NN and Hoang, VT and Dao, TL and Dudouet, P and Eldin, C and Gautret, P}, title = {Clinical patterns of somatic symptoms in patients suffering from post-acute long COVID: a systematic review.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {41}, number = {4}, pages = {515-545}, pmid = {35142947}, issn = {1435-4373}, mesh = {*COVID-19/complications/epidemiology ; Fatigue/epidemiology/etiology ; Female ; Humans ; *Medically Unexplained Symptoms ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long COVID-19 may affect patients after hospital discharge.<br><br>AIMS: This study aims to describe the burden of the long-term persistence of clinical symptoms in COVID-19 patients.<br><br>METHODS: We conducted a systematic review by using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline. The PubMed and Google Scholar databases were searched for studies that included information on the prevalence of somatic clinical symptoms lasting at least 4&#xa0;weeks after the onset of a PCR- or serology-confirmed diagnosis of COVID-19. The prevalence of persisting clinical symptoms was assessed and risk factors were described when investigated. Psychological symptoms and cognitive disorders were not evaluated in this study.<br><br>RESULTS: Thirty-seven articles met the inclusion criteria. Eighteen studies involved in-patients only with a duration of follow-up of either less than 12&#xa0;weeks, 12&#xa0;weeks to 6&#xa0;months, or more. In these studies, fatigue (16-64%), dyspnea (15-61%), cough (2-59%), arthralgia (8-55%), and thoracic pain (5-62%) were the most frequent persisting symptoms. In nineteen studies conducted in a majority of out-patients, the persistence of these symptoms was lower and 3% to 74% of patients reported prolonged smell and taste disorders. The main risk factors for persisting symptoms were being female, older, having comorbidities and severity at the acute phase of the disease.<br><br>CONCLUSION: COVID-19 patients should have access to dedicated multidisciplinary healthcare allowing a holistic approach. Effective outpatient care for patients with long-COVID-19 requires coordination across multiple sub-specialties, which can be proposed in specialized post-COVID units.}, }
@article {pmid35144718, year = {2022}, author = {Tang, SW and Leonard, BE and Helmeste, DM}, title = {Long COVID, neuropsychiatric disorders, psychotropics, present and future.}, journal = {Acta neuropsychiatrica}, volume = {34}, number = {3}, pages = {109-126}, doi = {10.1017/neu.2022.6}, pmid = {35144718}, issn = {1601-5215}, mesh = {Anxiety ; *COVID-19/complications/epidemiology ; Humans ; Pandemics ; Psychotropic Drugs/therapeutic use ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {Long COVID refers to the lingering symptoms which persist or appear after the acute illness. The dominant long COVID symptoms in the two years since the pandemic began (2020-2021) have been depression, anxiety, fatigue, concentration and cognitive impairments with few reports of psychosis. Whether other symptoms will appear later on is not yet known. For example, dopamine-dependent movement disorders generally take many years before first symptoms are seen. Post-stroke depression and anxiety may explain many of the early long COVID cases. Hemorrhagic, hypoxic and inflammatory damages of the central nervous system, unresolved systematic inflammation, metabolic impairment, cerebral vascular accidents such as stroke, hypoxia from pulmonary damages and fibrotic changes are among the major causes of long COVID. Glucose metabolic and hypoxic brain issues likely predispose subjects with pre-existing diabetes, cardiovascular or lung problems to long COVID as well. Preliminary data suggest that psychotropic medications may not be a danger but could instead be beneficial in combating COVID-19 infection. The same is true for diabetes medications such as metformin. Thus, a focus on sigma-1 receptor ligands and glucose metabolism is expected to be useful for new drug development as well as the repurposing of current drugs. The reported protective effects of psychotropics and antihistamines against COVID-19, the earlier reports of reduced number of sigma-1 receptors in post-mortem schizophrenic brains, with many antidepressant and antipsychotic drugs being antihistamines with significant affinity for the sigma-1 receptor, support the role of sigma and histamine receptors in neuroinflammation and viral infections. Literature and data in all these areas are accumulating at a fast rate. We reviewed and discussed the relevant and important literature.}, }
@article {pmid35155571, year = {2021}, author = {Rahimmanesh, I and Shariati, L and Dana, N and Esmaeili, Y and Vaseghi, G and Haghjooy Javanmard, S}, title = {Cancer Occurrence as the Upcoming Complications of COVID-19.}, journal = {Frontiers in molecular biosciences}, volume = {8}, number = {}, pages = {813175}, pmid = {35155571}, issn = {2296-889X}, abstract = {Previous studies suggested that patients with comorbidities including cancer had a higher risk of mortality or developing more severe forms of COVID-19. The interaction of cancer and COVID-19 is unrecognized and potential long-term effects of COVID-19 on cancer outcome remain to be explored. Furthermore, whether COVID-19 increases the risk of cancer in those without previous history of malignancies, has not yet been studied. Cancer progression, recurrence and metastasis depend on the complex interaction between the tumor and the host inflammatory response. Extreme proinflammatory cytokine release (cytokine storm) and multi-organ failure are hallmarks of severe COVID-19. Besides impaired T-Cell response, elevated levels of cytokines, growth factors and also chemokines in the plasma of patients in the acute phase of COVID-19 as well as tissue damage and chronic low-grade inflammation in "long COVID-19" syndrome may facilitate cancer progression and recurrence. Following a systemic inflammatory response syndrome, some counterbalancing compensatory anti-inflammatory mechanisms will be activated to restore immune homeostasis. On the other hand, there remains the possibility of the integration of SARS- CoV-2 into the host genome, which potentially may cause cancer. These mechanisms have also been shown to be implicated in both tumorigenesis and metastasis. In this review, we are going to focus on potential mechanisms and the molecular interplay, which connect COVID-19, inflammation, and immune-mediated tumor progression that may propose a framework to understand the possible role of COVID-19 infection in tumorgenesis and cancer progression.}, }
@article {pmid35159974, year = {2022}, author = {Visco, V and Vitale, C and Rispoli, A and Izzo, C and Virtuoso, N and Ferruzzi, GJ and Santopietro, M and Melfi, A and Rusciano, MR and Maglio, A and Di Pietro, P and Carrizzo, A and Galasso, G and Vatrella, A and Vecchione, C and Ciccarelli, M}, title = {Post-COVID-19 Syndrome: Involvement and Interactions between Respiratory, Cardiovascular and Nervous Systems.}, journal = {Journal of clinical medicine}, volume = {11}, number = {3}, pages = {}, pmid = {35159974}, issn = {2077-0383}, abstract = {Though the acute effects of SARS-CoV-2 infection have been extensively reported, the long-term effects are less well described. Specifically, while clinicians endure to battle COVID-19, we also need to develop broad strategies to manage post-COVID-19 symptoms and encourage those affected to seek suitable care. This review addresses the possible involvement of the lung, heart and brain in post-viral syndromes and describes suggested management of post-COVID-19 syndrome. Post-COVID-19 respiratory manifestations comprise coughing and shortness of breath. Furthermore, arrhythmias, palpitations, hypotension, increased heart rate, venous thromboembolic diseases, myocarditis and acute heart failure are usual cardiovascular events. Among neurological manifestations, headache, peripheral neuropathy symptoms, memory issues, lack of concentration and sleep disorders are most commonly observed with varying frequencies. Finally, mental health issues affecting mental abilities and mood fluctuations, namely anxiety and depression, are frequently seen. Finally, long COVID is a complex syndrome with protracted heterogeneous symptoms, and patients who experience post-COVID-19 sequelae require personalized treatment as well as ongoing support.}, }
@article {pmid35169700, year = {2022}, author = {Badenoch, JB and Rengasamy, ER and Watson, C and Jansen, K and Chakraborty, S and Sundaram, RD and Hafeez, D and Burchill, E and Saini, A and Thomas, L and Cross, B and Hunt, CK and Conti, I and Ralovska, S and Hussain, Z and Butler, M and Pollak, TA and Koychev, I and Michael, BD and Holling, H and Nicholson, TR and Rogers, JP and Rooney, AG}, title = {Persistent neuropsychiatric symptoms after COVID-19: a systematic review and meta-analysis.}, journal = {Brain communications}, volume = {4}, number = {1}, pages = {fcab297}, pmid = {35169700}, issn = {2632-1297}, support = {/WT_/Wellcome Trust/United Kingdom ; C0396/MRF_/MRF_/United Kingdom ; MR/J000914/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {The nature and extent of persistent neuropsychiatric symptoms after COVID-19 are not established. To help inform mental health service planning in the pandemic recovery phase, we systematically determined the prevalence of neuropsychiatric symptoms in survivors of COVID-19. For this pre-registered systematic review and meta-analysis (PROSPERO ID CRD42021239750), we searched MEDLINE, EMBASE, CINAHL and PsycINFO to 20 February 2021, plus our own curated database. We included peer-reviewed studies reporting neuropsychiatric symptoms at post-acute or later time-points after COVID-19 infection and in control groups where available. For each study, a minimum of two authors extracted summary data. For each symptom, we calculated a pooled prevalence using generalized linear mixed models. Heterogeneity was measured with I [2]. Subgroup analyses were conducted for COVID-19 hospitalization, severity and duration of follow-up. From 2844 unique titles, we included 51 studies (n = 18 917 patients). The mean duration of follow-up after COVID-19 was 77 days (range 14-182 days). Study quality was most commonly moderate. The most prevalent neuropsychiatric symptom was sleep disturbance [pooled prevalence = 27.4% (95% confidence interval 21.4-34.4%)], followed by fatigue [24.4% (17.5-32.9%)], objective cognitive impairment [20.2% (10.3-35.7%)], anxiety [19.1% (13.3-26.8%)] and post-traumatic stress [15.7% (9.9-24.1%)]. Only two studies reported symptoms in control groups, both reporting higher frequencies in COVID-19 survivors versus controls. Between-study heterogeneity was high (I [2 ]= 79.6-98.6%). There was little or no evidence of differential symptom prevalence based on hospitalization status, severity or follow-up duration. Neuropsychiatric symptoms are common and persistent after recovery from COVID-19. The literature on longer-term consequences is still maturing but indicates a particularly high prevalence of insomnia, fatigue, cognitive impairment and anxiety disorders in the first 6 months after infection.}, }
@article {pmid35174650, year = {2022}, author = {Clark, IA}, title = {Chronic cerebral aspects of long COVID, post-stroke syndromes and similar states share their pathogenesis and perispinal etanercept treatment logic.}, journal = {Pharmacology research &amp; perspectives}, volume = {10}, number = {2}, pages = {e00926}, pmid = {35174650}, issn = {2052-1707}, mesh = {COVID-19/*complications/metabolism/pathology ; Etanercept/administration &amp; dosage/*therapeutic use ; Humans ; Injections, Spinal ; Microglia/metabolism/pathology ; Stroke/*complications/metabolism ; Syndrome ; Tumor Necrosis Factor-alpha/metabolism ; Post-Acute COVID-19 Syndrome ; }, abstract = {The chronic neurological aspects of traumatic brain injury, post-stroke syndromes, long COVID-19, persistent Lyme disease, and influenza encephalopathy having close pathophysiological parallels that warrant being investigated in an integrated manner. A mechanism, common to all, for this persistence of the range of symptoms common to these conditions is described. While TNF maintains cerebral homeostasis, its excessive production through either pathogen-associated molecular patterns or damage-associated molecular patterns activity associates with the persistence of the symptoms common across both infectious and non-infectious conditions. The case is made that this shared chronicity arises from a positive feedback loop causing the persistence of the activation of microglia by the TNF that these cells generate. Lowering this excess TNF is the logical way to reducing this persistent, TNF-maintained, microglial activation. While too large to negotiate the blood-brain barrier effectively, the specific anti-TNF biological, etanercept, shows promise when administered by the perispinal route, which allows it to bypass this obstruction.}, }
@article {pmid35176758, year = {2022}, author = {Raman, B and Bluemke, DA and Lüscher, TF and Neubauer, S}, title = {Long COVID: post-acute sequelae of COVID-19 with a cardiovascular focus.}, journal = {European heart journal}, volume = {43}, number = {11}, pages = {1157-1172}, pmid = {35176758}, issn = {1522-9645}, support = {//National Institute for Health Research/ ; //Oxford Biomedical Research Centre/ ; RE/18/3/34214//Oxford British Heart Foundation (BHF) Centre of Research Excellence/ ; }, mesh = {*COVID-19/complications ; *Heart Diseases ; Humans ; *Myocarditis/etiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Emerging as a new epidemic, long COVID or post-acute sequelae of coronavirus disease 2019 (COVID-19), a condition characterized by the persistence of COVID-19 symptoms beyond 3 months, is anticipated to substantially alter the lives of millions of people globally. Cardiopulmonary symptoms including chest pain, shortness of breath, fatigue, and autonomic manifestations such as postural orthostatic tachycardia are common and associated with significant disability, heightened anxiety, and public awareness. A range of cardiovascular (CV) abnormalities has been reported among patients beyond the acute phase and include myocardial inflammation, myocardial infarction, right ventricular dysfunction, and arrhythmias. Pathophysiological mechanisms for delayed complications are still poorly understood, with a dissociation seen between ongoing symptoms and objective measures of cardiopulmonary health. COVID-19 is anticipated to alter the long-term trajectory of many chronic cardiac diseases which are abundant in those at risk of severe disease. In this review, we discuss the definition of long COVID and its epidemiology, with an emphasis on cardiopulmonary symptoms. We further review the pathophysiological mechanisms underlying acute and chronic CV injury, the range of post-acute CV sequelae, and impact of COVID-19 on multiorgan health. We propose a possible model for referral of post-COVID-19 patients to cardiac services and discuss future directions including research priorities and clinical trials that are currently underway to evaluate the efficacy of treatment strategies for long COVID and associated CV sequelae.}, }
@article {pmid35182760, year = {2022}, author = {Yelin, D and Moschopoulos, CD and Margalit, I and Gkrania-Klotsas, E and Landi, F and Stahl, JP and Yahav, D}, title = {ESCMID rapid guidelines for assessment and management of long COVID.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {28}, number = {7}, pages = {955-972}, pmid = {35182760}, issn = {1469-0691}, mesh = {*COVID-19/complications/diagnosis/therapy ; Evidence-Based Medicine ; Humans ; Quality of Life ; Recovery of Function ; Return to Work ; Post-Acute COVID-19 Syndrome ; }, abstract = {SCOPE: The aim of these guidelines is to provide evidence-based recommendations for the assessment and management of individuals with persistent symptoms after acute COVID-19 infection and to provide a definition for this entity, termed 'long COVID'.<br><br>METHODS: We performed a search of the literature on studies addressing epidemiology, symptoms, assessment, and treatment of long COVID. The recommendations were grouped by these headings and by organ systems for assessment and treatment. An expert opinion definition of long COVID is provided. Symptoms were reviewed by a search of the available literature. For assessment recommendations, we aimed to perform a diagnostic meta-analysis, but no studies provided relevant results. For treatment recommendations we performed a systematic review of the literature in accordance with the PRISMA statement. We aimed to evaluate patient-related outcomes, including quality of life, return to baseline physical activity, and return to work. Quality assessment of studies included in the systematic review is provided according to study design.<br><br>RECOMMENDATIONS: Evidence was insufficient to provide any recommendation other than conditional guidance. The panel recommends considering routine blood tests, chest imaging, and pulmonary functions tests for patients with persistent respiratory symptoms at 3&#xa0;months. Other tests should be performed mainly to exclude other conditions according to symptoms. For management, no evidence-based recommendations could be provided. Physical and respiratory rehabilitation should be considered. On the basis of limited evidence, the panel suggests designing high-quality prospective clinical studies/trials, including a control group, to further evaluate the assessment and management of individuals with persistent symptoms of COVID-19.}, }
@article {pmid35182777, year = {2022}, author = {Dotan, A and David, P and Arnheim, D and Shoenfeld, Y}, title = {The autonomic aspects of the post-COVID19 syndrome.}, journal = {Autoimmunity reviews}, volume = {21}, number = {5}, pages = {103071}, pmid = {35182777}, issn = {1873-0183}, mesh = {Autonomic Nervous System ; *COVID-19/complications ; Humans ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The SARS-CoV-2 outbreak, responsible for the widespread COVID-19, led to one of the most rogue pandemics in modern time, yet the major effects of the pandemic may still be ahead of us. SARS-CoV-2 had been found to possess autoimmune properties. Close to 20 distinct autoantibodies which target GPCR of the nervous system and renin-angiotensin system-related molecules were found significantly associated with the clinical severity of COVID-19. The new on-set of more than 10 various autoimmune disorders were documented as well. Additionally, clinical presentations of persisted symptoms were triggered in numerous recently recovered COVID-19 patients, which led to the formulation of the novel term "post-COVID19 syndrome". Manifestations related to post-COVID-19 syndrome exist among approximately 50-80% of symptomatic COVID-19 patients who recovered, and among patients reported more than 50 different long-term effects of the SARS-CoV-2 infection. Many of the common symptoms of the post-COVID19 syndrome are not explained by the virus-related injury alone. Similarly to chronic fatigue syndrome and fibromyalgia, autoimmune-mediated autonomic nervous system dysfunction may play a significant part in the pathogenesis of such symptoms, including chronic fatigue, cognitive impairment, mood related disorders, and numerous more. Importantly, therapeutic options such as immunomodulatory and immunosuppressive therapy may favor some post-COVID19 patients, while plasmapheresis and IVIG could be considered in severe cases. Nevertheless, as physical exercise has been found to stabilize the autonomic nervous system, exercise therapy might be a safer and more effective remedy for the post-COVID19 syndrome.}, }
@article {pmid35195253, year = {2022}, author = {Kell, DB and Laubscher, GJ and Pretorius, E}, title = {A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications.}, journal = {The Biochemical journal}, volume = {479}, number = {4}, pages = {537-559}, pmid = {35195253}, issn = {1470-8728}, mesh = {*Amyloid/blood/chemistry ; Anticoagulants/*therapeutic use ; *COVID-19/blood ; Fibrin/chemistry/metabolism ; Humans ; *Lung/metabolism/virology ; SARS-CoV-2/*metabolism ; *Thrombosis/drug therapy/metabolism/virology ; *COVID-19 Drug Treatment ; }, abstract = {Post-acute sequelae of COVID (PASC), usually referred to as 'Long COVID' (a phenotype of COVID-19), is a relatively frequent consequence of SARS-CoV-2 infection, in which symptoms such as breathlessness, fatigue, 'brain fog', tissue damage, inflammation, and coagulopathies (dysfunctions of the blood coagulation system) persist long after the initial infection. It bears similarities to other post-viral syndromes, and to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Many regulatory health bodies still do not recognize this syndrome as a separate disease entity, and refer to it under the broad terminology of 'COVID', although its demographics are quite different from those of acute COVID-19. A few years ago, we discovered that fibrinogen in blood can clot into an anomalous 'amyloid' form of fibrin that (like other β-rich amyloids and prions) is relatively resistant to proteolysis (fibrinolysis). The result, as is strongly manifested in platelet-poor plasma (PPP) of individuals with Long COVID, is extensive fibrin amyloid microclots that can persist, can entrap other proteins, and that may lead to the production of various autoantibodies. These microclots are more-or-less easily measured in PPP with the stain thioflavin T and a simple fluorescence microscope. Although the symptoms of Long COVID are multifarious, we here argue that the ability of these fibrin amyloid microclots (fibrinaloids) to block up capillaries, and thus to limit the passage of red blood cells and hence O2 exchange, can actually underpin the majority of these symptoms. Consistent with this, in a preliminary report, it has been shown that suitable and closely monitored 'triple' anticoagulant therapy that leads to the removal of the microclots also removes the other symptoms. Fibrin amyloid microclots represent a novel and potentially important target for both the understanding and treatment of Long COVID and related disorders.}, }
@article {pmid35198136, year = {2022}, author = {Stefanou, MI and Palaiodimou, L and Bakola, E and Smyrnis, N and Papadopoulou, M and Paraskevas, GP and Rizos, E and Boutati, E and Grigoriadis, N and Krogias, C and Giannopoulos, S and Tsiodras, S and Gaga, M and Tsivgoulis, G}, title = {Neurological manifestations of long-COVID syndrome: a narrative review.}, journal = {Therapeutic advances in chronic disease}, volume = {13}, number = {}, pages = {20406223221076890}, pmid = {35198136}, issn = {2040-6223}, abstract = {Accumulating evidence points toward a very high prevalence of prolonged neurological symptoms among coronavirus disease 2019 (COVID-19) survivors. To date, there are no solidified criteria for 'long-COVID' diagnosis. Nevertheless, 'long-COVID' is conceptualized as a multi-organ disorder with a wide spectrum of clinical manifestations that may be indicative of underlying pulmonary, cardiovascular, endocrine, hematologic, renal, gastrointestinal, dermatologic, immunological, psychiatric, or neurological disease. Involvement of the central or peripheral nervous system is noted in more than one-third of patients with antecedent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, while an approximately threefold higher incidence of neurological symptoms is recorded in observational studies including patient-reported data. The most frequent neurological manifestations of 'long-COVID' encompass fatigue; 'brain fog'; headache; cognitive impairment; sleep, mood, smell, or taste disorders; myalgias; sensorimotor deficits; and dysautonomia. Although very limited evidence exists to date on the pathophysiological mechanisms implicated in the manifestation of 'long-COVID', neuroinflammatory and oxidative stress processes are thought to prevail in propagating neurological 'long-COVID' sequelae. In this narrative review, we sought to present a comprehensive overview of our current understanding of clinical features, risk factors, and pathophysiological processes of neurological 'long-COVID' sequelae. Moreover, we propose diagnostic and therapeutic algorithms that may aid in the prompt recognition and management of underlying causes of neurological symptoms that persist beyond the resolution of acute COVID-19. Furthermore, as causal treatments for 'long-COVID' are currently unavailable, we propose therapeutic approaches for symptom-oriented management of neurological 'long-COVID' symptoms. In addition, we emphasize that collaborative research initiatives are urgently needed to expedite the development of preventive and therapeutic strategies for neurological 'long-COVID' sequelae.}, }
@article {pmid35203555, year = {2022}, author = {Chutipongtanate, S and Morrow, AL and Newburg, DS}, title = {Human Milk Oligosaccharides: Potential Applications in COVID-19.}, journal = {Biomedicines}, volume = {10}, number = {2}, pages = {}, pmid = {35203555}, issn = {2227-9059}, abstract = {Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has become a global health crisis with more than four million deaths worldwide. A substantial number of COVID-19 survivors continue suffering from long-COVID syndrome, a long-term complication exhibiting chronic inflammation and gut dysbiosis. Much effort is being expended to improve therapeutic outcomes. Human milk oligosaccharides (hMOS) are non-digestible carbohydrates known to exert health benefits in breastfed infants by preventing infection, maintaining immune homeostasis and nurturing healthy gut microbiota. These beneficial effects suggest the hypothesis that hMOS might have applications in COVID-19 as receptor decoys, immunomodulators, mucosal signaling agents, and prebiotics. This review summarizes hMOS biogenesis and classification, describes the possible mechanisms of action of hMOS upon different phases of SARS-CoV-2 infection, and discusses the challenges and opportunities of hMOS research for clinical applications in COVID-19.}, }
@article {pmid35205026, year = {2022}, author = {Bellanti, F and Lo Buglio, A and Vendemiale, G}, title = {Redox Homeostasis and Immune Alterations in Coronavirus Disease-19.}, journal = {Biology}, volume = {11}, number = {2}, pages = {}, pmid = {35205026}, issn = {2079-7737}, abstract = {The global Coronavirus Disease 2019 (COVID-19) pandemic is characterized by a wide variety of clinical features, from no or moderate symptoms to severe illness. COVID-19 is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that first affects the respiratory tract. Other than being limited to lungs, SARS-CoV-2 may lead to a multisystem disease that can even be durable (long COVID). The clinical spectrum of COVID-19 depends on variability in the immune regulation. Indeed, disease progression is consequent to failure in the immune regulation, characterized by an intensification of the pro-inflammatory response. Disturbance of systemic and organ-related redox balance may be a further mechanism underlying variability in COVID-19 severity. Other than being determinant for SARS-CoV-2 entry and fusion to the host cell, reactive species and redox signaling are deeply involved in the immune response. This review sums up the present knowledge on the role of redox balance in the regulation of susceptibility to SARS-CoV-2 infection and related immune response, debating the effectiveness of antioxidant compounds in the management of COVID-19.}, }
@article {pmid35207003, year = {2022}, author = {Vink, M and Vink-Niese, F}, title = {Is It Useful to Question the Recovery Behaviour of Patients with ME/CFS or Long COVID?.}, journal = {Healthcare (Basel, Switzerland)}, volume = {10}, number = {2}, pages = {}, pmid = {35207003}, issn = {2227-9032}, abstract = {For the last few decades, medical guidelines have recommended treating patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) with graded exercise therapy (GET) and cognitive behavioural therapy (CBT). Moreover, doctors have questioned the recovery behaviour of these patients and stimulated them to follow these treatments so that they would be able to go back to work. In this article, we reviewed trials of GET and CBT for ME/CFS that reported on work status before and after treatment to answer the question of whether doctors should continue to question the recovery behaviour of patients with ME/CFS. Our review shows that more patients are unable to work after treatment than before treatment with CBT and GET. It also highlights the fact that both treatments are unsafe for patients with ME/CFS. Therefore, questioning the recovery behaviour of patients with ME/CFS is pointless. This confirms the conclusion from the British National Institute for Health and Care Excellence (NICE), which has recently published its updated ME/CFS guideline and concluded that CBT and GET are not effective and do not lead to recovery. Studies on CBT and GET for long COVID have not yet been published. However, this review offers no support for their use in improving the recovery of patients with an ME/CFS-like illness after infection with COVID-19, nor does it lend any support to the practice of questioning the recovery behaviour of these patients.}, }
@article {pmid35207572, year = {2022}, author = {Fainardi, V and Meoli, A and Chiopris, G and Motta, M and Skenderaj, K and Grandinetti, R and Bergomi, A and Antodaro, F and Zona, S and Esposito, S}, title = {Long COVID in Children and Adolescents.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, pmid = {35207572}, issn = {2075-1729}, abstract = {Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) has caused significant mortality and morbidity worldwide. In children, the acute SARS-CoV-2 infection is often asymptomatic or paucisymptomatic, and life-threatening complications are rare. Nevertheless, there are two long-term consequences of SARS-CoV-2 infection in children that raise concern: multisystem inflammatory syndrome in children (MIS-C) and long COVID. While the understanding and the experience regarding the acute phase of SARS-CoV-2 infection have remarkably increased over time, scientific and clinical research is still exploring the long-term effects of COVID-19. In children, data on long COVID are scant. Reports are conflicting regarding its prevalence, duration and impact on daily life. This narrative review explored the latest literature regarding long COVID-19 in the pediatric population. We showed that long COVID in children might be a relevant clinical problem. In most cases, the prognosis is good, but some children may develop long-term symptoms with a significant impact on their daily life. The paucity of studies on long COVID, including a control group of children not infected by SARS-CoV-2, prevents us from drawing firm conclusions. Whether the neuropsychiatric symptoms widely observed in children and adolescents with long COVID are the consequence of SARS-CoV-2 infection or are due to the tremendous stress resulting from the restrictions and the pandemics is still not clear. In both cases, psychological support can play a fundamental role in managing COVID pandemics in children. More knowledge is needed to share a standardized definition of the syndrome and improve its management and treatment.}, }
@article {pmid35215212, year = {2022}, author = {Han, Q and Zheng, B and Daines, L and Sheikh, A}, title = {Long-Term Sequelae of COVID-19: A Systematic Review and Meta-Analysis of One-Year Follow-Up Studies on Post-COVID Symptoms.}, journal = {Pathogens (Basel, Switzerland)}, volume = {11}, number = {2}, pages = {}, pmid = {35215212}, issn = {2076-0817}, support = {MC_PC_19004/MRC_/Medical Research Council/United Kingdom ; MR/V027859/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Emerging evidence has shown that COVID-19 survivors could suffer from persistent symptoms. However, it remains unclear whether these symptoms persist over the longer term. This study aimed to systematically synthesise evidence on post-COVID symptoms persisting for at least 12 months. We searched PubMed and Embase for papers reporting at least one-year follow-up results of COVID-19 survivors published by 6 November 2021. Random-effects meta-analyses were conducted to estimate pooled prevalence of specific post-COVID symptoms. Eighteen papers that reported one-year follow-up data from 8591 COVID-19 survivors were included. Fatigue/weakness (28%, 95% CI: 18-39), dyspnoea (18%, 95% CI: 13-24), arthromyalgia (26%, 95% CI: 8-44), depression (23%, 95% CI: 12-34), anxiety (22%, 95% CI: 15-29), memory loss (19%, 95% CI: 7-31), concentration difficulties (18%, 95% CI: 2-35), and insomnia (12%, 95% CI: 7-17) were the most prevalent symptoms at one-year follow-up. Existing evidence suggested that female patients and those with more severe initial illness were more likely to suffer from the sequelae after one year. This study demonstrated that a sizeable proportion of COVID-19 survivors still experience residual symptoms involving various body systems one year later. There is an urgent need for elucidating the pathophysiologic mechanisms and developing and testing targeted interventions for long-COVID patients.}, }
@article {pmid35216286, year = {2022}, author = {Russo, A and Tellone, E and Barreca, D and Ficarra, S and Laganà, G}, title = {Implication of COVID-19 on Erythrocytes Functionality: Red Blood Cell Biochemical Implications and Morpho-Functional Aspects.}, journal = {International journal of molecular sciences}, volume = {23}, number = {4}, pages = {}, pmid = {35216286}, issn = {1422-0067}, mesh = {Anemia/virology ; Antiviral Agents/pharmacology ; COVID-19/*blood/complications/*diet therapy/etiology/metabolism ; Erythrocytes/metabolism/pathology/*virology ; Hemoglobins/metabolism ; Hemolysis ; Humans ; Oxidative Stress ; Post-Acute COVID-19 Syndrome ; }, abstract = {Several diseases (such as diabetes, cancer, and neurodegenerative disorders) affect the morpho-functional aspects of red blood cells, sometimes altering their normal metabolism. In this review, the hematological changes are evaluated, with particular focus on the morphology and metabolic aspects of erythrocytes. Changes in the functionality of such cells may, in fact, help provide important information about disease severity and progression. The viral infection causes significant damage to the blood cells that are altered in size, rigidity, and distribution width. Lower levels of hemoglobin and anemia have been reported in several studies, and an alteration in the concentration of antioxidant enzymes has been shown to promote a dangerous state of oxidative stress in red blood cells. Patients with severe COVID-19 showed an increase in hematological changes, indicating a progressive worsening as COVID-19 severity progressed. Therefore, monitored hematological alterations in patients with COVID-19 may play an important role in the management of the disease and prevent the risk of a severe course of the disease. Finally, monitored changes in erythrocytes and blood, in general, may be one of the causes of the condition known as Long COVID.}, }
@article {pmid35216882, year = {2022}, author = {Chuang, HJ and Hsiao, MY and Wang, TG and Liang, HW}, title = {A multi-disciplinary rehabilitation approach for people surviving severe COVID-19-a case series and literature review.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {121}, number = {12}, pages = {2408-2415}, pmid = {35216882}, issn = {0929-6646}, mesh = {Humans ; *COVID-19 ; Critical Illness ; Activities of Daily Living ; Taiwan ; }, abstract = {BACKGROUND/PURPOSE: COronaVIrus Disease 2019 (COVID-19) has caused tremendous casualties and morbidities worldwide. Multisystem manifestations, including muscle weakness, dyspnea, cognitive decline, dysphagia, and dysarthria are frequently reported among critically ill patients. The resultant activity limitations and participation restrictions call for an organized and multidisciplinary approach to rehabilitation. Taiwan had a rapid surge in community infection cases from May to July 2021, and our team established a team-based approach in response to the rehabilitation needs for the in-patients, especially the critically-ill group.<br><br>METHODS: We built a core treatment team and established a referral pathway for critically ill patients with COVID-19 based on a multidisciplinary approach. The care process and outcomes of a case series of patients who received in-patient rehabilitation after medical stabilization were presented.<br><br>RESULTS: Our clinical care module was established according to interim World Health Organization guidance and current research and demonstrated a high degree of feasibility. Five patients with multiple impairments received in-patient rehabilitation and experienced significant functional improvement. We documented improvements in motor function, swallowing function, and activities of daily living after the rehabilitation.<br><br>CONCLUSION: Our clinical experience suggests considerable benefits can be obtained from a well-organized and multidisciplinary rehabilitation approach for severe COVID-19 patients.}, }
@article {pmid35219440, year = {2022}, author = {Butler, M and Cross, B and Hafeez, D and Lim, MF and Morrin, H and Rengasamy, ER and Pollak, T and Nicholson, TR}, title = {Emerging Knowledge of the Neurobiology of COVID-19.}, journal = {The Psychiatric clinics of North America}, volume = {45}, number = {1}, pages = {29-43}, pmid = {35219440}, issn = {1558-3147}, mesh = {*COVID-19/complications ; Humans ; Nervous System Diseases/*virology ; Neurobiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Many patients with COVID-19 will experience acute or longer-term neuropsychiatric complications. The neurobiological mechanisms behind these are beginning to emerge; however, the neurotropic hypothesis is not strongly supported by clinical data. The inflammatory response to SARS-CoV-2 is likely to be responsible for delirium and other common acute neuropsychiatric manifestations. Vascular abnormalities such as endotheliopathies contribute to stroke and cerebral microbleeds, with their attendant neuropsychiatric sequelae. Longer-term neuropsychiatric syndromes fall into 2 broad categories: neuropsychiatric deficits occurring after severe (hospitalized) COVID-19 and "long COVID," which occurs in many patients with a milder acute COVID-19 illness.}, }
@article {pmid35227568, year = {2022}, author = {Serhan, CN and Libreros, S and Nshimiyimana, R}, title = {E-series resolvin metabolome, biosynthesis and critical role of stereochemistry of specialized pro-resolving mediators (SPMs) in inflammation-resolution: Preparing SPMs for long COVID-19, human clinical trials, and targeted precision nutrition.}, journal = {Seminars in immunology}, volume = {59}, number = {}, pages = {101597}, pmid = {35227568}, issn = {1096-3618}, support = {K99 HL153673/HL/NHLBI NIH HHS/United States ; R35 GM139430/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Humans ; *COVID-19 ; Docosahexaenoic Acids/therapeutic use ; *Eicosapentaenoic Acid/therapeutic use ; Inflammation ; Inflammation Mediators/metabolism ; Metabolome ; Pandemics ; Post-Acute COVID-19 Syndrome ; Clinical Trials as Topic ; }, abstract = {The COVID-19 pandemic has raised international awareness of the importance of rigorous scientific evidence and the havoc caused by uncontrolled excessive inflammation. Here we consider the evidence on whether the specialized pro-resolving mediators (SPMs) are ready to meet this challenge as well as targeted metabololipidomics of the resolution-inflammation metabolomes. Specific stereochemical mechanisms in the biosynthesis of SPMs from omega-3 essential fatty acids give rise to unique local-acting lipid mediators. SPMs possess stereochemically defined potent bioactive structures that are high-affinity ligands for cognate G protein-coupled surface receptors that evoke the cellular responses required for efficient resolution of acute inflammation. The SPMs biosynthesized from the major omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are coined Resolvins (resolution phase interaction products; E series and D-series), Protectins and Maresins (macrophage mediators in resolving inflammation). Their biosynthesis and stereochemical assignments are established and confirmed (>1,441 resolvin publications in PubMed.gov) as well as their functional roles on innate immune cells and adaptive immune cells (both lymphocyte T-cell subsets and B-cells). The resolution of a protective acute inflammatory response is governed mainly by phagocytes that actively clear apoptotic cells, debris, blood clots and pathogens. These resolution phase functions of the acute inflammatory response are enhanced by SPMs, which together prepare the inflammatory loci for homeostasis and stimulate tissue regeneration via activating stem cells and the biosynthesis of novel cys-SPMs (e.g. MCTRs, PCTRs and RCTRs). These cys-SPMs also activate regeneration, are organ protective and stimulate resolution of local inflammation. Herein, we review the biosynthesis and functions of the E-series resolvins, namely resolvin E1 (the first n-3 resolvin identified), resolvin E2, resolvin E3 and resolvin E4 biosynthesized from their precursor eicosapentaenoic acid (EPA), and the critical role of total organic synthesis in confirming SPM complete stereochemistry, establishing their potent functions in resolution of inflammation, and novel structures. The physical properties of each biologically derived SPM, i.e., ultra-violet (UV) absorbance, chromatographic behavior, and tandem mass spectrometry (MS[2]) fragmentation, were matched to SPMs biosynthesized and prepared by stereospecific total organic synthesis. We briefly review this approach, also used with the endogenous D-series resolvins, protectins and maresins confirming their potent functions in resolution of inflammation, that paves the way for their rigorous evaluation in human tissues and clinical trials. The assignment of complete stereochemistry for each of the E and D series Resolvins, Protectins and Maresins was a critical and required step that enabled human clinical studies as in SPM profiling in COVID-19 infections and experimental animal disease models that also opened the promise of resolution physiology, resolution pharmacology and targeted precision nutrition as new areas for monitoring health and disease mechanisms.}, }
@article {pmid35229544, year = {2022}, author = {Ashton, R and Ansdell, P and Hume, E and Maden-Wilkinson, T and Ryan, D and Tuttiett, E and Faghy, M}, title = {COVID-19 and the long-term cardio-respiratory and metabolic health complications.}, journal = {Reviews in cardiovascular medicine}, volume = {23}, number = {2}, pages = {53}, doi = {10.31083/j.rcm2302053}, pmid = {35229544}, issn = {2153-8174}, mesh = {*COVID-19/complications ; Cardiovascular System ; Humans ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2) transmission continues to impact people globally. Whilst the acute symptoms and management strategies are well documented, millions of people globally are experiencing a prolonged and debilitating symptom profile that is reported to last months and even years. COVID-19 is a multi-system disease however the magnitude of the effects and its associated legacy is presently not well understood. Early reports indicate that multidisciplinary approaches between clinical and non-clinical entities are needed to provide effective and rehabilitative patient support pathways and restore pre-COVID-19 quality of life and functional status. Accordingly, this review provides a summary of the impact on cardiovascular, inflammatory, respiratory, and musculoskeletal function following an acute COVID-19 infection along with the prolonged effects of long-COVID.}, }
@article {pmid35242762, year = {2022}, author = {Martínez-Salazar, B and Holwerda, M and Stüdle, C and Piragyte, I and Mercader, N and Engelhardt, B and Rieben, R and Döring, Y}, title = {COVID-19 and the Vasculature: Current Aspects and Long-Term Consequences.}, journal = {Frontiers in cell and developmental biology}, volume = {10}, number = {}, pages = {824851}, pmid = {35242762}, issn = {2296-634X}, abstract = {Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was first identified in December 2019 as a novel respiratory pathogen and is the causative agent of Corona Virus disease 2019 (COVID-19). Early on during this pandemic, it became apparent that SARS-CoV-2 was not only restricted to infecting the respiratory tract, but the virus was also found in other tissues, including the vasculature. Individuals with underlying pre-existing co-morbidities like diabetes and hypertension have been more prone to develop severe illness and fatal outcomes during COVID-19. In addition, critical clinical observations made in COVID-19 patients include hypercoagulation, cardiomyopathy, heart arrythmia, and endothelial dysfunction, which are indicative for an involvement of the vasculature in COVID-19 pathology. Hence, this review summarizes the impact of SARS-CoV-2 infection on the vasculature and details how the virus promotes (chronic) vascular inflammation. We provide a general overview of SARS-CoV-2, its entry determinant Angiotensin-Converting Enzyme II (ACE2) and the detection of the SARS-CoV-2 in extrapulmonary tissue. Further, we describe the relation between COVID-19 and cardiovascular diseases (CVD) and their impact on the heart and vasculature. Clinical findings on endothelial changes during COVID-19 are reviewed in detail and recent evidence from in vitro studies on the susceptibility of endothelial cells to SARS-CoV-2 infection is discussed. We conclude with current notions on the contribution of cardiovascular events to long term consequences of COVID-19, also known as "Long-COVID-syndrome". Altogether, our review provides a detailed overview of the current perspectives of COVID-19 and its influence on the vasculature.}, }
@article {pmid35256357, year = {2022}, author = {Brennan, A and Broughan, J and McCombe, G and Brennan, J and Collins, C and Fawsitt, R and Gallagher, J and Guérandel, A and O'Kelly, B and Quinlan, D and Lambert, JS and Cullen, W}, title = {Enhancing the management of long COVID in general practice: a scoping review.}, journal = {BJGP open}, volume = {6}, number = {3}, pages = {}, pmid = {35256357}, issn = {2398-3795}, abstract = {BACKGROUND: Long COVID is a multifaceted condition, and it has impacted a considerable proportion of those with acute COVID-19. Affected patients often have complex care needs requiring holistic and multidisciplinary care, the kind routinely provided in general practice. However, there is limited evidence regarding GP interventions.<br><br>AIM: This study aimed to identify key concepts and knowledge gaps around long COVID by conducting a scoping review of literature on the condition's management by GPs.<br><br>DESIGN &amp; SETTING: Arksey and O'Malley's six-stage scoping review framework, with recommendations by Levac et al, was used.<br><br>METHOD: PubMed, Google Scholar, the Cochrane Library, Scopus, and Google searches were conducted to identify relevant peer reviewed and grey literature, and study selection process was conducted according to the PRISMA Extension for Scoping Reviews guidelines. Braun and Clarke's 'Thematic Analysis' approach was used to interpret data.<br><br>RESULTS: Nineteen of 972 identified articles were selected for review. These included peer reviewed articles and grey literature spanning a wide range of countries. Six themes were identified regarding GP management of long COVID, these being: (1) GP uncertainty, (2) listening and empathy, (3) assessment and monitoring of symptoms, (4) coordinating access to appropriate services, (5) facilitating provision of continual and integrated multidisciplinary care and (6) need to provide or facilitate psychological support.<br><br>CONCLUSION: The findings show that GPs can play and have played a key role in the management of long COVID, and that patient care can be improved through better understanding of patient experiences, standardised approaches for symptom identification and treatment, and facilitation of access to multidisciplinary specialist services when needed. Future research evaluating focused GP interventions is needed.}, }
@article {pmid35260380, year = {2022}, author = {López-Sampalo, A and Bernal-López, MR and Gómez-Huelgas, R}, title = {Persistent COVID-19 syndrome. A narrative review.}, journal = {Revista clinica espanola}, volume = {222}, number = {4}, pages = {241-250}, pmid = {35260380}, issn = {2254-8874}, mesh = {*COVID-19/complications ; Disease Progression ; Female ; Humans ; Middle Aged ; Quality of Life ; SARS-CoV-2 ; Syndrome ; }, abstract = {As the coronavirus-2019 disease (COVID-19) pandemic, caused by the infection with severe acute respiratory syndrome (SARS-CoV-2) coronavirus type 2, has progressed, persistent COVID-19 syndrome is an increasingly recognized problem on which a significant volume of medical literature is developing. Symptoms may be persistent or appear, after an asymptomatic period, weeks or months after the initial infection. The clinical picture is as markedly heterogeneous and multisystemic as in the acute phase, so multidisciplinary management is required. In addition, their appearance is not related to the severity of the initial infection, so they can affect both mild patients, even asymptomatic, and seriously ill patients who have required hospitalization. Although it can affect people of any age, it is more common in middle-aged women. The sequelae can generate a high impact on the quality of life, and in the work and social environment. The objective of this paper is to review persistent COVID-19 syndrome, to know its clinical manifestations and the strategies for the management and follow-up of these patients.}, }
@article {pmid35264003, year = {2022}, author = {Buonsenso, D and Di Gennaro, L and De Rose, C and Morello, R and D'Ilario, F and Zampino, G and Piazza, M and Boner, AL and Iraci, C and O'Connell, S and Cohen, VB and Esposito, S and Munblit, D and Reena, J and Sigfrid, L and Valentini, P}, title = {Long-term outcomes of pediatric infections: from traditional infectious diseases to long Covid.}, journal = {Future microbiology}, volume = {17}, number = {}, pages = {551-571}, pmid = {35264003}, issn = {1746-0921}, mesh = {*COVID-19/complications ; Child ; *Communicable Diseases ; Humans ; Italy/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {There is limited evidence available on the long-term impact of SARS-CoV-2 infection in children. In this article, the authors analyze the recent evidence on pediatric long Covid and lessons learnt from a pediatric post-Covid unit in Rome, Italy. To gain a better understanding of the concerns raised by parents and physicians in relation to the potential long-term consequences of this novel infection, it is important to recognize that long-term effect of a post-infectious disease is not a new phenomenon.}, }
@article {pmid35264214, year = {2022}, author = {Esposito, S and Principi, N and Azzari, C and Cardinale, F and Di Mauro, G and Galli, L and Gattinara, GC and Fainardi, V and Guarino, A and Lancella, L and Licari, A and Mancino, E and Marseglia, GL and Leonardi, S and Nenna, R and Zampogna, S and Zona, S and Staiano, A and Midulla, F}, title = {Italian intersociety consensus on management of long covid in children.}, journal = {Italian journal of pediatrics}, volume = {48}, number = {1}, pages = {42}, pmid = {35264214}, issn = {1824-7288}, mesh = {Adolescent ; *COVID-19/complications ; Child ; Humans ; Pandemics ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome/diagnosis/therapy ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Two sequelae of pediatric COVID-19 have been identified, the multisystem inflammatory syndrome in children (MIS-C) and the long COVID. Long COVID is much less precisely defined and includes all the persistent or new clinical manifestations evidenced in subjects previously infected by SARS-CoV-2 beyond the period of the acute infection and that cannot be explained by an alternative diagnosis. In this Intersociety Consensus, present knowledge on pediatric long COVID as well as how to identify and manage children with long COVID are discussed.<br><br>MAIN FINDINGS: Although the true prevalence of long COVID in pediatrics is not exactly determined, it seems appropriate to recommend evaluating the presence of symptoms suggestive of long COVID near the end of the acute phase of the disease, between 4 and 12&#x2009;weeks from this. Long COVID in children and adolescents should be suspected in presence of persistent headache and fatigue, sleep disturbance, difficulty in concentrating, abdominal pain, myalgia or arthralgia. Persistent chest pain, stomach pain, diarrhea, heart palpitations, and skin lesions should be considered as possible symptoms of long COVID. It is recommended that the primary care pediatrician visits all subjects with a suspected or a proven diagnosis of SARS-CoV-2 infection after 4&#x2009;weeks to check for the presence of symptoms of previously unknown disease. In any case, a further check-up by the primary care pediatrician should be scheduled 3&#x2009;months after the diagnosis of SARS-CoV-2 infection to confirm normality or to address emerging problems. The subjects who present symptoms of any organic problem must undergo a thorough evaluation of the same, with a possible request for clinical, laboratory and / or radiological in-depth analysis in case of need. Children and adolescents with clear symptoms of mental stress will need to be followed up by existing local services for problems of this type.<br><br>CONCLUSIONS: Pediatric long COVID is a relevant problem that involve a considerable proportion of children and adolescents. Prognosis of these cases is generally good as in most of them symptoms disappear spontaneously. The few children with significant medical problems should be early identified after the acute phase of the infection and adequately managed to assure complete resolution. A relevant psychological support for all the children during COVID-19 pandemic must be organized by health authorities and government that have to treat this as a public health issue.}, }
@article {pmid35266533, year = {2022}, author = {Rienks, R and Holdsworth, D and Davos, CH and Halle, M and Bennett, A and Parati, G and Guettler, N and Nicol, ED}, title = {Cardiopulmonary assessment prior to returning to high-hazard occupations post-symptomatic COVID-19 infection: a position statement of the Aviation and Occupational Cardiology Task Force of the European Association of Preventive Cardiology.}, journal = {European journal of preventive cardiology}, volume = {29}, number = {13}, pages = {1724-1730}, pmid = {35266533}, issn = {2047-4881}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Occupations ; *Cardiology ; *Aviation ; Post-Acute COVID-19 Syndrome ; }, abstract = {This article provides an overview of the recommendations of the Aviation and Occupational Cardiology Task Force of the European Association of Preventive Cardiology on returning individuals to work in high-hazard occupations (such as flying, diving, and workplaces that are remote from healthcare facilities) following symptomatic Coronavirus Disease 2019 (COVID-19) infection. This process requires exclusion of significant underlying cardiopulmonary disease and this consensus statement (from experts across the field) outlines the appropriate screening and investigative processes that should be undertaken. The recommended response is based on simple screening in primary healthcare to determine those at risk, followed by first line investigations, including an exercise capacity assessment, to identify the small proportion of individuals who may have circulatory, pulmonary, or mixed disease. These individuals can then receive more advanced, targeted investigations. This statement provides a pragmatic, evidence-based approach for those (in all occupations) to assess employee health and capacity prior to a return to work following severe disease, or while continuing to experience significant post-COVID-19 symptoms (so-called 'long-COVID' or post-COVID-19 syndrome).}, }
@article {pmid35267974, year = {2022}, author = {Motti, ML and Tafuri, D and Donini, L and Masucci, MT and De Falco, V and Mazzeo, F}, title = {The Role of Nutrients in Prevention, Treatment and Post-Coronavirus Disease-2019 (COVID-19).}, journal = {Nutrients}, volume = {14}, number = {5}, pages = {}, pmid = {35267974}, issn = {2072-6643}, mesh = {*COVID-19/complications/prevention &amp; control ; Humans ; Nutrients ; Pandemics/prevention &amp; control ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {SARS-CoV-2 virus, infecting human cells via its spike protein, causes Coronavirus disease 2019 (COVID-19). COVID-19 is characterized by shortness of breath, fever, and pneumonia and is sometimes fatal. Unfortunately, to date, there is still no definite therapy to treat COVID-19. Therefore, the World Health Organization (WHO) approved only supportive care. During the COVID-19 pandemic, the need to maintain a correct intake of nutrients to support very weakened patients in overcoming disease arose. The literature available on nutrient intake for COVID-19 is mainly focused on prevention. However, the safe intake of micro- and/or macro-nutrients can be useful either for preventing infection and supporting the immune response during COVID-19, as well as in the post-acute phase, i.e., "long COVID", that is sometimes characterized by the onset of various long lasting and disabling symptoms. The aim of this review is to focus on the role of nutrient intake during all the different phases of the disease, including prevention, the acute phase, and finally long COVID.}, }
@article {pmid35271343, year = {2022}, author = {Merad, M and Blish, CA and Sallusto, F and Iwasaki, A}, title = {The immunology and immunopathology of COVID-19.}, journal = {Science (New York, N.Y.)}, volume = {375}, number = {6585}, pages = {1122-1127}, pmid = {35271343}, issn = {1095-9203}, support = {P30 CA196521/CA/NCI NIH HHS/United States ; R01 AI157488/AI/NIAID NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Adaptive Immunity ; Antibodies, Monoclonal/therapeutic use ; Antiviral Agents/therapeutic use ; COVID-19/*complications/*immunology/physiopathology/therapy/virology ; Female ; Humans ; Immunity, Innate ; Inflammation ; Male ; Risk Factors ; SARS-CoV-2/*immunology/physiology ; Severity of Illness Index ; Post-Acute COVID-19 Syndrome ; }, abstract = {Considerable research effort has been made worldwide to decipher the immune response triggered upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, identify the drivers of severe and fatal COVID-19, and understand what leads to the prolongation of symptoms after disease resolution. We review the results of almost 2 years of COVID-19 immunology research and discuss definitive findings and remaining questions regarding our understanding of COVID-19 pathophysiology. We discuss emerging understanding of differences in immune responses seen in those with and without Long Covid syndrome, also known as post-acute sequelae of SARS-CoV-2. We hope that the knowledge gained from this COVID-19 research will be applied in studies of inflammatory processes involved in critical and chronic illnesses, which remain a major unmet need.}, }
@article {pmid35272262, year = {2022}, author = {Soril, LJJ and Damant, RW and Lam, GY and Smith, MP and Weatherald, J and Bourbeau, J and Hernandez, P and Stickland, MK}, title = {The effectiveness of pulmonary rehabilitation for Post-COVID symptoms: A rapid review of the literature.}, journal = {Respiratory medicine}, volume = {195}, number = {}, pages = {106782}, pmid = {35272262}, issn = {1532-3064}, mesh = {Humans ; *COVID-19/rehabilitation/complications/physiopathology ; Post-Acute COVID-19 Syndrome ; Quality of Life ; SARS-CoV-2 ; Treatment Outcome ; Exercise Tolerance ; }, abstract = {BACKGROUND: Multi-disciplinary rehabilitation is recommended for individuals with post-acute sequelae of COVID-19 infection (i.e., symptoms 3-4 weeks after acute infection). There are emerging reports of use of pulmonary rehabilitation (PR) in the post-acute stages of COVID-19, however the appropriateness of PR for managing post-COVID symptoms remains unclear. To offer practical guidance with regards to post-COVID PR, a greater understanding of the clinical effectiveness literature is required.<br><br>METHODS: A rapid review of the published literature was completed. An electronic database search of the literature published between July 1, 2020 and June 1, 2021 was performed in MEDLINE, Pubmed, and EMBASE. Primary studies evaluating the clinical effectiveness of PR for individuals with post-COVID symptoms were included.<br><br>RESULTS: Nine studies evaluating the effectiveness of PR were identified; most were small, experimental or quasi-experimental studies, including 1 RCT, and were primarily of low quality. After attending PR, all studies reported improvements in exercise capacity, pulmonary function, and/or quality of life for individuals with post-COVID symptoms who had been hospitalized for their acute COVID-19 infection. Few studies evaluated changes in post-COVID symptom severity or frequency and, of these, improvements in dyspnea, fatigue, anxiety and depression were observed following PR. Further, no studies evaluated non-hospitalized patients or long-term outcomes beyond 3 months after initiating PR.<br><br>CONCLUSIONS: With limited high-quality evidence, any recommendations or practical guidance for PR programmes for those with post-COVID symptoms should consider factors such as feasibility, current PR capacity, and resource constraints.}, }
@article {pmid35276888, year = {2022}, author = {Marshall, RP and Droste, JN and Giessing, J and Kreider, RB}, title = {Role of Creatine Supplementation in Conditions Involving Mitochondrial Dysfunction: A Narrative Review.}, journal = {Nutrients}, volume = {14}, number = {3}, pages = {}, pmid = {35276888}, issn = {2072-6643}, mesh = {*Creatine/metabolism/pharmacology/therapeutic use ; Dietary Supplements ; Energy Metabolism ; *Exercise ; Humans ; Mitochondria/metabolism ; }, abstract = {Creatine monohydrate (CrM) is one of the most widely used nutritional supplements among active individuals and athletes to improve high-intensity exercise performance and training adaptations. However, research suggests that CrM supplementation may also serve as a therapeutic tool in the management of some chronic and traumatic diseases. Creatine supplementation has been reported to improve high-energy phosphate availability as well as have antioxidative, neuroprotective, anti-lactatic, and calcium-homoeostatic effects. These characteristics may have a direct impact on mitochondrion's survival and health particularly during stressful conditions such as ischemia and injury. This narrative review discusses current scientific evidence for use or supplemental CrM as a therapeutic agent during conditions associated with mitochondrial dysfunction. Based on this analysis, it appears that CrM supplementation may have a role in improving cellular bioenergetics in several mitochondrial dysfunction-related diseases, ischemic conditions, and injury pathology and thereby could provide therapeutic benefit in the management of these conditions. However, larger clinical trials are needed to explore these potential therapeutic applications before definitive conclusions can be drawn.}, }
@article {pmid35282780, year = {2022}, author = {Ceban, F and Leber, A and Jawad, MY and Yu, M and Lui, LMW and Subramaniapillai, M and Di Vincenzo, JD and Gill, H and Rodrigues, NB and Cao, B and Lee, Y and Lin, K and Mansur, RB and Ho, R and Burke, MJ and Rosenblat, JD and McIntyre, RS}, title = {Registered clinical trials investigating treatment of long COVID: a scoping review and recommendations for research.}, journal = {Infectious diseases (London, England)}, volume = {54}, number = {7}, pages = {467-477}, pmid = {35282780}, issn = {2374-4243}, mesh = {*COVID-19/complications ; Humans ; Research Design ; SARS-CoV-2 ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {BACKGROUND: A considerable proportion of individuals report persistent, debilitating and disparate symptoms despite resolution of acute COVID-19 infection (i.e. long COVID). Numerous registered clinical trials investigating treatment of long COVID are expected to be completed in 2021-2022. The aim of this review is to provide a scope of the candidate treatments for long COVID. A synthesis of ongoing long COVID clinical trials can inform methodologic approaches for future studies and identify key research vistas.<br><br>METHODS: Scoping searches were conducted on multiple national and international clinical trial registries. Interventional trials testing treatments for long COVID were selected. The search timeline was from database inception to 28 July 2021.<br><br>RESULTS: This scoping review included 59 clinical trial registration records from 22 countries with a total projected enrolment of 6718. Considerable heterogeneity was exhibited amongst component records with respect to the characterization of long COVID (i.e. name, symptoms- including frequency, intensity, trajectory and duration- mode of ascertainment, and definition of acute phase). In addition, the majority of proposed interventions were non-pharmacological and either targeted multiple long COVID symptoms simultaneously, or focussed on treatment of respiratory/pulmonary sequelae. Multiple interventions targeted inflammation, as well as tissue oxygenation and cellular recovery, and several interventions were repurposed from analogous conditions.<br><br>CONCLUSIONS: The results of this scoping review investigating ongoing clinical trials testing candidate treatments for long COVID suggest that a greater degree of definitional stringency and homogeneity is needed insofar as the characterization of long COVID and inclusion/exclusion criteria.}, }
@article {pmid35283306, year = {2022}, author = {Prendki, V and Tiseo, G and Falcone, M and , }, title = {Caring for older adults during the COVID-19 pandemic.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {28}, number = {6}, pages = {785-791}, pmid = {35283306}, issn = {1469-0691}, mesh = {Aged ; *COVID-19/epidemiology/therapy ; *Frailty/diagnosis/epidemiology ; Humans ; Pandemics ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Elderly patients represent a high-risk group with increased risk of death from COVID-19. Despite the number of published studies, several unmet needs in care for older adults exist.<br><br>OBJECTIVES: To discuss unmet needs of COVID-19 in this special population.<br><br>SOURCES: A literature review for studies on COVID-19 in elderly patients published between December 2019 and November 2021 was performed. Clinical questions were formulated to guide the literature search. The search was conducted in the MEDLINE database, combining specific search terms. Two reviewers independently conducted the search and selected the studies according to the prespecified clinical questions.<br><br>CONTENT: Elderly patients with COVID-19 have peculiar characteristics. They may have atypical clinical presentation, with no fever and with delirium or neurological manifestations as the most common signs, with potential delayed diagnosis and increased risk of death. The reported fatality rates among elderly patients with COVID-19 are extremely high. Several factors, including comorbidities, atypical presentation, and exclusion from intensive care unit care, contribute to this excess of mortality. Age alone is frequently used as a key factor to exclude the elderly from intensive care, but there is evidence that frailty rather than age better predicts the risk of poor outcome in this category. Durability of vaccine efficacy in the elderly remains debated, and the need for a third booster dose is becoming increasingly evident. Finally, efforts to care for elderly patients who have survived after acute COVID-19 should be implemented, considering the high rates of long COVID sequelae and the risk of longitudinal functional and cognitive decline.<br><br>IMPLICATIONS: We highlight peculiar aspects of COVID-19 in elderly patients and factors contributing to high risk of poor outcome in this category. We also illuminated gaps in current evidence, suggesting future research directions and underlining the need for further studies on the optimal management of elderly patients with COVID-19.}, }
@article {pmid35287333, year = {2022}, author = {Morrow, AK and Malone, LA and Kokorelis, C and Petracek, LS and Eastin, EF and Lobner, KL and Neuendorff, L and Rowe, PC}, title = {Long-Term COVID 19 Sequelae in Adolescents: the Overlap with Orthostatic Intolerance and ME/CFS.}, journal = {Current pediatrics reports}, volume = {10}, number = {2}, pages = {31-44}, pmid = {35287333}, issn = {2167-4841}, abstract = {PURPOSE OF REVIEW: To discuss emerging understandings of adolescent long COVID or post-COVID-19 conditions, including proposed clinical definitions, common symptoms, epidemiology, overlaps with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and orthostatic intolerance, and preliminary guidance on management.<br><br>RECENT FINDINGS: The recent World Health Organization clinical case definition of post-COVID-19 condition requires a history of probable or confirmed SARS-CoV-2 infection, with symptoms starting within 3&#xa0;months of the onset of COVID-19. Symptoms must last for at least 2&#xa0;months and cannot be explained by an alternative diagnosis. Common symptoms of the post-COVID-19 condition include, but are not limited to, fatigue, shortness of breath, and cognitive dysfunction. These symptoms generally have an impact on everyday functioning. The incidence of prolonged symptoms following SARS-CoV-2 infection has proven challenging to define, but it is now clear that those with relatively mild initial infections, without severe initial respiratory disease or end-organ injury, can still develop chronic impairments, with symptoms that overlap with conditions like ME/CFS (profound fatigue, unrefreshing sleep, post-exertional malaise, cognitive dysfunction, and orthostatic intolerance).<br><br>SUMMARY: We do not yet have a clear understanding of the mechanisms by which individuals develop post-COVID-19 conditions. There may be several distinct types of long COVID that require different treatments. At this point, there is no single pharmacologic agent to effectively treat all symptoms. Because some presentations of post-COVID-19 conditions mimic disorders such as ME/CFS, treatment guidelines for this and related conditions can be helpful for managing post-COVID-19 symptoms.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40124-022-00261-4.}, }
@article {pmid35289272, year = {2022}, author = {Costanza, A and Amerio, A and Aguglia, A and Serafini, G and Amore, M and Hasler, R and Ambrosetti, J and Bondolfi, G and Sampogna, G and Berardelli, I and Fiorillo, A and Pompili, M and Nguyen, KD}, title = {Hyper/neuroinflammation in COVID-19 and suicide etiopathogenesis: Hypothesis for a nefarious collision?.}, journal = {Neuroscience and biobehavioral reviews}, volume = {136}, number = {}, pages = {104606}, pmid = {35289272}, issn = {1873-7528}, mesh = {*COVID-19/complications ; Humans ; Neuroinflammatory Diseases ; SARS-CoV-2 ; Suicidal Ideation ; *Suicide ; Post-Acute COVID-19 Syndrome ; }, abstract = {Accumulating scientific and clinical evidence highlighted pathological hyperinflammation as a cardinal feature of SARS-CoV-2 infection and acute COVID-19 disease. With the emergence of long COVID-19 syndrome, several chronic health consequences, including neuropsychiatric sequelae, have gained attention from the public and medical communities. Since inflammatory mediators have also been accredited as putative biomarkers of suicidal ideations and behaviors, hyper- and neuroinflammation might share some colliding points, overlapping and being interconnected in the context of COVID-19. This review aims to provide a summary of current knowledge on the molecular and cellular mechanisms of COVID-19-associated hyper/neuroinflammation with focus on their relevance to the inflammatory hypothesis of suicide development. Subsequently, strategies to alleviate COVID-19 hyper/neuroinflammation by immunomodulatory agents (many of which at experimental stages) as well as psychopharmacologic/psychotherapeutic approaches are also mentioned. While suicide risk in COVID-19 survivors - until now little known - needs further analysis through longitudinal studies, current observations and mechanistic postulates warrant additional attention to this possibly emerging mental health concern.}, }
@article {pmid35294563, year = {2022}, author = {Hennigs, JK and Oqueka, T and Harbaum, L and Klose, H}, title = {[Organ-specific sequelae of COVID-19 in adults].}, journal = {Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz}, volume = {65}, number = {4}, pages = {462-470}, pmid = {35294563}, issn = {1437-1588}, mesh = {Adult ; *COVID-19/complications ; Disease Progression ; Germany ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Organ-specific sequelae after COVID-19 occur frequently and are highly diverse in their features. Sequelae and symptoms persisting for more than four weeks after COVID-19 define the condition "long COVID."Organ-specific sequelae of COVID-19 generally occur more often after severe disease. Yet, duration and intensity of organ-specific sequelae are highly variable. While pulmonary sequelae typically persist after more severe acute disease, COVID-19 sequelae may also develop weeks after infection and can affect any organ. The degree of SARS-CoV‑2 specificity of COVID-19 sequelae, however, remains unclear. Thus, diagnosis and treatment of COVID-19 sequelae represent an interdisciplinary challenge. Diagnostic and therapeutic approaches are guided by type, extent, and cause of the specific sequelae as targeted therapy options for long COVID are lacking.In the present work, we review current knowledge regarding the prevalence/incidence, duration, specificity, type, and extent of organ-specific COVID-19 sequelae and summarize current diagnostic and therapeutic strategies (as of November 2021).}, }
@article {pmid35307746, year = {2022}, author = {Noll, J and Reichert, M and Dietrich, M and Riedel, JG and Hecker, M and Padberg, W and Weigand, MA and Hecker, A}, title = {When to operate after SARS-CoV-2 infection? A review on the recent consensus recommendation of the DGC/BDC and the DGAI/BDA.}, journal = {Langenbeck's archives of surgery}, volume = {407}, number = {4}, pages = {1315-1332}, pmid = {35307746}, issn = {1435-2451}, mesh = {Humans ; *COVID-19 ; Critical Care ; Elective Surgical Procedures/adverse effects ; Pandemics ; SARS-CoV-2 ; Consensus Statements as Topic ; }, abstract = {Since the eruption of the worldwide SARS-CoV-2 pandemic in late 2019/early 2020, multiple elective surgical interventions were postponed. Through pandemic measures, elective operation capacities were reduced in favour of intensive care treatment for critically ill SARS-CoV-2 patients. Although intermittent low-incidence infection rates allowed an increase in elective surgery, surgeons have to include long-term pulmonary and extrapulmonary complications of SARS-CoV-2 infections (especially "Long Covid") in their perioperative management considerations and risk assessment procedures. This review summarizes recent consensus statements and recommendations regarding the timepoint for surgical intervention after SARS-CoV-2 infection released by respective German societies and professional representatives including DGC/BDC (Germany Society of Surgery/Professional Association of German Surgeons e.V.) and DGAI/BDA (Germany Society of Anesthesiology and Intensive Care Medicine/Professional Association of German Anesthesiologists e.V.) within the scope of the recent literature. The current literature reveals that patients with pre- and perioperative SARS-CoV-2 infection have a dramatically deteriorated postoperative outcome. Thereby, perioperative mortality is mainly caused by pulmonary and thromboembolic complications. Notably, perioperative mortality decreases to normal values over time depending on the duration of SARS-CoV-2 infection.}, }
@article {pmid35316977, year = {2022}, author = {Hollenberg, MD and Epstein, M}, title = {The innate immune response, microenvironment proteinases, and the COVID-19 pandemic: pathophysiologic mechanisms and emerging therapeutic targets.}, journal = {Kidney international supplements}, volume = {12}, number = {1}, pages = {48-62}, pmid = {35316977}, issn = {2157-1724}, abstract = {The coronavirus disease 2019 (COVID-19) pandemic, causing considerable mortality and morbidity worldwide, has fully engaged the biomedical community in attempts to elucidate the pathophysiology of COVID-19 and develop robust therapeutic strategies. To this end, the predominant research focus has been on the adaptive immune response to COVID-19 infections stimulated by mRNA and protein vaccines and on the duration and persistence of immune protection. In contrast, the role of the innate immune response to the viral challenge has been underrepresented. This overview focuses on the innate immune response to COVID-19 infection, with an emphasis on the roles of extracellular proteases in the tissue microenvironment. Proteinase-mediated signaling caused by enzymes in the extracellular microenvironment occurs upstream of the increased production of inflammatory cytokines that mediate COVID-19 pathology. These enzymes include the coagulation cascade, kinin-generating plasma kallikrein, and the complement system, as well as angiotensin-generating proteinases of the renin-angiotensin system. Furthermore, in the context of several articles in this Supplement elucidating and detailing the trajectory of diverse profibrotic pathways, we extrapolate these insights to explore how fibrosis and profibrotic pathways participate importantly in the pathogenesis of COVID-19. We propose that the lessons garnered from understanding the roles of microenvironment proteinases in triggering the innate immune response to COVID-19 pathology will identify potential therapeutic targets and inform approaches to the clinical management of COVID-19. Furthermore, the information may also provide a template for understanding the determinants of COVID-19-induced tissue fibrosis that may follow resolution of acute infection (so-called "long COVID"), which represents a major new challenge to our healthcare systems.}, }
@article {pmid35328506, year = {2022}, author = {Che Mohd Nassir, CMN and Zolkefley, MKI and Ramli, MD and Norman, HH and Abdul Hamid, H and Mustapha, M}, title = {Neuroinflammation and COVID-19 Ischemic Stroke Recovery-Evolving Evidence for the Mediating Roles of the ACE2/Angiotensin-(1-7)/Mas Receptor Axis and NLRP3 Inflammasome.}, journal = {International journal of molecular sciences}, volume = {23}, number = {6}, pages = {}, pmid = {35328506}, issn = {1422-0067}, mesh = {Angiotensin I/metabolism ; Angiotensin-Converting Enzyme 2/*metabolism ; COVID-19/complications/*metabolism/virology ; Humans ; Inflammasomes/*metabolism ; Ischemic Stroke/complications/*metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Neuroinflammatory Diseases/complications/*metabolism ; Peptide Fragments/metabolism ; Proteins/*metabolism ; Proto-Oncogene Mas/metabolism ; SARS-CoV-2/metabolism/physiology ; Signal Transduction ; }, abstract = {Cerebrovascular events, notably acute ischemic strokes (AIS), have been reported in the setting of novel coronavirus disease (COVID-19) infection. Commonly regarded as cryptogenic, to date, the etiology is thought to be multifactorial and remains obscure; it is linked either to a direct viral invasion or to an indirect virus-induced prothrombotic state, with or without the presence of conventional cerebrovascular risk factors. In addition, patients are at a greater risk of developing long-term negative sequelae, i.e., long-COVID-related neurological problems, when compared to non-COVID-19 stroke patients. Central to the underlying neurobiology of stroke recovery in the context of COVID-19 infection is reduced angiotensin-converting enzyme 2 (ACE2) expression, which is known to lead to thrombo-inflammation and ACE2/angiotensin-(1-7)/mitochondrial assembly receptor (MasR) (ACE2/Ang-(1-7)/MasR) axis inhibition. Moreover, after AIS, the activated nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome may heighten the production of numerous proinflammatory cytokines, mediating neuro-glial cell dysfunction, ultimately leading to nerve-cell death. Therefore, potential neuroprotective therapies targeting the molecular mechanisms of the aforementioned mediators may help to inform rehabilitation strategies to improve brain reorganization (i.e., neuro-gliogenesis and synaptogenesis) and secondary prevention among AIS patients with or without COVID-19. Therefore, this narrative review aims to evaluate the mediating role of the ACE2/Ang- (1-7)/MasR axis and NLRP3 inflammasome in COVID-19-mediated AIS, as well as the prospects of these neuroinflammation mediators for brain repair and in secondary prevention strategies against AIS in stroke rehabilitation.}, }
@article {pmid35329184, year = {2022}, author = {Neculicioiu, VS and Colosi, IA and Costache, C and Sevastre-Berghian, A and Clichici, S}, title = {Time to Sleep?-A Review of the Impact of the COVID-19 Pandemic on Sleep and Mental Health.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {6}, pages = {}, pmid = {35329184}, issn = {1660-4601}, mesh = {Adult ; *COVID-19/complications/epidemiology ; Communicable Disease Control ; Humans ; Mental Health ; Pandemics ; Sleep/physiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Sleep is intrinsically tied to mental and overall health. Short sleep duration accompanies the modern lifestyle, possibly reaching epidemic proportions. The pandemic and subsequent lockdowns determined a fundamental shift in the modern lifestyle and had profound effects on sleep and mental health. This paper aims to provide an overview of the relationship between sleep, mental health and COVID-19. Contrasting outcomes on sleep health have been highlighted by most reports during the pandemic in the general population. Consequently, while longer sleep durations have been reported, this change was accompanied by decreases in sleep quality and altered sleep timing. Furthermore, an increased impact of sleep deficiencies and mental health burden was generally reported in health care workers as compared with the adult general population. Although not among the most frequent symptoms during the acute or persistent phase, an increased prevalence of sleep deficiencies has been reported in patients with acute and long COVID. The importance of sleep in immune regulation is well known. Consequently, sleep deficiencies may influence multiple aspects of COVID-19, such as the risk, severity, and prognosis of the infection and even vaccine response.}, }
@article {pmid35329867, year = {2022}, author = {Maglietta, G and Diodati, F and Puntoni, M and Lazzarelli, S and Marcomini, B and Patrizi, L and Caminiti, C}, title = {Prognostic Factors for Post-COVID-19 Syndrome: A Systematic Review and Meta-Analysis.}, journal = {Journal of clinical medicine}, volume = {11}, number = {6}, pages = {}, pmid = {35329867}, issn = {2077-0383}, abstract = {Evidence shows that a substantial proportion of patients with COVID-19 experiences long-term consequences of the disease, but the predisposing factors are poorly understood. We conducted a systematic review and meta-analysis to identify factors present during COVID-19 hospitalization associated with an increased risk of exhibiting new or persisting symptoms (Post-COVID-19 Syndrome, PCS). MedLine and WebOfScience were last searched on 30 September 2021. We included English language clinical trials and observational studies investigating prognostic factors for PCS in adults previously hospitalized for COVID-19, reporting at least one individual prospective follow-up of minimum 12 weeks. Two authors independently assessed risk of bias, which was judged generally moderate. Risk factors were included in the analysis if their association with PCS was investigated by at least two studies. To summarize the prognostic effect of each factor (or group of factors), odds ratios were estimated using raw data. Overall, 20 articles met the inclusion criteria, involving 13,340 patients. Associations were statistically significant for two factors: female sex with any symptoms (OR 1.52; 95% CI 1.27-1.82), with mental health symptoms (OR 1.67, 95% CI 1.21-2.29) and with fatigue (OR 1.54, 95% CI 1.32-1.79); acute disease severity with respiratory symptoms (OR 1.66, 95% CI 1.03-2.68). The I[2] statistics tests were calculated to quantify the degree of study heterogeneity. This is the first meta-analysis measuring the association between factors present during COVID-19 hospitalization and long-term sequelae. The role of female sex and acute disease severity as independent prognostic factors must be confirmed in robust longitudinal studies with longer follow-up. Identifying populations at greatest risk for PCS can enable the development of targeted prevention and management strategies. Systematic review registration: PROSPERO CRD42021253467.}, }
@article {pmid35331679, year = {2022}, author = {Alharbi, KS and Singh, Y and Hassan Almalki, W and Rawat, S and Afzal, O and Alfawaz Altamimi, AS and Kazmi, I and Al-Abbasi, FA and Alzarea, SI and Singh, SK and Bhatt, S and Chellappan, DK and Dua, K and Gupta, G}, title = {Gut Microbiota Disruption in COVID-19 or Post-COVID Illness Association with severity biomarkers: A Possible Role of Pre / Pro-biotics in manipulating microflora.}, journal = {Chemico-biological interactions}, volume = {358}, number = {}, pages = {109898}, pmid = {35331679}, issn = {1872-7786}, mesh = {Biomarkers ; *COVID-19/complications ; *Gastrointestinal Diseases ; *Gastrointestinal Microbiome ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Coronavirus disease (COVID-19), a coronavirus-induced illness attributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, is thought to have first emerged on November 17, 2019. According to World Health Organization (WHO). COVID-19 has been linked to 379,223,560 documented occurrences and 5,693,245 fatalities globally as of 1st Feb 2022. Influenza A virus that has also been discovered diarrhea and gastrointestinal discomfort was found in the infected person, highlighting the need of monitoring them for gastro intestinal tract (GIT) symptoms regardless of whether the sickness is respiration related. The majority of the microbiome in the intestines is Firmicutes and Bacteroidetes, while Bacteroidetes, Proteobacteria, and Firmicutes are found in the lungs. Although most people overcome SARS-CoV-2 infections, many people continue to have symptoms months after the original sickness, called Long-COVID or Post COVID. The term "post-COVID-19 symptoms" refers to those that occur with or after COVID-19 and last for more than 12 weeks (long-COVID-19). The possible understanding of biological components such as inflammatory, immunological, metabolic activity biomarkers in peripheral blood is needed to evaluate the study. Therefore, this article aims to review the informative data that supports the idea underlying the disruption mechanisms of the microbiome of the gastrointestinal tract in the acute COVID-19 or post-COVID-mediated elevation of severity biomarkers.}, }
@article {pmid35334595, year = {2022}, author = {Wirth, KJ and Scheibenbogen, C}, title = {Dyspnea in Post-COVID Syndrome following Mild Acute COVID-19 Infections: Potential Causes and Consequences for a Therapeutic Approach.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {58}, number = {3}, pages = {}, pmid = {35334595}, issn = {1648-9144}, mesh = {*COVID-19/complications ; Dyspnea/etiology ; Exercise ; *Fatigue Syndrome, Chronic/etiology/therapy ; Humans ; Sodium ; }, abstract = {Dyspnea, shortness of breath, and chest pain are frequent symptoms of post-COVID syndrome (PCS). These symptoms are unrelated to organ damage in most patients after mild acute COVID infection. Hyperventilation has been identified as a cause of exercise-induced dyspnea in PCS. Since there is a broad overlap in symptomatology with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), causes for dyspnea and potential consequences can be deduced by a stringent application of assumptions made for ME/CFS in our recent review papers. One of the first stimuli of respiration in exercise is caused by metabolic feedback via skeletal muscle afferents. Hyperventilation in PCS, which occurs early on during exercise, can arise from a combined disturbance of a poor skeletal muscle energetic situation and autonomic dysfunction (overshooting respiratory response), both found in ME/CFS. The exaggerated respiratory response aggravating dyspnea does not only limit the ability to exercise but further impairs the muscular energetic situation: one of the buffering mechanisms to respiratory alkalosis is a proton shift from intracellular to extracellular space via the sodium-proton-exchanger subtype 1 (NHE1), thereby loading cells with sodium. This adds to two other sodium loading mechanisms already operative, namely glycolytic metabolism (intracellular acidosis) and impaired Na[+]/K[+]ATPase activity. High intracellular sodium has unfavorable effects on mitochondrial calcium and metabolism via sodium-calcium-exchangers (NCX). Mitochondrial calcium overload by high intracellular sodium reversing the transport mode of NCX to import calcium is a key driver for fatigue and chronification. Prevention of hyperventilation has a therapeutic potential by keeping intracellular sodium below the threshold where calcium overload occurs.}, }
@article {pmid35345699, year = {2022}, author = {Mitsikostas, DD and Moka, E and Orrillo, E and Aurilio, C and Vadalouca, A and Paladini, A and Varrassi, G}, title = {Neuropathic Pain in Neurologic Disorders: A Narrative Review.}, journal = {Cureus}, volume = {14}, number = {2}, pages = {e22419}, pmid = {35345699}, issn = {2168-8184}, abstract = {Neuropathic pain is defined as a painful condition caused by neurological lesions or diseases. Sometimes, neurological disorders may also be associated with neuropathic pain, which can be challenging to manage. For example, multiple sclerosis (MS) may cause chronic centralized painful symptoms due to nerve damage. Other chronic neuropathic pain syndromes may occur in the form of post-stroke pain, spinal cord injury pain, and other central pain syndromes. Chronic neuropathic pain is associated with dysfunction, disability, depression, disturbed sleep, and reduced quality of life. Early diagnosis may help improve outcomes, and pain control can be an important factor in restoring function. There are more than 100 different types of peripheral neuropathy and those involving sensory neurons can provoke painful symptoms. Accurate diagnosis of peripheral neuropathy is essential for pain control. Further examples are represented by gluten neuropathy, which is an extraintestinal manifestation of gluten sensitivity and presents as a form of peripheral neuropathy; in these unusual cases, neuropathy may be managed with diet. Neuropathic pain has been linked to CoronaVirus Disease (COVID) infection both during acute infection and as a post-viral syndrome known as long COVID. In this last case, neuropathic pain relates to the host's response to the virus. However, neuropathic pain may occur after any critical illness and has been observed as part of a syndrome following intensive care unit hospitalization.}, }
@article {pmid35350258, year = {2022}, author = {Staffolani, S and Iencinella, V and Cimatti, M and Tavio, M}, title = {Long COVID-19 syndrome as a fourth phase of SARS-CoV-2 infection.}, journal = {Le infezioni in medicina}, volume = {30}, number = {1}, pages = {22-29}, pmid = {35350258}, issn = {2532-8689}, abstract = {The SARS-CoV-2 pandemic has affected in the last two years a large number of subjects, with a high cost in terms of morbidity and mortality. The scientific community made progress in understanding risk factors, pathophysiology, clinical manifestations, diagnosis and treatment of acute SARS-CoV-2 infection. In the last months, another condition has become evident and caught the attention of the scientific community: the so-called long COVID syndrome. The pathophysiology of this condition is not known, even if some hypothesis have been made but not demonstrated yet. Long COVID is characterized by a very heterogeneous group of subacute and/or chronic symptoms and signs that follow the acute phase of SARS-CoV-2 infection and have a very variable duration. The presence of this syndrome in an individual is not dependent from the severity of the acute SARS-CoV-2 infection. Because of the extreme clinical heterogeneity, and also due to the lack of a shared and specific definition of the disease, it is very difficult to know the real prevalence and incidence of this condition. Some risk factors for the development of the disease have been identified: advanced age, elevated body mass index, comorbidities, specific symptoms of acute COVID-19 (in particular dyspnea), number of symptoms in the acute phase and female sex. The number of individuals affected by long COVID is high, even if it occurs only in a part of the subjects who had COVID-19. Therefore, long COVID constitutes now a major health issue and has to be managed in order to ensure an adequate access to care for all the people that need it. "Post COVID" clinics have been created in various countries, especially in Europe, for the management of people affected by long COVID syndrome. Guidelines have been written to help clinicians. An important role in the management of long COVID patients is played by the general practitioner, directly or indirectly linked to post COVID hospital clinics. The extreme heterogeneity of clinical presentation needs a patient-tailored, multidisciplinary approach. As NHS guidelines say, the three principal of care for long COVID patients are personalized care, multidisciplinary support and rehabilitation. More studies are needed in order to know better the pathophysiology of the disease. It is also necessary to create standardized and shared definitions of the disease, in order to better understand the epidemiology, the diagnostic criteria and to offer the right treatment to all the individuals who need it, without social or economic diffeences.}, }
@article {pmid35355961, year = {2022}, author = {Chadda, KR and Blakey, EE and Huang, CL and Jeevaratnam, K}, title = {Long COVID-19 and Postural Orthostatic Tachycardia Syndrome- Is Dysautonomia to Be Blamed?.}, journal = {Frontiers in cardiovascular medicine}, volume = {9}, number = {}, pages = {860198}, pmid = {35355961}, issn = {2297-055X}, abstract = {While the increased arrhythmic tendency during acute COVID-19 infection is recognised, the long-term cardiac electrophysiological complications are less well known. There are a high number of patients reporting ongoing symptoms post-infection, termed long COVID. A recent hypothesis is that long COVID symptoms could be attributed to dysautonomia, defined as malfunction of the autonomic nervous system (ANS). The most prevalent cardiovascular dysautonomia amongst young people is postural orthostatic tachycardia syndrome (POTS). Numerous reports have described the development of POTS as part of long COVID. Possible underlying mechanisms, although not mutually exclusive or exhaustive, include hypovolaemia, neurotropism, inflammation and autoimmunity. Treatment options for POTS and other long COVID symptoms are currently limited. Future research studies should aim to elucidate the underlying mechanisms of dysautonomia to enable the development of targeted therapies. Furthermore, it is important to educate healthcare professionals to recognise complications and conditions arising from COVID-19, such as POTS, to allow prompt diagnosis and access to early treatment.}, }
@article {pmid35359346, year = {2021}, author = {Walia, N and Lat, JO and Tariq, R and Tyagi, S and Qazi, AM and Salari, SW and Jafar, A and Kousar, T and Bieniek, S}, title = {Post-acute sequelae of COVID-19 and the mental health implications.}, journal = {Discoveries (Craiova, Romania)}, volume = {9}, number = {4}, pages = {e140}, pmid = {35359346}, issn = {2359-7232}, abstract = {Post-acute sequelae of COVID-19 (PASC) or more commonly known as Long COVID-19, is the term given to persistent symptoms 12 weeks from the initial presentation of COVID-19 infection. Several multi-organ symptoms have been reported by patients. Some common symptoms include headaches, fatigue, memory impairment and mental health complications such as anxiety and depression. People with previous psychiatric diagnosis are at greater risk of developing longer mental health implications from persistent COVID-19 symptoms. Additionally, healthcare workers are at increased risk of being long haulers leading to burnout and exhaustion. The objective of this review article is to provide comprehensive evidence from existing literature on various symptoms reported by patients experiencing Long COVID-19 and the rate of occurrence of such symptoms in different populations. A long-term disease surveillance is required to further understand the persistent symptoms or the long-term impact of this infection.}, }
@article {pmid35359614, year = {2022}, author = {Nittas, V and Gao, M and West, EA and Ballouz, T and Menges, D and Wulf Hanson, S and Puhan, MA}, title = {Long COVID Through a Public Health Lens: An Umbrella Review.}, journal = {Public health reviews}, volume = {43}, number = {}, pages = {1604501}, pmid = {35359614}, issn = {0301-0422}, abstract = {Objectives: To synthesize existing evidence on prevalence as well as clinical and socio-economic aspects of Long COVID. Methods: An umbrella review of reviews and a targeted evidence synthesis of their primary studies, including searches in four electronic databases, reference lists of included reviews, as well as related article lists of relevant publications. Results: Synthesis included 23 reviews and 102 primary studies. Prevalence estimates ranged from 7.5% to 41% in non-hospitalized adults, 2.3%-53% in mixed adult samples, 37.6% in hospitalized adults, and 2%-3.5% in primarily non-hospitalized children. Preliminary evidence suggests that female sex, age, comorbidities, the severity of acute disease, and obesity are associated with Long COVID. Almost 50% of primary studies reported some degree of Long COVID-related social and family-life impairment, long absence periods off work, adjusted workloads, and loss of employment. Conclusion: Long COVID will likely have a substantial public health impact. Current evidence is still heterogeneous and incomplete. To fully understand Long COVID, well-designed prospective studies with representative samples will be essential.}, }
@article {pmid35370531, year = {2022}, author = {Zwick, RH}, title = {[Outpatient pulmonary rehabilitation].}, journal = {Der Pneumologe}, volume = {19}, number = {3}, pages = {150-157}, pmid = {35370531}, issn = {1613-5636}, abstract = {BACKGROUND: Outpatient pulmonary rehabilitation (PR) plays a central role in the integrative care of patients with pulmonary diseases.<br><br>MATERIAL AND METHODS: The article gives an overview of the recent evidence on outpatient PR in various diseases, in various settings including the cost-effectiveness. This is based on a&#xa0;selective literature search in the PubMed and Medline databanks, current expert opinions and clinical experiences.<br><br>RESULTS: Early rehabilitation after exacerbation in COPD patients leads to a reduction of rehospitalizations (hazard ratio 0.83) and to a reduction of mortality (hazard ratio 0.63) over a period of 12&#xa0;months. Telerehabilitation is a&#xa0;promising future perspective in specific settings. Recent publications on bronchiectasis, interstitial lung diseases and pulmonary hypertension could confirm the safety and feasibility of outpatient PR and the cost-effectiveness could be demonstrated. Also, the evidence for inpatient as well as outpatient PR settings for patients with post-COVID and long COVID is growing.<br><br>CONCLUSION: There is growing equivalence with respect to the evidence on PR, independent of whether it is carried out in an outpatient or inpatient setting.}, }
@article {pmid35378898, year = {2022}, author = {Calcaterra, G and Fanos, V and Cataldi, L and Cugusi, L and Crisafulli, A and Bassareo, PP}, title = {Need for resuming sports and physical activity for children and adolescents following COVID-19 infection.}, journal = {Sport sciences for health}, volume = {18}, number = {4}, pages = {1179-1185}, pmid = {35378898}, issn = {1824-7490}, abstract = {INTRODUCTION: A decline in sports activities among children and adolescents was noted during the stay-at-home restrictions imposed by COVID-19. With the easing of restrictions, physical activities are being resumed.<br><br>EVIDENCE ACQUISITION: A data search was conducted to identify the role of parents in resuming sporting activities, the risks and benefits of doing so, the physical examination to be conducted prior to physical activity, the existence of guidelines/protocols for return to sports and physical activity, the role of comorbidities in influencing the restart of the same.<br><br>EVIDENCE SYNTHESIS: Parents should consult the child's physician prior to allowing he/she to resume physical exercise. In preparation for this, a careful physical examination should be performed. Children with COVID-19, even if asymptomatic, should not resume any physical activity until at least 10&#xa0;days after testing positive. Those with moderate or severe COVID-19 should be referred for cardiological evaluation. The level of activity should be resumed gradually, as per the GRTP protocol. Athletes with a positive COVID-19 test in the presence of concomitant medical conditions (diabetes, cardiovascular or respiratory or renal disease) should undergo medical evaluation prior to adhering to a GRTP. Those with complicated COVID19 infection or long Covid may need additional investigations.<br><br>CONCLUSIONS: While there is no doubt that it will bring multiple benefits in terms of general health, returning to play sport should be gradual and preceded by an accurate physical examination in those young subjects previously affected by the coronavirus disease, especially when their heart and/or lungs and/or kidneys were affected.}, }
@article {pmid35379408, year = {2022}, author = {Sharma, P and Bharti, S and Garg, I}, title = {Post COVID fatigue: Can we really ignore it?.}, journal = {The Indian journal of tuberculosis}, volume = {69}, number = {2}, pages = {238-241}, pmid = {35379408}, issn = {0019-5707}, mesh = {*COVID-19/complications ; Fatigue/etiology ; *Fatigue Syndrome, Chronic/complications/etiology ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long-COVID, also referred to as post-acute COVID-19, chronic COVID-19, post-COVID syndrome, or post-acute sequelae of SARS-CoV-2 infection (PASC), generally refers to symptoms that develop during or after acute COVID-19 illness, continue for ≥12 weeks, and are not explained by an alternative diagnosis. It is not yet known whether "long-COVID" represents a new syndrome unique to COVID-19 or overlaps with recovery from similar illnesses. It's difficult for physicians to predict when symptoms will improve as it varies differently in different people. Patient's recovery depends on various factors including age, associated comorbidities, severity of COVID-19 infection. Some symptoms, like fatigue, might continue even while others improve or go away. This review addresses the pathogenesis, presentation of post covid fatigue, its severity and its management.}, }
@article {pmid35383586, year = {2022}, author = {Carson, E and Hemenway, AN}, title = {A Scoping Review of Pharmacological Management of Postacute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in 2021.}, journal = {American journal of therapeutics}, volume = {29}, number = {3}, pages = {e305-e321}, pmid = {35383586}, issn = {1536-3686}, mesh = {*COVID-19/complications ; Disease Progression ; Humans ; Prospective Studies ; Retrospective Studies ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {BACKGROUND: Postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC), or long-COVID, are signs and symptoms that persist after the acute phase of Coronavirus disease 2019 infection has passed. PASC is newly recognized, and research is ongoing to answer questions about pathology, symptoms, diagnosis, and optimal treatment.<br><br>AREAS OF UNCERTAINTY: Use of pharmacologic treatment for symptoms of PASC is currently evolving. This scoping review aims to assess medical literature for any evidence supporting or refuting use of any medications to specifically treat PASC.<br><br>DATA SOURCES: PubMed, EMBASE, Web of Science, and gray literature sources were searched for any study of medication use for PASC. Studies were included if they described medication use in patients with PASC. There were no exclusion criteria based on study type or if results were reported. Studies were divided into completed works and ongoing research.<br><br>RESULTS: Fifty-two records were included in final analysis from an initial 3524 records found, including 2 randomized controlled trials, 7 prospective, open-label or observational studies, 14 case reports or case series, 1 survey, 1 correspondence, 1 retrospective analysis, and 26 studies in progress. Seven of the 26 completed works investigate ivabradine or beta-blockers, whereas 7 investigate local or systemic corticosteroids. Three investigate multi-ingredient nutritional supplements. The other 9 completed works as well as the 26 studies in progress investigate a wide variety of other treatments including drugs in development, drugs used for other conditions, herbals, supplements, and vitamins.<br><br>CONCLUSIONS: There is limited, but evolving, literature on medication treatment for PASC. Providers who opt to use pharmacologic therapy for PASC need to be vigilant in their knowledge of these evolving data.}, }
@article {pmid35390469, year = {2022}, author = {Yang, CP and Chang, CM and Yang, CC and Pariante, CM and Su, KP}, title = {Long COVID and long chain fatty acids (LCFAs): Psychoneuroimmunity implication of omega-3 LCFAs in delayed consequences of COVID-19.}, journal = {Brain, behavior, and immunity}, volume = {103}, number = {}, pages = {19-27}, pmid = {35390469}, issn = {1090-2139}, support = {G108/603/MRC_/Medical Research Council/United Kingdom ; MR/J002739/1/MRC_/Medical Research Council/United Kingdom ; MR/N029488/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*COVID-19/complications ; Fatty Acids ; *Fatty Acids, Omega-3/therapeutic use ; Humans ; Hypothalamo-Hypophyseal System ; Inflammation/drug therapy ; Pituitary-Adrenal System ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the lasting pandemic of coronavirus disease 2019 (COVID-19) and the post-acute phase sequelae of heterogeneous negative impacts in multiple systems known as the "long COVID." The mechanisms of neuropsychiatric complications of long COVID are multifactorial, including long-term tissue damages from direct CNS viral involvement, unresolved systemic inflammation and oxidative stress, maladaptation of the renin-angiotensin-aldosterone system and coagulation system, dysregulated immunity, the dysfunction of neurotransmitters and hypothalamus-pituitaryadrenal (HPA) axis, and the psychosocial stress imposed by societal changes in response to this pandemic. The strength of safety, well-acceptance, and accumulating scientific evidence has now afforded nutritional medicine a place in the mainstream of neuropsychiatric intervention and prophylaxis. Long chain omega-3 polyunsaturated fatty acids (omega-3 or n-3 PUFAs) might have favorable effects on immunity, inflammation, oxidative stress and psychoneuroimmunity at different stages of SARS-CoV-2 infection. Omega-3 PUFAs, particularly EPA, have shown effects in treating mood and neurocognitive disorders by reducing pro-inflammatory cytokines, altering the HPA axis, and modulating neurotransmission via lipid rafts. In addition, omega-3 PUFAs and their metabolites, including specialized pro-resolvin mediators, accelerate the process of cleansing chronic inflammation and restoring tissue homeostasis, and therefore offer a promising strategy for Long COVID. In this article, we explore in a systematic review the putative molecular mechanisms by which omega-3 PUFAs and their metabolites counteract the negative effects of long COVID on the brain, behavior, and immunity.}, }
@article {pmid35410644, year = {2022}, author = {Nielsen, SL and Ludwigsen, T and Johnsen, S and Miskowiak, KW}, title = {[Cognitive late sequelae of COVID-19].}, journal = {Ugeskrift for laeger}, volume = {184}, number = {15}, pages = {}, pmid = {35410644}, issn = {1603-6824}, mesh = {*COVID-19/complications ; Cognition ; Humans ; Neuropsychological Tests ; Quality of Life ; Post-Acute COVID-19 Syndrome ; }, abstract = {Cognitive sequelae of COVID-19 including memory and concentration difficulties have been observed in 40-65% of persons who have been hospitalised with COVID-19 and 27-50% of non-hospitalised individuals. The cognitive impairments are associated with reduced work function and quality of life. This review recommends systematic cognition screening at long-COVID clinics using brief and feasible objective cognitive screeners, such as the Screen for Cognitive Impairment in Psychiatry (SCIP) and Trail Making Test B or similar tests with sensitivity to cognitive impairment in young populations.}, }
@article {pmid35411333, year = {2022}, author = {Sanyaolu, A and Marinkovic, A and Prakash, S and Zhao, A and Balendra, V and Haider, N and Jain, I and Simic, T and Okorie, C}, title = {Post-acute Sequelae in COVID-19 Survivors: an Overview.}, journal = {SN comprehensive clinical medicine}, volume = {4}, number = {1}, pages = {91}, pmid = {35411333}, issn = {2523-8973}, abstract = {In the acute phase of SARS-CoV-2 infection, varying degrees of clinical manifestations have been noticed in patients. Some patients who recovered from the infection developed long-term effects which have become of interest to the scientific and medical communities, as it relates to pathogenesis and the multidisciplinary approach to treatment. Long COVID (long-term or long-haul) is the collective term used to define recovered individuals of SARS-CoV-2 infection who have presented with persistent COVID symptoms, as well as the emergence of disorders and complications. Following the review of literature from major scientific databases, this paper investigated long COVID and the resulting post-sequela effects on survivors, regardless of initial disease severity. The clinical manifestations and multisystem complications of the disease specifically, cardiovascular, neurologic and psychologic, hematologic, pulmonary, dermatologic, and other ailments were discussed. Patients with chronic COVID-19 were found to experience heart thrombosis leading to myocardial infarction, inflammation, lung fibrosis, stroke, venous thromboembolism, arterial thromboembolism, "brain fog", general mood dysfunctions, dermatological issues, and fatigue. As the disease continues to progress and spread, and with the emergence of new variants the management of these persisting symptoms will pose a challenge for healthcare providers and medical systems in the next period of the pandemic. However, more information is needed about long COVID, particularly concerning certain patient populations, variability in follow-up times, the prevalence of comorbidities, and the evolution of the spread of infection. Thus, continued research needs to be conducted concerning the disease pathology to develop preventative measures and management strategies to treat long COVID.}, }
@article {pmid35416359, year = {2022}, author = {Silva, CC and Bichara, CNC and Carneiro, FRO and Palacios, VRDCM and Berg, AVSVD and Quaresma, JAS and Magno Falcão, LF}, title = {Muscle dysfunction in the long coronavirus disease 2019 syndrome: Pathogenesis and clinical approach.}, journal = {Reviews in medical virology}, volume = {32}, number = {6}, pages = {e2355}, pmid = {35416359}, issn = {1099-1654}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; *Musculoskeletal System ; Muscles ; Post-Acute COVID-19 Syndrome ; }, abstract = {In long coronavirus disease 2019 (long COVID-19), involvement of the musculoskeletal system is characterised by the persistence or appearance of symptoms such as fatigue, muscle weakness, myalgia, and decline in physical and functional performance, even at 4 weeks after the onset of acute symptoms of COVID-19. Muscle injury biomarkers are altered during the acute phase of the disease. The cellular damage and hyperinflammatory state induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may contribute to the persistence of symptoms, hypoxaemia, mitochondrial damage, and dysregulation of the renin-angiotensin system. In addition, the occurrence of cerebrovascular diseases, involvement of the peripheral nervous system, and harmful effects of hospitalisation, such as the use of drugs, immobility, and weakness acquired in the intensive care unit, all aggravate muscle damage. Here, we review the multifactorial mechanisms of muscle tissue injury, aggravating conditions, and associated sequelae in long COVID-19.}, }
@article {pmid35417314, year = {2022}, author = {Beharry, M}, title = {Pediatric Anxiety and Depression in the Time of COVID-19.}, journal = {Pediatric annals}, volume = {51}, number = {4}, pages = {e154-e160}, doi = {10.3928/19382359-20220317-01}, pmid = {35417314}, issn = {1938-2359}, mesh = {Adolescent ; Anxiety/diagnosis/epidemiology/therapy ; *COVID-19/complications ; Child ; Depression/diagnosis/epidemiology/therapy ; Humans ; SARS-CoV-2 ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; }, abstract = {Pediatricians and other primary care clinicians are responsible for the screening of numerous health issues. As the coronavirus disease 2019 (COVID-19) pandemic persists, the adverse mental health effects on patients, their families, and the community at large are evident. Therefore, pediatricians are tasked with assessing, triaging, and initiating treatment for common mental health concerns such as anxiety and depression. Complicating the picture is long-COVID. This article reviews the epidemiology of pediatric and adolescent anxiety and depression and data about pediatric long-COVID. Additionally, strategies and tools for pediatricians and their office staff to address the mental health needs of their patients are outlined. [Pediatr Ann. 2022;51(4):e154-e160.].}, }
@article {pmid35417745, year = {2022}, author = {Horwitz, RI and Conroy, AH and Cullen, MR and Colella, K and Mawn, M and Singer, BH and Sim, I}, title = {Long COVID and Medicine's Two Cultures.}, journal = {The American journal of medicine}, volume = {135}, number = {8}, pages = {945-949}, doi = {10.1016/j.amjmed.2022.03.020}, pmid = {35417745}, issn = {1555-7162}, mesh = {*COVID-19/complications ; Humans ; *Medicine ; Post-Acute COVID-19 Syndrome ; }, abstract = {Medicine has separated the two cultures of biological science and social science in research, even though they are intimately connected in the lives of our patients. To understand the cause, progression, and treatment of long COVID , biology and biography, the patient's lived experience, must be studied together.}, }
@article {pmid35420565, year = {2022}, author = {Bonnet, U and Juckel, G}, title = {COVID-19 Outcomes: Does the Use of Psychotropic Drugs Make a Difference? Accumulating Evidence of a Beneficial Effect of Antidepressants-A Scoping Review.}, journal = {Journal of clinical psychopharmacology}, volume = {42}, number = {3}, pages = {284-292}, pmid = {35420565}, issn = {1533-712X}, mesh = {Antidepressive Agents/pharmacology/therapeutic use ; *COVID-19/complications ; Fluoxetine/pharmacology ; Fluvoxamine/pharmacology/therapeutic use ; Humans ; Prospective Studies ; Retrospective Studies ; SARS-CoV-2 ; Selective Serotonin Reuptake Inhibitors/adverse effects ; *Serotonin and Noradrenaline Reuptake Inhibitors ; *Trazodone ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {PURPOSE/BACKGROUND: Studies for repurposed drugs in severe acute respiratory syndrome coronavirus type 2-infected and coronavirus disease 2019 (COVID-19) patients are ongoing. According to preclinical research, antidepressants (ADs) might be useful in the treatment of COVID-19.<br><br>METHODS/PROCEDURES: We conducted a scoping review including clinical studies on AD effects on SARS-CoV-2 infection and COVID-19.<br><br>FINDING/RESULTS: As of January 2, 2022, we found 14 clinical studies, which could be included into this review. Among them, there were 2 randomized, placebo-controlled studies and 2 prospective parallel-group studies about the efficacy/effectiveness and tolerability of fluvoxamine. The remaining studies were mainly retrospective studies considering COVID-19 hospital populations predominantly exposed to fluoxetine (N = 3), other selective serotonin reuptake inhibitors (SSRI), selective norepinephrine reuptake inhibitors (SNRI), and trazodone. The vast majority were hospital studies and assessed COVID-19 severity (morbidity) and mortality as primary endpoints. The only outpatient study (fluvoxamine) investigated the COVID-19-related hospitalization rate, and 1 psychiatric hospital study (SSRI, SNRI, trazodone) focused on the SARS-CoV-2 infection rate.<br><br>IMPLICATIONS/CONCLUSIONS: At present, the best evidence of an "anti-COVID-19" potential of ADs exists for fluvoxamine and, to a lesser extent, for fluoxetine. Preliminary evidence had found that patients exposed to SSRI or SNRI substance classes might have a reduced mortality risk and that trazodone might reduce SARS-CoV-2 infection rates. Three studies found no relevant influence of ADs on COVID-19 morbidity and mortality, and 1 study described increased mortality. The latter study, however, did not differentiate between psychotropic medication and ADs. Tricyclics and monoamine oxidase inhibitors are still absolute "dark zones" in COVID-19 research. Further controlled studies testing the effectiveness/efficacy and tolerability/safety (as well as the treatment timing and duration) of different AD substance classes in COVID-19 and post/long-COVID patients of various populations are warranted.}, }
@article {pmid35422571, year = {2022}, author = {Ripani, U and Bisaccia, M and Meccariello, L}, title = {Dexamethasone and Nutraceutical Therapy Can Reduce the Myalgia Due to COVID-19 - a Systemic Review of the Active Substances that Can Reduce the Expression of Interlukin-6.}, journal = {Medical archives (Sarajevo, Bosnia and Herzegovina)}, volume = {76}, number = {1}, pages = {66-71}, pmid = {35422571}, issn = {1986-5961}, mesh = {Humans ; *COVID-19 Drug Treatment ; Dexamethasone/therapeutic use ; Dietary Supplements ; Inflammation ; Interleukin-6 ; Myalgia/etiology ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Myalgia reflects generalized inflammation and cytokine response and can be the onset symptom of 36% of patients with COVID-19. Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF- α) levels in plasma and upper respiratory secretions directly correlate with the magnitude of viral replication, fever, and respiratory and systemic symptoms, including musculoskeletal clinical manifestations.<br><br>OBJECTIVE: The aim of our work is to report literature scientific investigation clinical protocol to reduce the immunomodulation and inflammatory response nutraceutical therapy associated with dexamethasone and how can reduce the expression of Interlukina-6(IL-6) and myalgia due to COVID-19.<br><br>METHODS: We searched in Pubmed and Cochrane the nautriceutical drugs to treat the immune modulation of organism to COVID-19. We put these keywords: immune inflammation, desease descriptions, epidemiology COVID-19; immunomodulations; IL-6; Rheumatic Symptoms; Joint; Musculoskeletal Disorders; dexamethasone; Polydatin; Zinc; Melatonin; N- Acetyl Cysteine; Colostrum; L- Glutamine; Vitamin D3.<br><br>RESULTS: We found 61 papers. All the authors analyze them. After the Analyze we suggest the use of response nutraceutical therapy associated with dexamethasone can reduce the expression of Interlukina-6(IL-6) and myalgia due to COVID-19.<br><br>CONCLUSION: According the scientific literature nutraceutical therapy associated with dexamethasone can reduce the expression of Interlukina-6(IL-6) and myalgia due to COVID-19.}, }
@article {pmid35429399, year = {2022}, author = {Chen, C and Haupert, SR and Zimmermann, L and Shi, X and Fritsche, LG and Mukherjee, B}, title = {Global Prevalence of Post-Coronavirus Disease 2019 (COVID-19) Condition or Long COVID: A Meta-Analysis and Systematic Review.}, journal = {The Journal of infectious diseases}, volume = {226}, number = {9}, pages = {1593-1607}, doi = {10.1093/infdis/jiac136}, pmid = {35429399}, issn = {1537-6613}, mesh = {Humans ; *COVID-19 ; *Pneumonia, Viral/epidemiology ; *Coronavirus Infections/epidemiology ; Pandemics ; Prevalence ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: This study aims to examine the worldwide prevalence of post-coronavirus disease 2019 (COVID-19) condition, through a systematic review and meta-analysis.<br><br>METHODS: PubMed, Embase, and iSearch were searched on July 5, 2021 with verification extending to March 13, 2022. Using a random-effects framework with DerSimonian-Laird estimator, we meta-analyzed post-COVID-19 condition prevalence at 28+ days from infection.<br><br>RESULTS: Fifty studies were included, and 41 were meta-analyzed. Global estimated pooled prevalence of post-COVID-19 condition was 0.43 (95% confidence interval [CI], .39-.46). Hospitalized and nonhospitalized patients had estimates of 0.54 (95% CI, .44-.63) and 0.34 (95% CI, .25-.46), respectively. Regional prevalence estimates were Asia (0.51; 95% CI, .37-.65), Europe (0.44; 95% CI, .32-.56), and United States of America (0.31; 95% CI, .21-.43). Global prevalence for 30, 60, 90, and 120 days after infection were estimated to be 0.37 (95% CI, .26-.49), 0.25 (95% CI, .15-.38), 0.32 (95% CI, .14-.57), and 0.49 (95% CI, .40-.59), respectively. Fatigue was the most common symptom reported with a prevalence of 0.23 (95% CI, .17-.30), followed by memory problems (0.14; 95% CI, .10-.19).<br><br>CONCLUSIONS: This study finds post-COVID-19 condition prevalence is substantial; the health effects of COVID-19 seem to be prolonged and can exert stress on the healthcare system.}, }
@article {pmid35431398, year = {2022}, author = {Gao, Y and Liang, WQ and Li, YR and He, JX and Guan, WJ}, title = {The Short- and Long-Term Clinical, Radiological and Functional Consequences of COVID-19.}, journal = {Archivos de bronconeumologia}, volume = {58}, number = {}, pages = {32-38}, pmid = {35431398}, issn = {1579-2129}, mesh = {*COVID-19 ; Forecasting ; Humans ; Lung/diagnostic imaging ; Risk Factors ; }, abstract = {As with the rapid increase of the number of patients who have recovered from COVID-19 globally, there needs to be a major shift of the focus from rapid pathogen detection, treatment and prevention to the promotion of better recovery. Notwithstanding the scarcity of our understandings, recent studies have unraveled a plethora of pulmonary and systemic consequences which require medical attention. These consequences remained as of the end of follow-up which ranged from 1 month to 1 year. Here, we review the consequences of COVID-19 in terms of the residual symptoms, radiological and functional manifestations, and identify the potential risk factors that contribute to a prolonged recovery. We also summarize the benefits of clinical interventions (particularly the pulmonary rehabilitation program), and address several undetermined concerns and key future research directions.}, }
@article {pmid35431658, year = {2022}, author = {Zhu, F and Ang, JY}, title = {COVID-19 Infection in Children: Diagnosis and Management.}, journal = {Current infectious disease reports}, volume = {24}, number = {4}, pages = {51-62}, pmid = {35431658}, issn = {1523-3847}, abstract = {PURPOSE OF REVIEW: Due to the rapidly changing landscape of COVID-19, the purpose of this review is to provide a concise and updated summary of pediatric COVID-19 diagnosis and management.<br><br>RECENT FINDINGS: The relative proportion of pediatric cases have significantly increased following the emergence of the Omicron variant (from&#x2009;<&#x2009;2% in the early pandemic to 25% from 1/27 to 2/3/22). While children present with milder symptoms than adults, severe disease can still occur, particularly in children with comorbidities. There is a relative paucity of pediatric data in the management of COVID-19 and the majority of recommendations remain based on adult data.<br><br>SUMMARY: Fever and cough remain the most common clinical presentations, although atypical presentations such as "COVID toes," anosmia, and croup may be present. Children are at risk for post-infectious complications such as MIS-C and long COVID. Nucleic acid amplification tests through respiratory PCR remain the mainstay of diagnosis. The mainstay of management remains supportive care and prevention through vaccination is highly recommended. In patients at increased risk of progression, interventions such as monoclonal antibody therapy, PO Paxlovid, or IV remdesivir&#x2009;&#xd7;&#x2009;3&#xa0;days should be considered. In patients with severe disease, the use of remdesivir, dexamethasone, and immunomodulatory agents (tocilizumab, baricitinib) is recommended. Children can be at risk for thrombosis from COVID-19 and anticoagulation is recommended in children with markedly elevated D-dimer levels or superimposed clinical risk factors for hospital associated venous thromboembolism.}, }
@article {pmid35449732, year = {2022}, author = {Wang, C and Yu, C and Jing, H and Wu, X and Novakovic, VA and Xie, R and Shi, J}, title = {Long COVID: The Nature of Thrombotic Sequelae Determines the Necessity of Early Anticoagulation.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {861703}, pmid = {35449732}, issn = {2235-2988}, mesh = {Anticoagulants/therapeutic use ; *COVID-19/complications ; Humans ; Hypoxia ; Inflammation/complications ; Quality of Life ; SARS-CoV-2 ; *Thrombosis/etiology/prevention &amp; control ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {Many discharged COVID-19 patients affected by sequelae experience reduced quality of life leading to an increased burden on the healthcare system, their families and society at large. Possible pathophysiological mechanisms of long COVID include: persistent viral replication, chronic hypoxia and inflammation. Ongoing vascular endothelial damage promotes platelet adhesion and coagulation, resulting in the impairment of various organ functions. Meanwhile, thrombosis will further aggravate vasculitis contributing to further deterioration. Thus, long COVID is essentially a thrombotic sequela. Unfortunately, there is currently no effective treatment for long COVID. This article summarizes the evidence for coagulation abnormalities in long COVID, with a focus on the pathophysiological mechanisms of thrombosis. Extracellular vesicles (EVs) released by various types of cells can carry SARS-CoV-2 through the circulation and attack distant tissues and organs. Furthermore, EVs express tissue factor and phosphatidylserine (PS) which aggravate thrombosis. Given the persistence of the virus, chronic inflammation and endothelial damage are inevitable. Pulmonary structural changes such as hypertension, embolism and fibrosis are common in long COVID. The resulting impaired lung function and chronic hypoxia again aggravates vascular inflammation and coagulation abnormalities. In this article, we also summarize recent research on antithrombotic therapy in COVID-19. There is increasing evidence that early anticoagulation can be effective in improving outcomes. In fact, persistent systemic vascular inflammation and dysfunction caused by thrombosis are key factors driving various complications of long COVID. Early prophylactic anticoagulation can prevent the release of or remove procoagulant substances, thereby protecting the vascular endothelium from damage, reducing thrombotic sequelae, and improving quality of life for long-COVID patients.}, }
@article {pmid35453505, year = {2022}, author = {Margaria, JP and Moretta, L and Alves-Filho, JC and Hirsch, E}, title = {PI3K Signaling in Mechanisms and Treatments of Pulmonary Fibrosis Following Sepsis and Acute Lung Injury.}, journal = {Biomedicines}, volume = {10}, number = {4}, pages = {}, pmid = {35453505}, issn = {2227-9059}, abstract = {Pulmonary fibrosis is a pathological fibrotic process affecting the lungs of five million people worldwide. The incidence rate will increase even more in the next years due to the long-COVID-19 syndrome, but a resolving treatment is not available yet and usually prognosis is poor. The emerging role of the phosphatidylinositol 3-kinase (PI3K)/AKT signaling in fibrotic processes has inspired the testing of drugs targeting the PI3K/Akt pathway that are currently under clinical evaluation. This review highlights the progress in understanding the role of PI3K/Akt in the development of lung fibrosis and its causative pathological context, including sepsis as well as acute lung injury (ALI) and its consequent acute respiratory distress syndrome (ARDS). We further summarize current knowledge about PI3K inhibitors for pulmonary fibrosis treatment, including drugs under development as well as in clinical trials. We finally discuss how the design of inhaled compounds targeting the PI3K pathways might potentiate efficacy and improve tolerability.}, }
@article {pmid35454144, year = {2022}, author = {Piazza, M and Di Cicco, M and Pecoraro, L and Ghezzi, M and Peroni, D and Comberiati, P}, title = {Long COVID-19 in Children: From the Pathogenesis to the Biologically Plausible Roots of the Syndrome.}, journal = {Biomolecules}, volume = {12}, number = {4}, pages = {}, pmid = {35454144}, issn = {2218-273X}, mesh = {*COVID-19/complications ; Child ; Humans ; Inflammation ; SARS-CoV-2 ; Vitamins ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long Coronavirus disease-19 (COVID-19) refers to the persistence of symptoms related to the infection with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). This condition is described as persistent and can manifest in various combinations of signs and symptoms, such as fatigue, headache, dyspnea, depression, cognitive impairment, and altered perception of smells and tastes. Long COVID-19 may be due to long-term damage to different organs-such as lung, brain, kidney, and heart-caused by persisting viral-induced inflammation, immune dysregulation, autoimmunity, diffuse endothelial damage, and micro thrombosis. In this review, we discuss the potential and biologically plausible role of some vitamins, essential elements, and functional foods based on the hypothesis that an individual's dietary status may play an important adjunctive role in protective immunity against COVID-19 and possibly against its long-term consequences.}, }
@article {pmid35455008, year = {2022}, author = {Boaventura, P and Macedo, S and Ribeiro, F and Jaconiano, S and Soares, P}, title = {Post-COVID-19 Condition: Where Are We Now?.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {4}, pages = {}, pmid = {35455008}, issn = {2075-1729}, abstract = {COVID-19 is currently considered a systemic infection involving multiple systems and causing chronic complications. Compared to other post-viral fatigue syndromes, these complications are wider and more intense. The most frequent symptoms are profound fatigue, dyspnea, sleep difficulties, anxiety or depression, reduced lung capacity, memory/cognitive impairment, and hyposmia/anosmia. Risk factors for this condition are severity of illness, more than five symptoms in the first week of the disease, female sex, older age, the presence of comorbidities, and a weak anti-SARS-CoV-2 antibody response. Different lines of research have attempted to explain these protracted symptoms; chronic persistent inflammation, autonomic nervous system disruption, hypometabolism, and autoimmunity may play a role. Due to thyroid high ACE expression, the key molecular complex SARS-CoV-2 uses to infect the host cells, thyroid may be a target for the coronavirus infection. Thyroid dysfunction after SARS-CoV-2 infection may be a combination of numerous mechanisms, and its role in long-COVID manifestations is not yet established. The proposed mechanisms are a direct effect of SARS-CoV-2 on target cells, an indirect effect of systemic inflammatory immune response, and a dysfunction of the hypothalamic-pituitary-thyroid (HPT) axis leading to decreased serum TSH. Only a few studies have reported the thyroid gland status in the post-COVID-19 condition. The presence of post-COVID symptoms deserves recognition of COVID-19 as a cause of post-viral fatigue syndrome. It is important to recognize the affected individuals at an early stage so we can offer them the most adequate treatments, helping them thrive through the uncertainty of their condition.}, }
@article {pmid35456321, year = {2022}, author = {Cattadori, G and Di Marco, S and Baravelli, M and Picozzi, A and Ambrosio, G}, title = {Exercise Training in Post-COVID-19 Patients: The Need for a Multifactorial Protocol for a Multifactorial Pathophysiology.}, journal = {Journal of clinical medicine}, volume = {11}, number = {8}, pages = {}, pmid = {35456321}, issn = {2077-0383}, abstract = {The battle against COVID-19 has entered a new phase with Rehabilitation Centres being among the major players, because the medical outcome of COVID-19 patients does not end with the control of pulmonary inflammation marked by a negative virology test, as many patients continue to suffer from long-COVID-19 syndrome. Exercise training is known to be highly valuable in patients with cardiac or lung disease, and it exerts beneficial effects on the immune system and inflammation. We therefore reviewed past and recent papers about exercise training, considering the multifactorial features characterizing post-COVID-19 patients' clinical conditions. Consequently, we conceived a proposal for a post-COVID-19 patient exercise protocol as a combination of multiple recommended exercise training regimens. Specifically, we built pre-evaluation and exercise training for post-COVID-19 patients taking advantage of the various programs of exercise already validated for diseases that may share pathophysiological and clinical characteristics with long-COVID-19.}, }
@article {pmid35456998, year = {2022}, author = {Perła-Kaján, J and Jakubowski, H}, title = {COVID-19 and One-Carbon Metabolism.}, journal = {International journal of molecular sciences}, volume = {23}, number = {8}, pages = {}, pmid = {35456998}, issn = {1422-0067}, support = {2018/29/B/NZ4/00771//National Science Center/ ; 2019/33/B/NZ4/01760//National Science Center/ ; }, mesh = {*COVID-19/complications ; Carbon/metabolism ; Folic Acid/metabolism ; Homocysteine ; Humans ; Methionine/metabolism ; SARS-CoV-2 ; Vitamin B 12/metabolism ; Post-Acute COVID-19 Syndrome ; }, abstract = {Dysregulation of one-carbon metabolism affects a wide range of biological processes and is associated with a number of diseases, including cardiovascular disease, dementia, neural tube defects, and cancer. Accumulating evidence suggests that one-carbon metabolism plays an important role in COVID-19. The symptoms of long COVID-19 are similar to those presented by subjects suffering from vitamin B12 deficiency (pernicious anemia). The metabolism of a cell infected by the SARS-CoV-2 virus is reshaped to fulfill the need for massive viral RNA synthesis, which requires de novo purine biosynthesis involving folate and one-carbon metabolism. Many aspects of host sulfur amino acid metabolism, particularly glutathione metabolism underlying antioxidant defenses, are also taken over by the SARS-CoV-2 virus. The purpose of this review is to summarize recent findings related to one-carbon metabolism and sulfur metabolites in COVID-19 and discuss how they inform strategies to combat the disease.}, }
@article {pmid35457093, year = {2022}, author = {Mohamed, MS and Johansson, A and Jonsson, J and Schiöth, HB}, title = {Dissecting the Molecular Mechanisms Surrounding Post-COVID-19 Syndrome and Neurological Features.}, journal = {International journal of molecular sciences}, volume = {23}, number = {8}, pages = {}, pmid = {35457093}, issn = {1422-0067}, mesh = {*COVID-19/complications ; Gliosis ; Humans ; Quality of Life ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Many of the survivors of the novel coronavirus disease (COVID-19) are suffering from persistent symptoms, causing significant morbidity and decreasing their quality of life, termed "post-COVID-19 syndrome" or "long COVID". Understanding the mechanisms surrounding PCS is vital to developing the diagnosis, biomarkers, and possible treatments. Here, we describe the prevalence and manifestations of PCS, and similarities with previous SARS epidemics. Furthermore, we look at the molecular mechanisms behind the neurological features of PCS, where we highlight important neural mechanisms that may potentially be involved and pharmacologically targeted, such as glutamate reuptake in astrocytes, the role of NMDA receptors and transporters (EAAT2), ROS signaling, astrogliosis triggered by NF-κB signaling, KNDy neurons, and hypothalamic networks involving Kiss1 (a ligand for the G-protein-coupled receptor 54 (GPR54)), among others. We highlight the possible role of reactive gliosis following SARS-CoV-2 CNS injury, as well as the potential role of the hypothalamus network in PCS manifestations.}, }
@article {pmid35458189, year = {2022}, author = {Barrea, L and Verde, L and Grant, WB and Frias-Toral, E and Sarno, G and Vetrani, C and Ceriani, F and Garcia-Velasquez, E and Contreras-Briceño, J and Savastano, S and Colao, A and Muscogiuri, G}, title = {Vitamin D: A Role Also in Long COVID-19?.}, journal = {Nutrients}, volume = {14}, number = {8}, pages = {}, pmid = {35458189}, issn = {2072-6643}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Vitamin D/pharmacology/therapeutic use ; *Vitamin D Deficiency/complications/epidemiology ; Vitamins/therapeutic use ; Post-Acute COVID-19 Syndrome ; }, abstract = {Coronavirus disease 2019 (COVID-19) has quickly become a global pandemic. Reports from different parts of the world indicate that a significant proportion of people who have recovered from COVID-19 are suffering from various health problems collectively referred to as "long COVID-19". Common symptoms include fatigue, shortness of breath, cough, joint pain, chest pain, muscle aches, headaches, and so on. Vitamin D is an immunomodulatory hormone with proven efficacy against various upper respiratory tract infections. Vitamin D can inhibit hyperinflammatory reactions and accelerate the healing process in the affected areas, especially in lung tissue. Moreover, vitamin D deficiency has been associated with the severity and mortality of COVID-19 cases, with a high prevalence of hypovitaminosis D found in patients with COVID-19 and acute respiratory failure. Thus, there are promising reasons to promote research into the effects of vitamin D supplementation in COVID-19 patients. However, no studies to date have found that vitamin D affects post-COVID-19 symptoms or biomarkers. Based on this scenario, this review aims to provide an up-to-date overview of the potential role of vitamin D in long COVID-19 and of the current literature on this topic.}, }
@article {pmid35460319, year = {2022}, author = {Rakusa, M and Öztürk, S and Moro, E and Helbok, R and Bassetti, CL and Beghi, E and Bereczki, D and Bodini, B and Di Liberto, G and Jenkins, TM and Macerollo, A and Maia, LF and Martinelli-Boneschi, F and Pisani, A and Priori, A and Sauerbier, A and Soffietti, R and Taba, P and von Oertzen, TJ and Zedde, M and Crean, M and Burlica, A and Cavallieri, F and Sellner, J and , }, title = {COVID-19 vaccination hesitancy among people with chronic neurological disorders: A position paper.}, journal = {European journal of neurology}, volume = {29}, number = {8}, pages = {2163-2172}, pmid = {35460319}, issn = {1468-1331}, mesh = {*COVID-19/complications/prevention &amp; control ; *COVID-19 Vaccines/administration &amp; dosage ; Humans ; *Nervous System Diseases ; Pandemics ; SARS-CoV-2 ; Vaccination/psychology ; *Vaccination Hesitancy ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND AND PURPOSE: Health risks associated with SARS-CoV-2 infection are undisputed. Moreover, the capability of vaccination to prevent symptomatic, severe, and fatal COVID-19 is recognized. There is also early evidence that vaccination can reduce the chance for long COVID-19. Nonetheless, the willingness to get vaccinated and receive booster shots remains subpar among people with neurologic disorders. Vaccine scepticism not only jeopardizes collective efforts to end the COVID-19 pandemic but puts individual lives at risk, as some chronic neurologic diseases are associated with a higher risk for an unfavorable COVID-19 course.<br><br>METHODS: In this position paper, the NeuroCOVID-19 Task Force of the European Academy of Neurology (EAN) summarizes the current knowledge on the prognosis of COVID-19 among patients with neurologic disease, elucidates potential barriers to vaccination coverage, and formulates strategies to overcome vaccination hesitancy. A survey among the Task Force members on the phenomenon of vaccination hesitancy among people with neurologic disease supports the lines of argumentation.<br><br>RESULTS: The study revealed that people with multiple sclerosis and other nervous system autoimmune disorders are most skeptical of SARS-CoV-2 vaccination. The prevailing concerns included the chance of worsening the pre-existing neurological condition, vaccination-related adverse events, and drug interaction.<br><br>CONCLUSIONS: The EAN NeuroCOVID-19 Task Force reinforces the key role of neurologists as advocates of COVID-19 vaccination. Neurologists need to argue in the interest of their patients about the overwhelming individual and global benefits of COVID-19 vaccination. Moreover, they need to keep on eye on this vulnerable patient group, its concerns, and the emergence of potential safety signals.}, }
@article {pmid35462637, year = {2022}, author = {Saha, SA and Russo, AM and Chung, MK and Deering, TF and Lakkireddy, D and Gopinathannair, R}, title = {COVID-19 and Cardiac Arrhythmias: a Contemporary Review.}, journal = {Current treatment options in cardiovascular medicine}, volume = {24}, number = {6}, pages = {87-107}, pmid = {35462637}, issn = {1092-8464}, support = {IK6 BX006185/BX/BLRD VA/United States ; R01 HL111314/HL/NHLBI NIH HHS/United States ; R01 HL158071/HL/NHLBI NIH HHS/United States ; }, abstract = {PURPOSE OF REVIEW: A significant proportion of patients infected by the severe acute respiratory syndrome-coronavirus (SARS-CoV2) (COVID-19) also have disorders affecting the cardiac rhythm. In this review, we provide an in-depth review of the pathophysiological mechanisms underlying the associated arrhythmic complications of COVID-19 infection and provide pragmatic, evidence-based recommendations for the clinical management of these conditions.<br><br>RECENT FINDINGS: Arrhythmic manifestations of COVID-19 include atrial arrhythmias such as atrial fibrillation or atrial flutter, sinus node dysfunction, atrioventricular conduction abnormalities, ventricular tachyarrhythmias, sudden cardiac arrest, and cardiovascular dysautonomias including the so-called long COVID syndrome. Various pathophysiological mechanisms have been implicated, such as direct viral invasion, hypoxemia, local and systemic inflammation, changes in ion channel physiology, immune activation, and autonomic dysregulation. The development of atrial or ventricular arrhythmias in hospitalized COVID-19 patients has been shown to portend a higher risk of in-hospital death.<br><br>SUMMARY: Arrhythmic complications from acute COVID-19 infection are commonly encountered in clinical practice, and COVID-19 patients with cardiac complications tend to have worse clinical outcomes than those without. Management of these arrhythmias should be based on published evidence-based guidelines, with special consideration of the acuity of COVID-19 infection, concomitant use of antimicrobial and anti-inflammatory drugs, and the transient nature of some rhythm disorders. Some manifestations, such as the long COVID syndrome, may lead to residual symptoms several months after acute infection. As the pandemic evolves with the discovery of new SARS-CoV2 variants, development and use of newer anti-viral and immuno-modulator drugs, and the increasing adoption of vaccination, clinicians must remain vigilant for other arrhythmic manifestations that may occur in association with this novel but potentially deadly disease.}, }
@article {pmid35463767, year = {2022}, author = {Borlotti, A and Thomaides-Brears, H and Georgiopoulos, G and Banerjee, R and Robson, MD and Fusco, DN and Masci, PG}, title = {The Additive Value of Cardiovascular Magnetic Resonance in Convalescent COVID-19 Patients.}, journal = {Frontiers in cardiovascular medicine}, volume = {9}, number = {}, pages = {854750}, pmid = {35463767}, issn = {2297-055X}, abstract = {In COVID-19 the development of severe viral pneumonia that is coupled with systemic inflammatory response triggers multi-organ failure and is of major concern. Cardiac involvement occurs in nearly 60% of patients with pre-existing cardiovascular conditions and heralds worse clinical outcome. Diagnoses carried out in the acute phase of COVID-19 rely upon increased levels of circulating cardiac injury biomarkers and transthoracic echocardiography. These diagnostics, however, were unable to pinpoint the mechanisms of cardiac injury in COVID-19 patients. Identifying the main features of cardiac injury remains an urgent yet unmet need in cardiology, given the potential clinical consequences. Cardiovascular magnetic resonance (CMR) provides an unparalleled opportunity to gain a deeper insight into myocardial injury given its unique ability to interrogate the properties of myocardial tissue. This endeavor is particularly important in convalescent COVID-19 patients as many continue to experience chest pain, palpitations, dyspnea and exertional fatigue, six or more months after the acute illness. This review will provide a critical appraisal of research on cardiovascular damage in convalescent adult COVID-19 patients with an emphasis on the use of CMR and its value to our understanding of organ damage.}, }
@article {pmid35464473, year = {2022}, author = {Xiang, M and Jing, H and Wang, C and Novakovic, VA and Shi, J}, title = {Persistent Lung Injury and Prothrombotic State in Long COVID.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {862522}, pmid = {35464473}, issn = {1664-3224}, mesh = {Aftercare ; *COVID-19/complications ; Humans ; *Lung Injury/etiology ; Patient Discharge ; SARS-CoV-2 ; *Thrombophilia/etiology ; *Thrombosis/etiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Lung injury may persist during the recovery period of COVID-19 as shown through imaging, six-minute walk, and lung function tests. The pathophysiological mechanisms leading to long COVID have not been adequately explained. Our aim is to investigate the basis of pulmonary susceptibility during sequelae and the possibility that prothrombotic states may influence long-term pulmonary symptoms of COVID-19. The patient's lungs remain vulnerable during the recovery stage due to persistent shedding of the virus, the inflammatory environment, the prothrombotic state, and injury and subsequent repair of the blood-air barrier. The transformation of inflammation to proliferation and fibrosis, hypoxia-involved vascular remodeling, vascular endothelial cell damage, phosphatidylserine-involved hypercoagulability, and continuous changes in serological markers all contribute to post-discharge lung injury. Considering the important role of microthrombus and arteriovenous thrombus in the process of pulmonary functional lesions to organic lesions, we further study the possibility that prothrombotic states, including pulmonary vascular endothelial cell activation and hypercoagulability, may affect long-term pulmonary symptoms in long COVID. Early use of combined anticoagulant and antiplatelet therapy is a promising approach to reduce the incidence of pulmonary sequelae. Essentially, early treatment can block the occurrence of thrombotic events. Because impeded pulmonary circulation causes large pressure imbalances over the alveolar membrane leading to the infiltration of plasma into the alveolar cavity, inhibition of thrombotic events can prevent pulmonary hypertension, formation of lung hyaline membranes, and lung consolidation.}, }
@article {pmid35464506, year = {2022}, author = {Guerrero, M and Castroman, P and Quiroga, O and Berenguel Cook, M and Narvaez Tamayo, MA and Venturoni, L and Pergolizzi, J and Rekatsina, M and Varrassi, G}, title = {Pain Management and COVID-19: A Latin American Perspective.}, journal = {Cureus}, volume = {14}, number = {3}, pages = {e23100}, pmid = {35464506}, issn = {2168-8184}, abstract = {Vaccinations and therapeutics have been developed for COVID-19, but vaccine uptake varies markedly among countries. Public health responses have also varied, in particular, with lockdown efforts and school closing. All over the world, the pandemic exposed healthcare and economic weaknesses. COVID-19 exacerbated mental health issues by exposing the population to prolonged periods of fear, anxiety, financial stress, psychological uncertainties, and sometimes isolation from even family and friends. Chronic pain patients have been disproportionately affected. The pandemic-associated stresses may have exacerbated their already painful symptoms while at the same time interrupting their access to care. The ramifications of the COVID-19 post-viral syndrome ("long COVID-19") are not yet known. COVID-19 viral infection has been associated with neuropathic pain symptoms. Tele-triage and telehealth applications can help manage chronic pain patients in the COVID-19 era, but many interventional procedures, injections, or other treatments have been delayed. The role of palliative care for patients with terminal cases of infection must be re-examined. Palliative care is a relatively new medical specialty and allows terminally ill patients to die in as much comfort and peace as can be afforded to them. More training in palliative care for all clinicians is urgently needed. COVID-19 exposed much that is wrong or weak or inadequate in our healthcare systems, but it also allowed us to embrace new technologies and develop better systems to manage the challenge of a pandemic.}, }
@article {pmid35466278, year = {2022}, author = {Lazova, S and Dimitrova, Y and Hristova, D and Tzotcheva, I and Velikova, T}, title = {Cellular, Antibody and Cytokine Pathways in Children with Acute SARS-CoV-2 Infection and MIS-C-Can We Match the Puzzle?.}, journal = {Antibodies (Basel, Switzerland)}, volume = {11}, number = {2}, pages = {}, pmid = {35466278}, issn = {2073-4468}, abstract = {The newly identified strain of the Coronaviridae family called severe acute respiratory syndrome (SARS-CoV-2) recently became the most significant health threat for adults and children. Some main predictors of severe clinical course in patients with SARS-CoV-2 infection are age and concomitant health conditions. Therefore, the proper evaluation of SARS-CoV-2-specific immunity is urgently required to understand and predict the spectrum of possible clinical phenotypes and recommend vaccination options and regimens in children. Furthermore, it is critical to characterize the nature of SARS-CoV-2-specific immune responses in children following asymptomatic infection and COVID-19 and other related conditions such as multisystem inflammatory syndrome (MIS-C), para-infectious and late postinfectious consequences. Recent studies involving children revealed a variety of cytokines, T cells and antibody responses in the pathogenesis of the disease. Moreover, different clinical scenarios in children were observed-asymptomatic seroprevalence, acute SARS-CoV-2 infection, and rarely severe COVID-19 with typical cytokine storm, MIS-C, long COVID-19, etc. Therefore, to gain a better clinical view, adequate diagnostic criteria and treatment algorithms, it is essential to create a realistic picture of the immunological puzzle of SARS-CoV-2 infection in different age groups. Finally, it was demonstrated that children may exert a potent and prolonged adaptive anti-SARS-CoV-2 immune response, with significant cross-reactions against other human Corona Viruses, that might contribute to disease sparing effect in this age range. However, the immunopathology of the virus has to be elucidated first.}, }
@article {pmid35477864, year = {2022}, author = {Lin, S and Lau, LH and Chanchlani, N and Kennedy, NA and Ng, SC}, title = {Recent advances in clinical practice: management of inflammatory bowel disease during the COVID-19 pandemic.}, journal = {Gut}, volume = {71}, number = {7}, pages = {1426-1439}, pmid = {35477864}, issn = {1468-3288}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*COVID-19/complications/epidemiology ; COVID-19 Vaccines ; Chronic Disease ; Humans ; *Inflammatory Bowel Diseases/complications/drug therapy/epidemiology ; Pandemics/prevention &amp; control ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The COVID-19 pandemic has raised considerable concerns that patients with inflammatory bowel disease (IBD), particularly those treated with immunosuppressive therapies, may have an increased risk of SARS-CoV-2 acquisition, develop worse outcomes following COVID-19, and have suboptimal vaccine response compared with the general population. In this review, we summarise data on the risk of COVID-19 and associated outcomes, and latest guidance on SARS-CoV-2 vaccines in patients with IBD. Emerging evidence suggests that commonly used medications for IBD, such as corticosteroids but not biologicals, were associated with adverse outcomes to COVID-19. There has been no increased risk of de novo, or delayed, IBD diagnoses, however, an overall decrease in endoscopy procedures has led to a rise in the number of missed endoscopic-detected cancers during the pandemic. The impact of IBD medication on vaccine response has been a research priority recently. Data suggest that patients with IBD treated with antitumour necrosis factor (TNF) medications had attenuated humoral responses to SARS-CoV-2 vaccines, and more rapid antibody decay, compared with non-anti-TNF-treated patients. Reassuringly, rates of breakthrough infections and hospitalisations in all patients who received vaccines, irrespective of IBD treatment, remained low. International guidelines recommend that all patients with IBD treated with immunosuppressive therapies should receive, at any point during their treatment cycle, three primary doses of SARS-CoV-2 vaccines with a further booster dose as soon as possible. Future research should focus on our understanding of the rate of antibody decay in biological-treated patients, which patients require additional doses of SARS-CoV-2 vaccine, the long-term risks of COVID-19 on IBD disease course and activity, and the potential risk of long COVID-19 in patients with IBD.}, }
@article {pmid35486940, year = {2022}, author = {Gupta, M and Gupta, N and Esang, M}, title = {Long COVID in Children and Adolescents.}, journal = {The primary care companion for CNS disorders}, volume = {24}, number = {2}, pages = {}, doi = {10.4088/PCC.21r03218}, pmid = {35486940}, issn = {2155-7780}, mesh = {Adolescent ; *COVID-19/complications ; Child ; Humans ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome ; Post-Acute COVID-19 Syndrome ; }, abstract = {Objective: To review the empirical evidence regarding neuropsychiatric illness (long coronavirus disease [COVID]) in children and adolescents post-severe acute respiratory coronavirus disease 2 (SARS-CoV-2) infection. Data Sources: A search of PubMed, PsycINFO, Cochrane Library, and Google Scholar was conducted from the date of inception until February 2022 using the keywords corona*, COVID-19, SARS-CoV-2, mental health, depression, anxiety, neurological, psychiatric, long COVID, and post-COVID outcomes. Age filters were used to include children and adolescents aged ≤ 18 years. Study Selection: The search resulted in the identification of 526 articles; 48 articles met the inclusion criteria. Data Extraction: Results are presented using a narrative review format. Data regarding long COVID in children and adolescents post-SARS-CoV-2 infection were extracted to understand epidemiologic trends, preventive measures, and treatment options. Results: Studies during the initial phase of the pandemic reported a mixed range of symptoms from case reports or case series. However, multisystem inflammatory syndrome in children (MIS-C) was widely reported. During the subsequent phases, the emergence of new variants led to a surge of SARS-CoV-2 infections in pediatric populations. There were highly variable, mixed symptom clusters within 60 days post-infection, which resolved in many patients within 6 months. There were prolonged illnesses and impairments in some children and adolescents with long COVID, and many had similar symptoms even though they tested negative for COVID-19. Conclusions: Long COVID symptoms are both physical and mental in nature among children and adolescents. The impairments have the potential to affect long-term functioning and increase the overall burden on health care delivery. Despite current studies having methodological issues, there is a consensus to provide multidisciplinary and holistic care to those in need.}, }
@article {pmid35489015, year = {2022}, author = {Umesh, A and Pranay, K and Pandey, RC and Gupta, MK}, title = {Evidence mapping and review of long-COVID and its underlying pathophysiological mechanism.}, journal = {Infection}, volume = {50}, number = {5}, pages = {1053-1066}, pmid = {35489015}, issn = {1439-0973}, mesh = {*COVID-19/complications/epidemiology ; Hospitalization ; Humans ; Risk Factors ; *COVID-19 Drug Treatment ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE: Apart from the global disease burden of acute COVID-19 disease, the health complications arising after recovery have been recognized as a long-COVID or post-COVID-19 syndrome. Evidences of long-COVID symptoms involving various organ systems are rapidly growing in literature. The objective was to perform a rapid review and evidence mapping of systemic complications and symptoms of long-COVID and underlying pathophysiological mechanisms.<br><br>METHODS: Publications reporting clinical trials, observational cohort studies, case-control studies, case-series, meta-analysis, and systematic reviews, focusing on the squeal of the disease, consequences of COVID-19 treatment/hospitalization, long-COVID, chronic COVID syndrome, and post acute COVID-19 were reviewed in detail for the narrative synthesis of frequency, duration, risk factors, and pathophysiology.<br><br>RESULTS: The review highlights that pulmonary, neuro-psychological, and cardiovascular complications are major findings in most epidemiological studies. However, dysfunctional gastrointestinal, endocrine, and metabolic health are recent findings for which underlying pathophysiological mechanisms are poorly understood. Analysis of the clinical trial landscape suggests that more than 50% of the industry-sponsored trials are focused on pulmonary symptoms. In contrast to the epidemiological trends and academic trials, cardiovascular complications are not a focus of industry-sponsored trials, suggestive of the gaps in the research efforts.<br><br>CONCLUSION: The gap in epidemiological trends and academic trials, particularly concerning cardiovascular complications not being a focus of industry-sponsored trials is suggestive of the gaps in research efforts and longer follow-up durations would help identify other long-COVID-related health issues such as reproductive health and fertility.}, }
@article {pmid35490117, year = {2022}, author = {Zürcher, SJ and Banzer, C and Adamus, C and Lehmann, AI and Richter, D and Kerksieck, P}, title = {Post-viral mental health sequelae in infected persons associated with COVID-19 and previous epidemics and pandemics: Systematic review and meta-analysis of prevalence estimates.}, journal = {Journal of infection and public health}, volume = {15}, number = {5}, pages = {599-608}, pmid = {35490117}, issn = {1876-035X}, mesh = {Adult ; *COVID-19/epidemiology ; Humans ; *Influenza A Virus, H1N1 Subtype ; *Influenza A Virus, H7N9 Subtype ; Mental Health ; Pandemics ; Prevalence ; SARS-CoV-2 ; }, abstract = {AIMS: Post-viral mental health problems (MHP) in COVID-19 patients and survivors were anticipated already during early stages of this pandemic. We aimed to synthesize the prevalence of the anxiety, depression, post-traumatic and general distress domain associated with virus epidemics since 2002.<br><br>METHODS: In this systematic review and meta-analysis, we searched PubMed, PsycINFO, and Embase from 2002 to April 14, 2021 for peer-reviewed studies reporting prevalence of MHP in adults with laboratory-confirmed or suspected SARS-CoV-1, H1N1, MERS-CoV, H7N9, Ebolavirus, or SARS-CoV-2 infection. We included studies that assessed post-viral MHP with validated and frequently used scales. A three-level random-effects meta-analysis for dependent effect sizes was conducted to account for multiple outcome reporting. We pooled MHP across all domains and separately by severity (above mild or moderate-to-severe) and by acute (one month), ongoing (one to three months), and post-illness stages (longer than three months). A meta-regression was conducted to test for moderating effects, particularly for exploring estimate differences between SARS-Cov-2 and previous pandemics and epidemics. PROSPERO registration: CRD42020194535.<br><br>RESULTS: We identified 59 studies including between 14 and 1002 participants and providing 187 prevalence estimates. MHP, in general, decreased from acute to post-illness from 46.3% to 38.8% and for mild and moderate-to-severe from 22.3% to 18.8%, respectively. We found no evidence of moderating effects except for non-random sampling and H1N1 showing higher prevalence. There was a non-significant trend towards lower MHP for SARS-CoV-2 compared to previous epidemics.<br><br>CONCLUSIONS: MHP prevalence estimates decreased over time but were still on a substantial level at post-illness. Post-viral mental health problems caused by SARS-CoV-2 could have been expected much earlier, given the previous post-viral sequelae.}, }
@article {pmid35492595, year = {2022}, author = {Dos Santos, PK and Sigoli, E and Bragança, LJG and Cornachione, AS}, title = {The Musculoskeletal Involvement After Mild to Moderate COVID-19 Infection.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {813924}, pmid = {35492595}, issn = {1664-042X}, abstract = {COVID-19, a disease caused by the novel coronavirus SARS-CoV-2, has been drastically affecting the daily lives of millions of people. COVID-19 is described as a multiorgan disease that affects not only the respiratory tract of infected individuals, but it has considerable effects on the musculoskeletal system, causing excessive fatigue, myalgia, arthralgia, muscle weakness and skeletal muscle damage. These symptoms can persist for months, decreasing the quality of life of numerous individuals. Curiously, most studies in the scientific literature focus on patients who were hospitalized due to SARS-CoV-2 infection and little is known about the mechanism of action of COVID-19 on skeletal muscles, especially of individuals who had the mild to moderate forms of the disease (non-hospitalized patients). In this review, we focus on the current knowledge about the musculoskeletal system in COVID-19, highlighting the lack of researches investigating the mild to moderate cases of infection and pointing out why it is essential to care for these patients. Also, we will comment about the need of more experimental data to assess the musculoskeletal manifestations on COVID-19-positive individuals.}, }
@article {pmid35493431, year = {2022}, author = {Efstathiou, V and Stefanou, MI and Demetriou, M and Siafakas, N and Makris, M and Tsivgoulis, G and Zoumpourlis, V and Kympouropoulos, SP and Tsoporis, JN and Spandidos, DA and Smyrnis, N and Rizos, E}, title = {Long COVID and neuropsychiatric manifestations (Review).}, journal = {Experimental and therapeutic medicine}, volume = {23}, number = {5}, pages = {363}, pmid = {35493431}, issn = {1792-1015}, abstract = {There is accumulating evidence in the literature indicating that a number of patients with coronavirus disease 2019 (COVID-19) may experience a range of neuropsychiatric symptoms, persisting or even presenting following the resolution of acute COVID-19. Among the neuropsychiatric manifestations more frequently associated with 'long COVID' are depression, anxiety, post-traumatic stress disorder, sleep disturbances, fatigue and cognitive deficits, that can potentially be debilitating and negatively affect patients' wellbeing, albeit in the majority of cases symptoms tend to improve over time. Despite variations in results obtained from studies using different methodological approaches to define 'long COVID' syndrome, the most widely accepted factors associated with a higher risk of developing neuropsychiatric manifestations include the severity of foregoing COVID-19, the female sex, the presence of comorbidities, a history of mental health disease and an elevation in the levels of inflammatory markers, albeit further research is required to establish causal associations. To date, the pathophysiological mechanisms implicated in neuropsychiatric manifestations of 'long COVID' remain only partially elucidated, while the role of the indirect effects of the COVID-19 pandemic, such as social isolation and uncertainty concerning social, financial and health recovery post-COVID, have also been highlighted. Given the alarming effects of 'long-COVID', interdisciplinary cooperation for the early identification of patients who are at a high risk of persistent neuropsychiatric presentations, beyond COVID-19 recovery, is crucial to ensure that appropriate integrated physical and mental health support is provided, with the aim of mitigating the risks of long-term disability at a societal and individual level.}, }
@article {pmid35493814, year = {2022}, author = {Hirano, SI and Ichikawa, Y and Sato, B and Takefuji, Y and Satoh, F}, title = {Molecular Hydrogen as a Medical Gas for the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Possible Efficacy Based on a Literature Review.}, journal = {Frontiers in neurology}, volume = {13}, number = {}, pages = {841310}, pmid = {35493814}, issn = {1664-2295}, abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disorder that is characterized by fatigue that persists for more than 6 months, weakness, sleep disturbances, and cognitive dysfunction. There are multiple possible etiologies for ME/CFS, among which mitochondrial dysfunction plays a major role in abnormal energy metabolism. The potential of many substances for the treatment of ME/CFS has been examined; however, satisfactory outcomes have not yet been achieved. The development of new substances for curative, not symptomatic, treatments is desired. Molecular hydrogen (H2) ameliorates mitochondrial dysfunction by scavenging hydroxyl radicals, the most potent oxidant among reactive oxygen species. Animal experiments and clinical trials reported that H2 exerted ameliorative effects on acute and chronic fatigue. Therefore, we conducted a literature review on the mechanism by which H2 improves acute and chronic fatigue in animals and healthy people and showed that the attenuation of mitochondrial dysfunction by H2 may be involved in the ameliorative effects. Although further clinical trials are needed to determine the efficacy and mechanism of H2 gas in ME/CFS, our literature review suggested that H2 gas may be an effective medical gas for the treatment of ME/CFS.}, }
@article {pmid35507278, year = {2022}, author = {Tobler, DL and Pruzansky, AJ and Naderi, S and Ambrosy, AP and Slade, JJ}, title = {Long-Term Cardiovascular Effects of COVID-19: Emerging Data Relevant to the Cardiovascular Clinician.}, journal = {Current atherosclerosis reports}, volume = {24}, number = {7}, pages = {563-570}, pmid = {35507278}, issn = {1534-6242}, support = {K23 HL150159/HL/NHLBI NIH HHS/United States ; }, mesh = {*Acute Coronary Syndrome ; Arrhythmias, Cardiac ; *COVID-19/complications ; Heart ; *Heart Failure ; Humans ; SARS-CoV-2 ; *Ventricular Dysfunction, Right ; }, abstract = {PURPOSE OF REVIEW: COVID-19 is now a global pandemic and the illness affects multiple organ systems, including the cardiovascular system. Long-term cardiovascular consequences of COVID-19 are not yet fully characterized. This review seeks to consolidate available data on long-term cardiovascular complications of COVID-19 infection.<br><br>RECENT FINDINGS: Acute cardiovascular complications of COVID-19 infection include myocarditis, pericarditis, acute coronary syndrome, heart failure, pulmonary hypertension, right ventricular dysfunction, and arrhythmia. Long-term follow-up shows increased incidence of arrhythmia, heart failure, acute coronary syndrome, right ventricular dysfunction, myocardial fibrosis, hypertension, and diabetes mellitus. There is increased mortality in COVID-19 patients after hospital discharge, and initial myocardial injury is associated with increased mortality. Emerging data demonstrates increased incidence of cardiovascular illness and structural changes in recovered COVID-19 patients. Future research will be important in understanding the clinical significance of these structural abnormalities, and to determine the effect of vaccines on preventing long-term cardiovascular complications.}, }
@article {pmid35524067, year = {2022}, author = {Barrea, L and Vetrani, C and Caprio, M and Cataldi, M and Ghoch, ME and Elce, A and Camajani, E and Verde, L and Savastano, S and Colao, A and Muscogiuri, G}, title = {From the Ketogenic Diet to the Mediterranean Diet: The Potential Dietary Therapy in Patients with Obesity after CoVID-19 Infection (Post CoVID Syndrome).}, journal = {Current obesity reports}, volume = {11}, number = {3}, pages = {144-165}, pmid = {35524067}, issn = {2162-4968}, mesh = {*COVID-19 ; *Diet, Ketogenic/adverse effects ; *Diet, Mediterranean ; Humans ; Obesity/complications ; SARS-CoV-2 ; }, abstract = {PURPOSE OF REVIEW: This review primarily examines the evidence for areas of consensus and on-going uncertainty or controversy about diet and physical exercise approaches for in the post-CoVID. We propose an ideal dietary and physical activity approach that the patient with obesity should follow after CoVID-19 infection in order to reduce the clinical conditions associated with post-CoVID syndrome.<br><br>RECENT FINDINGS: The CoVID-19 disease pandemic, caused by the severe acute respiratory syndrome coronavirus-2, has spread all over the globe, infecting hundreds of millions of individuals and causing millions of death. It is also known to be is associated with several medical and psychological complications, especially in patients with obesity and weight-related disorders who in general pose a significant global public health problem, and in specific affected individuals are on a greater risk of developing poorer CoVID-19 clinical outcomes and experience a higher rate of mortality. Little is still known about the best nutritional approach to be adopted in this disease especially in the patients post-CoVID syndrome. To the best of our knowledge, no specific nutritional recommendations exist to manage in the patients post-CoVID syndrome. We report a presentation of nutritional therapeutic approach based on a ketogenic diet protocol followed by a transition to the Mediterranean diet in patients post-infection by CoVID, combined to a physical activity program to address conditions associated with post-CoVID syndrome.}, }
@article {pmid35524358, year = {2022}, author = {Buonsenso, D and Piazza, M and Boner, AL and Bellanti, JA}, title = {Long COVID: A proposed hypothesis-driven model of viral persistence for the pathophysiology of the syndrome.}, journal = {Allergy and asthma proceedings}, volume = {43}, number = {3}, pages = {187-193}, pmid = {35524358}, issn = {1539-6304}, mesh = {*COVID-19/complications/physiopathology ; *Cytokines/metabolism ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Background: Long COVID (coronavirus disease 2019) syndrome includes a group of patients who, after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibit lingering mild-to-moderate symptoms and develop medical complications that can have lasting health problems. In this report, we propose a model for the pathophysiology of the long COVID presentation based on increased proinflammatory cytokine production that results from the persistence of the SARS-CoV-2 virus or one of its molecular components. Associated with this hyperproduction of inflammatory cytokines is a heightened activity of nuclear factor κ B (NF-κB) and p38 mitogen-activated protein kinase signaling pathways that regulate cytokine production. Objective: The purpose of the present report was to review the causes of long COVID syndrome and suggest ways that can provide a basis for a better understanding of the clinical symptomatology for the of improved diagnostic and therapeutic procedures for the condition. Methods: Extensive research was conducted in medical literature data bases by applying terms such as "long COVID" associated with "persistence of the SARS-CoV-2 virus" "spike protein' "COVID-19" and "biologic therapies." Results and Conclusions: In this model of the long COVID syndrome, the persistence of SARS-CoV-2 is hypothesized to trigger a dysregulated immune system with subsequent heightened release of proinflammatory cytokines that lead to chronic low-grade inflammation and multiorgan symptomatology. The condition seems to have a genetic basis, which predisposes individuals to have a diminished immunologic capacity to completely clear the virus, with residual parts of the virus persisting. This persistence of virus and resultant hyperproduction of proinflammatory cytokines are proposed to form the basis of the syndrome.}, }
@article {pmid35529457, year = {2022}, author = {Di Girolamo, FG and Fiotti, N and Sisto, UG and Nunnari, A and Colla, S and Mearelli, F and Vinci, P and Schincariol, P and Biolo, G}, title = {Skeletal Muscle in Hypoxia and Inflammation: Insights on the COVID-19 Pandemic.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {865402}, pmid = {35529457}, issn = {2296-861X}, abstract = {SARS-CoV-2 infection is often associated with severe inflammation, oxidative stress, hypoxia and impaired physical activity. These factors all together contribute to muscle wasting and fatigue. In addition, there is evidence of a direct SARS-CoV-2 viral infiltration into skeletal muscle. Aging is often characterized by sarcopenia or sarcopenic obesity These conditions are risk factors for severe acute COVID-19 and long-COVID-19 syndrome. From these observations we may predict a strong association between COVID-19 and decreased muscle mass and functions. While the relationship between physical inactivity, chronic inflammation, oxidative stress and muscle dysfunction is well-known, the effects on muscle mass of COVID-19-related hypoxemia are inadequately investigated. The aim of this review is to highlight metabolic, immunity-related and redox biomarkers potentially affected by reduced oxygen availability and/or muscle fatigue in order to shed light on the negative impact of COVID-19 on muscle mass and function. Possible countermeasures are also reviewed.}, }
@article {pmid35552466, year = {2022}, author = {Gerhard, A and Prüß, H and Franke, C}, title = {[Manifestations of the central nervous system after COVID-19].}, journal = {Der Nervenarzt}, volume = {93}, number = {8}, pages = {769-778}, pmid = {35552466}, issn = {1433-0407}, mesh = {*COVID-19/complications ; Central Nervous System ; Humans ; *Nervous System Diseases/etiology ; *Posterior Leukoencephalopathy Syndrome ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Numerous diseases of the central nervous system (CNS), especially in the postacute phase after an infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been described. These include neuroimmunologically mediated diseases, such as encephalopathy, encephalitis, myelitis, acute disseminated encephalomyelitis (ADEM), acute necrotizing hemorrhagic leukoencephalitis (ANHLE) and neuromyelitis optica spectrum disorder (NMOSD) as well as others, such as posterior reversible encephalopathy syndrome (PRES), opsoclonus myoclonus ataxia (OMA) and cerebrovascular diseases. A parainfectious or postinfectious association is discussed but the pathophysiological mechanisms are so far unknown. Underlying mechanisms could be a virus-triggered overactivation of the immune system with hyperinflammation and cytokine storm but possibly also the development of specific autoantibodies against CNS tissue. Direct damage due to the invasion of SARS-CoV‑2 into the brain or spinal cord does not seem to play a relevant role. An exact clinical phenotyping and initiation of additional diagnostics are recommended, also to rule out other causes. To date no medicinal treatment options for CNS manifestations of long COVID exist; however, first results regarding inflammation and autoimmunity are promising and could lead to new treatment approaches.}, }
@article {pmid35562145, year = {2022}, author = {Lin, LC and Hollis, B and Hefti, MM}, title = {Neuropathology of COVID-19.}, journal = {Indian journal of pathology &amp; microbiology}, volume = {65}, number = {Supplement}, pages = {S146-S152}, doi = {10.4103/ijpm.ijpm_1103_21}, pmid = {35562145}, issn = {0974-5130}, mesh = {Aged ; Brain/pathology ; *COVID-19 ; Humans ; *Neurodegenerative Diseases/pathology ; Pandemics ; SARS-CoV-2 ; }, abstract = {The COVID-19 pandemic has placed global health care systems under unprecedented strain but has, at the same time, provided a unique opportunity for pathologists to turn autopsy findings into directly actionable insights into patient care. The current data on the neuropathology of COVID-19 remains preliminary and is limited by the lack of suitable controls, but certain tentative conclusions can be drawn. SARS-CoV-2 can infect multiple cell types in the central nervous system and does so in a subset of patients, although the clinical significance of direct infections remains in the central nervous system (CNS) and the peripheral nervous system (PNS) infections remains unclear. The best-described neuropathological manifestations of COVID-19 in the brain are variable patterns of neuroinflammation and vascular injury, although again, it remains unclear to what degree these findings are specifically due to COVID-19. There is also intriguing preliminary data to suggest a complex relationship between COVID-19 and neurodegeneration, with certain alleles that increase AD risk also increasing the risk of severe COVID-19, and conversely, the possibility that COVID-19 may increase the risk of neurodegenerative disease. The neuropathology of so-called "long-COVID" and the potential effects of COVID-19, or critical illness in general, on neurodegenerative disease remains unclear. There is thus an urgent need for long-term cohort studies of COVID-19 survivors, including brain donation, particularly in elderly patients, with careful recruitment of controls with similar non-COVID inflammatory illnesses.}, }
@article {pmid35564579, year = {2022}, author = {Fugazzaro, S and Contri, A and Esseroukh, O and Kaleci, S and Croci, S and Massari, M and Facciolongo, NC and Besutti, G and Iori, M and Salvarani, C and Costi, S and , }, title = {Rehabilitation Interventions for Post-Acute COVID-19 Syndrome: A Systematic Review.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {9}, pages = {}, pmid = {35564579}, issn = {1660-4601}, mesh = {*COVID-19/complications ; Dyspnea ; Exercise Therapy/methods ; Female ; Humans ; Male ; Quality of Life ; Post-Acute COVID-19 Syndrome ; }, abstract = {Increasing numbers of individuals suffer from post-acute COVID-19 syndrome (PACS), which manifests with persistent symptoms, the most prevalent being dyspnea, fatigue, and musculoskeletal, cognitive, and/or mental health impairments. This systematic review investigated the effectiveness of rehabilitation interventions for individuals with PACS. We searched the MEDLINE, Embase, Cochrane Register of Controlled Trials, CINHAL, Scopus, Prospero, and PEDro databases and the International Clinical Trials Registry Platform for randomized controlled trials (RCTs) up to November 2021. We screened 516 citations for eligibility, i.e., trials that included individuals with PACS exposed to exercise-based rehabilitation interventions. Five RCTs were included, accounting for 512 participants (aged 49.2-69.4 years, 65% males). Based on the revised Cochrane risk-of-bias tool (RoB 2.0), two RCTs had "low risk of bias", and three were in the "some concerns" category. Three RCTs compared experimental rehabilitation interventions with no or minimal rehabilitation, while two compared two active rehabilitation interventions. Rehabilitation seemed to improve dyspnea, anxiety, and kinesiophobia. Results on pulmonary function were inconsistent, while improvements were detected in muscle strength, walking capacity, sit-to-stand performance, and quality of life. Pending further studies based on qualitatively sound designs, these first findings seem to advocate for rehabilitation interventions to lessen disability due to PACS.}, }
@article {pmid35566253, year = {2022}, author = {Khazaal, S and Harb, J and Rima, M and Annweiler, C and Wu, Y and Cao, Z and Abi Khattar, Z and Legros, C and Kovacic, H and Fajloun, Z and Sabatier, JM}, title = {The Pathophysiology of Long COVID throughout the Renin-Angiotensin System.}, journal = {Molecules (Basel, Switzerland)}, volume = {27}, number = {9}, pages = {}, pmid = {35566253}, issn = {1420-3049}, mesh = {Angiotensin-Converting Enzyme 2 ; *COVID-19/complications ; Humans ; Peptidyl-Dipeptidase A/metabolism ; Renin-Angiotensin System/physiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19 has expanded across the world since its discovery in Wuhan (China) and has had a significant impact on people's lives and health. Long COVID is a term coined by the World Health Organization (WHO) to describe a variety of persistent symptoms after acute SARS-CoV-2 infection. Long COVID has been demonstrated to affect various SARS-CoV-2-infected persons, independently of the acute disease severity. The symptoms of long COVID, like acute COVID-19, consist in the set of damage to various organs and systems such as the respiratory, cardiovascular, neurological, endocrine, urinary, and immune systems. Fatigue, dyspnea, cardiac abnormalities, cognitive and attention impairments, sleep disturbances, post-traumatic stress disorder, muscle pain, concentration problems, and headache were all reported as symptoms of long COVID. At the molecular level, the renin-angiotensin system (RAS) is heavily involved in the pathogenesis of this illness, much as it is in the acute phase of the viral infection. In this review, we summarize the impact of long COVID on several organs and tissues, with a special focus on the significance of the RAS in the disease pathogenesis. Long COVID risk factors and potential therapy approaches are also explored.}, }
@article {pmid35568518, year = {2022}, author = {Reis, J and Buguet, A and Román, GC and Spencer, PS}, title = {The COVID-19 pandemic, an environmental neurology perspective.}, journal = {Revue neurologique}, volume = {178}, number = {6}, pages = {499-511}, pmid = {35568518}, issn = {0035-3787}, mesh = {*COVID-19/complications/epidemiology ; Humans ; *Neurology ; Pandemics/prevention &amp; control ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Neurologists have a particular interest in SARS-CoV-2 because the nervous system is a major participant in COVID-19, both in its acute phase and in its persistent post-COVID phase. The global spread of SARS-CoV-2 infection has revealed most of the challenges and risk factors that humanity will face in the future. We review from an environmental neurology perspective some characteristics that have underpinned the pandemic. We consider the agent, SARS-CoV-2, the spread of SARS-CoV-2 as influenced by environmental factors, its impact on the brain and some containment measures on brain health. Several questions remain, including the differential clinical impact of variants, the impact of SARS-CoV-2 on sleep and wakefulness, and the neurological components of Long-COVID syndrome. We touch on the role of national leaders and public health policies that have underpinned management of the COVID-19 pandemic. Increased awareness, anticipation and preparedness are needed to address comparable future challenges.}, }
@article {pmid35571085, year = {2022}, author = {Vollbracht, C and Kraft, K}, title = {Oxidative Stress and Hyper-Inflammation as Major Drivers of Severe COVID-19 and Long COVID: Implications for the Benefit of High-Dose Intravenous Vitamin C.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {899198}, pmid = {35571085}, issn = {1663-9812}, abstract = {Oxidative stress is a pivotal point in the pathophysiology of COVID-19 and presumably also in Long-COVID. Inflammation and oxidative stress are mutually reinforcing each other, thus contributing to the systemic hyperinflammatory state and coagulopathy which are cardinal pathological mechanisms of severe stages. COVID-19 patients, like other critically ill patients e.g. with pneumonia, very often show severe deficiency of the antioxidant vitamin C. So far, it has not been investigated how long this deficiency lasts or whether patients with long COVID symptoms also suffer from deficiencies. A vitamin C deficit has serious pathological consequences because vitamin C is one of the most effective antioxidants, but also co-factor of many enzymatic processes that affect the immune and nervous system, blood circulation and energy metabolism. Because of its anti-oxidative, anti-inflammatory, endothelial-restoring, and immunomodulatory effects the supportive intravenous (iv) use of supraphysiological doses has been investigated so far in 12 controlled or observational studies with altogether 1578 inpatients with COVID-19. In these studies an improved oxygenation, a decrease in inflammatory markers and a faster recovery were observed. In addition, early treatment with iv high dose vitamin C seems to reduce the risks of severe courses of the disease such as pneumonia and also mortality. Persistent inflammation, thrombosis and a dysregulated immune response (auto-immune phenomena and/or persistent viral load) seem to be major contributors to Long-COVID. Oxidative stress and inflammation are involved in the development and progression of fatigue and neuro-psychiatric symptoms in various diseases by disrupting tissue (e.g. autoantibodies), blood flow (e.g. immune thrombosis) and neurotransmitter metabolism (e.g. excitotoxicity). In oncological diseases, other viral infections and autoimmune diseases, which are often associated with fatigue, cognitive disorders, pain and depression similar to Long-COVID, iv high dose vitamin C was shown to significantly relieve these symptoms. Supportive iv vitamin C in acute COVID-19 might therefore reduce the risk of severe courses and also the development of Long-COVID.}, }
@article {pmid35576015, year = {2022}, author = {Schilling, C and Meyer-Lindenberg, A and Schweiger, JI}, title = {[Cognitive disorders and sleep disturbances in long COVID].}, journal = {Der Nervenarzt}, volume = {93}, number = {8}, pages = {779-787}, pmid = {35576015}, issn = {1433-0407}, mesh = {*COVID-19/complications ; Cognition ; Humans ; SARS-CoV-2 ; Sleep ; *Sleep Wake Disorders/diagnosis/therapy ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: During the last 2 years of the coronavirus disease 2019 (COVID-19) pandemic, knowledge about the long-term effects of the disease, the so-called long COVID, has rapidly grown; however, many questions remain unanswered, especially regarding the causes of persistent symptoms and their prognosis. Cognitive disorders and sleep disturbances are among the most frequent complaints. Both are associated with severe suffering and significant impairment in everyday functioning.<br><br>OBJECTIVE: What is known about the occurrence of cognitive disorders and sleep disturbances in long COVID? What are the influencing factors and what is known about the course over time and possible underlying mechanisms? What treatment options are available?<br><br>MATERIAL AND METHOD: In a&#xa0;narrative review, the most important findings on cognitive disorders and sleep disturbances in long COVID are presented. An overview of cohort studies with data on the prevalence and influencing factors of both symptom complexes is given. Current knowledge and hypotheses on pathophysiological mechanisms are presented and an outlook on treatment approaches is given.<br><br>RESULTS: About one in five of those affected report cognitive impairment more than 3&#xa0;months after severe acute respiratory syndrome coronavirus&#xa0;2 (SARS-CoV-2) infection and about one third report sleep disturbances. The latter comprise symptoms of insomnia as well as hypersomnia. Cognitive impairment and sleep disturbances occur in patients with all levels of initial disease severity. There are indications of an improvement of cognitive deficits over time but further longitudinal studies are needed.<br><br>CONCLUSION: In addition to the prognosis, the underlying disease mechanisms are still insufficiently understood. Furthermore, there is a&#xa0;great need for research on the efficacy and specific effective factors of therapeutic interventions.}, }
@article {pmid35576613, year = {2022}, author = {Diep, PT and Chaudry, M and Dixon, A and Chaudry, F and Kasabri, V}, title = {Oxytocin, the panacea for long-COVID? a review.}, journal = {Hormone molecular biology and clinical investigation}, volume = {43}, number = {3}, pages = {363-371}, doi = {10.1515/hmbci-2021-0034}, pmid = {35576613}, issn = {1868-1891}, mesh = {*COVID-19/complications ; Humans ; *Neuropeptides ; Oxytocin/pharmacology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: In this hypothesis paper we explore the underlying mechanisms for long-COVID and how the oxytocinergic neurones could be infected by SARS-CoV-2 leading to a reduction in plasma oxytocin (OXT). Furthermore, we aim to review the relevance of OXT and hypothalamic function in recovery from long-COVID symptoms and pathology, through exploring the pro-health effects of the OXT neuropeptide.<br><br>METHODS: A review of published literature was surveyed using Google Scholar and PubMed.<br><br>RESULTS: Numerous experimental data can be shown to correlate with OXT and long-COVID symptoms and conditions, thus providing strong circumstantial evidence to support our hypothesis. It is postulated that the reduction in plasma OXT due to acute and post-viral damage to the hypothalamus and oxytocinergic neurones contributes to the variable multi-system, remitting and relapsing nature of long-COVID. The intranasal route of OXT application was determined to be most appropriate and clinically relevant for the restoration of oxytocinergic function post COVID-19 infection.<br><br>CONCLUSIONS: We believe it is imperative to further investigate whether OXT alleviates the prolonged suffering of patients with long-COVID. Succinctly, OXT may be the much-needed post-pandemic panacea.}, }
@article {pmid35586759, year = {2022}, author = {Matsunaga, A and Tsuzuki, S and Morioka, S and Ohmagari, N and Ishizaka, Y}, title = {Long COVID: current status in Japan and knowledge about its molecular background.}, journal = {Global health &amp; medicine}, volume = {4}, number = {2}, pages = {83-93}, pmid = {35586759}, issn = {2434-9194}, abstract = {Even after recovering from coronavirus disease 2019 (COVID-19), patients can experience prolonged complaints, referred to as "long COVID". Similar to reports in Caucasians, a follow-up study in Japan revealed that fatigue, dyspnea, cough, anosmia/dysgeusia, and dyssomnia are common symptoms. Although the precise mode of long COVID remains elusive, multiple etiologies such as direct organ damage by infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), autoimmunity, prolonged inflammatory reactions, and psychiatric impairment seem to be involved. Notably, SARS-CoV-2 is neurotropic, and viral RNA and proteins are continuously detectable in multiple organs, including the brain. Viral proteins exert a number of different toxic effects on cells, suggesting that persistent infection is a key element for understanding long COVID. Here, we first reviewed the current status of long COVID in Japan, and then summarized literature that help us understand the molecular background of the symptoms. Finally, we discuss the feasibility of vaccination as a treatment for patients with long COVID.}, }
@article {pmid35594336, year = {2022}, author = {Castanares-Zapatero, D and Chalon, P and Kohn, L and Dauvrin, M and Detollenaere, J and Maertens de Noordhout, C and Primus-de Jong, C and Cleemput, I and Van den Heede, K}, title = {Pathophysiology and mechanism of long COVID: a comprehensive review.}, journal = {Annals of medicine}, volume = {54}, number = {1}, pages = {1473-1487}, pmid = {35594336}, issn = {1365-2060}, mesh = {*COVID-19/complications/epidemiology ; Humans ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: After almost 2 years of fighting against SARS-CoV-2 pandemic, the number of patients enduring persistent symptoms long after acute infection is a matter of concern. This set of symptoms was referred to as "long COVID", and it was defined more recently as "Post COVID-19 condition" by the World health Organization (WHO). Although studies have revealed that long COVID can manifest whatever the severity of inaugural illness, the underlying pathophysiology is still enigmatic.<br><br>AIM: To conduct a comprehensive review to address the putative pathophysiology underlying the persisting symptoms of long COVID.<br><br>METHOD: We searched 11 bibliographic databases (Cochrane Library, JBI EBP Database, Medline, Embase, PsycInfo, CINHAL, Ovid Nursing Database, Journals@Ovid, SciLit, EuropePMC, and CoronaCentral). We selected studies that put forward hypotheses on the pathophysiology, as well as those that encompassed long COVID patients in their research investigation.<br><br>RESULTS: A total of 98 articles were included in the systematic review, 54 of which exclusively addressed hypotheses on pathophysiology, while 44 involved COVID patients. Studies that included patients displayed heterogeneity with respect to the severity of initial illness, timing of analysis, or presence of a control group. Although long COVID likely results from long-term organ damage due to acute-phase infection, specific mechanisms following the initial illness could contribute to the later symptoms possibly affecting many organs. As such, autonomic nervous system damage could account for many symptoms without clear evidence of organ damage. Immune dysregulation, auto-immunity, endothelial dysfunction, occult viral persistence, as well as coagulation activation are the main underlying pathophysiological mechanisms so far.<br><br>CONCLUSION: Evidence on why persistent symptoms occur is still limited, and available studies are heterogeneous. Apart from long-term organ damage, many hints suggest that specific mechanisms following acute illness could be involved in long COVID symptoms. KEY MESSAGESLong-COVID is a multisystem disease that develops regardless of the initial disease severity. Its clinical spectrum comprises a wide range of symptoms.The mechanisms underlying its pathophysiology are still unclear. Although organ damage from the acute infection phase likely accounts for symptoms, specific long-lasting inflammatory mechanisms have been proposed, as well.Existing studies involving Long-COVID patients are highly heterogeneous, as they include patients with various COVID-19 severity levels and different time frame analysis, as well.}, }
@article {pmid35596571, year = {2022}, author = {Healey, Q and Sheikh, A and Daines, L and Vasileiou, E}, title = {Symptoms and signs of long COVID: A rapid review and meta-analysis.}, journal = {Journal of global health}, volume = {12}, number = {}, pages = {05014}, pmid = {35596571}, issn = {2047-2986}, support = {COV/LTE/20/15/CSO_/Chief Scientist Office/United Kingdom ; }, mesh = {Adult ; *COVID-19/complications ; Cohort Studies ; Humans ; Longitudinal Studies ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long COVID is defined as symptoms and signs related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that are present at least four weeks following acute infection. These symptoms and signs are poorly characterised but may be associated with significant morbidity. We sought to synthesise the evidence on their incidence to guide future research, policy and practice.<br><br>METHODS: We searched Medline and Embase for longitudinal cohort studies from January 2020 to July 2021 that investigated adults with long COVID at least four weeks after acute infection. Risk of bias was assessed using the Joanna Briggs Institute checklist for cohort studies. Random-effects meta-analyses were performed with subgroup analysis by follow-up time (4-12 vs more than 12 weeks).<br><br>RESULTS: 19 studies were included, 13 of which included patients hospitalised with COVID-19. The total sample size was 10&#x2009;643 and the follow-up time ranged from 30 to 340 days. Risk of bias was assessed as high in one study, moderate in two studies and low in the remaining 16 studies. The most common symptoms and signs seen at any time point in long COVID were fatigue (37%; 95% confidence interval (CI)&#x2009;=&#x2009;23-55), dyspnoea (21%; 95% CI&#x2009;=&#x2009;14-30), olfactory dysfunction (17%; 95% CI&#x2009;=&#x2009;9-29), myalgia (12%; 95% CI&#x2009;=&#x2009;5-25), cough (11%; 95% CI&#x2009;=&#x2009;6-20) and gustatory dysfunction (10%; 95% CI&#x2009;=&#x2009;7-17). High heterogeneity was seen for all meta-analyses and the presence of some funnel plot asymmetry may indicate reporting bias. No effect of follow-up time was found for any symptom or sign included in the subgroup analysis.<br><br>CONCLUSIONS: We have summarised evidence from longitudinal cohort studies on the most common symptoms and signs associated with long COVID. High heterogeneity seen in the meta-analysis means pooled incidence estimates should be interpreted with caution. This heterogeneity may be attributable to studies including patients from different health care settings and countries.}, }
@article {pmid35602927, year = {2022}, author = {Rolin, S and Chakales, A and Verduzco-Gutierrez, M}, title = {Rehabilitation Strategies for Cognitive and Neuropsychiatric Manifestations of COVID-19.}, journal = {Current physical medicine and rehabilitation reports}, volume = {10}, number = {3}, pages = {182-187}, pmid = {35602927}, issn = {2167-4833}, abstract = {PURPOSE OF REVIEW: Extrapulmonary manifestations of COVID-19 are abundant, including after recovery of acute SARS-CoV-2 infection. This review seeks to explore the cognitive and neuropsychiatric manifestations of COVID-19 and post-acute sequelae of SARS-CoV-2 (PASC), including Long COVID syndromes. Furthermore, the review will discuss rehabilitation strategies for the emerging neurological consequences of COVID-19 to help those experiencing long-term effects of COVID-19.<br><br>RECENT FINDINGS: There is emerging evidence depicting the neural involvement of COVID-19. Health priorities have shifted from understanding pathogenesis and treatment of pulmonary symptoms to targeting the acute and chronic sequelae of COVID-19, including cognitive and neuropsychiatric symptoms. The sequelae of COVID-19 often co-occur with other medical problems and is best managed by assessment and care across multiple disciplines. Symptoms following infection are similar to those found by other syndromes and disorders that disrupt the central nervous system.<br><br>SUMMARY: The acute and chronic sequelae of COVID-19 have become major targets of current health care providers given its significant public health impact, inclusive of cognitive and neuropsychiatric sequelae. Assessment and referral to rehabilitation based on each individual's needs and symptoms can decrease morbidity and improve quality of life.}, }
@article {pmid35606656, year = {2022}, author = {Hellwig, S and Domschke, K}, title = {[Post-COVID syndrome-Focus fatigue].}, journal = {Der Nervenarzt}, volume = {93}, number = {8}, pages = {788-796}, pmid = {35606656}, issn = {1433-0407}, mesh = {*COVID-19/complications/therapy ; Depression/therapy ; Fatigue/diagnosis/etiology/therapy ; *Fatigue Syndrome, Chronic/diagnosis/psychology/therapy ; Humans ; SARS-CoV-2 ; }, abstract = {The World Health Organization (WHO) defines post-coronavirus disease 2019 (COVID-19) as a condition which occurs in individuals with a history of probable or confirmed severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection 3 months after the onset of COVID-19 symptoms, lasts for at least 2 months and cannot be explained by an alternative diagnosis. Core symptoms of post-COVID syndrome are fatigue, dyspnea and cognitive dysfunction, which have an impact on everyday functional level. Neuropsychiatric late sequelae are common in COVID-19 patients, with incidence rates over 30%. Beside the abovementioned core symptoms, sleep disorders, depression and anxiety show increased incidences. According to current opinion, associated neuropsychiatric symptoms are subsumed under the term post-COVID syndrome but are also interpreted as comorbidities, which can promote the manifestation of a post-COVID syndrome. The key symptom fatigue shows symptom overlapping and comorbidity with psychiatric disorders. Imaging studies indicate an organic correlate of fatigue in post-COVID patients. Furthermore, psychosocial aspects and psychiatric comorbidities, such as depression and anxiety disorders as modulating and therefore potentially treatable factors were identified. Treatment of fatigue consists of pharmacological management with stimulants and antidepressants as well as nonpharmacological strategies, most notably cognitive behavioral therapy and exercise-focused interventions. The evidence for this comes from meta-analyses of tumor-associated or post-viral fatigue.}, }
@article {pmid35608715, year = {2023}, author = {Al-Kuraishy, HM and Al-Gareeb, AI and El-Bouseary, MM and Sonbol, FI and Batiha, GE}, title = {Hyperviscosity syndrome in COVID-19 and related vaccines: exploring of uncertainties.}, journal = {Clinical and experimental medicine}, volume = {23}, number = {3}, pages = {679-688}, pmid = {35608715}, issn = {1591-9528}, mesh = {Humans ; COVID-19 Vaccines/adverse effects ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; *COVID-19/prevention &amp; control ; Immunoglobulins ; *Vaccines ; *Immune System Diseases ; Vaccination ; Fibrinogen ; }, abstract = {Hyperviscosity syndrome (HVS) recently emerged as a complication of coronavirus disease 2019 (COVID-19) and COVID-19 vaccines. Therefore, the objectives of this critical review are to establish the association between COVID-19 and COVID-19 vaccines with the development of HVS. HVS may develop in various viral infections due to impairment of humoral and cellular immunity with elevation of immunoglobulins. COVID-19 can increase blood viscosity (BV) through modulation of fibrinogen, albumin, lipoproteins, and red blood cell (RBC) indices. HVS can cause cardiovascular and neurological complications in COVID-19 like myocardial infarction (MI) and stroke. HVS with or without abnormal RBCs function in COVID-19 participates in the reduction of tissue oxygenation with the development of cardio-metabolic complications and long COVID-19. Besides, HVS may develop in vaccine recipients with previous COVID-19 due to higher underlying Ig concentrations and rarely without previous COVID-19. Similarly, patients with metabolic syndrome are at the highest risk for propagation of HVS after COVID-19 vaccination. In conclusion, COVID-19 and related vaccines are linked with the development of HVS, mainly in patients with previous COVID-19 and underlying metabolic derangements. The possible mechanism of HVS in COVID-19 and related vaccines is increasing levels of fibrinogen and immunoglobulins. However, dehydration, oxidative stress, and inflammatory reactions are regarded as additional contributing factors in the pathogenesis of HVS in COVID-19. However, this critical review cannot determine the final causal relationship between COVID-19 and related vaccines and the development of HVS. Prospective and retrospective studies are warranted in this field.}, }
@article {pmid35631077, year = {2022}, author = {Pérez-Gómez, HR and Morfín-Otero, R and González-Díaz, E and Esparza-Ahumada, S and León-Garnica, G and Rodríguez-Noriega, E}, title = {The Multifaceted Manifestations of Multisystem Inflammatory Syndrome during the SARS-CoV-2 Pandemic.}, journal = {Pathogens (Basel, Switzerland)}, volume = {11}, number = {5}, pages = {}, pmid = {35631077}, issn = {2076-0817}, abstract = {The novel coronavirus SARS-CoV-2, which has similarities to the 2002-2003 severe acute respiratory syndrome coronavirus known as SARS-CoV-1, causes the infectious disease designated COVID-19 by the World Health Organization (Coronavirus Disease 2019). Although the first reports indicated that activity of the virus is centered in the lungs, it was soon acknowledged that SARS-CoV-2 causes a multisystem disease. Indeed, this new pathogen causes a variety of syndromes, including asymptomatic disease; mild disease; moderate disease; a severe form that requires hospitalization, intensive care, and mechanical ventilation; multisystem inflammatory disease; and a condition called long COVID or postacute sequelae of SARS-CoV-2 infection. Some of these syndromes resemble previously described disorders, including those with no confirmed etiology, such as Kawasaki disease. After recognition of a distinct multisystem inflammatory syndrome in children, followed by a similar syndrome in adults, various multisystem syndromes occurring during the pandemic associated or related to SARS-CoV-2 began to be identified. A typical pattern of cytokine and chemokine dysregulation occurs in these complex syndromes; however, the disorders have distinct immunological determinants that may help to differentiate them. This review discusses the origins of the different trajectories of the inflammatory syndromes related to SARS-CoV-2 infection.}, }
@article {pmid35633158, year = {2022}, author = {Ahmad, SJ and Feigen, CM and Vazquez, JP and Kobets, AJ and Altschul, DJ}, title = {Neurological Sequelae of COVID-19.}, journal = {Journal of integrative neuroscience}, volume = {21}, number = {3}, pages = {77}, doi = {10.31083/j.jin2103077}, pmid = {35633158}, issn = {0219-6352}, mesh = {Anosmia/virology ; *COVID-19/complications ; Cytokines ; Disease Progression ; Encephalitis/virology ; Headache/virology ; Hemorrhagic Stroke/virology ; Humans ; Inflammation ; *Nervous System Diseases/virology ; SARS-CoV-2 ; Stroke/virology ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Though primarily a pulmonary disease, Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus can generate devastating disease states that affect multiple organ systems including the central nervous system (CNS). The various neurological disorders associated with COVID-19 range in severity from mild symptoms such as headache, or myalgias to more severe symptoms such as stroke, psychosis, and anosmia. While some of the COVID-19 associated neurological complications are mild and reversible, a significant number of patients suffer from stroke. Studies have shown that COVID-19 infection triggers a wave of inflammatory cytokines that induce endothelial cell dysfunction and generate coagulopathy that increases the risk of stroke or thromboses. Inflammation of the endothelium following infection may also destabilize atherosclerotic plaque and induce thrombotic stroke. Although uncommon, there have also been reports of hemorrhagic stroke associated with COVID-19. The proposed mechanisms include a blood pressure increase caused by infection leading to a reduction in angiotensin converting enzyme-2 (ACE-2) levels that results in an imbalance of the renin-angiotensin system ultimately manifesting inflammation and vasoconstriction. Coagulopathy, as demonstrated by elevated prothrombin time (PT), has also been posited as a factor contributing to hemorrhagics stroke in patients with COVID-19. Other neurological conditions associated with COVID-19 include encephalopathy, anosmia, encephalitis, psychosis, brain fog, headache, depression, and anxiety. Though there are several hypotheses reported in the literature, a unifying pathophysiological mechanism of many of these disorders remains unclear. Pulmonary dysfunction leading to poor oxygenation of the brain may explain encephalopathy and other disorders in COVID-19 patients. Alternatively, a direct invasion of the CNS by the virus or breach of the blood-brain barrier by the systemic cytokines released during infection may be responsible for these conditions. Notwithstanding, the relationship between the inflammatory cytokine levels and conditions such as depression and anxiety is contradictory and perhaps the social isolation during the pandemic may in part be a contributing factor to some of the reported CNS disorders.<br><br>OBJECTIVE: In this article, we review the current literature pertaining to some of the most significant and common neurological disorders such as ischemic and hemorrhagic stroke, encephalopathy, encephalitis, brain fog, Long COVID, headache, Guillain-Barre syndrome, depression, anxiety, and sleep disorders in the setting of COVID-19. We summarize some of the most relevant literature to provide a better understanding of the mechanistic details regarding these disorders in order to help physicians monitor and treat patients for significant COVID-19 associated neurologic impairments.<br><br>METHODS: A literature review was carried out by the authors using PubMed with the search terms "COVID-19" and "Neurology", "Neurological Manifestations", "Neuropsychiatric Manifestations", "Stroke", "Encephalopathy", "Headache", "Guillain-Barre syndrome", "Depression", "Anxiety", "Encephalitis", "Seizure", "Spasm", and "ICUAW". Another search was carried out for "Long-COVID" and "Post-Acute COVID-19" and "Neurological Manifestations" or "Neuropsychiatric Manifestations". Articles such as case reports, case series, and cohort studies were included as references. No language restrictions were enforced. In the case of anxiety and depression, attempts were made to focus mainly on articles describing these conditions in infected patients.<br><br>RESULTS: A total of 112 articles were reviewed. The incidence, clinical outcomes, and pathophysiology of selected neurological disorders are discussed below. Given the recent advent of this disease, the incidence of certain neurologic sequelae was not always available. Putative mechanisms for each condition in the setting of COVID-19 are outlined.}, }
@article {pmid35633949, year = {2022}, author = {Izquierdo-Pujol, J and Moron-Lopez, S and Dalmau, J and Gonzalez-Aumatell, A and Carreras-Abad, C and Mendez, M and Rodrigo, C and Martinez-Picado, J}, title = {Post COVID-19 Condition in Children and Adolescents: An Emerging Problem.}, journal = {Frontiers in pediatrics}, volume = {10}, number = {}, pages = {894204}, pmid = {35633949}, issn = {2296-2360}, abstract = {The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection became a pandemic in 2020 and by March 2022 had caused more than 479 million infections and 6 million deaths worldwide. Several acute and long-term symptoms have been reported in infected adults, but it remains unclear whether children/adolescents also experience persistent sequelae. Hence, we conducted a review of symptoms and pathophysiology associated with post-coronavirus disease 2019 (post-COVID-19) condition in children and adolescents. We reviewed the scientific literature for reports on persistent COVID-19 symptoms after SARS-CoV-2 infection in both children/adolescents and adults from 1 January 2020 to 31 March 2022 (based on their originality and relevance to the broad scope of this review, 26 reports were included, 8 focused on adults and 18 on children/adolescents). Persistent sequelae of COVID-19 are less common in children/adolescents than in adults, possibly owing to a lower frequency of SARS-CoV-2 infection and to the lower impact of the infection itself in this age group. However, cumulative evidence has shown prolonged COVID-19 to be a clinical entity, with few pathophysiological associations at present. The most common post-COVID-19 symptoms in children/adolescents are fatigue, lack of concentration, and muscle pain. In addition, we found evidence of pathophysiology associated with fatigue and/or headache, persistent loss of smell and cough, and neurological and/or cardiovascular symptoms. This review highlights the importance of unraveling why SARS-CoV-2 infection may cause post-COVID-19 condition and how persistent symptoms might affect the physical, social, and psychological well-being of young people in the future.}, }
@article {pmid35636906, year = {2022}, author = {Hope, AA and Evering, TH}, title = {Postacute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 Infection.}, journal = {Infectious disease clinics of North America}, volume = {36}, number = {2}, pages = {379-395}, pmid = {35636906}, issn = {1557-9824}, support = {K01 HL140279/HL/NHLBI NIH HHS/United States ; }, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or long coronavirus disease (COVID) is an emerging syndrome characterized by multiple persisting or newly emergent symptoms following the acute phase of SARS-CoV-2 infection. For affected patients, these prolonged symptoms can have a relapsing and remitting course and may be associated with disability and frequent health care utilization. Although many symptom-driven treatments are available, management remains challenging and often requires a multidisciplinary approach. This article summarizes the emerging consensus on definitions, epidemiology, and pathophysiology of long COVID and discusses what is understood about prevention, evaluation, and treatment of this syndrome.}, }
@article {pmid35637934, year = {2022}, author = {Töpfner, N and ,  and Alberer, M and Ankermann, T and ,  and Bender, S and ,  and Berner, R and de Laffolie, J and ,  and Dingemann, J and ,  and Heinicke, D and ,  and Haas, JP and ,  and Hufnagel, M and Hummel, T and ,  and Huppertz, HI and ,  and Knuf, M and Kobbe, R and Lücke, T and ,  and Riedel, J and ,  and Rosenecker, J and ,  and Wölfle, J and ,  and Schneider, B and ,  and Schneider, D and ,  and Schriever, V and ,  and Schroeder, A and ,  and Stojanov, S and Tenenbaum, T and Trapp, S and ,  and Vilser, D and ,  and Brinkmann, F and Behrends, U}, title = {[Recommendation for standardized medical care for children and adolescents with long COVID].}, journal = {Monatsschrift Kinderheilkunde : Organ der Deutschen Gesellschaft fur Kinderheilkunde}, volume = {170}, number = {6}, pages = {539-547}, pmid = {35637934}, issn = {0026-9298}, abstract = {This current consensus paper for long COVID complements the existing AWMF S1 guidelines for long COVID with a detailed overview on the various clinical aspects of long COVID in children and adolescents. Members of 19 different pediatric societies of the DGKJ convent and collaborating societies together provide expert-based recommendations for the clinical management of long COVID based on the currently available but limited academic evidence for long COVID in children and adolescents. It contains screening questions for long COVID and suggestions for a structured, standardized pediatric medical history and diagnostic evaluation for patients with suspected long COVID. A time and resource-saving questionnaire, which takes the clinical complexity of long COVID into account, is offered via the DGKJ and DGPI websites as well as additional questionnaires suggested for an advanced screening of specific neurocognitive and/or psychiatric symptoms including post-exertional malaise (PEM) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). According to the individual medical history as well as clinical signs and symptoms a step by step diagnostic procedure and a multidisciplinary therapeutic approach are recommended.}, }
@article {pmid35646959, year = {2022}, author = {Cerasola, D and Argano, C and Corrao, S}, title = {Lessons From COVID-19: Physical Exercise Can Improve and Optimize Health Status.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {834844}, pmid = {35646959}, issn = {2296-858X}, abstract = {The outbreak of Coronavirus Disease 2019 (COVID-19) has caused increasing challenges for healthcare systems globally. The disease spread rapidly from Wuhan to the rest of the world, involving more than 400 million individuals and including more than 5 million deaths. In dealing with the pandemic, China and other countries took protective measures such as promoting social distancing, canceling public gatherings, closing schools, quarantining, and imposing lockdowns. All these measures lead to physical inactivity. Being physically inactive has significant repercussions on the status of physical and mental wellbeing, and it is associated with anxiety, stress, increased chronic disease risk, and worsening of chronic conditions. In this sense, the relevance of maintaining a healthy lifestyle through physical exercise has been outlined by the World Health Organization (WHO). The aim of this mini review is to discuss the importance of physical activity in the context of the COVID-19 pandemic, highlighting the benefits of physical activity and exercise that could be potentially effective treatment strategies for comorbid chronic conditions, long covid syndrome (LCS), and symptoms such as depression and anxiety.}, }
@article {pmid35658110, year = {2022}, author = {Wang, Y and Zheng, K and Gao, W and Lv, J and Yu, C and Wang, L and Wang, Z and Wang, B and Liao, C and Li, L}, title = {Asymptomatic and pre-symptomatic infection in Coronavirus Disease 2019 pandemic.}, journal = {Medical review (2021)}, volume = {2}, number = {1}, pages = {66-88}, pmid = {35658110}, issn = {2749-9642}, abstract = {With the presence of Coronavirus Disease 2019 (COVID-19) asymptomatic infections detected, their proportion, transmission potential, and other aspects such as immunity and related emerging challenges have attracted people's attention. We have found that based on high-quality research, asymptomatic infections account for at least one-third of the total cases, whereas based on systematic review and meta-analysis, the proportion is about one-fifth. Evaluating the true transmission potential of asymptomatic cases is difficult but critical, since it may affect national policies in response to COVID-19. We have summarized the current evidence and found, compared with symptomatic cases, the transmission capacity of asymptomatic individuals is weaker, even though they have similar viral load and relatively short virus shedding duration. As the outbreak progresses, asymptomatic infections have also been found to develop long COVID-19. In addition, the role of asymptomatic infection in COVID-19 remains to be further revealed as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge. Nevertheless, as asymptomatic infections transmit the SARS-CoV-2 virus silently, they still pose a substantial threat to public health. Therefore, it is essential to conduct screening to obtain more knowledge about the asymptomatic infections and to detect them as soon as possible; meanwhile, management of them is also a key point in the fight against COVID-19 community transmission. The different management of asymptomatic infections in various countries are compared and the experience in China is displayed in detail.}, }
@article {pmid35662932, year = {2022}, author = {Surma, S and Sahebkar, A and Urbański, J and Penson, PE and Banach, M}, title = {Curcumin - The Nutraceutical With Pleiotropic Effects? Which Cardiometabolic Subjects Might Benefit the Most?.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {865497}, pmid = {35662932}, issn = {2296-861X}, abstract = {Despite continuous advances in pharmacotherapy, atherosclerotic cardiovascular disease remains the world's leading killer. Atherosclerosis relates not only to an increased level of cholesterol, but involves the development of atherosclerotic plaques, which are formed as a result of processes including inflammation and oxidative stress. Therefore, in addition to the classical risk factors for ASCVD (such as type 2 diabetes, overweight, obesity, hypertension and metabolic syndrome), residual risk factors such as inflammation and oxidative stress should also be reduced. The most important intervention in ASCVD is prevention, which includes promoting a healthy diet based on products of natural origin. Curcumin, which is often present in the diet, has been demonstrate to confer several benefits to health. It has been shown in numerous clinical trials that curcumin exhibited anti-diabetic, lipid-lowering, antihypertensive, antioxidant and anti-inflammatory effects, as well as promoting weight loss. All this means that curcumin has a comprehensive impact on the most important risk factors of ASCVD and may be a beneficial support in the treatment of these diseases. Recently, it has also been shown that curcumin may have a beneficial effect on the course of SARS-CoV-2 infection and might be helpful in the prevention of long-COVID complications. The aim of this review is to summarize the current knowledge regarding the safety and efficacy of curcumin in the prevention and treatment of cardiometabolic diseases.}, }
@article {pmid35667737, year = {2022}, author = {Schwab, K and Schwitzer, E and Qadir, N}, title = {Postacute Sequelae of COVID-19 Critical Illness.}, journal = {Critical care clinics}, volume = {38}, number = {3}, pages = {455-472}, pmid = {35667737}, issn = {1557-8232}, mesh = {*COVID-19/complications/therapy ; Critical Illness/therapy ; Disease Progression ; Humans ; SARS-CoV-2 ; }, abstract = {With an ever-increasing number of COVID-19 survivors, providers are tasked with addressing the longer lasting symptoms of COVID-19, or postacute sequelae of SARS-CoV-2 infection (PASC). For critically ill patients, existing knowledge about postintensive care syndrome (PICS) represents a useful structure for understanding PASC. Post-ICU clinics leverage a multidisciplinary team to evaluate and treat the physical, cognitive, and psychological sequelae central to both PICS and PASC in critically ill patients. While management through both pharmacologic and nonpharmacologic modalities can be used, further research into both the optimal treatment and prevention of PASC represents a key public health imperative.}, }
@article {pmid35667743, year = {2022}, author = {Dangayach, NS and Newcombe, V and Sonnenville, R}, title = {Acute Neurologic Complications of COVID-19 and Postacute Sequelae of COVID-19.}, journal = {Critical care clinics}, volume = {38}, number = {3}, pages = {553-570}, pmid = {35667743}, issn = {1557-8232}, mesh = {*COVID-19/complications ; Disease Progression ; Fatigue/complications ; Headache/complications ; Humans ; *Nervous System Diseases/etiology/therapy ; *Stroke ; }, abstract = {Neurologic complications can be seen in mild to severe COVID-19 with a higher risk in patients with severe COVID-19. These can occur as a direct consequence of viral infection or consequences of treatments. The spectrum ranges from non-life-threatening, like headache, fatigue, malaise, anosmia, dysgeusia, to life-threatening complications, like stroke, encephalitis, coma, Guillain-Barre syndrome. A high index of suspicion can aid in early recognition and treatment. Outcomes depend on severity of underlying COVID-19, patient age, comorbidities, and severity of the complication. Postacute sequelae of COVID-19 range from fatigue, headache, dysosmia, brain fog, anxiety, depression to an overlap with postintensive care syndrome.}, }
@article {pmid35669940, year = {2022}, author = {Young, P}, title = {[Sleep disorders and fatigue syndrome in long COVID syndrome: case-based experiences from neurological/sleep medicine rehabilitation].}, journal = {Somnologie : Schlafforschung und Schlafmedizin = Somnology : sleep research and sleep medicine}, volume = {26}, number = {2}, pages = {73-79}, pmid = {35669940}, issn = {1432-9123}, abstract = {Sleep disturbances and clinically significant fatigue syndrome are regularly described for long COVID syndrome. The pathophysiological correlations remain unknown. The clinical presentation is variable and must be considered individually. Four case studies will be used to illustrate the symptoms that constitute long COVID syndrome and the treatment options available. Multimodal individualized rehabilitation seems to be suitable to return those affected to their premorbid performance and to achieve a considerable reduction in insomniac complaints.}, }
@article {pmid35682203, year = {2022}, author = {Yang, HJ and Setou, N and Koh, E}, title = {Utilization of Mind-Body Intervention for Integrative Health Care of COVID-19 Patients and Survivors.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {11}, pages = {}, pmid = {35682203}, issn = {1660-4601}, mesh = {Anxiety/psychology/therapy ; *COVID-19/epidemiology/therapy ; Communicable Disease Control ; Delivery of Health Care ; Humans ; Pandemics ; Randomized Controlled Trials as Topic ; Survivors ; *Yoga ; }, abstract = {Recent findings suggest a correlation between COVID-19 and diabetes, although the underlying causes are still little understood. COVID-19 infection tends to induce severe symptoms in patients with underlying diabetes, increasing their mortality rate. Moreover, COVID-19 itself appears to be a diabetogenic factor. In addition, mental health conditions, such as depression due to lockdown and anxiety about infection, were found to affect glycemic control and immunity, highlighting the importance of mental health care during the pandemic. Mind-Body Intervention (MBI), which includes meditation, yoga, and qigong, has emerged as a tool for mental health management due to its effects on stress reduction and the promotion of mental and physical well-being. Here, we review the latest randomized controlled trials to determine the effects of MBI on glycemic control and the immune system and discuss the underlying mechanisms by which MBI facilitates the virtuous cycle of stress management, glycemic control, and immune modulation. Furthermore, we examine the actual utilization of MBI during the COVID-19 pandemic era through recent studies. With proper online education, non-pharmacological MBI may be more widely used as an important tool for self-health care that complements the usual treatment of COVID-19 patients and survivors.}, }
@article {pmid35686389, year = {2022}, author = {Lee, J and Kwon, KH}, title = {The significant transformation of life into health and beauty in metaverse era.}, journal = {Journal of cosmetic dermatology}, volume = {21}, number = {12}, pages = {6575-6583}, doi = {10.1111/jocd.15151}, pmid = {35686389}, issn = {1473-2165}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Cosmetics ; Marketing ; }, abstract = {BACKGROUND: In 2019, coronavirus disease-19 (COVID-19) continues, and it is evolving and starting again. It is a situation to keep in mind that now is the era of With Corona (WC) and Long-COVID. "WC" will be a transformation of the quarantine system. The current situation is associated with health and beauty. Sustainability of healthy beauty is giving new meaning to well-being and well-dying.<br><br>OBJECTIVES: Therefore, in this study, we empirically analyzed the changes in the perception of health and beauty among cosmetic consumers in the metaverse, which are recently becoming an issue in the WC era.<br><br>METHODS: It was created by searching keywords such as "With Corona," "Health," "Life Beauty," "Customized inner beauty," "Customized cosmetics," "Metaverse," "DTC GT," etc. This study was conducted with reference to PubMed, Google Scholar, Riss, Scopus, and ResearchGate. Accordingly, a total of 472 papers were researched, and among them, 32 papers, which are the focus of the study, were finally included in this study.<br><br>RESULTS: As the era of WC changes, a new paradigm of converting the customer experience of the beauty market into a metaverse will be beginning. Accordingly, it is necessary to pay attention to changes in the cosmetic industry by reflecting the needs of consumers.<br><br>CONCLUSION: It is necessary to create a new mobile platform that encompasses three-dimensional health and beauty life using direct-to-customer genetic testing (DTC GT) with Web 3.0 in the metaverse that integrates life health and beauty in the WC era. Accordingly, it is expected that this article will be used as an invaluable marketing material in preparation for new changes in the metaverse cosmetics market in the future by clearly understanding the needs of consumers in the cosmetics industry, which are changing as they transformation to WC era.}, }
@article {pmid35698804, year = {2022}, author = {Jonigk, D and Werlein, C and Lee, PD and Kauczor, HU and Länger, F and Ackermann, M}, title = {Pulmonary and Systemic Pathology in COVID-19—Holistic Pathological Analyses.}, journal = {Deutsches Arzteblatt international}, volume = {119}, number = {25}, pages = {429-435}, pmid = {35698804}, issn = {1866-0452}, support = {MR/R025673/1/MRC_/Medical Research Council/United Kingdom ; MR/S007687/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*COVID-19/complications ; Humans ; Lung/diagnostic imaging ; Pandemics ; SARS-CoV-2 ; *Thrombosis ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The COVID-19 pandemic is the third worldwide coronavirus-associated disease outbreak in the past 20 years. Lung involvement, with acute respiratory distress syndrome (ARDS) in severe cases, is the main clinical feature of this disease; the cardiovascular system, the central nervous system, and the gastrointestinal tract can also be affected. The pathophysiology of both pulmonary and extrapulmonary organ damage was almost completely unknown when the pandemic began.<br><br>METHODS: This review is based on pertinent publications retrieved by a selective search concerning the structural changes and pathophysiology of COVID-19, with a focus on imaging techniques.<br><br>RESULTS: Immunohistochemical, electron-microscopic and molecular pathological analyses of tissues obtained by autopsy have improved our understanding of COVID-19 pathophysiology, including molecular regulatory mechanisms. Intussusceptive angiogenesis (IA) has been found to be a prominent pattern of damage in the affected organs of COVID-19 patients. In IA, an existing vessel changes by invagination of the endothelium and formation of an intraluminal septum, ultimately giving rise to two new lumina. This alters hemodynamics within the vessel, leading to a loss of laminar flow and its replacement by turbulent, inhomogeneous flow. IA, which arises because of ischemia due to thrombosis, is itself a risk factor for the generation of further microthrombi; these have been detected in the lungs, heart, liver, kidneys, brain, and placenta of COVID-19 patients.<br><br>CONCLUSION: Studies of autopsy material from various tissues of COVID-19 patients have revealed ultrastructural evidence of altered microvascularity, IA, and multifocal thrombi. These changes may contribute to the pathophysiology of post-acute interstitial fibrotic organ changes as well as to the clinical picture of long COVID.}, }
@article {pmid35700481, year = {2022}, author = {Avery, RK}, title = {Update on COVID-19 Therapeutics for Solid Organ Transplant Recipients, Including the Omicron Surge.}, journal = {Transplantation}, volume = {106}, number = {8}, pages = {1528-1537}, pmid = {35700481}, issn = {1534-6080}, mesh = {Antibodies, Viral ; *COVID-19/complications/therapy ; Humans ; Immunization, Passive ; *Organ Transplantation/adverse effects ; SARS-CoV-2 ; Transplant Recipients ; COVID-19 Serotherapy ; Post-Acute COVID-19 Syndrome ; }, abstract = {Major changes have occurred in therapeutics for coronavirus-19 (COVID-19) infection over the past 12-18 mo, most notably in early outpatient therapy. In most cases, solid organ transplant recipients were not included in the original clinical trials of these agents, so studies of real-world outcomes have been important in building our understanding of their utility. This review examines what is known about clinical outcomes in solid organ transplant recipients with newer therapies. SARS-CoV-2 monoclonal antibodies for early treatment or prophylaxis have likely prevented many hospitalizations and deaths. In addition, convalescent plasma, the oral drugs nirmatrelvir/ritonavir and molnupiravir, remdesivir for early outpatient treatment, anti-inflammatory therapy, and investigational virus-specific T-cell therapy will be discussed. Finally, the later consequences of COVID-19, such as secondary infections, long COVID symptoms, and persistent active infection, are identified as areas for future research.}, }
@article {pmid35714658, year = {2022}, author = {Munblit, D and Nicholson, T and Akrami, A and Apfelbacher, C and Chen, J and De Groote, W and Diaz, JV and Gorst, SL and Harman, N and Kokorina, A and Olliaro, P and Parr, C and Preller, J and Schiess, N and Schmitt, J and Seylanova, N and Simpson, F and Tong, A and Needham, DM and Williamson, PR and , }, title = {A core outcome set for post-COVID-19 condition in adults for use in clinical practice and research: an international Delphi consensus study.}, journal = {The Lancet. Respiratory medicine}, volume = {10}, number = {7}, pages = {715-724}, pmid = {35714658}, issn = {2213-2619}, support = {001/WHO_/World Health Organization/International ; MC_PC_19026/MRC_/Medical Research Council/United Kingdom ; MC_PC_20050/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; *COVID-19/complications ; Delphi Technique ; Humans ; Outcome Assessment, Health Care ; Research Design ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; }, abstract = {Health consequences that persist beyond the acute infection phase of COVID-19, termed post-COVID-19 condition (also commonly known as long COVID), vary widely and represent a growing global health challenge. Research on post-COVID-19 condition is expanding but, at present, no agreement exists on the health outcomes that should be measured in people living with the condition. To address this gap, we conducted an international consensus study, which included a comprehensive literature review and classification of outcomes for post-COVID-19 condition that informed a two-round online modified Delphi process followed by an online consensus meeting to finalise the core outcome set (COS). 1535 participants from 71 countries were involved, with 1148 individuals participating in both Delphi rounds. Eleven outcomes achieved consensus for inclusion in the final COS: fatigue; pain; post-exertion symptoms; work or occupational and study changes; survival; and functioning, symptoms, and conditions for each of cardiovascular, respiratory, nervous system, cognitive, mental health, and physical outcomes. Recovery was included a priori because it was a relevant outcome that was part of a previously published COS on COVID-19. The next step in this COS development exercise will be to establish the instruments that are most appropriate to measure these core outcomes. This international consensus-based COS should provide a framework for standardised assessment of adults with post-COVID-19 condition, aimed at facilitating clinical care and research worldwide.}, }
@article {pmid35720240, year = {2022}, author = {Bogariu, AM and Dumitrascu, DL}, title = {Digestive involvement in the Long-COVID syndrome.}, journal = {Medicine and pharmacy reports}, volume = {95}, number = {1}, pages = {5-10}, pmid = {35720240}, issn = {2668-0572}, abstract = {BACKGROUND AND AIM: The SARS-CoV-2 infection which caused a worldwide epidemic was considered first a lung disease. Later on, it was found that the disease caused by this virus, SARS-CoV-2, can affect most organs, including the digestive system. The long-term effects of this infection are now progressively detected and called Long-COVID. This review aims is to present the updated knowledge of the digestive sequelae after SARS-CoV-2 infection.<br><br>METHODS: A search was performed in the main medical literature databases. The following search terms were used: long-covid, gastrointestinal or gastric sequelae SARS-CoV-2 and COVID-19. Data on gastrointestinal symptoms after 12 weeks were collected and presented. Observational studies were included. Studies that focus only on acute COVID-19 infection (<4 weeks) were excluded.<br><br>RESULTS: The main symptoms that can occur in the long term are: diarrhea, nausea, vomiting, abdominal pain, along with increased liver enzymes. Patients with chronic diseases have a higher risk of developing long-term sequelae, but it is not documented that digestive sequelae are influenced by the presence of chronic diseases.<br><br>CONCLUSIONS: The SARS-CoV-2 virus can affect any part of the digestive system not only in the acute infection phase but also for longer time, leaving long-term sequelae.}, }
@article {pmid35724449, year = {2022}, author = {Newell, KL and Waickman, AT}, title = {Inflammation, immunity, and antigen persistence in post-acute sequelae of SARS-CoV-2 infectionImmunity and inflammaion in post-acute sequelae of SARS-CoV-2 infection.}, journal = {Current opinion in immunology}, volume = {77}, number = {}, pages = {102228}, pmid = {35724449}, issn = {1879-0372}, mesh = {*COVID-19/complications ; Humans ; Inflammation ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {SARS-CoV-2 infection is known to result in a range of symptoms with varying degrees of acute-phase severity. In a subset of individuals, an equally diverse collection of long-term sequelae has been reported after convalescence. As survivorship and therefore the number of individuals with 'long-COVID' continues to grow, an understanding of the prevalence, origins, and mechanisms of post-acute sequelae manifestation is critically needed. Here, we will explore proposed roles of the anti-SARS-CoV-2 immune response in the onset, severity, and persistence of SARS-CoV-2 post-acute sequelae. We discuss the potential roles of persistent virus and autoantigens in this syndrome, as well as the contributions of unresolved inflammation and tissue injury. Furthermore, we highlight recent evidence demonstrating the potential benefits of vaccination and immunity in the resolution of post-acute symptoms.}, }
@article {pmid35724689, year = {2022}, author = {Steenblock, C and Hassanein, M and Khan, EG and Yaman, M and Kamel, M and Barbir, M and Lorke, DE and Rock, JA and Everett, D and Bejtullah, S and Heimerer, A and Tahirukaj, E and Beqiri, P and Bornstein, SR}, title = {Diabetes and COVID-19: Short- and Long-Term Consequences.}, journal = {Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme}, volume = {54}, number = {8}, pages = {503-509}, pmid = {35724689}, issn = {1439-4286}, support = {Deutsche Forschungsgemeinschaft//288034826,314061271/ ; }, mesh = {*COVID-19/complications ; Communicable Disease Control ; *Diabetes Mellitus/epidemiology ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {When the corona pandemic commenced more than two years ago, it was quickly recognized that people with metabolic diseases show an augmented risk of severe COVID-19 and an increased mortality compared to people without these comorbidities. Furthermore, an infection with SARS-CoV-2 has been shown to lead to an aggravation of metabolic diseases and in single cases to new-onset metabolic disorders. In addition to the increased risk for people with diabetes in the acute phase of COVID-19, this patient group also seems to be more often affected by long-COVID and to experience more long-term consequences than people without diabetes. The mechanisms behind these discrepancies between people with and without diabetes in relation to COVID-19 are not completely understood yet and will require further research and follow-up studies during the following years. In the current review, we discuss why patients with diabetes have this higher risk of developing severe COVID-19 symptoms not only in the acute phase of the disease but also in relation to long-COVID, vaccine breakthrough infections and re-infections. Furthermore, we discuss the effects of lockdown on glycemic control.}, }
@article {pmid35726132, year = {2022}, author = {Sylvester, SV and Rusu, R and Chan, B and Bellows, M and O'Keefe, C and Nicholson, S}, title = {Sex differences in sequelae from COVID-19 infection and in long COVID syndrome: a review.}, journal = {Current medical research and opinion}, volume = {38}, number = {8}, pages = {1391-1399}, doi = {10.1080/03007995.2022.2081454}, pmid = {35726132}, issn = {1473-4877}, mesh = {*COVID-19/complications/epidemiology ; Disease Progression ; Female ; Humans ; Male ; Sex Characteristics ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: We conducted literature reviews to uncover differential effects of sex on sequelae from coronavirus disease 2019 (COVID-19) and on long COVID syndrome.<br><br>METHODS: Two authors independently searched OvidSP in Embase, Medline, Biosis, and Derwent Drug File. Publications reporting original, sex-disaggregated data for sequelae of COVID-19 (published before August 2020) and long COVID syndrome (published before June 2021) were included in the reviews. The association between COVID-19 sequelae (i.e. lasting <4&#x2009;weeks after symptom onset) and sex, and between long COVID syndrome (i.e. lasting >4&#x2009;weeks after symptom onset) and sex, was determined by odds ratio (OR) and 95% confidence interval (CI) (statistical significance defined by 95% CI not including 1).<br><br>RESULTS: Of 4346 publications identified, 23 and 12 met eligibility criteria for COVID-19 sequelae and long COVID syndrome, respectively. COVID-19 sequelae in the categories of psychiatric/mood (OR&#xa0;=&#xa0;1.80; 95% CI:&#xa0;1.35-2.41), ENT (OR&#xa0;=&#xa0;1.42; 95% CI:&#xa0;1.39-1.46), musculoskeletal (OR&#xa0;=&#xa0;1.15; 95% CI:&#xa0;1.14-1.16), and&#xa0;respiratory (OR&#xa0;=&#xa0;1.09; 95% CI:&#xa0;1.08-1.11) were significantly more likely among females (vs. males), whereas renal sequelae (OR&#xa0;=&#xa0;0.83; 95% CI:&#xa0;0.75-0.93) were significantly more likely among males. The likelihood of having long COVID syndrome was significantly greater among females (OR&#xa0;=&#xa0;1.22; 95% CI:&#xa0;1.13-1.32), with the odds of ENT (OR&#xa0;=&#xa0;2.28; 95% CI:&#xa0;1.94-2.67), GI (OR&#xa0;=&#xa0;1.60; 95% CI:&#xa0;1.04-2.44), psychiatric/mood (OR&#xa0;=&#xa0;1.58; 95% CI:&#xa0;1.37-1.82), neurological (OR&#xa0;=&#xa0;1.30; 95% CI:&#xa0;1.03-1.63), dermatological (OR&#xa0;=&#xa0;1.29; 95% CI:&#xa0;1.05-1.58), and other (OR&#xa0;=&#xa0;1.36; 95% CI:&#xa0;1.25-1.49) disorders significantly higher among females and the odds of endocrine (OR&#xa0;=&#xa0;0.75; 95% CI:&#xa0;0.69-0.81) and renal disorders (OR&#xa0;=&#xa0;0.74; 95% CI:&#xa0;0.64-0.86) significantly higher among males.<br><br>CONCLUSIONS: Sex-disaggregated differences for COVID-19 sequelae and long COVID syndrome were observed. Few COVID-19 studies report sex-disaggregated data, underscoring the need for further sex-based research/reporting of COVID-19 disease.}, }
@article {pmid35736349, year = {2022}, author = {da Silveira Gorman, R and Syed, IU}, title = {Connecting the Dots in Emerging Mast Cell Research: Do Factors Affecting Mast Cell Activation Provide a Missing Link between Adverse COVID-19 Outcomes and the Social Determinants of Health?.}, journal = {Medical sciences (Basel, Switzerland)}, volume = {10}, number = {2}, pages = {}, pmid = {35736349}, issn = {2076-3271}, mesh = {*COVID-19/complications ; Humans ; Mast Cells ; Pandemics ; Social Determinants of Health ; Post-Acute COVID-19 Syndrome ; }, abstract = {Evidence continues to emerge that the social determinants of health play a role in adverse outcomes related to COVID-19, including increased morbidity and mortality, increased risk of long COVID, and vaccine adverse effects. Therefore, a more nuanced understanding of the biochemical and cellular pathways of illnesses commonly associated with adverse social determinants of health is urgently needed. We contend that a commitment to understanding adverse outcomes in historically marginalized communities will increase community-level confidence in public health measures. Here, we synthesize emerging literature on mast cell disease, and the role of mast cells in chronic illness, alongside emerging research on mechanisms of COVID illness and vaccines. We propose that a focus on aberrant and/or hyperactive mast cell behavior associated with chronic underlying health conditions can elucidate adverse COVID-related outcomes and contribute to the pandemic recovery. Standards of care for mast cell activation syndrome (MCAS), as well as clinical reviews, experimental research, and case reports, suggest that effective and cost-efficient remedies are available, including antihistamines, vitamin C, and quercetin, among others. Primary care physicians, specialists, and public health workers should consider new and emerging evidence from the biomedical literature in tackling COVID-19. Specialists and researchers note that MCAS is likely grossly under-diagnosed; therefore, public health agencies and policy makers should urgently attend to community-based experiences of adverse COVID outcomes. It is essential that we extract and examine experiential evidence of marginalized communities from the broader political-ideological discourse.}, }
@article {pmid35739136, year = {2022}, author = {Lopez-Leon, S and Wegman-Ostrosky, T and Ayuzo Del Valle, NC and Perelman, C and Sepulveda, R and Rebolledo, PA and Cuapio, A and Villapol, S}, title = {Long-COVID in children and adolescents: a systematic review and meta-analyses.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {9950}, pmid = {35739136}, issn = {2045-2322}, mesh = {Adolescent ; *Ageusia ; *COVID-19/complications/epidemiology ; Child ; Child, Preschool ; Humans ; Infant ; Infant, Newborn ; Prevalence ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The objective of this systematic review and meta-analyses is to estimate the prevalence of long-COVID in children and adolescents and to present the full spectrum of symptoms present after acute COVID-19. We have used PubMed and Embase to identify observational studies published before February 10th, 2022 that included a minimum of 30 patients with ages ranging from 0 to 18 years that met the National Institute for Healthcare Excellence (NICE) definition of long-COVID, which consists of both ongoing (4 to 12 weeks) and post-COVID-19 (≥ 12 weeks) symptoms. Random-effects meta-analyses were performed using the MetaXL software to estimate the pooled prevalence with a 95% confidence interval (CI). Heterogeneity was assessed using I[2] statistics. The Preferred Reporting Items for Systematic Reviewers and Meta-analysis (PRISMA) reporting guideline was followed (registration PROSPERO CRD42021275408). The literature search yielded 8373 publications, of which 21 studies met the inclusion criteria, and a total of 80,071 children and adolescents were included. The prevalence of long-COVID was 25.24%, and the most prevalent clinical manifestations were mood symptoms (16.50%), fatigue (9.66%), and sleep disorders (8.42%). Children infected by SARS-CoV-2 had a higher risk of persistent dyspnea, anosmia/ageusia, and/or fever compared to controls. Limitations of the studies analyzed include lack of standardized definitions, recall, selection, misclassification, nonresponse and/or loss of follow-up, and a high level of heterogeneity.}, }
@article {pmid35740354, year = {2022}, author = {Chilosi, M and Doglioni, C and Ravaglia, C and Martignoni, G and Salvagno, GL and Pizzolo, G and Bronte, V and Poletti, V}, title = {Unbalanced IDO1/IDO2 Endothelial Expression and Skewed Keynurenine Pathway in the Pathogenesis of COVID-19 and Post-COVID-19 Pneumonia.}, journal = {Biomedicines}, volume = {10}, number = {6}, pages = {}, pmid = {35740354}, issn = {2227-9059}, abstract = {Despite intense investigation, the pathogenesis of COVID-19 and the newly defined long COVID-19 syndrome are not fully understood. Increasing evidence has been provided of metabolic alterations characterizing this group of disorders, with particular relevance of an activated tryptophan/kynurenine pathway as described in this review. Recent histological studies have documented that, in COVID-19 patients, indoleamine 2,3-dioxygenase (IDO) enzymes are differentially expressed in the pulmonary blood vessels, i.e., IDO1 prevails in early/mild pneumonia and in lung tissues from patients suffering from long COVID-19, whereas IDO2 is predominant in severe/fatal cases. We hypothesize that IDO1 is necessary for a correct control of the vascular tone of pulmonary vessels, and its deficiency in COVID-19 might be related to the syndrome's evolution toward vascular dysfunction. The complexity of this scenario is discussed in light of possible therapeutic manipulations of the tryptophan/kynurenine pathway in COVID-19 and post-acute COVID-19 syndromes.}, }
@article {pmid35745708, year = {2022}, author = {Ruggiero, V and Aquino, RP and Del Gaudio, P and Campiglia, P and Russo, P}, title = {Post-COVID Syndrome: The Research Progress in the Treatment of Pulmonary sequelae after COVID-19 Infection.}, journal = {Pharmaceutics}, volume = {14}, number = {6}, pages = {}, pmid = {35745708}, issn = {1999-4923}, abstract = {Post-COVID syndrome or long COVID is defined as the persistence of symptoms after confirmed SARS-CoV-2 infection, the pathogen responsible for coronavirus disease. The content herein presented reviews the reported long-term consequences and aftereffects of COVID-19 infection and the potential strategies to adopt for their management. Recent studies have shown that severe forms of COVID-19 can progress into acute respiratory distress syndrome (ARDS), a predisposing factor of pulmonary fibrosis that can irreversibly compromise respiratory function. Considering that the most serious complications are observed in the airways, the inhalation delivery of drugs directly to the lungs should be preferred, since it allows to lower the dose and systemic side effects. Although further studies are needed to optimize these techniques, recent studies have also shown the importance of in vitro models to recreate the SARS-CoV-2 infection and study its sequelae. The information reported suggests the necessity to develop new inhalation therapies in order to improve the quality of life of patients who suffer from this condition.}, }
@article {pmid35747600, year = {2022}, author = {Khoja, O and Silva Passadouro, B and Mulvey, M and Delis, I and Astill, S and Tan, AL and Sivan, M}, title = {Clinical Characteristics and Mechanisms of Musculoskeletal Pain in Long COVID.}, journal = {Journal of pain research}, volume = {15}, number = {}, pages = {1729-1748}, pmid = {35747600}, issn = {1178-7090}, abstract = {OBJECTIVE: Musculoskeletal (MSK) pain is being increasingly reported by patients as one of the most common persistent symptoms in post-COVID-19 syndrome or Long COVID. However, there is a lack of understanding of its prevalence, characteristics, and underlying pathophysiological mechanisms. The objective of this review is to identify and describe the features and characteristics of MSK pain in Long COVID patients.<br><br>METHODS: The narrative review involved a literature search of the following online databases: MEDLINE (OVID), EMBASE (OVID), CINAHL, PsyclNFO, and Web of Science (December 2019 to February 2022). We included observational studies that investigated the prevalence, characteristics, risk factors and mechanisms of MSK pain in Long COVID. After screening and reviewing the initial literature search results, a total of 35 studies were included in this review.<br><br>RESULTS: The overall reported prevalence of MSK pain in Long COVID ranged widely from 0.3% to 65.2%. The pain has been reported to be localized to a particular region or generalized and widespread. No consistent pattern of progression of MSK pain symptoms over time was identified. Female gender and higher BMI could be potential risk factors for Long COVID MSK pain, but no clear association has been found with age and ethnicity. Different pathophysiological mechanisms have been hypothesized to contribute to MSK pain in Long COVID including increased production of proinflammatory cytokines, immune cell hyperactivation, direct viral entry of neurological and MSK system cells, and psychological factors.<br><br>CONCLUSION: MSK pain is one of the most common symptoms in Long COVID. Most of the current literature on Long COVID focuses on reporting the prevalence of persistent MSK pain. Studies describing the pain characteristics are scarce. The precise mechanism of MSK pain in Long COVID is yet to be investigated. Future research must explore the characteristics, risk factors, natural progression, and underlying mechanisms of MSK pain in Long COVID.}, }
@article {pmid35752482, year = {2022}, author = {Ngeow, WC and Tang, L and Ho, JY and Tay, HW and Wong, RCW and Ahmad, MS and Marla, V and Sekar, K}, title = {The Provision of Dental Care to COVID-19 Survivors: A Concise Review.}, journal = {International dental journal}, volume = {72}, number = {4}, pages = {421-435}, pmid = {35752482}, issn = {1875-595X}, mesh = {*COVID-19/complications ; *Dental Care ; Humans ; SARS-CoV-2 ; Survivors ; Post-Acute COVID-19 Syndrome ; }, abstract = {AIMS: It has been reported that there are a certain percentage of COVID-19 patients who recover but suffer from devastating permanent organ damage or failure. Others suffer from long Covid syndrome, with prolonged symptoms that persist more than 12 weeks. However, there is scarcity of literature regarding the provision of dental treatment for these two groups of patients. This manuscript reviews the impact of multi-system involvement on the provision of dental care to these patients.<br><br>MATERIALS AND METHODS: A search of literature was done in PubMed-Medline and Scopus databases to review the available literature on COVID-19 impacts on pulmonary, cardiovascular, haematologic, renal, gastrointestinal, endocrine, and neurologic systems and respective management in dental clinical settings.<br><br>RESULTS: The literature search from PubMed-Medline and Scopus databases resulted in 74 salient articles that contributed to the concise review on COVID-19 effects on pulmonary, cardiovascular, haematologic, renal, gastrointestinal, endocrine, and neurologic systems and/or its respective dental management recommendations.<br><br>CONCLUSIONS: This concise review covers the management of post COVID-19 patients with pulmonary, cardiovascular, haematologic, renal, gastrointestinal, endocrine, or neurologic system complications.}, }
@article {pmid35753836, year = {2022}, author = {Pontali, E and Silva, DR and Marx, FM and Caminero, JA and Centis, R and D'Ambrosio, L and Garcia-Garcia, JM and Muhwa, JC and Tiberi, S and Migliori, GB}, title = {Breathing Back Better! A State of the Art on the Benefits of Functional Evaluation and Rehabilitation of Post-Tuberculosis and Post-COVID Lungs.}, journal = {Archivos de bronconeumologia}, volume = {58}, number = {11}, pages = {754-763}, pmid = {35753836}, issn = {1579-2129}, mesh = {Humans ; *COVID-19 ; *Tuberculosis ; Cost-Benefit Analysis ; Lung ; Post-Acute COVID-19 Syndrome ; }, abstract = {Currently, tuberculosis (TB) and COVID-19 account for substantial morbidity and mortality worldwide, not only during their acute phase, but also because of their sequelae. This scoping review aims to describe the specific aspects of post-TB and post-COVID (long-COVID-19) sequelae, and the implications for post-disease follow-up and rehabilitation. In particular, evidence on how to identify patients affected by sequelae is presented and discussed. A section of the review is dedicated to identifying patients eligible for pulmonary rehabilitation (PR), as not all patients with sequelae are eligible for PR. Components of PR are presented and discussed, as well as their effectiveness. Other essential components to implement comprehensive rehabilitation programmes such as counselling and health education of enrolled patients, evaluation of cost-effectiveness of PR and its impact on health systems as well as research priorities for the future are included in this scoping review.}, }
@article {pmid35763279, year = {2022}, author = {De Luca, P and Di Stadio, A and Colacurcio, V and Marra, P and Scarpa, A and Ricciardiello, F and Cassandro, C and Camaioni, A and Cassandro, E}, title = {Long COVID, audiovestibular symptoms and persistent chemosensory dysfunction: a systematic review of the current evidence.}, journal = {Acta otorhinolaryngologica Italica : organo ufficiale della Societa italiana di otorinolaringologia e chirurgia cervico-facciale}, volume = {42}, number = {Suppl. 1}, pages = {S87-S93}, pmid = {35763279}, issn = {1827-675X}, mesh = {*COVID-19/complications ; Hearing Disorders/diagnosis/virology ; Humans ; *Olfaction Disorders/diagnosis/virology ; SARS-CoV-2 ; *Taste Disorders/diagnosis/virology ; Vertigo/diagnosis/virology ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: The persistence of auditory, vestibular, olfactory, and gustatory dysfunction for an extended time after COVID-19 has been documented, which represents an emerging challenge of which ENT specialists must be aware. This systematic review aims to evaluate the prevalence of persistent audiovestibolar and olfactory/gustatory symptoms in patients with "long-COVID".<br><br>METHODS: The literature was systematically reviewed according to PRISMA guidelines; PubMed, Scopus and Google Scholar were screened by searching articles on audiovestibular symptoms and olfactory/gustatory dysfunction after SARS-CoV-2 infection. The keywords used were hearing loss, tinnitus, vertigo, smell disorders, parosmia, anosmia, hyposmia, dysgeusia combined with COVID-19 or SARS-CoV-2.<br><br>RESULTS: 1100 articles were identified. After removal of duplicates (382), 702 articles were excluded, and 16 were included in the systematic review. All articles included identified an association between SARS-CoV-2 infection and persistent hearing or chemosensory impairment. The studies were published over a period of 2 years, between 2019 and 2021.<br><br>CONCLUSIONS: The likelihood of patients with persistent audiovestibular symptoms related to COVID-19 was different among the articles; however, olfactory and gustatory disturbances were more consistently reported. Studies with longer follow-up are required to fully evaluate the long-term impact of these conditions.}, }
@article {pmid35768406, year = {2022}, author = {Hawke, LD and Nguyen, ATP and Ski, CF and Thompson, DR and Ma, C and Castle, D}, title = {Interventions for mental health, cognition, and psychological wellbeing in long COVID: a systematic review of registered trials.}, journal = {Psychological medicine}, volume = {52}, number = {13}, pages = {2426-2440}, pmid = {35768406}, issn = {1469-8978}, support = {WI1-179893//CIHR/Canada ; }, mesh = {Humans ; *Mental Health ; *COVID-19 ; Bias ; Post-Acute COVID-19 Syndrome ; Cognition ; }, abstract = {BACKGROUND: Among patients diagnosed with COVID-19, a substantial proportion are experiencing ongoing symptoms for months after infection, known as 'long COVID'. Long COVID is associated with a wide range of physical and neuropsychological symptoms, including impacts on mental health, cognition, and psychological wellbeing. However, intervention research is only beginning to emerge. This systematic review synthesizes currently registered trials examining interventions for mental health, cognition, and psychological wellbeing in patients with long COVID.<br><br>METHODS: Standard systematic review guidelines were followed. Trials registered in two large trial registries in 2020 to May 2022 were reviewed. Included studies were narratively synthesized by type of intervention and a risk-of-bias assessment was conducted.<br><br>RESULTS: Forty-two registered trials were included, with a total target sample size of 5814 participants. These include 11 psychological interventions, five pharmacological and other medical interventions, and five evaluating herbal, nutritional, or natural supplement interventions. An additional nine trials are examining cognitive and neurorehabilitation interventions and 12 are examining physiotherapy or physical rehabilitation. Most trials are randomized, but many are feasibility trials; trials are evaluating a wide spectrum of outcomes.<br><br>CONCLUSIONS: While there is a newly emerging body of research testing interventions for mental health, cognition, and psychological wellbeing in long COVID, the breadth and scope of the research remains limited. It is urgently incumbent on researchers to expand upon the intervention research currently under way, in order to generate high-quality evidence on a wide range of candidate interventions for diverse long COVID patient populations.}, }
@article {pmid35780756, year = {2022}, author = {Bertuccelli, M and Ciringione, L and Rubega, M and Bisiacchi, P and Masiero, S and Del Felice, A}, title = {Cognitive impairment in people with previous COVID-19 infection: A scoping review.}, journal = {Cortex; a journal devoted to the study of the nervous system and behavior}, volume = {154}, number = {}, pages = {212-230}, pmid = {35780756}, issn = {1973-8102}, mesh = {*COVID-19 ; *Cognitive Dysfunction ; Humans ; Pandemics ; SARS-CoV-2 ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 is a worldwide public health issue. Almost 2 years into the pandemic, the persistence of symptoms after the acute phase is a well-recognized phenomenon. We conducted a scoping review to map cognitive domain impairments, their frequency, and associated psycho-affective disorders in people with a previous COVID-19 infection. We searched PubMed/MEDLINE, Scopus, and PsycInfo to identify relevant reports published between December 1, 2019 and February 21, 2022. We followed the PRISMA (Preferred-Reporting-Items-for-Systematic-Reviews-and-Meta-Analyses) extension for scoping review guidelines. Three independent reviewers selected and charted 25 records out of 922. Memory, attention, and executive functions appeared to be the most affected domains. Delayed recall and learning were the most impaired domains of memory. Among the executive functions, abstraction, inhibition, set shifting, and sustained and selective attention were most commonly impaired. Language and visuo-spatial abilities were rarely affected, although this finding might be biased by the scarcity of reports. Neurological and respiratory conditions were often reported in association with cognitive deficits. Results on psycho-affective conditions were inconclusive due to the low frequency of reported data. Admission to an intensive care unit is not related to cognitive deficits. This review highlighted a potential effect of a previous post-COVID-19 infection on a pattern of memory, attention, and executive functions impairments. These findings need to be confirmed on larger cohorts with comprehensive neuropsychological batteries and correlated to neurophysiological and neurobiological substrates.}, }
@article {pmid35785029, year = {2022}, author = {Szukiewicz, D and Wojdasiewicz, P and Watroba, M and Szewczyk, G}, title = {Mast Cell Activation Syndrome in COVID-19 and Female Reproductive Function: Theoretical Background vs. Accumulating Clinical Evidence.}, journal = {Journal of immunology research}, volume = {2022}, number = {}, pages = {9534163}, pmid = {35785029}, issn = {2314-7156}, mesh = {*COVID-19/complications ; Female ; Humans ; *Mast Cell Activation Syndrome ; *Mastocytosis ; Pregnancy ; *Pregnancy Complications, Infectious ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Coronavirus disease 2019 (COVID-19), a pandemic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, can affect almost all systems and organs of the human body, including those responsible for reproductive function in women. The multisystem inflammatory response in COVID-19 shows many analogies with mast cell activation syndrome (MCAS), and MCAS may be an important component in the course of COVID-19. Of note, the female sex hormones estradiol (E2) and progesterone (P4) significantly influence mast cell (MC) behavior. This review presents the importance of MCs and the mediators from their granules in the female reproductive system, including pregnancy, and discusses the mechanism of potential disorders related to MCAS. Then, the available data on COVID-19 in the context of hormonal disorders, the course of endometriosis, female fertility, and the course of pregnancy were compiled to verify intuitively predicted threats. Surprisingly, although COVID-19 hyperinflammation and post-COVID-19 illness may be rooted in MCAS, the available clinical data do not provide grounds for treating this mechanism as significantly increasing the risk of abnormal female reproductive function, including pregnancy. Further studies in the context of post COVID-19 condition (long COVID), where inflammation and a procoagulative state resemble many aspects of MCAS, are needed.}, }
@article {pmid35785594, year = {2022}, author = {Pinzon, RT and Wijaya, VO and Jody, AA and Nunsio, PN and Buana, RB}, title = {Persistent neurological manifestations in long COVID-19 syndrome: A systematic review and meta-analysis.}, journal = {Journal of infection and public health}, volume = {15}, number = {8}, pages = {856-869}, pmid = {35785594}, issn = {1876-035X}, mesh = {*COVID-19/complications ; *Coronavirus Infections/epidemiology ; Humans ; Pandemics ; *Pneumonia, Viral/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Several studies have reported prolonged symptoms especially neurological symptoms following acute infection in patients with COVID-19, known as long COVID-19. There are only few studies investigating this population and relatively less known, including nervous system involvement. A systematic review and meta-analysis of these studies are required to understanding the prevalence of persistent neurological manifestations after COVID-19.<br><br>OBJECTIVE: To conduct a systematic review and meta-analysis on the persistent neurological manifestations in COVID-19 survivors.<br><br>METHODS: Authors conducted a literature search through PubMed and MedRxiv from January 1st, 2020 to October 2021 according to PRISMA guideline. Furthermore, the authors added additional sources by reviewing related references. Studies presenting the neurologic features of long COVID-19 patients in their data were included. Case reports and case series also included in this review. The quality of the studies was assessed based on the Oxford Centre for Evidence-Based Medicine guidelines. Selected studies were included in the meta-analysis of proportion and heterogeneity test.<br><br>FINDINGS: From 128 identified studies, 36 were eligible, with 9944 participants included. Most of the included studies had mean duration of follow-up after COVID-19 onset of less than 6 months. Fatigue was the most common (52.8%, 95%CI 19.9 - 84.4) symptoms of long COVID, followed by cognitive disorder (35.4%, 95%CI 2.1 - 81.7); paresthesia (33.3%, 95%CI 2.7 - 76.6); sleep disorder (32.9%, 95%CI 6.5 - 67.4); musculoskeletal pain (27.8%, 95%CI 12.7 - 46); and dizziness (26.4%, 95%CI 4.6 - 57.9).<br><br>CONCLUSION: Neurological manifestations are prevalent and persisting in patients with long COVID. The duration of the symptoms are vary among literatures. However, the frequency are mostly observed during the first six months after the illness onset.}, }
@article {pmid35787539, year = {2022}, author = {Poonja, S and Chaudhuri, KR and Miyasaki, JM}, title = {Movement disorders in COVID-19 times: impact on care in movement disorders and Parkinson disease.}, journal = {Current opinion in neurology}, volume = {35}, number = {4}, pages = {494-501}, pmid = {35787539}, issn = {1473-6551}, mesh = {*COVID-19/complications/epidemiology ; Humans ; *Movement Disorders/epidemiology/therapy ; Pandemics ; *Parkinson Disease/epidemiology/therapy ; SARS-CoV-2 ; *Telemedicine ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE OF REVIEW: The purpose of this review is to outline the impact of the COVID-19 pandemic on movement disorder holistic care, particularly in the care of people with Parkinson disease (PWP).<br><br>RECENT FINDINGS: As the pandemic unfolds, a flurry of literature was published regarding the impact of COVID-19 on people with Parkinson disease including the direct impact of infection, availability of ambulatory care, loss of community-based team care, and acceptability of telemedicine.<br><br>SUMMARY: COVID-19 has impacted the care of PWP in numerous ways. Recognizing infection in PWP poses challenges. Specific long-term complications, including emerging reports of long COVID syndrome is a growing concern. Caregivers and PWP have also been impacted by COVID-19 social isolation restrictions, with radical changes to the structure of social networks and support systems globally. In a matter of weeks, the global community saw an incredible uptake in telemedicine, which brought benefits and pitfalls. As PWP adapted to virtual platforms and the changing architecture of care delivery, the pandemic amplified many preexisting inequities amongst populations and countries, exposing a new 'digital divide'.}, }
@article {pmid35787541, year = {2022}, author = {Pai, N and Vella, SL}, title = {The physical and mental health consequences of social isolation and loneliness in the context of COVID-19.}, journal = {Current opinion in psychiatry}, volume = {35}, number = {5}, pages = {305-310}, pmid = {35787541}, issn = {1473-6578}, mesh = {*COVID-19/complications ; Humans ; *Loneliness/psychology ; Mental Health ; Pandemics ; Social Isolation/psychology ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE OF REVIEW: Social isolation and loneliness are known contributors to all-cause mortality as well as a range of physical and mental health conditions. Therefore, this article reviews current literature pertaining to the effects of social isolation and loneliness on physical and mental health during the current COVID-19 pandemic.<br><br>RECENT FINDINGS: Social isolation and loneliness contribute to a myriad of physical and mental health conditions. Specifically social isolation and loneliness contribute to the development of cardiovascular disease, diabetes mellitus, and cancer. However, most research indicated that poor lifestyle factors explained most of the association. Social isolation and loneliness are also associated with cognitive problems including dementia, immune system problems, and mental health conditions. Further social isolation and loneliness also spur behavioral issues that significantly affect physical and mental health.<br><br>SUMMARY: Evidence suggests that social isolation and loneliness have significant consequences on the physical and mental health of the individual and that the move toward ending all protections against COVID-19 has significant implications for the vulnerable. Further the similarities between the effects of social isolation and loneliness are compared to some of the conditions evident in long-COVID.}, }
@article {pmid35788744, year = {2022}, author = {Muñoz-Jurado, A and Escribano, BM and Agüera, E and Caballero-Villarraso, J and Galván, A and Túnez, I}, title = {SARS-CoV-2 infection in multiple sclerosis patients: interaction with treatments, adjuvant therapies, and vaccines against COVID-19.}, journal = {Journal of neurology}, volume = {269}, number = {9}, pages = {4581-4603}, pmid = {35788744}, issn = {1432-1459}, mesh = {Antibodies, Viral ; *COVID-19/complications ; COVID-19 Vaccines/adverse effects ; Humans ; *Multiple Sclerosis/complications/therapy ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The SARS-CoV-2 pandemic has raised particular concern for people with Multiple Sclerosis, as these people are believed to be at increased risk of infection, especially those being treated with disease-modifying therapies. Therefore, the objective of this review was to describe how COVID-19 affects people who suffer from Multiple Sclerosis, evaluating the risk they have of suffering an infection by this virus, according to the therapy to which they are subjected as well as the immune response of these patients both to infection and vaccines and the neurological consequences that the virus can have in the long term. The results regarding the increased risk of infection due to treatment are contradictory. B-cell depletion therapies may cause patients to have a lower probability of generating a detectable neutralizing antibody titer. However, more studies are needed to help understand how this virus works, paying special attention to long COVID and the neurological symptoms that it causes.}, }
@article {pmid35797144, year = {2022}, author = {Caorsi, R and Civino, A and Ravelli, A}, title = {Complications of severe acute respiratory syndrome coronavirus 2 infection in children.}, journal = {Current opinion in rheumatology}, volume = {34}, number = {5}, pages = {267-273}, doi = {10.1097/BOR.0000000000000892}, pmid = {35797144}, issn = {1531-6963}, mesh = {Adolescent ; *COVID-19/complications ; Child ; Humans ; Pandemics ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE OF REVIEW: Although during the initial stages of COVID-19 pandemic, the pediatric population seemed to be less affected, a number of SARS-CoV-2-related manifestations emerged over time, the principal of which is the multisystem inflammatory syndrome in children (MIS-C). Here we provide an update on the main pediatric disorders associated with SARS-CoV-2 infection.<br><br>RECENT FINDINGS: MIS-C is novel postinfectious manifestation with clinical features similar to Kawasaki disease and characterized by intense systemic inflammation affecting multiple organs. Many children required intensive care therapy because of circulatory shock, usually of myocardial origin. Appropriate treatment with immunomodulatory therapies led to favorable outcomes in most patients, with recovery of overall health and cardiac dysfunction. In addition to MIS-C, a variety of other complications of COVID-19 in children have been described, including thrombotic events, neurologic manifestations, and chilblain-like lesions. There is still uncertainty about the true prevalence of long COVID in children and its distinction from pandemic-related complaints.<br><br>SUMMARY: The experience gained so far with MIS-C and the other SARS-CoV-2-related complications in children and adolescents will facilitate accurate diagnosis and appropriate treatment. Further studies are needed to elucidate the pathophysiology of MIS-C and to determine the real impact of long-COVID in the pediatric age group.}, }
@article {pmid35805406, year = {2022}, author = {Houben, S and Bonnechère, B}, title = {The Impact of COVID-19 Infection on Cognitive Function and the Implication for Rehabilitation: A Systematic Review and Meta-Analysis.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {13}, pages = {}, pmid = {35805406}, issn = {1660-4601}, mesh = {*COVID-19 ; Cognition ; Humans ; }, abstract = {There is mounting evidence that patients with severe COVID-19 disease may have symptoms that continue beyond the acute phase, extending into the early chronic phase. This prolonged COVID-19 pathology is often referred to as 'Long COVID'. Simultaneously, case investigations have shown that COVID-19 individuals might have a variety of neurological problems. The accurate and accessible assessment of cognitive function in patients post-COVID-19 infection is thus of increasingly high importance for both public and individual health. Little is known about the influence of COVID-19 on the general cognitive levels but more importantly, at sub-functions level. Therefore, we first aim to summarize the current level of evidence supporting the negative impact of COVID-19 infection on cognitive functions. Twenty-seven studies were included in the systematic review representing a total of 94,103 participants (90,317 COVID-19 patients and 3786 healthy controls). We then performed a meta-analysis summarizing the results of five studies (959 participants, 513 patients) to quantify the impact of COVID-19 on cognitive functions. The overall effect, expressed in standardized mean differences, is -0.41 [95%CI -0.55; -0.27]. To prevent disability, we finally discuss the different approaches available in rehabilitation to help these patients and avoid long-term complications.}, }
@article {pmid35808102, year = {2022}, author = {Wu, Y and Rakotoarisoa, M and Angelov, B and Deng, Y and Angelova, A}, title = {Self-Assembled Nanoscale Materials for Neuronal Regeneration: A Focus on BDNF Protein and Nucleic Acid Biotherapeutic Delivery.}, journal = {Nanomaterials (Basel, Switzerland)}, volume = {12}, number = {13}, pages = {}, pmid = {35808102}, issn = {2079-4991}, support = {CZ.02.1.01/0.0/0.0/15_003/0000447 "Structural Dynamics of Biomolecular Systems" (ELIBIO)//European Regional Development Fund/ ; CZ.02.1.01/0.0/0.0/16_019/0000789 "Advanced research using high-intensity laser produced photons and particles"//European Regional Development Fund/ ; 3+3 program, No. 204, item 27 from 25.03.2020//JINR, Dubna/ ; WIUCASQD2019005//Wenzhou Institute, University of Chinese Academy of Sciences/ ; 31670841//National Natural Science Foundation China/ ; ANR-11-IDEX-0003-02 &quot;IDI 2017&quot; IDEX Paris-Saclay//Agence Nationale de la Recherche France/ ; }, abstract = {Enabling challenging applications of nanomedicine and precision medicine in the treatment of neurodegenerative disorders requires deeper investigations of nanocarrier-mediated biomolecular delivery for neuronal targeting and recovery. The successful use of macromolecular biotherapeutics (recombinant growth factors, antibodies, enzymes, synthetic peptides, cell-penetrating peptide-drug conjugates, and RNAi sequences) in clinical developments for neuronal regeneration should benefit from the recent strategies for enhancement of their bioavailability. We highlight the advances in the development of nanoscale materials for drug delivery in neurodegenerative disorders. The emphasis is placed on nanoformulations for the delivery of brain-derived neurotrophic factor (BDNF) using different types of lipidic nanocarriers (liposomes, liquid crystalline or solid lipid nanoparticles) and polymer-based scaffolds, nanofibers and hydrogels. Self-assembled soft-matter nanoscale materials show favorable neuroprotective characteristics, safety, and efficacy profiles in drug delivery to the central and peripheral nervous systems. The advances summarized here indicate that neuroprotective biomolecule-loaded nanoparticles and injectable hydrogels can improve neuronal survival and reduce tissue injury. Certain recently reported neuronal dysfunctions in long-COVID-19 survivors represent early manifestations of neurodegenerative pathologies. Therefore, BDNF delivery systems may also help in prospective studies on recovery from long-term COVID-19 neurological complications and be considered as promising systems for personalized treatment of neuronal dysfunctions and prevention or retarding of neurodegenerative disorders.}, }
@article {pmid35811273, year = {2022}, author = {Seghatchian, J and Pereira, P and Lanza, F}, title = {Spotlights on the latest opinions on identification, prevention, and management of newer CoV-2 variants: A roundup appraisal on innovative ideas and designer vaccines for Omicron.}, journal = {Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis}, volume = {61}, number = {6}, pages = {103499}, pmid = {35811273}, issn = {1473-0502}, mesh = {Humans ; *COVID-19/prevention &amp; control ; Communicable Disease Control ; SARS-CoV-2 ; *Vaccines ; Antibodies, Monoclonal ; Post-Acute COVID-19 Syndrome ; }, abstract = {Although mass vaccination combined with some other preventative strategies and lockdown was associated with some early signs that COVID-19 infection might be fading away, the over 35 sites mutated new South African variant, "Omicron", emerged almost globally. Certain predisposed hosts may develop severe inflammatory thrombotic or mild long-Covid conditions due to this variant, which depletes T-cells, neutralizes antibodies circulating in the body, and coincidentally induces hypercoagulability. The surge of Omicron combined with Delta variants may confer unresponsiveness to the currently available vaccines even when the second dose is given up to 90 days. A drop in the antibody levels by 30 % has been identified in omicron-infected individuals, and one in five people is resistant to antibody treatment. This poses major concerns in the transmissibility rate of this new variant, even in a heavy mass vaccinated environment. This heavily mutated Omicron with other spike sites facilitates viral entry into the cells through conformational changes, irrespective of circulating neutralising antibody. Based on this consideration, we believe that speeding up mixed-matched vaccines with higher T-cell stimulation ability may improve the current situation. Moreover, large orders for antiviral drugs and monoclonal antibodies that could tackle Omicron combined with other variants may be valuable. The use of free polyclonal antibody donations and, hopefully, T-cell immunotherapy, may represent further breakthrough therapeutic interventions. However, Omicron infection is relatively milder than the ongoing Delta variant but is extremely contagious, and therefore the development of novel interventions is highly demanding.}, }
@article {pmid35812094, year = {2022}, author = {Jacob, S and Kapadia, R and Soule, T and Luo, H and Schellenberg, KL and Douville, RN and Pfeffer, G}, title = {Neuromuscular Complications of SARS-CoV-2 and Other Viral Infections.}, journal = {Frontiers in neurology}, volume = {13}, number = {}, pages = {914411}, pmid = {35812094}, issn = {1664-2295}, abstract = {In this article we review complications to the peripheral nervous system that occur as a consequence of viral infections, with a special focus on complications of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We discuss neuromuscular complications in three broad categories; the direct consequences of viral infection, autoimmune neuromuscular disorders provoked by viral infections, and chronic neurodegenerative conditions which have been associated with viral infections. We also include discussion of neuromuscular disorders that are treated by immunomodulatory therapies, and how this affects patient susceptibility in the current context of the coronavirus disease 2019 (COVID-19) pandemic. COVID-19 is associated with direct consequences to the peripheral nervous system via presumed direct viral injury (dysgeusia/anosmia, myalgias/rhabdomyolysis, and potentially mononeuritis multiplex) and autoimmunity (Guillain Barré syndrome and variants). It has important implications for people receiving immunomodulatory therapies who may be at greater risk of severe outcomes from COVID-19. Thus far, chronic post-COVID syndromes (a.k.a: long COVID) also include possible involvement of the neuromuscular system. Whether we may observe neuromuscular degenerative conditions in the longer term will be an important question to monitor in future studies.}, }
@article {pmid35812220, year = {2022}, author = {Diniz, FC and Hipkiss, AR and Ferreira, GC}, title = {The Potential Use of Carnosine in Diabetes and Other Afflictions Reported in Long COVID Patients.}, journal = {Frontiers in neuroscience}, volume = {16}, number = {}, pages = {898735}, pmid = {35812220}, issn = {1662-4548}, abstract = {Carnosine is a dipeptide expressed in both the central nervous system and periphery. Several biological functions have been attributed to carnosine, including as an anti-inflammatory and antioxidant agent, and as a modulator of mitochondrial metabolism. Some of these mechanisms have been implicated in the pathophysiology of coronavirus disease-2019 (COVID-19). COVID-19 is caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). The clinical manifestation and recovery time for COVID-19 are variable. Some patients are severely affected by SARS-CoV-2 infection and may experience respiratory failure, thromboembolic disease, neurological symptoms, kidney damage, acute pancreatitis, and even death. COVID-19 patients with comorbidities, including diabetes, are at higher risk of death. Mechanisms underlying the dysfunction of the afflicted organs in COVID-19 patients have been discussed, the most common being the so-called cytokine storm. Given the biological effects attributed to carnosine, adjuvant therapy with this dipeptide could be considered as supportive treatment in patients with either COVID-19 or long COVID.}, }
@article {pmid35832078, year = {2022}, author = {Satta, S and Shahabipour, F and Gao, W and Lentz, SR and Perlman, S and Ashammakhi, N and Hsiai, T}, title = {Engineering viral genomics and nano-liposomes in microfluidic platforms for patient-specific analysis of SARS-CoV-2 variants.}, journal = {Theranostics}, volume = {12}, number = {10}, pages = {4779-4790}, pmid = {35832078}, issn = {1838-7640}, support = {UG3 TR003148/TR/NCATS NIH HHS/United States ; R01 HL129727/HL/NHLBI NIH HHS/United States ; R01 AI129269/AI/NIAID NIH HHS/United States ; P01 AI060699/AI/NIAID NIH HHS/United States ; R01 HL111437/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Neutralizing ; Antibodies, Viral ; *COVID-19/complications/diagnosis ; *Coronavirus Infections/prevention &amp; control ; Genomics ; Humans ; Liposomes ; Microfluidics ; Mutation ; Pandemics/prevention &amp; control ; Peptidyl-Dipeptidase A/metabolism ; *Pneumonia, Viral ; SARS-CoV-2/genetics ; Spike Glycoprotein, Coronavirus ; Post-Acute COVID-19 Syndrome ; }, abstract = {New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are continuing to spread globally, contributing to the persistence of the COVID-19 pandemic. Increasing resources have been focused on developing vaccines and therapeutics that target the Spike glycoprotein of SARS-CoV-2. Recent advances in microfluidics have the potential to recapitulate viral infection in the organ-specific platforms, known as organ-on-a-chip (OoC), in which binding of SARS-CoV-2 Spike protein to the angiotensin-converting enzyme 2 (ACE2) of the host cells occurs. As the COVID-19 pandemic lingers, there remains an unmet need to screen emerging mutations, to predict viral transmissibility and pathogenicity, and to assess the strength of neutralizing antibodies following vaccination or reinfection. Conventional detection of SARS-CoV-2 variants relies on two-dimensional (2-D) cell culture methods, whereas simulating the micro-environment requires three-dimensional (3-D) systems. To this end, analyzing SARS-CoV-2-mediated pathogenicity via microfluidic platforms minimizes the experimental cost, duration, and optimization needed for animal studies, and obviates the ethical concerns associated with the use of primates. In this context, this review highlights the state-of-the-art strategy to engineer the nano-liposomes that can be conjugated with SARS-CoV-2 Spike mutations or genomic sequences in the microfluidic platforms; thereby, allowing for screening the rising SARS-CoV-2 variants and predicting COVID-19-associated coagulation. Furthermore, introducing viral genomics to the patient-specific blood accelerates the discovery of therapeutic targets in the face of evolving viral variants, including B1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), c.37 (Lambda), and B.1.1.529 (Omicron). Thus, engineering nano-liposomes to encapsulate SARS-CoV-2 viral genomic sequences enables rapid detection of SARS-CoV-2 variants in the long COVID-19 era.}, }
@article {pmid35843340, year = {2023}, author = {Shih, AR and Misdraji, J}, title = {COVID-19: gastrointestinal and hepatobiliary manifestations.}, journal = {Human pathology}, volume = {132}, number = {}, pages = {39-55}, pmid = {35843340}, issn = {1532-8392}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; *Gastrointestinal Diseases/diagnosis/etiology ; Post-Acute COVID-19 Syndrome ; Gastrointestinal Tract ; }, abstract = {SARS-CoV-2 is the viral agent of COVID-19, a pandemic that surfaced in 2019. Although predominantly a respiratory ailment, patients with COVID-19 can have gastrointestinal (GI) and hepatobiliary manifestations. These manifestations are often mild and transient, but they can be severe and consequential. In the GI tract, ischemic enterocolitis is the most common and significant consequence of COVID-19. In the liver, the reported pathologic findings may often be related to consequences of severe systemic viral infection, but reports of hepatitis presumed to be due to SARS-CoV-2 suggest that direct viral infection of the liver may be a rare complication of COVID-19. In both the GI tract and liver, lingering symptoms of GI or hepatic injury after resolution of pulmonary infection may be part of the evolving spectrum of long COVID.}, }
@article {pmid35848380, year = {2022}, author = {Shanthanna, H and Nelson, AM and Kissoon, N and Narouze, S}, title = {The COVID-19 pandemic and its consequences for chronic pain: a narrative review.}, journal = {Anaesthesia}, volume = {77}, number = {9}, pages = {1039-1050}, pmid = {35848380}, issn = {1365-2044}, mesh = {*COVID-19/complications ; COVID-19 Vaccines ; *Chronic Pain/etiology/therapy ; Headache ; Humans ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The COVID-19 pandemic transformed everyday life, but the implications were most impactful for vulnerable populations, including patients with chronic pain. Moreover, persistent pain is increasingly recognised as a key manifestation of long COVID. This narrative review explores the consequences of the COVID-19 pandemic for chronic pain. Publications were identified related to the COVID-19 pandemic influence on the burden of chronic pain, development of new-onset pain because of long COVID with proposed mechanisms and COVID-19 vaccines and pain interventions. Broadly, mechanisms underlying pain due to SARS-CoV-2 infection could be caused by 'systemic inflammatory-immune mechanisms', 'direct neuropathic mechanisms' or 'secondary mechanisms due to the viral infection or treatment'. Existing chronic pain populations were variably impacted and social determinants of health appeared to influence the degree of effect. SARS-CoV-2 infection increased the absolute numbers of patients with pain and headache. In the acute phase, headache as a presenting symptom predicted a milder course. New-onset chronic pain was reportedly common and likely involves multiple mechanisms; however, its prevalence decreases over time and symptoms appear to fluctuate. Patients requiring intensive support were particularly susceptible to long COVID symptoms. Some evidence suggests steroid exposure (often used for pain interventions) may affect vaccine efficacy, but there is no evidence of clinical repercussions to date. Although existing chronic pain management could help with symptomatic relief, there is a need to advance research focusing on mechanism-based treatments within the domain of multidisciplinary care.}, }
@article {pmid35852546, year = {2022}, author = {Lehmann, HC}, title = {[Neuromuscular manifestations in long-COVID syndrome].}, journal = {Der Nervenarzt}, volume = {93}, number = {8}, pages = {761-768}, pmid = {35852546}, issn = {1433-0407}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The term long-COVID syndrome encompasses symptoms that occur after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, persisting over a period of several weeks, and which cannot be explained by another diagnosis. Long-COVID is considered to be a multiorgan condition. In this review article, the data regarding neuromuscular manifestations of long-COVID syndrome are summarized and evaluated based on criteria, such as effect size, plausibility, coherence, and experimental evidence. So far, myalgia and autonomic dysfunction (especially postural tachycardia syndrome) have been postulated as neuromuscular symptoms of long-COVID; however, the evidence to date is limited. In addition to very heterogeneous methodologies and different definitions of long-COVID in the clinical studies, conclusive experimental data supporting the described symptoms as a specific long-term consequence of COVID-19 are lacking.}, }
@article {pmid35853464, year = {2022}, author = {Bechmann, N and Maccio, U and Kotb, R and Dweik, RA and Cherfane, M and Moch, H and Bornstein, SR and Varga, Z}, title = {COVID-19 Infections in Gonads: Consequences on Fertility?.}, journal = {Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme}, volume = {54}, number = {8}, pages = {549-555}, pmid = {35853464}, issn = {1439-4286}, mesh = {Aged ; *COVID-19/complications ; COVID-19 Vaccines ; Female ; Fertility ; Gonads ; Humans ; Hypothalamo-Hypophyseal System ; Male ; Pandemics ; Pituitary-Adrenal System ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19 may influence human fertility and sexuality in several ways. Different cell types in gonads show a constitutive expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine subtype 2 (TMPRSS2), which provide potential entry pathways for SARS-CoV-2. In addition to the biological effects of a COVID-19 infection on the gonads, the impact of the ongoing COVID-19 pandemic on mental health issues and sexual behavior may affect reproduction. This review summarizes the current knowledge on the influence of COVID-19 on the gonads and discusses possible consequences on human fertility. In this context, the close interaction between the hypothalamic-pituitary-adrenal axis and the hypothalamic-pituitary-gonadal axis in response to COVID-19-related stress is discussed. Some women noticed changes in their menstrual cycle during the COVID-19 pandemic, which could be due to psychological stress, for example. In addition, occasional cases of reduced oocyte quality and ovarian function are described after COVID-19 infection. In men, COVID-19 may cause a short-term decrease in fertility by damaging testicular tissue and/or impairing spermatogenesis. Moreover, decreased ratio testosterone/LH and FSH/LH in COVID-19 compared to aged-matched healthy men has been reported. Available data do not suggest any effect of the available SARS-CoV-2 vaccines on fertility. The effects of long COVID on human fertility have been reported and include cases with premature ovarian failure and oligomenorrhoea in women and erectile dysfunction in men. Despite the increasing knowledge about the effects of COVID-19 infections on human gonads and fertility, the long-term consequences of the COVID-19 pandemic cannot yet be assessed in this context.}, }
@article {pmid35853576, year = {2022}, author = {Ormiston, CK and Świątkiewicz, I and Taub, PR}, title = {Postural orthostatic tachycardia syndrome as a sequela of COVID-19.}, journal = {Heart rhythm}, volume = {19}, number = {11}, pages = {1880-1889}, pmid = {35853576}, issn = {1556-3871}, support = {R01 DK118278/DK/NIDDK NIH HHS/United States ; R01 HL136407/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Postural Orthostatic Tachycardia Syndrome/diagnosis/epidemiology/therapy ; *Orthostatic Intolerance/epidemiology ; Pandemics ; *COVID-19/complications/epidemiology ; SARS-CoV-2 ; Tachycardia ; }, abstract = {Postural orthostatic tachycardia syndrome (POTS) is a complex multisystem disorder characterized by orthostatic intolerance and tachycardia and may be triggered by viral infection. Recent reports indicate that 2%-14% of coronavirus disease 2019 (COVID-19) survivors develop POTS and 9%-61% experience POTS-like symptoms, such as tachycardia, orthostatic intolerance, fatigue, and cognitive impairment within 6-8 months of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Pathophysiological mechanisms of post-COVID-19 POTS are not well understood. Current hypotheses include autoimmunity related to SARS-CoV-2 infection, autonomic dysfunction, direct toxic injury by SARS-CoV-2 to the autonomic nervous system, and invasion of the central nervous system by SARS-CoV-2. Practitioners should actively assess POTS in patients with post-acute COVID-19 syndrome symptoms. Given that the symptoms of post-COVID-19 POTS are predominantly chronic orthostatic tachycardia, lifestyle modifications in combination with the use of heart rate-lowering medications along with other pharmacotherapies should be considered. For example, ivabradine or β-blockers in combination with compression stockings and increasing salt and fluid intake has shown potential. Treatment teams should be multidisciplinary, including physicians of various specialties, nurses, psychologists, and physiotherapists. Additionally, more resources to adequately care for this patient population are urgently needed given the increased demand for autonomic specialists and clinics since the start of the COVID-19 pandemic. Considering our limited understanding of post-COVID-19 POTS, further research on topics such as its natural history, pathophysiological mechanisms, and ideal treatment is warranted. This review evaluates the current literature available on the associations between COVID-19 and POTS, possible mechanisms, patient assessment, treatments, and future directions to improving our understanding of post-COVID-19 POTS.}, }
@article {pmid35857271, year = {2022}, author = {di Filippo, L and Frara, S and Doga, M and Giustina, A}, title = {The osteo-metabolic phenotype of COVID-19: an update.}, journal = {Endocrine}, volume = {78}, number = {2}, pages = {247-254}, pmid = {35857271}, issn = {1559-0100}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; COVID-19 Vaccines ; Parathyroid Hormone ; Phenotype ; Post-Acute COVID-19 Syndrome ; }, abstract = {CONTEXT: In the multifaceted COVID-19 clinical scenario characterized by a multi-system disorder with negative implications not only on respiratory function but also on cardiac, hematological, neurological and endocrine-metabolic systems, a distinctive osteo-metabolic phenotype with an independent influence on disease severity and recovery of patients affected was early reported.<br><br>AIM: To summarize and update the main evidences regarding the distinct components of this phenotype in acute and Long COVID-19, reinforcing its clinical relevance and discussing the main pathophysiological and clinical-therapeutic implications of the most recent reported findings.<br><br>RESULTS: This emerging phenotype is characterized by a widespread acute hypocalcemia and hypovitaminosis D with an impaired compensatory parathyroid hormone response, and a high prevalence of skeletal complications such as vertebral fractures. The clinical relevance of this osteo-metabolic phenotype on acute COVID-19 is well characterized, and novel seminal evidences are progressively highlighting its importance also in predicting patient's long-term outcomes and Long COVID-19 occurrence.<br><br>CONCLUSIONS: These findings reinforced the central role of a multidisciplinary team, including endocrinologists, in evaluating these patients for a proactive search of each aspect of the osteo-metabolic phenotype components since they may represent suitable therapeutic targets to prevent SARS-CoV-2 infection, poor COVID-19 outcomes, Long COVID-19 occurrence and even possibly better responses to COVID-19 vaccination.}, }
@article {pmid35857581, year = {2022}, author = {Narasimhan, H and Wu, Y and Goplen, NP and Sun, J}, title = {Immune determinants of chronic sequelae after respiratory viral infection.}, journal = {Science immunology}, volume = {7}, number = {73}, pages = {eabm7996}, doi = {10.1126/sciimmunol.abm7996}, pmid = {35857581}, issn = {2470-9468}, mesh = {*COVID-19/complications/immunology ; Coronavirus ; Humans ; Pandemics ; *Respiratory Tract Infections/immunology/virology ; *Virus Diseases/complications/immunology ; Post-Acute COVID-19 Syndrome ; }, abstract = {The acute effects of various respiratory viral infections have been well studied, with extensive characterization of the clinical presentation as well as viral pathogenesis and host responses. However, over the course of the recent COVID-19 pandemic, the incidence and prevalence of chronic sequelae after acute viral infections have become increasingly appreciated as a serious health concern. Post-acute sequelae of COVID-19, alternatively described as "long COVID-19," are characterized by symptoms that persist for longer than 28 days after recovery from acute illness. Although there exists substantial heterogeneity in the nature of the observed sequelae, this phenomenon has also been observed in the context of other respiratory viral infections including influenza virus, respiratory syncytial virus, rhinovirus, severe acute respiratory syndrome coronavirus, and Middle Eastern respiratory syndrome coronavirus. In this Review, we discuss the various sequelae observed following important human respiratory viral pathogens and our current understanding of the immunological mechanisms underlying the failure of restoration of homeostasis in the lung.}, }
@article {pmid35862724, year = {2022}, author = {Bassett, M and Salemi, M and Rife Magalis, B}, title = {Lessons Learned and Yet-to-Be Learned on the Importance of RNA Structure in SARS-CoV-2 Replication.}, journal = {Microbiology and molecular biology reviews : MMBR}, volume = {86}, number = {3}, pages = {e0005721}, pmid = {35862724}, issn = {1098-5557}, mesh = {*COVID-19 ; Humans ; Pandemics ; RNA ; *SARS-CoV-2/genetics ; }, abstract = {SARS-CoV-2, the etiological agent responsible for the COVID-19 pandemic, is a member of the virus family Coronaviridae, known for relatively extensive (~30-kb) RNA genomes that not only encode for numerous proteins but are also capable of forming elaborate structures. As highlighted in this review, these structures perform critical functions in various steps of the viral life cycle, ultimately impacting pathogenesis and transmissibility. We examine these elements in the context of coronavirus evolutionary history and future directions for curbing the spread of SARS-CoV-2 and other potential human coronaviruses. While we focus on structures supported by a variety of biochemical, biophysical, and/or computational methods, we also touch here on recent evidence for novel structures in both protein-coding and noncoding regions of the genome, including an assessment of the potential role for RNA structure in the controversial finding of SARS-CoV-2 integration in "long COVID" patients. This review aims to serve as a consolidation of previous works on coronavirus and more recent investigation of SARS-CoV-2, emphasizing the need for improved understanding of the role of RNA structure in the evolution and adaptation of these human viruses.}, }
@article {pmid35868667, year = {2022}, author = {Zazzara, MB and Bellieni, A and Calvani, R and Coelho-Junior, HJ and Picca, A and Marzetti, E}, title = {Inflammaging at the Time of COVID-19.}, journal = {Clinics in geriatric medicine}, volume = {38}, number = {3}, pages = {473-481}, pmid = {35868667}, issn = {1879-8853}, mesh = {Aged ; *COVID-19/complications/therapy ; Cytokines ; Humans ; Inflammation/therapy ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Severe coronavirus disease 2019 (COVID-19) is associated with overproduction of proinflammatory cytokines. The ensuing cytokine storm contributes to the development of severe pneumonia and, possibly, to long-term symptom persistence (long COVID). The chronic state of low-grade inflammation that accompanies aging (inflammaging) might predispose older adults to severe COVID-19. Inflammaging may also contribute to symptom persistence following acute COVID-19. Antiinflammatory drugs and immunomodulatory agents can achieve significant therapeutic gain during acute COVID-19. Lifestyle interventions (eg, physical activity, diet) may be proposed as strategies to counteract inflammation and mitigate long-term symptom persistence.}, }
@article {pmid35868671, year = {2022}, author = {Rodriguez-Sanchez, I and Rodriguez-Mañas, L and Laosa, O}, title = {Long COVID-19: The Need for an Interdisciplinary Approach.}, journal = {Clinics in geriatric medicine}, volume = {38}, number = {3}, pages = {533-544}, pmid = {35868671}, issn = {1879-8853}, mesh = {Aged ; *COVID-19/complications ; Frail Elderly ; *Frailty ; Humans ; *Sarcopenia/etiology/prevention &amp; control ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long coronavirus disease 2019 (COVID-19) is characterized by persistent COVID-19 symptoms that last for at least 2 months. In the elderly population, apart from the typical symptoms (fatigue, cough, or dyspnea), unspecific symptoms coexist (functional deterioration, cognitive impairment, or delirium) that can mitigate the prevalence of this syndrome in this age group. Its main consequence is the functional decline, leading to sarcopenia, frailty, and disability, in addition to the nutritional and cognitive disorders. Thus, a multicomponent and individualized program (exercise, diet, cognitive stimulation) should be designed for older people with persistent COVID, where new technologies could be useful.}, }
@article {pmid35868672, year = {2022}, author = {Montes-Ibarra, M and Oliveira, CLP and Orsso, CE and Landi, F and Marzetti, E and Prado, CM}, title = {The Impact of Long COVID-19 on Muscle Health.}, journal = {Clinics in geriatric medicine}, volume = {38}, number = {3}, pages = {545-557}, pmid = {35868672}, issn = {1879-8853}, mesh = {Aged ; *COVID-19/complications ; Humans ; *Muscle Strength/physiology ; Muscle, Skeletal ; Quality of Life ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19 negatively impacts several organs and systems weeks or months after initial diagnosis. Skeletal muscle can be affected, leading to fatigue, lower mobility, weakness, and poor physical performance. Older adults are at increased risk of developing musculoskeletal symptoms during long COVID. Systemic inflammation, physical inactivity, and poor nutritional status are some of the mechanisms leading to muscle dysfunction in individuals with long COVID. Current evidence suggests that long COVID negatively impacts body composition, muscle function, and quality of life. Muscle mass and function assessments can contribute toward the identification, diagnosis, and management of poor muscle health resulting from long COVID.}, }
@article {pmid35868673, year = {2022}, author = {Grund, S and Bauer, JM}, title = {Malnutrition and Sarcopenia in COVID-19 Survivors.}, journal = {Clinics in geriatric medicine}, volume = {38}, number = {3}, pages = {559-564}, pmid = {35868673}, issn = {1879-8853}, mesh = {Aged ; *COVID-19/complications/epidemiology ; Geriatric Assessment/methods ; Humans ; *Malnutrition/diagnosis/epidemiology/etiology ; Nursing Homes ; Nutrition Assessment ; Nutritional Status ; *Sarcopenia/diagnosis/epidemiology/etiology ; Survivors ; }, abstract = {Malnutrition has been one of the most common complications of older COVID-19 survivors. COVID-19 associated symptoms like loss of appetite as well as changes in taste and smell may trigger the deterioration of nutritional status, while other complications of the disease may contribute to it, like respiratory failure that necessitates admission to the ICU. Especially in nursing home residents reduced food intake may be related to preexisting and also to incident geriatric syndromes like delirium. Sarcopenia has also been highly prevalent in older COVID-19 survivors. It is caused and exacerbated by COVID-19-associated inflammatory processes, total or partial immobilization, and malnutrition. COVID-19 survivors may be at high risk of developing the vicious circle that results from the interaction of deteriorating nutritional status and declining functionality. Regular monitoring of nutritional and functional status is, therefore, indicated in all older COVID-19 survivors. If malnutrition and/or functional decline have been identified in this patient population, low-threshold provision of individualized nutritional and exercise interventions should be installed. In those that are most seriously affected by malnutrition and sarcopenia ambulatory or inpatient rehabilitation has to be considered. Geriatric rehabilitation programs should be specifically adapted to the needs of older patients with COVID-19.}, }
@article {pmid35868674, year = {2022}, author = {Tosato, M and Ciciarello, F and Zazzara, MB and Pais, C and Savera, G and Picca, A and Galluzzo, V and Coelho-Júnior, HJ and Calvani, R and Marzetti, E and Landi, F and , }, title = {Nutraceuticals and Dietary Supplements for Older Adults with Long COVID-19.}, journal = {Clinics in geriatric medicine}, volume = {38}, number = {3}, pages = {565-591}, pmid = {35868674}, issn = {1879-8853}, mesh = {Aged ; *COVID-19/complications ; Dietary Supplements ; Humans ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The persistence of COVID-19 symptoms weeks or months after an initial SARS-CoV-2 infection has become one of the most burdensome legacies of the pandemic. This condition, known as long COVID syndrome, affects many persons of all age groups and is associated with substantial reductions of quality of life. Several mechanisms may be involved in long COVID syndrome, including chronic inflammation, metabolic perturbations, endothelial dysfunction, and gut dysbiosis. These pathogenic mechanisms overlap with those of the aging process and may aggravate pre-existing degenerative conditions. This review discusses bioactive foods, supplements, and nutraceuticals as possible interventions against long COVID syndrome.}, }
@article {pmid35868675, year = {2022}, author = {Lauria, A and Carfì, A and Benvenuto, F and Bramato, G and Ciciarello, F and Rocchi, S and Rota, E and Salerno, A and Stella, L and Tritto, M and Di Paola, A and Pais, C and Tosato, M and Janiri, D and Sani, G and Pagano, FC and Fantoni, M and Bernabei, R and Landi, F and Bizzarro, A and , }, title = {Neuropsychological Measures of Long COVID-19 Fog in Older Subjects.}, journal = {Clinics in geriatric medicine}, volume = {38}, number = {3}, pages = {593-603}, pmid = {35868675}, issn = {1879-8853}, mesh = {Aged ; *COVID-19/complications ; Humans ; Neuropsychological Tests ; Post-Acute COVID-19 Syndrome ; }, abstract = {Coronavirus disease 2019 is known to impact older people more severely and to cause persistent symptoms during the recovery phase, including cognitive and neurologic ones. We investigated the cognitive and neurologic features of 100 elderly patients with confirmed diagnosis of coronavirus disease 2019 evaluated in the postacute phase through a direct neuropsychological evaluation consisting on Mini Mental State Examination and 8 neuropsychological tests. Overall, a total of 33 participants were found to perform at a level considered to be pathologic; more specifically, 33%, 23%, and 20% failed on Trial Making, Digit Span Backwards, and Frontal Evaluation Battery tests, respectively.}, }
@article {pmid35874953, year = {2022}, author = {Park, JW and Wang, X and Xu, RH}, title = {Revealing the mystery of persistent smell loss in Long COVID patients.}, journal = {International journal of biological sciences}, volume = {18}, number = {12}, pages = {4795-4808}, pmid = {35874953}, issn = {1449-2288}, mesh = {*Anosmia/diagnosis/virology ; *COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19 is hopefully approaching its end in many countries as herd immunity develops and weaker strains of SARS-CoV-2 dominate. However, a new concern occurs over the long-term effects of COVID-19, collectively called "Long COVID", as some symptoms of the nervous system last even after patients recover from COVID-19. This review focuses on studies of anosmia, i.e., impairment of smell, which is the most common sensory defect during the disease course and is caused by olfactory dysfunctions. It remains mysterious how the olfactory functions are affected since the virus can't invade olfactory receptor neurons. We describe several leading hypotheses about the mystery in hope to provide insights into the pathophysiology and treatment strategies for anosmia.}, }
@article {pmid35874958, year = {2022}, author = {Koc, HC and Xiao, J and Liu, W and Li, Y and Chen, G}, title = {Long COVID and its Management.}, journal = {International journal of biological sciences}, volume = {18}, number = {12}, pages = {4768-4780}, pmid = {35874958}, issn = {1449-2288}, mesh = {*COVID-19/complications ; Health Personnel ; Humans ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The pandemic of COVID-19 is the biggest public health crisis in 21[st] Century. Besides the acute symptoms after infection, patients and society are also being challenged by the long-term health complications associated with COVID-19, commonly known as long COVID. While health professionals work hard to find proper treatments, large amount of knowledge has been accumulated in recent years. In order to deal with long COVID efficiently, it is important for people to keep up with current progresses and take proactive actions on long COVID. For this purpose, this review will first introduce the general background of long COVID, and then discuss its risk factors, diagnostic indicators and management strategies. This review will serve as a useful resource for people to understand and prepare for long COVID that will be with us in the foreseeable future.}, }
@article {pmid35881153, year = {2022}, author = {Elhiny, R and Al-Jumaili, AA and Yawuz, MJ}, title = {What might COVID-19 patients experience after recovery? A comprehensive review.}, journal = {The International journal of pharmacy practice}, volume = {30}, number = {5}, pages = {404-413}, pmid = {35881153}, issn = {2042-7174}, mesh = {Humans ; *COVID-19 ; Anxiety ; Vomiting ; *Gastrointestinal Diseases ; }, abstract = {OBJECTIVES: The objective of this review was to describe the COVID-19 complications after recovery.<br><br>METHODS: The researchers systematically reviewed studies that reported post-COVID-19 complications from three databases: PubMed, Google Scholar and the World Health Organization (WHO) COVID-19 database. The search was conducted between 21 November 2020 and 14 January 2021. Inclusion criteria were articles written in English, with primary data, reporting complications of COVID-19 after full recovery. The review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) 2020 statement.<br><br>KEY FINDINGS: This review included 69 studies with 146 725 patients from 22 countries related to post-COVID-19 complications. Thirty-six studies reported post-cure respiratory complications, ranging from dyspnoea to residual pulmonary fibrosis. Cardiac symptoms were reported in nine studies, including palpitation, chest pain and diastolic dysfunction. Neurological complications included post-traumatic stress syndrome, anxiety, depression, memory issues, insomnia and sleeping disturbance, cognitive impairments and stigma. Gastrointestinal symptoms included nausea, vomiting, diarrhoea and acute liver injury. The physical decline was the most common symptom reported in the musculoskeletal complications.<br><br>CONCLUSION: COVID-19 may cause several types of complications after recovery (testing negative PCR). The identified complications include respiratory, neurological/mental, cardiovascular, gastrointestinal tract, urinary tract, musculoskeletal and miscellaneous complications. However, the key impairments were pulmonary consequences, psychological problems and exercise intolerance. Thus, COVID-19 patients may need long-term follow-up.}, }
@article {pmid35886618, year = {2022}, author = {Su, Z and Cheshmehzangi, A and McDonnell, D and Ahmad, J and Šegalo, S and Xiang, YT and da Veiga, CP}, title = {The Advantages of the Zero-COVID-19 Strategy.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {14}, pages = {}, pmid = {35886618}, issn = {1660-4601}, mesh = {*COVID-19/complications/epidemiology/prevention &amp; control ; COVID-19 Vaccines ; Humans ; Pandemics/prevention &amp; control ; Public Health ; Post-Acute COVID-19 Syndrome ; }, abstract = {Introduction: To curb the COVID-19 pandemic, countries across the globe have adopted either a mitigation or anelimination policy, such as the zero-COVID-19 strategy. However, further research is needed to systematically investigate the advantages of the zero-COVID-19 strategy in the literature. To bridge the research gap, this study examines the zero-COVID-19 strategy in terms of its advantages as a global anti-pandemic framework. Methods: A literature review was conducted in PubMed, PsycINFO, and Scopus to locate academic articles that discussed the advantages of the zero-COVID-19 strategy. Braun and Clarke's thematic analysis approach was adopted to guide the data analysis process. Results: The findings of our study show that the advantages of the zero-COVID-19 strategy range from short-term (e.g., limited virus infections, hospitalizations, and deaths), to medium-term (e.g., reduced presence of other infectious diseases), and long-term (e.g., low incidence of long COVID-19). While local residents mainly leverage these advantages, they also impact the global community (e.g., stable global supply of essentials, such as COVID-19 vaccines). Conclusions: COVID-19 is catastrophic, yet controllable. Our study examined the advantages of the zero-COVID-19 strategy from a nuanced perspective and discussed how these advantages benefit both the local and the global community in pandemic control and management. Future studies could investigate the shortcomings of the zero-COVID-19 strategy, especially its unintended consequences, such as adverse impacts on vulnerable populations' mental health, so that society could more efficiently, economically, and empathetically capitalize on the potential of the zero-COVID-19 strategy for the betterment of personal and public health.}, }
@article {pmid35888154, year = {2022}, author = {Mumtaz, A and Sheikh, AAE and Khan, AM and Khalid, SN and Khan, J and Nasrullah, A and Sagheer, S and Sheikh, AB}, title = {COVID-19 Vaccine and Long COVID: A Scoping Review.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {7}, pages = {}, pmid = {35888154}, issn = {2075-1729}, abstract = {As the COVID-19 pandemic progresses, changing definitions and therapeutics regarding the post-acute sequela of COVID-19, particularly long COVID, have become a subject of great interest and study. The study aims to describe the pathophysiology and discuss different therapeutic agents currently available for long COVID. Another objective is to assess comparative efficacy between different types of vaccines on symptoms of long COVID. A preliminary search was conducted using Ovid Medline, Embase, medRxiv, and NIH COVID-19 portfolios. A total of 16 studies were included in our review. Despite some of the data showing variable results, most of the vaccinated patients reported improvement in long COVID symptoms with no significant difference between various types of vaccines. Further trials are needed to better identify the comparative efficacy of vaccines for long COVID and ascertain other therapeutic modalities.}, }
@article {pmid35896188, year = {2022}, author = {Tan, BKJ and Han, R and Zhao, JJ and Tan, NKW and Quah, ESH and Tan, CJ and Chan, YH and Teo, NWY and Charn, TC and See, A and Xu, S and Chapurin, N and Chandra, RK and Chowdhury, N and Butowt, R and von Bartheld, CS and Kumar, BN and Hopkins, C and Toh, ST}, title = {Prognosis and persistence of smell and taste dysfunction in patients with covid-19: meta-analysis with parametric cure modelling of recovery curves.}, journal = {BMJ (Clinical research ed.)}, volume = {378}, number = {}, pages = {e069503}, pmid = {35896188}, issn = {1756-1833}, support = {P20 GM103554/GM/NIGMS NIH HHS/United States ; }, mesh = {*COVID-19/complications ; Female ; Humans ; *Olfaction Disorders/etiology ; Prognosis ; Smell ; Taste ; Taste Disorders/etiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: To clarify in patients with covid-19 the recovery rate of smell and taste, proportion with persistent dysfunction of smell and taste, and prognostic factors associated with recovery of smell and taste.<br><br>DESIGN: Systematic review and meta-analysis.<br><br>DATA SOURCES: PubMed, Embase, Scopus, Cochrane Library, and medRxiv from inception to 3 October 2021.<br><br>REVIEW METHODS: Two blinded reviewers selected observational studies of adults (&#x2265;18 years) with covid-19 related dysfunction of smell or taste. Descriptive prognosis studies with time-to-event curves and prognostic association studies of any prognostic factor were included.<br><br>DATA EXTRACTION AND SYNTHESIS: Two reviewers extracted data, evaluated study bias using QUIPS, and appraised evidence quality using GRADE, following PRISMA and MOOSE reporting guidelines. Using iterative numerical algorithms, time-to-event individual patient data (IPD) were reconstructed and pooled to retrieve distribution-free summary survival curves, with recovery rates reported at 30 day intervals for participants who remained alive. To estimate the proportion with persistent smell and taste dysfunction, cure fractions from Weibull non-mixture cure models of plateaued survival curves were logit transformed and pooled in a two stage meta-analysis. Conventional aggregate data meta-analysis was performed to explore unadjusted associations of prognostic factors with recovery.<br><br>MAIN OUTCOME MEASURES: The primary outcomes were the proportions of patients remaining with smell or taste dysfunction. Secondary outcomes were the odds ratios of prognostic variables associated with recovery of smell and taste.<br><br>RESULTS: 18 studies (3699 patients) from 4180 records were included in reconstructed IPD meta-analyses. Risk of bias was low to moderate; conclusions remained unaltered after exclusion of four high risk studies. Evidence quality was moderate to high. Based on parametric cure modelling, persistent self-reported smell and taste dysfunction could develop in an estimated 5.6% (95% confidence interval 2.7% to 11.0%, I[2]=70%, &#x3c4;[2]=0.756, 95% prediction interval 0.7% to 33.5%) and 4.4% (1.2% to 14.6%, I[2]=67%, &#x3c4;[2]=0.684, 95% prediction interval 0.0% to 49.0%) of patients, respectively. Sensitivity analyses suggest these could be underestimates. At 30, 60, 90, and 180 days, respectively, 74.1% (95% confidence interval 64.0% to 81.3%), 85.8% (77.6% to 90.9%), 90.0% (83.3% to 94.0%), and 95.7% (89.5% to 98.3%) of patients recovered their sense of smell (I[2]=0.0-77.2%, &#x3c4;[2]=0.006-0.050) and 78.8% (70.5% to 84.7%), 87.7% (82.0% to 91.6%), 90.3% (83.5% to 94.3%), and 98.0% (92.2% to 95.5%) recovered their sense of taste (range of I[2]=0.0-72.1%, &#x3c4;[2]=0.000-0.015). Women were less likely to recover their sense of smell (odds ratio 0.52, 95% confidence interval 0.37 to 0.72, seven studies, I[2]=20%, &#x3c4;[2]=0.0224) and taste (0.31, 0.13 to 0.72, seven studies, I[2]=78%, &#x3c4;[2]=0.5121) than men, and patients with greater initial severity of dysfunction (0.48, 0.31 to 0.73, five studies, I[2]=10%, &#x3c4;[2]<0.001) or nasal congestion (0.42, 0.18 to 0.97, three studies, I[2]=0%, &#x3c4;[2]<0.001) were less likely to recover their sense of smell.<br><br>CONCLUSIONS: A substantial proportion of patients with covid-19 might develop long lasting change in their sense of smell or taste. This could contribute to the growing burden of long covid.<br><br>PROSPERO CRD42021283922.}, }
@article {pmid35906952, year = {2023}, author = {Altersberger, M and Goliasch, G and Khafaga, M and Schneider, M and Cho, Y and Winkler, R and Funk, GC and Binder, T and Huber, G and Zwick, RH and Genger, M}, title = {Echocardiography and Lung Ultrasound in Long COVID and Post-COVID Syndrome, a Review Document of the Austrian Society of Pneumology and the Austrian Society of Ultrasound in Medicine.}, journal = {Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine}, volume = {42}, number = {2}, pages = {269-277}, pmid = {35906952}, issn = {1550-9613}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *Pulmonary Medicine ; Austria ; *COVID-19 ; Echocardiography ; Lung/diagnostic imaging ; }, abstract = {Lung ultrasound has the potential to enable standardized follow-up without radiation exposure and with lower associated costs in comparison to CT scans. It is a valuable tool to follow up on patients after a COVID-19 infection and evaluate if there is pulmonary fibrosis developing. Echocardiography, including strain imaging, is a proven tool to assess various causes of dyspnea and adds valuable information in the context of long COVID care. Including two-dimensional (2D) strain imaging, a better comprehension of myocardial damage in post-COVID syndrome can be made. Especially 2D strain imaging (left and the right ventricular strain) can provide information about prognosis.}, }
@article {pmid35910083, year = {2022}, author = {James, LM and Georgopoulos, AP}, title = {At the Root of 3 "Long" Diseases: Persistent Antigens Inflicting Chronic Damage on the Brain and Other Organs in Gulf War Illness, Long-COVID-19, and Chronic Fatigue Syndrome.}, journal = {Neuroscience insights}, volume = {17}, number = {}, pages = {26331055221114817}, pmid = {35910083}, issn = {2633-1055}, abstract = {Several foreign antigens such as those derived from viruses and bacteria have been linked to long-term deleterious effects on the brain and other organs; yet, health outcomes subsequent to foreign antigen exposure vary depending in large part on the host's immune system, in general, and on human leukocyte antigen (HLA) composition, in particular. Here we first provide a brief description of 3 conditions characterized by persistent long-term symptoms, namely long-COVID-19, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and Gulf War Illness (GWI), followed by a brief overview of the role of HLA in the immune response to foreign antigens. We then discuss our Persistent Antigen (PA) hypothesis and highlight associations between antigen persistence due to HLA-antigen incongruence and chronic health conditions in general and the 3 "long" diseases above in particular. This review is not intended to cover the breadth and depth of symptomatology of those diseases but is specifically focused on the hypothesis that the presence of persistent antigens underlies their pathogenesis.}, }
@article {pmid35911550, year = {2022}, author = {Sze, S and Pan, D and Moss, AJ and Ong, CK and Pareek, M and Squire, IB and Clark, AL}, title = {Overstimulation of the ergoreflex-A possible mechanism to explain symptoms in long COVID.}, journal = {Frontiers in cardiovascular medicine}, volume = {9}, number = {}, pages = {940832}, pmid = {35911550}, issn = {2297-055X}, abstract = {Long COVID refers to a multitude of symptoms that persist long after SARS-CoV-2 infection. Fatigue and breathlessness are the most common symptoms of long COVID across a range of studies. They are also cardinal symptoms of chronic heart failure (CHF). In this review, we propose that fatigue and breathlessness in patients with long COVID may be explained by skeletal muscle abnormalities, in a manner similar to patients with CHF. The ergoreflex is a cardiorespiratory reflex activated by exercise, which couples ventilation and cardiovascular function to exercise intensity. At least part of the symptomatology of CHF is related to abnormal skeletal muscle and an enhanced ergoreflex, resulting in heightened sympathetic, vasoconstrictor and ventilator drives. Similarly, SARS-CoV-2 infection results in a hyperinflammatory and hypercatabolic state. This leads to reduction in skeletal muscle mass and altered function. We postulate that the ergoreflex is chronically overstimulated, resulting in fatigue and breathlessness. Exercise training preserves muscle mass and function as well as reduces ergoreflex activation; therefore may have a role in improving symptoms associated with long COVID. Should the ergoreflex be proven to be an important pathophysiological mechanism of long COVID, tailored exercise interventions should be trialed with the aim of improving both symptoms and perhaps outcomes in patients with long COVID.}, }
@article {pmid35912863, year = {2022}, author = {Ahamed, J and Laurence, J}, title = {Long COVID endotheliopathy: hypothesized mechanisms and potential therapeutic approaches.}, journal = {The Journal of clinical investigation}, volume = {132}, number = {15}, pages = {}, pmid = {35912863}, issn = {1558-8238}, support = {R01 HL148123/HL/NHLBI NIH HHS/United States ; }, mesh = {*COVID-19/complications/therapy ; Female ; Humans ; Inflammation ; SARS-CoV-2 ; *Thrombosis/etiology/therapy ; Post-Acute COVID-19 Syndrome ; }, abstract = {SARS-CoV-2-infected individuals may suffer a multi-organ system disorder known as "long COVID" or post-acute sequelae of SARS-CoV-2 infection (PASC). There are no standard treatments, the pathophysiology is unknown, and incidence varies by clinical phenotype. Acute COVID-19 correlates with biomarkers of systemic inflammation, hypercoagulability, and comorbidities that are less prominent in PASC. Macrovessel thrombosis, a hallmark of acute COVID-19, is less frequent in PASC. Female sex at birth is associated with reduced risk for acute COVID-19 progression, but with increased risk of PASC. Persistent microvascular endotheliopathy associated with cryptic SARS-CoV-2 tissue reservoirs has been implicated in PASC pathology. Autoantibodies, localized inflammation, and reactivation of latent pathogens may also be involved, potentially leading to microvascular thrombosis, as documented in multiple PASC tissues. Diagnostic assays illuminating possible therapeutic targets are discussed.}, }
@article {pmid35914765, year = {2023}, author = {Nalbandian, A and Desai, AD and Wan, EY}, title = {Post-COVID-19 Condition.}, journal = {Annual review of medicine}, volume = {74}, number = {}, pages = {55-64}, doi = {10.1146/annurev-med-043021-030635}, pmid = {35914765}, issn = {1545-326X}, support = {T32 HL007854/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; Female ; *COVID-19 ; Quality of Life ; SARS-CoV-2 ; *Cognitive Dysfunction/epidemiology/etiology ; Dyspnea ; }, abstract = {An estimated 10-15% of those infected with SARS-CoV-2 may have post-COVID-19 condition. Common lingering signs and symptoms include shortness of breath, fatigue, high heart rate, and memory and cognitive dysfunction even several months after infection, often impacting survivors' quality of life. The prevalence and duration of individual symptoms remain difficult to ascertain due to the lack of standardized research methods across various studies and limited patient follow-up in clinical studies. Nonetheless, data indicate post-COVID-19 condition may occur independent of acuity of initial infection, hospitalization status, age, or pre-existing comorbidities. Risk factors may include female sex and underlying respiratory or psychiatric disease. Supportive therapies to mitigate symptoms remain the mainstay of treatment. Reassuringly, most patients experience a reduction in symptoms by 1 year. The use of a universal case definition and shared research methods will allow for further clarity regarding the pervasiveness of this entity and its long-term health consequences.}, }
@article {pmid35915417, year = {2022}, author = {Tana, C and Bentivegna, E and Cho, SJ and Harriott, AM and García-Azorín, D and Labastida-Ramirez, A and Ornello, R and Raffaelli, B and Beltrán, ER and Ruscheweyh, R and Martelletti, P}, title = {Long COVID headache.}, journal = {The journal of headache and pain}, volume = {23}, number = {1}, pages = {93}, pmid = {35915417}, issn = {1129-2377}, mesh = {*COVID-19/complications ; Headache/diagnosis/etiology/therapy ; Humans ; *Migraine Disorders ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Headache is among the most frequent symptoms persisting or newly developing after coronavirus disease 2019 (COVID-19) as part of the so-called long COVID syndrome. The knowledge on long COVID headache is still limited, however growing evidence is defining the features of this novel condition, in particular regarding clinical characteristics, some pathophysiological mechanisms and first treatment recommendations. Long COVID headache can present in the form of worsening of a preexisting primary headache, or, more specifically, in the form of a new (intermittent or daily) headache starting during the acute infection or after a delay. It often presents together with other long COVID symptoms, most frequently with hyposmia. It can manifest with a migrainous or, more frequently, with a tension-type-like phenotype. Persistent activation of the immune system and trigeminovascular activation are thought to play a role. As there are virtually no treatment studies, treatment currently is largely guided by the existing guidelines for primary headaches with the corresponding phenotype. The present report, a collaborative work of the international group of the Junior Editorial Board of The Journal of Headache and Pain aims to summarize the most recent evidence about long COVID headache and suggests approaches to the diagnosis and treatment of this disorder.}, }
@article {pmid35925071, year = {2022}, author = {Pink, I and Welte, T}, title = {[Frequency, spectrum and risk factors of long COVID].}, journal = {Innere Medizin (Heidelberg, Germany)}, volume = {63}, number = {8}, pages = {813-818}, pmid = {35925071}, issn = {2731-7099}, mesh = {*Ageusia ; *COVID-19/complications/epidemiology ; Humans ; Risk Factors ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Between 10 and 20% of individuals infected with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) suffer from symptoms up to weeks after initial infection. The most frequently reported symptoms include fatigue, dyspnea, anosmia and ageusia, as well as headaches, joint pain, cough, cognitive impairment and impaired sleeping. After exclusion of other etiologies and symptom duration of more than 4 weeks after initial infection this is referred to as long COVID. In contrast to acute coronavirus disease 2019 (COVID-19), no specific risk factors have been identified as yet as being associated with the occurrence of this disease. Furthermore, there are varying hypotheses concerning the pathomechanism of long COVID. Dividing patients into groups is beneficial in the clinical context. Regardless of long COVID symptoms the risk of cardiovascular events is increased even 1 year after COVID-19.}, }
@article {pmid35925072, year = {2022}, author = {Bauernfeind, S and Schmidt, B}, title = {[The value of COVID-19 vaccination in the context of Long-COVID].}, journal = {Innere Medizin (Heidelberg, Germany)}, volume = {63}, number = {8}, pages = {840-850}, pmid = {35925072}, issn = {2731-7099}, mesh = {*COVID-19/complications/prevention &amp; control ; COVID-19 Vaccines/therapeutic use ; Humans ; SARS-CoV-2 ; Vaccination ; Post-Acute COVID-19 Syndrome ; }, abstract = {There are currently no strategies available on how to deal with Long-COVID (COVID "coronavirus disease"). COVID-19 vaccination could be both a preemptive and a therapeutic option for the future. The evaluation of the available studies is complicated by varying definitions. There are, however, indications that (complete) COVID-19 vaccination is able not only to prevent symptomatic infection but also to reduce the risk of Long-COVID. In some patients with Long-COVID, symptoms are modified after (first and/or second) COVID-19 vaccination; however, there is no clear evidence for a real therapeutic effect on Long-COVID.}, }
@article {pmid35925073, year = {2022}, author = {Sommer, N and Schmeck, B}, title = {[Pulmonary manifestations in long COVID].}, journal = {Innere Medizin (Heidelberg, Germany)}, volume = {63}, number = {8}, pages = {819-829}, pmid = {35925073}, issn = {2731-7099}, mesh = {*COVID-19/complications ; Humans ; Lung/diagnostic imaging ; *Lung Diseases, Interstitial/diagnosis ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Pulmonary manifestations are very common sequelae after severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infections, which are summarized under the term long COVID (coronavirus disease) syndrome.<br><br>AIM/METHODS: This article summarizes the current literature on pulmonary manifestations with a&#xa0;focus on expert opinions and recommendations.<br><br>RESULTS: After chronic fatigue, dyspnea is the most common symptom in patients with long COVID syndrome. Pathological findings are mainly found after a&#xa0;severe acute course of COVID-19 and include radiological changes with characteristics of interstitial lung diseases, restrictive ventilation patterns and limitations in diffusion capacity as the most common pathological finding. Although both symptoms and pathological pulmonary alterations improve over time, some patients may still suffer from abnormalities months after the acute infection. The relevance of the pathological findings, as well as the involvement of functional respiratory limitations, cardiopulmonary deconditioning, non-somatic causes and pre-existing lung diseases, is currently unclear. The advanced diagnostic assessment thus focusses on high-risk patients and includes, in addition to imaging and pulmonary function tests, a&#xa0;cardiopulmonary exercise test and, if the findings are unclear, an echocardiography to diagnose a&#xa0;pulmonary vascular component. The therapeutic options currently include treatment of the underlying causes of the symptoms (e.g. interstitial lung diseases, cough) according to the respective guidelines and rehabilitation measures.<br><br>DISCUSSION: The current knowledge about pulmonary manifestations in long COVID patients is constantly being expanded, but due to limited availability of clinical trials, there are still no evidence-based guidelines for the diagnosis and therapy of pulmonary manifestations in long COVID syndrome.}, }
@article {pmid35925074, year = {2022}, author = {Renz-Polster, H and Scheibenbogen, C}, title = {[Post-COVID syndrome with fatigue and exercise intolerance: myalgic encephalomyelitis/chronic fatigue syndrome].}, journal = {Innere Medizin (Heidelberg, Germany)}, volume = {63}, number = {8}, pages = {830-839}, pmid = {35925074}, issn = {2731-7099}, mesh = {*COVID-19/complications ; *Fatigue Syndrome, Chronic/diagnosis ; Humans ; Pain ; }, abstract = {BACKGROUND: A sizable part of post-COVID syndrome meets the diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). A doubling of cases of ME/CFS within the next years is therefore projected.<br><br>OBJECTIVES: Presentation of the current state of knowledge on ME/CFS.<br><br>MATERIALS AND METHODS: Unsystematic review of the literature and of own contributions in research and patient care.<br><br>RESULTS AND CONCLUSIONS: ME/CFS is a&#xa0;neuroimmunological disease, mostly infection-induced, usually persisting throughout life. Clinically it is characterized by fatigue lasting at least 6&#xa0;months and the defining core feature of exercise intolerance (post-exertional malaise, PEM). Exercise intolerance is defined as a&#xa0;worsening of symptoms after (even mild) everyday exertion, which usually begins after several hours or on the following day, is still noticeable at least 14&#xa0;h after exertion, and often lasts for several days (up to weeks or longer). Furthermore, ME/CFS is characterized by pain, disturbances of sleep, thinking and memory, and dysregulation of the circulatory, endocrine, and immune systems. As a&#xa0;separate clinical entity, ME/CFS should be distinguished from chronic fatigue, which occurs as a&#xa0;symptom of a&#xa0;range of very different diseases. The diagnosis of ME/CFS is made clinically using established international diagnostic criteria and requires careful stepwise diagnosis to exclude other diagnoses. A&#xa0;causal therapy for ME/CFS has not been established; the focus is on symptoms relief, treatment of the often accompanying orthostatic intolerance, and assistance with anticipatory energy management (pacing).}, }
@article {pmid35930484, year = {2022}, author = {Simon, M and Simmons, JE}, title = {A Review of Respiratory Post-Acute Sequelae of COVID-19 (PASC) and the Potential Benefits of Pulmonary Rehabilitation.}, journal = {Rhode Island medical journal (2013)}, volume = {105}, number = {7}, pages = {11-15}, pmid = {35930484}, issn = {2327-2228}, mesh = {*COVID-19/complications ; Humans ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {With the SARS-CoV-2 pandemic continuing into its third year, the number of patients who survive acute COVID-19 infection but go on to develop long-term symptoms is increasing daily. Those individuals who experience one or more of a variety of persistent symptoms post-COVID-19 are now diagnosed with the syndrome called post-acute sequelae of COVID-19 (PASC), often colloquially called "Long COVID." This article discusses relevant research and current hypotheses regarding the pathophysiology and management of respiratory symptoms of PASC, in order to provide primary care physicians with context for management of this heterogeneous population. We focus on the growing body of research that supports the use of pulmonary rehabilitation for patients with PASC to improve symptoms and quality of life.}, }
@article {pmid35930485, year = {2022}, author = {Khetpal, V and Berkowitz, J and Vijayakumar, S and Choudhary, G and Mukand, JA and Rudolph, JL and Wu, WC and Erqou, S}, title = {Long-term Cardiovascular Manifestations and Complications of COVID-19: Spectrum and Approach to Diagnosis and Management.}, journal = {Rhode Island medical journal (2013)}, volume = {105}, number = {7}, pages = {16-22}, pmid = {35930485}, issn = {2327-2228}, mesh = {Arrhythmias, Cardiac/diagnosis/etiology/therapy ; *COVID-19/complications ; COVID-19 Testing ; Chest Pain/etiology ; Humans ; *Myocarditis ; Post-Acute COVID-19 Syndrome ; }, abstract = {Survivors of coronavirus disease 2019 (COVID-19) may experience persistent symptoms, abnormal diagnostic test findings, incident disease in specific organ systems, or progression of existing disease. Post-acute COVID-19 syndrome (PACS) is defined by persistent, recurrent, or new symptoms, findings, or diagnoses beyond four weeks after the initial infection. PACS has been characterized as a multi-organ syndrome, often with cardiopulmonary symptoms that include fatigue, dyspnea, chest pain, and palpitations. Cardiovascular pathologies in PACS include new-onset arrhythmia, myocarditis, unmasked coronary artery disease, and diastolic dysfunction as well as abnormal findings on electrocardiogram, troponin testing, and cardiac magnetic resonance imaging. In this review, we discuss the cardiovascular symptoms, pathophysiology, clinical investigation, and management strategies for cardiopulmonary symptoms of PACS. We offer a treatment algorithm for primary care clinicians encountering patients with cardiopulmonary PACS and discuss ongoing research on this topic.}, }
@article {pmid35934258, year = {2022}, author = {Solomon, M and Liang, C}, title = {Human coronaviruses: The emergence of SARS-CoV-2 and management of COVID-19.}, journal = {Virus research}, volume = {319}, number = {}, pages = {198882}, pmid = {35934258}, issn = {1872-7492}, support = {//CIHR/Canada ; }, mesh = {Betacoronavirus/genetics ; *Coronavirus Infections/drug therapy ; Humans ; *Pneumonia, Viral/prevention &amp; control ; SARS-CoV-2/genetics ; *COVID-19 Drug Treatment ; }, abstract = {To date, a total of seven human coronaviruses (HCoVs) have been identified, all of which are important respiratory pathogens. Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has led to a global pandemic causing millions of infections and deaths. Here, we summarize the discovery and fundamental virology of HCoVs, discuss their zoonotic transmission and highlight the weak species barrier of SARS-CoV-2. We also discuss the possible origins of SARS-CoV-2 variants of concern identified to date and discuss the experimental challenges in characterizing mutations of interest and propose methods to circumvent them. As the COVID-19 treatment and prevention landscape rapidly evolves, we summarize current therapeutics and vaccines, and their implications on SARS-CoV-2 variants. Finally, we explore how interspecies transmission of SARS-CoV-2 may drive the emergence of novel strains, how disease severity may evolve and how COVID-19 will likely continue to burden healthcare systems globally.}, }
@article {pmid35938280, year = {2022}, author = {Gualano, MR and Rossi, MF and Borrelli, I and Santoro, PE and Amantea, C and Daniele, A and Tumminello, A and Moscato, U}, title = {Returning to work and the impact of post COVID-19 condition: A systematic review.}, journal = {Work (Reading, Mass.)}, volume = {73}, number = {2}, pages = {405-413}, doi = {10.3233/WOR-220103}, pmid = {35938280}, issn = {1875-9270}, mesh = {Humans ; *COVID-19/epidemiology ; Pandemics ; Quality of Life ; World Health Organization ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The COVID-19 pandemic is still ongoing, with rapidly increasing cases all over the world, and the emerging issue of post COVID-19 (or Long COVID-19) condition is impacting the occupational world.<br><br>OBJECTIVE: The aim of this systematic review was to evaluate the impact of lasting COVID-19 symptoms or disability on the working population upon their return to employment.<br><br>METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statements we performed a systematic review in December 2021, screening three databases (PubMed, ISI Web of Knowledge, Scopus), for articles investigating return to work in patients that were previously hospitalized due to COVID-19. A hand-searched was then performed through the references of the included systematic review. A quality assessment was performed on the included studies.<br><br>RESULTS: Out of the 263 articles found through the initial search, 11 studies were included in this systematic review. The selected studies were divided based on follow-up time, in two months follow-up, follow-up between two and six months, and six months follow-up. All the studies highlighted an important impact of post COVID-19 condition in returning to work after being hospitalized, with differences based on follow-up time, home Country and mean/median age of the sample considered.<br><br>CONCLUSIONS: This review highlighted post COVID-19 condition as a rising problem in occupational medicine, with consequences on workers' quality of life and productivity. The role of occupational physicians could be essential in applying limitations to work duties or hours and facilitating the return to employment in workers with a post COVID-19 condition.}, }
@article {pmid35949299, year = {2022}, author = {Bogdanov, VY and Khirmanov, VN}, title = {SARS-CoV-2, platelets, and endothelium: coexistence in space and time, or a pernicious ménage à trois?.}, journal = {Vascular biology (Bristol, England)}, volume = {4}, number = {1}, pages = {R35-R43}, pmid = {35949299}, issn = {2516-5658}, abstract = {As we enter year 3 of SARS-CoV-2 pandemic, long-term consequences of COVID-19 have become a major public health issue worldwide; however, the molecular and cellular underpinnings of 'long COVID' remain very poorly understood. A paradigm has recently emerged that thrombo-inflammatory consequences of SARS-CoV-2's impact on endothelial cells and platelets likely play a significant role in the development of chronic symptomatology associated with COVID-19. In this brief overview, we discuss the recent findings pertaining to the detection of SARS-CoV-2 virions in vascular cell subtypes, the contribution of the coagulation system to the development of 'long COVID', and the potential role of stem/progenitor cells in the viral and thrombotic dissemination in this disorder.}, }
@article {pmid35957578, year = {2023}, author = {Gary, JB and Gallagher, L and Joseph, PV and Reed, D and Gudis, DA and Overdevest, JB}, title = {Qualitative Olfactory Dysfunction and COVID-19: An Evidence-Based Review with Recommendations for the Clinician.}, journal = {American journal of rhinology &amp; allergy}, volume = {37}, number = {1}, pages = {95-101}, pmid = {35957578}, issn = {1945-8932}, support = {K23 DC019678/DC/NIDCD NIH HHS/United States ; T35 AG044303/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; Anosmia ; *COVID-19/complications/epidemiology ; *Olfaction Disorders/diagnosis/epidemiology/therapy ; Quality of Life ; SARS-CoV-2 ; Smell ; }, abstract = {BACKGROUND: Nearly 40% of patients who experience smell loss during SARS-CoV-2 infection may develop qualitative olfactory dysfunction, most commonly parosmia. Our evidence-based review summarizes the evolving literature and offers recommendations for the clinician on the management of patients experiencing parosmia associated with COVID-19.<br><br>METHODS: We performed a systematic search using independent queries in PubMed, Embase, Ovid, and Cochrane databases, then categorized articles according to themes that emerged regarding epidemiology, effect on quality of life, disease progression, prognosis, pathophysiology, diagnosis, and treatment of parosmia.<br><br>RESULTS: We identified 123 unique references meeting eligibility and performed title and abstract review with 2 independent reviewers, with 74 articles undergoing full-text review. An inductive approach to thematic development provided 7 central themes regarding qualitative olfactory dysfunction following COVID-19.<br><br>CONCLUSIONS: While other respiratory viruses are known to cause qualitative olfactory disturbances, the incidence of parosmia following COVID-19 is notable, and correlates negatively with age. The presence of parosmia predicts persistent quantitative olfactory dysfunction. Onset can occur months after infection, and symptoms may persist for well over 7 months. Affected patients report increased anxiety and decreased quality of life. Structured olfactory training with essential oils is the preferred treatment, where parosmia predicts recovery of aspects of quantitative smell loss when undergoing training. There is limited evidence that nasal corticosteroids may accelerate recovery of olfactory function. Patients should be prepared for the possibility that symptoms may persist for years, and providers should guide them to resources for coping with their psychosocial burden.}, }
@article {pmid35962520, year = {2023}, author = {Taghrir, MH and Akbarialiabad, H and Abdollahi, A and Ghahramani, N and Bastani, B and Paydar, S and Razani, B and Mwangi, J and Asadi-Pooya, AA and Roozbeh, J and Malekmakan, L and Kumar, M}, title = {Inequity and disparities mar existing global research evidence on Long COVID.}, journal = {Global health promotion}, volume = {30}, number = {1}, pages = {63-67}, pmid = {35962520}, issn = {1757-9767}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; RNA, Viral ; SARS-CoV-2 ; Geography ; }, abstract = {Since the pandemic began in December 2019, SARS-Cov2 has accentuated the wide gap and disparities in socioeconomic and healthcare access at individual, community, country, and regional levels. More than two years into the current pandemic, up to three-fourths of the patients are reporting continued signs and symptoms beyond the acute phase of COVID-19, and Long COVID portends to be a major challenge in the future ahead. With a comprehensive overview of the literature, we found that most studies concerning long COVID came from high and upper-middle income countries, and people of low-income and lower-and-middle income regions and vulnerable groups with comorbid conditions have been neglected. Apart from the level of income, there is a significant geographical heterogeneity in investigating the Post-Acute Sequelae of COVID-19 (PASC) or what we call now, long COVID. We believe that these recognizing health disparities is crucial from equity perspective and is the first step toward global health promotion.}, }
@article {pmid35966751, year = {2022}, author = {Kim, TH and Jeon, SR and Kang, JW and Kwon, S}, title = {Complementary and Alternative Medicine for Long COVID: Scoping Review and Bibliometric Analysis.}, journal = {Evidence-based complementary and alternative medicine : eCAM}, volume = {2022}, number = {}, pages = {7303393}, pmid = {35966751}, issn = {1741-427X}, abstract = {Prolonged symptoms after the clearance of acute coronavirus disease 2019 (COVID-19) infection, termed long COVID, are an emerging threat to the post-COVID-19 era. Complementary and alternative medicine (CAM) interventions may play a significant role in the management of long COVID. The present study aimed to identify published studies on the use of CAM interventions for long COVID and provide an overview of the research status using bibliometric analysis. The present scoping review searched MEDLINE, Embase, and Cochrane Library from inception until November 2021 and identified published studies on CAM interventions for long COVID. A narrative analysis of the study types and effectiveness and safety of the CAM interventions are presented and a bibliometric analysis of citation information and references of the included publications were analyzed using the Bibliometrix package for R. An electronic database search identified 16 publications (2 clinical studies and 14 study protocols of systematic reviews or clinical studies) that were included in the present study. Dyspnea or pulmonary dysfunction, quality of life, olfactory dysfunction, and psychological symptoms after COVID-19 infection were assessed in the included publications. The two clinical studies suggested that Chinese herbal medications were effective in relieving symptoms of pulmonary dysfunction. Bibliometric analysis revealed the current trend of research publication in this area was driven by study protocols written by Chinese, Korean, and Indian authors. Thus, the present scoping review and bibliometric analysis revealed that there are few studies published about the use of CAM for long COVID and long-term management for COVID-19 survivors. Original studies on CAM interventions, including randomized controlled trials and systematic reviews, are required to actively support evidence for their use in the management of long COVID. PROSPERO registration: this trial is registered with CRD42021281526.}, }
@article {pmid35970935, year = {2023}, author = {Nathanielsz, J and Toh, ZQ and Do, LAH and Mulholland, K and Licciardi, PV}, title = {SARS-CoV-2 infection in children and implications for vaccination.}, journal = {Pediatric research}, volume = {93}, number = {5}, pages = {1177-1187}, pmid = {35970935}, issn = {1530-0447}, mesh = {Adolescent ; Adult ; Humans ; Child ; *COVID-19/prevention &amp; control/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; COVID-19 Vaccines ; Pandemics ; Vaccination ; Systemic Inflammatory Response Syndrome ; }, abstract = {The COVID-19 pandemic caused by novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for more than 500 million cases worldwide as of April 2022. Initial estimates in 2020 found that children were less likely to become infected with SARS-CoV-2 and more likely to be asymptomatic or display mild COVID-19 symptoms. Our early understanding of COVID-19 transmission and disease in children led to a range of public health measures including school closures that have indirectly impacted child health and wellbeing. The emergence of variants of concern (particularly Delta and Omicron) has raised new issues about transmissibility in children, as preliminary data suggest that children may be at increased risk of infection, especially if unvaccinated. Global national prevalence data show that SARS-CoV-2 infection in children and adolescents is rising due to COVID-19 vaccination among adults and increased circulation of Delta and Omicron variants. To mitigate this, childhood immunisation programmes are being implemented globally to prevent direct and indirect consequences of COVID-19 including severe complications (e.g., MIS-C), debilitating long-COVID symptoms, and the indirect impacts of prolonged community and school closures on childhood education, social and behavioural development and mental health. This review explores the current state of knowledge on COVID-19 in children including COVID-19 vaccination strategies. IMPACT: Provides an up-to-date account of SARS-CoV-2 infections in children. Discusses the direct and indirect effects of COVID-19 in children. Provides the latest information on the current state of global COVID-19 vaccination in children.}, }
@article {pmid35976326, year = {2022}, author = {Guedes, BF}, title = {NeuroCOVID-19: a critical review.}, journal = {Arquivos de neuro-psiquiatria}, volume = {80}, number = {5 Suppl 1}, pages = {281-289}, pmid = {35976326}, issn = {1678-4227}, mesh = {*COVID-19/complications ; Humans ; *Nervous System Diseases/diagnosis ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The COVID-19 pandemic has challenged neurologists since its early days. Neurology consultation services were then overloaded by emergency department and intensive-care patients with acute neurological syndromes. These complications are better explained today, but the growing number of patients with reported longstanding neurological symptoms constitute an emerging, complex, and still poorly understood phenomenon.<br><br>OBJECTIVE: This review summarizes data on relevant neurological manifestations of acute SARS-CoV-2 infection and lasting post-infectious disease, also known as Long COVID. The complex history of Long COVID is examined to illustrate the upsides and challenges imposed by the active participation of patient communities in the production of medical knowledge.<br><br>METHODS: Narrative review.<br><br>RESULTS: Infection with the severe acute respiratory syndrome coronavirus 2 is associated with encephalopathy/delirium, cerebrovascular disease, headache, and peripheral nervous system involvement. Long COVID is a living concept jointly defined by patient communities, physicians and scientists, including neurologists.<br><br>CONCLUSION: Co-production of Long COVID knowledge between scientists and patients has initiated an era of patient-led research and evidence-based activism that acts as a two-edged sword - putting patient's suffering in the spotlight, but with a tradeoff in methodological consistency.}, }
@article {pmid35993433, year = {2022}, author = {Singh, J and Bhagaloo, L and Sy, E and Lavoie, AJ and Dehghani, P and Bardutz, HA and Mang, CS and Buttigieg, J and Neary, JP}, title = {Cardiac impairments in postacute COVID-19 with sustained symptoms: A review of the literature and proof of concept.}, journal = {Physiological reports}, volume = {10}, number = {16}, pages = {e15430}, pmid = {35993433}, issn = {2051-817X}, mesh = {*COVID-19/complications ; Echocardiography ; Humans ; Systole ; *Ventricular Dysfunction, Right ; Post-Acute COVID-19 Syndrome ; }, abstract = {Although acute COVID-19 is known to cause cardiac damage in some cases, there is still much to learn about the duration and relative permanence of the damage that may occur. Long COVID is a condition that can occur when COVID-19 symptoms remain in the postviral acute period. Varying accounts of long COVID have been described across the literature, however, cardiac impairments are sustained in many individuals and cardiovascular assessment is now considered to be an expected follow-up examination. The purpose of this review and proof of concept is to summarize the current research related to the assessment of cardiac function, including echocardiography and blood biomarker data, during the follow-up period in patients who recovered from COVID-19. Following a literature review, it was found that right ventricular dysfunction along with global longitudinal strain and diastolic dysfunction are common findings. Finally, more severe acute myocardial injury during the index hospitalization appears to exacerbate cardiac function. The available literature implies that cardiac function must be monitored in patients recovered from COVID-19 who remain symptomatic and that the impairments and severity vary from person-to-person. The proof-of-concept analysis of patients with cardiac disease and respiratory disease in comparison to those with sustained symptoms from COVID-19 suggests elevated systolic time interval in those with sustained symptoms from COVID-19, thus reducing heart performance indices. Future research must consider the details of cardiac complications during the acute infection period and relate this to the cardiac function in patients with long COVID during mid- and long-term follow-up.}, }
@article {pmid35999605, year = {2022}, author = {Wolf, S and Zechmeister-Koss, I and Erdös, J}, title = {Possible long COVID healthcare pathways: a scoping review.}, journal = {BMC health services research}, volume = {22}, number = {1}, pages = {1076}, pmid = {35999605}, issn = {1472-6963}, mesh = {*COVID-19/complications/epidemiology ; *Coronavirus ; *Coronavirus Infections/epidemiology/therapy ; Delivery of Health Care ; Humans ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Individuals of all ages and with all degrees of severity of the coronavirus disease (COVID) can suffer from persisting or reappearing symptoms called long COVID. Long COVID involves various symptoms, such as shortness of breath, fatigue, or organ damage. The growing number of long COVID cases places a burden on the patients and the broader economy and, hence, has gained more weight in political decisions. This scoping review aimed to give an overview of recommendations about possible long COVID healthcare pathways and requirements regarding decision-making and communication for healthcare professionals.<br><br>METHODS: A systematic search in four databases and biweekly update-hand searches were conducted. In addition to guidelines and reviews, expert opinions in consensus statements or clinical perspectives were also considered. Data were systematically extracted and subsequently narratively and graphically summarised.<br><br>RESULTS: Fourteen references, five guidelines, four reviews, one consensus paper, and four clinical perspectives were included. The evidence recommended that most long COVID-related healthcare should be in primary care. Patients with complex symptoms should be referred to specialized long COVID outpatient assessment clinics. In contrast, patients with one dominant symptom should be directed to the respective specialist for a second assessment. Depending on the patients' needs, further referral options include, e.g. rehabilitation or non-medical health services. Self-management and good communication between healthcare professionals and patients are crucial aspects of the long COVID management recommendations.<br><br>CONCLUSIONS: The quality of the included guidelines and reviews is limited in the methods applied due to the novelty of this topic and the associated urgency for research. Hence, an update review with more rigorous data is recommended. Furthermore, the systematic collection of real-world data on long COVID surveillance needs to be set up soon to gather further information on the duration and severity of long COVID and thereby facilitate long COVID care planning.}, }
@article {pmid36009268, year = {2022}, author = {Muchtaridi, M and Amirah, SR and Harmonis, JA and Ikram, EHK}, title = {Role of Nuclear Factor Erythroid 2 (Nrf2) in the Recovery of Long COVID-19 Using Natural Antioxidants: A Systematic Review.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {11}, number = {8}, pages = {}, pmid = {36009268}, issn = {2076-3921}, support = {2203/UN6.3.1/PT.00/2022//Padjadjaran University/ ; }, abstract = {Coronavirus disease 2019 (COVID-19) is an infectious disease with approximately 517 million confirmed cases, with the average number of cases revealing that patients recover immediately without hospitalization. However, several other cases found that patients still experience various symptoms after 3-12 weeks, which is known as a long COVID syndrome. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can activate nuclear factor kappa beta (NF-κβ) and unbind the nuclear factor erythroid 2-related factor 2 (Nrf2) with Kelch-like ECH-associated protein 1 (Keap1), causing inhibition of Nrf2, which has an important role in antioxidant response and redox homeostasis. Disrupting the Keap1-Nrf2 pathway enhances Nrf2 activity, and has been identified as a vital approach for the prevention of oxidative stress and inflammation. Hence, natural antioxidants from various sources have been identified as a promising strategy to prevent oxidative stress, which plays a role in reducing the long COVID-19 symptoms. Oxygen-rich natural antioxidant compounds provide an effective Nrf2 activation effect that interact with the conserved amino acid residues in the Keap1-binding pocket, such as Ser602, Ser363, Ser508, and Ser555. In this review, the benefits of various natural antioxidant compounds that can modulate the Nrf2 signaling pathway, which is critical in reducing and curing long COVID-19, are highlighted and discussed.}, }
@article {pmid36010203, year = {2022}, author = {Khaswal, A and Kumar, V and Kumar, S}, title = {Long-Term Health Consequences of SARS-CoV-2: Assumptions Based on SARS-CoV-1 and MERS-CoV Infections.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {12}, number = {8}, pages = {}, pmid = {36010203}, issn = {2075-4418}, support = {K99 AG065645/AG/NIA NIH HHS/United States ; R00 AG065645/AG/NIA NIH HHS/United States ; K99AG065645/AG/NIA NIH HHS/United States ; }, abstract = {Coronavirus Disease-2019 (COVID-19) is one of the worst pandemics in the history of the world. It is the third coronavirus disease that has afflicted humans in a short span of time. The world appears to be recovering from the grasp of this deadly pandemic; still, its post-disease health effects are not clearly understood. It is evident that the vast majority of COVID-19 patients usually recovered over time; however, disease manifestation is reported to still exist in some patients even after complete recovery. The disease is known to have left irreversible damage(s) among some patients and these damages are expected to cause mild or severe degrees of health effects. Apart from the apparent damage to the lungs caused by SARS-CoV-1, MERS-CoV, and SARS-CoV-2 infection, COVID-19-surviving patients display a wide spectrum of dysfunctions in different organ systems that is similar to what occurs with SARS-CoV-1 and MERS diseases. The major long COVID-19 manifestations include the following aspects: (1) central nervous system, (2) cardiovascular, (3) pulmonary, (4) gastrointestinal, (5) hematologic, (6) renal and (7) psycho-social systems. COVID-19 has a disease display manifestation in these organs and its related systems amongst a large number of recovered cases. Our study highlights the expected bodily consequences of the pandemic caused by SARS-CoV-2 infection based on the understanding of the long-term effects of SARS-CoV-1 and MERS-CoV.}, }
@article {pmid36011562, year = {2022}, author = {Franco, JVA and Garegnani, LI and Oltra, GV and Metzendorf, MI and Trivisonno, LF and Sgarbossa, N and Ducks, D and Heldt, K and Mumm, R and Barnes, B and Scheidt-Nave, C}, title = {Long-Term Health Symptoms and Sequelae Following SARS-CoV-2 Infection: An Evidence Map.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {16}, pages = {}, pmid = {36011562}, issn = {1660-4601}, mesh = {Adolescent ; Adult ; *COVID-19/complications ; Child ; Cross-Sectional Studies ; Humans ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Post-COVID-19 conditions, also known as 'Long-COVID-19', describe a longer and more complex course of illness than acute COVID-19 with no widely accepted uniform case definition. We aimed to map the available evidence on persistent symptoms and sequelae following SARS-CoV-2 in children and adults. We searched the Cochrane COVID-19 Study Register and the WHO COVID-19 Global literature on coronavirus disease database on 5 November 2021. We included longitudinal and cross-sectional studies and we extracted their characteristics, including the type of core outcomes for post-COVID-19 conditions. We included 565 studies (657 records). Most studies were uncontrolled cohort studies. The median follow-up time was 13 weeks (IQR 9 to 24). Only 72% of studies were conducted in high-income countries, 93% included unvaccinated adults with mild-to-critical disease, only 10% included children and adolescents, and less than 5% included children under the age of five. While most studies focused on health symptoms, including respiratory symptoms (71%), neurological symptoms (57%), fatigue (54%), pain (50%), mental functioning (43%), cardiovascular functioning (40%), and post-exertion symptoms (28%), cognitive function (26%), fewer studies assessed other symptoms such as overall recovery (24%), the need for rehabilitation (18%), health-related quality of life (16%), changes in work/occupation and study (10%), or survival related to long-COVID-19 (4%). There is a need for controlled cohort studies with long-term follow-up and a focus on overall recovery, health-related quality of life, and the ability to perform daily tasks. Studies need to be extended to later phases of the pandemic and countries with low resources.}, }
@article {pmid36016309, year = {2022}, author = {Stafie, CS and Solomon, SM and Sufaru, IG and Manaila, M and Stafie, II and Melinte, G and Simionescu, B and Leustean, L}, title = {Pathogenic Connections in Post-COVID Conditions: What Do We Know in the Large Unknown? A Narrative Review.}, journal = {Viruses}, volume = {14}, number = {8}, pages = {}, pmid = {36016309}, issn = {1999-4915}, mesh = {Adult ; *COVID-19/complications/pathology ; Child ; Humans ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {The coronavirus 2019 (COVID-19) disease has long-term effects, known as post-COVID conditions (PCC) or long-COVID. Post-COVID-19 syndrome is defined by signs and symptoms that occur during or after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection which persist for more than 12 weeks and cannot be supported by an alternative diagnosis. The cardiovascular damage caused by COVID-19 in the severe forms of the disease is induced by severe systemic inflammation, considered to be one of the causes of myocardial lesions, with increased levels of circulating cytokines and toxic response mediators. We have focused on conditions that can induce long-COVID-19, or multisystem inflammatory syndrome in adults or children (MIS-C/MIS-A), with an emphasis on endocrinological and metabolic disorders. Although described less frequently in children than in adults, long-COVID syndrome should not be confused with MIS-C, which is an acute condition characterized by multisystem involvement and paraclinical evidence of inflammation in a pediatric patient who tested positive for SARS-CoV-2. At the same time, we mention that the MIS-A symptoms remit within a few weeks, while the duration of long-COVID is measured in months. Long-COVID syndrome, along with its complications, MIS-A and MIS-C, represents an important challenge in the medical community. Underlying comorbidities can expose both COVID-19 adult and pediatric patients to a higher risk of negative outcomes not only during, but in the aftermath of the SARS-CoV-2 infection as well.}, }
@article {pmid36017003, year = {2022}, author = {Curran, CS and Kopp, JB}, title = {RAGE pathway activation and function in chronic kidney disease and COVID-19.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {970423}, pmid = {36017003}, issn = {2296-858X}, abstract = {The multi-ligand receptor for advanced glycation end-products (RAGE) and its ligands are contributing factors in autoimmunity, cancers, and infectious disease. RAGE activation is increased in chronic kidney disease (CKD) and coronavirus disease 2019 (COVID-19). CKD may increase the risk of COVID-19 severity and may also develop in the form of long COVID. RAGE is expressed in essentially all kidney cell types. Increased production of RAGE isoforms and RAGE ligands during CKD and COVID-19 promotes RAGE activity. The downstream effects include cellular dysfunction, tissue injury, fibrosis, and inflammation, which in turn contribute to a decline in kidney function, hypertension, thrombotic disorders, and cognitive impairment. In this review, we discuss the forms and mechanisms of RAGE and RAGE ligands in the kidney and COVID-19. Because various small molecules antagonize RAGE activity in animal models, targeting RAGE, its co-receptors, or its ligands may offer novel therapeutic approaches to slowing or halting progressive kidney disease, for which current therapies are often inadequate.}, }
@article {pmid36030055, year = {2022}, author = {Newhouse, A and Kritzer, MD and Eryilmaz, H and Praschan, N and Camprodon, JA and Fricchione, G and Chemali, Z}, title = {Neurocircuitry Hypothesis and Clinical Experience in Treating Neuropsychiatric Symptoms of Postacute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2.}, journal = {Journal of the Academy of Consultation-Liaison Psychiatry}, volume = {63}, number = {6}, pages = {619-627}, pmid = {36030055}, issn = {2667-2960}, support = {T32 MH112485/MH/NIMH NIH HHS/United States ; }, mesh = {Humans ; SARS-CoV-2 ; *COVID-19 ; Disease Progression ; *Cognitive Dysfunction ; Memory Disorders ; }, abstract = {Persistent symptoms following COVID-19 infection have been termed postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection. Many of these symptoms are neuropsychiatric, such as inattention, impaired memory, and executive dysfunction; these are often colloquially termed "brain fog". These symptoms are common and often persist long after the acute phase. The pattern of these deficits combined with laboratory, neuroimaging, electroencephalographic, and neuropsychological data suggest that these symptoms may be driven by direct and indirect damage to the frontal-subcortical neural networks. Here, we review this evidence, share our clinical experience at an academic medical center, and discuss potential treatment implications. While the exact etiology remains unknown, a neurocircuit-informed understanding of postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection can help guide pharmacology, neuromodulation, and physical and psychological therapeutic approaches.}, }
@article {pmid36031313, year = {2022}, author = {Cavallieri, F and Sellner, J and Zedde, M and Moro, E}, title = {Neurologic complications of coronavirus and other respiratory viral infections.}, journal = {Handbook of clinical neurology}, volume = {189}, number = {}, pages = {331-358}, pmid = {36031313}, issn = {0072-9752}, mesh = {*COVID-19/complications ; Humans ; *Nervous System Diseases ; *Peripheral Nervous System Diseases ; SARS-CoV-2 ; Seizures ; Post-Acute COVID-19 Syndrome ; }, abstract = {In humans, several respiratory viruses can have neurologic implications affecting both central and peripheral nervous system. Neurologic manifestations can be linked to viral neurotropism and/or indirect effects of the infection due to endothelitis with vascular damage and ischemia, hypercoagulation state with thrombosis and hemorrhages, systemic inflammatory response, autoimmune reactions, and other damages. Among these respiratory viruses, recent and huge attention has been given to the coronaviruses, especially the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic started in 2020. Besides the common respiratory symptoms and the lung tropism of SARS-CoV-2 (COVID-19), neurologic manifestations are not rare and often present in the severe forms of the infection. The most common acute and subacute symptoms and signs include headache, fatigue, myalgia, anosmia, ageusia, sleep disturbances, whereas clinical syndromes include mainly encephalopathy, ischemic stroke, seizures, and autoimmune peripheral neuropathies. Although the pathogenetic mechanisms of COVID-19 in the various acute neurologic manifestations are partially understood, little is known about long-term consequences of the infection. These consequences concern both the so-called long-COVID (characterized by the persistence of neurological manifestations after the resolution of the acute viral phase), and the onset of new neurological symptoms that may be linked to the previous infection.}, }
@article {pmid36032234, year = {2022}, author = {Joli, J and Buck, P and Zipfel, S and Stengel, A}, title = {Post-COVID-19 fatigue: A systematic review.}, journal = {Frontiers in psychiatry}, volume = {13}, number = {}, pages = {947973}, pmid = {36032234}, issn = {1664-0640}, abstract = {UNLABELLED: Fatigue is recognized as one of the most commonly presented long-term complaints in individuals previously infected with SARS-CoV-2. This systematic review was performed to describe symptoms, etiology, possible risk factors related to post-COVID-19 fatigue and the therapeutic approaches used for the treatment of post-COVID-19 fatigue. For the systematic literature search the databases PubMed, Web of Science, Cochrane Library, and PsycInfo were used. All articles that met the inclusion criteria were analyzed for demographics, clinical data and treatment. Included were studies which focused on an adult population (18-65 years old); elderly patients and patients with chronic somatic diseases which can also cause fatigue were excluded. We identified 2,851, screened 2,193 and finally included 20 studies with moderate to high methodological quality, encompassing 5,629 participants. Potential risk factors for post-COVID-19 fatigue were old age, female sex, severe clinical status in the acute phase of infection, a high number of comorbidities, and a prediagnosis of depression/anxiety. Lastly, a possible autoimmune etiology was suspected. Several treatment approaches have been tested mostly in small and uncontrolled studies so far: a Chinese herbal formulation improved breathlessness and fatigue. Moreover, molecular hydrogen (H2) inhalation had beneficial health effects in terms of improved physical (6-min walking test) and respiratory function in patients with post-COVID-19. Patients also noticed improvement in fatigue after undergoing hyperbaric oxygen therapy (HBOT) and enhanced external counterpulsation (EECP). Lastly. muscle strength and physical function were improved after undergoing an 8-weeks biweekly physical therapy course including aerobic training, strengthening exercises, diaphragmatic breathing techniques, and mindfulness training. However, larger and controlled studies e.g., investigating the effect of physical and / or psychotherapy for patients with post-COVID-19 fatigue are urgently warranted.<br><br>Unique Identifier: CRD42022320676, https://www.crd.york.ac.uk/PROSPERO/.}, }
@article {pmid36033820, year = {2022}, author = {Smith, CJ and Renshaw, P and Yurgelun-Todd, D and Sheth, C}, title = {Acute and chronic neuropsychiatric symptoms in novel coronavirus disease 2019 (COVID-19) patients: A qualitative review.}, journal = {Frontiers in public health}, volume = {10}, number = {}, pages = {772335}, pmid = {36033820}, issn = {2296-2565}, mesh = {Anxiety ; *COVID-19 ; Humans ; Pandemics ; SARS-CoV-2 ; *Stress Disorders, Post-Traumatic ; }, abstract = {The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared a global pandemic by the World Health Organization (WHO) on March 11th, 2020. It has had unprecedented adverse effects on healthcare systems, economies, and societies globally. SARS-CoV-2 is not only a threat to physical health but has also been shown to have a severe impact on neuropsychiatric health. Many studies and case reports across countries have demonstrated insomnia, depressed mood, anxiety, post-traumatic stress disorder (PTSD), and cognitive change in COVID-19 patients during the acute phase of the infection, as well as in apparently recovered COVID-19 patients. The goal of this narrative review is to synthesize and summarize the emerging literature detailing the neuropsychiatric manifestations of COVID-19 with special emphasis on the long-term implications of COVID-19.}, }
@article {pmid36039714, year = {2022}, author = {Abrignani, MG and Maloberti, A and Temporelli, PL and Binaghi, G and Cesaro, A and Ciccirillo, F and Oliva, F and Gabrielli, D and Riccio, C and Gulizia, MM and Colivicchi, F}, title = {[Long COVID: nosographic aspects and clinical epidemiology].}, journal = {Giornale italiano di cardiologia (2006)}, volume = {23}, number = {9}, pages = {651-662}, doi = {10.1714/3860.38447}, pmid = {36039714}, issn = {1972-6481}, mesh = {*COVID-19/complications/epidemiology/physiopathology/psychology ; Humans ; Quality of Life ; Risk Factors ; SARS-CoV-2/pathogenicity ; Survivors ; Post-Acute COVID-19 Syndrome ; }, abstract = {Recent evidence shows that a range of persistent or new symptoms can manifest after 4-12 weeks in a subset of patients who have recovered from acute SARS-CoV-2 infection, and this condition has been coined long COVID by COVID-19 survivors among social support groups. Long COVID can affect the whole spectrum of people with COVID-19, from those with very mild acute disease to the most severe forms. Like the acute form, long COVID has multisystemic aspects. Patients can manifest with a very heterogeneous multitude of symptoms, including fatigue, post-exertional malaise, dyspnea, cognitive impairment, sleep disturbances, anxiety and depression, muscle pain, brain fog, anosmia/dysgeusia, headache, and limitation of functional capacity, which impact their quality of life. Because of the extreme clinical heterogeneity, and also due to the lack of a shared, specific definition, it is very difficult to know the real prevalence and incidence of this condition. Risk factors for developing long COVID would be female sex, initial severity, and comorbidities. Globally, with the re-emergence of new waves, the population of people infected with SARS-CoV-2 continues to expand rapidly, necessitating a more thorough understanding of potential sequelae of COVID-19. This review summarizes up to date definitions and epidemiological aspects of long COVID.}, }
@article {pmid36041287, year = {2022}, author = {Hool, LC}, title = {Elucidating the role of the L-type calcium channel in excitability and energetics in the heart: The ISHR 2020 Research Achievement Award Lecture.}, journal = {Journal of molecular and cellular cardiology}, volume = {172}, number = {}, pages = {100-108}, doi = {10.1016/j.yjmcc.2022.08.001}, pmid = {36041287}, issn = {1095-8584}, mesh = {Animals ; Humans ; Calcium/metabolism ; *Calcium Channels, L-Type/physiology ; *Cardiomyopathies/metabolism ; COVID-19 ; Diabetes Mellitus, Type 2/metabolism ; Hypertrophy/metabolism ; Myocytes, Cardiac/metabolism ; Post-Acute COVID-19 Syndrome ; }, abstract = {Cardiovascular disease continues to be the leading health burden worldwide and with the rising rates in obesity and type II diabetes and ongoing effects of long COVID, it is anticipated that the burden of cardiovascular morbidity and mortality will increase. Calcium is essential to cardiac excitation and contraction. The main route for Ca[2+] influx is the L-type Ca[2+] channel (Cav1.2) and embryos that are homozygous null for the Cav1.2 gene are lethal at day 14 postcoitum. Acute changes in Ca[2+] influx through the channel contribute to arrhythmia and sudden death, and chronic increases in intracellular Ca[2+] contribute to pathological hypertrophy and heart failure. We use a multidisciplinary approach to study the regulation of the channel from the molecular level through to in vivo CRISPR mutant animal models. Here we describe some examples of our work from over 2 decades studying the role of the channel under physiological and pathological conditions. Our single channel analysis of purified human Cav1.2 protein in proteoliposomes has contributed to understanding direct molecular regulation of the channel including identifying the critical serine involved in the "fight or flight" response. Using the same approach we identified the cysteine responsible for altered function during oxidative stress. Chronic activation of the L-type Ca[2+] channel during oxidative stress occurs as a result of persistent glutathionylation of the channel that contributes to the development of hypertrophy. We describe for the first time that activation of the channel alters mitochondrial function (and energetics) on a beat-to-beat basis via movement of cytoskeletal proteins. In translational studies we have used this response to "report" mitochondrial function in models of cardiomyopathy and to test efficacy of novel therapies to prevent cardiomyopathy.}, }
@article {pmid36043493, year = {2022}, author = {Kell, DB and Pretorius, E}, title = {The potential role of ischaemia-reperfusion injury in chronic, relapsing diseases such as rheumatoid arthritis, Long COVID, and ME/CFS: evidence, mechanisms, and therapeutic implications.}, journal = {The Biochemical journal}, volume = {479}, number = {16}, pages = {1653-1708}, pmid = {36043493}, issn = {1470-8728}, mesh = {*Arthritis, Rheumatoid/therapy ; *COVID-19/complications ; *Fatigue Syndrome, Chronic/metabolism ; Humans ; Oxidative Stress/physiology ; *Reperfusion Injury/therapy ; Post-Acute COVID-19 Syndrome ; }, abstract = {Ischaemia-reperfusion (I-R) injury, initiated via bursts of reactive oxygen species produced during the reoxygenation phase following hypoxia, is well known in a variety of acute circumstances. We argue here that I-R injury also underpins elements of the pathology of a variety of chronic, inflammatory diseases, including rheumatoid arthritis, ME/CFS and, our chief focus and most proximally, Long COVID. Ischaemia may be initiated via fibrin amyloid microclot blockage of capillaries, for instance as exercise is started; reperfusion is a necessary corollary when it finishes. We rehearse the mechanistic evidence for these occurrences here, in terms of their manifestation as oxidative stress, hyperinflammation, mast cell activation, the production of marker metabolites and related activities. Such microclot-based phenomena can explain both the breathlessness/fatigue and the post-exertional malaise that may be observed in these conditions, as well as many other observables. The recognition of these processes implies, mechanistically, that therapeutic benefit is potentially to be had from antioxidants, from anti-inflammatories, from iron chelators, and via suitable, safe fibrinolytics, and/or anti-clotting agents. We review the considerable existing evidence that is consistent with this, and with the biochemical mechanisms involved.}, }
@article {pmid36053670, year = {2023}, author = {Chang, X and Ismail, NI and Rahman, A and Xu, D and Chan, RWY and Ong, SG and Ong, SB}, title = {Long COVID-19 and the Heart: Is Cardiac Mitochondria the Missing Link?.}, journal = {Antioxidants &amp; redox signaling}, volume = {38}, number = {7-9}, pages = {599-618}, pmid = {36053670}, issn = {1557-7716}, support = {K99 HL130416/HL/NHLBI NIH HHS/United States ; R00 HL130416/HL/NHLBI NIH HHS/United States ; R01 HL148756/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Cardiovascular Diseases/etiology ; *Heart Diseases ; *Myocarditis/complications/therapy ; Mitochondria ; }, abstract = {Significance: Although corona virus disease 2019 (COVID-19) has now gradually been categorized as an endemic, the long-term effect of COVID-19 in causing multiorgan disorders, including a perturbed cardiovascular system, is beginning to gain attention. Nonetheless, the underlying mechanism triggering post-COVID-19 cardiovascular dysfunction remains enigmatic. Are cardiac mitochondria the key to mediating cardiac dysfunction post-severe acute respiratory syndrome coronavirus 2 (post-SARS-CoV-2) infection? Recent Advances: Cardiovascular complications post-SARS-CoV-2 infection include myocarditis, myocardial injury, microvascular injury, pericarditis, acute coronary syndrome, and arrhythmias (fast or slow). Different types of myocardial damage or reduced heart function can occur after a lung infection or lung injury. Myocardial/coronary injury or decreased cardiac function is directly associated with increased mortality after hospital discharge in patients with COVID-19. The incidence of adverse cardiovascular events increases even in recovered COVID-19 patients. Disrupted cardiac mitochondria postinfection have been postulated to lead to cardiovascular dysfunction in the COVID-19 patients. Further studies are crucial to unravel the association between SARS-CoV-2 infection, mitochondrial dysfunction, and ensuing cardiovascular disorders (CVD). Critical Issues: The relationship between COVID-19 and myocardial injury or cardiovascular dysfunction has not been elucidated. In particular, the role of the cardiac mitochondria in this association remains to be determined. Future Directions: Elucidating the cause of cardiac mitochondrial dysfunction post-SARS-CoV-2 infection may allow a deeper understanding of long COVID-19 and resulting CVD, thus providing a potential therapeutic target. Antioxid. Redox Signal. 38, 599-618.}, }
@article {pmid36066294, year = {2022}, author = {Mangion, K and Berry, C}, title = {Multisystem involvement in COVID-19: what have we learnt?.}, journal = {British journal of hospital medicine (London, England : 2005)}, volume = {83}, number = {8}, pages = {1-5}, doi = {10.12968/hmed.2022.0290}, pmid = {36066294}, issn = {1759-7390}, mesh = {*COVID-19/complications ; Heart ; Humans ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The COVID-19 illness trajectory involves persistent cardio-renal inflammation, activation of the haemostatic pathway and lung involvement. Results of a study carried out by the authors' team demonstrate a link between post-COVID-19 syndrome (people who have long COVID) and multisystem disease, which partly explains the lingering impairments in patient-reported health-related quality of life, physical function and psychological wellbeing after COVID-19. This article discusses what hospital physicians need to be aware of when considering the likelihood of myocarditis in patients with post-COVID-19 syndrome and the implications in the longer term.}, }
@article {pmid36070309, year = {2022}, author = {Jansen, EB and Orvold, SN and Swan, CL and Yourkowski, A and Thivierge, BM and Francis, ME and Ge, A and Rioux, M and Darbellay, J and Howland, JG and Kelvin, AA}, title = {After the virus has cleared-Can preclinical models be employed for Long COVID research?.}, journal = {PLoS pathogens}, volume = {18}, number = {9}, pages = {e1010741}, pmid = {36070309}, issn = {1553-7374}, support = {OV5-170349//CIHR/Canada ; VRI-172779//CIHR/Canada ; OV2- 170357//CIHR/Canada ; }, mesh = {Animals ; *COVID-19/complications ; Cricetinae ; Ferrets ; Humans ; Mesocricetus ; Mice ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) can cause the life-threatening acute respiratory disease called COVID-19 (Coronavirus Disease 2019) as well as debilitating multiorgan dysfunction that persists after the initial viral phase has resolved. Long COVID or Post-Acute Sequelae of COVID-19 (PASC) is manifested by a variety of symptoms, including fatigue, dyspnea, arthralgia, myalgia, heart palpitations, and memory issues sometimes affecting between 30% and 75% of recovering COVID-19 patients. However, little is known about the mechanisms causing Long COVID and there are no widely accepted treatments or therapeutics. After introducing the clinical aspects of acute COVID-19 and Long COVID in humans, we summarize the work in animals (mice, Syrian hamsters, ferrets, and nonhuman primates (NHPs)) to model human COVID-19. The virology, pathology, immune responses, and multiorgan involvement are explored. Additionally, any studies investigating time points longer than 14 days post infection (pi) are highlighted for insight into possible long-term disease characteristics. Finally, we discuss how the models can be leveraged for treatment evaluation, including pharmacological agents that are currently in human clinical trials for treating Long COVID. The establishment of a recognized Long COVID preclinical model representing the human condition would allow the identification of mechanisms causing disease as well as serve as a vehicle for evaluating potential therapeutics.}, }
@article {pmid36071155, year = {2022}, author = {Mantovani, A and Morrone, MC and Patrono, C and Santoro, MG and Schiaffino, S and Remuzzi, G and Bussolati, G and , }, title = {Long Covid: where we stand and challenges ahead.}, journal = {Cell death and differentiation}, volume = {29}, number = {10}, pages = {1891-1900}, pmid = {36071155}, issn = {1476-5403}, mesh = {*COVID-19/complications ; Humans ; Lung/pathology ; SARS-CoV-2 ; Vaccination ; Post-Acute COVID-19 Syndrome ; }, abstract = {Post-acute sequelae of SARS-CoV-2 (PASC), also known as Post-Covid Syndrome, and colloquially as Long Covid, has been defined as a constellation of signs and symptoms which persist for weeks or months after the initial SARS-CoV-2 infection. PASC affects a wide range of diverse organs and systems, with manifestations involving lungs, brain, the cardiovascular system and other organs such as kidney and the neuromuscular system. The pathogenesis of PASC is complex and multifactorial. Evidence suggests that seeding and persistence of SARS-CoV-2 in different organs, reactivation, and response to unrelated viruses such as EBV, autoimmunity, and uncontrolled inflammation are major drivers of PASC. The relative importance of pathogenetic pathways may differ in different tissue and organ contexts. Evidence suggests that vaccination, in addition to protecting against disease, reduces PASC after breakthrough infection although its actual impact remains to be defined. PASC represents a formidable challenge for health care systems and dissecting pathogenetic mechanisms may pave the way to targeted preventive and therapeutic approaches.}, }
@article {pmid36072173, year = {2022}, author = {Dale, L}, title = {Neurological Complications of COVID-19: A Review of the Literature.}, journal = {Cureus}, volume = {14}, number = {8}, pages = {e27633}, pmid = {36072173}, issn = {2168-8184}, abstract = {Coronavirus disease 2019 (COVID-19) has caused the most unprecedented health crisis since the 1918 H1N1 pandemic. Whilst COVID-19 is traditionally considered to be a respiratory disease, it is important to understand that this virus has the potential to disseminate throughout the body causing multi-organ failure. Both peripheral and central neurological systems have been shown to be greatly affected. This review aims to look at the available literature published on COVID-19 and summarize the main neurological complications seen so far.}, }
@article {pmid36074666, year = {2022}, author = {Popescu, M and Terzea, DC and Carsote, M and Ghenea, AE and Costache, A and Popescu, IAS and Biciuşcă, V and Busuioc, CJ and Ghemigian, AM}, title = {COVID-19 infection: from stress-related cortisol levels to adrenal glands infarction.}, journal = {Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie}, volume = {63}, number = {1}, pages = {39-48}, pmid = {36074666}, issn = {2066-8279}, mesh = {Adrenal Glands ; *Adrenal Insufficiency/complications ; *COVID-19/complications ; Glucocorticoids ; Hemorrhage/complications ; Humans ; Hydrocortisone ; Infarction/complications ; Necrosis/complications ; Retrospective Studies ; *Thrombosis/complications ; Post-Acute COVID-19 Syndrome ; }, abstract = {Cortisol is a key element in acute stress including a severe infection. However, in coronavirus-associated disease, 20% of subjects experience hypocortisolemia due to direct or immune damage of pituitary and adrenal glands. One extreme form of adrenal insufficiency is found in 2∕3 of cases with viral and post-viral adrenal infarction (AI) (with∕without adrenal hemorrhage) that is mostly associated with a severe coronavirus disease 2019 (COVID-19) infection; it requires prompt glucocorticoid intervention. Some reports are incidental findings at computed tomography (CT)∕magnetic resonance imaging (MRI) scans for non-adrenal complications like pulmonary spreading and others are seen on post-mortem analysis. This is a review of PubMed-accessible, English papers focusing on AI in addition to the infection, between March 1, 2020 and November 1, 2021. Exclusion criteria were acute adrenal insufficiency without the histopathological (HP) and∕or imaging report of adrenal enlargement, necrosis, etc., respective adrenal failure due to pituitary causes, or non-COVID-19-related adrenal events. We identified a total of 84 patients (different levels of statistical evidence), as follows: a retrospective study on 51 individuals, two post-mortem studies comprising nine, respectively 12 patients, a case series of five subjects, seven single-case reports. HP aspects include necrosis associated with ischemia, cortical lipid degeneration (+/- focal adrenalitis), and infarcts at the level of adrenal cortex, blood clot into vessels, acute fibrinoid necrosis in arterioles and capsules, as well as subendothelial vacuolization. Collateral potential contributors to adrenal damage are thrombotic events, coagulation anomalies, antiphospholipid syndrome, endothelial dysfunction, severe COVID-19 infection with multiorgan failure, etc. Clinical picture is variable from acute primary adrenal insufficiency to asymptomatic or mild evolution, even a retrospective diagnostic; it may be a part of long COVID-19 syndrome; glucocorticoid therapy for non-adrenal considerations might mask cortisol deficient status due to AI∕hemorrhage. Despite its rarity, the COVID-19-associated AI/hemorrhage represents a challenging new chapter, a condition that is essential to be recognized due to its gravity since prompt intervention with glucocorticoid replacement is lifesaving.}, }
@article {pmid36079751, year = {2022}, author = {Rossi, AP and Muollo, V and Dalla Valle, Z and Urbani, S and Pellegrini, M and El Ghoch, M and Mazzali, G}, title = {The Role of Obesity, Body Composition, and Nutrition in COVID-19 Pandemia: A Narrative Review.}, journal = {Nutrients}, volume = {14}, number = {17}, pages = {}, pmid = {36079751}, issn = {2072-6643}, mesh = {Body Composition ; *COVID-19/complications ; Hospitalization ; Humans ; Nutritional Status ; Obesity/complications/epidemiology/therapy ; *Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic has spread worldwide, infecting nearly 500 million people, with more than 6 million deaths recorded globally. Obesity leads people to be more vulnerable, developing worse outcomes that can require hospitalization in intensive care units (ICU). This review focused on the available findings that investigated the link between COVID-19, body composition, and nutritional status. Most studies showed that not only body fat quantity but also its distribution seems to play a crucial role in COVID-19 severity. Compared to the body mass index (BMI), visceral adipose tissue and intrathoracic fat are better predictors of COVID-19 severity and indicate the need for hospitalization in ICU and invasive mechanical ventilation. High volumes of epicardial adipose tissue and its thickness can cause an infection located in the myocardial tissue, thereby enhancing severe COVID-related myocardial damage with impairments in coronary flow reserve and thromboembolism. Other important components such as sarcopenia and intermuscular fat augment the vulnerability in contracting COVID-19 and increase mortality, inflammation, and muscle damage. Malnutrition is prevalent in this population, but a lack of knowledge remains regarding the beneficial effects aimed at optimizing nutritional status to limit catabolism and preserve muscle mass. Finally, with the increase in patients recovering from COVID-19, evaluation and treatment in those with Long COVID syndrome may become highly relevant.}, }
@article {pmid36090762, year = {2022}, author = {Abraham, S and Manohar, SA and Patel, R and Saji, AM and Dani, SS and Ganatra, S}, title = {Strategies for Cardio-Oncology Care During the COVID-19 Pandemic.}, journal = {Current treatment options in cardiovascular medicine}, volume = {24}, number = {8}, pages = {137-153}, pmid = {36090762}, issn = {1092-8464}, abstract = {PURPOSE OF REVIEW: The COVID-19 pandemic has disrupted healthcare and has disproportionately affected the marginalized populations. Patients with cancer and cardiovascular disease (cardio-oncology population) are uniquely affected. In this review, we explore the current data on COVID-19 vulnerability and outcomes in these patients and discuss strategies for cardio-oncology care with a focus on healthcare innovation, health equity, and inclusion.<br><br>RECENT FINDINGS: The growing evidence suggest increased morbidity and mortality from COVID-19 in patients with comorbid cancer and cardiovascular disease. Additionally, de novo cardiovascular complications such as myocarditis, myocardial infarction, arrhythmia, heart failure, and thromboembolic events have increasingly emerged, possibly due to an accentuated host immune response and cytokine release syndrome.<br><br>SUMMARY: Patient-centric policies are helpful for cardio-oncology surveillance like remote monitoring, increased use of biomarker-based surveillance, imaging modalities like CT scan, and point-of-care ultrasound to minimize the exposure for high-risk patients. Abundant prior experience in cancer therapy scaffolded the repurposed use of corticosteroids, IL-6 inhibitors, and Janus kinase inhibitors in the treatment of COVID-19 infection. COVID-19 vaccine timing and dose frequency present a challenge due to overlapping toxicities and immune cell depletion in patients receiving cancer therapies. The SARS-CoV-2 pandemic laid bare social and ethnic disparities in healthcare but also steered in innovation to combat problems of patient outreach, particularly with virtual care. In the recovery phase, the backlog in cardio-oncology care, interplay of cancer therapy-related side effects, and long COVID-19 syndrome are crucial issues to address.}, }
@article {pmid36091707, year = {2022}, author = {Trott, M and Driscoll, R and Pardhan, S}, title = {The prevalence of sensory changes in post-COVID syndrome: A systematic review and meta-analysis.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {980253}, pmid = {36091707}, issn = {2296-858X}, abstract = {UNLABELLED: Post-COVID syndrome can be defined as symptoms of COVID-19 that persist for longer than 12 weeks, with several studies reporting persistent symptoms relating to the sensory organs (eyes, ears, and nose). The aim of this systematic review was to examine the prevalence of persistent anosmia, hyposmia, ageusia, and hypogeusia, as well as eye/vision and ear/hearing related long-COVID symptoms. Authors searched the electronic databases from inception to November 2021. Search terms included words related to long-COVID, smell, taste, eyes/vision, and ears/hearing, with all observational study designs being included. A random effects meta-analysis was undertaken, calculating the prevalence proportions of anosmia, hyposmia, ageusia, and hypogeusia, respectively. From the initial pool, 21 studies met the inclusion criteria (total n 4,707; median n per study 125; median age = 49.8; median percentage female = 59.2%) and 14 were included in the meta-analysis The prevalence of anosmia was 12.2% (95% CI 7.7-16.6%), hyposmia 29.9% (95% CI 19.9-40%), ageusia 11.7% (95% CI 6.1-17.3%), and hypogeusia 31.2% (95% 16.4-46.1%). Several eye/vision and ear/hearing symptoms were also reported. Considering that changes in the sensory organs are associated with decreases in quality of life, future research should examine the etiology behind the persistent symptoms.<br><br>[www.crd.york.ac.uk/prospero], identifier [CRD42021292804].}, }
@article {pmid36098262, year = {2022}, author = {Stephenson, T and Shafran, R and Ladhani, SN}, title = {Long COVID in children and adolescents.}, journal = {Current opinion in infectious diseases}, volume = {35}, number = {5}, pages = {461-467}, pmid = {36098262}, issn = {1473-6527}, support = {/DH_/Department of Health/United Kingdom ; }, mesh = {*COVID-19/complications/epidemiology ; Female ; Humans ; Mental Health ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE OF REVIEW: Although acute COVID-19 has been milder in children and young people compared with adults, there is a concern that they may suffer persistent symptoms. There is a need to define the clinical phenotype, determine those most at risk, the natural course of the condition and evaluate preventive and therapeutic strategies for both mental health and physical symptoms.<br><br>RECENT FINDINGS: More recent studies with control groups reported a lower prevalence of persistent symptoms in children and young people exposed to SARS-CoV-2. A systematic review and meta-analysis found that the frequency of the majority of reported persistent symptoms is similar in SARS-CoV-2 positive cases and controls. Children and young people infected with SARS-COV-2 had small but significant increases in persisting cognitive difficulties, headache and loss of smell. Factors associated with persisting, impairing symptoms include increased number of symptoms at the time of testing, female sex, older age, worse self-rated physical and mental health, and feelings of loneliness preinfection.<br><br>SUMMARY: This review highlights the importance of a control group in studies following SARS-CoV-2 infection, the need for case definitions and research to understand the outcomes of long COVID in children and young people.}, }
@article {pmid36100326, year = {2022}, author = {Sukocheva, OA and Maksoud, R and Beeraka, NM and Madhunapantula, SV and Sinelnikov, M and Nikolenko, VN and Neganova, ME and Klochkov, SG and Amjad Kamal, M and Staines, DR and Marshall-Gradisnik, S}, title = {Analysis of post COVID-19 condition and its overlap with myalgic encephalomyelitis/chronic fatigue syndrome.}, journal = {Journal of advanced research}, volume = {40}, number = {}, pages = {179-196}, pmid = {36100326}, issn = {2090-1224}, mesh = {*COVID-19/complications ; *Fatigue Syndrome, Chronic ; Humans ; SARS-CoV-2 ; Tumor Necrosis Factor-alpha ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) disease (COVID-19) triggers the development of numerous pathologies and infection-linked complications and exacerbates existing pathologies in nearly all body systems. Aside from the primarily targeted respiratory organs, adverse SARS-CoV-2 effects were observed in nervous, cardiovascular, gastrointestinal/metabolic, immune, and other systems in COVID-19 survivors. Long-term effects of this viral infection have been recently observed and represent distressing sequelae recognised by the World Health Organisation (WHO) as a distinct clinical entity defined as post-COVID-19 condition. Considering the pandemic is still ongoing, more time is required to confirm post COVID-19 condition diagnosis in the COVID-19 infected cohorts, although many reported post COVID-19 symptoms overlap with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).<br><br>AIMS OF REVIEW: In this study, COVID-19 clinical presentation and associated post-infection sequelae (post-COVID-19 condition) were reviewed and compared with ME/CFS symptomatology.<br><br>The onset, progression, and symptom profile of post COVID-19 condition patients have considerable overlap with ME/CFS. Considering the large scope and range of pro-inflammatory effects of this virus, it is reasonable to expect development of post COVID-19 clinical complications in a proportion of the affected population. There are reports of a later debilitating syndrome onset three months post COVID-19 infection (often described as long-COVID-19), marked by the presence of fatigue, headache, cognitive dysfunction, post-exertional malaise, orthostatic intolerance, and dyspnoea. Acute inflammation, oxidative stress, and increased levels of interleukin-6 (IL-6) and tumor necrosis factor &#x3b1; (TNF&#x3b1;), have been reported in SARS-CoV-2 infected patients. Longitudinal monitoring of post COVID-19 patients is warranted to understand the long-term effects of SARS-CoV-2 infection and the pathomechanism of post COVID-19 condition.}, }
@article {pmid36103031, year = {2023}, author = {Picone, P and Sanfilippo, T and Guggino, R and Scalisi, L and Monastero, R and Baschi, R and Mandalà, V and San Biagio, L and Rizzo, M and Giacomazza, D and Dispenza, C and Nuzzo, D}, title = {Neurological Consequences, Mental Health, Physical Care, and Appropriate Nutrition in Long-COVID-19.}, journal = {Cellular and molecular neurobiology}, volume = {43}, number = {5}, pages = {1685-1695}, pmid = {36103031}, issn = {1573-6830}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Mental Health ; Post-Acute COVID-19 Syndrome ; Pandemics ; }, abstract = {SARS-CoV-2 pandemic has caused a collapse of the world health systems. Now, vaccines and more effective therapies have reversed this crisis but the scenario is further aggravated by the appearance of a new pathology, occurring as SARS-CoV-2 infection consequence: the long-COVID-19. This term is commonly used to describe signs and symptoms that continue or develop after acute infection of COVID-19 up to several months. In this review, the consequences of the disease on mental health and the neurological implications due to the long-COVID are described. Furthermore, the appropriate nutritional approach and some recommendations to relieve the symptoms of the pathology are presented. Data collected indicated that in the next future the disease will affect an increasing number of individuals and that interdisciplinary action is needed to counteract it.}, }
@article {pmid36107254, year = {2022}, author = {Pellegrino, R and Chiappini, E and Licari, A and Galli, L and Marseglia, GL}, title = {Prevalence and clinical presentation of long COVID in children: a systematic review.}, journal = {European journal of pediatrics}, volume = {181}, number = {12}, pages = {3995-4009}, pmid = {36107254}, issn = {1432-1076}, mesh = {Child ; Adolescent ; Humans ; Female ; *COVID-19/epidemiology ; SARS-CoV-2 ; Prevalence ; Cross-Sectional Studies ; Communicable Disease Control ; Post-Acute COVID-19 Syndrome ; }, abstract = {UNLABELLED: A systematic literature review was conducted up to 15th February 2022 to summarize long COVID evidence and to assess prevalence and clinical presentation in children and adolescents. Articles reporting long COVID prevalence and symptoms based on original data in the paediatric population were included. Case series quality was assessed through the JBI Critical Appraisal Checklist. For observational studies, adherence to STROBE checklist was evaluated. Twenty-two articles were included: 19 observational studies (12 cohort/7 cross-sectional) and 3 case series. Nine studies provided a control group. We found a high variability in terms of prevalence (1.6-70%). The most frequently reported symptoms were fatigue (2-87%), headache (3.5-80%), arthro-myalgias (5.4-66%), chest tightness or pain (1.4-51%), and dyspnoea (2-57.1%). Five studies reported limitations in daily function due to long COVID. Alterations at brain imaging were described in one study, transient electrocardiographic abnormalities were described in a minority of children, while most authors did not evidence long-term pulmonary sequelae. Older age, female sex, and previous long-term pathological conditions were more frequently associated with persistent symptoms.<br><br>CONCLUSION: Long COVID evidence in children is limited, heterogeneous, and based on low-quality studies. The lockdown consequences are difficult to distinguish from long COVID symptoms. High-quality studies are required: WHO definition of long COVID should be used, controlled clinical studies should be encouraged, and the impact of new variants on long COVID prevalence should be investigated to ensure an objective analysis of long COVID characteristics in children and a proper allocation of healthcare system resources.<br><br>WHAT IS KNOWN: &#x2022; Children rarely develop a severe respiratory disease in the acute phase of COVID-19. &#x2022; A limited number of patients develop a multisystem inflammatory condition that can lead to multiorgan failure and shock.<br><br>WHAT IS NEW: &#x2022; Persistent symptoms after SARS-CoV-2 infection are reported in children&#xa0;and limitations in daily function due to long COVID symptoms affect school attendance. &#x2022; Functional complaints of post-acute COVID are difficult to be distinguished from those due to social restrictions.}, }
@article {pmid36108666, year = {2024}, author = {Llana, T and Zorzo, C and Mendez-Lopez, M and Mendez, M}, title = {Memory alterations after COVID-19 infection: a systematic review.}, journal = {Applied neuropsychology. Adult}, volume = {31}, number = {3}, pages = {292-305}, doi = {10.1080/23279095.2022.2123739}, pmid = {36108666}, issn = {2327-9109}, mesh = {Humans ; *COVID-19/complications ; *Memory Disorders/etiology ; Neuropsychological Tests ; }, abstract = {SARS-CoV-2 infection has a wide range of both acute and long-term symptoms. Memory alterations have been frequently reported in studies that explore cognition. The main objective of the systematic review is to update and further analyze the existing evidence of objective memory impairments in long-COVID-19 considering sample and study design characteristics, as well as to explore associations between memory performance and their epidemiological, clinical, and pathological features. A total of 13 studies were identified by searching in PubMed, Web of Science, and PsycInfo databases up to May 6, 2022. Most studies evaluated verbal component of memory in the short-term and long-term recall up to 30 min and mainly performed a single assessment completed at 4-6 months after the infection. The samples mainly consisted of middle-aged adults that required hospitalization. Samples were not stratified by sex, age, and severity. Poor verbal learning was reported in most cases (6-58%), followed by deficits in long-term (4-58%) and short-term (4-37%) verbal memory. Visuospatial component of memory was studied less than verbal component, showing impairment of long-term retention of visual items (10-49%). COVID-19 severity in the acute stage was not systematically associated with poor memory performance. Verbal memory deficits were associated with anxiety and depression. The existing literature on objective memory assessment in long-COVID suggests further research is warranted to confirm memory dysfunction in association with epidemiological, pathological, and clinical factors, using both verbal and visuospatial tests, and exploring in deep long-term memory deficits.}, }
@article {pmid36109264, year = {2022}, author = {Alghamdi, F and Owen, R and Ashton, REM and Obotiba, AD and Meertens, RM and Hyde, E and Faghy, MA and Knapp, KM and Rogers, P and Strain, WD}, title = {Post-acute COVID syndrome (long COVID): What should radiographers know and the potential impact for imaging services.}, journal = {Radiography (London, England : 1995)}, volume = {28 Suppl 1}, number = {}, pages = {S93-S99}, pmid = {36109264}, issn = {1532-2831}, mesh = {*COVID-19/complications/diagnostic imaging ; Humans ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: The COVID-19 pandemic caused an unprecedented health crisis resulting in over 6 million deaths worldwide, a figure, which continues to grow. In addition to the excess mortality, there are individuals who recovered from the acute stages, but suffered long-term changes in their health post COVID-19, commonly referred to as long COVID. It is estimated there are currently 1.8 million long COVID sufferers by May 2022 in the UK alone. The aim of this narrative literature review is to explore the signs, symptoms and diagnosis of long COVID and the potential impact on imaging services.<br><br>KEY FINDINGS: Long COVID is estimated to occur in 9.5% of those with two doses of vaccination and 14.6% if those with a single dose or no vaccination. Long COVID is defined by ongoing symptoms lasting for 12 or more weeks post acute infection. Symptoms are associated with reductions in the quality of daily life and may involve multisystem manifestations or present as a single symptom.<br><br>CONCLUSION: The full impact of long COVID on imaging services is yet to be realised, but there is likely to be significant increased demand for imaging, particularly in CT for the assessment of lung disease. Educators will need to include aspects related to long COVID pathophysiology and imaging presentations in curricula, underpinned by the rapidly evolving evidence base.<br><br>IMPLICATIONS FOR PRACTICE: Symptoms relating to long COVID are likely to become a common reason for imaging, with a particular burden on Computed Tomography services. Planning, education and updating protocols in line with a rapidly emerging evidence base is going to be essential.}, }
@article {pmid36120804, year = {2022}, author = {Lee, J and Kwon, KH}, title = {Future perspective safe cosmetics: Focused on associated with ISO natural organic index.}, journal = {Journal of cosmetic dermatology}, volume = {21}, number = {12}, pages = {6619-6627}, doi = {10.1111/jocd.15398}, pmid = {36120804}, issn = {1473-2165}, mesh = {Humans ; *COVID-19/epidemiology/prevention &amp; control ; *Cosmetics/adverse effects ; Skin ; }, abstract = {BACKGROUND: As we enter the era of long COVID, recent studies on the relationship between coronavirus disease-19 (COVID-19) and skin are being conducted from various angles. Awareness of the safety of healthy skin is increasing.<br><br>OBJECTIVES: Therefore, in this study, we empirically analyzed safe cosmetics, natural cosmetics, and organic cosmetics, which have recently become a critical issue.<br><br>METHODS: Keywords such as 'long COVID', 'COVID-19 Skin', 'ISO Natural Organic Index', 'edible', 'safe cosmetics', 'natural cosmetics', and 'organic cosmetics' were searched and created. This study was conducted using PubMed, Google Scholar, Riss, Scopus, and ResearchGate. Accordingly, a total of 689 papers were studied. This paper was successfully completed using a total of 41 references in this study using PRISMA flow diagram.<br><br>RESULTS: In the long COVID era, customers in the beauty and cosmetics market will have to apply ISO natural organic ingredients to the cosmetics and beauty industry, reflecting consumer demand for edible ingredients for safety issues. Therefore, it will be able to provide new strategy and implications for a safer cosmetic market that values health and beauty.<br><br>CONCLUSION: Therefore, in this literature review, interest in skin has increased due to the long corona, and it was determined that changes in the cosmetic market would be necessary by using the ISO natural organic index for the consumer's desire for healthy skin. Therefore, in this article, in the future development of eco-friendly organic cosmetics, in line with the natural and environment-friendly changes reminiscent of the efficacy or ingredients of products, it is necessary to develop cosmetics using the ISO natural organic index that meets the needs of consumers and a differentiated strategy.}, }
@article {pmid36141012, year = {2022}, author = {Catalano, A and Iacopetta, D and Ceramella, J and Maio, AC and Basile, G and Giuzio, F and Bonomo, MG and Aquaro, S and Walsh, TJ and Sinicropi, MS and Saturnino, C and Geronikaki, A and Salzano, G}, title = {Are Nutraceuticals Effective in COVID-19 and Post-COVID Prevention and Treatment?.}, journal = {Foods (Basel, Switzerland)}, volume = {11}, number = {18}, pages = {}, pmid = {36141012}, issn = {2304-8158}, support = {1062_R13_GREEN//Ministry of Education, Universities and Research/ ; }, abstract = {The beginning of the end or the end of the beginning? After two years mastered by coronavirus disease 19 (COVID-19) pandemic, we are now witnessing a turnaround. The reduction of severe cases and deaths from COVID-19 led to increasing importance of a new disease called post-COVID syndrome. The term post-COVID is used to indicate permanency of symptoms in patients who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Immune, antiviral, antimicrobial therapies, as well as ozone therapy have been used to treat COVID-19 disease. Vaccines have then become available and administered worldwide to prevent the insurgence of the disease. However, the pandemic is not over yet at all given the emergence of new omicron variants. New therapeutic strategies are urgently needed. In this view, great interest was found in nutraceutical products, including vitamins (C, D, and E), minerals (zinc), melatonin, probiotics, flavonoids (quercetin), and curcumin. This review summarizes the role of nutraceuticals in the prevention and/or treatment of COVID-19 disease and post-COVID syndrome.}, }
@article {pmid36141948, year = {2022}, author = {De Vincenzi, C and Pansini, M and Ferrara, B and Buonomo, I and Benevene, P}, title = {Consequences of COVID-19 on Employees in Remote Working: Challenges, Risks and Opportunities An Evidence-Based Literature Review.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {18}, pages = {}, pmid = {36141948}, issn = {1660-4601}, mesh = {*COVID-19/epidemiology ; Humans ; Mental Health ; Pandemics ; *Teleworking ; Workplace ; }, abstract = {The COVID-19 pandemic forced organizations across all sectors and sizes to undertake crucial changes in order to remain productive during the emergency. Among these, the shift towards remote working arrangements is still present in our workplaces, impacting employees' well-being and productivity. This systematic review aims to describe the pandemic's consequences on work organization by analyzing whether and how the shift towards remote or home-working impacted employees' productivity, performance, and well-being. Furthermore, it describes the role of individual and organizational factors in determining employees' adjustment to remote work. Sixty-seven peer-reviewed papers published from 2020 to 2022, written in English, were selected through the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Findings describe how remote working arrangements, the workplace and organizational factors, and the employees' individual traits and skills impacted employees' productivity and well-being. Furthermore, they provide a description of the organizational enforcement actions reported in the literature. Managerial and practical implications, such as enforcement actions, team management strategies, and initiatives to promote employees' physical and mental health, will be discussed in the paper.}, }
@article {pmid36142282, year = {2022}, author = {Dybowska, M and Wyrostkiewicz, D and Opoka, L and Lewandowska, K and Sobiecka, M and Tomkowski, W and Szturmowicz, M}, title = {Venous Thromboembolic Disease in COVID-19, Pathophysiology, Therapy and Prophylaxis.}, journal = {International journal of molecular sciences}, volume = {23}, number = {18}, pages = {}, pmid = {36142282}, issn = {1422-0067}, mesh = {Anticoagulants/therapeutic use ; *COVID-19/complications ; Heparin/therapeutic use ; Humans ; SARS-CoV-2 ; *Venous Thromboembolism/drug therapy/etiology/prevention &amp; control ; *Venous Thrombosis/drug therapy ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {For over two years, the world has been facing the epidemiological and health challenge of the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Growing problems are also complications after the development of COVID-19 in the form of post and long- COVID syndromes, posing a challenge for the medical community, both for clinicians and the scientific world. SARS-CoV-2 infection is associated with an increased risk of cardiovascular complications, especially thromboembolic complications, which are associated with both thrombosis of small and very small vessels due to immunothrombosis, and the development of venous thromboembolism. Low molecular wight heparin (LMHW) are the basic agents used in the prevention and treatment of thromboembolic complications in COVID-19. There is still a great deal of controversy regarding both the prevention and treatment of thromboembolic complications, including the prophylaxis dose or the optimal duration of anticoagulant treatment in patients with an episode of venous thromboembolism.}, }
@article {pmid36146672, year = {2022}, author = {Veronese, N and Bonica, R and Cotugno, S and Tulone, O and Camporeale, M and Smith, L and Trott, M and Bruyere, O and Mirarchi, L and Rizzo, G and Bavaro, DF and Barbagallo, M and Dominguez, LJ and Marotta, C and Silenzi, A and Nicastri, E and Saracino, A and Di Gennaro, F}, title = {Interventions for Improving Long COVID-19 Symptomatology: A Systematic Review.}, journal = {Viruses}, volume = {14}, number = {9}, pages = {}, pmid = {36146672}, issn = {1999-4915}, mesh = {Adult ; *COVID-19/complications/therapy ; Female ; Humans ; Luteolin ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Although the understanding of several aspects of long COVID-19 syndrome is increasing, there is limited literature regarding the treatment of these signs and symptoms. The aim of our systematic review was to understand which therapies have proved effective against the symptoms of long COVID-19.<br><br>METHODS: A systematic search for randomized controlled or clinical trials in several databases was conducted through 15 May 2022. Specific inclusion criteria included: (1) intervention studies, either randomized controlled (RCTs) or clinical trials; (2) diagnosis of long COVID-19, according to the World Health Organization criteria; (3) presence of long COVID-19 for at least 12 weeks after SARS-CoV-2 infection.<br><br>RESULTS: We initially found 1638 articles to screen. After removing 1602 works based on their title/abstract, we considered 35 full texts, and among them, two intervention studies were finally included. The first RCT focused on the greater improvement of treatment combining olfactory rehabilitation with oral supplementation with Palmitoylethanolamide and Luteolin in patients with olfactory dysfunction after COVID-19. The second study evaluated the positive impact of aromatherapy vs. standard care in adult females affected by fatigue.<br><br>CONCLUSION: Our systematic review found only two intervention studies focused on patients affected by long COVID-19. More intervention studies are needed to investigate potentially positive interventions for long COVID-19 symptoms.}, }
@article {pmid36148046, year = {2022}, author = {Blann, AD and Heitmar, R}, title = {SARS-CoV-2 and COVID-19: A Narrative Review.}, journal = {British journal of biomedical science}, volume = {79}, number = {}, pages = {10426}, pmid = {36148046}, issn = {2474-0896}, mesh = {*COVID-19/complications ; Humans ; Pandemics/prevention &amp; control ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The World Health Organisation has reported that the viral disease known as COVID-19, caused by SARS-CoV-2, is the leading cause of death by a single infectious agent. This narrative review examines certain components of the pandemic: its origins, early clinical data, global and UK-focussed epidemiology, vaccination, variants, and long COVID.}, }
@article {pmid36148558, year = {2023}, author = {Takao, M and Ohira, M}, title = {Neurological post-acute sequelae of SARS-CoV-2 infection.}, journal = {Psychiatry and clinical neurosciences}, volume = {77}, number = {2}, pages = {72-83}, doi = {10.1111/pcn.13481}, pmid = {36148558}, issn = {1440-1819}, support = {3-8//Intramural fund from NCNP/ ; 22dk0307115h0001//Japan Agency for Medical Research and Development/ ; JP21wm0425019//Japan Agency for Medical Research and Development/ ; 18K06506//Japan Society for the Promotion of Science/ ; 21K06417//Japan Society for the Promotion of Science/ ; 22H04923//Japan Society for the Promotion of Science/ ; //NCNP/ ; //the Research Committee of Prion Disease and Slow Virus Infection/ ; Slow V//Health and Labour Sciences Research Grants/ ; //Ministry of Health, Labour and Welfare, Japan/ ; }, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Ambulatory Care Facilities ; Anxiety ; Disease Progression ; }, abstract = {The novel coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can have two phases: acute (generally 4 weeks after onset) and chronic (>4 weeks after onset). Both phases include a wide variety of signs and symptoms including neurological and psychiatric symptoms. The signs and symptoms that are considered sequelae of COVID-19 are termed post-COVID condition, long COVID-19, and post-acute sequelae of SARS-CoV-2 infection (PASC). PASC symptoms include fatigue, dyspnea, palpitation, dysosmia, subfever, hypertension, alopecia, sleep problems, loss of concentration, amnesia, numbness, pain, gastrointestinal symptoms, depression, and anxiety. Because the specific pathophysiology of PASC has not yet been clarified, there are no definite criteria of the condition, hence the World Health Organization's definition is quite broad. Consequently, it is difficult to correctly diagnose PASC. Approximately 50% of patients may show at least one PASC symptom up to 12 months after COVID-19 infection; however, the exact prevalence of PASC has not been determined. Despite extensive research in progress worldwide, there are currently no clear diagnostic methodologies or treatments for PASC. In this review, we discuss the currently available information on PASC and highlight the neurological sequelae of COVID-19 infection. Furthermore, we provide clinical suggestions for diagnosing and caring for patients with PASC based on our outpatient clinic experience.}, }
@article {pmid36154545, year = {2022}, author = {Hadda, V and Suri, TM and Iyer, H and Jain, A and Mittal, S and Madan, K and Mohan, A and Seith Bhalla, A and Sindhwani, G and Dutt, N and Venkatnarayan, K and Nath, A and Dhooria, S and Kumar, R and Marwah, V and Karmakar, S and Chaudhry, D and Ayub, II and Dwivedi, DP and Tiwari, P and Koul, P and Behera, AK and Saxena, P and Sengupta, A and Mohapatra, PR and Goyal, A and Christopher, DJ and Guleria, R}, title = {A Delphi consensus statement for the management of post-COVID interstitial lung disease.}, journal = {Expert review of respiratory medicine}, volume = {16}, number = {9}, pages = {983-995}, doi = {10.1080/17476348.2022.2128770}, pmid = {36154545}, issn = {1747-6356}, mesh = {Humans ; Delphi Technique ; *COVID-19/complications ; *Lung Diseases, Interstitial/diagnosis/epidemiology/etiology ; Lung/diagnostic imaging ; }, abstract = {INTRODUCTION: As millions of people worldwide recover from COVID-19, a substantial proportion continue to have persistent symptoms, pulmonary function abnormalities, and radiological findings suggestive of post-COVID interstitial lung disease (ILD). To date, there is limited scientific evidence on the management of post-COVID ILD, necessitating a consensus-based approach.<br><br>AREAS COVERED: A panel of experts in pulmonology and thoracic radiology was constituted. Key questions regarding the management of post-COVID ILD were identified. A search was performed on PubMed and EMBASE and updated till 1 March 2022. The relevant literature regarding the epidemiology, pathophysiology, diagnosis and treatment of post-COVID ILD was summarized. Subsequently, suggestions regarding the management of these patients were framed, and a consensus was obtained using the Delphi approach. Those suggestions which were approved by over 80% of the panelists were accepted. The final document was approved by all panel members.<br><br>EXPERT OPINION: Dedicated facilities should be established for the care of patients with post-COVID ILD. Symptom screening, pulmonary function testing, and thoracic imaging have a role in the diagnosis. The pharmacologic and non-pharmacologic options for the management of post-COVID ILD are discussed. Further research into the pathophysiology and management of post-COVID ILD will improve our understanding of this condition.}, }
@article {pmid36158308, year = {2022}, author = {Goldstein Ferber, S and Shoval, G and Zalsman, G and Weller, A}, title = {Does COVID-19 related symptomatology indicate a transdiagnostic neuropsychiatric disorder? - Multidisciplinary implications.}, journal = {World journal of psychiatry}, volume = {12}, number = {8}, pages = {1004-1015}, pmid = {36158308}, issn = {2220-3206}, abstract = {The clinical presentation that emerges from the extensive coronavirus disease 2019 (COVID-19) mental health literature suggests high correlations among many conventional psychiatric diagnoses. Arguments against the use of multiple comorbidities for a single patient have been published long before the pandemic. Concurrently, diagnostic recommendations for use of transdiagnostic considerations for improved treatment have been also published in recent years. In this review, we pose the question of whether a transdiagnostic mental health disease, including psychiatric and neuropsychiatric symptomology, has emerged since the onset of the pandemic. There are many attempts to identify a syndrome related to the pandemic, but none of the validated scales is able to capture the entire psychiatric and neuropsychiatric clinical presentation in infected and non-infected individuals. These scales also only marginally touch the issue of etiology and prevalence. We suggest a working hypothesis termed Complex Stress Reaction Syndrome (CSRS) representing a global psychiatric reaction to the pandemic situation in the general population (Type A) and a neuropsychiatric reaction in infected individuals (Type B) which relates to neurocognitive and psychiatric features which are part (excluding systemic and metabolic dysfunctions) of the syndrome termed in the literature as long COVID. We base our propositions on multidisciplinary scientific data regarding mental health during the global pandemic situation and the effects of viral infection reviewed from Google Scholar and PubMed between February 1, 2022 and March 10, 2022. Search in-clusion criteria were "mental health", "COVID-19" and "Long COVID", English language and human studies only. We suggest that this more comprehensive way of understanding COVID-19 complex mental health reactions may promote better prevention and treatment and serve to guide implementation of recommended administrative regulations that were recently published by the World Psychiatric Association. This review may serve as a call for an international investigation of our working hypothesis.}, }
@article {pmid36159093, year = {2022}, author = {Swarnakar, R and Yadav, SL}, title = {Rehabilitation in long COVID-19: A mini-review.}, journal = {World journal of methodology}, volume = {12}, number = {4}, pages = {235-245}, pmid = {36159093}, issn = {2222-0682}, abstract = {We have been experiencing multiple waves of the coronavirus disease 2019 (COVID-19) pandemic. With these unprecedented waves, we have entered into an era of 'new normal'. This pandemic has enforced us to rethink the very basics of childhood learning: Habits, health etiquette, and hygiene. Rehabilitation has immense importance during this pandemic considering a few aspects. Multidisciplinary COVID-19 rehabilitation clinics are essential to address the demand. The equitable distribution of COVID-19 rehabilitation services for differently-abled individuals during the pandemic is an important aspect. Rehabilitation needs identification and further studies on various rehabilitation interventions are among the key unmet future research needs.}, }
@article {pmid36165028, year = {2022}, author = {Freedberg, DE and Chang, L}, title = {Gastrointestinal symptoms in COVID-19: the long and the short of it.}, journal = {Current opinion in gastroenterology}, volume = {38}, number = {6}, pages = {555-561}, doi = {10.1097/MOG.0000000000000876}, pmid = {36165028}, issn = {1531-7056}, support = {U54 DK123755/DK/NIDDK NIH HHS/United States ; OT2 OD024899/OD/NIH HHS/United States ; }, mesh = {*COVID-19/complications ; *Gastrointestinal Diseases/diagnosis/etiology ; Humans ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE OF REVIEW: A large and growing number of patients have persistent gastrointestinal symptoms that they attribute to COVID-19. SARS-CoV-2, the virus that causes COVID-19, replicates within the gut and acute COVID-19 is associated with alteration of the gut microbiome. This article reviews recent observational data related to gastrointestinal symptoms in 'long COVID' and discusses pathophysiologic mechanisms that might explain persistent post-COVID gastrointestinal symptoms.<br><br>RECENT FINDINGS: Gastrointestinal symptoms are present in half of the patients with acute COVID-19, persist 6 months after COVID-19 in 10-25% of patients, and are rated as the most bothersome symptom in 11% of all patients. These symptoms include heartburn, constipation, diarrhoea and abdominal pain and decline in prevalence with the passage of time. Long COVID gastrointestinal symptoms are associated with mental health symptoms (anxiety and depression) that predate COVID-19 and also with mental health symptoms that are concurrent, after recovery from COVID-19. The cause of long COVID gastrointestinal symptoms is unknown and hypotheses include the SARS-CoV-2 virus itself, which infects the gastrointestinal tract; COVID-19, which can be accompanied by gut microbiome changes, a profound systemic inflammatory response and critical illness; and/or effects of pandemic stress on gastrointestinal function and symptom perception, which may be unrelated to either SARS-CoV-2 or to COVID-19.<br><br>SUMMARY: New, persistent gastrointestinal symptoms are commonly reported after recovery from COVID-19. The pathophysiology of these symptoms is unknown but likely to be multifactorial.}, }
@article {pmid36170698, year = {2022}, author = {Vaiman, E and Gayduk, A and Strelnik, A and Smirnova, D and Davydkin, I and Fedyashov, I and Cumming, P and Shnayder, N and Nasyrova, R}, title = {Possible Clinical and Pharmacogenetic Predictors of the Efficacy and Safety of Carbamazepine in Post-COVID-19 Depression.}, journal = {Psychiatria Danubina}, volume = {34}, number = {Suppl 8}, pages = {31-37}, pmid = {36170698}, issn = {0353-5053}, mesh = {Anticonvulsants/adverse effects ; Antidepressive Agents/adverse effects ; Benzodiazepines ; *COVID-19/complications ; Carbamazepine/adverse effects ; Depression ; Humans ; Pharmacogenetics ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {BACKGROUND: Individuals who have suffered from novel coronavirus disease (COVID-19) are at risk for developing post-COVID neuropsychiatric disorders, which are an integral part of the Long COVID syndrome. Depression and/or anxiety are considered the most common psychiatric disorders after experiencing COVID-19. Certain antiepileptic drugs, notably, carbamazepine (CMZ), are effective in the treatment of mood disorders, especially as mood stabilizers in bipolar affective disorder (BAD), but the efficacy of CMZ in Long COVID remains to be established. The aim of the review was to investigate pharmacogenetic predictors of safety and efficacy of CMZ in patients with depressive symptoms of Long COVID during the post-infection period.<br><br>SUBJECTS AND METHODS: We carried out a systematic search for publications in English and Russian on the safety and efficacy of CMZ in depressive disorders of different etiologies in the PubMed, Web of Science, Springer, Clinical Keys, Google Schooler, E-Library databases using keywords and combined word searches (carbamazepine, COVID-19, depression, epilepsy, post-COVID-syndrome) for the period from January 01,2020 to June 10, 2022.<br><br>RESULTS: We review the main adverse drug reactions (ADRs) associated with CMZ, drug-drug interactions, and genetic predictors of the development of ADR. Here, we consider as risk factors, candidate genes for CMZ metabolism, CMZ transport, immunohistocompatibility genes, and candidate genes for QT prolongation.<br><br>CONCLUSIONS: The choice of antidepressant treatment for patients with Long COVID is fraught because of the frequent occurrence of subclinical (interictal) epileptiform activity in the EEG. Consequently, antidepressant medications with a proconvulsant effect are contraindicated for Long COVID patients. CMZ may be a promising alternative for the treatment of depressive disorders in Long COVID states, given its mood-stabilizer, antidepressant, and antiepileptic profile.}, }
@article {pmid36178611, year = {2022}, author = {DePace, NL and Colombo, J}, title = {Long-COVID Syndrome and the Cardiovascular System: A Review of Neurocardiologic Effects on Multiple Systems.}, journal = {Current cardiology reports}, volume = {24}, number = {11}, pages = {1711-1726}, pmid = {36178611}, issn = {1534-3170}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; SARS-CoV-2 ; *Cardiovascular System ; }, abstract = {PURPOSE OF REVIEW: Long-COVID syndrome is a multi-organ disorder that persists beyond 12 weeks post-acute SARS-CoV-2 infection (COVID-19). Here, we provide a definition for this syndrome and discuss neuro-cardiology involvement due to the effects of (1) angiotensin-converting enzyme 2 receptors (the entry points for the virus), (2) inflammation, and (3) oxidative stress (the resultant effects of the virus).<br><br>RECENT FINDINGS: These effects may produce a spectrum of cardio-neuro effects (e.g., myocardial injury, primary arrhythmia, and cardiac symptoms due to autonomic dysfunction) which may affect all systems of the body. We discuss the symptoms and suggest therapies that target the underlying autonomic dysfunction to relieve the symptoms rather than merely treating symptoms. In addition to treating the autonomic dysfunction, the therapy also treats chronic inflammation and oxidative stress. Together with a full noninvasive cardiac workup, a full assessment of the autonomic nervous system, specifying parasympathetic and sympathetic (P&amp;S) activity, both at rest and in response to challenges, is recommended. Cardiac symptoms must be treated directly. Cardiac treatment is often facilitated by treating the P&amp;S dysfunction. Cardiac symptoms of dyspnea, chest pain, and palpitations, for example, need to be assessed objectively to differentiate cardiac from neural (autonomic) etiology. Long-term myocardial injury commonly involves P&amp;S dysfunction. P&amp;S assessment usually connects symptoms of Long-COVID to the documented autonomic dysfunction(s).}, }
@article {pmid36186977, year = {2022}, author = {Schieffer, E and Schieffer, B}, title = {The rationale for the treatment of long-Covid symptoms - A cardiologist's view.}, journal = {Frontiers in cardiovascular medicine}, volume = {9}, number = {}, pages = {992686}, pmid = {36186977}, issn = {2297-055X}, abstract = {The ongoing coronavirus disease 2019 pandemic left us with thousands of patients suffering from neurological, cardiovascular, and psychiatric disorders named post-acute sequelae of COVID-19 or just long-Covid. In parallel, the vaccination campaigns against SARS-CoV-2 spike protein saved millions of lives worldwide but long-Covid symptoms also appeared rarely following vaccination with a strong overlap to the "canonical" long-Covid symptoms. A therapeutic strategy targeting both, post-VAC and post-SARS-CoV-2 long-Covid symptoms is warranted since exposure to the S-protein either by vaccination or SARS-CoV-2 infection may trigger identical immuno-inflammatory cascades resulting in long-Covid symptoms.}, }
@article {pmid36187294, year = {2022}, author = {Méndez-García, LA and Escobedo, G and Minguer-Uribe, AG and Viurcos-Sanabria, R and Aguayo-Guerrero, JA and Carrillo-Ruiz, JD and Solleiro-Villavicencio, H}, title = {Role of the renin-angiotensin system in the development of COVID-19-associated neurological manifestations.}, journal = {Frontiers in cellular neuroscience}, volume = {16}, number = {}, pages = {977039}, pmid = {36187294}, issn = {1662-5102}, abstract = {SARS-CoV-2 causes COVID-19, which has claimed millions of lives. This virus can infect various cells and tissues, including the brain, for which numerous neurological symptoms have been reported, ranging from mild and non-life-threatening (e.g., headaches, anosmia, dysgeusia, and disorientation) to severe and life-threatening symptoms (e.g., meningitis, ischemic stroke, and cerebral thrombosis). The cellular receptor for SARS-CoV-2 is angiotensin-converting enzyme 2 (ACE2), an enzyme that belongs to the renin-angiotensin system (RAS). RAS is an endocrine system that has been classically associated with regulating blood pressure and fluid and electrolyte balance; however, it is also involved in promoting inflammation, proliferation, fibrogenesis, and lipogenesis. Two pathways constitute the RAS with counter-balancing effects, which is the key to its regulation. The first axis (classical) is composed of angiotensin-converting enzyme (ACE), angiotensin (Ang) II, and angiotensin type 1 receptor (AT1R) as the main effector, which -when activated- increases the production of aldosterone and antidiuretic hormone, sympathetic nervous system tone, blood pressure, vasoconstriction, fibrosis, inflammation, and reactive oxygen species (ROS) production. Both systemic and local classical RAS' within the brain are associated with cognitive impairment, cell death, and inflammation. The second axis (non-classical or alternative) includes ACE2, which converts Ang II to Ang-(1-7), a peptide molecule that activates Mas receptor (MasR) in charge of opposing Ang II/AT1R actions. Thus, the alternative RAS axis enhances cognition, synaptic remodeling, cell survival, cell signal transmission, and antioxidant/anti-inflammatory mechanisms in the brain. In a physiological state, both RAS axes remain balanced. However, some factors can dysregulate systemic and local RAS arms. The binding of SARS-CoV-2 to ACE2 causes the internalization and degradation of this enzyme, reducing its activity, and disrupting the balance of systemic and local RAS, which partially explain the appearance of some of the neurological symptoms associated with COVID-19. Therefore, this review aims to analyze the role of RAS in the development of the neurological effects due to SARS-CoV-2 infection. Moreover, we will discuss the RAS-molecular targets that could be used for therapeutic purposes to treat the short and long-term neurological COVID-19-related sequelae.}, }
@article {pmid36187895, year = {2022}, author = {Lazova, S and Gerenska, D and Slabakova, Y and Velikova, T}, title = {Immunological features of the multisystem inflammatory syndrome associated with SARS-CoV-2 in children.}, journal = {American journal of clinical and experimental immunology}, volume = {11}, number = {4}, pages = {64-71}, pmid = {36187895}, issn = {2164-7712}, abstract = {A particular group of children developed severe multisystem inflammation associated with current or recent SARS-CoV-2 infection or contact with a COVID-19 patient in the previous few weeks. The condition was defined as multisystem inflammatory syndrome (MIS) in children (MIS-C). As the definition of CDC and WHO is fast widely accepted, the lack of an international consensus on the definition of the syndrome cases, however, leads to some difficulties for clinicians. Additionally, MIS-C shares some immunological, pathological features with the conditions, such as cytokine storm, long COVID and/or post-COVID syndrome. The picture is further complicated by the existence of the syndrome in adults (MIS-A). Therefore, we have compared these conditions from the immunological point of view in our review based on the published case reports, studies, systematic reviews and metaanalyses. This knowledge is essential not only for immunologists. The paediatricians must be familiar with the immunological bases of the syndrome and implement it in on-time recognition and diagnosis and minimize systemic damage of this life-threatening condition at the earliest stage possible. Further investigations still need to be done to find and develop the best effective therapy and prophylactics.}, }
@article {pmid36189287, year = {2022}, author = {Teo, WP and Goodwill, AM}, title = {Can exercise attenuate the negative effects of long COVID syndrome on brain health?.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {986950}, pmid = {36189287}, issn = {1664-3224}, mesh = {Brain/physiology ; Brain-Derived Neurotrophic Factor ; *COVID-19/complications ; Exercise/physiology ; Humans ; Syndrome ; Post-Acute COVID-19 Syndrome ; }, abstract = {The impetus for many governments globally to treat the novel coronavirus (COVID-19) as an endemic warrant more research into the prevention, and management of long COVID syndrome (LCS). Whilst the data on LCS remains scarce, reports suggest a large proportion of recovered individuals will experience ongoing neuropsychological symptoms, even with mild disease severity. The pathophysiology underlying LCS is multifaceted. Evidence suggests that altered inflammatory, neurotrophic, and neurotransmitter pathways within the brain contribute to neuropsychological symptoms reported following COVID-19. Exercise or regular physical activity has long been shown to have positive effects on brain health and cognition through exerting positive effects on inflammatory markers, neurotransmitters, and neurotropic factors analogous to the neurophysiological pathways proposed to be disrupted by COVID-19 infection. Thus, exercise may serve as an important lifestyle behavior in the management of LCS. In this opinion article, we present the evidence to support the positive role of exercise in the management of cognitive symptom that manifest with LCS and discuss important considerations and interactions with cardiorespiratory and exercise tolerance complications that often present for individuals experiencing LCS. We highlight the need for more research and training of sports medicine practitioners and clinical exercise physiologists in the management of LCS with exercise and call for further research to understand the optimal dose-responses and exercise prescription guidelines for cognitive benefits and minimizing other complications.}, }
@article {pmid36196612, year = {2022}, author = {Kim, Y and Kim, SE and Kim, T and Yun, KW and Lee, SH and Lee, E and Seo, JW and Jung, YH and Chong, YP}, title = {Preliminary Guidelines for the Clinical Evaluation and Management of Long COVID.}, journal = {Infection &amp; chemotherapy}, volume = {54}, number = {3}, pages = {566-597}, pmid = {36196612}, issn = {2093-2340}, abstract = {Long-lasting coronavirus disease 2019 (COVID-19) symptoms beyond 12 weeks, the so-called 'long COVID' have been increasingly reported worldwide. Long COVID can be manifested in various forms, and there is an increasing demand for proper assessment and management. However, it is challenging when trying to determine the best-practice standards of care based on the current evidence because there is no internationally agreed clinical definition or clear treatment pathway. Therefore, the present guidelines have been drafted to provide advice on diagnosis and management based on the latest updated available evidence and the consensus of expert opinion. So far, no standard test and drug treatment can be strongly recommended for patients with long COVID because of a lack of evidence. The present guidelines provide advice based on 12 key questions, including appropriate interventions for long COVID that can be used in clinical practice. Continuous careful observation and studies related to long COVID are needed for the long-term impact of COVID-19 and proper management for long COVID to be determined.}, }
@article {pmid36202473, year = {2022}, author = {O'Sullivan-Murphy, B and Driehuys, B and Mammarappallil, J}, title = {MR Imaging for the Evaluation of Diffuse Lung Disease: Where Are We?.}, journal = {Radiologic clinics of North America}, volume = {60}, number = {6}, pages = {1021-1032}, doi = {10.1016/j.rcl.2022.06.007}, pmid = {36202473}, issn = {1557-8275}, mesh = {Humans ; Lung/diagnostic imaging ; *Lung Diseases/diagnostic imaging ; Magnetic Resonance Imaging/methods ; *Xenon Isotopes ; }, abstract = {Patients with diffuse lung diseases require thorough medical and social history and physical examinations, coupled with a multitude of laboratory tests, pulmonary function tests, and radiologic imaging to discern and manage the specific disease. This review summarizes the current state of imaging of various diffuse lung diseases by hyperpolarized MR imaging. The potential of hyperpolarized MR imaging as a clinical tool is outlined as a novel imaging approach that enables further understanding of the cause of diffuse lung diseases, permits earlier detection of disease progression before that found with pulmonary function tests, and can delineate physiologic response to lung therapies.}, }
@article {pmid36210445, year = {2022}, author = {Batiha, GE and Al-Kuraishy, HM and Al-Gareeb, AI and Welson, NN}, title = {Pathophysiology of Post-COVID syndromes: a new perspective.}, journal = {Virology journal}, volume = {19}, number = {1}, pages = {158}, pmid = {36210445}, issn = {1743-422X}, mesh = {*COVID-19/complications ; Fatigue ; Female ; Histamine Antagonists ; Humans ; Inflammation Mediators ; *Mastocytosis/diagnosis ; SARS-CoV-2 ; }, abstract = {Most COVID-19 patients recovered with low mortality; however, some patients experienced long-term symptoms described as "long-COVID" or "Post-COVID syndrome" (PCS). Patients may have persisting symptoms for weeks after acute SARS-CoV-2 infection, including dyspnea, fatigue, myalgia, insomnia, cognitive and olfactory disorders. These symptoms may last for months in some patients. PCS may progress in association with the development of mast cell activation syndrome (MCAS), which is a distinct kind of mast cell activation disorder, characterized by hyper-activation of mast cells with inappropriate and excessive release of chemical mediators. COVID-19 survivors, mainly women, and patients with persistent severe fatigue for 10 weeks after recovery with a history of neuropsychiatric disorders are more prone to develop PCS. High D-dimer levels and blood urea nitrogen were observed to be risk factors associated with pulmonary dysfunction in COVID-19 survivors 3 months post-hospital discharge with the development of PCS. PCS has systemic manifestations that resolve with time with no further complications. However, the final outcomes of PCS are chiefly unknown. Persistence of inflammatory reactions, autoimmune mimicry, and reactivation of pathogens together with host microbiome alterations may contribute to the development of PCS. The deregulated release of inflammatory mediators in MCAS produces extraordinary symptoms in patients with PCS. The development of MCAS during the course of SARS-CoV-2 infection is correlated to COVID-19 severity and the development of PCS. Therefore, MCAS is treated by antihistamines, inhibition of synthesis of mediators, inhibition of mediator release, and inhibition of degranulation of mast cells.}, }
@article {pmid36215063, year = {2022}, author = {,  and Wulf Hanson, S and Abbafati, C and Aerts, JG and Al-Aly, Z and Ashbaugh, C and Ballouz, T and Blyuss, O and Bobkova, P and Bonsel, G and Borzakova, S and Buonsenso, D and Butnaru, D and Carter, A and Chu, H and De Rose, C and Diab, MM and Ekbom, E and El Tantawi, M and Fomin, V and Frithiof, R and Gamirova, A and Glybochko, PV and Haagsma, JA and Haghjooy Javanmard, S and Hamilton, EB and Harris, G and Heijenbrok-Kal, MH and Helbok, R and Hellemons, ME and Hillus, D and Huijts, SM and Hultström, M and Jassat, W and Kurth, F and Larsson, IM and Lipcsey, M and Liu, C and Loflin, CD and Malinovschi, A and Mao, W and Mazankova, L and McCulloch, D and Menges, D and Mohammadifard, N and Munblit, D and Nekliudov, NA and Ogbuoji, O and Osmanov, IM and Peñalvo, JL and Petersen, MS and Puhan, MA and Rahman, M and Rass, V and Reinig, N and Ribbers, GM and Ricchiuto, A and Rubertsson, S and Samitova, E and Sarrafzadegan, N and Shikhaleva, A and Simpson, KE and Sinatti, D and Soriano, JB and Spiridonova, E and Steinbeis, F and Svistunov, AA and Valentini, P and van de Water, BJ and van den Berg-Emons, R and Wallin, E and Witzenrath, M and Wu, Y and Xu, H and Zoller, T and Adolph, C and Albright, J and Amlag, JO and Aravkin, AY and Bang-Jensen, BL and Bisignano, C and Castellano, R and Castro, E and Chakrabarti, S and Collins, JK and Dai, X and Daoud, F and Dapper, C and Deen, A and Duncan, BB and Erickson, M and Ewald, SB and Ferrari, AJ and Flaxman, AD and Fullman, N and Gamkrelidze, A and Giles, JR and Guo, G and Hay, SI and He, J and Helak, M and Hulland, EN and Kereselidze, M and Krohn, KJ and Lazzar-Atwood, A and Lindstrom, A and Lozano, R and Malta, DC and Månsson, J and Mantilla Herrera, AM and Mokdad, AH and Monasta, L and Nomura, S and Pasovic, M and Pigott, DM and Reiner, RC and Reinke, G and Ribeiro, ALP and Santomauro, DF and Sholokhov, A and Spurlock, EE and Walcott, R and Walker, A and Wiysonge, CS and Zheng, P and Bettger, JP and Murray, CJL and Vos, T}, title = {Estimated Global Proportions of Individuals With Persistent Fatigue, Cognitive, and Respiratory Symptom Clusters Following Symptomatic COVID-19 in 2020 and 2021.}, journal = {JAMA}, volume = {328}, number = {16}, pages = {1604-1615}, pmid = {36215063}, issn = {1538-3598}, support = {K23 NR019019/NR/NINR NIH HHS/United States ; T32 AI007044/AI/NIAID NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Bayes Theorem ; *COVID-19/complications/epidemiology ; *Fatigue/epidemiology/etiology ; Pain/epidemiology/etiology ; SARS-CoV-2 ; Syndrome ; *Cognition Disorders/epidemiology/etiology ; *Respiratory Insufficiency/epidemiology/etiology ; Internationality ; Global Health/statistics &amp; numerical data ; Mood Disorders/epidemiology/etiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {IMPORTANCE: Some individuals experience persistent symptoms after initial symptomatic SARS-CoV-2 infection (often referred to as Long COVID).<br><br>OBJECTIVE: To estimate the proportion of males and females with COVID-19, younger or older than 20 years of age, who had Long COVID symptoms in 2020 and 2021 and their Long COVID symptom duration.<br><br>Bayesian meta-regression and pooling of 54 studies and 2 medical record databases with data for 1.2 million individuals (from 22 countries) who had symptomatic SARS-CoV-2 infection. Of the 54 studies, 44 were published and 10 were collaborating cohorts (conducted in Austria, the Faroe Islands, Germany, Iran, Italy, the Netherlands, Russia, Sweden, Switzerland, and the US). The participant data were derived from the 44 published studies (10&#x202f;501 hospitalized individuals and 42&#x202f;891 nonhospitalized individuals), the 10 collaborating cohort studies (10&#x202f;526 and 1906), and the 2 US electronic medical record databases (250&#x202f;928 and 846&#x202f;046). Data collection spanned March 2020 to January 2022.<br><br>EXPOSURES: Symptomatic SARS-CoV-2 infection.<br><br>MAIN OUTCOMES AND MEASURES: Proportion of individuals with at least 1 of the 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after SARS-CoV-2 infection in 2020 and 2021, estimated separately for hospitalized and nonhospitalized individuals aged 20 years or older by sex and for both sexes of nonhospitalized individuals younger than 20 years of age.<br><br>RESULTS: A total of 1.2 million individuals who had symptomatic SARS-CoV-2 infection were included (mean age, 4-66 years; males, 26%-88%). In the modeled estimates, 6.2% (95% uncertainty interval [UI], 2.4%-13.3%) of individuals who had symptomatic SARS-CoV-2 infection experienced at least 1 of the 3 Long COVID symptom clusters in 2020 and 2021, including 3.2% (95% UI, 0.6%-10.0%) for persistent fatigue with bodily pain or mood swings, 3.7% (95% UI, 0.9%-9.6%) for ongoing respiratory problems, and 2.2% (95% UI, 0.3%-7.6%) for cognitive problems after adjusting for health status before COVID-19, comprising an estimated 51.0% (95% UI, 16.9%-92.4%), 60.4% (95% UI, 18.9%-89.1%), and 35.4% (95% UI, 9.4%-75.1%), respectively, of Long COVID cases. The Long COVID symptom clusters were more common in women aged 20 years or older (10.6% [95% UI, 4.3%-22.2%]) 3 months after symptomatic SARS-CoV-2 infection than in men aged 20 years or older (5.4% [95% UI, 2.2%-11.7%]). Both sexes younger than 20 years of age were estimated to be affected in 2.8% (95% UI, 0.9%-7.0%) of symptomatic SARS-CoV-2 infections. The estimated mean Long COVID symptom cluster duration was 9.0 months (95% UI, 7.0-12.0 months) among hospitalized individuals and 4.0 months (95% UI, 3.6-4.6 months) among nonhospitalized individuals. Among individuals with Long COVID symptoms 3 months after symptomatic SARS-CoV-2 infection, an estimated 15.1% (95% UI, 10.3%-21.1%) continued to experience symptoms at 12 months.<br><br>CONCLUSIONS AND RELEVANCE: This study presents modeled estimates of the proportion of individuals with at least 1 of 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after symptomatic SARS-CoV-2 infection.}, }
@article {pmid36220127, year = {2022}, author = {Friedman, SA and Masters-Israilov, A and Robbins, MS}, title = {Secondary Headache Disorders: Approach, Workup, and Special Considerations for Select Populations.}, journal = {Seminars in neurology}, volume = {42}, number = {4}, pages = {418-427}, doi = {10.1055/s-0042-1757753}, pmid = {36220127}, issn = {1098-9021}, mesh = {Humans ; Female ; Pregnancy ; Aged ; *COVID-19/complications ; *Headache Disorders, Secondary/diagnosis/etiology/therapy ; Headache/diagnosis/etiology/therapy ; *Pseudotumor Cerebri/complications ; *Pregnancy Complications, Infectious ; Post-Acute COVID-19 Syndrome ; }, abstract = {Headache is one of the most common diagnoses in neurology. A thorough understanding of the clinical presentation of secondary headache, which can be life-threatening, is critical. This review provides an overview of the diagnostic approach to a patient with headache, including discussion of "red," "orange," and "green" flags. We emphasize particular scenarios to help tailor the clinical workup to individual circumstances such as in pregnant women, when particular attention must be paid to the effects of blood pressure and hypercoagulability, as well as in older adults, where there is a need for higher suspicion for an intracranial mass lesion or giant cell arteritis. Patients with risk factors for headache secondary to alterations in intracranial pressure, whether elevated (e.g., idiopathic intracranial hypertension) or decreased (e.g., cerebrospinal fluid leak), may require more specific diagnostic testing and treatment. Finally, headache in patients with COVID-19 or long COVID-19 is increasingly recognized and may have multiple etiologies.}, }
@article {pmid36220361, year = {2022}, author = {Lai, H and Yang, M and Sun, M and Pan, B and Wang, Q and Wang, J and Tian, J and Ding, G and Yang, K and Song, X and Ge, L}, title = {Risk of incident diabetes after COVID-19 infection: A systematic review and meta-analysis.}, journal = {Metabolism: clinical and experimental}, volume = {137}, number = {}, pages = {155330}, pmid = {36220361}, issn = {1532-8600}, mesh = {Male ; Humans ; Female ; *Diabetes Mellitus, Type 2/epidemiology ; Retrospective Studies ; COVID-19 Testing ; *COVID-19/epidemiology ; Risk Factors ; }, abstract = {BACKGROUND: COVID-19 might be a risk factor for various chronic diseases. However, the association between COVID-19 and the risk of incident diabetes remains unclear. We aimed to meta-analyze evidence on the relative risk of incident diabetes in patients with COVID-19.<br><br>METHODS: In this systematic review and meta-analysis, the Embase, PubMed, CENTRAL, and Web of Science databases were searched from December 2019 to June 8, 2022. We included cohort studies that provided data on the number, proportion, or relative risk of diabetes after confirming the COVID-19 diagnosis. Two reviewers independently screened studies for eligibility, extracted data, and assessed risk of bias. We used a random-effects meta-analysis to pool the relative risk with corresponding 95&#xa0;% confidence intervals. Prespecified subgroup and meta-regression analyses were conducted to explore the potential influencing factors. We converted the relative risk to the absolute risk difference to present the evidence. This study was registered in advance (PROSPERO CRD42022337841).<br><br>MAIN FINDINGS: Ten articles involving 11 retrospective cohorts with a total of 47.1 million participants proved eligible. We found a 64&#xa0;% greater risk (RR&#xa0;=&#xa0;1.64, 95%CI: 1.51 to 1.79) of diabetes in patients with COVID-19 compared with non-COVID-19 controls, which could increase the number of diabetes events by 701 (558 more to 865 more) per 10,000 persons. We detected significant subgroup effects for type of diabetes and sex. Type 2 diabetes has a higher relative risk than type 1. Moreover, men may be at a higher risk of overall diabetes than women. Sensitivity analysis confirmed the robustness of the results. No evidence was found for publication bias.<br><br>CONCLUSIONS: COVID-19 is strongly associated with the risk of incident diabetes, including both type 1 and type 2 diabetes. We should be aware of the risk of developing diabetes after COVID-19 and prepare for the associated health problems, given the large and growing number of people infected with COVID-19. However, the body of evidence still needs to be strengthened.}, }
@article {pmid36221293, year = {2022}, author = {Büttiker, P and Stefano, GB and Weissenberger, S and Ptacek, R and Anders, M and Raboch, J and Kream, RM}, title = {HIV, HSV, SARS-CoV-2 and Ebola Share Long-Term Neuropsychiatric Sequelae.}, journal = {Neuropsychiatric disease and treatment}, volume = {18}, number = {}, pages = {2229-2237}, pmid = {36221293}, issn = {1176-6328}, abstract = {Long COVID, in which disease-related symptoms persist for months after recovery, has led to a revival of the discussion of whether neuropsychiatric long-term symptoms after viral infections indeed result from virulent activity or are purely psychological phenomena. In this review, we demonstrate that, despite showing differences in structure and targeting, many viruses have highly similar neuropsychiatric effects on the host. Herein, we compare severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus 1 (HIV-1), Ebola virus disease (EVD), and herpes simplex virus 1 (HSV-1). We provide evidence that the mutual symptoms of acute and long-term anxiety, depression and post-traumatic stress among these viral infections are likely to result from primary viral activity, thus suggesting that these viruses share neuroinvasive strategies in common. Moreover, it appears that secondary induced environmental stress can lead to the emergence of psychopathologies and increased susceptibility to viral (re)infection in infected individuals. We hypothesize that a positive feedback loop of virus-environment-reinforced systemic responses exists. It is surmised that this cycle of primary virulent activity and secondary stress-induced reactivation, may be detrimental to infected individuals by maintaining and reinforcing the host's immunocompromised state of chronic inflammation, immunological strain, and maladaptive central-nervous-system activity. We propose that this state can lead to perturbed cognitive processing and promote aversive learning, which may manifest as acute, long-term neuropsychiatric illness.}, }
@article {pmid36223120, year = {2022}, author = {Durstenfeld, MS and Sun, K and Tahir, P and Peluso, MJ and Deeks, SG and Aras, MA and Grandis, DJ and Long, CS and Beatty, A and Hsue, PY}, title = {Use of Cardiopulmonary Exercise Testing to Evaluate Long COVID-19 Symptoms in Adults: A Systematic Review and Meta-analysis.}, journal = {JAMA network open}, volume = {5}, number = {10}, pages = {e2236057}, pmid = {36223120}, issn = {2574-3805}, support = {K23 AI157875/AI/NIAID NIH HHS/United States ; K24 AI112393/AI/NIAID NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; K12 HL143961/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; *COVID-19/complications/diagnosis ; Cross-Sectional Studies ; Exercise Test ; Humans ; Oxygen ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {IMPORTANCE: Reduced exercise capacity is commonly reported among individuals with COVID-19 symptoms more than 3 months after SARS-CoV-2 infection (long COVID-19 [LC]). Cardiopulmonary exercise testing (CPET) is the criterion standard to measure exercise capacity and identify patterns of exertional intolerance.<br><br>OBJECTIVES: To estimate the difference in exercise capacity among individuals with and without LC symptoms and characterize physiological patterns of limitations to elucidate possible mechanisms of LC.<br><br>DATA SOURCES: A search of PubMed, EMBASE, Web of Science, preprint servers, conference abstracts, and cited references was performed on December 20, 2021, and again on May 24, 2022. A preprint search of medrxiv.org, biorxiv.org, and researchsquare.com was performed on June 9, 2022.<br><br>STUDY SELECTION: Studies of adults with SARS-CoV-2 infection more than 3 months earlier that included CPET-measured peak oxygen consumption (V&#x307;o2) were screened independently by 2 blinded reviewers; 72 (2%) were selected for full-text review, and 35 (1%) met the inclusion criteria. An additional 3 studies were identified from preprint servers.<br><br>DATA EXTRACTION AND SYNTHESIS: Data extraction was performed by 2 independent reviewers according to the PRISMA reporting guideline. Data were pooled using random-effects models.<br><br>MAIN OUTCOMES AND MEASURES: Difference in peak V&#x307;o2 (in mL/kg/min) among individuals with and without persistent COVID-19 symptoms more than 3 months after SARS-CoV-2 infection.<br><br>RESULTS: A total of 38 studies were identified that performed CPET on 2160 individuals 3 to 18 months after SARS-CoV-2 infection, including 1228 with symptoms consistent with LC. Most studies were case series of individuals with LC or cross-sectional assessments within posthospitalization cohorts. Based on a meta-analysis of 9 studies including 464 individuals with LC symptoms and 359 without symptoms, the mean peak V&#x307;o2 was -4.9 (95% CI, -6.4 to -3.4) mL/kg/min among those with symptoms with a low degree of certainty. Deconditioning and peripheral limitations (abnormal oxygen extraction) were common, but dysfunctional breathing and chronotropic incompetence were also described. The existing literature was limited by small sample sizes, selection bias, confounding, and varying symptom definitions and CPET interpretations, resulting in high risk of bias and heterogeneity.<br><br>CONCLUSIONS AND RELEVANCE: The findings of this systematic review and meta-analysis study suggest that exercise capacity was reduced more than 3 months after SARS-CoV-2 infection among individuals with symptoms consistent with LC compared with individuals without LC symptoms, with low confidence. Potential mechanisms for exertional intolerance other than deconditioning include altered autonomic function (eg, chronotropic incompetence, dysfunctional breathing), endothelial dysfunction, and muscular or mitochondrial pathology.}, }
@article {pmid36223804, year = {2023}, author = {Ortega-Paz, L and Talasaz, AH and Sadeghipour, P and Potpara, TS and Aronow, HD and Jara-Palomares, L and Sholzberg, M and Angiolillo, DJ and Lip, GYH and Bikdeli, B}, title = {COVID-19-Associated Pulmonary Embolism: Review of the Pathophysiology, Epidemiology, Prevention, Diagnosis, and Treatment.}, journal = {Seminars in thrombosis and hemostasis}, volume = {49}, number = {8}, pages = {816-832}, doi = {10.1055/s-0042-1757634}, pmid = {36223804}, issn = {1098-9064}, mesh = {Humans ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; *Pulmonary Embolism/diagnosis/epidemiology/etiology ; *Venous Thrombosis/drug therapy ; Lung ; *Venous Thromboembolism/diagnosis/drug therapy/epidemiology ; *Thrombosis/drug therapy ; Anticoagulants/therapeutic use ; COVID-19 Testing ; }, abstract = {COVID-19 is associated with endothelial activation in the setting of a potent inflammatory reaction and a hypercoagulable state. The end result of this thromboinflammatory state is an excess in thrombotic events, in particular venous thromboembolism. Pulmonary embolism (PE) has been of special interest in patients with COVID-19 given its association with respiratory deterioration, increased risk of intensive care unit admission, and prolonged hospital stay. The pathophysiology and clinical characteristics of COVID-19-associated PE may differ from the conventional non-COVID-19-associated PE. In addition to embolic events from deep vein thrombi, in situ pulmonary thrombosis, particularly in smaller vascular beds, may be relevant in patients with COVID-19. Appropriate prevention of thrombotic events in COVID-19 has therefore become of critical interest. Several changes in viral biology, vaccination, and treatment management during the pandemic may have resulted in changes in incidence trends. This review provides an overview of the pathophysiology, epidemiology, clinical characteristics, and risk factors of COVID-19-associated PE. Furthermore, we briefly summarize the results from randomized controlled trials of preventive antithrombotic therapies in COVID-19, focusing on their findings related to PE. We discuss the acute treatment of COVID-19-associated PE, which is substantially similar to the management of conventional non-COVID-19 PE. Ultimately, we comment on the current knowledge gaps in the evidence and the future directions in the treatment and follow-up of COVID-19-associated PE, including long-term management, and its possible association with long-COVID.}, }
@article {pmid36225258, year = {2022}, author = {Li, Q and Liu, Y and Zhang, L}, title = {Cytoplasmic tail determines the membrane trafficking and localization of SARS-CoV-2 spike protein.}, journal = {Frontiers in molecular biosciences}, volume = {9}, number = {}, pages = {1004036}, pmid = {36225258}, issn = {2296-889X}, abstract = {The spike (S) glycoprotein of SARS-CoV-2 mediates viral entry through associating with ACE2 on host cells. Intracellular trafficking and palmitoylation of S protein are required for its function. The short cytoplasmic tail of S protein plays a key role in the intracellular trafficking, which contains the binding site for the host trafficking proteins such as COPI, COPII and SNX27. This cytoplasmic tail also contains the palmitoylation sites of S protein. Protein palmitoylation modification of S protein could be catalyzed by a family of zinc finger DHHC domain-containing protein palmitoyltransferases (ZDHHCs). The intracellular trafficking and membrane location facilitate surface expression of S protein and assembly of progeny virions. In this review, we summarize the function of S protein cytoplasmic tail in transportation and localization. S protein relies on intracellular trafficking pathways and palmitoylation modification to facilitate the life cycle of SARS-CoV-2, meanwhile it could interfere with the host transport pathways. The interplay between S protein and intracellular trafficking proteins could partially explain the acute symptoms or Long-COVID complications in multiple organs of COVID-19 patients.}, }
@article {pmid36226148, year = {2022}, author = {Roseti, L and Grigolo, B}, title = {COVID-19 and rheumatic diseases: A mini-review.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {997876}, pmid = {36226148}, issn = {2296-858X}, abstract = {Joint pain and arthralgia can be manifestations of COVID-19, and studies evaluating long COVID symptoms identified the persistence of these disorders. Moreover, some case reports highlighted the development of new inflammatory arthritis in patients with COVID-19, suggesting a possible relation. Viral infections and rheumatic diseases share a documented relationship; they have been associated with genetic and environmental risk factors responsible for some of them. There is crosstalk between viruses and the immune system during the development of several rheumatic diseases. Moreover, infections may participate in the pathogenesis of autoimmune rheumatic diseases and contribute to patient mortality. Therefore, it is crucial to provide a clearer insight into the interaction between viral infections and rheumatic diseases. Here, we provide a mini-review of the current literature with the aim of shedding light on the relationship between COVID-19 and rheumatic or musculoskeletal diseases, which is still unclear. Specifically, we examined several aspects: risk for the rheumatic population of acquiring the virus or developing severe symptoms, similarities of COVID-19 and arthritis, the possible rheumatic consequence of COVID-19, of rheumatic drugs and vaccines, and COVID-19 prevention in rheumatic patients through vaccination.}, }
@article {pmid36227021, year = {2023}, author = {Yang, DM and Chang, TJ and Hung, KF and Wang, ML and Cheng, YF and Chiang, SH and Chen, MF and Liao, YT and Lai, WQ and Liang, KH}, title = {Smart healthcare: A prospective future medical approach for COVID-19.}, journal = {Journal of the Chinese Medical Association : JCMA}, volume = {86}, number = {2}, pages = {138-146}, pmid = {36227021}, issn = {1728-7731}, mesh = {Humans ; *COVID-19 ; Artificial Intelligence ; Post-Acute COVID-19 Syndrome ; Pandemics/prevention &amp; control ; Delivery of Health Care ; }, abstract = {COVID-19 has greatly affected human life for over 3 years. In this review, we focus on smart healthcare solutions that address major requirements for coping with the COVID-19 pandemic, including (1) the continuous monitoring of severe acute respiratory syndrome coronavirus 2, (2) patient stratification with distinct short-term outcomes (eg, mild or severe diseases) and long-term outcomes (eg, long COVID), and (3) adherence to medication and treatments for patients with COVID-19. Smart healthcare often utilizes medical artificial intelligence (AI) and cloud computing and integrates cutting-edge biological and optoelectronic techniques. These are valuable technologies for addressing the unmet needs in the management of COVID. By leveraging deep learning/machine learning capabilities and big data, medical AI can perform precise prognosis predictions and provide reliable suggestions for physicians' decision-making. Through the assistance of the Internet of Medical Things, which encompasses wearable devices, smartphone apps, internet-based drug delivery systems, and telemedicine technologies, the status of mild cases can be continuously monitored and medications provided at home without the need for hospital care. In cases that develop into severe cases, emergency feedback can be provided through the hospital for rapid treatment. Smart healthcare can possibly prevent the development of severe COVID-19 cases and therefore lower the burden on intensive care units.}, }
@article {pmid36228563, year = {2022}, author = {Rizvi, AA and Kathuria, A and Al Mahmeed, W and Al-Rasadi, K and Al-Alawi, K and Banach, M and Banerjee, Y and Ceriello, A and Cesur, M and Cosentino, F and Galia, M and Goh, SY and Janez, A and Kalra, S and Kempler, P and Lessan, N and Lotufo, P and Papanas, N and Santos, RD and Stoian, AP and Toth, PP and Viswanathan, V and Rizzo, M and , }, title = {Post-COVID syndrome, inflammation, and diabetes.}, journal = {Journal of diabetes and its complications}, volume = {36}, number = {11}, pages = {108336}, pmid = {36228563}, issn = {1873-460X}, mesh = {Humans ; SARS-CoV-2 ; Pandemics ; *COVID-19/complications ; RNA, Viral ; *Diabetes Mellitus/epidemiology/therapy ; *Hyperglycemia/complications ; Inflammation/complications ; }, abstract = {The raging COVID-19 pandemic is in its third year of global impact. The SARS CoV 2 virus has a high rate of spread, protean manifestations, and a high morbidity and mortality in individuals with predisposing risk factors. The pathophysiologic mechanisms involve a heightened systemic inflammatory state, cardiometabolic derangements, and varying degrees of glucose intolerance. The latter can be evident as significant hyperglycemia leading to new-onset diabetes or worsening of preexisting disease. Unfortunately, the clinical course beyond the acute phase of the illness may persist in the form of a variety of symptoms that together form the so-called "Long COVID" or "Post-COVID Syndrome". It is thought that a chronic, low-grade inflammatory and immunologic state persists during this phase, which may last for weeks or months. Although numerous insights have been gained into COVID-related hyperglycemia and diabetes, its prediction, course, and management remain to be fully elucidated.}, }
@article {pmid36231717, year = {2022}, author = {Gao, P and Liu, J and Liu, M}, title = {Effect of COVID-19 Vaccines on Reducing the Risk of Long COVID in the Real World: A Systematic Review and Meta-Analysis.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {19}, pages = {}, pmid = {36231717}, issn = {1660-4601}, mesh = {*COVID-19/complications/epidemiology/prevention &amp; control ; *COVID-19 Vaccines/therapeutic use ; Humans ; SARS-CoV-2 ; Vaccination ; Post-Acute COVID-19 Syndrome ; }, abstract = {The coronavirus disease 2019 (COVID-19) is still in a global pandemic state. Some studies have reported that COVID-19 vaccines had a protective effect against long COVID. However, the conclusions of the studies on the effect of COVID-19 vaccines on long COVID were not consistent. This study aimed to systematically review relevant studies in the real world, and performed a meta-analysis to explore the relationship between vaccination and long COVID. We systematically searched PubMed, Embase, Web of science, and ScienceDirect from inception to 19 September 2022. The PICO (P: patients; I: intervention; C: comparison; O: outcome) was as follows: patients diagnosed with COVID-19 (P); vaccination with COVID-19 vaccines (I); the patients were divided into vaccinated and unvaccinated groups (C); the outcomes were the occurrence of long COVID, as well as the various symptoms of long COVID (O). A fixed-effect model and random-effects model were chosen based on the heterogeneity between studies in order to pool the effect value. The results showed that the vaccinated group had a 29% lower risk of developing long COVID compared with the unvaccinated group (RR = 0.71, 95% CI: 0.58-0.87, p < 0.01). Compared with patients who were not vaccinated, vaccination showed its protective effect in patients vaccinated with two doses (RR = 0.83, 95% CI: 0.74-0.94, p < 0.01), but not one dose (RR = 0.83, 95% CI: 0.65-1.07, p = 0.14). In addition, vaccination was effective against long COVD in patients either vaccinated before SARS-CoV-2 infection/COVID-19 (RR = 0.82, 95% CI: 0.74-0.91, p < 0.01) or vaccinated after SARS-CoV-2 infection/COVID-19 (RR = 0.83, 95% CI: 0.74-0.92, p < 0.01). For long COVID symptoms, vaccination reduced the risk of cognitive dysfunction/symptoms, kidney diseases/problems, myalgia, and sleeping disorders/problems sleeping. Our study shows that COVID-19 vaccines had an effect on reducing the risk of long COVID in patients vaccinated before or after SARS-CoV-2 infection/COVID-19. We suggest that the vaccination rate should be improved as soon as possible, especially for a complete vaccination course. There should be more studies to explore the basic mechanisms of the protective effect of COVID-19 vaccines on long COVID in the future.}, }
@article {pmid36232592, year = {2022}, author = {Khodanovich, MY and Kamaeva, DA and Naumova, AV}, title = {Role of Demyelination in the Persistence of Neurological and Mental Impairments after COVID-19.}, journal = {International journal of molecular sciences}, volume = {23}, number = {19}, pages = {}, pmid = {36232592}, issn = {1422-0067}, support = {22-15-00481//Russian Science Foundation/ ; }, mesh = {*Attention Deficit Disorder with Hyperactivity ; *COVID-19/complications ; *Demyelinating Diseases/complications ; Humans ; Quality of Life ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long-term neurological and mental complications of COVID-19, the so-called post-COVID syndrome or long COVID, affect the quality of life. The most persistent manifestations of long COVID include fatigue, anosmia/hyposmia, insomnia, depression/anxiety, and memory/attention deficits. The physiological basis of neurological and psychiatric disorders is still poorly understood. This review summarizes the current knowledge of neurological sequelae in post-COVID patients and discusses brain demyelination as a possible mechanism of these complications with a focus on neuroimaging findings. Numerous reviews, experimental and theoretical studies consider brain demyelination as one of the mechanisms of the central neural system impairment. Several factors might cause demyelination, such as inflammation, direct effect of the virus on oligodendrocytes, and cerebrovascular disorders, inducing myelin damage. There is a contradiction between the solid fundamental basis underlying demyelination as the mechanism of the neurological injuries and relatively little published clinical evidence related to demyelination in COVID-19 patients. The reason for this probably lies in the fact that most clinical studies used conventional MRI techniques, which can detect only large, clearly visible demyelinating lesions. A very limited number of studies use specific methods for myelin quantification detected changes in the white matter tracts 3 and 10 months after the acute phase of COVID-19. Future research applying quantitative MRI assessment of myelin in combination with neurological and psychological studies will help in understanding the mechanisms of post-COVID complications associated with demyelination.}, }
@article {pmid36233559, year = {2022}, author = {Clerbaux, LA and Mayasich, SA and Muñoz, A and Soares, H and Petrillo, M and Albertini, MC and Lanthier, N and Grenga, L and Amorim, MJ}, title = {Gut as an Alternative Entry Route for SARS-CoV-2: Current Evidence and Uncertainties of Productive Enteric Infection in COVID-19.}, journal = {Journal of clinical medicine}, volume = {11}, number = {19}, pages = {}, pmid = {36233559}, issn = {2077-0383}, support = {CEECIND/02373/2020//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e Tecnologia/ ; CEECIND/01049/2020//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e Tecnologia/ ; }, abstract = {The gut has been proposed as a potential alternative entry route for SARS-CoV-2. This was mainly based on the high levels of SARS-CoV-2 receptor expressed in the gastrointestinal (GI) tract, the observations of GI disorders (such as diarrhea) in some COVID-19 patients and the detection of SARS-CoV-2 RNA in feces. However, the underlying mechanisms remain poorly understood. It has been proposed that SARS-CoV-2 can productively infect enterocytes, damaging the intestinal barrier and contributing to inflammatory response, which might lead to GI manifestations, including diarrhea. Here, we report a methodological approach to assess the evidence supporting the sequence of events driving SARS-CoV-2 enteric infection up to gut adverse outcomes. Exploring evidence permits to highlight knowledge gaps and current inconsistencies in the literature and to guide further research. Based on the current insights on SARS-CoV-2 intestinal infection and transmission, we then discuss the potential implication on clinical practice, including on long COVID. A better understanding of the GI implication in COVID-19 is still needed to improve disease management and could help identify innovative therapies or preventive actions targeting the GI tract.}, }
@article {pmid36242969, year = {2022}, author = {Aden, D and Zaheer, S and Kumar, R and Raj, S and Khan, T and Varshney, S}, title = {Beyond COVID-19 and SARS-CoV-2, cardiovascular outcomes of "long covid" from a pathological perspective - a look back and road ahead.}, journal = {Pathology, research and practice}, volume = {239}, number = {}, pages = {154144}, pmid = {36242969}, issn = {1618-0631}, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19/complications ; Lung ; Post-Acute COVID-19 Syndrome ; }, abstract = {With the decrease in severity of COVID-19 there is a sense of relief in the general population. However, there has been an increased incidence of cardiovascular and other organ complications post-infection, which have raised concerns about long COVID. The term "long COVID" was first used by Perego on social media to denote the persistence of symptoms weeks or months after initial SARS-CoV-2 infection and the term 'long haulers' was first described by Watson and by Yong to identify post-COVID conditions. There has been an increased incidence of sudden cardiac death and MI post-COVID-19 in healthy individuals, sports persons and prominent movie stars. Potential mechanisms contributing to the pathophysiology of post-acute COVID-19 may include 1) Damage to tissues and cells that are important for blood flow, so clotting of blood is increased. 2) Persistence of fragments of virus or its sub-particles/ protein material in a wide range of body sites and, 3) an immune system gone haywire. As the majority of countries across the globe are easing coronavirus precautionary measures, there is an urgent need by health care organizations and policymakers worldwide to generate awareness by educating the public at large, about the ill effects of long-COVID and varied types of post-acute sequelae of COVID-19.}, }
@article {pmid36247234, year = {2022}, author = {Norouzi Masir, M and Shirvaliloo, M}, title = {Symptomatology and microbiology of the gastrointestinal tract in post-COVID conditions.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {6}, number = {10}, pages = {667-676}, pmid = {36247234}, issn = {2397-9070}, abstract = {Post-COVID conditions, also known as post-acute sequelae of SARS-CoV-2 (PASC), refer to the persistence of symptoms in COVID-19 long-haulers. Various manifestations of post-COVID conditions are general symptoms and/or manifestations of damage in multiple organs. Besides, SARS-CoV-2 can involve the gastrointestinal tract, resulting in sequelae such as diarrhea, abdominal pain, nausea, anorexia, vomiting, constipation, abdominal distension, acid reflux, and/or gastrointestinal bleeding. Previous investigations point to SARS-CoV-2 entry into enterocytes enhances by the angiotensin-converting enzyme 2 (ACE2) receptors. Interestingly, ACE2 receptors are abundantly expressed in the gut, implying infection with SARS-CoV-2 might occur through this route as well as in the respiratory tract. According to mounting evidence, SARS-CoV-2 RNA has been identified in fecal specimens of patients with COVID-19 during and beyond the acute phase. In addition, studies have shown gut microbiome composition is altered in patients with PASC, hence, another putative mechanism linked to gastrointestinal symptoms is gut dysbiosis. The presence of the gut-lung axis in COVID-19 might have major implications for disease pathogenesis and treatment. This review discussed the prevalence of gastrointestinal symptoms and pathophysiology underlying possible infection of the gut in patients with PASC. Also, SARS-COV-2 induced NLRP3 inflammasome-dependent inflammatory pathways are briefly addressed.}, }
@article {pmid36253560, year = {2023}, author = {Xu, SW and Ilyas, I and Weng, JP}, title = {Endothelial dysfunction in COVID-19: an overview of evidence, biomarkers, mechanisms and potential therapies.}, journal = {Acta pharmacologica Sinica}, volume = {44}, number = {4}, pages = {695-709}, pmid = {36253560}, issn = {1745-7254}, mesh = {Animals ; Humans ; Biomarkers ; *COVID-19/pathology ; *Endothelial Cells/pathology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {The fight against coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection is still raging. However, the pathophysiology of acute and post-acute manifestations of COVID-19 (long COVID-19) is understudied. Endothelial cells are sentinels lining the innermost layer of blood vessel that gatekeep micro- and macro-vascular health by sensing pathogen/danger signals and secreting vasoactive molecules. SARS-CoV-2 infection primarily affects the pulmonary system, but accumulating evidence suggests that it also affects the pan-vasculature in the extrapulmonary systems by directly (via virus infection) or indirectly (via cytokine storm), causing endothelial dysfunction (endotheliitis, endothelialitis and endotheliopathy) and multi-organ injury. Mounting evidence suggests that SARS-CoV-2 infection leads to multiple instances of endothelial dysfunction, including reduced nitric oxide (NO) bioavailability, oxidative stress, endothelial injury, glycocalyx/barrier disruption, hyperpermeability, inflammation/leukocyte adhesion, senescence, endothelial-to-mesenchymal transition (EndoMT), hypercoagulability, thrombosis and many others. Thus, COVID-19 is deemed as a (micro)vascular and endothelial disease. Of translational relevance, several candidate drugs which are endothelial protective have been shown to improve clinical manifestations of COVID-19 patients. The purpose of this review is to provide a latest summary of biomarkers associated with endothelial cell activation in COVID-19 and offer mechanistic insights into the molecular basis of endothelial activation/dysfunction in macro- and micro-vasculature of COVID-19 patients. We envisage further development of cellular models and suitable animal models mimicking endothelial dysfunction aspect of COVID-19 being able to accelerate the discovery of new drugs targeting endothelial dysfunction in pan-vasculature from COVID-19 patients.}, }
@article {pmid36253950, year = {2024}, author = {Zheng, X and Qian, M and Ye, X and Zhang, M and Zhan, C and Li, H and Luo, T}, title = {Implications for long COVID: A systematic review and meta-aggregation of experience of patients diagnosed with COVID-19.}, journal = {Journal of clinical nursing}, volume = {33}, number = {1}, pages = {40-57}, pmid = {36253950}, issn = {1365-2702}, mesh = {Humans ; Aftercare ; Patient Discharge ; *Post-Acute COVID-19 Syndrome/diagnosis/epidemiology ; Qualitative Research ; }, abstract = {AIMS AND OBJECTIVES: This review aims to synthesize the available evidence of what patients experience when infected with COVID-19, both in hospital and post-discharge settings.<br><br>DESIGN: This review was conducted using the Joanna Briggs Institute (JBI) methodology for qualitative systematic reviews and evidence synthesis. Reporting of results was presented according to the Enhancing Transparency in Reporting the Synthesis of Qualitative Research (ENTREQ) checklist.<br><br>BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to be a public health crisis worldwide. Many patients diagnosed with COVID-19 have varied levels of persisting mental disorders. Previous studies have reported the degree, prevalence and outcome of psychological problems. Minimal research explored the experience of patients with long COVID. The real-life experience of patients with COVID-19 from diagnosis to post-discharge can deepen the understanding of nurses, physicians and policymakers.<br><br>METHODS: All studies describing the experience of patients were included. Two authors independently appraised the methodological quality of the included studies using the JBI Critical Appraisal Checklist for Qualitative Research 2020.<br><br>RESULTS: This systematic review aggregated patients' experience of being diagnosed with COVID-19 in both hospitalized and post-discharge settings. Finally, 17 studies met inclusion criteria and quality appraisal guidelines. The selected studies in the meta-synthesis resulted in 12 categories, and further were concluded as five synthesized findings: physical symptoms caused by the virus, positive and negative emotional responses to the virus, positive coping strategies as facilitators of epidemic prevention and control, negative coping strategies as obstacles of epidemic prevention and control, and unmet needs for medical resource.<br><br>CONCLUSIONS: The psychological burden of patients diagnosed with COVID-19 is heavy and persistent. Social support is essential in the control and prevention of the epidemic. Nurses and other staff should pay more attention to the mental health of the infected patients both in and after hospitalization.<br><br>Nurses should care about the persistent mental trauma of COVID-19 survivors and provide appropriate psychological interventions to mitigate the negative psychological consequences of them. Besides, nurses, as healthcare professionals who may have the most touch with patients, should evaluate the level of social support and deploy it for them. It is also needed for nurses to listen to patient's needs and treat them with carefulness and adequate patience in order to decrease the unmet needs of patients.}, }
@article {pmid36272444, year = {2023}, author = {Sacks-Zimmerman, A and Bergquist, TF and Farr, EM and Cornwell, MA and Kanellopoulos, D}, title = {Rehabilitation of Neuropsychiatric Symptoms in Patients With Long COVID: Position Statement.}, journal = {Archives of physical medicine and rehabilitation}, volume = {104}, number = {2}, pages = {350-354}, pmid = {36272444}, issn = {1532-821X}, mesh = {Adult ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Quality of Life ; *Mental Disorders ; Chronic Disease ; }, abstract = {Long COVID, a term used to describe ongoing symptoms after COVID-19 infection, parallels the course of other postviral syndromes. Neuropsychiatric symptoms of long COVID can be persistent and interfere with quality of life and functioning. Within the biopsychosocial framework of chronic illness, rehabilitation professionals can address the neuropsychiatric sequelae of long COVID. However, current practice models are not designed to address concurrent psychiatric and cognitive symptoms in adults living with long COVID. Thus, we present a biopsychosocial framework for long COVID and provide treatment strategies based on evidence from current literature of postviral chronic illness. These recommendations will guide rehabilitation professionals in identifying common neuropsychiatric symptoms in long COVID that can be targeted for intervention and addressing these symptoms via integrative interventions taking into account the biopsychosocial presentation of long COVID symptoms.}, }
@article {pmid36280088, year = {2022}, author = {Ferreira, LC and Gomes, CEM and Rodrigues-Neto, JF and Jeronimo, SMB}, title = {Genome-wide association studies of COVID-19: Connecting the dots.}, journal = {Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases}, volume = {106}, number = {}, pages = {105379}, pmid = {36280088}, issn = {1567-7257}, mesh = {Humans ; *COVID-19/genetics ; SARS-CoV-2/genetics ; Genome-Wide Association Study ; Post-Acute COVID-19 Syndrome ; Antiviral Agents ; Membrane Transport Proteins ; }, abstract = {Genome-wide association studies (GWASs) are a research approach used to identify genetic variants associated with common diseases, like COVID-19. The lead genetic variants (n = 41) reported by the eleven largest COVID-19 GWASs are mapped to 22 different chromosomal regions. The loci 3q21.31 (LZTFL1 and chemokine receptor genes) and 9q34.2 (ABO), associated with disease severity and susceptibility to infection, respectively, were the most replicated findings across studies. Genes involved with mucociliary clearance (CEP97, FOXP4), viral-entry (ACE2, SLC6A20) and mucosal immunity (MIR6891) are associated with the risk of SARS-CoV-2 infection while genes of antiviral immune response (IFNAR2, OAS1), leukocyte trafficking (CCR9, CXCR6) and lung injury (DPP9, NOTCH4) are associated with severe disease. The biological processes underlying the risk of infection occur prominently, but not exclusively, in the upper airways whereas the severe COVID-19-associated processes in alveolar-capillary interface. The COVID-19 GWASs has unraveled key genetic mechanisms of SARS-CoV-2 pathogenesis, although the genetic basis of other COVID-19 related phenotypes (long COVID and neurological impairment) remains to be elucidated.}, }
@article {pmid36281239, year = {2022}, author = {Pink, I and Welte, T}, title = {[Not Available].}, journal = {Pneumo news}, volume = {14}, number = {5}, pages = {43-49}, pmid = {36281239}, issn = {2199-3866}, }
@article {pmid36281870, year = {2024}, author = {Hon, KLE and Leung, AKC and Leung, KKY and Wong, AHC}, title = {Impact of "Long Covid" on Children: Global and Hong Kong Perspectives.}, journal = {Current pediatric reviews}, volume = {20}, number = {1}, pages = {59-65}, doi = {10.2174/1573396319666221021154949}, pmid = {36281870}, issn = {1875-6336}, mesh = {Adolescent ; Child ; Humans ; *COVID-19/epidemiology/complications ; SARS-CoV-2 ; Hong Kong/epidemiology ; Pandemics/prevention &amp; control ; Post-Acute COVID-19 Syndrome ; Systemic Inflammatory Response Syndrome ; }, abstract = {BACKGROUND: The coronavirus disease (COVID-19) pandemic spares no nation or city, and the virus is responsible for the escalating incidence and mortality worldwide.<br><br>OBJECTIVE: This article reviews the impact of "Long Covid" on Children.<br><br>METHODS: A PubMed search was conducted in December 2021 in Clinical Queries using the key terms "COVID-19" OR "long COVID". The search was restricted to children and adolescent aged < 18 years and English literature.<br><br>RESULTS: Many large-scale studies have provided strong scientific evidence as to the detrimental and irreversible sequelae of COVID-19 on the health, psychology, and development of affected children. Many insights into managing this disease can be obtained from comparing the management of influenza. COVID-19 is generally a mild respiratory disease in children. Several syndromes, such as multisystem inflammatory syndrome in children (MIS-C) and COVID toe, are probably not specific to SARS-CoV-2. "Long COVID", or the long-term effects of SARS-CoV-2 infection, or the prolonged isolation and containment strategies on education and psychosocial influences on children associated with the pandemic, are significant.<br><br>CONCLUSION: Healthcare providers must be aware of the potential effects of quarantine on children's mental health. More importantly, healthcare providers must appreciate the importance of the decisions and actions made by governments, non-governmental organizations, the community, schools, and parents in reducing the possible effects of this situation. Multifaceted age-specific and developmentally appropriate strategies must be adopted by healthcare authorities to lessen the negative impact of quarantine on the psychological well-being of children.}, }
@article {pmid36283919, year = {2023}, author = {Lai, CC and Hsu, CK and Yen, MY and Lee, PI and Ko, WC and Hsueh, PR}, title = {Long COVID: An inevitable sequela of SARS-CoV-2 infection.}, journal = {Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi}, volume = {56}, number = {1}, pages = {1-9}, pmid = {36283919}, issn = {1995-9133}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Quality of Life ; Lung ; Disease Progression ; }, abstract = {At present, there are more than 560 million confirmed cases of the coronavirus disease 2019 (COVID-19) worldwide. Although more than 98% of patients with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection can survive acute COVID, a significant portion of survivors can develop residual health problems, which is termed as long COVID. Although severe COVID-19 is generally associated with a high risk of long COVID, patients with asymptomatic or mild disease can also show long COVID. The definition of long COVID is inconsistent and its clinical manifestations are protean. In addition to general symptoms, such as fatigue, long COVID can affect many organ systems, including the respiratory, neurological, psychosocial, cardiovascular, gastrointestinal, and metabolic systems. Moreover, patients with long COVID may experience exercise intolerance and impaired daily function and quality of life. Long COVID may be caused by SARS-CoV-2 direct injury or its associated immune/inflammatory response. Assessment of patients with long COVID requires comprehensive evaluation, including history taking, physical examination, laboratory tests, radiography, and functional tests. However, there is no known effective treatment for long COVID. Based on the limited evidence, vaccines may help to prevent the development of long COVID. As long COVID is a new clinical entity that is constantly evolving, there are still many unknowns, and further investigation is warranted to enhance our understanding of this disease.}, }
@article {pmid36288726, year = {2022}, author = {Monje, M and Iwasaki, A}, title = {The neurobiology of long COVID.}, journal = {Neuron}, volume = {110}, number = {21}, pages = {3484-3496}, pmid = {36288726}, issn = {1097-4199}, support = {U19 CA264504/CA/NCI NIH HHS/United States ; R01 CA258384/CA/NCI NIH HHS/United States ; DP1 NS111132/NS/NINDS NIH HHS/United States ; R01 NS092597/NS/NINDS NIH HHS/United States ; R01 AI157488/AI/NIAID NIH HHS/United States ; P50 CA165962/CA/NCI NIH HHS/United States ; R01 CA263500/CA/NCI NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; *Nervous System Diseases ; *Mental Disorders ; Post-Acute COVID-19 Syndrome ; }, abstract = {Persistent neurological and neuropsychiatric symptoms affect a substantial fraction of people after COVID-19 and represent a major component of the post-acute COVID-19 syndrome, also known as long COVID. Here, we review what is understood about the pathobiology of post-acute COVID-19 impact on the CNS and discuss possible neurobiological underpinnings of the cognitive symptoms affecting COVID-19 survivors. We propose the chief mechanisms that may contribute to this emerging neurological health crisis.}, }
@article {pmid36289827, year = {2022}, author = {Fernández-de-Las-Peñas, C and Nijs, J and Neblett, R and Polli, A and Moens, M and Goudman, L and Shekhar Patil, M and Knaggs, RD and Pickering, G and Arendt-Nielsen, L}, title = {Phenotyping Post-COVID Pain as a Nociceptive, Neuropathic, or Nociplastic Pain Condition.}, journal = {Biomedicines}, volume = {10}, number = {10}, pages = {}, pmid = {36289827}, issn = {2227-9059}, support = {LONG COVID EXP//Comunidad de Madrid/ ; NNF21OC0067235//Novo Nordisk Foundation/ ; }, abstract = {Pain after an acute Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) condition (post-COVID pain) is becoming a new healthcare emergency. Precision medicine refers to an evidence-based method of grouping patients based on their diagnostic/symptom presentation and then tailoring specific treatments accordingly. Evidence suggests that post-COVID pain can be categorized as nociceptive (i.e., pain attributable to the activation of the peripheral receptive terminals of primary afferent neurons in response to noxious chemical, mechanical, or thermal stimuli), neuropathic (i.e., pain associated with a lesion or disease of the somatosensory nervous system and limited to a "neuroanatomically plausible" distribution of the system), nociplastic (i.e., pain arising from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors or evidence for disease or lesion of the somatosensory system causing the pain), or mixed type (when two pain phenotypes co-exist). Each of these pain phenotypes may require a different treatment approach to maximize treatment effectiveness. Accordingly, the ability to classify post-COVID pain patients into one of these phenotypes would likely be critical for producing successful treatment outcomes. The 2021 International Association for the Study of Pain (IASP) clinical criteria and grading system provide a framework for classifying pain within a precision pain medicine approach. Here we present data supporting the possibility of grouping patients with post-COVID pain into pain phenotypes, using the 2021 IASP classification criteria, with a specific focus on nociplastic pain, which is probably the primary mechanism involved in post-COVID pain. Nociplastic pain, which is usually associated with comorbid symptomology (e.g., poor sleep quality, fatigue, cognitive-emotional disturbances, etc.) and is considered to be more difficult to treat than other pain types, may require a more nuanced multimodal treatment approach to achieve better treatment outcomes.}, }
@article {pmid36291027, year = {2022}, author = {Cherusseri, J and Savio, CM and Khalid, M and Chaudhary, V and Numan, A and Varma, SJ and Menon, A and Kaushik, A}, title = {SARS-CoV-2-on-Chip for Long COVID Management.}, journal = {Biosensors}, volume = {12}, number = {10}, pages = {}, pmid = {36291027}, issn = {2079-6374}, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19/diagnosis ; COVID-19 Testing ; Point-of-Care Systems ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a "wicked evil" in this century due to its extended progression and huge human mortalities. Although the diagnosis of SARS-CoV-2 viral infection is made simple and practical by employing reverse transcription polymerase chain reaction (RT-PCR) investigation, the process is costly, complex, time-consuming, and requires experts for testing and the constraints of a laboratory. Therefore, these challenges have raised the paradigm of on-site portable biosensors on a single chip, which reduces human resources and enables remote access to minimize the overwhelming burden on the existing global healthcare sector. This article reviews the recent advancements in biosensors for long coronavirus disease (COVID) management using a multitude of devices, such as point-of-care biosensors and lab-on-chip biosensors. Furthermore, it details the shift in the paradigm of SARS-CoV-2-on-chip biosensors from the laboratory to on-site detection with intelligent and economical operation, representing near-future diagnostic technologies for public health emergency management.}, }
@article {pmid36293160, year = {2022}, author = {Scurati, R and Papini, N and Giussani, P and Alberti, G and Tringali, C}, title = {The Challenge of Long COVID-19 Management: From Disease Molecular Hallmarks to the Proposal of Exercise as Therapy.}, journal = {International journal of molecular sciences}, volume = {23}, number = {20}, pages = {}, pmid = {36293160}, issn = {1422-0067}, mesh = {Humans ; *COVID-19/therapy ; SARS-CoV-2 ; Quality of Life ; Nerve Growth Factors ; }, abstract = {Long coronavirus disease 19 (COVID-19) is the designation given to a novel syndrome that develops within a few months after infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and that is presenting with increasing incidence because of the numerous cases of infection. Long COVID-19 is characterized by a sequela of clinical symptoms that concern different organs and tissues, from nervous, respiratory, gastrointestinal, and renal systems to skeletal muscle and cardiovascular apparatus. The main common molecular cause for all long COVID-19 facets appears to be related to immune dysregulations, the persistence of inflammatory status, epigenetic modifications, and alterations of neurotrophin release. The prevention and management of long COVID-19 are still inappropriate because many aspects need further clarification. Exercise is known to exert a deep action on molecular dysfunctions elicited by long COVID-19 depending on training intensity, duration, and continuity. Evidence suggests that it could improve the quality of life of long COVID-19 patients. This review explores the main clinical features and the known molecular mechanisms underlying long COVID-19 in the perspective of considering exercise as a co-medication in long COVID-19 management.}, }
@article {pmid36293857, year = {2022}, author = {Wrona, M and Skrypnik, D}, title = {New-Onset Diabetes Mellitus, Hypertension, Dyslipidaemia as Sequelae of COVID-19 Infection-Systematic Review.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {20}, pages = {}, pmid = {36293857}, issn = {1660-4601}, support = {502-14-21191730-11315 ; ID: 4089//Poznan University of Medical Sciences/ ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; *Diabetes Mellitus/epidemiology/etiology ; *Hypertension/epidemiology/etiology ; *Dyslipidemias/epidemiology/etiology ; Glucose ; Lipids ; }, abstract = {As the population recovers from the coronavirus disease 2019 (COVID-19) pandemic, a subset of individuals is emerging as post-coronavirus disease (post-COVID) patients who experience multifactorial long-term symptoms several weeks after the initial recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aim of this systematic review is to present the latest scientific reports that evaluate changes in glucose levels, blood pressure readings and lipid profiles after recovery from COVID-19 to verify the hypothesis that new-onset diabetes mellitus, arterial hypertension and dyslipidaemia are a possible sequela of a COVID-19 infection. The open access databases PubMed and Google Scholar were searched. Articles investigating patients with residual clinical signs and biochemical alteration indicating diabetes, hypertension and dyslipidaemia at least a month after recovering from COVID-19 were included. It has been shown that a select number of patients were diagnosed with new-onset diabetes, arterial hypertension and dyslipidaemia after COVID-19 infection. Alterations in glucose levels, blood pressure and lipid profiles months after initial infection shows the importance of considering diabetes mellitus, arterial hypertension and dyslipidaemia as part of the multifactorial diagnostic criteria post-COVID to better provide evidence-based clinical care.}, }
@article {pmid36294186, year = {2022}, author = {Hiremath, S and Doukrou, M and Flannery, H and Carey, C and Gregorowski, A and Ward, J and Hargreaves, D and Segal, TY}, title = {Key Features of a Multi-Disciplinary Hospital-Based Rehabilitation Program for Children and Adolescents with Moderate to Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome ME/CFS.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {20}, pages = {}, pmid = {36294186}, issn = {1660-4601}, mesh = {Child ; Humans ; Adolescent ; *Fatigue Syndrome, Chronic/therapy ; Retrospective Studies ; *COVID-19 ; Hospitals ; }, abstract = {PURPOSE OF THE STUDY: There is limited published data on treatment or outcomes of children and young people (CYP) with moderate or severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Here, we describe outcomes of moderate and severe ME/CFS in CYP treated in a tertiary adolescent service. This information is useful when planning services for CYP and families affected by moderate/severe ME/CFS and to guide future management trials and commissioning decisions.<br><br>STUDY DESIGN: A retrospective review was conducted of medical records of the 27 CYP who received ward-based treatment in 2015. Notes were retrospectively reviewed to assess progress in four markers of wellbeing over the period of treatment: (i) mobility, (ii) education, (iii) sleep and (iv) involvement in social/recreational activities.<br><br>RESULTS: A total of 23/27 (85%) showed improvement in one or more domains over their period of ward-based therapy. 19/27 (70%) of patients showed improvement in physical ability. In 15/23 patients (65%), there was an improvement in ability to access education, in 12/24 (50%) sleep improved, and 16/27 (59%) demonstrated an improvement in socialising/ability perform recreational activities.<br><br>CONCLUSION/IMPLICATIONS: A multidisciplinary hospital-based rehabilitation programme for moderate and severe ME/CFS was associated with improvement in at least one area of wellbeing in 85% of the CYP we reviewed. These data may be used as a baseline to evaluate the impact of other models of delivering care for this patient group. It may be useful when considering other groups such as those affected by Post-COVID Syndrome.}, }
@article {pmid36295814, year = {2022}, author = {Alenazy, MF and Aljohar, HI and Alruwaili, AR and Daghestani, MH and Alonazi, MA and Labban, RS and El-Ansary, AK and Balto, HA}, title = {Gut Microbiota Dynamics in Relation to Long-COVID-19 Syndrome: Role of Probiotics to Combat Psychiatric Complications.}, journal = {Metabolites}, volume = {12}, number = {10}, pages = {}, pmid = {36295814}, issn = {2218-1989}, support = {RSP2022R179//King Saud University, Riyadh, Saudi Arabia/ ; }, abstract = {Increasing numbers of patients who recover from COVID-19 report lasting symptoms, such as fatigue, muscle weakness, dementia, and insomnia, known collectively as post-acute COVID syndrome or long COVID. These lasting symptoms have been examined in different studies and found to influence multiple organs, sometimes resulting in life-threating conditions. In this review, these symptoms are discussed in connection to the COVID-19 and long-COVID-19 immune changes, highlighting oral and psychiatric health, as this work focuses on the gut microbiota's link to long-COVID-19 manifestations in the liver, heart, kidney, brain, and spleen. A model of this is presented to show the biological and clinical implications of gut microbiota in SARS-CoV-2 infection and how they could possibly affect the therapeutic aspects of the disease. Probiotics can support the body's systems in fighting viral infections. This review focuses on current knowledge about the use of probiotics as adjuvant therapies for COVID-19 patients that might help to prevent long-COVID-19 complications.}, }
@article {pmid36298472, year = {2022}, author = {Rapti, V and Tsaganos, T and Vathiotis, IA and Syrigos, NK and Li, P and Poulakou, G}, title = {New Insights into SARS-CoV-2 and Cancer Cross-Talk: Does a Novel Oncogenesis Driver Emerge?.}, journal = {Vaccines}, volume = {10}, number = {10}, pages = {}, pmid = {36298472}, issn = {2076-393X}, abstract = {Since the pandemic's onset, a growing population of individuals has recovered from SARS-CoV-2 infection and its long-term effects in some of the convalescents are gradually being reported. Although the precise etiopathogenesis of post-acute COVID-19 sequelae (PACS) remains elusive, the mainly accepted rationale is that SARS-CoV-2 exerts long-lasting immunomodulatory effects, promotes chronic low-grade inflammation, and causes irreversible tissue damage. So far, several viruses have been causally linked to human oncogenesis, whereas chronic inflammation and immune escape are thought to be the leading oncogenic mechanisms. Excessive cytokine release, impaired T-cell responses, aberrant activation of regulatory signaling pathways (e.g., JAK-STAT, MAPK, NF-kB), and tissue damage, hallmarks of COVID-19 disease course, are also present in the tumor microenvironment. Therefore, the intersection of COVID-19 and cancer is partially recognized and the long-term effects of the virus on oncogenesis and cancer progression have not been explored yet. Herein, we present an up-to-date review of the current literature regarding COVID-19 and cancer cross-talk, as well as the oncogenic pathways stimulated by SARS-CoV-2.}, }
@article {pmid36314211, year = {2023}, author = {Golzari-Sorkheh, M and Weaver, DF and Reed, MA}, title = {COVID-19 as a Risk Factor for Alzheimer's Disease.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {91}, number = {1}, pages = {1-23}, doi = {10.3233/JAD-220800}, pmid = {36314211}, issn = {1875-8908}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; *Alzheimer Disease/epidemiology/complications ; Neuroinflammatory Diseases ; *Nervous System Diseases/etiology ; Risk Factors ; }, abstract = {Severe acute respiratory disease coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) pandemic. Although a primarily respiratory disease, recent reports indicate that it also affects the central nervous system (CNS). Over 25% of COVID-19 patients report neurological symptoms such as memory loss, anosmia, hyposmia, confusion, and headaches. The neurological outcomes may be a result of viral entry into the CNS and/or resulting neuroinflammation, both of which underlie an elevated risk for Alzheimer's disease (AD). Herein, we ask: Is COVID-19 a risk factor for AD? To answer, we identify the literature and review mechanisms by which COVID-19-mediated neuroinflammation can contribute to the development of AD, evaluate the effects of acute versus chronic phases of infection, and lastly, discuss potential therapeutics to address the rising rates of COVID-19 neurological sequelae.}, }
@article {pmid36317068, year = {2022}, author = {Tarantino, U and Visconti, VV and Bonanni, R and Gatti, A and Marcozzi, M and Calabrò, D and Cariati, I}, title = {Osteosarcopenia and Long-COVID: a dangerous combination.}, journal = {Therapeutic advances in musculoskeletal disease}, volume = {14}, number = {}, pages = {1759720X221130485}, pmid = {36317068}, issn = {1759-720X}, abstract = {SARS-CoV-2 has caused a global pandemic and an unprecedented public health crisis, infecting more than 580 million people worldwide. Moreover, recent evidence has suggested the emergence of a new syndrome known as Long-COVID, a term used to describe a diverse set of physical and mental symptoms that persist after a diagnosed SARS-CoV-2 infection. Epidemiological data have identified myalgias, muscle and joint dysfunction, and bone fragility as common sequelae in patients with moderate and severe forms of this disease. Significant musculoskeletal dysfunction has also been detected in some healed patients, although knowledge about pathophysiological mechanisms of Long-COVID is still rather scarce. In this context, SARS-CoV-2 infection has been suggested to amplify the effects of aging on the musculoskeletal system by aggravating the osteosarcopenic state. Based on this evidence, our review focused on the muscle and bone tissue alterations induced by SARS-CoV-2 infection and Long-COVID, summarizing the current knowledge on the underlying biological mechanisms and highlighting the need for a multidisciplinary approach to predict the musculoskeletal targets and long-term consequences of COVID-19 disease.}, }
@article {pmid36322364, year = {2022}, author = {Mohammad, KO and Lin, A and Rodriguez, JBC}, title = {Cardiac Manifestations of Post-Acute COVID-19 Infection.}, journal = {Current cardiology reports}, volume = {24}, number = {12}, pages = {1775-1783}, pmid = {36322364}, issn = {1534-3170}, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; RNA, Viral ; Heart ; Arrhythmias, Cardiac ; }, abstract = {PURPOSE OF REVIEW: There is emerging evidence that the post-acute and chronic phases of COVID-19 infection are associated with various significant cardiovascular sequelae.<br><br>RECENT FINDINGS: Long COVID has been shown to be associated with multiple cardiovascular sequelae including direct myocardial injury, arrhythmias, and cardiomyopathies. Hypotheses on the mechanism of myocardial injury include direct viral infiltration and autoimmune dysregulation. Long COVID is associated with persistent cardiac ischemia in patients with no previous history of coronary disease, atrial and ventricular arrhythmias, and the development of new-onset heart failure in previously healthy patients. Onset of long COVID may be related to severity of the initial SARS-CoV2 infection. Cardiac MRI is a valuable tool in assessing myocarditis and the development of cardiomyopathies in the setting of long COVID. Both patients with and without pre-existing cardiovascular disease are at risk of developing myocardial injury in the setting of long COVID. Future studies will elucidate both cardiovascular mortality and cardiac rehabilitation in the post-acute and chronic phases of COVID-19.}, }
@article {pmid36324314, year = {2022}, author = {Suba Rao, HR and Hamzaid, NA and Ahmad, MY and Hamzah, N}, title = {Physiological factors affecting the mechanical performance of peripheral muscles: A perspective for long COVID patients through a systematic literature review.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {958333}, pmid = {36324314}, issn = {1664-042X}, abstract = {Background: Peripheral muscle weakness can be measured quantitatively in long COVID patients. Mechanomyography (MMG) is an alternative tool to measure muscle strength non-invasively. Objective: This literature review aims to provide evidence on the efficacy of MMG in measuring muscle strength for long COVID patients and to determine the physiological factors that may affect the use of MMG in assessing muscle performance. Methods: A systematic literature review was conducted using EBSCO's MEDLINE Complete. A total of five out of 2,249 potential publications fulfilled the inclusion criteria. Results: The selected studies addressed muscle performance based on the physiological effects of age, gender, and physical activity level. MMG is sensitive in measuring muscle strength for long COVID patients due to its higher signal-to-noise ratio and lightweight accelerometers. Its neglectable skin impedance and low risk of influences during the recording of surface motions make MMG a reliable tool. Conclusion: Muscle performance is affected by age, gender, and physical activity level. Sensors, such as MMG, as well as the length of the muscle and the characteristics of the muscle activity, are important considerations when choosing a sensor for diagnostic evaluation. The efficacy of MMG in measuring muscle strength for long COVID patients and the physiological factors that may affect the use of MMG in assessing muscle performance are discussed.}, }
@article {pmid36324612, year = {2022}, author = {Efstathiou, V and Stefanou, MI and Demetriou, M and Siafakas, N and Katsantoni, E and Makris, M and Tsivgoulis, G and Zoumpourlis, V and Kympouropoulos, SP and Tsoporis, JN and Spandidos, DA and Ferentinos, P and Smyrnis, N and Rizos, E}, title = {New‑onset neuropsychiatric sequelae and 'long‑COVID' syndrome (Review).}, journal = {Experimental and therapeutic medicine}, volume = {24}, number = {5}, pages = {705}, pmid = {36324612}, issn = {1792-1015}, abstract = {The ongoing coronavirus disease 2019 (COVID-19) pandemic has had a widespread impact on individuals' mental health through indirect psychological and social mechanisms, related to factors such as fear of infection or death, social isolation, lack of social support and financial instability. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has also been associated with the development or recurrence of neuropsychiatric symptoms, both during the acute phase, as well as during the post-acute 'long-COVID' phase. In addition to the COVID-19 survivors with a mental health history that are at a high risk of experiencing a range of neuropsychiatric symptoms following resolution of acute COVID-19, there is accumulating evidence that a diagnosis of COVID-19 may also be associated with new-onset neuropsychiatric morbidity among survivors without pre-existing mental health disorders. In particular, studies investigating the incidence of post-acute neuropsychiatric sequelae, based mostly on retrospective cohort study designs and data from national health registries, have reported the development of new-onset manifestations, including depression, anxiety, psychotic symptoms, sleep disturbances and fatigue. Nevertheless, when COVID-19 survivors were compared with SARS-CoV-2-negative controls and especially survivors of other disorders (such as influenza), the findings regarding the risk of incident neuropsychiatric manifestations varied among studies. While there is evidence of an association between SARS-CoV-2 infection and the subsequent occurrence of new-onset neuropsychiatric symptoms, especially among patients with increased disease severity, further research using methodological approaches less susceptible to confounding bias is required to establish causal relationships.}, }
@article {pmid36326545, year = {2022}, author = {Zawilska, JB and Kuczyńska, K}, title = {Psychiatric and neurological complications of long COVID.}, journal = {Journal of psychiatric research}, volume = {156}, number = {}, pages = {349-360}, pmid = {36326545}, issn = {1879-1379}, mesh = {Child ; Humans ; Adolescent ; *Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; SARS-CoV-2 ; }, abstract = {COVID-19 was primarily considered a pulmonary disease with extrapulmonary manifestations. As the pandemic spread, there has been growing evidence that the disease affects various organs/systems, including the central and peripheral nervous systems. Accumulation of clinical data demonstrates that in a large population of survivors impairments in the function of one or more organs may persist for a long time, a phenomenon commonly known as post COVID or long COVID. Fatigue and cognitive dysfunction, such as concentration problems, short-term memory deficits, general memory loss, a specific decline in attention, language and praxis abilities, encoding and verbal fluency, impairment of executive functions, and psychomotor coordination, are amongst the most common and debilitating features of neuropsychatric symptoms of post COVID syndrome. Several patients also suffer from compromised sleep, depression, anxiety and post-traumatic stress disorder. Patients with long COVID may demonstrate brain hypometabolism, hypoperfusion of the cerebral cortex and changes in the brain structure and functional connectivity. Children and adolescents represent a minority of COVID-19 cases, so not surprisingly data on the long-term sequelae after SARS-CoV-2 infections in these age groups are scarce. Although the pathogenesis, clinical characteristics, epidemiology, and risk factors of the acute phase of COVID-19 have been largely explained, these areas are yet to be explored in long COVID. This review aims to provide an update on what is currently known about long COVID effects on mental health.}, }
@article {pmid36326730, year = {2022}, author = {Kessler, A and Heightman, M and Brennan, E}, title = {Post-COVID-19 respiratory problems: burden and management.}, journal = {Current opinion in supportive and palliative care}, volume = {16}, number = {4}, pages = {203-209}, doi = {10.1097/SPC.0000000000000619}, pmid = {36326730}, issn = {1751-4266}, mesh = {Humans ; Female ; *COVID-19/complications/epidemiology ; Quality of Life ; Respiratory Function Tests ; *Lung Diseases, Interstitial ; Lung ; }, abstract = {PURPOSE OF REVIEW: To describe the burden of post-COVID respiratory sequelae in posthospital and nonhospitalized COVID-19 survivors and to describe the priorities of clinical management.<br><br>RECENT FINDINGS: Due to varying definitions of 'Long COVID' or 'Post-COVID', the prevalence of post-COVID sequelae or persisting symptoms is challenging to estimate but ranges from 2.3 to 51%. Risk factors for persistent post-COVID symptoms include age, female sex, deprivation, presence of comorbidities; and in posthospital COVID-19 survivors, the severity of acute infection. Common post-COVID respiratory symptoms include breathlessness, cough and chest pain and many individuals also experience exercise intolerance. The most common pulmonary function test abnormality is impaired diffusing capacity for carbon monoxide. In posthospital COVID-19 survivors, the prevalence of interstitial lung damage is 5-11%. Disordered breathing is common in all post-COVID patients and respiratory physiotherapy is helpful.<br><br>SUMMARY: The vast numbers of COVID-19 infections globally implies that a large number of people will be affected by post-COVID sequelae even with conservative estimates. A significant number of people are affected for several months and up to years following acute infection. Post-COVID sequelae have a detrimental impact on quality of life and ability to work.}, }
@article {pmid36339677, year = {2022}, author = {Amekran, Y and Damoun, N and El Hangouche, AJ}, title = {Postural orthostatic tachycardia syndrome and post-acute COVID-19.}, journal = {Global cardiology science &amp; practice}, volume = {2022}, number = {1-2}, pages = {e202213}, pmid = {36339677}, issn = {2305-7823}, abstract = {While the acute illness of COVID-19 was the initial focus of concern, there are increasing reports of patients with chronic symptoms, known as long-COVID. Dysautonomia may be a possible post-acute neurological complication explaining the persistent symptoms observed in long COVID. Postural tachycardia syndrome (POTS), a form of dysautonomia characterized by sustained tachycardia and orthostatic intolerance, has been increasingly reported in patients after SARS-CoV-2 infection. In this context, this review aimed to report and discuss the available literature pertaining to post COVID-19 POTS.}, }
@article {pmid36343180, year = {2022}, author = {Yonts, A Brugler}, title = {Pediatric Long-COVID: A Review of the Definition, Epidemiology, Presentation, and Pathophysiology.}, journal = {Pediatric annals}, volume = {51}, number = {11}, pages = {e416-e420}, doi = {10.3928/19382359-20220913-06}, pmid = {36343180}, issn = {1938-2359}, mesh = {Child ; Humans ; *COVID-19/diagnosis/epidemiology ; SARS-CoV-2 ; Activities of Daily Living ; Post-Acute COVID-19 Syndrome ; }, abstract = {Although children have been largely spared the most severe consequences of acute infection with SARS-CoV-2 virus, it is estimated that up to one-quarter of the more than 14 million children diagnosed as having coronavirus disease 2019 (COVID-19) have developed persistent symptoms of fatigue, postexertional malaise, neurologic and cognitive symptoms, and other symptoms that interfere with activities of daily living for months after their initial illness. Pediatric postacute sequelae of COVID-19 (pPASC), or long-COVID, is a complex, heterogeneous, postviral condition involving multiple body systems and is likely attributable to several concurrent underlying physiologic processes, including damage from direct viral invasion, endovascular dysfunction and microthrombosis, viral persistence, and the development of autoimmunity. In this review, we explore the current state of the literature regarding definition, epidemiology, clinical presentation, and proposed pathophysiologic mechanisms of pPASC. [Pediatr Ann. 2022;51(11):e416-e420.].}, }
@article {pmid36343181, year = {2022}, author = {Yonts, A Brugler and Burton, J and Jones Herbert, L}, title = {A Review of Current Evaluation and Management Strategies in Pediatric Postacute Sequelae of COVID-19.}, journal = {Pediatric annals}, volume = {51}, number = {11}, pages = {e421-e425}, doi = {10.3928/19382359-20220913-08}, pmid = {36343181}, issn = {1938-2359}, mesh = {Adolescent ; Child ; Humans ; *COVID-19/therapy ; SARS-CoV-2 ; Disease Progression ; Post-Acute COVID-19 Syndrome ; }, abstract = {Pediatric postacute sequelae of COVID-19 (pPASC), or long COVID, is a complex, heterogeneous, multisystem syndrome that leads to disruption in the lives of children and adolescents for months, and possibly years, after recovery from acute SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. While the underlying pathophysiologic mechanisms of PASC are still under investigation, clinicians are facing the immediate challenges of treating these patients. In this article, we provide an overview of the current multidisciplinary evaluation of patients with pPASC. We also offer guidance on the medical, psychological, and rehabilitative management strategies based on experience with both pPASC and patients with other postviral syndromes. [Pediatr Ann. 2022;51(11):e421-e425.].}, }
@article {pmid36349400, year = {2023}, author = {Chee, YJ and Fan, BE and Young, BE and Dalan, R and Lye, DC}, title = {Clinical trials on the pharmacological treatment of long COVID: A systematic review.}, journal = {Journal of medical virology}, volume = {95}, number = {1}, pages = {e28289}, pmid = {36349400}, issn = {1096-9071}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Multiple Organ Failure ; }, abstract = {The postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC), also known as post-acute coronavirus disease 19 (COVID-19) or the long COVID syndrome (long COVID) is an emerging public health concern. A substantial proportion of individuals may remain symptomatic months after initial recovery. An updated review of published and ongoing trials focusing on managing long COVID will help identify gaps and address the unmet needs of patients suffering from this potentially debilitating syndrome. A comprehensive literature search was conducted on the international databases and clinical trial registries from inception to 31 July 2022. This review included 6 published trials and 54 trial registration records. There is significant heterogeneity in the characterization of long COVID and ascertainment of primary outcomes. Most of the trials are focused on individual symptoms of long COVID or isolated organ dysfunction, classified according to cardiovascular, respiratory and functional capacity, neurological and psychological, fatigue, and olfactory dysfunction. Most of the interventions are related to the mechanisms causing the individual symptoms. Although the six published trials showed significant improvement in the symptoms or organ dysfunction studied, these initial studies lack internal and external validity limiting the generalizability. This review provides an update of the pharmacological agents that could be used to treat long COVID. Further standardization of the diagnostic criteria, inclusion of participants with concomitant chronic cardiometabolic diseases and standardization of outcomes will be essential in future clinical trials.}, }
@article {pmid36352492, year = {2022}, author = {Dirican, E and Bal, T}, title = {COVID-19 disease severity to predict persistent symptoms: a systematic review and meta-analysis.}, journal = {Primary health care research &amp; development}, volume = {23}, number = {}, pages = {e69}, pmid = {36352492}, issn = {1477-1128}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Dyspnea/diagnosis/etiology ; Fatigue/diagnosis/etiology ; Severity of Illness Index ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: It is unclear, whether the initial disease severity may help to predict which COVID-19 patients at risk of developing persistent symptoms.<br><br>AIM: The aim of this study was to examine whether the initial disease severity affects the risk of persistent symptoms in post-acute COVID-19 syndrome and long COVID.<br><br>METHODS: A systematic search was conducted using PUBMED, Google Scholar, EMBASE, and ProQuest databases to identify eligible articles published after January 2020 up to and including 30 August 2021. Pooled odds ratio (OR) and confidence intervals (CIs) were calculated using random effects meta-analysis.<br><br>FINDINGS: After searching a total of 7733 articles, 20 relevant observational studies with a total of 7840 patients were selected for meta-analysis. The pooled OR for persistent dyspnea in COVID-19 survivors with a severe versus nonsevere initial disease was 2.17 [95%CI 1.62 to 2.90], and it was 1.33 [95%CI 0.75 to 2.33] for persistent cough, 1.30 [95%CI 1.06 to 1.58] for persistent fatigue, 1.02 [95%CI 0.73 to 1.40] for persistent anosmia, 1.22 [95%CI 0.69 to 2.16] for persistent chest pain, and 1.30 [95%CI 0.93 to 1.81] for persistent palpitation.<br><br>CONCLUSIONS: Contrary to expectations, we did not observe an association between the initial COVID-19 disease severity and common persistent symptoms except for dyspnea and fatigue. In addition, it was found that being in the acute or prolonged post-COVID phase did not affect the risk of symptoms. Primary care providers should be alert to potential most prevalent persistent symptoms in all COVID-19 survivors, which are not limited to patients with critical-severe initial disease.}, }
@article {pmid36353967, year = {2023}, author = {Corvol, H and Prevost, B and Aubertin, G and Thouvenin, G and Taytard, J and Nathan, N}, title = {COVID-19 and pediatric pulmonology: Feedback from an expert center after the first year of the pandemic.}, journal = {Pediatric pulmonology}, volume = {58}, number = {2}, pages = {392-397}, pmid = {36353967}, issn = {1099-0496}, mesh = {Young Adult ; Humans ; Child ; Adolescent ; Aged ; *COVID-19 ; SARS-CoV-2 ; Pandemics ; Post-Acute COVID-19 Syndrome ; Feedback ; *Pulmonary Medicine ; }, abstract = {The coronavirus disease 2019 (COVID-19) outbreak has evolved with different waves corresponding to subsequent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations. While the most severe cases have been observed in the elderly and in individuals with underlying comorbidities, severe pediatric and young adult cases have been observed, as well as post-infectious inflammatory syndromes and persistent symptoms leading to long-COVID. This manuscript describes the experience of a pediatric respiratory unit during the first year of the pandemic and reviews the corresponding literature with a special emphasis on children and young people with underlying conditions, such as immunosuppression, sickle cell disease, and cystic fibrosis.}, }
@article {pmid36358996, year = {2022}, author = {Cardinali, DP and Brown, GM and Pandi-Perumal, SR}, title = {Possible Application of Melatonin in Long COVID.}, journal = {Biomolecules}, volume = {12}, number = {11}, pages = {}, pmid = {36358996}, issn = {2218-273X}, mesh = {Humans ; *Melatonin/therapeutic use ; SARS-CoV-2 ; *Fatigue Syndrome, Chronic/drug therapy/diagnosis ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {Clinical sequelae and symptoms for a considerable number of COVID-19 patients can linger for months beyond the acute stage of SARS-CoV-2 infection, "long COVID". Among the long-term consequences of SARS-CoV-2 infection, cognitive issues (especially memory loss or "brain fog"), chronic fatigue, myalgia, and muscular weakness resembling myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are of importance. Melatonin may be particularly effective at reducing the signs and symptoms of SARS-CoV-2 infection due to its functions as an antioxidant, anti-inflammatory, and immuno-modulatory agent. Melatonin is also a chronobiotic medication effective in treating delirium and restoring the circadian imbalance seen in COVID patients in the intensive care unit. Additionally, as a cytoprotector, melatonin aids in the prevention of several COVID-19 comorbidities, including diabetes, metabolic syndrome, and ischemic and non-ischemic cardiovascular diseases. This narrative review discusses the application of melatonin as a neuroprotective agent to control cognitive deterioration ("brain fog") and pain in the ME/CFS syndrome-like documented in long COVID. Further studies on the therapeutic use of melatonin in the neurological sequelae of SARS-CoV-2 infection are warranted.}, }
@article {pmid36360471, year = {2022}, author = {Al-Mhanna, SB and Mohamed, M and Noor, NM and Afolabi, HA and Irekeola, AA and Bello, KE and Aldhahi, MI and Wan Ghazali, WS}, title = {Effectiveness of Pulmonary Rehabilitation among COVID-19 Patients: A Systematic Review and Meta-Analysis.}, journal = {Healthcare (Basel, Switzerland)}, volume = {10}, number = {11}, pages = {}, pmid = {36360471}, issn = {2227-9032}, abstract = {Background: Many COVID-19 patients presented with detrimental features, such as impaired respiratory function, physical capacity, and overall poor quality of life. The present study evaluates the effectiveness of pulmonary rehabilitation on COVID-19 patients. Methods: We searched PubMed, Scopus, ScienceDirect, and Google Scholar from 2019 to 2021. The protocol was registered in PROSPERO with the registration number CRD42021273618. We performed statistical analyses via random effects and expressed the outcomes as standardized mean difference (SMD) for continuous variables, with 95% confidence intervals (CI). Results: We included six trials involving 432 patients. The primary outcome showed a significant improvement in physical function (SMD 0.83, 95% CI −0.58 to 1.09; p < 0.001; four trials, 266 participants; high-quality evidence). There was significant difference in anxiety (SMD −0.80, 95% CI −1.23 to −0.37; p = 0.003), physical activity intensity levels (SMD −1.27, 95% CI −2.23 to −0.32; p = 0.009), sleep quality (MD −0.05, 95% CI −0.83 to −0.16; p = 0.004), peripheral muscle performance of lower limbs (SMD 0.90, 95% CI −0.60 to 1.20; p < 0.001), and dyspnoea outcomes (SMD −0.55, 95% CI −0.87 to −0.23; p = 0.007). Conclusions: Pulmonary rehabilitation is an effective adjuvant therapy that minimizes COVID-19 severity in the intervention group compared to the conventional treatment. The findings of this study will need to be considered in the framework of the clinical outcome as observed in the intervention outcome. Additionally, safer data on guideline rehabilitation would be needed to examine whether pulmonary rehabilitation would be a fruitful intervention to reduce COVID-19 severity.}, }
@article {pmid36362782, year = {2022}, author = {De Luca, R and Bonanno, M and Calabrò, RS}, title = {Psychological and Cognitive Effects of Long COVID: A Narrative Review Focusing on the Assessment and Rehabilitative Approach.}, journal = {Journal of clinical medicine}, volume = {11}, number = {21}, pages = {}, pmid = {36362782}, issn = {2077-0383}, abstract = {Long COVID is a clinical syndrome characterized by profound fatigue, neurocognitive difficulties, muscle pain, weakness, and depression, lasting beyond the 3-12 weeks following infection with SARS-CoV-2. Among the symptoms, neurocognitive and psychiatric sequelae, including attention and memory alterations, as well as anxiety and depression symptoms, have become major targets of current healthcare providers given the significant public health impact. In this context, assessment tools play a crucial role in the early screening of cognitive alterations due to Long COVID. Among others, the general cognitive assessment tools, such as the Montreal Cognitive assessment, and more specific ones, including the State Trait Inventory of Cognitive Fatigue and the Digit Span, may be of help in investigating the main neurocognitive alterations. Moreover, appropriate neurorehabilitative programs using specific methods and techniques (conventional and/or advanced) through a multidisciplinary team are required to treat COVID-19-related cognitive and behavioral abnormalities. In this narrative review, we sought to describe the main neurocognitive and psychiatric symptoms as well as to provide some clinical advice for the assessment and treatment of Long COVID.}, }
@article {pmid36369208, year = {2022}, author = {Calabrese, C and Kirchner, E and Calabrese, LH}, title = {Long COVID and rheumatology: Clinical, diagnostic, and therapeutic implications.}, journal = {Best practice &amp; research. Clinical rheumatology}, volume = {36}, number = {4}, pages = {101794}, pmid = {36369208}, issn = {1532-1770}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Rheumatology ; Quality of Life ; COVID-19 Testing ; }, abstract = {As of this writing, it is estimated that there have been nearly 600 million cases of coronavirus disease 2019 (COVID-19) around the world with over six million deaths. While shocking, these figures do not fully illustrate the morbidity associated with this disease. It is also estimated that between 10% and 30% of those who survive COVID-19 develop persistent symptoms after the acute infection has passed. These individuals, who most often experienced initial infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) considered mild to moderate in severity, often display a broad array of symptoms. Collectively, this disorder or syndrome is now referred to as Long COVID (among other designations), and it represents a national/international health crisis. The most frequently reported symptoms associated with Long COVID include chronic fatigue with post exertional features, neurocognitive dysfunction, breathlessness, and somatic pain. Long COVID can range in severity from mild to severely debilitating, with resultant loss of quality of life and productivity. For now, there are many unanswered questions surrounding Long COVID: how can it be best defined, what is needed for accurate diagnosis, what is causing it, and how should it be best managed. How rheumatologists will engage in the Long COVID pandemic is another question; at the minimum, we will be called upon to evaluate and manage our own patients with immune-mediated inflammatory diseases who have developed it. This review focuses on addressing the disease essentials, providing both declarative and procedural knowledge to prepare rheumatologists for how to address Long COVID: understanding its origins, its current case definitions, epidemiology, pathobiology and clinical manifestations. Finally, it will provide an outline on how to clinically approach patients with possible Long COVID and initiate treatment and/or guide them on how to best manage it.}, }
@article {pmid36382632, year = {2022}, author = {Ambrosino, P and Sanduzzi Zamparelli, S and Mosella, M and Formisano, R and Molino, A and Spedicato, GA and Papa, A and Motta, A and Di Minno, MND and Maniscalco, M}, title = {Clinical assessment of endothelial function in convalescent COVID-19 patients: a meta-analysis with meta-regressions.}, journal = {Annals of medicine}, volume = {54}, number = {1}, pages = {3234-3249}, pmid = {36382632}, issn = {1365-2060}, mesh = {Humans ; *COVID-19 ; Endothelium ; }, abstract = {BACKGROUND: Endothelial dysfunction has been proposed to play a key role in the pathogenesis of coronavirus disease 2019 (COVID-19) and its post-acute sequelae. Flow-mediated dilation (FMD) is recognized as an accurate clinical method to assess endothelial function. Thus, we performed a meta-analysis of the studies evaluating FMD in convalescent COVID-19 patients and controls with no history of COVID-19.<br><br>METHODS: A systematic literature search was conducted in the main scientific databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Using the random effects method, differences between cases and controls were expressed as mean difference (MD) with 95% confidence intervals (95% CI). The protocol was registered on PROSPERO with reference number CRD42021289684.<br><br>RESULTS: Twelve studies were included in the final analysis. A total of 644 convalescent COVID-19 patients showed significantly lower FMD values as compared to 662 controls (MD: -2.31%; 95% CI: -3.19, -1.44; p&#x2009;<&#x2009;0.0001). Similar results were obtained in the sensitivity analysis of the studies that involved participants in either group with no cardiovascular risk factors or history of coronary artery disease (MD: -1.73%; 95% CI: -3.04, -0.41; p&#x2009;=&#x2009;0.010). Interestingly, when considering studies separately based on enrolment within or after 3&#x2009;months of symptom onset, results were further confirmed in both short- (MD: -2.20%; 95% CI: -3.35, -1.05; p&#x2009;<&#x2009;0.0001) and long-term follow-up (MD: -2.53%; 95% CI: -4.19, -0.86; p&#x2009;=&#x2009;0.003). Meta-regression models showed that an increasing prevalence of post-acute sequelae of COVID-19 was linked to a higher difference in FMD between cases and controls (Z-score: -2.09; p&#x2009;=&#x2009;0.037).<br><br>CONCLUSIONS: Impaired endothelial function can be documented in convalescent COVID-19 patients, especially when residual clinical manifestations persist. Targeting endothelial dysfunction through pharmacological and rehabilitation strategies may represent an attractive therapeutic option.Key messagesThe mechanisms underlying the post-acute sequelae of coronavirus disease 2019 (COVID-19) have not been fully elucidated.Impaired endothelial function can be documented in convalescent COVID-19 patients for up to 1 year after infection, especially when residual clinical manifestations persist.Targeting endothelial dysfunction may represent an attractive therapeutic option in the post-acute phase of COVID-19.}, }
@article {pmid36385229, year = {2022}, author = {Wagner, C and Griesel, M and Mikolajewska, A and Metzendorf, MI and Fischer, AL and Stegemann, M and Spagl, M and Nair, AA and Daniel, J and Fichtner, F and Skoetz, N}, title = {Systemic corticosteroids for the treatment of COVID-19: Equity-related analyses and update on evidence.}, journal = {The Cochrane database of systematic reviews}, volume = {11}, number = {11}, pages = {CD014963}, pmid = {36385229}, issn = {1469-493X}, mesh = {Humans ; Aged ; Aged, 80 and over ; Adrenal Cortex Hormones/adverse effects ; Methylprednisolone ; Dexamethasone/adverse effects ; *Invasive Fungal Infections ; Randomized Controlled Trials as Topic ; *COVID-19 Drug Treatment ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Systemic corticosteroids are used to treat people with COVID-19 because they counter hyper-inflammation. Existing evidence syntheses suggest a slight benefit on mortality. Nonetheless, size of effect, optimal therapy regimen, and selection of patients who are likely to benefit most are factors that remain to be evaluated.<br><br>OBJECTIVES: To assess whether and at which doses systemic corticosteroids are effective and safe in the treatment of people with COVID-19, to explore equity-related aspects in subgroup analyses, and to keep up to date with the evolving evidence base using a living systematic review approach.<br><br>SEARCH METHODS: We searched the Cochrane COVID-19 Study Register (which includes PubMed, Embase, CENTRAL, ClinicalTrials.gov, WHO ICTRP, and medRxiv), Web of Science (Science Citation Index, Emerging Citation Index), and the WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies to 6 January 2022.<br><br>SELECTION CRITERIA: We included randomised controlled trials (RCTs) that evaluated systemic corticosteroids for people with COVID-19. We included any type or dose of systemic corticosteroids and the following comparisons: systemic corticosteroids plus standard care versus standard care, different types, doses and timings (early versus late) of corticosteroids. We excluded corticosteroids in combination with other active substances versus standard care, topical or inhaled corticosteroids, and corticosteroids for long-COVID treatment.<br><br>DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. To assess the risk of bias in included studies, we used the Cochrane 'Risk of bias' 2 tool for RCTs. We rated the certainty of the evidence using the GRADE approach for the following outcomes: all-cause mortality up to 30 and 120 days, discharged alive (clinical improvement), new need for invasive mechanical ventilation or death (clinical worsening), serious adverse events, adverse events, hospital-acquired infections, and invasive fungal infections.<br><br>MAIN RESULTS: We included 16 RCTs in 9549 participants, of whom 8271 (87%) originated from high-income countries. A total of 4532 participants were randomised to corticosteroid arms and the majority received dexamethasone (n = 3766). These studies included participants mostly older than 50 years and male. We also identified 42 ongoing and 23 completed studies lacking published results or relevant information on the study design. Hospitalised individuals with a confirmed or suspected diagnosis of symptomatic COVID-19 Systemic corticosteroids plus standard care versus standard care plus/minus placebo We included 11 RCTs (8019 participants), one of which did not report any of our pre-specified outcomes and thus our analyses included outcome data from 10 studies. Systemic corticosteroids plus standard care compared to standard care probably reduce all-cause mortality (up to 30 days) slightly (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.84 to 0.97; 7898 participants; estimated absolute effect: 274 deaths per 1000 people not receiving systemic corticosteroids compared to 246 deaths per 1000 people receiving the intervention (95% CI 230 to 265 per 1000 people); moderate-certainty evidence). The evidence is very uncertain about the effect on all-cause mortality (up to 120 days) (RR 0.74, 95% CI 0.23 to 2.34; 485 participants). The chance of clinical improvement (discharged alive at day 28) may slightly increase (RR 1.07, 95% CI 1.03 to 1.11; 6786 participants; low-certainty evidence) while the risk of clinical worsening (new need for invasive mechanical ventilation or death) may slightly decrease (RR 0.92, 95% CI 0.84 to 1.01; 5586 participants; low-certainty evidence). For serious adverse events (two RCTs, 678 participants), adverse events (three RCTs, 447 participants), hospital-acquired infections (four RCTs, 598 participants), and invasive fungal infections (one study, 64 participants), we did not perform any analyses beyond the presentation of descriptive statistics due to very low-certainty evidence (high risk of bias, heterogeneous definitions, and underreporting). Different types, dosages or timing of systemic corticosteroids We identified one RCT (86 participants) comparing methylprednisolone to dexamethasone, thus the evidence is very uncertain about the effect of methylprednisolone on all-cause mortality (up to 30 days) (RR 0.51, 95% CI 0.24 to 1.07; 86 participants). None of the other outcomes of interest were reported in this study. We included four RCTs (1383 participants) comparing high-dose dexamethasone (12 mg or higher) to low-dose dexamethasone (6 mg to 8 mg). High-dose dexamethasone compared to low-dose dexamethasone may reduce all-cause mortality (up to 30 days) (RR 0.87, 95% CI 0.73 to 1.04; 1269 participants; low-certainty evidence), but the evidence is very uncertain about the effect of high-dose dexamethasone on all-cause mortality (up to 120 days) (RR 0.93, 95% CI 0.79 to 1.08; 1383 participants) and it may have little or no impact on clinical improvement (discharged alive at 28 days) (RR 0.98, 95% CI 0.89 to 1.09; 200 participants; low-certainty evidence). Studies did not report data on clinical worsening (new need for invasive mechanical ventilation or death). For serious adverse events, adverse events, hospital-acquired infections, and invasive fungal infections, we did not perform analyses beyond the presentation of descriptive statistics due to very low-certainty evidence. We could not identify studies for comparisons of different timing and systemic corticosteroids versus other active substances. Equity-related subgroup analyses We conducted the following subgroup analyses to explore equity-related factors: sex, age (< 70 years; &#x2265; 70 years), ethnicity (Black, Asian or other versus White versus unknown) and place of residence (high-income versus low- and middle-income countries). Except for age and ethnicity, no evidence for differences could be identified. For all-cause mortality up to 30 days, participants younger than 70 years seemed to benefit from systemic corticosteroids in comparison to those aged 70 years and older. The few participants from a Black, Asian, or other minority ethnic group showed a larger estimated effect than the many White participants. Outpatients with asymptomatic or mild disease There are no studies published in populations with asymptomatic infection or mild disease.<br><br>AUTHORS' CONCLUSIONS: Systemic corticosteroids probably slightly reduce all-cause mortality up to 30 days in people hospitalised because of symptomatic COVID-19, while the evidence is very uncertain about the effect on all-cause mortality up to 120 days. For younger people (under 70 years of age) there was a potential advantage, as well as for Black, Asian, or people of a minority ethnic group; further subgroup analyses showed no relevant effects. Evidence related to the most effective type, dose, or timing of systemic corticosteroids remains immature. Currently, there is no evidence on asymptomatic or mild disease (non-hospitalised participants). Due to the low to very low certainty of the current evidence, we cannot assess safety adequately to rule out harmful effects of the treatment, therefore there is an urgent need for good-quality safety data. Findings of equity-related subgroup analyses should be interpreted with caution because of their explorative nature, low precision, and missing data. We identified 42 ongoing and 23 completed studies lacking published results or relevant information on the study design, suggesting there may be possible changes of the effect estimates and certainty of the evidence in the future.}, }
@article {pmid36385449, year = {2023}, author = {Kubota, T and Kuroda, N and Sone, D}, title = {Neuropsychiatric aspects of long COVID: A comprehensive review.}, journal = {Psychiatry and clinical neurosciences}, volume = {77}, number = {2}, pages = {84-93}, pmid = {36385449}, issn = {1440-1819}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; Anxiety Disorders ; }, abstract = {Although some patients have persistent symptoms or develop new symptoms following coronavirus disease 2019 (COVID-19) infection, neuropsychiatric aspects of long COVID are not well known. This review summarizes and provides an update on the neuropsychiatric dimensions of long COVID. Its neuropsychiatric manifestations commonly include fatigue, cognitive impairment, sleep disorders, depression, anxiety, and post-traumatic stress disorder. There are no specific tests for long COVID, but some characteristic findings such as hypometabolism on positron emission tomography have been reported. The possible mechanisms of long COVID include inflammation, ischemic effects, direct viral invasion, and social and environmental changes. Some patient characteristics and the severity and complications of acute COVID-19 infection may be associated with an increased risk of neuropsychiatric symptoms. Long COVID may resolve spontaneously or persist, depending on the type of neuropsychiatric symptoms. Although established treatments are lacking, various psychological and pharmacological treatments have been attempted. Vaccination against COVID-19 infection plays a key role in the prevention of long coronavirus disease. With differences among the SARS-CoV-2 variants, including the omicron variant, the aspects of long COVID are likely to change in the future. Further studies clarifying the aspects of long COVID to develop effective treatments are warranted.}, }
@article {pmid36387947, year = {2022}, author = {Porter, N and Jason, LA}, title = {Mindfulness Meditation Interventions for Long COVID: Biobehavioral Gene Expression and Neuroimmune Functioning.}, journal = {Neuropsychiatric disease and treatment}, volume = {18}, number = {}, pages = {2599-2626}, pmid = {36387947}, issn = {1176-6328}, abstract = {Some individuals infected with SARS CoV-2 have developed Post-Acute Sequelae of SARS CoV-2 infection (PASC) or what has been referred to as Long COVID. Efforts are underway to find effective treatment strategies for those with Long COVID. One possible approach involves alternative medical interventions, which have been widely used to treat and manage symptoms of a variety of medical problems including post-viral infections. Meditation has been found to reduce fatigue and unrefreshing sleep, and for those with post-viral infections, it has enhanced immunity, and reduced inflammatory-driven pathogenesis. Our article summarizes the literature on what is known about mindfulness meditation interventions, and reviews evidence on how it may apply to those with Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Evidence is reviewed suggesting effective and sustainable outcomes may be achieved for symptomatology and underlying pathology of post-viral fatigue (PASC and ME/CFS).}, }
@article {pmid36396269, year = {2022}, author = {Dix, E and Roy, K}, title = {COVID-19: Brain Effects.}, journal = {The Psychiatric clinics of North America}, volume = {45}, number = {4}, pages = {625-637}, pmid = {36396269}, issn = {1558-3147}, mesh = {Humans ; Aged ; *COVID-19 ; Brain/pathology ; Aging ; }, abstract = {Severe acute respiratory syndrome coronavirus 2, the novel coronavirus responsible for the coronavirus disease (COVID-19), affects the brain. Neurologic and neuropsychiatric symptoms may manifest in the acute and post-acute phases of illness. The vulnerability of the brain with aging further increases the burden of disease in the elderly, who are at the highest risk of complications and death from COVID-19. The mechanisms underlying the effects of COVID-19 on the brain are not fully known. Emerging evidence vis-à-vis pathogenesis and etiologies of COVID-19 brain effects is promising and may pave the way for future research and development of interventions.}, }
@article {pmid36400555, year = {2023}, author = {Hovaguimian, A}, title = {Dysautonomia: Diagnosis and Management.}, journal = {Neurologic clinics}, volume = {41}, number = {1}, pages = {193-213}, doi = {10.1016/j.ncl.2022.08.002}, pmid = {36400555}, issn = {1557-9875}, mesh = {Humans ; *COVID-19 ; *Primary Dysautonomias/diagnosis/etiology/therapy ; Post-Acute COVID-19 Syndrome ; }, abstract = {Dysautonomias are a heterogenous group of disorders that can cause variable symptoms ranging from isolated impairment of one autonomic function to multisystem failure. The causes are also diverse and can be central or peripheral and primary (owing to an intrinsic neurologic cause) or secondary (owing to a disorder that secondarily causes damage to the autonomic nervous system). This review covers common phenotypes of dysautonomias, primary and secondary causes, initial clinical workups, interpretation of common autonomic tests, and first-line treatments. A brief review of autonomic impairment associated with acute and long-COVID is also presented.}, }
@article {pmid36405232, year = {2022}, author = {Sakellaropoulos, SG and Ali, M and Papadis, A and Mohammed, M and Mitsis, A and Zivzivadze, Z}, title = {Is Long COVID Syndrome a Transient Mitochondriopathy Newly Discovered: Implications of CPET.}, journal = {Cardiology research}, volume = {13}, number = {5}, pages = {264-267}, pmid = {36405232}, issn = {1923-2829}, abstract = {The new outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has an impact worldwide, primarily as a medical emergency. Even that the total constellation is considered as a pandemic of acute respiratory disease, coronavirus disease 2019 (COVID-19) gives rise to dysfunction in multiple organs (e.g., brain, lungs, heart, muscles) that impairs cardiopulmonary (CP) function. Parallel to the CP consequences of COVID-19 is a significant reduction in physical activity. Cardiopulmonary exercise testing (CPET) is daily used in clinical practice to define prognosis, provide risk stratification and treatment strategy. As such, the significance of CPET is crucial concerning clinical assessments of COVID-19 patients. Furthermore, new studies aim at understanding the effects of SARS-CoV-2 infection in long term. Multiple studies have investigated the cardiopulmonary function and impairment of exercise endurance in such patients, as well as a possible prolonged physical impairment. With this review, we summarize the COVID-19-associated pathophysiology for the Long COVID (LC) syndrome as well as the importance of performing CPET.}, }
@article {pmid36412084, year = {2023}, author = {Astin, R and Banerjee, A and Baker, MR and Dani, M and Ford, E and Hull, JH and Lim, PB and McNarry, M and Morten, K and O'Sullivan, O and Pretorius, E and Raman, B and Soteropoulos, DS and Taquet, M and Hall, CN}, title = {Long COVID: mechanisms, risk factors and recovery.}, journal = {Experimental physiology}, volume = {108}, number = {1}, pages = {12-27}, pmid = {36412084}, issn = {1469-445X}, support = {RE/18/3/34214//British Heart Foundation/United Kingdom ; COV-LT2-0043//Department of Health/United Kingdom ; MR/V036750/1//Medical Research Council/United Kingdom ; NIHR200937//Department of Health/United Kingdom ; MR/S026495/1//Medical Research Council/United Kingdom ; MR/W004798/1//Medical Research Council/United Kingdom ; COV/LT2/0022//Department of Health/United Kingdom ; BRC-1215-20005//Department of Health/United Kingdom ; }, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Risk Factors ; *Autonomic Nervous System Diseases ; }, abstract = {NEW FINDINGS: What is the topic of this review? The emerging condition of long COVID, its epidemiology, pathophysiological impacts on patients of different backgrounds, physiological mechanisms emerging as explanations of the condition, and treatment strategies being trialled. The review leads from a Physiological Society online conference on this topic. What advances does it highlight? Progress in understanding the pathophysiology and cellular mechanisms underlying Long COVID and potential therapeutic and management strategies.<br><br>ABSTRACT: Long COVID, the prolonged illness and fatigue suffered by a small proportion of those infected with SARS-CoV-2, is placing an increasing burden on individuals and society. A Physiological Society virtual meeting in February 2022 brought clinicians and researchers together to discuss the current understanding of long COVID mechanisms, risk factors and recovery. This review highlights the themes arising from that meeting. It considers the nature of long COVID, exploring its links with other post-viral illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome, and highlights how long COVID research can help us better support those suffering from all post-viral syndromes. Long COVID research started particularly swiftly in populations routinely monitoring their physical performance - namely the military and elite athletes. The review highlights how the high degree of diagnosis, intervention and monitoring of success in these active populations can suggest management strategies for the wider population. We then consider how a key component of performance monitoring in active populations, cardiopulmonary exercise training, has revealed long COVID-related changes in physiology - including alterations in peripheral muscle function, ventilatory inefficiency and autonomic dysfunction. The nature and impact of dysautonomia are further discussed in relation to postural orthostatic tachycardia syndrome, fatigue and treatment strategies that aim to combat sympathetic overactivation by stimulating the vagus nerve. We then interrogate the mechanisms that underlie long COVID symptoms, with a focus on impaired oxygen delivery due to micro-clotting and disruption of cellular energy metabolism, before considering treatment strategies that indirectly or directly tackle these mechanisms. These include remote inspiratory muscle training and integrated care pathways that combine rehabilitation and drug interventions with research into long COVID healthcare access across different populations. Overall, this review showcases how physiological research reveals the changes that occur in long COVID and how different therapeutic strategies are being developed and tested to combat this condition.}, }
@article {pmid36420234, year = {2022}, author = {Sloop, GD and Pop, G and Weidman, JJ and St Cyr, JA}, title = {COVID-19 Demonstrates That Inflammation Is a Hyperviscous State.}, journal = {Cureus}, volume = {14}, number = {10}, pages = {e30603}, pmid = {36420234}, issn = {2168-8184}, abstract = {Many of the complications of severe coronavirus disease-2019 (COVID-19) are caused by blood hyperviscosity driven by marked hyperfibrinogenemia. This results in a distinctive hyperviscosity syndrome which affects areas of high and low shear. A change in blood viscosity causes a threefold inverse change in blood flow, which increases the risk of thrombosis in both arteries and veins despite prophylactic anticoagulation. Increased blood viscosity decreases perfusion of all tissues, including the lungs, heart, and brain. Decreased perfusion of the lungs causes global ventilation-perfusion mismatch which results in silent hypoxemia and decreased efficacy of positive pressure ventilation in treating pulmonary failure in COVID-19. Increased blood viscosity causes a mismatch in oxygen supply and demand in the heart, resulting in myocarditis and ventricular diastolic dysfunction. Decreased perfusion of the brain causes demyelination because of a sublethal cell injury to oligodendrocytes. Hyperviscosity can cause stasis in capillaries, which can cause endothelial necrosis. This can lead to the rarefaction of capillary beds, which is noted in "long-COVID." The genome of the virus which causes COVID-19, severe acute respiratory syndrome coronavirus 2, contains an extraordinarily high number of the oligonucleotide virulence factor 5'-purine-uridine-uridine-purine-uridine-3', which binds to toll-like receptor 8, hyperactivating innate immunity. This can lead to a marked elevation in fibrinogen levels and an increased prevalence of neutrophil extracellular traps in pulmonary failure, as seen in COVID-19 patients.}, }
@article {pmid36420736, year = {2023}, author = {Zhang, HP and Sun, YL and Wang, YF and Yazici, D and Azkur, D and Ogulur, I and Azkur, AK and Yang, ZW and Chen, XX and Zhang, AZ and Hu, JQ and Liu, GH and Akdis, M and Akdis, CA and Gao, YD}, title = {Recent developments in the immunopathology of COVID-19.}, journal = {Allergy}, volume = {78}, number = {2}, pages = {369-388}, pmid = {36420736}, issn = {1398-9995}, mesh = {*COVID-19 Vaccines/adverse effects ; SARS-CoV-2 ; Child ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; *Anaphylaxis ; Systemic Inflammatory Response Syndrome ; }, abstract = {There has been an important change in the clinical characteristics and immune profile of Coronavirus disease 2019 (COVID-19) patients during the pandemic thanks to the extensive vaccination programs. Here, we highlight recent studies on COVID-19, from the clinical and immunological characteristics to the protective and risk factors for severity and mortality of COVID-19. The efficacy of the COVID-19 vaccines and potential allergic reactions after administration are also discussed. The occurrence of new variants of concerns such as Omicron BA.2, BA.4, and BA.5 and the global administration of COVID-19 vaccines have changed the clinical scenario of COVID-19. Multisystem inflammatory syndrome in children (MIS-C) may cause severe and heterogeneous disease but with a lower mortality rate. Perturbations in immunity of T cells, B cells, and mast cells, as well as autoantibodies and metabolic reprogramming may contribute to the long-term symptoms of COVID-19. There is conflicting evidence about whether atopic diseases, such as allergic asthma and rhinitis, are associated with a lower susceptibility and better outcomes of COVID-19. At the beginning of pandemic, the European Academy of Allergy and Clinical Immunology (EAACI) developed guidelines that provided timely information for the management of allergic diseases and preventive measures to reduce transmission in the allergic clinics. The global distribution of COVID-19 vaccines and emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with reduced pathogenic potential dramatically decreased the morbidity, severity, and mortality of COVID-19. Nevertheless, breakthrough infection remains a challenge for disease control. Hypersensitivity reactions (HSR) to COVID-19 vaccines are low compared to other vaccines, and these were addressed in EAACI statements that provided indications for the management of allergic reactions, including anaphylaxis to COVID-19 vaccines. We have gained a depth knowledge and experience in the over 2 years since the start of the pandemic, and yet a full eradication of SARS-CoV-2 is not on the horizon. Novel strategies are warranted to prevent severe disease in high-risk groups, the development of MIS-C and long COVID-19.}, }
@article {pmid36424958, year = {2022}, author = {Paul, S and Mishra, CM}, title = {Do we need to vaccinate every child against COVID-19: What evidence suggests-A systematic review of opinions.}, journal = {Frontiers in public health}, volume = {10}, number = {}, pages = {1002992}, pmid = {36424958}, issn = {2296-2565}, mesh = {Child ; Humans ; COVID-19 Vaccines ; Post-Acute COVID-19 Syndrome ; *COVID-19/prevention &amp; control/complications ; Adult ; Vaccination ; Systemic Inflammatory Response Syndrome ; }, abstract = {It is still debatable whether all children should receive the COVID-19 vaccine. The comparatively mild cases and low risk of COVID-19 in children compared to adults, as well as the lack of clarity on the relative effects of the disease and vaccine, indicate that the risk-benefit ratio of vaccination in children is more nuanced. To consider and highlight the complexity of policy decisions regarding COVID-19 vaccination in children, we outlined the points regarding for and against vaccination of children against COVID-19 in this systemic review. Using Medical Search Headings (MeSH) terms and keywords, we searched PubMed, PubMed Central, Scopus, and Google Scholar. The primary search term was COVID-19 vaccination (all synonyms), factors (all synonyms), and among children (all synonyms). A total of 367 articles were searched. Finally, 64 articles met the inclusion criteria and were included in the review. The major theme/tone of 28 (43.75%) articles was in favor of children's COVID vaccination, and they were highlighting the positive factors, whereas the major theme/tone of 20 (31.25%) articles was against it. Approximately 16 (25.0%) articles were in a neutral position. Major factors highlighted by articles in favor of childhood COVID vaccination were as follows: the increasing rate of disease burden (29 articles), prevention of interruption of academic activities of children or school reopening (24 articles), and a role in defense against COVID infection (21 articles). Major factors against childhood vaccination were as follows: mild infection among children (27 articles), ethical concerns and legal problems regarding the consent of minors (17 articles), and vaccine hesitancy among parents for childhood vaccination (11 articles). Whereas, factors of uncertainty were the role in the reduction of community transmission (19 articles), protection against MIS-C (10 articles), and defense against long COVID (7 articles). Considering all the factors of COVID-19 disease progression among children, a cautious approach will be essential before proceeding with COVID-19 vaccination in children.}, }
@article {pmid36426658, year = {2024}, author = {Rochmawati, E and Iskandar, AC and Kamilah, F}, title = {Persistent symptoms among post-COVID-19 survivors: A systematic review and meta-analysis.}, journal = {Journal of clinical nursing}, volume = {33}, number = {1}, pages = {29-39}, doi = {10.1111/jocn.16471}, pmid = {36426658}, issn = {1365-2702}, mesh = {Humans ; *COVID-19/epidemiology ; Chest Pain ; Cough ; Dyspnea ; Fatigue/epidemiology ; }, abstract = {BACKGROUND: Single studies support the presence of several post-COVID-19 symptoms; however, there is no evidence for the synthesis of symptoms.<br><br>OBJECTIVE: We attempt to provide an overview of the persistent symptoms that post-COVID-19 patients encounter, as well as the duration of these symptoms to help them plan their rehabilitation.<br><br>DESIGN: Systematic review and meta-analysis.<br><br>PARTICIPANTS: A total of 16 studies involving 8756 patients post-COVID-19 were included.<br><br>METHODS: The CINAHL, PubMed, EMBASE, Scopus, and Web of Science databases were searched from 2019 to August 2021. Observational studies that reported data on post-COVID-19 symptoms were included. The methodological quality of the studies was assessed using the Joanna Briggs Institute Critical Appraisal for Observational Studies. We included medium- to high-quality studies. We used a random-effects model for the meta-analytical pooled prevalence of each post-COVID-19 symptom, and I[2] statistics for heterogeneity.<br><br>RESULTS: From the 2481 studies identified, 16 met the inclusion criteria. The sample included 7623 hospitalised and 1133 non-hospitalised patients. We found the most prevalent symptoms were fatigue and dyspnea with a pooled prevalence ranging from 42% (27%-58%). Other post-COVID-19 symptoms included sleep disturbance 28% (14%-45%), cough 25% (10%-44%), anosmia/ageusia 24% (7%-47%), fever 21% (4%-47%), myalgia 17% (2%-41%), chest pain 11% (5%-20%), and headache 9% (2%-20%). In addition to physical symptoms, anxiety/depression was also prevalent 27% (8%-53%).<br><br>CONCLUSIONS: Fatigue and dyspnea were the most prevalent post-COVID-19 symptoms and experienced up to 12&#x2009;months.<br><br>Multiple persistent symptoms are still experienced until 12&#x2009;months of post-Covid 19. This meta-analysis should provide some awareness to nurses to highlights the unmet healthcare needs of post-COVID-19 patients. Long-term monitoring for the evaluation and treatment of symptoms and conditions and rehabilitation programs should be conducted.}, }
@article {pmid36436792, year = {2023}, author = {Huang, Q and Jia, M and Sun, Y and Jiang, B and Cui, D and Feng, L and Yang, W}, title = {One-Year Temporal Changes in Long COVID Prevalence and Characteristics: A Systematic Review and Meta-Analysis.}, journal = {Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research}, volume = {26}, number = {6}, pages = {934-942}, doi = {10.1016/j.jval.2022.11.011}, pmid = {36436792}, issn = {1524-4733}, mesh = {Humans ; Female ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Prevalence ; *Mental Disorders ; Risk Factors ; }, abstract = {OBJECTIVES: This study aimed to explore the 1-year temporal change in prevalence, variety, and potential risk factors of long COVID symptoms and to further predict the prognostic trends of long COVID.<br><br>METHODS: We searched electronic databases for related studies published from January 2020 to February 2022 and conducted 1-group meta-analysis and locally weighted regression to explore the monthly temporal change in the prevalence of each long COVID symptom in 1-year follow-up period.<br><br>RESULTS: A total of 137 studies were included in meta-analysis, including 134&#x2009;093 participants. The temporal change of any long COVID symptom showed a steep decrease initially (from 92% at acute phase to 55% at 1-month follow-up), followed by stabilization at approximately 50% during 1-year follow-up. Six months or more after the acute phase, the odds ratio of population characteristic-related factors increased, such as female (from 1.62 to 1.82), whereas the odds ratio value of acute phase-related factors (severe or critical cases and hospitalization) decreased. As for specific symptoms, approximately two-thirds of the symptoms did not significantly reduce during the 1-year follow-up, and the neuropsychiatric symptoms showed a higher long-term prevalence (approximately 25%) and longer persistence than physical symptoms.<br><br>CONCLUSIONS: The temporal changes in the prevalence and characteristics speculate that long COVID may persist longer than expected. In particular, we should pay more attention to neuropsychiatric symptoms and other symptoms for which there is no significant downward trend in prevalence. The influence of acute phase-related factors for long COVID gradually decreases over time, whereas the influence of population characteristic-related factors gradually increases.}, }
@article {pmid36440302, year = {2022}, author = {Laranjeira, TA and Menezes, AS}, title = {A Systematic Review of Post-COVID Electrocardiographic Changes in Young Athletes.}, journal = {Cureus}, volume = {14}, number = {11}, pages = {e31829}, pmid = {36440302}, issn = {2168-8184}, abstract = {Post-coronavirus disease (COVID) syndrome involves the presentation of various new, returning, or ongoing symptoms, more than four weeks after COVID-19 infection. Post-infectious myocarditis is a potential sequela, associated with greater arrhythmogenic potential. Thus, it is an outcome that should be considered in athletes. An undiagnosed heart condition associated with adrenergic stimulus caused by high-intensity exercises can lead to sudden cardiac death. Electrocardiography (ECG) plays a role in cardiac screening for potential cardiac changes associated with myocarditis. Therefore, this study aimed to evaluate the occurrence of electrocardiographic alterations in athletes during the post-COVID period. A systematic review of longitudinal observational studies in the PubMed, LILACS, and CENTRAL databases that evaluated athletes in the post-COVID period with ECG was performed. A total of four articles involving 5371 patients were included in the analysis. The athletes mostly presented with mild asymptomatic or symptomatic COVID-19. A low prevalence of electrocardiographic alterations suggestive of cardiac involvement by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in this population. Electrocardiographic abnormalities indicative of myocarditis are uncommon in young athletes throughout the post-COVID era. However, anomalies that may signify and need further cardiovascular testing were found.}, }
@article {pmid36449260, year = {2023}, author = {Di Gennaro, F and Belati, A and Tulone, O and Diella, L and Fiore Bavaro, D and Bonica, R and Genna, V and Smith, L and Trott, M and Bruyere, O and Mirarchi, L and Cusumano, C and Dominguez, LJ and Saracino, A and Veronese, N and Barbagallo, M}, title = {Incidence of long COVID-19 in people with previous SARS-Cov2 infection: a systematic review and meta-analysis of 120,970 patients.}, journal = {Internal and emergency medicine}, volume = {18}, number = {5}, pages = {1573-1581}, pmid = {36449260}, issn = {1970-9366}, support = {ffr//Universit&#xe0; degli Studi di Palermo/ ; }, mesh = {Female ; Humans ; Middle Aged ; Male ; *COVID-19/complications/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Incidence ; RNA, Viral ; }, abstract = {The long-term consequences of the coronavirus disease 19 (COVID-19) are likely to be frequent but results hitherto are inconclusive. Therefore, we aimed to define the incidence of long-term COVID signs and symptoms as defined by the World Health Organization, using a systematic review and meta-analysis of observational studies. A systematic search in several databases was carried out up to 12 January 2022 for observational studies reporting the cumulative incidence of long COVID signs and symptoms divided according to body systems affected. Data are reported as incidence and 95% confidence intervals (CIs). Several sensitivity and meta-regression analyses were performed. Among 11,162 papers initially screened, 196 were included, consisting of 120,970 participants (mean age: 52.3 years; 48.8% females) who were followed-up for a median of six months. The incidence of any long COVID symptomatology was 56.9% (95% CI 52.2-61.6). General long COVID signs and symptoms were the most frequent (incidence of 31%) and digestive issues the least frequent (7.7%). The presence of any neurological, general and cardiovascular long COVID symptomatology was most frequent in females. Higher mean age was associated with higher incidence of psychiatric, respiratory, general, digestive and skin conditions. The incidence of long COVID symptomatology was different according to continent and follow-up length. Long COVID is a common condition in patients who have been infected with SARS-CoV-2, regardless of the severity of the acute illness, indicating the need for more cohort studies on this topic.}, }
@article {pmid36460367, year = {2022}, author = {Vishnu Sharma, M and Arora, VK and Anupama, N}, title = {Role of chest radiography in the diagnosis of pulmonary tuberculosis during nCovid19 pandemic.}, journal = {The Indian journal of tuberculosis}, volume = {69}, number = {4}, pages = {385-388}, doi = {10.1016/j.ijtb.2022.03.008}, pmid = {36460367}, issn = {0019-5707}, mesh = {Humans ; Pandemics ; *COVID-19/diagnosis ; *Bronchopneumonia ; *Tuberculosis, Pulmonary/diagnostic imaging/epidemiology ; Radiography ; Post-Acute COVID-19 Syndrome ; }, abstract = {Pulmonary tuberculosis and nCovid 19 share many common risk factors. nCovid19 may increase the risk to develop pulmonary tuberculosis. Pulmonary tuberculosis may precede, co-exist or follow nCovid19. Careful evaluation of chest radiography is useful to differentiate tuberculosis from nCovid19 bronchopneumonia. Symptoms of tuberculosis may be mistaken for long covid. A normal chest x ray in the absence of sputum production may help to rule out tuberculosis in such cases. All patients with nCovid19 bronchopneumonia should undergo a careful chest x ray evaluation for any lesions suggestive of tuberculosis. All patients with chest radiological abnormality should undergo sputum examination to rule tuberculosis as atypical radiological manifestations may be more common in patients with nCovid19. Symptoms, signs, clinical features and chest radiographic features of Pulmonary tuberculosis and nCovid19 bronchopneumonia may overlap in some cases. Correlation of chest radiographic findings with epidemiologic history, clinical presentation, and RT-PCR test results or in later stages antibody titres will help in confirming or excluding the diagnosis in suspected cases of nCovid19. In pulmonary tuberculosis definitive diagnosis should be established by bacteriological confirmation. Molecular diagnostic tools should be used to confirm or exclude tuberculosis in suspect cases as the results are rapid, accurate and reliable.}, }
@article {pmid36462147, year = {2023}, author = {Karavanaki, K and Rodolaki, K and Soldatou, A and Karanasios, S and Kakleas, K}, title = {Covid-19 infection in children and adolescents and its association with type 1 diabetes mellitus (T1d) presentation and management.}, journal = {Endocrine}, volume = {80}, number = {2}, pages = {237-252}, pmid = {36462147}, issn = {1559-0100}, mesh = {Adult ; *COVID-19/complications ; Pandemics ; Child ; Humans ; Post-Acute COVID-19 Syndrome ; Adolescent ; SARS-CoV-2 ; *Diabetes Mellitus, Type 1/complications/therapy ; Systemic Inflammatory Response Syndrome ; *Diabetes Mellitus, Type 2/complications/epidemiology ; }, abstract = {Children seem to be affected by the new SARS-CoV-2 virus less severely than adults, with better prognosis and low mortality. Serious complications of COVID-19 infection in children include multisystem inflammatory response syndrome in COVID-19 infection (MIS-C), myo-or pericarditis and, less frequently, long COVID syndrome. On the other hand, adults with type 1 (T1D) or type 2 diabetes (T2D) are among the most vulnerable groups affected by COVID-19, with increased morbidity and mortality. Moreover, an association of SARS-CoV-2 with diabetes has been observed, possibly affecting the frequency and severity of the first clinical presentation of T1D or T2D, as well as the development of acute diabetes after COVID-19 infection. The present review summarizes the current data on the incidence of T1D among children and adolescents during the COVID-19 pandemic, as well as its severity. Moreover, it reports on the types of newly diagnosed diabetes after COVID infection and the possible pathogenetic mechanisms. Additionally, this study presents current data on the effect of SARS-CoV-2 on diabetes control in patients with known T1D and on the severity of clinical presentation of COVID infection in these patients. Finally, this review discusses the necessity of immunization against COVID 19 in children and adolescents with T1D.}, }
@article {pmid36462554, year = {2023}, author = {Faghy, MA and Ashton, REM and Parizher, G and Smith, A and Arena, R and Gough, LA and Emery, MS}, title = {COVID-19 and elite sport: Cardiovascular implications and return-to-play.}, journal = {Progress in cardiovascular diseases}, volume = {76}, number = {}, pages = {61-68}, pmid = {36462554}, issn = {1873-1740}, mesh = {Humans ; *COVID-19/epidemiology ; Return to Sport ; Post-Acute COVID-19 Syndrome ; *Sports ; Athletes ; }, abstract = {Curtailing elite sports during the coronavirus disease 2019 (COVID-19) pandemic was necessary to prevent widespread viral transmission. Now that elite sport and international competitions have been largely restored, there is still a need to devise appropriate screening and management pathways for athletes with a history of, or current, COVID-19 infection. These approaches should support the decision-making process of coaches, sports medicine practitioners and the athlete about the suitability to return to training and competition activities. In the absence of longitudinal data sets from athlete populations, the incidence of developing prolonged and debilitating symptoms (i.e., Long COVID) that affects a return to training and competition remains a challenge to sports and exercise scientists, sports medicine practitioners and clinical groups. As the world attempts to adjust toward 'living with COVID-19' the very nature of elite and international sporting competition poses a risk to athlete welfare that must be screened for and managed with bespoke protocols that consider the cardiovascular implications for performance.}, }
@article {pmid36465192, year = {2022}, author = {Chatterjee, E and Khan, T and Renzi, LS and Charles, EJ and Mandalaneni, K}, title = {A Bibliometric Analysis of COVID-19 Scientific Literature From the English-Speaking Caribbean.}, journal = {Cureus}, volume = {14}, number = {11}, pages = {e30958}, pmid = {36465192}, issn = {2168-8184}, abstract = {The COVID-19 pandemic has led to a global crisis and has affected the Caribbean islands, leading to significant health and socioeconomic consequences in this region. Efforts to mitigate the burden of this disease have led to an accelerated amount of research in the English-speaking Caribbean (ESC). This bibliometric analysis aimed to evaluate the COVID-19-related scientific literature from the ESC nations. A total of 175 articles were included and analyzed from an initial PubMed search (n = 638) for COVID-19-related scientific literature from the ESC nations published between January 1, 2020, and June 30, 2022. Microsoft Excel 2016 (Microsoft Corporation, Redmond, Washington) and the VOSviewer (version 1.6.18) were used to characterize countries, authorship, journals, affiliations, and keywords of the COVID-19-related articles. Trinidad and Tobago (38%), Jamaica (22%), Barbados (20%), and Grenada (15%) contributed to the greatest number of publications. The University of the West Indies (UWI) campuses in Trinidad and Tobago, Jamaica and Barbados, and St. George's University in Grenada were the most prolific institutions. Srikanth Umakanthan from the UWI was the most prolific author. Cureus, SN Comprehensive Clinical Medicine, and Frontiers in Public Health were the first three most productive journals; 59% of the 175 articles had either the first or last author affiliated with an institution in the ESC, and 19% of the articles were country-focused: Trinidad and Tobago (16/175), Jamaica (9/175), Barbados (5/175), and Antigua and Barbuda (2/175). Among the top themes of research, 27% were outbreak response and rearrangements, epidemiological studies (23%), clinical management (23%), and medical education (13%). Over the last two years, an interest stimulated by the pandemic has expanded the research in ESC countries. However, gaps in the knowledge exist, especially in the epidemiology of COVID-19 complications in the sub-populations of chronic non-communicable diseases, post-COVID syndrome, and the long-COVID syndrome in the region. Hence, there is enormous scope for more research across the region.}, }
@article {pmid36466122, year = {2023}, author = {Nouraeinejad, A}, title = {Brain fog as a Long-term Sequela of COVID-19.}, journal = {SN comprehensive clinical medicine}, volume = {5}, number = {1}, pages = {9}, pmid = {36466122}, issn = {2523-8973}, abstract = {Increasing data indicate that people infected with COVID-19 are at high risk for developing long-term neurological complications, such as "brain fog" or cognitive impairment. However, little is known about the long-term outcomes of COVID-19 survivors. This also applies to the prevalence, risk factors, and pathobiological findings associated with these consequences. Although cognitive complications are anticipated in patients who require a long-lasting hospital stay or intubation, milder cases of COVID-19 with no record of hospitalization have also been shown to experience assessable cognitive challenges. Cognitive impairment can have a devastating impact on daily functioning. Understanding the long-term effect of COVID-19 on cognitive function is vital for applying specific schemes to those who wish to return to their jobs productively.}, }
@article {pmid36466841, year = {2022}, author = {Jing, H and Wu, X and Xiang, M and Liu, L and Novakovic, VA and Shi, J}, title = {Pathophysiological mechanisms of thrombosis in acute and long COVID-19.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {992384}, pmid = {36466841}, issn = {1664-3224}, mesh = {Humans ; *COVID-19/complications ; *Thrombosis/etiology ; Anticoagulants/therapeutic use ; Phosphatidylserines ; Cytokine Release Syndrome ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19 patients have a high incidence of thrombosis, and thromboembolic complications are associated with severe COVID-19 and high mortality. COVID-19 disease is associated with a hyper-inflammatory response (cytokine storm) mediated by the immune system. However, the role of the inflammatory response in thrombosis remains incompletely understood. In this review, we investigate the crosstalk between inflammation and thrombosis in the context of COVID-19, focusing on the contributions of inflammation to the pathogenesis of thrombosis, and propose combined use of anti-inflammatory and anticoagulant therapeutics. Under inflammatory conditions, the interactions between neutrophils and platelets, platelet activation, monocyte tissue factor expression, microparticle release, and phosphatidylserine (PS) externalization as well as complement activation are collectively involved in immune-thrombosis. Inflammation results in the activation and apoptosis of blood cells, leading to microparticle release and PS externalization on blood cells and microparticles, which significantly enhances the catalytic efficiency of the tenase and prothrombinase complexes, and promotes thrombin-mediated fibrin generation and local blood clot formation. Given the risk of thrombosis in the COVID-19, the importance of antithrombotic therapies has been generally recognized, but certain deficiencies and treatment gaps in remain. Antiplatelet drugs are not in combination with anticoagulant treatments, thus fail to dampen platelet procoagulant activity. Current treatments also do not propose an optimal time for anticoagulation. The efficacy of anticoagulant treatments depends on the time of therapy initiation. The best time for antithrombotic therapy is as early as possible after diagnosis, ideally in the early stage of the disease. We also elaborate on the possible mechanisms of long COVID thromboembolic complications, including persistent inflammation, endothelial injury and dysfunction, and coagulation abnormalities. The above-mentioned contents provide therapeutic strategies for COVID-19 patients and further improve patient outcomes.}, }
@article {pmid36468825, year = {2022}, author = {Negrini, S and Kiekens, C and Cordani, C and Arienti, C and DE Groote, W}, title = {Cochrane "evidence relevant to" rehabilitation of people with post COVID-19 condition. What it is and how it has been mapped to inform the development of the World Health Organization recommendations.}, journal = {European journal of physical and rehabilitation medicine}, volume = {58}, number = {6}, pages = {853-856}, pmid = {36468825}, issn = {1973-9095}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Humans ; *COVID-19/epidemiology ; Evidence-Based Medicine ; *Pandemics ; Post-Acute COVID-19 Syndrome ; Systematic Reviews as Topic ; }, abstract = {Cochrane Rehabilitation developed a series of actions to provide the global rehabilitation community with the best available evidence to respond to the COVID-19 pandemic. These initiatives constituted the REH-COVER (Rehabilitation COVID-19 evidence-based response) action. In March 2020, the first initiative started in agreement with the European Journal of Physical and Rehabilitation Medicine (EJPRM): the rapid systematic review of all papers relevant to COVID-19 rehabilitation to inform rehabilitation health professionals rapidly. Currently, we are facing the long-term consequences of COVID-19, initially called "long Covid" and now named post COVID-19 condition (PCC), which led to the request by the WHO Rehabilitation Programme for evidence synthesis to support the development of specific recommendations. Cochrane Rehabilitation provided the best available evidence from the REH-COVER rapid living systematic review results, a systematic scoping review on the models of care and a summary of "evidence relevant to" the rehabilitation for adults with PCC. Based on this evidence, expert groups developed the 16 recommendations for the rehabilitation of adults with PCC recently published in Chapter 24 of the WHO "Clinical management of COVID-19 living guideline." This paper aims to introduce the Special Section of EJPRM reporting the work performed by Cochrane Rehabilitation to produce a summary of the existing "evidence relevant to" the rehabilitation of adults with PCC. The paper reports the methodology (overview of systematic reviews with mapping) and introduces the concept of "evidence relevant to" rehabilitation.}, }
@article {pmid36471421, year = {2023}, author = {Taghadosi, M and Safarzadeh, E and Asgarzadeh, A and Roghani, SA and Shamsi, A and Jalili, C and Assar, S and Soufivand, P and Pournazari, M and Feizollahi, P and Nicknam, MH and Asghariazar, V and Vaziri, S and Shahriari, H and Mohammadi, A}, title = {Partners in crime: Autoantibodies complicit in COVID-19 pathogenesis.}, journal = {Reviews in medical virology}, volume = {33}, number = {2}, pages = {e2412}, pmid = {36471421}, issn = {1099-1654}, mesh = {SARS-CoV-2 ; Child ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Humans ; Autoantibodies ; Systemic Inflammatory Response Syndrome ; }, abstract = {Autoantibodies (AABs) play a critical role in the pathogenesis of autoimmune diseases (AIDs) and serve as a diagnostic and prognostic tool in assessing these complex disorders. Viral infections have long been recognized as a principal environmental factor affecting the production of AABs and the development of autoimmunity. COVID-19 has primarily been considered a hyperinflammatory syndrome triggered by a cytokine storm. In the following, the role of maladaptive B cell response and AABs became more apparent in COVID-19 pathogenesis. The current review will primarily focus on the role of extrafollicular B cell response, Toll-like receptor-7 (TLR-7) activation, and neutrophil extracellular traps (NETs) formation in the development of AABs following SARS-CoV-2 infection. In the following, this review will clarify how these AABs dysregulate immune response to SARS-CoV-2 by disrupting cytokine function and triggering neutrophil hyper-reactivity. Finally, the pathologic effects of these AABs will be further described in COVID-19 associate clinical manifestations, including venous and arterial thrombosis, a multisystem inflammatory syndrome in children (MIS-C), acute respiratory distress syndrome (ARDS), and recently described post-acute sequelae of COVID-19 (PASC) or long-COVID.}, }
@article {pmid36473651, year = {2022}, author = {Graña, C and Ghosn, L and Evrenoglou, T and Jarde, A and Minozzi, S and Bergman, H and Buckley, BS and Probyn, K and Villanueva, G and Henschke, N and Bonnet, H and Assi, R and Menon, S and Marti, M and Devane, D and Mallon, P and Lelievre, JD and Askie, LM and Kredo, T and Ferrand, G and Davidson, M and Riveros, C and Tovey, D and Meerpohl, JJ and Grasselli, G and Rada, G and Hróbjartsson, A and Ravaud, P and Chaimani, A and Boutron, I}, title = {Efficacy and safety of COVID-19 vaccines.}, journal = {The Cochrane database of systematic reviews}, volume = {12}, number = {12}, pages = {CD015477}, pmid = {36473651}, issn = {1469-493X}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Humans ; Middle Aged ; Aged ; Adolescent ; *2019-nCoV Vaccine mRNA-1273 ; *COVID-19/prevention &amp; control ; SARS-CoV-2 ; Vaccines, Inactivated ; COVID-19 Vaccines ; }, abstract = {BACKGROUND: Different forms of vaccines have been developed to prevent the SARS-CoV-2 virus and subsequent COVID-19 disease. Several are in widespread use globally. OBJECTIVES: To assess the efficacy and safety of COVID-19 vaccines (as a full primary vaccination series or a booster dose) against SARS-CoV-2.<br><br>SEARCH METHODS: We searched the Cochrane COVID-19 Study Register and the COVID-19 L&#xb7;OVE platform (last search date 5 November 2021). We also searched the WHO International Clinical Trials Registry Platform, regulatory agency websites, and Retraction Watch.<br><br>SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing COVID-19 vaccines to placebo, no vaccine, other active vaccines, or other vaccine schedules.<br><br>DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. We used GRADE to assess the certainty of evidence for all except immunogenicity outcomes.&#xa0; We synthesized data for each vaccine separately and presented summary effect estimates with 95% confidence intervals (CIs).&#xa0; MAIN RESULTS: We included and analyzed 41 RCTs assessing 12 different vaccines, including homologous and heterologous vaccine schedules and the effect of booster doses. Thirty-two RCTs were multicentre and five were multinational. The sample sizes of RCTs were 60 to 44,325 participants. Participants were aged: 18 years or older in 36 RCTs; 12 years or older in one RCT; 12 to 17 years in two RCTs; and three to 17 years in two RCTs. Twenty-nine RCTs provided results for individuals aged over 60 years, and three RCTs included immunocompromized patients. No trials included pregnant women. Sixteen RCTs had two-month follow-up or less, 20 RCTs had two to six months, and five RCTs had greater than six to 12 months or less. Eighteen reports were based on preplanned interim analyses. Overall risk of bias was low for all outcomes in eight RCTs, while 33 had concerns for at least one outcome. We identified 343 registered RCTs with results not yet available.&#xa0; This abstract reports results for the critical outcomes of confirmed symptomatic COVID-19, severe and critical COVID-19, and serious adverse events only for the 10 WHO-approved vaccines. For remaining outcomes and vaccines, see main text. The evidence for mortality was generally sparse and of low or very low certainty for all WHO-approved vaccines, except AD26.COV2.S (Janssen), which probably reduces the risk of all-cause mortality (risk ratio (RR) 0.25, 95% CI 0.09 to 0.67; 1 RCT, 43,783 participants; high-certainty evidence). Confirmed symptomatic COVID-19 High-certainty evidence found that BNT162b2 (BioNtech/Fosun Pharma/Pfizer), mRNA-1273 (ModernaTx), ChAdOx1 (Oxford/AstraZeneca), Ad26.COV2.S, BBIBP-CorV (Sinopharm-Beijing), and BBV152 (Bharat Biotect) reduce the incidence of symptomatic COVID-19 compared to placebo (vaccine efficacy (VE): BNT162b2: 97.84%, 95% CI 44.25% to 99.92%; 2 RCTs, 44,077 participants; mRNA-1273: 93.20%, 95% CI 91.06% to 94.83%; 2 RCTs, 31,632 participants; ChAdOx1: 70.23%, 95% CI 62.10% to 76.62%; 2 RCTs, 43,390 participants; Ad26.COV2.S: 66.90%, 95% CI 59.10% to 73.40%; 1 RCT, 39,058 participants; BBIBP-CorV: 78.10%, 95% CI 64.80% to 86.30%; 1 RCT, 25,463 participants; BBV152: 77.80%, 95% CI 65.20% to 86.40%; 1 RCT, 16,973 participants). Moderate-certainty evidence found that NVX-CoV2373 (Novavax) probably reduces the incidence of symptomatic COVID-19 compared to placebo (VE 82.91%, 95% CI 50.49% to 94.10%; 3 RCTs, 42,175 participants). There is low-certainty evidence for CoronaVac (Sinovac) for this outcome (VE 69.81%, 95% CI 12.27% to 89.61%; 2 RCTs, 19,852 participants). Severe or critical COVID-19 High-certainty evidence found that BNT162b2, mRNA-1273, Ad26.COV2.S, and BBV152 result in a large reduction in incidence of severe or critical disease due to COVID-19 compared to placebo (VE: BNT162b2: 95.70%, 95% CI 73.90% to 99.90%; 1 RCT, 46,077 participants; mRNA-1273: 98.20%, 95% CI 92.80% to 99.60%; 1 RCT, 28,451 participants; AD26.COV2.S: 76.30%, 95% CI 57.90% to 87.50%; 1 RCT, 39,058 participants; BBV152: 93.40%, 95% CI 57.10% to 99.80%; 1 RCT, 16,976 participants). Moderate-certainty evidence found that NVX-CoV2373 probably reduces the incidence of severe or critical COVID-19 (VE 100.00%, 95% CI 86.99% to 100.00%; 1 RCT, 25,452 participants). Two trials reported high efficacy of CoronaVac for severe or critical disease with wide CIs, but these results could not be pooled. Serious adverse events (SAEs) mRNA-1273, ChAdOx1 (Oxford-AstraZeneca)/SII-ChAdOx1 (Serum Institute of India), Ad26.COV2.S, and BBV152 probably result in little or no difference in SAEs compared to placebo (RR: mRNA-1273: 0.92, 95% CI 0.78 to 1.08; 2 RCTs, 34,072 participants; ChAdOx1/SII-ChAdOx1: 0.88, 95% CI 0.72 to 1.07; 7 RCTs, 58,182 participants; Ad26.COV2.S: 0.92, 95% CI 0.69 to 1.22; 1 RCT, 43,783 participants); BBV152: 0.65, 95% CI 0.43 to 0.97; 1 RCT, 25,928 participants). In each of these, the likely absolute difference in effects was fewer than 5/1000 participants. Evidence for SAEs is uncertain for BNT162b2, CoronaVac, BBIBP-CorV, and NVX-CoV2373 compared to placebo (RR: BNT162b2: 1.30, 95% CI 0.55 to 3.07; 2 RCTs, 46,107 participants; CoronaVac: 0.97, 95% CI 0.62 to 1.51; 4 RCTs, 23,139 participants; BBIBP-CorV: 0.76, 95% CI 0.54 to 1.06; 1 RCT, 26,924 participants; NVX-CoV2373: 0.92, 95% CI 0.74 to 1.14; 4 RCTs, 38,802 participants). For the evaluation of heterologous schedules, booster doses, and efficacy against variants of concern, see main text of review.<br><br>AUTHORS' CONCLUSIONS: Compared to placebo, most vaccines reduce, or likely reduce, the proportion of participants with confirmed symptomatic COVID-19, and for some, there is high-certainty evidence that they reduce severe or critical disease. There is probably little or no difference between most vaccines and placebo for serious adverse events. Over 300 registered RCTs are evaluating the efficacy of COVID-19 vaccines, and this review is updated regularly on the COVID-NMA platform (covid-nma.com). Implications for practice Due to the trial exclusions, these results cannot be generalized to pregnant women, individuals with a history of SARS-CoV-2 infection, or immunocompromized people. Most trials had a short follow-up and were conducted before the emergence of variants of concern. Implications for research Future research should evaluate the long-term effect of vaccines, compare different vaccines and vaccine schedules, assess vaccine efficacy and safety in specific populations, and include outcomes such as preventing long COVID-19. Ongoing evaluation of vaccine efficacy and effectiveness against emerging variants of concern is also vital.}, }
@article {pmid36479679, year = {2022}, author = {Koczulla, AR and Ankermann, T and Behrends, U and Berlit, P and Berner, R and Böing, S and Brinkmann, F and Frank, U and Franke, C and Glöckl, R and Gogoll, C and Häuser, W and Hohberger, B and Huber, G and Hummel, T and Köllner, V and Krause, S and Kronsbein, J and Maibaum, T and Otto-Thöne, A and Pecks, U and Peters, EMJ and Peters, S and Pfeifer, M and Platz, T and Pletz, M and Powitz, F and Rabe, KF and Scheibenbogen, C and Schneider, D and Stallmach, A and Stegbauer, M and Tenenbaum, T and Töpfner, N and von Versen-Höynck, F and Wagner, HO and Waller, C and Widmann, CN and Winterholler, C and Wirtz, H and Zwick, R}, title = {[German S1 Guideline Long-/Post-COVID].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {76}, number = {12}, pages = {855-907}, doi = {10.1055/a-1946-3230}, pmid = {36479679}, issn = {1438-8790}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, abstract = {The German Society of Pneumology initiated 2021 the AWMF S1 guideline Long COVID/Post-COVID. In a broad interdisciplinary approach, this S1 guideline was designed based on the current state of knowledge.The clinical recommendations describe current Long COVID/Post-COVID symptoms, diagnostic approaches, and therapies.In addition to the general and consensus introduction, a subject-specific approach was taken to summarize the current state of knowledge.The guideline has an explicit practical claim and will be developed and adapted by the author team based on the current increase in knowledge.}, }
@article {pmid36480981, year = {2022}, author = {Mansell, V and Hall Dykgraaf, S and Kidd, M and Goodyear-Smith, F}, title = {Long COVID and older people.}, journal = {The lancet. Healthy longevity}, volume = {3}, number = {12}, pages = {e849-e854}, doi = {10.1016/S2666-7568(22)00245-8}, pmid = {36480981}, issn = {2666-7568}, mesh = {Humans ; Aged ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; COVID-19 Vaccines ; Quality of Life ; Communicable Disease Control ; }, abstract = {Long COVID is a poorly understood condition, with a wide spectrum of effects on multiple body systems and variable presentation in different individuals. Long COVID is of particular concern among older people (ie, aged 65 years or older), who are at greater risk than younger people of persisting symptoms associated with COVID-19. In addition, COVID-19 might trigger or exacerbate chronic conditions that occur commonly in older people, such as cardiovascular diseases, respiratory diseases, neurodegenerative conditions, and functional decline. In addition, the disruptive effects of COVID-19 for older people should not be underestimated; lockdowns and other restrictions might have reduced the social interactions of older people, and they are also likely to have lost a spouse or loved one during the pandemic, which can contribute to mental and physical decline. COVID-19 vaccination appears to reduce the effects of long COVID, and older people, especially those living in aged care facilities, should remain up-to-date with their COVID-19 vaccinations. Health-care staff should also consider long COVID in the differential diagnosis of relevant symptoms in older people, rather than assume increasing frailty, and should pursue early multidisciplinary assessment and management of persisting symptoms. Addressing physical, psychological, and functional sequelae will mitigate the effect of long COVID and improve the health and quality of life of older people.}, }
@article {pmid36496030, year = {2023}, author = {Harding, JL and Oviedo, SA and Ali, MK and Ofotokun, I and Gander, JC and Patel, SA and Magliano, DJ and Patzer, RE}, title = {The bidirectional association between diabetes and long-COVID-19 - A systematic review.}, journal = {Diabetes research and clinical practice}, volume = {195}, number = {}, pages = {110202}, pmid = {36496030}, issn = {1872-8227}, support = {P30 DK111024/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications/epidemiology ; *Diabetes Mellitus/epidemiology ; Risk Factors ; Disease Progression ; }, abstract = {Some evidence suggests that diabetes may be a risk factor for the development of post-acute sequelae of COVID-19 (PASC). Recent data also indicate that new-onset diabetes may be a complication of COVID-19. Here, we review the existing evidence. Following PRISMA guidelines, we conducted a systematic review through August 8, 2022. We included longitudinal studies reporting on the risk of PASC (i.e., sequelae that extend beyond four weeks after initial infection) in people with and without diabetes, and studies reporting on the risk of new-onset diabetes in people with vs without COVID-19 with a minimum of 4-weeks of follow-up. All studies were published in English. Among 5,532 studies screened, 39 were included in the final review. Among 25 studies reporting on diabetes and PASC, 44 % (n = 11) identified diabetes as a significant risk factor for PASC (increased relative risk ranging from 7 % to 342 %) while 56 % (n = 14) did not. Among 14 studies reporting on new-onset diabetes, 12 (86 %) reported that COVID-19 (vs no COVID) was significantly associated with new-onset diabetes with increased risks ranging from 11 % to 276 %. COVID-19 survivors may be at increased risk for new-onset diabetes, but whether pre-existing diabetes is also a risk factor for PASC remains unclear.}, }
@article {pmid36497138, year = {2022}, author = {Kobusiak-Prokopowicz, M and Fułek, K and Fułek, M and Kaaz, K and Mysiak, A and Kurpas, D and Beszłej, JA and Brzecka, A and Leszek, J}, title = {Cardiovascular, Pulmonary, and Neuropsychiatric Short- and Long-Term Complications of COVID-19.}, journal = {Cells}, volume = {11}, number = {23}, pages = {}, pmid = {36497138}, issn = {2073-4409}, mesh = {Humans ; *COVID-19/complications ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Lung ; }, abstract = {Beginning with the various strategies of the SARS-CoV-2 virus to invade our bodies and manifest infection, and ending with the recent long COVID, we are witnessing the evolving course of the disease in addition to the pandemic. Given the partially controlled course of the COVID-19 pandemic, the greatest challenge currently lies in managing the short- and long-term complications of COVID-19. We have assembled current knowledge of the broad spectrum of cardiovascular, pulmonary, and neuropsychiatric sequelae following SARS-CoV-2 infection to understand how these clinical manifestations collectively lead to a severe form of the disease. The ultimate goal would be to better understand these complications and find ways to prevent clinical deterioration.}, }
@article {pmid36498103, year = {2022}, author = {Du, M and Ma, Y and Deng, J and Liu, M and Liu, J}, title = {Comparison of Long COVID-19 Caused by Different SARS-CoV-2 Strains: A Systematic Review and Meta-Analysis.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {23}, pages = {}, pmid = {36498103}, issn = {1660-4601}, support = {72122001, 71934002//National Natural Science Foundation of China/ ; 2021ZD0114101, 2021ZD0114104, 2021ZD0114105//National Key Research and Development Project of China/ ; 2021LY038//National Statistical Science Research Project/ ; 202204/WT_/Wellcome Trust/United Kingdom ; KY202101004//National Science and Technology Project on Development Assistance for Technology, Developing China-ASEAN Public Health Research and Development Collaborating Center/ ; }, mesh = {Humans ; SARS-CoV-2/genetics ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Pandemics ; Fatigue/epidemiology ; *Sleep Wake Disorders ; }, abstract = {Although many studies of long COVID-19 were reported, there was a lack of systematic research which assessed the differences of long COVID-19 in regard to what unique SARS-CoV-2 strains caused it. As such, this systematic review and meta-analysis aims to evaluate the characteristics of long COVID-19 that is caused by different SARS-CoV-2 strains. We systematically searched the PubMed, EMBASE, and ScienceDirect databases in order to find cohort studies of long COVID-19 as defined by the WHO (Geneva, Switzerland). The main outcomes were in determining the percentages of long COVID-19 among patients who were infected with different SARS-CoV-2 strains. Further, this study was registered in PROSPERO (CRD42022339964). A total of 51 studies with 33,573 patients was included, of which three studies possessed the Alpha and Delta variants, and five studies possessed the Omicron variant. The highest pooled estimate of long COVID-19 was found in the CT abnormalities (60.5%; 95% CI: 40.4%, 80.6%) for the wild-type strain; fatigue (66.1%; 95% CI: 42.2%, 89.9%) for the Alpha variant; and ≥1 general symptoms (28.4%; 95% CI: 7.9%, 49.0%) for the Omicron variant. The pooled estimates of ≥1 general symptoms (65.8%; 95% CI: 47.7%, 83.9%) and fatigue were the highest symptoms found among patients infected with the Alpha variant, followed by the wild-type strain, and then the Omicron variant. The pooled estimate of myalgia was highest among patients infected with the Omicron variant (11.7%; 95%: 8.3%, 15.1%), compared with those infected with the wild-type strain (9.4%; 95%: 6.3%, 12.5%). The pooled estimate of sleep difficulty was lowest among the patients infected with the Delta variant (2.5%; 95%: 0.2%, 4.9%) when compared with those infected with the wild-type strain (24.5%; 95%: 17.5%, 31.5%) and the Omicron variant (18.7%; 95%: 1.0%, 36.5%). The findings of this study suggest that there is no significant difference between long COVID-19 that has been caused by different strains, except in certain general symptoms (i.e., in the Alpha or Omicron variant) and in sleep difficulty (i.e., the wild-type strain). In the context of the ongoing COVID-19 pandemic and its emerging variants, directing more attention to long COVID-19 that is caused by unique strains, as well as implementing targeted intervention measures to address it are vital.}, }
@article {pmid36510683, year = {2023}, author = {Martín Sánchez, FJ and Martínez-Sellés, M and Molero García, JM and Moreno Guillén, S and Rodríguez-Artalejo, FJ and Ruiz-Galiana, J and Cantón, R and De Lucas Ramos, P and García-Botella, A and García-Lledó, A and Hernández-Sampelayo, T and Gómez-Pavón, J and González Del Castillo, J and Martín-Delgado, MC and Bouza, E}, title = {Insights for COVID-19 in 2023.}, journal = {Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia}, volume = {36}, number = {2}, pages = {114-124}, pmid = {36510683}, issn = {1988-9518}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; COVID-19 Vaccines ; SARS-CoV-2 ; }, abstract = {Predictions for a near end of the pandemic by the World Health Organization should be interpreted with caution. Current evidence indicates that the efficacy of a fourth dose of classical mRNA vaccines (BT162b2 or mRNA-1273) is low and short-lived in preventing SARS-CoV-2 infection in its predominant variant (Omicron). However, its efficacy is high against severe symptomatic infection, hospitalization and death. The new vaccines being introduced are bivalent and active against the Omicron variants. Potential new vaccines to be introduced in the coming year include a vaccine based on a recombinant protein that emulates the receptor binding domain of the Spike protein under development by the Spanish company Hipra, as well as vaccines for nasal or oral administration. Available information suggests that vaccines against COVID-19 can be administered in association with influenza vaccination without particular complications. New drugs against COVID-19, both antiviral and anti-inflammatory, are under investigation, but this does not seem to be the case with monoclonal antibodies. The indication to use masks in some circumstances will be maintained next year in view of the accumulation of scientific data on their efficacy. Finally, the long COVID or Post-COVID syndrome may continue to affect a very high proportion of patients who have had the disease, requiring combined diagnostic and therapeutic resources.}, }
@article {pmid36514781, year = {2022}, author = {He, ST and Wu, K and Cheng, Z and He, M and Hu, R and Fan, N and Shen, L and Li, Q and Fan, H and Tong, Y}, title = {Long COVID: The latest manifestations, mechanisms, and potential therapeutic interventions.}, journal = {MedComm}, volume = {3}, number = {4}, pages = {e196}, pmid = {36514781}, issn = {2688-2663}, abstract = {COVID-19 caused by SARS-CoV-2 infection affects humans not only during the acute phase of the infection, but also several weeks to 2 years after the recovery. SARS-CoV-2 infects a variety of cells in the human body, including lung cells, intestinal cells, vascular endothelial cells, olfactory epithelial cells, etc. The damages caused by the infections of these cells and enduring immune response are the basis of long COVID. Notably, the changes in gene expression caused by viral infection can also indirectly contribute to long COVID. We summarized the occurrences of both common and uncommon long COVID, including damages to lung and respiratory system, olfactory and taste deficiency, damages to myocardial, renal, muscle, and enduring inflammation. Moreover, we provided potential treatments for long COVID symptoms manifested in different organs and systems, which were based on the pathogenesis and the associations between symptoms in different organs. Importantly, we compared the differences in symptoms and frequency of long COVID caused by breakthrough infection after vaccination and infection with different variants of concern, in order to provide a comprehensive understanding of the characteristics of long COVID and propose improvement for tackling COVID-19.}, }
@article {pmid36525872, year = {2023}, author = {Capela Santos, D and Jaconiano, S and Macedo, S and Ribeiro, F and Ponte, S and Soares, P and Boaventura, P}, title = {Yoga for COVID-19: An ancient practice for a new condition - A literature review.}, journal = {Complementary therapies in clinical practice}, volume = {50}, number = {}, pages = {101717}, pmid = {36525872}, issn = {1873-6947}, mesh = {Humans ; *Yoga/psychology ; *Meditation ; Post-Acute COVID-19 Syndrome ; COVID-19 Drug Treatment ; *COVID-19/therapy ; }, abstract = {A substantial proportion of people with acute COVID-19 develop post-COVID-19 condition (previously known as long-COVID) characterized by symptoms that persist for months after the initial infection, including neuropsychological sequelae. Post-COVID-19 condition frequency varies greatly according to different studies, with values ranging from 4 to 80% of the COVID-19 patients. Yoga is a psycho-somatic approach that increases physical, mental, emotional and spiritual strength, and connection. Yoga practice enhances innate immunity and mental health, so it can be used as complementary therapy in the COVID-19 treatment, namely the post-COVID-19 condition. In this article, we conducted a literature review on yoga and COVID-19, finding that an intervention comprising asana, pranayama, and meditation may be a strategy of choice for these patients' recovery. However, further studies are needed to show its effectiveness in this, still unknown, context.}, }
@article {pmid36531139, year = {2022}, author = {Lokugamage, AU and Robinson, N and Pathberiya, SDC and Wong, S and Douglass, C}, title = {Respectful maternity care in the UK using a decolonial lens.}, journal = {SN social sciences}, volume = {2}, number = {12}, pages = {267}, pmid = {36531139}, issn = {2662-9283}, abstract = {Respectful maternity care (RMC) is part of a global movement addressing the previous absence of human rights in global safe maternal care guidance. RMC is grounded in kindness, compassion, dignity and respectful working conditions. The decolonisation movement in healthcare seeks to dismantle structural biases set up from a historically white, male, heteronormative Eurocentric medical system. This article applies a decolonising lens to the RMC agenda and examines barriers to its implementation in UK healthcare systems. Searches of peer-reviewed journals about decolonising maternity care in the UK revealed little. Drawing from wider information bases, we examine power imbalances constructed throughout a history of various colonial biases yet lingering in maternity care. The overarching findings of our analysis revealed 3 areas of focus: professional structures and institutional biases; power imbalances between types of staff and stakeholders of care; and person-centred care through a decolonial lens. To uproot inequity and create fairer and more respectful maternity care for women, birthing people and staff, it is vital that contemporary maternity institutions understand the decolonial perspective. This novel enquiry offers a scaffolding to undertake this process. Due to significant differences in colonial history between Western colonising powers, it is important to decolonise with respect to these different territories, histories and challenges.}, }
@article {pmid36532316, year = {2023}, author = {Fenton, C and Lee, A}, title = {Antidepressants with anti-inflammatory properties may be useful in long COVID depression.}, journal = {Drugs &amp; therapy perspectives : for rational drug selection and use}, volume = {39}, number = {2}, pages = {65-70}, pmid = {36532316}, issn = {1172-0360}, abstract = {Long COVID, which is characterised by the presence of persistent symptoms following a COVID infection, may also cause long COVID depression (LCD). Although the risk factors for LCD are not directly characterised, prior mental health visits were associated with an increased risk for long COVID, whereas antidepressant use was not. Current evidence suggests that pro-inflammatory factors in the brain are linked to LCD, thus anti-inflammatory agents may be useful in mitigating LCD. Limited evidence suggests that selective serotonin reuptake inhibitors may also be effective in the treatment of LCD.}, }
@article {pmid36534494, year = {2022}, author = {Zięba, N and Stryjewska-Makuch, G and Goroszkiewicz, K and Zieliński, M and Dadok, A and Pietrzyk, B and Gajewska, J and Miśkiewicz-Orczyk, K and Lisowska, G}, title = {Assessment of life quality and health perception among recovered COVID-19 patients: multivariate analysis - own material and a review of previous reports on life quality assessment among convalescents.}, journal = {Medycyna pracy}, volume = {73}, number = {6}, pages = {449-456}, doi = {10.13075/mp.5893.01297}, pmid = {36534494}, issn = {2353-1339}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Quality of Life ; Pandemics ; Multivariate Analysis ; Perception ; }, abstract = {BACKGROUND: The SARS-CoV-2 virus, causing acute respiratory disease, is responsible for the COVID-19 pandemic, which began in early 2020. In addition to symptoms typical of respiratory tract infections, the virus causes a number of non-specific, often long-lasting effects that hinder the daily functioning of individuals. The aim of the study was a subjective assessment of life quality and health perception among recovered COVID-19 patients.<br><br>MATERIAL AND METHODS: The study included 337 subjects who had been infected with SARS-CoV-2 confirmed by a positive RT-PCR test. The study participants were of legal age. The convalescents completed a questionnaire that contained 26 questions about gender, height, body weight, blood type, general and specific symptoms, comorbidities, hospital stay and duration of specific symptoms, the severity of which was assessed on the Visual Analogue Scale (VAS). The subjects determined whether the COVID-19 infection influenced their health perception and life quality.<br><br>RESULTS: According to 46% of the respondents, COVID-19 had an impact on their quality of life and health. The chance for patients to notice the negative effects of COVID-19 on their current health status and life quality increased with each subsequent symptom of the disease by 49%, with each day of its occurrence by 3%, and with each VAS point of the severity of all infection symptoms by 30%.<br><br>CONCLUSIONS: The study shows that COVID-19 disease affects life quality and overall health perception after recovery. Significant impact of COVID-19 on the quality of life should be a signal to create mental support and rehabilitation programs for convalescents to minimize discomfort and shorten the duration of absenteeism from work. Med Pr. 2022;73(6):449-56.}, }
@article {pmid36535297, year = {2022}, author = {Vitiello, A and Ferrara, F and Zovi, A}, title = {Mechanisms and Clinical Perspectives of COVID-19-induced Cardiovascular Disease.}, journal = {Discovery medicine}, volume = {34}, number = {173}, pages = {181-187}, pmid = {36535297}, issn = {1944-7930}, mesh = {Humans ; *Cardiovascular Diseases ; *COVID-19 ; *Heart Diseases ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {COVID-19 infection can cause damage to various systems, such as cardiovascular, respiratory, and neurological, both during the course of the disease and in the period after recovery, caused by the effects of so-called "Long COVID." Cardiovascular complications caused by COVID-19 infection are not yet fully understood and characterized. Cardiovascular complications caused by COVID-19 include pericarditis, myocarditis, dysrhythmias, ischemic and non-ischemic heart disease, and thromboembolic disease. The pathophysiological and molecular mechanisms of cardiovascular damage caused by SARS-CoV-2 are still being studied. More severe COVID-19 cases with the multisystem inflammatory syndrome (MIS) have frequent involvement of cardiovascular damage. In addition, recent evidence shows that months later, individuals who have had a COVID-19 infection may be at a greater risk of suffering heart disease than individuals who have not had the infection. In this brief literature review, we summarize the current evidence in the literature on cardiovascular damage caused by COVID-19, during the period of infection and in the long COVID, and possible concomitant risk factors, which may play an important role.}, }
@article {pmid36535564, year = {2023}, author = {Zuin, M and Rigatelli, G and Battisti, V and Costola, G and Roncon, L and Bilato, C}, title = {Increased risk of acute myocardial infarction after COVID-19 recovery: A systematic review and meta-analysis.}, journal = {International journal of cardiology}, volume = {372}, number = {}, pages = {138-143}, pmid = {36535564}, issn = {1874-1754}, mesh = {Humans ; Male ; Middle Aged ; Female ; *COVID-19/complications ; SARS-CoV-2 ; *Myocardial Infarction/diagnosis/epidemiology/complications ; }, abstract = {BACKGROUND: Few studies have analyzed the incidence and the risk of acute myocardial infarction (AMI) during the post-acute phase of COVID-19 infection.<br><br>OBJECTIVE: To assess the incidence and risk of AMI in COVID-19 survivors after SARS-CoV-2 infection by a systematic review and meta-analysis of the available data.<br><br>METHODS: Data were obtained searching MEDLINE and Scopus for all studies published at any time up to September 1, 2022 and reporting the risk of incident AMI in patients recovered from COVID-19 infection. AMI risk was evaluated using the Mantel-Haenszel random effects models with Hazard ratio (HR) as the effect measure with 95% confidence interval (CI) while heterogeneity was assessed using Higgins and Thomson I[2] statistic.<br><br>RESULTS: Among 2765 articles obtained by our search strategy, four studies fulfilled the inclusion criteria for a total of 20,875,843 patients (mean age 56.1&#xa0;years, 59.1% males). Of them, 1,244,604 had COVID-19 infection. Over a mean follow-up of 8.5&#xa0;months, among COVID-19 recovered patients AMI occurred in 3.5 cases per 1.000 individuals compared to 2.02 cases per 1.000 individuals in the control cohort, defined as those who did not experience COVID-19 infection in the same period). COVID-19 patients showed an increased risk of incident AMI (HR: 1.93, 95% CI: 1.65-2.26, p&#xa0;<&#xa0;0.0001, I[2]&#xa0;=&#xa0;83.5%). Meta-regression analysis demonstrated that the risk of AMI was directly associated with age (p&#xa0;=&#xa0;0.01) and male gender (p&#xa0;=&#xa0;0.001), while an indirect relationship was observed when the length of follow-up was utilized as moderator (p&#xa0;<&#xa0;0.001).<br><br>CONCLUSION: COVID-19 recovered patients had an increased risk of AMI.}, }
@article {pmid36539006, year = {2023}, author = {Harber, MP and Peterman, JE and Imboden, M and Kaminsky, L and Ashton, REM and Arena, R and Faghy, MA}, title = {Cardiorespiratory fitness as a vital sign of CVD risk in the COVID-19 era.}, journal = {Progress in cardiovascular diseases}, volume = {76}, number = {}, pages = {44-48}, pmid = {36539006}, issn = {1873-1740}, mesh = {Humans ; *Cardiorespiratory Fitness/physiology ; Post-Acute COVID-19 Syndrome ; Pandemics ; *Cardiovascular Diseases/diagnosis/epidemiology/prevention &amp; control ; *COVID-19/epidemiology/complications ; Vital Signs ; Risk Factors ; Physical Fitness/physiology ; }, abstract = {The severe health consequences of the corona virus disease 2019 (COVID-19) pandemic have been exacerbated by the prevalence of cardiovascular disease (CVD) risk factors, such as physical inactivity, obesity, hypertension, and diabetes. Further, policy decisions during the pandemic augmented unhealthy lifestyle behaviors and health inequalities, likely increasing the global disease burden. Cardiorespiratory fitness (CRF) is a well-established biomarker associated with CVD risk. Emerging data demonstrate that high CRF offers some protection against severe outcomes from COVID-19 infection, highlighting the importance of CRF for population health and the potential for limiting the severity of future pandemics. CRF is best assessed by cardiopulmonary exercise testing (CPET), which will be an important tool for understanding the prolonged pathophysiology of COVID-19, the emergence of long-COVID, and the lasting effects of COVID-19 on CVD risk. Utilization of CRF and CPET within clinical settings should become commonplace because of lessons learned from the COVID-19 pandemic.}, }
@article {pmid36539931, year = {2025}, author = {Pak, VM and Lee, J}, title = {Examining the role of micronutrients on improving long COVID sleep-related symptoms.}, journal = {Journal of clinical nursing}, volume = {34}, number = {12}, pages = {5040-5049}, pmid = {36539931}, issn = {1365-2702}, mesh = {Humans ; *Micronutrients/therapeutic use ; *COVID-19/complications ; *Sleep Wake Disorders/drug therapy/etiology ; Ascorbic Acid/therapeutic use ; Zinc/therapeutic use ; SARS-CoV-2 ; }, abstract = {AIMS AND OBJECTIVES: Long COVID is defined as the continuation of symptoms for four or more weeks after initial contraction of the virus. This review article examines the role of four select micronutrients (zinc, vitamins C, D and polyphenols) for their anti-inflammatory and therapeutic potential to improve sleep-related symptoms in persons with long COVID.<br><br>BACKGROUND: Evidence suggests a link between long COVID and increased inflammation. There are currently no therapeutic interventions for common sleep-related symptoms associated with long COVID. Micronutrients, due to their antioxidant and anti-inflammatory properties, may have a role in the treatment of sleep-related symptoms in the context of long COVID.<br><br>DESIGN: A narrative literature review was conducted and guided by the PRISMA checklist.<br><br>METHODS: All articles were screened from PubMed, ScienceDirect, NCBI or Google Scholar and were limited to human studies. The following keywords were used: 'COVID-19', 'sleep symptoms', 'zinc', 'vitamin C', 'vitamin D', 'polyphenols' and 'micronutrients'.<br><br>RESULTS: There are currently no studies that examine the usage of micronutrients and its impacts on long-term, sleep-related symptoms post-COVID-19 infection. We focussed our review on prior studies that examined micronutrients in the context of sleep symptoms and inflammation, while exploring the potential for micronutrients to help improve sleep-related symptoms associated with long COVID.<br><br>CONCLUSIONS: There is evidence to suggest that sleep-related symptoms associated with long COVID, such as fatigue and poor sleep quality, are associated with inflammation. Zinc, vitamins C, D and polyphenols all have the potential to improve both inflammation and sleep quality to alleviate symptoms. Future research should further examine these micronutrients in the context of long COVID to improve sleep and quality of life.<br><br>This article provides implications for clinicians to be at the forefront of research on the usage of micronutrients to improve sleep-related symptoms in persons with long COVID.}, }
@article {pmid36542805, year = {2023}, author = {Ora, J and Calzetta, L and Frugoni, C and Puxeddu, E and Rogliani, P}, title = {Expert guidance on the management and challenges of long-COVID syndrome: a systematic review.}, journal = {Expert opinion on pharmacotherapy}, volume = {24}, number = {3}, pages = {315-330}, doi = {10.1080/14656566.2022.2161365}, pmid = {36542805}, issn = {1744-7666}, mesh = {Humans ; *COVID-19 ; *Stress Disorders, Post-Traumatic ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Long-COVID is a condition characterized by the permanence of symptoms beyond 4 weeks after an initial infection. It affects 1 out of 5 people and is loosely related to the severity of acute infection and pathological mechanisms, which are yet to be understood.<br><br>AREAS COVERED: This article looks at currently available and under-studied therapies for long-COVID syndrome. It particularly gives focus to ongoing trials and reviews the underlying mechanisms. A comprehensive literature search was performed on PubMed and clincaltrial.gov of clinical trials concerning the management of long-COVID syndrome.<br><br>EXPERT OPINION: 'Long-COVID' syndrome is a new emergency characterized by several symptoms such as fatigue, dyspnea, cognitive and attention disorders, sleep disorders, post-traumatic stress disorder, muscle pain, and concentration problems. Despite the many guidelines available to date, there are no established treatments of long-COVID. Pharmacological research is studying known drugs that act on the reduction or modulation of systemic inflammation, or innovative drugs used in similar pathologies. Rehabilitation now seems to be the safest treatment to offer, whereas we will have to wait for the pharmacological research trials in progress as well as plan new trials based on a better understanding of the pathogenic mechanisms.}, }
@article {pmid36550205, year = {2023}, author = {Shibata, S and Kobayashi, K and Tanaka, M and Asayama, K and Yamamoto, E and Nakagami, H and Hoshide, S and Kishi, T and Matsumoto, C and Mogi, M and Morimoto, S and Yamamoto, K and Mukoyama, M and Kario, K and Node, K and Rakugi, H}, title = {COVID-19 pandemic and hypertension: an updated report from the Japanese Society of Hypertension project team on COVID-19.}, journal = {Hypertension research : official journal of the Japanese Society of Hypertension}, volume = {46}, number = {3}, pages = {589-600}, pmid = {36550205}, issn = {1348-4214}, mesh = {Humans ; *COVID-19/complications ; COVID-19 Vaccines ; *Hypertension/complications ; Pandemics ; Post-Acute COVID-19 Syndrome ; Renin-Angiotensin System ; SARS-CoV-2 ; }, abstract = {The number of reported cases with coronavirus disease 2019 (COVID-19) has exceeded 620 million worldwide, still having a profound impact on people's health and daily lives since its occurrence and outbreak in December 2019. From the early phase of the COVID-19 pandemic, there has been a concern that the rapid spread of this communicable disease can negatively influence non-communicable diseases. Accumulating data indicate that the restriction on the access to medical care, psychological distress, and life-style changes triggered by the pandemic have indeed affected blood pressure control in hypertensive patients. Since our previous report in 2020 that summarized the findings of the literature related to COVID-19 and hypertension, there has been a considerable progress in our understanding of the association between these two disorders; nonetheless, there are remaining challenges and emerging questions in the field. In this article, we aim to summarize the latest information on the impact of the pandemic on blood pressure control, the use of the renin-angiotensin system inhibitors in patients with COVID-19, and the blood pressure changes as one of the possible post-acute sequelae of COVID-19 (also known as long COVID). We also summarize the evidence of telemedicine and COVID-19 vaccination in hypertensive subjects, based on data available as of June 2022.}, }
@article {pmid36551869, year = {2022}, author = {Nunn, AVW and Guy, GW and Brysch, W and Bell, JD}, title = {Understanding Long COVID; Mitochondrial Health and Adaptation-Old Pathways, New Problems.}, journal = {Biomedicines}, volume = {10}, number = {12}, pages = {}, pmid = {36551869}, issn = {2227-9059}, abstract = {Many people infected with the SARS-CoV-2 suffer long-term symptoms, such as "brain fog", fatigue and clotting problems. Explanations for "long COVID" include immune imbalance, incomplete viral clearance and potentially, mitochondrial dysfunction. As conditions with sub-optimal mitochondrial function are associated with initial severity of the disease, their prior health could be key in resistance to long COVID and recovery. The SARs virus redirects host metabolism towards replication; in response, the host can metabolically react to control the virus. Resolution is normally achieved after viral clearance as the initial stress activates a hormetic negative feedback mechanism. It is therefore possible that, in some individuals with prior sub-optimal mitochondrial function, the virus can "tip" the host into a chronic inflammatory cycle. This might explain the main symptoms, including platelet dysfunction. Long COVID could thus be described as a virally induced chronic and self-perpetuating metabolically imbalanced non-resolving state characterised by mitochondrial dysfunction, where reactive oxygen species continually drive inflammation and a shift towards glycolysis. This would suggest that a sufferer's metabolism needs to be "tipped" back using a stimulus, such as physical activity, calorie restriction, or chemical compounds that mimic these by enhancing mitochondrial function, perhaps in combination with inhibitors that quell the inflammatory response.}, }
@article {pmid36553888, year = {2022}, author = {Vásconez-González, J and Izquierdo-Condoy, JS and Fernandez-Naranjo, R and Ortiz-Prado, E}, title = {A Systematic Review and Quality Evaluation of Studies on Long-Term Sequelae of COVID-19.}, journal = {Healthcare (Basel, Switzerland)}, volume = {10}, number = {12}, pages = {}, pmid = {36553888}, issn = {2227-9032}, abstract = {COVID-19 made its debut as a pandemic in 2020; since then, more than 607 million cases and at least 6.5 million deaths have been reported worldwide. While the burden of disease has been described, the long-term effects or chronic sequelae are still being clarified. The aim of this study was to present an overview of the information available on the sequelae of COVID-19 in people who have suffered from the infection. A systematic review was carried out in which cohort studies, case series, and clinical case reports were included, and the PubMed, Scielo, SCOPUS, and Web of Science databases were extracted. Information was published from 2020 to 1 June 2022, and we included 26 manuscripts: 9 for pulmonary, 6 for cardiac, 2 for renal, 8 for neurological and psychiatric, and 6 for cutaneous sequelae. Studies showed that the most common sequelae were those linked to the lungs, followed by skin, cutaneous, and psychiatric alterations. Women reported a higher incidence of the sequelae, as well as those with comorbidities and more severe COVID-19 history. The COVID-19 pandemic has not only caused death and disease since its appearance, but it has also sickened millions of people around the globe who potentially suffer from serious illnesses that will continue to add to the list of health problems, and further burden healthcare systems around the world.}, }
@article {pmid36553942, year = {2022}, author = {Surapaneni, KM and Singhal, M and Saggu, SR and Bhatt, A and Shunmathy, P and Joshi, A}, title = {A Scoping Review on Long COVID-19: Physiological and Psychological Symptoms Post-Acute, Long-Post and Persistent Post COVID-19.}, journal = {Healthcare (Basel, Switzerland)}, volume = {10}, number = {12}, pages = {}, pmid = {36553942}, issn = {2227-9032}, abstract = {Background: The identification of persistent symptoms of chronic/long COVID-19 is crucial in understanding the management of long haulers of post COVID-19. Methods: Pub Med (Medline) database was scoped for original articles based on a search strategy related to the objectives. The selected articles post-screening were analyzed for variables relating to chronic/long COVID-19. Results were analyzed using descriptive statistics. Results: A total of 33 studies were reviewed. A total of 60% of the studies were observational studies and most of them were from high income countries. Almost half of the studies were in phase 3 of post-COVID-19, i.e., symptoms lasting >24 weeks. Among the physiological and psychological symptoms studied, fatigue, dyspnea, cough, headache, memory loss, depression, brain fog and lack of concentration were found to be the most frequently reported symptoms. Excessive sleep, constipation and neuropathic pain were among the least reported symptoms. Prior hospitalization, the female gender was found to be a risk factor. Limitations were reported by all studies. Conclusions: The major physiological and psychological symptoms of long COVID-19 have been explained with risk factors and its impact on patients’ lifestyles. The findings of this review hope to facilitate clinicians to draw conclusions to manage the long-term effects of post/chronic COVID-19.}, }
@article {pmid36554098, year = {2022}, author = {Kokolevich, ZM and Crowe, M and Mendez, D and Biros, E and Reznik, JE}, title = {Most Common Long COVID Physical Symptoms in Working Age Adults Who Experienced Mild COVID-19 Infection: A Scoping Review.}, journal = {Healthcare (Basel, Switzerland)}, volume = {10}, number = {12}, pages = {}, pmid = {36554098}, issn = {2227-9032}, abstract = {BACKGROUND: One-third of patients who recover from COVID-19 present with long COVID. Their symptoms are broad, affecting their physical functioning and, ultimately, their quality of life. Many of those individuals who develop long COVID, possibly from a mild COVID-19 infection, are in the 18-65 age group. This prolongation of malaise directly influences national workforce economies.<br><br>OBJECTIVES: To summarise the commonly reported physical symptoms of long COVID in order to inform potential adjustments in healthcare for the employable population.<br><br>METHODS: The Embase, CINAHL, Medline, SCOPUS, and WHO COVID-19 databases were searched. The study selection process was based on the PRISMA guidelines. The extracted data were synthesised and presented narratively.<br><br>RESULTS: 7403 studies were accessed, comprising 60 cohort studies and 10 case series/studies, representing 289,213 patients who met our criteria. The most frequently reported physical symptoms were fatigue (92%), shortness of breath (SOB) (81.8%), muscle pain (43.6%), and joint pain (34.5%).<br><br>CONCLUSIONS: The range of reported physical symptoms was broad and varied; the main ones being fatigue, breathlessness/SOB, and pain. Similarities observed between long COVID and other post-acute infection syndromes may help formulate protocols to manage and promote recovery for long COVID patients. Inconsistencies were evident, particularly with a lack of adherence to the standardised definitions of long COVID.}, }
@article {pmid36555931, year = {2022}, author = {Notarte, KI and de Oliveira, MHS and Peligro, PJ and Velasco, JV and Macaranas, I and Ver, AT and Pangilinan, FC and Pastrana, A and Goldrich, N and Kavteladze, D and Gellaco, MML and Liu, J and Lippi, G and Henry, BM and Fernández-de-Las-Peñas, C}, title = {Age, Sex and Previous Comorbidities as Risk Factors Not Associated with SARS-CoV-2 Infection for Long COVID-19: A Systematic Review and Meta-Analysis.}, journal = {Journal of clinical medicine}, volume = {11}, number = {24}, pages = {}, pmid = {36555931}, issn = {2077-0383}, support = {LONG COVID EXP CM//Comunidad de Madrid/ ; }, abstract = {Identification of predictors of long COVID-19 is essential for managing healthcare plans of patients. This systematic literature review and meta-analysis aimed to identify risk factors not associated with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, but rather potentially predictive of the development of long COVID-19. MEDLINE, CINAHL, PubMed, EMBASE, and Web of Science databases, as well as medRxiv and bioRxiv preprint servers were screened through 15 September 2022. Peer-reviewed studies or preprints evaluating potential pre-SARS-CoV-2 infection risk factors for the development of long-lasting symptoms were included. The methodological quality was assessed using the Quality in Prognosis Studies (QUIPSs) tool. Random-effects meta-analyses with calculation of odds ratio (OR) were performed in those risk factors where a homogenous long COVID-19 definition was used. From 1978 studies identified, 37 peer-reviewed studies and one preprint were included. Eighteen articles evaluated age, sixteen articles evaluated sex, and twelve evaluated medical comorbidities as risk factors of long COVID-19. Overall, single studies reported that old age seems to be associated with long COVID-19 symptoms (n = 18); however, the meta-analysis did not reveal an association between old age and long COVID-19 (n = 3; OR 0.86, 95% CI 0.73 to 1.03, p = 0.17). Similarly, single studies revealed that female sex was associated with long COVID-19 symptoms (n = 16); which was confirmed in the meta-analysis (n = 7; OR 1.48, 95% CI 1.17 to 1.86, p = 0.01). Finally, medical comorbidities such as pulmonary disease (n = 4), diabetes (n = 1), obesity (n = 6), and organ transplantation (n = 1) were also identified as potential risk factors for long COVID-19. The risk of bias of most studies (71%, n = 27/38) was moderate or high. In conclusion, pooled evidence did not support an association between advancing age and long COVID-19 but supported that female sex is a risk factor for long COVID-19. Long COVID-19 was also associated with some previous medical comorbidities.}, }
@article {pmid36556137, year = {2022}, author = {Bernal-Utrera, C and Montero-Almagro, G and Anarte-Lazo, E and Gonzalez-Gerez, JJ and Rodriguez-Blanco, C and Saavedra-Hernandez, M}, title = {Therapeutic Exercise Interventions through Telerehabilitation in Patients with Post COVID-19 Symptoms: A Systematic Review.}, journal = {Journal of clinical medicine}, volume = {11}, number = {24}, pages = {}, pmid = {36556137}, issn = {2077-0383}, abstract = {The worldwide incidence of COVID-19 has generated a pandemic of sequelae. These sequelae require multidisciplinary rehabilitative work to address the multisystemic symptoms that patients will present with now and in the future. The aim of the present systematic review is to analyze the current situation of telerehabilitation in patients with COVID-19 sequelae and its effectiveness. Searches were conducted on the following databases: PubMed, Scopus, PEDro, and Web of Science (WOS). There was no complete homogeneity among the five selected articles, so we differentiated two clinical subgroups for the clustering of outcome measures: (group one) patients with post-discharge symptoms and (group two) patients with permanent symptoms or “long COVID-19” defined as persistent symptoms > 2 months. For group one, post-discharge sequelae, improvements were obtained in cardiovascular parameters, and physical test studies in group two presented very favorable results in all the cardiorespiratory measures and physical tests evaluated. Telerehabilitation through therapeutic exercise based on mixed protocols of aerobic, respiratory, and low-load strength exercises appear to be an effective and safe strategy for the recovery of short- and long-term post-COVID-19 sequelae.}, }
@article {pmid36556290, year = {2022}, author = {Perrottelli, A and Sansone, N and Giordano, GM and Caporusso, E and Giuliani, L and Melillo, A and Pezzella, P and Bucci, P and Mucci, A and Galderisi, S}, title = {Cognitive Impairment after Post-Acute COVID-19 Infection: A Systematic Review of the Literature.}, journal = {Journal of personalized medicine}, volume = {12}, number = {12}, pages = {}, pmid = {36556290}, issn = {2075-4426}, abstract = {The present study aims to provide a critical overview of the literature on the relationships between post-acute COVID-19 infection and cognitive impairment, highlighting the limitations and confounding factors. A systematic search of articles published from 1 January 2020 to 1 July 2022 was performed in PubMed/Medline. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only studies using validated instruments for the assessment of cognitive impairment were included. Out of 5515 screened records, 72 studies met the inclusion criteria. The available evidence revealed the presence of impairment in executive functions, speed of processing, attention and memory in subjects recovered from COVID-19. However, several limitations of the literature reviewed should be highlighted: most studies were performed on small samples, not stratified by severity of disease and age, used as a cross-sectional or a short-term longitudinal design and provided a limited assessment of the different cognitive domains. Few studies investigated the neurobiological correlates of cognitive deficits in individuals recovered from COVID-19. Further studies with an adequate methodological design are needed for an in-depth characterization of cognitive impairment in individuals recovered from COVID-19.}, }
@article {pmid36556422, year = {2022}, author = {Tofarides, AG and Christaki, E and Milionis, H and Nikolopoulos, GK}, title = {Effect of Vaccination against SARS-CoV-2 on Long COVID-19: A Narrative Review.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {12}, pages = {}, pmid = {36556422}, issn = {2075-1729}, abstract = {Vaccines against SARS-CoV-2 have saved millions of lives and played an important role in containing the COVID-19 pandemic. Vaccination against SARS-CoV-2 is also associated with reduced disease severity and, perhaps, with COVID-19 symptom burden. In this narrative review, we present, in a clinically relevant question-and-answer manner, the evidence regarding the association between vaccination against SARS-CoV-2 and long COVID-19. We discuss how the mechanism of action of vaccines could interplay with the pathophysiology of post-COVID-19 condition. Furthermore, we describe how specific factors, such as the number of vaccine doses and the type of SARS-CoV-2 variants, may affect post-COVID-19 condition. We also discuss the role of timing for vaccination in relation to the onset of long COVID-19 symptoms, as it seems to affect the frequency and severity of the condition. Additionally, we describe the potential modifying effect of age, as well as the association of type and level of immune response with long COVID-19. We also describe how system-specific long COVID-19 sequelae, namely neurocognitive-psychologic symptoms and cardiovascular pathology, could be altered by vaccination. Last, we address the question of whether seasonal influenza vaccination has a meaningful impact on the frequency of long COVID-19.}, }
@article {pmid36557705, year = {2022}, author = {Talotta, R}, title = {Impaired VEGF-A-Mediated Neurovascular Crosstalk Induced by SARS-CoV-2 Spike Protein: A Potential Hypothesis Explaining Long COVID-19 Symptoms and COVID-19 Vaccine Side Effects?.}, journal = {Microorganisms}, volume = {10}, number = {12}, pages = {}, pmid = {36557705}, issn = {2076-2607}, abstract = {Long coronavirus disease-19 (COVID-19) is a newly discovered syndrome characterized by multiple organ manifestations that persist for weeks to months, following the recovery from acute disease. Occasionally, neurological and cardiovascular side effects mimicking long COVID-19 have been reported in recipients of COVID-19 vaccines. Hypothetically, the clinical similarity could be due to a shared pathogenic role of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike (S) protein produced by the virus or used for immunization. The S protein can bind to neuropilin (NRP)-1, which normally functions as a coreceptor for the vascular endothelial growth factor (VEGF)-A. By antagonizing the docking of VEGF-A to NRP-1, the S protein could disrupt physiological pathways involved in angiogenesis and nociception. One consequence could be the increase in unbound forms of VEGF-A that could bind to other receptors. SARS-CoV-2-infected individuals may exhibit increased plasma levels of VEGF-A during both acute illness and convalescence, which could be responsible for diffuse microvascular and neurological damage. A few studies suggest that serum VEGF-A may also be a potential biomarker for long COVID-19, whereas evidence for COVID-19 vaccines is lacking and merits further investigation.}, }
@article {pmid36558835, year = {2022}, author = {Rojas, K and Verdugo-Molinares, MG and Ochoa-Ruiz, AG and Canales, A and Reza-Zaldivar, EE and Limón-Rojas, A and Vallejo-Cardona, AA}, title = {Approximations to Diagnosis and Therapy of COVID-19 in Nervous Systems Using Extracellular Vesicles.}, journal = {Pathogens (Basel, Switzerland)}, volume = {11}, number = {12}, pages = {}, pmid = {36558835}, issn = {2076-0817}, abstract = {The SARS-CoV-2 virus was first identified at the end of December 2019, causing the disease known as COVID-19, which, due to the high degree of contagion, was declared a global pandemic as of 2020. The end of the isolation was in 2022, thanks to the global multidisciplinary work of the massive vaccination campaigns. Even with the current knowledge about this virus and the COVID-19 disease, there are many questions and challenges regarding diagnosis and therapy in the fight against this virus. One of the big problems is the so-called "long COVID", prolonged symptomatology characterized as a multiorgan disorder manifested as brain fog, fatigue, and shortness of breath, which persist chronically after the disease resolution. Therefore, this review proposes using extracellular vesicles (EVs) as a therapeutic or diagnostic option to confront the sequelae of the disease at the central nervous system level. Development: the review of updated knowledge about SARS-CoV-2 and COVID-19 is generally addressed as well as the current classification of extracellular vesicles and their proposed use in therapy and diagnosis. Through an analysis of examples, extracellular vesicles are highlighted to learn what happens in the central nervous system during and after COVID-19 and as a therapeutic option. Conclusions: even though there are limitations in the knowledge of the neurological manifestations of COVID-19, it is possible to observe the potential use of extracellular vesicles in therapy or as a diagnostic method and even the importance of their study for the knowledge of the pathophysiology of the disease.}, }
@article {pmid36558963, year = {2022}, author = {Esposito, S and Autore, G and Argentiero, A and Ramundo, G and Perrone, S and Principi, N}, title = {Update on COVID-19 Therapy in Pediatric Age.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {15}, number = {12}, pages = {}, pmid = {36558963}, issn = {1424-8247}, abstract = {With the extension of the COVID-19 pandemic, the large use of COVID-19 vaccines among adults and the emergence of SARS-CoV-2 variants means that the epidemiology of COVID-19 in pediatrics, particularly among younger children, has substantially changed. The prevalence of pediatric COVID-19 significantly increased, several severe cases among children were reported, and long-COVID in pediatric age was frequently observed. The main aim of this paper is to discuss which types of treatment are presently available for pediatric patients with COVID-19, which of them are authorized for the first years of life, and which are the most important limitations of COVID-19 therapy in pediatric age. Four different antivirals, remdesivir (RVD), the combination nirmatrelvir plus ritonavir (Paxlovid), molnupiravir (MPV), and the monoclonal antibody bebtelovimab (BEB), are presently approved or authorized for emergency use for COVID-19 treatment by most of the national health authorities, although with limitations according to the clinical relevance of disease and patient's characteristics. Analyses in the literature show that MPV cannot be used in pediatric age for the risk of adverse events regarding bone growth. The other antivirals can be used, at least in older children, and RDV can be used in all children except in neonates. However, careful research on pharmacokinetic and clinical data specifically collected in neonates and children are urgently needed for the appropriate management of pediatric COVID-19.}, }
@article {pmid36560392, year = {2022}, author = {Pourmasumi, S and Nazari, A and Ahmadi, Z and Kouni, SN and de Gregorio, C and Koniari, I and Dousdampanis, P and Mplani, V and Plotas, P and Assimakopoulos, S and Gogos, C and Aidonisdis, G and Roditis, P and Matsas, N and Velissaris, D and Calogiuri, G and Hung, MY and Altay, S and Kounis, NG}, title = {The Effect of Long COVID-19 Infection and Vaccination on Male Fertility; A Narrative Review.}, journal = {Vaccines}, volume = {10}, number = {12}, pages = {}, pmid = {36560392}, issn = {2076-393X}, abstract = {Earlier research has suggested that the male reproductive system could be particularly vulnerable to SARS-CoV-2 (COVID-19) infection, and infections involving this novel disease not only pose serious health threats but could also cause male infertility. Data from multi-organ research during the recent outbreak indicate that male infertility might not be diagnosed as a possible consequence of COVID-19 infection. Several review papers have summarized the etiology factors on male fertility, but to date no review paper has been published defining the effect of COVID-19 infection on male fertility. Therefore, the aim of this study is to review the published scientific evidence regarding male fertility potential, the risk of infertility during the COVID-19 pandemic, and the impact of COVID-19 vaccination on the male reproductive system. The effects of COVID-19 infection and the subsequent vaccination on seminal fluid, sperm count, sperm motility, sperm morphology, sperm viability, testes and sex hormones are particularly reviewed.}, }
@article {pmid36560633, year = {2022}, author = {Fernández-de-Las-Peñas, C and Notarte, KI and Peligro, PJ and Velasco, JV and Ocampo, MJ and Henry, BM and Arendt-Nielsen, L and Torres-Macho, J and Plaza-Manzano, G}, title = {Long-COVID Symptoms in Individuals Infected with Different SARS-CoV-2 Variants of Concern: A Systematic Review of the Literature.}, journal = {Viruses}, volume = {14}, number = {12}, pages = {}, pmid = {36560633}, issn = {1999-4915}, mesh = {Humans ; *SARS-CoV-2/genetics ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Databases, Factual ; }, abstract = {The association of SARS-CoV-2 variants with long-COVID symptoms is still scarce, but new data are appearing at a fast pace. This systematic review compares the prevalence of long-COVID symptoms according to relevant SARS-CoV-2 variants in COVID-19 survivors. The MEDLINE, CINAHL, PubMed, EMBASE and Web of Science databases, as well as the medRxiv and bioRxiv preprint servers, were searched up to 25 October 2022. Case-control and cohort studies analyzing the presence of post-COVID symptoms appearing after an acute SARS-CoV-2 infection by the Alpha (B.1.1.7), Delta (B.1.617.2) or Omicron (B.1.1.529/BA.1) variants were included. Methodological quality was assessed using the Newcastle-Ottawa Scale. From 430 studies identified, 5 peer-reviewed studies and 1 preprint met the inclusion criteria. The sample included 355 patients infected with the historical variant, 512 infected with the Alpha variant, 41,563 infected with the Delta variant, and 57,616 infected with the Omicron variant. The methodological quality of all studies was high. The prevalence of long-COVID was higher in individuals infected with the historical variant (50%) compared to those infected with the Alpha, Delta or Omicron variants. It seems that the prevalence of long-COVID in individuals infected with the Omicron variant is the smallest, but current data are heterogeneous, and long-term data have, at this stage, an obviously shorter follow-up compared with the earlier variants. Fatigue is the most prevalent long-COVID symptom in all SARS-CoV-2 variants, but pain is likewise prevalent. The available data suggest that the infection with the Omicron variant results in fewer long-COVID symptoms compared to previous variants; however, the small number of studies and the lack of the control of cofounders, e.g., reinfections or vaccine status, in some studies limit the generality of the results. It appears that individuals infected with the historical variant are more likely to develop long-COVID symptomatology.}, }
@article {pmid36560641, year = {2022}, author = {Ratcliffe, NA and Castro, HC and Gonzalez, MS and Mello, CB and Dyson, P}, title = {Reaching the Final Endgame for Constant Waves of COVID-19.}, journal = {Viruses}, volume = {14}, number = {12}, pages = {}, pmid = {36560641}, issn = {1999-4915}, mesh = {Humans ; *COVID-19/epidemiology/prevention &amp; control ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Antiviral Agents/therapeutic use ; }, abstract = {Despite intramuscular vaccines saving millions of lives, constant devastating waves of SARS-CoV-2 infections continue. The elimination of COVID-19 is challenging, but necessary in order to avoid millions more people who would suffer from long COVID if we fail. Our paper describes rapidly advancing and innovative therapeutic strategies for the early stage of infection with COVID-19 so that tolerating continuing cycles of infection should be unnecessary in the future. These therapies include new vaccines with broader specificities, nasal therapies and antiviral drugs some targeting COVID-19 at the first stage of infection and preventing the virus entering the body in the first place. Our article describes the advantages and disadvantages of each of these therapeutic options which in various combinations could eventually prevent renewed waves of infection. Finally, important consideration is given to political, social and economic barriers that since 2020 hindered vaccine application and are likely to interfere again with any COVID-19 endgame.}, }
@article {pmid36560801, year = {2022}, author = {Fernández-Lázaro, D and Santamaría, G and Sánchez-Serrano, N and Lantarón Caeiro, E and Seco-Calvo, J}, title = {Efficacy of Therapeutic Exercise in Reversing Decreased Strength, Impaired Respiratory Function, Decreased Physical Fitness, and Decreased Quality of Life Caused by the Post-COVID-19 Syndrome.}, journal = {Viruses}, volume = {14}, number = {12}, pages = {}, pmid = {36560801}, issn = {1999-4915}, mesh = {Humans ; Female ; Male ; *COVID-19/therapy ; Quality of Life ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Physical Fitness ; }, abstract = {In the current global scenario, many COVID-19 survivors present a severe deterioration in physical strength, respiratory function, and quality of life due to persistent symptoms and post-acute consequences of SARS-CoV-2 infection. These alterations are known as post-COVID-19 syndrome for which there is no specific and effective treatment for their management. Currently, therapeutic exercise strategies (ThEx) are effective in many diseases by reducing the appearance of complications and side effects linked to treatment, and are consequently of great relevance. In this study, we review the effect of ThEX in reversing decreased strength, impaired respiratory function, decreased physical fitness, and decreased quality of life (QoL) caused by post-COVID-19 syndrome. A literature search was conducted through the electronic databases, Medline (PubMed), SciELO and Cochrane Library Plus for this structured narrative review for studies published from database retrieval up till 12 December 2022. A total of 433 patients with post-COVID-19 syndrome condition (60% women) were included in the nine studies which met the inclusion/exclusion criteria. Overall, post-COVID-19 syndrome patients who followed a ThEx intervention showed improvements in strength, respiratory function, physical fitness and QoL, with no exercise-derived side effects. Thus, ThEx based on strength, aerobic and respiratory training could be an adjuvant non-pharmacological tool in the modulation of post-COVID-19 syndrome.}, }
@article {pmid36564007, year = {2023}, author = {da Fonseca Lima, EJ and Leite, RD}, title = {COVID-19 vaccination in children: a public health priority.}, journal = {Jornal de pediatria}, volume = {99 Suppl 1}, number = {Suppl 1}, pages = {S28-S36}, pmid = {36564007}, issn = {1678-4782}, mesh = {Vaccination ; *COVID-19 Vaccines ; Adolescent ; Child ; Health Priorities ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology/prevention &amp; control/complications ; Vaccines, Inactivated ; Systemic Inflammatory Response Syndrome ; }, abstract = {OBJECTIVE: Covid-19 had a direct impact on children's health. The aim of this review was to analyze epidemiological and clinical data, the consequences of the pandemic, and vaccination aspects in this group.<br><br>SOURCES OF DATA: The searches were carried out from January 2020 to November 2022, in the MEDLINE databases (PubMed) and publications of the Brazilian Ministry of Health and the Brazilian Society of Pediatrics.<br><br>SUMMARY OF FINDINGS: Covid-19 has a mild presentation in most children; however, the infection can progress to the severe form and, in some cases, to MIS-C. The prevalence of the so-called long Covid in children was 25.24%. Moreover, several indirect impacts occurred on the health of children and adolescents. Vaccination played a crucial role in enabling the reduction of severe disease and mortality rates. Children and adolescents, as a special population, were excluded from the initial clinical trials and, therefore, vaccination was introduced later in this group. Despite its importance, there have been difficulties in the efficient implementation of vaccination in the pediatric population. The CoronaVac vaccines are authorized in Brazil for children over three years of age and the pediatric presentations of the Pfizer vaccine have shown significant effectiveness and safety.<br><br>CONCLUSIONS: Covid-19 in the pediatric age group was responsible for the illness and deaths of a significant number of children. For successful immunization, major barriers have to be overcome. Real-world data on the safety and efficacy of several pediatric vaccines is emphasized, and the authors need a uniform message about the importance of immunization for all children.}, }
@article {pmid36570463, year = {2022}, author = {Zhang, J}, title = {Investigating neurological symptoms of infectious diseases like COVID-19 leading to a deeper understanding of neurodegenerative disorders such as Parkinson's disease.}, journal = {Frontiers in neurology}, volume = {13}, number = {}, pages = {968193}, pmid = {36570463}, issn = {1664-2295}, abstract = {Apart from common respiratory symptoms, neurological symptoms are prevalent among patients with COVID-19. Research has shown that infection with SARS-CoV-2 accelerated alpha-synuclein aggregation, induced Lewy-body-like pathology, caused dopaminergic neuron senescence, and worsened symptoms in patients with Parkinson's disease (PD). In addition, SARS-CoV-2 infection can induce neuroinflammation and facilitate subsequent neurodegeneration in long COVID, and increase individual vulnerability to PD or parkinsonism. These findings suggest that a post-COVID-19 parkinsonism might follow the COVID-19 pandemic. In order to prevent a possible post-COVID-19 parkinsonism, this paper reviewed neurological symptoms and related findings of COVID-19 and related infectious diseases (influenza and prion disease) and neurodegenerative disorders (Alzheimer's disease, PD and amyotrophic lateral sclerosis), and discussed potential mechanisms underlying the neurological symptoms and the relationship between the infectious diseases and the neurodegenerative disorders, as well as the therapeutic and preventive implications in the neurodegenerative disorders. Infections with a relay of microbes (SARS-CoV-2, influenza A viruses, gut bacteria, etc.) and prion-like alpha-synuclein proteins over time may synergize to induce PD. Therefore, a systematic approach that targets these pathogens and the pathogen-induced neuroinflammation and neurodegeneration may provide cures for neurodegenerative disorders. Further, antiviral/antimicrobial drugs, vaccines, immunotherapies and new therapies (e.g., stem cell therapy) need to work together to treat, manage or prevent these disorders. As medical science and technology advances, it is anticipated that better vaccines for SARS-CoV-2 variants, new antiviral/antimicrobial drugs, effective immunotherapies (alpha-synuclein antibodies, vaccines for PD or parkinsonism, etc.), as well as new therapies will be developed and made available in the near future, which will help prevent a possible post-COVID-19 parkinsonism in the 21st century.}, }
@article {pmid36570602, year = {2023}, author = {Halili, A}, title = {Temporal model for central sensitization: A hypothesis for mechanism and treatment using systemic manual therapy, a focused review.}, journal = {MethodsX}, volume = {10}, number = {}, pages = {101942}, pmid = {36570602}, issn = {2215-0161}, abstract = {The purpose of this focused review is to develop a consolidated hypothesis as to the causes and mechanisms of central sensitization and a related model for a treatment approach using Systemic Manual Therapy (SMT). The key to understanding central sensitization is a firm grasp on structure and function of the Locus-coeruleus noradrenaline system (LC-NA). This system uses an elaborate switching mechanism to control the level and rate of activation of multiple systems. This review evaluates the mechanisms and temporal relationships behind four components: salient stimuli, threat coding, aberrant afferent input, and oxidative stress. The five-stage temporal model for central sensitization includes phasic activation of the LC-NA system, salient stimuli, threat coding of salient stimuli, central sensitization, and neural degeneration. The three components of treatment include temporarily reducing afferent visceral input, shifting humoral inflammatory activity away from the brain and outside the body, and reducing oxidative stress by making oxygenated blood more available around the LC and other stressed areas in the brain. The SMT protocols that could help in reduction of visceral afferent input are GUOU, Barral and LAUG. Protocols that should shift humoral inflammatory activity away from the brain or completely out of the body include UD and DCS. One protocol that can potentially reduce oxidative stress by making oxygenated blood more available around the LC is CCCV. Future research and hypothesis-testing strategies as well as limitations are further discussed.}, }
@article {pmid36574210, year = {2023}, author = {Liao, B and Deng, YK and Zeng, M and Liu, Z}, title = {Long-term Consequences of COVID-19: Chemosensory Disorders.}, journal = {Current allergy and asthma reports}, volume = {23}, number = {2}, pages = {111-119}, pmid = {36574210}, issn = {1534-6315}, mesh = {Humans ; Female ; *COVID-19/complications/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Quality of Life ; *Olfaction Disorders/epidemiology/etiology/diagnosis ; Taste Disorders/epidemiology/etiology ; }, abstract = {PURPOSE OF REVIEW: A number of sequelae after acute coronavirus disease 2019 (COVID-19) significantly affect the quality of life of patients. The chemosensory disorders including olfactory dysfunction (OD) and gustatory dysfunction (GD) are two of the commonest symptoms complained by patients with COVID-19. Although chemosensory function has been reported improved in over 60% of COVID-19 patients in a short time after acute infection, it may last as a major symptom for patients with long COVID-19. This narrative review discussed current literatures on OD and GD in long COVID-19 including the prevalence, risk factors, possible mechanisms, and potential therapies.<br><br>RECENT FINDINGS: Although the prevalence of OD and GD has declined continuously after acute COVID-19, a considerable number of patients had persistent chemosensory disorders 3&#xa0;months to 2&#xa0;years after symptom onset. Female gender, initial severity of dysfunction, nasal congestion, emotional distress and depression, and SARS-CoV-2 variants have been identified as risk factors for persistent OD and GD in long COVID-19. The pathogenesis of OD and GD in long COVID-19 remains unknown, but may be analogous to the persistent OD and GD post common respiratory viral infection. Corticosteroids and olfactory training might be a potential choice regarding the treatment of lasting OD and GD after SARS-CoV-2 infection; however, more studies are needed to prove it. OD and GD are common long-term consequences of COVID-19 and influenced by gender, initial severity of dysfunction, emotional distress and depression, and SARS-CoV-2 variants. More studies are needed to illustrate their pathogenesis and to establish therapeutic strategies.}, }
@article {pmid36575228, year = {2023}, author = {Matsumoto, C and Shibata, S and Kishi, T and Morimoto, S and Mogi, M and Yamamoto, K and Kobayashi, K and Tanaka, M and Asayama, K and Yamamoto, E and Nakagami, H and Hoshide, S and Mukoyama, M and Kario, K and Node, K and Rakugi, H}, title = {Long COVID and hypertension-related disorders: a report from the Japanese Society of Hypertension Project Team on COVID-19.}, journal = {Hypertension research : official journal of the Japanese Society of Hypertension}, volume = {46}, number = {3}, pages = {601-619}, pmid = {36575228}, issn = {1348-4214}, mesh = {Humans ; *COVID-19/complications ; *Hypertension ; Post-Acute COVID-19 Syndrome ; Quality of Life ; SARS-CoV-2 ; }, abstract = {The coronavirus disease 2019 (COVID-19) affects infected patients even after the acute phase and impairs their health and quality of life by causing a wide variety of symptoms, referred to as long COVID. Although the evidence is still insufficient, hypertension is suspected to be a potential risk factor for long COVID, and the occurrence of cardiovascular diseases seems to be a key facet of multiple conditions observed in long COVID. Nonetheless, there are few reports that comprehensively review the impacts of long COVID on hypertension and related disorders. As a sequel to our previous report in 2020 which reviewed the association of COVID-19 and hypertension, we summarize the possible influences of long COVID on hypertension-related organs, including the cardiovascular system, kidney, and endocrine system, as well as the pathophysiological mechanisms associated with the disorders in this review. Given that the clinical course of COVID-19 is highly affected by age and sex, we also review the impacts of these factors on long COVID. Lastly, we discuss areas of uncertainty and future directions, which may lead to better understanding and improved prognosis of clinical problems associated with COVID-19.}, }
@article {pmid36575843, year = {2022}, author = {Melrose, J and Smith, MM}, title = {Natural and Semi-Synthetic Flavonoid Anti-SARS-CoV-2 Agents for the Treatment of Long COVID-19 Disease and Neurodegenerative Disorders of Cognitive Decline.}, journal = {Frontiers in bioscience (Elite edition)}, volume = {14}, number = {4}, pages = {27}, doi = {10.31083/j.fbe1404027}, pmid = {36575843}, issn = {1945-0508}, mesh = {Humans ; SARS-CoV-2 ; *COVID-19 ; Flavonoids/therapeutic use/pharmacology ; Post-Acute COVID-19 Syndrome ; Molecular Docking Simulation ; Antiviral Agents/therapeutic use/pharmacology ; Anti-Inflammatory Agents/therapeutic use ; *Neurodegenerative Diseases/drug therapy ; *Cognitive Dysfunction/drug therapy ; }, abstract = {The aim of this review is to highlight the beneficial attributes of flavonoids, a diverse family of widely-distributed polyphenolic phytochemicals that have beneficial cell and tissue protective properties. Phytochemicals are widely distributed in plants, herbs and shrubs used in traditional complimentary medical formulations for centuries. The bioactive components that convey beneficial medicinal effects in these complex herbal preparations are now being identified using network pharmacology and molecular docking procedures that identify their molecular targets. Flavonoids have anti-oxidant, anti-inflammatory, antiviral, antibacterial and anti-cancer properties that have inspired the development of potent multifunctional derivatised flavonoids of improved efficacy. The antiviral properties of flavonoids and the emergence of the severe acute respiratory syndrome (SARS-CoV-2) pandemic has resulted in a resurgence of interest in phytochemicals in the search for efficacious compounds that can prevent viral infection or replication, with many promising plant compounds identified. Promising semi-synthetic flavonoid derivatives have also been developed that inhibit multiple pathological neurodegenerative processes; these offer considerable promise in the treatment of diseases of cognitive decline. Clinical trials are currently being undertaken to evaluate the efficacy of dietary supplements rich in flavonoids for the treatment of virally-mediated diseases. Such trials are expected to identify flavonoids with cell and tissue protective properties that can be harnessed in biomedical applications that may serve as supportive adjunctive procedures to conventional anti-viral drug therapies against diseases such as COVID-19.}, }
@article {pmid36579511, year = {2022}, author = {Sampogna, G and Di Vincenzo, M and Giallonardo, V and Perris, F and Volpicelli, A and Del Vecchio, V and Luciano, M and Fiorillo, A}, title = {The Psychiatric Consequences of Long-COVID: A Scoping Review.}, journal = {Journal of personalized medicine}, volume = {12}, number = {11}, pages = {}, pmid = {36579511}, issn = {2075-4426}, abstract = {The COVID-19 pandemic has represented a new form of traumatic event, affecting the general population worldwide and causing severe disruption of daily routine. A new urgent concern is related to the burden associated with COVID-19 symptoms that persist beyond the onset of infection, the so-called long-COVID syndrome. The present paper aims to: (1) describe the most frequent psychiatric symptoms reported by patients affected by long-COVID syndrome; (2) evaluate methodological discrepancies among the available studies; (3) inform clinicians and policy-makers on the possible strategies to be promoted in order to manage the psychiatric consequences of long-COVID syndrome. Twenty-one papers have been included in the present review, mostly with a cross-sectional or cohort design. Significant heterogeneity of long-COVID syndrome definitions was found. The presence of psychiatric symptoms was evaluated with very different assessment tools. The most common psychiatric symptoms of the long-COVID syndrome included fatigue, cognitive disturbances/impairment, depression, and anxiety symptoms. The rate of fatigue varied from 93.2-82.3% to 11.5%, cognitive impairment/cognitive dysfunction from 61.4% to 23.5% and depressive-anxiety symptoms from 23.5%to 9.5%.}, }
@article {pmid36580406, year = {2024}, author = {Barker, KK and Whooley, O and Madden, EF and Ahrend, EE and Greene, RN}, title = {The long tail of COVID and the tale of long COVID: Diagnostic construction and the management of ignorance.}, journal = {Sociology of health &amp; illness}, volume = {46}, number = {S1}, pages = {189-207}, pmid = {36580406}, issn = {1467-9566}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Sociology ; Uncertainty ; COVID-19 Testing ; }, abstract = {We bring together insights from the sociology of diagnosis and the sociology of ignorance to examine the early diagnostic unfolding of 'Long COVID' (LC). Originally described by patient activists, researchers set out to ponder its unwieldy clinical boundaries. Using a scoping review method in tandem with qualitative content analytic techniques, we analyse medicine's initial struggles to construct a LC diagnosis. Paying attention to the dynamics of ignorance, we highlight three consequential conceptual manoeuvres in the early classifications of LC: causal agnosticism concerning the relationship between COVID-19 and LC, evasion of lumping LC with similar conditions; and the predictable splitting off of medically explainable cases from the LC designation. These manoeuvres are not maleficent, inept or unreasonable. They are practical but impactful responses to the classificatory dilemmas present in the construction of diagnoses amidst ignorance. Although there are unique aspects to LC, we suggest that its early fate is nevertheless emblematic of medicine's diagnostic standardisation processes more generally. To varying degrees, diagnoses are ignorance management strategies; they create a pathway through the uncertainty at the core of disease realities. However, while diagnoses circumscribe some types of ignorance, they produce others through the creation of blind spots and paths not taken.}, }
@article {pmid36580648, year = {2023}, author = {Barie, PS and Brindle, ME and Khadaroo, RG and Klassen, TL and Huston, JM}, title = {Omicron, Long-COVID, and the Safety of Elective Surgery for Adults and Children: Joint Guidance from the Therapeutics and Guidelines Committee of the Surgical Infection Society and the Surgery Strategic Clinical Network, Alberta Health Services.}, journal = {Surgical infections}, volume = {24}, number = {1}, pages = {6-18}, doi = {10.1089/sur.2022.274}, pmid = {36580648}, issn = {1557-8674}, mesh = {Adult ; Child ; Humans ; *Post-Acute COVID-19 Syndrome ; Alberta ; Multiple Organ Failure ; *COVID-19/epidemiology ; SARS-CoV-2 ; Health Services ; }, abstract = {Background: Active and recent coronavirus disease 2019 (COVID-19) infections are associated with morbidity and mortality after surgery in adults. Current recommendations suggest delaying elective surgery in survivors for four to 12 weeks, depending on initial illness severity. Recently, the predominant causes of COVID-19 are the highly transmissible/less virulent Omicron variant/subvariants. Moreover, increased survivability of primary infections has engendered the long-COVID syndrome, with protean manifestations that may persist for months. Considering the more than 600,000,000 COVID-19 survivors, surgeons will likely be consulted by recovered patients seeking elective operations. Knowledge gaps of the aftermath of Omicron infections raise questions whether extant guidance for timing of surgery still applies to adults or should apply to the pediatric population. Methods: Scoping review of relevant English-language literature. Results: Most supporting data derive from early in the pandemic when the Alpha variant of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) predominated. The Omicron variant/subvariants generally cause milder infections with less organ dysfunction; many infections are asymptomatic, especially in children. Data are scant with respect to adult surgical outcomes after Omicron infection, and especially so for pediatric surgical outcomes at any stage of the pandemic. Conclusions: Numerous knowledge gaps persist with respect to the disease, the recovered pre-operative patient, the nature of the proposed procedure, and supporting data. For example, should the waiting period for all but urgent elective surgery be extended beyond 12 weeks, e.g., after serious/critical illness, or for patients with long-COVID and organ dysfunction? Conversely, can the waiting periods for asymptomatic patients or vaccinated patients be shortened? How shall children be risk-stratified, considering the distinctiveness of pediatric COVID-19 and the paucity of data? Forthcoming guidelines will hopefully answer these questions but may require ongoing modifications based on additional new data and the epidemiology of emerging strains.}, }
@article {pmid36580747, year = {2023}, author = {Jammoul, M and Naddour, J and Madi, A and Reslan, MA and Hatoum, F and Zeineddine, J and Abou-Kheir, W and Lawand, N}, title = {Investigating the possible mechanisms of autonomic dysfunction post-COVID-19.}, journal = {Autonomic neuroscience : basic &amp; clinical}, volume = {245}, number = {}, pages = {103071}, pmid = {36580747}, issn = {1872-7484}, mesh = {Humans ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Autonomic Nervous System Diseases/etiology ; *Orthostatic Intolerance ; }, abstract = {Patients with long COVID suffer from many neurological manifestations that persist for 3 months following infection by SARS-CoV-2. Autonomic dysfunction (AD) or dysautonomia is one complication of long COVID that causes patients to experience fatigue, dizziness, syncope, dyspnea, orthostatic intolerance, nausea, vomiting, and heart palpitations. The pathophysiology behind AD onset post-COVID is largely unknown. As such, this review aims to highlight the potential mechanisms by which AD occurs in patients with long COVID. The first proposed mechanism includes the direct invasion of the hypothalamus or the medulla by SARS-CoV-2. Entry to these autonomic centers may occur through the neuronal or hematogenous routes. However, evidence so far indicates that neurological manifestations such as AD are caused indirectly. Another mechanism is autoimmunity whereby autoantibodies against different receptors and glycoproteins expressed on cellular membranes are produced. Additionally, persistent inflammation and hypoxia can work separately or together to promote sympathetic overactivation in a bidirectional interaction. Renin-angiotensin system imbalance can also drive AD in long COVID through the downregulation of relevant receptors and formation of autoantibodies. Understanding the pathophysiology of AD post-COVID-19 may help provide early diagnosis and better therapy for patients.}, }
@article {pmid36582234, year = {2022}, author = {Haunhorst, S and Bloch, W and Javelle, F and Krüger, K and Baumgart, S and Drube, S and Lemhöfer, C and Reuken, P and Stallmach, A and Müller, M and Zielinski, CE and Pletz, MW and Gabriel, HHW and Puta, C}, title = {A scoping review of regulatory T cell dynamics in convalescent COVID-19 patients - indications for their potential involvement in the development of Long COVID?.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1070994}, pmid = {36582234}, issn = {1664-3224}, mesh = {Humans ; CD4-Positive T-Lymphocytes ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; T-Lymphocytes, Regulatory ; }, abstract = {BACKGROUND: Recovery from coronavirus disease 2019 (COVID-19) can be impaired by the persistence of symptoms or new-onset health complications, commonly referred to as Long COVID. In a subset of patients, Long COVID is associated with immune system perturbations of unknown etiology, which could be related to compromised immunoregulatory mechanisms.<br><br>OBJECTIVE: The objective of this scoping review was to summarize the existing literature regarding the frequency and functionality of Tregs in convalescent COVID-19 patients and to explore indications for their potential involvement in the development of Long COVID.<br><br>DESIGN: A systematic search of studies investigating Tregs during COVID-19 convalescence was conducted on MEDLINE (via Pubmed) and Web of Science.<br><br>RESULTS: The literature search yielded 17 relevant studies, of which three included a distinct cohort of patients with Long COVID. The reviewed studies suggest that the Treg population of COVID-19 patients can reconstitute quantitatively and functionally during recovery. However, the comparison between recovered and seronegative controls revealed that an infection-induced dysregulation of the Treg compartment can be sustained for at least several months. The small number of studies investigating Tregs in Long COVID allowed no firm conclusions to be drawn about their involvement in the syndrome's etiology. Yet, even almost one year post-infection Long COVID patients exhibit significantly altered proportions of Tregs within the CD4+ T cell population.<br><br>CONCLUSIONS: Persistent alterations in cell frequency in Long COVID patients indicate that Treg dysregulation might be linked to immune system-associated sequelae. Future studies should aim to address the association of Treg adaptations with different symptom clusters and blood parameters beyond the sole quantification of cell frequencies while adhering to consensualized phenotyping strategies.}, }
@article {pmid36582565, year = {2022}, author = {Yousif, E and Premraj, S}, title = {A Review of Long COVID With a Special Focus on Its Cardiovascular Manifestations.}, journal = {Cureus}, volume = {14}, number = {11}, pages = {e31933}, pmid = {36582565}, issn = {2168-8184}, abstract = {The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has been the cause of the century's worst pandemic so far: coronavirus disease 2019 (COVID-19). It has led to unprecedented mortality and morbidity, resulting in devastating consequences worldwide. The acute manifestations of COVID-19 including respiratory as well as multisystem involvement have been causes of great concern among physicians. However, the long-term effects of the coronavirus have left many patients battling with chronic symptoms, ranging from extreme fatigue to cardiomyopathy. In this article, we review the chronic manifestations of COVID-19 with a focus on cardiovascular manifestations. We discuss the pathophysiology, post-acute sequelae, clinical manifestations, approach to the laboratory diagnosis of cardiovascular manifestations of long COVID, and a proposed multidisciplinary treatment method. We also explore the relationship between vaccination and the long COVID syndrome.}, }
@article {pmid36591299, year = {2022}, author = {Elizalde-Díaz, JP and Miranda-Narváez, CL and Martínez-Lazcano, JC and Martínez-Martínez, E}, title = {The relationship between chronic immune response and neurodegenerative damage in long COVID-19.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1039427}, pmid = {36591299}, issn = {1664-3224}, mesh = {Humans ; Chemokines ; COVID-19 ; Immunity ; Interferon-alpha ; Interleukin-6 ; Ligands ; *Post-Acute COVID-19 Syndrome/complications/immunology/physiopathology ; SARS-CoV-2 ; *Neurodegenerative Diseases/etiology/immunology/physiopathology ; }, abstract = {In the past two years, the world has faced the pandemic caused by the severe acute respiratory syndrome 2 coronavirus (SARS-CoV-2), which by August of 2022 has infected around 619 million people and caused the death of 6.55 million individuals globally. Although SARS-CoV-2 mainly affects the respiratory tract level, there are several reports, indicating that other organs such as the heart, kidney, pancreas, and brain can also be damaged. A characteristic observed in blood serum samples of patients suffering COVID-19 disease in moderate and severe stages, is a significant increase in proinflammatory cytokines such as interferon-α (IFN-α), interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6) and interleukin-18 (IL-18), as well as the presence of autoantibodies against interferon-α (IFN-α), interferon-λ (IFN-λ), C-C motif chemokine ligand 26 (CCL26), CXC motif chemokine ligand 12 (CXCL12), family with sequence similarity 19 (chemokine (C-C motif)-like) member A4 (FAM19A4), and C-C motif chemokine ligand 1 (CCL1). Interestingly, it has been described that the chronic cytokinemia is related to alterations of blood-brain barrier (BBB) permeability and induction of neurotoxicity. Furthermore, the generation of autoantibodies affects processes such as neurogenesis, neuronal repair, chemotaxis and the optimal microglia function. These observations support the notion that COVID-19 patients who survived the disease present neurological sequelae and neuropsychiatric disorders. The goal of this review is to explore the relationship between inflammatory and humoral immune markers and the major neurological damage manifested in post-COVID-19 patients.}, }
@article {pmid36597293, year = {2022}, author = {Du, Y and Zhang, J and Wu, LJ and Zhang, Q and Wang, YX}, title = {The Epidemiology, Diagnosis and Prognosis of Long-COVID.}, journal = {Biomedical and environmental sciences : BES}, volume = {35}, number = {12}, pages = {1133-1139}, doi = {10.3967/bes2022.143}, pmid = {36597293}, issn = {2214-0190}, mesh = {Humans ; *COVID-19/diagnosis/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, }
@article {pmid36601750, year = {2023}, author = {McWhirter, L and Carson, A}, title = {Functional cognitive disorders: clinical presentations and treatment approaches.}, journal = {Practical neurology}, volume = {23}, number = {2}, pages = {104-110}, doi = {10.1136/pn-2022-003608}, pmid = {36601750}, issn = {1474-7766}, mesh = {Humans ; *Cognition Disorders/diagnosis/etiology/therapy ; *Cognitive Dysfunction/diagnosis/therapy ; Cognition ; }, abstract = {Functional cognitive disorders (FCDs) are a common cause of subjective and mild cognitive impairment. Isolated FCDs commonly present to the cognitive clinic, but examination of the nature of the symptoms suggests that they can also be understood as a transdiagnostic feature of many other conditions. This article examines methods of formulating the cognitive difficulties in order to identify treatment targets in people with FCDs.}, }
@article {pmid36612567, year = {2022}, author = {Binns, CW and Lee, MK and Doan, TTD and Lee, A and Pham, M and Zhao, Y}, title = {COVID and Gender: A Narrative Review of the Asia-Pacific Region.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {1}, pages = {}, pmid = {36612567}, issn = {1660-4601}, mesh = {Male ; Female ; Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Pandemics/prevention &amp; control ; Communicable Disease Control ; Asia/epidemiology ; }, abstract = {The COVID-19 pandemic has been the largest infectious disease epidemic to affect the human race since the great influenza pandemic of 1918-19 and is close to approaching the number of deaths from the earlier epidemic. A review of available data and the numerous currently available studies on COVID-19 shows that the rate of clinical cases is about 10% greater in females than males in Asia. However, the number of deaths is greater in males than in females. Women are more likely to experience the psychological effects of COVID-19 during and after acute infections. A significant proportion of acute COVID-19 infections continue and their prolonged symptoms have been reported. Further studies are needed, including detailed serology, to measure and monitor the incidence of COVID-19. The pandemic has had a widespread impact on broader societies including shortages of food, lockdowns and isolation. The number of orphans in developing countries has increased. Women have had to bear the major impacts of these community effects. More research is required to develop better vaccines acting against new strains of the virus and to develop systems to distribute vaccines to all people.}, }
@article {pmid36613731, year = {2022}, author = {Tyagi, SC and Pushpakumar, S and Sen, U and Mokshagundam, SPL and Kalra, DK and Saad, MA and Singh, M}, title = {COVID-19 Mimics Pulmonary Dysfunction in Muscular Dystrophy as a Post-Acute Syndrome in Patients.}, journal = {International journal of molecular sciences}, volume = {24}, number = {1}, pages = {}, pmid = {36613731}, issn = {1422-0067}, support = {HL-74185, HL-139047, DK116591 and AR-71789/NH/NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; Matrix Metalloproteinase 9/metabolism ; Mice, Inbred mdx ; Tumor Necrosis Factor-alpha/metabolism ; Post-Acute COVID-19 Syndrome ; Neopterin/metabolism ; *COVID-19/pathology ; SARS-CoV-2 ; *Muscular Dystrophy, Duchenne/genetics ; Fibrosis ; Muscle, Skeletal/metabolism ; Disease Models, Animal ; }, abstract = {Although progressive wasting and weakness of respiratory muscles are the prominent hallmarks of Duchenne muscular dystrophy (DMD) and long-COVID (also referred as the post-acute sequelae of COVID-19 syndrome); however, the underlying mechanism(s) leading to respiratory failure in both conditions remain unclear. We put together the latest relevant literature to further understand the plausible mechanism(s) behind diaphragm malfunctioning in COVID-19 and DMD conditions. Previously, we have shown the role of matrix metalloproteinase-9 (MMP9) in skeletal muscle fibrosis via a substantial increase in the levels of tumor necrosis factor-α (TNF-α) employing a DMD mouse model that was crossed-bred with MMP9-knockout (MMP9-KO or MMP9[-/-]) strain. Interestingly, recent observations from clinical studies show a robust increase in neopterin (NPT) levels during COVID-19 which is often observed in patients having DMD. What seems to be common in both (DMD and COVID-19) is the involvement of neopterin (NPT). We know that NPT is generated by activated white blood cells (WBCs) especially the M1 macrophages in response to inducible nitric oxide synthase (iNOS), tetrahydrobiopterin (BH4), and tetrahydrofolate (FH4) pathways, i.e., folate one-carbon metabolism (FOCM) in conjunction with epigenetics underpinning as an immune surveillance protection. Studies from our laboratory, and others researching DMD and the genetically engineered humanized (hACE2) mice that were administered with the spike protein (SP) of SARS-CoV-2 revealed an increase in the levels of NPT, TNF-α, HDAC, IL-1β, CD147, and MMP9 in the lung tissue of the animals that were subsequently accompanied by fibrosis of the diaphragm depicting a decreased oscillation phenotype. Therefore, it is of interest to understand how regulatory processes such as epigenetics involvement affect DNMT, HDAC, MTHFS, and iNOS that help generate NPT in the long-COVID patients.}, }
@article {pmid36614882, year = {2022}, author = {Mattioli, AV and Selleri, V and Zanini, G and Nasi, M and Pinti, M and Stefanelli, C and Fedele, F and Gallina, S}, title = {Physical Activity and Diet in Older Women: A Narrative Review.}, journal = {Journal of clinical medicine}, volume = {12}, number = {1}, pages = {}, pmid = {36614882}, issn = {2077-0383}, abstract = {Physical activity and diet are essential for maintaining good health and preventing the development of non-communicable diseases, especially in the older adults. One aspect that is often over-looked is the different response between men and women to exercise and nutrients. The body's response to exercise and to different nutrients as well as the choice of foods is different in the two sexes and is strongly influenced by the different hormonal ages in women. The present narrative review analyzes the effects of gender on nutrition and physical activity in older women. Understanding which components of diet and physical activity affect the health status of older women would help target non-pharmacological but lifestyle-related therapeutic interventions. It is interesting to note that this analysis shows a lack of studies dedicated to older women and a lack of studies dedicated to the interactions between diet and physical activity in women. Gender medicine is a current need that still finds little evidence.}, }
@article {pmid36618714, year = {2023}, author = {Fessel, J}, title = {Fluoxetine plus lithium for treatment of mental health impairment in Long Covid.}, journal = {Discover mental health}, volume = {3}, number = {1}, pages = {1}, pmid = {36618714}, issn = {2731-4383}, abstract = {PURPOSES: (1) To summarize the mental conditions that may accompany persistent symptoms following acute infection by SARS-CoV-2, often termed Long Covid; (2) to formulate treatment based upon the brain cells that are dominantly affected.<br><br>METHODS: (1) Review the reports relating to the mental symptoms occurring in Long Covid. (2) Review the drugs that address the brain cells affected in Long Covid, and suggest pharmacotherapy for those patients whose response to psychotherapy is suboptimal.<br><br>RESULTS: Long Covid affects&#x2009;~&#x2009;10% of patients infected by SARS-CoV-2, and mental symptoms affect&#x2009;~&#x2009;20% of persons with Long Covid. The brain cell-types that have been demonstrated as dominantly affected in Long Covid are astrocytes, oligodendrocytes, neurons, endothelial cells/pericytes, and microglia. Lithium and fluoxetine each address all of those four cell-types. Low dosage of each is likely to be well-tolerated and to cause neither clinically important adverse events (AE) nor serious adverse events (SAE).<br><br>CONCLUSION: For those patients whose response to psychotherapy is suboptimal, lithium and fluoxetine should be administered in combination for both depth of benefit and reduction of dosages.}, }
@article {pmid36625747, year = {2023}, author = {Jeong, YJ and Wi, YM and Park, H and Lee, JE and Kim, SH and Lee, KS}, title = {Current and Emerging Knowledge in COVID-19.}, journal = {Radiology}, volume = {306}, number = {2}, pages = {e222462}, pmid = {36625747}, issn = {1527-1315}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Tomography, X-Ray Computed ; }, abstract = {COVID-19 has emerged as a pandemic leading to a global public health crisis of unprecedented morbidity. A comprehensive insight into the imaging of COVID-19 has enabled early diagnosis, stratification of disease severity, and identification of potential sequelae. The evolution of COVID-19 can be divided into early infectious, pulmonary, and hyperinflammatory phases. Clinical features, imaging features, and management are different among the three phases. In the early stage, peripheral ground-glass opacities are predominant CT findings, and therapy directly targeting SARS-CoV-2 is effective. In the later stage, organizing pneumonia or diffuse alveolar damage pattern are predominant CT findings and anti-inflammatory therapies are more beneficial. The risk of severe disease or hospitalization is lower in breakthrough or Omicron variant infection compared with nonimmunized or Delta variant infections. The protection rates of the fourth dose of mRNA vaccination were 34% and 67% against overall infection and hospitalizations for severe illness, respectively. After acute COVID-19 pneumonia, most residual CT abnormalities gradually decreased in extent, but they may remain as linear or multifocal reticular or cystic lesions. Advanced insights into the pathophysiologic and imaging features of COVID-19 along with vaccine benefits have improved patient care, but emerging knowledge of post-COVID-19 condition, or long COVID, also presents radiology with new challenges.}, }
@article {pmid36632532, year = {2023}, author = {Rowe, K}, title = {Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) in Adolescents: Practical Guidance and Management Challenges.}, journal = {Adolescent health, medicine and therapeutics}, volume = {14}, number = {}, pages = {13-26}, pmid = {36632532}, issn = {1179-318X}, abstract = {This paper reviews the current understanding of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and whether any treatment strategies have been effective. ME/CFS is a condition of as yet unknown etiology that commonly follows an infective process. It includes a new onset of fatigue (of more than 3-6 month duration and not relieved by rest), post-exertional malaise, cognitive difficulties and unrefreshing sleep, and frequently orthostatic intolerance, somatic symptoms and pain. Long COVID has renewed interest in the condition and stimulated research with findings suggestive of a multisystem neuroimmune disease. There are no definitively effective treatments. Despite earlier recommendations regarding graded exercise therapy and cognitive behavior therapy, the current recommendations are managing symptoms, with lifestyle management and supportive care. This paper provides an outline of strategies that young people and their families have reported as helpful in managing a chronic illness that impacts their life socially, physically, emotionally, cognitively and educationally. As the illness frequently occurs at a time of rapid developmental changes, reducing these impacts is reported to be as important as managing the physical symptoms. Young people face a mean duration of 5 years illness (range 1-16 years) with a likely residual 20% having significant restrictions after 10 years. Their feedback has suggested that symptom management, self-management strategies, advocacy and educational liaison have been the most helpful. They value professionals who will listen and take them seriously, and after excluding alternative diagnoses, they explain the diagnosis, are supportive and assist in monitoring their progress. Remaining engaged in education was the best predictor of later functioning. This allowed for social connections, as well as potential independence and fulfilling some aspirations. The need to consider the impact of this chronic illness on all aspects of adolescent development, as part of management, is highlighted.}, }
@article {pmid36633452, year = {2023}, author = {Hallek, M and Adorjan, K and Behrends, U and Ertl, G and Suttorp, N and Lehmann, C}, title = {Post-COVID Syndrome.}, journal = {Deutsches Arzteblatt international}, volume = {120}, number = {4}, pages = {48-55}, pmid = {36633452}, issn = {1866-0452}, mesh = {Adult ; Adolescent ; Child ; Humans ; *COVID-19 ; SARS-CoV-2 ; Inflammation ; Pandemics/prevention &amp; control ; Vaccination ; }, abstract = {BACKGROUND: As defined by the WHO, the term post-COVID syndrome (PCS) embraces a group of symptoms that can occur following the acute phase of a SARS-CoV-2 infection and as a consequence thereof. PCS is found mainly in adults, less frequently in children and adolescents. It can develop both in patients who initially had only mild symptoms or none at all and in those who had a severe course of coronavirus disease 2019 (COVID-19).<br><br>METHODS: The data presented here were derived from a systematic literature review.<br><br>RESULTS: PCS occurs in up to 15% of unvaccinated adults infected with SARS-CoV-2. The prevalence has decreased in the most recent phase of the pandemic and is lower after vaccination. The pathogenesis of PCS has not yet been fully elucidated. Virustriggered inflammation, autoimmunity, endothelial damage (to blood vessels), and persistence of virus are thought to be causative. Owing to the broad viral tropism, different organs are involved and the symptoms vary. To date, there are hardly any evidence-based recommendations for definitive diagnosis of PCS or its treatment.<br><br>CONCLUSION: The gaps in our knowledge mean that better documentation of the prevalence of PCS is necessary to compile the data on which early detection, diagnosis, and treatment can be based. To ensure the best possible care of patients with PCS, regional PCS centers and networks embracing existing structures from all healthcare system sectors and providers should be set up and structured diagnosis and treatment algorithms should be established. Given the sometimes serious consequences of PCS for those affected, it seems advisable to keep the number of SARS-CoV-2 infections low by protective measures tailored to the prevailing pandemic situation.}, }
@article {pmid36639608, year = {2023}, author = {Davis, HE and McCorkell, L and Vogel, JM and Topol, EJ}, title = {Long COVID: major findings, mechanisms and recommendations.}, journal = {Nature reviews. Microbiology}, volume = {21}, number = {3}, pages = {133-146}, pmid = {36639608}, issn = {1740-1534}, support = {UL1 TR002550/TR/NCATS NIH HHS/United States ; }, mesh = {Child ; Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; COVID-19 Testing ; *Biomedical Research ; }, abstract = {Long COVID is an often debilitating illness that occurs in at least 10% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. More than 200 symptoms have been identified with impacts on multiple organ systems. At least 65 million individuals worldwide are estimated to have long COVID, with cases increasing daily. Biomedical research has made substantial progress in identifying various pathophysiological changes and risk factors and in characterizing the illness; further, similarities with other viral-onset illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome have laid the groundwork for research in the field. In this Review, we explore the current literature and highlight key findings, the overlap with other conditions, the variable onset of symptoms, long COVID in children and the impact of vaccinations. Although these key findings are critical to understanding long COVID, current diagnostic and treatment options are insufficient, and clinical trials must be prioritized that address leading hypotheses. Additionally, to strengthen long COVID research, future studies must account for biases and SARS-CoV-2 testing issues, build on viral-onset research, be inclusive of marginalized populations and meaningfully engage patients throughout the research process.}, }
@article {pmid36642173, year = {2023}, author = {Ashraf, N and Abou Shaar, B and Taha, RM and Arabi, TZ and Sabbah, BN and Alkodaymi, MS and Omrani, OA and Makhzoum, T and Almahfoudh, NE and Al-Hammad, QA and Hejazi, W and Obeidat, Y and Osman, N and Al-Kattan, KM and Berbari, EF and Tleyjeh, IM}, title = {A systematic review of trials currently investigating therapeutic modalities for post-acute COVID-19 syndrome and registered on WHO International Clinical Trials Platform.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {29}, number = {5}, pages = {570-577}, pmid = {36642173}, issn = {1469-0691}, mesh = {Humans ; *COVID-19/therapy ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Transcranial Direct Current Stimulation ; World Health Organization ; }, abstract = {BACKGROUND: Post-acute COVID-19 syndrome (PACS) is a well-recognized, complex, systemic disease which is associated with substantial morbidity. There is a paucity of established interventions for the treatment of patients with this syndrome.<br><br>OBJECTIVES: To systematically review registered trials currently investigating therapeutic modalities for PACS.<br><br>DATA SOURCES: A search was conducted up to the 16 September, 2022, using the COVID-19 section of the WHO Internal Clinical Trials Registry Platform.<br><br>Interventional clinical trials of any sample size examining any therapeutic modality targeting persistent symptoms among individuals after diagnosis with COVID-19.<br><br>METHODS: Data on trial characteristics and intervention characteristics were collected and summarized.<br><br>RESULTS: After screening 17&#xa0;125 trials, 388 trials, from 42 countries, were eligible. In total, we had 406 interventions, of which 368 were mono-therapeutic strategies, whereas 38 were intervention combinations. Among 824 primary outcomes identified, there were >300 different outcomes. Rehabilitation was the most employed class of intervention in 169 trials. We encountered 76 trials examining the pharmacological agents of various classes, with the most common agent being colchicine. Complementary and alternative medicine encompassed 64 trials exploring traditional Chinese medicine, Ayurveda, homeopathic medications, naturopathic medications, vitamins, dietary supplements, and botanicals. Psychotherapeutic and educational interventions were also employed in 12 and 4 trials, respectively. Other interventions, including transcranial direct current stimulation, transcutaneous auricular vagus nerve stimulation, general electrical stimulation, cranial electrotherapy stimulation, various stem cell interventions, and oxygen therapy interventions, were also employed.<br><br>CONCLUSION: We identified 388 registered trials, with a high degree of heterogeneity, exploring 144 unique mono-therapeutic interventions for PACS. Most studies target general alleviation of symptoms. There is a need for further high-quality and methodologically robust PACS treatment trials to be conducted with standardization of outcomes while following WHO's recommendation for uniform evaluation and treatment.}, }
@article {pmid36646086, year = {2023}, author = {Habet, V and Oliveira, CR}, title = {Clinical Epidemiology of Pediatric Coronavirus Disease 2019 and its Postacute Sequelae.}, journal = {Seminars in respiratory and critical care medicine}, volume = {44}, number = {1}, pages = {66-74}, pmid = {36646086}, issn = {1098-9048}, support = {K23 AI159518/AI/NIAID NIH HHS/United States ; L40 AI120154/AI/NIAID NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {Quality of Life ; Disease Progression ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome ; Child ; Humans ; *COVID-19/epidemiology/complications ; Post-Acute COVID-19 Syndrome ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic has affected individuals of all ages across. Although children generally experience a benign illness from COVID-19, the emergence of novel variants of the virus has resulted in significant changes in the morbidity and mortality rates for this age group. Currently, COVID-19 is the eighth leading cause of pediatric deaths in the United States. In addition to acute respiratory illness, some children can develop a severe postinfectious condition known as a multisystem inflammatory syndrome in children, which can progress to rapid-onset cardiogenic shock. Recovery from COVID-19 can also be slow for some children, resulting in persistent or reoccurring symptoms for months, commonly referred to as long COVID. These postinfectious sequelae are often distressing for children and their parents, can negatively impact the quality of life, and impose a considerable burden on the health care system. In this article, we review the clinical epidemiology of pediatric COVID-19 and outline the management considerations for its acute and postacute manifestations.}, }
@article {pmid36646091, year = {2023}, author = {Lutchmansingh, DD and Higuero Sevilla, JP and Possick, JD and Gulati, M}, title = {"Long Haulers".}, journal = {Seminars in respiratory and critical care medicine}, volume = {44}, number = {1}, pages = {130-142}, doi = {10.1055/s-0042-1759568}, pmid = {36646091}, issn = {1098-9048}, mesh = {Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Quality of Life ; SARS-CoV-2 ; Algorithms ; Disease Progression ; }, abstract = {Post-COVID conditions continue to afflict patients long after acute severe acute respiratory syndrome-coronavirus-2 (SARS CoV-2) infection. Over 50 symptoms across multiple organ systems have been reported, with pulmonary, cardiovascular, and neuropsychiatric sequelae occurring most frequently. Multiple terms have been used to describe post-COVID conditions including long COVID, long-haul COVID, postacute coronavirus disease 2019 (COVID-19), postacute sequelae of SARS-CoV-2 infection, long-term effects of COVID, and chronic COVID-19; however, standardized assessments and treatment algorithms for patients have generally been lacking. This review discusses the epidemiology and risk factors for post-COVID conditions and provides a general overview of the diagnostic assessment and treatment of specific manifestations. Data derived from the multitude of observational studies and scientific investigations into pathogenesis are providing a clearer understanding of the distinct phenotypes of post-COVID conditions. Insight gained from these studies and ongoing interventional trials continues to lead to the development of clinical protocols directed toward improving COVID-19 survivors' quality of life and preventing or reducing long-term morbidity.}, }
@article {pmid36648876, year = {2023}, author = {Vink, M and Vink-Niese, A}, title = {The Draft Report by the Institute for Quality and Efficiency in Healthcare Does Not Provide Any Evidence That Graded Exercise Therapy and Cognitive Behavioral Therapy Are Safe and Effective Treatments for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.}, journal = {Diseases (Basel, Switzerland)}, volume = {11}, number = {1}, pages = {}, pmid = {36648876}, issn = {2079-9721}, abstract = {The German Institute for Quality and Efficiency in Healthcare (IQWiG) recently published its draft report to the government about myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The IQWiG concluded that graded exercise therapy (GET) and cognitive behavioral therapy (CBT) should be recommended in the treatment for mild and moderate ME/CFS based on two CBT and two GET studies. In this article, we reviewed the evidence used by IQWiG to support their claims, because their conclusion is diametrically opposed to the conclusion by the British National Institute for Health and Care Excellence (NICE) in its recently updated ME/CFS guidelines. Our analysis shows that the trials IQWiG used in support suffered from serious flaws, which included badly designed control groups; relying on subjective primary outcomes in non-blinded studies; alliance and response shift bias, including patients in their trials who did not have the disease under investigation, selective reporting, making extensive endpoint changes and low to very low adherence of treatments. Our analysis also shows that the report itself used one CBT and one GET study that both examined a different treatment. The report also used a definition of CBT that does not reflect the way it is being used in ME/CFS or was tested in the studies. The report noted that one study used a wrong definition of post-exertional malaise (PEM), the main characteristic of the disease, according to the report. Yet, it ignored the consequence of this, that less than the required minimum percentage of patients had the disease under investigation in that study. It also ignored the absence of improvement on most of the subjective outcomes, as well as the fact that the IQWiG methods handbook states that one should use objective outcomes and not rely on subjective outcomes in non-blinded studies. The report concluded that both treatments did not lead to objective improvement in the six-minute walk test but then ignored that. The report did not analyze the other objective outcomes of the studies (step test and occupational and benefits status), which showed a null effect. Finally, the report states that the studies do not report on safety yet assumes that the treatments are safe based on a tendency towards small subjective improvements in fatigue and physical functioning, even though the adherence to the treatments was (very) low and the studies included many patients who did not have the disease under investigation and, consequently, did not suffer from exertion intolerance contrary to ME/CFS patients. At the same time, it ignored and downplayed all the evidence that both treatments are not safe, even when the evidence was produced by a British university. In conclusion, the studies used by the report do not provide any evidence that CBT and GET are safe and effective. Consequently, the report and the studies do not provide any support for the recommendation to use CBT and GET for ME/CFS or long COVID, which, in many cases, is the same or resembles ME/CFS, after an infection with SARS-CoV-2.}, }
@article {pmid36652923, year = {2024}, author = {Zanini, G and Selleri, V and Roncati, L and Coppi, F and Nasi, M and Farinetti, A and Manenti, A and Pinti, M and Mattioli, AV}, title = {Vascular "Long COVID": A New Vessel Disease?.}, journal = {Angiology}, volume = {75}, number = {1}, pages = {8-14}, pmid = {36652923}, issn = {1940-1574}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Microcirculation ; Blood Platelets ; }, abstract = {Vascular sequelae following (SARS-CoV-2 coronavirus disease) (COVID)-19 infection are considered as "Long Covid (LC)" disease, when occurring 12 weeks after the original infection. The paucity of specific data can be obviated by translating pathophysiological elements from the original Severe Acute Respiratory Syndrome-Corona Virus (SARS-CoV-2) infection (In a microcirculatory system, a first "endotheliitis," is often followed by production of "Neutrophil Extracellular Trap," and can evolve into a more complex leukocytoklastic-like and hyperimmune vasculitis. In medium/large-sized vessels, this corresponds to endothelial dysfunction, leading to an accelerated progression of pre-existing atherosclerotic plaques through an increased deposition of platelets, circulating inflammatory cells and proteins. Associated dysregulated immune and pro-coagulant conditions can directly cause thrombo-embolic arterial or venous complications. In order to implement appropriate treatment, physicians need to consider vascular pathologies observed after SARS-Cov-2 infections as possible "LC" disease.}, }
@article {pmid36657113, year = {2022}, author = {Gallegos, M and Martino, P and Caycho-Rodríguez, T and Calandra, M and Razumovskiy, A and Arias-Gallegos, WL and Castro-Peçanha, V and Cervigni, M}, title = {What is post-COVID-19 syndrome? Definition and update.}, journal = {Gaceta medica de Mexico}, volume = {158}, number = {6}, pages = {442-446}, doi = {10.24875/GMM.M22000725}, pmid = {36657113}, issn = {0016-3813}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Latin America/epidemiology ; Public Health ; }, abstract = {This work addresses the origin and development of post-COVID-19 syndrome, which consists of the persistence of different symptoms over time as a consequence of SARS-CoV-2 infection. Based on a narrative review of the scientific literature, a brief analysis of the new term is made, specifying the conceptual definition, characteristic symptoms, the various implications for people's health, and the responses to specific care measures that have been implemented. It concludes with a wake-up call to the governments of Latin America and the Caribbean in order for care and surveillance to be provided to this public health problem.}, }
@article {pmid36660968, year = {2023}, author = {Morello, R and Martino, L and Buonsenso, D}, title = {Diagnosis and management of post-COVID (Long COVID) in children: a moving target.}, journal = {Current opinion in pediatrics}, volume = {35}, number = {2}, pages = {184-192}, pmid = {36660968}, issn = {1531-698X}, mesh = {Child ; Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; COVID-19 Testing ; Mental Health ; }, abstract = {PURPOSE OF REVIEW: This review describes recent findings about post-COVID condition (PCC, or Long COVID) in children, including current knowledge about its epidemiology, clinical presentation, pathogenesis and care.<br><br>RECENT FINDINGS: There is no internationally agreed definition of PCC, although now most researchers agree that it is a complex clinical symptomatology persisting for at least 3&#x200a;months after COVID-19, without an alternative diagnosis. There are several uncertainties about paediatric PCC. So far, available literature suggest that 1-3% of recognized children with Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV-2) infection may develop PCC. Its pathogenesis is unknown, although there is increasing evidence about possible abnormalities in the immune responses, cellular metabolism and intestinal microbiota, along with chronic endothelitis.<br><br>SUMMARY: Management of PCC in children is complex and require a multidisciplinary approach, with the goal of offering the best care possible to support diagnostics, research, mental health and access to research projects.}, }
@article {pmid36671555, year = {2023}, author = {Righetto, I and Gasparotto, M and Casalino, L and Vacca, M and Filippini, F}, title = {Exogenous Players in Mitochondria-Related CNS Disorders: Viral Pathogens and Unbalanced Microbiota in the Gut-Brain Axis.}, journal = {Biomolecules}, volume = {13}, number = {1}, pages = {}, pmid = {36671555}, issn = {2218-273X}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Brain-Gut Axis ; *Central Nervous System Diseases ; *Gastrointestinal Microbiome ; Mitochondria ; }, abstract = {Billions of years of co-evolution has made mitochondria central to the eukaryotic cell and organism life playing the role of cellular power plants, as indeed they are involved in most, if not all, important regulatory pathways. Neurological disorders depending on impaired mitochondrial function or homeostasis can be caused by the misregulation of "endogenous players", such as nuclear or cytoplasmic regulators, which have been treated elsewhere. In this review, we focus on how exogenous agents, i.e., viral pathogens, or unbalanced microbiota in the gut-brain axis can also endanger mitochondrial dynamics in the central nervous system (CNS). Neurotropic viruses such as Herpes, Rabies, West-Nile, and Polioviruses seem to hijack neuronal transport networks, commandeering the proteins that mitochondria typically use to move along neurites. However, several neurological complications are also associated to infections by pandemic viruses, such as Influenza A virus and SARS-CoV-2 coronavirus, representing a relevant risk associated to seasonal flu, coronavirus disease-19 (COVID-19) and "Long-COVID". Emerging evidence is depicting the gut microbiota as a source of signals, transmitted via sensory neurons innervating the gut, able to influence brain structure and function, including cognitive functions. Therefore, the direct connection between intestinal microbiota and mitochondrial functions might concur with the onset, progression, and severity of CNS diseases.}, }
@article {pmid36671900, year = {2022}, author = {Khondakar, KR and Kaushik, A}, title = {Role of Wearable Sensing Technology to Manage Long COVID.}, journal = {Biosensors}, volume = {13}, number = {1}, pages = {}, pmid = {36671900}, issn = {2079-6374}, mesh = {Humans ; *COVID-19/diagnosis ; Post-Acute COVID-19 Syndrome ; *Wearable Electronic Devices ; Body Temperature ; Technology ; }, abstract = {Long COVID consequences have changed the perception towards disease management, and it is moving towards personal healthcare monitoring. In this regard, wearable devices have revolutionized the personal healthcare sector to track and monitor physiological parameters of the human body continuously. This would be largely beneficial for early detection (asymptomatic and pre-symptomatic cases of COVID-19), live patient conditions, and long COVID monitoring (COVID recovered patients and healthy individuals) for better COVID-19 management. There are multitude of wearable devices that can observe various human body parameters for remotely monitoring patients and self-monitoring mode for individuals. Smart watches, smart tattoos, rings, smart facemasks, nano-patches, etc., have emerged as the monitoring devices for key physiological parameters, such as body temperature, respiration rate, heart rate, oxygen level, etc. This review includes long COVID challenges for frequent monitoring of biometrics and its possible solution with wearable device technologies for diagnosis and post-therapy of diseases.}, }
@article {pmid36673555, year = {2023}, author = {Valverde-Martínez, M&#xc1; and López-Liria, R and Martínez-Cal, J and Benzo-Iglesias, MJ and Torres-Álamo, L and Rocamora-Pérez, P}, title = {Telerehabilitation, A Viable Option in Patients with Persistent Post-COVID Syndrome: A Systematic Review.}, journal = {Healthcare (Basel, Switzerland)}, volume = {11}, number = {2}, pages = {}, pmid = {36673555}, issn = {2227-9032}, abstract = {The number of patients with post-COVID-19 syndrome continues to increase considerably, having serious healthcare, social and economic repercussions. The objective of this study is to describe the effectiveness of telerehabilitation to alleviate the symptoms of post-COVID-19 syndrome. A systematic review was conducted using the information available on four databases (PubMed, Medline, Scielo and PEDRo) on these patients until November 2022. The MeSH search terms were: Post-COVID syndrome, Post-COVID-19, Long COVID, Telerehabilitation, Physiotherapy, Rehabilitation, Virtual, Home care. Six articles were included which provided information on 140 patients, detailing their symptomatology, assessment, treatment and monitoring. The variables measured were dyspnea, fatigue, physical performance and quality of life. All studies included aerobic and anaerobic exercises. Most notable among the techniques used were rib cage expansion exercises, respiratory control and thoracic cage stretching, patient education, Mindfulness and virtual reality games to address physical, mental and relaxation aspects. The use of telerehabilitation could be an effective tool for the treatment of persistent symptoms after suffering from COVID-19. It has been shown in these studies that patients improve both their physical performance and their quality of life.}, }
@article {pmid36674665, year = {2023}, author = {Vasichkina, E and Alekseeva, D and Kudryavtsev, I and Glushkova, A and Starshinova, AY and Malkova, A and Kudlay, D and Starshinova, A}, title = {COVID-19 Heart Lesions in Children: Clinical, Diagnostic and Immunological Changes.}, journal = {International journal of molecular sciences}, volume = {24}, number = {2}, pages = {}, pmid = {36674665}, issn = {1422-0067}, support = {075-15-2022-301//Federal Almazov North-West Medical Research Centre/ ; }, mesh = {Adult ; *Myocarditis/diagnosis ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome ; Child ; *COVID-19/complications/diagnosis ; Humans ; COVID-19 Testing ; Post-Acute COVID-19 Syndrome ; }, abstract = {In the beginning of COVID-19, the proportion of confirmed cases in the pediatric population was relatively small and there was an opinion that children often had a mild or asymptomatic course of infection. Our understanding of the immune response, diagnosis and treatment of COVID-19 is highly oriented towards the adult population. At the same time, despite the fact that COVID-19 in children usually occurs in a mild form, there is an incomplete understanding of the course as an acute infection and its subsequent manifestations such as Long-COVID-19 or Post-COVID-19, PASC in the pediatric population, correlations with comorbidities and immunological changes. In mild COVID-19 in childhood, some authors explain the absence of population decreasing T and B lymphocytes. Regardless of the patient's condition, they can have the second phase, related to the exacerbation of inflammation in the heart tissue even if the viral infection was completely eliminated-post infectious myocarditis. Mechanism of myocardial dysfunction development in MIS-C are not fully understood. It is known that various immunocompetent cells, including both resident inflammatory cells of peripheral tissues (for example macrophages, dendritic cells, resident memory T-lymphocytes and so on) and also circulating in the peripheral blood immune cells play an important role in the immunopathogenesis of myocarditis. It is expected that hyperproduction of interferons and the enhanced cytokine response of T cells 1 and 2 types contribute to dysfunction of the myocardium. However, the role of Th1 in the pathogenesis of myocarditis remains highly controversial. At the same time, the clinical manifestations and mechanisms of damage, including the heart, both against the background and after COVID-19, in children differ from adults. Further studies are needed to evaluate whether transient or persistent cardiac complications are associated with long-term adverse cardiac events.}, }
@article {pmid36680082, year = {2022}, author = {Haque, A and Pant, AB}, title = {Long Covid: Untangling the Complex Syndrome and the Search for Therapeutics.}, journal = {Viruses}, volume = {15}, number = {1}, pages = {}, pmid = {36680082}, issn = {1999-4915}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, abstract = {Long Covid can affect anyone who has previously had acute COVID-19. The root causes of this syndrome are still unknown, and no effective therapeutics are available. This complex syndrome, with a wide array of symptoms, is still evolving. Given the dire situation, it is important to identify the causes of Long Covid and the changes occurring within the immune system of affected patients to figure out how to treat it. The immune system intersects with the persistent viral fragments and blood clots that are implicated in this syndrome; understanding how these complex systems interact may help in untangling the puzzling physiopathology of Long Covid and identifying mitigation measures to provide patients some relief. In this paper, we discuss evidence-based findings and formulate hypotheses on the mechanisms underlying Long Covid's physiopathology and propose potential therapeutic options.}, }
@article {pmid36690284, year = {2023}, author = {Ashton, RE and Philips, BE and Faghy, M}, title = {The acute and chronic implications of the COVID-19 virus on the cardiovascular system in adults: A systematic review.}, journal = {Progress in cardiovascular diseases}, volume = {76}, number = {}, pages = {31-37}, pmid = {36690284}, issn = {1873-1740}, mesh = {Humans ; Adult ; SARS-CoV-2 ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Heart ; *Cardiovascular Diseases/diagnosis/epidemiology ; }, abstract = {Despite coronavirus disease 2019 (COVID-19) primarily being identified as a respiratory illness, some patients who seemingly recovered from initial infection, developed chronic multi-system complications such as cardiovascular (CV), pulmonary and neurological issues leading to multiple organ injuries. However, to date, there is a dearth of understanding of the acute and chronic implications of a COVID-19 infection on the CV system in adults. A systematic review of the literature was conducted according to PRISMA guidelines and prospectively registered via Prospero (ID: CRD42022360444). The MEDLINE Ovid, Cochrane Library and PubMed databases were searched from inception to August 2022. The search strategy keywords and MeSH terms used included: 1) COVID; 2) coronavirus; 3) long COVID; 4) cardiovascular; and 5) cardiovascular disease. Reference lists of all relevant systematic reviews identified were searched for additional studies. A total of 11,332 records were retrieved from database searches, of which 310 records were duplicates. A further 9887 were eliminated following screening of titles and abstracts. After full-text screening of 1135 articles, 9 manuscripts were included for review. The evidence of CV implications post-COVID-19 infection is clear, and this must be addressed with appropriate management strategies that recognise the acute and chronic nature of cardiac injury in COVID-19 patients. Efficacious management strategies will be needed to address long standing issues and morbidity.}, }
@article {pmid36695893, year = {2023}, author = {Ludwig, B and Olbert, E and Trimmel, K and Seidel, S and Rommer, PS and Müller, C and Struhal, W and Berger, T}, title = {[Myalgic encephalomyelitis/chronic fatigue syndrome: an overview of current evidence].}, journal = {Der Nervenarzt}, volume = {94}, number = {8}, pages = {725-733}, pmid = {36695893}, issn = {1433-0407}, mesh = {Humans ; *Fatigue Syndrome, Chronic/diagnosis/therapy/epidemiology ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Comorbidity ; }, abstract = {Over the past 5 years both media and scientific interest has surged regarding the disorder myalgic encephalomyelitis and chronic fatigue syndrome (ME/CFS), not least because of the clinically similar manifestation in long COVID or post-COVID. In this review we discuss the process of clinical diagnosis and randomized controlled therapeutic studies on ME/CFS, and the similarities or differences to long COVID and post-COVID. So far, neither clear pathophysiologically causal nor therapeutic evidence-based results on ME/CFS have been identified in the many years of scientific research. Given the evident psychiatric comorbidity rates in patients with a diagnosis of ME/CFS, a psychosomatic etiology of this syndrome should be considered. Furthermore, a precise and reliable diagnostic classification based on stricter criteria would benefit both pathophysiological and therapeutic research.}, }
@article {pmid36700201, year = {2022}, author = {Linnhoff, S and Koehler, L and Haghikia, A and Zaehle, T}, title = {The therapeutic potential of non-invasive brain stimulation for the treatment of Long-COVID-related cognitive fatigue.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {935614}, pmid = {36700201}, issn = {1664-3224}, mesh = {Humans ; *Transcranial Direct Current Stimulation/methods ; Transcranial Magnetic Stimulation/methods ; Post-Acute COVID-19 Syndrome ; Quality of Life ; *COVID-19/complications/therapy ; Brain/physiology ; Cognition/physiology ; }, abstract = {Following an acute COVID-19 infection, a large number of patients experience persisting symptoms for more than four weeks, a condition now classified as Long-COVID syndrome. Interestingly, the likelihood and severity of Long-COVID symptoms do not appear to be related to the severity of the acute COVID-19 infection. Fatigue is amongst the most common and debilitating symptoms of Long-COVID. Other symptomes include dyspnoea, chest pain, olfactory disturbances, and brain fog. Fatigue is also frequently reported in many other neurological diseases, affecting a broad range of everyday activities. However, despite its clinical significance, limited progress has been made in understanding its causes and developing effective treatment options. Non-invasive brain stimulation (NIBS) methods offer the unique opportunity to modulate fatigue-related maladaptive neuronal activity. Recent data show promising results of NIBS applications over frontoparietal regions to reduce fatigue symptoms. In this current paper, we review recent data on Long-COVID and Long-COVID-related fatigue (LCOF), with a special focus on cognitive fatigue. We further present widely used NIBS methods, such as transcranial direct current stimulation, transcranial alternating current stimulation, and transcutaneous vagus nerve stimulation and propose their use as possible therapeutic strategies to alleviate individual pathomechanisms of LCOF. Since NIBS methods are safe and well-tolerated, they have the potential to enhance the quality of life in a broad group of patients.}, }
@article {pmid36700308, year = {2023}, author = {Liu, ST and Lin, SC and Chang, JP and Yang, KJ and Chu, CS and Yang, CC and Liang, CS and Sun, CF and Wang, SC and Satyanarayanan, SK and Su, KP}, title = {The Clinical Observation of Inflammation Theory for Depression: The Initiative of the Formosa Long COVID Multicenter Study (FOCuS).}, journal = {Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology}, volume = {21}, number = {1}, pages = {10-18}, pmid = {36700308}, issn = {1738-1088}, abstract = {There is growing evidence that the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with increased risks of psychiatric sequelae. Depression, anxiety, cognitive impairments, sleep disturbance, and fatigue during and after the acute phase of COVID-19 are prevalent, long-lasting, and exerting negative consequences on well-being and imposing a huge burden on healthcare systems and society. This current review presented timely updates of clinical research findings, particularly focusing on the pathogenetic mechanisms underlying the neuropsychiatric sequelae, and identified potential key targets for developing effective treatment strategies for long COVID. In addition, we introduced the Formosa Long COVID Multicenter Study (FOCuS), which aims to apply the inflammation theory to the pathogenesis and the psychosocial and nutrition treatments of post-COVID depression and anxiety.}, }
@article {pmid36703736, year = {2022}, author = {Jiang, L and An, X and Duan, Y and Lian, F and Jin, D and Zhang, Y and Yang, C and Zhang, Y and Kang, X and Sun, Y}, title = {The pathological mechanism of the COVID-19 convalescence and its treatment with traditional Chinese medicine.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {1054312}, pmid = {36703736}, issn = {1663-9812}, abstract = {The severe acute respiratory syndrome coronavirus - 2 (SARS - CoV - 2) was reported to cause the Wuhan outbreak of the corona virus disease 2019(COVID-19). To date, the COVID-19 has infected more than 600 million people gloabally. As a growing number of patients recover from acute infections and are discharged from hospitals, the proportion of patients in the recovery period is gradually increasing. Many of these individuals have been reported to experience multiple symptoms during the convalescence, such as fatigue, dyspnea and pain which are designated as "long-COVID", "post-COVID syndrome" or "recovery sequelae. We searched for recent articles published in PubMed on COVID-19 convalescence and found that the pathogenesis of COVID-19 convalescence is not yet well recognized. It may be associated with incomplete recovery of immune system, parenchymal organ damage (liver or lung), coagulation abnormalities, "second hit" caused by viral infection, and Phenomenon of Cell Senescence-Associated Secretory Phenotype (SASP). Some drugs and psychological factors of patients also play a non-negligible role in it. We also found that the effect of traditional Chinese medicine (TCM) is effective in the treatment of the COVID-19 recovery phase, which can not only relieve the corresponding symptoms, but also improve the indicators and pulmonary fibrosis. Bufei Huoxue Capsule, as the only drug explicitly mentioned for COVID-19 recovery period, can exert strong rehabilitative effects on physiological activity in patients recovering from COVID-19. In addition, in previous studies, traditional Chinese medicine has been confirmed to have the ability to resist cytokine storms, as well as improve coagulation and myocardial damage, which makes it have potential therapeutic advantages in targeting the hyperimmune response, coagulation abnormalities and myocardial damage existing in the recovery period. In conclusion, the clinical symptoms of patients convalescing from COVID-19 are complex, and its pathogenesis has not been elucidated. traditional Chinese medicine, as a traditional treatment, its specific action and mechanism need to be confirmed by more studies, so that it can play a better role.}, }
@article {pmid36708022, year = {2023}, author = {Yong, SJ and Halim, A and Halim, M and Liu, S and Aljeldah, M and Al Shammari, BR and Alwarthan, S and Alhajri, M and Alawfi, A and Alshengeti, A and Khamis, F and Alsalman, J and Alshukairi, AN and Abukhamis, NA and Almaghrabi, FS and Almuthree, SA and Alsulaiman, AM and Alshehail, BM and Alfaraj, AH and Alhawaj, SA and Mohapatra, RK and Rabaan, AA}, title = {Inflammatory and vascular biomarkers in post-COVID-19 syndrome: A systematic review and meta-analysis of over 20 biomarkers.}, journal = {Reviews in medical virology}, volume = {33}, number = {2}, pages = {e2424}, doi = {10.1002/rmv.2424}, pmid = {36708022}, issn = {1099-1654}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Biomarkers ; SARS-CoV-2 ; C-Reactive Protein ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 may inflict a post-viral condition known as post-COVID-19 syndrome (PCS) or long-COVID. Studies measuring levels of inflammatory and vascular biomarkers in blood, serum, or plasma of COVID-19 survivors with PCS versus non-PCS controls have produced mixed findings. Our review sought to meta-analyse those studies. A systematic literature search was performed across five databases until 25 June 2022, with an updated search on 1 November 2022. Data analyses were performed with Review Manager and R Studio statistical software. Twenty-four biomarkers from 23 studies were meta-analysed. Higher levels of C-reactive protein (Standardized mean difference (SMD) = 0.20; 95% CI: 0.02-0.39), D-dimer (SMD = 0.27; 95% CI: 0.09-0.46), lactate dehydrogenase (SMD = 0.30; 95% CI: 0.05-0.54), and leukocytes (SMD = 0.34; 95% CI: 0.02-0.66) were found in COVID-19 survivors with PCS than in those without PCS. After sensitivity analyses, lymphocytes (SMD = 0.30; 95% CI: 0.12-0.48) and interleukin-6 (SMD = 0.30; 95% CI: 0.12-0.49) were also significantly higher in PCS than non-PCS cases. No significant differences were noted in the remaining biomarkers investigated (e.g., ferritin, platelets, troponin, and fibrinogen). Subgroup analyses suggested the biomarker changes were mainly driven by PCS cases diagnosed via manifestation of organ abnormalities rather than symptomatic persistence, as well as PCS cases with duration of <6 than ≥6 months. In conclusion, our review pinpointed certain inflammatory and vascular biomarkers associated with PCS, which may shed light on potential new approaches to understanding, diagnosing, and treating PCS.}, }
@article {pmid36708608, year = {2023}, author = {Mullard, JCR and Kawalek, J and Parkin, A and Rayner, C and Mir, G and Sivan, M and Greenhalgh, T}, title = {Towards evidence-based and inclusive models of peer support for long covid: A hermeneutic systematic review.}, journal = {Social science &amp; medicine (1982)}, volume = {320}, number = {}, pages = {115669}, pmid = {36708608}, issn = {1873-5347}, support = {COV-LT2-0016/DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Hermeneutics ; Delivery of Health Care ; Peer Group ; }, abstract = {Since the first wave of COVID-19 in March 2020 the number of people living with post-COVID syndrome has risen rapidly at global pace, however, questions still remain as to whether there is a hidden cohort of sufferers not accessing mainstream clinics. This group are likely to be constituted by already marginalised people at the sharp end of existing health inequalities and not accessing formal clinics. The challenge of supporting such patients includes the question of how best to organise and facilitate different forms of support. As such, we aim to examine whether peer support is a potential option for hidden or hardly reached populations of long COVID sufferers with a specific focus on the UK, though not exclusively. Through a systematic hermeneutic literature review of peer support in other conditions (57 papers), we evaluate the global potential of peer support for the ongoing needs of people living with long COVID. Through our analysis, we highlight three key peer support perspectives in healthcare reflecting particular theoretical perspectives, goals, and understandings of what is 'good health', we call these: biomedical (disease control/management), relational (intersubjective mutual support) and socio-political (advocacy, campaigning &amp; social context). Additionally, we identify three broad models for delivering peer support: service-led, community-based and social media. Attention to power relations, social and cultural capital, and a co-design approach are key when developing peer support services for disadvantaged and underserved groups. Models from other long-term conditions suggest that peer support for long COVID can and should go beyond biomedical goals and harness the power of relational support and collective advocacy. This may be particularly important when seeking to reduce health inequalities and improve access for a potentially hidden cohort of sufferers.}, }
@article {pmid36709083, year = {2023}, author = {Mantovani, A and Rescigno, M and Forni, G and Tognon, F and Putoto, G and Ictho, J and Lochoro, P}, title = {COVID-19 vaccines and a perspective on Africa.}, journal = {Trends in immunology}, volume = {44}, number = {3}, pages = {172-187}, pmid = {36709083}, issn = {1471-4981}, mesh = {Humans ; COVID-19 Vaccines ; *COVID-19 ; Pandemics/prevention &amp; control ; *Vaccines ; Immunity, Innate ; Vaccination ; }, abstract = {Vaccines have dramatically changed the COVID-19 pandemic. Over 30 vaccines that were developed on four main platforms are currently being used globally, but a deep dissection of the immunological mechanisms by which they operate is limited to only a few of them. Here, we review the evidence describing specific aspects of the modes of action of COVID-19 vaccines; these include innate immunity, trained innate immunity, and mucosal responses. We also discuss the use of COVID-19 vaccines in the African continent which is ridden with inequality in its access to vaccines and vaccine-related immunological research. We argue that strengthening immunology research in Africa should inform on fundamental aspects of vaccination, including the relevance of genetics, trained innate immunity, and microbiome diversity.}, }
@article {pmid36719069, year = {2023}, author = {Teodoro, T and Chen, J and Gelauff, J and Edwards, MJ}, title = {Functional neurological disorder in people with long COVID: A systematic review.}, journal = {European journal of neurology}, volume = {30}, number = {5}, pages = {1505-1514}, doi = {10.1111/ene.15721}, pmid = {36719069}, issn = {1468-1331}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; *Conversion Disorder ; Anosmia ; Fatigue/etiology ; }, abstract = {BACKGROUND AND PURPOSE: Acute health events, including infections, can trigger the onset of functional neurological disorder (FND). It was hypothesized that a proportion of people with long COVID might be experiencing functional symptoms.<br><br>METHODS: A systematic review of studies containing original data on long COVID was performed. The frequency and characteristics of neurological symptoms were reviewed, looking for positive evidence suggesting an underlying functional disorder and the hypothesized causes of long COVID.<br><br>RESULTS: In all, 102 studies were included in our narrative synthesis. The most consistently reported neurological symptoms were cognitive difficulties, headaches, pain, dizziness, fatigue, sleep-related symptoms and ageusia/anosmia. Overall, no evidence was found that any authors had systematically looked for positive features of FND. An exception was three studies describing temporal inconsistency. In general, the neurological symptoms were insufficiently characterized to support or refute a diagnosis of FND. Moreover, only 13 studies specifically focused on long COVID after mild infection, where the impact of confounders from the general effects of severe illness would be mitigated. Only one study hypothesized that some people with long COVID might have a functional disorder, and another eight studies a chronic-fatigue-syndrome-like response.<br><br>DISCUSSION: Neurological symptoms are prevalent in long COVID, but poorly characterized. The similarities between some manifestations of long COVID and functional disorders triggered by acute illnesses are striking. Unfortunately, the current literature is plagued by confounders, including the mixing of patients with initial mild infection with those with severe acute medical complications. The hypothesis that long COVID might in part correspond to a functional disorder remains untested.}, }
@article {pmid36727514, year = {2023}, author = {Gerlach, J and Baig, AM and Fabrowski, M and Viduto, V}, title = {The immune paradox of SARS-CoV-2: Lymphocytopenia and autoimmunity evoking features in COVID-19 and possible treatment modalities.}, journal = {Reviews in medical virology}, volume = {33}, number = {2}, pages = {e2423}, doi = {10.1002/rmv.2423}, pmid = {36727514}, issn = {1099-1654}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Autoimmunity ; *Lymphopenia ; }, abstract = {SARS-CoV-2 causes multiorgan damage to vital organs and tissue that are known to be due to a combination of tissue tropisms and cytokine-mediated damage that it can incite in COVID-19. The effects of SARS-Co-2 on the lymphocytes and therefore on the immune response have attracted attention recently in COVID-19 to understand its effects in causing a chronic state of ongoing infection with Long-COVID. The associated lymphopaenia and autoimmune disease state, which is an apparent paradox, needs to be researched to dissect possible mechanisms underlying this state. This paper attempts to unravel the aforesaid immune paradox effects of SARS-CoV-2 on the lymphocytes and discusses appropriate treatment modalities with antiviral drugs and nutraceuticals which could prove virucidal in SARS-CoV-2 seeding monocytes and lymphocytes in patients with COVID-19 and Long-COVID. Importantly it proposes a new in vitro treatment modality of immune regulating cells that can help patients fight the lymphopaenia associated with COVID-19 and Long-COVID.}, }
@article {pmid36728728, year = {2024}, author = {Krug, E and Geckeler, KC and Frishman, WH}, title = {Cardiovascular Manifestations of Long COVID: A Review.}, journal = {Cardiology in review}, volume = {32}, number = {5}, pages = {402-407}, doi = {10.1097/CRD.0000000000000520}, pmid = {36728728}, issn = {1538-4683}, mesh = {Humans ; *COVID-19/complications/epidemiology ; *Cardiovascular Diseases/etiology/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Risk Factors ; }, abstract = {The acute phase of severe acute respiratory syndrome coronavirus 2 [coronavirus disease (COVID)] infection has many well-documented cardiovascular manifestations, however, the long-term sequelae are less understood. In this focused review, we explore the risk factors, character, and rates of cardiovascular events in patients with Long COVID, which is defined as symptoms occurring more than 4 weeks following initial infection. Research has identified increased rates of cerebrovascular disease, dysrhythmias, ischemic and inflammatory heart disease, cardiopulmonary symptoms, and thrombotic events among those with Long COVID, though the risk rates and potential mechanisms behind each cardiovascular event vary. Finally, we discuss the current gaps in the literature as well as how COVID compares to other viral infections when it comes to causing long-term cardiovascular sequelae.}, }
@article {pmid36729627, year = {2023}, author = {Moscucci, F and Gallina, S and Bucciarelli, V and Aimo, A and Pelà, G and Cadeddu-Dessalvi, C and Nodari, S and Maffei, S and Meloni, A and Deidda, M and Mercuro, G and Pedrinelli, R and Penco, M and Sciomer, S and Mattioli, AV}, title = {Impact of COVID-19 on the cardiovascular health of women: a review by the Italian Society of Cardiology Working Group on 'gender cardiovascular diseases'.}, journal = {Journal of cardiovascular medicine (Hagerstown, Md.)}, volume = {24}, number = {Suppl 1}, pages = {e15-e23}, pmid = {36729627}, issn = {1558-2035}, mesh = {Female ; Humans ; Male ; *COVID-19/complications ; *Cardiovascular Diseases/diagnosis/epidemiology/complications ; SARS-CoV-2/metabolism ; Angiotensin-Converting Enzyme 2 ; Post-Acute COVID-19 Syndrome ; Quality of Life ; Peptidyl-Dipeptidase A/metabolism ; Renin-Angiotensin System/physiology ; *Cardiology ; }, abstract = {The coronavirus disease 19 (COVID-19), due to coronavirus 2 (SARS-CoV-2) infection, presents with an extremely heterogeneous spectrum of symptoms and signs. COVID-19 susceptibility and mortality show a significant sex imbalance, with men being more prone to infection and showing a higher rate of hospitalization and mortality than women. In particular, cardiovascular diseases (preexistent or arising upon infection) play a central role in COVID-19 outcomes, differently in men and women. This review will discuss the potential mechanisms accounting for sex/gender influence in vulnerability to COVID-19. Such variability can be ascribed to both sex-related biological factors and sex-related behavioural traits. Sex differences in cardiovascular disease and COVID-19 involve the endothelial dysfunction, the innate immune system and the renin-angiotensin system (RAS). Furthermore, the angiotensin-converting enzyme 2 (ACE2) is involved in disease pathogenesis in cardiovascular disease and COVID-19 and it shows hormone-dependent actions. The incidence of myocardial injury during COVID-19 is sex-dependent, predominantly in association with a greater degree of inflammation and coagulation disorders among men. Its pathogenesis is not fully elucidated, but the main theories foresee a direct role for the ACE2 receptor, the hyperimmune response and the RAS imbalance, which may also lead to isolated presentation of COVID-19-mediated myopericarditis. Moreover, the latest evidence on cardiovascular diseases and their relationship with COVID-19 during pregnancy will be discussed. Finally, authors will analyse the prevalence of the long-covid syndrome between the two sexes and its impact on the quality of life and cardiovascular health.}, }
@article {pmid36731604, year = {2023}, author = {Crosier, R and Kafil, TS and Paterson, DI}, title = {Imaging for Cardiovascular Complications of COVID-19: Cardiac Manifestations in Context.}, journal = {The Canadian journal of cardiology}, volume = {39}, number = {6}, pages = {779-792}, pmid = {36731604}, issn = {1916-7075}, support = {//CIHR/Canada ; }, mesh = {Humans ; *COVID-19/complications ; *COVID-19 Vaccines/adverse effects ; Heart ; *Myocarditis/diagnostic imaging/etiology ; Post-Acute COVID-19 Syndrome ; RNA, Messenger ; }, abstract = {After the first confirmed case in 2019, COVID-19 rapidly spread worldwide and overwhelmed the medical community. In the intervening time, we have learned about COVID-19's clinical manifestations and have developed effective therapies and preventative vaccines. Severe COVID-19 infection is associated with many cardiovascular disorders in the acute phase, and patients recovered from illness can also manifest long-term sequelae, including long COVID syndrome. Furthermore, severe acute respiratory syndrome-related coronavirus-2 messenger RNA (mRNA) vaccination can trigger rare cases of myopericarditis. We have gained significant knowledge of the acute and long-term cardiovascular complications of COVID-19- and mRNA vaccine-associated myocarditis through clinical and investigative studies using cardiac imaging. In this review, we describe how cardiovascular imaging can be used to understand the cardiovascular complications and cardiac injury associated with acute COVID-19 infection, review the imaging findings in patients recovered from illness, and discuss the role and limitations of cardiac imaging in COVID-19 mRNA vaccine-associated myocarditis.}, }
@article {pmid36736577, year = {2023}, author = {Banko, A and Miljanovic, D and Cirkovic, A}, title = {Systematic review with meta-analysis of active herpesvirus infections in patients with COVID-19: Old players on the new field.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {130}, number = {}, pages = {108-125}, pmid = {36736577}, issn = {1878-3511}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; Herpesvirus 4, Human ; Cytomegalovirus/genetics ; *COVID-19/epidemiology ; SARS-CoV-2 ; *Herpesviridae Infections/epidemiology ; *Herpesviridae/genetics ; Simplexvirus ; *Herpesvirus 6, Human/genetics ; }, abstract = {OBJECTIVES: Herpesviruses are ubiquitous and after primary infection they establish lifelong latency. The impairment of maintaining latency with short-term or long-term consequences could be triggered by other infection. Therefore, reactivation of herpesviruses in COVID-19 patients represents an emerging issue.<br><br>DESIGN AND METHODS: This study provided the first systematic review with meta-analysis of studies that evaluated active human herpesvirus (HHV) infection (defined as the presence of IgM antibodies or HHV-DNA) in COVID-19 patients and included 36 publications collected by searching through PubMed, SCOPUS, and Web of science until November 2022.<br><br>RESULTS: The prevalence of active EBV, HHV6, HSV, CMV, HSV1, and VZV infection in COVID-19 population was 41% (95% CI =27%-57%), 3% (95% CI=17%-54%), 28% (95% CI=1%-85%), 25% (95% CI=1%-63%), 22% (95% CI=10%-35%), and 18% (95% CI=4%-34%), respectively. There was a 6 times higher chance for active EBV infection in patients with severe COVID-19 than in non-COVID-19 controls (OR=6.45, 95% CI=1.09-38.13, p=0.040), although there was no difference in the prevalence of all evaluated active herpesvirus infections between COVID-19 patients and non-COVID-19 controls.<br><br>CONCLUSIONS: Future research of herpesvirus and SARS-CoV-2 coinfections must be prioritized to define: who, when and how to be tested, as well as how to effectively treat HHVs reactivations in acute and long COVID-19 patients.}, }
@article {pmid36744129, year = {2023}, author = {Lai, YJ and Liu, SH and Manachevakul, S and Lee, TA and Kuo, CT and Bello, D}, title = {Biomarkers in long COVID-19: A systematic review.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1085988}, pmid = {36744129}, issn = {2296-858X}, abstract = {PURPOSE: Long COVID, also known as post-acute sequelae of COVID-19, refers to the constellation of long-term symptoms experienced by people suffering persistent symptoms for one or more months after SARS-CoV-2 infection. Blood biomarkers can be altered in long COVID patients; however, biomarkers associated with long COVID symptoms and their roles in disease progression remain undetermined. This study aims to systematically evaluate blood biomarkers that may act as indicators or therapeutic targets for long COVID.<br><br>METHODS: A systematic literature review in PubMed, Embase, and CINAHL was performed on 18 August 2022. The search keywords long COVID-19 symptoms and biomarkers were used to filter out the eligible studies, which were then carefully evaluated.<br><br>RESULTS: Identified from 28 studies and representing six biological classifications, 113 biomarkers were significantly associated with long COVID: (1) Cytokine/Chemokine (38, 33.6%); (2) Biochemical markers (24, 21.2%); (3) Vascular markers (20, 17.7%); (4) Neurological markers (6, 5.3%); (5) Acute phase protein (5, 4.4%); and (6) Others (20, 17.7%). Compared with healthy control or recovered patients without long COVID symptoms, 79 biomarkers were increased, 29 were decreased, and 5 required further determination in the long COVID patients. Of these, up-regulated Interleukin 6, C-reactive protein, and tumor necrosis factor alpha might serve as the potential diagnostic biomarkers for long COVID. Moreover, long COVID patients with neurological symptoms exhibited higher levels of neurofilament light chain and glial fibrillary acidic protein whereas those with pulmonary symptoms exhibited a higher level of transforming growth factor beta.<br><br>CONCLUSION: Long COVID patients present elevated inflammatory biomarkers after initial infection. Our study found significant associations between specific biomarkers and long COVID symptoms. Further investigations are warranted to identify a core set of blood biomarkers that can be used to diagnose and manage long COVID patients in clinical practice.}, }
@article {pmid36750167, year = {2023}, author = {Barnes, HW and Demirdjian, S and Haddock, NL and Kaber, G and Martinez, HA and Nagy, N and Karmouty-Quintana, H and Bollyky, PL}, title = {Hyaluronan in the pathogenesis of acute and post-acute COVID-19 infection.}, journal = {Matrix biology : journal of the International Society for Matrix Biology}, volume = {116}, number = {}, pages = {49-66}, pmid = {36750167}, issn = {1569-1802}, support = {R01 DC019965/DC/NIDCD NIH HHS/United States ; R01 HL138510/HL/NHLBI NIH HHS/United States ; R01 HL148184/HL/NHLBI NIH HHS/United States ; R01 HL157100/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Hyaluronic Acid ; Inflammation/pathology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged as the cause of a global pandemic. Infection with SARS-CoV-2 can result in COVID-19 with both acute and chronic disease manifestations that continue to impact many patients long after the resolution of viral replication. There is therefore great interest in understanding the host factors that contribute to COVID-19 pathogenesis. In this review, we address the role of hyaluronan (HA), an extracellular matrix polymer with roles in inflammation and cellular metabolism, in COVID-19 and critically evaluate the hypothesis that HA promotes COVID-19 pathogenesis. We first provide a brief overview of COVID-19 infection. Then we briefly summarize the known roles of HA in airway inflammation and immunity. We then address what is known about HA and the pathogenesis of COVID-19 acute respiratory distress syndrome (COVID-19 ARDS). Next, we examine potential roles for HA in post-acute SARS-CoV-2 infection (PASC), also known as "long COVID" as well as in COVID-associated fibrosis. Finally, we discuss the potential therapeutics that target HA as a means to treat COVID-19, including the repurposed drug hymecromone (4-methylumbelliferone). We conclude that HA is a promising potential therapeutic target for the treatment of COVID-19.}, }
@article {pmid36754119, year = {2023}, author = {Parhizgar, P and Yazdankhah, N and Rzepka, AM and Chung, KYC and Ali, I and Lai Fat Fur, R and Russell, V and Cheung, AM}, title = {Beyond Acute COVID-19: A Review of Long-term Cardiovascular Outcomes.}, journal = {The Canadian journal of cardiology}, volume = {39}, number = {6}, pages = {726-740}, pmid = {36754119}, issn = {1916-7075}, support = {VR4-172729//CIHR/Canada ; }, mesh = {Adult ; Humans ; *Myocarditis ; Post-Acute COVID-19 Syndrome ; Acute Disease ; *COVID-19/epidemiology ; Canada/epidemiology ; SARS-CoV-2 ; Disease Progression ; }, abstract = {Statistics Canada estimated that approximately 1.4 million Canadians suffer from long COVID. Although cardiovascular changes during acute SARS-CoV-2 infection are well documented, long-term cardiovascular sequelae are less understood. In this review, we sought to characterize adult cardiovascular outcomes in the months after acute COVID-19 illness. In our search we identified reports of outcomes including cardiac dysautonomia, myocarditis, ischemic injuries, and ventricular dysfunction. Even in patients without overt cardiac outcomes, subclinical changes have been observed. Cardiovascular sequelae after SARS-CoV-2 infection can stem from exacerbation of preexisting conditions, ongoing inflammation, or as a result of damage that occurred during acute infection. For example, myocardial fibrosis has been reported months after hospital admission for COVID-19 illness, and might be a consequence of myocarditis and myocardial injury during acute disease. In turn, myocardial fibrosis can contribute to further outcomes including dysrhythmias and heart failure. Severity of acute infection might be a risk factor for long-term cardiovascular consequences, however, cardiovascular changes have also been reported in young, healthy individuals who had asymptomatic or mild acute disease. Although evolving evidence suggests that previous SARS-CoV-2 infection might be a risk factor for cardiovascular disease, there is heterogeneity in existing evidence, and some studies are marred by measured and unmeasured confounders. Many investigations have also been limited by relatively short follow-up. Future studies should focus on longer term outcomes (beyond 1 year) and identifying the prevalence of outcomes in different populations on the basis of acute and long COVID disease severity.}, }
@article {pmid36769807, year = {2023}, author = {Chourasia, P and Goyal, L and Kansal, D and Roy, S and Singh, R and Mahata, I and Sheikh, AB and Shekhar, R}, title = {Risk of New-Onset Diabetes Mellitus as a Post-COVID-19 Condition and Possible Mechanisms: A Scoping Review.}, journal = {Journal of clinical medicine}, volume = {12}, number = {3}, pages = {}, pmid = {36769807}, issn = {2077-0383}, abstract = {Long-term effects of COVID-19 are becoming more apparent even as the severity of acute infection is decreasing due to vaccinations and treatment. In this scoping review, we explored the current literature for the relationship between COVID-19 infection and new-onset diabetes mellitus four weeks after acute infection. We systematically searched the peer-reviewed literature published in English between 1 January 2020 and 31 August 2022 to study the risk of new-onset diabetes mellitus post-COVID-19 infection. This scoping review yielded 11 articles based on our inclusion and exclusion criteria. Except for one, all studies suggested an increased risk of new-onset diabetes mellitus 4 weeks after acute infection. This risk appears most in the first six months after the acute COVID-19 infection and seems to increase in a graded fashion based on the severity of the initial COVID-19 infection. Our review suggests a possible association of new-onset diabetes mellitus 4 weeks after acute COVID-19 infection. Since the severity of COVID-19 infection is associated with the development of post-infectious diabetes, vaccination that reduces the severity of acute COVID-19 infection might help to reduce the risk of post-COVID-19 diabetes mellitus. More studies are needed to better understand and quantify the association of post-COVID-19 conditions with diabetes and the role of vaccination in influencing it.}, }
@article {pmid36773054, year = {2023}, author = {Ferrara, F and Zovi, A and Masi, M and Langella, R and Trama, U and Boccellino, M and Vitiello, A}, title = {Long COVID could become a widespread post-pandemic disease? A debate on the organs most affected.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {396}, number = {7}, pages = {1583-1589}, pmid = {36773054}, issn = {1432-1912}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; tau Proteins ; Pandemics ; SARS-CoV-2 ; Fatigue ; }, abstract = {Long COVID is an emerging problem in the current health care scenario. It is a syndrome with common symptoms of shortness of breath, fatigue, cognitive dysfunction, and other conditions that have a high impact on daily life. They are fluctuating or relapsing states that occur in patients with a history of SARS-CoV-2 infection for at least 2 months. They are usually conditions that at 3 months after onset cannot be explained by an alternative diagnosis. Currently very little is known about this syndrome. A thorough review of the literature highlights that the cause is attributable to deposits of tau protein. Massive phosphorylation of tau protein in response to SARS-CoV-2 infection occurred in brain samples from autopsies of people previously affected with COVID-19. The neurological disorders resulting from this clinical condition are termed tauopathies and can give different pathological symptoms depending on the involved anatomical region of the brain. Peripheral small-fiber neuropathies are also evident among patients with Long COVID leading to fatigue, which is the main symptom of this syndrome. Certainly more research studies could confirm the association between tau protein and Long COVID by defining the main role of tau protein as a biomarker for the diagnosis of this syndrome that is widespread in the post-pandemic period.}, }
@article {pmid36774332, year = {2023}, author = {Watanabe, A and Iwagami, M and Yasuhara, J and Takagi, H and Kuno, T}, title = {Protective effect of COVID-19 vaccination against long COVID syndrome: A systematic review and meta-analysis.}, journal = {Vaccine}, volume = {41}, number = {11}, pages = {1783-1790}, pmid = {36774332}, issn = {1873-2518}, mesh = {Humans ; Female ; Adult ; Middle Aged ; Aged ; *Post-Acute COVID-19 Syndrome ; *COVID-19/prevention &amp; control ; COVID-19 Vaccines ; Prospective Studies ; SARS-CoV-2 ; }, abstract = {BACKGROUND: The relationship between coronavirus disease 2019 (COVID-19) vaccination and long COVID has not been firmly established. We conducted a systematic review and meta-analysis to evaluate the association between COVID-19 vaccination and long COVID.<br><br>METHODS: PubMed and EMBASE databases were searched on September 2022 without language restrictions (CRD42022360399) to identify prospective trials and observational studies comparing patients with and without vaccination before severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. We also included studies reporting symptomatic changes of ongoing long COVID following vaccination among those with a history of SARS-CoV-2 infection. Odds ratios (ORs) for each outcome were synthesized using a random-effects model. Symptomatic changes after vaccination were synthesized by a one-group meta-analysis.<br><br>RESULTS: Six observational studies involving 536,291 unvaccinated and 84,603 vaccinated (before SARS-CoV-2 infection) patients (mean age, 41.2-66.6; female, 9.0-67.3%) and six observational studies involving 8,199 long COVID patients (mean age, 40.0 to 53.5; female, 22.2-85.9%) who received vaccination after SARS-CoV-2 infection were included. Two-dose vaccination was associated with a lower risk of long COVID compared to no vaccination (OR, 0.64; 95% confidence interval [CI], 0.45-0.92) and one-dose vaccination (OR, 0.60; 95% CI, 0.43-0.83). Two-dose vaccination compared to no vaccination was associated with a lower risk of persistent fatigue (OR, 0.62; 95% CI, 0.41-0.93) and pulmonary disorder (OR, 0.50; 95% CI, 0.47-0.52). Among those with ongoing long COVID symptoms, 54.4% (95% CI, 34.3-73.1%) did not report symptomatic changes following vaccination, while 20.3% (95% CI, 8.1-42.4%) experienced symptomatic improvement after two weeks to six months of COVID-19 vaccination.<br><br>CONCLUSIONS: COVID-19 vaccination before SARS-CoV-2 infection was associated with a lower risk of long COVID, while most of those with ongoing long COVID did not experience symptomatic changes following vaccination.}, }
@article {pmid36776887, year = {2023}, author = {Udoakang, AJ and Djomkam Zune, AL and Tapela, K and Nganyewo, NN and Olisaka, FN and Anyigba, CA and Tawiah-Eshun, S and Owusu, IA and Paemka, L and Awandare, GA and Quashie, PK}, title = {The COVID-19, tuberculosis and HIV/AIDS: Ménage à Trois.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1104828}, pmid = {36776887}, issn = {1664-3224}, support = {/WT_/Wellcome Trust/United Kingdom ; MR/P028071/1/MRC_/Medical Research Council/United Kingdom ; /CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Humans ; *Acquired Immunodeficiency Syndrome/epidemiology ; *COVID-19 ; HIV ; *Coinfection/epidemiology ; Pandemics ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Tuberculosis/diagnosis ; }, abstract = {In December 2019, a novel pneumonic condition, Coronavirus disease 2019 (COVID- 19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), broke out in China and spread globally. The presentation of COVID-19 is more severe in persons with underlying medical conditions such as Tuberculosis (TB), Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) and other pneumonic conditions. All three diseases are of global concern and can significantly affect the lungs with characteristic cytokine storm, immunosuppression, and respiratory failure. Co-infections of SARS-CoV-2 with HIV and Mycobacterium tuberculosis (Mtb) have been reported, which may influence their pathogenesis and disease progression. Pulmonary TB and HIV/AIDS patients could be more susceptible to SARS-CoV-2 infection leading to lethal synergy and disease severity. Therefore, the biological and epidemiological interactions of COVID-19, HIV/AIDS, and TB need to be understood holistically. While data is needed to predict the impact of the COVID-19 pandemic on these existing diseases, it is necessary to review the implications of the evolving COVID-19 management on HIV/AIDS and TB control, including therapy and funding. Also, the impact of long COVID on patients, who may have this co-infection. Thus, this review highlights the implications of COVID-19, HIV/AIDS, and TB co-infection compares disease mechanisms, addresses growing concerns, and suggests a direction for improved diagnosis and general management.}, }
@article {pmid36790825, year = {2023}, author = {Ostermann, PN and Schaal, H}, title = {Human brain organoids to explore SARS-CoV-2-induced effects on the central nervous system.}, journal = {Reviews in medical virology}, volume = {33}, number = {2}, pages = {e2430}, doi = {10.1002/rmv.2430}, pmid = {36790825}, issn = {1099-1654}, mesh = {Humans ; *SARS-CoV-2/physiology ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Central Nervous System ; Brain ; Organoids ; }, abstract = {Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). In less than three years, an estimated 600 million infections with SARS-CoV-2 occurred worldwide, resulting in a pandemic with tremendous impact especially on economic and health sectors. Initially considered a respiratory disease, COVID-19, along with its long-term sequelae (long-COVID) rather is a systemic disease. Neurological symptoms like dementia or encephalopathy were reported early during the pandemic as concomitants of the acute phase and as characteristics of long-COVID. An excessive inflammatory immune response is hypothesized to play a major role in this context. However, direct infection of neural cells may also contribute to the neurological aspects of (long)-COVID-19. To mainly explore such direct effects of SARS-CoV-2 on the central nervous system, human brain organoids provide a useful platform. Infecting these three-dimensional tissue cultures allows the study of viral neurotropism as well as of virus-induced effects on single cells or even the complex cellular network within the organoid. In this review, we summarize the experimental studies that used SARS-CoV-2-infected human brain organoids to unravel the complex nature of (long)-COVID-19-related neurological manifestations.}, }
@article {pmid36795701, year = {2023}, author = {Hossain, MM and Das, J and Rahman, F and Nesa, F and Hossain, P and Islam, AMK and Tasnim, S and Faizah, F and Mazumder, H and Purohit, N and Ramirez, G}, title = {Living with "long COVID": A systematic review and meta-synthesis of qualitative evidence.}, journal = {PloS one}, volume = {18}, number = {2}, pages = {e0281884}, pmid = {36795701}, issn = {1932-6203}, mesh = {Humans ; *COVID-19/epidemiology ; Qualitative Research ; Health Personnel/psychology ; Social Support ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: Long-term health consequences of coronavirus disease (COVID-19), also known as "long COVID," has become a global health concern. In this systematic review, we aimed to synthesize the qualitative evidence on lived experiences of people living with long COVID that may inform health policymaking and practice.<br><br>METHODS: We searched six major databases and additional sources and systematically retrieved relevant qualitative studies and conducted a meta-synthesis of key findings using the Joanna Briggs Institute (JBI) guidelines and reporting standards of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist.<br><br>RESULTS: We found 15 articles representing 12 studies out of 619 citations from different sources. These studies provided 133 findings that were categorized into 55 categories. All categories were aggregated to the following synthesized findings: living with complex physical health problems, psychosocial crises of long COVID, slow recovery and rehabilitation, digital resources and information management, changes in social support, and experiences with healthcare providers, services, and systems. Ten studies were from the UK, and others were from Denmark and Italy, which highlights a critical lack of evidence from other countries.<br><br>CONCLUSIONS: More representative research is needed to understand long COVID-related experiences from diverse communities and populations. The available evidence informs a high burden of biopsychosocial challenges among people with long COVID that would require multilevel interventions such as strengthening health and social policies and services, engaging patients and caregivers in making decisions and developing resources, and addressing health and socioeconomic disparities associated with long COVID through evidence-based practice.}, }
@article {pmid36795973, year = {2023}, author = {Karbalaeimahdi, M and Farajnia, S and Bargahi, N and Ghadiri-Moghaddam, F and Rasouli Jazi, HR and Bakhtiari, N and Ghasemali, S and Zarghami, N}, title = {The Role of Interferons in Long Covid Infection.}, journal = {Journal of interferon &amp; cytokine research : the official journal of the International Society for Interferon and Cytokine Research}, volume = {43}, number = {2}, pages = {65-76}, doi = {10.1089/jir.2022.0193}, pmid = {36795973}, issn = {1557-7465}, mesh = {Humans ; Interferons/therapeutic use ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Neurodegenerative Diseases ; Lung ; }, abstract = {Although the new generation of vaccines and anti-COVID-19 treatment regimens facilitated the management of acute COVID-19 infections, concerns about post-COVID-19 syndrome or Long Covid are rising. This issue can increase the incidence and morbidity of diseases such as diabetes, and cardiovascular, and lung infections, especially among patients suffering from neurodegenerative disease, cardiac arrhythmias, and ischemia. There are numerous risk factors that cause COVID-19 patients to experience post-COVID-19 syndrome. Three potential causes attributed to this disorder include immune dysregulation, viral persistence, and autoimmunity. Interferons (IFNs) are crucial in all aspects of post-COVID-19 syndrome etiology. In this review, we discuss the critical and double-edged role of IFNs in post-COVID-19 syndrome and how innovative biomedical approaches that target IFNs can reduce the occurrence of Long Covid infection.}, }
@article {pmid36799524, year = {2023}, author = {Czarnowska, A and Zajkowska, J and Kułakowska, A}, title = {Impact of SARS-CoV-2 on the nervous system.}, journal = {Neurologia i neurochirurgia polska}, volume = {57}, number = {1}, pages = {26-35}, doi = {10.5603/PJNNS.a2023.0009}, pmid = {36799524}, issn = {0028-3843}, mesh = {Humans ; SARS-CoV-2 ; *COVID-19/epidemiology ; Pandemics ; *Nervous System Diseases/epidemiology/etiology ; }, abstract = {INTRODUCTION: The ongoing COVID-19 pandemic is the largest global public health struggle. The spread of the novel coronavirus had resulted in almost 7 million deaths worldwide by January 2023.<br><br>STATE OF THE ART: The most common symptoms during the acute phase of COVID-19 are respiratory. However, many individuals present various neurological deficits at different stages of the infection. Furthermore, there are post-infectious complications that can be present within weeks after the initial symptoms. Both the central and peripheral nervous systems (CNS and PNS, respectively) can be affected. Many potential mechanisms and hypotheses regarding the neuropathology behind COVID-19 have been proposed.<br><br>CLINICAL IMPLICATIONS: The distribution of neurological symptoms during COVID-19 infection among studies differs greatly, which is mostly due to differing inclusion criteria. One of the most significant is incidence involving CNS circulation. In this review, we present basic information regarding the novel coronavirus, the possible routes along which the pathogen can reach the nervous system, neuropathology mechanisms, and neurological symptoms following COVID-19.<br><br>FUTURE DIRECTIONS: It seems that many factors, resulting both from the properties of the virus and from systemic responses to infection, play a role in developing neurological symptoms. The long-term effect of the virus on the nervous system is still unknown.}, }
@article {pmid36806080, year = {2023}, author = {van der Zalm, MM and Dona', D and Rabie, H}, title = {Pediatric coronavirus disease 2019 in Africa.}, journal = {Current opinion in pediatrics}, volume = {35}, number = {2}, pages = {176-183}, pmid = {36806080}, issn = {1531-698X}, support = {K43 TW011028/TW/FIC NIH HHS/United States ; }, mesh = {SARS-CoV-2 ; Africa/epidemiology ; *COVID-19/epidemiology/complications ; Humans ; Post-Acute COVID-19 Syndrome ; Infant ; Child ; Systemic Inflammatory Response Syndrome ; }, abstract = {PURPOSE OF REVIEW: Three years into the coronavirus disease 2019 (COVID-19) pandemic, data on pediatric COVID-19 from African settings is limited. Understanding the impact of the pandemic in this setting with a high burden of communicable and noncommunicable diseases is critical to implementing effective interventions in public health programs.<br><br>RECENT FINDINGS: More severe COVID-19 has been reported in African settings, with especially infants and children with underlying comorbidities at highest risk for more severe disease. Data on the role of tuberculosis and HIV remain sparse. Compared to better resourced settings more children with multisystem inflammatory disease (MISC) are younger than 5&#x200a;years and there is higher morbidity in all settings and increased mortality in some settings. Several reports suggest decreasing prevalence and severity of MIS-C disease with subsequent severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variant waves. Whether this decrease continues remains to be determined. Thus far, data on long-COVID in African settings is lacking and urgently needed considering the severity of the disease seen in the African population.<br><br>SUMMARY: Considering the differences seen in the severity of disease and short-term outcomes, there is an urgent need to establish long-term outcomes in children with COVID-19 and MIS-C in African children, including lung health assessment.}, }
@article {pmid36807444, year = {2023}, author = {Islam, MS and Wang, Z and Abdel-Mohsen, M and Chen, X and Montaner, LJ}, title = {Tissue injury and leukocyte changes in post-acute sequelae of SARS-CoV-2: review of 2833 post-acute patient outcomes per immune dysregulation and microbial translocation in long COVID.}, journal = {Journal of leukocyte biology}, volume = {113}, number = {3}, pages = {236-254}, doi = {10.1093/jleuko/qiac001}, pmid = {36807444}, issn = {1938-3673}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *COVID-19 ; Leukocytes ; Antigens, Viral ; Autoantibodies ; Disease Progression ; }, abstract = {A significant number of persons with coronavirus disease 2019 (COVID-19) experience persistent, recurrent, or new symptoms several months after the acute stage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This phenomenon, termed post-acute sequelae of SARS-CoV-2 (PASC) or long COVID, is associated with high viral titers during acute infection, a persistently hyperactivated immune system, tissue injury by NETosis-induced micro-thrombofibrosis (NETinjury), microbial translocation, complement deposition, fibrotic macrophages, the presence of autoantibodies, and lymphopenic immune environments. Here, we review the current literature on the immunological imbalances that occur during PASC. Specifically, we focus on data supporting common immunopathogenesis and tissue injury mechanisms shared across this highly heterogenous disorder, including NETosis, coagulopathy, and fibrosis. Mechanisms include changes in leukocyte subsets/functions, fibroblast activation, cytokine imbalances, lower cortisol, autoantibodies, co-pathogen reactivation, and residual immune activation driven by persistent viral antigens and/or microbial translocation. Taken together, we develop the premise that SARS-CoV-2 infection results in PASC as a consequence of acute and/or persistent single or multiple organ injury mediated by PASC determinants to include the degree of host responses (inflammation, NETinjury), residual viral antigen (persistent antigen), and exogenous factors (microbial translocation). Determinants of PASC may be amplified by comorbidities, age, and sex.}, }
@article {pmid36813418, year = {2023}, author = {Meringer, H and Wang, A and Mehandru, S}, title = {The Pathogenesis of Gastrointestinal, Hepatic, and Pancreatic Injury in Acute and Long Coronavirus Disease 2019 Infection.}, journal = {Gastroenterology clinics of North America}, volume = {52}, number = {1}, pages = {1-11}, pmid = {36813418}, issn = {1558-1942}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Gastrointestinal Tract ; Liver ; Dysbiosis ; *Gastrointestinal Diseases ; }, abstract = {The gastrointestinal (GI) tract is targeted by severe acute respiratory syndrome coronavirus-2. The present review examines GI involvement in patients with long coronavirus disease and discusses the underlying pathophysiological mechanisms that include viral persistence, mucosal and systemic immune dysregulation, microbial dysbiosis, insulin resistance, and metabolic abnormalities. Due to the complex and potentially multifactorial nature of this syndrome, rigorous clinical definitions and pathophysiology-based therapeutic approaches are warranted.}, }
@article {pmid36813419, year = {2023}, author = {Summa, KC and Hanauer, SB}, title = {COVID-19 and Inflammatory Bowel Disease.}, journal = {Gastroenterology clinics of North America}, volume = {52}, number = {1}, pages = {103-113}, pmid = {36813419}, issn = {1558-1942}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; COVID-19 Vaccines ; Pandemics ; *Inflammatory Bowel Diseases ; }, abstract = {The COVID-19 pandemic caused by the SARS-CoV-2 virus represents an unprecedented global health crisis. Safe and effective vaccines were rapidly developed and deployed that reduced COVID-19-related severe disease, hospitalization, and death. Patients with inflammatory bowel disease are not at increased risk of severe disease or death from COVID-19, and data from large cohorts of patients with inflammatory bowel disease demonstrate that COVID-19 vaccination is safe and effective. Ongoing research is clarifying the long-term impact of SARS-CoV-2 infection on patients with inflammatory bowel disease, long-term immune responses to COVID-19 vaccination, and optimal timing for repeated COVID-19 vaccination doses.}, }
@article {pmid36813422, year = {2023}, author = {Rizvi, A and Ziv, Y and Crawford, JM and Trindade, AJ}, title = {Gastrointestinal and Hepatobiliary Symptoms and Disorders with Long (Chronic) COVID Infection.}, journal = {Gastroenterology clinics of North America}, volume = {52}, number = {1}, pages = {139-156}, pmid = {36813422}, issn = {1558-1942}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Disease Progression ; }, abstract = {Long COVID is a novel syndrome characterizing new or persistent symptoms weeks after COVID-19 infection and involving multiple organ systems. This review summarizes the gastrointestinal and hepatobiliary sequelae of long COVID syndrome. It describes potential biomolecular mechanisms, prevalence, preventative measures, potential therapies, and health care and economic impact of long COVID syndrome, particularly of its gastrointestinal (GI) and hepatobiliary manifestations.}, }
@article {pmid36813431, year = {2023}, author = {Friedel, DM and Cappell, MS}, title = {Diarrhea and Coronavirus Disease 2019 Infection.}, journal = {Gastroenterology clinics of North America}, volume = {52}, number = {1}, pages = {59-75}, pmid = {36813431}, issn = {1558-1942}, mesh = {Humans ; *COVID-19/complications ; COVID-19 Vaccines ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Diarrhea ; *Gastrointestinal Diseases/diagnosis ; }, abstract = {The global coronavirus disease-2019 (COVID-19) pandemic has caused significant morbidity and mortality, thoroughly affected daily living, and caused severe economic disruption throughout the world. Pulmonary symptoms predominate and account for most of the associated morbidity and mortality. However, extrapulmonary manifestations are common in COVID-19 infections, including gastrointestinal (GI) symptoms, such as diarrhea. Diarrhea affects approximately 10% to 20% of COVID-19 patients. Diarrhea can occasionally be the presenting and only COVID-19 symptom. Diarrhea in COVID-19 subjects is usually acute but is occasionally chronic. It is typically mild-to-moderate and nonbloody. It is usually much less clinically important than pulmonary or potential thrombotic disorders. Occasionally the diarrhea can be profuse and life-threatening. The entry receptor for COVID-19, angiotensin converting enzyme-2, is found throughout the GI tract, especially in the stomach and small intestine, which provides a pathophysiologic basis for local GI infection. COVID-19 virus has been documented in feces and in GI mucosa. Treatment of COVID-19 infection, especially antibiotic therapy, is a common culprit of the diarrhea, but secondary infections including bacteria, especially Clostridioides difficile, are sometimes implicated. Workup for diarrhea in hospitalized patients usually includes routine chemistries; basic metabolic panel; and a complete hemogram; sometimes stool studies, possibly including calprotectin or lactoferrin; and occasionally abdominal CT scan or colonoscopy. Treatment for the diarrhea is intravenous fluid infusion and electrolyte supplementation as necessary, and symptomatic antidiarrheal therapy, including Loperamide, kaolin-pectin, or possible alternatives. Superinfection with C difficile should be treated expeditiously. Diarrhea is prominent in post-COVID-19 (long COVID-19), and is occasionally noted after COVID-19 vaccination. The spectrum of diarrhea in COVID-19 patients is presently reviewed including the pathophysiology, clinical presentation, evaluation, and treatment.}, }
@article {pmid36815864, year = {2023}, author = {Velichkovsky, BB and Razvaliaeva, AY and Khlebnikova, AA and Manukyan, PA and Kasatkin, VN and Barmin, AV}, title = {Systematic Review and Meta-Analysis of Clinically Relevant Executive Functions Tests Performance after COVID-19.}, journal = {Behavioural neurology}, volume = {2023}, number = {}, pages = {1094267}, pmid = {36815864}, issn = {1875-8584}, mesh = {Humans ; Executive Function ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Cognition ; *Cognition Disorders/psychology ; }, abstract = {It is widely known that COVID-19 has a number of prolonged effects on general health, wellbeing, and cognitive functioning. However, studies using differentiated performance measures of cognitive functions are still not widely spread making it hard to assess the exact functions that get impaired. Taking into account the similarities between post-COVID 'brain fog' and chemofog, we hypothesized that executive functions (EF) would be impaired. Literature search yielded six studies with 14 effect sizes of interest; pooled effect size was small to medium (d = -0.35). Combined with a narrative synthesis of six studies without a comparison group, these results show that EF get impaired after COVID-19; although, in most cases the impairment is transient and does not seem to be severe. These results specify the picture of 'brain fog' and may help to discover its mechanisms and ways of helping people with long COVID.}, }
@article {pmid36824451, year = {2023}, author = {Xiang, M and Wu, X and Jing, H and Novakovic, VA and Shi, J}, title = {The intersection of obesity and (long) COVID-19: Hypoxia, thrombotic inflammation, and vascular endothelial injury.}, journal = {Frontiers in cardiovascular medicine}, volume = {10}, number = {}, pages = {1062491}, pmid = {36824451}, issn = {2297-055X}, abstract = {The role of hypoxia, vascular endothelial injury, and thrombotic inflammation in worsening COVID-19 symptoms has been generally recognized. Damaged vascular endothelium plays a crucial role in forming in situ thrombosis, pulmonary dysfunction, and hypoxemia. Thrombotic inflammation can further aggravate local vascular endothelial injury and affect ventilation and blood flow ratio. According to the results of many studies, obesity is an independent risk factor for a variety of severe respiratory diseases and contributes to high mechanical ventilation rate, high mortality, and slow recovery in COVID-19 patients. This review will explore the mechanisms by which obesity may aggravate the acute phase of COVID-19 and delay long COVID recovery by affecting hypoxia, vascular endothelial injury, and thrombotic inflammation. A systematic search of PubMed database was conducted for papers published since January 2020, using the medical subject headings of "COVID-19" and "long COVID" combined with the following keywords: "obesity," "thrombosis," "endothelial injury," "inflammation," "hypoxia," "treatment," and "anticoagulation." In patients with obesity, the accumulation of central fat restricts the expansion of alveoli, exacerbating the pulmonary dysfunction caused by SARS-CoV-2 invasion, inflammatory damage, and lung edema. Abnormal fat secretion and immune impairment further aggravate the original tissue damage and inflammation diffusion. Obesity weakens baseline vascular endothelium function leading to an early injury and pre-thrombotic state after infection. Enhanced procoagulant activity and microthrombi promote early obstruction of the vascular. Obesity also prolongs the duration of symptoms and increases the risk of sequelae after hospital discharge. Persistent viral presence, long-term inflammation, microclots, and hypoxia may contribute to the development of persistent symptoms, suggesting that patients with obesity are uniquely susceptible to long COVID. Early interventions, including supplemental oxygen, comprehensive antithrombotic therapy, and anti-inflammatory drugs, show effectiveness in many studies in the prevention of serious hypoxia, thromboembolic events, and systemic inflammation, and are therefore recommended to reduce intensive care unit admission, mortality, and sequelae.}, }
@article {pmid36825730, year = {2023}, author = {Pakkir Maideen, NM and Hassan Jumale, A and Ramadan Barakat, I and Khalifa Albasti, A}, title = {Potential of Black Seeds (Nigella sativa) in the Management of Long COVID or Post-acute Sequelae of COVID-19 (PASC) and Persistent COVID-19 Symptoms - An Insight.}, journal = {Infectious disorders drug targets}, volume = {23}, number = {4}, pages = {e230223213955}, doi = {10.2174/1871526523666230223112045}, pmid = {36825730}, issn = {2212-3989}, mesh = {Animals ; Humans ; Plant Extracts/pharmacology ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; *Nigella sativa ; Seeds ; }, abstract = {BACKGROUND: Some individuals may experience symptoms persisting for many months after the recovery from COVID-19 and patients with Long COVID are managed mainly with symptomatic treatment and supportive care.<br><br>OBJECTIVE: This review article focuses on the beneficial effects of black seeds (Nigella sativa) in the management of long COVID and persistent COVID symptoms.<br><br>METHODS: The literature was searched in databases such as LitCOVID, Web of Science, Google Scholar, bioRxiv, medRxiv, Science Direct, EBSCO, Scopus, Embase, and reference lists to identify studies, which evaluated various effects of black seeds (N. sativa) related to signs and symptoms of long COVID.<br><br>RESULTS: Black seeds (N. sativa) have shown potential anti-COVID, antiviral, anti-inflammatory, antioxidant, immunomodulatory, antihypertensive, anti-obesity, antidiabetic, antihyperlipidemic, and antiasthmatic properties in various clinical, animal, in vitro, in vivo, and in silico studies, which would help the patients recovered from COVID to mitigate Long COVID complications.<br><br>CONCLUSION: Patients experiencing Long COVID may use black seeds (N. sativa) as adjunctive therapy in combination with symptomatic treatment and supportive care to prevent further deterioration and hospitalization. The safety and efficacy of N. sativa in patients with Long-COVID would further be established by future randomized controlled clinical trials.}, }
@article {pmid36829952, year = {2023}, author = {Akanchise, T and Angelova, A}, title = {Potential of Nano-Antioxidants and Nanomedicine for Recovery from Neurological Disorders Linked to Long COVID Syndrome.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, pmid = {36829952}, issn = {2076-3921}, abstract = {Long-term neurological complications, persisting in patients who cannot fully recover several months after severe SARS-CoV-2 coronavirus infection, are referred to as neurological sequelae of the long COVID syndrome. Among the numerous clinical post-acute COVID-19 symptoms, neurological and psychiatric manifestations comprise prolonged fatigue, "brain fog", memory deficits, headache, ageusia, anosmia, myalgias, cognitive impairments, anxiety, and depression lasting several months. Considering that neurons are highly vulnerable to inflammatory and oxidative stress damages following the overproduction of reactive oxygen species (ROS), neuroinflammation and oxidative stress have been suggested to dominate the pathophysiological mechanisms of the long COVID syndrome. It is emphasized that mitochondrial dysfunction and oxidative stress damages are crucial for the pathogenesis of neurodegenerative disorders. Importantly, antioxidant therapies have the potential to slow down and prevent disease progression. However, many antioxidant compounds display low bioavailability, instability, and transport to targeted tissues, limiting their clinical applications. Various nanocarrier types, e.g., liposomes, cubosomes, solid lipid nanoparticles, micelles, dendrimers, carbon-based nanostructures, nanoceria, and other inorganic nanoparticles, can be employed to enhance antioxidant bioavailability. Here, we highlight the potential of phytochemical antioxidants and other neuroprotective agents (curcumin, quercetin, vitamins C, E and D, melatonin, rosmarinic acid, N-acetylcysteine, and Ginkgo Biloba derivatives) in therapeutic strategies for neuroregeneration. A particular focus is given to the beneficial role of nanoparticle-mediated drug-delivery systems in addressing the challenges of antioxidants for managing and preventing neurological disorders as factors of long COVID sequelae.}, }
@article {pmid36830790, year = {2023}, author = {Tian, J and Kaufman, DL}, title = {The GABA and GABA-Receptor System in Inflammation, Anti-Tumor Immune Responses, and COVID-19.}, journal = {Biomedicines}, volume = {11}, number = {2}, pages = {}, pmid = {36830790}, issn = {2227-9059}, support = {UL1 TR001881/TR/NCATS NIH HHS/United States ; }, abstract = {GABA and GABAA-receptors (GABAA-Rs) play major roles in neurodevelopment and neurotransmission in the central nervous system (CNS). There has been a growing appreciation that GABAA-Rs are also present on most immune cells. Studies in the fields of autoimmune disease, cancer, parasitology, and virology have observed that GABA-R ligands have anti-inflammatory actions on T cells and antigen-presenting cells (APCs), while also enhancing regulatory T cell (Treg) responses and shifting APCs toward anti-inflammatory phenotypes. These actions have enabled GABAA-R ligands to ameliorate autoimmune diseases, such as type 1 diabetes (T1D), multiple sclerosis (MS), and rheumatoid arthritis, as well as type 2 diabetes (T2D)-associated inflammation in preclinical models. Conversely, antagonism of GABAA-R activity promotes the pro-inflammatory responses of T cells and APCs, enhancing anti-tumor responses and reducing tumor burden in models of solid tumors. Lung epithelial cells also express GABA-Rs, whose activation helps maintain fluid homeostasis and promote recovery from injury. The ability of GABAA-R agonists to limit both excessive immune responses and lung epithelial cell injury may underlie recent findings that GABAA-R agonists reduce the severity of disease in mice infected with highly lethal coronaviruses (SARS-CoV-2 and MHV-1). These observations suggest that GABAA-R agonists may provide off-the-shelf therapies for COVID-19 caused by new SARS-CoV-2 variants, as well as novel beta-coronaviruses, which evade vaccine-induced immune responses and antiviral medications. We review these findings and further advance the notions that (1) immune cells possess GABAA-Rs to limit inflammation in the CNS, and (2) this natural "braking system" on inflammatory responses may be pharmacologically engaged to slow the progression of autoimmune diseases, reduce the severity of COVID-19, and perhaps limit neuroinflammation associated with long COVID.}, }
@article {pmid36830913, year = {2023}, author = {Ong, IZ and Kolson, DL and Schindler, MK}, title = {Mechanisms, Effects, and Management of Neurological Complications of Post-Acute Sequelae of COVID-19 (NC-PASC).}, journal = {Biomedicines}, volume = {11}, number = {2}, pages = {}, pmid = {36830913}, issn = {2227-9059}, abstract = {With a growing number of patients entering the recovery phase following infection with SARS-CoV-2, understanding the long-term neurological consequences of the disease is important to their care. The neurological complications of post-acute sequelae of SARS-CoV-2 infection (NC-PASC) represent a myriad of symptoms including headaches, brain fog, numbness/tingling, and other neurological symptoms that many people report long after their acute infection has resolved. Emerging reports are being published concerning COVID-19 and its chronic effects, yet limited knowledge of disease mechanisms has challenged therapeutic efforts. To address these issues, we review broadly the literature spanning 2020-2022 concerning the proposed mechanisms underlying NC-PASC, outline the long-term neurological sequelae associated with COVID-19, and discuss potential clinical interventions.}, }
@article {pmid36834176, year = {2023}, author = {Chandan, JS and Brown, KR and Simms-Williams, N and Bashir, NZ and Camaradou, J and Heining, D and Turner, GM and Rivera, SC and Hotham, R and Minhas, S and Nirantharakumar, K and Sivan, M and Khunti, K and Raindi, D and Marwaha, S and Hughes, SE and McMullan, C and Marshall, T and Calvert, MJ and Haroon, S and Aiyegbusi, OL and , }, title = {Non-Pharmacological Therapies for Post-Viral Syndromes, Including Long COVID: A Systematic Review.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {4}, pages = {}, pmid = {36834176}, issn = {1660-4601}, support = {MC_PC_20050/MRC_/Medical Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; *Virus Diseases ; Mental Health ; }, abstract = {BACKGROUND: Post-viral syndromes (PVS), including Long COVID, are symptoms sustained from weeks to years following an acute viral infection. Non-pharmacological treatments for these symptoms are poorly understood. This review summarises the evidence for the effectiveness of non-pharmacological treatments for PVS.<br><br>METHODS: We conducted a systematic review to evaluate the effectiveness of non-pharmacological interventions for PVS, as compared to either standard care, alternative non-pharmacological therapy, or placebo. The outcomes of interest were changes in symptoms, exercise capacity, quality of life (including mental health and wellbeing), and work capability. We searched five databases (Embase, MEDLINE, PsycINFO, CINAHL, MedRxiv) for randomised controlled trials (RCTs) published between 1 January 2001 to 29 October 2021. The relevant outcome data were extracted, the study quality was appraised using the Cochrane risk-of-bias tool, and the findings were synthesised narratively.<br><br>FINDINGS: Overall, five studies of five different interventions (Pilates, music therapy, telerehabilitation, resistance exercise, neuromodulation) met the inclusion criteria. Aside from music-based intervention, all other selected interventions demonstrated some support in the management of PVS in some patients.<br><br>INTERPRETATION: In this study, we observed a lack of robust evidence evaluating the non-pharmacological treatments for PVS, including Long COVID. Considering the prevalence of prolonged symptoms following acute viral infections, there is an urgent need for clinical trials evaluating the effectiveness and cost-effectiveness of non-pharmacological treatments for patients with PVS.<br><br>REGISTRATION: The study protocol was registered with PROSPERO [CRD42021282074] in October 2021 and published in BMJ Open in 2022.}, }
@article {pmid36834984, year = {2023}, author = {Reyes-Long, S and Cortés-Altamirano, JL and Bandala, C and Avendaño-Ortiz, K and Bonilla-Jaime, H and Bueno-Nava, A and Ávila-Luna, A and Sánchez-Aparicio, P and Clavijo-Cornejo, D and Dotor-LLerena, AL and Cabrera-Ruiz, E and Alfaro-Rodríguez, A}, title = {Role of the MicroRNAs in the Pathogenic Mechanism of Painful Symptoms in Long COVID: Systematic Review.}, journal = {International journal of molecular sciences}, volume = {24}, number = {4}, pages = {}, pmid = {36834984}, issn = {1422-0067}, mesh = {Humans ; *Chronic Pain/genetics ; *COVID-19/complications/genetics ; *MicroRNAs/genetics ; *Post-Acute COVID-19 Syndrome/genetics ; }, abstract = {The ongoing pandemic of COVID-19 has caused more than 6.7 million tragic deaths, plus, a large percentage of people who survived it present a myriad of chronic symptoms that last for at least 6 months; this has been named as long COVID. Some of the most prevalent are painful symptoms like headache, joint pain, migraine, neuropathic-like pain, fatigue and myalgia. MicroRNAs are small non-coding RNAs that regulate genes, and their involvement in several pathologies has been extensively shown. A deregulation of miRNAs has been observed in patients with COVID-19. The objective of the present systematic review was to show the prevalence of chronic pain-like symptoms of patients with long COVID and based on the expression of miRNAs in patients with COVID-19, and to present a proposal on how they may be involved in the pathogenic mechanisms of chronic pain-like symptoms. A systematic review was carried out in online databases for original articles published between March 2020 to April 2022; the systematic review followed the PRISMA guidelines, and it was registered in PROSPERO with registration number CRD42022318992. A total of 22 articles were included for the evaluation of miRNAs and 20 regarding long COVID; the overall prevalence of pain-like symptoms was around 10 to 87%, plus, the miRNAs that were commonly up and downregulated were miR-21-5p, miR-29a,b,c-3p miR-92a,b-3p, miR-92b-5p, miR-126-3p, miR-150-5p, miR-155-5p, miR-200a, c-3p, miR-320a,b,c,d,e-3p, and miR-451a. The molecular pathways that we hypothesized to be modulated by these miRNAs are the IL-6/STAT3 proinflammatory axis and the compromise of the blood-nerve barrier; these two mechanisms could be associated with the prevalence of fatigue and chronic pain in the long COVID population, plus they could be novel pharmacological targets in order to reduce and prevent these symptoms.}, }
@article {pmid36835589, year = {2023}, author = {Bhatia-Dey, N and Csoka, AB and Heinbockel, T}, title = {Chemosensory Ability and Sensitivity in Health and Disease: Epigenetic Regulation and COVID-19.}, journal = {International journal of molecular sciences}, volume = {24}, number = {4}, pages = {}, pmid = {36835589}, issn = {1422-0067}, support = {P30 AI117970/AI/NIAID NIH HHS/United States ; NSF IOS-1355034//National Science Foundation/ ; n/a//Howard University College of Medicine/ ; P30AI117970/NH/NIH HHS/United States ; }, mesh = {Animals ; Humans ; *COVID-19/complications ; *Olfaction Disorders ; Post-Acute COVID-19 Syndrome ; Pandemics ; Epigenesis, Genetic ; }, abstract = {Throughout the animal kingdom, our two chemical senses, olfaction and gustation, are defined by two primary factors: genomic architecture of the organisms and their living environment. During the past three years of the global COVID-19 pandemic, these two sensory modalities have drawn much attention at the basic science and clinical levels because of the strong association of olfactory and gustatory dysfunction with viral infection. Loss of our sense of smell alone, or together with a loss of taste, has emerged as a reliable indicator of COVID-19 infection. Previously, similar dysfunctions have been detected in a large cohort of patients with chronic conditions. The research focus remains on understanding the persistence of olfactory and gustatory disturbances in the post-infection phase, especially in cases with long-term effect of infection (long COVID). Also, both sensory modalities show consistent age-related decline in studies aimed to understand the pathology of neurodegenerative conditions. Some studies using classical model organisms show an impact on neural structure and behavior in offspring as an outcome of parental olfactory experience. The methylation status of specific odorant receptors, activated in parents, is passed on to the offspring. Furthermore, experimental evidence indicates an inverse correlation of gustatory and olfactory abilities with obesity. Such diverse lines of evidence emerging from basic and clinical research studies indicate a complex interplay of genetic factors, evolutionary forces, and epigenetic alterations. Environmental factors that regulate gustation and olfaction could induce epigenetic modulation. However, in turn, such modulation leads to variable effects depending on genetic makeup and physiological status. Therefore, a layered regulatory hierarchy remains active and is passed on to multiple generations. In the present review, we attempt to understand the experimental evidence that indicates variable regulatory mechanisms through multilayered and cross-reacting pathways. Our analytical approach will add to enhancement of prevailing therapeutic interventions and bring to the forefront the significance of chemosensory modalities for the evaluation and maintenance of long-term health.}, }
@article {pmid36836515, year = {2023}, author = {Bazdar, S and Kwee, AKAL and Houweling, L and de Wit-van Wijck, Y and Mohamed Hoesein, FAA and Downward, GS and Nossent, EJ and Maitland-van der Zee, AH and , }, title = {A Systematic Review of Chest Imaging Findings in Long COVID Patients.}, journal = {Journal of personalized medicine}, volume = {13}, number = {2}, pages = {}, pmid = {36836515}, issn = {2075-4426}, support = {//Health Holland/ ; //Top Sector Life Sciences &amp; Health (LSHM20104; LSHM20068)/ ; //Novartis (Netherlands)/ ; }, abstract = {Long COVID is the persistence of one or more COVID-19 symptoms after the initial viral infection, and there is evidence supporting its association with lung damage. In this systematic review, we provide an overview of lung imaging and its findings in long COVID patients. A PubMed search was performed on 29 September 2021, for English language studies in which lung imaging was performed in adults suffering from long COVID. Two independent researchers extracted the data. Our search identified 3130 articles, of which 31, representing the imaging findings of 342 long COVID patients, were retained. The most common imaging modality used was computed tomography (CT) (N = 249). A total of 29 different imaging findings were reported, which were broadly categorized into interstitial (fibrotic), pleural, airway, and other parenchymal abnormalities. A direct comparison between cases, in terms of residual lesions, was available for 148 patients, of whom 66 (44.6%) had normal CT findings. Although respiratory symptoms belong to the most common symptoms in long COVID patients, this is not necessarily linked to radiologically detectable lung damage. Therefore, more research is needed on the role of the various types of lung (and other organ) damage which may or may not occur in long COVID.}, }
@article {pmid36836568, year = {2023}, author = {Conti, V and Corbi, G and Sabbatino, F and De Pascale, D and Sellitto, C and Stefanelli, B and Bertini, N and De Simone, M and Liguori, L and Di Paola, I and De Bernardo, M and Tesse, A and Rosa, N and Pagliano, P and Filippelli, A}, title = {Long COVID: Clinical Framing, Biomarkers, and Therapeutic Approaches.}, journal = {Journal of personalized medicine}, volume = {13}, number = {2}, pages = {}, pmid = {36836568}, issn = {2075-4426}, abstract = {More than two years after the onset of the COVID-19 pandemic, healthcare providers are facing an emergency within an emergency, the so-called long COVID or post-COVID-19 syndrome (PCS). Patients diagnosed with PCS develop an extended range of persistent symptoms and/or complications from COVID-19. The risk factors and clinical manifestations are many and various. Advanced age, sex/gender, and pre-existing conditions certainly influence the pathogenesis and course of this syndrome. However, the absence of precise diagnostic and prognostic biomarkers may further complicate the clinical management of patients. This review aimed to summarize recent evidence on the factors influencing PCS, possible biomarkers, and therapeutic approaches. Older patients recovered approximately one month earlier than younger patients, with higher rates of symptoms. Fatigue during the acute phase of COVID-19 appears to be an important risk factor for symptom persistence. Female sex, older age, and active smoking are associated with a higher risk of developing PCS. The incidence of cognitive decline and the risk of death are higher in PCS patients than in controls. Complementary and alternative medicine appears to be associated with improvement in symptoms, particularly fatigue. The heterogeneous nature of post-COVID symptoms and the complexity of patients with PCS, who are often polytreated due to concomitant clinical conditions, suggest a holistic and integrated approach to provide useful guidance for the treatment and overall management of long COVID.}, }
@article {pmid36837463, year = {2023}, author = {Sakurada, Y and Otsuka, Y and Tokumasu, K and Sunada, N and Honda, H and Nakano, Y and Matsuda, Y and Hasegawa, T and Ochi, K and Hagiya, H and Ueda, K and Kataoka, H and Otsuka, F}, title = {Trends in Long COVID Symptoms in Japanese Teenage Patients.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {59}, number = {2}, pages = {}, pmid = {36837463}, issn = {1648-9144}, support = {JP22K20927//Japan Society for the Promotion of Science/ ; JP22K20927//This work was supported by JSPS KAKENHI (Y.O.) and Ryobi Teien Memory Foundation (2022) in Japan (F.O.)./ ; }, mesh = {Adult ; Child ; Adolescent ; Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; East Asian People ; SARS-CoV-2 ; Fatigue ; Headache ; Observational Studies as Topic ; }, abstract = {Background: Since the start of the global pandemic of coronavirus disease 2019 (COVID-19), not only adults but also many children have suffered from it. However, the clinical characteristics of long COVID in children remain unclear. Methods: In this retrospective observational study conducted in a single facility, we reviewed the medical records of all long COVID patients who visited Okayama University Hospital from February 2021 to October 2022, and we compared the clinical characteristics of long COVID in teenagers (11 to 18 years of age) with those in adults. Results: Data for 452 long COVID patients including 54 teenagers (11.9%) were analyzed. Fatigue was the most frequent symptom in teenagers (55.6% of the patients) and also in adults. On the other hand, the percentage of teenagers who complained of headache, which was the second most frequent complaint, was significantly higher than the percentage of adults (35.2% vs. 21.9%, p < 0.05). A comparison of the frequencies of symptoms depending on the viral variant showed that fatigue and headache were predominant symptoms in the Omicron variant phase. Of the 50 teenagers who were enrolled in schools, 28 (56.0%) could not attend school due to long COVID symptoms. The most common symptoms as reasons for absence from school were fatigue (85.7% of the patients), headache (42.9%), and insomnia (32.1%). Conclusions: Attention should be paid to the symptoms of fatigue and headache in teenagers with long COVID.}, }
@article {pmid36837480, year = {2023}, author = {Coman, AE and Ceasovschih, A and Petroaie, AD and Popa, E and Lionte, C and Bologa, C and Haliga, RE and Cosmescu, A and Slănină, AM and Bacușcă, AI and Șorodoc, V and Șorodoc, L}, title = {The Significance of Low Magnesium Levels in COVID-19 Patients.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {59}, number = {2}, pages = {}, pmid = {36837480}, issn = {1648-9144}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Magnesium ; Lung ; }, abstract = {Magnesium is the fourth most common mineral in the human body and the second richest intracellular cation. This element is necessary for many physiological reactions, especially in the cardiovascular and respiratory systems. COVID-19 is an infectious disease caused by SARS-CoV-2. The majority of people who become ill as a result of COVID-19 have mild-to-moderate symptoms and recover without specific treatment. Moreover, there are people who develop severe forms of COVID-19, which require highly specialized medical assistance. Magnesium deficiency may play a role in the pathophysiology of infection with SARS-CoV-2. The primary manifestation of COVID-19 remains respiratory, but the virus can spread to other organs and tissues, complicating the clinical picture and culminating in multiorgan failure. The key mechanisms involved in the disease include direct viral cytotoxicity, endothelial dysfunction, and exaggerated release of inflammatory cytokines. The aim of this review was to summarize the available data regarding the role of magnesium in COVID-19 patients and its particularities in different clinical settings.}, }
@article {pmid36839224, year = {2023}, author = {Mey, JT and Kirwan, JP and Axelrod, CL}, title = {The Role of Nutrition in Mitigating the Effects of COVID-19 from Infection through PASC.}, journal = {Nutrients}, volume = {15}, number = {4}, pages = {}, pmid = {36839224}, issn = {2072-6643}, support = {U54 GM104940/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Acute Disease ; Disease Progression ; Nutritional Status ; }, abstract = {The expansive and rapid spread of the SARS-CoV-2 virus has resulted in a global pandemic of COVID-19 infection and disease. Though initially perceived to be acute in nature, many patients report persistent and recurrent symptoms beyond the infectious period. Emerging as a new epidemic, "long-COVID", or post-acute sequelae of coronavirus disease (PASC), has substantially altered the lives of millions of people globally. Symptoms of both COVID-19 and PASC are individual, but share commonality to established respiratory viruses, which include but are not limited to chest pain, shortness of breath, fatigue, along with adverse metabolic and pulmonary health effects. Nutrition plays a critical role in immune function and metabolic health and thus is implicated in reducing risk or severity of symptoms for both COVID-19 and PASC. However, despite the impact of nutrition on these key physiological functions related to COVID-19 and PASC, the precise role of nutrition in COVID-19 infection and PASC onset or severity remains to be elucidated. This narrative review will discuss established and emerging nutrition approaches that may play a role in COVID-19 and PASC, with references to the established nutrition and clinical practice guidelines that should remain the primary resources for patients and practitioners.}, }
@article {pmid36841740, year = {2023}, author = {Bucciol, G and ,  and Meyts, I}, title = {Inherited and acquired errors of type I interferon immunity govern susceptibility to COVID-19 and multisystem inflammatory syndrome in children.}, journal = {The Journal of allergy and clinical immunology}, volume = {151}, number = {4}, pages = {832-840}, pmid = {36841740}, issn = {1097-6825}, support = {R01 AI088364/AI/NIAID NIH HHS/United States ; R01 AI163029/AI/NIAID NIH HHS/United States ; UL1 RR024143/RR/NCRR NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; }, mesh = {SARS-CoV-2 ; Child ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Male ; Young Adult ; Humans ; *Interferon Type I ; Systemic Inflammatory Response Syndrome ; }, abstract = {Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/coronavirus disease 2019 (COVID-19) pandemic, global sequencing efforts have led in the field of inborn errors of immunity, and inspired particularly by previous research on life-threatening influenza, they have revealed that known and novel inborn errors affecting type I interferon immunity underlie critical COVID-19 in up to 5% of cases. In addition, neutralizing autoantibodies against type I interferons have been identified in up to 20% of patients with critical COVID-19 who are older than 80 years and 20% of fatal cases, with a higher prevalence in men and individuals older than 70 years. Also, inborn errors impairing regulation of type I interferon responses and RNA degradation have been found as causes of multisystem inflammatory syndrome in children, a life-threatening hyperinflammatory condition complicating otherwise mild initial SARS-CoV-2 infection in children and young adults. Better understanding of these immunologic mechanisms can aid in designing treatments for severe COVID-19, multisystem inflammatory syndrome in children, long COVID, and neuro-COVID.}, }
@article {pmid36846556, year = {2022}, author = {Kavanagh, E}, title = {Long Covid brain fog: a neuroinflammation phenomenon?.}, journal = {Oxford open immunology}, volume = {3}, number = {1}, pages = {iqac007}, pmid = {36846556}, issn = {2633-6960}, abstract = {Neuroinflammation is a process triggered by an attack on the immune system. Activation of microglia in response to an immune system challenge can lead to a significant impact on cognitive processes, such as learning, memory and emotional regulation. Long Covid is an ongoing problem, affecting an estimated 1.3 million people within the UK alone, and one of its more significant, and as yet unexplained, symptoms is brain fog. Here, we discuss the potential role of neuroinflammation in Long Covid cognitive difficulties. Inflammatory cytokines have been found to play a significant role in reductions in LTP and LTD, a reduction in neurogenesis, and in dendritic sprouting. The potential behavioural consequences of such impacts are discussed. It is hoped that this article will allow for greater examination of the effects of inflammatory factors on brain function, most particularly in terms of their role in chronic conditions.}, }
@article {pmid36846561, year = {2022}, author = {Haunhorst, S and Bloch, W and Wagner, H and Ellert, C and Krüger, K and Vilser, DC and Finke, K and Reuken, P and Pletz, MW and Stallmach, A and Puta, C}, title = {Long COVID: a narrative review of the clinical aftermaths of COVID-19 with a focus on the putative pathophysiology and aspects of physical activity.}, journal = {Oxford open immunology}, volume = {3}, number = {1}, pages = {iqac006}, pmid = {36846561}, issn = {2633-6960}, abstract = {The pandemic coronavirus disease 2019 (COVID-19) can cause multi-systemic symptoms that can persist beyond the acute symptomatic phase. The post-acute sequelae of COVID-19 (PASC), also referred to as long COVID, describe the persistence of symptoms and/or long-term complications beyond 4 weeks from the onset of the acute symptoms and are estimated to affect at least 20% of the individuals infected with SARS-CoV-2 regardless of their acute disease severity. The multi-faceted clinical picture of long COVID encompasses a plethora of undulating clinical manifestations impacting various body systems such as fatigue, headache, attention disorder, hair loss and exercise intolerance. The physiological response to exercise testing is characterized by a reduced aerobic capacity, cardiocirculatory limitations, dysfunctional breathing patterns and an impaired ability to extract and use oxygen. Still, to this day, the causative pathophysiological mechanisms of long COVID remain to be elucidated, with long-term organ damage, immune system dysregulation and endotheliopathy being among the hypotheses discussed. Likewise, there is still a paucity of treatment options and evidence-based strategies for the management of the symptoms. In sum, this review explores different aspects of long COVID and maps the literature on what is known about its clinical manifestations, potential pathophysiological mechanisms, and treatment options.}, }
@article {pmid36846562, year = {2022}, author = {Patcai, J}, title = {Is 'Long Covid' similar to 'Long SARS'?.}, journal = {Oxford open immunology}, volume = {3}, number = {1}, pages = {iqac002}, pmid = {36846562}, issn = {2633-6960}, }
@article {pmid36851614, year = {2023}, author = {Vojdani, A and Vojdani, E and Saidara, E and Maes, M}, title = {Persistent SARS-CoV-2 Infection, EBV, HHV-6 and Other Factors May Contribute to Inflammation and Autoimmunity in Long COVID.}, journal = {Viruses}, volume = {15}, number = {2}, pages = {}, pmid = {36851614}, issn = {1999-4915}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Herpesvirus 4, Human ; *Herpesvirus 6, Human ; Autoimmunity ; *Fatigue Syndrome, Chronic ; *Epstein-Barr Virus Infections/complications ; SARS-CoV-2 ; Inflammation ; }, abstract = {A novel syndrome called long-haul COVID or long COVID is increasingly recognized in a significant percentage of individuals within a few months after infection with SARS-CoV-2. This disorder is characterized by a wide range of persisting, returning or even new but related symptoms that involve different tissues and organs, including respiratory, cardiac, vascular, gastrointestinal, musculo-skeletal, neurological, endocrine and systemic. Some overlapping symptomatologies exist between long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Very much like with long ME/CFS, infections with herpes family viruses, immune dysregulation, and the persistence of inflammation have been reported as the most common pattern for the development of long COVID. This review describes several factors and determinants of long COVID that have been proposed, elaborating mainly on viral persistence, reactivation of latent viruses such as Epstein-Barr virus and human herpesvirus 6 which are also associated with the pathology of ME/CFS, viral superantigen activation of the immune system, disturbance in the gut microbiome, and multiple tissue damage and autoimmunity. Based on these factors, we propose diagnostic strategies such as the measurement of IgG and IgM antibodies against SARS-CoV-2, EBV, HHV-6, viral superantigens, gut microbiota, and biomarkers of autoimmunity to better understand and manage this multi-factorial disorder that continues to affect millions of people in the world.}, }
@article {pmid36851746, year = {2023}, author = {Yan, MZ and Yang, M and Lai, CL}, title = {Post-COVID-19 Syndrome Comprehensive Assessment: From Clinical Diagnosis to Imaging and Biochemical-Guided Diagnosis and Management.}, journal = {Viruses}, volume = {15}, number = {2}, pages = {}, pmid = {36851746}, issn = {1999-4915}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/diagnosis ; Disease Outbreaks ; Disease Progression ; COVID-19 Testing ; }, abstract = {The COVID-19 outbreak was first reported in 2019, causing massive morbidity and mortality. The majority of the COVID-19 patients survived and developed Post-COVID-19 Syndrome (PC19S) of varying severity. Currently, the diagnosis of PC19S is achieved through history and symptomatology that cannot be explained by an alternative diagnosis. However, the heavy reliance on subjective reporting is prone to reporting errors. Besides, there is no unified diagnostic assessment tool to classify the clinical severity of patients. This leads to significant difficulties when managing patients in terms of public resource utilization, clinical progression monitorization and rehabilitation plan formulation. This narrative review aims to review current evidence of diagnosis based on triple assessment: clinical symptomatology, biochemical analysis and imaging evidence. Further assessment tools can be developed based on triple assessment to monitor patient's clinical progression, prognosis and intervals of monitoring. It also highlights the high-risk features of patients for closer and earlier monitoring. Rehabilitation programs and related clinical trials are evaluated; however, most of them focus on cardiorespiratory fitness and psychiatric presentations such as anxiety and depression. Further research is required to establish an objective and comprehensive assessment tool to facilitate clinical management and rehabilitation plans.}, }
@article {pmid36853484, year = {2023}, author = {El-Tallawy, SN and Perglozzi, JV and Ahmed, RS and Kaki, AM and Nagiub, MS and LeQuang, JK and Hadarah, MM}, title = {Pain Management in the Post-COVID Era-An Update: A Narrative Review.}, journal = {Pain and therapy}, volume = {12}, number = {2}, pages = {423-448}, pmid = {36853484}, issn = {2193-8237}, abstract = {An extensive computer search (from January 2020 to January 2023) was conducted including literature from the PubMed, Scopus, MEDLINE, Web of Science, and EMBASE databases. According to preset criteria, a total of 58 articles were included in this review article. Generally, any patient who becomes infected with COVID-19 can develop post-COVID-19 conditions. The course of COVID-19 is divided into three main stages: acute COVID-19 (up to 4 weeks), post-acute COVID-19 (from 4 to 12 weeks), and post-COVID (from 12 weeks to 6 months). If a more protracted course of COVID (over 6 months) is demonstrated, the term "long-COVID" is used. Although the acute stage of COVID-19 infection most commonly manifests with acute respiratory symptoms, one very common symptom of the disease is pain, while the most common symptoms of post-COVID syndrome are shortness of breath, dry cough, fatigue, loss of olfactory and gustatory function, tightness and chest pain, sleep and mood disturbances, body aches, muscle and joint pain, sore throat, fever, and persistent headaches. All observations demonstrated a high incidence of chronic pain syndromes of various localization in the post- and long-COVID period. Post-COVID chronic pain might include a newly developed chronic pain as a part of post-viral syndrome; worsening of preexisting chronic pain due to the associated changes in the medical services, or a de novo chronic pain in healthy individuals who are not infected with COVID. Chronic pain during and post-COVID-19 pandemic is an important health issue due to the significant impacts of pain on the patients, health care systems, and society as well. Therefore, it is important that patients with chronic pain receive effective treatment according to their specific needs. Accordingly, the main goal of this review article is to provide a broad description about the post-COVID pain and to explore the impact of long COVID-19 on chronic pain patients, and also to give brief reports about the prevalence, risk factors, possible mechanisms, different presentations, and the management tools through a systematic approach.}, }
@article {pmid36855220, year = {2023}, author = {Albright, C and Limoges, J and Rempel, GR}, title = {Living with pulmonary sequelae of COVID-19 and the implications for clinical nursing practice: A qualitative systematised review.}, journal = {Journal of clinical nursing}, volume = {32}, number = {21-22}, pages = {7650-7660}, doi = {10.1111/jocn.16664}, pmid = {36855220}, issn = {1365-2702}, mesh = {Adult ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Qualitative Research ; *Nursing Care ; Clinical Competence ; }, abstract = {AIM: To synthesise qualitative research on pulmonary sequelae of COVID-19 and identify patient needs and experiences to develop nursing care strategies.<br><br>BACKGROUND: Qualitative research on long COVID by subtype has not yet occurred. As pulmonary sequelae constitute a serious long COVID subtype, exploring patient experience and needs can generate knowledge to guide nursing practice.<br><br>DESIGN: Systematised review methodology utilised on a purposive sample of published articles and reported using the PRISMA guidelines and checklists. Searched MEDLINE, Cumulative Index to Nursing and Allied Health, and Google Scholar, for English or French articles published from February 2020 to June 2022; qualitative research with adults recovering from COVID-19 with evidence of pulmonary sequelae.<br><br>METHODS: Established principles for data extraction followed related to data reduction, data presentation, data comparison, and conclusion formulation and verification. Analysis was informed by Thorne's Interpretive Description and extended with Meleis' transitions theory, Mishel's uncertainty in illness theory and Moore et al.'s holistic theory of unpleasant symptoms. The quality of included studies was assessed Joanna Briggs Institute critical appraisal tool for qualitative research.<br><br>RESULTS: Four articles with six pooled participants provided data to yield three main themes: (1) a novel health-illness transition, (2) lung injury and pulmonary fibrosis as antecedent to illness uncertainty, (3) and pulmonary symptoms that are compounded by fatigue and weakness.<br><br>CONCLUSION: Pulmonary sequelae of COVID-19 confers a unique health-illness transition, uncertainties and symptoms that can be addressed by theory informed nursing practice.<br><br>Advocacy, optimising the nurse-patient relationship, offering up-to-date information and addressing uncertainty may help patients cope with pulmonary sequelae, a complex subtype of long COVID with important considerations for clinical nursing care. Despite a lack of evidence-informed clinical pathways, nurses can support patients to understand novel treatments, support discharge planning and acknowledge the synergistic nature of pulmonary symptoms and fatigue to support health-illness transitions.<br><br>This article involved analysis of previously published works.}, }
@article {pmid36856339, year = {2023}, author = {Philip, B and Mukherjee, P and Khare, Y and Ramesh, P and Zaidi, S and Sabry, H and Harky, A}, title = {COVID-19 and its long-term impact on the cardiovascular system.}, journal = {Expert review of cardiovascular therapy}, volume = {21}, number = {3}, pages = {211-218}, doi = {10.1080/14779072.2023.2184800}, pmid = {36856339}, issn = {1744-8344}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Cardiovascular System ; *Cardiovascular Diseases/diagnosis ; *Myocarditis ; }, abstract = {INTRODUCTION: TheSARS-CoV-2 virus caused a pandemic affecting healthcare deliveryglobally. Despite the presentation of COVID-19 infection beingfrequently dominated by respiratory symptoms; it is now notorious tohave potentially serious cardiovascular sequelae. This articleexplores current data to provide a comprehensive overview of thepathophysiology, cardiovascular risk factors, and implications ofCOVID-19.<br><br>AREAS COVERED: Inherentstructure of SARS-CoV-2, and its interaction with both ACE-2 andnon-ACE-2 mediated pathways have been implicated in the developmentof cardiovascular manifestations, progressively resulting in acuterespiratory distress syndrome, multiorgan failure, cytokine releasesyndrome, and subsequent myocardial damage. The interplay betweenexisting and de novo cardiac complications must be noted. Forindividuals taking cardiovascular medications, pharmacologicinteractions are a crucial component. Short-term cardiovascularimpacts include arrhythmia, myocarditis, pericarditis, heart failure,and thromboembolism, whereas long-term impacts include diabetes andhypertension. To identify suitable studies, a PubMed literaturesearch was performed including key words such as 'Covid 19,''Cardiovascular disease,' 'Long covid,' etc.<br><br>EXPERT OPINION: Moresophisticated planning and effective management for cardiologyhealthcare provision is crucial, especially for accommodatingchallenges associated with Long-COVID. With the potential applicationof AI and automated data, there are many avenues and sequelae thatcan be approached for investigation.}, }
@article {pmid36857191, year = {2023}, author = {Fernández-de-Las-Peñas, C and Cuadrado, ML and Gómez-Mayordomo, V and García-Azorín, D and Arendt-Nielsen, L}, title = {Headache as a COVID-19 onset symptom or Post-COVID symptom according to the SARS-CoV-2 Variant.}, journal = {Expert review of neurotherapeutics}, volume = {23}, number = {2}, pages = {179-186}, doi = {10.1080/14737175.2023.2185138}, pmid = {36857191}, issn = {1744-8360}, mesh = {*Post-Acute COVID-19 Syndrome/complications/physiopathology/virology ; *Headache/etiology/physiopathology/virology ; *COVID-19/complications/physiopathology/virology ; Risk Factors ; Humans ; SARS-CoV-2 ; Animals ; Acute Disease ; }, abstract = {INTRODUCTION: COVID19 associated headaches are highly common and there is currently an unmet need to better understand their association with SARSCoV2 variants. Headaches are a prevalent symptom in the acute phase of COVID19 and are associated with a better prognosis and better immune response. They are also a relevant post-COVID symptom.<br><br>AREAS COVERED: This article analyses the differences in the prevalence of headache as an onset symptom and in post-COVID headache among the different SARS-CoV-2 variants: the historical strain, Alpha, Delta and Omicron. The different pathophysiological mechanisms by which SARS-CoV-2 infection may cause headache are also discussed.<br><br>EXPERT OPINION: The presence of headache at the acute phase is a risk factor for post-COVID headache, whereas a history of primary headache does not appear to be associated with post-COVID headache. The prevalence of headache as an onset symptom appears to be variable for the different SARS-CoV-2 variants, but current data are inconclusive. However, the current evidence also suggests that headache represents a prevalent symptom in the acute and post-infection COVID-19 phase, regardless of SARS-CoV-2 variant.}, }
@article {pmid36866647, year = {2023}, author = {Tronco Hernandez, YA and Julian, A and Weekes, EC and Murphy, J and Frost, G and Hickson, M}, title = {Developing a consensus to support health and social care professionals and patients manage nutrition in the context of COVID-19 recovery.}, journal = {Journal of human nutrition and dietetics : the official journal of the British Dietetic Association}, volume = {36}, number = {4}, pages = {1242-1252}, doi = {10.1111/jhn.13163}, pmid = {36866647}, issn = {1365-277X}, mesh = {Humans ; *COVID-19 ; Delivery of Health Care ; Health Personnel ; Nutritional Status ; Social Support ; }, abstract = {BACKGROUND: The long-term effects on people who have had COVID-19 affect nutrition and can be influenced by diet conversely. Specific nutritional guidelines, however, were scarce at the beginning of 2020, and empirical literature was also lacking. Conventional research methodologies needed to be adapted to review the available literature that could be relevant to the United Kingdom and policy documents as well as collect the views of health and care staff. The aim of this paper is to describe the method to develop consensus statements from experts to address the necessary nutritional support and what emerged from this.<br><br>METHODS: A nominal group technique (NGT) was adapted to the virtual world; we purposefully selected a range of professionals (dietitians, nurses, occupational therapists, etc.) and patients with long-term effects of COVID to present them with the most updated evidence and aim to reach key guidelines to address COVID-19 recovery.<br><br>RESULTS: We were able to reach consensus statements that were developed and reviewed by relevant healthcare staff at the front line to address the nutritional needs of patients recovering from COVID-19 and those suffering from its long-term effects. This adapted NGT process led us to understand that a virtual repository of concise guidelines and recommendations was needed. This was developed to be freely accessed by both patients recovering from COVID-19 and health professionals who manage them.<br><br>CONCLUSIONS: We successfully obtained key consensus statements from the adapted NGT, which showed the need for the nutrition and COVID-19 knowledge hub. This hub has been developed, updated, reviewed, endorsed and improved across the subsequent 2 years.}, }
@article {pmid36868374, year = {2023}, author = {Hilbold, E and Bär, C and Thum, T}, title = {COVID-19: Insights into long-term manifestations and lockdown impacts.}, journal = {Journal of sport and health science}, volume = {12}, number = {4}, pages = {438-463}, pmid = {36868374}, issn = {2213-2961}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Pandemics ; *Middle East Respiratory Syndrome Coronavirus ; Communicable Disease Control ; }, abstract = {Coronaviruses are pathogens thought to primarily affect the respiratory tracts of humans. The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 was also marked mainly by its symptoms of respiratory illness, which were named coronavirus disease 2019 (COVID-19). Since its initial discovery, many other symptoms have been linked to acute SARS-CoV-2 infections as well as to the long-term outcomes of COVID-19 patients. Among these symptoms are different categories of cardiovascular diseases (CVDs), which continue to be the main cause of death worldwide. The World Health Organization estimates that 17.9 million people die from CVDs each year, accounting for ∼32% of all deaths globally. Physical inactivity is one of the most important behavioral risk factors for CVDs. The COVID-19 pandemic has affected CVDs as well as the physical activity in different ways. Here, we provide an overview of the current status as well as future challenges and possible solutions.}, }
@article {pmid36873058, year = {2023}, author = {Meißner, T}, title = {[Not Available].}, journal = {Die Heilberufe}, volume = {75}, number = {3}, pages = {36-37}, doi = {10.1007/s00058-023-3034-y}, pmid = {36873058}, issn = {0017-9604}, }
@article {pmid36875356, year = {2023}, author = {Yuan, N and Lv, ZH and Sun, CR and Wen, YY and Tao, TY and Qian, D and Tao, FP and Yu, JH}, title = {Post-acute COVID-19 symptom risk in hospitalized and non-hospitalized COVID-19 survivors: A systematic review and meta-analysis.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1112383}, pmid = {36875356}, issn = {2296-2565}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Ageusia ; Anxiety ; Observational Studies as Topic ; }, abstract = {BACKGROUND: Post-acute coronavirus disease 2019 (COVID-19) symptoms occurred in most of the COVID-19 survivors. However, few studies have examined the issue of whether hospitalization results in different post-acute COVID-19 symptom risks. This study aimed to compare potential COVID-19 long-term effects in hospitalized and non-hospitalized COVID-19 survivors.<br><br>METHODS: This study is designed as a systematic review and meta-analysis of observational studies. A systematic search of six databases was performed for identifying articles published from inception until April 20th, 2022, which compared post-acute COVID-19 symptom risk in hospitalized and non-hospitalized COVID-19 survivors using a predesigned search strategy included terms for SARS-CoV-2 (eg, COVID, coronavirus, and 2019-nCoV), post-acute COVID-19 Syndrome (eg, post-COVID, post COVID conditions, chronic COVID symptom, long COVID, long COVID symptom, long-haul COVID, COVID sequelae, convalescence, and persistent COVID symptom), and hospitalization (hospitalized, in hospital, and home-isolated). The present meta-analysis was conducted according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement using R software 4.1.3 to create forest plots. Q statistics and the I [2] index were used to evaluate heterogeneity in this meta-analysis.<br><br>RESULTS: Six observational studies conducted in Spain, Austria, Switzerland, Canada, and the USA involving 419 hospitalized and 742 non-hospitalized COVID-19 survivors were included. The number of COVID-19 survivors in included studies ranged from 63 to 431, and follow-up data were collected through visits in four studies and another two used an electronic questionnaire, visit and telephone, respectively. Significant increase in the risks of long dyspnea (OR = 3.18, 95% CI = 1.90-5.32), anxiety (OR = 3.09, 95% CI = 1.47-6.47), myalgia (OR = 2.33, 95% CI = 1.02-5.33), and hair loss (OR = 2.76, 95% CI = 1.07-7.12) risk were found in hospitalized COVID-19 survivors compared with outpatients. Conversely, persisting ageusia risk was significantly reduced in hospitalized COVID-19 survivors than in non-hospitalized patients.<br><br>CONCLUSION: The findings suggested that special attention and patient-centered rehabilitation service based on a needs survey should be provided for hospitalized COVID-19 survivors who experienced high post-acute COVID-19 symptoms risk.}, }
@article {pmid36876049, year = {2023}, author = {Bruzzone, C and Conde, R and Embade, N and Mato, JM and Millet, O}, title = {Metabolomics as a powerful tool for diagnostic, pronostic and drug intervention analysis in COVID-19.}, journal = {Frontiers in molecular biosciences}, volume = {10}, number = {}, pages = {1111482}, pmid = {36876049}, issn = {2296-889X}, abstract = {COVID-19 currently represents one of the major health challenges worldwide. Albeit its infectious character, with onset affectation mainly at the respiratory track, it is clear that the pathophysiology of COVID-19 has a systemic character, ultimately affecting many organs. This feature enables the possibility of investigating SARS-CoV-2 infection using multi-omic techniques, including metabolomic studies by chromatography coupled to mass spectrometry or by nuclear magnetic resonance (NMR) spectroscopy. Here we review the extensive literature on metabolomics in COVID-19, that unraveled many aspects of the disease including: a characteristic metabotipic signature associated to COVID-19, discrimination of patients according to severity, effect of drugs and vaccination treatments and the characterization of the natural history of the metabolic evolution associated to the disease, from the infection onset to full recovery or long-term and long sequelae of COVID.}, }
@article {pmid36879504, year = {2023}, author = {Opsteen, S and Files, JK and Fram, T and Erdmann, N}, title = {The role of immune activation and antigen persistence in acute and long COVID.}, journal = {Journal of investigative medicine : the official publication of the American Federation for Clinical Research}, volume = {71}, number = {5}, pages = {545-562}, pmid = {36879504}, issn = {1708-8267}, support = {K08 AI129705/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Convalescence ; SARS-CoV-2 ; Inflammation ; }, abstract = {In late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered the global coronavirus disease 2019 (COVID-19) pandemic. Although most infections cause a self-limited syndrome comparable to other upper respiratory viral pathogens, a portion of individuals develop severe illness leading to substantial morbidity and mortality. Furthermore, an estimated 10%-20% of SARS-CoV-2 infections are followed by post-acute sequelae of COVID-19 (PASC), or long COVID. Long COVID is associated with a wide variety of clinical manifestations including cardiopulmonary complications, persistent fatigue, and neurocognitive dysfunction. Severe acute COVID-19 is associated with hyperactivation and increased inflammation, which may be an underlying cause of long COVID in a subset of individuals. However, the immunologic mechanisms driving long COVID development are still under investigation. Early in the pandemic, our group and others observed immune dysregulation persisted into convalescence after acute COVID-19. We subsequently observed persistent immune dysregulation in a cohort of individuals experiencing long COVID. We demonstrated increased SARS-CoV-2-specific CD4[+] and CD8[+] T-cell responses and antibody affinity in patients experiencing long COVID symptoms. These data suggest a portion of long COVID symptoms may be due to chronic immune activation and the presence of persistent SARS-CoV-2 antigen. This review summarizes the COVID-19 literature to date detailing acute COVID-19 and convalescence and how these observations relate to the development of long COVID. In addition, we discuss recent findings in support of persistent antigen and the evidence that this phenomenon contributes to local and systemic inflammation and the heterogeneous nature of clinical manifestations seen in long COVID.}, }
@article {pmid36880667, year = {2023}, author = {Gareau, MG and Barrett, KE}, title = {Role of the microbiota-gut-brain axis in postacute COVID syndrome.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {324}, number = {4}, pages = {G322-G328}, pmid = {36880667}, issn = {1522-1547}, support = {R01 AT009365/AT/NCCIH NIH HHS/United States ; }, mesh = {Humans ; *Brain-Gut Axis ; *COVID-19 ; Pandemics ; Post-Acute COVID-19 Syndrome ; Disease Progression ; }, abstract = {The COVID-19 pandemic has resulted in the infection of hundreds of millions of individuals over the past 3 years, coupled with millions of deaths. Along with these more acute impacts of infection, a large subset of patients has developed symptoms that collectively comprise "postacute sequelae of COVID-19" (PASC, also known as long COVID), which can persist for months and maybe even years. In this review, we outline the current knowledge on the role of impaired microbiota-gut-brain (MGB) axis signaling in the development of PASC and the potential mechanisms involved, which may lead to a better understanding of disease progression and treatment options in the future.}, }
@article {pmid36884145, year = {2023}, author = {Kumar, P and Jat, KR}, title = {Post-COVID-19 Sequelae in Children.}, journal = {Indian journal of pediatrics}, volume = {90}, number = {6}, pages = {605-611}, pmid = {36884145}, issn = {0973-7693}, mesh = {Adult ; Humans ; Child ; *COVID-19/complications/epidemiology ; SARS-CoV-2 ; Communicable Disease Control ; Affect ; Cough ; Disease Progression ; }, abstract = {Coronavirus disease 19 (COVID-19), caused by the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), has been implicated in having post-COVID-19 sequelae in both adults and children. There is a lack of good data on the prevalence and risk factors for post-COVID-19 sequelae in children. The authors aimed to review the current literature on post-COVID sequelae. The prevalence of post-COVID sequelae in children is highly variable among studies, with an average of 25%. The sequelae may affect many organ systems, though mood symptoms, fatigue, cough, dyspnea, and sleep problems are common. In many studies, it is difficult to establish a causal association due to the lack of a control group. Furthermore, it is difficult to differentiate whether the neuropsychiatric symptoms in children after COVID-19 are due to infection or a result of lockdowns and social restrictions imposed by the pandemic. Children with COVID-19 should be followed by a multidisciplinary team and screened for symptoms, followed by focused laboratory evaluations as needed. There is no specific treatment for the sequelae. Only symptomatic and supportive treatment is required in most cases. More research is necessary to standardize the definitions of sequelae, establish a causal association, assess various treatment options, and the effects of different virus variants, and finally, see the impact of vaccination on the sequelae.}, }
@article {pmid36892678, year = {2023}, author = {Thurner, C and Stengel, A}, title = {Long-COVID syndrome: physical-mental interplay in the spotlight.}, journal = {Inflammopharmacology}, volume = {31}, number = {2}, pages = {559-564}, pmid = {36892678}, issn = {1568-5608}, mesh = {Humans ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; *Mental Disorders/etiology/therapy ; Anxiety ; Depression ; }, abstract = {Patients suffering from Long-COVID syndrome experience a variety of different symptoms on a physical, but also on a psychological and social level. Previous psychiatric conditions such as depression and anxiety have been identified as separate risk factors for developing Long-COVID syndrome. This suggests a complex interplay of different physical and mental factors rather than a simple cause-effect relationship of a specific biological pathogenic process. The biopsychosocial model provides a foundation for understanding these interactions and integrating them into a broader perspective of the patient suffering from the disease instead of the individual symptoms, pointing towards the need of treatment options on a psychological as well as social level besides biological targets. This leads to our conclusion, that the biopsychosocial model should be the underlying philosophy of understanding, diagnosing and treating patients suffering from Long-COVID syndrome, moving away from the strictly biomedical understanding suspected by many patients, treaters and the media while also reducing the stigma still associated with the suggestion of a physical-mental interplay.}, }
@article {pmid36899824, year = {2023}, author = {Theoharides, TC and Kempuraj, D}, title = {Role of SARS-CoV-2 Spike-Protein-Induced Activation of Microglia and Mast Cells in the Pathogenesis of Neuro-COVID.}, journal = {Cells}, volume = {12}, number = {5}, pages = {}, pmid = {36899824}, issn = {2073-4409}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2/metabolism ; Spike Glycoprotein, Coronavirus/metabolism ; Post-Acute COVID-19 Syndrome ; Microglia/metabolism ; Mast Cells/metabolism ; Inflammation ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). About 45% of COVID-19 patients experience several symptoms a few months after the initial infection and develop post-acute sequelae of SARS-CoV-2 (PASC), referred to as "Long-COVID," characterized by persistent physical and mental fatigue. However, the exact pathogenetic mechanisms affecting the brain are still not well-understood. There is increasing evidence of neurovascular inflammation in the brain. However, the precise role of the neuroinflammatory response that contributes to the disease severity of COVID-19 and long COVID pathogenesis is not clearly understood. Here, we review the reports that the SARS-CoV-2 spike protein can cause blood-brain barrier (BBB) dysfunction and damage neurons either directly, or via activation of brain mast cells and microglia and the release of various neuroinflammatory molecules. Moreover, we provide recent evidence that the novel flavanol eriodictyol is particularly suited for development as an effective treatment alone or together with oleuropein and sulforaphane (ViralProtek[®]), all of which have potent anti-viral and anti-inflammatory actions.}, }
@article {pmid36899952, year = {2023}, author = {Leng, A and Shah, M and Ahmad, SA and Premraj, L and Wildi, K and Li Bassi, G and Pardo, CA and Choi, A and Cho, SM}, title = {Pathogenesis Underlying Neurological Manifestations of Long COVID Syndrome and Potential Therapeutics.}, journal = {Cells}, volume = {12}, number = {5}, pages = {}, pmid = {36899952}, issn = {2073-4409}, support = {K23 HL157610/HL/NHLBI NIH HHS/United States ; L30 HL165486/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; RNA, Viral ; *Nervous System Diseases/etiology ; Inflammation/complications ; Post-Acute COVID-19 Syndrome ; }, abstract = {The development of long-term symptoms of coronavirus disease 2019 (COVID-19) more than four weeks after primary infection, termed "long COVID" or post-acute sequela of COVID-19 (PASC), can implicate persistent neurological complications in up to one third of patients and present as fatigue, "brain fog", headaches, cognitive impairment, dysautonomia, neuropsychiatric symptoms, anosmia, hypogeusia, and peripheral neuropathy. Pathogenic mechanisms of these symptoms of long COVID remain largely unclear; however, several hypotheses implicate both nervous system and systemic pathogenic mechanisms such as SARS-CoV2 viral persistence and neuroinvasion, abnormal immunological response, autoimmunity, coagulopathies, and endotheliopathy. Outside of the CNS, SARS-CoV-2 can invade the support and stem cells of the olfactory epithelium leading to persistent alterations to olfactory function. SARS-CoV-2 infection may induce abnormalities in innate and adaptive immunity including monocyte expansion, T-cell exhaustion, and prolonged cytokine release, which may cause neuroinflammatory responses and microglia activation, white matter abnormalities, and microvascular changes. Additionally, microvascular clot formation can occlude capillaries and endotheliopathy, due to SARS-CoV-2 protease activity and complement activation, can contribute to hypoxic neuronal injury and blood-brain barrier dysfunction, respectively. Current therapeutics target pathological mechanisms by employing antivirals, decreasing inflammation, and promoting olfactory epithelium regeneration. Thus, from laboratory evidence and clinical trials in the literature, we sought to synthesize the pathophysiological pathways underlying neurological symptoms of long COVID and potential therapeutics.}, }
@article {pmid36917411, year = {2023}, author = {Williams, LD and Zis, P}, title = {COVID-19-Related Burning Eye Syndrome and Burning Mouth Syndrome: A Systematic Review and Meta-analysis.}, journal = {Pain and therapy}, volume = {12}, number = {3}, pages = {621-630}, pmid = {36917411}, issn = {2193-8237}, abstract = {BACKGROUND: Previous research highlights burning eye syndrome (BES) and burning mouth syndrome (BMS) as chronic complications of COVID-19 infection. The aim of this systematic review and meta-analysis is to establish the prevalence of COVID-19-related BES and COVID-19-related BMS and describe their phenomenology.<br><br>METHODOLOGY: A literature search in the PubMed database was performed, and seven papers (five on BES and two on BMS) were eligible to be included in this systematic review and meta-analysis.<br><br>RESULTS: The pooled prevalence of COVID-19-related BES was 9.9% (95% CI 3.4-25.4%). The frequency of COVID-19-related BMS is only reported in isolated cases and ranges from 4% in mild-to-moderate cases to 15% in severe, hospitalized cases, with female patients being mostly affected. COVID-19 severity is a potential risk factor for both BES and BMS. Neither syndrome occurs in isolation. COVID-19-related BES usually appears within the first week post-infection, persisting up to 9&#xa0;weeks later. COVID-19-related BMS occurs during and after initial infection, and may also persist as a chronic disease.<br><br>CONCLUSIONS: Both BES and BMS are neuropathic COVID-19 infection complications, still under-studied and under-investigated, despite the fact that both are prevalent. Both COVID-19-related BES and COVID-19-related BMS could potentially be initial long COVID syndrome manifestations, and further research should be carried out in this field.}, }
@article {pmid36920723, year = {2023}, author = {Schloss, JV}, title = {Nutritional deficiencies that may predispose to long COVID.}, journal = {Inflammopharmacology}, volume = {31}, number = {2}, pages = {573-583}, pmid = {36920723}, issn = {1568-5608}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Pandemics ; *Malnutrition/complications/epidemiology ; Zinc ; }, abstract = {Multiple nutritional deficiencies (MND) confound studies designed to assess the role of a single nutrient in contributing to the initiation and progression of disease states. Despite the perception of many healthcare practitioners, up to 25% of Americans are deficient in five-or-more essential nutrients. Stress associated with the COVID-19 pandemic further increases the prevalence of deficiency states. Viral infections compete for crucial nutrients with immune cells. Viral replication and proliferation of immunocompetent cells critical to the host response require these essential nutrients, including zinc. Clinical studies have linked levels of more than 22 different dietary components to the likelihood of COVID-19 infection and the severity of the disease. People at higher risk of infection due to MND are also more likely to have long-term sequelae, known as Long COVID.}, }
@article {pmid36928222, year = {2023}, author = {Asakawa, T and Cai, Q and Shen, J and Zhang, Y and Li, Y and Chen, P and Luo, W and Zhang, J and Zhou, J and Zeng, H and Weng, R and Hu, F and Feng, H and Chen, J and Huang, J and Zhang, X and Zhao, Y and Fang, L and Yang, R and Huang, J and Wang, F and Liu, Y and Lu, H}, title = {Sequelae of long COVID, known and unknown: A review of updated information.}, journal = {Bioscience trends}, volume = {17}, number = {2}, pages = {85-116}, doi = {10.5582/bst.2023.01039}, pmid = {36928222}, issn = {1881-7823}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Pandemics ; Public Health ; }, abstract = {Over three years have passed since the COVID-19 pandemic started. The dangerousness and impact of COVID-19 should definitely not be ignored or underestimated. Other than the symptoms of acute infection, the long-term symptoms associated with SARS-CoV-2 infection, which are referred to here as "sequelae of long COVID (LC)", are also a conspicuous global public health concern. Although such sequelae were well-documented, the understanding of and insights regarding LC-related sequelae remain inadequate due to the limitations of previous studies (the follow-up, methodological flaws, heterogeneity among studies, etc.). Notably, robust evidence regarding diagnosis and treatment of certain LC sequelae remain insufficient and has been a stumbling block to better management of these patients. This awkward situation motivated us to conduct this review. Here, we comprehensively reviewed the updated information, particularly focusing on clinical issues. We attempt to provide the latest information regarding LC-related sequelae by systematically reviewing the involvement of main organ systems. We also propose paths for future exploration based on available knowledge and the authors' clinical experience. We believe that these take-home messages will be helpful to gain insights into LC and ultimately benefit clinical practice in treating LC-related sequelae.}, }
@article {pmid36931142, year = {2023}, author = {Zheng, YB and Zeng, N and Yuan, K and Tian, SS and Yang, YB and Gao, N and Chen, X and Zhang, AY and Kondratiuk, AL and Shi, PP and Zhang, F and Sun, J and Yue, JL and Lin, X and Shi, L and Lalvani, A and Shi, J and Bao, YP and Lu, L}, title = {Prevalence and risk factor for long COVID in children and adolescents: A meta-analysis and systematic review.}, journal = {Journal of infection and public health}, volume = {16}, number = {5}, pages = {660-672}, pmid = {36931142}, issn = {1876-035X}, mesh = {Prevalence ; Adolescent ; Child ; Risk Factors ; Female ; *COVID-19/epidemiology/complications ; Humans ; Aged ; Post-Acute COVID-19 Syndrome ; Systemic Inflammatory Response Syndrome ; }, abstract = {BACKGROUND: Millions of COVID-19 pediatric survivors are facing the risk of long COVID after recovery from acute COVID-19. The primary objective of this study was to systematically review the available literature and determine the pooled prevalence of, and risk factors for long COVID among the pediatric survivors.<br><br>METHODS: Studies that assessed the prevalence of, or risk factors associated with long COVID among pediatric COVID-19 survivors were systematically searched in PubMed, Embase, and Cochrane Library up to December 11th, 2022. Random effects model was performed to estimate the pooled prevalence of long COVID among pediatric COVID-19 patients. Subgroup analyses and meta-regression on the estimated prevalence of long COVID were performed by stratification with follow-up duration, mean age, sex ratio, percentage of multisystem inflammatory syndrome, hospitalization rate at baseline, and percentage of severe illness.<br><br>RESULTS: Based on 40 studies with 12,424 individuals, the pooled prevalence of any long COVID was 23.36 % ([95 % CI 15.27-32.53]). The generalized symptom (19.57 %, [95 % CI 9.85-31.52]) was reported most commonly, followed by respiratory (14.76 %, [95 % CI 7.22-24.27]), neurologic (13.51 %, [95 % CI 6.52-22.40]), and psychiatric (12.30 %, [95% CI 5.38-21.37]). Dyspnea (22.75 %, [95% CI 9.38-39.54]), fatigue (20.22 %, [95% CI 9.19-34.09]), and headache (15.88 %, [95 % CI 6.85-27.57]) were most widely reported specific symptoms. The prevalence of any symptom during 3-6, 6-12, and>&#xa0;12 months were 26.41 % ([95 % CI 14.33-40.59]), 20.64 % ([95 % CI 17.06-24.46]), and 14.89 % ([95 % CI 6.09-26.51]), respectively. Individuals with aged over ten years, multisystem inflammatory syndrome, or had severe clinical symptoms exhibited higher prevalence of long COVID in multi-systems. Factors such as older age, female, poor physical or mental health, or had severe infection or more symptoms were more likely to have long COVID in pediatric survivors.<br><br>CONCLUSIONS: Nearly one quarter of pediatric survivors suffered multisystem long COVID, even at 1 year after infection. Ongoing monitoring, comprehensive prevention and intervention is warranted for pediatric survivors, especially for individuals with high risk factors.}, }
@article {pmid36937488, year = {2023}, author = {Stoian, M and Procopiescu, B and Șeitan, S and Scarlat, G}, title = {Post-COVID-19 syndrome: Insights into a novel post-infectious systemic disorder.}, journal = {Journal of medicine and life}, volume = {16}, number = {2}, pages = {195-202}, pmid = {36937488}, issn = {1844-3117}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Pandemics ; Risk Factors ; }, abstract = {Coronavirus disease 2019 (COVID-19) is currently considered a complex systemic infectious and inflammatory disease, determined by the infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and the cause of one of the most important epidemiological phenomena in the last century - the COVID-19 pandemic. This infectious-inflammatory disease may generate a wide range of clinical manifestations and biological modifications, explained by the ubiquitous nature of the SARS-CoV-2 receptors, represented by the angiotensin-converting enzyme-2 (ACE-2), and by the host's violent immune and proinflammatory reaction to the viral infection. These manifestations include immunological disturbances, which, according to certain clinical findings, may persist post-infection, in the form of a presumed systemic inflammatory entity, defined by several clinical concepts with a common pathological significance: post-COVID-19 multisystem (or systemic) inflammatory syndrome, post-COVID syndrome or long-COVID. Although the pathophysiological mechanisms of the post-COVID-19 syndrome are elusive at the present moment, there are currently several studies that describe a systemic inflammatory or autoimmune phenomenon following the remission of the COVID-19 infection in some patients, which suggests the existence of molecular and cellular immune abnormalities, most probably due to the host's initial violent immune response to the viral infection, in the form of three overlapping entities: secondary hemophagocytic lymph histiocytosis (HLH), macrophage activation syndrome (MAS) and cytokine release syndrome (CRS). Thus, this is reminiscent of different classic autoimmune diseases, in which various infections are risk factors in developing the autoimmune process.}, }
@article {pmid36943540, year = {2023}, author = {Muzyka, I and Revenko, O and Kovalchuk, I and Savytska, M and Bekesevych, A and Zayachkivska, O}, title = {What is the role of brown adipose tissue in metabolic health: lessons learned and future perspectives in the long COVID?.}, journal = {Inflammopharmacology}, volume = {}, number = {}, pages = {1-9}, pmid = {36943540}, issn = {1568-5608}, abstract = {Metabolic physiology plays a key role in maintaining our health and resilience. Metabolic disorders can lead to serious illnesses, including obesity. The pathogenesis of the new long COVID syndrome in individuals with long-term recovery after SARS-Co-2 infection is still incomplete. Thus there is growing attention in the study of adipose tissue activities, especially brown adipose tissue (BAT) and associated resilience which plays a crucial role in different types of obesity as potential targets for pharmacologic and nutritional interventions in the context of obesity and long COVID. The number of studies examining mechanisms underlying BAT has grown rapidly in the last 10 years despite of role of BAT in individuals with COVID-19 and long COVID is modest. Therefore, this review aims to sum up data examining BAT activities, its resilience in health, obesity, and the possible link to long COVID. The search was conducted on studies published in English mostly between 2004 and 2022 in adult humans and animal models. Database searches were conducted using PubMed, Scopus, and Google Scholar for key terms including adipose tissue, BAT, adipokinins, obesity, VPF/VEGF, and pathogenesis. From the initial search through the database were identified relevant articles that met inclusion and exclusion criteria and our data regarding adipose tissues were presented in this review. It will discuss adiposity tissue activities. Current literature suggests that there are BAT integral effects to whitening and browning fat phenomenons which reflect the homeostatic metabolic adaptive ability for environmental demand or survival/adaptive mechanisms. We also review neural and vascular impacts in BAT that play a role in resilience and obesity. Finally, we discuss the role of BAT in the context of long COVID in basic research and clinical research.}, }
@article {pmid36943909, year = {2023}, author = {Rinn, R and Gao, L and Schoeneich, S and Dahmen, A and Anand Kumar, V and Becker, P and Lippke, S}, title = {Digital Interventions for Treating Post-COVID or Long-COVID Symptoms: Scoping Review.}, journal = {Journal of medical Internet research}, volume = {25}, number = {}, pages = {e45711}, pmid = {36943909}, issn = {1438-8871}, mesh = {Adult ; Humans ; *COVID-19 ; Health Personnel ; Mental Health ; *Post-Acute COVID-19 Syndrome/rehabilitation ; *Telerehabilitation ; }, abstract = {BACKGROUND: Patients with post-COVID/long-COVID symptoms need support, and health care professionals need to be able to provide evidence-based patient care. Digital interventions can meet these requirements, especially if personal contact is limited.<br><br>OBJECTIVE: We reviewed evidence-based digital interventions that are currently available to help manage physical and mental health in patients with post-COVID/long-COVID symptoms.<br><br>METHODS: A scoping review was carried out summarizing novel digital health interventions for treating post-COVID/long-COVID patients. Using the PICO (population, intervention, comparison, outcome) scheme, original studies were summarized, in which patients with post-COVID/long-COVID symptoms used digital interventions to help aid recovery.<br><br>RESULTS: From all scanned articles, 8 original studies matched the inclusion criteria. Of the 8 studies, 3 were "pretest" studies, 3 described the implementation of a telerehabilitation program, 1 was a post-COVID/long-COVID program, and 1 described the results of qualitative interviews with patients who used an online peer-support group. Following the PICO scheme, we summarized previous studies. Studies varied in terms of participants (P), ranging from adults in different countries, such as former hospitalized patients with COVID-19, to individuals in disadvantaged communities in the United Kingdom, as well as health care workers. In addition, the studies included patients who had previously been infected with COVID-19 and who had ongoing symptoms. Some studies focused on individuals with specific symptoms, including those with either post-COVID-19 or long-term symptoms, while other studies included patients based on participation in online peer-support groups. The interventions (I) also varied. Most interventions used a combination of psychological and physical exercises, but they varied in duration, frequency, and social dimensions. The reviewed studies investigated the physical and mental health conditions of patients with post-COVID/long-COVID symptoms. Most studies had no control (C) group, and most studies reported outcomes (O) or improvements in physiological health perception, some physical conditions, fatigue, and some psychological aspects such as depression. However, some studies found no improvements in bowel or bladder problems, concentration, short-term memory, unpleasant dreams, physical ailments, perceived bodily pain, emotional ailments, and perceived mental health.<br><br>CONCLUSIONS: More systematic research with larger sample sizes is required to overcome sampling bias and include health care professionals' perspectives, as well as help patients mobilize support from health care professionals and social network partners. The evidence so far suggests that patients should be provided with digital interventions to manage symptoms and reintegrate into everyday life, including work.}, }
@article {pmid36946597, year = {2023}, author = {Lenze, EJ and Reiersen, AM and Zorumski, CF and Santosh, PJ}, title = {Beyond "Psychotropic": Repurposing Psychiatric Drugs for COVID-19, Alzheimer's Disease, and Cancer.}, journal = {The Journal of clinical psychiatry}, volume = {84}, number = {3}, pages = {}, pmid = {36946597}, issn = {1555-2101}, support = {UL1 TR002345/TR/NCATS NIH HHS/United States ; }, mesh = {*Drug Repositioning ; *COVID-19/complications ; *Alzheimer Disease/drug therapy ; *Neoplasms/drug therapy ; *COVID-19 Drug Treatment ; *Mental Disorders/complications/drug therapy ; Humans ; Animals ; Fluvoxamine/therapeutic use ; *Psychotropic Drugs/therapeutic use ; Selective Serotonin Reuptake Inhibitors/therapeutic use ; Post-Acute COVID-19 Syndrome/complications/drug therapy ; }, abstract = {Importance: "Psychotropic" drugs have widespread reach and impact throughout the brain and body. Thus, many of these drugs could be repurposed for non-psychiatric indications of high public health impact. Observations: The selective serotonin reuptake inhibitor (SSRI) fluvoxamine was shown efficacious as a COVID-19 treatment based on randomized controlled trials (RCTs), and a benefit of other antidepressants has been posited based on observational and preclinical studies. In this review, we illuminate features of SSRIs and other psychiatric drugs that make them candidates to repurpose for non-psychiatric indications. We summarize research that led to fluvoxamine's use in COVID-19 and provide guidance on how to use it safely. We summarize studies suggestive of benefit of other antidepressants versus COVID-19 and long COVID. We also describe putative mechanisms of psychiatric drugs in treating long COVID, Alzheimer's disease, cancer, and other conditions. Conclusion and Relevance: There is a potentially great clinical and public health impact of psychotropic drug repurposing. Challenges exist to such repurposing efforts, but solutions exist for researchers, regulators, and funders that overcome these challenges.}, }
@article {pmid36947108, year = {2023}, author = {Sherif, ZA and Gomez, CR and Connors, TJ and Henrich, TJ and Reeves, WB and , }, title = {Pathogenic mechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC).}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {36947108}, issn = {2050-084X}, support = {K08 HL141623/HL/NHLBI NIH HHS/United States ; K23 AI141686/AI/NIAID NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Autoimmunity ; Blood Coagulation ; Disease Progression ; }, abstract = {COVID-19, with persistent and new onset of symptoms such as fatigue, post-exertional malaise, and cognitive dysfunction that last for months and impact everyday functioning, is referred to as Long COVID under the general category of post-acute sequelae of SARS-CoV-2 infection (PASC). PASC is highly heterogenous and may be associated with multisystem tissue damage/dysfunction including acute encephalitis, cardiopulmonary syndromes, fibrosis, hepatobiliary damages, gastrointestinal dysregulation, myocardial infarction, neuromuscular syndromes, neuropsychiatric disorders, pulmonary damage, renal failure, stroke, and vascular endothelial dysregulation. A better understanding of the pathophysiologic mechanisms underlying PASC is essential to guide prevention and treatment. This review addresses potential mechanisms and hypotheses that connect SARS-CoV-2 infection to long-term health consequences. Comparisons between PASC and other virus-initiated chronic syndromes such as myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome will be addressed. Aligning symptoms with other chronic syndromes and identifying potentially regulated common underlining pathways may be necessary for understanding the true nature of PASC. The discussed contributors to PASC symptoms include sequelae from acute SARS-CoV-2 injury to one or more organs, persistent reservoirs of the replicating virus or its remnants in several tissues, re-activation of latent pathogens such as Epstein-Barr and herpes viruses in COVID-19 immune-dysregulated tissue environment, SARS-CoV-2 interactions with host microbiome/virome communities, clotting/coagulation dysregulation, dysfunctional brainstem/vagus nerve signaling, dysautonomia or autonomic dysfunction, ongoing activity of primed immune cells, and autoimmunity due to molecular mimicry between pathogen and host proteins. The individualized nature of PASC symptoms suggests that different therapeutic approaches may be required to best manage specific patients.}, }
@article {pmid36947300, year = {2023}, author = {Muzyka, I and Yakhnytska, M and Savytska, M and Zayachkivska, O}, title = {Long COVID prevalence and physiology-centered risks: population-based study in Ukraine.}, journal = {Inflammopharmacology}, volume = {31}, number = {2}, pages = {597-602}, pmid = {36947300}, issn = {1568-5608}, mesh = {Adult ; Male ; Humans ; Female ; Middle Aged ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Ukraine/epidemiology ; Cohort Studies ; Prevalence ; Prospective Studies ; SARS-CoV-2 ; }, abstract = {AIM: Multifaceted long COVID caused by SARS-COV-2 affects all populations in the World and takes priority over any other research topics for health care. The purpose of study is to identify physiology-centered risks, prevalence, symptoms and laboratory findings in patients with long COVID in Ukraine.<br><br>METHODS: A prospective, cohort study was carried out on 332 patients with long COVID after 4&#xa0;weeks and more after acute infection COVID-19 from Jul 1, 2021, to Jul 1, 2022. Physiology-centered risks related to age, gender, body mass index (BMI), marital status and educational capacity, smoking, lifestyle, physical activity, and laboratory findings (before disease), and symptom distribution were analyzed.<br><br>RESULTS: The cohort for the study consisted of 166 females and 107 males (mean age&#x2009;=&#x2009;42; including young 18 (5.4%) and middle- and old-aged adults 314 (96.4%)). Increased BMI was in 61%, and less physical activity-65%. There were 4 clusters of symptoms related to physical, neurocognitive, pulmonary, and pain conditions. 95% of participants had&#x2009;&#x2265;&#x2009;3 symptoms. The most common symptoms were fatigue (90%), muscular pain (85%), anosmia (70%), hair loss (70%), sleep disorders (70%), dyspnea (30%), and brain fog (25%). Among laboratory finding increased CRP (92.6%) and fibrinogen (82.7%) dominated. There are no differences between hospitalized and non-hospitalized patients in distribution symptoms.<br><br>CONCLUSIONS: The prevalence of long COVID is 23%, and its physiology-centered risk factors are related to age more 38&#xa0;years, female sex, unhealthy lifestyle, increased BMI, and increased inflammatory markers during COVID-19. The most common symptoms are associated with neurocognitive and pain clusters.}, }
@article {pmid36948378, year = {2023}, author = {Gross, M and Lansang, NM and Gopaul, U and Ogawa, EF and Heyn, PC and Santos, FH and Sood, P and Zanwar, PP and Schwertfeger, J and Faieta, J}, title = {What Do I Need to Know About Long-Covid-related Fatigue, Brain Fog, and Mental Health Changes?.}, journal = {Archives of physical medicine and rehabilitation}, volume = {104}, number = {6}, pages = {996-1002}, pmid = {36948378}, issn = {1532-821X}, support = {IK1 RX003636/RX/RRD VA/United States ; }, mesh = {Humans ; *Mental Health ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Fatigue/etiology ; Brain ; }, }
@article {pmid36949968, year = {2023}, author = {Kirkpatrick, K and Khan, MH and Deng, Y and Shah, KB}, title = {A Review of Stellate Ganglion Block as an Adjunctive Treatment Modality.}, journal = {Cureus}, volume = {15}, number = {2}, pages = {e35174}, pmid = {36949968}, issn = {2168-8184}, abstract = {Peripheral nerve blocks are becoming increasingly used as adjunctive treatment modalities for a variety of conditions refractory to medical management. Right or left stellate ganglion blocks (SGB) are a specific type of peripheral nerve block that target the sympathetic blockade of neuronal impulses using the injection of local anesthetic and steroids into nerve bundles in the cervical area. This review article is intended to summarize the common uses of stellate ganglion blocks and explain the procedural technique, which has evolved with technological advances in ultrasonography. The similarities between these disease processes are centered around sympathetic hyperactivity. This sympathetic overdrive state is created by increased levels of nerve growth factor (NGF), which causes a cascade of sympathetic sprouting resulting in increased norepinephrine (NE) systemically. Reversal of this cascade by local anesthetic injection into the stellate ganglion thereby reduces NGF and sympathetic sprouting subsequently lowering overall norepinephrine levels. This is the unifying theory by which SGB is able to provide resolution for the varied clinical conditions described in this article. This review article discusses the physiology of several conditions where stellate ganglion blocks are being investigated as an adjunct treatment modality, including anosmia, PTSD, long-COVID, chronic fatigue syndrome, menopausal hot flashes, and ventricular tachyarrhythmias. Overall, the current literature supporting the use of stellate ganglion blocks for several esoteric conditions is limited; however, case reports to date have shown promising evidence-based results supporting their use as an adjunctive treatment among patients with refractory symptoms to existing treatment algorithms. In conclusion, SGB should be considered among patients with refractory symptoms for medical management in the conditions discussed in this article. Further research is needed to delineate which patients will benefit from the use of SGB, the use of subsequent blocks and timelines in between injections, and unilateral versus bilateral blockade.}, }
@article {pmid36950279, year = {2023}, author = {Stefanou, E and Karvelas, N and Bennett, S and Kole, C}, title = {Cerebrovascular Manifestations of SARS-CoV-2: A Comprehensive Review.}, journal = {Current treatment options in neurology}, volume = {25}, number = {4}, pages = {71-92}, pmid = {36950279}, issn = {1092-8480}, abstract = {PURPOSE OF REVIEW: The risks of cerebrovascular manifestations due to SARS-CoV-2 infection are significantly increased within the first 6 months of the infection. Our work aims to give an update on current clinical aspects of diagnosis and treatment of cerebrovascular manifestations during acute and long-term SARS-CoV-2 infection.<br><br>RECENT FINDINGS: The incidence of acute ischemic stroke and haemorrhagic stroke during acute SARS-CoV-2 patients is estimated at 0.9 to 4.6% and 0.5-0.9%, respectively, and were associated with increased mortality. The majority presented with hemiparesis, dysarthria, sensory deficits, and a NIHSS score within 5-15. In addition, beyond the first 30 days of infection people with COVID-19 exhibited increased risk of stroke. During acute phase, age, hypertension, diabetes, and medical history of vascular disease were increased in patients with COVID-19 with new onset of cerebrovascular manifestations, while during long-COVID-19, the risk of cerebrovascular manifestations were found increased regardless of these factors. The management of patients with large-vessel ischemic stroke fulfilling the intravenous thrombolysis criteria are successfully treated according to the guidelines, while hyperosmolar therapy is typically administered in 4- to 6-h intervals. In addition, prophylaxis of anticoagulation therapy is associated with a better prognosis and low mortality during acute and post hospital discharge of patients with COVID-19.<br><br>SUMMARY: In this work, we provide a comprehensive review of the current literature on acute and post-acute COVID-19 cerebrovascular sequelae, symptomatology, and its pathophysiology mechanisms. Moreover, we discuss therapeutic strategies for these patients during acute and long-term care and point populations at risk. Our findings suggest that older patients with risk factors such as hypertension, diabetes, and medical history of vascular disease are more likely to develop cerebrovascular complications.}, }
@article {pmid36963989, year = {2023}, author = {Nunes, JM and Kell, DB and Pretorius, E}, title = {Cardiovascular and haematological pathology in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): A role for viruses.}, journal = {Blood reviews}, volume = {60}, number = {}, pages = {101075}, pmid = {36963989}, issn = {1532-1681}, mesh = {Humans ; *Fatigue Syndrome, Chronic/etiology/diagnosis ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; SARS-CoV-2 ; }, abstract = {ME/CFS is a debilitating chronic condition that often develops after viral or bacterial infection. Insight from the study of Long COVID/Post Acute Sequelae of COVID-19 (PASC), the post-viral syndrome associated with SARS-CoV-2 infection, might prove to be useful for understanding pathophysiological mechanisms of ME/CFS. Disease presentation is similar between the two conditions, and a subset of Long COVID patients meet the diagnostic criteria for ME/CFS. Since Long COVID is characterized by significant vascular pathology - including endothelial dysfunction, coagulopathy, and vascular dysregulation - the question of whether or not the same biological abnormalities are of significance in ME/CFS arises. Cardiac abnormalities have for a while now been documented in ME/CFS cohorts, with recent studies demonstrating major deficits in cerebral blood flow, and hence vascular dysregulation. A growing body of research is demonstrating that ME/CFS is accompanied by platelet hyperactivation, anomalous clotting, a procoagulant phenotype, and endothelial dysfunction. Endothelial damage and dysregulated clotting can impair substance exchange between blood and tissues, and result in hypoperfusion, which may contribute to the manifestation of certain ME/CFS symptoms. Here we review the ME/CFS literature to summarize cardiovascular and haematological findings documented in patients with the condition, and, in this context, briefly discuss the potential role of previously-implicated pathogens. Overall, cardiac and haematological abnormalities are present within ME/CFS cohorts. While atherosclerotic heart disease is not significantly associated with ME/CFS, suboptimal cardiovascular function defined by reduced cardiac output, impaired cerebral blood flow, and vascular dysregulation are, and these abnormalities do not appear to be influenced by deconditioning. Rather, these cardiac abnormalities may result from dysfunction in the (autonomic) nervous system. Plenty of recently published studies are demonstrating significant platelet hyperactivity and endothelial dysfunction in ME/CFS, as well as anomalous clotting processes. It is of particular importance to determine to what extent these cardiovascular and haematological abnormalities contribute to symptom severity, and if these two systems can be targeted for therapeutic purposes. Viral reservoirs of herpesviruses exist in ME/CFS, and most likely contribute to cardiovascular and haematological dysfunction directly or indirectly. This review highlights the potential of studying cardiac functioning, the vasculature, and coagulation system in ME/CFS.}, }
@article {pmid36964859, year = {2023}, author = {Muzyka, I and Revenko, O and Kovalchuk, I and Savytska, M and Bekesevych, A and Kasko, R and Zayachkivska, O}, title = {What is the role of brown adipose tissue in metabolic health: lessons learned and future perspectives in the long COVID?.}, journal = {Inflammopharmacology}, volume = {31}, number = {2}, pages = {585-595}, pmid = {36964859}, issn = {1568-5608}, mesh = {Animals ; Adult ; Humans ; *Adipose Tissue, Brown/metabolism ; Post-Acute COVID-19 Syndrome ; *COVID-19/metabolism ; Obesity/metabolism ; }, abstract = {Metabolic physiology plays a key role in maintaining our health and resilience. Metabolic disorders can lead to serious illnesses, including obesity. The pathogenesis of the new long COVID syndrome in individuals with long-term recovery after SARS-Co-2 infection is still incomplete. Thus there is growing attention in the study of adipose tissue activities, especially brown adipose tissue (BAT) and associated resilience which plays a crucial role in different types of obesity as potential targets for pharmacologic and nutritional interventions in the context of obesity and long COVID. The number of studies examining mechanisms underlying BAT has grown rapidly in the last 10 years despite of role of BAT in individuals with COVID-19 and long COVID is modest. Therefore, this review aims to sum up data examining BAT activities, its resilience in health, obesity, and the possible link to long COVID. The search was conducted on studies published in English mostly between 2004 and 2022 in adult humans and animal models. Database searches were conducted using PubMed, Scopus, and Google Scholar for key terms including adipose tissue, BAT, adipokines, obesity, VPF/VEGF, and pathogenesis. From the initial search through the database were identified relevant articles that met inclusion and exclusion criteria and our data regarding adipose tissues were presented in this review. It will discuss adiposity tissue activities. Current literature suggests that there are BAT integral effects to whitening and browning fat phenomena which reflect the homeostatic metabolic adaptive ability for environmental demand or survival/adaptive mechanisms. We also review neural and vascular impacts in BAT that play a role in resilience and obesity. Finally, we discuss the role of BAT in the context of long COVID in basic research and clinical research.}, }
@article {pmid36964860, year = {2023}, author = {Szabo, S and Zayachkivska, O and Hussain, A and Muller, V}, title = {What is really 'Long COVID'?.}, journal = {Inflammopharmacology}, volume = {31}, number = {2}, pages = {551-557}, pmid = {36964860}, issn = {1568-5608}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Brain ; Post-Acute COVID-19 Syndrome ; China/epidemiology ; }, abstract = {The previous acute respiratory diseases caused by viruses originating from China or the middle east (e.g., SARS, MERS) remained fast developing short diseases without major sequalae or any long-lasting complications. The new COVID-19, on the other hand, not only that it rapidly spread over the world, but some patients never fully recovered or even if they did, a few weeks later started to complain not only of shortness of breath, if any, but general weakness, muscle pains and 'brain fog', i.e., fuzzy memories. Thus, these signs and symptoms were eventually labelled 'long COVID', for which the most widely used definition is 'new signs and symptoms occurring 4-8 weeks after recovering from acute stage of COVID-19'. The other most frequent manifestations associated with long COVID include headache, loss of memory, smell and of hair, nausea, and vomiting. Thus, long COVID is not a simple disease, but complex disorder of several organ systems malfunctioning; hence, it is probably more appropriate to call this a syndrome. The pathogenesis of long COVID syndrome is poorly understood, but initial and persistent vascular endothelial injury that often triggers the formation of microthrombi that if dislodged as emboli, damage several organs, especially in the brain, heart and kidney, by creating microinfarcts. The other major contributory mechanistic factor is the persistent cytokine storm that may last longer in long COVID patients than in others, probably triggered by aggregates of SARS-Co-2 discovered recently in the adrenal cortex, kidney and brain. The prevalence of long COVID is relatively high, e.g., initially varied 3-30%, and recent data indicate that 2.5% of UK population suffers from this syndrome, while in the US 14.7% of acute COVID-19 patients continued to have symptoms longer than 2 months. Thus, the long COVID syndrome deserves to be further investigated, both from clinical and basic research perspectives.}, }
@article {pmid36964995, year = {2023}, author = {Haslam, A and Olivier, T and Prasad, V}, title = {The definition of long COVID used in interventional studies.}, journal = {European journal of clinical investigation}, volume = {53}, number = {8}, pages = {e13989}, doi = {10.1111/eci.13989}, pmid = {36964995}, issn = {1365-2362}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Randomized Controlled Trials as Topic ; }, abstract = {INTRODUCTION: There has been little consensus for a specific definition of long COVID, though several organizations have created varying ones. We sought to examine the definition of long COVID used in ongoing clinical trials.<br><br>METHODS: We searched 'long COVID' and related terms on both PubMed and clinicaltrials.gov for randomized studies that either included patients with long COVID or had a persistent or long-term COVID-related outcome and abstracted long COVID definition components.<br><br>RESULTS: Of the 92 studies, a laboratory-only confirmed diagnosis of COVID-19 was stipulated in 54.3% (n&#x2009;=&#x2009;50) studies. We found eight different time durations specified for how long symptoms needed to have occurred, ranging from 4 to 52&#x2009;weeks, with 12&#x2009;weeks being the most common (34.8%; n&#x2009;=&#x2009;32). 35.9% (n&#x2009;=&#x2009;33) did not specify a time duration. There were 57 different symptoms specified in total, with a median of one symptom identified per study (range 0-32). 8.7% of trials adhered to NICE or WHO definitions.<br><br>CONCLUSION: Standardized definitions of long COVID should be applied in studies assessing this condition to unify and harmonize research on this topic.}, }
@article {pmid36966955, year = {2023}, author = {Gradidge, PJ and Torres, G and Constantinou, D and Zanwar, PP and Pinto, SM and Negm, A and Heyn, PC and , }, title = {Exercise Reporting Template for Long COVID Patients: A Rehabilitation Practitioner Guide.}, journal = {Archives of physical medicine and rehabilitation}, volume = {104}, number = {6}, pages = {991-995}, pmid = {36966955}, issn = {1532-821X}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Exercise ; Disease Progression ; }, }
@article {pmid36968333, year = {2023}, author = {Sari, DM and Wijaya, LCG}, title = {General rehabilitation for the Post-COVID-19 condition: A narrative review.}, journal = {Annals of thoracic medicine}, volume = {18}, number = {1}, pages = {10-14}, pmid = {36968333}, issn = {1817-1737}, abstract = {COVID-19 significantly impacts the acute phase or the period after being infected by severe acute respiratory syndrome coronavirus-2. Studies have shown it has affected multiorgan and needs continuous care by a multidisciplinary team. Nowadays, guidance is required to assist the recovery process of survivors who reported at least one symptom as a residual effect. This study aims to describe the rehabilitation management of post-COVID-19 conditions. As the number of survivors seems to be increasing, it is expected that COVID-19 survivors will recover through a holistic approach by all physicians. Comprehensive rehabilitation for long COVID or COVID-19-related illnesses includes exercising, nutrition, education, managing voice, breathlessness, neurocognitive problems, mental health, feeding problems, and daily activities. Specific recommendations have already been published to support rehabilitation for survivors in every targeted organ. Supportive care, especially rehabilitation programs, is recently an urgent knowledge in this pandemic.}, }
@article {pmid36968793, year = {2023}, author = {Hashimoto, K}, title = {Overview of the potential use of fluvoxamine for COVID-19 and long COVID.}, journal = {Discover mental health}, volume = {3}, number = {1}, pages = {9}, pmid = {36968793}, issn = {2731-4383}, abstract = {Coronavirus disease 2019 (COVID-19) has presented a serious worldwide threat to public health since its emergence in late 2019. From a safety point of view, drug repurposing has received particular attention. Several clinical studies have demonstrated that the use of fluvoxamine, a selective serotonin reuptake inhibitor with potent sigma-1 receptor agonism, in the early-stage of infection might be associated with the prevention of clinical deterioration in individuals with SARS-CoV-2 infection, although several reports have shown that a low dose of fluvoxamine may be ineffective. There is increasing evidence that SARS-CoV-2 can cross the blood-brain barrier, resulting in a number of psychiatric and neurologic symptoms in COVID-19 survivors. Importantly, about half of COVID-19 survivors experience a variety of long-term sequelae, including psychiatric and neurologic symptoms, known as long COVID. In this priority review, the author presents an overview of the potential use of fluvoxamine in the treatment of COVID-19 and long COVID.}, }
@article {pmid36969241, year = {2023}, author = {Bonilla, H and Peluso, MJ and Rodgers, K and Aberg, JA and Patterson, TF and Tamburro, R and Baizer, L and Goldman, JD and Rouphael, N and Deitchman, A and Fine, J and Fontelo, P and Kim, AY and Shaw, G and Stratford, J and Ceger, P and Costantine, MM and Fisher, L and O'Brien, L and Maughan, C and Quigley, JG and Gabbay, V and Mohandas, S and Williams, D and McComsey, GA}, title = {Therapeutic trials for long COVID-19: A call to action from the interventions taskforce of the RECOVER initiative.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1129459}, pmid = {36969241}, issn = {1664-3224}, support = {K23 AI157875/AI/NIAID NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; }, mesh = {United States ; Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Virus Diseases ; Motivation ; }, abstract = {Although most individuals recover from acute SARS-CoV-2 infection, a significant number continue to suffer from Post-Acute Sequelae of SARS-CoV-2 (PASC), including the unexplained symptoms that are frequently referred to as long COVID, which could last for weeks, months, or even years after the acute phase of illness. The National Institutes of Health is currently funding large multi-center research programs as part of its Researching COVID to Enhance Recover (RECOVER) initiative to understand why some individuals do not recover fully from COVID-19. Several ongoing pathobiology studies have provided clues to potential mechanisms contributing to this condition. These include persistence of SARS-CoV-2 antigen and/or genetic material, immune dysregulation, reactivation of other latent viral infections, microvascular dysfunction, and gut dysbiosis, among others. Although our understanding of the causes of long COVID remains incomplete, these early pathophysiologic studies suggest biological pathways that could be targeted in therapeutic trials that aim to ameliorate symptoms. Repurposed medicines and novel therapeutics deserve formal testing in clinical trial settings prior to adoption. While we endorse clinical trials, especially those that prioritize inclusion of the diverse populations most affected by COVID-19 and long COVID, we discourage off-label experimentation in uncontrolled and/or unsupervised settings. Here, we review ongoing, planned, and potential future therapeutic interventions for long COVID based on the current understanding of the pathobiological processes underlying this condition. We focus on clinical, pharmacological, and feasibility data, with the goal of informing future interventional research studies.}, }
@article {pmid36969243, year = {2023}, author = {Ancona, G and Alagna, L and Alteri, C and Palomba, E and Tonizzo, A and Pastena, A and Muscatello, A and Gori, A and Bandera, A}, title = {Gut and airway microbiota dysbiosis and their role in COVID-19 and long-COVID.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1080043}, pmid = {36969243}, issn = {1664-3224}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Dysbiosis ; *Gastrointestinal Microbiome/physiology ; }, abstract = {The gut microbiota plays a crucial role in human health and disease. Gut dysbiosis is known to be associated with increased susceptibility to respiratory diseases and modifications in the immune response and homeostasis of the lungs (the so-called gut-lung axis). Furthermore, recent studies have highlighted the possible role of dysbiosis in neurological disturbances, introducing the notion of the "gut-brain axis." During the last 2 years, several studies have described the presence of gut dysbiosis during coronavirus disease 2019 (COVID-19) and its relationship with disease severity, SARS-CoV-2 gastrointestinal replication, and immune inflammation. Moreover, the possible persistence of gut dysbiosis after disease resolution may be linked to long-COVID syndrome and particularly to its neurological manifestations. We reviewed recent evidence on the association between dysbiosis and COVID-19, investigating the possible epidemiologic confounding factors like age, location, sex, sample size, the severity of disease, comorbidities, therapy, and vaccination status on gut and airway microbial dysbiosis in selected studies on both COVID-19 and long-COVID. Moreover, we analyzed the confounding factors strictly related to microbiota, specifically diet investigation and previous use of antibiotics/probiotics, and the methodology used to study the microbiota (α- and β-diversity parameters and relative abundance tools). Of note, only a few studies focused on longitudinal analyses, especially for long-term observation in long-COVID. Lastly, there is a lack of knowledge regarding the role of microbiota transplantation and other therapeutic approaches and their possible impact on disease progression and severity. Preliminary data seem to suggest that gut and airway dysbiosis might play a role in COVID-19 and in long-COVID neurological symptoms. Indeed, the development and interpretation of these data could have important implications for future preventive and therapeutic strategies.}, }
@article {pmid36977491, year = {2023}, author = {Bandara, T and Deshmukh, HA and Abdalla, M and Sathyapalan, T}, title = {Metabolic and Endocrine Complications of Long-COVID-19: A Review.}, journal = {Experimental and clinical endocrinology &amp; diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association}, volume = {131}, number = {6}, pages = {367-374}, doi = {10.1055/a-2063-8697}, pmid = {36977491}, issn = {1439-3646}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Endocrine System ; }, abstract = {Over the past two years, the outbreak of coronavirus disease of 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has centralized the interest of the health care systems and the scientific world. The majority of COVID-19-infected individuals recover fully. However, about 12-50% of patients experience various mid- and long-term effects after recovering from the initial illness. These mid- and long-term effects are collectively known as post-COVID-19 condition or 'long-COVID'. In the coming months, the long-term consequences of COVID-19 on the metabolic and endocrine systems may expect to rise and pose a global healthcare challenge. This review article discusses the possible metabolic and endocrine complications of long-COVID and the relevant research findings.}, }
@article {pmid36977809, year = {2023}, author = {Stefano, GB and Büttiker, P and Weissenberger, S and Anders, M and Raboch, J and Ptacek, R and Kream, RM}, title = {Potential Prion Involvement in Long COVID-19 Neuropathology, Including Behavior.}, journal = {Cellular and molecular neurobiology}, volume = {43}, number = {6}, pages = {2621-2626}, pmid = {36977809}, issn = {1573-6830}, mesh = {Humans ; Animals ; *Prions/metabolism ; Post-Acute COVID-19 Syndrome ; Reactive Oxygen Species ; *COVID-19 ; SARS-CoV-2 ; Mammals/metabolism ; }, abstract = {Prion' is a term used to describe a protein infectious particle responsible for several neurodegenerative diseases in mammals, e.g., Creutzfeldt-Jakob disease. The novelty is that it is protein based infectious agent not involving a nucleic acid genome as found in viruses and bacteria. Prion disorders exhibit, in part, incubation periods, neuronal loss, and induce abnormal folding of specific normal cellular proteins due to enhancing reactive oxygen species associated with mitochondria energy metabolism. These agents may also induce memory, personality and movement abnormalities as well as depression, confusion and disorientation. Interestingly, some of these behavioral changes also occur in COVID-19 and mechanistically include mitochondrial damage caused by SARS-CoV-2 and subsequenct production of reactive oxygen species. Taken together, we surmise, in part, long COVID may involve the induction of spontaneous prion emergence, especially in individuals susceptible to its origin may thus explain some of its manesfestions post-acute viral infection.}, }
@article {pmid36981968, year = {2023}, author = {Avittan, H and Kustovs, D}, title = {Cognition and Mental Health in Pediatric Patients Following COVID-19.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {6}, pages = {}, pmid = {36981968}, issn = {1660-4601}, mesh = {Humans ; Child ; *COVID-19/epidemiology ; Mental Health ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Anxiety/epidemiology/psychology ; Cognition ; }, abstract = {The global coronavirus pandemic has significantly impacted public health and has been a research subject since its emergence in 2019. The acute phase of the disease leads to pulmonary and non-pulmonary manifestations, which in some individuals may progress to long-lasting symptoms. In this article, we conducted a narrative review of the current literature to summarize current knowledge regarding long COVID syndrome in children, focusing on cognitive symptoms. The review included a search of three databases (PubMed, Embase, and Web of Science) using the key phrases "post COVID-19 cognitive pediatric", "long COVID pediatric", "mental health long COVID children", and "COVID-19 cognitive symptoms". A total of 102 studies were included. The review revealed that the main long-term cognitive symptoms following COVID-19 were memory and concentration deficits, sleep disturbances, and psychiatric states such as anxiety and stress. In addition to the direct physiological effects of a viral infection, there are psychological, behavioral, and social factors contributing to cognitive impairment, which should be addressed regarding the pediatric population. The high prevalence of neurocognitive symptoms in children following COVID-19 emphasizes the importance of understanding the mechanisms of nervous system involvement.}, }
@article {pmid36982194, year = {2023}, author = {Tate, WP and Walker, MOM and Peppercorn, K and Blair, ALH and Edgar, CD}, title = {Towards a Better Understanding of the Complexities of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID.}, journal = {International journal of molecular sciences}, volume = {24}, number = {6}, pages = {}, pmid = {36982194}, issn = {1422-0067}, support = {no grant number//ANZMES -NZA ME/CFS natiuonal disease advisory association/ ; }, mesh = {Humans ; *Fatigue Syndrome, Chronic/etiology/therapy/diagnosis ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; Causality ; }, abstract = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex condition arising in susceptible people, predominantly following viral infection, but also other stressful events. The susceptibility factors discussed here are both genetic and environmental although not well understood. While the dysfunctional physiology in ME/CFS is becoming clearer, understanding has been hampered by different combinations of symptoms in each affected person. A common core set of mainly neurological symptoms forms the modern clinical case definition, in the absence of an accessible molecular diagnostic test. This landscape has prompted interest in whether ME/CFS patients can be classified into a particular phenotype/subtype that might assist better management of their illness and suggest preferred therapeutic options. Currently, the same promising drugs, nutraceuticals, or behavioral therapies available can be beneficial, have no effect, or be detrimental to each individual patient. We have shown that individuals with the same disease profile exhibit unique molecular changes and physiological responses to stress, exercise and even vaccination. Key features of ME/CFS discussed here are the possible mechanisms determining the shift of an immune/inflammatory response from transient to chronic in ME/CFS, and how the brain and CNS manifests the neurological symptoms, likely with activation of its specific immune system and resulting neuroinflammation. The many cases of the post viral ME/CFS-like condition, Long COVID, following SARS-CoV-2 infection, and the intense research interest and investment in understanding this condition, provide exciting opportunities for the development of new therapeutics that will benefit ME/CFS patients.}, }
@article {pmid36982693, year = {2023}, author = {Mancini, M and Natoli, S and Gardoni, F and Di Luca, M and Pisani, A}, title = {Dopamine Transmission Imbalance in Neuroinflammation: Perspectives on Long-Term COVID-19.}, journal = {International journal of molecular sciences}, volume = {24}, number = {6}, pages = {}, pmid = {36982693}, issn = {1422-0067}, support = {ID 3433068//Fondazione Regionale per la Ricerca Biomedica, Regione Lombardia/ ; }, mesh = {Humans ; Dopamine/metabolism ; Neuroinflammatory Diseases ; *COVID-19 ; SARS-CoV-2/metabolism ; *Parkinson Disease/metabolism ; alpha-Synuclein/metabolism ; }, abstract = {Dopamine (DA) is a key neurotransmitter in the basal ganglia, implicated in the control of movement and motivation. Alteration of DA levels is central in Parkinson's disease (PD), a common neurodegenerative disorder characterized by motor and non-motor manifestations and deposition of alpha-synuclein (α-syn) aggregates. Previous studies have hypothesized a link between PD and viral infections. Indeed, different cases of parkinsonism have been reported following COVID-19. However, whether SARS-CoV-2 may trigger a neurodegenerative process is still a matter of debate. Interestingly, evidence of brain inflammation has been described in postmortem samples of patients infected by SARS-CoV-2, which suggests immune-mediated mechanisms triggering the neurological sequelae. In this review, we discuss the role of proinflammatory molecules such as cytokines, chemokines, and oxygen reactive species in modulating DA homeostasis. Moreover, we review the existing literature on the possible mechanistic interplay between SARS-CoV-2-mediated neuroinflammation and nigrostriatal DAergic impairment, and the cross-talk with aberrant α-syn metabolism.}, }
@article {pmid36985286, year = {2023}, author = {Amiama-Roig, A and Pérez-Martínez, L and Rodríguez Ledo, P and Verdugo-Sivianes, EM and Blanco, JR}, title = {Should We Expect an Increase in the Number of Cancer Cases in People with Long COVID?.}, journal = {Microorganisms}, volume = {11}, number = {3}, pages = {}, pmid = {36985286}, issn = {2076-2607}, abstract = {The relationship between viral infections and the risk of developing cancer is well known. Multiple mechanisms participate in and determine this process. The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in the deaths of millions of people worldwide. Although the effects of COVID-19 are limited for most people, a large number of people continue to show symptoms for a long period of time (long COVID). Several studies have suggested that cancer could also be a potential long-term complication of the virus; however, the causes of this risk are not yet well understood. In this review, we investigated arguments that could support or reject this possibility.}, }
@article {pmid36987476, year = {2023}, author = {Bankole, AA and Nwaonu, J and Saeed, J}, title = {Impact of SARS-CoV-2/COVID-19 on Provision of Medical Care to Patients With Systemic Autoimmune Rheumatic Disease and the Practice of Rheumatology.}, journal = {Cureus}, volume = {15}, number = {2}, pages = {e35402}, pmid = {36987476}, issn = {2168-8184}, abstract = {The SARS-CoV-2 pandemic has had a significant impact on the healthcare field that resulted in changes to the way safe and effective medical care is delivered. The effects range from service disruption including ambulatory clinic closure due to both patient and provider concerns, to lack of capacity in hospital services. In rheumatology, there were other effects including viral infection-related autoantibody production, concerns about the use of systemic immunosuppression in the presence of an infectious pandemic and even concerns for viral infection-induced flares of rheumatic disease. Coronavirus disease 2019 (COVID-19) led to the rapid adoption of innovative technologies that permitted the introduction and increased use of telemedicine via a number of platforms. Rapid discoveries and innovations led to the development of diagnostic and therapeutic agents in the management of COVID-19. Scientific advancement and discoveries around COVID-19 infection, symptoms, autoantibody production, chronic sequela and the repurposing of rheumatic immunosuppressive agents led to improved survival and an expanded role for the rheumatologist. Rheumatologists may sometimes be involved in the diagnosis and management of the hospitalized COVID-19 patient. In the ambulatory clinic, a rheumatologist also helps to differentiate between symptoms of long COVID and those of systemic autoimmune rheumatic disease (SARD). Rheumatologists must also grapple with the concerns related to immunosuppressive therapy and the risk of COVID-19 infections. In addition, there are concerns around vaccine effectiveness in people with SARD and those on immunosuppressive medications. Although the SARS-CoV-2 pandemic and the effects on healthcare resulted in difficulties, both patients and providers have risen to the challenge. The long-term outcome of COVID-19 for the medical system and rheumatologists in particular is not yet fully understood and will need further study. This review concentrates on the changing role of the rheumatologists, improved understanding of rheumatic disease and immunosuppressive therapies in the wake of the pandemic and how this has led to an improvement in the care of patients with COVID-19.}, }
@article {pmid36990297, year = {2023}, author = {Ceban, F and Kulzhabayeva, D and Rodrigues, NB and Di Vincenzo, JD and Gill, H and Subramaniapillai, M and Lui, LMW and Cao, B and Mansur, RB and Ho, RC and Burke, MJ and Rhee, TG and Rosenblat, JD and McIntyre, RS}, title = {COVID-19 vaccination for the prevention and treatment of long COVID: A systematic review and meta-analysis.}, journal = {Brain, behavior, and immunity}, volume = {111}, number = {}, pages = {211-229}, pmid = {36990297}, issn = {1090-2139}, mesh = {Humans ; *COVID-19 Vaccines ; Post-Acute COVID-19 Syndrome ; *COVID-19/prevention &amp; control ; SARS-CoV-2 ; Vaccination ; Phenols ; Thiazoles ; }, abstract = {Empirical evidence addressing the association between SARS-CoV-2 vaccination and long COVID would guide public health priorities and inform personal health decisions. Herein, the co-primary objectives are to determine the differential risk of long COVID in vaccinated versus unvaccinated patients, and the trajectory of long COVID following vaccination. Of 2775 articles identified via systematic search, 17 were included, and 6 were meta-analyzed. Meta-analytic results determined that at least one vaccine dose was associated with a protective effect against long COVID (OR 0.539, 95% CI 0.295-0.987, p = 0.045, N = 257 817). Qualitative analysis revealed that trajectories of pre-existing long COVID following vaccination were mixed, with most patients reporting no changes. The evidence herein supports SARS-CoV-2 vaccination for the prevention of long COVID, and recommends long COVID patients adhere to standard SARS-CoV-2 vaccination schedules.}, }
@article {pmid36990762, year = {2023}, author = {O'Driscoll, DM and Young, AC}, title = {Contemporary Concise Review 2022: Sleep.}, journal = {Respirology (Carlton, Vic.)}, volume = {28}, number = {6}, pages = {518-524}, doi = {10.1111/resp.14500}, pmid = {36990762}, issn = {1440-1843}, mesh = {Humans ; *Sleep Initiation and Maintenance Disorders/epidemiology/therapy ; Pandemics ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications/epidemiology ; Sleep ; *Sleep Apnea, Obstructive/complications/epidemiology/therapy ; }, abstract = {COVID-19 AND SLEEP: The COVID-19 pandemic is associated with an increase in insomnia and impaired sleep quality Health care workers are particularly susceptible and improved with cognitive behavioural therapy for insomnia (CBT-I) Long COVID has significant effects on sleep OSA impacts on the severity of acute COVID-19 illness OBSTRUCTIVE SLEEP APNOEA: Large trials of clinically representative patients confirm the cardiovascular benefits of CPAP treatment in OSA CPAP may improve long-term cognitive outcomes in OSA, but further research is needed Racial disparities in OSA prevalence and mortality risk are becoming evident Periodic evaluation of OSA risk in pregnancy is important as timing may be key for intervention to prevent or treat cardiovascular risk factors INSOMNIA: Comorbid insomnia and obstructive sleep apnoea (COMISA) can frequently co-exist and the combined negative effects of both may be deleterious, particularly to cardiovascular health There is evidence for effectiveness with novel orexin receptor antagonists.}, }
@article {pmid36990807, year = {2023}, author = {Maher, M and Owens, L}, title = {SARS-CoV-2 infection and female reproductive health: A narrative review.}, journal = {Best practice &amp; research. Clinical endocrinology &amp; metabolism}, volume = {37}, number = {4}, pages = {101760}, pmid = {36990807}, issn = {1878-1594}, mesh = {Pregnancy ; Female ; Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Pandemics ; Post-Acute COVID-19 Syndrome ; Reproductive Health ; }, abstract = {The COVID-19 pandemic has had a profound global impact, affecting people's physical and mental health, and their social and economic circumstances. Mitigation measures have disproportionately affected women. Studies have reported menstrual cycle and psychological disturbance associated with the pandemic. Pregnancy is a risk factor for severe COVID-19 disease. Reports have also demonstrated associations between COVID-19 infection, vaccination and Long COVID syndrome and reproductive health disturbance. However, studies are limited and there may be significant geographical variation. Also there is bias amongst published studies, and menstrual cycle data was not included in COVID-19 and vaccine trials. Longitudinal population based studies are required. In this review we discuss existing data, along with recommendations for further research required in this area. We also discuss a pragmatic approach to women presenting with reproductive health disturbance in the era of the pandemic, encompassing a multi-system assessment of psychological, reproductive health and lifestyle.}, }
@article {pmid36992283, year = {2023}, author = {Dhawan, M and Rabaan, AA and Alwarthan, S and Alhajri, M and Halwani, MA and Alshengeti, A and Najim, MA and Alwashmi, ASS and Alshehri, AA and Alshamrani, SA and AlShehail, BM and Garout, M and Al-Abdulhadi, S and Al-Ahmed, SH and Thakur, N and Verma, G}, title = {Regulatory T Cells (Tregs) and COVID-19: Unveiling the Mechanisms, and Therapeutic Potentialities with a Special Focus on Long COVID.}, journal = {Vaccines}, volume = {11}, number = {3}, pages = {}, pmid = {36992283}, issn = {2076-393X}, abstract = {The COVID-19 pandemic has caused havoc all around the world. The causative agent of COVID-19 is the novel form of the coronavirus (CoV) named SARS-CoV-2, which results in immune system disruption, increased inflammation, and acute respiratory distress syndrome (ARDS). T cells have been important components of the immune system, which decide the fate of the COVID-19 disease. Recent studies have reported an important subset of T cells known as regulatory T cells (Tregs), which possess immunosuppressive and immunoregulatory properties and play a crucial role in the prognosis of COVID-19 disease. Recent studies have shown that COVID-19 patients have considerably fewer Tregs than the general population. Such a decrement may have an impact on COVID-19 patients in a number of ways, including diminishing the effect of inflammatory inhibition, creating an inequality in the Treg/Th17 percentage, and raising the chance of respiratory failure. Having fewer Tregs may enhance the likelihood of long COVID development in addition to contributing to the disease's poor prognosis. Additionally, tissue-resident Tregs provide tissue repair in addition to immunosuppressive and immunoregulatory activities, which may aid in the recovery of COVID-19 patients. The severity of the illness is also linked to abnormalities in the Tregs' phenotype, such as reduced expression of FoxP3 and other immunosuppressive cytokines, including IL-10 and TGF-beta. Hence, in this review, we summarize the immunosuppressive mechanisms and their possible roles in the prognosis of COVID-19 disease. Furthermore, the perturbations in Tregs have been associated with disease severity. The roles of Tregs are also explained in the long COVID. This review also discusses the potential therapeutic roles of Tregs in the management of patients with COVID-19.}, }
@article {pmid36995436, year = {2023}, author = {Fedorchenko, Y and Zimba, O}, title = {Long COVID in autoimmune rheumatic diseases.}, journal = {Rheumatology international}, volume = {43}, number = {7}, pages = {1197-1207}, pmid = {36995436}, issn = {1437-160X}, mesh = {Humans ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Autoimmune Diseases/complications ; *Rheumatic Diseases/drug therapy ; }, abstract = {Consequences of Corona Virus Disease-19 (COVID-19) in patients with rheumatic diseases (RDs) are clinically diverse. SARS-CoV-2 infection has been associated with various autoimmune and rheumatic manifestations over the past three years. Emerging evidence points to the possibility of Long COVID predisposition in rheumatic patients due to the changes in immune regulatory response. The aim of this article was to overview data on the pathobiology of Long COVID in patients with RDs. Related risk factors, clinical characteristics, and prognosis of Long COVID in RDs were analyzed. Relevant articles were retrieved from Medline/PubMed, Scopus, and Directory of Open Access Journals (DOAJ). Diverse mechanisms of viral persistence, chronic low-grade inflammation, lasting production of autoantibodies, endotheliopathy, vascular complications, and permanent tissue damage have been described in association with Long COVID. Patients with RDs who survive COVID-19 often experience severe complications due to the immune disbalance resulting in multiple organ damage. Regular monitoring and treatment are warranted in view of the accumulating evidence.}, }
@article {pmid36998202, year = {2023}, author = {Hammarström, P and Nyström, S}, title = {Viruses and amyloids - a vicious liaison.}, journal = {Prion}, volume = {17}, number = {1}, pages = {82-104}, pmid = {36998202}, issn = {1933-690X}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Viruses ; *Virus Diseases/complications ; Amyloid ; Viral Proteins ; }, abstract = {The crosstalk between viral infections, amyloid formation and neurodegeneration has been discussed with varying intensity since the last century. Several viral proteins are known to be amyloidogenic. Post-acute sequalae (PAS) of viral infections is known for several viruses. SARS-CoV-2 and COVID-19 implicate connections between amyloid formation and severe outcomes in the acute infection, PAS and neurodegenerative diseases. Is the amyloid connection causation or just correlation? In this review we highlight several aspects where amyloids and viruses meet. The evolutionary driving forces that dictate protein amyloid formation propensity are different for viruses compared to prokaryotes and eukaryotes, while posttranslational endoproteolysis appears to be a common mechanism leading up to amyloid formation for both viral and human proteins. Not only do human and viral proteins form amyloid irrespective of each other but there are also several examples of co-operativity between amyloids, viruses and the inter-, and intra-host spread of the respective entity. Abnormal blood clotting in severe and long COVID and as a side effect in some vaccine recipients has been connected to amyloid formation of both the human fibrin and the viral Spike-protein. We conclude that there are many intersects between viruses and amyloids and, consequently, amyloid and virus research need to join forces here. We emphasize the need to accelerate development and implementation in clinical practice of antiviral drugs to preclude PAS and downstream neurological damage. There is also an ample need for retake on suitable antigen targets for the further development of next generation of vaccines against the current and coming pandemics.}, }
@article {pmid37004544, year = {2023}, author = {Peron, JPS}, title = {Direct and indirect impact of SARS-CoV-2 on the brain.}, journal = {Human genetics}, volume = {142}, number = {8}, pages = {1317-1326}, pmid = {37004544}, issn = {1432-1203}, support = {2020/06145-4//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; 2017/26170-0//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; 316646/2021-0//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; }, mesh = {Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Brain ; *Brain Diseases ; }, abstract = {Although COVID-19 is mostly a pulmonary disease, it is now well accepted that it can cause a much broader spectrum of signs and symptoms and affect many other organs and tissue. From mild anosmia to severe ischemic stroke, the impact of SARS-CoV-2 on the central nervous system is still a great challenge to scientists and health care practitioners. Besides the acute and severe neurological problems described, as encephalopathies, leptomeningitis, and stroke, after 2 years of pandemic, the chronic impact observed during long-COVID or the post-acute sequelae of COVID-19 (PASC) greatly intrigues scientists worldwide. Strikingly, even asymptomatic, and mild diseased patients may evolve with important neurological and psychiatric symptoms, as confusion, memory loss, cognitive decline, chronic fatigue, associated or not with anxiety and depression. Thus, the knowledge on the correlation between COVID-19 and the central nervous system is of great relevance. In this sense, here we discuss some important mechanisms obtained from in vitro and in vivo investigation regarding how SARS-CoV-2 impacts the brain and its cells and function.}, }
@article {pmid37005767, year = {2023}, author = {Glassman, I and Le, N and Mirhosseini, M and Alcantara, CA and Asif, A and Goulding, A and Muneer, S and Singh, M and Robison, J and Guilford, F and Venketaraman, V}, title = {The Role of Glutathione in Prevention of COVID-19 Immunothrombosis: A Review.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {28}, number = {3}, pages = {59}, pmid = {37005767}, issn = {2768-6698}, support = {R15 HL143545/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/prevention &amp; control ; Thromboinflammation ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Glutathione/therapeutic use ; }, abstract = {Immunothrombosis has emerged as a dominant pathological process exacerbating morbidity and mortality in acute- and long-COVID-19 infections. The hypercoagulable state is due in part to immune system dysregulation, inflammation and endothelial cell damage, as well as a reduction in defense systems. One defense mechanism in particular is glutathione (GSH), a ubiquitously found antioxidant. Evidence suggests that reduction in GSH increases viral replication, pro-inflammatory cytokine release, and thrombosis, as well as decreases macrophage-mediated fibrin removal. The collection of adverse effects as a result of GSH depletion in states like COVID-19 suggest that GSH depletion is a dominant mechanism of immunothrombosis cascade. We aim to review the current literature on the influence of GSH on COVID-19 immunothrombosis pathogenesis, as well as the beneficial effects of GSH as a novel therapeutic for acute- and long-COVID-19.}, }
@article {pmid37020055, year = {2023}, author = {Percze, AR and Nagy, A and Polivka, L and Barczi, E and Czaller, I and Kovats, Z and Varga, JT and Ballai, JH and Muller, V and Horvath, G}, title = {Fatigue, sleepiness and sleep quality are SARS-CoV-2 variant independent in patients with long COVID symptoms.}, journal = {Inflammopharmacology}, volume = {31}, number = {6}, pages = {2819-2825}, pmid = {37020055}, issn = {1568-5608}, mesh = {Humans ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Sleep Quality ; Sleepiness ; Retrospective Studies ; *COVID-19/complications ; Fatigue/complications/epidemiology ; }, abstract = {Acute infections with SARS-CoV-2 variants of concerns (VOCs) differ in clinical presentation. Discrepancies in their long-term sequelae, commonly referred to as long COVID, however, remain to be explored. We retrospectively analyzed data of 287 patients presented at the post-COVID care of the Pulmonology Department, Semmelweis University, Budapest, Hungary, and infected with SARS-CoV-2 during a period of 3 major epidemic waves in Hungary (February-July 2021, VOC: B.1.1.7, Alpha, N = 135; August-December 2021, VOC: B.1.617.2, Delta, N = 89; and January-June 2022, VOC: B.1.1.529, Omicron; N = 63), > 4 weeks after acute COVID-19. Overall, the ratio of long COVID symptomatic (LC) and asymptomatic (NS) patients was 2:1. Self-reported questionnaires on fatigue (Fatigue Severity Scale, FSS), sleepiness (Epworth Sleepiness Scale, ESS) and sleep quality (Pittsburgh Sleep Quality Index, PSQI) showed higher scores for LC (4.79 ± 0.12, 7.45 ± 0.33 and 7.46 ± 0.27, respectively) than NS patients (2.85 ± 0.16, 5.23 ± 0.32 and 4.26 ± 0.29, respectively; p < 0.05 for all vs. LC). By comparing data of the three waves, mean FSS and PSQI scores of LC patients, but not ESS scores, exceeded the normal range in all, with no significant inter-wave differences. Considering FSS ≥ 4 and PSQI > 5 cutoff values, LC patients commonly exhibited problematic fatigue (≥ 70%) and poor sleep quality (> 60%) in all three waves. Comparative analysis of PSQI component scores of LC patients identified no significant differences between the three waves. Our findings highlight the importance of concerted efforts to manage both fatigue and sleep disturbances in long COVID patient care. This multifaceted approach should be followed in all cases infected with either VOCs of SARS-CoV-2.}, }
@article {pmid37027455, year = {2023}, author = {Zakia, H and Pradana, K and Iskandar, S}, title = {Risk factors for psychiatric symptoms in patients with long COVID: A systematic review.}, journal = {PloS one}, volume = {18}, number = {4}, pages = {e0284075}, pmid = {37027455}, issn = {1932-6203}, mesh = {Adult ; Humans ; Female ; Aged ; Male ; Post-Acute COVID-19 Syndrome ; COVID-19 Testing ; *COVID-19/complications/epidemiology ; *Stress Disorders, Post-Traumatic/psychology ; Risk Factors ; }, abstract = {Prolonged symptoms of COVID-19 have been found in many patients, often known as Long COVID. Psychiatric symptoms are commonly seen in Long COVID patients and could last for weeks, even months, after recovery. However, the symptoms and risk factors associated with it remain unclear. In the current systematic review, we provide an overview of psychiatric symptoms in Long COVID patients and risk factors associated with the development of those symptoms. Articles were systematically searched on SCOPUS, PubMed, and EMBASE up to October 2021. Studies involving adults and geriatric participants with a confirmed previous COVID-19 diagnosis and reported psychiatric symptoms that persist for more than four weeks after the initial infection were included. The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) for observational studies. Prevalence rates and risk factors associated with psychiatric symptoms were collected. This present study was registered at PROSPERO (CRD42021240776). In total, 23 studies were included. Several limitations in this review were the heterogeneity of studies' outcomes and designs, studies limited to articles published in English, and the psychiatric symptoms mainly were assessed using self-report questionnaires. The most prevalent reported psychiatric symptoms, from the most to the least reported, were anxiety, depression, post-traumatic stress disorder (PTSD), poor sleep qualities, somatic symptoms, and cognitive deficits. Being female and having previous psychiatric diagnoses were risk factors for the development of the reported symptoms.}, }
@article {pmid37029295, year = {2023}, author = {Arnsten, AFT and Ishizawa, Y and Xie, Z}, title = {Scientific rationale for the use of α2A-adrenoceptor agonists in treating neuroinflammatory cognitive disorders.}, journal = {Molecular psychiatry}, volume = {28}, number = {11}, pages = {4540-4552}, pmid = {37029295}, issn = {1476-5578}, support = {R01 AG061190/AG/NIA NIH HHS/United States ; R01 AG041274/AG/NIA NIH HHS/United States ; R01 AG062509/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; Calcium Signaling ; *Cognitive Dysfunction ; *Delirium ; Guanfacine/pharmacology/therapeutic use ; Neuroinflammatory Diseases ; Post-Acute COVID-19 Syndrome ; Prefrontal Cortex ; Receptors, Adrenergic, alpha-2 ; }, abstract = {Neuroinflammatory disorders preferentially impair the higher cognitive and executive functions of the prefrontal cortex (PFC). This includes such challenging disorders as delirium, perioperative neurocognitive disorder, and the sustained cognitive deficits from "long-COVID" or traumatic brain injury. There are no FDA-approved treatments for these symptoms; thus, understanding their etiology is important for generating therapeutic strategies. The current review describes the molecular rationale for why PFC circuits are especially vulnerable to inflammation, and how α2A-adrenoceptor (α2A-AR) actions throughout the nervous and immune systems can benefit the circuits in PFC needed for higher cognition. The layer III circuits in the dorsolateral PFC (dlPFC) that generate and sustain the mental representations needed for higher cognition have unusual neurotransmission and neuromodulation. They are wholly dependent on NMDAR neurotransmission, with little AMPAR contribution, and thus are especially vulnerable to kynurenic acid inflammatory signaling which blocks NMDAR. Layer III dlPFC spines also have unusual neuromodulation, with cAMP magnification of calcium signaling in spines, which opens nearby potassium channels to rapidly weaken connectivity and reduce neuronal firing. This process must be tightly regulated, e.g. by mGluR3 or α2A-AR on spines, to prevent loss of firing. However, the production of GCPII inflammatory signaling reduces mGluR3 actions and markedly diminishes dlPFC network firing. Both basic and clinical studies show that α2A-AR agonists such as guanfacine can restore dlPFC network firing and cognitive function, through direct actions in the dlPFC, but also by reducing the activity of stress-related circuits, e.g. in the locus coeruleus and amygdala, and by having anti-inflammatory actions in the immune system. This information is particularly timely, as guanfacine is currently the focus of large clinical trials for the treatment of delirium, and in open label studies for the treatment of cognitive deficits from long-COVID.}, }
@article {pmid37030518, year = {2023}, author = {Quinn, KL and Lam, GY and Walsh, JF and Bhéreur, A and Brown, AD and Chow, CW and Chung, KYC and Cowan, J and Crampton, N and Décary, S and Falcone, EL and Graves, L and Gross, DP and Hanneman, K and Harvey, PJ and Holmes, S and Katz, GM and Parhizgar, P and Sharkawy, A and Tran, KC and Waserman, S and Zannella, VE and Cheung, AM}, title = {Cardiovascular Considerations in the Management of People With Suspected Long COVID.}, journal = {The Canadian journal of cardiology}, volume = {39}, number = {6}, pages = {741-753}, pmid = {37030518}, issn = {1916-7075}, mesh = {Adult ; Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/complications/epidemiology/therapy ; Canada/epidemiology ; SARS-CoV-2 ; Heart ; }, abstract = {Approximately 15% of adult Canadians with SARS-CoV-2 infection develop lingering symptoms beyond 12 weeks after acute infection, known as post-COVID condition or long COVID. Some of the commonly reported long COVID cardiovascular symptoms include fatigue, shortness of breath, chest pain, and palpitations. Suspected long-term cardiovascular complications of SARS-CoV-2 infection might present as a constellation of symptoms that can be challenging for clinicians to diagnose and treat. When assessing patients with these symptoms, clinicians need to keep in mind myalgic encephalomyelitis/chronic fatigue syndrome, postexertional malaise and postexertional symptom exacerbation, dysautonomia with cardiac manifestations such as inappropriate sinus tachycardia, and postural orthostatic tachycardia syndrome, and occasionally mast cell activation syndrome. In this review we summarize the globally evolving evidence around management of cardiac sequelae of long COVID. In addition, we include a Canadian perspective, consisting of a panel of expert opinions from people with lived experience and experienced clinicians across Canada who have been involved in management of long COVID. The objective of this review is to offer some practical guidance to cardiologists and generalist clinicians regarding diagnostic and treatment approaches for adult patients with suspected long COVID who continue to experience unexplained cardiac symptoms.}, }
@article {pmid37034158, year = {2023}, author = {Yang, Z and Ma, Y and Bi, W and Tang, J}, title = {Exploring the research landscape of COVID-19-induced olfactory dysfunction: A bibliometric study.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1164901}, pmid = {37034158}, issn = {1662-4548}, abstract = {Since the outbreak of COVID-19, olfactory dysfunction (OD) has become an important and persistent legacy problem that seriously affects the quality of life. The purpose of this paper is to quantitatively analyze and visualize the current research status and development trend of COVID-19 related OD by using VOSviewer software. Based on the Web of Science database, a total of 1,592 relevant documents were retrieved in January 2023, with publication time spanning from 2020 to 2023. The bibliometric analysis revealed that the most influential research results in the field of COVID-19 related OD were concentrated in journals of related disciplines such as otorhinolaryngology, medicine, general and internal, virology, neurosciences, etc. The knowledge base of the research is mainly formed in two fields: COVID-19 clinical research and OD specialized research. The research hotspots are mainly concentrated in six directions: COVID-19, long COVID, smell, anosmia, OD, and recovery. Based on the results of the bibliometric analysis, the temporal trends of COVID-19 related OD studies were visually revealed, and relevant suggestions for future research were proposed.}, }
@article {pmid37034420, year = {2023}, author = {Porter, AL and Markley, M and Newman, N}, title = {The long COVID research literature.}, journal = {Frontiers in research metrics and analytics}, volume = {8}, number = {}, pages = {1149091}, pmid = {37034420}, issn = {2504-0537}, abstract = {While the COVID-19 pandemic morphs into less malignant forms, the virus has spawned a series of poorly understood, post-infection symptoms with staggering ramifications, i. e., long COVID (LC). This bibliometric study profiles the rapidly growing LC research domain [5,243 articles from PubMed and Web of Science (WoS)] to make its knowledge content more accessible. The article addresses What? Where? Who? and When? questions. A 13-topic Concept Grid presents bottom-up topic clusters. We break out those topics with other data fields, including disciplinary concentrations, topical details, and information on research "players" (countries, institutions, and authors) engaging in those topics. We provide access to results via a Dashboard website. We find a strongly growing, multidisciplinary LC research domain. That domain appears tightly connected based on shared research knowledge. However, we also observe notable concentrations of research activity in different disciplines. Data trends over 3 years of LC research suggest heightened attention to psychological and neurodegenerative symptoms, fatigue, and pulmonary involvement.}, }
@article {pmid37037165, year = {2023}, author = {Espín, E and Yang, C and Shannon, CP and Assadian, S and He, D and Tebbutt, SJ}, title = {Cellular and molecular biomarkers of long COVID: a scoping review.}, journal = {EBioMedicine}, volume = {91}, number = {}, pages = {104552}, pmid = {37037165}, issn = {2352-3964}, mesh = {Humans ; Female ; Middle Aged ; Male ; *COVID-19/diagnosis/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; Quality of Life ; Canada ; Biomarkers ; }, abstract = {BACKGROUND: Long-COVID (LC) encompasses diverse symptoms lasting months after the initial SARS-CoV-2 infection. Symptoms can be debilitating and affect the quality of life of individuals with LC and their families. Although the symptoms of LC are well described, the aetiology of LC remains unclear, and consequently, patients may be underdiagnosed. Identification of LC specific biomarkers is therefore paramount for the diagnosis and clinical management of the syndrome. This scoping review describes the molecular and cellular biomarkers that have been identified to date with potential use for diagnosis or prediction of LC.<br><br>METHODS: This review was conducted using the Joanna Briggs Institute (JBI) Methodology for Scoping Reviews. A search was executed in the MEDLINE and EMBASE databases, as well as in the grey literature for original studies, published until October 5th, 2022, reporting biomarkers identified in participants with LC symptoms (from all ages, ethnicities, and sex), with a previous infection of SARS-CoV-2. Non-English studies, cross-sectional studies, studies without a control group, and pre-prints were excluded. Two reviewers independently evaluated the studies, extracted population data and associated biomarkers.<br><br>FINDINGS: 23 cohort studies were identified, involving 2163 LC patients [median age 51.8 years, predominantly female sex (61.10%), white (75%), and non-vaccinated (99%)]. A total of 239 candidate biomarkers were identified, consisting mainly of immune cells, immunoglobulins, cytokines, and other plasma proteins. 19 of the 239 candidate biomarkers identified were evaluated by the authors, by means of receiver operating characteristic (ROC) curves.<br><br>INTERPRETATION: Diverse cellular and molecular biomarkers for LC have been proposed. Validation of candidate biomarkers in independent samples should be prioritized. Modest reported performance (particularly in larger studies) suggests LC may encompass many distinct aetiologies, which should be explored e.g., by stratifying by symptom clusters and/or sex.<br><br>FUNDING: Dr. Tebbutt has received funding from the Canadian Institutes of Health Research (177747) to conduct this work. The funding source was not involved in this scoping review, or in the decision to submit this manuscript for publication.}, }
@article {pmid37046272, year = {2023}, author = {Müller, L and Di Benedetto, S}, title = {Aged brain and neuroimmune responses to COVID-19: post-acute sequelae and modulatory effects of behavioral and nutritional interventions.}, journal = {Immunity &amp; ageing : I &amp; A}, volume = {20}, number = {1}, pages = {17}, pmid = {37046272}, issn = {1742-4933}, abstract = {Advanced age is one of the significant risk determinants for coronavirus disease 2019 (COVID-19)-related mortality and for long COVID complications. The contributing factors may include the age-related dynamical remodeling of the immune system, known as immunosenescence and chronic low-grade systemic inflammation. Both of these factors may induce an inflammatory milieu in the aged brain and drive the changes in the microenvironment of neurons and microglia, which are characterized by a general condition of chronic inflammation, so-called neuroinflammation. Emerging evidence reveals that the immune privilege in the aging brain may be compromised. Resident brain cells, such as astrocytes, neurons, oligodendrocytes and microglia, but also infiltrating immune cells, such as monocytes, T cells and macrophages participate in the complex intercellular networks and multiple reciprocal interactions. Especially changes in microglia playing a regulatory role in inflammation, contribute to disturbing of the brain homeostasis and to impairments of the neuroimmune responses. Neuroinflammation may trigger structural damage, diminish regeneration, induce neuronal cell death, modulate synaptic remodeling and in this manner negatively interfere with the brain functions.In this review article, we give insights into neuroimmune interactions in the aged brain and highlight the impact of COVID-19 on the functional systems already modulated by immunosenescence and neuroinflammation. We discuss the potential ways of these interactions with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and review proposed neuroimmune mechanisms and biological factors that may contribute to the development of persisting long COVID conditions. We summarize the potential mechanisms responsible for long COVID, including inflammation, autoimmunity, direct virus-mediated cytotoxicity, hypercoagulation, mitochondrial failure, dysbiosis, and the reactivation of other persisting viruses, such as the Cytomegalovirus (CMV). Finally, we discuss the effects of various interventional options that can decrease the propagation of biological, physiological, and psychosocial stressors that are responsible for neuroimmune activation and which may inhibit the triggering of unbalanced inflammatory responses. We highlight the modulatory effects of bioactive nutritional compounds along with the multimodal benefits of behavioral interventions and moderate exercise, which can be applied as postinfectious interventions in order to improve brain health.}, }
@article {pmid37047556, year = {2023}, author = {Hulme, J}, title = {COVID-19 and Diarylamidines: The Parasitic Connection.}, journal = {International journal of molecular sciences}, volume = {24}, number = {7}, pages = {}, pmid = {37047556}, issn = {1422-0067}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2/metabolism ; Post-Acute COVID-19 Syndrome ; Peptidyl-Dipeptidase A/metabolism ; Renin-Angiotensin System ; }, abstract = {As emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants (Omicron) continue to outpace and negate combinatorial vaccines and monoclonal antibody therapies targeting the spike protein (S) receptor binding domain (RBD), the appetite for developing similar COVID-19 treatments has significantly diminished, with the attention of the scientific community switching to long COVID treatments. However, treatments that reduce the risk of "post-COVID-19 syndrome" and associated sequelae remain in their infancy, particularly as no established criteria for diagnosis currently exist. Thus, alternative therapies that reduce infection and prevent the broad range of symptoms associated with 'post-COVID-19 syndrome' require investigation. This review begins with an overview of the parasitic-diarylamidine connection, followed by the renin-angiotensin system (RAS) and associated angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSSR2) involved in SARS-CoV-2 infection. Subsequently, the ability of diarylamidines to inhibit S-protein binding and various membrane serine proteases associated with SARS-CoV-2 and parasitic infections are discussed. Finally, the roles of diarylamidines (primarily DIZE) in vaccine efficacy, epigenetics, and the potential amelioration of long COVID sequelae are highlighted.}, }
@article {pmid37051070, year = {2023}, author = {Negi, K and Agarwal, M and Pahuja, I and Bhardwaj, B and Rawat, M and Bhaskar, A and Dwivedi, VP}, title = {Combating the challenges of COVID-19 pandemic: Insights into molecular mechanisms, immune responses and therapeutics against SARS-CoV-2.}, journal = {Oxford open immunology}, volume = {4}, number = {1}, pages = {iqad001}, pmid = {37051070}, issn = {2633-6960}, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes lethal coronavirus disease (COVID-19). SARS-CoV-2 has been the chief source of threat to public health and safety from 2019 to the present. SARS-CoV-2 caused a sudden and significant rise in hospitalization due to respiratory issues and pneumonia. We are consistently uncovering new information about SARS-CoV-2, and yet so much is to explore to implement efficient interventions to combat the emergent variants and spread of the ongoing pandemic. Information regarding the existing COVID-19 pandemic is streamlining continuously. However, clinical symptoms of SARS-CoV-2 infections spanning from asymptomatic infection to severe death-instigating disease remain consistent with preliminary reports. In this review, we have briefly introduced highlights of the COVID-19 pandemic and features of SARS-CoV-2. We have focused on current knowledge of innate and adaptive immune responses during SARS-CoV-2 infections and persisting clinical features of recovered patients. Furthermore, we have discussed how these immune responses are not tightly regulated and imbalance can direct the latter phases of COVID-19, long-COVID symptoms, and cause detrimental immunopathogenesis. COVID-19 vaccines are also discussed in detail to describe the efforts going around the world to control and prevent the infection. Overall, we have summarized the current knowledge on the immunology of SARS-CoV-2 infection and the utilization of that knowledge in the development of a suitable COVID-19 therapeutics and vaccines.}, }
@article {pmid37054413, year = {2023}, author = {Cheng, AM and Dollar, E and Angier, H}, title = {Outpatient Management of COVID-19: Rapid Evidence Review.}, journal = {American family physician}, volume = {107}, number = {4}, pages = {370-381}, pmid = {37054413}, issn = {1532-0650}, mesh = {Humans ; *COVID-19 ; *Outpatients ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {New COVID-19 variants of concern continue to develop. Incubation period, transmissibility, immune escape, and treatment effectiveness differ by variants of concern. Physicians should be aware that the characteristics of the predominant variants of concern determine aspects of diagnosis and treatment. Multiple testing modalities exist; the most appropriate testing strategy varies depending on the clinical scenario, with factors of test sensitivity, turnaround time, and the expertise required for specimen collection. Three types of vaccines are available in the United States, and all people six months and older should be encouraged to receive one because vaccination is effective in reducing the incidence of and hospitalizations and deaths associated with COVID-19. Vaccination may also reduce the incidence of post-acute sequelae of SARS-CoV-2 infection (i.e., long COVID). Consider medications, such as nirmatrelvir/ritonavir, as first-line treatment for eligible patients diagnosed with COVID-19 unless logistical or supply constraints occur. National Institutes of Health guidelines and local health care partner resources can be used to determine eligibility. Long-term health effects of having COVID-19 are under investigation.}, }
@article {pmid37055095, year = {2023}, author = {Kewalramani, N and Heenan, KM and McKeegan, D and Chaudhuri, N}, title = {Post-COVID Interstitial Lung Disease-The Tip of the Iceberg.}, journal = {Immunology and allergy clinics of North America}, volume = {43}, number = {2}, pages = {389-410}, pmid = {37055095}, issn = {1557-8607}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Lung Diseases, Interstitial/diagnosis/epidemiology/etiology ; *Respiration Disorders ; }, abstract = {The proportion of symptomatic patients with post-coronavirus 2019 (COVID-19) condition (long COVID) represents a significant burden on the individual as well as on the health care systems. A greater understanding of the natural evolution of symptoms over a longer period and the impacts of interventions will improve our understanding of the long-term impacts of the COVID-19 disease. This review will discuss the emerging evidence for the development of post-COVID interstitial lung disease focusing on the pathophysiological mechanisms, incidence, diagnosis, and impact of this potentially new and emerging respiratory disease.}, }
@article {pmid37056914, year = {2023}, author = {Otani, K and Fukushima, H and Matsuishi, K}, title = {COVID-19 delirium and encephalopathy: Pathophysiology assumed in the first 3 years of the ongoing pandemic.}, journal = {Brain disorders (Amsterdam, Netherlands)}, volume = {10}, number = {}, pages = {100074}, pmid = {37056914}, issn = {2666-4593}, abstract = {BACKGROUND: The coronavirus disease (COVID-19) continues to spread worldwide. It has a high rate of delirium, even in young patients without comorbidities. Infected patients required isolation because of the high infectivity and virulence of COVID-19. The high prevalence of delirium in COVID-19 primarily results from encephalopathy and neuroinflammation caused by acute respiratory distress syndrome (ARDS)-associated cytokine storm. Acute respiratory distress syndrome has been linked to delirium and psychotic symptoms in the subacute phase (4 to 12 weeks), termed post-acute COVID-19 syndrome (PACS), and to brain fog, cognitive dysfunction, and fatigue, termed "long COVID," which persists beyond 12 weeks. However, no review article that mentions "COVID-19 delirium" have never been reported.<br><br>BASIC PROCEDURES: This narrative review summarizes data on delirium associated with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and related neurological symptoms of persistent post-infection illness (PACS or long COVID) after persistence of cognitive dysfunction. Thus, we describe the pathophysiological hypothesis of COVID-19 delirium and its continuation as long COVID. This review also describes the treatment of delirium complicated by COVID-19 pneumonia.<br><br>MAIN FINDINGS: SARS-CoV-2 infection is associated with encephalopathy and delirium. An association between COVID-19 infection and Alzheimer's disease has been suggested, and studies are being conducted from multiple facets including genetics, cytology, and postmortem study.<br><br>PRINCIPAL CONCLUSIONS: This review suggests that COVID-19 has important short and long-term neuropsychiatric effects. Several hypotheses have been proposed that highlight potential neurobiological mechanisms as causal factors, including neuronal-inflammatory pathways by cytokine storm and cellular senescence, and chronic inflammation.}, }
@article {pmid37060396, year = {2023}, author = {Zuin, M and Rigatelli, G and Bilato, C and Pasquetto, G and Mazza, A}, title = {Risk of Incident New-Onset Arterial Hypertension After COVID-19 Recovery: A Systematic Review and Meta-analysis.}, journal = {High blood pressure &amp; cardiovascular prevention : the official journal of the Italian Society of Hypertension}, volume = {30}, number = {3}, pages = {227-233}, pmid = {37060396}, issn = {1179-1985}, mesh = {Male ; Humans ; Female ; Middle Aged ; *COVID-19/diagnosis/epidemiology ; *Hypertension/diagnosis/epidemiology ; Comorbidity ; Risk Factors ; *Neoplasms ; }, abstract = {INTRODUCTION: Arterial Hypertension (HT) has been described as a common comorbidity and independent risk factor of short-term outcome in COVID-19 patients. However, data regarding the risk of new-onset HT during the post-acute phase of COVID-19 are scant.<br><br>AIM: We assess the risk of new-onset HT in COVID-19 survivors within one year from the index infection by a systematic review and meta-analysis of the available data.<br><br>METHODS: Data were obtained searching MEDLINE and Scopus for all studies published at any time up to February 11, 2023, and reporting the long-term risk of new-onset HT in COVID-19 survivors. Risk data were pooled using the Mantel-Haenszel random effects models with Hazard ratio (HR) as the effect measure with 95% confidence interval (CI). Heterogeneity among studies was assessed using I[2] statistic.<br><br>RESULTS: Overall, 19,293,346 patients (mean age 54.6 years, 54.6% males) were included in this analysis. Of them, 758,698 survived to COVID-19 infection. Over a mean follow-up of 6.8 months, new-onset HT occurred to 12.7 [95% CI 11.4-13.5] out of 1000 patients survived to COVID-19 infection compared to 8.17 [95% CI 7.34-8.53] out of 1000 control subjects. Pooled analysis revealed that recovered COVID-19 patients presented an increased risk of new-onset HT (HR 1.70, 95% CI 1.46-1.97, p&#x2009;<&#x2009;0.0001, I[2]&#x2009;=&#x2009;78.9%) within seven months. This risk was directly influenced by age (p&#x2009;=&#x2009;0.001), female sex (p&#x2009;=&#x2009;0.03) and cancer (p&#x2009;<&#x2009;0.0001) while an indirect association was observed using the follow-up length as moderator (p&#x2009;<&#x2009;0.0001).<br><br>CONCLUSIONS: Our findings suggest that new-onset HT represents an important post-acute COVID-19 sequelae.}, }
@article {pmid37061399, year = {2024}, author = {Chuang, HJ and Lin, CW and Hsiao, MY and Wang, TG and Liang, HW}, title = {Long COVID and rehabilitation.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {123 Suppl 1}, number = {}, pages = {S61-S69}, pmid = {37061399}, issn = {0929-6646}, mesh = {Adult ; Child ; Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Quality of Life ; Exercise Therapy ; Dyspnea ; }, abstract = {Coronavirus disease 2019 (COVID-19) has caused tremendous morbidity and mortality worldwide. The large number of post-COVID survivors has drawn attention to the management of post-COVID condition, known as long COVID. This review examines current knowledge of long COVID, regarding its epidemiology, mechanism, and clinical presentations in both adults and children. We also review the rehabilitation principles, modules, and effects, and share Taiwan's efforts to provide a top-down, nationwide care framework for long COVID patients. Dyspnea, chronic cough, and fatigue are the most commonly reported symptoms in the first 6 months after infection, but cognitive impairment and psychological symptoms may persist beyond this time. Several possible mechanisms behind these symptoms were proposed, but remained unconfirmed. These symptoms negatively impact individuals' function, activities, participation and quality of life. Rehabilitation is a key element of management to achieve functional improvement. Early management should start with comprehensive evaluation and identification of red flags. Exercise-based therapy, an essential part of management of long COVID, can be conducted with different modules, including telerehabilitation. Post-exertional symptom exacerbation and orthostatic hypotension should be carefully monitored during exercise. Randomized control trials with a large sample size are needed to determine the optimal timing, dosage, and modules.}, }
@article {pmid37064788, year = {2023}, author = {Martins-Gonçalves, R and Hottz, ED and Bozza, PT}, title = {Acute to post-acute COVID-19 thromboinflammation persistence: Mechanisms and potential consequences.}, journal = {Current research in immunology}, volume = {4}, number = {}, pages = {100058}, pmid = {37064788}, issn = {2590-2555}, abstract = {Concerns for the long-term effects of COVID-19 infection have grown due to frequently reported persisting symptoms that can affect multiple systems for longer than 4 weeks after initial infection, a condition known as long-COVID-19 or post-acute COVID-19 syndrome (PACS). Even nonhospitalized survivors have an elevated risk for the development of thromboinflammatory-associated events, such as ischemic stroke and heart failure, pulmonary embolism and deep vein thrombosis. Recent findings point to the persistence of many mechanisms of hypercoagulability identified to be associated with disease severity and mortality in the acute phase of the disease, such as sustained inflammation and endotheliopathy, accompanied by abnormal fibrin generation and impaired fibrinolysis. Platelets seem to be central to the sustained hypercoagulable state, displaying hyperreactivity to stimuli and increased adhesive capacity. Platelets also contribute to elevated levels of thromboinflammatory mediators and pro-coagulant extracellular vesicles in individuals with ongoing PACS. Despite new advances in the understanding of mechanisms sustaining thromboinflammation in PACS, little is known about what triggers this persistence. In this graphical review, we provide a schematic representation of the known mechanisms and consequences of persisting thromboinflammation in COVID-19 survivors and summarize the hypothesized triggers maintaining this prothrombotic state.}, }
@article {pmid37068519, year = {2023}, author = {Navis, A}, title = {A Review of Neurological Symptoms in Long COVID and Clinical Management.}, journal = {Seminars in neurology}, volume = {43}, number = {2}, pages = {286-296}, doi = {10.1055/s-0043-1767781}, pmid = {37068519}, issn = {1098-9021}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/complications/therapy ; SARS-CoV-2 ; Autoimmunity ; Fatigue ; }, abstract = {Long COVID is a clinical diagnosis generally referring to the persistence or development of new symptoms, affecting multiple organ systems after SARS-CoV-2 COVID-19 infection. Long COVID is thought to affect ∼20% of people after infection, including all age ranges and severity of infection. Fatigue, postexertional malaise, and respiratory and cardiac symptoms are commonly described. Neurological symptoms such as cognitive changes, sensory disturbances, headaches, and dysautonomia are common as well. The underlying pathophysiology remains unclear but immune dysregulation, autoimmunity, persistent viral reservoirs, and microvascular dysfunction have been implicated. As there are no tests at this time to diagnose long COVID, work-up should be focused on assessing reversible or treatable causes of symptoms. Furthermore, no treatments for long COVID currently exist, and management remains focused on a multimodal approach and symptom management, with many people showing improvement in symptoms over time.}, }
@article {pmid37070369, year = {2023}, author = {Keenan, PM and Doody, O}, title = {An update of the reported effects of the COVID-19 pandemic on person with intellectual disability and their carers: a scoping review.}, journal = {Annals of medicine}, volume = {55}, number = {1}, pages = {2196437}, pmid = {37070369}, issn = {1365-2060}, mesh = {Humans ; *COVID-19/epidemiology ; *Intellectual Disability/epidemiology ; Caregivers ; Pandemics ; Health Promotion ; }, abstract = {BACKGROUND: The effects of the COVID-19 pandemic has been felt by all groups in society and people with intellectual disability are especially vulnerable due to underlying conditions/health problems, multi-morbidity, limitations in understanding, frailty and social circumstances. This places people with intellectual disability, their families and carers at increased risk of stress and in need of support.<br><br>OBJECTIVE: To update and chart the evidence of the effects of the COVID-19 pandemic on people with intellectual disability, their families and carers reported within the research in 2021.<br><br>METHODS: A scoping review of research published in 2021 across 7 databases.<br><br>RESULTS: 84 studies met the inclusion criteria, and the findings highlight people with intellectual disability are at a greater risk to COVID-19 health outcomes due to underlying health concerns and access issues. The effects of COVID-19 can be seen from a personal, social and health perspective for people with intellectual disability, their carers and families. However, COVID-19 did have some unanticipated benefits such as: less demand on time, greater opportunity to engage with people of value and building resilience.<br><br>CONCLUSIONS: COVID-19 presents many challenges but for people with intellectual disability compounding existing obstacles encountered in access issues, service provision and supports available. There is a need to identify and describe the experiences of people with intellectual disability, their families and carers in the medium-long term during COVID-19. Greater supports and evidence of effective interventions to promote health, deliver services and support individual with intellectual disability is needed as there is little evidence of clinical care for people with intellectual disability during COVID-19.}, }
@article {pmid37070922, year = {2023}, author = {Hu, CL and Zheng, MJ and He, XX and Liu, DC and Jin, ZQ and Xu, WH and Lin, PY and Cheng, JW and Wei, QG}, title = {COVID-19 and bone health.}, journal = {European review for medical and pharmacological sciences}, volume = {27}, number = {7}, pages = {3191-3200}, doi = {10.26355/eurrev_202304_31953}, pmid = {37070922}, issn = {2284-0729}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Bone Density ; *Osteoporosis ; }, abstract = {A few patients who have recovered from COVID-19 develop persistent or new symptoms that last for weeks or months; this is called "long COVID" or "post-COVID-19 syndrome." Over time, awareness of the short- and long-term consequences of COVID-19 has increased. The pulmonary consequences are now fairly well established, but little is known about the extrapulmonary system of COVID-19, particularly its effects on bones. Current evidence and reports indicate a direct relationship between SARS-CoV-2 infection and bone health, with SARS-CoV-2 having a significant negative effect on bone health. In this review, we analyzed the impact of SARS-CoV-2 infection on bone health and assessed the impact of COVID-19 on the diagnosis and treatment of osteoporosis.}, }
@article {pmid37074754, year = {2024}, author = {Lenz, C and Slack, MPE and Shea, KM and Reinert, RR and Taysi, BN and Swerdlow, DL}, title = {Long-Term effects of COVID-19: a review of current perspectives and mechanistic insights.}, journal = {Critical reviews in microbiology}, volume = {50}, number = {3}, pages = {315-328}, doi = {10.1080/1040841X.2023.2190405}, pmid = {37074754}, issn = {1549-7828}, mesh = {Humans ; *COVID-19/epidemiology/virology ; *SARS-CoV-2 ; Risk Factors ; Cardiovascular Diseases/virology/epidemiology/etiology ; Comorbidity ; }, abstract = {Although SARS-CoV-2, responsible for COVID-19, is primarily a respiratory infection, a broad spectrum of cardiac, pulmonary, neurologic, and metabolic complications can occur. More than 50 long-term symptoms of COVID-19 have been described, and as many as 80% of patients may develop ≥1 long-term symptom. To summarize current perspectives of long-term sequelae of COVID-19, we conducted a PubMed search describing the long-term cardiovascular, pulmonary, gastrointestinal, and neurologic effects post-SARS-CoV-2 infection and mechanistic insights and risk factors for the above-mentioned sequelae. Emerging risk factors of long-term sequelae include older age (≥65 years), female sex, Black or Asian race, Hispanic ethnicity, and presence of comorbidities. There is an urgent need to better understand ongoing effects of COVID-19. Prospective studies evaluating long-term effects of COVID-19 in all body systems and patient groups will facilitate appropriate management and assess burden of care. Clinicians should ensure patients are followed up and managed appropriately, especially those in at-risk groups. Healthcare systems worldwide need to develop approaches to follow-up and support patients recovering from COVID-19. Surveillance programs can enhance prevention and treatment efforts for those most vulnerable.}, }
@article {pmid37076602, year = {2023}, author = {Li, G and Hilgenfeld, R and Whitley, R and De Clercq, E}, title = {Therapeutic strategies for COVID-19: progress and lessons learned.}, journal = {Nature reviews. Drug discovery}, volume = {22}, number = {6}, pages = {449-475}, pmid = {37076602}, issn = {1474-1784}, mesh = {Animals ; Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Antiviral Agents/therapeutic use/pharmacology ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic has stimulated tremendous efforts to develop therapeutic strategies that target severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and/or human proteins to control viral infection, encompassing hundreds of potential drugs and thousands of patients in clinical trials. So far, a few small-molecule antiviral drugs (nirmatrelvir-ritonavir, remdesivir and molnupiravir) and 11 monoclonal antibodies have been marketed for the treatment of COVID-19, mostly requiring administration within 10 days of symptom onset. In addition, hospitalized patients with severe or critical COVID-19 may benefit from treatment with previously approved immunomodulatory drugs, including glucocorticoids such as dexamethasone, cytokine antagonists such as tocilizumab and Janus kinase inhibitors such as baricitinib. Here, we summarize progress with COVID-19 drug discovery, based on accumulated findings since the pandemic began and a comprehensive list of clinical and preclinical inhibitors with anti-coronavirus activities. We also discuss the lessons learned from COVID-19 and other infectious diseases with regard to drug repurposing strategies, pan-coronavirus drug targets, in vitro assays and animal models, and platform trial design for the development of therapeutics to tackle COVID-19, long COVID and pathogenic coronaviruses in future outbreaks.}, }
@article {pmid37077615, year = {2023}, author = {Mudgal, SK and Gaur, R and Rulaniya, S and T, L and Agarwal, R and Kumar, S and Varshney, S and Sharma, S and Bhattacharya, S and Kalyani, V}, title = {Pooled Prevalence of Long COVID-19 Symptoms at 12 Months and Above Follow-Up Period: A Systematic Review and Meta-Analysis.}, journal = {Cureus}, volume = {15}, number = {3}, pages = {e36325}, pmid = {37077615}, issn = {2168-8184}, abstract = {Current data suggests that coronavirus disease 2019 (COVID-19) survivors experience long-lasting problems. It is not yet understood how long these symptoms last. The goal of this study was to compile all the data that was currently available to evaluate COVID-19's long-term effects at 12 months and above. We looked for studies published by December 15, 2022, in PubMed and Embase that discussed follow-up findings for COVID-19 survivors who had been alive for at least a year. A random-effect model was carried out to determine the combined prevalence of different long-COVID symptoms. The Joanna Briggs Institute tool was used to assess the risk of bias for the included studies, and the I2 statistics were used to evaluate the heterogeneity. After reviewing 3,209 studies, 46 were deemed admissible, with an aggregate COVID-19 population of 17976. At 12 months and above, 57% of patients reported a minimum of one symptom, and the five most prevalent symptoms were: dyspnea on exertion (34%, 95% CI 0.2; 0.94); difficulty in concentration (32%, 95% CI 0.16; 0.52); fatigue (31%, 95% CI 0.22; 0.40); frailty (31%, 95% CI 0.06; 0.78); and arthromyalgia (28%, 95% CI 0.09; 0.6). The findings of the present study showed that at 12 months and beyond, a sizable fraction of COVID-19 survivors still have lasting symptoms that impair several body systems. Long-COVID patients require an urgent understanding of pathophysiological processes and the development of tailored treatments.}, }
@article {pmid37078648, year = {2023}, author = {Tana, C and Giamberardino, MA and Martelletti, P}, title = {Long COVID and especially headache syndromes.}, journal = {Current opinion in neurology}, volume = {36}, number = {3}, pages = {168-174}, doi = {10.1097/WCO.0000000000001153}, pmid = {37078648}, issn = {1473-6551}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Headache/diagnosis/epidemiology/therapy ; *Migraine Disorders/complications ; }, abstract = {PURPOSE OF REVIEW: This is an expert overview on recent literature about the complex relationship between coronavirus disease 2019 (COVID-19) and headache.<br><br>RECENT FINDINGS: Long COVID is a clinical syndrome characterized by the presence of persistent symptoms following the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Headache is one of the most common symptoms and is described most often as throbbing pain, associated with photo and phonofobia and worsening with physical exercise. In acute COVID-19, headache is usually described as moderate or severe, diffuse and oppressive although sometimes it has been described with a migraine-like phenotype, especially in patients with a previous history of migraine. Headache intensity during acute phase seems to be the most important predictor of duration of headache over time. Some COVID-19 cases can be associated with cerebrovascular complications, and red flags of secondary headaches (e.g. new worsening or unresponsive headache, or new onset of neurological focal signs) should be urgently investigated with imaging. Treatment goals are the reduction of number and intensity of headache crises, and the prevention of chronic forms.<br><br>SUMMARY: This review can help clinicians to approach patients with headache and infection from SARS-CoV-2, with particular attention to persistent headache in long COVID.}, }
@article {pmid37080828, year = {2023}, author = {Turner, S and Khan, MA and Putrino, D and Woodcock, A and Kell, DB and Pretorius, E}, title = {Long COVID: pathophysiological factors and abnormalities of coagulation.}, journal = {Trends in endocrinology and metabolism: TEM}, volume = {34}, number = {6}, pages = {321-344}, pmid = {37080828}, issn = {1879-3061}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Inflammation ; *Thrombosis ; }, abstract = {Acute COVID-19 infection is followed by prolonged symptoms in approximately one in ten cases: known as Long COVID. The disease affects ~65 million individuals worldwide. Many pathophysiological processes appear to underlie Long COVID, including viral factors (persistence, reactivation, and bacteriophagic action of SARS CoV-2); host factors (chronic inflammation, metabolic and endocrine dysregulation, immune dysregulation, and autoimmunity); and downstream impacts (tissue damage from the initial infection, tissue hypoxia, host dysbiosis, and autonomic nervous system dysfunction). These mechanisms culminate in the long-term persistence of the disorder characterized by a thrombotic endothelialitis, endothelial inflammation, hyperactivated platelets, and fibrinaloid microclots. These abnormalities of blood vessels and coagulation affect every organ system and represent a unifying pathway for the various symptoms of Long COVID.}, }
@article {pmid37084750, year = {2023}, author = {Piechotta, V and Siemens, W and Thielemann, I and Toews, M and Koch, J and Vygen-Bonnet, S and Kothari, K and Grummich, K and Braun, C and Kapp, P and Labonté, V and Wichmann, O and Meerpohl, JJ and Harder, T}, title = {Safety and effectiveness of vaccines against COVID-19 in children aged 5-11 years: a systematic review and meta-analysis.}, journal = {The Lancet. Child &amp; adolescent health}, volume = {7}, number = {6}, pages = {379-391}, pmid = {37084750}, issn = {2352-4650}, mesh = {COVID-19 Vaccines/adverse effects ; mRNA Vaccines ; Child ; *Myocarditis ; *Vaccines ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/prevention &amp; control/complications ; BNT162 Vaccine ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome ; }, abstract = {BACKGROUND: To date, more than 761 million confirmed SARS-CoV-2 infections have been recorded globally, and more than half of all children are estimated to be seropositive. Despite high SARS-CoV-2 infection incidences, the rate of severe COVID-19 in children is low. We aimed to assess the safety and efficacy or effectiveness of COVID-19 vaccines approved in the EU for children aged 5-11 years.<br><br>METHODS: In this systematic review and meta-analysis, we included studies of any design identified through searching the COVID-19 L&#xb7;OVE (living overview of evidence) platform up to Jan 23, 2023. We included studies with participants aged 5-11 years, with any COVID-19 vaccine approved by the European Medicines Agency-ie, mRNA vaccines BNT162b2 (Pfizer-BioNTech), BNT162b2 Bivalent (against original strain and omicron [BA.4 or BA.5]), mRNA-1273 (Moderna), or mRNA-1273.214 (against original strain and omicron BA.1). Efficacy and effectiveness outcomes were SARS-CoV-2 infection (PCR-confirmed or antigen-test confirmed), symptomatic COVID-19, hospital admission due to COVID-19, COVID-19-related mortality, multisystem inflammatory syndrome in children (MIS-C), and long-term effects of COVID-19 (long COVID or post-COVID-19 condition as defined by study investigators or per WHO definition). Safety outcomes of interest were serious adverse events, adverse events of special interest (eg, myocarditis), solicited local and systemic events, and unsolicited adverse events. We assessed risk of bias and rated the certainty of evidence (CoE) using the Grading of Recommendations Assessment, Development and Evaluation approach. This study was prospectively registered with PROSPERO, CRD42022306822.<br><br>FINDINGS: Of 5272 screened records, we included 51 (1&#xb7;0%) studies (n=17 [33%] in quantitative synthesis). Vaccine effectiveness after two doses against omicron infections was 41&#xb7;6% (95% CI 28&#xb7;1-52&#xb7;6; eight non-randomised studies of interventions [NRSIs]; CoE low), 36&#xb7;2% (21&#xb7;5-48&#xb7;2; six NRSIs; CoE low) against symptomatic COVID-19, 75&#xb7;3% (68&#xb7;0-81&#xb7;0; six NRSIs; CoE moderate) against COVID-19-related hospitalisations, and 78% (48-90, one NRSI; CoE very low) against MIS-C. Vaccine effectiveness against COVID-19-related mortality was not estimable. Crude event rates for deaths in unvaccinated children were less than one case per 100&#x2009;000 children, and no events were reported for vaccinated children (four NRSIs; CoE low). No study on vaccine effectiveness against long-term effects was identified. Vaccine effectiveness after three doses was 55% (50-60; one NRSI; CoE moderate) against omicron infections, and 61% (55-67; one NRSI; CoE moderate) against symptomatic COVID-19. No study reported vaccine efficacy or effectiveness against hospitalisation following a third dose. Safety data suggested no increased risk of serious adverse events (risk ratio [RR] 0&#xb7;83 [95% CI 0&#xb7;21-3&#xb7;33]; two randomised controlled trials; CoE low), with approximately 0&#xb7;23-1&#xb7;2 events per 100&#x2009;000 administered vaccines reported in real-life observations. Evidence on the risk of myocarditis was uncertain (RR 4&#xb7;6 [0&#xb7;1-156&#xb7;1]; one NRSI; CoE low), with 0&#xb7;13-1&#xb7;04 observed events per 100&#x2009;000 administered vaccines. The risk of solicited local reactions was 2&#xb7;07 (1&#xb7;80-2&#xb7;39; two RCTs; CoE moderate) after one dose and 2&#xb7;06 (1&#xb7;70-2&#xb7;49; two RCTs; CoE moderate) after two doses. The risk of solicited systemic reactions was 1&#xb7;09 (1&#xb7;04-1&#xb7;16; two RCTs; CoE moderate) after one dose and 1&#xb7;49 (1&#xb7;34-1&#xb7;65; two RCTs; CoE moderate) after two doses. The risk of unsolicited adverse events after two doses (RR 1&#xb7;21 [1&#xb7;07-1&#xb7;38]; CoE moderate) was higher among mRNA-vaccinated compared with unvaccinated children.<br><br>INTERPRETATION: In children aged 5-11 years, mRNA vaccines are moderately effective against infections with the omicron variant, but probably protect well against COVID-19 hospitalisations. Vaccines were reactogenic but probably safe. Findings of this systematic review can serve as a basis for public health policy and individual decision making on COVID-19 vaccination in children aged 5-11 years.<br><br>FUNDING: German Federal Joint Committee.}, }
@article {pmid37089476, year = {2023}, author = {Kisielinski, K and Hirsch, O and Wagner, S and Wojtasik, B and Funken, S and Klosterhalfen, B and Kanti Manna, S and Prescher, A and Sukul, P and Sönnichsen, A}, title = {Physio-metabolic and clinical consequences of wearing face masks-Systematic review with meta-analysis and comprehensive evaluation.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1125150}, pmid = {37089476}, issn = {2296-2565}, mesh = {Humans ; Young Adult ; Adult ; Middle Aged ; *COVID-19/epidemiology ; Masks ; SARS-CoV-2 ; Pandemics ; Carbon Dioxide ; Post-Acute COVID-19 Syndrome ; *Respiratory Protective Devices ; Dyspnea ; }, abstract = {BACKGROUND: As face masks became mandatory in most countries during the COVID-19 pandemic, adverse effects require substantiated investigation.<br><br>METHODS: A systematic review of 2,168 studies on adverse medical mask effects yielded 54 publications for synthesis and 37 studies for meta-analysis (on n = 8,641, m = 2,482, f = 6,159, age = 34.8 &#xb1; 12.5). The median trial duration was only 18 min (IQR = 50) for our comprehensive evaluation of mask induced physio-metabolic and clinical outcomes.<br><br>RESULTS: We found significant effects in both medical surgical and N95 masks, with a greater impact of the second. These effects included decreased SpO2 (overall Standard Mean Difference, SMD = -0.24, 95% CI = -0.38 to -0.11, p < 0.001) and minute ventilation (SMD = -0.72, 95% CI = -0.99 to -0.46, p < 0.001), simultaneous increased in blood-CO2 (SMD = +0.64, 95% CI = 0.31-0.96, p < 0.001), heart rate (N95: SMD = +0.22, 95% CI = 0.03-0.41, p = 0.02), systolic blood pressure (surgical: SMD = +0.21, 95% CI = 0.03-0.39, p = 0.02), skin temperature (overall SMD = +0.80 95% CI = 0.23-1.38, p = 0.006) and humidity (SMD +2.24, 95% CI = 1.32-3.17, p < 0.001). Effects on exertion (overall SMD = +0.9, surgical = +0.63, N95 = +1.19), discomfort (SMD = +1.16), dyspnoea (SMD = +1.46), heat (SMD = +0.70), and humidity (SMD = +0.9) were significant in n = 373 with a robust relationship to mask wearing (p < 0.006 to p < 0.001). Pooled symptom prevalence (n = 8,128) was significant for: headache (62%, p < 0.001), acne (38%, p < 0.001), skin irritation (36%, p < 0.001), dyspnoea (33%, p < 0.001), heat (26%, p < 0.001), itching (26%, p < 0.001), voice disorder (23%, p < 0.03), and dizziness (5%, p = 0.01).<br><br>DISCUSSION: Masks interfered with O2-uptake and CO2-release and compromised respiratory compensation. Though evaluated wearing durations are shorter than daily/prolonged use, outcomes independently validate mask-induced exhaustion-syndrome (MIES) and down-stream physio-metabolic disfunctions. MIES can have long-term clinical consequences, especially for vulnerable groups. So far, several mask related symptoms may have been misinterpreted as long COVID-19 symptoms. In any case, the possible MIES contrasts with the WHO definition of health.<br><br>CONCLUSION: Face mask side-effects must be assessed (risk-benefit) against the available evidence of their effectiveness against viral transmissions. In the absence of strong empirical evidence of effectiveness, mask wearing should not be mandated let alone enforced by law.<br><br>https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021256694, identifier: PROSPERO 2021 CRD42021256694.}, }
@article {pmid37091856, year = {2023}, author = {Meftah, E and Rahmati, R and Zari Meidani, F and Khodadadi, S and Chitzan-Zadeh, K and Esfahanian, F and Afshar, S}, title = {Subacute thyroiditis following COVID-19: A systematic review.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1126637}, pmid = {37091856}, issn = {1664-2392}, mesh = {Humans ; Female ; Male ; *COVID-19/complications ; Thyroxine/therapeutic use ; COVID-19 Vaccines/therapeutic use ; *Thyroiditis, Subacute/drug therapy/epidemiology/etiology ; }, abstract = {BACKGROUND: Subacute thyroiditis (SAT) is a self-limiting thyroid inflammatory disease occurring specifically after upper respiratory tract infections. Since COVID-19 is a respiratory disease leading to multi-organ involvements, we aimed to systematically review the literature regarding SAT secondary to COVID-19.<br><br>METHODS: We searched Scopus, PubMed/MEDLINE, Cochrane, Web of Science, ProQuest, and LitCovid databases using the terms "subacute thyroiditis" and "COVID-19" and their synonyms from inception to November 3, 2022. We included the original articles of the patients with SAT secondary to COVID-19. Studies reporting SAT secondary to COVID-19 vaccination or SAT symptoms' manifestation before the COVID-19 infection were not included.<br><br>RESULTS: Totally, 820 articles were retained. Having removed the duplicates, 250 articles remained, out of which 43 articles (40 case reports and three case series) with a total of 100 patients, were eventually selected. The patients aged 18-85 years (Mean: 42.70, SD: 11.85) and 68 (68%) were women. The time from the onset of COVID-19 to the onset of SAT symptoms varied from zero to 168 days (Mean: 28.31, SD: 36.92). The most common symptoms of SAT were neck pain in 69 patients (69%), fever in 54 (54%), fatigue and weakness in 34 (34%), and persistent palpitations in 31 (31%). The most common ultrasonographic findings were hypoechoic regions in 73 (79%), enlarged thyroid in 46 (50%), and changes in thyroid vascularity in 14 (15%). Thirty-one patients (31%) were hospitalized, and 68 (68%) were treated as outpatients. Corticosteroids were the preferred treatment in both the inpatient and outpatient settings (25 inpatients (81%) and 44 outpatients (65%)). Other preferred treatments were nonsteroidal anti-inflammatory drugs (nine inpatients (29%) and 17 outpatients (25%)) and beta-blockers (four inpatients (13%) and seven outpatients (10%)). After a mean duration of 61.59 days (SD: 67.07), 21 patients (23%) developed hypothyroidism and thus, levothyroxine-based treatment was used in six of these patients and the rest of these patients did not receive levothyroxine.<br><br>CONCLUSION: SAT secondary to COVID-19 seems to manifest almost similarly to the conventional SAT. However, except for the case reports and case series, lack of studies has limited the quality of the data at hand.}, }
@article {pmid37094584, year = {2023}, author = {Abbate, G and De Iulio, B and Thomas, G and Priday, A and Biondi-Zoccai, G and Markley, R and Abbate, A}, title = {Postural Orthostatic Tachycardia Syndrome After COVID-19: A Systematic Review of Therapeutic Interventions.}, journal = {Journal of cardiovascular pharmacology}, volume = {82}, number = {1}, pages = {23-31}, doi = {10.1097/FJC.0000000000001432}, pmid = {37094584}, issn = {1533-4023}, mesh = {Male ; Humans ; Female ; Young Adult ; Adult ; Middle Aged ; *Postural Orthostatic Tachycardia Syndrome/diagnosis/epidemiology/therapy ; Post-Acute COVID-19 Syndrome ; *COVID-19/diagnosis/epidemiology/therapy ; Adrenergic beta-Antagonists/therapeutic use ; *Midodrine/therapeutic use ; Heart Rate ; }, abstract = {Postural orthostatic tachycardia syndrome (POTS) is a clinical syndrome of inappropriate increase in heart rate on standing that has been recently also associated with Coronavirus Disease 2019 (COVID-19) as part of the postacute sequelae of COVID-19 (PASC) or long-COVID. We herein aimed to systematically review reported cases of POTS after COVID-19 and determine the characteristics of the subjects, the diagnostic approach used, and the treatment strategies. We searched the literature according to the following criteria: (1) diagnosis of POTS according to standard definition; (2) timely association with a probable or definite diagnosis of COVID-19; and (3) a description of the individual subject(s). We identified 21 reports meeting criteria between March 2020 and September 2022, including 68 subjects (51 females and 17 males, 3:1 ratio) with a mean age of 34 ± 12 years, with reports deriving from the United States, Norway, Sweden, Israel, Ireland, United Kingdom, Singapore, and Japan. Most cases had mild COVID-19 symptoms. The most common POTS symptoms were palpitations, chest pain, lightheadedness, and debilitating fatigue. The diagnosis was established by means of head-up tilt table or active stand test. Nonpharmacologic treatments (fluids, sodium intake, and compression stockings) were virtually always used, but largely ineffective. Subjects received different treatments, the most common being beta-adrenergic blockers (ie, propranolol), mineral corticosteroids (ie, fludrocortisone), midodrine, and ivabradine. Symptoms tended to improve over time, but most patients remained symptomatic for several months. In conclusion, POTS after COVID-19 is a clinical condition affecting young individuals, and disproportionately young women, occurring as part of PASC-long-COVID, often debilitating, which can be easily diagnosed with a thorough clinical assessment and measuring changes in orthostatic heart rate and blood pressure. POTS after COVID-19 seems to be poorly responsive to nonpharmacological treatments but with symptoms improving with pharmacological interventions. Given the limited data available, additional research is urgently needed with respect to its epidemiology, pathophysiology, and treatments.}, }
@article {pmid37095536, year = {2023}, author = {Yin, JX and Agbana, YL and Sun, ZS and Fei, SW and Zhao, HQ and Zhou, XN and Chen, JH and Kassegne, K}, title = {Increased interleukin-6 is associated with long COVID-19: a systematic review and meta-analysis.}, journal = {Infectious diseases of poverty}, volume = {12}, number = {1}, pages = {43}, pmid = {37095536}, issn = {2049-9957}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Interleukin-6 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19) can involve persistence, sequelae, and other clinical complications that last weeks to months to evolve into long COVID-19. Exploratory studies have suggested that interleukin-6 (IL-6) is related to COVID-19; however, the correlation between IL-6 and long COVID-19 is unknown. We designed a systematic review and meta-analysis to assess the relationship between IL-6 levels and long COVID-19.<br><br>METHODS: Databases were systematically searched for articles with data on long COVID-19 and IL-6 levels published before September 2022. A total of 22 published studies were eligible for inclusion following the PRISMA guidelines. Analysis of data was undertaken by using Cochran's Q test and the Higgins I-squared (I[2]) statistic for heterogeneity. Random-effect meta-analyses were conducted to pool the IL-6 levels of long COVID-19 patients and to compare the differences in IL-6 levels among the long COVID-19, healthy, non-postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (non-PASC), and acute COVID-19 populations. The funnel plot and Egger's test were used to assess potential publication bias. Sensitivity analysis was used to test the stability of the results.<br><br>RESULTS: An increase in IL-6 levels was observed after SARS-CoV-2 infection. The pooled estimate of IL-6 revealed a mean value of 20.92&#xa0;pg/ml (95% CI&#x2009;=&#x2009;9.30-32.54&#xa0;pg/ml, I[2]&#x2009;=&#x2009;100%, P&#x2009;<&#x2009;0.01) for long COVID-19 patients. The forest plot showed high levels of IL-6 for long COVID-19 compared with healthy controls (mean difference&#x2009;=&#x2009;9.75&#xa0;pg/ml, 95% CI&#x2009;=&#x2009;5.75-13.75&#xa0;pg/ml, I[2]&#x2009;=&#x2009;100%, P&#x2009;<&#x2009;0.00001) and PASC category (mean difference&#x2009;=&#x2009;3.32&#xa0;pg/ml, 95% CI&#x2009;=&#x2009;0.22-6.42&#xa0;pg/ml, I[2]&#x2009;=&#x2009;88%, P&#x2009;=&#x2009;0.04). The symmetry of the funnel plots was not obvious, and Egger's test showed that there was no significant small study effect in all groups.<br><br>CONCLUSIONS: This study showed that increased IL-6 correlates with long COVID-19. Such an informative revelation suggests IL-6 as a basic determinant to predict long COVID-19 or at least inform on the "early stage" of long COVID-19.}, }
@article {pmid37102680, year = {2023}, author = {Bradbury, J and Wilkinson, S and Schloss, J}, title = {Nutritional Support During Long COVID: A Systematic Scoping Review.}, journal = {Journal of integrative and complementary medicine}, volume = {29}, number = {11}, pages = {695-704}, doi = {10.1089/jicm.2022.0821}, pmid = {37102680}, issn = {2768-3613}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *Sarcopenia ; *COVID-19 ; Vitamins/therapeutic use ; *Malnutrition/prevention &amp; control ; Nutritional Support ; Glutathione ; Anti-Inflammatory Agents ; Inflammation ; }, abstract = {Introduction: Long COVID is a term that encompasses a range of signs, symptoms, and sequalae that continue or develop after an acute COVID-19 infection. The lack of early recognition of the condition contributed to delays in identifying factors that may contribute toward its development and prevention. The aim of this study was to scope the available literature to identify potential nutritional interventions to support people with symptoms associated with long COVID. Methods: This study was designed as a systematic scoping review of the literature (registration PROSPERO CRD42022306051). Studies with participants aged 18 years or older, with long COVID and who underwent a nutritional intervention were included in the review. Results: A total of 285 citations were initially identified, with five papers eligible for inclusion: two were pilot studies of nutritional supplements in the community, and three were nutritional interventions as part of inpatient or outpatient multidisciplinary rehabilitation programs. There were two broad categories of interventions: those that focused on compositions of nutrients (including micronutrients such as vitamin and mineral supplements) and those that were incorporated as part of multidisciplinary rehabilitation programs. Nutrients included in more than one study were multiple B group vitamins, vitamin C, vitamin D, and acetyl-l-carnitine. Discussion: Two studies trialed nutritional supplements for long COVID in community samples. Although these initial reports were positive, they are based on poorly designed studies and therefore cannot provide conclusive evidence. Nutritional rehabilitation was an important aspect of recovery from severe inflammation, malnutrition, and sarcopenia in hospital rehabilitation programs. Current gaps in the literature include a potential role for anti-inflammatory nutrients such as the omega 3 fatty acids, which are currently undergoing clinical trials, glutathione-boosting treatments such as N-acetylcysteine, alpha-lipoic acid, or liposomal glutathione in long COVID, and a possible adjunctive role for anti-inflammatory dietary interventions. This review provides preliminary evidence that nutritional interventions may be an important part of a rehabilitation program for people with severe long COVID symptomatology, including severe inflammation, malnutrition, and sarcopenia. For those in the general population with long COVID symptoms, the role of specific nutrients has not yet been studied well enough to recommend any particular nutrient or dietary intervention as a treatment or adjunctive treatment. Clinical trials of single nutrients are currently being conducted, and future systematic reviews could focus on single nutrient or dietary interventions to identify their nuanced mechanisms of action. Further clinical studies incorporating complex nutritional interventions are also warranted to strengthen the evidence base for using nutrition as a useful adjunctive treatment for people living with long COVID.}, }
@article {pmid37103631, year = {2024}, author = {Wu, X and Xiang, M and Jing, H and Wang, C and Novakovic, VA and Shi, J}, title = {Damage to endothelial barriers and its contribution to long COVID.}, journal = {Angiogenesis}, volume = {27}, number = {1}, pages = {5-22}, pmid = {37103631}, issn = {1573-7209}, mesh = {Animals ; Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Endothelial Cells/physiology ; *Vascular Diseases ; }, abstract = {The world continues to contend with COVID-19, fueled by the emergence of viral variants. At the same time, a subset of convalescent individuals continues to experience persistent and prolonged sequelae, known as long COVID. Clinical, autopsy, animal and in vitro studies all reveal endothelial injury in acute COVID-19 and convalescent patients. Endothelial dysfunction is now recognized as a central factor in COVID-19 progression and long COVID development. Different organs contain different types of endothelia, each with specific features, forming different endothelial barriers and executing different physiological functions. Endothelial injury results in contraction of cell margins (increased permeability), shedding of glycocalyx, extension of phosphatidylserine-rich filopods, and barrier damage. During acute SARS-CoV-2 infection, damaged endothelial cells promote diffuse microthrombi and destroy the endothelial (including blood-air, blood-brain, glomerular filtration and intestinal-blood) barriers, leading to multiple organ dysfunction. During the convalescence period, a subset of patients is unable to fully recover due to persistent endothelial dysfunction, contributing to long COVID. There is still an important knowledge gap between endothelial barrier damage in different organs and COVID-19 sequelae. In this article, we mainly focus on these endothelial barriers and their contribution to long COVID.}, }
@article {pmid37106076, year = {2023}, author = {Seifart, U}, title = {Post-COVID-More than chronic fatigue?.}, journal = {Herz}, volume = {48}, number = {3}, pages = {229-233}, pmid = {37106076}, issn = {1615-6692}, mesh = {Humans ; *Fatigue Syndrome, Chronic/diagnosis/epidemiology/therapy ; Microcirculation ; Post-Acute COVID-19 Syndrome ; Quality of Life ; *COVID-19/epidemiology ; }, abstract = {After the first COVID-19 survivors were medically treated in Germany from spring 2020 onwards, various courses of the disease emerged that, in addition to the acute infection, led to prolonged symptoms (long COVID), but also to a symptomatic course beyond 12 weeks, which is referred to as "post-COVID syndrome" (PCS). Currently, the incidence of PCS is estimated to be approximately 15% of all symptomatically infected patients, although over- or underestimations may occur due to the soft definition and lack of control groups. The etiology of PCS is currently unknown. The following pathogenetic processes are discussed in particular: an endothelial dysfunction with microcirculatory disturbances and subsequent organ damage, a residual virus or virus particles, and/or an excessive autoimmune process. Due to the large number of organs that may be affected, PCS presents as a very complex clinical picture with up to 200 described symptoms. An evidence-based causal therapy for PCS has not yet been established. The guideline-based inpatient rehabilitation measures adapted to the individual patient resources have proven to be an effective therapy and should therefore be involved in the therapeutic concept at an early stage. Post-COVID syndrome is a multicomplex disease that can have a considerable impact on the quality of life, but also on the professional performance of the affected patients. Thus, it is clearly more than just a chronic fatigue syndrome. In the interest of our patients, treating physicians should take this disease seriously, clarify the differential diagnoses, and provide sensitive therapeutic care.}, }
@article {pmid37107929, year = {2023}, author = {Suh, HW and Kwon, CY and Lee, B}, title = {Long-Term Impact of COVID-19 on Heart Rate Variability: A Systematic Review of Observational Studies.}, journal = {Healthcare (Basel, Switzerland)}, volume = {11}, number = {8}, pages = {}, pmid = {37107929}, issn = {2227-9032}, support = {IITP-2023-2020-0-01791//Ministry of Science and ICT/ ; }, abstract = {Coronavirus disease 2019 (COVID-19) sequelae (or long COVID) has become a clinically significant concern. Several studies have reported the relationship between heart rate variability (HRV) parameters and COVID-19. This review investigates the long-term association between COVID-19 and HRV parameters. Four electronic databases were searched up to 29 July 2022. We included observational studies comparing HRV parameters (measurement durations: 1 min or more) in participants with and without a history of COVID-19. We used assessment tools developed by the National Heart, Lung, and Blood Institute group to evaluate the methodological quality of included studies. Eleven cross-sectional studies compared HRV parameters in individuals who recovered from acute COVID-19 infection to controls (n = 2197). Most studies reported standard deviation of normal-to-normal intervals (SDNN) and root mean square of the successive differences. The methodological quality of the included studies was not optimal. The included studies generally found decreased SDNN and parasympathetic activity in post-COVID-19 individuals. Compared to controls, decreases in SDNN were observed in individuals who recovered from COVID-19 or had long COVID. Most of the included studies emphasized parasympathetic inhibition in post-COVID-19 conditions. Due to the methodological limitations of measuring HRV parameters, the findings should be further validated by robust prospective longitudinal studies.}, }
@article {pmid37113165, year = {2023}, author = {Sarmiento Varón, L and González-Puelma, J and Medina-Ortiz, D and Aldridge, J and Alvarez-Saravia, D and Uribe-Paredes, R and Navarrete, MA}, title = {The role of machine learning in health policies during the COVID-19 pandemic and in long COVID management.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1140353}, pmid = {37113165}, issn = {2296-2565}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Pandemics ; Post-Acute COVID-19 Syndrome ; Health Policy ; Machine Learning ; }, abstract = {The ongoing COVID-19 pandemic is arguably one of the most challenging health crises in modern times. The development of effective strategies to control the spread of SARS-CoV-2 were major goals for governments and policy makers. Mathematical modeling and machine learning emerged as potent tools to guide and optimize the different control measures. This review briefly summarizes the SARS-CoV-2 pandemic evolution during the first 3 years. It details the main public health challenges focusing on the contribution of mathematical modeling to design and guide government action plans and spread mitigation interventions of SARS-CoV-2. Next describes the application of machine learning methods in a series of study cases, including COVID-19 clinical diagnosis, the analysis of epidemiological variables, and drug discovery by protein engineering techniques. Lastly, it explores the use of machine learning tools for investigating long COVID, by identifying patterns and relationships of symptoms, predicting risk indicators, and enabling early evaluation of COVID-19 sequelae.}, }
@article {pmid37125676, year = {2023}, author = {Koh, YC and Ho, CT and Pan, MH}, title = {The Role of Mitochondria in Phytochemically Mediated Disease Amelioration.}, journal = {Journal of agricultural and food chemistry}, volume = {71}, number = {18}, pages = {6775-6788}, doi = {10.1021/acs.jafc.2c08921}, pmid = {37125676}, issn = {1520-5118}, mesh = {Humans ; Resveratrol/pharmacology ; *Curcumin/pharmacology/metabolism ; Post-Acute COVID-19 Syndrome ; *COVID-19/metabolism ; Mitochondria/metabolism ; Mitochondrial Dynamics ; }, abstract = {Mitochondrial dysfunction may cause cell death, which has recently emerged as a cancer prevention and treatment strategy mediated by chemotherapy drugs or phytochemicals. However, most existing drugs cannot target cancerous cells and may adversely affect normal cells via side effects. Mounting studies have revealed that phytochemicals such as resveratrol could ameliorate various diseases with dysfunctional or damaged mitochondria. For instance, resveratrol can regulate mitophagy, inhibit oxidative stress and preserve membrane potential, induce mitochondrial biogenesis, balance mitochondrial fusion and fission, and enhance the functionality of the electron transport chain. However, there are only a few studies suggesting that phytochemicals could potentially protect against the cytotoxicity of some current cancer drugs, especially those that damage mitochondria. Besides, COVID-19 and long COVID have also been reported to be correlated to mitochondrial dysfunction. Curcumin has been reported bringing a positive impact on COVID-19 and long COVID. Therefore, in this study, the benefits of resveratrol and curcumin to be applied for cancer treatment/prevention and disease amelioration were reviewed. Besides, this review also provides some perspectives on phytochemicals to be considered as a treatment adjuvant for COVID-19 and long COVID by targeting mitochondrial rescue. Hopefully, this review can provide new insight into disease treatment with phytochemicals targeting mitochondria.}, }
@article {pmid37126363, year = {2023}, author = {El-Maradny, YA and Rubio-Casillas, A and Uversky, VN and Redwan, EM}, title = {Intrinsic factors behind long-COVID: I. Prevalence of the extracellular vesicles.}, journal = {Journal of cellular biochemistry}, volume = {124}, number = {5}, pages = {656-673}, doi = {10.1002/jcb.30415}, pmid = {37126363}, issn = {1097-4644}, mesh = {Humans ; SARS-CoV-2 ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Prevalence ; *Extracellular Vesicles ; }, abstract = {It can be argued that the severity of COVID-19 has decreased in many countries. This could be a result of the broad coverage of the population by vaccination campaigns, which often reached an almost compulsory status in many places. Furthermore, significant roles were played by the multiple mutations in the body of the virus, which led to the emergence of several new SARS-CoV-2 variants with enhanced infectivity but dramatically reduced pathogenicity. However, the challenges associated with the development of various side effects and their persistence for long periods exceeding 20 months as a result of the SARS-CoV-2 infection, or taking available vaccines against it, are spreading horizontally and vertically in number and repercussions. For example, the World Health Organization announced that there are more than 17 million registered cases of long-COVID (also known as post-COVID syndrome) in the European Union countries alone. Furthermore, by using the PubMed search engine, one can find that more than 10 000 articles have been published focusing exclusively on long-COVID. In light of these enormous and ever-increasing numbers of cases and published articles, most of which are descriptive of the various long-COVID symptoms, the need to know the reasons behind this phenomenon raises several important questions. Is long-COVID caused by the continued presence of the virus or one/several of its components in the recovering individual body for long periods of time, which urges the body to respond in a way that leads to long-COVID development? Or are there some latent and limited reasons related to the recovering patients themselves? Or is it a sum of both? Many observations support a positive answer to the first question, whereas others back the second question but typically without releasing a fundamental reason/signal behind it. Whatever the answer is, it seems that the real reasons behind this widespread phenomenon remain unclear. This report opens a series of articles, in which we will try to shed light on the underlying causes that could be behind the long-COVID phenomenon.}, }
@article {pmid37130538, year = {2023}, author = {Teixido, L and Andreeva, E and Gartmann, J and Lemhöfer, C and Sturm, C and Gutenbrunner, C}, title = {[Outpatient rehabilitative care for patients with Long-COVID - a guideline-based clinical practice guideline].}, journal = {Laryngo- rhino- otologie}, volume = {102}, number = {7}, pages = {521-532}, doi = {10.1055/a-1985-0450}, pmid = {37130538}, issn = {1438-8685}, mesh = {Humans ; *COVID-19/epidemiology ; Outpatients ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Even after weeks and months, persisting and also newly occurring symptoms after SARS-CoV-2 infection are common and lead in many cases to a broad spectrum of impairments and participation restrictions in all areas of daily life. Scientific evidence on therapeutic options still is limited. The aim of this work is therefore to provide pragmatic treatment recommendations analogous to the current therapeutic appliances guideline.<br><br>METHOD: In addition to a search in six electronic databases, the experiences from the treatment of more than hundred affected persons from the post-COVID outpatient rehabilitation service were used. Additionally, experiences with patients with similar symptoms from other diseases were included. All authors worked together to develop the pragmatic recommendations for the treatment of the main symptoms within the framework of outpatient therapy measures. A list of recommended diagnostics and functional assessments prior to therapy was also developed.<br><br>RESULTS: For the main symptoms fatigue, dyspnoea and cognitive impairment, the catalog of therapeutic products offers a wide range of therapeutic options under the diagnosis U09.9. The therapy packages should be composed individually and adapted to the patient's performance level that regularly should be (re-)assessed. Informing the patient about possible relapses and deteriorations and how to deal with them should be also part of the treatment regimen.<br><br>DISCUSSION: Physical modalities and rehabilitation interventions should be used in out-patient rehabilitation setting for the treatment of Long-COVID. In this regard, it is also important to take into account and treat serious complications after the disease, such as post-intensive care syndrome. Due to the rapid evolution of the knowledge a frequent review of scientific papers and recommendations should be conducted. High-quality intervention studies are necessary to achieve greater evidence in this field.}, }
@article {pmid37130814, year = {2023}, author = {Golla, R and Vuyyuru, SK and Kante, B and Kedia, S and Ahuja, V}, title = {Disorders of gut-brain interaction in post-acute COVID-19 syndrome.}, journal = {Postgraduate medical journal}, volume = {99}, number = {1174}, pages = {834-843}, doi = {10.1136/pmj-2022-141749}, pmid = {37130814}, issn = {1469-0756}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Brain ; Pandemics ; }, abstract = {The novel coronavirus SARS-CoV-2 is responsible for the devastating pandemic which has caused more than 5 million deaths across the world until today. Apart from causing acute respiratory illness and multiorgan dysfunction, there can be long-term multiorgan sequalae after recovery, which is termed 'long COVID-19' or 'post-acute COVID-19 syndrome'. Little is known about long-term gastrointestinal (GI) consequences, occurrence of post-infection functional gastrointestinal disorders and impact the virus may have on overall intestinal health. In this review, we put forth the various mechanisms which may lead to this entity and possible ways to diagnose and manage this disorder. Hence, making physicians aware of this spectrum of disease is of utmost importance in the present pandemic and this review will help clinicians understand and suspect the occurrence of functional GI disease post recovery from COVID-19 and manage it accordingly, avoiding unnecessary misconceptions and delay in treatment.}, }
@article {pmid37140960, year = {2023}, author = {Chen, B and Julg, B and Mohandas, S and Bradfute, SB and , }, title = {Viral persistence, reactivation, and mechanisms of long COVID.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {37140960}, issn = {2050-084X}, support = {K08 HL141623/HL/NHLBI NIH HHS/United States ; R01 AI162223/AI/NIAID NIH HHS/United States ; R37 AI148064/AI/NIAID NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; }, mesh = {United States ; Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; RNA, Viral ; SARS-CoV-2 ; Disease Progression ; }, abstract = {The COVID-19 global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has infected hundreds of millions of individuals. Following COVID-19 infection, a subset can develop a wide range of chronic symptoms affecting diverse organ systems referred to as post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. A National Institutes of Health-sponsored initiative, RECOVER: Researching COVID to Enhance Recovery, has sought to understand the basis of long COVID in a large cohort. Given the range of symptoms that occur in long COVID, the mechanisms that may underlie these diverse symptoms may also be diverse. In this review, we focus on the emerging literature supporting the role(s) that viral persistence or reactivation of viruses may play in PASC. Persistence of SARS-CoV-2 RNA or antigens is reported in some organs, yet the mechanism by which they do so and how they may be associated with pathogenic immune responses is unclear. Understanding the mechanisms of persistence of RNA, antigen or other reactivated viruses and how they may relate to specific inflammatory responses that drive symptoms of PASC may provide a rationale for treatment.}, }
@article {pmid37144614, year = {2023}, author = {Peluso, MJ and Antar, AAR}, title = {Long COVID in people living with HIV.}, journal = {Current opinion in HIV and AIDS}, volume = {18}, number = {3}, pages = {126-134}, pmid = {37144614}, issn = {1746-6318}, support = {K23 AI157875/AI/NIAID NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; R01 AI158013/AI/NIAID NIH HHS/United States ; R21 AI167648/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; SARS-CoV-2 ; *HIV Infections/complications ; Awareness ; }, abstract = {PURPOSE OF REVIEW: It is now recognized that SARS-CoV-2 infection can have a long-term impact on health. This review summarizes the current state of knowledge regarding Long COVID in people living with HIV (PLWH).<br><br>RECENT FINDINGS: PLWH may be at elevated risk of experiencing Long COVID. Although the mechanisms contributing to Long COVID are incompletely understood, there are several demographic and clinical factors that might make PLWH vulnerable to developing Long COVID.<br><br>SUMMARY: PLWH should be aware that new or worsening symptoms following SARS-CoV-2 infection might represent Long COVID. HIV providers should be aware of this clinical entity and be mindful that their patients recovering from SARS-CoV-2 infection may be at higher risk.}, }
@article {pmid37145350, year = {2023}, author = {Moukayed, M}, title = {A Narrative Review on the Potential Role of Vitamin D3 in the Prevention, Protection, and Disease Mitigation of Acute and Long COVID-19.}, journal = {Current nutrition reports}, volume = {12}, number = {2}, pages = {215-223}, pmid = {37145350}, issn = {2161-3311}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Cholecalciferol ; Post-Acute COVID-19 Syndrome ; Risk Factors ; }, abstract = {PURPOSE OF REVIEW: The coronavirus disease 2019 (COVID-19) pandemic has challenged global health systems and economies from January 2020. COVID-19 caused by the infectious severe acute respiratory syndrome coronavirus (SARS-CoV-2) has acute respiratory and cardiometabolic symptoms that can be severe and lethal. Long-term physiological and psychological symptoms, known as long COVID-19, persist affecting multiple organ systems. While vaccinations support the fight against SARS-CoV-2, other effective mechanisms of population protection should exist given the presence of yet unvaccinated and at-risk vulnerable groups, global disease comorbidities, and short-lived vaccine responses. The review proposes vitamin D3 as a plausible molecule for prevention, protection, and disease mitigation of acute and long COVID-19.<br><br>RECENT FINDINGS: Epidemiological studies have shown that individuals who were deficient in vitamin D3 had worse COVID-19 health outcomes and mortality rates. Higher doses of vitamin D3 supplementation may improve health and survivorship in individuals of various age groups, comorbidities, and severity of disease symptoms. Vitamin D3's biological effects can provide protection and repair in multiple organ systems affected by SARS-CoV-2. Vitamin D3 supplementation can potentially support disease-mitigation in acute and long COVID-19.}, }
@article {pmid37150350, year = {2023}, author = {Kuodi, P and Gorelik, Y and Gausi, B and Bernstine, T and Edelstein, M}, title = {Characterization of post-COVID syndromes by symptom cluster and time period up to 12 months post-infection: A systematic review and meta-analysis.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {134}, number = {}, pages = {1-7}, doi = {10.1016/j.ijid.2023.05.003}, pmid = {37150350}, issn = {1878-3511}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Public Health ; }, abstract = {OBJECTIVES: The objective of this study was to characterize post-COVID condition symptoms and symptom clusters, their duration, and prevalence.<br><br>METHODS: We conducted a systematic review and random-effects meta-analysis of studies reporting post-COVID-19 symptoms and clusters, respectively. We searched MEDLINE (via PubMed), Scopus, Web of Science, Science Direct, Google Scholar, EBSCOhost, EMBASE, PsycINFO, Cochrane Library, and Mednar for literature reporting on the post-COVID condition up to August 2022.<br><br>RESULTS: In the 76 included studies, we found that although most symptoms were reported less frequently 7-12 months after infection compared to earlier, over 20% of patients reported at least one post-COVID condition-compatible symptom. In the seven studies reporting post-COVID symptom clusters, neurological clustering was consistently identified, followed by cardiorespiratory and systemic/inflammatory.<br><br>CONCLUSION: Post-COVID symptom clustering provides direction for research into the etiology, diagnosis, and management of post-COVID conditions. Studies reporting post-COVID symptom clusters remain rare due to the focus on individual symptom reporting. Studies on post-COVID symptom clusters should replace individual symptom reporting to accelerate our understanding of this emerging public health issue.}, }
@article {pmid37153597, year = {2023}, author = {Perumal, R and Shunmugam, L and Naidoo, K and Abdool Karim, SS and Wilkins, D and Garzino-Demo, A and Brechot, C and Parthasarathy, S and Vahlne, A and Nikolich, J&#x17d;}, title = {Long COVID: a review and proposed visualization of the complexity of long COVID.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1117464}, pmid = {37153597}, issn = {1664-3224}, support = {MC_PC_16022/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Public Health ; Risk Factors ; }, abstract = {Post-Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus - 2 (SARS-CoV-2) infection, or Long COVID, is a prevailing second pandemic with nearly 100 million affected individuals globally and counting. We propose a visual description of the complexity of Long COVID and its pathogenesis that can be used by researchers, clinicians, and public health officials to guide the global effort toward an improved understanding of Long COVID and the eventual mechanism-based provision of care to afflicted patients. The proposed visualization or framework for Long COVID should be an evidence-based, dynamic, modular, and systems-level approach to the condition. Furthermore, with further research such a framework could establish the strength of the relationships between pre-existing conditions (or risk factors), biological mechanisms, and resulting clinical phenotypes and outcomes of Long COVID. Notwithstanding the significant contribution that disparities in access to care and social determinants of health have on outcomes and disease course of long COVID, our model focuses primarily on biological mechanisms. Accordingly, the proposed visualization sets out to guide scientific, clinical, and public health efforts to better understand and abrogate the health burden imposed by long COVID.}, }
@article {pmid37163427, year = {2023}, author = {Wei, ZD and Liang, K and Shetty, AK}, title = {Complications of COVID-19 on the Central Nervous System: Mechanisms and Potential Treatment for Easing Long COVID.}, journal = {Aging and disease}, volume = {14}, number = {5}, pages = {1492-1510}, pmid = {37163427}, issn = {2152-5250}, support = {R01 NS106907/NS/NINDS NIH HHS/United States ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invades human cells by binding to the angiotensin-converting-enzyme-2 (ACE-2) using a spike protein and leads to Coronavirus disease-2019 (COVID-19). COVID-19 primarily causes a respiratory infection that can lead to severe systemic inflammation. It is also common for some patients to develop significant neurological and psychiatric symptoms. The spread of SARS-CoV-2 to the CNS likely occurs through several pathways. Once spread in the CNS, many acute symptoms emerge, and such infections could also transpire into severe neurological complications, including encephalitis or ischemic stroke. After recovery from the acute infection, a significant percentage of patients develop "long COVID," a condition in which several symptoms of COVID-19 persist for prolonged periods. This review aims to discuss acute and chronic neurological problems after SARS-CoV-2 infection. The potential mechanisms by which SARS-CoV-2 enters the CNS and causes neuroinflammation, neuropathological changes observed in post-mortem brains of COVID-19 patients, and cognitive and mood problems in COVID-19 survivors are discussed in the initial part. The later part of the review deliberates the causes of long COVID, approaches for noninvasive tracking of neuroinflammation in long COVID patients, and the potential therapeutic strategies that could ease enduring CNS symptoms observed in long COVID.}, }
@article {pmid37167353, year = {2023}, author = {Chappell, MC}, title = {Renin-Angiotensin System and Sex Differences in COVID-19: A Critical Assessment.}, journal = {Circulation research}, volume = {132}, number = {10}, pages = {1320-1337}, pmid = {37167353}, issn = {1524-4571}, support = {R01 HL146818/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; Male ; Female ; *Renin-Angiotensin System/physiology ; *COVID-19 ; Angiotensin-Converting Enzyme 2/metabolism ; Peptidyl-Dipeptidase A/physiology ; SARS-CoV-2 ; Sex Characteristics ; Post-Acute COVID-19 Syndrome ; Angiotensin-Converting Enzyme Inhibitors/pharmacology ; }, abstract = {The current epidemic of corona virus disease (COVID-19) has resulted in an immense health burden that became the third leading cause of death and potentially contributed to a decline in life expectancy in the United States. The severe acute respiratory syndrome-related coronavirus-2 binds to the surface-bound peptidase angiotensin-converting enzyme 2 (ACE2, EC 3.4.17.23) leading to tissue infection and viral replication. ACE2 is an important enzymatic component of the renin-angiotensin system (RAS) expressed in the lung and other organs. The peptidase regulates the levels of the peptide hormones Ang II and Ang-(1-7), which have distinct and opposing actions to one another, as well as other cardiovascular peptides. A potential consequence of severe acute respiratory syndrome-related coronavirus-2 infection is reduced ACE2 activity by internalization of the viral-ACE2 complex and subsequent activation of the RAS (higher ratio of Ang II:Ang-[1-7]) that may exacerbate the acute inflammatory events in COVID-19 patients and possibly contribute to the effects of long COVID-19. Moreover, COVID-19 patients present with an array of autoantibodies to various components of the RAS including the peptide Ang II, the enzyme ACE2, and the AT1 AT2 and Mas receptors. Greater disease severity is also evident in male COVID-19 patients, which may reflect underlying sex differences in the regulation of the 2 distinct functional arms of the RAS. The current review provides a critical evaluation of the evidence for an activated RAS in COVID-19 subjects and whether this system contributes to the greater severity of severe acute respiratory syndrome-related coronavirus-2 infection in males as compared with females.}, }
@article {pmid37167361, year = {2023}, author = {Tsai, EJ and Cˇiháková, D and Tucker, NR}, title = {Cell-Specific Mechanisms in the Heart of COVID-19 Patients.}, journal = {Circulation research}, volume = {132}, number = {10}, pages = {1290-1301}, pmid = {37167361}, issn = {1524-4571}, support = {R01 HL138528/HL/NHLBI NIH HHS/United States ; R01 HL118183/HL/NHLBI NIH HHS/United States ; R01 HL136586/HL/NHLBI NIH HHS/United States ; K01 HL140187/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; *Myocarditis ; Endothelial Cells ; Hospital Mortality ; Post-Acute COVID-19 Syndrome ; Heart ; *Heart Diseases ; Troponin ; Myocytes, Cardiac ; }, abstract = {From the onset of the pandemic, evidence of cardiac involvement in acute COVID-19 abounded. Cardiac presentations ranged from arrhythmias to ischemia, myopericarditis/myocarditis, ventricular dysfunction to acute heart failure, and even cardiogenic shock. Elevated serum cardiac troponin levels were prevalent among hospitalized patients with COVID-19; the higher the magnitude of troponin elevation, the greater the COVID-19 illness severity and in-hospital death risk. Whether these consequences were due to direct SARS-CoV-2 infection of cardiac cells or secondary to inflammatory responses steered early cardiac autopsy studies. SARS-CoV-2 was reportedly detected in endothelial cells, cardiac myocytes, and within the extracellular space. However, findings were inconsistent and different methodologies had their limitations. Initial autopsy reports suggested that SARS-CoV-2 myocarditis was common, setting off studies to find and phenotype inflammatory infiltrates in the heart. Nonetheless, subsequent studies rarely detected myocarditis. Microthrombi, cardiomyocyte necrosis, and inflammatory infiltrates without cardiomyocyte damage were much more common. In vitro and ex vivo experimental platforms have assessed the cellular tropism of SARS-CoV-2 and elucidated mechanisms of viral entry into and replication within cardiac cells. Data point to pericytes as the primary target of SARS-CoV-2 in the heart. Infection of pericytes can account for the observed pericyte and endothelial cell death, innate immune response, and immunothrombosis commonly observed in COVID-19 hearts. These processes are bidirectional and synergistic, rendering a definitive order of events elusive. Single-cell/nucleus analyses of COVID-19 myocardial tissue and isolated cardiac cells have provided granular data about the cellular composition and cell type-specific transcriptomic signatures of COVID-19 and microthrombi-positive COVID-19 hearts. Still, much remains unknown and more in vivo studies are needed. This review seeks to provide an overview of the current understanding of COVID-19 cardiac pathophysiology. Cell type-specific mechanisms and the studies that provided such insights will be highlighted. Given the unprecedented pace of COVID-19 research, more mechanistic details are sure to emerge since the writing of this review. Importantly, our current knowledge offers significant clues about the cardiac pathophysiology of long COVID-19, the increased postrecovery risk of cardiac events, and thus, the future landscape of cardiovascular disease.}, }
@article {pmid37168008, year = {2023}, author = {Alabsi, H and Emerson, K and Lin, DJ}, title = {Neurorecovery after Critical COVID-19 Illness.}, journal = {Seminars in neurology}, volume = {43}, number = {2}, pages = {312-320}, doi = {10.1055/s-0043-1768714}, pmid = {37168008}, issn = {1098-9021}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Nervous System Diseases/diagnosis/etiology/therapy ; Acute Disease ; }, abstract = {With the hundreds of millions of people worldwide who have been, and continue to be, affected by pandemic coronavirus disease (COVID-19) and its chronic sequelae, strategies to improve recovery and rehabilitation from COVID-19 are critical global public health priorities. Neurologic complications have been associated with acute COVID-19 infection, usually in the setting of critical COVID-19 illness. Neurologic complications are also a core feature of the symptom constellation of long COVID and portend poor outcomes. In this article, we review neurologic complications and their mechanisms in critical COVID-19 illness and long COVID. We focus on parallels with neurologic disease associated with non-COVID critical systemic illness. We conclude with a discussion of how recent findings can guide both neurologists working in post-acute neurologic rehabilitation facilities and policy makers who influence neurologic resource allocation.}, }
@article {pmid37174696, year = {2023}, author = {Shevchuk, O and Palii, S and Pak, A and Chantada, N and Seoane, N and Korda, M and Campos-Toimil, M and Álvarez, E}, title = {Vessel-on-a-Chip: A Powerful Tool for Investigating Endothelial COVID-19 Fingerprints.}, journal = {Cells}, volume = {12}, number = {9}, pages = {}, pmid = {37174696}, issn = {2073-4409}, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19 ; Endothelial Cells ; Post-Acute COVID-19 Syndrome ; Lab-On-A-Chip Devices ; }, abstract = {Coronavirus disease (COVID-19) causes various vascular and blood-related reactions, including exacerbated responses. The role of endothelial cells in this acute response is remarkable and may remain important beyond the acute phase. As we move into a post-COVID-19 era (where most people have been or will be infected by the SARS-CoV-2 virus), it is crucial to define the vascular consequences of COVID-19, including the long-term effects on the cardiovascular system. Research is needed to determine whether chronic endothelial dysfunction following COVID-19 could lead to an increased risk of cardiovascular and thrombotic events. Endothelial dysfunction could also serve as a diagnostic and therapeutic target for post-COVID-19. This review covers these topics and examines the potential of emerging vessel-on-a-chip technology to address these needs. Vessel-on-a-chip would allow for the study of COVID-19 pathophysiology in endothelial cells, including the analysis of SARS-CoV-2 interactions with endothelial function, leukocyte recruitment, and platelet activation. "Personalization" could be implemented in the models through induced pluripotent stem cells, patient-specific characteristics, or genetic modified cells. Adaptation for massive testing under standardized protocols is now possible, so the chips could be incorporated for the personalized follow-up of the disease or its sequalae (long COVID) and for the research of new drugs against COVID-19.}, }
@article {pmid37175509, year = {2023}, author = {Costanzo, M and De Giglio, MAR and Roviello, GN}, title = {Deciphering the Relationship between SARS-CoV-2 and Cancer.}, journal = {International journal of molecular sciences}, volume = {24}, number = {9}, pages = {}, pmid = {37175509}, issn = {1422-0067}, mesh = {Humans ; SARS-CoV-2 ; *Epstein-Barr Virus Infections/complications ; *Papillomavirus Infections/complications ; Post-Acute COVID-19 Syndrome ; Herpesvirus 4, Human ; *COVID-19/complications ; *Neoplasms/pathology ; Oncogenic Viruses/genetics ; Cell Transformation, Neoplastic ; *Hepatitis C/complications ; }, abstract = {Some viruses are known to be associated with the onset of specific cancers. These microorganisms, oncogenic viruses or oncoviruses, can convert normal cells into cancer cells by modulating the central metabolic pathways or hampering genomic integrity mechanisms, consequently inhibiting the apoptotic machinery and/or enhancing cell proliferation. Seven oncogenic viruses are known to promote tumorigenesis in humans: human papillomavirus (HPV), hepatitis B and C viruses (HBV, HCV), Epstein-Barr virus (EBV), human T-cell leukemia virus 1 (HTLV-1), Kaposi sarcoma-associated herpesvirus (KSHV), and Merkel cell polyomavirus (MCPyV). Recent research indicates that SARS-CoV-2 infection and COVID-19 progression may predispose recovered patients to cancer onset and accelerate cancer development. This hypothesis is based on the growing evidence regarding the ability of SARS-CoV-2 to modulate oncogenic pathways, promoting chronic low-grade inflammation and causing tissue damage. Herein, we summarize the main relationships known to date between virus infection and cancer, providing a summary of the proposed biochemical mechanisms behind the cellular transformation. Mechanistically, DNA viruses (such as HPV, HBV, EBV, and MCPyV) encode their virus oncogenes. In contrast, RNA viruses (like HCV, HTLV-1) may encode oncogenes or trigger host oncogenes through cis-/-trans activation leading to different types of cancer. As for SARS-CoV-2, its role as an oncogenic virus seems to occur through the inhibition of oncosuppressors or controlling the metabolic and autophagy pathways in the infected cells. However, these effects could be significant in particular scenarios like those linked to severe COVID-19 or long COVID. On the other hand, looking at the SARS-CoV-2─cancer relationship from an opposite perspective, oncolytic effects and anti-tumor immune response were triggered by SARS-CoV-2 infection in some cases. In summary, our work aims to recall comprehensive attention from the scientific community to elucidate the effects of SARS-CoV-2 and, more in general, β-coronavirus infection on cancer susceptibility for cancer prevention or supporting therapeutic approaches.}, }
@article {pmid37175745, year = {2023}, author = {Chen, TH and Chang, CJ and Hung, PH}, title = {Possible Pathogenesis and Prevention of Long COVID: SARS-CoV-2-Induced Mitochondrial Disorder.}, journal = {International journal of molecular sciences}, volume = {24}, number = {9}, pages = {}, pmid = {37175745}, issn = {1422-0067}, mesh = {Humans ; SARS-CoV-2 ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Inflammation ; *Mitochondrial Diseases ; }, abstract = {Patients who have recovered from coronavirus disease 2019 (COVID-19) infection may experience chronic fatigue when exercising, despite no obvious heart or lung abnormalities. The present lack of effective treatments makes managing long COVID a major challenge. One of the underlying mechanisms of long COVID may be mitochondrial dysfunction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can alter the mitochondria responsible for energy production in cells. This alteration leads to mitochondrial dysfunction which, in turn, increases oxidative stress. Ultimately, this results in a loss of mitochondrial integrity and cell death. Moreover, viral proteins can bind to mitochondrial complexes, disrupting mitochondrial function and causing the immune cells to over-react. This over-reaction leads to inflammation and potentially long COVID symptoms. It is important to note that the roles of mitochondrial damage and inflammatory responses caused by SARS-CoV-2 in the development of long COVID are still being elucidated. Targeting mitochondrial function may provide promising new clinical approaches for long-COVID patients; however, further studies are needed to evaluate the safety and efficacy of such approaches.}, }
@article {pmid37175942, year = {2023}, author = {Vassiliou, AG and Vrettou, CS and Keskinidou, C and Dimopoulou, I and Kotanidou, A and Orfanos, SE}, title = {Endotheliopathy in Acute COVID-19 and Long COVID.}, journal = {International journal of molecular sciences}, volume = {24}, number = {9}, pages = {}, pmid = {37175942}, issn = {1422-0067}, mesh = {Humans ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; *Vascular Diseases/pathology ; Lung/pathology ; Biomarkers ; }, abstract = {The pulmonary endothelium is a highly regulated organ that performs a wide range of functions under physiological and pathological conditions. Since endothelial dysfunction has been demonstrated to play a direct role in sepsis and acute respiratory distress syndrome, its role in COVID-19 has also been extensively investigated. Indeed, apart from the COVID-19-associated coagulopathy biomarkers, new biomarkers were recognised early during the pandemic, including markers of endothelial cell activation or injury. We systematically searched the literature up to 10 March 2023 for studies examining the association between acute and long COVID-19 severity and outcomes and endothelial biomarkers.}, }
@article {pmid37175995, year = {2023}, author = {Gonzalez-Garcia, P and Fiorillo Moreno, O and Zarate Peñata, E and Calderon-Villalba, A and Pacheco Lugo, L and Acosta Hoyos, A and Villarreal Camacho, JL and Navarro Quiroz, R and Pacheco Londoño, L and Aroca Martinez, G and Moares, N and Gabucio, A and Fernandez-Ponce, C and Garcia-Cozar, F and Navarro Quiroz, E}, title = {From Cell to Symptoms: The Role of SARS-CoV-2 Cytopathic Effects in the Pathogenesis of COVID-19 and Long COVID.}, journal = {International journal of molecular sciences}, volume = {24}, number = {9}, pages = {}, pmid = {37175995}, issn = {1422-0067}, support = {2021//Fundaci&#xf3;n Carolina/ ; 2021//Universidad Sim&#xf3;n Bol&#xed;var/ ; PI-0030-2017//Regional Government of Andalusia/ ; 125380763038, 125380763188 and SGR code BPIN 2020000100144.//Colciencias/ ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2/metabolism ; Post-Acute COVID-19 Syndrome ; Peptidyl-Dipeptidase A/metabolism ; Host Microbial Interactions ; }, abstract = {Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection triggers various events from molecular to tissue level, which in turn is given by the intrinsic characteristics of each patient. Given the molecular diversity characteristic of each cellular phenotype, the possible cytopathic, tissue and clinical effects are difficult to predict, which determines the heterogeneity of COVID-19 symptoms. The purpose of this article is to provide a comprehensive review of the cytopathic effects of SARS-CoV-2 on various cell types, focusing on the development of COVID-19, which in turn may lead, in some patients, to a persistence of symptoms after recovery from the disease, a condition known as long COVID. We describe the molecular mechanisms underlying virus-host interactions, including alterations in protein expression, intracellular signaling pathways, and immune responses. In particular, the article highlights the potential impact of these cytopathies on cellular function and clinical outcomes, such as immune dysregulation, neuropsychiatric disorders, and organ damage. The article concludes by discussing future directions for research and implications for the management and treatment of COVID-19 and long COVID.}, }
@article {pmid37176630, year = {2023}, author = {Granholm, AC}, title = {Long-Term Effects of SARS-CoV-2 in the Brain: Clinical Consequences and Molecular Mechanisms.}, journal = {Journal of clinical medicine}, volume = {12}, number = {9}, pages = {}, pmid = {37176630}, issn = {2077-0383}, support = {R01 AG071228/AG/NIA NIH HHS/United States ; RF1 AG061566/AG/NIA NIH HHS/United States ; RF1 AG070153/AG/NIA NIH HHS/United States ; P01 AG014449/AG/NIA NIH HHS/United States ; R01AG061566/GF/NIH HHS/United States ; }, abstract = {Numerous investigations have demonstrated significant and long-lasting neurological manifestations of COVID-19. It has been suggested that as many as four out of five patients who sustained COVID-19 will show one or several neurological symptoms that can last months after the infection has run its course. Neurological symptoms are most common in people who are less than 60 years of age, while encephalopathy is more common in those over 60. Biological mechanisms for these neurological symptoms need to be investigated and may include both direct and indirect effects of the virus on the brain and spinal cord. Individuals with Alzheimer's disease (AD) and related dementia, as well as persons with Down syndrome (DS), are especially vulnerable to COVID-19, but the biological reasons for this are not clear. Investigating the neurological consequences of COVID-19 is an urgent emerging medical need, since close to 700 million people worldwide have now had COVID-19 at least once. It is likely that there will be a new burden on healthcare and the economy dealing with the long-term neurological consequences of severe SARS-CoV-2 infections and long COVID, even in younger generations. Interestingly, neurological symptoms after an acute infection are strikingly similar to the symptoms observed after a mild traumatic brain injury (mTBI) or concussion, including dizziness, balance issues, anosmia, and headaches. The possible convergence of biological pathways involved in both will be discussed. The current review is focused on the most commonly described neurological symptoms, as well as the possible molecular mechanisms involved.}, }
@article {pmid37178769, year = {2023}, author = {Nicolai, L and Kaiser, R and Stark, K}, title = {Thromboinflammation in long COVID-the elusive key to postinfection sequelae?.}, journal = {Journal of thrombosis and haemostasis : JTH}, volume = {21}, number = {8}, pages = {2020-2031}, pmid = {37178769}, issn = {1538-7836}, mesh = {Humans ; *COVID-19/complications ; *Thrombosis ; Inflammation ; Post-Acute COVID-19 Syndrome ; Thromboinflammation ; Disease Progression ; }, abstract = {Long COVID is a public health emergency affecting millions of people worldwide, characterized by heterogeneous symptoms across multiple organ systems. Here, we discuss the current evidence linking thromboinflammation to postacute sequelae of COVID-19. Studies have found persistence of vascular damage with increased circulating markers of endothelial dysfunction, coagulation abnormalities with heightened thrombin generation capacity, and abnormalities in platelet counts in postacute sequelae of COVID-19. Neutrophil phenotype resembles acute COVID-19 with an increase in activation and Neutrophil Extracellular Trap formation. These insights are potentially linked by elevated platelet-neutrophil aggregate formation. This hypercoagulable state in turn can lead to microvascular thrombosis, evidenced by microclots and elevated D-dimer in the circulation as well as perfusion abnormalities in the lungs and brains of patients with long COVID. Also, COVID-19 survivors experience an increased rate of arterial and venous thrombotic events. We discuss 3 important, potentially intertwined hypotheses that might contribute to thromboinflammation in long COVID: lasting structural changes, most prominently endothelial damage, caused during initial infection; a persistent viral reservoir; and immunopathology driven by a misguided immune system. Finally, we outline the necessity for large, well-characterized clinical cohorts and mechanistic studies to clarify the contribution of thromboinflammation to long COVID.}, }
@article {pmid37179568, year = {2023}, author = {Kenny, G and Townsend, L and Savinelli, S and Mallon, PWG}, title = {Long COVID: Clinical characteristics, proposed pathogenesis and potential therapeutic targets.}, journal = {Frontiers in molecular biosciences}, volume = {10}, number = {}, pages = {1157651}, pmid = {37179568}, issn = {2296-889X}, abstract = {The emergence of persistent ill-health in the aftermath of SARS-CoV-2 infection has presented significant challenges to patients, healthcare workers and researchers. Termed long COVID, or post-acute sequelae of COVID-19 (PASC), the symptoms of this condition are highly variable and span multiple body systems. The underlying pathophysiology remains poorly understood, with no therapeutic agents proven to be effective. This narrative review describes predominant clinical features and phenotypes of long COVID alongside the data supporting potential pathogenesis of these phenotypes including ongoing immune dysregulation, viral persistence, endotheliopathy, gastrointestinal microbiome disturbance, autoimmunity, and dysautonomia. Finally, we describe current potential therapies under investigation, as well as future potential therapeutic options based on the proposed pathogenesis research.}, }
@article {pmid37182545, year = {2023}, author = {Srikanth, S and Boulos, JR and Dover, T and Boccuto, L and Dean, D}, title = {Identification and diagnosis of long COVID-19: A scoping review.}, journal = {Progress in biophysics and molecular biology}, volume = {182}, number = {}, pages = {1-7}, pmid = {37182545}, issn = {1873-1732}, support = {P20 GM121342/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/diagnosis ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Quality of Life ; COVID-19 Testing ; }, abstract = {Long COVID-19 (LC-19) is a condition that has affected a high percentage of the population that recovered from the initial disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). LC-19 diagnosis is currently poorly defined because of its variable, multisystem, episodic symptoms, and lack of uniformity in the critical time points associated with the disease. Considering the number of cases, workers' compromised efficiency or inability to return to their duties can affect organizations and impact economies. LC-19 represents a significant burden on multiple levels and effectively reduces quality of life. These factors necessitate the establishment of firm parameters of diagnoses to provide a foundation for ongoing and future studies of clinical characteristics, epidemiology, risk factors, and therapy. In this scoping review, we conducted a literature search across multiple publication sites to identify papers of interest regarding the diagnosis of LC-19. We identified 225 records of interest and categorized them into seven categories. Based on our findings, there are only 11 original papers that outline the diagnostic process in detail with little overlap. This scoping review highlights the lack of consensus regarding the definition and, thereby, the LC-19 diagnosis processes. Due to no clear directive and considering the many unknowns surrounding the natural history of the disease and further recovery/sequelae from COVID-19, continued discussion and agreement on a definition/diagnosis will help future research and management of these patients.}, }
@article {pmid37184668, year = {2023}, author = {Szabo, S}, title = {The post-COVID stress syndrome: from the three-stage stress response of Hans Selye to COVID-19.}, journal = {Inflammopharmacology}, volume = {31}, number = {6}, pages = {2799-2806}, pmid = {37184668}, issn = {1568-5608}, mesh = {Male ; Humans ; Rats ; Animals ; *COVID-19 ; Hydrocortisone ; Stress, Physiological ; SARS-CoV-2 ; Adrenal Cortex Hormones ; Glucocorticoids ; }, abstract = {Stress is the nonspecific response of the body to any demand made upon it, as defined by Hans Selye more than 80 years ago, based on his animal experiments at McGill University in Montreal, Canada. By emphasizing 'nonspecificity' he tried to underline that stress response is elicited my several factors, like nowadays in COVID-19, e.g., fear of infection, social isolation, death in family, loss of employment, etc. Thus, COVID-19 has been the largest new human stressor in the twenty-first century. Selye's studies in rats also revealed 3 stages of stress response: the short initial "alarm reaction" is followed by a longer "stage of resistance", associated with increased levels of corticosterone that is often terminated by a "stage of exhaustion", referring to an exhausted adrenal cortex when the secretion of glucocorticoids drops. Fast forward, that is exactly what has been documented in severe cases of infections caused by the SARS-CoV-2 virus: in hospitalized COVID-19 patients initially the blood levels of cortisol not only have been elevated, but only those with high concentration of this natural anti-inflammatory corticosteroid survived vs. those who had low levels of cortisol, suggesting diminished adrenocortical functions. Furthermore, patients with very severe cases of COVID-19 who ended up in intensive care units had significantly low cortisol blood levels, compared to patients with equal severity of diseases due to other causes. Thus, these 'natural phenomena' in clinical medicine, unfortunately confirmed Selye's studies in experimental animals several decades ago. Still, the good news is that astute clinicians empirically recognized this and started to give potent synthetic glucocorticoids such as dexamethasone to severe COVD-19 patients and this beneficial effect of exogenous corticoids has been extensively confirmed in the scientific literature.}, }
@article {pmid37185117, year = {2023}, author = {Burnett, DM and Skinner, CE}, title = {Year in Review: Long COVID and Pulmonary Rehabilitation.}, journal = {Respiratory care}, volume = {68}, number = {6}, pages = {846-851}, pmid = {37185117}, issn = {1943-3654}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Exercise ; Dyspnea ; Fatigue/etiology ; Quality of Life ; }, abstract = {There have been an estimated 100 million people diagnosed with COVID-19 in the United States, with a majority of patients reporting persistent symptoms expressed as long COVID. The 2 most frequently reported long COVID symptoms are shortness of breath and fatigue. Exercise training during pulmonary rehabilitation (PR) is a successful strategy for improving the lives of people with persistent respiratory symptoms caused by a variety of lung diseases. This narrative review assessed the impact of exercise interventions on functional exercise capacity measures and related symptoms (dyspnea, fatigue) in people with long COVID over the last year. Articles were accessed through electronic databases including PubMed, Embase, CINAHL Plus with full text (EBSCO), and LitCovid. Findings for this Year in Review revealed that exercise interventions and PR show promise for improving functional exercise capacity, dyspnea, and fatigue in people with long COVID. This review supports the need for more rigorous scientific studies on the benefits of structured PR in people with long COVID who have respiratory-related symptoms.}, }
@article {pmid37189823, year = {2023}, author = {Vilaplana-Carnerero, C and Giner-Soriano, M and Dominguez, &#xc0; and Morros, R and Pericas, C and Álamo-Junquera, D and Toledo, D and Gallego, C and Redondo, A and Grau, M}, title = {Atherosclerosis, Cardiovascular Disease, and COVID-19: A Narrative Review.}, journal = {Biomedicines}, volume = {11}, number = {4}, pages = {}, pmid = {37189823}, issn = {2227-9059}, abstract = {Atherosclerosis is a chronic inflammatory and degenerative process that mainly occurs in large- and medium-sized arteries and is morphologically characterized by asymmetric focal thickenings of the innermost layer of the artery, the intima. This process is the basis of cardiovascular diseases (CVDs), the most common cause of death worldwide. Some studies suggest a bidirectional link between atherosclerosis and the consequent CVD with COVID-19. The aims of this narrative review are (1) to provide an overview of the most recent studies that point out a bidirectional relation between COVID-19 and atherosclerosis and (2) to summarize the impact of cardiovascular drugs on COVID-19 outcomes. A growing body of evidence shows that COVID-19 prognosis in individuals with CVD is worse compared with those without. Moreover, various studies have reported the emergence of newly diagnosed patients with CVD after COVID-19. The most common treatments for CVD may influence COVID-19 outcomes. Thus, their implication in the infection process is briefly discussed in this review. A better understanding of the link among atherosclerosis, CVD, and COVID-19 could proactively identify risk factors and, as a result, develop strategies to improve the prognosis for these patients.}, }
@article {pmid37192595, year = {2023}, author = {Scholkmann, F and May, CA}, title = {COVID-19, post-acute COVID-19 syndrome (PACS, "long COVID") and post-COVID-19 vaccination syndrome (PCVS, "post-COVIDvac-syndrome"): Similarities and differences.}, journal = {Pathology, research and practice}, volume = {246}, number = {}, pages = {154497}, pmid = {37192595}, issn = {1618-0631}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; COVID-19 Vaccines ; SARS-CoV-2 ; Vaccination ; }, abstract = {Worldwide there have been over 760 million confirmed coronavirus disease 2019 (COVID-19) cases, and over 13 billion COVID-19 vaccine doses have been administered as of April 2023, according to the World Health Organization. An infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to an acute disease, i.e. COVID-19, but also to a post-acute COVID-19 syndrome (PACS, "long COVID"). Currently, the side effects of COVID-19 vaccines are increasingly being noted and studied. Here, we summarise the currently available indications and discuss our conclusions that (i) these side effects have specific similarities and differences to acute COVID-19 and PACS, that (ii) a new term should be used to refer to these side effects (post-COVID-19 vaccination syndrome, PCVS, colloquially "post-COVIDvac-syndrome"), and that (iii) there is a need to distinguish between acute COVID-19 vaccination syndrome (ACVS) and post-acute COVID-19 vaccination syndrome (PACVS) - in analogy to acute COVID-19 and PACS ("long COVID"). Moreover, we address mixed forms of disease caused by natural SARS-CoV-2 infection and COVID-19 vaccination. We explain why it is important for medical diagnosis, care and research to use the new terms (PCVS, ACVS and PACVS) in order to avoid confusion and misinterpretation of the underlying causes of disease and to enable optimal medical therapy. We do not recommend to use the term "Post-Vac-Syndrome" as it is imprecise. The article also serves to address the current problem of "medical gaslighting" in relation to PACS and PCVS by raising awareness among the medical professionals and supplying appropriate terminology for disease.}, }
@article {pmid37194484, year = {2023}, author = {MCCarthy, MW}, title = {Metformin as a potential treatment for COVID-19.}, journal = {Expert opinion on pharmacotherapy}, volume = {24}, number = {10}, pages = {1199-1203}, doi = {10.1080/14656566.2023.2215385}, pmid = {37194484}, issn = {1744-7666}, mesh = {Humans ; Middle Aged ; *COVID-19 ; SARS-CoV-2 ; *Metformin/therapeutic use ; Post-Acute COVID-19 Syndrome ; COVID-19 Vaccines ; }, abstract = {INTRODUCTION: Early treatment for SARS-CoV-2 infection is essential to limit the clinical progression of COVID-19. However, limited therapeutic options are available for standard-risk patients, including those under age 50 who have received the primary series of COVID-19 vaccination as well as a bivalent booster.<br><br>AREAS COVERED: Metformin is a widely used, inexpensive antihyperglycemic for the treatment of diabetes mellitus type 2 as well as polycystic ovarian syndrome, with a well-described safety profile.<br><br>EXPERT OPINION: Although the mechanism of action has not been fully elucidated, metformin is known to alter glucose metabolism and is under investigation as an antiviral agent, demonstrating in vitro and in vivo activity against SARS-CoV-2. Recent work suggests metformin may also serve as a therapeutic option for patients with COVID-19 as well as those with post-acute sequelae of SARS-CoV-2 infection, known more commonly as 'long COVID-19.' This manuscript examines what is known about metformin for the treatment of COVID-19 and explores how this drug may be used in the future to address the SARS-CoV-2 pandemic.}, }
@article {pmid37195978, year = {2023}, author = {Mat Hassan, N and Salim, HS and Amaran, S and Yunus, NI and Yusof, NA and Daud, N and Fry, D}, title = {Prevalence of mental health problems among children with long COVID: A systematic review and meta-analysis.}, journal = {PloS one}, volume = {18}, number = {5}, pages = {e0282538}, pmid = {37195978}, issn = {1932-6203}, mesh = {Adolescent ; Humans ; Child ; *COVID-19/epidemiology ; Mental Health ; Post-Acute COVID-19 Syndrome ; Pandemics ; Prevalence ; Cross-Sectional Studies ; Anxiety/epidemiology/diagnosis ; Depression/epidemiology/diagnosis ; }, abstract = {INTRODUCTION: The number of children with mental health problems has more than doubled since the COVID-19 pandemic. However, the effect of long Covid on children's mental health is still debatable. Recognising long Covid as a risk factor for mental health problems in children will increase awareness and screening for mental health problems following COVID-19 infection, resulting in earlier intervention and lower morbidity. Therefore, this study aimed to determine the proportion of mental health problems post-COVID-19 infection in children and adolescents, and to compare them with the population with no previous COVID-19 infection.<br><br>METHODOLOGY: A systematic search was done in seven databases using pre-defined search terms. Cross-sectional, cohort and interventional studies reporting the proportion of mental health problems among children with long COVID in the English language from 2019 to May 2022 were included. Selection of papers, extraction of data and quality assessment were done independently by two reviewers. Studies with satisfactory quality were included in meta-analysis using R and Revman software programmes.<br><br>RESULTS: The initial search retrieved 1848 studies. After screening, 13 studies were included in the quality assessments. Meta-analysis showed children who had previous COVID-19 infection had more than two times higher odds of having anxiety or depression, and 14% higher odds of having appetite problems, compared to children with no previous infection. The pooled prevalence of mental health problems among the population were as follows; anxiety: 9%(95% CI:1, 23), depression: 15%(95% CI:0.4, 47), concentration problems: 6%(95% CI: 3, 11), sleep problems: 9%(95% CI:5, 13), mood swings: 13% (95%CI:5, 23) and appetite loss: 5%(95% CI:1, 13). However, studies were heterogenous and lack data from low- and middle-income countries.<br><br>CONCLUSION: Anxiety, depression and appetite problems were significantly increased among post-COVID-19 infected children, compared to those without a previous infection, which may be attributed to long COVID. The findings underscore the importance of screening and early intervention of children post-COVID-19 infection at one month and between three to four months.}, }
@article {pmid37201006, year = {2023}, author = {Evcik, D}, title = {Musculoskeletal involvement: COVID-19 and post COVID 19.}, journal = {Turkish journal of physical medicine and rehabilitation}, volume = {69}, number = {1}, pages = {1-7}, pmid = {37201006}, issn = {2587-1250}, abstract = {The worldwide pandemic of coronavirus disease 2019 (COVID-19) was known to predominantly affect the lungs, but it was realized that COVID-19 had a large variety of clinical involvement. Cardiovascular, gastrointestinal, neurological, and musculoskeletal systems are involved by direct or indirect mechanisms with various manifestations. The musculoskeletal involvement can manifest during COVID-19 infection, due to medications used for the treatment of COVID-19, and in the post/long COVID-19 syndrome. The major symptoms are fatigue, myalgia/arthralgia, back pain, low back pain, and chest pain. During the last two years, musculoskeletal involvement increased, but no clear consensus was obtained about the pathogenesis. However, there is valuable data that supports the hypothesis of angiotensinconverting enzyme 2, inflammation, hypoxia, and muscle catabolism. Additionally, medications that were used for treatment also have musculoskeletal adverse effects, such as corticosteroid-induced myopathy and osteoporosis. Therefore, while deciding the drugs, priorities and benefits should be taken into consideration. Symptoms that begin three months from the onset of the COVID-19 infection, continue for at least two months, and cannot be explained by another diagnosis is accepted as post/long COVID-19 syndrome. Prior symptoms may persist and fluctuate, or new symptoms may manifest. In addition, there must be at least one symptom of infection. Most common musculoskeletal symptoms are myalgia, arthralgia, fatigue, back pain, muscle weakness, sarcopenia, impaired exercise capacity, and physical performance. In addition, the female sex, obesity, elderly patients, hospitalization, prolonged immobility, having mechanical ventilation, not having vaccination, and comorbid disorders can be accepted as clinical predictors for post/long COVID-19 syndrome. Musculoskeletal pain is also a major problem and tends to be in chronic form. There is no consensus on the mechanism, but inflammation and angiotensin-converting enzyme 2 seem to play an important role. Localized and generalized pain may occur after COVID-19, and general pain is at least as common as localized pain. An accurate diagnosis allows physicians to initiate pain management and proper rehabilitation programs.}, }
@article {pmid37204997, year = {2023}, author = {Narasimhan, B and Calambur, A and Moras, E and Wu, L and Aronow, W}, title = {Postural Orthostatic Tachycardia Syndrome in COVID-19: A Contemporary Review of Mechanisms, Clinical Course and Management.}, journal = {Vascular health and risk management}, volume = {19}, number = {}, pages = {303-316}, pmid = {37204997}, issn = {1178-2048}, mesh = {Humans ; *Postural Orthostatic Tachycardia Syndrome/diagnosis/epidemiology/therapy ; Post-Acute COVID-19 Syndrome ; *COVID-19/diagnosis ; Disease Progression ; }, abstract = {The long-term implications of COVID-19 have garnered increasing interest in recent months, with Long-COVID impacting over 65 million individuals worldwide. Postural orthostatic tachycardia syndrome (POTS) has emerged as an important component of the Long-COVID umbrella, estimated to affect between 2 and 14% of survivors. POTS remains very challenging to diagnose and manage - this review aims to provide a brief overview of POTS as a whole and goes on to summarize the available literature pertaining to POTS in the setting of COVID-19. We provide a review of available clinical reports, outline proposed pathophysiological mechanisms and end with a brief note on management considerations.}, }
@article {pmid37209039, year = {2023}, author = {D'Souza, F and Buzzetti, R and Pozzilli, P}, title = {Diabetes, COVID-19, and questions unsolved.}, journal = {Diabetes/metabolism research and reviews}, volume = {39}, number = {5}, pages = {e3666}, doi = {10.1002/dmrr.3666}, pmid = {37209039}, issn = {1520-7560}, mesh = {Humans ; COVID-19 Vaccines ; *COVID-19/complications/epidemiology ; *Diabetes Mellitus/epidemiology ; *Hyperglycemia ; Disease Progression ; }, abstract = {Recent evidence suggests a role for Diabetes Mellitus in adverse outcomes from COVID-19 infection; yet the underlying mechanisms are not clear. Moreover, attention has turned to prophylactic vaccination to protect the population from COVID-19-related illness and mortality. We performed a comprehensive peer-reviewed literature search on an array of key terms concerning diabetes and COVID-19 seeking to address the following questions: 1. What role does diabetes play as an accelerator for adverse outcomes in COVID-19?; 2. What mechanisms underlie the differences in outcomes seen in people with diabetes?; 3. Are vaccines against COVID-19 efficacious in people with diabetes? The current literature demonstrates that diabetes is associated with an increased risk of adverse outcomes from COVID-19 infection, and post-COVID sequelae. Potential mechanisms include dysregulation of Angiotensin Converting Enzyme 2, Furin, CD147, and impaired immune cell responses. Hyperglycaemia is a key exacerbator of these mechanisms. Limited studies are available on COVID-19 vaccination in people with diabetes; however, the current literature suggests that vaccination is protective against adverse outcomes for this population. In summary, people with diabetes are a high-risk group that should be prioritised in vaccination efforts. Glycaemic optimisation is paramount to protecting this group from COVID-19-associated risk. Unsolved questions remain as to the molecular mechanisms underlying the adverse outcomes seen in people with diabetes; the functional impact of post-COVID symptoms on people with diabetes, their persistence, and management; how long-term vaccine efficacy is affected by diabetes, and the antibody levels that confer protection from adverse outcomes in COVID-19.}, }
@article {pmid37209261, year = {2024}, author = {Kole, C and Stefanou, &#x395; and Karvelas, N and Schizas, D and Toutouzas, KP}, title = {Acute and Post-Acute COVID-19 Cardiovascular Complications: A Comprehensive Review.}, journal = {Cardiovascular drugs and therapy}, volume = {38}, number = {5}, pages = {1017-1032}, pmid = {37209261}, issn = {1573-7241}, mesh = {Humans ; *COVID-19/complications/epidemiology/therapy ; *Cardiovascular Diseases/epidemiology/etiology ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Risk Factors ; Acute Disease ; }, abstract = {PURPOSE OF REVIEW: The risk of cardiovascular complications due to SARS-CoV-2 are significantly increased within the first 6 months of the infection. Patients with COVID-19 have an increased risk of death, and there is evidence that many may experience a wide range of post-acute cardiovascular complications. Our work aims to provide an update on current clinical aspects of diagnosis and treatment of cardiovascular manifestations during acute and long-term COVID-19.<br><br>RECENT FINDINGS: SARS-CoV-2 has been shown to be associated with increased incidence of cardiovascular complications such as myocardial injury, heart failure, and dysrhythmias, as well as coagulation abnormalities not only during the acute phase but also beyond the first 30 days of the infection, associated with high mortality and poor outcomes. Cardiovascular complications during long-COVID-19 were found regardless of comorbidities such as age, hypertension, and diabetes; nevertheless, these populations remain at high risk for the worst outcomes during post-acute COVID-19. Emphasis should be given to the management of these patients. Treatment with low-dose oral propranolol, a beta blocker, for heart rate management may be considered, since it was found to significantly attenuate tachycardia and improve symptoms in postural tachycardia syndrome, while for patients on ACE inhibitors or angiotensin-receptor blockers (ARBs), under no circumstances should these medications be withdrawn. In addition, in patients at high risk after hospitalization due to COVID-19, thromboprophylaxis with rivaroxaban 10 mg/day for 35 days improved clinical outcomes compared with no extended thromboprophylaxis. In this work we provide a comprehensive review on acute and post-acute COVID-19 cardiovascular complications, symptomatology, and pathophysiology mechanisms. We also discuss therapeutic strategies for these patients during acute and long-term care and highlight populations at risk. Our findings suggest that older patients with risk factors such as hypertension, diabetes, and medical history of vascular disease have worse outcomes during acute SARS-CoV-2 infection and are more likely to develop cardiovascular complications during long-COVID-19.}, }
@article {pmid37215236, year = {2023}, author = {SeyedAlinaghi, S and Bagheri, A and Razi, A and Mojdeganlou, P and Mojdeganlou, H and Afsahi, AM and Afzalian, A and Paranjkhoo, P and Shahidi, R and Mirzapour, P and Pashaei, Z and Habibi, MA and Shahbazi, P and Nooralioghli Parikhani, S and Farizani Gohari, NS and Popoola, Y and Mehraeen, E and Hackett, D}, title = {Late Complications of COVID-19; An Umbrella Review on Current Systematic Reviews.}, journal = {Archives of academic emergency medicine}, volume = {11}, number = {1}, pages = {e28}, pmid = {37215236}, issn = {2645-4904}, abstract = {INTRODUCTION: Several clinical manifestations have been discovered for COVID-19 since the emergence of SARS-CoV-2, which can be classified into early, medium, and long-term complications. However, late complications can be present after recovery from acute COVID-19 illness. The present study aims to comprehensively review the available evidence of late complications related to COVID-19.<br><br>METHOD: A search was conducted, using keywords, through electronic databases, which included Scopus, Web of Science, PubMed, and Embase up to August 29, 2022. Study selection was performed according to a strict inclusion and exclusion criteria. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) checklist was followed, and studies were appraised using the National Institute of Health (NIH) quality assessment and risk of bias tool.<br><br>RESULTS: In total, 50 studies were included, and nine distinct COVID-19 late complication categories were identified. A review of these studies revealed that neurologic and psychiatric (n=41), respiratory (n=27), musculoskeletal and rheumatologic (n=22), cardiovascular (n=9), and hepatic and gastrointestinal (n=6) complications were the most prevalent complications of long COVID-19.<br><br>CONCLUSION: Almost all human body systems are affected by late complications of COVID-19 with different severity and prevalence. Fatigue and some other neuropsychiatric symptoms are the most common late complications among long COVID-19 patients. Respiratory symptoms including dyspnea (during exercise), cough, and chest tightness were the next most prevalent long-term complications of COVID-19. Since these complications are persistent and late, being aware of the signs and symptoms is essential for the healthcare providers and patients.}, }
@article {pmid37216955, year = {2023}, author = {Singh, SJ and Baldwin, MM and Daynes, E and Evans, RA and Greening, NJ and Jenkins, RG and Lone, NI and McAuley, H and Mehta, P and Newman, J and Novotny, P and Smith, DJF and Stanel, S and Toshner, M and Brightling, CE}, title = {Respiratory sequelae of COVID-19: pulmonary and extrapulmonary origins, and approaches to clinical care and rehabilitation.}, journal = {The Lancet. Respiratory medicine}, volume = {11}, number = {8}, pages = {709-725}, pmid = {37216955}, issn = {2213-2619}, support = {MR/W006111/1/MRC_/Medical Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; SARS-CoV-2 ; Dyspnea/etiology/therapy ; *Pulmonary Fibrosis ; Disease Progression ; }, abstract = {Although the exact prevalence of post-COVID-19 condition (also known as long COVID) is unknown, more than a third of patients with COVID-19 develop symptoms that persist for more than 3 months after SARS-CoV-2 infection. These sequelae are highly heterogeneous in nature and adversely affect multiple biological systems, although breathlessness is a frequently cited symptom. Specific pulmonary sequelae, including pulmonary fibrosis and thromboembolic disease, need careful assessment and might require particular investigations and treatments. COVID-19 outcomes in people with pre-existing respiratory conditions vary according to the nature and severity of the respiratory disease and how well it is controlled. Extrapulmonary complications such as reduced exercise tolerance and frailty might contribute to breathlessness in post-COVID-19 condition. Non-pharmacological therapeutic options, including adapted pulmonary rehabilitation programmes and physiotherapy techniques for breathing management, might help to attenuate breathlessness in people with post-COVID-19 condition. Further research is needed to understand the origins and course of respiratory symptoms and to develop effective therapeutic and rehabilitative strategies.}, }
@article {pmid37217235, year = {2023}, author = {George, AS and Lopes, CA and Vijayasingham, L and Mothupi, MC and Musizvingoza, R and Mishra, G and Stevenson, J and Remme, M}, title = {A shared agenda for gender and COVID-19 research: priorities based on broadening engagement in science.}, journal = {BMJ global health}, volume = {8}, number = {5}, pages = {}, pmid = {37217235}, issn = {2059-7908}, mesh = {Male ; Humans ; Female ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Lactation ; Public Policy ; }, abstract = {While the acute and collective crisis from the pandemic is over, an estimated 2.5 million people died from COVID-19 in 2022, tens of millions suffer from long COVID and national economies still reel from multiple deprivations exacerbated by the pandemic. Sex and gender biases deeply mark these evolving experiences of COVID-19, impacting the quality of science and effectiveness of the responses deployed. To galvanise change by strengthening evidence-informed inclusion of sex and gender in COVID-19 practice, we led a virtual collaboration to articulate and prioritise gender and COVID-19 research needs. In addition to standard prioritisation surveys, feminist principles mindful of intersectional power dynamics underpinned how we reviewed research gaps, framed research questions and discussed emergent findings. The collaborative research agenda-setting exercise engaged over 900 participants primarily from low/middle-income countries in varied activities. The top 21 research questions included the importance of the needs of pregnant and lactating women and information systems that enable sex-disaggregated analysis. Gender and intersectional aspects to improving vaccine uptake, access to health services, measures against gender-based violence and integrating gender in health systems were also prioritised. These priorities are shaped by more inclusive ways of working, which are critical for global health as it faces further uncertainties in the aftermath of COVID-19. It remains imperative to address the basics in gender and health (sex-disaggregated data and sex-specific needs) and also advance transformational goals to advance gender justice across health and social policies, including those related to global research.}, }
@article {pmid37226033, year = {2023}, author = {Nouraeinejad, A}, title = {The functional and structural changes in the hippocampus of COVID-19 patients.}, journal = {Acta neurologica Belgica}, volume = {123}, number = {4}, pages = {1247-1256}, pmid = {37226033}, issn = {2240-2993}, mesh = {Humans ; *COVID-19 ; *Alzheimer Disease ; Hippocampus ; Learning ; Memory Disorders ; }, abstract = {Since the hippocampus is predominantly susceptible to injuries caused by COVID-19, there are increasing data indicating the likelihood of post-infection memory loss and quickening neurodegenerative disorders, such as Alzheimer's disease. This is due to the fact that the hippocampus has imperative functions in spatial and episodic memory as well as learning. COVID-19 activates microglia in the hippocampus and induces a CNS cytokine storm, leading to loss of hippocampal neurogenesis. The functional and structural changes in the hippocampus of COVID-19 patients can explain neuronal degeneration and reduced neurogenesis in the human hippocampus. This will open a window to explain memory and cognitive dysfunctions in "long COVID" through the resultant loss of hippocampal neurogenesis.}, }
@article {pmid37233729, year = {2023}, author = {Mohandas, S and Jagannathan, P and Henrich, TJ and Sherif, ZA and Bime, C and Quinlan, E and Portman, MA and Gennaro, M and Rehman, J and , }, title = {Immune mechanisms underlying COVID-19 pathology and post-acute sequelae of SARS-CoV-2 infection (PASC).}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {37233729}, issn = {2050-084X}, support = {R01 HL162308/HL/NHLBI NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; R01 HL163978/HL/NHLBI NIH HHS/United States ; K08 HL141623/HL/NHLBI NIH HHS/United States ; U01 AI150741/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/complications ; Disease Progression ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {With a global tally of more than 500 million cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections to date, there are growing concerns about the post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Recent studies suggest that exaggerated immune responses are key determinants of the severity and outcomes of the initial SARS-CoV-2 infection as well as subsequent PASC. The complexity of the innate and adaptive immune responses in the acute and post-acute period requires in-depth mechanistic analyses to identify specific molecular signals as well as specific immune cell populations which promote PASC pathogenesis. In this review, we examine the current literature on mechanisms of immune dysregulation in severe COVID-19 and the limited emerging data on the immunopathology of PASC. While the acute and post-acute phases may share some parallel mechanisms of immunopathology, it is likely that PASC immunopathology is quite distinct and heterogeneous, thus requiring large-scale longitudinal analyses in patients with and without PASC after an acute SARS-CoV-2 infection. By outlining the knowledge gaps in the immunopathology of PASC, we hope to provide avenues for novel research directions that will ultimately lead to precision therapies which restore healthy immune function in PASC patients.}, }
@article {pmid37234076, year = {2023}, author = {Pollack, B and von Saltza, E and McCorkell, L and Santos, L and Hultman, A and Cohen, AK and Soares, L}, title = {Female reproductive health impacts of Long COVID and associated illnesses including ME/CFS, POTS, and connective tissue disorders: a literature review.}, journal = {Frontiers in rehabilitation sciences}, volume = {4}, number = {}, pages = {1122673}, pmid = {37234076}, issn = {2673-6861}, abstract = {Long COVID disproportionately affects premenopausal women, but relatively few studies have examined Long COVID's impact on female reproductive health. We conduct a review of the literature documenting the female reproductive health impacts of Long COVID which may include disruptions to the menstrual cycle, gonadal function, ovarian sufficiency, menopause, and fertility, as well as symptom exacerbation around menstruation. Given limited research, we also review the reproductive health impacts of overlapping and associated illnesses including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), postural orthostatic tachycardia syndrome (POTS), connective tissue disorders like Ehlers-Danlos syndrome (EDS), and endometriosis, as these illnesses may help to elucidate reproductive health conditions in Long COVID. These associated illnesses, whose patients are 70%-80% women, have increased rates of dysmenorrhea, amenorrhea, oligomenorrhea, dyspareunia, endometriosis, infertility, vulvodynia, intermenstrual bleeding, ovarian cysts, uterine fibroids and bleeding, pelvic congestion syndrome, gynecological surgeries, and adverse pregnancy complications such as preeclampsia, maternal mortality, and premature birth. Additionally, in Long COVID and associated illnesses, symptoms can be impacted by the menstrual cycle, pregnancy, and menopause. We propose priorities for future research and reproductive healthcare in Long COVID based on a review of the literature. These include screening Long COVID patients for comorbid and associated conditions; studying the impacts of the menstrual cycle, pregnancy, and menopause on symptoms and illness progression; uncovering the role of sex differences and sex hormones in Long COVID and associated illnesses; and addressing historical research and healthcare inequities that have contributed to detrimental knowledge gaps for this patient population.}, }
@article {pmid37238686, year = {2023}, author = {Maiese, K}, title = {Cellular Metabolism: A Fundamental Component of Degeneration in the Nervous System.}, journal = {Biomolecules}, volume = {13}, number = {5}, pages = {}, pmid = {37238686}, issn = {2218-273X}, support = {/RA/ARRA NIH HHS/United States ; }, mesh = {Humans ; AMP-Activated Protein Kinases/metabolism ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; TOR Serine-Threonine Kinases/metabolism ; *Diabetes Mellitus ; *Alzheimer Disease/metabolism ; *Neurodegenerative Diseases/metabolism ; *Metabolic Diseases ; Brain/metabolism ; }, abstract = {It is estimated that, at minimum, 500 million individuals suffer from cellular metabolic dysfunction, such as diabetes mellitus (DM), throughout the world. Even more concerning is the knowledge that metabolic disease is intimately tied to neurodegenerative disorders, affecting both the central and peripheral nervous systems as well as leading to dementia, the seventh leading cause of death. New and innovative therapeutic strategies that address cellular metabolism, apoptosis, autophagy, and pyroptosis, the mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), growth factor signaling with erythropoietin (EPO), and risk factors such as the apolipoprotein E (APOE-ε4) gene and coronavirus disease 2019 (COVID-19) can offer valuable insights for the clinical care and treatment of neurodegenerative disorders impacted by cellular metabolic disease. Critical insight into and modulation of these complex pathways are required since mTOR signaling pathways, such as AMPK activation, can improve memory retention in Alzheimer's disease (AD) and DM, promote healthy aging, facilitate clearance of β-amyloid (Aß) and tau in the brain, and control inflammation, but also may lead to cognitive loss and long-COVID syndrome through mechanisms that can include oxidative stress, mitochondrial dysfunction, cytokine release, and APOE-ε4 if pathways such as autophagy and other mechanisms of programmed cell death are left unchecked.}, }
@article {pmid37238755, year = {2023}, author = {Pérez de la Lastra, JM and Curieses Andrés, CM and Andrés Juan, C and Plou, FJ and Pérez-Lebeña, E}, title = {Hydroxytyrosol and Arginine as Antioxidant, Anti-Inflammatory and Immunostimulant Dietary Supplements for COVID-19 and Long COVID.}, journal = {Foods (Basel, Switzerland)}, volume = {12}, number = {10}, pages = {}, pmid = {37238755}, issn = {2304-8158}, support = {Project ProID2020010134//Agencia Canaria de Investigaci&#xf3;n, Innovaci&#xf3;n y Sociedad de la Informaci&#xf3;n/ ; Grant PID2019-105838RB-C31//Spanish Ministry of Economy and Competitiveness/ ; project PLEC2022-009507//Spanish Ministry of Science and Innovation/ ; }, abstract = {Phytochemicals from plant extracts are becoming increasingly popular in the world of food science and technology because they have positive effects on human health. In particular, several bioactive foods and dietary supplements are being investigated as potential treatments for chronic COVID. Hydroxytyrosol (HXT) is a natural antioxidant, found in olive oil, with antioxidant anti-inflammatory properties that has been consumed by humans for centuries without reported adverse effects. Its use was approved by the European Food Safety Authority as a protective agent for the cardiovascular system. Similarly, arginine is a natural amino acid with anti-inflammatory properties that can modulate the activity of immune cells, reducing the production of pro-inflammatory cytokines such as IL-6 and TNF-α. The properties of both substances may be particularly beneficial in the context of COVID-19 and long COVID, which are characterised by inflammation and oxidative stress. While l-arginine promotes the formation of [•]NO, HXT prevents oxidative stress and inflammation in infected cells. This combination could prevent the formation of harmful peroxynitrite, a potent pro-inflammatory substance implicated in pneumonia and COVID-19-associated organ dysfunction, as well as reduce inflammation, improve immune function, protect against free radical damage and prevent blood vessel injury. Further research is needed to fully understand the potential benefits of HXT and arginine in the context of COVID-19.}, }
@article {pmid37242804, year = {2023}, author = {Akanchise, T and Angelova, A}, title = {Ginkgo Biloba and Long COVID: In Vivo and In Vitro Models for the Evaluation of Nanotherapeutic Efficacy.}, journal = {Pharmaceutics}, volume = {15}, number = {5}, pages = {}, pmid = {37242804}, issn = {1999-4923}, abstract = {Coronavirus infections are neuroinvasive and can provoke injury to the central nervous system (CNS) and long-term illness consequences. They may be associated with inflammatory processes due to cellular oxidative stress and an imbalanced antioxidant system. The ability of phytochemicals with antioxidant and anti-inflammatory activities, such as Ginkgo biloba, to alleviate neurological complications and brain tissue damage has attracted strong ongoing interest in the neurotherapeutic management of long COVID. Ginkgo biloba leaf extract (EGb) contains several bioactive ingredients, e.g., bilobalide, quercetin, ginkgolides A-C, kaempferol, isorhamnetin, and luteolin. They have various pharmacological and medicinal effects, including memory and cognitive improvement. Ginkgo biloba, through its anti-apoptotic, antioxidant, and anti-inflammatory activities, impacts cognitive function and other illness conditions like those in long COVID. While preclinical research on the antioxidant therapies for neuroprotection has shown promising results, clinical translation remains slow due to several challenges (e.g., low drug bioavailability, limited half-life, instability, restricted delivery to target tissues, and poor antioxidant capacity). This review emphasizes the advantages of nanotherapies using nanoparticle drug delivery approaches to overcome these challenges. Various experimental techniques shed light on the molecular mechanisms underlying the oxidative stress response in the nervous system and help comprehend the pathophysiology of the neurological sequelae of SARS-CoV-2 infection. To develop novel therapeutic agents and drug delivery systems, several methods for mimicking oxidative stress conditions have been used (e.g., lipid peroxidation products, mitochondrial respiratory chain inhibitors, and models of ischemic brain damage). We hypothesize the beneficial effects of EGb in the neurotherapeutic management of long-term COVID-19 symptoms, evaluated using either in vitro cellular or in vivo animal models of oxidative stress.}, }
@article {pmid37243259, year = {2023}, author = {Baroni, C and Potito, J and Perticone, ME and Orausclio, P and Luna, CM}, title = {How Does Long-COVID Impact Prognosis and the Long-Term Sequelae?.}, journal = {Viruses}, volume = {15}, number = {5}, pages = {}, pmid = {37243259}, issn = {1999-4915}, mesh = {Humans ; *COVID-19/complications ; Diarrhea ; Disease Progression ; Post-Acute COVID-19 Syndrome ; Prognosis ; SARS-CoV-2 ; }, abstract = {CONTEXT: We reviewed what has been studied and published during the last 3 years about the consequences, mainly respiratory, cardiac, digestive, and neurological/psychiatric (organic and functional), in patients with COVID-19 of prolonged course.<br><br>OBJECTIVE: To conduct a narrative review synthesizing current clinical evidence of abnormalities of signs, symptoms, and complementary studies in COVID-19 patients who presented a prolonged and complicated course.<br><br>METHODS: A review of the literature focused on the involvement of the main organic functions mentioned, based almost exclusively on the systematic search of publications written in English available on PubMed/MEDLINE.<br><br>RESULTS: Long-term respiratory, cardiac, digestive, and neurological/psychiatric dysfunction are present in a significant number of patients. Lung involvement is the most common; cardiovascular involvement may happen with or without symptoms or clinical abnormalities; gastrointestinal compromise includes the loss of appetite, nausea, gastroesophageal reflux, diarrhea, etc.; and neurological/psychiatric compromise can produce a wide variety of signs and symptoms, either organic or functional. Vaccination is not associated with the emergence of long-COVID, but it may happen in vaccinated people.<br><br>CONCLUSIONS: The severity of illness increases the risk of long-COVID. Pulmonary sequelae, cardiomyopathy, the detection of ribonucleic acid in the gastrointestinal tract, and headaches and cognitive impairment may become refractory in severely ill COVID-19 patients.}, }
@article {pmid37245047, year = {2023}, author = {Natarajan, A and Shetty, A and Delanerolle, G and Zeng, Y and Zhang, Y and Raymont, V and Rathod, S and Halabi, S and Elliot, K and Shi, JQ and Phiri, P}, title = {A systematic review and meta-analysis of long COVID symptoms.}, journal = {Systematic reviews}, volume = {12}, number = {1}, pages = {88}, pmid = {37245047}, issn = {2046-4053}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; COVID-19 Testing ; Post-Acute COVID-19 Syndrome ; Mental Health ; }, abstract = {BACKGROUND: Ongoing symptoms or the development of new symptoms following a SARS-CoV-2 diagnosis has caused a complex clinical problem known as "long COVID" (LC). This has introduced further pressure on global healthcare systems as there appears to be a need for ongoing clinical management of these patients. LC personifies heterogeneous symptoms at varying frequencies. The most complex symptoms appear to be driven by the neurology and neuropsychiatry spheres.<br><br>METHODS: A systematic protocol was developed, peer reviewed, and published in PROSPERO. The systematic review included publications from the 1st of December 2019-30th June 2021 published in English. Multiple electronic databases were used. The dataset has been analyzed using a random-effects model and a subgroup analysis based on geographical location. Prevalence and 95% confidence intervals (CIs) were established based on the data identified.<br><br>RESULTS: Of the 302 studies, 49 met the inclusion criteria, although 36 studies were included in the meta-analysis. The 36 studies had a collective sample size of 11,598 LC patients. 18 of the 36 studies were designed as cohorts and the remainder were cross-sectional. Symptoms of mental health, gastrointestinal, cardiopulmonary, neurological, and pain were reported.<br><br>CONCLUSIONS: The quality that differentiates this meta-analysis is that they are cohort and cross-sectional studies with follow-up. It is evident that there is limited knowledge available of LC and current clinical management strategies may be suboptimal as a result. Clinical practice improvements will require more comprehensive clinical research, enabling effective evidence-based approaches to better support patients.}, }
@article {pmid37249286, year = {2023}, author = {Malekpour, M and Khanmohammadi, S and Meybodi, MJE and Shekouh, D and Rahmanian, MR and Kardeh, S and Azarpira, N}, title = {COVID-19 as a trigger of Guillain-Barré syndrome: A review of the molecular mechanism.}, journal = {Immunity, inflammation and disease}, volume = {11}, number = {5}, pages = {e875}, pmid = {37249286}, issn = {2050-4527}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; *Guillain-Barre Syndrome/etiology/complications ; Post-Acute COVID-19 Syndrome ; Pandemics ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a pandemic with serious complications. After coronavirus disease 2019 (COVID-19), several post-acute COVID-19 syndromes (PACSs) and long-COVID sequels were reported. PACSs involve many organs, including the nervous, gustatory, and immune systems. One of the PACSs after SARS-CoV-2 infection and vaccination is Guillain-Barré syndrome (GBS). The incidence rate of GBS after SARS-CoV-2 infection or vaccination is low. However, the high prevalence of COVID-19 and severe complications of GBS, for example, autonomic dysfunction and respiratory failure, highlight the importance of post-COVID-19 GBS. It is while patients with simultaneous COVID-19 and GBS seem to have higher admission rates to the intensive care unit, and demyelination is more aggressive in post-COVID-19 GBS patients. SARS-CoV-2 can trigger GBS via several pathways like direct neurotropism and neurovirulence, microvascular dysfunction and oxidative stress, immune system disruption, molecular mimicry, and autoantibody production. Although there are few molecular studies on the molecular and cellular mechanisms of GBS occurrence after SARS-CoV-2 infection and vaccination, we aimed to discuss the possible pathomechanism of post-COVID-19 GBS by gathering the most recent molecular evidence.}, }
@article {pmid37255048, year = {2023}, author = {Riera-Canales, C and Llanos-Chea, A}, title = {COVID-19 and the gastrointestinal tract in children.}, journal = {Current opinion in pediatrics}, volume = {35}, number = {5}, pages = {585-589}, pmid = {37255048}, issn = {1531-698X}, mesh = {Child ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; *Inflammatory Bowel Diseases ; *Irritable Bowel Syndrome ; Gastrointestinal Tract ; }, abstract = {PURPOSE OF REVIEW: This is an overview of the effects of COVID-19 in the gastrointestinal tract in children, and current evidence of the impact of COVID-19 in pediatric patients with chronic gastrointestinal conditions, including inflammatory bowel disease (IBD), chronic liver disease, and disorders of the gut-brain interaction.<br><br>RECENT FINDINGS: Children with COVID-19 have a milder course and more favorable outcomes than adults, even in those with immunosuppression due to IBD or liver transplantation. Children with chronic gastrointestinal conditions do not have worse clinical outcomes than healthy children and infection itself has not been linked to an increased incidence of conditions such as IBD and celiac disease, but results regarding post-infectious irritable bowel syndrome are mixed.<br><br>SUMMARY: Research specific to pediatrics is needed, particularly in post-infectious disorders of the gut-brain interaction (PI-DGBIs) and long COVID-19. Data extrapolated from adult trials may not apply to children, as their clinical course is different. PI-DGBIs and long COVID-19 require special attention, as they represent a major morbidity burden in children.}, }
@article {pmid37255928, year = {2023}, author = {El-Rhermoul, FZ and Fedorowski, A and Eardley, P and Taraborrelli, P and Panagopoulos, D and Sutton, R and Lim, PB and Dani, M}, title = {Autoimmunity in Long Covid and POTS.}, journal = {Oxford open immunology}, volume = {4}, number = {1}, pages = {iqad002}, pmid = {37255928}, issn = {2633-6960}, abstract = {Orthostatic intolerance and other autonomic dysfunction syndromes are emerging as distinct symptom clusters in Long Covid. Often accompanying these are common, multi-system constitutional features such as fatigue, malaise and skin rashes which can signify generalized immune dysregulation. At the same time, multiple autoantibodies are identified in both Covid-related autonomic disorders and non-Covid autonomic disorders, implying a possible underlying autoimmune pathology. The lack of specificity of these findings precludes direct interpretations of cause and association, but their prevalence with its supporting evidence is compelling.}, }
@article {pmid37264687, year = {2023}, author = {Rahmati, M and Yon, DK and Lee, SW and Udeh, R and McEVoy, M and Kim, MS and Gyasi, RM and Oh, H and López Sánchez, GF and Jacob, L and Li, Y and Koyanagi, A and Shin, JI and Smith, L}, title = {New-onset type 1 diabetes in children and adolescents as postacute sequelae of SARS-CoV-2 infection: A systematic review and meta-analysis of cohort studies.}, journal = {Journal of medical virology}, volume = {95}, number = {6}, pages = {e28833}, doi = {10.1002/jmv.28833}, pmid = {37264687}, issn = {1096-9071}, mesh = {Child ; Humans ; Adolescent ; *COVID-19/complications/epidemiology ; *Diabetes Mellitus, Type 1/complications/epidemiology ; SARS-CoV-2 ; *Diabetic Ketoacidosis ; Post-Acute COVID-19 Syndrome ; Cohort Studies ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents may increase risk for a variety of post-acute sequelae including new-onset type 1 diabetes mellitus (T1DM). Therefore, this meta-analysis aims to estimate the risk of developing new-onset type 1 diabetes in children and adolescents as post-acute sequelae of SARS-CoV-2 infection. PubMed/MEDLINE, CENTRAL, and EMBASE were systematically searched up to March 20, 2023. A systematic review and subsequent meta-analyses were performed to calculate the pooled effect size, expressed as risk ratio (RR) with corresponding 95% confidence interval (CI) of each outcome based on a one-stage approach and the random-effects estimate of the pooled effect sizes of each outcome were generated with the use of the DerSimonian-Laird method. Eight reports from seven studies involving 11 220 530 participants (2 140 897 patients with a history of diagnosed SARS-CoV-2 infection and 9 079 633 participants in the respective control groups) were included. The included studies reported data from four U.S. medical claims databases covering more than 503 million patients (IQVIA, HealthVerity, TriNetX, and Cerner Real-World Data), and three national health registries for all children and adolescents in Norway, Scotland, and Denmark. It was shown that the risk of new-onset T1DM following SARS-CoV-2 infection in children and adolescents was 42% (95% CI 13%-77%, p = 0.002) higher compared with non-COVID-19 control groups. The risk of developing new-onset T1DM following SARS-CoV-2 infection was significantly higher (67%, 95% CI 32 %-112%, p = 0.0001) in children and adolescents between 0 and 11 years, but not in those between 12 and 17 years (RR = 1.10, 95% CI 0.54-2.23, p = 0.79). We also found that the higher risk for developing new-onset T1DM following SARS-CoV-2 infection only exists in studies from the United States (RR = 1.70, 95% CI 1.37-2.11, p = 0.00001) but not Europe (RR = 1.02, 95% CI 0.67-1.55, p = 0.93). Furthermore, we found that SARS-CoV-2 infection was associated with an elevation in the risk of diabetic ketoacidosis (DKA) in children and adolescents compared with non-COVID-19 control groups (RR = 2.56, 95% CI 1.07-6.11, p = 0.03). Our findings mainly obtained from US medical claims databases, suggest that SARS-CoV-2 infection is associated with higher risk of developing new-onset T1DM and diabetic ketoacidosis in children and adolescents. These findings highlight the need for targeted measures to raise public health practitioners and physician awareness to provide intervention strategies to reduce the risk of developing T1DM in children and adolescents who have had COVID-19.}, }
@article {pmid37265584, year = {2023}, author = {Perumal, R and Shunmugam, L and Naidoo, K and Wilkins, D and Garzino-Demo, A and Brechot, C and Vahlne, A and Nikolich, J}, title = {Biological mechanisms underpinning the development of long COVID.}, journal = {iScience}, volume = {26}, number = {6}, pages = {106935}, pmid = {37265584}, issn = {2589-0042}, support = {MC_PC_16022/MRC_/Medical Research Council/United Kingdom ; }, abstract = {As COVID-19 evolves from a pandemic to an endemic disease, the already staggering number of people that have been or will be infected with SARS-CoV-2 is only destined to increase, and the majority of humanity will be infected. It is well understood that COVID-19, like many other viral infections, leaves a significant fraction of the infected with prolonged consequences. Continued high number of SARS-CoV-2 infections, viral evolution with escape from post-infection and vaccinal immunity, and reinfections heighten the potential impact of Long COVID. Hence, the impact of COVID-19 on human health will be seen for years to come until more effective vaccines and pharmaceutical treatments become available. To that effect, it is imperative that the mechanisms underlying the clinical manifestations of Long COVID be elucidated. In this article, we provide an in-depth analysis of the evidence on several potential mechanisms of Long COVID and discuss their relevance to its pathogenesis.}, }
@article {pmid37267081, year = {2023}, author = {Nguyen, NN and Dudouet, P and Dhiver, C and Gautret, P}, title = {Pericarditis related to post-acute COVID infection: A case report and review of the literature.}, journal = {Acta microbiologica et immunologica Hungarica}, volume = {70}, number = {2}, pages = {100-110}, doi = {10.1556/030.2023.02055}, pmid = {37267081}, issn = {1588-2640}, mesh = {Humans ; Female ; Male ; *COVID-19/complications ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; *Pericarditis/diagnosis/drug therapy/etiology ; Aspirin/therapeutic use ; Colchicine/therapeutic use ; Chest Pain/complications/drug therapy ; }, abstract = {Cardiovascular involvement has been described in acute and recovered COVID-19 patients. Here, we present a case of symptomatic pericarditis with persistent symptoms for at least six months after the acute infection and report 66 published cases of pericarditis in discharged COVID patients. Patient mean age ± SD was 49.7 ± 13.3 years, ranging from 15 to 75 years and 57.6% were female. A proportion of 89.4% patients reported at least one comorbidity, with autoimmune and allergic disorders, hypertension and dyslipidaemia, as the most frequent. Only 8.3% of patients experienced severe symptoms of acute COVID-19. The time between acute COVID and pericarditis symptoms varied from 14 to 255 days. Chest pain (90.9%), tachycardia (60.0%) and dyspnoea (38.2%) were the most frequent symptoms in post-acute pericarditis. A proportion of 45.5% and 87% of patients had an abnormal electrocardiogram and abnormal transthoracic ultrasound, respectively. Colchicine combined with non-steroidal anti-inflammatory drug (NSAID) or acetylsalicylic acid (aspirin) were prescribed to 39/54 (72%) patients. Of them, 12 were switched to corticosteroid therapy due to non-response to the first-line treatment. Only 6 patients had persisting symptoms and were considered as non-respondent to therapy.Our report highlights that pericarditis should be suspected in COVID-19 patients with persistent chest pain and dyspnoea when pulmonary function is normal. Treatment with non-steroidal anti-inflammatory and colchicine is usually effective but corticosteroids are sometimes required.}, }
@article {pmid37267758, year = {2023}, author = {Müller, S and Schultze, JL}, title = {Systems analysis of human innate immunity in COVID-19.}, journal = {Seminars in immunology}, volume = {68}, number = {}, pages = {101778}, pmid = {37267758}, issn = {1096-3618}, support = {GRK2168 &#x2013; 272482170//German Research Foundation (/ ; 390873048//Excellence Cluster ImmunoSensation2, project/ ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Immunity, Innate ; Systems Analysis ; }, abstract = {Recent developments in sequencing technologies, the computer and data sciences, as well as increasingly high-throughput immunological measurements have made it possible to derive holistic views on pathophysiological processes of disease and treatment effects directly in humans. We and others have illustrated that incredibly predictive data for immune cell function can be generated by single cell multi-omics (SCMO) technologies and that these technologies are perfectly suited to dissect pathophysiological processes in a new disease such as COVID-19, triggered by SARS-CoV-2 infection. Systems level interrogation not only revealed the different disease endotypes, highlighted the differential dynamics in context of disease severity, and pointed towards global immune deviation across the different arms of the immune system, but was already instrumental to better define long COVID phenotypes, suggest promising biomarkers for disease and therapy outcome predictions and explains treatment responses for the widely used corticosteroids. As we identified SCMO to be the most informative technologies in the vest to better understand COVID-19, we propose to routinely include such single cell level analysis in all future clinical trials and cohorts addressing diseases with an immunological component.}, }
@article {pmid37277617, year = {2023}, author = {Kuck, KH and Schlüter, M and Vogler, J and Heeger, CH and Tilz, RR}, title = {Has COVID-19 changed the spectrum of arrhythmias and the incidence of sudden cardiac death?.}, journal = {Herz}, volume = {48}, number = {3}, pages = {212-217}, pmid = {37277617}, issn = {1615-6692}, mesh = {Humans ; *Atrial Fibrillation ; Incidence ; Post-Acute COVID-19 Syndrome ; Hospital Mortality ; *COVID-19 ; SARS-CoV-2 ; Death, Sudden, Cardiac/epidemiology/etiology/prevention &amp; control ; }, abstract = {Arrhythmic manifestations of COVID-19 include atrial arrhythmias such as atrial fibrillation or atrial flutter, sinus node dysfunction, atrioventricular conduction abnormalities, ventricular tachyarrhythmias, sudden cardiac arrest, and cardiovascular dysautonomias including the so-called long COVID syndrome. Various pathophysiological mechanisms have been implicated, such as direct viral invasion, hypoxemia, local and systemic inflammation, changes in ion channel physiology, immune activation, and autonomic dysregulation. The development of atrial or ventricular arrhythmias in hospitalized COVID-19 patients has been shown to portend a higher risk of in-hospital death. Management of these arrhythmias should be based on published evidence-based guidelines, with special consideration of the acuity of COVID-19 infection, concomitant use of antimicrobial and anti-inflammatory drugs, and the transient nature of some rhythm disorders. In view of new SARS-CoV‑2 variants that may evolve, the development and use of newer antiviral and immunomodulator drugs, and the increasing adoption of vaccination, clinicians must remain vigilant for other arrhythmic manifestations that may occur in association with this novel but potentially deadly disease.}, }
@article {pmid37286535, year = {2023}, author = {Chen, P and Wu, M and He, Y and Jiang, B and He, ML}, title = {Metabolic alterations upon SARS-CoV-2 infection and potential therapeutic targets against coronavirus infection.}, journal = {Signal transduction and targeted therapy}, volume = {8}, number = {1}, pages = {237}, pmid = {37286535}, issn = {2059-3635}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Lipid Metabolism ; }, abstract = {The coronavirus disease 2019 (COVID-19) caused by coronavirus SARS-CoV-2 infection has become a global pandemic due to the high viral transmissibility and pathogenesis, bringing enormous burden to our society. Most patients infected by SARS-CoV-2 are asymptomatic or have mild symptoms. Although only a small proportion of patients progressed to severe COVID-19 with symptoms including acute respiratory distress syndrome (ARDS), disseminated coagulopathy, and cardiovascular disorders, severe COVID-19 is accompanied by high mortality rates with near 7 million deaths. Nowadays, effective therapeutic patterns for severe COVID-19 are still lacking. It has been extensively reported that host metabolism plays essential roles in various physiological processes during virus infection. Many viruses manipulate host metabolism to avoid immunity, facilitate their own replication, or to initiate pathological response. Targeting the interaction between SARS-CoV-2 and host metabolism holds promise for developing therapeutic strategies. In this review, we summarize and discuss recent studies dedicated to uncovering the role of host metabolism during the life cycle of SARS-CoV-2 in aspects of entry, replication, assembly, and pathogenesis with an emphasis on glucose metabolism and lipid metabolism. Microbiota and long COVID-19 are also discussed. Ultimately, we recapitulate metabolism-modulating drugs repurposed for COVID-19 including statins, ASM inhibitors, NSAIDs, Montelukast, omega-3 fatty acids, 2-DG, and metformin.}, }
@article {pmid37287442, year = {2023}, author = {Kioi, Y and Yorifuji, H and Higami, Y and Katada, Y}, title = {Serositis and lymphopenia are common features of systemic lupus erythematosus following SARS-CoV-2 infection: A case report and literature review.}, journal = {International journal of rheumatic diseases}, volume = {26}, number = {11}, pages = {2267-2271}, doi = {10.1111/1756-185X.14767}, pmid = {37287442}, issn = {1756-185X}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; *Serositis/diagnosis/etiology ; *Lupus Erythematosus, Systemic/complications/diagnosis/drug therapy ; *Lymphopenia/diagnosis/etiology ; *Pleural Effusion/diagnosis/etiology ; *Anemia ; *Thrombocytopenia ; }, abstract = {The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect a number of human systems, including the respiratory, cardiovascular, neurological, gastrointestinal, and musculoskeletal systems. These symptoms persist long after the acute infection has healed and is called "long COVID". Interestingly, there have been a series of reports that SARS-CoV-2 infections trigger the development of various autoimmune diseases such as systemic lupus erythematosus (SLE), inflammatory arthritis, myositis, vasculitis. Here, we report a novel case of SLE characterized by persistent pleural effusion and lymphopenia following SARS-CoV-2 infection. This is the first case in the Western Pacific region to our knowledge. Furthermore, we reviewed 10 similar cases including our case. By looking at the characteristics of each case, we found that serositis and lymphopenia are common features of SLE following SARS-CoV-2 infection. Our finding suggests that patients with prolonged pleural effusion and/or lymphopenia after COVID-19 should be checked for autoantibodies.}, }
@article {pmid37288652, year = {2023}, author = {Rahmati, M and Udeh, R and Yon, DK and Lee, SW and Dolja-Gore, X and McEVoy, M and Kenna, T and Jacob, L and López Sánchez, GF and Koyanagi, A and Shin, JI and Smith, L}, title = {A systematic review and meta-analysis of long-term sequelae of COVID-19 2-year after SARS-CoV-2 infection: A call to action for neurological, physical, and psychological sciences.}, journal = {Journal of medical virology}, volume = {95}, number = {6}, pages = {e28852}, doi = {10.1002/jmv.28852}, pmid = {37288652}, issn = {1096-9071}, mesh = {Humans ; Female ; Male ; *COVID-19/complications/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Anxiety/epidemiology ; Carbon Monoxide ; Disease Progression ; }, abstract = {Long-term sequelae conditions of COVID-19 at least 2-year following SARS-CoV-2 infection are unclear and little is known about their prevalence, longitudinal trajectory, and potential risk factors. Therefore, we conducted a comprehensive meta-analysis of survivors' health-related consequences and sequelae at 2-year following SARS-CoV-2 infection. PubMed/MEDLINE, CENTRAL, and EMBASE were systematically searched up to February 10, 2023. A systematic review and meta-analysis were performed to calculate the pooled effect size, expressed as event rate (ER) with corresponding 95% confidence interval (CI) of each outcome. Twelve studies involving 1 289 044 participants from 11 countries were included. A total of 41.7% of COVID-19 survivors experienced at least one unresolved symptom and 14.1% were unable to return to work at 2-year after SARS-CoV-2 infection. The most frequent symptoms and investigated findings at 2-year after SARS-CoV-2 infection were fatigue (27.4%; 95% CI 17%-40.9%), sleep difficulties (25.1%; 95% CI 22.4%-27.9%), impaired diffusion capacity for carbon monoxide (24.6%; 95% CI 10.8%-46.9%), hair loss (10.2%; 95% CI 7.3%-14.2%), and dyspnea (10.1%; 95% CI 4.3%-21.9%). Individuals with severe infection suffered more from anxiety (OR = 1.69, 95% CI 1.17-2.44) and had more impairments in forced vital capacity (OR = 9.70, 95% CI 1.94-48.41), total lung capacity (OR = 3.51, 95% CI 1.77-6.99), and residual volume (OR = 3.35, 95% CI 1.85-6.07) after recovery. Existing evidence suggest that participants with a higher risk of long-term sequelae were older, mostly female, had pre-existing medical comorbidities, with more severe status, underwent corticosteroid therapy, and higher inflammation at acute infection. Our findings suggest that 2-year after recovery from SARS-CoV-2 infection, 41.7% of survivors still suffer from either neurological, physical, and psychological sequela. These findings indicate that there is an urgent need to preclude persistent or emerging long-term sequelae and provide intervention strategies to reduce the risk of long COVID.}, }
@article {pmid37292432, year = {2023}, author = {Montani, D and Savale, L and Noel, N and Meyrignac, O and Colle, R and Gasnier, M and Corruble, E and Beurnier, A and Jutant, EM and Pham, T and Lecoq, AL and Papon, JF and Figuereido, S and Harrois, A and Humbert, M and Monnet, X and , }, title = {[Post-COVID-19 syndrome].}, journal = {Bulletin de l'Academie nationale de medecine}, volume = {207}, number = {6}, pages = {812-820}, pmid = {37292432}, issn = {0001-4079}, abstract = {In the aftermath of acute infection with the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), a large number of symptoms persist or appear, constituting a real syndrome called "long COVID-19" or "post-COVID- 19" or "post-acute COVID-19 syndrome". Its incidence is very high, half of patients showing at least one symptom at 4-6 months after Coronarovirus infectious disease 2019 (COVID-19). They can affect many organs. The most common symptom is persistent fatigue, similar to that seen after other viral infections. Radiological pulmonary sequelae are relatively rare and not extensive. On the other hand, functional respiratory symptoms, primarily dyspnoea, are much more frequent. Dysfunctional breathing is a significant cause of dyspnoea. Cognitive disorders and psychological symptoms are also very common, with anxiety, depression and post-traumatic stress symptoms being widely described. On the other hand, cardiac, endocrine, cutaneous, digestive or renal sequelae are rarer. The symptoms generally improve after several months, even if their prevalence at two years remains significant. Most of the symptoms are favored by the severity of the initial illness, and the psychic symptoms by the female sex. The pathophysiology of most symptoms is poorly understood. The influence of the treatments used in the acute phase is also important. Vaccination, on the other hand, seems to reduce their incidence. The sheer number of affected patients makes long-term COVID-19 syndrome a public health challenge.}, }
@article {pmid37298527, year = {2023}, author = {Bicknell, B and Liebert, A and Borody, T and Herkes, G and McLachlan, C and Kiat, H}, title = {Neurodegenerative and Neurodevelopmental Diseases and the Gut-Brain Axis: The Potential of Therapeutic Targeting of the Microbiome.}, journal = {International journal of molecular sciences}, volume = {24}, number = {11}, pages = {}, pmid = {37298527}, issn = {1422-0067}, mesh = {Animals ; Humans ; Brain-Gut Axis ; *Neurodegenerative Diseases/metabolism ; *Autism Spectrum Disorder/metabolism ; Dysbiosis/metabolism ; Post-Acute COVID-19 Syndrome ; *COVID-19/metabolism ; *Microbiota ; Brain/metabolism ; }, abstract = {The human gut microbiome contains the largest number of bacteria in the body and has the potential to greatly influence metabolism, not only locally but also systemically. There is an established link between a healthy, balanced, and diverse microbiome and overall health. When the gut microbiome becomes unbalanced (dysbiosis) through dietary changes, medication use, lifestyle choices, environmental factors, and ageing, this has a profound effect on our health and is linked to many diseases, including lifestyle diseases, metabolic diseases, inflammatory diseases, and neurological diseases. While this link in humans is largely an association of dysbiosis with disease, in animal models, a causative link can be demonstrated. The link between the gut and the brain is particularly important in maintaining brain health, with a strong association between dysbiosis in the gut and neurodegenerative and neurodevelopmental diseases. This link suggests not only that the gut microbiota composition can be used to make an early diagnosis of neurodegenerative and neurodevelopmental diseases but also that modifying the gut microbiome to influence the microbiome-gut-brain axis might present a therapeutic target for diseases that have proved intractable, with the aim of altering the trajectory of neurodegenerative and neurodevelopmental diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, autism spectrum disorder, and attention-deficit hyperactivity disorder, among others. There is also a microbiome-gut-brain link to other potentially reversible neurological diseases, such as migraine, post-operative cognitive dysfunction, and long COVID, which might be considered models of therapy for neurodegenerative disease. The role of traditional methods in altering the microbiome, as well as newer, more novel treatments such as faecal microbiome transplants and photobiomodulation, are discussed.}, }
@article {pmid37300737, year = {2023}, author = {Lesnak, JB and Mazhar, K and Price, TJ}, title = {Neuroimmune Mechanisms Underlying Post-acute Sequelae of SARS-CoV-2 (PASC) Pain, Predictions from a Ligand-Receptor Interactome.}, journal = {Current rheumatology reports}, volume = {25}, number = {9}, pages = {169-181}, pmid = {37300737}, issn = {1534-6307}, support = {U19 NS130608/NS/NINDS NIH HHS/United States ; U19NS130608/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; SARS-CoV-2 ; Neuroimmunomodulation ; *COVID-19/complications ; Ligands ; Disease Progression ; *Musculoskeletal Pain ; }, abstract = {PURPOSE OF REVIEW: Individuals with post-acute sequelae of SARS-CoV-2 (PASC) complain of persistent musculoskeletal pain. Determining how COVID-19 infection produces persistent pain would be valuable for the development of therapeutics aimed at alleviating these symptoms.<br><br>RECENT FINDINGS: To generate hypotheses regarding neuroimmune interactions in PASC, we used a ligand-receptor interactome to make predictions about how ligands from PBMCs in individuals with COVID-19 communicate with dorsal root ganglia (DRG) neurons to induce persistent pain. In a structured literature review of -omics COVID-19 studies, we identified ligands capable of binding to receptors on DRG neurons, which stimulate signaling pathways including immune cell activation and chemotaxis, the complement system, and type I interferon signaling. The most consistent finding across immune cell types was an upregulation of genes encoding the alarmins S100A8/9 and MHC-I. This ligand-receptor interactome, from our hypothesis-generating literature review, can be used to guide future research surrounding mechanisms of PASC-induced pain.}, }
@article {pmid37310140, year = {2023}, author = {Dobrowolska, K and Zarębska-Michaluk, D and Poniedziałek, B and Jaroszewicz, J and Flisiak, R and Rzymski, P}, title = {Overview of autoantibodies in COVID-19 convalescents.}, journal = {Journal of medical virology}, volume = {95}, number = {6}, pages = {e28864}, doi = {10.1002/jmv.28864}, pmid = {37310140}, issn = {1096-9071}, mesh = {Adult ; Humans ; Autoantibodies ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Seroepidemiologic Studies ; *Blood Group Antigens ; }, abstract = {Accumulating evidence shows that SARS-CoV-2 can potentially trigger autoimmune processes, which can be responsible for the long-term consequences of COVID-19. Therefore, this paper aims to review the autoantibodies reported in COVID-19 convalescents. Six main groups were distinguished: (i) autoantibodies against components of the immune system, (ii) autoantibodies against components of the cardiovascular system, (iii) thyroid autoantibodies, (iv) autoantibodies specific for rheumatoid diseases, (v) antibodies against G-protein coupled receptors, and (vi) other autoantibodies. The evidence reviewed here clearly highlights that SARS-CoV-2 infection may induce humoral autoimmune responses. However, the available studies share number of limitations, such as: (1) the sole presence of autoantibodies does not necessarily implicate the clinically-relevant risks, (2) functional investigations were rarely performed and it is often unknown whether observed autoantibodies are pathogenic, (3) the control seroprevalence, in healthy, noninfected individuals was often not reported; thus it is sometimes unknown whether the detected autoantibodies are the result of SARS-CoV-2 infection or the accidental post-COVID-19 detection, (4) the presence of autoantibodies was rarely correlated with symptoms of the post-COVID-19 syndrome, (5) the size of the studied groups were often small, (6) the studies focused predominantly on adult populations, (7) age- and sex-related differences in seroprevalence of autoantibodies were rarely explored, (8) genetic predispositions that may be involved in generation of autoantibodies during SARS-CoV-2 infections were not investigated, and (9) the autoimmune reactions following infection with SARS-CoV-2 variants that vary in the clinical course of infection remain unexplored. Further longitudinal studies are advocated to assess the link between identified autoantibodies and particular clinical outcomes in COVID-19 convalescents.}, }
@article {pmid37315370, year = {2023}, author = {Imam, MT and Almalki, ZS and Alzahrani, AR and Al-Ghamdi, SS and Falemban, AH and Alanazi, IM and Shahzad, N and Muhammad Alrooqi, M and Jabeen, Q and Shahid, I}, title = {COVID-19 and severity of liver diseases: Possible crosstalk and clinical implications.}, journal = {International immunopharmacology}, volume = {121}, number = {}, pages = {110439}, pmid = {37315370}, issn = {1878-1705}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Pandemics ; Post-Acute COVID-19 Syndrome ; *Liver Diseases/metabolism ; }, abstract = {COVID-19-infected individuals and those who recovered from the infection have been demonstrated to have elevated liver enzymes or abnormal liver biochemistries, particularly with preexisting liver diseases, liver metabolic disorders, viral hepatitis, and other hepatic comorbidities. However, possible crosstalk and intricate interplay between COVID-19 and liver disease severity are still elusive, and the available data are murky and confined. Similarly, the syndemic of other blood-borne infectious diseases, chemical-induced liver injuries, and chronic hepatic diseases continued to take lives while showing signs of worsening due to the COVID-19 crisis. Moreover, the pandemic is not over yet and is transitioning to becoming an epidemic in recent years; hence, monitoring liver function tests (LFTs) and assessing hepatic consequences of COVID-19 in patients with or without liver illnesses would be of paramount interest. This pragmatic review explores the correlations between COVID-19 and liver disease severity based on abnormal liver biochemistries and other possible mechanisms in individuals of all ages from the emergence of the COVID-19 pandemic to the post-pandemic period. The review also alludes to clinical perspectives of such interactions to curb overlapping hepatic diseases in people who recovered from the infection or living with long COVID-19.}, }
@article {pmid37316184, year = {2023}, author = {Tabor, JB and Brett, BL and Nelson, L and Meier, T and Penner, LC and Mayer, AR and Echemendia, RJ and McAllister, T and Meehan, WP and Patricios, J and Makdissi, M and Bressan, S and Davis, GA and Premji, Z and Schneider, KJ and Zetterberg, H and McCrea, M}, title = {Role of biomarkers and emerging technologies in defining and assessing neurobiological recovery after sport-related concussion: a systematic review.}, journal = {British journal of sports medicine}, volume = {57}, number = {12}, pages = {789-797}, doi = {10.1136/bjsports-2022-106680}, pmid = {37316184}, issn = {1473-0480}, mesh = {Humans ; *Brain Concussion/diagnosis ; Biomarkers ; Data Collection ; Databases, Factual ; Genetic Testing ; }, abstract = {OBJECTIVE: Determine the role of fluid-based biomarkers, advanced neuroimaging, genetic testing and emerging technologies in defining and assessing neurobiological recovery after sport-related concussion (SRC).<br><br>DESIGN: Systematic review.<br><br>DATA SOURCES: Searches of seven databases from 1 January 2001 through 24 March 2022 using keywords and index terms relevant to concussion, sports and neurobiological recovery. Separate reviews were conducted for studies involving neuroimaging, fluid biomarkers, genetic testing and emerging technologies. A standardised method and data extraction tool was used to document the study design, population, methodology and results. Reviewers also rated the risk of bias and quality of each study.<br><br>Studies were included if they: (1) were published in English; (2) represented original research; (3) involved human research; (4) pertained only to SRC; (5) included data involving neuroimaging (including electrophysiological testing), fluid biomarkers or genetic testing or other advanced technologies used to assess neurobiological recovery after SRC; (6) had a minimum of one data collection point within 6 months post-SRC; and (7) contained a minimum sample size of 10 participants.<br><br>RESULTS: A total of 205 studies met inclusion criteria, including 81 neuroimaging, 50 fluid biomarkers, 5 genetic testing, 73 advanced technologies studies (4 studies overlapped two separate domains). Numerous studies have demonstrated the ability of neuroimaging and fluid-based biomarkers to detect the acute effects of concussion and to track neurobiological recovery after injury. Recent studies have also reported on the diagnostic and prognostic performance of emerging technologies in the assessment of SRC. In sum, the available evidence reinforces the theory that physiological recovery may persist beyond clinical recovery after SRC. The potential role of genetic testing remains unclear based on limited research.<br><br>CONCLUSIONS: Advanced neuroimaging, fluid-based biomarkers, genetic testing and emerging technologies are valuable research tools for the study of SRC, but there is not sufficient evidence to recommend their use in clinical practice.<br><br>PROSPERO REGISTRATION NUMBER: CRD42020164558.}, }
@article {pmid37317282, year = {2023}, author = {Halma, MTJ and Plothe, C and Marik, P and Lawrie, TA}, title = {Strategies for the Management of Spike Protein-Related Pathology.}, journal = {Microorganisms}, volume = {11}, number = {5}, pages = {}, pmid = {37317282}, issn = {2076-2607}, abstract = {In the wake of the COVID-19 crisis, a need has arisen to prevent and treat two related conditions, COVID-19 vaccine injury and long COVID-19, both of which can trace at least part of their aetiology to the spike protein, which can cause harm through several mechanisms. One significant mechanism of harm is vascular, and it is mediated by the spike protein, a common element of the COVID-19 illness, and it is related to receiving a COVID-19 vaccine. Given the significant number of people experiencing these two related conditions, it is imperative to develop treatment protocols, as well as to consider the diversity of people experiencing long COVID-19 and vaccine injury. This review summarizes the known treatment options for long COVID-19 and vaccine injury, their mechanisms, and their evidentiary basis.}, }
@article {pmid37325147, year = {2023}, author = {Dong, T and Wang, M and Liu, J and Ma, P and Pang, S and Liu, W and Liu, A}, title = {Diagnostics and analysis of SARS-CoV-2: current status, recent advances, challenges and perspectives.}, journal = {Chemical science}, volume = {14}, number = {23}, pages = {6149-6206}, pmid = {37325147}, issn = {2041-6520}, abstract = {The disastrous spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has induced severe public healthcare issues and weakened the global economy significantly. Although SARS-CoV-2 infection is not as fatal as the initial outbreak, many infected victims suffer from long COVID. Therefore, rapid and large-scale testing is critical in managing patients and alleviating its transmission. Herein, we review the recent advances in techniques to detect SARS-CoV-2. The sensing principles are detailed together with their application domains and analytical performances. In addition, the advantages and limits of each method are discussed and analyzed. Besides molecular diagnostics and antigen and antibody tests, we also review neutralizing antibodies and emerging SARS-CoV-2 variants. Further, the characteristics of the mutational locations in the different variants with epidemiological features are summarized. Finally, the challenges and possible strategies are prospected to develop new assays to meet different diagnostic needs. Thus, this comprehensive and systematic review of SARS-CoV-2 detection technologies may provide insightful guidance and direction for developing tools for the diagnosis and analysis of SARS-CoV-2 to support public healthcare and effective long-term pandemic management and control.}, }
@article {pmid37326700, year = {2024}, author = {Gloeckl, R and Leitl, D and Schneeberger, T and Jarosch, I and Koczulla, AR}, title = {Rehabilitative interventions in patients with persistent post COVID-19 symptoms-a review of recent advances and future perspectives.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {274}, number = {8}, pages = {1819-1828}, pmid = {37326700}, issn = {1433-8491}, mesh = {Humans ; *COVID-19/rehabilitation ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {The SARS-CoV-2 pandemic has not only caused millions of deaths but left also millions of people with persistent symptoms behind. These long-term COVID-19 sequelae cause a considerable burden on individuals´ health, healthcare systems, and economies worldwide given the high rate of SARS-CoV-2 infections. Therefore, rehabilitative interventions and strategies are needed to counteract the post COVID-19 sequelae. The importance of rehabilitation for patients with persistent COVID-19 symptoms has been recently also highlighted in a Call for Action by the World Health Organisation. Based on previously published research, but also in line with clinical experience, COVID-19 is not one specific disease but rather presents in different phenotypes that vary in their pathophysiological mechanisms, symptomatic manifestations, and potential interventional approaches. This review provides a proposal for differentiating post COVID-19 patients in non-organ-specific phenotypes that may help clinicians to evaluate patients and to plan therapeutic options. Furthermore, we present current unmet needs and suggest a potential pathway for a specific rehabilitation approach in people with persistent post-COVID symptoms.}, }
@article {pmid37328666, year = {2023}, author = {Murugan, AK and Alzahrani, AS}, title = {Potential impacts of SARS-CoV-2 on parathyroid: current advances and trends.}, journal = {Endocrine}, volume = {81}, number = {3}, pages = {391-408}, pmid = {37328666}, issn = {1559-0100}, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19 ; Furin/metabolism ; COVID-19 Vaccines ; Parathyroid Glands/metabolism ; Angiotensin-Converting Enzyme 2 ; Post-Acute COVID-19 Syndrome ; Peptidyl-Dipeptidase A ; }, abstract = {Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection affects several important organs including endocrine glands. Experimental studies demonstrated that the virus exploits the ACE2, a transmembrane glycoprotein on the cell surface as a receptor for cellular entry. This entry process is exclusively facilitated by other intracellular protein molecules such as TMPRSS2, furin, NRP1, and NRP2. Recent findings documented the involvement of the SARS-CoV-2 in inducing various parathyroid disorders including hypoparathyroidism and hypocalcemia, which received significant attention. This review extensively describes rapidly evolving knowledge on the potential part of SARS-CoV-2 in emerging various parathyroid disorders due to SARS-CoV-2 infection particularly parathyroid malfunction in COVID-19 cases, and post-COVID-19 conditions. Further, it presents the expression level of various molecules such as ACE2, TMPRSS2, furin, NRP1, and NRP2 in the parathyroid cells that facilitate the SARS-CoV-2 entry into the cell, and discusses the possible mechanism of parathyroid gland infection. Besides, it explores parathyroid malfunction in COVID-19 vaccine-administered cases. It also explains the possible long-COVID-19 effect on parathyroid and post-COVID-19 management of parathyroid. A complete understanding of the mechanisms of SARS-CoV-2-triggered pathogenesis in parathyroid dysfunctions may curtail treatment options and aid in the management of SARS-CoV-2-infected cases.}, }
@article {pmid37328773, year = {2023}, author = {Wang, C and Ramasamy, A and Verduzco-Gutierrez, M and Brode, WM and Melamed, E}, title = {Acute and post-acute sequelae of SARS-CoV-2 infection: a review of risk factors and social determinants.}, journal = {Virology journal}, volume = {20}, number = {1}, pages = {124}, pmid = {37328773}, issn = {1743-422X}, support = {K08 AA027837/AA/NIAAA NIH HHS/United States ; NIAAA K08 T26-1616-11/NH/NIH HHS/United States ; }, mesh = {Humans ; Female ; Male ; Post-Acute COVID-19 Syndrome ; *Epstein-Barr Virus Infections ; Social Determinants of Health ; *COVID-19/complications ; Herpesvirus 4, Human ; SARS-CoV-2 ; Risk Factors ; Disease Progression ; }, abstract = {SARS-CoV-2 infection leading to Coronavirus Disease 2019 (COVID-19) has caused more than 762 million infections worldwide, with 10-30% of patients suffering from post-acute sequelae of SARS-CoV-2 infections (PASC). Initially thought to primarily affect the respiratory system, it is now known that SARS-CoV-2 infection and PASC can cause dysfunction in multiple organs, both during the acute and chronic stages of infection. There are also multiple risk factors that may predispose patients to worse outcomes from acute SARS-CoV-2 infection and contribute to PASC, including genetics, sex differences, age, reactivation of chronic viruses such as Epstein Barr Virus (EBV), gut microbiome dysbiosis, and behavioral and lifestyle factors, including patients' diet, alcohol use, smoking, exercise, and sleep patterns. In addition, there are important social determinants of health, such as race and ethnicity, barriers to health equity, differential cultural perspectives and biases that influence patients' access to health services and disease outcomes from acute COVID-19 and PASC. Here, we review risk factors in acute SARS-CoV-2 infection and PASC and highlight social determinants of health and their impact on patients affected with acute and chronic sequelae of COVID-19.}, }
@article {pmid37334371, year = {2023}, author = {Bellucci, G and Albanese, A and Rizzi, C and Rinaldi, V and Salvetti, M and Ristori, G}, title = {The value of Interferon β in multiple sclerosis and novel opportunities for its anti-viral activity: a narrative literature review.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1161849}, pmid = {37334371}, issn = {1664-3224}, mesh = {Humans ; Interferon-beta/therapeutic use ; *Multiple Sclerosis/drug therapy ; *COVID-19 ; *Epstein-Barr Virus Infections/complications ; SARS-CoV-2 ; Pandemics ; Post-Acute COVID-19 Syndrome ; Herpesvirus 4, Human ; Interferons/therapeutic use/pharmacology ; Antiviral Agents/therapeutic use/pharmacology ; }, abstract = {Interferon-beta (IFN-β) for Multiple Sclerosis (MS) is turning 30. The COVID-19 pandemic rejuvenated the interest in interferon biology in health and disease, opening translational opportunities beyond neuroinflammation. The antiviral properties of this molecule are in accord with the hypothesis of a viral etiology of MS, for which a credible culprit has been identified in the Epstein-Barr Virus. Likely, IFNs are crucial in the acute phase of SARS-CoV-2 infection, as demonstrated by inherited and acquired impairments of the interferon response that predispose to a severe COVID-19 course. Accordingly, IFN-β exerted protection against SARS-CoV-2 in people with MS (pwMS). In this viewpoint, we summarize the evidence on IFN-β mechanisms of action in MS with a focus on its antiviral properties, especially against EBV. We synopsize the role of IFNs in COVID-19 and the opportunities and challenges of IFN-β usage for this condition. Finally, we leverage the lessons learned in the pandemic to suggest a role of IFN-β in long-COVID-19 and in special MS subpopulations.}, }
@article {pmid37340400, year = {2023}, author = {Al-Jabr, H and Hawke, LD and Thompson, DR and Clifton, A and Shenton, M and Castle, DJ and Ski, CF}, title = {Interventions to support mental health in people with long COVID: a scoping review.}, journal = {BMC public health}, volume = {23}, number = {1}, pages = {1186}, pmid = {37340400}, issn = {1471-2458}, mesh = {Humans ; Mental Health ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Mental Disorders/therapy/diagnosis ; Anxiety/therapy ; }, abstract = {INTRODUCTION: Long COVID (LC) is a multisystem disease with symptoms lasting weeks or months beyond the acute COVID-19 infection. Several manifestations are reported by people with LC, including effects on mental health, with varying degrees of psychological distress and disturbances to daily activities. Research conducted to identify effective interventions to support mental health among people with LC has been limited by the breadth and scope of studies.<br><br>AIM: This review aims to identify interventions being tested to support mental health of people with LC.<br><br>METHODS: A scoping review was conducted by searching five databases for articles published between January 2020 and early October 2022 to identify research evaluating interventions focused on improving mental health symptoms associated with LC. Results from all sources were checked for eligibility by two reviewers, and agreements were resolved by discussion. Gray literature and reference list of included studies and relevant reviews were scrutinised to identify any additional studies. Data extraction was conducted by one reviewer and checked by another reviewer for accuracy.<br><br>RESULTS: Of the 940 studies identified, 17 were included, the design of which varied but included mainly case studies (n&#x2009;=&#x2009;6) and clinical trials (n&#x2009;=&#x2009;5). Several interventions were described, ranging from single interventions (e.g., pharmacologic) to more holistic, comprehensive suites of services (pharmacologic and non-pharmacologic). Several mental health outcomes were measured, mostly anxiety and depression. All included studies were reported to be associated with improvements in participants' mental health outcomes.<br><br>CONCLUSION: This scoping review identified studies reporting on a variety of interventions to support mental health among people with LC. Although positive changes were reported by all studies, some were case studies and thus their findings must be interpreted with caution. There is a need for more research to be conducted to identify the impact of interventions on mental health of people with LC.}, }
@article {pmid37342500, year = {2023}, author = {Komaroff, AL and Lipkin, WI}, title = {ME/CFS and Long COVID share similar symptoms and biological abnormalities: road map to the literature.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1187163}, pmid = {37342500}, issn = {2296-858X}, support = {U54 AI138370/AI/NIAID NIH HHS/United States ; }, abstract = {Some patients remain unwell for months after "recovering" from acute COVID-19. They develop persistent fatigue, cognitive problems, headaches, disrupted sleep, myalgias and arthralgias, post-exertional malaise, orthostatic intolerance and other symptoms that greatly interfere with their ability to function and that can leave some people housebound and disabled. The illness (Long COVID) is similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as well as to persisting illnesses that can follow a wide variety of other infectious agents and following major traumatic injury. Together, these illnesses are projected to cost the U.S. trillions of dollars. In this review, we first compare the symptoms of ME/CFS and Long COVID, noting the considerable similarities and the few differences. We then compare in extensive detail the underlying pathophysiology of these two conditions, focusing on abnormalities of the central and autonomic nervous system, lungs, heart, vasculature, immune system, gut microbiome, energy metabolism and redox balance. This comparison highlights how strong the evidence is for each abnormality, in each illness, and helps to set priorities for future investigation. The review provides a current road map to the extensive literature on the underlying biology of both illnesses.}, }
@article {pmid37342987, year = {2023}, author = {Sarri, G and Liu, W and Zabotka, L and Freitag, A and Claire, R and Wangge, G and Elvidge, J and Dawoud, D and Bennett, D and Wen, X and Li, X and Rentsch, CT and Uddin, MJ and Ali, MS and Gokhale, M and Déruaz-Luyet, A and Moga, DC and Guo, JJ and Zullo, AR and Patorno, E and Lin, KJ}, title = {Prognostic Factors of COVID-19: An Umbrella Review Endorsed by the International Society for Pharmacoepidemiology.}, journal = {Clinical pharmacology and therapeutics}, volume = {114}, number = {3}, pages = {604-613}, pmid = {37342987}, issn = {1532-6535}, support = {R21 AG061632/AG/NIA NIH HHS/United States ; R03 AG070661/AG/NIA NIH HHS/United States ; R01 AG065722/AG/NIA NIH HHS/United States ; K01 AG073651/AG/NIA NIH HHS/United States ; R01 AG077620/AG/NIA NIH HHS/United States ; U01 FD007213/FD/FDA HHS/United States ; }, mesh = {Adult ; Child ; Humans ; Male ; Female ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Pharmacoepidemiology ; Prognosis ; Hospitalization ; }, abstract = {During the coronavirus disease 2019 (COVID-19) pandemic, the urgency for updated evidence to inform public health and clinical care placed systematic literature reviews (SLRs) at the cornerstone of research. We aimed to summarize evidence on prognostic factors for COVID-19 outcomes through published SLRs and to critically assess quality elements in the findings' interpretation. An umbrella review was conducted via electronic databases from January 2020 to April 2022. All SLRs (and meta-analyses) in English were considered. Data screening and extraction were conducted by two independent reviewers. AMSTAR 2 tool was used to assess SLR quality. The study was registered with PROSPERO (CRD4202232576). Out of 4,564 publications, 171 SLRs were included of which 3 were umbrella reviews. Our primary analysis included 35 SLRs published in 2022, which incorporated studies since the beginning of the pandemic. Consistent findings showed that, for adults, older age, obesity, heart disease, diabetes, and cancer were more strongly predictive of risk of hospitalization, intensive care unit admission, and mortality due to COVID-19. Male sex was associated with higher risk of short-term adverse outcomes, but female sex was associated with higher risk of long COVID. For children, socioeconomic determinants that may unravel COVID-19 disparities were rarely reported. This review highlights key prognostic factors of COVID-19, which can help clinicians and health officers identify high-risk groups for optimal care. Findings can also help optimize confounding adjustment and patient phenotyping in comparative effectiveness research. A living SLR approach may facilitate dissemination of new findings. This paper is endorsed by the International Society for Pharmacoepidemiology.}, }
@article {pmid37346808, year = {2023}, author = {Tang, J and Song, T and Kuang, M and Feng, Y and Liu, G and Liu, H}, title = {Recent Advancements on Long COVID in China: A Narrative Review.}, journal = {International journal of general medicine}, volume = {16}, number = {}, pages = {2585-2593}, pmid = {37346808}, issn = {1178-7074}, abstract = {The COVID-19 pandemic is a huge public health crisis in the 21st century. In addition to the acute symptoms, a considerable proportion of patients worldwide have suffered from post-COVID-19 syndrome, commonly known as Long COVID. The impact of Long COVID on individual and public health burden cannot be ignored. According to recent researches, Long COVID has been affecting multiple organ systems throughout the body, with respiratory, mental, nervous and digestive symptoms often seen in Chinese population. Clinical studies have proved that symptoms were alleviated by a variety of treatments, such as physical therapy, rehabilitation training, psychological support, behavioral cognitive therapy, stem cell therapy, etc. Based on the current clinical evidence, it is recommended to strengthen the scientific research on Long COVID and actively carry out early monitoring and intervention in the future, so as to effectively prevent the long-term disease burden and economic pressure.}, }
@article {pmid37350206, year = {2023}, author = {El Moussaoui, M and Guiot, J and Frippiat, F and Darcis, G}, title = {[An emerging cause of chronic fatigue and pain : post-COVID-19 condition or long COVID].}, journal = {Revue medicale de Liege}, volume = {78}, number = {5-6}, pages = {299-304}, pmid = {37350206}, issn = {0370-629X}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *Fatigue Syndrome, Chronic/diagnosis/epidemiology/etiology ; *COVID-19/complications ; SARS-CoV-2 ; Pain ; }, abstract = {Some individuals who have been infected with SARS-CoV-2 can experience long-term effects from their infection, known as post-COVID conditions, post-acute sequelae of COVID-19 or long COVID. Different underlying mechanisms can lead to long COVID, none of which are mutually exclusive. Lingering symptoms can persist years after SARS-CoV-2 infection, including fatigue, muscle weakness, tachycardia, dyspnea and various neurological symptoms. The symptomatology is partly similar to that reported by people with chronic fatigue syndrome and other unwell studied long-lasting diseases that may occur after other infections. People who have experienced more severe COVID-19 illness are at higher risk of developing long COVID, although anyone who was infected can experience post-COVID conditions. Importantly, unvaccinated individuals are more likely to develop long COVID. Here we review the current knowledge and discuss key findings regarding the epidemiology and physiopathology of long COVID. We briefly review current diagnostic and treatment options that remain so far largely insufficient.}, }
@article {pmid37351002, year = {2023}, author = {Hovagemyan, F and Dugerdil, A and Braggion, A and Mallet, L and Flahault, A}, title = {Psychiatric consequences and issues of long COVID on patients with prior psychiatric comorbidities: a scoping review.}, journal = {Frontiers in psychiatry}, volume = {14}, number = {}, pages = {1181767}, pmid = {37351002}, issn = {1664-0640}, abstract = {SARS-CoV-2 is a growing field of research and mental health in long COVID is one of its interesting domains. This scoping review aims at studying the outcomes of mental health in patients already known for psychiatric illness. This was done by researching the literature in two databases (Embase and PubMed) for articles studying mental health consequences of long COVID in patients already known for psychiatric history. Eleven studies were included. 6/11 studies found an effect of long COVID, with varying severity of outcomes studied, with either a worsening in length or severity. 4/11 did not find any correlation between worsening symptoms and psychiatric history. The methods for assessing which psychiatric symptoms to include and how to determine prior history were heterogeneous, making direct comparison sometimes difficult. The data seem to show worse effects of long COVID on mental health of patients with prior mental illness, with limitations regarding the heterogeneity of the studies' designs and focuses. It also highlights how neglected this population of patients is in the current state of research.}, }
@article {pmid37351054, year = {2023}, author = {Najafi, MB and Javanmard, SH}, title = {Post-COVID-19 Syndrome Mechanisms, Prevention and Management.}, journal = {International journal of preventive medicine}, volume = {14}, number = {}, pages = {59}, pmid = {37351054}, issn = {2008-7802}, abstract = {As the population of patients recovering from COVID-19 grows, post COVID-19 challenges are recognizing by ongoing evidences at once. Long COVID is defined as a syndrome with a range of persistent symptoms that remain long after (beyond 12 weeks) the acute SARS-CoV-2 infection. Studies have shown that long COVID can cause multi-organ damages with a wide spectrum of manifestations. Many systems, but not limited to, including respiratory, cardiovascular, nervous, gastrointestinal, and musculoskeletal systems, are involved in long COVID. Fatigue and dyspnea are the most common symptoms of long COVID. Long COVID-19 may be driven by tissue damage caused by virus-specific pathophysiologic changes or secondary to pathological long-lasting inflammatory response because of viral persistence, immune dysregulation, and autoimmune reactions. Some risk factors like sex and age, more than five early symptoms, and specific biomarkers have been revealed as a probable long COVID predicator discussed in this review. It seems that vaccination is the only way for prevention of long COVID and it can also help patients who had already long COVID. Managing long COVID survivors recommended being in a multidisciplinary approach, and a framework for identifying those at high risk for post-acute COVID-19 must be proposed. Possible therapeutic options and useful investigation tools for follow-up are suggested in this review. In sum, as evidence and researches are regularly updated, we provide the current understanding of the epidemiology, clinical manifestation, suspected pathophysiology, associated risk factors, and treatment options of long COVID in this review.}, }
@article {pmid37354724, year = {2023}, author = {Lin, CW and Wang, YH and Li, YE and Chiang, TY and Chiu, LW and Lin, HC and Chang, CT}, title = {COVID-related dysphonia and persistent long-COVID voice sequelae: A systematic review and meta-analysis.}, journal = {American journal of otolaryngology}, volume = {44}, number = {5}, pages = {103950}, pmid = {37354724}, issn = {1532-818X}, mesh = {Humans ; Male ; Female ; *Dysphonia/epidemiology/etiology/diagnosis ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications/epidemiology ; *Voice ; Voice Training ; }, abstract = {PURPOSE: Dysphonia is a common symptom due to the coronavirus disease of the 2019 (COVID-19) infection. Nonetheless, it is often underestimated for its impact on human's health. We conducted this first study to investigate the global prevalence of COVID-related dysphonia as well as related clinical factors during acute COVID-19 infection, and after a mid- to long-term follow-up following the recovery.<br><br>METHODS: Five electronic databases including PubMed, Embase, ScienceDirect, the Cochrane Library, and Web of Science were systematically searched for relevant articles until Dec, 2022, and the reference of the enrolled studies were also reviewed. Dysphonia prevalence during and after COVID-19 infection, and voice-related clinical factors were analyzed; the random-effects model was adopted for meta-analysis. The one-study-removal method was used for sensitivity analysis. Publication bias was determined with funnel plots and Egger's tests.<br><br>RESULTS: Twenty-one articles comprising 13,948 patients were identified. The weighted prevalence of COVID-related dysphonia during infection was 25.1&#xa0;% (95&#xa0;% CI: 14.9 to 39.0&#xa0;%), and male was significantly associated with lower dysphonia prevalence (coefficients: -0.116, 95&#xa0;% CI: -0.196 to -0.036; P&#xa0;=&#xa0;.004) during this period. Besides, after recovery, the weighted prevalence of COVID-related dysphonia declined to 17.1&#xa0;% (95&#xa0;% CI: 11.0 to 25.8&#xa0;%). 20.1&#xa0;% (95&#xa0;% CI: 8.6 to 40.2&#xa0;%) of the total patients experienced long-COVID dysphonia.<br><br>CONCLUSIONS: A quarter of the COVID-19 patients, especially female, suffered from voice impairment during infection, and approximately 70&#xa0;% of these dysphonic patients kept experiencing long-lasting voice sequelae, which should be noticed by global physicians.}, }
@article {pmid37357041, year = {2023}, author = {Noureddine, S and Roux-Claudé, P and Eberst, G and Westeel, V and Barnig, C and Claudé, F}, title = {[The role of the cardiopulmonary exercise test and pulmonary rehabilitation in long COVID-19].}, journal = {Revue des maladies respiratoires}, volume = {40}, number = {7}, pages = {604-622}, pmid = {37357041}, issn = {1776-2588}, mesh = {Humans ; *COVID-19 ; Exercise Test ; Post-Acute COVID-19 Syndrome ; Quality of Life ; SARS-CoV-2 ; Dyspnea/diagnosis/etiology ; }, abstract = {INTRODUCTION: Long COVID refers to persistent symptoms, lasting more than 4 weeks after acute SARS-CoV-2 infection, even though the infection itself has been successfully controlled and remedied. Patient complaints are diverse, and the underlying physiopathological mechanisms are not well understood. Dyspnea and muscle fatigue are among the most commonly reported symptoms.<br><br>STATE OF THE ART: Cardiopulmonary exercise test (CPET) has been recognized as a useful tool in investigation of unexplained dyspnea. In patients with chronic lung disease, pulmonary rehabilitation is a program designed to counteract dyspnea, to increase exercise capacity and to improve quality of life.<br><br>PERSPECTIVES: Publications on CPET and pulmonary rehabilitation are needed in order to deepen comprehension and enhance management of long-COVID-19.<br><br>CONCLUSIONS: CPET reports have shown that symptoms persisting in the aftermath of acute SARS-CoV-2 infection may be related to deconditioning, a common occurrence after ICU stay, to cardiac dysautonomia subsequent to critical infections and, finally, to dysfunctional breathing subsequent to mild infections. These findings justify pulmonary rehabilitation, which has proven to be effective regardless of the severity of the initial infection, not only immediately after hospital discharge, but also at later points in time.}, }
@article {pmid37362775, year = {2023}, author = {Zhang, J and Zhang, Y and Xia, Y and Sun, J}, title = {Microbiome and intestinal pathophysiology in post-acute sequelae of COVID-19.}, journal = {Genes &amp; diseases}, volume = {11}, number = {3}, pages = {}, pmid = {37362775}, issn = {2352-3042}, abstract = {Long COVID, also known for post-acute sequelae of COVID-19, describes the people who have the signs and symptoms that continue or develop after the acute COVID-19 phase. Long COVID patients suffer from an inflammation or host responses towards the virus approximately 4 weeks after initial infection with the SARS CoV-2 virus and continue for an uncharacterized duration. Anyone infected with COVID-19 before could experience long-COVID conditions, including the patients who were infected with SARS CoV-2 virus confirmed by tests and those who never knew they had an infection early. People with long COVID may experience health problems from different types and combinations of symptoms over time, such as fatigue, dyspnea, cognitive impairments, and gastrointestinal (GI) symptoms (e.g., nausea, vomiting, diarrhea, decreased or loss of appetite, abdominal pain, and dysgeusia). The critical role of the microbiome in these GI symptoms and long COVID were reported in clinical patients and experimental models. Here, we provide an overall view of the critical role of the GI tract and microbiome in the development of long COVID, including the clinical GI symptoms in patients, dysbiosis, viral-microbiome interactions, barrier function, and inflammatory bowel disease patients with long COVID. We highlight the potential mechanisms and possible treatment based on GI health and microbiome. Finally, we discuss challenges and future direction in the long COVID clinic and research.}, }
@article {pmid37363154, year = {2023}, author = {Chollet, F and Planton, M and Sailler, L and De Almeida, S and Alvarez, M and Pariente, J}, title = {[Neurological forms of long COVID in adults: Critical approach].}, journal = {Bulletin de l'Academie nationale de medecine}, volume = {}, number = {}, pages = {}, pmid = {37363154}, issn = {0001-4079}, abstract = {Now recognized by health authorities, long COVID is identified as a frequent condition complicating the evolution of SARS-CoV-2 infection. Its polymorphic and sometimes disconcerting clinical expression raises questions about its mechanism. Patterns of clinical expression suggest extensive involvement of the nervous system through an almost ubiquitous cognitive complaint. This article reviews the neurological symptoms and forms of these patients, and the neuropsychological explorations aimed at objectifying a cognitive deficit. The studies published until now confronted with the clinical mode of expression, did not make it possible to define a deficit neuropsychological profile at the level of the groups, and evoked more a functional impairment than a lesion. However, each series mentions a small number of patients in whom a cognitive deficit is objectified. The uncertainties about the causes of the prolonged forms of COVID, the heterogeneity of the published studies, and the virtual absence of temporal evolution data should make one cautious about the interpretation of these data but should in no way delay or prevent taking into account care of these patients.}, }
@article {pmid37363156, year = {2023}, author = {Lemogne, C and Ranque, B}, title = {[Role of psychological factors in post-COVID-19 condition].}, journal = {Bulletin de l'Academie nationale de medecine}, volume = {}, number = {}, pages = {}, pmid = {37363156}, issn = {0001-4079}, abstract = {Even after a mild episode of coronavirus disease 2019 (COVID-19), many patients suffer from persistent symptoms that can impair their quality of life for months. The potential role of psychological mechanisms in this post-COVID-19 condition, often referred to as long COVID, has been discussed early in the pandemic. Evidence supporting this hypothesis is now accumulating. First, a history of anxiety or depression is now an established risk factor for post-COVID-19 condition with a dose-response relationship and effect size similar to those of other known risk factors. This association extends to other forms of psychological distress, including perceived stress and loneliness. Second, specific beliefs about COVID-19 have been associated with the risk of subsequent similar symptoms, occurring weeks to several months later. Other studies, which have yet to be replicated, suggest an influence of the context of the initial infection (first versus second wave of the pandemic, before the emergence of significant variants and vaccination) and the trust in various sources of information about COVID-19 on the risk of subsequent symptoms. Bayesian models of perception can account for these results particularly well within a theoretical framework similar to that advanced for functional somatic disorders, integrating increased symptom expectations with decreased perception of the body internal state (interoception) and intolerance of uncertainty in the context of symptoms initially triggered by an infectious episode. These psychological mechanisms should obviously not be considered as exclusive. However, since they are modifiable, they could be targeted in clinical trials, within an integrative and multidisciplinary approach.}, }
@article {pmid37363406, year = {2023}, author = {Li, BB and Feng, CW and Qu, YY and Sun, ZR and Chen, T and Wang, YL and Wang, QY and Lu, J and Shao, YY and Yang, TS}, title = {Research progress on central mechanism of acupuncture treatment for chronic fatigue syndrome.}, journal = {World journal of acupuncture-moxibustion}, volume = {}, number = {}, pages = {}, pmid = {37363406}, issn = {1003-5257}, abstract = {Chronic fatigue syndrome is a neurological disorder characterized by extreme fatigue that lasts for a long time and doesn't alleviate with rest. The number of the cases has been increasing during the era of COVID-19 pandemic. Acupuncture may have some effect on chronic fatigue syndrome, but its mechanism remains unclear. This article was to summarize the specific manifestations of abnormal central mechanism in patients with chronic fatigue syndrome through laboratory tests and neuroimaging. It was found from the laboratory evaluation that there were changes in the structure of the frontal cortex, thalamus and other brain tissues; factors, including IFN-α and IL-10 in cerebrospinal fluid were found abnormal; results of oxidative and nitrosative stress and changes in neurobiochemical substances, e.g. hypothalamus hormone levels and neurotransmitter concentrations, were observed. With magnetic resonance imaging and positron emission tomography, it was shown that the partial brain of persons with chronic fatigue syndrome had morphological changes with diminished grey matter and white; changes in cerebral blood flow velocity caused by decreased perfusion and functional activity with abnormal connectivity in brain were detected. In addition, there was significant decrease in glucose metabolism accompanied with neuroinflammatory response; metabolic disorders of serotonergic, cholinergic, glutamatergic and γ-aminobutyric acid energy neurotransmitters were also discovered. The regulatory effect of acupuncture on the above central neurological abnormalities in chronic fatigue syndrome model animals was elaborated, and the direction for further research was analyzed in order to provide ideas for further research on the central mechanism of acupuncture treatment for chronic fatigue syndrome.}, }
@article {pmid37363407, year = {2023}, author = {Feng, BW and Rong, PJ}, title = {Acupoint stimulation for long COVID: A promising intervention:.}, journal = {World journal of acupuncture-moxibustion}, volume = {}, number = {}, pages = {}, pmid = {37363407}, issn = {1003-5257}, abstract = {"Long COVID" is a sustained symptom following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). According to recent statistics, at least 65 million people have long COVID, which poses a long-term threat to human health. The pathogenic mechanisms of coronavirus disease 2019 (COVID-19) are complex and affect multiple organs and systems. Common symptoms include palpitations, breathing difficulties, attention and memory deficits, fatigue, anxiety, and depression. It is difficult to achieve satisfactory treatment effect with a single intervention. Currently, treatment strategies for long COVID are still in the exploratory stage, and there is an urgent need to find appropriate and effective methods for long COVID treatment. Traditional Chinese medicine is effective in treating the various phases of COVID-19. Previous studies have shown that acupoint stimulation therapy is effective in improving palpitations, dyspnea, cognitive impairment, anxiety, depression, and other symptoms in patients. According to previous studies, acupoint stimulation may improve various symptoms related to long COVID. This paper discusses the potential application value of acupoint stimulation in the treatment of long COVID-related symptoms, based on the common sequelae of various systems involved in long COVID, and the effect of acupoint stimulation in the treatment of similar symptoms and diseases in recent years.}, }
@article {pmid37364827, year = {2023}, author = {Mortazavi, S and de Peralta-Venturina, M and Marchevsky, AM}, title = {Nonspecific interstitial pneumonia pattern is a frequent finding in patients with post-acute COVID-19 syndrome treated with bilateral orthotopic lung transplantation: current best evidence.}, journal = {Human pathology}, volume = {141}, number = {}, pages = {90-101}, pmid = {37364827}, issn = {1532-8392}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/pathology ; *Idiopathic Interstitial Pneumonias/pathology ; *Lung Diseases, Interstitial/etiology/surgery/diagnosis ; Lung/surgery/pathology ; *Lung Transplantation/adverse effects ; *Cysts/pathology ; Fibrosis ; }, abstract = {Patients with post-acute COVID-19 (PA-COVID) syndrome or long COVID-19 syndrome develop persistent symptoms and complications that last beyond 4 weeks of the initial infection. There is limited information regarding the pulmonary pathology in PA-COVID patients who require bilateral orthotopic lung transplantation (BOLT). Our experience with 40 lung explants from 20 PA-COVID patients who underwent BOLT is described. Clinicopathologic findings are correlated with best evidence from literature. The lung parenchyma showed bronchiectasis (n = 20) and severe interstitial fibrosis with areas resembling the nonspecific interstitial pneumonia (NSIP) pattern of fibrosis (n = 20), interstitial fibrosis not otherwise specified (n = 20), and fibrotic cysts (n = 9). None of the explants exhibited a usual interstitial pneumonia pattern of fibrosis. Other parenchymal changes included multinucleated giant cells (n = 17), hemosiderosis (n = 16), peribronchiolar metaplasia (n = 19), obliterative bronchiolitis (n = 6), and microscopic honeycombing (n = 5). Vascular abnormalities included thrombosis of a lobar artery (n = 1) and microscopic thrombi in small vessels (n = 7). Systematic literature review identified 7 articles reporting the presence in 12 patients of interstitial fibrosis showing the NSIP pattern (n = 3), organizing pneumonia/diffuse alveolar damage (n = 4) and not otherwise specified (n = 3) patterns. All but one of these studies also reported the presence of multinucleated giant cells and none of the studies reported the presence of severe vascular abnormalities. PA-COVID patients undergoing BOLT show a pattern of fibrosis that resembles a mixed cellular-fibrotic NSIP pattern and generally lack severe vascular complications. As the NSIP pattern of fibrosis is often associated with autoimmune diseases, additional studies are needed to understand the mechanism of disease and learn whether this information can be used for therapeutic purposes.}, }
@article {pmid37368329, year = {2023}, author = {Fesharaki Zadeh, A and Arnsten, AFT and Wang, M}, title = {Scientific Rationale for the Treatment of Cognitive Deficits from Long COVID.}, journal = {Neurology international}, volume = {15}, number = {2}, pages = {725-742}, pmid = {37368329}, issn = {2035-8385}, support = {P30 AG066508/AG/NIA NIH HHS/United States ; R01 AG061190/AG/NIA NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; }, abstract = {Sustained cognitive deficits are a common and debilitating feature of "long COVID", but currently there are no FDA-approved treatments. The cognitive functions of the dorsolateral prefrontal cortex (dlPFC) are the most consistently afflicted by long COVID, including deficits in working memory, motivation, and executive functioning. COVID-19 infection greatly increases kynurenic acid (KYNA) and glutamate carboxypeptidase II (GCPII) in brain, both of which can be particularly deleterious to PFC function. KYNA blocks both NMDA and nicotinic-alpha-7 receptors, the two receptors required for dlPFC neurotransmission, and GCPII reduces mGluR3 regulation of cAMP-calcium-potassium channel signaling, which weakens dlPFC network connectivity and reduces dlPFC neuronal firing. Two agents approved for other indications may be helpful in restoring dlPFC physiology: the antioxidant N-acetyl cysteine inhibits the production of KYNA, and the α2A-adrenoceptor agonist guanfacine regulates cAMP-calcium-potassium channel signaling in dlPFC and is also anti-inflammatory. Thus, these agents may be helpful in treating the cognitive symptoms of long COVID.}, }
@article {pmid37370581, year = {2023}, author = {Cerfoglio, S and Capodaglio, P and Rossi, P and Verme, F and Boldini, G and Cvetkova, V and Ruggeri, G and Galli, M and Cimolin, V}, title = {Tele-Rehabilitation Interventions for Motor Symptoms in COVID-19 Patients: A Narrative Review.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {10}, number = {6}, pages = {}, pmid = {37370581}, issn = {2306-5354}, abstract = {The COVID-19 pandemic brought new challenges to global healthcare systems regarding the care of acute patients and the delivery of rehabilitation programs to post-acute or chronic patients. Patients who survive severe forms of COVID-19 often report incomplete healing and long-term symptoms. The need of these patients for rehabilitation has been recognized as a public health problem. In this context, the application of tele-rehabilitation has been explored to reduce the burden on healthcare systems. The purpose of this narrative review is to present an overview of the state of the art regarding the application of remote motor rehabilitation programs for paucisymptomatic acute and post-acute COVID-19 patients, with a focus on the motor aspects of tele-rehabilitation. Following an extensive search on PubMed, the Web of Science, and Scopus, specific studies have been reviewed and compared in terms of study objectives and participants, experimental protocols and methods for home-based interventions, functional assessment, and rehabilitation outcomes. Overall, this review suggests the feasibility and the effectiveness of tele-rehabilitation as a promising tool to complement face-to-face rehabilitation interventions. However, further improvements are needed to overcome the limitations and the current lack of knowledge in the field.}, }
@article {pmid37370884, year = {2023}, author = {Sansone, F and Pellegrino, GM and Caronni, A and Bonazza, F and Vegni, E and Lué, A and Bocci, T and Pipolo, C and Giusti, G and Di Filippo, P and Di Pillo, S and Chiarelli, F and Sferrazza Papa, GF and Attanasi, M}, title = {Long COVID in Children: A Multidisciplinary Review.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {12}, pages = {}, pmid = {37370884}, issn = {2075-4418}, support = {NA//University of Milan/ ; }, abstract = {Long COVID syndrome has emerged as a long-lasting consequence of acute SARS-CoV-2 infection in adults. In addition, children may be affected by Long COVID, with potential clinical issues in different fields, including problems in school performance and daily activities. Yet, the pathophysiologic bases of Long COVID in children are largely unknown, and it is difficult to predict who will develop the syndrome. In this multidisciplinary clinical review, we summarise the latest scientific data regarding Long COVID and its impact on children. Special attention is given to diagnostic tests, in order to help the physicians to find potential disease markers and quantify impairment. Specifically, we assess the respiratory, upper airways, cardiac, neurologic and motor and psychological aspects. Finally, we also propose a multidisciplinary clinical approach.}, }
@article {pmid37375496, year = {2023}, author = {Lafon-Hughes, L}, title = {Towards Understanding Long COVID: SARS-CoV-2 Strikes the Host Cell Nucleus.}, journal = {Pathogens (Basel, Switzerland)}, volume = {12}, number = {6}, pages = {}, pmid = {37375496}, issn = {2076-0817}, abstract = {Despite what its name suggests, the effects of the COVID-19 pandemic causative agent "Severe Acute Respiratory Syndrome Coronavirus-2" (SARS-CoV-2) were not always confined, neither temporarily (being long-term rather than acute, referred to as Long COVID) nor spatially (affecting several body systems). Moreover, the in-depth study of this ss(+) RNA virus is defying the established scheme according to which it just had a lytic cycle taking place confined to cell membranes and the cytoplasm, leaving the nucleus basically "untouched". Cumulative evidence shows that SARS-CoV-2 components disturb the transport of certain proteins through the nuclear pores. Some SARS-CoV-2 structural proteins such as Spike (S) and Nucleocapsid (N), most non-structural proteins (remarkably, Nsp1 and Nsp3), as well as some accessory proteins (ORF3d, ORF6, ORF9a) can reach the nucleoplasm either due to their nuclear localization signals (NLS) or taking a shuttle with other proteins. A percentage of SARS-CoV-2 RNA can also reach the nucleoplasm. Remarkably, controversy has recently been raised by proving that-at least under certain conditions-, SARS-CoV-2 sequences can be retrotranscribed and inserted as DNA in the host genome, giving rise to chimeric genes. In turn, the expression of viral-host chimeric proteins could potentially create neo-antigens, activate autoimmunity and promote a chronic pro-inflammatory state.}, }
@article {pmid37378093, year = {2023}, author = {Sayegh, MN and Goins, AE and Hall, MAK and Shin, YM}, title = {Presentations, Diagnosis, and Treatment of Post-COVID Viral Myocarditis in the Inpatient Setting: A Narrative Review.}, journal = {Cureus}, volume = {15}, number = {5}, pages = {e39338}, pmid = {37378093}, issn = {2168-8184}, abstract = {While coronavirus disease 2019 (COVID-19) infection rates have declined, and mortality outcomes have improved with vaccines, targeted antiviral therapies, and improved care practices over the course of the pandemic, post-acute sequelae of SARS CoV-2 infection (PASC, also referred to as "long COVID") has emerged as a significant concern, even among individuals who appear to have fully recovered from their initial infection. Acute COVID-19 infection is associated with myocarditis and cardiomyopathies, but the prevalence and presentation of post-infectious myocarditis are unclear. We provide a narrative review of post-COVID myocarditis, including symptoms and signs, physical exam findings, diagnosis, and treatment strategies. Post-COVID myocarditis has a wide range of presentations, from very mild symptoms to severe ones that can include sudden cardiac death. Several studies have noted what appears to be a bimodal distribution of affected patients, with individuals under age 16 (particularly males) most affected, followed by those over age 50. The gold standard of diagnosis for myocarditis is endomyocardial biopsy and cardiac magnetic resonance imaging with a confirmed diagnosis of COVID-19. However, if these are not available, other studies such as electrocardiogram, echocardiography, and inflammatory markers can guide clinicians to diagnose post-COVID myocarditis when appropriate. Treatment is largely supportive and may include oxygen therapy, intravenous hydration, diuretics, steroids, and antivirals. Post-COVID myocarditis is rare but important to recognize as more patients present with this condition in the inpatient setting.}, }
@article {pmid37378781, year = {2023}, author = {Taner, N and Haskologlu, IC and Erdag, E and Mercan, M and Chuckwunyere, U and Ulker, D and Sehirli, AO and Abacioglu, N}, title = {Chronobiological Efficacy of Combined Therapy of Pelargonium Sidoides and Melatonin in Acute and Persistent Cases of COVID-19: A Hypothetical Approach.}, journal = {Advances in experimental medicine and biology}, volume = {1412}, number = {}, pages = {427-442}, pmid = {37378781}, issn = {0065-2598}, mesh = {Humans ; Phytotherapy ; Plant Extracts/therapeutic use ; *Pelargonium ; *Melatonin/therapeutic use ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Antiviral Agents/therapeutic use ; Plant Roots ; }, abstract = {Since the outbreak of the first SARS-CoV-2 epidemic in China, pharmacists have rapidly engaged and developed strategies for pharmaceutical care and supply. According to the guidelines of the International Pharmaceutical Federation (FIP), clinical pharmacists/hospital pharmacists, as members of care teams, play one of the most important roles in the pharmaceutical care of patients with COVID-19. During this pandemic, many immuno-enhancing adjuvant agents have become critical in addition to antivirals and vaccines in order to overcome the disease more easily. The liquid extract obtained from the Pelargonium sidoides plant is used for many indications such as colds, coughs, upper respiratory tract infections, sore throat, and acute bronchitis. The extract obtained from the roots of the plant has been observed to have antiviral and immunomodulatory activity. In addition to its anti-inflammatory and antioxidant effects, melatonin plays a role in suppressing the cytokine storm that can develop during COVID-19 infection. Knowing that the severity and duration of COVID-19 symptoms vary within 24 hours and/or in different time periods indicates that COVID-19 requires a chronotherapeutic approach. Our goal in the management of acute and long COVID is to synchronize the medication regimen with the patient's biological rhythm. This chapter provides a comprehensive review of the existing and emerging literature on the chronobiological use of Pelargonium sidoides and melatonin during acute and prolonged COVID-19 episodes.}, }
@article {pmid37379850, year = {2023}, author = {Kim, J and Young, GS}, title = {Neuroimaging of COVID-19.}, journal = {Seminars in neurology}, volume = {43}, number = {2}, pages = {205-218}, doi = {10.1055/s-0043-1767771}, pmid = {37379850}, issn = {1098-9021}, mesh = {Humans ; *COVID-19/complications ; *Posterior Leukoencephalopathy Syndrome ; Post-Acute COVID-19 Syndrome ; *Guillain-Barre Syndrome ; Inflammation ; }, abstract = {We review the wide variety of common neuroimaging manifestations related to coronavirus disease 2019 (COVID-19) and COVID therapies, grouping the entities by likely pathophysiology, recognizing that the etiology of many entities remains uncertain. Direct viral invasion likely contributes to olfactory bulb abnormalities. COVID meningoencephalitis may represent direct viral infection and/or autoimmune inflammation. Para-infectious inflammation and inflammatory demyelination at the time of infection are likely primary contributors to acute necrotizing encephalopathy, cytotoxic lesion of the corpus callosum, and diffuse white matter abnormality. Later postinfectious inflammation and demyelination may manifest as acute demyelinating encephalomyelitis, Guillain-Barré syndrome, or transverse myelitis. The hallmark vascular inflammation and coagulopathy of COVID-19 may produce acute ischemic infarction, microinfarction contributing to white matter abnormality, space-occupying hemorrhage or microhemorrhage, venous thrombosis, and posterior reversible encephalopathy syndrome. Adverse effects of therapies including zinc, chloroquine/hydroxychloroquine, antivirals, and vaccines, and current evidence regarding "long COVID" is briefly reviewed. Finally, we present a case of bacterial and fungal superinfection related to immune dysregulation from COVID.}, }
@article {pmid37380640, year = {2023}, author = {Ding, Q and Zhao, H}, title = {Long-term effects of SARS-CoV-2 infection on human brain and memory.}, journal = {Cell death discovery}, volume = {9}, number = {1}, pages = {196}, pmid = {37380640}, issn = {2058-7716}, abstract = {The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have caused several waves of outbreaks. From the ancestral strain to Omicron variant, SARS-CoV-2 has evolved with the high transmissibility and increased immune escape against vaccines. Because of the multiple basic amino acids in the S1-S2 junction of spike protein, the widespread distribution of angiotensin-converting enzyme 2 (ACE2) receptor in human body and the high transmissibility, SARS-CoV-2 can infect multiple organs and has led to over 0.7 billion infectious cases. Studies showed that SARS-CoV-2 infection can cause more than 10% patients with the Long-COVID syndrome, including pathological changes in brains. This review mainly provides the molecular foundations for understanding the mechanism of SARS-CoV-2 invading human brain and the molecular basis of SARS-CoV-2 infection interfering with human brain and memory, which are associated with the immune dysfunction, syncytia-induced cell death, the persistence of SARS-CoV-2 infection, microclots and biopsychosocial aspects. We also discuss the strategies for reducing the Long-COVID syndrome. Further studies and analysis of shared researches will allow for further clarity regarding the long-term health consequences.}, }
@article {pmid37385286, year = {2023}, author = {Buonsenso, D and Martino, L and Morello, R and Mariani, F and Fearnley, K and Valentini, P}, title = {Viral persistence in children infected with SARS-CoV-2: current evidence and future research strategies.}, journal = {The Lancet. Microbe}, volume = {4}, number = {9}, pages = {e745-e756}, pmid = {37385286}, issn = {2666-5247}, mesh = {Adult ; Child ; Research Design ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; *SARS-CoV-2/genetics ; RNA, Viral ; Systemic Inflammatory Response Syndrome ; }, abstract = {In this Personal View, we discuss current knowledge on SARS-CoV-2 RNA or antigen persistence in children infected with SARS-CoV-2. Based on the evidence that the virus can persist in adults, we have done a literature review and analysed studies that looked for SARS-CoV-2 RNA or antigens in children undergoing autopsy, biopsy, or surgery for either death from COVID-19 or multisystem inflammatory syndrome, or assessments for long COVID-19 or other conditions. Our analysis suggests that in children, independent from disease severity, SARS-CoV-2 can spread systemically and persist for weeks to months. We discuss what is known about the biological effects of viral persistence for other viral infections and highlight new scenarios for clinical, pharmacological, and basic research exploration. Such an approach will improve the understanding and management of post-viral syndromes.}, }
@article {pmid37386857, year = {2024}, author = {Składanek, JA and Leśkiewicz, M and Gumiężna, K and Baruś, P and Piasecki, A and Klimczak-Tomaniak, D and Sygitowicz, G and Kochman, J and Grabowski, M and Tomaniak, M}, title = {Long COVID and its cardiovascular consequences: What is known?.}, journal = {Advances in clinical and experimental medicine : official organ Wroclaw Medical University}, volume = {33}, number = {3}, pages = {299-308}, doi = {10.17219/acem/167482}, pmid = {37386857}, issn = {1899-5276}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Cardiovascular System ; Arrhythmias, Cardiac ; }, abstract = {The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused high morbidity and mortality and has been a source of substantial challenges for healthcare systems globally. Despite a full recovery, a significant proportion of patients demonstrate a broad spectrum of cardiovascular, pulmonary and neurological symptoms that are believed to be caused by long-term tissue damage and pathological inflammation, which play a vital role in disease development. Microvascular dysfunction also causes significant health problems. This review aimed to critically appraise the current data on the long-term cardiovascular sequelae of coronavirus disease 2019 (COVID-19), with a primary focus on cardiovascular symptoms such as chest pain, fatigue, palpitations, and breathlessness, and more significant disease entities including myocarditis, pericarditis and postural tachycardia syndrome. Potential risk factors identified in recent studies that contribute towards the development of long COVID are also included alongside a summary of recent advances in diagnostics and putative treatment options.}, }
@article {pmid37388814, year = {2023}, author = {Marshall, GD}, title = {The pathophysiology of postacute sequelae of COVID-19 (PASC): Possible role for persistent inflammation.}, journal = {Asia Pacific allergy}, volume = {13}, number = {2}, pages = {77-84}, pmid = {37388814}, issn = {2233-8276}, support = {U54 GM115428/GM/NIGMS NIH HHS/United States ; }, abstract = {UNLABELLED: As the SARS-CoV-2-induced pandemic wanes, a substantial number of patients with acute Corona Virus-induced disease (COVID-19 continue to have symptoms for a prolonged time after initial infection. These patients are said to have postacute sequelae of COVID (PASC) or "long COVID". The underlying pathophysiology of this syndrome is poorly understood and likely quite heterogeneous. The role of persistent, possibly deviant inflammation as a major factor in comorbidity is suspected.<br><br>OBJECTIVE: To review data that address the relative importance of inflammation in the pathophysiology spectrum of PASC and to address how this would impact diagnosis and approach to therapy in patients identified as having such inflammatory abnormalities.<br><br>METHODS: A review of public databases, including PubMed, MeSH, NLM catalog, and clinical trial databases such as clinicaltrials.gov.<br><br>RESULTS: The literature supports a prominent role for various forms and types of inflammation in the pathophysiologic spectrum of PASC. Such inflammation can be persistent ant CoV-2-specific responses, new onset autoimmune responses, or a loss of normal immunoregulation resulting in widespread, sustained inflammatory pathologies that can affect both broad constitutional symptoms (such as fatigue, neurocognitive dysfunction, and anxiety/depression) and organ-specific dysfunction and/or failure.<br><br>CONCLUSIONS: PASC is a significant clinical entity with similarities to and differences from other postviral syndromes. Significant research efforts are ongoing to better understand specific aberrant inflammatory pathways present in individual patients for the purpose of developing and implementing effective therapies and ultimately prophylaxis strategies to prevent the progression of COVID-19 as well as likely future viral illnesses and pandemics.}, }
@article {pmid37389095, year = {2023}, author = {Sumantri, S and Rengganis, I}, title = {Immunological dysfunction and mast cell activation syndrome in long COVID.}, journal = {Asia Pacific allergy}, volume = {13}, number = {1}, pages = {50-53}, pmid = {37389095}, issn = {2233-8276}, abstract = {At least 65 million people around the world suffer from long COVID-19, with the majority of cases occurring in the productive age (36-50 years old). Individuals with long COVID-19 are confounded with multiple organ system dysfunctions, long-term organ injury sequelae, and a decreased quality of life. There is an overlapping of risk factors between long COVID-19 and other postviral infection syndromes, so advances in research could also benefit other groups of patients. Long COVID-19 is the consequence of multiple immune system dysregulation, such as T-cell depletion, innate immune cell hyperactivity, lack of naive T and B cells, and elevated signature of pro-inflammatory cytokines, together with persistent severe acute respiratory syndrome-coronavirus 2 reservoir and other consequences of acute infection. There is an activated condition of mast cells in long COVID-19, with abnormal granulation and excessive inflammatory cytokine release. A study by Weinstock et al. indicates that patients with long COVID-19 suffer the same clinical syndrome as patients with mast cell activation syndrome (MCAS). Diagnosis and treatment of MCAS in patients with long COVID-19 will provide further symptomatic relief, and manage mast cell-mediated hyperinflammation states, which could be useful in the long-term control and recovery of such patients.}, }
@article {pmid37392341, year = {2023}, author = {Li, M and Wu, X and Shi, J and Niu, Y}, title = {Endothelium dysfunction and thrombosis in COVID-19 with type 2 diabetes.}, journal = {Endocrine}, volume = {82}, number = {1}, pages = {15-27}, pmid = {37392341}, issn = {1559-0100}, support = {81970924//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Anticoagulants/therapeutic use ; Post-Acute COVID-19 Syndrome ; Endothelial Cells ; *Diabetes Mellitus, Type 2/complications/drug therapy ; Quality of Life ; *Venous Thromboembolism/complications/drug therapy/prevention &amp; control ; *Thrombosis/epidemiology/etiology/drug therapy ; Endothelium ; }, abstract = {SARS-CoV-2 can directly or indirectly damage endothelial cells. Endothelial injury, especially phosphatidylserine (PS) exposure on the outer membrane of cells, can more easily promote thrombosis. Type 2 diabetes(T2D) patients were more susceptible to COVID-19, they had more severe symptoms, higher risk of thrombotic complications, and longer duration of post-COVID-19 sequelae. This review provided a detailed overview of the mechanisms underlying endothelial dysfunction in T2D patients with COVID-19 (including long COVID), which may be influenced by hyperglycemia, hypoxia, and pro-inflammatory environments. The mechanisms of thrombosis in T2D patients with COVID-19 are also explored, particularly the effects of increased numbers of PS-exposing particles, blood cells, and endothelial cells on hypercoagulability. Given the high risk of thrombosis in T2D patients with COVID-19, early antithrombotic therapy can both minimize the impact of the disease on patients and maximize the chances of improvement, thereby alleviating patient suffering. We provided detailed guidance on antithrombotic drugs and dosages for mild, moderate, and severe patients, emphasizing that the optimal timing of thromboprophylaxis is a critical factor in influencing prognosis. Considering the potential interactions between antidiabetic, anticoagulant, and antiviral drugs, we proposed practical and comprehensive management recommendations to supplement the incomplete efficacy of vaccines in the diabetic population, reduce the incidence of post-COVID-19 sequelae, and improve patient quality of life.}, }
@article {pmid37394273, year = {2023}, author = {Wang, EJ and Dolomisiewicz, E and Karri, J and Tontisirin, N and Cohen, SP}, title = {Antimicrobial therapies for chronic pain (part 2): the prevention and treatment of chronic pain.}, journal = {The Korean journal of pain}, volume = {36}, number = {3}, pages = {299-315}, pmid = {37394273}, issn = {2005-9159}, abstract = {The discovery and development of antimicrobial therapies represents one of the most significant advancements in modern medicine. Although the primary therapeutic intent of antimicrobials is to eliminate their target pathogens, several antimicrobials have been shown to provide analgesia as a secondary benefit. Antimicrobials have demonstrated analgesic effects in conditions that involve dysbiosis or potential subclinical infection (e.g ., chronic low back pain with Modic type 1 changes; chronic prostatitis/chronic pelvic pain; irritable bowel syndrome; inflammatory bowel disease; functional gastrointestinal disorders/dyspepsia; myalgic encephalomyelitis/chronic fatigue syndrome), and might even prevent the chronification of pain after acute infections that are associated with excessive systemic inflammation (e.g ., post COVID-19 condition/long Covid, rheumatic fever). Clinical studies often assess the analgesic effects of antimicrobial therapies in an observational manner, without the ability to identify causative relationships, and significant gaps in the understanding remain regarding the analgesic potential of antimicrobials. Numerous interrelated patient-specific, antimicrobial-specific, and disease-specific factors altogether contribute to the perception and experience of pain, and each of these requires further study. Given worldwide concerns regarding antimicrobial resistance, antimicrobials must continue to be used judiciously and are unlikely to be repurposed as primary analgesic medications. However, when equipoise exists among several antimicrobial treatment options, the potential analgesic benefits of certain antimicrobial agents might be a valuable aspect to consider in clinical decision-making. This article (the second in a two-part series) aims to comprehensively review the evidence on the prevention and treatment of chronic pain using antimicrobial therapies and suggest a framework for future studies on this topic.}, }
@article {pmid37396704, year = {2023}, author = {Del Carpio-Orantes, L}, title = {Etiopathogenic theories about long COVID.}, journal = {World journal of virology}, volume = {12}, number = {3}, pages = {204-208}, pmid = {37396704}, issn = {2220-3249}, abstract = {The main etiopathogenic theories of long coronavirus disease (COVID) are listed and a conjunction of them is carried out with the objective of deciphering the pathophysiology of the entity, finally the main lines of treatment existing in real life are discussed (Paxlovid, use of antibiotics in dysbiosis, triple anticoagulant therapy, temelimab).}, }
@article {pmid37398713, year = {2023}, author = {Weldon, EJ and Hong, B and Hayashi, J and Goo, C and Carrazana, E and Viereck, J and Liow, K}, title = {Mechanisms and Severity of Exercise Intolerance Following COVID-19 and Similar Viral Infections: A Comparative Review.}, journal = {Cureus}, volume = {15}, number = {5}, pages = {e39722}, pmid = {37398713}, issn = {2168-8184}, abstract = {Approximately 19% of the population is suffering from "Long COVID", also known as post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PASC), which often results in exercise intolerance. As COVID infections continue to be common, studying the long-term consequences of coronavirus disease (COVID) on physical function has become increasingly important. This narrative review will aim to summarize the current literature surrounding exercise intolerance following COVID infection in terms of mechanism, current management approaches, and comparison with similar conditions and will aim to define limitations in the current literature. Multiple organ systems have been implicated in the onset of long-lasting exercise intolerance post-COVID, including cardiac impairment, endothelial dysfunction, decreased VO2 max and oxygen extraction, deconditioning due to bed rest, and fatigue. Treatment modalities for severe COVID have also been shown to cause myopathy and/or worsen deconditioning. Besides COVID-specific pathophysiology, general febrile illness as commonly experienced during infection will cause hypermetabolic muscle catabolism, impaired cooling, and dehydration, which acutely cause exercise intolerance. The mechanisms of exercise intolerance seen with PASC also appear similar to post-infectious fatigue syndrome and infectious mononucleosis. However, the severity and duration of the exercise intolerance seen with PASC is greater than that of any of the isolated mechanisms described above and thus is likely a combination of the proposed mechanisms. Physicians should consider post-infectious fatigue syndrome (PIFS), especially if fatigue persists after six months following COVID recovery. It is important for physicians, patients, and social systems to anticipate exercise intolerance lasting for weeks to months in patients with long COVID. These findings underscore the importance of long-term management of patients with COVID and the need for ongoing research to identify effective treatments for exercise intolerance in this population. By recognizing and addressing exercise intolerance in patients with long COVID, clinicians can provide proper supportive interventions, such as exercise programs, physical therapy, and mental health counseling, to improve patient outcomes.}, }
@article {pmid37402856, year = {2023}, author = {Hashimoto, K}, title = {Detrimental effects of COVID-19 in the brain and therapeutic options for long COVID: The role of Epstein-Barr virus and the gut-brain axis.}, journal = {Molecular psychiatry}, volume = {28}, number = {12}, pages = {4968-4976}, pmid = {37402856}, issn = {1476-5578}, support = {21H00184//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 21H05612//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 21H02846//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; }, mesh = {Humans ; *Brain/virology ; *Brain-Gut Axis/physiology ; *COVID-19/complications ; Epstein-Barr Virus Infections/complications ; *Gastrointestinal Microbiome/physiology ; *Herpesvirus 4, Human/pathogenicity ; Pandemics ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in a serious public health burden worldwide. In addition to respiratory, heart, and gastrointestinal symptoms, patients infected with SARS-CoV-2 experience a number of persistent neurological and psychiatric symptoms, known as long COVID or "brain fog". Studies of autopsy samples from patients who died from COVID-19 detected SARS-CoV-2 in the brain. Furthermore, increasing evidence shows that Epstein-Barr virus (EBV) reactivation after SARS-CoV-2 infection might play a role in long COVID symptoms. Moreover, alterations in the microbiome after SARS-CoV-2 infection might contribute to acute and long COVID symptoms. In this article, the author reviews the detrimental effects of COVID-19 on the brain, and the biological mechanisms (e.g., EBV reactivation, and changes in the gut, nasal, oral, or lung microbiomes) underlying long COVID. In addition, the author discusses potential therapeutic approaches based on the gut-brain axis, including plant-based diet, probiotics and prebiotics, fecal microbiota transplantation, and vagus nerve stimulation, and sigma-1 receptor agonist fluvoxamine.}, }
@article {pmid37404150, year = {2023}, author = {Bocchino, M and Rea, G and Capitelli, L and Lieto, R and Bruzzese, D}, title = {Chest CT Lung Abnormalities 1 Year after COVID-19: A Systematic Review and Meta-Analysis.}, journal = {Radiology}, volume = {308}, number = {1}, pages = {e230535}, doi = {10.1148/radiol.230535}, pmid = {37404150}, issn = {1527-1315}, mesh = {Adult ; Humans ; *COVID-19/pathology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; Lung/diagnostic imaging/pathology ; Tomography, X-Ray Computed/methods ; *Bronchiectasis ; *Pulmonary Fibrosis/pathology ; Disease Progression ; }, abstract = {Background Radiological lung sequelae may explain the persistence of respiratory complaints in post-COVID-19 condition (long-COVID). Purpose To perform a systematic review and meta-analysis of the prevalence and type of COVID-19 residual lung abnormalities at 1-year chest CT. Materials and Methods A literature search of PubMed, Web of Science, Embase, and Medline databases was performed from January 2020 to January 2023. Full-text reports of CT lung sequelae in adults (≥18 years) with confirmed COVID-19 at 1-year follow-up were included. The prevalence of any residual lung abnormality and type (fibrotic or not) was analyzed according to the Fleischner Glossary. The meta-analysis included studies with chest CT data assessable in no less than 80% of individuals. A random-effects model was used to estimate pooled prevalence. Multiple sub-group (country, journal category, methodological quality, study setting, outcomes) and meta-regression analyses were performed to identify potential sources of heterogeneity. I[2] statistics estimated low (25%), moderate (26-50%) and high (>50%) heterogeneity. 95% Prediction Intervals (95% PIs) were computed to describe the expected estimates range. Results Of 22 709 records, 21 studies were reviewed (20 prospective, 9 from China, and 7 in radiology journals). The meta-analysis included 14 studies with chest CT data in 1854 of 2043 individuals (M/F: 1109/934). Estimates of lung sequelae were highly heterogeneous (7.1-96.7%), with a pooled frequency of 43.5% (I[2]=94%; 95% PI: 5.9%, 90.4%). This also applied to single non-fibrotic changes, including ground glass opacity, consolidations, nodules/masses, parenchymal bands, and reticulations. The prevalence range of fibrotic traction bronchiectasis/bronchiolectasis was 1.6-25.7% (I[2]=93%; 95% PI: 0.0%, 98.6%;); honeycombing was unremarkable (0-1.1%; I[2]=58%; 95% PI: 0%, 60%). Lung sequelae were unrelated to any characteristics of interest. Conclusion The prevalence of COVID-19 lung sequelae at 1-year chest CT is highly heterogeneous among studies. Heterogeneity determinants remain unknown suggesting caution in data interpretation with no convincing evidence. PROSPERO (CRD42022341258) Keywords: COVID-19 pneumonia, pulmonary fibrosis, chest CT, long-COVID, systematic review, metaanalysis See also the editorial by Parraga and Svenningsen in this issue.}, }
@article {pmid37405337, year = {2023}, author = {Puntmann, VO and Valbuena-López, S}, title = {ESC Congress 2022 Imaging Highlights.}, journal = {European cardiology}, volume = {18}, number = {}, pages = {e12}, pmid = {37405337}, issn = {1758-3764}, abstract = {Cardiac imaging is an ever-evolving area, with imaging parameters and application in constant re-evaluation. This was reflected in many imaging debates and by the increased number of scientific contributions at the European Society of Cardiology Congress in 2022. While clinical trials tried to answer clinical questions related to the performance of different imaging modalities, many high-quality presentations focused on new imaging biomarkers in different scenarios, such as heart failure with preserved ejection fraction, valvular heart disease or long COVID. This highlights the need for the translation of cardiac imaging technology from research interests towards established measures of clinical practice.}, }
@article {pmid37415689, year = {2023}, author = {Marchi, M and Grenzi, P and Serafini, V and Capoccia, F and Rossi, F and Marrino, P and Pingani, L and Galeazzi, GM and Ferrari, S}, title = {Psychiatric symptoms in Long-COVID patients: a systematic review.}, journal = {Frontiers in psychiatry}, volume = {14}, number = {}, pages = {1138389}, pmid = {37415689}, issn = {1664-0640}, abstract = {OBJECTIVE: People who have been infected by COVID-19 showing persistent symptoms after 4 weeks from recovery are thought to suffer from Long-COVID syndrome (LC). There is uncertainty on the clinical manifestations of LC. We undertook a systematic review to summarize the available evidence about the main psychiatric manifestations of LC.<br><br>METHOD: PubMed (Medline), Scopus, CINHAL, PsycINFO, and EMBASE were searched until May 2022. Studies reporting estimation of emerging psychiatric symptoms and/or psychiatric diagnoses among adult people with LC were included. Pooled prevalence for each psychiatric condition was calculated in absence of control groups to compare with.<br><br>RESULTS: Thirty-three reports were included in the final selection, corresponding to 282,711 participants with LC. After 4 weeks from COVID-19 infection recovery, participants reported the following psychiatric symptoms: depression, anxiety, post-traumatic symptoms (PTS), cognitive and sleeping disturbances (i.e., insomnia or hypersomnia). The most common psychiatric manifestation resulted to be sleep disturbances, followed by depression, PTS, anxiety, and cognitive impairment (i.e., attention and memory deficits). However, some estimates were affected by important outlier effect played by one study. If study weight was not considered, the most reported condition was anxiety.<br><br>CONCLUSIONS: LC may have non-specific psychiatric manifestations. More research is needed to better define LC and to differentiate it from other post-infectious or post-hospitalization syndromes.<br><br>PROSPERO (CRD42022299408).}, }
@article {pmid37418268, year = {2023}, author = {Katz, GM and Bach, K and Bobos, P and Cheung, A and Décary, S and Goulding, S and Herridge, MS and McNaughton, CD and Palmer, KS and Razak, FA and Zhang, B and Quinn, KL}, title = {Understanding How Post-COVID-19 Condition Affects Adults and Health Care Systems.}, journal = {JAMA health forum}, volume = {4}, number = {7}, pages = {e231933}, doi = {10.1001/jamahealthforum.2023.1933}, pmid = {37418268}, issn = {2689-0186}, mesh = {Humans ; Adult ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Delivery of Health Care ; }, abstract = {IMPORTANCE: Post-COVID-19 condition (PCC), also known as long COVID, encompasses the range of symptoms and sequelae that affect many people with prior SARS-CoV-2 infection. Understanding the functional, health, and economic effects of PCC is important in determining how health care systems may optimally deliver care to individuals with PCC.<br><br>OBSERVATIONS: A rapid review of the literature showed that PCC and the effects of hospitalization for severe and critical illness may limit a person's ability to perform day-to-day activities and employment, increase their risk of incident health conditions and use of primary and short-term health care services, and have a negative association with household financial stability. Care pathways that integrate primary care, rehabilitation services, and specialized assessment clinics are being developed to support the health care needs of people with PCC. However, comparative studies to determine optimal care models based on their effectiveness and costs remain limited. The effects of PCC are likely to have large-scale associations with health systems and economies and will require substantial investment in research, clinical care, and health policy to mitigate these effects.<br><br>CONCLUSIONS AND RELEVANCE: An accurate understanding of additional health care and economic needs at the individual and health system levels is critical to informing health care resource and policy planning, including identification of optimal care pathways to support people affected by PCC.}, }
@article {pmid37419527, year = {2023}, author = {Tabacof, L and Nicolau, E and Rivera, A and Putrino, D}, title = {Post-COVID Conditions and Burden of Disease.}, journal = {Physical medicine and rehabilitation clinics of North America}, volume = {34}, number = {3}, pages = {499-511}, doi = {10.1016/j.pmr.2023.04.007}, pmid = {37419527}, issn = {1558-1381}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Cost of Illness ; }, abstract = {Post-COVID condition (PCC), also known as long COVID, is a multi-systemic illness estimated to affect 10% to 20% of those infected, regardless of age, baseline health status, or initial symptom severity. PCC has affected millions of lives, with long-lasting debilitating effects, but unfortunately it remains an underrecognized and therefore poorly documented condition. Defining and disseminating the burden of PCC is essential for developing effective public health strategies to address this issue in the long term.}, }
@article {pmid37419529, year = {2023}, author = {Hunter, TL and Sarno, DL and Jumreornvong, O and Esparza, R and Flores, LE and Silver, JK}, title = {The Role of Surgical Prehabilitation During the COVID-19 Pandemic and Beyond.}, journal = {Physical medicine and rehabilitation clinics of North America}, volume = {34}, number = {3}, pages = {523-538}, pmid = {37419529}, issn = {1558-1381}, mesh = {Humans ; Aged ; *Frailty ; Frail Elderly ; Preoperative Exercise ; Ethnicity ; Pandemics ; *COVID-19/epidemiology ; Minority Groups ; }, abstract = {The challenging circumstances of the COVID-19 pandemic caused a regression in baseline health of disadvantaged populations, including individuals with frail syndrome, older age, disability, and racial-ethnic minority status. These patients often have more comorbidities and are associated with increased risk of poor postoperative complications, hospital readmissions, longer length of stay, nonhome discharges, poor patient satisfaction, and mortality. There is critical need to advance frailty assessments to improve preoperative health in older populations. Establishing a gold standard for measuring frailty will improve identification of vulnerable, older patients, and subsequently direct designs for population-specific, multimodal prehabilitation to reduce postoperative morbidity and mortality.}, }
@article {pmid37419534, year = {2023}, author = {Copley, M and Kozminski, B and Gentile, N and Geyer, R and Friedly, J}, title = {Postacute Sequelae of SARS-CoV-2: Musculoskeletal Conditions and Pain.}, journal = {Physical medicine and rehabilitation clinics of North America}, volume = {34}, number = {3}, pages = {585-605}, pmid = {37419534}, issn = {1558-1381}, mesh = {Humans ; SARS-CoV-2 ; *COVID-19/complications ; *Musculoskeletal Diseases/diagnosis/etiology ; Pain ; Post-Acute COVID-19 Syndrome ; }, abstract = {Musculoskeletal and pain sequelae of COVID-19 are common in both the acute infection and patients experiencing longer term symptoms associated with recovery, known as postacute sequelae of COVID-19 (PASC). Patients with PASC may experience multiple manifestations of pain and other concurrent symptoms that complicate their experience of pain. In this review, the authors explore what is currently known about PASC-related pain and its pathophysiology as well as strategies for diagnosis and management.}, }
@article {pmid37419535, year = {2023}, author = {Abbott, Z and Summers, W and Niehaus, W}, title = {Fatigue in Post-Acute Sequelae of Coronavirus Disease 2019.}, journal = {Physical medicine and rehabilitation clinics of North America}, volume = {34}, number = {3}, pages = {607-621}, pmid = {37419535}, issn = {1558-1381}, mesh = {Humans ; *COVID-19 ; Quality of Life ; Fatigue/etiology ; }, abstract = {Fatigue from post-acute sequelae of coronavirus disease 2019 is a complex constellation of symptoms that could be driven by a wide spectrum of underlying etiologies. Despite this, there seems to be hope for treatment plans that focus on addressing possible etiologies and creating a path to improving quality of life and a paced return to activity.}, }
@article {pmid37419537, year = {2023}, author = {Chen, EY and Burton, JM and Johnston, A and Morrow, AK and Yonts, AB and Malone, LA}, title = {Considerations in Children and Adolescents Related to Coronavirus Disease 2019 (COVID-19).}, journal = {Physical medicine and rehabilitation clinics of North America}, volume = {34}, number = {3}, pages = {643-655}, pmid = {37419537}, issn = {1558-1381}, support = {P50 HD103538/HD/NICHD NIH HHS/United States ; }, mesh = {Humans ; Adolescent ; Child ; *COVID-19 ; SARS-CoV-2 ; Quality of Life ; Post-Acute COVID-19 Syndrome ; Life Style ; Disease Progression ; }, abstract = {Pediatric post-acute sequelae of SARS-CoV-2 (PASC) or "long COVID" are a complex multisystemic disease that affects children's physical, social, and mental health. PASC has a variable presentation, time course, and severity and can affect children even with mild or asymptomatic acute COVID-19 symptoms. Screening for PASC in children with a history of SARS-CoV-2 infection is important for early detection and intervention. A multifaceted treatment approach and utilization of multidisciplinary care, if available, are beneficial in managing the complexities of PASC. Lifestyle interventions, physical rehabilitation, and mental health management are important treatment approaches to improve pediatric PASC patients' quality of life.}, }
@article {pmid37419538, year = {2023}, author = {Katz, NB and Hunter, TL and Flores, LE and Silver, JK}, title = {Addressing Rehabilitation Health Care Disparities During the Coronavirus Disease-2019 Pandemic and Beyond.}, journal = {Physical medicine and rehabilitation clinics of North America}, volume = {34}, number = {3}, pages = {657-675}, pmid = {37419538}, issn = {1558-1381}, mesh = {Humans ; Child ; *COVID-19/epidemiology ; Ethnicity ; Healthcare Disparities ; SARS-CoV-2 ; Pandemics ; Minority Groups ; Health Services Accessibility ; }, abstract = {The coronavirus disease-2019 pandemic exposed and expanded upon preexisting health care disparities. Individuals with disabilities and those who identify with racial/ethnic minority groups have been disproportionately adversely impacted. These inequities are likely present in the proportions of individuals impacted by post-acute sequelae of severe acute respiratory syndrome coronavirus 2 infection requiring specialized rehabilitation. Specific populations including, but not limited to pregnant, pediatric, and older individuals, may also necessitate tailored medical care during acute infection and beyond. Telemedicine may reduce the care gap. Further research and clinical guidance are needed to provide equitable, culturally competent, and individualized care to these historically or socially marginalized and underrepresented populations.}, }
@article {pmid37419539, year = {2023}, author = {Estores, IM and Ackerman, P}, title = {Integrative Medicine in Long COVID.}, journal = {Physical medicine and rehabilitation clinics of North America}, volume = {34}, number = {3}, pages = {677-688}, doi = {10.1016/j.pmr.2023.03.006}, pmid = {37419539}, issn = {1558-1381}, mesh = {Humans ; United States ; Post-Acute COVID-19 Syndrome ; *Integrative Medicine/methods ; *COVID-19 ; *Complementary Therapies/methods ; }, abstract = {Physiatry and Integrative Medicine practice approaches the care of patients holistically to achieve recovery and optimal function. The current lack of knowledge on proven treatments for long COVID has resulted in a surge in both demand and use of complementary and integrative health (CIH) treatments. This overview summarizes CIH therapies using the framework of the United States National Center for Complementary and Integrative Health, divided into nutritional, psychological, physical, and combinations of these categories. Representative therapies selected based on the availability of published and ongoing research for post-COVID conditions are described.}, }
@article {pmid37419540, year = {2023}, author = {Barshikar, S and Laguerre, M and Gordon, P and Lopez, M}, title = {Integrated Care Models for Long Coronavirus Disease.}, journal = {Physical medicine and rehabilitation clinics of North America}, volume = {34}, number = {3}, pages = {689-700}, pmid = {37419540}, issn = {1558-1381}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Consensus ; *Physical and Rehabilitation Medicine ; SARS-CoV-2 ; *Delivery of Health Care, Integrated ; Disease Progression ; }, abstract = {Professional or governmental agencies and organizations have developed guidelines to define the problem and evaluate and manage patients with Post-Acute Sequelae of SARS CoV-2 (PASC). Multidisciplinary models largely exist in academic centers and larger cities; however, most care for PASC patients is provided by the primary care providers. The American Academy of Physical Medicine and Rehabilitation has been in the forefront in releasing consensus statements as a part of the long COVID collaborative.}, }
@article {pmid37433988, year = {2023}, author = {Altmann, DM and Whettlock, EM and Liu, S and Arachchillage, DJ and Boyton, RJ}, title = {The immunology of long COVID.}, journal = {Nature reviews. Immunology}, volume = {23}, number = {10}, pages = {618-634}, pmid = {37433988}, issn = {1474-1741}, support = {MR/V036939/1/MRC_/Medical Research Council/United Kingdom ; MR/V036939/1/DH_/Department of Health/United Kingdom ; LT2-027/DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; }, abstract = {Long COVID is the patient-coined term for the disease entity whereby persistent symptoms ensue in a significant proportion of those who have had COVID-19, whether asymptomatic, mild or severe. Estimated numbers vary but the assumption is that, of all those who had COVID-19 globally, at least 10% have long COVID. The disease burden spans from mild symptoms to profound disability, the scale making this a huge, new health-care challenge. Long COVID will likely be stratified into several more or less discrete entities with potentially distinct pathogenic pathways. The evolving symptom list is extensive, multi-organ, multisystem and relapsing-remitting, including fatigue, breathlessness, neurocognitive effects and dysautonomia. A range of radiological abnormalities in the olfactory bulb, brain, heart, lung and other sites have been observed in individuals with long COVID. Some body sites indicate the presence of microclots; these and other blood markers of hypercoagulation implicate a likely role of endothelial activation and clotting abnormalities. Diverse auto-antibody (AAB) specificities have been found, as yet without a clear consensus or correlation with symptom clusters. There is support for a role of persistent SARS-CoV-2 reservoirs and/or an effect of Epstein-Barr virus reactivation, and evidence from immune subset changes for broad immune perturbation. Thus, the current picture is one of convergence towards a map of an immunopathogenic aetiology of long COVID, though as yet with insufficient data for a mechanistic synthesis or to fully inform therapeutic pathways.}, }
@article {pmid37434321, year = {2023}, author = {White, P and Abbey, S and Angus, B and Ball, HA and Buchwald, DS and Burness, C and Carson, AJ and Chalder, T and Clauw, DJ and Coebergh, J and David, AS and Dworetzky, BA and Edwards, MJ and Espay, AJ and Etherington, J and Fink, P and Flottorp, S and Garcin, B and Garner, P and Glasziou, P and Hamilton, W and Henningsen, P and Hoeritzauer, I and Husain, M and Huys, AML and Knoop, H and Kroenke, K and Lehn, A and Levenson, JL and Little, P and Lloyd, A and Madan, I and van der Meer, JWM and Miller, A and Murphy, M and Nazareth, I and Perez, DL and Phillips, W and Reuber, M and Rief, W and Santhouse, A and Serranova, T and Sharpe, M and Stanton, B and Stewart, DE and Stone, J and Tinazzi, M and Wade, DT and Wessely, SC and Wyller, V and Zeman, A}, title = {Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {94}, number = {12}, pages = {1056-1063}, doi = {10.1136/jnnp-2022-330463}, pmid = {37434321}, issn = {1468-330X}, mesh = {Humans ; *Fatigue Syndrome, Chronic/diagnosis/therapy ; Surveys and Questionnaires ; Exercise Therapy ; *Cognitive Behavioral Therapy ; }, abstract = {Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling long-term condition of unknown cause. The National Institute for Health and Care Excellence (NICE) published a guideline in 2021 that highlighted the seriousness of the condition, but also recommended that graded exercise therapy (GET) should not be used and cognitive-behavioural therapy should only be used to manage symptoms and reduce distress, not to aid recovery. This U-turn in recommendations from the previous 2007 guideline is controversial.We suggest that the controversy stems from anomalies in both processing and interpretation of the evidence by the NICE committee. The committee: (1) created a new definition of CFS/ME, which 'downgraded' the certainty of trial evidence; (2) omitted data from standard trial end points used to assess efficacy; (3) discounted trial data when assessing treatment harm in favour of lower quality surveys and qualitative studies; (4) minimised the importance of fatigue as an outcome; (5) did not use accepted practices to synthesise trial evidence adequately using GRADE (Grading of Recommendations, Assessment, Development and Evaluations trial evidence); (6) interpreted GET as mandating fixed increments of change when trials defined it as collaborative, negotiated and symptom dependent; (7) deviated from NICE recommendations of rehabilitation for related conditions, such as chronic primary pain and (8) recommended an energy management approach in the absence of supportive research evidence.We conclude that the dissonance between this and the previous guideline was the result of deviating from usual scientific standards of the NICE process. The consequences of this are that patients may be denied helpful treatments and therefore risk persistent ill health and disability.}, }
@article {pmid37434326, year = {2023}, author = {Krishna, B and Wills, M and Sithole, N}, title = {Long COVID: what is known and what gaps need to be addressed.}, journal = {British medical bulletin}, volume = {147}, number = {1}, pages = {6-19}, pmid = {37434326}, issn = {1471-8391}, support = {G112259/DH_/Department of Health/United Kingdom ; 225023/Z/22/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *COVID-19/complications/epidemiology ; Disease Progression ; Fatigue/etiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Long COVID is a chronic condition that follows after acute COVID-19 and is characterized by a wide range of persistent, cyclic symptoms.<br><br>SOURCES OF DATA: PubMed search for publications featuring 'Long COVID' or 'post-acute sequelae of COVID-19'.<br><br>AREAS OF AGREEMENT: Long COVID occurs frequently post-acute COVID-19, with a majority of people experiencing at least one symptom (such as cough, fatigue, myalgia, anosmia and dyspnoea) 4&#xa0;weeks after infection.<br><br>AREAS OF CONTROVERSY: The specific symptoms and the minimum duration of symptoms required to be defined as Long COVID.<br><br>GROWING POINTS: There is a consistent reduction in Long COVID incidence amongst vaccinated individuals, although the extent of this effect remains unclear.<br><br>There is an urgent need to understand the causes of Long COVID, especially extreme fatigue more than 6&#xa0;months after infection. We must understand who is at risk and whether reinfections similarly risk Long COVID.}, }
@article {pmid37437914, year = {2023}, author = {Kelly, JD and Curteis, T and Rawal, A and Murton, M and Clark, LJ and Jafry, Z and Shah-Gupta, R and Berry, M and Espinueva, A and Chen, L and Abdelghany, M and Sweeney, DA and Quint, JK}, title = {SARS-CoV-2 post-acute sequelae in previously hospitalised patients: systematic literature review and meta-analysis.}, journal = {European respiratory review : an official journal of the European Respiratory Society}, volume = {32}, number = {169}, pages = {}, pmid = {37437914}, issn = {1600-0617}, support = {K23 AI146268/AI/NIAID NIH HHS/United States ; L30 AI126521/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Disease Progression ; Dyspnea ; }, abstract = {BACKGROUND: Many individuals hospitalised with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection experience post-acute sequelae of SARS-CoV-2 infection (PASC), sometimes referred to as "long COVID". Our objective was to conduct a systematic literature review and meta-analysis to identify PASC-associated symptoms in previously hospitalised patients and determine the frequency and temporal nature of PASC.<br><br>METHODS: Searches of MEDLINE, Embase, Cochrane Library (2019-2021), World Health Organization International Clinical Trials Registry Platform and reference lists were performed from November to December 2021. Articles were assessed by two reviewers against eligibility criteria and a risk of bias tool. Symptom data were synthesised by random effects meta-analyses.<br><br>RESULTS: Of 6942 records, 52 studies with at least 100 patients were analysed; &#x223c;70% were Europe-based studies. Most data were from the first wave of the pandemic. PASC symptoms were analysed from 28&#x2005;days after hospital discharge. At 1-4&#x2005;months post-acute SARS-CoV-2 infection, the most frequent individual symptoms were fatigue (29.3% (95% CI 20.1-40.6%)) and dyspnoea (19.6% (95% CI 12.8-28.7%)). Many patients experienced at least one symptom at 4-8&#x2005;months (73.1% (95% CI 44.2-90.3%)) and 8-12&#x2005;months (75.0% (95% CI 56.4-87.4%)).<br><br>CONCLUSIONS: A wide spectrum of persistent PASC-associated symptoms were reported over the 1-year follow-up period in a significant proportion of participants. Further research is needed to better define PASC duration and determine whether factors such as disease severity, vaccination and treatments have an impact on PASC.}, }
@article {pmid37444803, year = {2023}, author = {Estebanez-Pérez, MJ and Martín-Valero, R and Vinolo-Gil, MJ and Pastora-Bernal, JM}, title = {Effectiveness of Digital Physiotherapy Practice Compared to Usual Care in Long COVID Patients: A Systematic Review.}, journal = {Healthcare (Basel, Switzerland)}, volume = {11}, number = {13}, pages = {}, pmid = {37444803}, issn = {2227-9032}, abstract = {Long COVID syndrome has been recognized as a public health problem. Digital physiotherapy practice is an alternative that can better meet the needs of patients. The aim of this review was to synthesize the evidence of digital physiotherapy practice in Long COVID patients. A systematic review was carried out until December 2022. The review was complemented by an assessment of the risk of bias and methodological quality. A narrative synthesis of results was conducted, including subgroup analyses by intervention and clinical outcomes. Six articles, including 540 participants, were selected. Five articles were considered of high enough methodological quality. Parallel-group, single-blind, randomized controlled trials were the most commonly used research design. Tele-supervised home-based exercise training was the most commonly used intervention. Great heterogeneity in clinical outcomes and measurement tools was found. A subgroup analysis showed that digital physiotherapy is effective in improving clinical outcomes. Significant differences in favor of digital interventions over usual care were reported. Nevertheless, discrepancies regarding effectiveness were found. Improvements in clinical outcomes with digital physiotherapy were found to be at least non-inferior to usual care. This review provides new evidence that digital physiotherapy practice is an appropriate intervention for Long COVID patients, despite the inherent limitations of the review. Registration: CRD42022379004.}, }
@article {pmid37445634, year = {2023}, author = {Tsilingiris, D and Vallianou, NG and Karampela, I and Christodoulatos, GS and Papavasileiou, G and Petropoulou, D and Magkos, F and Dalamaga, M}, title = {Laboratory Findings and Biomarkers in Long COVID: What Do We Know So Far? Insights into Epidemiology, Pathogenesis, Therapeutic Perspectives and Challenges.}, journal = {International journal of molecular sciences}, volume = {24}, number = {13}, pages = {}, pmid = {37445634}, issn = {1422-0067}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/diagnosis/epidemiology ; SARS-CoV-2 ; Acute-Phase Proteins ; Biomarkers ; Inflammation ; }, abstract = {Long COVID (LC) encompasses a constellation of long-term symptoms experienced by at least 10% of people after the initial SARS-CoV-2 infection, and so far it has affected about 65 million people. The etiology of LC remains unclear; however, many pathophysiological pathways may be involved, including viral persistence; a chronic, low-grade inflammatory response; immune dysregulation and a defective immune response; the reactivation of latent viruses; autoimmunity; persistent endothelial dysfunction and coagulopathy; gut dysbiosis; hormonal and metabolic dysregulation; mitochondrial dysfunction; and autonomic nervous system dysfunction. There are no specific tests for the diagnosis of LC, and clinical features including laboratory findings and biomarkers may not specifically relate to LC. Therefore, it is of paramount importance to develop and validate biomarkers that can be employed for the prediction, diagnosis and prognosis of LC and its therapeutic response, although this effort may be hampered by challenges pertaining to the non-specific nature of the majority of clinical manifestations in the LC spectrum, small sample sizes of relevant studies and other methodological issues. Promising candidate biomarkers that are found in some patients are markers of systemic inflammation, including acute phase proteins, cytokines and chemokines; biomarkers reflecting SARS-CoV-2 persistence, the reactivation of herpesviruses and immune dysregulation; biomarkers of endotheliopathy, coagulation and fibrinolysis; microbiota alterations; diverse proteins and metabolites; hormonal and metabolic biomarkers; and cerebrospinal fluid biomarkers. At present, there are only two reviews summarizing relevant biomarkers; however, they do not cover the entire umbrella of current biomarkers, their link to etiopathogenetic mechanisms or the diagnostic work-up in a comprehensive manner. Herein, we aim to appraise and synopsize the available evidence on the typical laboratory manifestations and candidate biomarkers of LC, their classification based on pathogenetic mechanisms and the main LC symptomatology in the frame of the epidemiological and clinical aspects of the syndrome and furthermore assess limitations and challenges as well as potential implications in candidate therapeutic interventions.}, }
@article {pmid37446047, year = {2023}, author = {Ailioaie, LM and Ailioaie, C and Litscher, G}, title = {Infection, Dysbiosis and Inflammation Interplay in the COVID Era in Children.}, journal = {International journal of molecular sciences}, volume = {24}, number = {13}, pages = {}, pmid = {37446047}, issn = {1422-0067}, mesh = {*Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Quality of Life ; Systemic Inflammatory Response Syndrome ; Child ; Humans ; Dysbiosis/complications ; Disease Progression ; Inflammation ; Adolescent ; SARS-CoV-2 ; }, abstract = {For over three years, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents has generated repercussions, especially a few weeks after infection, for symptomatic patients who tested positive, for asymptomatic ones, or even just the contacts of an infected person, and evolved from severe forms such as multisystem inflammatory syndrome in children (MIS-C) to multifarious clinical manifestations in long COVID (LC). Referred to under the umbrella term LC, the onset of persistent and highly heterogeneous symptoms such as fatigue, post-exertion malaise, cognitive dysfunction, and others have a major impact on the child's daily quality of life for months. The first aim of this review was to highlight the circumstances of the pathophysiological changes produced by COVID-19 in children and to better understand the hyperinflammation in COVID-19 and how MIS-C, as a life-threatening condition, could have been avoided in some patients. Another goal was to better identify the interplay between infection, dysbiosis, and inflammation at a molecular and cellular level, to better guide scientists, physicians, and pediatricians to advance new lines of medical action to avoid the post-acute sequelae of SARS-CoV-2 infection. The third objective was to identify symptoms and their connection to molecular pathways to recognize LC more easily. The fourth purpose was to connect the triggering factors of LC with related sequelae following acute SARS-CoV-2 injuries to systems and organs, the persistence of the virus, and some of its components in hidden reservoirs, including the gut and the central nervous system. The reactivation of other latent infectious agents in the host's immune environments, the interaction of this virus with the microbiome, immune hyperactivation, and autoimmunity generated by molecular mimicry between viral agents and host proteins, could initiate a targeted and individualized management. New high-tech solutions, molecules, probiotics, and others should be discovered to innovatively solve the interplay between RNA persistent viruses, microbiota, and our immune system.}, }
@article {pmid37449405, year = {2023}, author = {Sonnweber, T and Birgit, S and Weiss, G and Löffler-Ragg, J}, title = {Pulmonary recovery after COVID-19 - a review.}, journal = {Expert review of respiratory medicine}, volume = {17}, number = {6}, pages = {447-457}, doi = {10.1080/17476348.2023.2210837}, pmid = {37449405}, issn = {1747-6356}, mesh = {Adult ; Humans ; *COVID-19/pathology ; SARS-CoV-2 ; Lung/diagnostic imaging/pathology ; }, abstract = {INTRODUCTION: COVID-19 is caused by infection with the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). As the respiratory tract is the primary site of infection and host-mediated inflammatory responses, pathologies and dysfunction of the respiratory system characterize the severe disease and are typically associated with the need for oxygen supply or even ventilator support. In survivors of severe COVID-19, computed tomography follow-up frequently reveals structural lung abnormalities, and one-third of individuals who were hospitalized during acute COVID-19 demonstrate persisting lung abnormalities for at least 12 months after disease onset.<br><br>AREAS COVERED: This review summarizes current evidence on pulmonary recovery after COVID-19, focusing on adult patients who suffered from COVID-19 pneumonia.<br><br>EXPERT OPINION: Severe COVID-19 is associated with a high frequency of persisting lung abnormalities at follow-up. The long-term consequences of these findings remain elusive and urge further evaluation to identify individuals at risk for COVID-19 long-term consequences.}, }
@article {pmid37452676, year = {2023}, author = {Dickey, T and Junqueira, H}, title = {COVID-19 scent dog research highlights and synthesis during the pandemic of December 2019-April 2023.}, journal = {Journal of osteopathic medicine}, volume = {123}, number = {11}, pages = {509-521}, pmid = {37452676}, issn = {2702-3648}, mesh = {Dogs ; Humans ; Animals ; *COVID-19/epidemiology/prevention &amp; control ; SARS-CoV-2 ; Pandemics/prevention &amp; control ; COVID-19 Testing ; Odorants ; Post-Acute COVID-19 Syndrome ; }, abstract = {CONTEXT: This review was undertaken to provide information concerning the advancement of research in the area of COVID-19 screening and testing during the worldwide pandemic from December 2019 through April 2023. In this review, we have examined the safety, effectiveness, and practicality of utilizing trained scent dogs in clinical and public situations for COVID-19 screening. Specifically, results of 29 trained scent dog screening peer-reviewed studies were compared with results of real-time reverse-transcription polymerase chain reaction (RT-PCR) and rapid antigen (RAG) COVID-19 testing methods.<br><br>OBJECTIVES: The review aims to systematically evaluate the strengths and weaknesses of utilizing trained scent dogs in COVID-19 screening.<br><br>METHODS: At the time of submission of our earlier review paper in August 2021, we found only four peer-reviewed COVID-19 scent dog papers: three clinical research studies and one preprint perspective paper. In March and April 2023, the first author conducted new literature searches of the MEDLINE/PubMed, Google Scholar, and Cochrane Library websites. Again, the keyword phrases utilized for the searches included "COVID detection dogs," "COVID scent dogs," and "COVID sniffer dogs." The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 Checklist was followed to ensure that our review adhered to evidence-based guidelines for reporting. Utilizing the results of the reviewed papers, we compiled statistics to intercompare and summarize basic information concerning the scent dogs and their training, the populations of the study participants, the types of sampling methods, the comparative tests utilized, and the effectiveness of the scent dog screening.<br><br>RESULTS: A total of 8,043 references were identified through our literature search. After removal of duplicates, there were 7,843 references that were screened. Of these, 100 were considered for full-text eligibility, 43 were included for qualitative synthesis, and 29 were utilized for quantitative analysis. The most relevant peer-reviewed COVID-19 scent dog references were identified and categorized. Utilizing all of the scent dog results provided for this review, we found that 92.3&#x202f;% of the studies reached sensitivities exceeding 80 and 32.0&#x202f;% of the studies exceeding specificities of 97&#x202f;%. However, 84.0&#x202f;% of the studies reported specificities above 90&#x202f;%. Highlights demonstrating the effectiveness of the scent dogs include: (1) samples of breath, saliva, trachea-bronchial secretions and urine as well as face masks and articles of clothing can be utilized; (2) trained COVID-19 scent dogs can detect presymptomatic and asymptomatic patients; (3) scent dogs can detect new SARS-CoV-2 variants and Long COVID-19; and (4) scent dogs can differentiate SARS-CoV-2 infections from infections with other novel respiratory viruses.<br><br>CONCLUSIONS: The effectiveness of the trained scent dog method is comparable to or in some cases superior to the real-time RT-PCR test and the RAG test. Trained scent dogs can be effectively utilized to provide quick (seconds to minutes), nonintrusive, and accurate results in public settings and thus reduce the spread of the COVID-19 virus or other viruses. Finally, scent dog research as described in this paper can serve to increase the medical community's and public's knowledge and acceptance of medical scent dogs as major contributors to global efforts to fight diseases.}, }
@article {pmid37457901, year = {2023}, author = {Quan, M and Wang, X and Gong, M and Wang, Q and Li, Y and Jia, J}, title = {Post-COVID cognitive dysfunction: current status and research recommendations for high risk population.}, journal = {The Lancet regional health. Western Pacific}, volume = {38}, number = {}, pages = {100836}, pmid = {37457901}, issn = {2666-6065}, abstract = {Post-COVID cognitive dysfunction (PCCD) is a condition in which patients with a history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, usually three months from the onset, exhibit subsequent cognitive impairment in various cognitive domains, and cannot be explained by an alternative diagnosis. While our knowledge of the risk factors and management strategy of PCCD is still incomplete, it is necessary to integrate current epidemiology, diagnosis and treatment evidence, and form consensus criteria to better understand this disease to improve disease management. Identifying the risk factors and vulnerable population of PCCD and providing reliable strategies for effective prevention and management is urgently needed. In this paper, we reviewed epidemiology, diagnostic markers, risk factors and available treatments on the disease, formed research recommendation framework for vulnerable population, under the background of post-COVID period.}, }
@article {pmid37458167, year = {2023}, author = {García-González, L and Martí-Sarrias, A and Puertas, MC and Bayón-Gil, &#xc1; and Resa-Infante, P and Martinez-Picado, J and Navarro, A and Acosta, S}, title = {Understanding the neurological implications of acute and long COVID using brain organoids.}, journal = {Disease models &amp; mechanisms}, volume = {16}, number = {7}, pages = {}, pmid = {37458167}, issn = {1754-8411}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Brain ; Organoids ; }, abstract = {As early as in the acute phase of the coronavirus disease 2019 (COVID-19) pandemic, the research community voiced concerns about the long-term implications of infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), like many other viruses, can trigger chronic disorders that last months or even years. Long COVID, the chronic and persistent disorder lasting more than 12 weeks after the primary infection with SARS-CoV-2, involves a variable number of neurological manifestations, ranging from mild to severe and even fatal. In vitro and in vivo modeling suggest that SARS-CoV-2 infection drives changes within neurons, glia and the brain vasculature. In this Review, we summarize the current understanding of the neuropathology of acute and long COVID, with particular emphasis on the knowledge derived from brain organoid models. We highlight the advantages and main limitations of brain organoids, leveraging their human-derived origin, their similarity in cellular and tissue architecture to human tissues, and their potential to decipher the pathophysiology of long COVID.}, }
@article {pmid37459027, year = {2023}, author = {Sreelakshmi, PR and Tandale, BV and Jadhav, AV and Vaidya, RR and Walimbhe, AM and Jadhav, S}, title = {A scoping review of persistent symptoms after COVID infection at different follow-up periods.}, journal = {Indian journal of public health}, volume = {67}, number = {2}, pages = {292-300}, doi = {10.4103/ijph.ijph_1178_22}, pmid = {37459027}, issn = {0019-557X}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Follow-Up Studies ; India/epidemiology ; }, abstract = {The clinical entity termed as long COVID has gained importance in the recent past. As this phenomenon is still evolving, it is important to document the magnitude of the syndrome during different time periods. This scoping review attempts to synthesize evidence generated from longitudinal studies which have follow-up periods beyond 3 months, up to 12 months. The review also documents the reported prevalence of long COVID for the different regions of the World Health Organization. Longitudinal studies published till March 2022 were systematically searched on PubMed, Google Scholar, and medRxiv. Among the identified 594 studies, 48 were included in this review. Data from selected studies were synthesized. The overall pooled prevalence of long COVID was 49% (40%-58%). The pooled estimates after 3 months, 4-6 months, 7-9 months, and 10-12 months were 44% (32%-57%), 50% (43%-57%), 49% (37%-62%), and 54% (46%-62%), respectively. Eastern Mediterranean Region (EMR) had the highest pooled prevalence of 63% (34%-92%] and the South East Asian Region (SEAR) had the least pooled estimate of 15% (10%-21%). The study brings out the high prevalence of long COVID even after 12 months of follow-up. It also shows the regional differences in the reported prevalence of the syndrome. This review highlights the need for well-planned follow-up studies, especially in developing nations to understand the magnitude and the pattern of long COVID-related symptoms as they emerge.}, }
@article {pmid37460909, year = {2023}, author = {Constantin, T and Pék, T and Horváth, Z and Garan, D and Szabó, AJ}, title = {Multisystem inflammatory syndrome in children (MIS-C): Implications for long COVID.}, journal = {Inflammopharmacology}, volume = {31}, number = {5}, pages = {2221-2236}, pmid = {37460909}, issn = {1568-5608}, mesh = {Adult ; SARS-CoV-2 ; Pandemics ; Child ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Systemic Inflammatory Response Syndrome ; }, abstract = {The COVID-19 pandemic caused by the coronavirus 2 of the severe acute respiratory syndrome (SARS-CoV-2) has significantly affected people around the world, leading to substantial morbidity and mortality. Although the pandemic has affected people of all ages, there is increasing evidence that children are less susceptible to SARS-CoV-2 infection and are more likely to experience milder symptoms than adults. However, children with COVID-19 can still develop serious complications, such as multisystem inflammatory syndrome in children (MIS-C). This narrative review of the literature provides an overview of the epidemiology and immune pathology of SARS-CoV-2 infection and MIS-C in children. The review also examines the genetics of COVID-19 and MIS-C in children, including the genetic factors that can influence the susceptibility and severity of the diseases and their implications for personalized medicine and vaccination strategies. By examining current evidence and insights from the literature, this review aims to contribute to the development of effective prevention and treatment strategies for COVID-19, MIS-C, and long COVID syndromes in children.}, }
@article {pmid37466117, year = {2023}, author = {Abrams, RMC and Zhou, L and Shin, SC}, title = {Persistent post-COVID-19 neuromuscular symptoms.}, journal = {Muscle &amp; nerve}, volume = {68}, number = {4}, pages = {350-355}, doi = {10.1002/mus.27940}, pmid = {37466117}, issn = {1097-4598}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Myalgia/etiology ; Paresthesia/etiology ; Quality of Life ; Fatigue/etiology ; *Primary Dysautonomias ; }, abstract = {Neuromuscular symptoms may develop or persist after resolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Besides residual sensorimotor symptoms associated with acute neuromuscular complications of coronavirus disease-2019 (COVID-19), such as Guillain-Barré syndrome, critical illness neuromyopathy, and rhabdomyolysis, patients may report persistent autonomic symptoms, sensory symptoms, and muscle symptoms in the absence of these acute complications, including palpitations, orthostatic dizziness and intolerance, paresthesia, myalgia, and fatigue. These symptoms may be associated with long COVID, also known as post-COVID-19 conditions or postacute sequelae of SARS-CoV-2 infection, which may significantly impact quality of life. Managing these symptoms represents a challenge for health-care providers. Recent advances have identified small-fiber neuropathy as a potential etiology that may underlie autonomic dysfunction and paresthesia in some long COVID patients. The pathogenic mechanisms underlying myalgia and fatigue remain elusive and need to be investigated. Herein we review the current state of knowledge regarding the evaluation and management of patients with persistent post-COVID-19 neuromuscular symptoms.}, }
@article {pmid37468320, year = {2023}, author = {Maurya, DK and Sharma, D}, title = {Culinary spices and herbs in managing early and long-COVID-19 complications: A comprehensive review.}, journal = {Phytotherapy research : PTR}, volume = {37}, number = {11}, pages = {4908-4931}, doi = {10.1002/ptr.7957}, pmid = {37468320}, issn = {1099-1573}, support = {//Department of Atomic Energy, Govt. of India/ ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Pandemics ; *COVID-19 ; SARS-CoV-2 ; Food ; }, abstract = {Human race is preparing for the upsurge and aftermath of COVID-19 pandemic complicated by novel variants, new waves, variable mortality rate, and post-COVID complications. Despite use of repurposed drugs, symptomatic treatments and licensing of multiple vaccines, the daily number of cases and rate of transmission are significant. Culinary spices and herbs have been historically used in pandemic and non-pandemic times to reduce respiratory viral burden. Specific food items and culinary spices can boost the levels of protective immunity and also offer therapeutic benefits against impervious bugs via well-known as well as less-known but scientifically testable mechanisms. Here, we analyzed the phytochemicals profile of Ayurvedic herbs and inferred from the clinical trials/observational studies to provide a focused and succinct perspective on the relevance of "food-based" traditional decoction to moderate COVID-19 disease and long-COVID via modulation of immunity and reinstatement of homeostasis. We also underscore the druggable targets in pathogenesis of COVID-19 which are relevant to the ongoing clinical trials using spices and herbs. This information will provide a strong scientific rationale for standardization of the traditional herbs-based therapies and adopting the use of herbs, spices, and their formulations for reducing SARS-CoV-2 transmission, long-COVID symptoms, and COVID-19 disease progression.}, }
@article {pmid37470218, year = {2024}, author = {Gallorini, M and Carradori, S and Panieri, E and Sova, M and Saso, L}, title = {Modulation of NRF2: Biological Dualism in Cancer, Targets and Possible Therapeutic Applications.}, journal = {Antioxidants &amp; redox signaling}, volume = {40}, number = {10-12}, pages = {636-662}, doi = {10.1089/ars.2022.0213}, pmid = {37470218}, issn = {1557-7716}, mesh = {Humans ; Kelch-Like ECH-Associated Protein 1/metabolism ; *Neoplasms/drug therapy ; *NF-E2-Related Factor 2/metabolism ; Oxidative Stress/physiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Significance: The nuclear factor erythroid 2-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 (KEAP1) system is a master regulator of redox homeostasis and cell adaptation to a variety of exogenous and endogenous stressors. Accumulating evidence from the last decade indicates that the impairment of the redox balance leads to oxidative stress (OS), a common alteration occurring in many human acute and chronic inflammatory diseases, such as cancer, diabetes, neurodegeneration, and metabolic disorders, and aging. Recent Advances: Being located at the intersection of crucial signaling pathways, NRF2 can influence several cellular functions, which extend beyond the maintenance of the redox balance and include cellular metabolism, proteostasis, mitochondrial function and inflammation. For this reason, there is a growing interest in the pharmacologic manipulation of NRF2 for therapeutic purposes, which requires the accurate knowledge of the cell context and the specific time frame both of NRF2 activation and inhibition. This appears to be an important prerequisite and reflects the extreme complexity of the NRF2 signaling, characterized by an intrinsic dualism that mediates beneficial or detrimental effects even in the same biological process. Critical Issues: Of crucial importance will be to understand whether the NRF2 activity modulation might be exploited to exert beneficial outcomes in patients suffering from pathological conditions, in which the OS and the deregulation of inflammatory processes play a crucial role. Future Directions: In this review, we discuss the dual involvement of NRF2 in aging, neurodegeneration, metabolic diseases, long-COVID-19, and carcinogenesis and we present an overview of the most recent therapeutic modulators of NRF2, particularly emphasizing on those selected for clinical trials. Antioxid. Redox Signal. 40, 636-662.}, }
@article {pmid37474660, year = {2023}, author = {Aiyegbusi, OL and McMullan, C and Hughes, SE and Turner, GM and Subramanian, A and Hotham, R and Davies, EH and Frost, C and Alder, Y and Agyen, L and Buckland, L and Camaradou, J and Chong, A and Jeyes, F and Kumar, S and Matthews, KL and Moore, P and Ormerod, J and Price, G and Saint-Cricq, M and Stanton, D and Walker, A and Haroon, S and Denniston, AK and Calvert, MJ and , }, title = {Considerations for patient and public involvement and engagement in health research.}, journal = {Nature medicine}, volume = {29}, number = {8}, pages = {1922-1929}, pmid = {37474660}, issn = {1546-170X}, support = {MC_PC_20050/MRC_/Medical Research Council/United Kingdom ; MC_PC_21015/MRC_/Medical Research Council/United Kingdom ; MC_PC_19005/MRC_/Medical Research Council/United Kingdom ; MC_PC_21055/MRC_/Medical Research Council/United Kingdom ; MC_PC_21028/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Checklist ; Patient Participation ; Patients ; }, abstract = {Patient and public involvement and engagement (PPIE) can provide valuable insights into the experiences of those living with and affected by a disease or health condition. Inclusive collaboration between patients, the public and researchers can lead to productive relationships, ensuring that health research addresses patient needs. Guidelines are available to support effective PPIE; however, evaluation of the impact of PPIE strategies in health research is limited. In this Review, we evaluate the impact of PPIE in the 'Therapies for Long COVID in non-hospitalised individuals' (TLC) Study, using a combination of group discussions and interviews with patient partners and researchers. We identify areas of good practice and reflect on areas for improvement. Using these insights and the results of a survey, we synthesize two checklists of considerations for PPIE, and we propose that research teams use these checklists to optimize the impact of PPIE for both patients and researchers in future studies.}, }
@article {pmid37475124, year = {2023}, author = {Pandharipande, P and Williams Roberson, S and Harrison, FE and Wilson, JE and Bastarache, JA and Ely, EW}, title = {Mitigating neurological, cognitive, and psychiatric sequelae of COVID-19-related critical illness.}, journal = {The Lancet. Respiratory medicine}, volume = {11}, number = {8}, pages = {726-738}, pmid = {37475124}, issn = {2213-2619}, support = {K23 AG072030/AG/NIA NIH HHS/United States ; R01 GM120484/GM/NIGMS NIH HHS/United States ; RF1 AG075341/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Quality of Life ; Post-Acute COVID-19 Syndrome ; Critical Illness/therapy/psychology ; Cognition ; }, abstract = {Despite advances in the treatment and mitigation of critical illness caused by infection with SARS-CoV-2, millions of survivors have a devastating, post-acute infection syndrome known as long COVID. A large proportion of patients with long COVID have nervous system dysfunction, which is also seen in the distinct but overlapping condition of post-intensive care syndrome (PICS), putting survivors of COVID-19-related critical illness at high risk of long-lasting morbidity affecting multiple organ systems and, as a result, engendering measurable deficits in quality of life and productivity. In this Series paper, we discuss neurological, cognitive, and psychiatric sequelae in patients who have survived critical illness due to COVID-19. We review current knowledge of the epidemiology and pathophysiology of persistent neuropsychological impairments, and outline potential preventive strategies based on safe, evidence-based approaches to the management of pain, agitation, delirium, anticoagulation, and ventilator weaning during critical illness. We highlight priorities for current and future research, including possible therapeutic approaches, and offer considerations for health services to address the escalating health burden of long COVID.}, }
@article {pmid37475125, year = {2023}, author = {Parotto, M and Gyöngyösi, M and Howe, K and Myatra, SN and Ranzani, O and Shankar-Hari, M and Herridge, MS}, title = {Post-acute sequelae of COVID-19: understanding and addressing the burden of multisystem manifestations.}, journal = {The Lancet. Respiratory medicine}, volume = {11}, number = {8}, pages = {739-754}, doi = {10.1016/S2213-2600(23)00239-4}, pmid = {37475125}, issn = {2213-2619}, mesh = {Adult ; Humans ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Critical Illness ; Disease Progression ; }, abstract = {Individuals with SARS-CoV-2 infection can develop symptoms that persist well beyond the acute phase of COVID-19 or emerge after the acute phase, lasting for weeks or months after the initial acute illness. The post-acute sequelae of COVID-19, which include physical, cognitive, and mental health impairments, are known collectively as long COVID or post-COVID-19 condition. The substantial burden of this multisystem condition is felt at individual, health-care system, and socioeconomic levels, on an unprecedented scale. Survivors of COVID-19-related critical illness are at risk of the well known sequelae of acute respiratory distress syndrome, sepsis, and chronic critical illness, and these multidimensional morbidities might be difficult to differentiate from the specific effects of SARS-CoV-2 and COVID-19. We provide an overview of the manifestations of post-COVID-19 condition after critical illness in adults. We explore the effects on various organ systems, describe potential pathophysiological mechanisms, and consider the challenges of providing clinical care and support for survivors of critical illness with multisystem manifestations. Research is needed to reduce the incidence of post-acute sequelae of COVID-19-related critical illness and to optimise therapeutic and rehabilitative care and support for patients.}, }
@article {pmid37475709, year = {2024}, author = {Kerzhner, O and Berla, E and Har-Even, M and Ratmansky, M and Goor-Aryeh, I}, title = {Consistency of inconsistency in long-COVID-19 pain symptoms persistency: A systematic review and meta-analysis.}, journal = {Pain practice : the official journal of World Institute of Pain}, volume = {24}, number = {1}, pages = {120-159}, doi = {10.1111/papr.13277}, pmid = {37475709}, issn = {1533-2500}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Pain/epidemiology ; Chronic Disease ; }, abstract = {INTRODUCTION: Individuals recovering from acute COVID-19 episodes may continue to suffer from various ongoing symptoms, collectively referred to as Long-COVID. Long-term pain symptoms are amongst the most common and clinically significant symptoms to be reported for this post-COVID-19 syndrome.<br><br>OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the proportions of persisting pain symptoms experienced by individuals past the acute phase of COVID-19 and to identify their associated functional consequences and inflammatory correlates.<br><br>METHODS: Two online databases were systematically searched from their inception until 31 March 2022. We searched primary research articles in English, which evaluated individuals after laboratory-confirmed COVID-19 acute phase resolution and specifically reported on pain symptoms and their inflammatory and/or functional outcomes.<br><br>RESULTS: Of the 611 identified articles, 26 were included, used for data extraction, and assessed for their methodological quality and risk of bias by two independent reviewers. Pain symptoms were grouped under one of six major pain domains, serving as our primary co-outcomes. Proportional meta-analyses of pooled logit-transformed values of single proportions were performed using the random-effects-restricted maximum-likelihood model. An estimated 8%, 6%, 18%, 18%, 17%, and 12% of individuals continued to report the persistence of chest, gastrointestinal, musculoskeletal joint, musculoskeletal muscle, general body, and nervous system-related pain symptoms, respectively, for up to one year after acute phase resolution of COVID-19. Considerable levels of heterogeneity were demonstrated across all results. Functional and quality-of-life impairments and some inflammatory biomarker elevations were associated with the persistence of long-COVID pain symptoms.<br><br>CONCLUSION: This study's findings suggest that although not well characterized, long-COVID pain symptoms are being experienced by non-negligible proportions of those recovering from acute COVID-19 episodes, thus highlighting the importance of future research efforts to focus on this aspect.}, }
@article {pmid37476923, year = {2023}, author = {Jiang, L and Li, X and Nie, J and Tang, K and Bhutta, ZA}, title = {A Systematic Review of Persistent Clinical Features After SARS-CoV-2 in the Pediatric Population.}, journal = {Pediatrics}, volume = {152}, number = {2}, pages = {}, pmid = {37476923}, issn = {1098-4275}, mesh = {Adolescent ; Child ; Female ; Humans ; Infant, Newborn ; Infant ; Child, Preschool ; Young Adult ; Adult ; *SARS-CoV-2 ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; Prospective Studies ; }, abstract = {CONTEXT: Long-term health effects after coronavirus disease 2019 (COVID-19) have been increasingly reported but their prevalence and significance in the pediatric population remains uncertain.<br><br>OBJECTIVE: To present the prevalence and characteristics of the long-term clinical features of COVID-19 (long COVID) in the global pediatric population.<br><br>DATA SOURCES: PubMed, Embase, Web of Science, Cochrane Library, WHO COVID-19 database, google scholar, medRxiv, bioRxiv, and multiple national public health databases.<br><br>STUDY SELECTION: Published articles and preprints from December, 2019 to December, 2022 investigating the epidemiology and characteristics of persistent clinical features at least 3 months after COVID-19 in children and adolescents (0-19 years old) were included.<br><br>DATA EXTRACTION: Study characteristics and detailed description of long COVID were extracted into a predefined form.<br><br>RESULTS: Twenty seven cohorts and 4 cross-sectional studies met the inclusion criteria and involved over 15&#x2009;000 pediatric participants. A total of more than 20 persistent symptoms and clinical features were reported among children and adolescents. 16.2% (95% confidence interval 8.5% to 28.6%) of the pediatric participants experienced 1 or more persistent symptom(s) at least 3 months post COVID-19. Female gender might be associated with developing certain long COVID symptoms.<br><br>LIMITATIONS: Included studies presented with great heterogeneity because of significant variations in the definition of "long COVID," follow up duration, and method. There could be nonresponse and other potential bias.<br><br>CONCLUSIONS: Persistent clinical features beyond 3 months among children and adolescents with proven COVID-19 are common and the symptom spectrum is wide. High-quality, prospective studies with proper controls are necessary in the future.}, }
@article {pmid37486510, year = {2024}, author = {Cadore, NA and Lord, VO and Recamonde-Mendoza, M and Kowalski, TW and Vianna, FSL}, title = {Meta-analysis of Transcriptomic Data from Lung Autopsy and Cellular Models of SARS-CoV-2 Infection.}, journal = {Biochemical genetics}, volume = {62}, number = {2}, pages = {892-914}, pmid = {37486510}, issn = {1573-4927}, support = {88887.518451/2020-00//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; 150181/2023-0//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; }, mesh = {Humans ; Autopsy ; Axonemal Dyneins/metabolism ; *COVID-19/genetics/metabolism/pathology ; Gene Expression Profiling ; Lung/metabolism/pathology ; Post-Acute COVID-19 Syndrome ; *Pulmonary Fibrosis/metabolism/pathology ; SARS-CoV-2/metabolism ; Transcriptome ; }, abstract = {Severe COVID-19 is a systemic disorder involving excessive inflammatory response, metabolic dysfunction, multi-organ damage, and several clinical features. Here, we performed a transcriptome meta-analysis investigating genes and molecular mechanisms related to COVID-19 severity and outcomes. First, transcriptomic data of cellular models of SARS-CoV-2 infection were compiled to understand the first response to the infection. Then, transcriptomic data from lung autopsies of patients deceased due to COVID-19 were compiled to analyze altered genes of damaged lung tissue. These analyses were followed by functional enrichment analyses and gene-phenotype association. A biological network was constructed using the disturbed genes in the lung autopsy meta-analysis. Central genes were defined considering closeness and betweenness centrality degrees. A sub-network phenotype-gene interaction analysis was performed. The meta-analysis of cellular models found genes mainly associated with cytokine signaling and other pathogen response pathways. The meta-analysis of lung autopsy tissue found genes associated with coagulopathy, lung fibrosis, multi-organ damage, and long COVID-19. Only genes DNAH9 and FAM216B were found perturbed in both meta-analyses. BLNK, FABP4, GRIA1, ATF3, TREM2, TPPP, TPPP3, FOS, ALB, JUNB, LMNA, ADRB2, PPARG, TNNC1, and EGR1 were identified as central elements among perturbed genes in lung autopsy and were found associated with several clinical features of severe COVID-19. Central elements were suggested as interesting targets to investigate the relation with features of COVID-19 severity, such as coagulopathy, lung fibrosis, and organ damage.}, }
@article {pmid37487957, year = {2024}, author = {Maccarone, MC and Coraci, D and Regazzo, G and Sarandria, N and Scanu, A and Masiero, S}, title = {Evolution of musculoskeletal symptoms in Long COVID syndrome: a lexical analysis to approach requirements for an interdisciplinary management.}, journal = {Joint bone spine}, volume = {91}, number = {1}, pages = {105623}, doi = {10.1016/j.jbspin.2023.105623}, pmid = {37487957}, issn = {1778-7254}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Quality of Life ; SARS-CoV-2 ; Arthralgia ; }, abstract = {Long COVID syndrome is characterized by new, returning, or persistent symptoms after the initial SARS-CoV-2 infection. Among the potential long-term effects of COVID-19, several different musculoskeletal symptoms have been reported in many patients with an important impact on quality of life. The rehabilitation needs of Long COVID patients could be dynamic. However, to date there are no studies that have evaluated how the rehabilitation needs of patients with Long COVID syndrome have changed over time. We conducted a literature review to summarize the most recurrent manifestations of the Long COVID syndrome during the three years of the pandemic, as well as the evolution of musculoskeletal symptoms, through lexical analysis. This approach allowed us to investigate the literature, highlighting how the most used words to describe Long COVID symptoms and outcomes have changed over different periods. Our analysis showed an increasing involvement of the musculoskeletal system in Long COVID symptomatology, as evidenced by the progressive growth of fatigue and weakness symptoms over time. In addition, arthralgia has always been associated with Long COVID. The lexical analysis we conducted emphasizes the need for interdisciplinary management, as the symptoms reported are interconnected. Moreover, this novel approach highlights that the Long COVID syndrome can be interpreted as a dynamic entity requiring up-to-date rehabilitative interventions. The worldwide healthcare systems should be founded on multidisciplinary teams to guarantee early and comprehensive rehabilitation to reduce the socio-sanitary burden associated with this syndrome.}, }
@article {pmid37489358, year = {2023}, author = {Reiss, AB and Greene, C and Dayaramani, C and Rauchman, SH and Stecker, MM and De Leon, J and Pinkhasov, A}, title = {Long COVID, the Brain, Nerves, and Cognitive Function.}, journal = {Neurology international}, volume = {15}, number = {3}, pages = {821-841}, pmid = {37489358}, issn = {2035-8385}, abstract = {SARS-CoV-2, a single-stranded RNA coronavirus, causes an illness known as coronavirus disease 2019 (COVID-19). Long-term complications are an increasing issue in patients who have been infected with COVID-19 and may be a result of viral-associated systemic and central nervous system inflammation or may arise from a virus-induced hypercoagulable state. COVID-19 may incite changes in brain function with a wide range of lingering symptoms. Patients often experience fatigue and may note brain fog, sensorimotor symptoms, and sleep disturbances. Prolonged neurological and neuropsychiatric symptoms are prevalent and can interfere substantially in everyday life, leading to a massive public health concern. The mechanistic pathways by which SARS-CoV-2 infection causes neurological sequelae are an important subject of ongoing research. Inflammation- induced blood-brain barrier permeability or viral neuro-invasion and direct nerve damage may be involved. Though the mechanisms are uncertain, the resulting symptoms have been documented from numerous patient reports and studies. This review examines the constellation and spectrum of nervous system symptoms seen in long COVID and incorporates information on the prevalence of these symptoms, contributing factors, and typical course. Although treatment options are generally lacking, potential therapeutic approaches for alleviating symptoms and improving quality of life are explored.}, }
@article {pmid37490194, year = {2023}, author = {Gonzalez-Fernandez, E and Huang, J}, title = {Cognitive Aspects of COVID-19.}, journal = {Current neurology and neuroscience reports}, volume = {23}, number = {9}, pages = {531-538}, pmid = {37490194}, issn = {1534-6293}, mesh = {Humans ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; *Alzheimer Disease/complications/epidemiology ; *Cognitive Dysfunction/epidemiology/etiology ; Cognition ; }, abstract = {PURPOSE OF REVIEW: Since the beginning of the coronavirus disease 2019 pandemic, many lasting neurological sequelae including cognitive impairment have been recognized as part of the so-called long COVID syndrome. This narrative review summarizes the cognitive aspects of COVID-19.<br><br>RECENT FINDINGS: Studies have consistently identified attention, memory, and executive functions as the cognitive domains most often affected by COVID-19 infection. Many studies have also reported neuroimaging, biofluid, and neurophysiological abnormalities that could potentially reflect the pathophysiological aspects of post-COVID cognitive impairment. While patients suffering from dementia have an elevated risk of COVID-19 infection, increasing evidence has also indicated that COVID-19 infection may increase the risks of Alzheimer's disease, suggesting bidirectional relationships. Post-COVID cognitive dysfunction is a pervasive and multifaceted problem and we are surely in our infancy of understanding. Future elucidation into the long-term effects, mechanisms, and therapies will depend on a concerted effort from clinicians, researchers, patients, and policy-makers alike.}, }
@article {pmid37490975, year = {2023}, author = {Akbari, A and Hadizadeh, A and Islampanah, M and Salavati Nik, E and Atkin, SL and Sahebkar, A}, title = {COVID-19, G protein-coupled receptor, and renin-angiotensin system autoantibodies: Systematic review and meta-analysis.}, journal = {Autoimmunity reviews}, volume = {22}, number = {9}, pages = {103402}, doi = {10.1016/j.autrev.2023.103402}, pmid = {37490975}, issn = {1873-0183}, mesh = {Humans ; *Renin-Angiotensin System ; Autoantibodies ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Receptors, G-Protein-Coupled ; }, abstract = {INTRODUCTION: There are an increasing number of reports of autoantibodies (AAbs) against host proteins such as G-protein coupled receptors (GPCRs) and the renin-angiotensin system (RAS) in COVID-19 disease. Here we have undertaken a systematic review and meta-analysis of all reports of AAbs against GPCRs and RAS in COVID-19 patients including those with long-COVID or post-COVID symptoms.<br><br>METHODS: PubMed, Embase, Web of Science, and Scopus databases were searched to find papers on the role of GPCR and RAS AAbs in the presence and severity of COVID-19 or post- COVID symptoms available through March 21, 2023. Data on the prevalence of AngII or ACE, comparing AngII or ACE between COVID-19 and non-COVID-19, or comparing AngII or ACE between COVID-19 patients with different disease stages were pooled and a meta-analysed using random- or fixed-effects models were undertaken.<br><br>RESULTS: The search yielded a total of 1042 articles, of which 68 studies were included in this systematic review and nine in the meta-analysis. Among 18 studies that investigated GPCRs and COVID-19 severity, 18 distinct AAbs were detected. In addition, nine AAbs were found in case reports that assessed post- COVID, and 19 AAbs were found in other studies that assessed post- COVID or long- COVID symptoms. Meta-analysis revealed a significantly higher number of seropositive ACE2 AAbs in COVID-19 patients (odds ratio&#xa0;=&#xa0;7.766 [2.056, 29.208], p&#xa0;=&#xa0;0.002) and particularly in severe disease (odds ratio&#xa0;=&#xa0;11.49 [1.04, 126.86], p&#xa0;=&#xa0;0.046), whereas AngII-AAbs seropositivity was no different between COVID-19 and control subjects (odds ratio&#xa0;=&#xa0;2.890 [0.546-15.283], p&#xa0;=&#xa0;0.21).<br><br>CONCLUSIONS: GPCR and RAS AAbs may play an important role in COVID-19 severity, the development of disease progression, long-term symptoms COVID and post- COVID symptoms.}, }
@article {pmid37491461, year = {2023}, author = {Su, S and Zhao, Y and Zeng, N and Liu, X and Zheng, Y and Sun, J and Zhong, Y and Wu, S and Ni, S and Gong, Y and Zhang, Z and Gao, N and Yuan, K and Yan, W and Shi, L and Ravindran, AV and Kosten, T and Shi, J and Bao, Y and Lu, L}, title = {Epidemiology, clinical presentation, pathophysiology, and management of long COVID: an update.}, journal = {Molecular psychiatry}, volume = {28}, number = {10}, pages = {4056-4069}, pmid = {37491461}, issn = {1476-5578}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Risk Factors ; }, abstract = {The increasing number of coronavirus disease 2019 (COVID-19) infections have highlighted the long-term consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection called long COVID. Although the concept and definition of long COVID are described differently across countries and institutions, there is general agreement that it affects multiple systems, including the immune, respiratory, cardiovascular, gastrointestinal, neuropsychological, musculoskeletal, and other systems. This review aims to provide a synthesis of published epidemiology, symptoms, and risk factors of long COVID. We also summarize potential pathophysiological mechanisms and biomarkers for precise prevention, early diagnosis, and accurate treatment of long COVID. Furthermore, we suggest evidence-based guidelines for the comprehensive evaluation and management of long COVID, involving treatment, health systems, health finance, public attitudes, and international cooperation, which is proposed to improve the treatment strategies, preventive measures, and public health policy making of long COVID.}, }
@article {pmid37491810, year = {2023}, author = {Zuin, M and Mazzitelli, M and Rigatelli, G and Bilato, C and Cattelan, AM}, title = {Risk of ischemic stroke in patients recovered from COVID-19 infection: A systematic review and meta-analysis.}, journal = {European stroke journal}, volume = {8}, number = {4}, pages = {915-922}, pmid = {37491810}, issn = {2396-9881}, mesh = {Male ; Adult ; Humans ; Female ; *COVID-19/complications ; *Ischemic Stroke/epidemiology ; SARS-CoV-2 ; *Stroke/epidemiology ; }, abstract = {BACKGROUND: Data regarding the risk of ischemic stroke within 1 year after the post-acute phase of COVID-19 remain scant. We assess the risk of ischemic stroke in COVID-19 survivors after SARS-CoV-2 infection by performing a systematic review and meta-analysis of the available data.<br><br>METHODS: Following the PRISMA guidelines, we searched Medline and Scopus to locate all articles published up to February 11, 2023, reporting the risk of incident ischemic stroke in adult patients recovered from COVID-19 infection compared to non-infected patients (controls) defined as those who did not experience the infection over the same follow-up period. Ischemic stroke risk was evaluated using the Mantel-Haenszel random effects models with adjusted Hazard ratio (HR) as the effect measure with 95% confidence interval (CI) while heterogeneity was assessed using Higgins I[2] statistic.<br><br>RESULTS: Overall, 23,559,428 patients (mean age 56, 1&#x2009;year, 54.3% males), of whom 1,595,984 had COVID-19, were included. Over a mean follow-up of 9.2&#x2009;months, ischemic stroke occurred in 4.40 [95% CI: 4.36-4.43] out of 1000 patients survived to COVID-19 compared to 3.25 [95% CI:3.21-3.29] out of 1000 controls. Recovered COVID-19 patients presented a higher risk of ischemic stroke ((HR: 2.06, 95% CI: 1.75-2.41, p&#x2009;<&#x2009;0.0001, I[2]&#x2009;=&#x2009;63.7%) compared to people who did not have COVID-19. COVID-19 patients hospitalized at the time of the infection have a subsequent higher risk of stroke during the follow-up compared to those non-hospitalized.<br><br>CONCLUSIONS: Recovered COVID-19 patients have a higher risk of ischemic stroke compared to subjects from the general population within 9&#x2009;months from the index infection.}, }
@article {pmid37504277, year = {2023}, author = {Zaira, B and Yulianti, T and Levita, J}, title = {Correlation between Hepatocyte Growth Factor (HGF) with D-Dimer and Interleukin-6 as Prognostic Markers of Coagulation and Inflammation in Long COVID-19 Survivors.}, journal = {Current issues in molecular biology}, volume = {45}, number = {7}, pages = {5725-5740}, pmid = {37504277}, issn = {1467-3045}, abstract = {In general, an individual who experiences the symptoms of Severe Acute Respiratory Syndrome Coronavirus 2 or SARS-CoV-2 infection is declared as recovered after 2 weeks. However, approximately 10-20% of these survivors have been reported to encounter long-term health problems, defined as 'long COVID-19', e.g., blood coagulation which leads to stroke with an estimated incidence of 3%, and pulmonary embolism with 5% incidence. At the time of infection, the immune response produces pro-inflammatory cytokines that stimulate stromal cells to produce pro-hepatocyte growth factor (pro-HGF) and eventually is activated into hepatocyte growth factor (HGF), which helps the coagulation process in endothelial and epithelial cells. HGF is a marker that appears as an inflammatory response that leads to coagulation. Currently, there is no information on the effect of SARS-CoV-2 infection on serum HGF concentrations as a marker of the prognosis of coagulation in long COVID-19 survivors. This review discusses the pathophysiology between COVID-19 and HGF, IL-6, and D-dimer.}, }
@article {pmid37504553, year = {2023}, author = {Schnekenberg, L and Sedghi, A and Schoene, D and Pallesen, LP and Barlinn, J and Woitek, F and Linke, A and Puetz, V and Barlinn, K and Mangner, N and Siepmann, T}, title = {Assessment and Therapeutic Modulation of Heart Rate Variability: Potential Implications in Patients with COVID-19.}, journal = {Journal of cardiovascular development and disease}, volume = {10}, number = {7}, pages = {}, pmid = {37504553}, issn = {2308-3425}, abstract = {Cardiac damage has been attributed to SARS-CoV-2-related pathology contributing to increased risk of vascular events. Heart rate variability (HRV) is a parameter of functional neurocardiac integrity with low HRV constituting an independent predictor of cardiovascular mortality. Whether structural cardiac damage translates into neurocardiac dysfunction in patients infected with SARS-CoV-2 remains poorly understood. Hypothesized mechanisms of possible neurocardiac dysfunction in COVID-19 comprise direct systemic neuroinvasion of autonomic control centers, ascending virus propagation along cranial nerves and cardiac autonomic neuropathy. While the relationship between the autonomic nervous system and the cytokine cascade in general has been studied extensively, the interplay between the inflammatory response caused by SARS-CoV-2 and autonomic cardiovascular regulation remains largely unclear. We reviewed the current literature on the potential diagnostic and prognostic value of autonomic neurocardiac function assessment via analysis of HRV including time domain and spectral analysis techniques in patients with COVID-19. Furthermore, we discuss potential therapeutic targets of modulating neurocardiac function in this high-risk population including HRV biofeedback and the impact of long COVID on HRV as well as the approaches of clinical management. These topics might be of particular interest with respect to multimodal pandemic preparedness concepts.}, }
@article {pmid37509643, year = {2023}, author = {Cojocaru, E and Cojocaru, C and Vlad, CE and Eva, L}, title = {Role of the Renin-Angiotensin System in Long COVID's Cardiovascular Injuries.}, journal = {Biomedicines}, volume = {11}, number = {7}, pages = {}, pmid = {37509643}, issn = {2227-9059}, abstract = {The renin-angiotensin system (RAS) is one of the biggest challenges of cardiovascular medicine. The significance of the RAS in the chronic progression of SARS-CoV-2 infection and its consequences is one of the topics that are currently being mostly discussed. SARS-CoV-2 undermines the balance between beneficial and harmful RAS pathways. The level of soluble ACE2 and membrane-bound ACE2 are both upregulated by the endocytosis of the SARS-CoV-2/ACE2 complex and the tumor necrosis factor (TNF)-α-converting enzyme (ADAM17)-induced cleavage. Through the link between RAS and the processes of proliferation, the processes of fibrous remodelling of the myocardium are initiated from the acute phase of the disease, continuing into the long COVID stage. In the long term, RAS dysfunction may cause an impairment of its beneficial effects leading to thromboembolic processes and a reduction in perfusion of target organs. The main aspects of ACE2-a key pathogenic role in COVID-19 as well as the mechanisms of RAS involvement in COVID cardiovascular injuries are studied. Therapeutic directions that can be currently anticipated in relation to the various pathogenic pathways of progression of cardiovascular damage in patients with longCOVID have also been outlined.}, }
@article {pmid37510097, year = {2023}, author = {Hameed, R and Bahadur, AR and Singh, SB and Sher, J and Todua, M and Moradi, LM and Bastakoti, S and Arslan, M and Ajmal, H and Lee, GY and Ayubcha, C and Werner, TJ and Alavi, A and Revheim, ME}, title = {Neurological and Psychiatric Manifestations of Long COVID-19 and Their [[18]F]FDG PET Findings: A Review.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {14}, pages = {}, pmid = {37510097}, issn = {2075-4418}, support = {T32 GM007753/GM/NIGMS NIH HHS/United States ; }, abstract = {For more than two years, lingering sequalae of COVID-19 have been extensively investigated. Approximately 10% of individuals infected by COVID-19 have been found to experience long-term symptoms termed "long COVID-19". The neurological and psychiatric manifestations of long COVID-19 are of particular concern. While pathogenesis remains unclear, emerging imaging studies have begun to better elucidate certain pathological manifestation. Of specific interest is imaging with [[18]F]FDG PET which directly reflects cellular glycolysis often linked to metabolic and inflammatory processes. Seeking to understand the molecular basis of neurological features of long COVID-19, this review encompasses the most recent [[18]F]FDG PET literature in this area.}, }
@article {pmid37510774, year = {2023}, author = {Golomb, BA and Han, JH and Langsjoen, PH and Dinkeloo, E and Zemljic-Harpf, AE}, title = {Statin Use in Relation to COVID-19 and Other Respiratory Infections: Muscle and Other Considerations.}, journal = {Journal of clinical medicine}, volume = {12}, number = {14}, pages = {}, pmid = {37510774}, issn = {2077-0383}, support = {R01 HL063055/HL/NHLBI NIH HHS/United States ; RO1 HL63055-05/NH/NIH HHS/United States ; }, abstract = {Statins have been widely advocated for use in COVID-19 based on large favorable observational associations buttressed by theoretical expected benefits. However, past favorable associations of statins to pre-COVID-19 infection outcomes (also buttressed by theoretical benefits) were unsupported in meta-analysis of RCTs, RR = 1.00. Initial RCTs in COVID-19 appear to follow this trajectory. Healthy-user/tolerator effects and indication bias may explain these disparities. Moreover, cholesterol drops in proportion to infection severity, so less severely affected individuals may be selected for statin use, contributing to apparent favorable statin associations to outcomes. Cholesterol transports fat-soluble antioxidants and immune-protective vitamins. Statins impair mitochondrial function in those most reliant on coenzyme Q10 (a mevalonate pathway product also transported on cholesterol)-i.e., those with existing mitochondrial compromise, whom data suggest bear increased risks from both COVID-19 and from statins. Thus, statin risks of adverse outcomes are amplified in those patients at risk of poor COVID-19 outcomes-i.e., those in whom adjunctive statin therapy may most likely be given. High reported rates of rhabdomyolysis in hospitalized COVID-19 patients underscore the notion that statin-related risks as well as benefits must be considered. Advocacy for statins in COVID-19 should be suspended pending clear evidence of RCT benefits, with careful attention to risk modifiers.}, }
@article {pmid37511753, year = {2023}, author = {Kotzalidis, GD and Ferrara, OM and Margoni, S and Ieritano, V and Restaino, A and Bernardi, E and Fischetti, A and Catinari, A and Monti, L and Chieffo, DPR and Simonetti, A and Sani, G}, title = {Are the Post-COVID-19 Posttraumatic Stress Disorder (PTSD) Symptoms Justified by the Effects of COVID-19 on Brain Structure? A Systematic Review.}, journal = {Journal of personalized medicine}, volume = {13}, number = {7}, pages = {}, pmid = {37511753}, issn = {2075-4426}, abstract = {COVID-19 affects brain function, as deduced by the "brain fog" that is often encountered in COVID-19 patients and some cognitive impairment that is observed in many a patient in the post-COVID-19 period. Approximately one-third of patients, even when they have recovered from the acute somatic disease, continue to show posttraumatic stress disorder (PTSD) symptoms. We hypothesized that the persistent changes induced by COVID-19 on brain structure would overlap with those associated with PTSD. We performed a thorough PubMed search on 25 April 2023 using the following strategy: ((posttraumatic OR PTSD) AND COVID-19 AND (neuroimaging OR voxel OR VBM OR freesurfer OR structural OR ROI OR whole-brain OR hippocamp* OR amygd* OR "deep gray matter" OR "cortical thickness" OR caudate OR striatum OR accumbens OR putamen OR "regions of interest" OR subcortical)) OR (COVID-19 AND brain AND (voxel[ti] OR VBM[ti] OR magnetic[ti] OR resonance[ti] OR imaging[ti] OR neuroimaging[ti] OR neuroimage[ti] OR positron[ti] OR photon*[ti] OR PET[ti] OR SPET[ti] OR SPECT[ti] OR spectroscop*[ti] OR MRS[ti])), which produced 486 records and two additional records from other sources, of which 36 were found to be eligible. Alterations were identified and described and plotted against the ordinary PTSD imaging findings. Common elements were hypometabolism in the insula and caudate nucleus, reduced hippocampal volumes, and subarachnoid hemorrhages, while white matter hyperintensities were widespread in both PTSD and post-COVID-19 brain infection. The comparison partly supported our initial hypothesis. These data may contribute to further investigation of the effects of long COVID on brain structure and function.}, }
@article {pmid37514997, year = {2023}, author = {Miteva, D and Kitanova, M and Batselova, H and Lazova, S and Chervenkov, L and Peshevska-Sekulovska, M and Sekulovski, M and Gulinac, M and Vasilev, GV and Tomov, L and Velikova, T}, title = {The End or a New Era of Development of SARS-CoV-2 Virus: Genetic Variants Responsible for Severe COVID-19 and Clinical Efficacy of the Most Commonly Used Vaccines in Clinical Practice.}, journal = {Vaccines}, volume = {11}, number = {7}, pages = {}, pmid = {37514997}, issn = {2076-393X}, support = {project &#x2116; BG-RRP-2.004-0008-C01//the European Union-NextGenerationEU, through the National Recovery and Resilience Plan of the Republic of Bulgaria,/ ; }, abstract = {Although the chief of the World Health Organization (WHO) has declared the end of the coronavirus disease 2019 (COVID-19) as a global health emergency, the disease is still a global threat. To be able to manage such pandemics in the future, it is necessary to develop proper strategies and opportunities to protect human life. The data on the SARS-CoV-2 virus must be continuously analyzed, and the possibilities of mutation and the emergence of new, more infectious variants must be anticipated, as well as the options of using different preventive and therapeutic techniques. This is because the fast development of severe acute coronavirus 2 syndrome (SARS-CoV-2) variants of concern have posed a significant problem for COVID-19 pandemic control using the presently available vaccinations. This review summarizes data on the SARS-CoV-2 variants that are responsible for severe COVID-19 and the clinical efficacy of the most commonly used vaccines in clinical practice. The consequences after the disease (long COVID or post-COVID conditions) continue to be the subject of studies and research, and affect social and economic life worldwide.}, }
@article {pmid37519257, year = {2023}, author = {Abu-Ismail, L and Taha, MJJ and Abuawwad, MT and Al-Bustanji, Y and Al-Shami, K and Nashwan, A and Yassin, M}, title = {COVID-19 and Anemia: What Do We Know So Far?.}, journal = {Hemoglobin}, volume = {47}, number = {3}, pages = {122-129}, doi = {10.1080/03630269.2023.2236546}, pmid = {37519257}, issn = {1532-432X}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; *Anemia/etiology ; *Thrombosis ; Pandemics ; }, abstract = {On 11 March 2020, the World Health Organization (WHO) declared the novel SARS-CoV-2 virus responsible for causing COVID-19, a global pandemic. The virus primarily targets the respiratory system but can also affect other systems, notably causing hematological pathologies. Anemia, a common hematologic disorder, is characterized by the reduced oxygen-carrying capacity of red blood cells. The existing literature has a suspected link between anemia and severe COVID-19 cases. Researchers are currently investigating the long-term complications of COVID-19 in anemic patients, as these complications may play a crucial role in predicting patient prognosis. Anemic individuals are at a higher risk of experiencing severe COVID-19 infections due to several contributing pathophysiological mechanisms, including thrombotic, hemorrhagic, and autoimmune etiologies. The primary effect of these mechanisms is a decrease in circulating hemoglobin levels, reducing oxygen availability for cells. This exacerbates the hypoxia caused by COVID-19-induced acute respiratory distress syndrome (ARDS). This review offers a comprehensive overview of the evidence regarding the long-term complications of COVID-19 in anemic patients.}, }
@article {pmid37522912, year = {2023}, author = {Costa, UM}, title = {[Occupational Therapy Guideline for the management of sequelae of viral diseases with SARS-CoV-2 : Supplement to the S1 guidelines for the management of post-viral conditions exemplified by post-COVID-19].}, journal = {Wiener klinische Wochenschrift}, volume = {135}, number = {Suppl 4}, pages = {599-618}, pmid = {37522912}, issn = {1613-7671}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; *Occupational Therapy ; Quality of Life ; }, abstract = {Sequelae of viral disease with SARS-CoV-2 impact clients' biopsychosocial health, thus their daily life, with limitations resp. barriers in their occupational capacities and opportunities. Occupational therapists have numerous and, with constantly growing evidence, personalised therapeutic means, measures, and methods in any intervention phase relevant to these according health problems, supporting i. e. coping, occupational adaptation, quality of life and participatory re-shaping of (daily) life. Based on ongoing research findings and practice evidence, this document contains recommendations for occupational therapy intervention for clients with biopsychosocial health conditions post COVID-19.}, }
@article {pmid37525488, year = {2024}, author = {Goldenberg, DL}, title = {Applying Lessons From Rheumatology to Better Understand Long COVID.}, journal = {Arthritis care &amp; research}, volume = {76}, number = {1}, pages = {49-56}, doi = {10.1002/acr.25210}, pmid = {37525488}, issn = {2151-4658}, mesh = {Humans ; *Fatigue Syndrome, Chronic/diagnosis/therapy ; *Fibromyalgia/diagnosis/therapy ; Post-Acute COVID-19 Syndrome ; *Rheumatology ; *COVID-19 ; SARS-CoV-2 ; }, abstract = {Long COVID can sometimes be attributed to organ damage and well-characterized pathophysiology, but more often there is no evidence of organ damage or abnormal biomarkers. This is most evident in patients with mild to moderate initial SARS-CoV-2 infection who were not hospitalized. Their persistent symptoms are strikingly similar to those of fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome, including fatigue, post-exertional malaise, myalgias/arthralgias, and sleep and cognitive disturbances in 50% to 100% of cases. Analogous pathophysiologic pathways in fibromyalgia (FM), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and long COVID include host-microbial interactions in the absence of direct tissue invasion and absence of systemic autoimmunity, with evidence for immune dysregulation as well as autonomic, peripheral, and central nervous system dysfunction. Current treatment of long COVID has been based on multidisciplinary management recommended for FM and ME/CFS and has been formalized and made widely available by funding for nationwide long COVID clinics. Long COVID and its treatment should be distinguished by the presence or absence of organ damage. The acknowledged role of patient engagement in research and open dialogue regarding work and disability noted in long COVID may have meaningful impact on patients with FM and ME/CFS. Hopefully, advances in basic long COVID research will aid in understanding FM and ME/CFS, and rheumatologists should thus be involved in such research and patient care.}, }
@article {pmid37531071, year = {2023}, author = {Shaikh, A and Khan, SD and Baloch, F and Virani, SS and Samad, Z}, title = {The COVID-19 Pandemic and Coronary Heart Disease: the Next Surge.}, journal = {Current atherosclerosis reports}, volume = {25}, number = {9}, pages = {559-569}, pmid = {37531071}, issn = {1534-6242}, support = {U54 TW012089/TW/FIC NIH HHS/United States ; D43 TW011625/TW/FIC NIH HHS/United States ; }, mesh = {Humans ; *COVID-19 ; Pandemics ; Post-Acute COVID-19 Syndrome ; *Coronary Disease/epidemiology ; *Myocardial Infarction/epidemiology ; }, abstract = {PURPOSE OF REVIEW: In this narrative review, we highlight different ways in which the COVID-19 pandemic has impacted coronary heart disease (CHD) burden and how a surge in morbidity and mortality may be expected in the near future. We also discuss potential solutions, and the direction subsequent research and corrective actions should take.<br><br>RECENT FINDINGS: COVID-19 has been implicated in the development and worsening of CHD via acute and chronic mechanisms in the form of plaque rupture, destabilization, and sustenance of a chronic inflammatory state leading to long COVID syndrome and increased rates of myocardial infarction. However, indirectly the pandemic is likely to further escalate the CHD burden through poor health behaviors such as tobacco consumption, reduced physical activity, economic devastation and its associated sequelae, and regular cardiac care interruptions and delays. COVID-19 has increased the total CHD burden and will require extensive resource allocation and multifaceted strategies to curb future rise.}, }
@article {pmid37532784, year = {2023}, author = {Cao, Q and Du, X and Jiang, XY and Tian, Y and Gao, CH and Liu, ZY and Xu, T and Tao, XX and Lei, M and Wang, XQ and Ye, LL and Duan, DD}, title = {Phenome-wide association study and precision medicine of cardiovascular diseases in the post-COVID-19 era.}, journal = {Acta pharmacologica Sinica}, volume = {44}, number = {12}, pages = {2347-2357}, pmid = {37532784}, issn = {1745-7254}, mesh = {Humans ; *Cardiovascular Diseases/genetics ; *COVID-19 ; Phenomics ; Precision Medicine ; SARS-CoV-2/genetics ; Post-Acute COVID-19 Syndrome ; Endothelial Cells ; }, abstract = {SARS-CoV-2 infection causes injuries of not only the lungs but also the heart and endothelial cells in vasculature of multiple organs, and induces systemic inflammation and immune over-reactions, which makes COVID-19 a disease phenome that simultaneously affects multiple systems. Cardiovascular diseases (CVD) are intrinsic risk and causative factors for severe COVID-19 comorbidities and death. The wide-spread infection and reinfection of SARS-CoV-2 variants and the long-COVID may become a new common threat to human health and propose unprecedented impact on the risk factors, pathophysiology, and pharmacology of many diseases including CVD for a long time. COVID-19 has highlighted the urgent demand for precision medicine which needs new knowledge network to innovate disease taxonomy for more precise diagnosis, therapy, and prevention of disease. A deeper understanding of CVD in the setting of COVID-19 phenome requires a paradigm shift from the current phenotypic study that focuses on the virus or individual symptoms to phenomics of COVID-19 that addresses the inter-connectedness of clinical phenotypes, i.e., clinical phenome. Here, we summarize the CVD manifestations in the full clinical spectrum of COVID-19, and the phenome-wide association study of CVD interrelated to COVID-19. We discuss the underlying biology for CVD in the COVID-19 phenome and the concept of precision medicine with new phenomic taxonomy that addresses the overall pathophysiological responses of the body to the SARS-CoV-2 infection. We also briefly discuss the unique taxonomy of disease as Zheng-hou patterns in traditional Chinese medicine, and their potential implications in precision medicine of CVD in the post-COVID-19 era.}, }
@article {pmid37533859, year = {2023}, author = {Vlaicu, SI and Tatomir, A and Cuevas, J and Rus, V and Rus, H}, title = {COVID, complement, and the brain.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1216457}, pmid = {37533859}, issn = {1664-3224}, support = {I01 BX001458/BX/BLRD VA/United States ; R01 NS042011/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; Mice ; Animals ; *Complement Membrane Attack Complex/metabolism ; Endothelial Cells/metabolism ; SARS-CoV-2/metabolism ; *COVID-19 ; Brain/metabolism ; }, abstract = {The brains of COVID-19 patients are affected by the SARS-CoV-2 virus, and these effects may contribute to several COVID-19 sequelae, including cognitive dysfunction (termed "long COVID" by some researchers). Recent advances concerning the role of neuroinflammation and the consequences for brain function are reviewed in this manuscript. Studies have shown that respiratory SARS-CoV-2 infection in mice and humans is associated with selective microglial reactivity in the white matter, persistently impaired hippocampal neurogenesis, a decrease in the number of oligodendrocytes, and myelin loss. Brain MRI studies have revealed a greater reduction in grey matter thickness in the orbitofrontal cortex and parahippocampal gyrus, associated with a greater reduction in global brain size, in those with SARS-CoV-2 and a greater cognitive decline. COVID-19 can directly infect endothelial cells of the brain, potentially promoting clot formation and stroke; complement C3 seems to play a major role in this process. As compared to controls, the brain tissue of patients who died from COVID-19 have shown a significant increase in the extravasation of fibrinogen, indicating leakage in the blood-brain barrier; furthermore, recent studies have documented the presence of IgG, IgM, C1q, C4d, and C5b-9 deposits in the brain tissue of COVID-19 patients. These data suggest an activation of the classical complement pathway and an immune-mediated injury to the endothelial cells. These findings implicate both the classical and alternative complement pathways, and they indicate that C3b and the C5b-9 terminal complement complex (membrane attack complex, MAC) are acting in concert with neuroinflammatory and immune factors to contribute to the neurological sequelae seen in patients with COVID.}, }
@article {pmid37534972, year = {2023}, author = {Yong, SJ and Halim, A and Halim, M and Ming, LC and Goh, KW and Alfaresi, M and AlShehail, BM and Al Fares, MA and Alissa, M and Sulaiman, T and Alsalem, Z and Alwashmi, ASS and Khamis, F and Al Kaabi, NA and Albayat, H and Alsheheri, A and Garout, M and Alsalman, J and Alfaraj, AH and Alhajri, M and Dhama, K and Alburaiky, LM and Alsanad, AH and AlShurbaji, AT and Rabaan, AA}, title = {Experimental drugs in randomized controlled trials for long-COVID: what's in the pipeline? A systematic and critical review.}, journal = {Expert opinion on investigational drugs}, volume = {32}, number = {7}, pages = {655-667}, doi = {10.1080/13543784.2023.2242773}, pmid = {37534972}, issn = {1744-7658}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Randomized Controlled Trials as Topic ; *Fatigue Syndrome, Chronic/drug therapy ; Drugs, Investigational/therapeutic use ; Amides ; Glutarates ; Imidazoles ; }, abstract = {INTRODUCTION: Over three years have passed since the emergence of coronavirus disease 2019 (COVID-19), and yet the treatment for long-COVID, a post-COVID-19 syndrome, remains long overdue. Currently, there is no standardized treatment available for long-COVID, primarily due to the lack of funding for post-acute infection syndromes (PAIS). Nevertheless, the past few years have seen a renewed interest in long-COVID research, with billions of dollars allocated for this purpose. As a result, multiple randomized controlled trials (RCTs) have been funded in the quest to find an effective treatment for long-COVID.<br><br>AREAS COVERED: This systematic review identified and evaluated the potential of current drug treatments for long-COVID, examining both completed and ongoing RCTs.<br><br>EXPERT OPINION: We identified four completed and 22 ongoing RCTs, investigating 22 unique drugs. However, most drugs were deemed to not have high potential for treating long-COVID, according to three pre-specified domains, a testament to the ordeal of treating long-COVID. Given that long-COVID is highly multifaceted with several proposed subtypes, treatments likely need to be tailored accordingly. Currently, rintatolimod appears to have modest to high potential for treating the myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) subtype, LTY-100 and Treamid for pulmonary fibrosis subtype, and metformin for general long-COVID prevention.}, }
@article {pmid37540896, year = {2023}, author = {Nicotra, A and Masserini, F and Calcaterra, F and Di Vito, C and Doneddu, PE and Pomati, S and Nobile-Orazio, E and Riva, A and Mavilio, D and Pantoni, L}, title = {What do we mean by long COVID? A scoping review of the cognitive sequelae of SARS-CoV-2 infection.}, journal = {European journal of neurology}, volume = {30}, number = {12}, pages = {3968-3978}, doi = {10.1111/ene.16027}, pmid = {37540896}, issn = {1468-1331}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; SARS-CoV-2 ; Disease Progression ; Fatigue/etiology ; Cognition ; }, abstract = {BACKGROUND AND PURPOSE: Many COVID-19 patients report persistent symptoms, including cognitive disturbances. We performed a scoping review on this topic, focusing primarily on cognitive manifestations.<br><br>METHODS: Abstracts and full texts of studies published on PubMed (until May 2023) addressing cognitive involvement persisting after SARS-CoV-2 infection were reviewed, focusing on terms used to name the cognitive syndrome, reported symptoms, their onset time and duration, and testing batteries employed. Reported psychiatric symptoms, their assessment tools, and more general manifestations were also extracted.<br><br>RESULTS: Among the 947 records identified, 180 studies were included. Only one third of them used a label to define the syndrome. A minority of studies included patients according to stringent temporal criteria of syndrome onset (34%), whereas more studies reported a minimum required symptom duration (77%). The most frequently reported cognitive symptoms were memory and attentional-executive disturbances, and among psychiatric complaints, the most frequent were anxiety symptoms, depression, and sleep disturbances. Most studies reported fatigue among general symptoms. Thirty-six studies employed cognitive measures: screening tests alone (n&#x2009;=&#x2009;19), full neuropsychological batteries (n&#x2009;=&#x2009;25), or both (n&#x2009;=&#x2009;29); 30 studies performed psychiatric testing. Cognitive deficits were demonstrated in 39% of subjects, the most frequently affected domains being attention/executive functions (90%) and memory (67%).<br><br>CONCLUSIONS: Currently, no agreement exists on a label for post-COVID-19 cognitive syndrome. The time of symptom onset after acute infection and symptom duration are still discussed. Memory and attention-executive complaints and deficits, together with fatigue, anxiety, and depression symptoms, are consistently reported, but the objective evaluation of these symptoms is not standardized.}, }
@article {pmid37545414, year = {2023}, author = {Howe de la Torre, S and Parlatini, V and Cortese, S}, title = {Long-term central nervous system (CNS) consequences of COVID-19 in children.}, journal = {Expert review of neurotherapeutics}, volume = {23}, number = {8}, pages = {703-720}, doi = {10.1080/14737175.2023.2239500}, pmid = {37545414}, issn = {1744-8360}, mesh = {Child ; Humans ; Adolescent ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Central Nervous System ; *Sleep Wake Disorders ; }, abstract = {INTRODUCTION: Neurological/neuropsychiatric symptoms are commonly reported by children/young people with long COVID, especially headache, fatigue, cognitive deficits, anosmia and ageusia, dizziness, mood symptoms, and sleep problems. However, reported prevalence estimates are highly variable due to study heterogeneity and often small sample size; most studies only considered short-term follow-ups; and, apart from mood and sleep problems, neuropsychiatric conditions have received less attention. Considering the potential debilitating effects of neurological/neuropsychiatric conditions, a comprehensive review of the topic is timely, and needed to support clinical recognition as well as to set the direction for future research.<br><br>AREAS COVERED: The authors discuss neurological/neuropsychiatric manifestations of long COVID in pediatric populations, with a focus on prevalence, associated demographic characteristics, and potential pathogenetic mechanisms.<br><br>EXPERT OPINION: Children/young people may develop persistent neurological/neuropsychiatric symptoms following acute SARS-CoV-2 infection, which may affect daily functioning and well-being. Studies in larger samples with longer follow-ups are needed to clarify prevalence and symptom duration; as well as less investigated risk factors, including genetic predisposition, ethnicity, and comorbidities. Controlled studies may help separate infection-related direct effects from pandemic-related psychosocial stressors. Clarifying pathogenetic mechanisms is paramount to develop more targeted and effective treatments; whilst screening programs and psychoeducation may enhance early recognition.}, }
@article {pmid37545721, year = {2023}, author = {Comeau, D and Martin, M and Robichaud, GA and Chamard-Witkowski, L}, title = {Neurological manifestations of post-acute sequelae of COVID-19: which liquid biomarker should we use?.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1233192}, pmid = {37545721}, issn = {1664-2295}, abstract = {Long COVID syndrome, also known as post-acute sequelae of COVID-19 (PASC), is characterized by persistent symptoms lasting 3-12 weeks post SARS-CoV-2 infection. Patients suffering from PASC can display a myriad of symptoms that greatly diminish quality of life, the most frequent being neuropsychiatric. Thus, there is an eminent need to diagnose and treat PASC related neuropsychiatric manifestation (neuro-PASC). Evidence suggests that liquid biomarkers could potentially be used in the diagnosis and monitoring of patients. Undoubtedly, such biomarkers would greatly benefit clinicians in the management of patients; however, it remains unclear if these can be reliably used in this context. In this mini review, we highlight promising liquid (blood and cerebrospinal fluid) biomarkers, namely, neuronal injury biomarkers NfL, GFAP, and tau proteins as well as neuroinflammatory biomarkers IL-6, IL-10, TNF-α, and CPR associated with neuro-PASC and discuss their limitations in clinical applicability.}, }
@article {pmid37548112, year = {2024}, author = {Wild, JM and Gleeson, FV and Svenningsen, S and Grist, JT and Saunders, LC and Collier, GJ and Sharma, M and Tcherner, S and Mozaffaripour, A and Matheson, AM and Parraga, G}, title = {Review of Hyperpolarized Pulmonary Functional [129] Xe MR for Long-COVID.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {59}, number = {4}, pages = {1120-1134}, doi = {10.1002/jmri.28940}, pmid = {37548112}, issn = {1522-2586}, support = {MR/M008894/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *COVID-19/diagnostic imaging/complications ; *Magnetic Resonance Imaging/methods ; *Lung/diagnostic imaging ; *Xenon Isotopes ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Pulmonary Gas Exchange ; }, abstract = {The respiratory consequences of acute COVID-19 infection and related symptoms tend to resolve 4 weeks post-infection. However, for some patients, new, recurrent, or persisting symptoms remain beyond the acute phase and persist for months, post-infection. The symptoms that remain have been referred to as long-COVID. A number of research sites employed [129] Xe magnetic resonance imaging (MRI) during the pandemic and evaluated patients post-infection, months after hospitalization or home-based care as a way to better understand the consequences of infection on [129] Xe MR gas-exchange and ventilation imaging. A systematic review and comprehensive search were employed using MEDLINE via PubMed (April 2023) using the National Library of Medicine's Medical Subject Headings and key words: post-COVID-19, MRI, [129] Xe, long-COVID, COVID pneumonia, and post-acute COVID-19 syndrome. Fifteen peer-reviewed manuscripts were identified including four editorials, a single letter to the editor, one review article, and nine original research manuscripts (2020-2023). MRI and MR spectroscopy results are summarized from these prospective, controlled studies, which involved small sample sizes ranging from 9 to 76 participants. Key findings included: 1) [129] Xe MRI gas-exchange and ventilation abnormalities, 3 months post-COVID-19 infection, and 2) a combination of MRI gas-exchange and ventilation abnormalities alongside persistent symptoms in patients hospitalized and not hospitalized for COVID-19, 1-year post-infection. The persistence of respiratory symptoms and [129] Xe MRI abnormalities in the context of normal or nearly normal pulmonary function test results and chest computed tomography (CT) was consistent. Longitudinal improvements were observed in long-term follow-up of long-COVID patients but mean [129] Xe gas-exchange, ventilation heterogeneity values and symptoms remained abnormal, 1-year post-infection. Pulmonary functional MRI using inhaled hyperpolarized [129] Xe gas has played a role in detecting gas-exchange and ventilation abnormalities providing complementary information that may help develop our understanding of the root causes of long-COVID. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 5.}, }
@article {pmid37549214, year = {2023}, author = {Torres, G and Constantinou, D and Gradidge, P and Patel, D and Patricios, J}, title = {Exercise is the Most Important Medicine for COVID-19.}, journal = {Current sports medicine reports}, volume = {22}, number = {8}, pages = {284-289}, pmid = {37549214}, issn = {1537-8918}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Exercise ; }, abstract = {COVID-19 infection and long COVID affect multiple organ systems, including the respiratory, cardiovascular, renal, digestive, neuroendocrine, musculoskeletal systems, and sensory organs. Exerkines, released during exercise, have a potent crosstalk effect between multiple body systems. This review describes the evidence of how exerkines can mitigate the effects of COVID-19 in each organ system that the virus affects. The evidence presented in the review suggests that exercise should be considered a first-line strategy in the prevention and treatment of COVID-19 infection and long COVID disease.}, }
@article {pmid37554293, year = {2023}, author = {Sousa, RAL and Yehia, A and Abulseoud, OA}, title = {Attenuation of ferroptosis as a potential therapeutic target for neuropsychiatric manifestations of post-COVID syndrome.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1237153}, pmid = {37554293}, issn = {1662-4548}, abstract = {Coronavirus disease-19 (COVID-19), caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), is associated with the persistence of pre-existing or the emergence of new neurological and psychiatric manifestations as a part of a multi-system affection known collectively as "post-COVID syndrome." Cognitive decline is the most prominent feature among these manifestations. The underlying neurobiological mechanisms remain under intense investigation. Ferroptosis is a form of cell death that results from the excessive accumulation of intracellular reactive iron, which mediates lipid peroxidation. The accumulation of lipid-based reactive oxygen species (ROS) and the impairment of glutathione peroxidase 4 (GPX4) activity trigger ferroptosis. The COVID-19-associated cytokine storm enhances the levels of circulating pro-inflammatory cytokines and causes immune-cell hyper-activation that is tightly linked to iron dysregulation. Severe COVID-19 presents with iron overload as one of the main features of its pathogenesis. Iron overload promotes a state of inflammation and immune dysfunction. This is well demonstrated by the strong association between COVID-19 severity and high levels of ferritin, which is a well-known inflammatory and iron overload biomarker. The dysregulation of iron, the high levels of lipid peroxidation biomarkers, and the inactivation of GPX4 in COVID-19 patients make a strong case for ferroptosis as a potential mechanism behind post-COVID neuropsychiatric deficits. Therefore, here we review the characteristics of iron and the attenuation of ferroptosis as a potential therapeutic target for neuropsychiatric post-COVID syndrome.}, }
@article {pmid37561435, year = {2024}, author = {Saltzman, LY and Longo, M and Hansel, TC}, title = {Long-COVID stress symptoms: Mental health, anxiety, depression, or posttraumatic stress.}, journal = {Psychological trauma : theory, research, practice and policy}, volume = {16}, number = {7}, pages = {1169-1178}, doi = {10.1037/tra0001567}, pmid = {37561435}, issn = {1942-969X}, mesh = {Humans ; Anxiety/psychology/etiology ; *Depression/etiology/psychology ; *Post-Acute COVID-19 Syndrome/complications/diagnosis/psychology ; *Stress Disorders, Post-Traumatic/etiology/psychology/therapy ; }, abstract = {OBJECTIVE: Currently, there is no single profile of mental health sequela in long-coronavirus disease (COVID) patients, impacting identification, treatment, and exacerbating stigma among this population. This article highlights the rationale for mental health professionals to consider a summary of mental health symptoms in long-COVID patients.<br><br>METHOD: This article provides an overview of the existing literature regarding the health and mental health impact of long COVID on patients and proposes an approach to conceptualizing mental health symptoms in individuals living with long COVID. This article summarizes the health and mental health impacts of long COVID and underscores the limitations of the current approach to measuring and screening mental health symptoms in long-COVID patients.<br><br>RESULTS: Long-COVID patients have reported new and worsening mental health symptoms; most frequently reported are depression, anxiety, posttraumatic stress disorder (PTSD), and insomnia. The article concludes by proposing the notion of long-COVID stress symptoms and calls for mental health researchers to identify the unique and complex mental health profiles emerging among this patient population.<br><br>CONCLUSIONS: Though some long-COVID patients survived life-threatening illnesses and may, therefore, meet the formal criteria for PTSD, many will present with posttraumatic symptomology that mimics PTSD but may not arise from life-threatening medical trauma. A better understanding of the mental health burden of long-COVID stress symptoms is essential to providing efficient and effective mental health treatment, supporting physicians treating long-COVID patients, and enhancing access to and utilization of medical services. (PsycInfo Database Record (c) 2024 APA, all rights reserved).}, }
@article {pmid37564427, year = {2023}, author = {Soriano-Arandes, A and Brett, A and Buonsenso, D and Emilsson, L and de la Fuente Garcia, I and Gkentzi, D and Helve, O and Kepp, KP and Mossberg, M and Muka, T and Munro, A and Papan, C and Perramon-Malavez, A and Schaltz-Buchholzer, F and Smeesters, PR and Zimmermann, P}, title = {Policies on children and schools during the SARS-CoV-2 pandemic in Western Europe.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1175444}, pmid = {37564427}, issn = {2296-2565}, mesh = {*SARS-CoV-2 ; Europe/epidemiology ; Pandemics ; Child ; *COVID-19/epidemiology/complications ; Humans ; Aged ; Post-Acute COVID-19 Syndrome ; Systemic Inflammatory Response Syndrome ; }, abstract = {During the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mitigation policies for children have been a topic of considerable uncertainty and debate. Although some children have co-morbidities which increase their risk for severe coronavirus disease (COVID-19), and complications such as multisystem inflammatory syndrome and long COVID, most children only get mild COVID-19. On the other hand, consistent evidence shows that mass mitigation measures had enormous adverse impacts on children. A central question can thus be posed: What amount of mitigation should children bear, in response to a disease that is disproportionally affecting older people? In this review, we analyze the distinct child versus adult epidemiology, policies, mitigation trade-offs and outcomes in children in Western Europe. The highly heterogenous European policies applied to children compared to adults did not lead to significant measurable differences in outcomes. Remarkably, the relative epidemiological importance of transmission from school-age children to other age groups remains uncertain, with current evidence suggesting that schools often follow, rather than lead, community transmission. Important learning points for future pandemics are summarized.}, }
@article {pmid37565145, year = {2023}, author = {Lechuga, GC and Morel, CM and De-Simone, SG}, title = {Hematological alterations associated with long COVID-19.}, journal = {Frontiers in physiology}, volume = {14}, number = {}, pages = {1203472}, pmid = {37565145}, issn = {1664-042X}, abstract = {Long COVID-19 is a condition characterized by persistent symptoms lasting beyond the acute phase of COVID-19. Long COVID-19 produces diverse symptomatology and can impact organs and systems, including the hematological system. Several studies have reported, in COVID-19 patients, hematological abnormalities. Most of these alterations are associated with a higher risk of severe disease and poor outcomes. This literature review identified studies reporting hematological parameters in individuals with Long COVID-19. Findings suggest that Long COVID-19 is associated with a range of sustained hematological alterations, including alterations in red blood cells, anemia, lymphopenia, and elevated levels of inflammatory markers such as ferritin, D-dimer, and IL-6. These alterations may contribute to a better understanding of the pathophysiology of Long COVID-19 and its associated symptoms. However, further research is needed to elucidate the underlying mechanisms and potential treatments for these hematological changes in individuals with Long COVID-19.}, }
@article {pmid37567514, year = {2023}, author = {Assaf, S and Stenberg, H and Jesenak, M and Tarasevych, SP and Hanania, NA and Diamant, Z}, title = {Asthma in the era of COVID-19.}, journal = {Respiratory medicine}, volume = {218}, number = {}, pages = {107373}, doi = {10.1016/j.rmed.2023.107373}, pmid = {37567514}, issn = {1532-3064}, mesh = {Humans ; *COVID-19/epidemiology/complications ; SARS-CoV-2 ; *Asthma/diagnosis ; Comorbidity ; Adrenal Cortex Hormones/therapeutic use ; }, abstract = {Since its global invasion in 2019, COVID-19 has affected several aspects of patients' lives and posed a significant impact on the health care system. Several patient populations were identified to be at high risk of contracting SARS-CoV-2 infection and/or developing severe COVID-19-related sequelae. Conversely, anyone who has contracted SARS-CoV-2 is at risk to experience symptoms and signs consistent with post-COVID manifestations. Patients with asthma were initially thought to be at increased risk and severity for SARS-CoV-2 infection. However, accumulating evidence demonstrates that asthma endotypes/phenotypes and comorbidities influence the risk stratification in this population. Furthermore, initial concerns about the potentially increased risk of poor outcomes with asthma treatments such as inhaled corticosteroids and biologics have not been substantiated. In this review, we provide an update on COVID-19 and asthma, including risk of susceptibility, clinical manifestations and course in this population as well as discuss recommendations for management.}, }
@article {pmid37568896, year = {2023}, author = {Vasilev, Y and Blokhin, I and Khoruzhaya, A and Kodenko, M and Kolyshenkov, V and Nanova, O and Shumskaya, Y and Omelyanskaya, O and Vladzymyrskyy, A and Reshetnikov, R}, title = {Routine Brain MRI Findings on the Long-Term Effects of COVID-19: A Scoping Review.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {15}, pages = {}, pmid = {37568896}, issn = {2075-4418}, support = {122112400040-1//Reference datasets for sustainable development of artificial intelligence-based diagnostics to minimize the long-term impact of the COVID-19 pandemic on the health of the Moscow population/ ; }, abstract = {RATIONALE AND OBJECTIVES: Post-COVID condition (PCC) is associated with long-term neuropsychiatric symptoms. Magnetic resonance imaging (MRI) in PCC examines the brain metabolism, connectivity, and morphometry. Such techniques are not easily available in routine practice. We conducted a scoping review to determine what is known about the routine MRI findings in PCC patients.<br><br>MATERIALS AND METHODS: The PubMed database was searched up to 11 April 2023. We included cohort, cross-sectional, and before-after studies in English. Articles with only advanced MRI sequences (DTI, fMRI, VBM, PWI, ASL), preprints, and case reports were excluded. The National Heart, Lung, and Blood Institute and PRISMA Extension tools were used for quality assurance.<br><br>RESULTS: A total of 7 citations out of 167 were included. The total sample size was 451 patients (average age 51 &#xb1; 8 years; 67% female). Five studies followed a single recovering cohort, while two studies compared findings between two severity groups. The MRI findings were perivascular spaces (47%), microbleeds (27%) and white matter lesions (10%). All the studies agreed that PCC manifestations are not associated with specific MRI findings.<br><br>CONCLUSION: The results of the included studies are heterogeneous due to the low agreement on the types of MRI abnormalities in PCC. Our findings indicate that the routine brain MRI protocol has little value for long COVID diagnostics.}, }
@article {pmid37575987, year = {2023}, author = {Sen, S and Khosla, S and Awan, O and Cohen, S and Gollie, JM}, title = {Endothelial dysfunction in autoimmune, pulmonary, and kidney systems, and exercise tolerance following SARS-CoV-2 infection.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1197061}, pmid = {37575987}, issn = {2296-858X}, support = {I21 RX004371/RX/RRD VA/United States ; IK2 RX003423/RX/RRD VA/United States ; }, abstract = {Long COVID is characterized by persistent symptoms beyond 3-months of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) infection that last for at least 2 months and cannot be explained by an alternative diagnosis. Autonomic, immunologic, endothelial, and hypercoagulation are implicated as possible mechanisms of long COVID symptoms. Despite recognition of the public health challenges posed by long COVID, the current understanding of the pathophysiological underpinnings is still evolving. In this narrative review, we explore the long-term effects of SARS-CoV-2 infection on T cell activation such as autoimmune disorders and endothelial cell dysfunction involving vascular impairments within pulmonary and renal architecture. We have described how endothelial dysfunction and vascular abnormalities may underscore findings of exercise intolerance by way of impaired peripheral oxygen extraction in individuals with long COVID.}, }
@article {pmid37577106, year = {2023}, author = {Gawey, B and Yang, J and Bauer, B and Song, J and Wang, XJ}, title = {The use of complementary and alternative medicine for the treatment of gastrointestinal symptoms in Long COVID: a systematic review.}, journal = {Therapeutic advances in chronic disease}, volume = {14}, number = {}, pages = {20406223231190548}, pmid = {37577106}, issn = {2040-6223}, abstract = {BACKGROUND: Most people with coronavirus disease 2019 (COVID-19) experience resolution of symptoms within days to weeks following initial infection. In a subset of individuals, symptoms persist longer than 4 weeks, known as 'Long COVID'. Many gastrointestinal (GI) symptoms persist as part of this syndrome; yet, an approach to treatment remains unclear. Prior studies have demonstrated the efficacy of complementary and alternative medicine (CAM) for the treatment of acute COVID-19 infections, but little data exist regarding the potential use of CAM in the treatment of Long COVID.<br><br>OBJECTIVES: Identify CAM approaches useful in treating the GI symptoms of Long COVID.<br><br>DESIGN: A systematic review of studies reporting on the use of CAM for the treatment of GI symptoms of Long COVID was performed.<br><br>DATA SOURCES AND METHODS: Five electronic databases were searched from January 2019 to November 2022. Studies describing the use of CAM to treat GI symptoms of Long COVID were included and assessed by two independent reviewers. Studies not reporting on GI symptoms or using CAM were excluded. Studies chosen for final review underwent quality and bias assessment using predetermined criteria. The extracted data were synthesized utilizing a framework derived from the National Center of Complementary and Integrative Health categories.<br><br>RESULTS: The initial search yielded 396 articles. After applying the eligibility criteria, a total of four studies (three case reports and one case series) were included for final review. Two studies used nutritional supplements and two studies used traditional Chinese medicine. Reductions in nausea, loss of appetite, diarrhea, acid reflux, epigastric pain, and bloating were reported.<br><br>CONCLUSION: This is the first systematic review to explore the role of CAM in treating GI manifestations of Long COVID. The review identified four studies, all reporting reductions in the GI symptoms of Long COVID. Despite the positive studies included in this review, the overall search yielded few results, all of which were non-experimental. As the post-infectious sequelae of COVID-19 become better recognized in the wake of the pandemic, higher-quality clinical studies are needed.}, }
@article {pmid37581906, year = {2023}, author = {Dalko, K and Kraft, B and Jahn, P and Schildmann, J and Hofstetter, S}, title = {Cocreation of Assistive Technologies for Patients With Long COVID: Qualitative Analysis of a Literature Review on the Challenges of Patient Involvement in Health and Nursing Sciences.}, journal = {Journal of medical Internet research}, volume = {25}, number = {}, pages = {e46297}, pmid = {37581906}, issn = {1438-8871}, mesh = {Humans ; Patient Participation ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Communication ; *Self-Help Devices ; }, abstract = {BACKGROUND: Digital assistive technologies have the potential to address the pressing need for adequate therapy options for patients with long COVID (also known as post-COVID-19 condition) by enabling the implementation of individual and independent rehabilitation programs. However, the involvement of the target patient group is necessary to develop digital devices that are closely aligned to the needs of this particular patient group.<br><br>OBJECTIVE: Participatory design approaches, such as cocreation, may be a solution for achieving usability and user acceptance. However, there are currently no set methods for implementing cocreative development processes incorporating patients. This study addresses the following research questions: what are the tasks and challenges associated with the involvement of patient groups? What lessons can be learned regarding the adequate involvement of patients with long COVID?<br><br>METHODS: First, a literature review based on a 3-stage snowball process was conducted to identify the tasks and challenges emerging in the context of the cocreation of digital assistive devices and services with patient groups. Second, a qualitative analysis was conducted in an attempt to extract relevant findings and criteria from the identified studies. Third, using the method of theory adaptation, this paper presents recommendations for the further development of the existing concepts of cocreation in relation to patients with long COVID.<br><br>RESULTS: The challenges of an active involvement of patients in cocreative development in health care include hierarchical barriers and differences in the levels of specific knowledge between professionals and patients. In the case of long COVID, patients themselves are still inexperienced in dealing with their symptoms and are hardly organized into established groups. This amplifies general hurdles and leads to questions of group identity, power structure, and knowledge creation, which are not sufficiently addressed by the current methods of cocreation.<br><br>CONCLUSIONS: The adaptation of transdisciplinary methods to cocreative development approaches focusing on collaborative and inclusive communication can address the recurring challenges of actively integrating patients with long COVID into development processes.}, }
@article {pmid37586104, year = {2024}, author = {Zheng, C and Chen, XK and Sit, CH and Liang, X and Li, MH and Ma, AC and Wong, SH}, title = {Effect of Physical Exercise-Based Rehabilitation on Long COVID: A Systematic Review and Meta-analysis.}, journal = {Medicine and science in sports and exercise}, volume = {56}, number = {1}, pages = {143-154}, pmid = {37586104}, issn = {1530-0315}, mesh = {Humans ; Female ; *Quality of Life ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Exercise Therapy ; Exercise ; }, abstract = {PURPOSE: The number of persons living with post-coronavirus disease 2019 (COVID-19) conditions or long COVID continues to rise worldwide; however, the etiology and the treatment of long COVID remain nebulous. Therefore, efficient, feasible, and cost-effective therapeutic strategies for a large population with long COVID remain warranted. Physical exercise-based rehabilitation is a promising strategy for long COVID, although its therapeutic effects remain to be determined. This systematic review and meta-analysis aimed to examine the effects of physical exercise-based rehabilitation on long COVID.<br><br>METHODS: The electronic databases Medline, Embase, Global Health (Ovid), CINAHL (EBSCO), Web of Science, WHO Global Research Database on COVID-19, LitCovid, and Google Scholar were searched from their inception to November 2022. The identified articles were independently screened by three reviewers, and a random-effects model was used to determine the mean differences in the meta-analysis.<br><br>RESULTS: Twenty-three studies involving 1579 individuals who had COVID-19 (752 women) were included. Physical exercise-based rehabilitation showed beneficial effects on long COVID-related symptoms characterized by dyspnea, fatigue, and depression, as well as on the 6-min walk test, forced expiratory volume in 1 s/forced vital capacity, and quality of life in people who had COVID-19.<br><br>CONCLUSIONS: Physical exercise-based rehabilitation is a potential therapeutic strategy against long COVID and can be applied as a routine clinical practice in people who have recovered from COVID-19. However, customized physical exercise-based rehabilitation programs and their effects on specific types of long COVID require future large-scale studies.}, }
@article {pmid37586358, year = {2024}, author = {Zhou, S and Zhang, A and Liao, H and Liu, Z and Yang, F}, title = {Pathological Interplay and Clinical Complications between COVID-19 and Cardiovascular Diseases: An Overview in 2023.}, journal = {Cardiology}, volume = {149}, number = {1}, pages = {60-70}, pmid = {37586358}, issn = {1421-9751}, mesh = {Humans ; *COVID-19/complications ; *Cardiovascular Diseases/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Arrhythmias, Cardiac/complications ; Myocytes, Cardiac ; }, abstract = {BACKGROUND: The coronavirus disease 2019 (COVID-19) involves all organs of the body, of which the interaction with cardiovascular diseases is the most important.<br><br>SUMMARY: Numerous studies have reported that COVID-19 patients complicated with cardiovascular comorbidities (hypertension, coronary heart disease, chronic heart failure (HF), cerebrovascular disease) are more likely to develop into critical illness and have higher mortality. Conversely, COVID-19 may also cause myocardial injury in patients through various pathological mechanisms such as direct virus attack on cardiomyocytes, overactivation of immune response, microthrombus formation, which may lead to fatal acute ST-segment elevation myocardial infarction, arrhythmia, acute worsening of chronic HF, etc. In addition, the symptoms of the so-called long-COVID may remain in some patients who survived the acute viral infection. Positional tachycardia has been widely reported, and cardiovascular autonomic disorders are thought to play a pathogenic role.<br><br>KEY MESSAGE: The review summarizes the interaction between COVID-19 and cardiovascular disease in terms of pathological mechanism, clinical features, and sequelae. Therapeutic and rehabilitation programs after COVID-19 infection are compiled and need to be further standardized in the future.}, }
@article {pmid37594232, year = {2023}, author = {Jennings, S and Corrin, T and Waddell, L}, title = {A systematic review of the evidence on the associations and safety of COVID-19 vaccination and post COVID-19 condition.}, journal = {Epidemiology and infection}, volume = {151}, number = {}, pages = {e145}, pmid = {37594232}, issn = {1469-4409}, mesh = {Humans ; *COVID-19/prevention &amp; control ; COVID-19 Vaccines/adverse effects ; Vaccination/adverse effects ; Uncertainty ; }, abstract = {Post COVID-19 condition (PCC) refers to persistent or recurring symptoms (>8 weeks) occurring ≤12 weeks following acute COVID-19. The objective of this systematic review was to assess the evidence on the risk of PCC with vaccination before or after COVID-19 or after developing PCC, and the safety of vaccination among those already experiencing PCC. A search was conducted up to 13 December 2022 and standard systematic review methodology was followed. Thirty-one observational studies were included. There is moderate confidence that two doses of vaccine given pre-infection reduced the odds of PCC (pooled OR (pOR) 0.67, 95% CI 0.60-0.74, I2 = 59.9%), but low confidence that one dose may not reduce the odds (pOR 0.64, 95% CI 0.31#x2013;1.31, I2 = 99.2%), and the evidence is very uncertain about the effect of three doses (pOR 0.45, 95% CI 0.10#x2013;1.99, I2 = 30.9%). One of three studies suggested vaccination shortly after COVID-19 may offer additional protection from developing PCC compared to unvaccinated individuals, but this evidence was very uncertain. For those with PCC, vaccination was not associated with worsening PCC symptoms (10 studies) and appears safe (3 studies), but it is unclear if vaccination may change established PCC symptoms.}, }
@article {pmid37595172, year = {2023}, author = {Riepl, M and Kaiser, J}, title = {Compounding for the Treatment of COVID-19 and Long COVID, Part 4: The Legacy of Chronic COVID.}, journal = {International journal of pharmaceutical compounding}, volume = {27}, number = {4}, pages = {284-293}, pmid = {37595172}, issn = {1092-4221}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {People infected by severe acute respiratory coronavirus 2 (SARS-CoV-2) risk the development of not only acute coronavirus- disease-2019 (COVID-19) - the signs and symptoms of which range from none to severe illness that requires intensive treatment - but also long COVID (i.e., chronic COVID), a cyclical, progressive, multiphasic illness characterized by myriad debilitating conditions that persist long term. In some patients, those sequelae result in psychiatric disorders that can lead to suicide or other forms of self-harm, incidences of which have increased exponentially since before the COVID pandemic. It has been suggested that long COVID develops in an estimated 10% to 35% of people diagnosed as having COVID-19. Because the success of therapy for either form of COVID can be complicated by each patient's pharmacogenomic profile, personal treatment preferences, medical needs, and/or dosing requirements, we have found that in some people so afflicted, manufactured medications are ineffective or intolerable, and that for those individuals, a customized compound often provides relief and promotes recovery. The primary focus of this article is long COVID. The pathogenesis of that disease is reviewed, therapies for the signs and symptoms it engenders are examined, and 2 compounded formulations effective in treating both acute and chronic COVID-19 are presented.}, }
@article {pmid37595965, year = {2023}, author = {Brown, RL and Benjamin, L and Lunn, MP and Bharucha, T and Zandi, MS and Hoskote, C and McNamara, P and Manji, H}, title = {Pathophysiology, diagnosis, and management of neuroinflammation in covid-19.}, journal = {BMJ (Clinical research ed.)}, volume = {382}, number = {}, pages = {e073923}, doi = {10.1136/bmj-2022-073923}, pmid = {37595965}, issn = {1756-1833}, support = {MR/T001313/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; Neuroinflammatory Diseases ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Stroke ; COVID-19 Testing ; }, abstract = {Although neurological complications of SARS-CoV-2 infection are relatively rare, their potential long term morbidity and mortality have a significant impact, given the large numbers of infected patients. Covid-19 is now in the differential diagnosis of a number of common neurological syndromes including encephalopathy, encephalitis, acute demyelinating encephalomyelitis, stroke, and Guillain-Barré syndrome. Physicians should be aware of the pathophysiology underlying these presentations to diagnose and treat patients rapidly and appropriately. Although good evidence has been found for neurovirulence, the neuroinvasive and neurotropic potential of SARS-CoV-2 is limited. The pathophysiology of most complications is immune mediated and vascular, or both. A significant proportion of patients have developed long covid, which can include neuropsychiatric presentations. The mechanisms of long covid remain unclear. The longer term consequences of infection with covid-19 on the brain, particularly in terms of neurodegeneration, will only become apparent with time and long term follow-up.}, }
@article {pmid37599993, year = {2023}, author = {Jegatheeswaran, L and Gokani, SA and Luke, L and Klyvyte, G and Espehana, A and Garden, EM and Tarantino, A and Al Omari, B and Philpott, CM}, title = {Assessment of COVID-19-related olfactory dysfunction and its association with psychological, neuropsychiatric, and cognitive symptoms.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1165329}, pmid = {37599993}, issn = {1662-4548}, abstract = {PURPOSE OF REVIEW: To provide a detailed overview of the assessment of COVID-19-related olfactory dysfunction and its association with psychological, neuropsychiatric, and cognitive symptoms.<br><br>RECENT FINDINGS: COVID-19-related olfactory dysfunction can have a detrimental impact to the quality of life of patients. Prior to the COVID-19 pandemic, olfactory and taste disorders were a common but under-rated, under-researched and under-treated sensory loss. The pandemic has exacerbated the current unmet need for accessing good healthcare for patients living with olfactory disorders and other symptoms secondary to COVID-19. This review thus explores the associations that COVID-19 has with psychological, neuropsychiatric, and cognitive symptoms, and provide a framework and rationale for the assessment of patients presenting with COVID-19 olfactory dysfunction.<br><br>SUMMARY: Acute COVID-19 infection and long COVID is not solely a disease of the respiratory and vascular systems. These two conditions have strong associations with psychological, neuropsychiatric, and cognitive symptoms. A systematic approach with history taking and examination particularly with nasal endoscopy can determine the impact that this has on the patient. Specific olfactory disorder questionnaires can demonstrate the impact on quality of life, while psychophysical testing can objectively assess and monitor olfaction over time. The role of cross-sectional imaging is not yet described for COVID-19-related olfactory dysfunction. Management options are limited to conservative adjunctive measures, with some medical therapies described.}, }
@article {pmid37605390, year = {2024}, author = {Hon, KLE and Leung, AKC and Tan, YW and Leung, KKY and Chan, PKS}, title = {SARS-CoV-2 Encephalitis versus Influenza Encephalitis: More Similarities than Differences.}, journal = {Current pediatric reviews}, volume = {20}, number = {4}, pages = {525-531}, pmid = {37605390}, issn = {1875-6336}, mesh = {Humans ; *Influenza, Human/complications/diagnosis/drug therapy ; *COVID-19/complications/diagnosis ; *Encephalitis, Viral/drug therapy/diagnosis ; *SARS-CoV-2 ; Child ; Antiviral Agents/therapeutic use ; }, abstract = {BACKGROUND: From time to time, physicians face challenging diagnostic and therapeutic issues concerning the acute management of children with viral encephalitis.<br><br>OBJECTIVES: The aim of this article is to provide an updated narrative review on the similarities and differences between SARS-CoV-2 and influenza encephalitis.<br><br>METHODS: A PubMed search was performed with the function "Clinical Queries" using the key terms "SARS-CoV-2" OR "Influenza" AND "Encephalitis". The search strategy included metaanalyses, clinical trials, randomized controlled trials, reviews and observational studies. The search was restricted to the English literature and pediatric population. This article compares similarities and contrasts between SARS-CoV-2 and influenza-associated encephalitis.<br><br>RESULTS: Encephalitis is an uncommon manifestation of both influenza and SARS-CoV-2. Both viruses are associated with fever and respiratory symptoms. However, SARS-CoV-2 patients may only have mild symptoms or be asymptomatic as silent carriers, rendering the disease spread difficult to control. Influenza patients usually have more severe symptomatology and are often bed bound for several days limiting its spread. Influenza is associated with seasonal and annual outbreaks, whereas SARS-CoV-2 has become endemic. Complications of encephalitis are rare in both viral infections but, when present, may carry serious morbidity and mortality. Many long-term sequelae of COVID- 19 infections (long COVID-19) have been described but not with influenza infections. Mortality associated with encephalitis appears higher with influenza than with SARS-CoV-2. Prophylaxis by immunization is available for both influenza and SARS-CoV-2. Specific efficacious antivirals are also available with oseltamivir for influenza and nirmatrelvir/ritonavir for SARS-CoV-2. Steroids are indicated with more severe SARS-CoV-2 but their role is not distinct in influenza disease.<br><br>CONCLUSION: Encephalitis is a rare complication of influenza and SARS-CoV-2 infections. Both carry significant morbidity and mortality. Efficacious vaccines for prophylaxis and antivirals for treatment are available for both viruses.}, }
@article {pmid37623461, year = {2023}, author = {Menotti, S and Giampietro, A and Raia, S and Veleno, M and Angelini, F and Tartaglione, T and Gaudino, S and Doglietto, F and De Marinis, L and Pontecorvi, A and Bianchi, A and Chiloiro, S}, title = {Unveiling the Etiopathogenic Spectrum of Hypophysitis: A Narrative Review.}, journal = {Journal of personalized medicine}, volume = {13}, number = {8}, pages = {}, pmid = {37623461}, issn = {2075-4426}, abstract = {Hypophysitis, a rare inflammatory disorder of the pituitary gland, has seen an uptick in reported cases in recent years. Our objective is to summarize the most recent research on the etiopathogenesis, molecular mechanisms, and genetics of both primary and secondary hypophysitis. Primary autoimmune hypophysitis (PAH): During the acute phase of the disease, the pituitary gland in enlarged due to the infiltration of T and B lymphocytes. The chronic phase is characterized by progressive and irreversible pituitary atrophy. APA may play a role in the management, diagnosis, and prognosis of PAH. Specific autoantibodies such as anti-GH, anti-PIT-1, and anti-T-PIT have been found in patients with hypophysitis and hypopituitarism. A recent study suggested that a mechanism of escaping clonal deletion and mounting an immune response against self antigens can explain the unusual nature of the immune response observed in PAH patients. A cytokine array shows the presence of gamma-interferon and interleukin-17. Patients carrying mutations in the PIT1 or PROP1 genes may present PAH. Individuals carrying the HLA DQ8 haplotype are four times more likely to develop PAH. Immune checkpoint inhibitors induce hypophysitis (IIHs): IIHs is an increasingly frequent toxicity of in patients on treatment with inhibitors targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death-1 (PD-1). ICIs inhibit the CTLA-4 pathway, leading to overactivation of T lymphocytes. The binding of PD-1/PD-L1 suppresses the activity of T cells, promotes the conversion of T-helpers into T-regulatory cells, and activates pro-survival signaling pathways in cancer cells. Cytokines play a crucial role in IIHs. B-cell infiltration has been observed in IIHs, suggesting that antibody-mediated pituitary injury may contribute. Genetic polymorphisms of CTLA-4 and PD-1 genes can increase the risk of IIHs. HLA alleles may also be involved in the onset of IIHs; this HLA association presents a possible alternative mechanistic hypothesis. IIHs may also be linked to a paraneoplastic syndrome triggered by ectopic expression of pituitary specific antigens. SARS-CoV-2-related hypophysitis: Recently, the literature has reported occurrences of hypophysitis associated with the SARS-CoV-2 virus; long COVID-19 may also present as infundibulo-neuro-hypophysitis. The virus enters the central nervous system because of its distinct interaction with angiotensin-converting enzyme receptors via spike proteins binding the capillary endothelium, and it directly damages the pituitary cells. The effect of SARS-CoV-2 can occur indirectly through inflammation and the release of cytokines. The exact mechanism remains ambiguous. The available data on endocrine complications associated with the SARS-CoV-2 vaccine are scant. Nonetheless, isolated cases of hypophysitis have been documented. Treatment of hypophysitis: Glucocorticoids are the cornerstone in managing primary hypophysitis, given their targeted action on inflammation. A better understanding of the etiopathogenesis and molecular mechanism of hypophysitis can lead to more effective and personalized treatment strategies.}, }
@article {pmid37626710, year = {2023}, author = {Meléndez-Oliva, E and Martínez-Pozas, O and Cuenca-Zaldívar, JN and Villafañe, JH and Jiménez-Ortega, L and Sánchez-Romero, EA}, title = {Efficacy of Pulmonary Rehabilitation in Post-COVID-19: A Systematic Review and Meta-Analysis.}, journal = {Biomedicines}, volume = {11}, number = {8}, pages = {}, pmid = {37626710}, issn = {2227-9059}, abstract = {BACKGROUND: This systematic review and meta-analysis examines how pulmonary rehabilitation impacts in patients suffering from subacute and long COVID-19 infections, gauging enhancements in of dyspnea, physical function, quality of life, psychological state (anxiety and depression), and fatigue.<br><br>METHODS: Three electronic databases (PubMed, Web of Science, Cochrane Library) were systematically searched for full-text articles published from inception to January 2023. Randomized, quasi-experimental, and observational studies were included, with adults diagnosed with subacute or long COVID-19 who received pulmonary rehabilitation as intervention. Outcomes related to dyspnea, physical function, quality of life, fatigue, and psychological status were included. Risk of bias was assessed with Cochrane Risk of Bias Tool for Randomized Controlled Trials and Risk of bias in non-randomized studies of intervention. The review was registered before starting in PROSPERO (CRD: 42022373075).<br><br>RESULTS: Thirty-four studies were included, involving 1970 patients with subacute and long COVID-19. The meta-analysis demonstrated moderate to large effects on dyspnea, physical function, quality of life, and depressive symptoms compared to usual care intervention. No significant differences were found in fatigue compared to usual care, nor in anxiety levels after pulmonary rehabilitation intervention.<br><br>CONCLUSIONS: Pulmonary rehabilitation has the potential to improve health outcomes in patients with subacute and long COVID-19. However, due to the high risk of bias of included studies, conclusions should be taken with caution.}, }
@article {pmid37626735, year = {2023}, author = {Santoro, L and Zaccone, V and Falsetti, L and Ruggieri, V and Danese, M and Miro, C and Di Giorgio, A and Nesci, A and D'Alessandro, A and Moroncini, G and Santoliquido, A}, title = {Role of Endothelium in Cardiovascular Sequelae of Long COVID.}, journal = {Biomedicines}, volume = {11}, number = {8}, pages = {}, pmid = {37626735}, issn = {2227-9059}, abstract = {The global action against coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 infection, shed light on endothelial dysfunction. Although SARS-CoV-2 primarily affects the pulmonary system, multiple studies have documented pan-vascular involvement in COVID-19. The virus is able to penetrate the endothelial barrier, damaging it directly or indirectly and causing endotheliitis and multi-organ injury. Several mechanisms cooperate to development of endothelial dysfunction, including endothelial cell injury and pyroptosis, hyperinflammation and cytokine storm syndrome, oxidative stress and reduced nitric oxide bioavailability, glycocalyx disruption, hypercoagulability, and thrombosis. After acute-phase infection, some patients reported signs and symptoms of a systemic disorder known as long COVID, in which a broad range of cardiovascular (CV) disorders emerged. To date, the exact pathophysiology of long COVID remains unclear: in addition to the persistence of acute-phase infection mechanisms, specific pathways of CV damage have been postulated, such as persistent viral reservoirs in the heart or an autoimmune response to cardiac antigens through molecular mimicry. The aim of this review is to provide an overview of the main molecular patterns of enduring endothelial activation following SARS-CoV-2 infection and to offer the latest summary of CV complications in long COVID.}, }
@article {pmid37626764, year = {2023}, author = {Kaszuba, M and Madej, N and Pilinski, R and Sliwka, A}, title = {Post-COVID-19 Symptoms in Adults with Asthma-Systematic Review.}, journal = {Biomedicines}, volume = {11}, number = {8}, pages = {}, pmid = {37626764}, issn = {2227-9059}, abstract = {BACKGROUND: Research on the longer-term sequelae of COVID-19 in patients with asthma is limited.<br><br>OBJECTIVE: To assess the frequency and severity of long-term symptoms of COVID-19 in the population of asthma patients.<br><br>METHODS: A systematic review of the published literature was conducted in accordance with the recommendations of the PRISMA statement. EMBASE, MEDLINE/PubMed, Web of Science, CINAHL, and Scopus Scholar were searched for terms related to asthma and post or long COVID-19, and for systematic reviews related to specific questions within our review, up to June 2022.<br><br>RESULTS: Data from 9 references publications included in the review were extracted. A total of 1466 adult asthmatic patients with COVID-19 infection were described in all the publications mentioned above. Of the long-term symptoms reported after COVID-19, patients indicated: lower respiratory symptoms, fatigue, cognitive symptoms, psychological problems, and other such as skin rashes, gastrointestinal disorders, tachycardia, palpitations, ocular disorders, ageusia/hypogeusia, anosmia/hyposmia, and poor sleep quality. These symptoms in similar intensity were observed in the comparison groups without a diagnosis of asthma.<br><br>CONCLUSIONS: The published data neither confirm nor deny that long-term COVID-19 symptoms in patients with asthma diagnosis are different in strength and frequency from patients without asthma diagnosis. To indicate associations between asthma and COVID-19 infection and severity, as well as the frequency of long-term symptoms of COVID-19, more longitudinal research is needed in chronic asthma patients with different phenotypes, intensity of treatment, and degree of asthma control.}, }
@article {pmid37626992, year = {2023}, author = {Shabani, Z and Liu, J and Su, H}, title = {Vascular Dysfunctions Contribute to the Long-Term Cognitive Deficits Following COVID-19.}, journal = {Biology}, volume = {12}, number = {8}, pages = {}, pmid = {37626992}, issn = {2079-7737}, support = {R01 HL122774/NH/NIH HHS/United States ; R01 NS027713/NS/NINDS NIH HHS/United States ; NS112819/NH/NIH HHS/United States ; IK6 BX004600/BX/BLRD VA/United States ; R01 HL122774/HL/NHLBI NIH HHS/United States ; I01 BX003335/BX/BLRD VA/United States ; NS027713/NH/NIH HHS/United States ; R01 NS102886/NS/NINDS NIH HHS/United States ; R01 NS112819/NS/NINDS NIH HHS/United States ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded RNA virus and a member of the corona virus family, primarily affecting the upper respiratory system and the lungs. Like many other respiratory viruses, SARS-CoV-2 can spread to other organ systems. Apart from causing diarrhea, another very common but debilitating complication caused by SARS-CoV-2 is neurological symptoms and cognitive difficulties, which occur in up to two thirds of hospitalized COVID-19 patients and range from shortness of concentration and overall declined cognitive speed to executive or memory function impairment. Neuro-cognitive dysfunction and "brain fog" are frequently present in COVID-19 cases, which can last several months after the infection, leading to disruption of daily life. Cumulative evidence suggests that SARS-CoV-2 affects vasculature in the extra-pulmonary systems directly or indirectly, leading to impairment of endothelial function and even multi-organ damage. The post COVID-19 long-lasting neurocognitive impairments have not been studied fully and their underlying mechanism remains elusive. In this review, we summarize the current understanding of the effects of COVID-19 on vascular dysfunction and how vascular dysfunction leads to cognitive impairment in patients.}, }
@article {pmid37628475, year = {2023}, author = {Sick, J and König, D}, title = {Exercise Training in Non-Hospitalized Patients with Post-COVID-19 Syndrome-A Narrative Review.}, journal = {Healthcare (Basel, Switzerland)}, volume = {11}, number = {16}, pages = {}, pmid = {37628475}, issn = {2227-9032}, abstract = {Post COVID-19 Syndrome (PCS) is the persistence of symptoms after an infection with SARS-CoV-2 in both hospitalized and non-hospitalized COVID-19 survivors. Exercise was proposed as a rehabilitation measure for PCS and early studies focused on patients post-hospital discharge. The objective of this review is to summarize the results of trials investigating exercise interventions in non-hospitalized subjects with PCS and propose practical recommendations concerning safe exercise programming. A literature search in the databases MEDLINE and Scopus was conducted until 26 July 2023 and resulted in seven studies that met the criteria. In total, 935 subjects with PCS were investigated. Exercise enhanced aerobic fitness and physical function and relieved symptoms of dyspnea, fatigue and depression. Participants reported lower Post COVID-19 Functional Status scores post-intervention. The exercise programs were well tolerated with no adverse events. To ensure safety, medical examinations should take place in advance and there should be a regular evaluation of the individual responses to the training. Caution is advised when working with patients suffering from post-exertional malaise or diagnosed with myalgic encephalomyelitis/chronic fatigue syndrome. There is a growing need for additional randomized controlled trials to investigate the effectiveness and safety of exercise in individuals with PCS.}, }
@article {pmid37628830, year = {2023}, author = {Sfera, A and Rahman, L and Zapata-Martín Del Campo, CM and Kozlakidis, Z}, title = {Long COVID as a Tauopathy: Of "Brain Fog" and "Fusogen Storms".}, journal = {International journal of molecular sciences}, volume = {24}, number = {16}, pages = {}, pmid = {37628830}, issn = {1422-0067}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; *Tauopathies ; Brain ; }, abstract = {Long COVID, also called post-acute sequelae of SARS-CoV-2, is characterized by a multitude of lingering symptoms, including impaired cognition, that can last for many months. This symptom, often called "brain fog", affects the life quality of numerous individuals, increasing medical complications as well as healthcare expenditures. The etiopathogenesis of SARS-CoV-2-induced cognitive deficit is unclear, but the most likely cause is chronic inflammation maintained by a viral remnant thriving in select body reservoirs. These viral sanctuaries are likely comprised of fused, senescent cells, including microglia and astrocytes, that the pathogen can convert into neurotoxic phenotypes. Moreover, as the enteric nervous system contains neurons and glia, the virus likely lingers in the gastrointestinal tract as well, accounting for the intestinal symptoms of long COVID. Fusogens are proteins that can overcome the repulsive forces between cell membranes, allowing the virus to coalesce with host cells and enter the cytoplasm. In the intracellular compartment, the pathogen hijacks the actin cytoskeleton, fusing host cells with each other and engendering pathological syncytia. Cell-cell fusion enables the virus to infect the healthy neighboring cells. We surmise that syncytia formation drives cognitive impairment by facilitating the "seeding" of hyperphosphorylated Tau, documented in COVID-19. In our previous work, we hypothesized that the SARS-CoV-2 virus induces premature endothelial senescence, increasing the permeability of the intestinal and blood-brain barrier. This enables the migration of gastrointestinal tract microbes and/or their components into the host circulation, eventually reaching the brain where they may induce cognitive dysfunction. For example, translocated lipopolysaccharides or microbial DNA can induce Tau hyperphosphorylation, likely accounting for memory problems. In this perspective article, we examine the pathogenetic mechanisms and potential biomarkers of long COVID, including microbial cell-free DNA, interleukin 22, and phosphorylated Tau, as well as the beneficial effect of transcutaneous vagal nerve stimulation.}, }
@article {pmid37629143, year = {2023}, author = {Boufidou, F and Medić, S and Lampropoulou, V and Siafakas, N and Tsakris, A and Anastassopoulou, C}, title = {SARS-CoV-2 Reinfections and Long COVID in the Post-Omicron Phase of the Pandemic.}, journal = {International journal of molecular sciences}, volume = {24}, number = {16}, pages = {}, pmid = {37629143}, issn = {1422-0067}, mesh = {Adolescent ; Child ; Aged ; Humans ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *COVID-19/epidemiology ; Reinfection ; Pandemics ; }, abstract = {We are reviewing the current state of knowledge on the virological and immunological correlates of long COVID, focusing on recent evidence for the possible association between the increasing number of SARS-CoV-2 reinfections and the parallel pandemic of long COVID. The severity of reinfections largely depends on the severity of the initial episode; in turn, this is determined both by a combination of genetic factors, particularly related to the innate immune response, and by the pathogenicity of the specific variant, especially its ability to infect and induce syncytia formation at the lower respiratory tract. The cumulative risk of long COVID as well as of various cardiac, pulmonary, or neurological complications increases proportionally to the number of SARS-CoV-2 infections, primarily in the elderly. Therefore, the number of long COVID cases is expected to remain high in the future. Reinfections apparently increase the likelihood of long COVID, but less so if they are mild or asymptomatic as in children and adolescents. Strategies to prevent SARS-CoV-2 reinfections are urgently needed, primarily among older adults who have a higher burden of comorbidities. Follow-up studies using an established case definition and precise diagnostic criteria of long COVID in people with or without reinfection may further elucidate the contribution of SARS-CoV-2 reinfections to the long COVID burden. Although accumulating evidence supports vaccination, both before and after the SARS-CoV-2 infection, as a preventive strategy to reduce the risk of long COVID, more robust comparative observational studies, including randomized trials, are needed to provide conclusive evidence of the effectiveness of vaccination in preventing or mitigating long COVID in all age groups. Thankfully, answers not only on the prevention, but also on treatment options and rates of recovery from long COVID are gradually starting to emerge.}, }
@article {pmid37631968, year = {2023}, author = {Hawkings, MJ and Vaselli, NM and Charalampopoulos, D and Brierley, L and Elliot, AJ and Buchan, I and Hungerford, D}, title = {A Systematic Review of the Prevalence of Persistent Gastrointestinal Symptoms and Incidence of New Gastrointestinal Illness after Acute SARS-CoV-2 Infection.}, journal = {Viruses}, volume = {15}, number = {8}, pages = {}, pmid = {37631968}, issn = {1999-4915}, support = {PDF-2018-11-ST2-006/DH_/Department of Health/United Kingdom ; NIHR-200910/DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; Incidence ; *COVID-19/complications/epidemiology ; Prevalence ; SARS-CoV-2 ; *Inflammatory Bowel Diseases ; }, abstract = {It is known that SARS-CoV-2 infection can result in gastrointestinal symptoms. For some, these symptoms may persist beyond acute infection, in what is known as 'post-COVID syndrome'. We conducted a systematic review to examine the prevalence of persistent gastrointestinal symptoms and the incidence of new gastrointestinal illnesses following acute SARS-CoV-2 infection. We searched the scientific literature using MedLine, SCOPUS, Europe PubMed Central and medRxiv from December 2019 to July 2023. Two reviewers independently identified 45 eligible articles, which followed participants for various gastrointestinal outcomes after acute SARS-CoV-2 infection. The study quality was assessed using the Joanna Briggs Institute Critical Appraisal Tools. The weighted pooled prevalence for persistent gastrointestinal symptoms of any nature and duration was 10.8% compared with 4.9% in healthy controls. For seven studies at low risk of methodological bias, the symptom prevalence ranged from 0.2% to 24.1%, with a median follow-up time of 18 weeks. We also identified a higher risk for future illnesses such as irritable bowel syndrome, dyspepsia, hepatic and biliary disease, liver disease and autoimmune-mediated illnesses such as inflammatory bowel disease and coeliac disease in historically SARS-CoV-2-exposed individuals. Our review has shown that, from a limited pool of mostly low-quality studies, previous SARS-CoV-2 exposure may be associated with ongoing gastrointestinal symptoms and the development of functional gastrointestinal illness. Furthermore, we show the need for high-quality research to better understand the SARS-CoV-2 association with gastrointestinal illness, particularly as population exposure to enteric infections returns to pre-COVID-19-restriction levels.}, }
@article {pmid37637608, year = {2023}, author = {Paruchuri, SSH and Farwa, UE and Jabeen, S and Pamecha, S and Shan, Z and Parekh, R and Lakkimsetti, M and Alamin, E and Sharma, V and Haider, S and Khan, J and Razzaq, W}, title = {Myocarditis and Myocardial Injury in Long COVID Syndrome: A Comprehensive Review of the Literature.}, journal = {Cureus}, volume = {15}, number = {7}, pages = {e42444}, pmid = {37637608}, issn = {2168-8184}, abstract = {The repercussions of coronavirus disease 2019 (COVID-19) have been devastating on a global scale. Long COVID, which affects patients for weeks or even months after their initial infection, is not limited to individuals with severe symptoms and can affect people of all ages. The condition can impact various physiological systems, leading to chronic health conditions and long-term disabilities that present significant challenges for healthcare systems worldwide. This review explores the link between long COVID and cardiovascular complications such as myocardial injury and myocarditis. It also highlights the prevalence of these complications and identifies risk factors for their development in long COVID patients. Myocardial injury occurs due to direct cellular damage and T-cell-mediated cytotoxicity resulting in elevated cardiac biomarkers. Diagnostic techniques like electrocardiogram, troponin level testing, and magnetic resonance imaging can help identify myocarditis, but endomyocardial biopsy is considered the gold-standard diagnostic technique. Guideline-directed medical therapy is recommended for COVID-19 myocarditis patients for better prognosis while being monitored under comprehensive care management approaches. Therefore, it's critical to develop effective screening techniques specifically for vulnerable populations while conducting further research that addresses the effects of long COVID on society's physical health.}, }
@article {pmid37646620, year = {2023}, author = {Edward, JA and Peruri, A and Rudofker, E and Shamapant, N and Parker, H and Cotter, R and Sabin, K and Lawley, J and Cornwell, WK}, title = {Characteristics and Treatment of Exercise Intolerance in Patients With Long COVID.}, journal = {Journal of cardiopulmonary rehabilitation and prevention}, volume = {43}, number = {6}, pages = {400-406}, doi = {10.1097/HCR.0000000000000821}, pmid = {37646620}, issn = {1932-751X}, support = {K23 HL132048/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; Exercise Therapy ; Exercise ; }, abstract = {The post-acute sequalae of SARS-CoV-2, also known as "Long COVID," is characterized by profound fatigue, impaired functional capacity with post-exertional malaise, orthostatic intolerance, and tachycardia. At least 25-30% of individuals impacted by SARS-CoV-2 will go on to experience the Long COVID syndrome, underscoring the detrimental impact this condition has on society. Although efforts are underway to further understand risk factors for Long COVID and identify strategies to prevent disease development entirely, implementation of treatment strategies is warranted to alleviate symptom burden among those affected. This review provides a rationale for exercise prescriptions tailored to the Long COVID patient based on the pathophysiology underlying this syndrome, as well as the previously demonstrated benefits of exercise training in other similar populations whose clinical manifestations result from cardiac deconditioning. Herein, we discuss methods to tailor exercise protocols, accommodating exercise intolerance and post-exertional malaise that may otherwise limit the ability to participate in a training protocol, as well as data demonstrating that a focused exercise prescription may effectively alleviate symptom burden in these patients. Long COVID results, in large part, from deconditioning, which may result from as little as 20 hr of inactivity. Exercise prescriptions tailored to patients with Long COVID may effectively alleviate symptom burden associated with this condition and in the absence of overt contraindications should be considered in management.}, }
@article {pmid37646849, year = {2024}, author = {Shafiee, A and Seighali, N and Teymouri Athar, M and Abdollahi, AK and Jafarabady, K and Bakhtiyari, M}, title = {Levels of brain-derived neurotrophic factor (BDNF) among patients with COVID-19: a systematic review and meta-analysis.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {274}, number = {5}, pages = {1137-1152}, pmid = {37646849}, issn = {1433-8491}, mesh = {Humans ; *Brain-Derived Neurotrophic Factor/blood ; *COVID-19/complications ; SARS-CoV-2 ; }, abstract = {Many individuals have been suffering from consistent neurological and neuropsychiatric manifestations even after the remission of coronavirus disease (COVID-19). Brain-derived neurotrophic factor (BDNF) is a protein involved in the regulation of several processes, including neuroplasticity, neurogenesis, and neuronal differentiation, and has been linked to a range of neurological and psychiatric disorders. In this study, we aimed to synthesize the available evidence on the profile of BDNF in COVID-19. A comprehensive search was done in the Web of Science core collection, Scopus, and MEDLINE (PubMed), and Embase to identify relevant studies reporting the level of BDNF in patients with COVID-19 or those suffering from long COVID. We used the NEWCASTLE-OTTAWA tool for quality assessment. We pooled the effect sizes of individual studies using the random effect model for our meta-analysis. Fifteen articles were included in the systematic review. The sample sizes ranged from 16 to 183 participants. Six studies compared the level of BDNF in COVID-19 patients with healthy controls. The pooled estimate of the standardized mean difference in BDNF level between patients with COVID-19 and healthy individuals was - 0.84 (95% CI - 1.49 to - 0.18, p = 0.01, I2 = 81%) indicating a significantly lower BDNF level in patients with COVID-19. Seven studies assessed BDNF in different severity statuses of patients with COVID-19. The pooled estimate of the standardized mean difference in BDNF level was - 0.53 (95% CI - 0.85 to - 0.21, p = 0.001, I2 = 46%), indicating a significantly lower BDNF level in patients with more severe COVID-19. Three studies evaluated BDNF levels in COVID-19 patients through different follow-up periods. Only one study assessed the BDNF levels in long COVID patients. Sensitivity analyses did not alter the significance of the association. In this study, we showed a significant dysregulation of BDNF following COVID-19 infection. These findings may support the pathogenesis behind the long-lasting effects of this disease among infected patients. PROSPERO: CRD42023413536.}, }
@article {pmid37655303, year = {2023}, author = {Joffe, AR and Elliott, A}, title = {Long COVID as a functional somatic symptom disorder caused by abnormally precise prior expectations during Bayesian perceptual processing: A new hypothesis and implications for pandemic response.}, journal = {SAGE open medicine}, volume = {11}, number = {}, pages = {20503121231194400}, pmid = {37655303}, issn = {2050-3121}, abstract = {This review proposes a model of Long-COVID where the constellation of symptoms are in fact genuinely experienced persistent physical symptoms that are usually functional in nature and therefore potentially reversible, that is, Long-COVID is a somatic symptom disorder. First, we describe what is currently known about Long-COVID in children and adults. Second, we examine reported "Long-Pandemic" effects that create a risk for similar somatic symptoms to develop in non-COVID-19 patients. Third, we describe what was known about somatization and somatic symptom disorder before the COVID-19 pandemic, and suggest that by analogy, Long-COVID may best be conceptualized as one of these disorders, with similar symptoms and predisposing, precipitating, and perpetuating factors. Fourth, we review the phenomenon of mass sociogenic (functional) illness, and the concept of nocebo effects, and suggest that by analogy, Long-COVID is compatible with these descriptions. Fifth, we describe the current theoretical model of the mechanism underlying functional disorders, the Bayesian predictive coding model for perception. This model accounts for moderators that can make symptom inferences functionally inaccurate and therefore can explain how to understand common predisposing, precipitating, and perpetuating factors. Finally, we discuss the implications of this framework for improved public health messaging during a pandemic, with recommendations for the management of Long-COVID symptoms in healthcare systems. We argue that the current public health approach has induced fear of Long-COVID in the population, including from constant messaging about disabling symptoms of Long-COVID and theorizing irreversible tissue damage as the cause of Long-COVID. This has created a self-fulfilling prophecy by inducing the very predisposing, precipitating, and perpetuating factors for the syndrome. Finally, we introduce the term "Pandemic-Response Syndrome" to describe what previously was labeled Long-COVID. This alternative perspective aims to stimulate research and serve as a lesson learned to avoid a repeat performance in the future.}, }
@article {pmid37657964, year = {2023}, author = {Zhao, S and Toniolo, S and Hampshire, A and Husain, M}, title = {Effects of COVID-19 on cognition and brain health.}, journal = {Trends in cognitive sciences}, volume = {27}, number = {11}, pages = {1053-1067}, pmid = {37657964}, issn = {1879-307X}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Brain/diagnostic imaging ; Cognition ; Neuroimaging ; }, abstract = {COVID-19 is associated with a range of neurological, cognitive, and mental health symptoms both acutely and chronically that can persist for many months after infection in people with long-COVID syndrome. Investigations of cognitive function and neuroimaging have begun to elucidate the nature of some of these symptoms. They reveal that, although cognitive deficits may be related to brain imaging abnormalities in some people, symptoms can also occur in the absence of objective cognitive deficits or neuroimaging changes. Furthermore, cognitive impairment may be detected even in asymptomatic individuals. We consider the evidence regarding symptoms, cognitive deficits, and neuroimaging, as well as their possible underlying mechanisms.}, }
@article {pmid37665495, year = {2023}, author = {Gómez-Dabó, L and Melgarejo-Martínez, L and Caronna, E and Pozo-Rosich, P}, title = {Headache in COVID-19 and Long COVID: to Know Facts for Clinical Practice.}, journal = {Current neurology and neuroscience reports}, volume = {23}, number = {10}, pages = {551-560}, pmid = {37665495}, issn = {1534-6293}, mesh = {Humans ; *COVID-19/complications/epidemiology ; *Headache/etiology/therapy/epidemiology ; SARS-CoV-2 ; Risk Factors ; }, abstract = {PURPOSE OF REVIEW: Headache is one of the most frequent symptoms of the acute and post-acute phase of COVID-19. Specific epidemiology, clinical features, risk factors, pathophysiology, and treatment have been reported in these two scenarios. With this narrative review of the literature, we aim to provide updated knowledge on headache in the COVID-19 setting and give clinicians a practical approach on this topic to guide them in their clinical practice.<br><br>RECENT FINDINGS: Headache mechanisms in COVID-19 are still poorly understood. Strong evidence is also lacking on how to best treat and manage these patients, especially those with persistent and disabling headache after COVID-19. Data are also scarce on the characteristics of headache in COVID-19 caused by the new SARS-CoV-2 (Omicron) variants and how these may influence the acute and persistent symptoms of COVID-19. Patients with pre-existing primary headache disorders remain a particularly concerning population due to their biological predisposition in suffering from headaches and the potential risk of worsening in the setting of SARS-CoV-2 infection. Although there is an exponential growth of scientific evidence, studies are often controversial and focused on the first wave of the pandemic, making COVID-19 headache still a challenging matter for clinicians. New research is therefore needed.}, }
@article {pmid37667052, year = {2023}, author = {Proal, AD and VanElzakker, MB and Aleman, S and Bach, K and Boribong, BP and Buggert, M and Cherry, S and Chertow, DS and Davies, HE and Dupont, CL and Deeks, SG and Eimer, W and Ely, EW and Fasano, A and Freire, M and Geng, LN and Griffin, DE and Henrich, TJ and Iwasaki, A and Izquierdo-Garcia, D and Locci, M and Mehandru, S and Painter, MM and Peluso, MJ and Pretorius, E and Price, DA and Putrino, D and Scheuermann, RH and Tan, GS and Tanzi, RE and VanBrocklin, HF and Yonker, LM and Wherry, EJ}, title = {SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC).}, journal = {Nature immunology}, volume = {24}, number = {10}, pages = {1616-1627}, pmid = {37667052}, issn = {1529-2916}, support = {K08 HL143183/HL/NHLBI NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; R01 DK123749/DK/NIDDK NIH HHS/United States ; R01 HL173059/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; RNA, Viral/genetics ; SARS-CoV-2 ; Antiviral Agents ; Disease Progression ; }, abstract = {Millions of people are suffering from Long COVID or post-acute sequelae of COVID-19 (PASC). Several biological factors have emerged as potential drivers of PASC pathology. Some individuals with PASC may not fully clear the coronavirus SARS-CoV-2 after acute infection. Instead, replicating virus and/or viral RNA-potentially capable of being translated to produce viral proteins-persist in tissue as a 'reservoir'. This reservoir could modulate host immune responses or release viral proteins into the circulation. Here we review studies that have identified SARS-CoV-2 RNA/protein or immune responses indicative of a SARS-CoV-2 reservoir in PASC samples. Mechanisms by which a SARS-CoV-2 reservoir may contribute to PASC pathology, including coagulation, microbiome and neuroimmune abnormalities, are delineated. We identify research priorities to guide the further study of a SARS-CoV-2 reservoir in PASC, with the goal that clinical trials of antivirals or other therapeutics with potential to clear a SARS-CoV-2 reservoir are accelerated.}, }
@article {pmid37669692, year = {2023}, author = {Clark, AD and Cumpstey, AF and Santolini, J and Jackson, AA and Feelisch, M}, title = {Uncoupled redox stress: how a temporal misalignment of redox-regulated processes and circadian rhythmicity exacerbates the stressed state.}, journal = {Open biology}, volume = {13}, number = {9}, pages = {230151}, pmid = {37669692}, issn = {2046-2441}, mesh = {Animals ; Humans ; *Ecosystem ; Health Promotion ; *COVID-19 ; SARS-CoV-2 ; Circadian Rhythm ; Oxidation-Reduction ; }, abstract = {Diurnal and seasonal rhythmicity, entrained by environmental and nutritional cues, is a vital part of all life on Earth operating at every level of organization; from individual cells, to multicellular organisms, whole ecosystems and societies. Redox processes are intrinsic to physiological function and circadian regulation, but how they are integrated with other regulatory processes at the whole-body level is poorly understood. Circadian misalignment triggered by a major stressor (e.g. viral infection with SARS-CoV-2) or recurring stressors of lesser magnitude such as shift work elicit a complex stress response that leads to desynchronization of metabolic processes. This in turn challenges the system's ability to achieve redox balance due to alterations in metabolic fluxes (redox rewiring). We infer that the emerging 'alternative redox states' do not always revert readily to their evolved natural states; 'Long COVID' and other complex disorders of unknown aetiology are the clinical manifestations of such rearrangements. To better support and successfully manage bodily resilience to major stress and other redox challenges needs a clear perspective on the pattern of the hysteretic response for the interaction between the redox system and the circadian clock. Characterization of this system requires repeated (ideally continuous) recording of relevant clinical measures of the stress responses and whole-body redox state (temporal redox phenotyping). The human/animal body is a complex 'system of systems' with multi-level buffering capabilities, and it requires consideration of the wider dynamic context to identify a limited number of stress-markers suitable for routine clinical decision making. Systematically mapping the patterns and dynamics of redox biomarkers along the stressor/disease trajectory will provide an operational model of whole-body redox regulation/balance that can serve as basis for the identification of effective interventions which promote health by enhancing resilience.}, }
@article {pmid37674565, year = {2023}, author = {Nyasulu, PS and Tamuzi, JL and Erasmus, RT}, title = {Burden, causation, and particularities of Long COVID in African populations: A rapid systematic review.}, journal = {IJID regions}, volume = {8}, number = {}, pages = {137-144}, pmid = {37674565}, issn = {2772-7076}, abstract = {OBJECTIVES: To determine the prevalence of long COVID, its most common symptoms, comorbidities, and pathophysiological mechanisms in African populations.<br><br>METHODS: A systematic review of long COVID in African populations was conducted. The random effects model was used to calculate the pooled prevalence rates (95% CI). A narrative synthesis was also performed.<br><br>RESULTS: We included 14 studies from seven African countries, totaling 6030 previously SARS-CoV-2 infected participants and 2954 long COVID patients. Long COVID had a pooled prevalence of 41% (26-56%). Fatigue, dyspnea, and confusion or lack of concentration were the most common symptoms, with prevalence rates (95% CI) of 41% (26-56%), 25% (12-38%), and 40% (12-68%), respectively. Long COVID was mainly associated with advanced age, being female, more than three long COVID symptoms in the acute phase, initial fatigue and dyspnea, COVID-19 severity, pre-existing obesity, hypertension, diabetes mellitus, and the presence of any chronic illness (P &#x2264;0.05). High microclot and platelet-poor plasma viscosity explained the pathophysiology of long COVID.<br><br>CONCLUSION: Long COVID prevalence in Africa was comparable to the global prevalence. The most common symptoms were higher in Africa. Comorbidities associated with long COVID may lead to additional complications in African populations due to hypercoagulation and thrombosis.Systematic review registration: PROSPERO CRD42023430024.}, }
@article {pmid37678512, year = {2023}, author = {Løkke, FB and Hansen, KS and Dalgaard, LS and Öbrink-Hansen, K and Schiøttz-Christensen, B and Leth, S}, title = {Long-term complications after infection with SARS-CoV-1, influenza and MERS-CoV - Lessons to learn in long COVID?.}, journal = {Infectious diseases now}, volume = {53}, number = {8}, pages = {104779}, doi = {10.1016/j.idnow.2023.104779}, pmid = {37678512}, issn = {2666-9919}, mesh = {Humans ; *Severe acute respiratory syndrome-related coronavirus ; *COVID-19/complications ; *Middle East Respiratory Syndrome Coronavirus ; Post-Acute COVID-19 Syndrome ; *Influenza, Human/complications/epidemiology ; SARS-CoV-2 ; Pandemics ; Quality of Life ; }, abstract = {The COVID-19 pandemic has affected millions of people worldwide, and while the mortality rate remains the primary concern, it is becoming increasingly apparent that many COVID-19 survivors experience long-term sequelae, representing a major concern for both themselves and healthcare providers. Comparing long-term sequelae following COVID-19 to those of other respiratory viruses such as influenza, MERS-CoV, and SARS-CoV-1 is an essential step toward understanding the extent and impact of these sequelae. A literature search was carried out using the PubMed. database. Search-terms included "persistent", "long-term", "chronic", and MeSH-terms for SARS-CoV-1, MERS-CoV and Influenza. Only English-language articles were selected. Articles were screened by title/abstract and full-text readings. Key points for comparison were persistent symptoms > 4 weeks, virus type, study design, population size, admission status, methods, and findings. Thirty-one articles were included: 19 on SARS-CoV-1, 10 on influenza, and 2 on MERS-CoV-survivors. Damage to the respiratory system was the main long-term manifestation after the acute phase of infection. Quality of life-related and psychological sequelae were the second and third most widely reported symptoms, respectively. Consistent with long-term sequelae from COVID-19, persisting cardiovascular, neurological, musculoskeletal, gastrointestinal impairments were also reported. In summary, the long-term sequelae following COVID-19 are a significant concern, and while long-term sequelae following influenza, MERS-CoV, and SARS-CoV-1 have also been reported, their prevalence and severity are less clear. It is essential to continue to study and monitor the long-term effects of all respiratory viruses so as to improve our understanding and develop strategies for prevention and treatment.}, }
@article {pmid37681886, year = {2023}, author = {Vishwakarma, N and Goud, RB and Tirupattur, MP and Katwa, LC}, title = {The Eye of the Storm: Investigating the Long-Term Cardiovascular Effects of COVID-19 and Variants.}, journal = {Cells}, volume = {12}, number = {17}, pages = {}, pmid = {37681886}, issn = {2073-4409}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Heart ; *Cardiovascular System ; Disease Progression ; }, abstract = {COVID-19 had stormed through the world in early March of 2019, and on 5 May 2023, SARS-CoV-2 was officially declared to no longer be a global health emergency. The rise of new COVID-19 variants XBB.1.5 and XBB.1.16, a product of recombinant variants and sub-strains, has fueled a need for continued surveillance of the pandemic as they have been deemed increasingly infectious. Regardless of the severity of the variant, this has caused an increase in hospitalizations, a strain in resources, and a rise of concern for public health. In addition, there is a growing population of patients experiencing cardiovascular complications as a result of post-acute sequelae of COVID-19. This review aims to focus on what was known about SARS-CoV-2 and its past variants (Alpha, Delta, Omicron) and how the knowledge has grown today with new emerging variants, with an emphasis on cardiovascular complexities. We focus on the possible mechanisms that cause the observations of chronic cardiac conditions seen even after patients have recovered from the infection. Further understanding of these mechanisms will help to close the gap in knowledge on post-acute sequelae of COVID-19 and the differences between the effects of variants.}, }
@article {pmid37683768, year = {2023}, author = {Nazari, P and Pozzilli, P}, title = {Type 2 diabetes and Covid-19: Lessons learnt, unanswered questions and hints for the future.}, journal = {Diabetes research and clinical practice}, volume = {204}, number = {}, pages = {110896}, doi = {10.1016/j.diabres.2023.110896}, pmid = {37683768}, issn = {1872-8227}, mesh = {Humans ; *COVID-19/epidemiology ; *Diabetes Mellitus, Type 2/complications/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Prediabetic State ; }, abstract = {Type 2 diabetes (T2DM) and COVID-19 represent a considerable burden of disease for patients and healthcare systems. New evidence is transpiring detailing the existence of a bidirectional relationship between T2DM and COVID-19. Alongside the acute influence of pre-existing T2DM on the course of COVID-19 and the exacerbation of dysglycemia following acute infection, long-term sequalae resulting from the synergistic interplay between the two is emerging, namely the development of COVID-induced diabetes and long-COVID in patients with pre-existing diabetes. This review presents our current understanding of the bidirectionality between these two conditions with a view to highlighting questions which remain unanswered and suggesting avenues for future research. In doing so, it emphasises critical gaps where concentrated research efforts are likely to yield the most beneficial improvements in understanding of the relationship between the two conditions, translating to tangible optimisations in care for the affected population.}, }
@article {pmid37686834, year = {2023}, author = {Chen, TB and Chang, CM and Yang, CC and Tsai, IJ and Wei, CY and Yang, HW and Yang, CP}, title = {Neuroimmunological Effect of Vitamin D on Neuropsychiatric Long COVID Syndrome: A Review.}, journal = {Nutrients}, volume = {15}, number = {17}, pages = {}, pmid = {37686834}, issn = {2072-6643}, mesh = {Humans ; *Vitamin D ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; SARS-CoV-2 ; Vitamins ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19). COVID-19 is now recognized as a multiorgan disease with a broad spectrum of manifestations. A substantial proportion of individuals who have recovered from COVID-19 are experiencing persistent, prolonged, and often incapacitating sequelae, collectively referred to as long COVID. To date, definitive diagnostic criteria for long COVID diagnosis remain elusive. An emerging public health threat is neuropsychiatric long COVID, encompassing a broad range of manifestations, such as sleep disturbance, anxiety, depression, brain fog, and fatigue. Although the precise mechanisms underlying the neuropsychiatric complications of long COVID are presently not fully elucidated, neural cytolytic effects, neuroinflammation, cerebral microvascular compromise, breakdown of the blood-brain barrier (BBB), thrombosis, hypoxia, neurotransmitter dysregulation, and provoked neurodegeneration are pathophysiologically linked to long-term neuropsychiatric consequences, in addition to systemic hyperinflammation and maladaptation of the renin-angiotensin-aldosterone system. Vitamin D, a fat-soluble secosteroid, is a potent immunomodulatory hormone with potential beneficial effects on anti-inflammatory responses, neuroprotection, monoamine neurotransmission, BBB integrity, vasculometabolic functions, gut microbiota, and telomere stability in different phases of SARS-CoV-2 infection, acting through both genomic and nongenomic pathways. Here, we provide an up-to-date review of the potential mechanisms and pathophysiology of neuropsychiatric long COVID syndrome and the plausible neurological contributions of vitamin D in mitigating the effects of long COVID.}, }
@article {pmid37688764, year = {2023}, author = {Fundora, MP and Kamidani, S and Oster, ME}, title = {COVID Vaccination as a Strategy for Cardiovascular Disease Prevention.}, journal = {Current cardiology reports}, volume = {25}, number = {10}, pages = {1327-1335}, pmid = {37688764}, issn = {1534-3170}, mesh = {Humans ; COVID-19 Vaccines ; *Cardiovascular Diseases/prevention &amp; control ; Post-Acute COVID-19 Syndrome ; *COVID-19/prevention &amp; control ; SARS-CoV-2 ; Vaccination ; }, abstract = {PURPOSE OF REVIEW: Cardiovascular (CV) disease is a known complication of SARS-CoV-2 infection. A clear benefit of COVID-19 vaccination is a reduction mortality; however, COVID-19 vaccination may also prevent cardiovascular disease (CVD). We aim to describe CV pathology associated with SARS-CoV-2 infection and describe how COVID-19 vaccination is a strategy for CVD prevention.<br><br>RECENT FINDINGS: The risks and benefits of COVID-19 vaccination have been widely studied. Analysis of individuals with and without pre-existing CVD has shown that COVID-19 vaccination can prevent morbidity associated with SARS-CoV-2 infection and reduce mortality. COVID-19 vaccination is effective in preventing myocardial infarction, cerebrovascular events, myopericarditis, and long COVID, all associated with CVD risk factors. Vaccination reduces mortality in patients with pre-existing CVD. Further study investigating ideal vaccination schedules for individuals with CVD should be undertaken to protect this vulnerable group and address new risks from variants of concern.}, }
@article {pmid37689093, year = {2023}, author = {Seibert, FS and Stervbo, U and Wiemers, L and Skrzypczyk, S and Hogeweg, M and Bertram, S and Kurek, J and Anft, M and Westhoff, TH and Babel, N}, title = {Severity of neurological Long-COVID symptoms correlates with increased level of autoantibodies targeting vasoregulatory and autonomic nervous system receptors.}, journal = {Autoimmunity reviews}, volume = {22}, number = {11}, pages = {103445}, doi = {10.1016/j.autrev.2023.103445}, pmid = {37689093}, issn = {1873-0183}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Cross-Sectional Studies ; SARS-CoV-2 ; Autoantibodies ; Autonomic Nervous System ; Fatigue ; *Nervous System Diseases/diagnosis ; Receptor, Muscarinic M3 ; }, abstract = {BACKGROUND: The Long-COVID syndrome constitutes a plethora of persisting symptoms with neurological disorders being the most disabling ones. The pathogenesis of Long-COVID is currently under heavy scrutiny and existing data on the role of auto-immune reaction to G-protein coupled receptors (GPCR) are conflicting.<br><br>METHODS: This monocentric, cross-sectional study included patients who suffered a mild to moderate SARS-CoV-2 infection up to 12&#xa0;months prior to enrollment with (n&#xa0;=&#xa0;72) or without (n&#xa0;=&#xa0;58) Long-COVID diagnosis according to the German S1 guideline or with no known history of SARS-CoV-2 infection (n&#xa0;=&#xa0;70). While autoantibodies specific for the vasoregulation associated Adrenergic Receptor (ADR) B1 and B2 and the CNS and vasoregulation associated muscarinic acetylcholine receptor (CHR) M3 and M4 were measured by ELISA, neurological disorders were quantified by internationally standardized questionnaires.<br><br>RESULTS: The prevalence and concentrations of evaluated autoantibodes were significantly higher in Long-COVID compared to the 2 other groups (p&#xa0;=&#xa0;2.1*10[-9]) with a significantly higher number of patients with simultaneous detection of more than one autoantibody in the Long-COVID group (p&#xa0;=&#xa0;0.0419). Importantly, the overall inflammatory state was low in all 3 groups. ARB1 and ARB2 correlated negatively CERAD Trail Marking A and B (R&#xa0;&#x2264; -0.26, p&#xa0;&#x2264; 0.043), while CHRM3 correlated positively with Chadler Fatigue Scale (R&#xa0;=&#xa0;0.37, p&#xa0;=&#xa0;0.0087).<br><br>CONCLUSIONS: Concentrations of autoantibodies correlates to the intensity of neurological disorders including psychomotor speed, visual search, attention, and fatigue.}, }
@article {pmid37690286, year = {2023}, author = {Gupta, T and Najumuddin,  and Rajendran, D and Gujral, A and Jangra, A}, title = {Metabolism configures immune response across multi-systems: Lessons from COVID-19.}, journal = {Advances in biological regulation}, volume = {90}, number = {}, pages = {100977}, doi = {10.1016/j.jbior.2023.100977}, pmid = {37690286}, issn = {2212-4934}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Heart Failure ; Inflammation ; Obesity ; Immunity ; *Diabetes Mellitus ; }, abstract = {Several studies over the last decade demonstrate the recruitment of immune cells, increased inflammatory cytokines, and chemokine in patients with metabolic diseases, including heart failure, parenchymal inflammation, obesity, tuberculosis, and diabetes mellitus. Metabolic rewiring of immune cells is associated with the severity and prevalence of these diseases. The risk of developing COVID-19/SARS-CoV-2 infection increases in patients with metabolic dysfunction (heart failure, diabetes mellitus, and obesity). Several etiologies, including fatigue, dyspnea, and dizziness, persist even months after COVID-19 infection, commonly known as Post-Acute Sequelae of CoV-2 (PASC) or long COVID. A chronic inflammatory state and metabolic dysfunction are the factors that contribute to long COVID. Here, this study explores the potential link between pathogenic metabolic and immune alterations across different organ systems that could underlie COVID-19 and PASC. These interactions could be utilized for targeted future therapeutic approaches.}, }
@article {pmid37694571, year = {2024}, author = {Kempuraj, D and Aenlle, KK and Cohen, J and Mathew, A and Isler, D and Pangeni, RP and Nathanson, L and Theoharides, TC and Klimas, NG}, title = {COVID-19 and Long COVID: Disruption of the Neurovascular Unit, Blood-Brain Barrier, and Tight Junctions.}, journal = {The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry}, volume = {30}, number = {4}, pages = {421-439}, doi = {10.1177/10738584231194927}, pmid = {37694571}, issn = {1089-4098}, mesh = {*COVID-19 ; Humans ; *Blood-Brain Barrier/virology/pathology/metabolism ; *Tight Junctions/metabolism/virology ; *SARS-CoV-2 ; Brain/virology/pathology ; Betacoronavirus ; Pandemics ; Coronavirus Infections ; Endothelial Cells/virology/metabolism/pathology ; Angiotensin-Converting Enzyme 2/metabolism ; Post-Acute COVID-19 Syndrome ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), could affect brain structure and function. SARS-CoV-2 can enter the brain through different routes, including the olfactory, trigeminal, and vagus nerves, and through blood and immunocytes. SARS-CoV-2 may also enter the brain from the peripheral blood through a disrupted blood-brain barrier (BBB). The neurovascular unit in the brain, composed of neurons, astrocytes, endothelial cells, and pericytes, protects brain parenchyma by regulating the entry of substances from the blood. The endothelial cells, pericytes, and astrocytes highly express angiotensin converting enzyme 2 (ACE2), indicating that the BBB can be disturbed by SARS-CoV-2 and lead to derangements of tight junction and adherens junction proteins. This leads to increased BBB permeability, leakage of blood components, and movement of immune cells into the brain parenchyma. SARS-CoV-2 may also cross microvascular endothelial cells through an ACE2 receptor-associated pathway. The exact mechanism of BBB dysregulation in COVID-19/neuro-COVID is not clearly known, nor is the development of long COVID. Various blood biomarkers could indicate disease severity and neurologic complications in COVID-19 and help objectively diagnose those developing long COVID. This review highlights the importance of neurovascular and BBB disruption, as well as some potentially useful biomarkers in COVID-19, and long COVID/neuro-COVID.}, }
@article {pmid37697012, year = {2024}, author = {Kiyak, C and Ijezie, OA and Ackah, JA and Armstrong, M and Cowen, J and Cetinkaya, D and Burianová, H and Akudjedu, TN}, title = {Topographical Distribution of Neuroanatomical Abnormalities Following COVID-19 Invasion : A Systematic Literature Review.}, journal = {Clinical neuroradiology}, volume = {34}, number = {1}, pages = {13-31}, pmid = {37697012}, issn = {1869-1447}, support = {(2021/22) Quality-Related (QR) Fund//Bournemouth University/ ; }, mesh = {Humans ; Brain/diagnostic imaging/pathology ; *COVID-19/diagnostic imaging/complications ; *Neuroimaging ; SARS-CoV-2 ; }, abstract = {PURPOSE: This systematic review is aimed at synthesising the literature base to date on the frequency and topographical distribution of neuroanatomical changes seen on imaging following COVID-19 invasion with a focus on both the acute and chronic phases of the disease.<br><br>METHODS: In this study, 8 databases were systematically searched to identify relevant articles published from December 2019 to March 2022 and supplemented with a&#xa0;manual reference search. Data were extracted from the included studies and narrative synthesis was employed to integrate the findings.<br><br>RESULTS: A&#xa0;total of 110 studies met the inclusion criteria and comprised 119,307 participants (including 31,073 acute and 143 long COVID-19&#xa0;patients manifesting neurological alterations) and controls. Considerable variability in both the localisation and nature of neuroanatomical abnormalities are noted along the continuum with a&#xa0;wide range of neuropathologies relating to the cerebrovascular/neurovascular system, (sub)cortical structures (including deep grey and white matter structures), brainstem, and predominant regional and/or global alterations in the cerebellum with varying degrees of spinal involvement.<br><br>CONCLUSION: Structural regional alterations on neuroimaging are frequently demonstrated in both the acute and chronic phases of SARS-CoV&#x2011;2 infection, particularly prevalent across subcortical, prefrontal/frontal and cortico-limbic brain areas as well as the cerebrovascular/neurovascular system. These findings contribute to our understanding of the acute and chronic effects of the virus on the nervous system and has the potential to provide information on acute and long-term treatment and neurorehabilitation decisions.}, }
@article {pmid37702769, year = {2023}, author = {Cotugno, N and Amodio, D and Buonsenso, D and Palma, P}, title = {Susceptibility of SARS-CoV2 infection in children.}, journal = {European journal of pediatrics}, volume = {182}, number = {11}, pages = {4851-4857}, pmid = {37702769}, issn = {1432-1076}, support = {PRIN: 2022ZCLC3X//Ministero dell'Universit&#xe0; e della Ricerca/ ; 5x1000//Ministero della Salute/ ; }, mesh = {Adult ; *COVID-19/complications ; Systemic Inflammatory Response Syndrome ; Child ; Humans ; Post-Acute COVID-19 Syndrome ; RNA, Viral ; SARS-CoV-2 ; *Myocarditis/etiology ; }, abstract = {Coronavirus disease 2019 in children presents with distinct phenotype in comparison to adults. Overall, the pediatric infection with a generally milder clinical course of the acute infection compared to adults still faces several unknown aspects. Specifically, the presence of a wide range of inflammatory manifestations, including multisystem inflammatory syndrome in children (MIS-C), myocarditis, and long COVID in the period after infection suggests a particular susceptibility of some children upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Albeit peculiar complications such as long covid are less frequent in children compared to adults, research on the relationship between inflammatory syndromes and SARS-CoV-2 is rapidly evolving. Conclusions: new studies and findings continue to emerge, providing further insights into the underlying mechanisms and potential therapeutic strategies. In the present work, we revised current knowledge of the main factors accounting for such variability upon SARS-CoV-2 infection over the pediatric age group. What is Known: • COVID19 in children overall showed a milder course compared to adults during the acute phase of the infection. • Children showed to be susceptible to a wide range of post infectious complications including multisystem inflammatory syndrome in children (MIS-C), myocarditis, neuroinflammation, and long COVID. What is New: • Mechanisms underlying susceptibility to a severe course of the infection were recently shown to pertain to the host. • A specific combination of HLA was recently shown to be associated to higher susceptibility to MIS-C in children.}, }
@article {pmid37704072, year = {2025}, author = {Hawley, HB}, title = {Long COVID: Clinical Findings, Pathology, and Endothelial Molecular Mechanisms.}, journal = {The American journal of medicine}, volume = {138}, number = {1}, pages = {91-97}, doi = {10.1016/j.amjmed.2023.08.008}, pmid = {37704072}, issn = {1555-7162}, mesh = {Humans ; *COVID-19/complications ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; Endothelium, Vascular/pathology ; Complement Activation ; }, abstract = {Persistence of COVID-19 symptoms may follow severe acute respiratory syndrome coronavirus 2 infection. The incidence of long COVID increases with the severity of acute disease, but even mild disease can be associated with sequelae. The symptoms vary widely, with fatigue, shortness of breath, and cognitive dysfunction the most common. Abnormalities of multiple organs have been documented, and histopathology has revealed widespread microthrombi. Elevated levels of complement are present in acute COVID-19 patients and may persist at lower levels in long COVID. Evidence supports complement activation, with endotheliopathy-associated disease as the molecular mechanism causing both acute and long COVID.}, }
@article {pmid37706263, year = {2023}, author = {Udeh, R and Utrero-Rico, A and Dolja-Gore, X and Rahmati, M and McEVoy, M and Kenna, T}, title = {Lactate dehydrogenase contribution to symptom persistence in long COVID: A pooled analysis.}, journal = {Reviews in medical virology}, volume = {33}, number = {6}, pages = {e2477}, doi = {10.1002/rmv.2477}, pmid = {37706263}, issn = {1099-1654}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/diagnosis ; L-Lactate Dehydrogenase ; Plasma ; PubMed ; }, abstract = {There's critical need for risk predictors in long COVID. This meta-analysis evaluates the evidence for an association between plasma lactate dehydrogenase (LDH) and long COVID and explores the contribution of LDH to symptoms persistent across the distinct post-acute sequelae of COVID-19 (PASC) domains. PubMed, EMBASE, Web of Science, and Google Scholar were searched for articles published up to 20 March 2023 for studies that reported data on LDH levels in COVID-19 survivors with and without PASC. Random-effect meta-analysis was employed to estimate the standardized mean difference (SMD) with corresponding 95% confidence interval of each outcome. There were a total of 8289 study participants (3338 PASC vs. 4951 controls) from 46 studies. Our meta-analysis compared to the controls showed a significant association between LDH elevation and Resp-PASC [SMD = 1.07, 95%CI = 0.72, 1.41, p = 0.01] but not Cardio-PASC [SMD = 1.79, 95%CI = -0.02, 3.61, p = 0.05], Neuro-PASC [SMD = 0.19, 95%CI = -0.24, 0.61, p = 0.40], and Gastrointestinal-PASC [SMD = 0.45, 95%CI = -1.08, 1.98, p = 0.56]. This meta-analysis suggests elevated LDH can be used for predicting Resp-PASC, but not Cardio-PASC, Neuro-PASC or gastrointestinal-PASC. Thus, elevated plasma LDH following COVID infection may be considered as a disease biomarker.}, }
@article {pmid37707639, year = {2023}, author = {Martínez-Lavín, M and Miguel-Álvarez, A}, title = {Hypothetical framework for post-COVID 19 condition based on a fibromyalgia pathogenetic model.}, journal = {Clinical rheumatology}, volume = {42}, number = {11}, pages = {3167-3171}, pmid = {37707639}, issn = {1434-9949}, mesh = {Humans ; *Fibromyalgia ; *COVID-19/complications ; *Fatigue Syndrome, Chronic ; *Neuralgia ; Ganglia, Spinal ; Post-Acute COVID-19 Syndrome ; }, abstract = {There is a clear clinical overlap between fibromyalgia, myalgic encephalomyelitis, and post-COVID 19 condition. Chronic fatigue, cognitive impairment, and widespread pain characterize these 3 syndromes. A steady line of investigation posits fibromyalgia as stress-evoked sympathetically maintained neuropathic pain syndrome and places dorsal root ganglia dysregulation with the ensuing small fiber neuropathy at the epicenter of fibromyalgia pathogenesis. This article discusses emerging evidence suggesting that similar mechanism may operate in post-COVID 19 condition.}, }
@article {pmid37714919, year = {2023}, author = {Marjenberg, Z and Leng, S and Tascini, C and Garg, M and Misso, K and El Guerche Seblain, C and Shaikh, N}, title = {Risk of long COVID main symptoms after SARS-CoV-2 infection: a systematic review and meta-analysis.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {15332}, pmid = {37714919}, issn = {2045-2322}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Quality of Life ; SARS-CoV-2 ; Dyspnea ; Fatigue/etiology ; }, abstract = {This review aimed to summarise the relative risk (RR) of the main symptoms of long COVID in people infected with SARS-CoV-2 compared to uninfected controls, as well as the difference in health-related quality of life (HRQoL) after infection. MEDLINE, EMBASE, PubMed, NLM-LitCovid, WHO-COVID-19, arXiv and Europe-PMC were searched up to 23rd March 2022. Studies reporting risk (four or more weeks after infection) of fatigue, shortness of breath, and cognitive dysfunction, as well as comparative HRQoL outcomes, were included. Pairwise random-effects meta-analyses were performed to pool risks of individual symptoms. Thirty-three studies were identified; twenty studies reporting symptom risks were included in the meta-analyses. Overall, infection with SARS-CoV-2 carried significantly higher risk of fatigue (RR 1.72, 95% confidence intervals [CIs] 1.41, 2.10), shortness of breath (RR 2.60, 95% CIs 1.96, 3.44), memory difficulties (RR 2.53, 95% CIs 1.30, 4.93), and concentration difficulties (RR 2.14, 95% CIs 1.25, 3.67). Quality of life findings were varied and comparisons between studies were challenging due to different HRQoL instruments used and study heterogeneity, although studies indicated that severe hospitalised COVID is associated with a significantly poorer HRQoL after infection. These risks are likely to constantly change as vaccines, reinfections, and new variants alter global immunity.}, }
@article {pmid37715729, year = {2023}, author = {Lewthwaite, H and Byrne, A and Brew, B and Gibson, PG}, title = {Treatable traits for long COVID.}, journal = {Respirology (Carlton, Vic.)}, volume = {28}, number = {11}, pages = {1005-1022}, doi = {10.1111/resp.14596}, pmid = {37715729}, issn = {1440-1843}, mesh = {Adult ; Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Chronic Disease ; Fatigue/etiology ; Pain ; }, abstract = {Long COVID, or post-acute COVID-19 sequelae, is experienced by an estimated one in eight adults following acute COVID-19. Long COVID is a new and complex chronic health condition that typically includes multiple symptoms that cross organ systems and fluctuate over time; a one-size-fits-all approach is, therefore, not likely to be appropriate nor relevant for long COVID treatment. 'Treatable Traits' is a personalized medicine approach, purpose-built to address the complexity and heterogeneity of complex chronic conditions. This comprehensive review aimed to understand how a treatable traits approach could be applied to long COVID, by first identifying the most prevalent long COVID treatable traits and then the available evidence for strategies to target these traits. An umbrella review of 22 systematic reviews identified 34 symptoms and complications common with long COVID, grouped into eight long COVID treatable trait clusters: neurological, chest, psychological, pain, fatigue, sleep impairment, functional impairment and other. A systematic review of randomized control trials identified 18 studies that explored different intervention approaches for long COVID prevention (k = 4) or management (k = 14). While a single study reported metformin as effective for long COVID prevention, the findings need to be replicated and consensus is required around how to define long COVID as a clinical trial endpoint. For long COVID management, current evidence supports exercise training or respiratory muscle training for long COVID treatable traits in the chest and functional limitation clusters. While there are studies exploring interventions targeting other long COVID treatable traits, further high-quality RCTs are needed, particularly targeting treatable traits in the clusters of fatigue, psychological, pain and sleep impairment.}, }
@article {pmid37718435, year = {2023}, author = {Ruiz-Pablos, M and Paiva, B and Zabaleta, A}, title = {Epstein-Barr virus-acquired immunodeficiency in myalgic encephalomyelitis-Is it present in long COVID?.}, journal = {Journal of translational medicine}, volume = {21}, number = {1}, pages = {633}, pmid = {37718435}, issn = {1479-5876}, mesh = {Humans ; *Fatigue Syndrome, Chronic ; Herpesvirus 4, Human ; Post-Acute COVID-19 Syndrome ; *Epstein-Barr Virus Infections/complications ; *COVID-19/complications ; SARS-CoV-2 ; }, abstract = {Both myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) and long COVID (LC) are characterized by similar immunological alterations, persistence of chronic viral infection, autoimmunity, chronic inflammatory state, viral reactivation, hypocortisolism, and microclot formation. They also present with similar symptoms such as asthenia, exercise intolerance, sleep disorders, cognitive dysfunction, and neurological and gastrointestinal complaints. In addition, both pathologies present Epstein-Barr virus (EBV) reactivation, indicating the possibility of this virus being the link between both pathologies. Therefore, we propose that latency and recurrent EBV reactivation could generate an acquired immunodeficiency syndrome in three steps: first, an acquired EBV immunodeficiency develops in individuals with "weak" EBV HLA-II haplotypes, which prevents the control of latency I cells. Second, ectopic lymphoid structures with EBV latency form in different tissues (including the CNS), promoting inflammatory responses and further impairment of cell-mediated immunity. Finally, immune exhaustion occurs due to chronic exposure to viral antigens, with consolidation of the disease. In the case of LC, prior to the first step, there is the possibility of previous SARS-CoV-2 infection in individuals with "weak" HLA-II haplotypes against this virus and/or EBV.}, }
@article {pmid37719243, year = {2023}, author = {Oliveira, A and Fabbri, G and Gille, T and Bargagli, E and Duchemann, B and Evans, R and Pinnock, H and Holland, AE and Renzoni, E and Ekström, M and Jones, S and Wijsenbeek, M and Dinh-Xuan, AT and Vagheggini, G}, title = {Holistic management of patients with progressive pulmonary fibrosis.}, journal = {Breathe (Sheffield, England)}, volume = {19}, number = {3}, pages = {230101}, pmid = {37719243}, issn = {1810-6838}, abstract = {UNLABELLED: Progressive pulmonary fibrosis (PF) is a complex interstitial lung disease that impacts substantially on patients' daily lives, requiring personalised and integrated care. We summarise the main needs of patients with PF and their caregivers, and suggest a supportive care approach. Individualised care, education, emotional and psychological support, specialised treatments, and better access to information and resources are necessary. Management should start at diagnosis, be tailored to the patient's needs, and consider end-of-life care. Pharmacological and non-pharmacological interventions should be individualised, including oxygen therapy and pulmonary rehabilitation, with digital healthcare utilised as appropriate. Further research is needed to address technical issues related to oxygen delivery and digital healthcare.<br><br>EDUCATIONAL AIMS: To identify the main needs of patients with PF and their caregivers.To describe the components of a comprehensive approach to a supportive care programme for patients with PF.To identify further areas of research to address technical issues related to the management of patients with PF.}, }
@article {pmid37719983, year = {2023}, author = {Marques, KC and Quaresma, JAS and Falcão, LFM}, title = {Cardiovascular autonomic dysfunction in "Long COVID": pathophysiology, heart rate variability, and inflammatory markers.}, journal = {Frontiers in cardiovascular medicine}, volume = {10}, number = {}, pages = {1256512}, pmid = {37719983}, issn = {2297-055X}, abstract = {Long COVID is characterized by persistent signs and symptoms that continue or develop for more than 4 weeks after acute COVID-19 infection. Patients with Long COVID experience a cardiovascular autonomic imbalance known as dysautonomia. However, the underlying autonomic pathophysiological mechanisms behind this remain unclear. Current hypotheses include neurotropism, cytokine storms, and inflammatory persistence. Certain immunological factors indicate autoimmune dysfunction, which can be used to identify patients at a higher risk of Long COVID. Heart rate variability can indicate autonomic imbalances in individuals suffering from Long COVID, and measurement is a non-invasive and low-cost method for assessing cardiovascular autonomic modulation. Additionally, biochemical inflammatory markers are used for diagnosing and monitoring Long COVID. These inflammatory markers can be used to improve the understanding of the mechanisms driving the inflammatory response and its effects on the sympathetic and parasympathetic pathways of the autonomic nervous system. Autonomic imbalances in patients with Long COVID may result in lower heart rate variability, impaired vagal activity, and substantial sympathovagal imbalance. New research on this subject must be encouraged to enhance the understanding of the long-term risks that cardiovascular autonomic imbalances can cause in individuals with Long COVID.}, }
@article {pmid37720220, year = {2023}, author = {Ng, CYJ and Bun, HH and Zhao, Y and Zhong, LLD}, title = {TCM "medicine and food homology" in the management of post-COVID disorders.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1234307}, pmid = {37720220}, issn = {1664-3224}, mesh = {Humans ; *COVID-19 ; Public Health ; Food ; Long-Term Care ; World Health Organization ; }, abstract = {BACKGROUND: The World Health Organization declared that COVID-19 is no longer a public health emergency of global concern on May 5, 2023. Post-COVID disorders are, however, becoming more common. Hence, there lies a growing need to develop safe and effective treatment measures to manage post-COVID disorders. Investigating the use of TCM medicinal foods in the long-term therapy of post-COVID illnesses may be beneficial given contemporary research's emphasis on the development of medicinal foods.<br><br>SCOPE AND APPROACH: The use of medicinal foods for the long-term treatment of post-COVID disorders is highlighted in this review. Following a discussion of the history of the TCM "Medicine and Food Homology" theory, the pathophysiological effects of post-COVID disorders will be briefly reviewed. An analysis of TCM medicinal foods and their functions in treating post-COVID disorders will then be provided before offering some insight into potential directions for future research and application.<br><br>KEY FINDINGS AND DISCUSSION: TCM medicinal foods can manage different aspects of post-COVID disorders. The use of medicinal foods in the long-term management of post-COVID illnesses may be a safe and efficient therapy choice because they are typically milder in nature than chronic drug use. These findings may also be applied in the long-term post-disease treatment of similar respiratory disorders.}, }
@article {pmid37720384, year = {2023}, author = {Li, H and Xia, J and Bennett, D and Roque, F and Bam, RA and Tavares, ABT and Gokhale, M and Ida, F and Rhee, JJ and Soriano Gabarro, M and Song, Y}, title = {Long-COVID-19 clinical and health outcomes: an umbrella review.}, journal = {Therapeutic advances in infectious disease}, volume = {10}, number = {}, pages = {20499361231198335}, pmid = {37720384}, issn = {2049-9361}, abstract = {BACKGROUND: A growing interest in long-term sequelae of COVID-19 has prompted several systematic literature reviews (SLRs) to evaluate long-COVID-19 effects. However, many of these reviews lack in-depth information on the timing, duration, and severity of these conditions.<br><br>OBJECTIVES: Our aim was to synthesize both qualitative and quantitative evidence on prevalence and outcomes of long-term effect of COVID-19 through an umbrella review.<br><br>DESIGN: Umbrella review of relevant SLRs on long-COVID-19 in terms of prolonged symptoms and clinical conditions, and comprehensively synthesized the latest existing evidence.<br><br>DATA SOURCES AND METHODS: We systematically identified and appraised prior systematic reviews/meta-analyses using MEDLINE, Embase, and Cochrane database of systematic review from 2020 to 2021 following the preferred reporting items for systematic reviews and meta-analyses guidance. We summarized and categorized all relevant clinical symptoms and outcomes in adults with COVID-19 using the Medical Dictionary for Regulatory Activities System Organ Class (MedDRA SOC).<br><br>RESULTS: We identified 967 systematic reviews/meta-analyses; 36 were retained for final data extraction. The most prevalent SOC were social circumstances (40%), blood and lymphatic system disorders (39%), and metabolism and nutrition disorder (38%). The most frequently reported SOC outcomes within each MedDRA category were poor quality of life (59%), wheezing and dyspnea (19-49%), fatigue (30-64%), chest pain (16%), decreased or loss of appetite (14-17%), abdominal discomfort or digestive disorder (12-18%), arthralgia with or without myalgia (16-24%), paresthesia (27%) and hair loss (14-25%), and hearing loss or tinnitus (15%).<br><br>CONCLUSION: This study confirmed a high prevalence of several long COVID-19 outcomes according to the MedDRA categories and indicated that the majority of evidence was rated as moderate to low.<br><br>REGISTRATION: The review was registered at PROSPERO (https://www.crd.york.ac.uk/prospero/) (CRD42022303557).}, }
@article {pmid37725376, year = {2023}, author = {Pouliopoulou, DV and Macdermid, JC and Saunders, E and Peters, S and Brunton, L and Miller, E and Quinn, KL and Pereira, TV and Bobos, P}, title = {Rehabilitation Interventions for Physical Capacity and Quality of Life in Adults With Post-COVID-19 Condition: A Systematic Review and Meta-Analysis.}, journal = {JAMA network open}, volume = {6}, number = {9}, pages = {e2333838}, pmid = {37725376}, issn = {2574-3805}, mesh = {Humans ; Adult ; Female ; Middle Aged ; Male ; *Quality of Life ; Post-Acute COVID-19 Syndrome ; Bayes Theorem ; *COVID-19 ; Dyspnea/etiology ; Randomized Controlled Trials as Topic ; }, abstract = {IMPORTANCE: Current rehabilitation guidelines for patients with post-COVID-19 condition (PCC) are primarily based on expert opinions and observational data, and there is an urgent need for evidence-based rehabilitation interventions to support patients with PCC.<br><br>OBJECTIVE: To synthesize the findings of existing studies that report on physical capacity (including functional exercise capacity, muscle function, dyspnea, and respiratory function) and quality of life outcomes following rehabilitation interventions in patients with PCC.<br><br>DATA SOURCES: A systematic electronic search was performed from January 2020 until February 2023, in MEDLINE, Scopus, CINAHL, and the Clinical Trials Registry. Key terms that were used to identify potentially relevant studies included long-covid, post-covid, sequelae, exercise therapy, rehabilitation, physical activity, physical therapy, and randomized controlled trial.<br><br>STUDY SELECTION: This study included randomized clinical trials that compared respiratory training and exercise-based rehabilitation interventions with either placebo, usual care, waiting list, or control in patients with PCC.<br><br>DATA EXTRACTION AND SYNTHESIS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A pairwise bayesian random-effects meta-analysis was performed using vague prior distributions. Risk of bias was assessed using the Cochrane risk of bias tool version 2, and the certainty of evidence was evaluated using the GRADE system by 2 independent researchers.<br><br>MAIN OUTCOMES AND MEASURES: The primary outcome was functional exercise capacity, measured at the closest postintervention time point by the 6-minute walking test. Secondary outcomes were fatigue, lower limb muscle function, dyspnea, respiratory function, and quality of life. All outcomes were defined a priori. Continuous outcomes were reported as standardized mean differences (SMDs) with 95% credible intervals (CrIs) and binary outcomes were summarized as odds ratios with 95% CrIs. The between-trial heterogeneity was quantified using the between-study variance, &#x3c4;2, and 95% CrIs.<br><br>RESULTS: Of 1834 identified records, 1193 were screened, and 14 trials (1244 patients; 45% female participants; median [IQR] age, 50 [47 to 56] years) were included in the analyses. Rehabilitation interventions were associated with improvements in functional exercise capacity (SMD, -0.56; 95% CrI, -0.87 to -0.22) with moderate certainty in 7 trials (389 participants). These improvements had a 99% posterior probability of superiority when compared with current standard care. The value of &#x3c4;2 (0.04; 95% CrI, 0.00 to 0.60) indicated low statistical heterogeneity. However, there was significant uncertainty and imprecision regarding the probability of experiencing exercise-induced adverse events (odds ratio, 1.68; 95% CrI, 0.32 to 9.94).<br><br>CONCLUSIONS AND RELEVANCE: The findings of this systematic review and meta-analysis suggest that rehabilitation interventions are associated with improvements in functional exercise capacity, dyspnea, and quality of life, with a high probability of improvement compared with the current standard care; the certainty of evidence was moderate for functional exercise capacity and quality of life and low for other outcomes. Given the uncertainty surrounding the safety outcomes, additional trials with enhanced monitoring of adverse events are necessary.}, }
@article {pmid37726566, year = {2024}, author = {Shmueli, M and Lendner, I and Ben-Shimol, S}, title = {Effect of the COVID-19 pandemic on the pediatric infectious disease landscape.}, journal = {European journal of pediatrics}, volume = {183}, number = {3}, pages = {1001-1009}, pmid = {37726566}, issn = {1432-1076}, mesh = {Child ; Humans ; *COVID-19/epidemiology ; Pandemics/prevention &amp; control ; *Influenza, Human ; Anti-Bacterial Agents/therapeutic use ; *Antimicrobial Stewardship ; *Influenza Vaccines ; }, abstract = {This narrative review aims to present an overview of the COVID-19 pandemic's effects on the landscape of pediatric infectious diseases. While COVID-19 generally results in mild symptoms and a favorable prognosis in children, the pandemic brought forth significant consequences. These included persistent symptoms among infected children ("long COVID"), a profound transformation in healthcare utilization (notably through the widespread adoption of telemedicine), and the implementation of optimization strategies within healthcare settings. Furthermore, the pandemic resulted in alterations in the circulation patterns of respiratory pathogens, including influenza, RSV, and Streptococcus pneumoniae. The possible reasons for those changes are discussed in this review. COVID-19 effect was not limited to respiratory infectious diseases, as other diseases, including urinary tract and gastrointestinal infections, have displayed decreased transmission rates, likely attributable to heightened hygiene measures and shifts in care-seeking behaviors. Finally, the disruption of routine childhood vaccination programs has resulted in reduced immunization coverage and an upsurge in vaccine hesitancy. In addition, the pandemic was associated with issues of antibiotic misuse and over-prescription. Conclusion: In conclusion, the COVID-19 pandemic has left a profound and multifaceted impact on the landscape of pediatric infectious diseases, ranging from the emergence of "long COVID" in children to significant changes in healthcare delivery, altered circulation patterns of various pathogens, and concerning disruptions in vaccination programs and antibiotic usage. What is Known: • COVID-19 usually presents with mild symptoms in children, although severe and late manifestations are possible. • The pandemic resulted in a dramatically increased use of health care services, as well as alterations in the circulation patterns of respiratory pathogens, decreased rates of other, non-respiratory, infections, disruption of routine childhood vaccination programs, and antibiotic misuse. What is New: • Possible strategies to tackle future outbreaks are presented, including changes in health care services utilization, implementation of updated vaccine programs and antibiotic stewardship protocols. • The decline in RSV and influenza circulation during COVID-19 was probably not primarily related to NPI measures, and rather related to other, non-NPI measures implementation, including specific pathogen-host interactions on the level of the biological niche (the nasopharynx).}, }
@article {pmid37727133, year = {2024}, author = {Franchini, M and Maggi, F and Focosi, D}, title = {ABO blood group-related mechanism of infection of SARS-CoV-2: an overview of systematic reviews.}, journal = {Clinical chemistry and laboratory medicine}, volume = {62}, number = {3}, pages = {396-401}, pmid = {37727133}, issn = {1437-4331}, mesh = {Humans ; *SARS-CoV-2 ; ABO Blood-Group System/genetics ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Systematic Reviews as Topic ; }, abstract = {Among the host genetic factors playing a role in the susceptibility to infectious diseases, the ABO blood group system is of utmost importance. Following the first reports in early 2020, the association between ABO blood groups and SARS-CoV-2 infection or COVID-19 severity has been thoroughly investigated. The aim of this narrative review is to provide an overview of systematic reviews regarding the link between ABO blood groups and such risks. The possible molecular mechanisms underlying these associations will also be discussed. ABO blood group has a robust association with susceptibility to infection but not with disease severity, and studies on long COVID anre still missing.Prov.}, }
@article {pmid37729625, year = {2023}, author = {Wang, J and Liu, R and Ma, H and Zhang, W}, title = {The Pathogenesis of COVID-19-Related Taste Disorder and Treatments.}, journal = {Journal of dental research}, volume = {102}, number = {11}, pages = {1191-1198}, doi = {10.1177/00220345231182926}, pmid = {37729625}, issn = {1544-0591}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Dysgeusia/complications ; Post-Acute COVID-19 Syndrome ; Taste Disorders/etiology ; *Taste Buds ; Taste ; }, abstract = {COVID-19, mainly manifested as acute respiratory distress syndrome, has afflicted millions of people worldwide since 2019. Taste dysfunction is a common early-stage symptom of COVID-19 infection that burdens patients for weeks or even permanently in some cases. Owing to its subjectivity and complexity, the mechanism of taste disorder is poorly studied. Previous studies have reported that the COVID-19 entry receptors are highly expressed in taste buds, thereby intensifying the cytocidal effect. Taste receptor cells are vulnerable to inflammation, and the COVID-19-induced cytokine storm causes secondary damage to taste function. Interferon and various proinflammatory cytokines can trigger cell apoptosis and disrupt the renewal of taste bud stem cells. This immune response can be further enhanced by the accumulation of Angiotensin II (Ang II) caused by an unbalanced local renin-angiotensin system (RAS) system. In addition, severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is neurotropic and can invade the brain through the olfactory bulb, affecting the nervous system. Other factors, such as host zinc deficiency, genetic susceptibility, sialic acid, and some neurotransmitters, also contribute to the pathogenesis process. Although several medical interventions have displayed effectiveness, only a few strategies exist for the treatment of postinfectious dysgeusia. Stem cell-based taste regeneration offers promise for long-term taste disorders. Clinical studies have demonstrated that stem cells can treat long COVID-19 through immune regulation. In dysgeusia, the differentiation of taste bud stem cells can be stimulated through exogenous epithelial-derived and neural-derived factors to regenerate taste buds. Tongue organoids are also emerging as functional taste buds, offering new insights into the study of taste regeneration. This review presents the current evidence of the pathogenesis of COVID-19-related dysgeusia, summarizes currently available treatments, and suggests future directions of taste regeneration therapy.}, }
@article {pmid37731320, year = {2023}, author = {Easter, QT and Matuck, BF and Warner, BM and Byrd, KM}, title = {Biogeographical Impacts of Dental, Oral, and Craniofacial Microbial Reservoirs.}, journal = {Journal of dental research}, volume = {102}, number = {12}, pages = {1303-1314}, pmid = {37731320}, issn = {1544-0591}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *Microbiota ; Mouth/microbiology ; Bacteria ; Multiomics ; }, abstract = {The human mouth, or oral cavity, is at the crossroads of our external and internal environments, and it is increasingly evident that local colonization of dental, oral, and craniofacial (DOC) tissues and cells by bacteria and viruses may also have systemic effects across myriad diseases and disorders. Better understanding of this phenomenon will require a holistic understanding of host-microbial interactions in both spatiotemporal and biogeographical contexts while also considering person-, organ-, tissue-, cell-, and molecular-level variation. After the acute phase interaction with microbes, the establishment of site-specific reservoirs constitutes an important relationship to understand within the human body; however, despite a preliminary understanding of how viral reservoirs originate and persist across the human body, the landscape of single-cell and spatial multiomic tools has challenged our current understanding of what cells and niches can support microbial reservoirs. The lack of complete understanding impacts research into these relevant topics and implementing precision care for microbial-induced or microbial-influenced diseases. Here, via the lens of acute and chronic microbial infections of the DOC tissues, the goal of this review is to highlight and link the emerging spatiotemporal biogeography of host-viral interactomics at 3 levels: (1) DOC cell types in distinct tissues, (2) DOC-associated microbes, and (3) niche-specific DOC pathologies. Further, we will focus on the impact of postacute infectious syndromes such as long COVID, neurodegenerative disorders, and other underappreciated postviral conditions. We will provide hypotheses about how DOC tissues may play roles systemically in these conditions. Throughout, we will underscore how COVID-19 has catalyzed a new understanding of these biological questions, discuss future directions to study these phenomena, and highlight the utility of noninvasive oral biofluids in screening, monitoring, and intervening to prevent and/or ameliorate human infectious diseases.}, }
@article {pmid37733584, year = {2024}, author = {Weissert, R}, title = {Nervous system-related tropism of SARS-CoV-2 and autoimmunity in COVID-19 infection.}, journal = {European journal of immunology}, volume = {54}, number = {1}, pages = {e2250230}, doi = {10.1002/eji.202250230}, pmid = {37733584}, issn = {1521-4141}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Autoimmunity ; Post-Acute COVID-19 Syndrome ; Endothelial Cells ; Nervous System ; Tropism ; }, abstract = {The effects of SARS-CoV-2 in COVID-19 on the nervous system are incompletely understood. SARS-CoV-2 can infect endothelial cells, neurons, astrocytes, and oligodendrocytes with consequences for the host. There are indications that infection of these CNS-resident cells may result in long-term effects, including emergence of neurodegenerative diseases. Indirect effects of infection with SARS-CoV-2 relate to the induction of autoimmune disease involving molecular mimicry or/and bystander activation of T- and B cells and emergence of autoantibodies against various self-antigens. Data obtained in preclinical models of coronavirus-induced disease gives important clues for the understanding of nervous system-related assault of SARS-CoV-2. The pathophysiology of long-COVID syndrome and post-COVID syndrome in which autoimmunity and immune dysregulation might be the driving forces are still incompletely understood. A better understanding of nervous-system-related immunity in COVID-19 might support the development of therapeutic approaches. In this review, the current understanding of SARS-CoV-2 tropism for the nervous system, the associated immune responses, and diseases are summarized. The data indicates that there is viral tropism of SARS-CoV-2 in the nervous system resulting in various disease conditions. Prevention of SARS-CoV-2 infection by means of vaccination is currently the best strategy for the prevention of subsequent tissue damage involving the nervous system.}, }
@article {pmid37738512, year = {2024}, author = {Röltgen, K and Boyd, SD}, title = {Antibody and B Cell Responses to SARS-CoV-2 Infection and Vaccination: The End of the Beginning.}, journal = {Annual review of pathology}, volume = {19}, number = {}, pages = {69-97}, doi = {10.1146/annurev-pathmechdis-031521-042754}, pmid = {37738512}, issn = {1553-4014}, support = {U54 CA260517/CA/NCI NIH HHS/United States ; R01 AI130398/AI/NIAID NIH HHS/United States ; R01 AI127877/AI/NIAID NIH HHS/United States ; U19 AI057229/AI/NIAID NIH HHS/United States ; U19 AI167903/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Pandemics ; *COVID-19 ; SARS-CoV-2 ; Antibodies ; Vaccination ; }, abstract = {As the COVID-19 pandemic has evolved during the past years, interactions between human immune systems, rapidly mutating and selected SARS-CoV-2 viral variants, and effective vaccines have complicated the landscape of individual immunological histories. Here, we review some key findings for antibody and B cell-mediated immunity, including responses to the highly mutated omicron variants; immunological imprinting and other impacts of successive viral antigenic variant exposures on antibody and B cell memory; responses in secondary lymphoid and mucosal tissues and non-neutralizing antibody-mediated immunity; responses in populations vulnerable to severe disease such as those with cancer, immunodeficiencies, and other comorbidities, as well as populations showing apparent resistance to severe disease such as many African populations; and evidence of antibody involvement in postacute sequelae of infection or long COVID. Despite the initial phase of the pandemic ending, human populations will continue to face challenges presented by this unpredictable virus.}, }
@article {pmid37742748, year = {2023}, author = {Steiner, S and Fehrer, A and Hoheisel, F and Schoening, S and Aschenbrenner, A and Babel, N and Bellmann-Strobl, J and Finke, C and Fluge, &#xd8; and Froehlich, L and Goebel, A and Grande, B and Haas, JP and Hohberger, B and Jason, LA and Komaroff, AL and Lacerda, E and Liebl, M and Maier, A and Mella, O and Nacul, L and Paul, F and Prusty, BK and Puta, C and Riemekasten, G and Ries, W and Rowe, PC and Sawitzki, B and Shoenfeld, Y and Schultze, JL and Seifert, M and Sepúlveda, N and Sotzny, F and Stein, E and Stingl, M and Ufer, F and Veauthier, C and Westermeier, F and Wirth, K and Wolfarth, B and Zalewski, P and Behrends, U and Scheibenbogen, C}, title = {Understanding, diagnosing, and treating Myalgic encephalomyelitis/chronic fatigue syndrome - State of the art: Report of the 2nd international meeting at the Charité Fatigue Center.}, journal = {Autoimmunity reviews}, volume = {22}, number = {11}, pages = {103452}, doi = {10.1016/j.autrev.2023.103452}, pmid = {37742748}, issn = {1873-0183}, mesh = {Humans ; *Fatigue Syndrome, Chronic/diagnosis/epidemiology/therapy ; Pandemics ; Post-Acute COVID-19 Syndrome ; Prevalence ; }, abstract = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a devastating disease affecting millions of people worldwide. Due to the 2019 pandemic of coronavirus disease (COVID-19), we are facing a significant increase of ME/CFS prevalence. On May 11th to 12th, 2023, the second international ME/CFS conference of the Charité Fatigue Center was held in Berlin, Germany, focusing on pathomechanisms, diagnosis, and treatment. During the two-day conference, more than 100 researchers from various research fields met on-site and over 700 attendees participated online to discuss the state of the art and novel findings in this field. Key topics from the conference included: the role of the immune system, dysfunction of endothelial and autonomic nervous system, and viral reactivation. Furthermore, there were presentations on innovative diagnostic measures and assessments for this complex disease, cutting-edge treatment approaches, and clinical studies. Despite the increased public attention due to the COVID-19 pandemic, the subsequent rise of Long COVID-19 cases, and the rise of funding opportunities to unravel the pathomechanisms underlying ME/CFS, this severe disease remains highly underresearched. Future adequately funded research efforts are needed to further explore the disease etiology and to identify diagnostic markers and targeted therapies.}, }
@article {pmid37748518, year = {2024}, author = {Iba, T and Connors, JM and Levy, JH}, title = {What Role Does Microthrombosis Play in Long COVID?.}, journal = {Seminars in thrombosis and hemostasis}, volume = {50}, number = {4}, pages = {527-536}, doi = {10.1055/s-0043-1774795}, pmid = {37748518}, issn = {1098-9064}, mesh = {Humans ; *COVID-19/complications ; *SARS-CoV-2 ; *Thrombosis/etiology ; *Post-Acute COVID-19 Syndrome ; Anticoagulants/therapeutic use ; Thromboinflammation ; }, abstract = {Soon after the outbreak of coronavirus disease 2019 (COVID-19), unexplained sustained fatigue, cognitive disturbance, and muscle ache/weakness were reported in patients who had recovered from acute COVID-19 infection. This abnormal condition has been recognized as "long COVID (postacute sequelae of COVID-19 [PASC])" with a prevalence estimated to be from 10 to 20% of convalescent patients. Although the pathophysiology of PASC has been studied, the exact mechanism remains obscure. Microclots in circulation can represent one of the possible causes of PASC. Although hypercoagulability and thrombosis are critical mechanisms of acute COVID-19, recent studies have reported that thromboinflammation continues in some patients, even after the virus has cleared. Viral spike proteins and RNA can be detected months after patients have recovered, findings that may be responsible for persistent thromboinflammation and the development of microclots. Despite this theory, long-term results of anticoagulation, antiplatelet therapy, and vascular endothelial protection are inconsistent, and could not always show beneficial treatment effects. In summary, PASC reflects a heterogeneous condition, and microclots cannot explain all the presenting symptoms. After clarification of the pathomechanisms of each symptom, a symptom- or biomarker-based stratified approach should be considered for future studies.}, }
@article {pmid37750203, year = {2023}, author = {Clark, IA and Vissel, B}, title = {Autocrine positive feedback of tumor necrosis factor from activated microglia proposed to be of widespread relevance in chronic neurological disease.}, journal = {Pharmacology research &amp; perspectives}, volume = {11}, number = {5}, pages = {e01136}, pmid = {37750203}, issn = {2052-1707}, mesh = {Humans ; Chronic Disease ; Cytokines ; Etanercept/pharmacology/therapeutic use ; Microglia ; *Nervous System Diseases/drug therapy ; Tumor Necrosis Factor Inhibitors ; *Tumor Necrosis Factor-alpha/physiology ; Feedback, Physiological ; }, abstract = {Over a decade's experience of post-stroke rehabilitation by administering the specific anti-TNF biological, etanercept, by the novel perispinal route, is consistent with a wide range of chronically diminished neurological function having been caused by persistent excessive cerebral levels of TNF. We propose that this TNF persistence, and cerebral disease chronicity, largely arises from a positive autocrine feedback loop of this cytokine, allowing the persistence of microglial activation caused by the excess TNF that these cells produce. It appears that many of these observations have never been exploited to construct a broad understanding and treatment of certain chronic, yet reversible, neurological illnesses. We propose that this treatment allows these chronically activated microglia to revert to their normal quiescent state, rather than simply neutralizing the direct harmful effects of this cytokine after its release from microglia. Logically, this also applies to the chronic cerebral aspects of various other neurological conditions characterized by activated microglia. These include long COVID, Lyme disease, post-stroke syndromes, traumatic brain injury, chronic traumatic encephalopathy, post-chemotherapy, post-irradiation cerebral dysfunction, cerebral palsy, fetal alcohol syndrome, hepatic encephalopathy, the antinociceptive state of morphine tolerance, and neurogenic pain. In addition, certain psychiatric states, in isolation or as sequelae of infectious diseases such as Lyme disease and long COVID, are candidates for being understood through this approach and treated accordingly. Perispinal etanercept provides the prospect of being able to treat various chronic central nervous system illnesses, whether they are of infectious or non-infectious origin, through reversing excess TNF generation by microglia.}, }
@article {pmid37753372, year = {2023}, author = {Ogarek, N and Oboza, P and Olszanecka-Glinianowicz, M and Kocelak, P}, title = {SARS-CoV-2 infection as a potential risk factor for the development of cancer.}, journal = {Frontiers in molecular biosciences}, volume = {10}, number = {}, pages = {1260776}, pmid = {37753372}, issn = {2296-889X}, abstract = {The COVID-19 pandemic has a significant impact on public health and the estimated number of excess deaths may be more than three times higher than documented in official statistics. Numerous studies have shown an increased risk of severe COVID-19 and death in patients with cancer. In addition, the role of SARS-CoV-2 as a potential risk factor for the development of cancer has been considered. Therefore, in this review, we summarise the available data on the potential effects of SARS-CoV-2 infection on oncogenesis, including but not limited to effects on host signal transduction pathways, immune surveillance, chronic inflammation, oxidative stress, cell cycle dysregulation, potential viral genome integration, epigenetic alterations and genetic mutations, oncolytic effects and reactivation of dormant cancer cells. We also investigated the potential long-term effects and impact of the antiviral therapy used in COVID-19 on cancer development and its progression.}, }
@article {pmid37760965, year = {2023}, author = {Boura, I and Qamar, MA and Daddoveri, F and Leta, V and Poplawska-Domaszewicz, K and Falup-Pecurariu, C and Ray Chaudhuri, K}, title = {SARS-CoV-2 and Parkinson's Disease: A Review of Where We Are Now.}, journal = {Biomedicines}, volume = {11}, number = {9}, pages = {}, pmid = {37760965}, issn = {2227-9059}, abstract = {Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has been discussed in the context of Parkinson's disease (PD) over the last three years. Now that we are entering the long-term phase of this pandemic, we are intrigued to look back and see how and why the community of patients with PD was impacted and what knowledge we have collected so far. The relationship between COVID-19 and PD is likely multifactorial in nature. Similar to other systemic infections, a probable worsening of PD symptoms secondary to COVID-19, either transient or persistent (long COVID), has been demonstrated, while the COVID-19-related mortality of PD patients may be increased compared to the general population. These observations could be attributed to direct or indirect damage from SARS-CoV-2 in the central nervous system (CNS) or could result from general infection-related parameters (e.g., hospitalization or drugs) and the sequelae of the COVID-19 pandemic (e.g., quarantine). A growing number of cases of new-onset parkinsonism or PD following SARS-CoV-2 infection have been reported, either closely (post-infectious) or remotely (para-infectious) after a COVID-19 diagnosis, although such a link remains hypothetical. The pathophysiological substrate of these phenomena remains elusive; however, research studies, particularly pathology studies, have suggested various COVID-19-induced degenerative changes with potential associations with PD/parkinsonism. We review the literature to date for answers considering the relationship between SARS-CoV-2 infection and PD/parkinsonism, examining pathophysiology, clinical manifestations, vaccination, and future directions.}, }
@article {pmid37761716, year = {2023}, author = {Calvache-Mateo, A and Heredia-Ciuró, A and Martín-Núñez, J and Hernández-Hernández, S and Reychler, G and López-López, L and Valenza, MC}, title = {Efficacy and Safety of Respiratory Telerehabilitation in Patients with Long COVID-19: A Systematic Review and Meta-Analysis.}, journal = {Healthcare (Basel, Switzerland)}, volume = {11}, number = {18}, pages = {}, pmid = {37761716}, issn = {2227-9032}, support = {19/02609//Ministerio de educaci&#xf3;n, cultura y deporte (ES)/ ; 20/01670//Ministerio de educaci&#xf3;n, cultura y deporte (ES)/ ; 21/00451//Ministerio de educaci&#xf3;n, cultura y deporte (ES)/ ; }, abstract = {The aim of this review was to identify, map, and synthesize the extent and nature of research activity on the use of telerehabilitation to support Long COVID-19 rehabilitation and examine the efficacy and safety of respiratory telerehabilitation in patients with Long COVID-19. A systematic review and meta-analysis of randomized controlled trials were performed. We included controlled trials that tested the effect of respiratory telerehabilitation interventions in patients with Long COVID-19 versus no intervention, usual care, placebo, or face-to-face intervention. The data were pooled, and a meta-analysis was completed for quality of life, dyspnea, lung function, anxiety and depression, respiratory muscle strength, functional capacity, and lower limb strength. Finally, 10 studies were included. The meta-analysis results show significant differences in favor of respiratory telerehabilitation in quality of life (p = 0.02), dyspnea (p < 0.00001), respiratory muscle strength (p < 0.001), functional capacity (p < 0.0001), and lower limb strength (p = 0.01) but not in lung function (p = 0.28) and anxiety and depression (p = 0.55). In addition, there were no statistically significant differences in adverse effects (p = 0.06) between the telerehabilitation and comparator groups. The results suggest that these interventions can improve quality of life, reduce dyspnea, and increase respiratory and lower extremity muscle strength as well as functional capacity in patients with Long COVID-19.}, }
@article {pmid37774781, year = {2023}, author = {Bellanti, JA and Novak, P and Faitelson, Y and Bernstein, JA and Castells, MC}, title = {The Long Road of Long COVID: Specific Considerations for the Allergist/Immunologist.}, journal = {The journal of allergy and clinical immunology. In practice}, volume = {11}, number = {11}, pages = {3335-3345}, doi = {10.1016/j.jaip.2023.09.014}, pmid = {37774781}, issn = {2213-2201}, mesh = {Humans ; Allergists ; *COVID-19 ; *Diabetes Mellitus, Type 2 ; *Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; Post-Acute COVID-19 Syndrome ; Quality of Life ; RNA, Viral ; SARS-CoV-2 ; }, abstract = {Long COVID (coronavirus disease 2019) syndrome, also known as post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is a new disorder that can develop after an acute infection with the SARS-CoV-2 virus. The condition is characterized by multiorgan system involvement with a wide range of symptoms that can vary in severity from mild to debilitating. Some of the common symptoms associated with long COVID syndrome include cardiovascular issues such as heart palpitations and chest pain; thrombotic events (eg, blood clotting disorders); metabolic problems (eg, type 2 diabetes); dysautonomia; paroxysmal orthostatic tachycardia syndrome; myalgic encephalomyelitis/chronic fatigue syndrome; reactivation of the Epstein-Barr virus; the presence of autoantibodies; chronic spontaneous urticaria (hives); and connective tissue diseases. Whereas long COVID syndrome can affect individuals from various backgrounds, certain populations may be at higher risk such as individuals of Hispanic and Latino heritage, as well as those with low socioeconomic status, although approximately one-third of affected patients have no known risk factors or preexisting conditions. Many survivors of COVID-19 struggle with multiple symptoms, increased disability, reduced function, and poor quality of life. Whereas vaccination has been the most significant intervention able to decrease the severity of acute SARS-Cov2 infection and curtail deaths, limited data are available related to its modulating effect on long COVID necessitating the need for further investigation. Furthermore, several inflammatory pathways have been proposed for the pathogenesis of long COVID that are the targets for ongoing clinical studies evaluating novel pharmacological agents. The purpose of the present report is to review the many factors associated with long COVID with a focus on those aspects that have relevance to the allergist-immunologist.}, }
@article {pmid37780134, year = {2023}, author = {Ogbonna, O and Bull, F and Spinks, B and Williams, D and Lewis, R and Edwards, A}, title = {The Impact of Being Homeless on the Clinical Outcomes of COVID-19: Systematic Review.}, journal = {International journal of public health}, volume = {68}, number = {}, pages = {1605893}, pmid = {37780134}, issn = {1661-8564}, mesh = {Humans ; *COVID-19/epidemiology ; Pandemics ; Post-Acute COVID-19 Syndrome ; *Ill-Housed Persons ; Mental Health ; }, abstract = {Objective: The homeless population experiences inequality in health compared with the general population, which may have widened during the COVID-19 pandemic. However, the impact of being homeless on the outcomes of COVID-19 is uncertain. This systematic review aimed to analyse the impact of experiencing homelessness on the clinical outcomes of COVID-19, including the effects on health inequalities. Methods: A review protocol was developed and registered in PROSPERO (PROSPERO registration 2022 CRD42022304941). Nine databases were searched in November 2022 to identify studies on homeless populations which contained primary research on the following outcomes of COVID-19: incidence, hospitalisation, mortality, long COVID, mental wellbeing, and evidence of inequalities. Included studies were summarised with narrative synthesis. Results: The searches yielded 8,233 initial hits; after screening, 41 studies were included. Overall, evidence showed that those in crowded living settings had a higher risk of COVID-19 infection compared to rough sleepers and the general population. The homeless population had higher rates of hospitalisation and mortality than the general population, lower vaccination rates, and suffered negative mental health impacts. Conclusion: This systematic review shows the homeless population is more susceptible to COVID-19 outcomes. Further research is needed to determine the actual impact of the pandemic on this population, and of interventions to mitigate overall risk, given the low certainty of findings from some of the low-quality evidence available. In addition, further research is required to ascertain the impact of long COVID on those experiencing homelessness, since the present review yielded no studies on this topic.}, }
@article {pmid37789860, year = {2023}, author = {Esposito, S and Deolmi, M and Ramundo, G and Puntoni, M and Caminiti, C and Principi, N}, title = {True prevalence of long COVID in children: a narrative review.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1225952}, pmid = {37789860}, issn = {1664-302X}, abstract = {Contrary to what is true for adults, little is known about pediatric long COVID (LC). Studies enrolling children are relatively few and extremely heterogeneous. This does not allow to draw definitive conclusions on the frequency and pathogenesis of pediatric LC and limits the development of appropriate and effective measures to contain the clinical, social and economic impact of this condition on the pediatric population. Depending on the methods used to collect and analyze data, studies have found that the incidence rate of pediatric LC may vary from about 25% to less than 5%. However, despite true prevalence of pediatric LC cannot be exactly defined, studies comparing children with previous COVID-19 and uninfected controls have shown that most of the clinical manifestations detected in infected children, mainly mood symptoms, mental health disorders and heart abnormalities could be diagnosed with similar frequency and severity in uninfected subjects also. This seems to indicate that SARS-CoV-2 is the cause of pediatric LC only in a part of children and other factors play a relevant role in this regard. Pandemic itself with the persistent disruption of child lives may have caused persistent stress in all the pediatric population causing mood symptoms, mental health disorders or several organ and body system functional alterations, regardless SARS-CoV-2 infection. These suppositions suggest the need for long-term physical control of all the children after COVID-19 especially when they were already suffering from an underlying disease or have had a severe disease. Moreover, attention should be paid to the assessment of change in children's emotional and behavioral functioning in order to assure adequate interventions for the best emotional and behavioral well being. However, whatever its origin, it seems highly likely that the prevalence of the pediatric LC is set to decline in the future. Preliminary observations seem to suggest that recently developed SARS-CoV-2 variants are associated with less severe COVID-19. This suggests that, as already seen in adults, a lower number of pediatric virus-associated LC cases should occur. Furthermore, the use of COVID-19 vaccines, reducing incidence and severity of SARS-CoV-2 infection, may reduce risk of LC development. Finally, elimination of restrictive measures should significantly reduce mood symptoms and mental health disorders.}, }
@article {pmid37793728, year = {2023}, author = {Grach, SL and Seltzer, J and Chon, TY and Ganesh, R}, title = {Diagnosis and Management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.}, journal = {Mayo Clinic proceedings}, volume = {98}, number = {10}, pages = {1544-1551}, doi = {10.1016/j.mayocp.2023.07.032}, pmid = {37793728}, issn = {1942-5546}, mesh = {Humans ; *Fatigue Syndrome, Chronic/diagnosis/etiology/therapy ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; COVID-19 Testing ; }, abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic neurologic disease often preceded by infection. There has been increased interest in ME/CFS recently because of its significant overlap with the post-COVID syndrome (long COVID or post-acute sequelae of COVID), with several studies estimating that half of patients with post-COVID syndrome fulfill ME/CFS criteria. Our concise review describes a generalist approach to ME/CFS, including diagnosis, evaluation, and management strategies.}, }
@article {pmid37795061, year = {2023}, author = {Sapna, F and Deepa, F and Sakshi, F and Sonam, F and Kiran, F and Perkash, RS and Bendari, A and Kumar, A and Rizvi, Y and Suraksha, F and Varrassi, G}, title = {Unveiling the Mysteries of Long COVID Syndrome: Exploring the Distinct Tissue and Organ Pathologies Linked to Prolonged COVID-19 Symptoms.}, journal = {Cureus}, volume = {15}, number = {9}, pages = {e44588}, pmid = {37795061}, issn = {2168-8184}, abstract = {The ongoing battle against the coronavirus disease 2019 (COVID-19) pandemic has encountered a complex aspect with the emergence of long COVID syndrome. There has been a growing prevalence of COVID-19-affected individuals experiencing persistent and diverse symptoms that extend beyond the initial infection phase. The phenomenon known as long COVID syndrome raises significant questions about the underlying mechanisms driving these enduring symptoms. This comprehensive analysis explores the complex domain of long COVID syndrome with a view to shed light on the specific tissue and organ pathologies contributing to its intricate nature. This review aims to analyze the various clinical manifestations of this condition across different bodily systems and explore potential mechanisms such as viral persistence, immune dysregulation, autoimmunity, and molecular mimicry. The goal is to gain a better understanding of the intricate network of pathologies contributing to long COVID syndrome. Understanding these distinct pathological indicators provides valuable insights into comprehending the complexities of long COVID and presents opportunities for developing more accurate diagnostic and therapeutic strategies, thereby improving the quality of patient care by effectively addressing the ever-changing medical challenge in a more focused manner.}, }
@article {pmid37797257, year = {2023}, author = {Baker, MG and Kvalsvig, A and Plank, MJ and Geoghegan, JL and Wall, T and Tukuitonga, C and Summers, J and Bennett, J and Kerr, J and Turner, N and Roberts, S and Ward, K and Betty, B and Huang, QS and French, N and Wilson, N}, title = {Continued mitigation needed to minimise the high health burden from COVID-19 in Aotearoa New Zealand.}, journal = {The New Zealand medical journal}, volume = {136}, number = {1583}, pages = {67-91}, doi = {10.26635/6965.6247}, pmid = {37797257}, issn = {1175-8716}, mesh = {Humans ; *COVID-19/epidemiology/prevention &amp; control ; New Zealand/epidemiology ; Post-Acute COVID-19 Syndrome ; Pandemics/prevention &amp; control ; Maori People ; }, abstract = {In this article we review the COVID-19 pandemic experience in Aotearoa New Zealand and consider the optimal ongoing response strategy. We note that this pandemic virus looks likely to result in future waves of infection that diminish in size over time, depending on such factors as viral evolution and population immunity. However, the burden of disease remains high with thousands of infections, hundreds of hospitalisations and tens of deaths each week, and an unknown burden of long-term illness (long COVID). Alongside this there is a considerable burden from other important respiratory illnesses, including influenza and RSV, that needs more attention. Given this impact and the associated health inequities, particularly for Māori and Pacific Peoples, we consider that an ongoing respiratory disease mitigation strategy is appropriate for New Zealand. As such, the previously described "vaccines plus" approach (involving vaccination and public health and social measures), should now be integrated with the surveillance and control of other important respiratory infections. Now is also a time for New Zealand to build on the lessons from the COVID-19 pandemic to enhance preparedness nationally and internationally. New Zealand's experience suggests elimination (or ideally exclusion) should be the default first choice for future pandemics of sufficient severity.}, }
@article {pmid37801299, year = {2023}, author = {El-Maradny, YA and Rubio-Casillas, A and Mohamed, KI and Uversky, VN and Redwan, EM}, title = {Intrinsic factors behind long-COVID: II. SARS-CoV-2, extracellular vesicles, and neurological disorders.}, journal = {Journal of cellular biochemistry}, volume = {124}, number = {10}, pages = {1466-1485}, doi = {10.1002/jcb.30486}, pmid = {37801299}, issn = {1097-4644}, mesh = {Humans ; SARS-CoV-2 ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; *Nervous System Diseases/diagnosis/etiology ; *Extracellular Vesicles ; }, abstract = {With the decline in the number of new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections, the World Health Organization announced the end of the SARS-CoV-2 pandemic. However, the repercussions of this viral pandemic may remain with us for a longer period of time, as it has remodeled the lives of humankind in many ways, including social and economic. Of course, its most important repercussions remain on the human health level. Long-coronavirus disease (COVID) or post-COVID is a state for which we do not have a concrete definition, a specific international classification of diseases Code, clear diagnostic tools, or well-known effective cures as of yet. In this second article from the Intrinsic Factors behind long-COVID Series, we try to link long-COVID symptoms with their causes, starting from the nervous system. Extracellular vesicles (ECVs) play very complex and ramified roles in the bodies of both healthy and not-healthy individuals. ECVs may facilitate the entry of many bioactive molecules and pathogens into the tissues and cells of the nervous system across the blood-brain barrier. Based on the size, quantity, and quality of their cargo, ECVs are directly proportional to the pathological condition and its severity through intertwined mechanisms that evoke inflammatory immune responses typically accompanied by pathological symptoms over variable time periods according to the type of these symptoms.}, }
@article {pmid37805875, year = {2023}, author = {De Vitis, R and Passiatore, M and Cilli, V and Apicella, M and Taccardo, G}, title = {SARS-COV-2 INFECTION AND INVOLVEMENT OF PERIPHERAL NERVOUS SYSTEM: A CASE SERIES OF CARPAL TUNNEL SYNDROME AGGRAVATION OR NEW ONSET WITH COVID-19 DISEASE AND A REVIEW OF LITERATURE.}, journal = {Georgian medical news}, volume = {}, number = {340-341}, pages = {61-66}, pmid = {37805875}, issn = {1512-0112}, mesh = {Humans ; *Carpal Tunnel Syndrome/diagnosis/epidemiology/etiology ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; SARS-CoV-2 ; Median Nerve ; *Median Neuropathy/complications ; }, abstract = {COVID-19 may be asymptomatic or have a typical presentation with fever, cough, anosmia, lymphocytopenia. In some cases, it occurs with a "chimeric" presentation, with more subtle and ambiguous symptoms which may be initially misdiagnosed and are referred to in long covid condition. A possible central and peripheral nervous system involvement has been recognized. We present our experience and review the literature about association between carpal tunnel syndrome (CTS) and hand's arthritis presenting a case series of patients who firmly state that their condition of CTS arised or got worse during a typical presentation of COVID-19. The outbreak of COVID-19 has resulted in significant global healthcare implications. While the respiratory manifestations of COVID-19 have been widely studied, there is emerging evidence suggesting potential associations between COVID-19 and various other health conditions. This review of the literature aims to investigate the potential relationship between COVID-19 and the development or exacerbation of CTS. By synthesizing the available literature on this topic, we aim to provide a comprehensive overview of the current knowledge and enhance our understanding of the potential implications of COVID-19 on CTS. Case series: In this article we report 13 cases of typical presentations of COVID-19 with fever, myalgia, and respiratory system involvement, with a simultaneous aggravation of the median nerve pre-existing neuralgia and some cases that developed a median nerve neuralgia during COVID-19, which came to the attention of the hand surgeon. Some cases had stable symptomatic CTS and were on waiting list for surgical carpal tunnel release, some cases were previously asymptomatic and developed a median nerve neuralgia during COVID-19. All patients referred to a rapid worsening of acral paraesthesia and neuralgic pain of the same quality of CTS and in the median nerve topography. Some patients developed typical COVID-19 symptoms and died; the others were surgically treated. CTS could be an atypical presentations of COVID-19 or a condition of long-covid disease and clinical and epidemiological significance needs to be fully studied. We presented cases of worsening of the median nerve neuralgia which presented among other symptoms of COVID infection. We conclude a causal relation may exist and needs to be further investigated.}, }
@article {pmid37808250, year = {2022}, author = {Zhou, X and Zhang, K and Liu, L and Zhao, Q and Huang, M and Shao, R and Wang, Y and Qu, B and Wang, Y}, title = {Anti-fatigue effect from Ginseng Radix et Rhizoma: a suggestive and promising treatment for long COVID.}, journal = {Acupuncture and herbal medicine}, volume = {2}, number = {2}, pages = {69-77}, pmid = {37808250}, issn = {2765-8619}, abstract = {Two years after the coronavirus disease 2019 (COVID-19) outbreak, an increasing number of patients continue to suffer from long COVID (LC), persistent symptoms, and/or delayed or long-term complications beyond the initial 4 weeks from the onset of symptoms. Constant fatigue is one of the most common LC symptoms, leading to severely reduced quality of life among patients. Ginseng Radix et Rhizoma-known as the King of Herbs in traditional Chinese medicine-has shown clinical anti-fatigue effects. In this review, we summarize the underlying anti-fatigue mechanisms of Ginseng Radix et Rhizoma extracts and their bioactive compounds, with a special focus on anti-viral, immune remodeling, endocrine system regulation, and metabolism, suggesting that Ginseng Radix et Rhizoma is a potentially promising treatment for LC, especially in regard to targeting fatigue.}, }
@article {pmid37811128, year = {2023}, author = {Luo, S and Zheng, Z and Bird, SR and Plebanski, M and Figueiredo, B and Jessup, R and Stelmach, W and Robinson, JA and Xenos, S and Olasoji, M and Wan, DWL and Sheahan, J and Itsiopoulos, C}, title = {An Overview of Long COVID Support Services in Australia and International Clinical Guidelines, With a Proposed Care Model in a Global Context.}, journal = {Public health reviews}, volume = {44}, number = {}, pages = {1606084}, pmid = {37811128}, issn = {0301-0422}, abstract = {Objective: To identify gaps among Australian Long COVID support services and guidelines alongside recommendations for future health programs. Methods: Electronic databases and seven government health websites were searched for Long COVID-specific programs or clinics available in Australia as well as international and Australian management guidelines. Results: Five Long COVID specific guidelines and sixteen Australian services were reviewed. The majority of Australian services provided multidisciplinary rehabilitation programs with service models generally consistent with international and national guidelines. Most services included physiotherapists and psychologists. While early investigation at week 4 after contraction of COVID-19 is recommended by the Australian, UK and US guidelines, this was not consistently implemented. Conclusion: Besides Long COVID clinics, future solutions should focus on early identification that can be delivered by General Practitioners and all credentialed allied health professions. Study findings highlight an urgent need for innovative care models that address individual patient needs at an affordable cost. We propose a model that focuses on patient-led self-care with further enhancement via multi-disciplinary care tools.}, }
@article {pmid37811836, year = {2023}, author = {Muyayalo, KP and Gong, GS and Kiyonga Aimeé, K and Liao, AH}, title = {Impaired immune response against SARS-CoV-2 infection is the major factor indirectly altering reproductive function in COVID-19 patients: a narrative review.}, journal = {Human fertility (Cambridge, England)}, volume = {26}, number = {4}, pages = {778-796}, doi = {10.1080/14647273.2023.2262757}, pmid = {37811836}, issn = {1742-8149}, mesh = {Humans ; Female ; Male ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Peptidyl-Dipeptidase A/physiology ; Inflammation ; Immunity ; }, abstract = {Coronavirus disease 2019 (COVID-19) is an infectious disease affecting multiple systems and organs, including the reproductive system. SARS-CoV-2, the virus that causes COVID-19, can damage reproductive organs through direct (angiotensin converting enzyme-2, ACE-2) and indirect mechanisms. The immune system plays an essential role in the homeostasis and function of the male and female reproductive systems. Therefore, an altered immune response related to infectious and inflammatory diseases can affect reproductive function and fertility in both males and females. This narrative review discussed the dysregulation of innate and adaptive systems induced by SARS-CoV-2 infection. We reviewed the evidence showing that this altered immune response in COVID-19 patients is the major indirect mechanism leading to adverse reproduction outcomes in these patients. We summarized studies reporting the long-term effect of SARS-CoV-2 infection on women's reproductive function and proposed the chronic inflammation and chronic autoimmunity characterizing long COVID as potential underlying mechanisms. Further studies are needed to clarify the role of autoimmunity and chronic inflammation (long COVID) in altered female reproduction function in COVID-19.}, }
@article {pmid37814605, year = {2023}, author = {Lim, JK and Njei, B}, title = {Clinical and Histopathological Discoveries in Patients with Hepatic Injury and Cholangiopathy Who Have Died of COVID-19: Insights and Opportunities for Intervention.}, journal = {Hepatic medicine : evidence and research}, volume = {15}, number = {}, pages = {151-164}, pmid = {37814605}, issn = {1179-1535}, abstract = {The COVID-19 pandemic has had a profound impact on global health, necessitating a comprehensive understanding of its diverse manifestations. Cholangiopathy, a condition characterized by biliary dysfunction, has emerged as a significant complication in COVID-19 patients. In this review, we report the epidemiology of COVID-19, describe the hepatotropism of SARS-CoV-2, and present the histopathology of acute liver injury (ALI) in COVID-19. Additionally, we explore the relationship between pre-existing chronic liver disease and COVID-19, shedding light on the increased susceptibility of these individuals to develop cholangiopathy. Through an in-depth analysis of cholangiopathy in COVID-19 patients, we elucidate its clinical manifestations, diagnostic criteria, and underlying pathogenesis involving inflammation, immune dysregulation, and vascular changes. Furthermore, we provide a summary of studies investigating post-COVID-19 cholangiopathy, highlighting the long-term effects and potential management strategies for this condition, and discussing opportunities for intervention, including therapeutic targets, diagnostic advancements, supportive care, and future research needs.}, }