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Bibliography on: Long Covid: Review Papers

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Robert J. Robbins is a biologist, an educator, a science administrator, a publisher, an information technologist, and an IT leader and manager who specializes in advancing biomedical knowledge and supporting education through the application of information technology. More About:  RJR | OUR TEAM | OUR SERVICES | THIS WEBSITE

RJR: Recommended Bibliography 15 May 2025 at 01:52 Created: 

Long Covid: Review Papers

Wikipedia: Long Covid refers to a group of health problems persisting or developing after an initial COVID-19 infection. Symptoms can last weeks, months or years and are often debilitating. Long COVID is characterised by a large number of symptoms, which sometimes disappear and reappear. Commonly reported symptoms of long COVID are fatigue, memory problems, shortness of breath, and sleep disorder. Many other symptoms can also be present, including headaches, loss of smell or taste, muscle weakness, fever, and cognitive dysfunction and problems with mental health. Symptoms often get worse after mental or physical effort, a process called post-exertional malaise. The causes of long COVID are not yet fully understood. Hypotheses include lasting damage to organs and blood vessels, problems with blood clotting, neurological dysfunction, persistent virus or a reactivation of latent viruses and autoimmunity. Diagnosis of long COVID is based on suspected or confirmed COVID-19 infection, symptoms and by excluding alternative diagnoses. Estimates of the prevalence of long COVID vary based on definition, population studied, time period studied, and methodology, generally ranging between 5% and 50%. Prevalence is less after vaccination.

Created with PubMed® Query: ( "long covid" AND review[SB] ) NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

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RevDate: 2025-05-14

Vu PD, S Abdi (2025)

Post-acute sequelae SARS-CoV-2 infection and neuropathic pain: a narrative review of the literature and future directions.

Pain management [Epub ahead of print].

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.

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.

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.

RevDate: 2025-05-14

Brewer KD, Santo NV, Samanta A, et al (2025)

Advances in Therapeutics for Chronic Lung Diseases: From Standard Therapies to Emerging Breakthroughs.

Journal of clinical medicine, 14(9): pii:jcm14093118.

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.

RevDate: 2025-05-14

Moustakli E, Stavros S, Michaelidis TM, et al (2025)

Long-Term Effects of COVID-19 on Women's Reproductive Health and Its Association with Autoimmune Diseases, Including Multiple Sclerosis.

Journal of clinical medicine, 14(9): pii:jcm14093057.

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.

RevDate: 2025-05-10
CmpDate: 2025-05-08

O'Mahoney LL, Routen A, Gillies C, et al (2025)

The risk of Long Covid symptoms: a systematic review and meta-analysis of controlled studies.

Nature communications, 16(1):4249.

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.

RevDate: 2025-05-09
CmpDate: 2025-05-07

Smail SW, Albarzinji N, Salih RH, et al (2025)

Microbiome dysbiosis in SARS-CoV-2 infection: implication for pathophysiology and management strategies of COVID-19.

Frontiers in cellular and infection microbiology, 15:1537456.

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.

RevDate: 2025-05-12

El-Naas A, Hamad O, Nair S, et al (2025)

New Onset of Type 1 and Type 2 Diabetes Post-COVID-19 Infection: A Systematic Review.

Emerging microbes & infections [Epub ahead of print].

AbstractCOVID-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 analyze 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.

RevDate: 2025-05-05

Vieira Junior JCA, Sander MRL, Matos JAO, et al (2025)

Neurological Post-Acute Sequelae of COVID-19 in Non-Hospitalized Patients: An Integrative Review.

Biological research for nursing [Epub ahead of print].

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.

RevDate: 2025-05-06
CmpDate: 2025-05-01

Bontempo AC, Bontempo JM, PR Duberstein (2025)

Ignored, dismissed, and minimized: Understanding the harmful consequences of invalidation in health care-A systematic meta-synthesis of qualitative research.

Psychological bulletin, 151(4):399-427.

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).

RevDate: 2025-05-01
CmpDate: 2025-04-30

Wang R, Lin M, Yu S, et al (2025)

Predictors of post-COVID-19 syndrome: a meta-analysis.

Journal of infection in developing countries, 19(4):490-497.

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.

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.

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.

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.

RevDate: 2025-04-30
CmpDate: 2025-04-30

Millhouse PW, Bloom RW, Beckstrand JN, et al (2025)

The Ganglia of the Head and Neck: Clinical Relevance for the Interventional Pain Physician.

Current pain and headache reports, 29(1):80.

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.

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.

RevDate: 2025-04-28

Jason LA, BZ Katz (2025)

Predisposing and Precipitating Factors in Epstein-Barr Virus-Caused Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Microorganisms, 13(4):.

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.

RevDate: 2025-04-28

Loboda D, Golba KS, Gurowiec P, et al (2025)

Variability in Arterial Stiffness and Vascular Endothelial Function After COVID-19 During 1.5 Years of Follow-Up-Systematic Review and Meta-Analysis.

Life (Basel, Switzerland), 15(4):.

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.

RevDate: 2025-04-27

Lan L, Wang Y, Chen Y, et al (2025)

A Review on the Prevalence and Treatment of Antibiotic Resistance Genes in Hospital Wastewater.

Toxics, 13(4):.

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.

RevDate: 2025-04-22

Bjorvatn B, Merikanto I, Chung F, et al (2025)

Sleep During Pandemic Times: Summary of Findings and Future Outlook Through the Lens of the International COVID Sleep Study (ICOSS).

Journal of sleep research [Epub ahead of print].

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.

RevDate: 2025-04-24
CmpDate: 2025-04-22

Cornish F, Sabaine B, Soares L, et al (2025)

The erasure of infection-associated chronic conditions: Critical interpretive synthesis of literature on healthcare for long COVID and related conditions in Brazil.

Global public health, 20(1):2490720.

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.

RevDate: 2025-04-17
CmpDate: 2025-04-17

Rubio-Casillas A, Rodríguez-Quintero CM, Hromić-Jahjefendić A, et al (2025)

The essential role of prebiotics in restoring gut health in long COVID.

Progress in molecular biology and translational science, 213:385-411.

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.

RevDate: 2025-04-17
CmpDate: 2025-04-17

Adilović M (2025)

COVID-19 related complications.

Progress in molecular biology and translational science, 213:259-314.

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.

RevDate: 2025-04-19
CmpDate: 2025-04-17

Morello R, De Rose C, Martino L, et al (2025)

Role of nutrient supplements in children with post-COVID condition: a retrospective preliminary observation and narrative review.

Italian journal of pediatrics, 51(1):119.

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.

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.

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).

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.

RevDate: 2025-04-16

Serafini RA, Frere JJ, Giosan IM, et al (2025)

SARS-CoV-2-induced sensory perturbations: A narrative review of clinical phenotypes, molecular pathologies, and possible interventions.

Brain, behavior, & immunity - health, 45:100983.

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.

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.

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.

RevDate: 2025-04-14
CmpDate: 2025-04-12

Marchesi N, Allegri M, Bruno GM, et al (2025)

Exploring the Potential of Dietary Supplements to Alleviate Pain Due to Long COVID.

Nutrients, 17(7):.

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.

RevDate: 2025-04-12

Abbas AH, Haji MR, Shimal AA, et al (2025)

A multidisciplinary review of long COVID to address the challenges in diagnosis and updated management guidelines.

Annals of medicine and surgery (2012), 87(4):2105-2117.

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.

RevDate: 2025-04-30
CmpDate: 2025-04-11

Gao J, Zhao D, Nouri HR, et al (2025)

Transcriptional Regulation of Mouse Mast Cell Differentiation and the Role of Human Lung Mast Cells in Airway Inflammation.

Immunological reviews, 331(1):e70026.

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.

RevDate: 2025-04-10
CmpDate: 2025-04-10

Verduzco-Gutierrez M, Fleming TK, AM Azola (2025)

Considerations for Long COVID Rehabilitation in Women.

Physical medicine and rehabilitation clinics of North America, 36(2):371-387.

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.

RevDate: 2025-05-11
CmpDate: 2025-04-08

Bona JP (2024)

Knowledge Representation and Management in the Age of Long Covid and Large Language Models: a 2022-2023 Survey.

Yearbook of medical informatics, 33(1):216-222.

OBJECTIVES: To select, present, and summarize cutting edge work in the field of Knowledge Representation and Management (KRM) published in 2022 and 2023.

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.

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.

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.

RevDate: 2025-04-23
CmpDate: 2025-04-09

Chung J, Pierce J, Franklin C, et al (2025)

Translating animal models of SARS-CoV-2 infection to vascular, neurological and gastrointestinal manifestations of COVID-19.

Disease models & mechanisms, 18(9):.

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.

RevDate: 2025-04-07

Sadowski J, Ostrowska SA, Klaudel T, et al (2025)

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 of neurovirology [Epub ahead of print].

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.

RevDate: 2025-04-03

Diener HC (2025)

[Not Available].

MMW Fortschritte der Medizin, 167(6):30.

RevDate: 2025-04-02

Tarasco MC, Iacomino N, Mantegazza R, et al (2025)

COVID-19, Epstein-Barr virus reactivation and autoimmunity: Casual or causal liaisons?.

Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi pii:S1684-1182(25)00076-3 [Epub ahead of print].

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.

RevDate: 2025-05-08
CmpDate: 2025-05-08

Iqbal MM, Iqbal A, RA Evans (2025)

Long COVID update: respiratory sequelae and symptoms.

Current opinion in supportive and palliative care, 19(2):95-102.

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.

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.

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.

RevDate: 2025-04-30
CmpDate: 2025-04-30

Ocampo FF, KB Holroyd (2025)

Updates on the neurological manifestations of SARS-CoV-2 infection.

Current opinion in infectious diseases, 38(3):234-241.

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.

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.

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.

RevDate: 2025-05-01
CmpDate: 2025-04-28

Sterian M, Naganathan T, Corrin T, et al (2025)

Evidence on the associations and safety of COVID-19 vaccination and post COVID-19 condition: an updated living systematic review.

Epidemiology and infection, 153:e62.

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%).

RevDate: 2025-03-30
CmpDate: 2025-03-28

Chen YH, Jan JS, Yang CH, et al (2025)

Cognitive Sequelae of COVID-19: Mechanistic Insights and Therapeutic Approaches.

CNS neuroscience & therapeutics, 31(3):e70348.

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.

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.

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.

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.

RevDate: 2025-03-29

Caliman-Sturdza OA, Gheorghita R, A Lobiuc (2025)

Neuropsychiatric Manifestations of Long COVID-19: A Narrative Review of Clinical Aspects and Therapeutic Approaches.

Life (Basel, Switzerland), 15(3):.

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.

RevDate: 2025-03-29

Stasi C (2025)

Post-COVID-19 Pandemic Sequelae in Liver Diseases.

Life (Basel, Switzerland), 15(3):.

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.

RevDate: 2025-03-27

Wei C, Jiang W, Luo M, et al (2025)

BBB breakdown caused by plasma membrane pore formation.

Trends in cell biology pii:S0962-8924(25)00064-9 [Epub ahead of print].

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.

RevDate: 2025-04-12
CmpDate: 2025-03-26

Kukreti S, Lu MT, Yeh CY, et al (2025)

Physiological Sensors Equipped in Wearable Devices for Management of Long COVID Persisting Symptoms: Scoping Review.

Journal of medical Internet research, 27:e69506.

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.

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.

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 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.

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.

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.

RevDate: 2025-03-26

Nyasulu PS, Tamuzi JL, Oliveira RKF, et al (2025)

COVID-19 and Parasitic Co-Infection: A Hypothetical Link to Pulmonary Vascular Disease.

Infectious disease reports, 17(2):.

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.

RevDate: 2025-03-26
CmpDate: 2025-03-23

McDowell CP, Tyner B, Shrestha S, et al (2025)

Effectiveness and tolerance of exercise interventions for long COVID: a systematic review of randomised controlled trials.

BMJ open, 15(3):e082441.

OBJECTIVES: To examine the effectiveness of exercise interventions to improve long COVID symptoms and the tolerance of exercise interventions among people with long COVID.

DESIGN: Systematic review.

DATA SOURCES: Medline via EBSCOhost, Embase via OVID and CENTRAL via the Cochrane Library up to 28 February 2023.

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.

DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data, and studies were narratively synthesised.

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.

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.

RevDate: 2025-05-09
CmpDate: 2025-03-30

Das Sarma J (2025)

Murine β-coronavirus spike protein: A major determinant of neuropathogenic properties.

Virology, 606:110499.

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.

RevDate: 2025-03-19

Patrascu R, CS Dumitru (2025)

Advances in Understanding Inflammation and Tissue Damage: Markers of Persistent Sequelae in COVID-19 Patients.

Journal of clinical medicine, 14(5):.

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.

RevDate: 2025-03-19

Mara G, Nini G, C Cotoraci (2025)

Impact of Pulmonary Comorbidities on COVID-19: Acute and Long-Term Evaluations.

Journal of clinical medicine, 14(5):.

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.

RevDate: 2025-03-18

Sanger BD, Alarachi A, McNeely HE, et al (2025)

Brain Fog and Cognitive Dysfunction in Posttraumatic Stress Disorder: An Evidence-Based Review.

Psychology research and behavior management, 18:589-606.

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".

RevDate: 2025-05-12
CmpDate: 2025-04-04

Baalbaki N, Slob EMA, Kazer SW, et al (2025)

The Omics Landscape of Long COVID-A Comprehensive Systematic Review to Advance Biomarker, Target and Drug Discovery.

Allergy, 80(4):932-948.

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.

RevDate: 2025-05-13
CmpDate: 2025-03-14

Li S, Dai B, Hou Y, et al (2025)

Effect of pulmonary rehabilitation for patients with long COVID-19: a systematic review and meta-analysis of randomized controlled trials.

Therapeutic advances in respiratory disease, 19:17534666251323482.

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.

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.

DESIGN: Systematic review and meta-analysis.

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.

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 ⩽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.

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.

TRIAL REGISTRATION: PROSPERO ID: CRD42024455008.

RevDate: 2025-05-12
CmpDate: 2025-05-12

Li D, Long F, Zhang S, et al (2025)

Mechanisms and treatment progress of neurological diseases of COVID and L-C19 in children.

Physiology international, 112(1):12-32.

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.

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.

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.

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.

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.

RevDate: 2025-05-13
CmpDate: 2025-03-13

Rudolph AE, Al Akoury N, Bogdanenko N, et al (2025)

Factors affecting the impact of COVID-19 vaccination on post COVID-19 conditions among adults: A systematic literature review.

Human vaccines & immunotherapeutics, 21(1):2474772.

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.

RevDate: 2025-05-12
CmpDate: 2025-05-12

Sun DS, Lien TS, HH Chang (2025)

Virus-Induced Pathogenic Antibodies: Lessons from Long COVID and Dengue Hemorrhage Fever.

International journal of molecular sciences, 26(5):.

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.

RevDate: 2025-05-12
CmpDate: 2025-03-13

Weigel B, Inderyas M, Eaton-Fitch N, et al (2025)

Health-related quality of life in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post COVID-19 Condition: a systematic review.

Journal of translational medicine, 23(1):318.

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.

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).

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.

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.

RevDate: 2025-05-12
CmpDate: 2025-05-12

Schwartz J, Capistrano K, Hussein H, et al (2025)

Oral SARS-CoV-2 Infection and Risk for Long Covid.

Reviews in medical virology, 35(2):e70029.

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).

RevDate: 2025-05-12
CmpDate: 2025-03-12

Taher MK, Salzman T, Banal A, et al (2025)

Global prevalence of post-COVID-19 condition: a systematic review and meta-analysis of prospective evidence.

Health promotion and chronic disease prevention in Canada : research, policy and practice, 45(3):112-138.

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).

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.

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.

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.

RevDate: 2025-03-13

Velati D, M Puoti (2025)

Real-world experience with therapies for SARS-CoV-2: Lessons from the Italian COVID-19 studies.

Le infezioni in medicina, 33(1):64-75.

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.

RevDate: 2025-03-13

Monsalve DM, Acosta-Ampudia Y, Acosta NG, et al (2025)

NETosis: A key player in autoimmunity, COVID-19, and long COVID.

Journal of translational autoimmunity, 10:100280.

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.

RevDate: 2025-05-09
CmpDate: 2025-05-09

Emery I, C Rosen (2025)

Adult Long Coronavirus Disease 2019: Definition, Prevalence Pathophysiology, and Clinical Manifestations.

Infectious disease clinics of North America, 39(2):345-360.

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.

RevDate: 2025-05-12
CmpDate: 2025-03-10

Cavarelli M (2025)

Ghosts of the virus : unmasking the persistent threat of SARS-CoV-2 in Long COVID.

Virologie (Montrouge, France), 29(1):57-68.

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.

RevDate: 2025-05-12
CmpDate: 2025-03-10

Cavarelli M (2025)

[Ghosts of the virus : unmasking the persistent threat of SARS-CoV-2 in Long COVID].

Virologie (Montrouge, France), 29(1):41-53.

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.

RevDate: 2025-03-08

Sakellaropoulos SG, Sakellaropoulos PG, Steinberg BS, et al (2025)

Five Years of Long COVID Syndrome: An Updated Review on Cardiometabolic and Psychiatric Aspects.

Cardiology research, 16(2):81-85.

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.

RevDate: 2025-03-08

Talkington GM, Kolluru P, Gressett TE, et al (2024)

Neurological sequelae of long COVID: a comprehensive review of diagnostic imaging, underlying mechanisms, and potential therapeutics.

Frontiers in neurology, 15:1465787.

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.

RevDate: 2025-03-03

Wang J, Xiong Y, Song Z, et al (2025)

Progress in research on osteoporosis secondary to SARS-CoV-2 infection.

Animal models and experimental medicine [Epub ahead of print].

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.

RevDate: 2025-05-10
CmpDate: 2025-05-10

Naiditch H, Betts MR, Larman HB, et al (2024)

Immunologic and inflammatory consequences of SARS-CoV-2 infection and its implications in renal disease.

Frontiers in immunology, 15:1376654.

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.

RevDate: 2025-03-01

Leitzke M, Roach DT, Hesse S, et al (2025)

Long COVID - a critical disruption of cholinergic neurotransmission?.

Bioelectronic medicine, 11(1):5.

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.

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 (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 α4β2 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.

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.

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.

RevDate: 2025-02-28

Aliberti A, Gasparro R, Mignogna M, et al (2025)

Unveiling the Oral Lesions, Dysgeusia and Osteonecrosis Related to COVID-19: A Comprehensive Systematic Review.

Journal of clinical medicine, 14(4):.

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.

RevDate: 2025-05-10
CmpDate: 2025-02-26

Smyth NJ, S Blitshteyn (2025)

Language Matters: What Not to Say to Patients with Long COVID, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, and Other Complex Chronic Disorders.

International journal of environmental research and public health, 22(2):.

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.

RevDate: 2025-02-28

Whitaker-Hardin B, McGregor KM, Uswatte G, et al (2025)

A Narrative Review of the Efficacy of Long COVID Interventions on Brain Fog, Processing Speed, and Other Related Cognitive Outcomes.

Biomedicines, 13(2):.

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.

RevDate: 2025-02-27

Ayyoub S, Dhillon NK, O Tura-Ceide (2025)

Genetics of Long COVID: Exploring the Molecular Drivers of Persistent Pulmonary Vascular Disease Symptoms.

Infectious disease reports, 17(1):.

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.

RevDate: 2025-05-09
CmpDate: 2025-02-24

Mink S, Wilhelm F, Cadamuro J, et al (2025)

Anti-SARS-CoV-2 Antibodies in Long-COVID-Markers of Protection or Elevated Risk? A Systematic Review.

Reviews in medical virology, 35(2):e70027.

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.

RevDate: 2025-02-25

Łukomska E, Kloc K, Kowalska M, et al (2025)

Healthcare Resource Utilization (HCRU) and Direct Medical Costs Associated with Long COVID or Post-COVID-19 Conditions: Findings from a Literature Review.

Journal of market access & health policy, 13(1):7.

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.

RevDate: 2025-02-21

Ivlev I, Wagner J, Phillips T, et al (2025)

Interventions for Long COVID: A Narrative Review.

Journal of general internal medicine [Epub ahead of print].

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.

RevDate: 2025-05-09
CmpDate: 2025-05-09

Zhang Y, Chen H, Li Y, et al (2025)

Animal Models for Long COVID: Current Advances, Limitations, and Future Directions.

Journal of medical virology, 97(2):e70237.

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.

RevDate: 2025-02-22

Ewing AG, Salamon S, Pretorius E, et al (2025)

Review of organ damage from COVID and Long COVID: a disease with a spectrum of pathology.

Medical review (2021), 5(1):66-75.

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.

RevDate: 2025-04-16
CmpDate: 2025-04-11

Tsang MS, Zhou IW, Zhang AL, et al (2025)

Chinese herbal medicine for dyspnea and persistent symptoms of long COVID: A systematic review and meta-analysis of randomized controlled trials.

Journal of integrative medicine, 23(2):126-137.

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.

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).

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.

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.

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].

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 = -0.2, 95% confidence interval [CI] = -0.65 to 0.25) with moderate certainty, and reduces fatigue on the Borg Scale (MD = -0.48, 95% CI = -0.74 to -0.22) with low certainty. CHM clinically reduces depression on Hamilton Depression Rating Scale score (MD = -6.00, 95% CI = -7.56 to -4.44) and anxiety on Hamilton Anxiety Rating Scale score (MD = -6.10, 95% CI = -7.67 to -4.53), and reduces insomnia on the Insomnia Severity Index (MD = -4.86, 95% CI = -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 = -15.92, 95% CI = -10.20 to 42.05) with substantial heterogeneity (I[2] = 68%) and low certainty.

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.

RevDate: 2025-05-08
CmpDate: 2025-05-08

Panesar A, Gharanei P, Khovanova N, et al (2024)

Thyroid function during COVID-19 and post-COVID complications in adults: a systematic review.

Frontiers in endocrinology, 15:1477389.

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.

RevDate: 2025-02-20

Smadja DM, MM Abreu (2025)

Hyperthermia and targeting heat shock proteins: innovative approaches for neurodegenerative disorders and Long COVID.

Frontiers in neuroscience, 19:1475376.

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.

RevDate: 2025-05-08
CmpDate: 2025-03-12

Foreman L, Child B, Saywell I, et al (2025)

Cognitive reserve moderates the effect of COVID-19 on cognition: A systematic review and meta-analysis of individual participant data.

Neuroscience and biobehavioral reviews, 171:106067.

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.

RevDate: 2025-04-25
CmpDate: 2025-04-25

Syed AM, Karius AK, Ma J, et al (2025)

Mitochondrial Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Physiology (Bethesda, Md.), 40(4):0.

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.

RevDate: 2025-05-08
CmpDate: 2025-05-08

Talwar S, Harker JA, Openshaw PJM, et al (2025)

Autoimmunity in long COVID.

The Journal of allergy and clinical immunology, 155(4):1082-1094.

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.

RevDate: 2025-05-08
CmpDate: 2025-05-08

Smith DS, Postma M, Fisman D, et al (2025)

Cost-effectiveness models assessing COVID-19 booster vaccines across eight countries: A review of methods and data inputs.

Vaccine, 51:126879.

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.

RevDate: 2025-05-07
CmpDate: 2025-02-22

Soltsov M, Jang DH, Kim JH, et al (2025)

Understanding neural mechanisms and the use of targeted non-invasive brain stimulation for treatment of post-stroke fatigue: A scoping review.

Journal of the neurological sciences, 470:123399.

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.

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 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.

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.

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.

RevDate: 2025-05-07
CmpDate: 2025-03-01

Schurr M, Graf J, Junne F, et al (2025)

Psychotherapy in patients with long/post-COVID - A systematic review on the feasibility, acceptability, safety, and efficacy of available and emerging interventions.

Journal of psychosomatic research, 190:112048.

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.

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.

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.

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.

RevDate: 2025-04-26
CmpDate: 2025-04-26

Proal AD, Aleman S, Bomsel M, et al (2025)

Targeting the SARS-CoV-2 reservoir in long COVID.

The Lancet. Infectious diseases, 25(5):e294-e306.

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.

RevDate: 2025-02-14

Zhang T, Li Z, Mei Q, et al (2025)

Cardiovascular outcomes in long COVID-19: a systematic review and meta-analysis.

Frontiers in cardiovascular medicine, 12:1450470.

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.

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.

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.

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.

PROSPERO [CRD42022353965].

RevDate: 2025-05-07
CmpDate: 2025-05-07

Dieter RS, Kempaiah P, Dieter EG, et al (2025)

Cardiovascular Symposium on Perspectives in Long COVID.

Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis, 31:10760296251319963.

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.

RevDate: 2025-05-07
CmpDate: 2025-05-07

Kell DB, E Pretorius (2025)

The Proteome Content of Blood Clots Observed Under Different Conditions: Successful Role in Predicting Clot Amyloid(ogenicity).

Molecules (Basel, Switzerland), 30(3):.

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.

RevDate: 2025-02-15

Honorato-Cia C, Cacho-Asenjo E, Martinez-Simon A, et al (2025)

Long COVID Research, 2020-2024: A PubMed-Based Bibliometric Analysis.

Healthcare (Basel, Switzerland), 13(3):.

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.

RevDate: 2025-05-07
CmpDate: 2025-02-13

Dorczok MC, Mittmann G, Mossaheb N, et al (2025)

Dietary Supplementation for Fatigue Symptoms in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)-A Systematic Review.

Nutrients, 17(3):.

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.

RevDate: 2025-05-07
CmpDate: 2025-05-07

Salzmann S, de Vroege L, Engelmann P, et al (2025)

Assessment of psychosocial aspects in adults in post-COVID-19 condition: the EURONET-SOMA recommendations on core outcome domains for clinical and research use.

BMC medicine, 23(1):81.

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.

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.

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.

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.

RevDate: 2025-05-08
CmpDate: 2025-02-10

Alie MS, Tesema GA, Abebe GF, et al (2025)

The prolonged health sequelae "of the COVID-19 pandemic" in sub-Saharan Africa: a systematic review and meta-analysis.

Frontiers in public health, 13:1415427.

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.

OBJECTIVE: This study aimed to systematically synthesize evidence on the persistent sequelae of COVID-19 and their predictors in sub-Saharan Africa.

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.

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 = 4.34 (95% CI: 1.28-14.72)], providing a comprehensive understanding of the factors influencing long COVID-19 outcomes.

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.

Clinicaltrial.gov, identifier CRD42024501158.

RevDate: 2025-03-15

Pouliopoulou DV, Hawthorne M, MacDermid JC, et al (2025)

Prevalence and Impact of Postexertional Malaise on Recovery in Adults With Post-COVID-19 Condition: A Systematic Review With Meta-analysis.

Archives of physical medicine and rehabilitation pii:S0003-9993(25)00501-5 [Epub ahead of print].

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.

DATA SOURCES: We searched MEDLINE, Embase, CENTRAL, CINAHL, PsychINFO, and clinical trial registries from inception until February 11, 2025.

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.

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.

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.

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.

RevDate: 2025-05-06
CmpDate: 2025-05-06

Kumar M, Baig MS, K Bhardwaj (2025)

Advancements in the development of antivirals against SARS-Coronavirus.

Frontiers in cellular and infection microbiology, 15:1520811.

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.

RevDate: 2025-05-06
CmpDate: 2025-02-06

Tudorache Pantazi MA, Gadea-Doménech M, R Espert Tortajada (2025)

[Cognition and Long COVID: A PRISMA Systematic Review of Longitudinal Studies].

Revista de neurologia, 79(12):37385.

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.

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.

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.

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.

RevDate: 2025-05-06
CmpDate: 2025-05-06

Low ZXB, Yong SJ, Alrasheed HA, et al (2025)

Serotonergic psychedelics as potential therapeutics for post-COVID-19 syndrome (or Long COVID): A comprehensive review.

Progress in neuro-psychopharmacology & biological psychiatry, 137:111279.

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.

OBJECTIVES: Our review aims to elucidate potential mechanisms by which serotonergic psychedelics may alleviate the symptoms of PCS.

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.

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.

RevDate: 2025-05-05
CmpDate: 2025-02-05

Araújo FC, Amaral ACD, Silva HJ, et al (2025)

Autoantibodies as potential prognostic factors for clinical outcomes related to COVID-19: a systematic review of inception prospective cohort studies with GRADE recommendations.

Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas, 58:e13965.

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.

RevDate: 2025-04-25
CmpDate: 2025-02-05

Prediger KM, Ribeiro AC, SCDSA Uehara (2025)

Prevalent symptoms and characteristics of the Long COVID-19 population: a scoping review.

Revista latino-americana de enfermagem, 33:e4479.

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.

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.

RevDate: 2025-05-05
CmpDate: 2025-03-27

Tcheroyan R, Makhoul P, S Simpson (2025)

An updated review of pulmonary radiological features of acute and chronic COVID-19.

Current opinion in pulmonary medicine, 31(3):183-195.

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.

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.

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.

RevDate: 2025-02-05

Schwendinger F, Infanger D, Maurer DJ, et al (2024)

Medium- to long-term health condition of patients post-COVID-19, exercise intolerance and potential mechanisms: A narrative review and perspective.

SAGE open medicine, 12:20503121241296701.

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.

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 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.

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. ⩾18 months) and well-matched control groups are lacking. The findings may aid the development of rehabilitation regimes for post-COVID-19 syndrome.

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.

RevDate: 2025-02-06

Livieratos A, Lockley SW, S Tsiodras (2025)

Post infectious fatigue and circadian rhythm disruption in long-COVID and other infections: a need for further research.

EClinicalMedicine, 80:103073.

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.

RevDate: 2025-05-05
CmpDate: 2025-05-05

Khan MS, Miller AJ, Ejaz A, et al (2025)

Cerebral Blood Flow in Orthostatic Intolerance.

Journal of the American Heart Association, 14(3):e036752.

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.

RevDate: 2025-05-09
CmpDate: 2025-05-04

Saha A, Choudhary S, Walia P, et al (2025)

Transformative approaches in SARS-CoV-2 management: Vaccines, therapeutics and future direction.

Virology, 604:110394.

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.

RevDate: 2025-05-05
CmpDate: 2025-04-29

Braun J (2025)

[Chronic pain syndrome in musculoskeletal diseases-how different are fibromyalgia and long COVID?-Part 2].

Zeitschrift fur Rheumatologie, 84(4):320-329.

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.

RevDate: 2025-04-29
CmpDate: 2025-04-29

Braun J (2025)

[Chronic pain syndrome in musculoskeletal diseases-how different are fibromyalgia and long Covid?-Part 1].

Zeitschrift fur Rheumatologie, 84(4):312-319.

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.

RevDate: 2025-02-04

Han Y, Dai Y, Wang K, et al (2025)

Post-pandemic insights on COVID-19 and premature ovarian insufficiency.

Open life sciences, 20(1):20221028.

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.

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RJR Experience and Expertise

Researcher

Robbins holds BS, MS, and PhD degrees in the life sciences. He served as a tenured faculty member in the Zoology and Biological Science departments at Michigan State University. He is currently exploring the intersection between genomics, microbial ecology, and biodiversity — an area that promises to transform our understanding of the biosphere.

Educator

Robbins has extensive experience in college-level education: At MSU he taught introductory biology, genetics, and population genetics. At JHU, he was an instructor for a special course on biological database design. At FHCRC, he team-taught a graduate-level course on the history of genetics. At Bellevue College he taught medical informatics.

Administrator

Robbins has been involved in science administration at both the federal and the institutional levels. At NSF he was a program officer for database activities in the life sciences, at DOE he was a program officer for information infrastructure in the human genome project. At the Fred Hutchinson Cancer Research Center, he served as a vice president for fifteen years.

Technologist

Robbins has been involved with information technology since writing his first Fortran program as a college student. At NSF he was the first program officer for database activities in the life sciences. At JHU he held an appointment in the CS department and served as director of the informatics core for the Genome Data Base. At the FHCRC he was VP for Information Technology.

Publisher

While still at Michigan State, Robbins started his first publishing venture, founding a small company that addressed the short-run publishing needs of instructors in very large undergraduate classes. For more than 20 years, Robbins has been operating The Electronic Scholarly Publishing Project, a web site dedicated to the digital publishing of critical works in science, especially classical genetics.

Speaker

Robbins is well-known for his speaking abilities and is often called upon to provide keynote or plenary addresses at international meetings. For example, in July, 2012, he gave a well-received keynote address at the Global Biodiversity Informatics Congress, sponsored by GBIF and held in Copenhagen. The slides from that talk can be seen HERE.

Facilitator

Robbins is a skilled meeting facilitator. He prefers a participatory approach, with part of the meeting involving dynamic breakout groups, created by the participants in real time: (1) individuals propose breakout groups; (2) everyone signs up for one (or more) groups; (3) the groups with the most interested parties then meet, with reports from each group presented and discussed in a subsequent plenary session.

Designer

Robbins has been engaged with photography and design since the 1960s, when he worked for a professional photography laboratory. He now prefers digital photography and tools for their precision and reproducibility. He designed his first web site more than 20 years ago and he personally designed and implemented this web site. He engages in graphic design as a hobby.

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Although new treatments and vaccines have greatly reduced the acute threat of covid-19, many people who contract the disease find themselves with a persistent set of symptoms that are at best uncomfortable and at worst debilitating — long covid. R. Robbins

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Collection of publications by R J Robbins

Reprints and preprints of publications, slide presentations, instructional materials, and data compilations written or prepared by Robert Robbins. Most papers deal with computational biology, genome informatics, using information technology to support biomedical research, and related matters.

Research Gate page for R J Robbins

ResearchGate is a social networking site for scientists and researchers to share papers, ask and answer questions, and find collaborators. According to a study by Nature and an article in Times Higher Education , it is the largest academic social network in terms of active users.

Curriculum Vitae for R J Robbins

short personal version

Curriculum Vitae for R J Robbins

long standard version

RJR Picks from Around the Web (updated 11 MAY 2018 )