@article {pmid40934937,
year = {2025},
author = {Wilhelm, F and Cadamuro, J and Mink, S},
title = {Autoantibodies in long COVID: a systematic review.},
journal = {The Lancet. Infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/S1473-3099(25)00411-6},
pmid = {40934937},
issn = {1474-4457},
abstract = {Post-COVID-19 condition (also known as long COVID) affects a substantial proportion of individuals who have been infected with SARS-CoV-2, profoundly affecting their daily lives and work. Diagnosis and prognosis of long COVID are complex and hindered by heterogeneous symptoms and the absence of validated biomarkers. This systematic review synthesises current evidence on the association between autoantibodies and long COVID, with the goal of evaluating their prognostic and diagnostic utility. Studies published in the PubMed and MEDLINE databases between Jan 1, 2020, and June 10, 2025, were considered. Study selection and quality assessment were done independently by two researchers. Of the 1113 publications screened, 44 studies met the inclusion criteria, with a total of 7571 participants, including 3372 individuals with long COVID. 31 (71%) studies reported an association between autoantibodies and long COVID; however, there was substantial heterogeneity in study design, type and timing of antibody measurements, and long COVID definitions. Several autoantibodies have been associated with long COVID occurrence, symptoms, and severity. Antinuclear antibodies, and autoantibodies targeting G protein-coupled receptors and chemokines, have emerged as potential biomarkers for aiding in the diagnosis, prognosis, and assessment of disease severity in long COVID. However, larger studies are needed to confirm the diagnostic and prognostic utility of these autoantibodies in the context of long COVID.},
}

@article {pmid40930270,
year = {2025},
author = {Walker, TA and Kohler, JZ and Haddad, MM},
title = {Long COVID: Current landscape of neurocognitive sequalae and opportunities to improve care management.},
journal = {Brain, behavior, and immunity},
volume = {},
number = {},
pages = {106108},
doi = {10.1016/j.bbi.2025.106108},
pmid = {40930270},
issn = {1090-2139},
}

@article {pmid40922860,
year = {2025},
author = {Potluri, S and Chittiprol, N and Varaganti, V and Avr, V and Vadakedath, S and Arvapally, D and Vemulapalli, C and Begum, GS and Madamsetti, N and Kandi, V},
title = {The Association of SARS-CoV-2 Infection and COVID-19 Vaccination With Sudden Death: An Explorative Review.},
journal = {Cureus},
volume = {17},
number = {8},
pages = {e89527},
pmid = {40922860},
issn = {2168-8184},
abstract = {Since its discovery, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has become the epicenter of public health concern. This was mainly attributed to the complexity of COVID-19 that resulted in variable disease progression with some developing asymptomatic infections, some suffering mild to moderate infections that resolved without the need for hospitalizations, and a few infected persons developing severe infections that required intensive care unit (ICU) admission and mechanical ventilation. The COVID-19 pandemic spread globally, affecting billions of people and killing millions. Most of the consequences were related to the novelty of the virus, poor understanding of its pathogenesis, and the lack of a specific antiviral drug and vaccine. The vaccines, although manufactured and made available to the public, were approved for emergency use before the completion of human clinical trials. Moreover, the continuous emergence of viruses following mutations resulted in the emergence of viral variants. This has led to doubts over the efficacy of vaccines. Vaccine inequity, represented by the disproportionate availability and distribution of vaccines among the rich and poor, concerns over long-term safety, and hesitancy, affected COVID-19 vaccination, thereby increasing the spread of SARS-CoV-2. Although the COVID-19 pandemic is no longer considered a public health emergency of international concern (PHEIC), the repercussions of the pandemic are still evident in the form of long COVID and post-COVID functional health status (PCFHS), wherein individuals who were previously infected continue to suffer organ dysfunction, primarily affecting the lungs and other organs of the body. During and after the pandemic, COVID-19 and probably vaccination were attributed to the death of many individuals, which were categorized as sudden death (SD) and sudden unnatural death (SUD). It is unclear if these deaths were a result of previous SARS-CoV-2 infection and prior COVID-19 vaccination or both. There are several instances of infected and recovered individuals who were healthy but suddenly developed complications and died. Through this explorative review, we aim to comprehend the role that SARS-CoV-2 infection and/or COVID-19 vaccination play in predisposing people to cardiovascular system (CVS) and central nervous system (CNS) disorders that can result in SD and SUD.},
}

@article {pmid40910058,
year = {2025},
author = {Mazzali, C and Magnoni, P and Zucchi, A and Maifredi, G and Cavalieri d'Oro, L and Gambino, ML and Fanetti, AC and Perotti, PG and Villa, M and Valsecchi, MG and Vigani, D and Lucifora, C and Russo, AG},
title = {Strategies for population-level identification of post-acute sequelae of COVID-19 through health administrative data.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1637112},
pmid = {40910058},
issn = {2296-2565},
mesh = {Humans ; *COVID-19/complications/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; },
abstract = {INTRODUCTION: Post-acute sequelae of COVID-19 (PASC) encompass several clinical outcomes, from new-onset symptoms to both acute and chronic diagnoses, including pulmonary and extrapulmonary manifestations. Health administrative data (HAD) from health information systems allow population-level analyses of such outcomes. Our primary aim was to identify clinical conditions potentially attributable to SARS-CoV-2 infection, and the types of HAD and "diagnostic criteria" used for their detection.

METHODS: We performed a literature review to identify HAD-based cohort studies assessing the association between SARS-CoV-2 infection and medium-/long-term outcomes in the general population. From each included study, we extracted data on design, algorithms used for outcome identification (sources, coding systems, codes, time criteria/thresholds), and whether significant associations with SARS-CoV-2 infection were reported.

RESULTS: We identified six studies investigating acute and chronic conditions grouped by clinical domain (cardiovascular, respiratory, neurologic, mental health, endocrine/metabolic, pediatric, miscellaneous). Two studies also addressed the onset of specific symptoms. Cardio/cerebrovascular conditions were most studied, with significant associations reported for deep vein thrombosis, heart failure, atrial fibrillation, and coronary artery disease. Conditions in other domains were less investigated, with inconsistent findings. Only three studies were designed as test-positive vs. test-negative comparisons.

DISCUSSION: Heterogeneity in data sources, study design, and outcome definitions hinder the comparability of studies and explain the inconsistencies in findings about associations with SARS-CoV-2 infection. Rigorously designed studies on large populations with wide availability of data from health information systems are needed for population-level analyses on PASC, and especially on its impact on chronic diseases and their future burden on healthcare systems.},
}

Humans
*COVID-19/complications/epidemiology
Post-Acute COVID-19 Syndrome
SARS-CoV-2

@article {pmid40908304,
year = {2025},
author = {Ivković, V and Anandh, U and Bell, S and Kronbichler, A and Soler, MJ and Bruchfeld, A},
title = {Long COVID and the kidney.},
journal = {Nature reviews. Nephrology},
volume = {},
number = {},
pages = {},
pmid = {40908304},
issn = {1759-507X},
abstract = {Long coronavirus disease (COVID) - commonly defined as symptoms and/or long-term effects that persist for at least 3 months after acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and cannot be explained by an alternative diagnosis - is a complex, multifaceted and heterogeneous disease that affects many organ systems, including the kidney. COVID-19 can cause acute kidney injury, and several studies have reported an increased risk of chronic kidney disease (CKD) following COVID-19, suggesting that CKD can be a manifestation of long COVID. Furthermore, patients with CKD are at an increased risk of severe COVID-19 and of long COVID. COVID-19 has also been associated with the development of COVID-19-associated nephropathy, which is a collapsing form of focal segmental glomerulosclerosis, and an increased incidence of new-onset vasculitis. Some early reports described associations of COVID-19 and/or SARS-CoV-2 vaccines with relapse or new-onset of other glomerular diseases, but this link was not confirmed in large population-based studies. SARS-CoV-2 vaccination reduces the risk of COVID-19 and long COVID and is particularly important for protecting vulnerable populations such as patients with CKD. Structured long-term follow-up of patients with COVID-19 and post-infectious sequelae is needed to provide further insight into the trajectory of long COVID and enable identification of those at risk of CKD.},
}

@article {pmid40904575,
year = {2025},
author = {Shen, S and Zhao, X and Pei, J and Wang, B and Hou, J and Chai, R and Guo, Y and Li, F and Hao, J and Wu, Z},
title = {Exploring the psychological impact of long COVID: symptoms, mechanisms, and treatments.},
journal = {Frontiers in psychiatry},
volume = {16},
number = {},
pages = {1555370},
pmid = {40904575},
issn = {1664-0640},
abstract = {Long COVID (LC) refers to a multisystem condition that persists after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). In addition to physical symptoms, the psychological impact is particularly pronounced. This review summarizes the manifestations, potential mechanisms, epidemiological characteristics, and current interventions related to psychological disorders in LC. Drawing on domestic and international literature, it highlights anxiety, depression, cognitive dysfunction, and post-traumatic stress disorder (PTSD) as the primary psychological symptoms. These symptoms may be associated with neuroinflammation, immune abnormalities, vascular dysfunction, and psychosocial stress. Although research in this area is still developing, psychotherapy, pharmacotherapy, neuromodulation, and lifestyle interventions show promise as treatment approaches. This review aims to provide insights that can inform future research on clinical treatments and psychological care for individuals with LC.},
}

@article {pmid40802287,
year = {2025},
author = {Coughtrey, A and Pereira, SMP and Ladhani, S and Shafran, R and Stephenson, T},
title = {Long COVID in children and young people: then and now.},
journal = {Current opinion in infectious diseases},
volume = {38},
number = {5},
pages = {487-492},
pmid = {40802287},
issn = {1473-6527},
mesh = {Humans ; *COVID-19/complications/epidemiology/physiopathology ; Child ; Adolescent ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Fatigue ; Young Adult ; },
abstract = {PURPOSE OF REVIEW: On 11 March 2020, the WHO characterized COVID-19 as a pandemic. A clinical case definition for post-COVID-19 condition in children and adolescents by expert consensus was agreed by the WHO in 2023. It is now 5 years since the WHO declared a pandemic, and this review aims to summarize key advances in our understanding of long COVID over those 5 years.

RECENT FINDINGS: That symptoms could persist in adults and CYP for months after initial infection was first reported in Autumn 2020. Long COVID in adults is frequently characterized by symptoms of fatigue and breathlessness but brain-fog, joint and muscle pain have been reported much more commonly in adult follow-up than CYP. The most common persisting symptoms experienced by CYP after COVID-19 infection in initial studies, often with less than a year of follow-up, were fatigue, headache, shortness of breath and persisting loss of smell and taste. With longer follow-up, up to 2 years, the commonest symptoms still include not only fatigue, headache and shortness of breath but also sleep difficulties, whereas loss of smell and taste persisted only in a minority. However, many symptoms were almost as common in test-negative controls, raising questions about the causal role of SARS-CoV-2 virus. Predictors of long COVID, as defined, were female sex, history of asthma, allergy problems, learning difficulties at school and family history of ongoing COVID-19 problems.

SUMMARY: The implications of the findings for clinical practice and research are that long COVID is not the same in CYP as adults; both their physical and mental health should be studied; and intervention trials are needed.},
}

Humans
*COVID-19/complications/epidemiology/physiopathology
Child
Adolescent
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Fatigue
Young Adult

@article {pmid40748012,
year = {2025},
author = {Waxse, BJ and Rao, S},
title = {Data science for pediatric infectious disease: utilizing COVID-19 as a model.},
journal = {Current opinion in infectious diseases},
volume = {38},
number = {5},
pages = {493-498},
doi = {10.1097/QCO.0000000000001139},
pmid = {40748012},
issn = {1473-6527},
mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; Child ; *Data Science/methods ; SARS-CoV-2 ; Pediatrics ; Pandemics ; Public Health ; },
abstract = {PURPOSE OF REVIEW: During the COVID-19 pandemic, governments and public health agencies used data science tools and data sources in real time to evaluate pathogen transmissibility, disease burden, healthcare capacity, and evaluate treatment and preventive measures. The purpose of the review is to highlight the application of these data sources and methods during the COVID-19 response.

RECENT FINDINGS: Advances in the development of common data models enabled multisite data networks to overcome healthcare data fragmentation, enabling national surveillance platforms, and offering unprecedented statistical power to conduct national surveillance and detect emerging clinical entities like MIS-C and long COVID in diverse pediatric populations. These integrated networks were also used in evaluating the effectiveness of vaccines and therapies. New surveillance approaches combining traditional clinical data with novel data sources including wastewater detection, web-based search engines, and mobility patterns yielded comprehensive ensemble approaches that informed public health policy.

SUMMARY: The COVID-19 pandemic highlighted the importance of timely evidence for decision-making during outbreak responses and the benefits of using data science tools to help provide real time, actionable insights, which can help guide our public health response to infectious diseases threats in the future.},
}

Humans
*COVID-19/epidemiology/prevention & control
Child
*Data Science/methods
SARS-CoV-2
Pediatrics
Pandemics
Public Health

@article {pmid40536011,
year = {2025},
author = {Moen, JK and Baker, CA and Iwasaki, A},
title = {Neuroimmune pathophysiology of long COVID.},
journal = {Psychiatry and clinical neurosciences},
volume = {79},
number = {9},
pages = {514-530},
pmid = {40536011},
issn = {1440-1819},
support = {/HHMI/Howard Hughes Medical Institute/United States ; R01 AI157488/AI/NIAID NIH HHS/United States ; R01AI157488//National Institute of Allergy and Infectious Diseases/ ; N/A/HHMI/Howard Hughes Medical Institute/United States ; },
mesh = {Humans ; *COVID-19/immunology/complications/physiopathology ; Post-Acute COVID-19 Syndrome ; *Neuroimmunomodulation/physiology ; *Nervous System Diseases/immunology/physiopathology/etiology ; SARS-CoV-2 ; Animals ; *Peripheral Nervous System Diseases/immunology/physiopathology/etiology ; Fatigue/physiopathology/immunology ; },
abstract = {Although COVID-19 was originally considered a respiratory illness, it is now well established that SARS-CoV-2 infection can have far-reaching impacts on the nervous system. Neurological symptoms such as chemosensory dysfunction are frequently observed during acute infection and approximately 10% of COVID-19 cases will go on to develop new or persistent long-term symptoms, a condition known in the literature as post-acute symptoms of COVID-19 (PASC) or by the patient-coined term Long COVID. Common neurological symptoms in Long COVID include new onset cognitive difficulties, dysautonomia, fatigue, and peripheral neuropathy. The emergence of Long COVID has prompted renewed interest in the study of post-acute infection syndromes (PAIS), particularly in the area of neuroimmune interactions. In this review we provide a comprehensive overview of the current body of literature on neurological manifestations of SARS-CoV-2 infection and Long COVID, with an emphasis on neuroimmune mechanisms drawn largely from autopsy studies and animal models. A more complete understanding of neuroimmune crosstalk in Long COVID will not only guide the development of therapies for this highly disabling condition but will also contribute to our general understanding of neuroimmune interactions in health and disease.},
}

Humans
*COVID-19/immunology/complications/physiopathology
Post-Acute COVID-19 Syndrome
*Neuroimmunomodulation/physiology
*Nervous System Diseases/immunology/physiopathology/etiology
SARS-CoV-2
Animals
*Peripheral Nervous System Diseases/immunology/physiopathology/etiology
Fatigue/physiopathology/immunology

@article {pmid40883647,
year = {2025},
author = {Fayyad-Kazan, M},
title = {MicroRNAs in SARS-CoV-2 infection: emerging modulators of inflammation, pathogenesis, and therapeutic potential.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {40883647},
issn = {1568-5608},
abstract = {Since the onset of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), elucidating the molecular regulators of viral pathogenesis and host response has been a critical international research objective. Among these, microRNAs (miRNAs), small non-coding RNAs, that modulate gene expression post-transcriptionally-have emerged as central orchestrators of host-virus interactions. This review exhaustively examines the roles of host-derived miRNAs in SARS-CoV-2 infection, including their roles in viral entry, replication, immune evasion, inflammation, and tissue injury. Dysregulation of certain miRNAs, such as miR-155, miR-146a, and miR-21, has been implicated in disease severity, comorbidities (such as diabetes, obesity), neurological complications, and pregnancy complications. In long COVID (PASC), chronic miRNA changes are linked to persistent inflammation, fibrosis, and cardiometabolic impairment. We emphasize current breakthroughs in miRNA research, including machine learning algorithms for miRNA-based disease stratification, CRISPR-engineered miRNA modulation, exosomal miRNA delivery platforms, and miRNA-adjuvanted vaccines. These advances highlight the potential of miRNAs as diagnostic biomarkers and therapeutic targets. Nevertheless, shortcomings persist in clinical validation, delivery optimization, and tissue-specific miRNA function elucidation. These gaps must be addressed to involve miRNAs in controlling current and future viral infections. This review consolidated differentially expressed miRNAs across disease stages, comorbidities, and clinical settings, providing a valuable resource for translational research and therapeutic innovation.},
}

@article {pmid40875678,
year = {2025},
author = {Schapowal, A},
title = {[Long COVID, Post-COVID-Syndrom: Langzeitfolgen von SARS-CoV-2-Infektionen und Nutzen von Ginkgo biloba].},
journal = {Complementary medicine research},
volume = {},
number = {},
pages = {1-8},
doi = {10.1159/000548075},
pmid = {40875678},
issn = {2504-2106},
abstract = {Background Long COVID and Post-COVID Syndrome are long-term consequences of SARS-CoV-2 infections, causing a range of physical, cognitive, and psychological symptoms such as fatigue, shortness of breath, memory impairment, and sleep disturbances. The exact pathophysiology remains unclear but is thought to involve persistent viral particles, microvascular dysfunction, autoimmune reactions, and autonomic nervous system dysregulation. Summary Diagnosing Long COVID is challenging due to the lack of standardized tests. A multimodal treatment approach is recommended, incorporating symptomatic medication, physiotherapy, psychotherapy, as well as nutritional and exercise therapy. One promising complementary therapeutic option is the use of standardized Ginkgo biloba extracts. Their antioxidant, anti-inflammatory, and neuroprotective properties may help alleviate cognitive impairments, fatigue, and cardiovascular symptoms. Initial studies and case reports suggest positive effects, but further clinical trials are necessary to confirm efficacy. Key Messages Long COVID and Post-COVID Syndrome affect multiple organ systems and significantly reduce quality of life. Diagnosis remains difficult due to the absence of specific tests. A multimodal therapy approach is currently the most promising strategy. Standardized Ginkgo biloba extracts show potential benefits for neurocognitive and cardiovascular symptoms in early studies.},
}

@article {pmid40872911,
year = {2025},
author = {Zambrano-Sánchez, G and Rivadeneira, J and Manterola, C and Otzen, T and Fuenmayor-González, L},
title = {Immunization as Protection Against Long COVID in the Americas: A Scoping Review.},
journal = {Vaccines},
volume = {13},
number = {8},
pages = {},
doi = {10.3390/vaccines13080822},
pmid = {40872911},
issn = {2076-393X},
support = {Folio (85220114).//ANID + SUBVENCIÓN A INSTALACIÓN EN LA ACADEMIA CONVOCATORIA AÑO 2022/ ; },
abstract = {INTRODUCTION: Long COVID syndrome is defined as persistent or new symptoms that appear after an acute SARS-CoV-2 infection and last at least three months without explanation. It is estimated that between 10% and 20% of those infected develop long COVID; however, data is not precise in Latin America. Although high immunization rates have reduced acute symptoms and the pandemic's impact, there is a lack of evidence of its efficacy in preventing long COVID in the region.

METHODS: This scoping review followed PRISMA-ScR guidelines. Studies on vaccinated adults with long COVID from Central and South America and the Caribbean were included (Mexico was also considered). A comprehensive search across multiple databases was conducted. Data included study design, participant characteristics, vaccine type, and efficacy outcomes. Results are presented narratively and in tables.

RESULTS: Out of 3466 initial records, 8 studies met the inclusion criteria after rigorous selection processes. These studies encompassed populations from Brazil, Mexico, Latin America, and Bonaire, with 11,333 participants, 69.3% of whom were female. Vaccination, particularly with three or more doses, substantially reduces the risk and duration of long COVID. Variability was noted in the definitions and outcomes assessed across studies.

CONCLUSIONS: This scoping review highlights that SARS-CoV-2 vaccination exhibits potential in reducing the burden of long COVID in the Americas. However, discrepancies in vaccine efficacy were observed depending on the study design, the population studied, and the vaccine regimen employed. Further robust, region-specific investigations are warranted to delineate the effects of vaccination on long COVID outcomes.},
}

@article {pmid40872813,
year = {2025},
author = {Muthiah, D and Vaddadi, K and Liu, L},
title = {Breathless Aftermath: Post-COVID-19 Pulmonary Fibrosis.},
journal = {Viruses},
volume = {17},
number = {8},
pages = {},
doi = {10.3390/v17081098},
pmid = {40872813},
issn = {1999-4915},
support = {R01HL157450, R21AI189861 and P30GM149368//National Institutes of Health grants, Oklahoma Center for Adult Stem Cell Research and the Lundberg-Kienlen Endowment fund (to LL)/ ; },
mesh = {Humans ; *COVID-19/complications ; *Pulmonary Fibrosis/etiology/epidemiology/diagnosis/therapy/pathology/virology ; SARS-CoV-2 ; Lung/pathology/virology ; Post-Acute COVID-19 Syndrome ; Quality of Life ; },
abstract = {A significant number of individuals recovering from COVID-19 continue to experience persistent symptoms, collectively referred to as Post-Acute Sequelae of SARS-CoV-2 infection (PASC), or long COVID. Among these complications, post-COVID-19 pulmonary fibrosis (PC19-PF) is one of the most severe long-term outcomes, characterized by progressive lung scarring, chronic respiratory impairment, and reduced quality of life. Despite the increasing prevalence of PC19-PF, its underlying mechanisms remain poorly understood. In this review, we provide a comprehensive overview of PC19-PF, including its epidemiology, clinical manifestations, diagnostic strategies, and mechanistic insights. Additionally, we highlight the shared pathways between PC19-PF and other fibrotic lung diseases and discuss emerging therapeutic strategies. This review consolidates emerging insights from both clinical and experimental studies to advance our understanding of PC19-PF pathogenesis and guide the development of mechanism-based therapeutic approaches.},
}

Humans
*COVID-19/complications
*Pulmonary Fibrosis/etiology/epidemiology/diagnosis/therapy/pathology/virology
SARS-CoV-2
Lung/pathology/virology
Post-Acute COVID-19 Syndrome
Quality of Life

@article {pmid40872762,
year = {2025},
author = {Cao, Y and Wang, Y and Huang, D and Tan, YJ},
title = {The Role of SARS-CoV-2 Nucleocapsid Protein in Host Inflammation.},
journal = {Viruses},
volume = {17},
number = {8},
pages = {},
doi = {10.3390/v17081046},
pmid = {40872762},
issn = {1999-4915},
support = {T2EP30121-0012//Ministry of Education/ ; },
mesh = {Humans ; *Coronavirus Nucleocapsid Proteins/immunology/metabolism ; *COVID-19/immunology/virology ; *SARS-CoV-2/immunology ; *Inflammation/immunology/virology ; *Phosphoproteins/immunology/metabolism ; Host-Pathogen Interactions ; Animals ; },
abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has posed substantial health threats and triggered widespread global economic disruption. The nucleocapsid (N) protein of SARS-CoV-2 is not only a key structural protein but also instrumental in mediating the host immune response, contributing significantly to inflammation and viral pathogenesis. Due to its immunogenic properties, SARS-CoV-2 N protein also interacts with host factors associated with various pre-existing inflammatory conditions and may possibly contribute to the long-term symptoms suffered by some COVID-19 patients after recovery-known as long COVID. This review provides a comprehensive overview of recent advances in elucidating the biological functions of the N protein. In particular, it highlights the mechanisms by which the N protein contributes to host inflammatory responses and elaborates on its association with long COVID and pre-existing inflammatory disorders.},
}

Humans
*Coronavirus Nucleocapsid Proteins/immunology/metabolism
*COVID-19/immunology/virology
*SARS-CoV-2/immunology
*Inflammation/immunology/virology
*Phosphoproteins/immunology/metabolism
Host-Pathogen Interactions
Animals

@article {pmid40869200,
year = {2025},
author = {Lesgards, JF and Cerdan, D and Perronne, C},
title = {Do Long COVID and COVID Vaccine Side Effects Share Pathophysiological Picture and Biochemical Pathways?.},
journal = {International journal of molecular sciences},
volume = {26},
number = {16},
pages = {},
doi = {10.3390/ijms26167879},
pmid = {40869200},
issn = {1422-0067},
mesh = {Humans ; *COVID-19/immunology/prevention & control/physiopathology ; *COVID-19 Vaccines/adverse effects/immunology ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus/immunology/metabolism ; Post-Acute COVID-19 Syndrome ; },
abstract = {COVID affects around 400 million individuals today with a strong economic impact on the global economy. The list of long COVID symptoms is extremely broad because it is derived from neurological, cardiovascular, respiratory, immune, and renal dysfunctions and damages. We review here these pathophysiological manifestations and the predictors of this multi-organ pathology like the persistence of the virus, altered endothelial function, unrepaired tissue damage, immune dysregulation, and gut dysbiosis. We also discuss the similarities between long COVID and vaccine side effects together with possible common immuno-inflammatory pathways. Since the spike protein is present in SARS-CoV-2 (and its variants) but also produced by the COVID vaccines, its toxicity may also apply to all mRNA or adenoviral DNA vaccines as they are based on the production of a very similar spike protein to the virus. After COVID infection or vaccination, the spike protein can last for months in the body and may interact with ACE2 receptors and mannan-binding lectin (MBL)/mannan-binding lectin serine protease 2 (MASP-2), which are present almost everywhere in the organism. As a result, the spike protein may be able to trigger inflammation in a lot of organs and systems similar to COVID infection. We suggest that three immuno-inflammatory pathways are particularly key and responsible for long COVID and COVID vaccine side effects, as it has been shown for COVID, which may explain in large part their strong similarities: the renin-angiotensin-aldosterone system (RAAS), the kininogen-kinin-kallikrein system (KKS), and the lectin complement pathway. We propose that therapeutic studies should focus on these pathways to propose better cures for both long COVID as well as for COVID vaccine side effects.},
}

Humans
*COVID-19/immunology/prevention & control/physiopathology
*COVID-19 Vaccines/adverse effects/immunology
SARS-CoV-2/immunology
Spike Glycoprotein, Coronavirus/immunology/metabolism
Post-Acute COVID-19 Syndrome

@article {pmid40868989,
year = {2025},
author = {Cimmino, G and D'Elia, S and Morello, M and Titolo, G and Luisi, E and Solimene, A and Serpico, C and Conte, S and Natale, F and Loffredo, FS and Bianco, A and Golino, P},
title = {Cardio-Pulmonary Features of Long COVID: From Molecular and Histopathological Characteristics to Clinical Implications.},
journal = {International journal of molecular sciences},
volume = {26},
number = {16},
pages = {},
doi = {10.3390/ijms26167668},
pmid = {40868989},
issn = {1422-0067},
mesh = {Humans ; *COVID-19/complications/pathology ; SARS-CoV-2 ; *Cardiovascular Diseases/etiology/pathology ; Lung/pathology/virology ; Post-Acute COVID-19 Syndrome ; },
abstract = {Long COVID is a persistent post-viral syndrome with the significant involvement of both the cardiovascular and pulmonary systems, often extending well beyond the acute phase of SARS-CoV-2 infection. Emerging evidence has highlighted a spectrum of chronic alterations, including endothelial dysfunction, microvascular inflammation, perivascular fibrosis, and in some cases, the persistence of viral components in the cardiac and pulmonary tissues. At the molecular level, a sustained inflammatory milieu-characterized by elevated pro-inflammatory cytokines such as interleukin 6 (IL-6)-and chronic platelet hyperreactivity contribute to a prothrombotic state. These mechanisms are implicated in microvascular damage, cardiac strain, and impaired gas exchange, correlating with clinical manifestations such as fatigue, dyspnea, chest discomfort, and reduced exercise capacity. In certain patients, especially those who were not hospitalized during the acute phase, cardiac MRI and myocardial biopsy may reveal signs of myocardial inflammation and autonomic dysregulation. These often subclinical cardiovascular alterations underscore the need for improved diagnostic strategies, integrating molecular and histopathological markers during post-COVID evaluations. Recognizing persistent inflammatory and thrombotic activity may inform risk stratification and individualized therapeutic approaches. The interdependence between pulmonary fibrosis and cardiac dysfunction highlights the importance of multidisciplinary care. In this context, molecular and tissue-based diagnostics play a pivotal role in elucidating the long-term cardio-pulmonary sequelae of long COVID and guiding targeted interventions. Early identification and structured follow-up are essential to mitigate the burden of chronic complications in affected individuals.},
}

Humans
*COVID-19/complications/pathology
SARS-CoV-2
*Cardiovascular Diseases/etiology/pathology
Lung/pathology/virology
Post-Acute COVID-19 Syndrome

@article {pmid40868961,
year = {2025},
author = {Florea, CE and Bălaș-Maftei, B and Rotaru, A and Abudanii, PL and Vieru, ST and Grigoriu, M and Stoian, A and Manciuc, C},
title = {Multiorgan Involvement and Particularly Liver Injury in Long COVID: A Narrative Review.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {8},
pages = {},
doi = {10.3390/life15081314},
pmid = {40868961},
issn = {2075-1729},
abstract = {Since the start of the COVID-19 pandemic, increasing evidence has shown that SARS-CoV-2 infection can cause long-term symptoms, collectively known as long COVID, and that patients with mild COVID-19 can also be affected by persistent fatigue, cognitive impairment, dyspnea, muscle pain, etc. Recent research has also found multiple organ systems, including the liver, to be significant sites of ongoing injury. This narrative review summarizes current knowledge on organ involvement during and after COVID-19, with particular focus on early and delayed hepatic manifestations and associated risk factors. Pathogenesis appears to be multifactorial, involving direct virus action, the body's immune-mediated inflammatory response, microvascular damage, drug-induced hepatotoxicity, and, in some cases, reactivation or exacerbation of pre-existing liver conditions. The hepatic clinical manifestations range from asymptomatic elevations of transaminases to cholangiopathy and even fibrosis. These can persist or progress for months after the initial infection with SARS-CoV-2 is resolved, requiring prolonged monitoring and interdisciplinary care, especially in the presence of metabolic disorders, obesity, or hepatitis. Neurological, cardiovascular, and other sequelae are discussed in parallel, with attention paid to common inflammatory and thrombotic pathways. This review concludes that liver dysfunction is of particular interest in long-COVID due to the liver's central role in metabolism and inflammation. While further research is being conducted into organ-specific and systemic interactions, the available evidence makes a compelling case for extended monitoring and integrated management strategies post infection.},
}

@article {pmid40868058,
year = {2025},
author = {Gonzaga, A and Martinez-Navarrete, G and Macia, L and Anton-Bonete, M and Cahuana, G and Tejedo, JR and Zorrilla-Muñoz, V and Fernandez-Jover, E and Andreu, E and Eguizabal, C and Pérez-Martínez, A and Solano, C and Hernández-Blasco, LM and Soria, B},
title = {Non-Viral Therapy in COVID-19: Where Are We Standing? How Our Experience with COVID May Help Us Develop Cell Therapies for Long COVID Patients.},
journal = {Biomedicines},
volume = {13},
number = {8},
pages = {},
doi = {10.3390/biomedicines13081801},
pmid = {40868058},
issn = {2227-9059},
support = {ICI21/00016//Instituto de Salud Carlos III/ ; AVI-GVA-COVID19-068//Valencian Agency of Innovation(AVI)/ ; GVA-COVID19/2021-047//Valencian Agency of Innovation(AVI)/ ; NA//Al-Andalus Biopharma SL/ ; },
abstract = {Objectives: COVID-19, caused by the SARS-CoV-2 virus, has infected over 777 million individuals and led to approximately 7 million deaths worldwide. Despite significant efforts to develop effective therapies, treatment remains largely supportive, especially for severe complications like acute respiratory distress syndrome (ARDS). Numerous compounds from diverse pharmacological classes are currently undergoing preclinical and clinical evaluation, targeting both the virus and the host immune response. Methods: Despite the large number of articles published and after a preliminary attempt was published, we discarded the option of a systematic review. Instead, we have done a description of therapies with these results and a tentative mechanism of action. Results: Preliminary studies and early-phase clinical trials have demonstrated the potential of Mesenchymal Stem Cells (MSCs) in mitigating severe lung damage in COVID-19 patients. Previous research has shown MSCs to be effective in treating various pulmonary conditions, including acute lung injury, idiopathic pulmonary fibrosis, ARDS, asthma, chronic obstructive pulmonary disease, and lung cancer. Their ability to reduce inflammation and promote tissue repair supports their potential role in managing COVID-19-related complications. This review demonstrates the utility of MSCs in the acute phase of COVID-19 and postulates the etiopathogenic role of mitochondria in Long-COVID. Even more, their combination with other therapies is also analyzed. Conclusions: While the therapeutic application of MSCs in COVID-19 is still in early stages, emerging evidence suggests promising outcomes. As research advances, MSCs may become an integral part of treatment strategies for severe COVID-19, particularly in addressing immune-related lung injury and promoting recovery. However, a full pathogenic mechanism may explain or unify the complexity of signs and symptoms of Long COVID and Post-Acute Sequelae (PASC).},
}

@article {pmid40867811,
year = {2025},
author = {Villegas Sánchez, V and Chávez Pacheco, JL and Palacios Arreola, MI and Sierra-Vargas, MP and Colín Godinez, LA and Ahumada Topete, VH and Fernández Plata, R and Higuera-Iglesias, A and Lara-Lemus, R and Aquino-Gálvez, A and Torres-Espíndola, LM and Castillejos-López, M},
title = {A Systematic Review of Genetic Variants in Glutathione S-Transferase Genes and Their Dual Role in SARS-CoV-2 Pathogenesis: From Acute Respiratory Complications to Long COVID.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {14},
number = {8},
pages = {},
doi = {10.3390/antiox14080912},
pmid = {40867811},
issn = {2076-3921},
abstract = {Oxidative stress (OS) occurs when there is an imbalance between oxidants and antioxidants, leading to disruptions in cellular signaling and causing damage to molecules. Glutathione S-transferase (GST) enzymes are crucial for maintaining redox balance by facilitating glutathione conjugation. Increased oxidative damage has been noted during the COVID-19 pandemic, and its persistence may be linked to the onset of long COVID. This systematic review aimed to assess the relationship between GST gene polymorphisms and the prognosis of COVID-19, including long COVID. Adhering to the PRISMA guidelines, a thorough search was carried out in MEDLINE, CENTRAL, PubMed, and EMBASE for studies published from September 2020 to February 2025. Out of an initial selection of 462 articles, ten studies (four concerning COVID-19 severity and six related to long COVID) satisfied the inclusion criteria. The findings regarding GST polymorphisms were not consistent, especially concerning the GSTM1 and GSTT1 isoforms. Nevertheless, evidence indicates a sustained state of oxidative stress in patients with long COVID. The majority of research has focused on cytosolic GSTs, while the functions of microsomal and mitochondrial GST families remain largely unexplored. These findings suggest that further research into the various GST subfamilies and their genetic variants is necessary to enhance our understanding of their impact on COVID-19 severity and the pathophysiology of long COVID.},
}

@article {pmid40866305,
year = {2025},
author = {Bombardieri, AM and Denoue, CF},
title = {Cervical sympathetic block to treat Long COVID: a scoping review.},
journal = {Regional anesthesia and pain medicine},
volume = {},
number = {},
pages = {},
doi = {10.1136/rapm-2025-106879},
pmid = {40866305},
issn = {1532-8651},
abstract = {BACKGROUND: Long COVID is a complex and poorly understood condition characterized by persistent symptoms such as autonomic dysfunction, fatigue, neurocognitive impairment, and olfactory disturbances. Current treatments offer limited and inconsistent benefits. Dysregulation of the sympathetic nervous system is increasingly recognized as a contributor to Long COVID pathophysiology. Cervical sympathetic block (CSB), a procedure that modulates sympathetic tone, has emerged as a potential therapeutic approach.

OBJECTIVE: To review the existing literature on CSB, for Long COVID, focusing on symptom outcomes, proposed mechanisms, and procedural considerations.

EVIDENCE REVIEW: A structured literature search across PubMed, Embase, Scopus, and Web of Science identified studies published between 2022 and March 2025 reporting on CSB in adults with Long COVID. Eligible articles included case reports, case series, observational studies, and one randomized controlled trial evaluating symptom outcomes after the procedure.

FINDINGS: Sixteen studies involving 224 patients were included. Most reported improvement in fatigue, brain fog, and autonomic symptoms, including reduced heart rate and enhanced orthostatic tolerance. Cognitive and psychiatric symptoms such as memory impairment, anxiety, and depression showed variable improvement. Olfactory recovery was inconsistent and appeared to depend on symptom severity. Symptom relief was observed after both unilateral and bilateral blocks, with some responses lasting up to 1 year. No serious complications were reported.

CONCLUSIONS: CSB may offer symptom relief in Long COVID, particularly for fatigue, brain fog, and dysautonomia. However, the evidence remains preliminary and limited by small sample sizes and methodological heterogeneity. Controlled trials are needed to establish efficacy and patient selection criteria.},
}

@article {pmid40857408,
year = {2025},
author = {Bayarri-Olmos, R and Bain, W and Iwasaki, A},
title = {The role of complement in long COVID pathogenesis.},
journal = {JCI insight},
volume = {10},
number = {16},
pages = {},
doi = {10.1172/jci.insight.194314},
pmid = {40857408},
issn = {2379-3708},
mesh = {Humans ; *COVID-19/immunology/complications ; *Complement System Proteins/immunology ; SARS-CoV-2/immunology ; Immunity, Innate/immunology ; Inflammation/immunology ; Complement Activation ; Post-Acute COVID-19 Syndrome ; },
abstract = {Long COVID is a debilitating condition that can develop after a SARS-CoV-2 infection and is characterized by a wide range of chronic symptoms, including weakness, neurocognitive impairment, malaise, fatigue, and many others, that affect multiple organ systems. At least 10% of individuals with a previous infection may develop long COVID, which affects their ability to perform daily functions and work. Despite its severity and widespread impact, this multisystemic condition remains poorly understood. Recent studies suggest that dysregulation of the complement system, a key component of the innate immune response, may contribute to the pathogenesis of long COVID, particularly in connection with coagulation, inflammation, and vascular injury. In this Review, we examine the evidence linking complement system dysregulation to long COVID and explore its potential role in driving disease pathology.},
}

Humans
*COVID-19/immunology/complications
*Complement System Proteins/immunology
SARS-CoV-2/immunology
Immunity, Innate/immunology
Inflammation/immunology
Complement Activation
Post-Acute COVID-19 Syndrome

@article {pmid40801614,
year = {2025},
author = {Sonkodi, B},
title = {Underlying Piezo2 Channelopathy-Induced Neural Switch of COVID-19 Infection.},
journal = {Cells},
volume = {14},
number = {15},
pages = {},
pmid = {40801614},
issn = {2073-4409},
mesh = {Humans ; *COVID-19/metabolism ; *Ion Channels/metabolism ; SARS-CoV-2 ; Neurons/metabolism/pathology ; *Channelopathies/metabolism ; Pandemics ; Animals ; },
abstract = {The focal "hot spot" neuropathologies in COVID-19 infection are revealing footprints of a hidden underlying collapse of a novel ultrafast ultradian Piezo2 signaling system within the nervous system. Paradoxically, the same initiating pathophysiology may underpin the systemic findings in COVID-19 infection, namely the multiorgan SARS-CoV-2 infection-induced vascular pathologies and brain-body-wide systemic pro-inflammatory signaling, depending on the concentration and exposure to infecting SARS-CoV-2 viruses. This common initiating microdamage is suggested to be the primary damage or the acquired channelopathy of the Piezo2 ion channel, leading to a principal gateway to pathophysiology. This Piezo2 channelopathy-induced neural switch could not only explain the initiation of disrupted cell-cell interactions, metabolic failure, microglial dysfunction, mitochondrial injury, glutamatergic synapse loss, inflammation and neurological states with the central involvement of the hippocampus and the medulla, but also the initiating pathophysiology without SARS-CoV-2 viral intracellular entry into neurons as well. Therefore, the impairment of the proposed Piezo2-induced quantum mechanical free-energy-stimulated ultrafast proton-coupled tunneling seems to be the principal and critical underlying COVID-19 infection-induced primary damage along the brain axes, depending on the loci of SARS-CoV-2 viral infection and intracellular entry. Moreover, this initiating Piezo2 channelopathy may also explain resultant autonomic dysregulation involving the medulla, hippocampus and heart rate regulation, not to mention sleep disturbance with altered rapid eye movement sleep and cognitive deficit in the short term, and even as a consequence of long COVID. The current opinion piece aims to promote future angles of science and research in order to further elucidate the not entirely known initiating pathophysiology of SARS-CoV-2 infection.},
}

Humans
*COVID-19/metabolism
*Ion Channels/metabolism
SARS-CoV-2
Neurons/metabolism/pathology
*Channelopathies/metabolism
Pandemics
Animals

@article {pmid40801304,
year = {2025},
author = {Ellen, A},
title = {From Stagnation to Strategy: Challenges in Advancing Long COVID Research.},
journal = {Journal of evaluation in clinical practice},
volume = {31},
number = {5},
pages = {e70180},
pmid = {40801304},
issn = {1365-2753},
mesh = {Humans ; *COVID-19/physiopathology/complications/epidemiology/therapy ; *Biomedical Research/organization & administration ; SARS-CoV-2 ; Comorbidity ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: Long COVID is a debilitating multisystemic condition and is a major public health burden, yet the pathophysiology remains poorly understood and there are no effective treatments. Despite the urgent need for better management strategies, research into long COVID is losing momentum.

OBJECTIVES: To help tackle this loss of momentum, this article analyses the major challenges impeding progress and proposes innovative strategies to navigate them and to reinvigorate this research field.

METHOD: The analysis of the long COVID research domain drew on a broad range of scientific literature to identify major barriers to research and potential pathways forward.

RESULTS: The research highlighted critical obstacles, including the lack of reliable biomarkers which has necessitated a reliance on symptom reporting that is inherently heterogenous, temporally complex and often confounded by symptoms arising from pre-existing comorbidities. The absence of pre-infection baseline data further complicates the distinction between long COVID-specific pathophysiology and the effects of pre-existing co-morbidities. Additionally, the long COVID patient population has heterogenous multiorgan pathology, and this diversity makes it difficult to identify and interpret clinical findings.

CONCLUSION: Addressing these methodological and conceptual challenges is essential to accelerate the understanding of long COVID pathophysiology and guide the development of effective interventions.},
}

Humans
*COVID-19/physiopathology/complications/epidemiology/therapy
*Biomedical Research/organization & administration
SARS-CoV-2
Comorbidity
Post-Acute COVID-19 Syndrome

@article {pmid40622467,
year = {2025},
author = {Chatterjee, D and Maparu, K},
title = {Long COVID syndrome: exploring therapies for managing and overcoming persistent symptoms.},
journal = {Inflammopharmacology},
volume = {33},
number = {7},
pages = {4097-4113},
pmid = {40622467},
issn = {1568-5608},
mesh = {Humans ; *COVID-19/therapy/complications/epidemiology/physiopathology ; Post-Acute COVID-19 Syndrome ; COVID-19 Drug Treatment ; SARS-CoV-2 ; Risk Factors ; },
abstract = {Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), is a growing global health concern, affecting 10-35% of COVID-19 survivors. Characterized by persistent multisystem symptoms lasting beyond 12 weeks, common manifestations include fatigue, dyspnea, chest pain, cognitive impairment, depression, and anxiety. The underlying pathophysiology remains unclear but is likely to involve immune dysregulation, persistent inflammation, endothelial dysfunction, gut dysbiosis, and viral persistence. This review examines the epidemiology, risk factors, and clinical manifestations of long COVID, with a focus on its impact on cardiopulmonary, neurological, and mental health. Therapeutic approaches include pharmacological interventions such as anti-inflammatory agents, antioxidants, neuroprotective drugs, and repurposed medications. Non-pharmacological strategies, such as physical rehabilitation, cognitive therapy, dietary modification, and emerging therapies like stem cell therapy, as well as immunomodulatory approaches, offer promising avenues for recovery. We also highlight ongoing clinical trials evaluating targeted therapies for long-term COVID syndrome. Future research should focus on elucidating the pathophysiological mechanisms, identifying biomarkers, and optimizing personalized treatment strategies for long-term COVID-19 management.},
}

Humans
*COVID-19/therapy/complications/epidemiology/physiopathology
Post-Acute COVID-19 Syndrome
COVID-19 Drug Treatment
SARS-CoV-2
Risk Factors

@article {pmid35272262,
year = {2022},
author = {Soril, LJJ and Damant, RW and Lam, GY and Smith, MP and Weatherald, J and Bourbeau, J and Hernandez, P and Stickland, MK},
title = {The effectiveness of pulmonary rehabilitation for Post-COVID symptoms: A rapid review of the literature.},
journal = {Respiratory medicine},
volume = {195},
number = {},
pages = {106782},
pmid = {35272262},
issn = {1532-3064},
mesh = {Humans ; *COVID-19/rehabilitation/complications/physiopathology ; Post-Acute COVID-19 Syndrome ; Quality of Life ; SARS-CoV-2 ; Treatment Outcome ; Exercise Tolerance ; },
abstract = {BACKGROUND: Multi-disciplinary rehabilitation is recommended for individuals with post-acute sequelae of COVID-19 infection (i.e., symptoms 3-4 weeks after acute infection). There are emerging reports of use of pulmonary rehabilitation (PR) in the post-acute stages of COVID-19, however the appropriateness of PR for managing post-COVID symptoms remains unclear. To offer practical guidance with regards to post-COVID PR, a greater understanding of the clinical effectiveness literature is required.

METHODS: A rapid review of the published literature was completed. An electronic database search of the literature published between July 1, 2020 and June 1, 2021 was performed in MEDLINE, Pubmed, and EMBASE. Primary studies evaluating the clinical effectiveness of PR for individuals with post-COVID symptoms were included.

RESULTS: Nine studies evaluating the effectiveness of PR were identified; most were small, experimental or quasi-experimental studies, including 1 RCT, and were primarily of low quality. After attending PR, all studies reported improvements in exercise capacity, pulmonary function, and/or quality of life for individuals with post-COVID symptoms who had been hospitalized for their acute COVID-19 infection. Few studies evaluated changes in post-COVID symptom severity or frequency and, of these, improvements in dyspnea, fatigue, anxiety and depression were observed following PR. Further, no studies evaluated non-hospitalized patients or long-term outcomes beyond 3 months after initiating PR.

CONCLUSIONS: With limited high-quality evidence, any recommendations or practical guidance for PR programmes for those with post-COVID symptoms should consider factors such as feasibility, current PR capacity, and resource constraints.},
}

Humans
*COVID-19/rehabilitation/complications/physiopathology
Post-Acute COVID-19 Syndrome
Quality of Life
SARS-CoV-2
Treatment Outcome
Exercise Tolerance

@article {pmid40809128,
year = {2024},
author = {Sun, J and Aikawa, M and Ashktorab, H and Beckmann, ND and Enger, ML and Espinosa, JM and Gai, X and Horne, BD and Keim, P and Lasky-Su, J and Letts, R and Maier, CL and Mandal, M and Nichols, L and Roan, NR and Russell, MW and Rutter, J and Saade, GR and Sharma, K and Shiau, S and Thibodeau, SN and Yang, S and Miele, L and , },
title = {A multi-omics strategy to understand PASC through the RECOVER cohorts: a paradigm for a systems biology approach to the study of chronic conditions.},
journal = {Frontiers in systems biology},
volume = {4},
number = {},
pages = {1422384},
pmid = {40809128},
issn = {2674-0702},
abstract = {Post-Acute Sequelae of SARS-CoV-2 infection (PASC or "Long COVID"), includes numerous chronic conditions associated with widespread morbidity and rising healthcare costs. PASC has highly variable clinical presentations, and likely includes multiple molecular subtypes, but it remains poorly understood from a molecular and mechanistic standpoint. This hampers the development of rationally targeted therapeutic strategies. The NIH-sponsored "Researching COVID to Enhance Recovery" (RECOVER) initiative includes several retrospective/prospective observational cohort studies enrolling adult, pregnant adult and pediatric patients respectively. RECOVER formed an "OMICS" multidisciplinary task force, including clinicians, pathologists, laboratory scientists and data scientists, charged with developing recommendations to apply cutting-edge system biology technologies to achieve the goals of RECOVER. The task force met biweekly over 14 months, to evaluate published evidence, examine the possible contribution of each "omics" technique to the study of PASC and develop study design recommendations. The OMICS task force recommended an integrated, longitudinal, simultaneous systems biology study of participant biospecimens on the entire RECOVER cohorts through centralized laboratories, as opposed to multiple smaller studies using one or few analytical techniques. The resulting multi-dimensional molecular dataset should be correlated with the deep clinical phenotyping performed through RECOVER, as well as with information on demographics, comorbidities, social determinants of health, the exposome and lifestyle factors that may contribute to the clinical presentations of PASC. This approach will minimize lab-to-lab technical variability, maximize sample size for class discovery, and enable the incorporation of as many relevant variables as possible into statistical models. Many of our recommendations have already been considered by the NIH through the peer-review process, resulting in the creation of a systems biology panel that is currently designing the studies we proposed. This system biology strategy, coupled with modern data science approaches, will dramatically improve our prospects for accurate disease subtype identification, biomarker discovery and therapeutic target identification for precision treatment. The resulting dataset should be made available to the scientific community for secondary analyses. Analogous system biology approaches should be built into the study designs of large observational studies whenever possible.},
}

@article {pmid40805931,
year = {2025},
author = {Mazzonetto, LF and Cordeiro, JFC and Correia, IM and Oliveira, AS and Moraes, C and Brilhadori, J and Gomide, EBG and Kudlacek, M and Machado, DRL and Anjos, JRCD and Santos, APD},
title = {Physical Training Protocols for Improving Dyspnea and Fatigue in Long COVID: A Systematic Review with Meta-Analysis.},
journal = {Healthcare (Basel, Switzerland)},
volume = {13},
number = {15},
pages = {},
pmid = {40805931},
issn = {2227-9032},
abstract = {Objective: This study aimed to evaluate physical training protocols for alleviating long COVID symptoms, especially dyspnea and fatigue, through a systematic review with meta-analysis. Method: Data were collected from EMBASE, LILACS, PubMed, Scopus, CINAHL, Web of Science, and grey literature (Google Scholar, medRxiv). Studies evaluating dyspnea and/or fatigue before and after physical rehabilitation, using validated questionnaires, were included. Studies lacking pre- and post-assessments or physical training were excluded. Two reviewers independently extracted data on intervention type, duration, frequency, intensity, and assessment methods for dyspnea and fatigue. Bias risk was evaluated using the Cochrane tool. Results: Combined methods, such as respiratory muscle training with strength and aerobic exercise, were common for long COVID symptoms. Aerobic exercise notably improved dyspnea and/or fatigue. Among 25 studies, four had a low risk of bias. Meta-analysis of two studies found no significant reduction in fatigue. Conclusion: Combined training methods, particularly aerobic exercise, alleviate dyspnea and fatigue in long COVID. More high-quality studies are needed to confirm these findings.},
}

@article {pmid40804645,
year = {2025},
author = {Paval, NE and Căliman-Sturdza, OA and Lobiuc, A and Dimian, M and Sirbu, IO and Covasa, M},
title = {MicroRNAs in long COVID: roles, diagnostic biomarker potential and detection.},
journal = {Human genomics},
volume = {19},
number = {1},
pages = {90},
pmid = {40804645},
issn = {1479-7364},
support = {285/30.11.2022//Ministerul Cercetării, Inovării şi Digitalizării/ ; },
abstract = {Long COVID or Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), marked by persistent symptoms lasting weeks to months after acute SARS-CoV-2 infection, affects multiple organ systems including the respiratory, cardiovascular, neurological, gastrointestinal, and renal systems. These prolonged effects stem from chronic inflammation, immune dysregulation, and direct viral injury. MicroRNAs (miRNAs)-small non-coding RNAs involved in gene regulation-play a pivotal role in this process by modulating immune responses, inflammation, and cellular stress. Altered miRNA expression patterns during and after infection contribute to the pathogenesis of Long COVID. While conventional miRNA detection techniques have been valuable, they face limitations in sensitivity, throughput, and detecting RNA modifications. This review highlights Oxford Nanopore Sequencing (ONS) as a promising alternative, offering real-time, long-read, amplification-free RNA sequencing that preserves native modifications. ONS enables direct sequencing of full-length miRNAs and their precursors, providing novel insights into miRNA processing and regulatory roles. Despite current challenges with short-read accuracy, ongoing technical advances are improving ONS performance. Its integration in miRNA profiling holds significant potential for uncovering novel regulatory interactions and advancing clinical biomarker discovery in Long COVID and other conditions.},
}

@article {pmid40799952,
year = {2025},
author = {Di Micco, P and Siniscalchi, C and Imbalzano, E and Russo, V and Camporese, G and Lodigiani, C and Meschi, T and Perrella, A},
title = {COVID-19: A Disease Driven by Protease/Antiprotease Imbalance? A Specific Review Five Years into the Pandemic.},
journal = {Infection and drug resistance},
volume = {18},
number = {},
pages = {3967-3975},
pmid = {40799952},
issn = {1178-6973},
abstract = {COVID-19, caused by SARS-CoV-2, has profoundly impacted global health since late 2019. Beyond respiratory complications, the disease involves systemic manifestations driven by immune dysregulation, inflammation, and coagulopathy. Among the many mechanisms implicated in severe disease, a growing body of evidence suggests a central role for the imbalance between proteases and antiproteases. This review examines how dysregulated protease activity contributes to viral entry, cytokine activation, vascular injury, and thrombosis. We focus on the integration of proteolytic systems such as the renin-angiotensin system, coagulation cascade, and neutrophil extracellular traps with established pathways like endothelial dysfunction and immune hyperactivation. Furthermore, we highlight therapeutic strategies aimed at restoring proteolytic balance and discuss the potential relevance of this paradigm in the management of long COVID.},
}

@article {pmid40772993,
year = {2025},
author = {Siqueira, IFB and Figueiredo, LA and Fernandes, CEM and Cintra, LP and de Oliveira, GF and Rios, MA and Maciel, R and Ferretjans, R and Guimarães, NS and Magno, LAV},
title = {Metabolic brain changes in post-acute COVID-19: systematic review and meta-analysis of [18F]-FDG-PET findings.},
journal = {Brain structure & function},
volume = {230},
number = {7},
pages = {128},
pmid = {40772993},
issn = {1863-2661},
mesh = {Humans ; *COVID-19/metabolism/diagnostic imaging/complications ; Positron-Emission Tomography/methods ; Fluorodeoxyglucose F18 ; *Brain/metabolism/diagnostic imaging ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Radiopharmaceuticals ; Glucose/metabolism ; },
abstract = {Individuals with long COVID exhibit neurological and psychiatric symptoms that often persist well beyond the initial SARS-CoV-2 infection. Studies using [18F]-FDG positron emission tomography (FDG-PET) have revealed diverse abnormalities in brain glucose metabolism during the post-acute phase of COVID-19. We conducted a systematic review and meta-analysis to assess the spatial distribution and heterogeneity of brain metabolic changes in patients in the post-acute phase of COVID-19 relative to controls. We searched the MEDLINE, EMBASE, and CENTRAL databases in June 2025 for studies reporting FDG-PET data in patients with post-acute COVID-19 who have persistent neurological symptoms. Of the 14 eligible studies (584 scans), 13 reported glucose hypometabolism across frontoparietal regions, with the frontal cortex being the most consistently affected. This finding was confirmed by meta-analysis, which revealed a large and significant effect in the frontal cortex (Hedges' g = 1.34; 95% CI: 0.79-1.88; p < 0.001), despite high heterogeneity (I[2] = 93.6%). The systematic review indicates that brain metabolism generally improves over time, with widely varying recovery timelines, and consistently correlates hypometabolism with neurological symptom burden. These findings underscore the clinical relevance of frontoparietal hypometabolism in post-acute COVID-19 and its association with neurocognitive deficits, highlighting the need for longitudinal, quantitative PET studies to elucidate temporal dynamics and inform therapeutic development.},
}

Humans
*COVID-19/metabolism/diagnostic imaging/complications
Positron-Emission Tomography/methods
Fluorodeoxyglucose F18
*Brain/metabolism/diagnostic imaging
Post-Acute COVID-19 Syndrome
SARS-CoV-2
Radiopharmaceuticals
Glucose/metabolism

@article {pmid40685660,
year = {2025},
author = {Davis, S and Mon-Yee, M and Sutton, A and Leaviss, J and Forsyth, JE and Burton, C},
title = {Cost effectiveness of non-pharmacological interventions for fatigue in patients with long-term conditions: a systematic literature review.},
journal = {Expert review of pharmacoeconomics & outcomes research},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/14737167.2025.2537194},
pmid = {40685660},
issn = {1744-8379},
abstract = {INTRODUCTION: We aimed to assess the cost-effectiveness of non-pharmacological interventions for fatigue in patients with chronic conditions in the UK.

METHODS: This systematic review of cost-effectiveness studies aligns with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 statement. Data sources: Electronic databases and citation searches. Inclusion criteria: Studies including adults with one or more long-term health condition, either physical or mental. Exclusion criteria: Studies associated with cancer, long-COVID, post-viral fatigue, medically unexplained conditions, developmental disorders and injuries. Assessment: A single reviewer completed a two-stage sifting process.

RESULTS: Four studies met the inclusion criteria. They included patients with either multiple sclerosis or inflammatory rheumatic conditions, and assessed either cognitive behavioral therapy (CBT) or a personalized exercise program (PEP). CBT was either dominated by usual care or had an incremental cost-effectiveness ratio (ICER) over £30,000. PEP dominated CBT, with the ICER for PEP versus usual care ranging from £13,159 to £35,424.

CONCLUSIONS: The economic literature on this topic is much more limited than the clinical effectiveness literature, both in terms of interventions and populations covered. Future research should focus on a de novo economic evaluation to identify interventions with a high potential to be cost-effective across multiple conditions.

REGISTRATION: PROSPERO (CRD42023440141).},
}

@article {pmid40549427,
year = {2025},
author = {Luo, X and Li, Y and Xu, J and Zheng, Z and Ying, F and Huang, G},
title = {AI in Medical Questionnaires: Scoping Review.},
journal = {Journal of medical Internet research},
volume = {27},
number = {},
pages = {e72398},
pmid = {40549427},
issn = {1438-8871},
mesh = {Humans ; *Artificial Intelligence ; Surveys and Questionnaires ; COVID-19/epidemiology ; *Mental Disorders/diagnosis ; SARS-CoV-2 ; },
abstract = {UNLABELLED: This systematic review aimed to explore the current applications, potential benefits, and issues of artificial intelligence (AI) in medical questionnaires, focusing on its role in 3 main functions: assessment, development, and prediction. The global mental health burden remains severe. The World Health Organization reports that >1 billion people worldwide experience mental disorders, with the prevalence of depression and anxiety among children and adolescents at 2.6% and 6.5%, respectively. However, commonly used clinical questionnaires such as the Hamilton Depression Rating Scale and the Beck Depression Inventory suffer from several problems, including the high degree of overlap of symptoms of depression with those of other psychiatric disorders and a lack of professional supervision during administration of the questionnaires, which often lead to inaccurate diagnoses. In the wake of the COVID-19 pandemic, the health care system is facing the dual challenges of a surge in patient numbers and the complexity of mental health issues. AI technology has now been shown to have great promise in improving diagnostic accuracy, assisting clinical decision-making, and simplifying questionnaire development and data analysis. To systematically assess the value of AI in medical questionnaires, this study searched 5 databases (PubMed, Embase, Cochrane Library, Web of Science, and China National Knowledge Infrastructure) for the period from database inception to September 2024. Of 49,091 publications, a total of 14 (0.03%) studies met the inclusion criteria. AI technologies showed significant advantages in assessment, such as distinguishing myalgic encephalomyelitis or chronic fatigue syndrome from long COVID-19 with 92.18% accuracy. In questionnaire development, natural language processing using generative models such as ChatGPT was used to construct culturally competent scales. In terms of disease prediction, one study had an area under the curve of 0.790 for cataract surgery risk prediction. Overall, 24 AI technologies were identified, covering traditional algorithms such as random forest, support vector machine, and k-nearest neighbor, as well as deep learning models such as convolutional neural networks, Bidirectional Encoder Representations From Transformers, and ChatGPT. Despite the positive findings, only 21% (3/14) of the studies had entered the clinical validation phase, whereas the remaining 79% (11/14) were still in the exploratory phase of research. Most of the studies (10/14, 71%) were rated as being of moderate methodological quality, with major limitations including lack of a control group, incomplete follow-up data, and inadequate validation systems. In summary, the integrated application of AI in medical questionnaires has significant potential to improve diagnostic efficiency, accelerate scale development, and promote early intervention. Future research should pay more attention to model interpretability, system compatibility, validation standardization, and ethical governance to effectively address key challenges such as data privacy, clinical integration, and transparency.

BACKGROUND: The World Health Organization reports that >1 billion people worldwide experience mental disorders, with the prevalence of depression and anxiety among children and adolescents at 2.6% and 6.5%, respectively. However, commonly used clinical questionnaires such as the Hamilton Depression Rating Scale and the Beck Depression Inventory suffer from several problems, including the high degree of overlap of symptoms of depression with those of other psychiatric disorders and a lack of professional supervision during administration of the questionnaires, which often lead to inaccurate diagnoses. In the wake of the COVID-19 pandemic, the health care system is facing the dual challenges of a surge in patient numbers and the complexity of mental health issues. Artificial Intelligence (AI) technology has now been shown to have great promise in improving diagnostic accuracy, assisting clinical decision-making, and simplifying questionnaire development and data analysis.

OBJECTIVE: This review aimed to explore the current applications, potential benefits, and issues of AI in medical questionnaires, focusing on its role in 3 main functions: assessment, development, and prediction. The global mental health burden remains severe.

METHODS: The review included peer-reviewed studies that applied AI technologies to medical, psychological, or physiological questionnaires and reported measurable outcomes; non–peer-reviewed, non-English/Chinese, ethically noncompliant, or AI-unrelated studies were excluded. Five databases (PubMed, Embase, Cochrane Library, Web of Science, and CNKI) were searched from inception through September 2024. Three independent reviewers conducted data extraction, quality appraisal using the Joanna Briggs Institute tools, and narrative synthesis of AI applications across questionnaire assessment, development, and prediction tasks.

RESULTS: Of 49,091 publications, a total of 14 (0.03%) studies met the inclusion criteria. AI technologies showed advantages in assessment, such as distinguishing myalgic encephalomyelitis or chronic fatigue syndrome from long COVID-19 with 92.18% accuracy. In questionnaire development, natural language processing using generative models such as ChatGPT was used to construct culturally competent scales. In terms of disease prediction, one study had an area under the curve of 0.790 for cataract surgery risk prediction. Overall, 24 AI technologies were identified, covering traditional algorithms such as random forest, support vector machine, and k-nearest neighbor, as well as deep learning models such as convolutional neural networks, Bidirectional Encoder Representations From Transformers, and ChatGPT. Despite the positive findings, only 21% (3/14) of the studies had entered the clinical validation phase, whereas the remaining 79% (11/14) were still in the exploratory phase of research. Most of the studies (10/14, 71%) were rated as being of moderate methodological quality, with major limitations including lack of a control group, incomplete follow-up data, and inadequate validation systems.

CONCLUSIONS: In summary, the integrated application of AI in medical questionnaires has significant potential to improve diagnostic efficiency, accelerate scale development, and promote early intervention. Future research should pay more attention to model interpretability, system compatibility, validation standardization, and ethical governance to effectively address key challenges such as data privacy, clinical integration, and transparency.},
}

Humans
*Artificial Intelligence
Surveys and Questionnaires
COVID-19/epidemiology
*Mental Disorders/diagnosis
SARS-CoV-2

@article {pmid40300093,
year = {2025},
author = {Rane Levendovszky, S and Patel, P and Zhu, C and Rutman, AM and Basha, MM},
title = {Neuroimaging biomarkers of post-acute sequelae of Coronavirus Disease 2019.},
journal = {The British journal of radiology},
volume = {98},
number = {1172},
pages = {1165-1175},
doi = {10.1093/bjr/tqaf090},
pmid = {40300093},
issn = {1748-880X},
support = {R01 HL162743/HL/NHLBI NIH HHS/United States ; //Chronic Post COVID-19 Infection Neuroimaging and Cerebrovascular Imaging/ ; //Bayer Healthcare LLC/ ; //Long terms effects of COVID-19/ ; },
mesh = {Humans ; *COVID-19/complications/diagnostic imaging ; *Neuroimaging/methods ; *Brain/diagnostic imaging/pathology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Biomarkers ; Magnetic Resonance Imaging/methods ; Diffusion Tensor Imaging ; },
abstract = {COVID-19, caused by SARS-CoV-2, has led to the condition known as Long COVID or post-acute sequelae of COVID-19 (PASC), where individuals experience persistent debilitating symptoms long after the initial infection. We provide here a comprehensive review of findings in the central nervous system associated with PASC. Neuroimaging has been instrumental in identifying brain changes associated with PASC. Structural MRI studies consistently reveal grey matter volume reductions in the frontal and temporal lobes and white matter hyperintensities, particularly in the periventricular regions. Studies especially found these changes to correlate strongly with cognitive deficits. Diffusion tensor imaging has shown increased tissue damage and oedema in the brain's white matter tracts, particularly in the sagittal stratum and thalamic radiation. Resting-state functional MRI studies indicate altered brain connectivity in PASC patients, especially in those with post-traumatic stress symptoms. Reduced connectivity within and between critical networks, such as the default mode network and the executive control network, has been observed. These changes correlate with cognitive impairments, such as attention and memory deficits. Dynamic functional connectivity analyses further reveal that PASC patients spend less time in states with rich inter-regional connectivity, and transitions between connectivity states were linked to post-traumatic stress disorder symptoms. Positron emission tomography scans have shown hypometabolism in the frontal and temporal lobes, particularly in regions associated with memory and executive functions. Hypometabolism in the hippocampus and thalamus is linked to symptoms like anosmia and fatigue. Despite the heterogeneity in clinical presentations and diagnostic criteria, these neuroimaging findings underscore the significant impact of COVID-19 on brain structure and function. Continued research using advanced imaging techniques is essential for a deeper understanding of PASC's neurological effects. This will aid in developing targeted interventions and improving outcomes for those affected by Long COVID and inform studies investigating downstream effects of viral infections on the brain.},
}

Humans
*COVID-19/complications/diagnostic imaging
*Neuroimaging/methods
*Brain/diagnostic imaging/pathology
Post-Acute COVID-19 Syndrome
SARS-CoV-2
Biomarkers
Magnetic Resonance Imaging/methods
Diffusion Tensor Imaging

@article {pmid39083202,
year = {2024},
author = {Huang, Y and Wang, W and Liu, Y and Wang, Z and Cao, B},
title = {COVID-19 vaccine updates for people under different conditions.},
journal = {Science China. Life sciences},
volume = {67},
number = {11},
pages = {2323-2343},
pmid = {39083202},
issn = {1869-1889},
mesh = {Humans ; *COVID-19 Vaccines/immunology/administration & dosage ; *COVID-19/prevention & control/immunology/epidemiology ; *SARS-CoV-2/immunology ; Vaccine Efficacy ; Immunocompromised Host/immunology ; },
abstract = {SARS-CoV-2 has caused global waves of infection since December 2019 and continues to persist today. The emergence of SARS-CoV-2 variants with strong immune evasion capabilities has compromised the effectiveness of existing vaccines against breakthrough infections. Therefore, it is important to determine the best utilization strategies for different demographic groups given the variety of vaccine options available. In this review, we will discuss the protective efficacy of vaccines during different stages of the epidemic and emphasize the importance of timely updates to target prevalent variants, which can significantly improve immune protection. While it is recognized that vaccine effectiveness may be lower in certain populations such as the elderly, individuals with chronic comorbidities (e.g., diabetes with poor blood glucose control, those on maintenance dialysis), or those who are immunocompromised compared to the general population, administering multiple doses can result in a strong protective immune response that outweighs potential risks. However, caution should be exercised when considering vaccines that might trigger an intense immune response in populations prone to inflammatory flare or other complications. In conclusion, individuals with special conditions require enhanced and more effective immunization strategies to prevent infection or reinfection, as well as to avoid the potential development of long COVID.},
}

Humans
*COVID-19 Vaccines/immunology/administration & dosage
*COVID-19/prevention & control/immunology/epidemiology
*SARS-CoV-2/immunology
Vaccine Efficacy
Immunocompromised Host/immunology

@article {pmid38973985,
year = {2024},
author = {Dalmau, R and Alanazi, AM and Arora, M and Banerjee, A and Bianco, E and Gaalema, DE and Goma, FM and Hasegawa, K and Komiyama, M and Pérez Ríos, M and Willett, J and Wang, Y},
title = {A Complex Interplay: Navigating the Crossroads of Tobacco Use, Cardiovascular Disease, and the COVID-19 Pandemic: A WHF Policy Brief.},
journal = {Global heart},
volume = {19},
number = {1},
pages = {55},
pmid = {38973985},
issn = {2211-8179},
mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; *Cardiovascular Diseases/epidemiology/prevention & control ; *Tobacco Use/epidemiology ; *SARS-CoV-2 ; Pandemics ; Risk Factors ; Health Policy ; },
abstract = {The Coronavirus Disease 2019, commonly referred to as COVID-19, is responsible for one of the deadliest pandemics in human history. The direct, indirect and lasting repercussions of the COVID-19 pandemic on individuals and public health, as well as health systems can still be observed, even today. In the midst of the initial chaos, the role of tobacco as a prognostic factor for unfavourable COVID-19 outcomes was largely neglected. As of 2023, numerous studies have confirmed that use of tobacco, a leading risk factor for cardiovascular and other diseases, is strongly associated with increased risks of severe COVID-19 complications (e.g., hospitalisation, ICU admission, need for mechanical ventilation, long COVID, etc.) and deaths from COVID-19. In addition, evidence suggests that COVID-19 directly affects multiple organs beyond the respiratory system, disproportionately impacting individuals with comorbidities. Notably, people living with cardiovascular disease are more prone to experiencing worse outcomes, as COVID-19 often inherently manifests as thrombotic cardiovascular complications. As such, the triad of tobacco, COVID-19 and cardiovascular disease constitutes a dangerous cocktail. The lockdowns and social distancing measures imposed by governments have also had adverse effects on our lifestyles (e.g., shifts in diets, physical activity, tobacco consumption patterns, etc.) and mental well-being, all of which affect cardiovascular health. In particular, vulnerable populations are especially susceptible to tobacco use, cardiovascular disease and the psychological fallout from the pandemic. Therefore, national pandemic responses need to consider health equity as well as the social determinants of health. The pandemic has also had catastrophic impacts on many health systems, bringing some to the brink of collapse. As a result, many health services, such as services for cardiovascular disease or tobacco cessation, were severely disrupted due to fears of transmission and redirection of resources for COVID-19 care. Unfortunately, the return to pre-pandemic levels of cardiovascular disease care activity has stagnated. Nevertheless, digital solutions, such as telemedicine and apps, have flourished, and may help reduce the gaps. Advancing tobacco control was especially challenging due to interference from the tobacco industry. The industry exploited lingering uncertainties to propagate misleading information on tobacco and COVID-19 in order to promote its products. Regrettably, the links between tobacco use and risk of SARS-CoV-2 infection remain inconclusive. However, a robust body of evidence has, since then, demonstrated that tobacco use is associated with more severe COVID-19 illness and complications. Additionally, the tobacco industry also repeatedly attempted to forge partnerships with governments under the guise of corporate social responsibility. The implementation of the WHO Framework Convention on Tobacco Control could address many of the aforementioned challenges and alleviate the burden of tobacco, COVID-19, and cardiovascular disease. In particular, the implementation of Article 5.3 could protect public health policies from the vested interests of the industry. The world can learn from the COVID-19 pandemic to better prepare for future health emergencies of international concern. In light of the impact of tobacco on the COVID-19 pandemic, it is imperative that tobacco control remains a central component in pandemic preparedness and response plans.},
}

Humans
*COVID-19/epidemiology/prevention & control
*Cardiovascular Diseases/epidemiology/prevention & control
*Tobacco Use/epidemiology
*SARS-CoV-2
Pandemics
Risk Factors
Health Policy

@article {pmid37832998,
year = {2023},
author = {Voss, JG and Pinto, MD and Burton, CW},
title = {How do the Social Determinants of Health Impact the Post-Acute Sequelae of COVID-19: A Critical Review.},
journal = {The Nursing clinics of North America},
volume = {58},
number = {4},
pages = {541-568},
doi = {10.1016/j.cnur.2023.07.004},
pmid = {37832998},
issn = {1558-1357},
mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; Social Determinants of Health ; Disease Progression ; },
abstract = {The review critically analyzes the social determinants of health (SDOH) variables in the current literature of patients with post-acute sequelae (PASC) of COVID-19 in the United States. Race, gender, and age were discussed as well as health outcomes, severity of illness, and phenotypes of long-COVID. Most research was retrospectively with samples that had access to health insurance, which did not capture populations with poor or no access to health care. More research is needed that directly addresses the impact on SDOH on PASC. The current literature is sparse and provides little actionable information.},
}

Humans
*COVID-19
Post-Acute COVID-19 Syndrome
Retrospective Studies
Social Determinants of Health
Disease Progression

@article {pmid37797257,
year = {2023},
author = {Baker, MG and Kvalsvig, A and Plank, MJ and Geoghegan, JL and Wall, T and Tukuitonga, C and Summers, J and Bennett, J and Kerr, J and Turner, N and Roberts, S and Ward, K and Betty, B and Huang, QS and French, N and Wilson, N},
title = {Continued mitigation needed to minimise the high health burden from COVID-19 in Aotearoa New Zealand.},
journal = {The New Zealand medical journal},
volume = {136},
number = {1583},
pages = {67-91},
doi = {10.26635/6965.6247},
pmid = {37797257},
issn = {1175-8716},
mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; New Zealand/epidemiology ; Post-Acute COVID-19 Syndrome ; Pandemics/prevention & control ; Maori People ; },
abstract = {In this article we review the COVID-19 pandemic experience in Aotearoa New Zealand and consider the optimal ongoing response strategy. We note that this pandemic virus looks likely to result in future waves of infection that diminish in size over time, depending on such factors as viral evolution and population immunity. However, the burden of disease remains high with thousands of infections, hundreds of hospitalisations and tens of deaths each week, and an unknown burden of long-term illness (long COVID). Alongside this there is a considerable burden from other important respiratory illnesses, including influenza and RSV, that needs more attention. Given this impact and the associated health inequities, particularly for Māori and Pacific Peoples, we consider that an ongoing respiratory disease mitigation strategy is appropriate for New Zealand. As such, the previously described "vaccines plus" approach (involving vaccination and public health and social measures), should now be integrated with the surveillance and control of other important respiratory infections. Now is also a time for New Zealand to build on the lessons from the COVID-19 pandemic to enhance preparedness nationally and internationally. New Zealand's experience suggests elimination (or ideally exclusion) should be the default first choice for future pandemics of sufficient severity.},
}

Humans
*COVID-19/epidemiology/prevention & control
New Zealand/epidemiology
Post-Acute COVID-19 Syndrome
Pandemics/prevention & control
Maori People

@article {pmid36731604,
year = {2023},
author = {Crosier, R and Kafil, TS and Paterson, DI},
title = {Imaging for Cardiovascular Complications of COVID-19: Cardiac Manifestations in Context.},
journal = {The Canadian journal of cardiology},
volume = {39},
number = {6},
pages = {779-792},
pmid = {36731604},
issn = {1916-7075},
support = {//CIHR/Canada ; },
mesh = {Humans ; *COVID-19/complications ; *COVID-19 Vaccines/adverse effects ; Heart ; *Myocarditis/diagnostic imaging/etiology ; Post-Acute COVID-19 Syndrome ; RNA, Messenger ; },
abstract = {After the first confirmed case in 2019, COVID-19 rapidly spread worldwide and overwhelmed the medical community. In the intervening time, we have learned about COVID-19's clinical manifestations and have developed effective therapies and preventative vaccines. Severe COVID-19 infection is associated with many cardiovascular disorders in the acute phase, and patients recovered from illness can also manifest long-term sequelae, including long COVID syndrome. Furthermore, severe acute respiratory syndrome-related coronavirus-2 messenger RNA (mRNA) vaccination can trigger rare cases of myopericarditis. We have gained significant knowledge of the acute and long-term cardiovascular complications of COVID-19- and mRNA vaccine-associated myocarditis through clinical and investigative studies using cardiac imaging. In this review, we describe how cardiovascular imaging can be used to understand the cardiovascular complications and cardiac injury associated with acute COVID-19 infection, review the imaging findings in patients recovered from illness, and discuss the role and limitations of cardiac imaging in COVID-19 mRNA vaccine-associated myocarditis.},
}

Humans
*COVID-19/complications
*COVID-19 Vaccines/adverse effects
Heart
*Myocarditis/diagnostic imaging/etiology
Post-Acute COVID-19 Syndrome
RNA, Messenger

@article {pmid35462637,
year = {2022},
author = {Saha, SA and Russo, AM and Chung, MK and Deering, TF and Lakkireddy, D and Gopinathannair, R},
title = {COVID-19 and Cardiac Arrhythmias: a Contemporary Review.},
journal = {Current treatment options in cardiovascular medicine},
volume = {24},
number = {6},
pages = {87-107},
pmid = {35462637},
issn = {1092-8464},
support = {IK6 BX006185/BX/BLRD VA/United States ; R01 HL111314/HL/NHLBI NIH HHS/United States ; R01 HL158071/HL/NHLBI NIH HHS/United States ; },
abstract = {PURPOSE OF REVIEW: A significant proportion of patients infected by the severe acute respiratory syndrome-coronavirus (SARS-CoV2) (COVID-19) also have disorders affecting the cardiac rhythm. In this review, we provide an in-depth review of the pathophysiological mechanisms underlying the associated arrhythmic complications of COVID-19 infection and provide pragmatic, evidence-based recommendations for the clinical management of these conditions.

RECENT FINDINGS: Arrhythmic manifestations of COVID-19 include atrial arrhythmias such as atrial fibrillation or atrial flutter, sinus node dysfunction, atrioventricular conduction abnormalities, ventricular tachyarrhythmias, sudden cardiac arrest, and cardiovascular dysautonomias including the so-called long COVID syndrome. Various pathophysiological mechanisms have been implicated, such as direct viral invasion, hypoxemia, local and systemic inflammation, changes in ion channel physiology, immune activation, and autonomic dysregulation. The development of atrial or ventricular arrhythmias in hospitalized COVID-19 patients has been shown to portend a higher risk of in-hospital death.

SUMMARY: Arrhythmic complications from acute COVID-19 infection are commonly encountered in clinical practice, and COVID-19 patients with cardiac complications tend to have worse clinical outcomes than those without. Management of these arrhythmias should be based on published evidence-based guidelines, with special consideration of the acuity of COVID-19 infection, concomitant use of antimicrobial and anti-inflammatory drugs, and the transient nature of some rhythm disorders. Some manifestations, such as the long COVID syndrome, may lead to residual symptoms several months after acute infection. As the pandemic evolves with the discovery of new SARS-CoV2 variants, development and use of newer anti-viral and immuno-modulator drugs, and the increasing adoption of vaccination, clinicians must remain vigilant for other arrhythmic manifestations that may occur in association with this novel but potentially deadly disease.},
}

@article {pmid34870392,
year = {2021},
author = {Zimmermann, P and Pittet, LF and Curtis, N},
title = {How Common is Long COVID in Children and Adolescents?.},
journal = {The Pediatric infectious disease journal},
volume = {40},
number = {12},
pages = {e482-e487},
pmid = {34870392},
issn = {1532-0987},
mesh = {Adolescent ; COVID-19/*complications/epidemiology/ethnology/*pathology ; Child ; Humans ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {In children, the risk of coronavirus disease (COVID) being severe is low. However, the risk of persistent symptoms following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is uncertain in this age group, and the features of "long COVID" are poorly characterized. We reviewed the 14 studies to date that have reported persistent symptoms following COVID in children and adolescents. Almost all the studies have major limitations, including the lack of a clear case definition, variable follow-up times, inclusion of children without confirmation of SARS-CoV-2 infection, reliance on self- or parent-reported symptoms without clinical assessment, nonresponse and other biases, and the absence of a control group. Of the 5 studies which included children and adolescents without SARS-CoV-2 infection as controls, 2 did not find persistent symptoms to be more prevalent in children and adolescents with evidence of SARS-CoV-2 infection. This highlights that long-term SARS-CoV-2 infection-associated symptoms are difficult to distinguish from pandemic-associated symptoms.},
}

Adolescent
COVID-19/*complications/epidemiology/ethnology/*pathology
Child
Humans
*SARS-CoV-2
Post-Acute COVID-19 Syndrome

@article {pmid34631916,
year = {2021},
author = {Sandler, CX and Wyller, VBB and Moss-Morris, R and Buchwald, D and Crawley, E and Hautvast, J and Katz, BZ and Knoop, H and Little, P and Taylor, R and Wensaas, KA and Lloyd, AR},
title = {Long COVID and Post-infective Fatigue Syndrome: A Review.},
journal = {Open forum infectious diseases},
volume = {8},
number = {10},
pages = {ofab440},
pmid = {34631916},
issn = {2328-8957},
abstract = {Fatigue is a dominant feature of both acute and convalescent coronavirus disease 2019 (COVID-19) (sometimes termed "long-COVID"), with up to 46% of patients reporting fatigue that lasts from weeks to months. The investigators of the international Collaborative on Fatigue Following Infection (COFFI) conducted a systematic review of post-COVID fatigue and a narrative review on fatigue after other infections, and made recommendations for clinical and research approaches to assessing fatigue after COVID-19. In the majority of COVID-19 cohort studies, persistent fatigue was reported by a significant minority of patients, ranging from 13% to 33% at 16-20 weeks post-symptom onset. Data from the prospective cohort studies in COFFI and others indicate that fatigue is also a prevalent outcome from many acute systemic infections, notably infectious mononucleosis, with a case rate for clinically significant Post-infective fatigue after exclusion of recognized medical and psychiatric causes, ranging from 10%-35% at 6 months. To better characterize post-COVID fatigue, the COFFI investigators recommend the following: application of validated screening questionnaires for case detection; standardized interviews encompassing fatigue, mood, and other symptoms; and investigative approaches to identify end-organ damage and mental health conditions.},
}

@article {pmid33857435,
year = {2021},
author = {Song, WJ and Hui, CKM and Hull, JH and Birring, SS and McGarvey, L and Mazzone, SB and Chung, KF},
title = {Confronting COVID-19-associated cough and the post-COVID syndrome: role of viral neurotropism, neuroinflammation, and neuroimmune responses.},
journal = {The Lancet. Respiratory medicine},
volume = {9},
number = {5},
pages = {533-544},
pmid = {33857435},
issn = {2213-2619},
mesh = {COVID-19/*complications/*physiopathology ; Cough/*etiology/physiopathology ; Humans ; Inflammation/*etiology/physiopathology ; Nervous System Diseases/*etiology/physiopathology ; *Neuroimmunomodulation ; SARS-CoV-2 ; Syndrome ; },
abstract = {Cough is one of the most common presenting symptoms of COVID-19, along with fever and loss of taste and smell. Cough can persist for weeks or months after SARS-CoV-2 infection, often accompanied by chronic fatigue, cognitive impairment, dyspnoea, or pain-a collection of long-term effects referred to as the post-COVID syndrome or long COVID. We hypothesise that the pathways of neurotropism, neuroinflammation, and neuroimmunomodulation through the vagal sensory nerves, which are implicated in SARS-CoV-2 infection, lead to a cough hypersensitivity state. The post-COVID syndrome might also result from neuroinflammatory events in the brain. We highlight gaps in understanding of the mechanisms of acute and chronic COVID-19-associated cough and post-COVID syndrome, consider potential ways to reduce the effect of COVID-19 by controlling cough, and suggest future directions for research and clinical practice. Although neuromodulators such as gabapentin or opioids might be considered for acute and chronic COVID-19 cough, we discuss the possible mechanisms of COVID-19-associated cough and the promise of new anti-inflammatories or neuromodulators that might successfully target both the cough of COVID-19 and the post-COVID syndrome.},
}

COVID-19/*complications/*physiopathology
Cough/*etiology/physiopathology
Humans
Inflammation/*etiology/physiopathology
Nervous System Diseases/*etiology/physiopathology
*Neuroimmunomodulation
SARS-CoV-2
Syndrome

@article {pmid40819231,
year = {2025},
author = {Levin, J and Bradshaw, M},
title = {The Challenge of Long COVID: Is the Pandemic Really Over?.},
journal = {Public health reports (Washington, D.C. : 1974)},
volume = {},
number = {},
pages = {333549251358665},
doi = {10.1177/00333549251358665},
pmid = {40819231},
issn = {1468-2877},
abstract = {Sequelae of SARS-CoV-2 infection began appearing among patients who had COVID-19 within months of the first wave of the COVID-19 pandemic in 2020. This phenomenon, termed post-COVID-19 condition and also known as long COVID, has been a source of controversy among physicians, as presentation of long COVID has been a somewhat mysterious constellation of signs and symptoms that seem mostly impervious to efficacious treatment. Although a considerable amount has been learned about the pathophysiology and other biomedical features of long COVID, the epidemiologic parameters of long COVID, including incidence and prevalence, are uncertain in the United States and globally. The best estimates are that millions of people have long COVID. Despite the declining incidence of COVID-19, the low case fatality of long COVID suggests that its prevalence is poised to continue to grow. This increasing prevalence of long COVID presents a challenge for the public health sector. Here, we examine the public health implications of long COVID. We offer policy recommendations, including ending congratulatory talk that the pandemic is over, encouraging more focused attention from the United States and global nongovernmental organizations, and establishing a multinational research initiative to better understand and respond to long COVID and other postviral and postinfectious chronic conditions. Although COVID-19 may not be as widespread and disruptive as in the early months of the pandemic, it would be a mistake to presume that, because the acute crisis is behind us, the pandemic is past. Long COVID is an ongoing public health threat and merits our concern.},
}

@article {pmid40769733,
year = {2025},
author = {Wilson, CM and Boright, LE and Henshaw, AM and Naccarato, A},
title = {Role of rehabilitation in palliative care after the COVID-19 pandemic: a narrative review.},
journal = {Annals of palliative medicine},
volume = {14},
number = {4},
pages = {379-392},
doi = {10.21037/apm-25-6},
pmid = {40769733},
issn = {2224-5839},
mesh = {Humans ; *COVID-19/rehabilitation/epidemiology ; *Palliative Care/organization & administration ; Pandemics ; SARS-CoV-2 ; },
abstract = {BACKGROUND AND OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic resulted in an historic disruption and transformation of the healthcare system, including the management of individuals with serious illness. Rehabilitation for patients facing serious or life-threatening illness is underutilized and poorly understood, resulting in unwarranted suffering, disability, and poorly coordinated care. This narrative review aims to describe the impact of the COVID-19 pandemic on the role and scope of rehabilitation within the context of serious illness and palliative care.

METHODS: A focused review of the literature included selected articles identified from three databases published from January 2020 to January 2025. Findings were synthesized narratively, with a focus on identifying themes and gaps in the literature related to two main topics: (I) the evidence related to rehabilitation for those with serious or life-threatening COVID-19 during the pandemic and (II) how rehabilitation for patients with serious illness has been transformed after emerging from the pandemic (including non-COVID diagnoses such as cancer, neurologic conditions, etc.).

KEY CONTENT AND FINDINGS: The key themes identified during the COVID-19 pandemic emphasized the need for early rehabilitation, interdisciplinary care, and an emphasis on cardiopulmonary principles for rehabilitation. Themes identified during the pandemic also included the emerging role of telerehabilitation, and need for evidence and clinical guidelines for serious illnesses (including long COVID). Themes related to the transformative effect on palliative rehabilitation after the pandemic included an increased importance and focus on coordination of care and interdisciplinary care for those with serious illness and increased focus on mental health and social determinants of health (SDOH). Additionally, there appears to be increased infrastructure and activity related to research, advocacy, and awareness for palliative rehabilitation.

CONCLUSIONS: The COVID-19 global pandemic highlighted the need for high quality, coordinated palliative care, including rehabilitation services, for patients facing a serious or life-threatening illness. Due to the benefits to a person's quality of life (QoL), dignity, and comfort, there is increasing evidence of the importance of seamless, ongoing access to rehabilitation services for patients with serious illness.},
}

Humans
*COVID-19/rehabilitation/epidemiology
*Palliative Care/organization & administration
Pandemics
SARS-CoV-2

@article {pmid40762988,
year = {2025},
author = {Gusmão, ACS and Scaléa, ACR and Uehara, SCDSA},
title = {Symptoms of long COVID in children and adolescents: a scoping review.},
journal = {Revista da Escola de Enfermagem da U S P},
volume = {59},
number = {},
pages = {e20240435},
pmid = {40762988},
issn = {1980-220X},
mesh = {Humans ; Adolescent ; Child ; *COVID-19/complications/diagnosis/epidemiology/physiopathology ; Age Factors ; },
abstract = {OBJECTIVE: To map the symptoms of Long Covid (LC) presented by children and adolescents.

METHOD: This is a scoping review, using the search engines Web of Science, Scopus, Virtual Health Library, and PUBMED, following the principles of the Joanna Briggs Institute.

RESULTS: Sixteen studies were selected, which showed that fatigue, headache, dyspnea, and cough were the most frequent symptoms of LC. There is a tendency for the development of child-adolescent LC related to the increase in age range, and the correlation between LC and predominant sex proved to be inconclusive. The presence of comorbidities, such as obesity, respiratory, neurological and renal diseases, was the most reported and a study showed an association between Covid-19 vaccine protection and LC.

CONCLUSION: This review points to a plurality of symptomatic manifestations of LC in children and adolescents, changing according to age group and health history.},
}

Humans
Adolescent
Child
*COVID-19/complications/diagnosis/epidemiology/physiopathology
Age Factors

@article {pmid40754067,
year = {2025},
author = {Peine, C and Stoliaroff-Pepin, A and Reinacher, U and Heldt, K and Sarganas, G and Piechotta, V and Mikolajewska, A and Pilic, A and Barkowski, N and Bleve, D and Giebeler, MH and Poser, S and Searle, L and Kißner, E and Nitsche, L and Bayram, F and Siemens, W and Ziegler, A and Meerpohl, JJ and Sandmann, F and Wichmann, O and Harder, T},
title = {Effectiveness of COVID-19 vaccines against post COVID-19 condition/long COVID: systematic review and meta-analysis.},
journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cmi.2025.07.026},
pmid = {40754067},
issn = {1469-0691},
abstract = {BACKGROUND: Persons infected with SARS-CoV-2 can develop long-term symptoms known as post-COVID-19-condition (PCC; symptoms ≥three months after infection) or long-COVID (LC; symptoms ≥one month after infection). Vaccination against COVID-19 might prevent PCC/LC, but the extent of protection is unclear.

OBJECTIVE: Aim of this systematic review was to evaluate vaccine efficacy/effectiveness (VE) of COVID-19 vaccines given prior to SARS-CoV-2-infection in preventing PCC or LC.

METHODS DATA SOURCES: Studies were identified in Embase, MEDLINE, PreView, COVID-19 L.OVE repository and Cochrane Library up to August 1, 2024.

Randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSI) that investigated immunization with a COVID-19 vaccine before SARS-CoV-2-infection were eligible, irrespective of participant age and sex.

ASSESSMENT OF RISK OF BIAS: Risk of bias was assessed using ROBINS-I.

METHODS OF DATA SYNTHESIS: Primary outcome was PCC, secondary outcomes were LC, time until reconvalescence, limitations in every day activity, and quality of life. Meta-analyses were primarily conducted using the random-effects model.

RESULTS: 6423 records were screened and 65 non-randomized studies of interventions (NRSI) reporting adjusted estimates were included, comprising >5.7 mio.

PARTICIPANTS: VE for ≥one vaccine dose against PCC was 41.0% (95% confidence interval (CI) 27.8%; 51.7%; 22 NRSI, certainty of evidence: low). VE after one, two or three doses versus unvaccinated was 19.1% (-119.4%; 70.2%, three NRSI), 43.2% (4.5%; 66.2%; four NRSI) and 70.0% (30.0%; 87.0%; one NRSI), respectively. In <18-years-olds, VE against PCC was 26% for ≥one dose (-4%; 48%, one NRSI) and in >60-years-olds 41% (17%; 59%, one NRSI). VE after pre-Omicron-SARS-CoV-2 infection was 32.1% (-54.3%; 70.1%, three NRSI) and 20.9% (-10.1%; 43.3%, two NRSI) after Omicron-infection. Sensitivity analyses indicated no influence of risk of bias and effect measure.

CONCLUSIONS: COVID-19 vaccines may be moderately effective in preventing PCC/LC. VE may increase with number of vaccine doses administered.},
}

@article {pmid40744021,
year = {2025},
author = {Komaroff, AL and Dantzer, R},
title = {Causes of symptoms and symptom persistence in long COVID and myalgic encephalomyelitis/chronic fatigue syndrome.},
journal = {Cell reports. Medicine},
volume = {},
number = {},
pages = {102259},
doi = {10.1016/j.xcrm.2025.102259},
pmid = {40744021},
issn = {2666-3791},
abstract = {Debilitating symptoms for many years can follow acute COVID-19 ("long COVID"), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and various post-acute infection syndromes (PAISs). Together, long COVID and ME/CFS affect 60-400 million individuals, globally. Many similar underlying biological abnormalities have been identified in both conditions including autoantibodies against neural targets, endothelial dysfunction, acquired mitochondrial dysfunction, and a pro-inflammatory gut microbiome. Each of these abnormalities may directly cause some of the symptoms. In addition, the symptoms also may be caused by ancient, evolutionarily conserved symptomatic and metabolic responses to vital threats-sickness behavior and torpor-responses mediated by specific, recently discovered neural circuits. These neural circuits constitute a symptom-generating pathway, activated by neuroinflammation, which may be targeted by therapeutics to quell neuroinflammation. Many factors cause the symptoms to become chronic, including persistent infectious agents (and/or their nucleic acids and antigens) and the fact that many of the underlying biological abnormalities reinforce each other, creating ongoing physiological vicious cycles.},
}

@article {pmid40736492,
year = {2025},
author = {Grad, R and Ebell, MH},
title = {Top 20 Research Studies of 2024 for Primary Care Physicians.},
journal = {American family physician},
volume = {112},
number = {1},
pages = {34-41},
pmid = {40736492},
issn = {1532-0650},
mesh = {Humans ; Anti-Bacterial Agents/therapeutic use ; *Physicians, Primary Care ; COVID-19 ; *Primary Health Care ; SARS-CoV-2 ; },
abstract = {This article summarizes the top 20 research studies of 2024 identified as POEMs (patient-oriented evidence that matters). Based on a network meta-analysis, the oral antibiotics most likely to be effective for community-acquired pneumonia are telithromycin (not available in the United States), azithromycin, amoxicillin-clavulanate, and the quinolones levofloxacin and nemonoxacin (not available in the United States). The oral antivirals molnupiravir and nirmatrelvir-ritonavir reduce hospitalizations in immunocompromised patients with COVID-19. In average-risk infants, a single dose of nirsevimab reduces hospitalizations due to respiratory syncytial virus. Amoxicillin with or without clavulanate is more effective than placebo for children with symptoms of acute sinusitis. Benzyl benzoate 25% is highly effective for scabies in adolescents and adults. Lactobacillus-containing probiotics reduce the incidence of recurrent urinary tract infections (UTIs) in premenopausal women with frequent UTIs. Low-dose amitriptyline is effective as second-line therapy for irritable bowel syndrome. For patients with uncomplicated gallstones, conservative management is a reasonable option. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists are better than older drugs at improving patient-oriented outcomes for type 2 diabetes. Continuous or intermittent glucose monitoring is minimally effective for control of type 2 diabetes and can be harmful. Phentermine-topiramate and GLP-1 receptor agonists are the most effective drugs for promoting weight loss. Semaglutide is effective for secondary prevention of cardiovascular disease in people with obesity and no diabetes. SGLT-2 inhibitors and GLP-1 receptor agonists decrease cardiovascular death in older adults with type 2 diabetes and heart failure. Beta blockers do not prevent subsequent events after myocardial infarction in patients with preserved ejection fraction. For patients who do not quit smoking after a trial of varenicline or combined nicotine replacement therapy, a higher dose of either drug can increase quit rates. e-Cigarettes increase abstinence from smoking, but long-term vaping is a consequence for some. Oral naltrexone and acamprosate are safe and effective treatments for alcohol use disorder. Cognitive behavior therapy can reduce fatigue attributed to long COVID. New monoclonal antibodies for Alzheimer disease are harmful, expensive, and minimally effective. Clinicians may choose to deliver bad news in person or by telephone, using their judgment or patient preference to decide which is best for the patient.},
}

Humans
Anti-Bacterial Agents/therapeutic use
*Physicians, Primary Care
COVID-19
*Primary Health Care
SARS-CoV-2

@article {pmid40733521,
year = {2025},
author = {Mahajan, S and Mahajan, S and Patgiri, S},
title = {Association and Interaction of Epstein-Barr Virus with SARS-CoV-2 Infection-A Review.},
journal = {Viruses},
volume = {17},
number = {7},
pages = {},
pmid = {40733521},
issn = {1999-4915},
mesh = {Humans ; *COVID-19/virology/complications/immunology ; *Herpesvirus 4, Human/physiology ; *Epstein-Barr Virus Infections/virology/complications/drug therapy ; *SARS-CoV-2/physiology ; Virus Activation ; },
abstract = {Despite the significant decrease in SARS-CoV-2-related mortality, COVID-19 continues to impose a high public health burden due to the high rate of post-COVID-19 pathological conditions, broadly termed Long COVID, that continue for any period of time and are generally multisystemic. However, recent studies have strengthened the evidence that the reactivation of the Epstein-Barr virus (EBV) in the post-COVID-19 era has significantly contributed to the exacerbation and prolongation of Long COVID symptoms. The mechanism and pathophysiology of EBV reactivation in Long COVID patients still need further exploration due to limited studies. This review summarises the various studies linking EBV reactivation in Long COVID along with its pathophysiology and novel therapeutics for EBV in a post-COVID-19 era.},
}

Humans
*COVID-19/virology/complications/immunology
*Herpesvirus 4, Human/physiology
*Epstein-Barr Virus Infections/virology/complications/drug therapy
*SARS-CoV-2/physiology
Virus Activation

@article {pmid40729821,
year = {2025},
author = {Kell, DB and Kell, L and Kenny, LC and Merriel, A and Moore, JB and Pretorius, E},
title = {The roles of placental senescence, autophagy and senotherapeutics in the development and prevention of pre-eclampsia: A focus on ergothioneine.},
journal = {Journal of reproductive immunology},
volume = {171},
number = {},
pages = {104621},
doi = {10.1016/j.jri.2025.104621},
pmid = {40729821},
issn = {1872-7603},
abstract = {Cellular senescence is a well-established biological phenomenon in eukaryotes. It involves DNA damage, telomere shortening, a senescence-associated secretory phenotype (SASP), and the inability of cells to replicate. It is associated with ageing, and also with oxidative stress. Given the importance of oxidative stress in pre-eclampsia, there is considerable evidence, that we review, that senescence plays an important role in both normal placental development and in the development of both early- and late-term pre-eclampsia. Autophagy is capable of delaying or even reversing the development of senescence, and certain small molecules such as sulforaphane and spermidine can stimulate autophagy, including via the redox-sensitive transcription factor Nrf2. Ergothioneine is a thiohistidine antioxidant that is protective against a variety of cardiovascular and other diseases. Ergothioneine also interacts with Nrf2, and pre-eclampsia occurs far less frequently in individuals with higher plasma ergothioneine levels. Together, these elements provide a self-consistent, molecular and systems biology explanation for at least one mechanism by which ergothioneine may be protective against pre-eclampsia.},
}

@article {pmid40723876,
year = {2025},
author = {Richardson, E and Mo, CC and Calabretta, E and Corrado, F and Kocoglu, MH and Baron, RM and Connors, JM and Iacobelli, M and Wei, LJ and Benjamin, EJ and Rapoport, AP and Díaz-Ricart, M and Martínez-Mellado, AJ and Carlo-Stella, C and Richardson, PG and Moraleda, JM},
title = {Defibrotide for Protecting Against and Managing Endothelial Injury in Hematologic Malignancies and COVID-19.},
journal = {Biomolecules},
volume = {15},
number = {7},
pages = {},
pmid = {40723876},
issn = {2218-273X},
mesh = {Humans ; *Hematologic Neoplasms/drug therapy/complications/pathology ; *Polydeoxyribonucleotides/therapeutic use/pharmacology ; *COVID-19/complications/pathology/virology ; SARS-CoV-2 ; Hepatic Veno-Occlusive Disease/drug therapy ; *COVID-19 Drug Treatment ; Graft vs Host Disease/drug therapy ; Cytokine Release Syndrome/drug therapy ; *Fibrinolytic Agents/therapeutic use/pharmacology ; },
abstract = {Defibrotide, which is approved for treating hepatic veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS), exhibits pleiotropic anti-inflammatory, anti-thrombotic, and fibrinolytic properties, conferring broad endothelial protective effects. Given these mechanisms, defibrotide has potential utility in various conditions involving endothelial injury or activation. In this review we outline the endothelial-protective mechanisms of defibrotide and comprehensively summarize current evidence supporting its applications in hematologic malignancies, including the prevention and treatment of hepatic VOD/SOS, graft-versus-host disease, and transplant-associated thrombotic microangiopathy. Additionally, we discuss its role in mitigating key toxicities linked to chimeric antigen receptor (CAR) T-cell therapies and bispecific antibodies, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). We also explore emerging evidence on defibrotide's potential in SARS-CoV-2 infection-associated endotheliopathies, including acute COVID-19 and post-acute sequelae of SARS-CoV-2 infection ("long-COVID"), and the endothelial protective activity of defibrotide in these settings. Finally, we highlight potential future applications of defibrotide in hematologic malignancies and viral infections, emphasizing its multimodal mechanism of action.},
}

Humans
*Hematologic Neoplasms/drug therapy/complications/pathology
*Polydeoxyribonucleotides/therapeutic use/pharmacology
*COVID-19/complications/pathology/virology
SARS-CoV-2
Hepatic Veno-Occlusive Disease/drug therapy
*COVID-19 Drug Treatment
Graft vs Host Disease/drug therapy
Cytokine Release Syndrome/drug therapy
*Fibrinolytic Agents/therapeutic use/pharmacology

@article {pmid40721817,
year = {2025},
author = {Yogendra, R and Perlowski, A and Johng, B and Dahshan, H and Orr, C and Jeffers, D and Husain, K and Patterson, BK},
title = {Perioperative and anesthetic considerations for post-acute sequelae of COVID (PASC)/long COVID.},
journal = {Perioperative medicine (London, England)},
volume = {14},
number = {1},
pages = {80},
pmid = {40721817},
issn = {2047-0525},
abstract = {Post-acute sequelae of COVID (PASC), commonly known as long COVID, presents with a broad spectrum of medical conditions and symptoms persisting beyond 3 months post-SARS-CoV-2 infection, affecting over 18 million Americans and 65 million people worldwide. Despite its prevalence, to date, there are no specific clinical guidelines for the perioperative management of PASC patients. PASC is a complex, multisystemic condition leading to neurological, respiratory, and endocrine sequelae, potentially resulting from persistent viral presence, immune dysregulation, and/or end-organ damage. This manuscript discusses the implications of these sequelae on anesthesia practice, emphasizing the need for vigilance in pre-operative assessments to identify PASC and associated conditions through detailed patient history, understanding of off-label medication use, and familiarity with medical terminologies like POTS, MCAS, and brain fog. Key perioperative considerations include cautious use of anesthetics, especially in patients with neurological and cardiovascular complications. Pulmonary management strategies for PASC patients, such as lung-protective ventilation and non-invasive post-operative support, could mitigate any perioperative respiratory complications. Finally, we underscore the importance of a multidisciplinary approach to manage PASC patients effectively during surgery, advocating for personalized anesthetic plans and calling for more evidence-driven guidelines for this emerging patient group as research progresses.},
}

@article {pmid40717478,
year = {2025},
author = {Bajić, D and Todorović, N and Popović, ML and Plazačić, M and Mihajlović, A},
title = {Immunity's core reset: Synbiotics and gut microbiota in the COVID-19 era.},
journal = {Innate immunity},
volume = {31},
number = {},
pages = {17534259251362023},
pmid = {40717478},
issn = {1753-4267},
mesh = {Humans ; *COVID-19/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; *Synbiotics/administration & dosage ; *SARS-CoV-2/immunology ; *Dysbiosis/immunology/microbiology ; Probiotics/therapeutic use ; Prebiotics/administration & dosage ; Inflammation/immunology ; },
abstract = {The gut microbiome plays a crucial role in shaping immune responses, and its connection to immunity has never been more relevant than in the COVID-19 era. The interaction between gut microbes and the immune system, known as microbiome-immunity crosstalk, influences both how the body responds to infections and how well it recovers. COVID-19, whether in its acute phase or lingering as long COVID, has been linked to disturbances in the gut microbiome. During infection, many patients experience dysbiosis-an imbalance in gut bacteria-that can contribute to immune dysfunction and excessive inflammation. This imbalance may not only worsen the severity of the disease but also prolong recovery, leading to persistent symptoms like fatigue, brain fog, and digestive issues. Long COVID, in particular, has been associated with ongoing immune dysregulation, where the body's defense system remains in a state of heightened activation, causing chronic inflammation. Given the strong link between gut health and immunity, there is growing interest in strategies to restore microbial balance. Synbiotics-combinations of probiotics (beneficial bacteria) and prebiotics (nutrients that support them)-are being explored as a potential therapeutic approach. By replenishing beneficial gut microbes, synbiotics may help regulate immune responses, reduce inflammation, and support overall recovery from COVID-19. Emerging research suggests that improving gut health could enhance the body's ability to fight infections and recover more efficiently. As we continue to understand the long-term impact of COVID-19, focusing on the gut microbiome offers a promising path forward. Supporting a balanced and diverse microbiome through diet, lifestyle, and targeted interventions like synbiotics may provide a natural way to strengthen immunity and improve health outcomes in both acute and long COVID cases.},
}

Humans
*COVID-19/immunology/microbiology
*Gastrointestinal Microbiome/immunology
*Synbiotics/administration & dosage
*SARS-CoV-2/immunology
*Dysbiosis/immunology/microbiology
Probiotics/therapeutic use
Prebiotics/administration & dosage
Inflammation/immunology

@article {pmid40708204,
year = {2025},
author = {Malerba, M and Purghè, B and Ragnoli, B and Manfredi, M and Baldanzi, G},
title = {Molecular profiling of exhaled breath condensate in respiratory diseases.},
journal = {Annals of medicine},
volume = {57},
number = {1},
pages = {2537910},
pmid = {40708204},
issn = {1365-2060},
mesh = {Humans ; Breath Tests/methods ; *COVID-19/metabolism/diagnosis ; Metabolomics/methods ; Proteomics/methods ; SARS-CoV-2 ; Exhalation ; Pulmonary Disease, Chronic Obstructive/diagnosis/metabolism ; Asthma/diagnosis/metabolism ; Mass Spectrometry/methods ; Biomarkers/analysis ; *Respiratory Tract Diseases/diagnosis/metabolism ; },
abstract = {BACKGROUND: Respiratory disorders, , continue to pose a major global health burden. Their complexity and heterogeneity challenge accurate diagnosis, effective monitoring, and therapeutic decision-making. Exhaled breath condensate (EBC) provides a reliable, non-invasive means of sampling the molecular environment of the airways.

AIM: This review presents the state-of-the-art in EBC-based omics approaches-particularly metabolomics and proteomics-to characterize molecular signatures associated with chronic respiratory (e.g. asthma, chronic obstructive pulmonary disease, and rhinitis) and infectious diseases (e.g. COVID-19).

RESULTS: We critically examine findings from studies applying nuclear magnetic resonance (NMR), mass spectrometry (MS), and sensor-based technologies to analyze EBC across various respiratory conditions. NMR, valued for its reproducibility and minimal sample preparation, consistently discriminates among disease phenotypes, identifies distinct metabotypes, and monitors treatment response over time. MS-based approaches afford enhanced sensitivity and specificity, enabling detailed profiling of inflammatory mediators, such as lipid-derived eicosanoids and amino acid derivatives. Proteomic studies reveal protein-level alterations associated with inflammation and tissue remodeling. In COVID-19 and long COVID, metabolomic and volatile compound profiling distinguishes affected individuals from healthy controls suggesting clinical potential. However, inconsistent sample processing and lack of analytical standardization remain limiting factors.

CONCLUSIONS: EBC profiling shows clear promise for improving diagnosis, monitoring, and stratification in respiratory medicine. Yet, translation into clinical practice is hindered by limited standardization and validation. Broader, longitudinal studies will be essential to establish robust molecular signatures across disease states. This review underscores the timely need to implement breathomics investigations to gain mechanistic insight into the underlying biology of respiratory diseases.},
}

Humans
Breath Tests/methods
*COVID-19/metabolism/diagnosis
Metabolomics/methods
Proteomics/methods
SARS-CoV-2
Exhalation
Pulmonary Disease, Chronic Obstructive/diagnosis/metabolism
Asthma/diagnosis/metabolism
Mass Spectrometry/methods
Biomarkers/analysis
*Respiratory Tract Diseases/diagnosis/metabolism

@article {pmid40707035,
year = {2025},
author = {Meagher, T},
title = {Long Covid in Year 5: Some Progress, Still Many Questions.},
journal = {Journal of insurance medicine (New York, N.Y.)},
volume = {52},
number = {2},
pages = {61-65},
doi = {10.17849/insm-52-2-1-5.2},
pmid = {40707035},
issn = {0743-6661},
mesh = {Humans ; *COVID-19/complications/epidemiology/physiopathology ; Fatigue Syndrome, Chronic ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; },
abstract = {Long Covid was first described in 2020. Five years later, progress in disease characterization has been considerable, and definitions continue to evolve. Several disease mechanisms are under study, and evidence for multiple endotypes is accumulating. No clinical biomarker has been identified, nor has an effective therapy been developed. Overlap with other post-infectious syndromes, particularly myalgic encephalomyelitis/chronic fatigue syndrome, is now more evident. For most individuals, symptoms of long Covid progressively disappear over time. Recurrent Covid-19 infections are now an important contributor to the pool of affected individuals. While symptoms limit activity in as many as 20%, inability to work is less common. The anticipated surge of disability claims from insured individuals has not materialized.},
}

Humans
*COVID-19/complications/epidemiology/physiopathology
Fatigue Syndrome, Chronic
Post-Acute COVID-19 Syndrome
SARS-CoV-2

@article {pmid40696830,
year = {2025},
author = {Paulose, M and Adams, NN and Martin, KR and Grant, A},
title = {Lived Experiences of New-Onset Long Covid Pain and Its Impact on Health-Related Quality of Life. A Scoping Review of Current Evidence.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {4},
pages = {e70352},
pmid = {40696830},
issn = {1369-7625},
support = {//The authors received no specific funding for this work./ ; },
mesh = {Humans ; *Quality of Life/psychology ; *COVID-19/complications/psychology ; *Chronic Pain/psychology/etiology ; SARS-CoV-2 ; },
abstract = {INTRODUCTION: Long Covid (LC) is a multisystem condition that can cause persistent symptoms such as breathlessness, fatigue, cognitive problems and pain, with major effects on individuals and healthcare systems. Globally, nearly 400 million people have been affected. New-onset pain is among the most commonly reported symptoms and may develop into chronic pain, contributing to reduced health-related quality of life (HRQoL) and highlighting the need for appropriate care. Given its global prevalence, exploring how people experience new-onset LC pain and how it impacts their lives can help improve pain management and support services.

METHODS: A mixed-methods scoping review was conducted following the Joanna Briggs Institute (JBI) guidance and the Preferred Reporting Items for Systematic Reviews Extension for Scoping Reviews (PRISMA-ScR). The review mapped and synthesised evidence from eligible primary research articles (quantitative, qualitative and mixed-methods) published in English between December 2019 and June 2024. Seven studies using cross-sectional, case-control and observational designs (n = 30 to 2507 participants) were included, with data collected from Europe and Asia.

RESULTS: While qualitative data on lived experience were limited, 69.5% of LC patients reported new-onset pain, most commonly musculoskeletal (MSK) pain (73.2%). Psychological symptoms such as post-traumatic stress disorder (PTSD) were also reported (38%). Pain medications were widely used. Findings suggest that new-onset LC pain affects physical, psychological and social well-being. No studies involving children or adolescents were identified, indicating a gap in the evidence on paediatric experiences of new-onset LC pain.

CONCLUSION: This review highlights major gaps in the literature, especially the lack of qualitative research on how people experience new-onset LC pain. Future research should explore these experiences in depth, with involvement from patients and the public, to inform the development of appropriate treatment and support strategies.

During the review process, opportunities to involve PPI were not fully explored due to limited awareness of how to support meaningful involvement in a scoping review, alongside time and resource constraints. Such involvement could have helped shape the review question, refine the search terms and interpret the findings in ways that better reflect lived experience. This is acknowledged as both a limitation and a learning point. PPI will be actively embedded in the next phases of the research.},
}

Humans
*Quality of Life/psychology
*COVID-19/complications/psychology
*Chronic Pain/psychology/etiology
SARS-CoV-2

@article {pmid40684905,
year = {2025},
author = {Gershon, AS and Fung, D and Lam, GY},
title = {Diagnosing Respiratory Long COVID: A Practical Approach.},
journal = {Chest},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.chest.2025.06.028},
pmid = {40684905},
issn = {1931-3543},
abstract = {Long COVID or a post-COVID condition, defined as the persistence of symptoms at least 3 months after acute COVID-19 infection, is a novel condition in which a definitive diagnostic marker and treatment have yet to be found. This condition, which has been estimated to impact > 65 million individuals worldwide, manifests with multisystem involvement, most commonly presenting with fatigue, brain fog, dyspnea, cough, or a combination thereof. The burden of these symptoms can range from mild to severe, with many patients reporting an inability to return to usual activities. Herein, we present several hypothetical but clinically representative case reports to allow discussion around how we approach the diagnosis of respiratory symptoms of long COVID in those with and without chronic lung disease.},
}

@article {pmid40683613,
year = {2025},
author = {Chen, K and Wang, Z and Li, J and Xu, Y and Gu, S and Li, H and Li, J and Zhang, Y and Mao, N},
title = {Chronic inflammation in Long COVID relationship to autoimmune diseases.},
journal = {Autoimmunity reviews},
volume = {24},
number = {10},
pages = {103882},
doi = {10.1016/j.autrev.2025.103882},
pmid = {40683613},
issn = {1873-0183},
abstract = {The new coronavirus pandemic has been ongoing for nearly five years. In addition to the severe symptoms in the acute phase, it is accompanied by long-term complications and sequelae involving the respiratory, neurological, immune, circulatory, and gastrointestinal systems for several months or even years, which is called the Long COVID. Many studies have suggested that systemic chronic inflammation caused by residual viral components may be one of the pathophysiologic mechanisms of Long COVID. In this paper, we will review the autoimmune diseases caused by chronic inflammation. In particular, cytokine storminess, pro-inflammatory responses of inflammatory vesicles, mast cell activation syndrome, changes in the gut microbiota, molecular mimicry, reactivation of latent viruses, and coagulation abnormalities are among the pathways that contribute to autoimmune diseases, including Systemic Lupus Erythematosus, Guillain-Barré syndrome, rheumatoid arthritis. We intervene in the treatment of the disease with probiotics, immunoglobulins, the RECOVER clinical trial model, and immunomodulatory drugs. The aim is to enhance understanding of the pathophysiological mechanism of Long COVID and to provide a reference for the immunotherapy of patients.},
}

@article {pmid40680383,
year = {2025},
author = {Chen, TH and Jeng, TH and Lee, MY and Wang, HC and Tsai, KF and Chou, CK},
title = {Viral mitochondriopathy in COVID-19.},
journal = {Redox biology},
volume = {85},
number = {},
pages = {103766},
pmid = {40680383},
issn = {2213-2317},
abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), disrupts cellular mitochondria, leading to widespread chronic inflammation and multi-organ dysfunction. Viral proteins cause mitochondrial bioenergetic collapse, disrupt mitochondrial dynamics, and impair ionic homeostasis, while avoiding antiviral defenses, including mitochondrial antiviral signaling. These changes drive both acute COVID-19 and its longer-term effects, known as "long COVID". This review examines new findings on the mechanisms by which SARS-CoV-2 affects mitochondria and for the impact on chronic immunity, long-term health risks, and potential treatments.},
}

@article {pmid40677535,
year = {2024},
author = {Mundra, P and Kailani, Z and Yaghoobi, M and Matthews, P and Tobis, M and Sadeghian, S and Albashir, S},
title = {Liver injury in post-acute COVID-19 syndrome: A systematic review and meta-analysis of early observational studies.},
journal = {Canadian liver journal},
volume = {7},
number = {4},
pages = {470-489},
pmid = {40677535},
issn = {2561-4444},
abstract = {BACKGROUND: Post-acute COVID-19 syndrome (PACS; long COVID) is characterized by persistent or delayed symptoms at least 4 weeks from acute COVID-19 infection. Given the well-documented incidence of liver injury in acute COVID-19, this systematic review aims to assess the odds of liver injury in earlier experiencers of PACS.

METHODS: Observational studies published prior to March 2022 were screened for data describing liver injury (defined per primary study) in patients with PACS.

RESULTS: A total of 2,117 abstracts and 35 full texts were screened, of which 26 met the inclusion criteria. The mean time since acute COVID infection across all studies was 195.5 days. Seven studies included COVID-negative control groups. Twenty-three studies measured lab findings, and nine studies measured imaging or elastography. Five studies were eligible for meta-analysis of odds ratios, which did not demonstrate a statistically significant difference in odds for liver injury in patients with PACS compared with COVID-negative patients (OR 2.22 [95% CI 0.51-9.61; p = 0.28]). Newcastle-Ottawa Scale assessments for all studies found 24 of 26 studies with high to very high risk of bias. ROBINS-E assessments for studies included in the meta-analysis found five of five studies with high to very high risk of bias.

CONCLUSIONS: Overall, our findings demonstrate no statistical difference in odds ratios of liver injury in patients with PACS compared with COVID-negative controls. As such, routine assessment and monitoring of liver injury in patients with PACS may not be required; however, higher quality data with lower risk of bias are required to make recommendations of higher certainty.},
}

@article {pmid40671020,
year = {2025},
author = {Wang, Y and Li, X and Hui, H and Yang, D},
title = {Efficacy and safety of traditional Chinese medicine for post-COVID-19 syndrome: a systematic review and meta-analysis.},
journal = {Journal of translational medicine},
volume = {23},
number = {1},
pages = {801},
pmid = {40671020},
issn = {1479-5876},
mesh = {Humans ; *Medicine, Chinese Traditional/methods/adverse effects ; *COVID-19/complications ; *Drugs, Chinese Herbal/therapeutic use/adverse effects ; Randomized Controlled Trials as Topic ; Treatment Outcome ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Fatigue/drug therapy ; Cough/drug therapy ; *COVID-19 Drug Treatment ; },
abstract = {BACKGROUND: Post-COVID-19 syndrome, characterized by persistent symptoms such as fatigue, dyspnea, cough, insomnia, and exercise intolerance, poses a significant challenge to global healthcare systems. Traditional Chinese Medicine (TCM) has been used to manage post-viral syndromes, but high-quality evidence for its effectiveness in post-COVID-19 recovery is limited. This study aimed to evaluate the clinical efficacy and safety of Chinese herbal medicine (CHM) in treating post-COVID-19 syndrome through a systematic review and meta-analysis of randomized controlled trials (RCTs).

METHODS: Five electronic databases (PubMed, Embase, Web of Science, Cochrane Library and CNKI) were systematically searched up to March 15, 2025. RCTs comparing CHM with placebo or usual care in patients with confirmed post-COVID-19 syndrome were included. Primary outcomes were symptom severity measured by the Visual Analogue Scale (VAS); secondary outcomes included relief rates of cough, fatigue, chest tightness, dyspnea, insomnia, and exercise intolerance. Data were pooled using a random-effects model, and heterogeneity was assessed using I[2] statistics.

RESULTS: Ten RCTs involving 2401 patients were included. CHM showed a greater reduction in VAS scores compared to controls (MD = -1.03; 95% CI -2.10 to 0.03; P = 0.0577), with higher heterogeneity (I[2] = 92%). Although this result did not reach conventional statistical significance, it suggests a potentially meaningful clinical trend favoring CHM. Subgroup analysis indicated both short-term and long-term CHM treatments improved VAS scores, with a stronger effect in long-term treatment. CHM significantly improved chest tightness (RR = 1.40; 95% CI 1.21-1.61; P < 0.0001; I[2] = 0%) and insomnia (RR = 1.23; 95% CI 1.03-1.47; P = 0.0216; I[2] = 0%). A trend toward improvement was observed in fatigue (RR = 1.58, 95% CI 0.95-2.64; P = 0.0781) and dyspnea (RR = 1.39, 95% CI 0.99-1.95; P = 0.0554), although these results did not reach statistical significance. No significant difference was observed in terms of 6-min walking distance (MD = 13.95 m, 95% CI -11.64 to 39.55; P = 0.2853). Adverse event rates were comparable between the herbal and control groups (RR = 0.72, 95% CI 0.49-1.07; P = 0.1052).

CONCLUSIONS: This meta-analysis indicates that Traditional Chinese Medicine (TCM) may help relieve certain post-COVID-19 symptoms, especially chest tightness and insomnia. Trends toward benefit were also noted for fatigue and dyspnea, though without statistical significance. Given the non-significant VAS results and high heterogeneity, these findings should be interpreted cautiously. Further large-scale, high-quality trials are needed to validate these outcomes and optimize treatment strategies.

https://www.crd.york.ac.uk/PROSPERO/home , CRD420251016442.},
}

Humans
*Medicine, Chinese Traditional/methods/adverse effects
*COVID-19/complications
*Drugs, Chinese Herbal/therapeutic use/adverse effects
Randomized Controlled Trials as Topic
Treatment Outcome
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Fatigue/drug therapy
Cough/drug therapy
*COVID-19 Drug Treatment

@article {pmid40670058,
year = {2025},
author = {Aretouli, E and Malik, M and Widmann, C and Parker, AM and Oh, ES and Vannorsdall, TD},
title = {Cognitive and mental health outcomes in long covid.},
journal = {BMJ (Clinical research ed.)},
volume = {390},
number = {},
pages = {e081349},
doi = {10.1136/bmj-2024-081349},
pmid = {40670058},
issn = {1756-1833},
mesh = {Humans ; *COVID-19/psychology/complications ; SARS-CoV-2 ; Mental Health ; *Cognitive Dysfunction/etiology ; Post-Acute COVID-19 Syndrome ; *Anxiety/etiology ; Risk Factors ; *Depression/etiology ; },
abstract = {Roughly one in five adults who meet criteria for long covid present with objective or subjective cognitive dysfunction or elevated symptoms of depression or anxiety lasting ≥12 weeks from an acute covid illness. These neuropsychiatric sequelae have considerable functional consequences at the level of the individual, society, and the broader economy. Neuropsychiatric long covid symptoms are thought to be causally diverse, and a range of risk factors as well as biological, psychological, and environmental mechanisms have been hypothesized to contribute to symptom development and persistence. When present, objective cognitive deficits tend to be modest for most individuals, with some evidence suggesting increased risk of dysfunction and decline specifically for older adults with a history of severe acute illness. Longitudinal data suggest a delayed emergence of psychiatric symptoms may occur in the weeks and months after an acute covid illness. Emerging research points to the early recovery period as a potential window of opportunity for intervention to alter patient trajectories, though evidence based treatment remains lacking.},
}

Humans
*COVID-19/psychology/complications
SARS-CoV-2
Mental Health
*Cognitive Dysfunction/etiology
Post-Acute COVID-19 Syndrome
*Anxiety/etiology
Risk Factors
*Depression/etiology

@article {pmid40663038,
year = {2025},
author = {Avais, LS and Pacheco, EC and Gomes, LPOZ and Baldani, MH and Martins, CM and Waldman, EA and Gonzalez, JPJ and Steen, TY and Borges, PKO},
title = {Oral Manifestations in the Post COVID-19 Condition: A Systematic Review With Meta-Analysis.},
journal = {Reviews in medical virology},
volume = {35},
number = {4},
pages = {e70057},
pmid = {40663038},
issn = {1099-1654},
support = {//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; //Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; },
mesh = {Humans ; *COVID-19/complications/virology ; *Mouth Diseases/epidemiology/etiology/virology ; SARS-CoV-2/pathogenicity ; *Taste Disorders/epidemiology/virology ; Prevalence ; Xerostomia ; },
abstract = {Post-COVID-19 condition, or Long COVID, is characterised by symptoms persisting or emerging beyond 12 weeks after acute infection. Among over 200 reported symptoms, oral manifestations such as taste loss and dry mouth have been identified. This systematic review reports the frequency and characteristics of these symptoms. Registered in PROSPERO and following PRISMA guidelines, the review included observational studies on COVID-19-positive adults presenting oral symptoms in the post-COVID-19 condition. A search in six databases (Medline/PubMed, Embase, Web of Science, Cochrane, SCOPUS, and LILACS) was conducted in January 2024. Risk of bias was assessed using Joanna Briggs Institute's critical appraisal tools, and certainty of evidence via GRADE. A meta-analysis using the inverse variance method estimated oral symptom prevalence. Of 4552 articles, 107 were included. Taste dysfunction persisted in 8% (95% CI 6%-10%) of patients beyond 12 weeks. Combined taste and smell alterations had a prevalence of 17% (95% CI 13%-21%). Less frequent symptoms included hyposalivation, periodontitis, mouth ulcers, tongue mucosal changes, facial tingling, sensitivity in the trigeminal nerve, difficulty swallowing, and lesions in the hard palate. Taste alterations were the most commonly reported symptom, underscoring the need for clinical recognition and appropriate management by oral health professionals. Additionally, the wide range of other oral manifestations highlights the necessity for further research to better understand their prevalence, underlying mechanisms, and clinical implications in post-COVID-19 patients.},
}

Humans
*COVID-19/complications/virology
*Mouth Diseases/epidemiology/etiology/virology
SARS-CoV-2/pathogenicity
*Taste Disorders/epidemiology/virology
Prevalence
Xerostomia

@article {pmid40649991,
year = {2025},
author = {Hein, ZM and Thazin, and Kumar, S and Che Ramli, MD and Che Mohd Nassir, CMN},
title = {Immunomodulatory Mechanisms Underlying Neurological Manifestations in Long COVID: Implications for Immune-Mediated Neurodegeneration.},
journal = {International journal of molecular sciences},
volume = {26},
number = {13},
pages = {},
pmid = {40649991},
issn = {1422-0067},
mesh = {Humans ; *COVID-19/immunology/complications ; SARS-CoV-2/immunology ; *Neurodegenerative Diseases/immunology/etiology ; Blood-Brain Barrier/immunology ; Biomarkers ; Post-Acute COVID-19 Syndrome ; *Immunomodulation ; },
abstract = {The COVID-19 pandemic has revealed the profound and lasting impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the nervous system. Beyond acute infection, SARS-CoV-2 acts as a potent immunomodulatory agent, disrupting immune homeostasis and contributing to persistent inflammation, autoimmunity, and neurodegeneration. Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by a spectrum of neurological symptoms, including cognitive dysfunction, fatigue, neuropathy, and mood disturbances. These are linked to immune dysregulation involving cytokine imbalance, blood-brain barrier (BBB) disruption, glial activation, and T-cell exhaustion. Key biomarkers such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NFL) correlate with disease severity and chronicity. This narrative review examines the immunopathological mechanisms underpinning the neurological sequelae of long COVID, focusing on neuroinflammation, endothelial dysfunction, and molecular mimicry. We also assess the role of viral variants in shaping neuroimmune outcomes and explore emerging diagnostic and therapeutic strategies, including biomarker-guided and immune-targeted interventions. By delineating how SARS-CoV-2 reshapes neuroimmune interactions, this review aims to support the development of precision-based diagnostics and targeted therapies for long COVID-related neurological dysfunction. Emerging approaches include immune-modulatory agents (e.g., anti-IL-6), neuroprotective drugs, and strategies for repurposing antiviral or anti-inflammatory compounds in neuro-COVID. Given the high prevalence of comorbidities, personalized therapies guided by biomarkers and patient-specific immune profiles may be essential. Advancements in vaccine technologies and targeted biologics may also hold promise for prevention and disease modification. Finally, continued interdisciplinary research is needed to clarify the complex virus-immune-brain axis in long COVID and inform effective clinical management.},
}

Humans
*COVID-19/immunology/complications
SARS-CoV-2/immunology
*Neurodegenerative Diseases/immunology/etiology
Blood-Brain Barrier/immunology
Biomarkers
Post-Acute COVID-19 Syndrome
*Immunomodulation

@article {pmid40643301,
year = {2025},
author = {Beka, SG and Griffiths, RF and Myers, JA and Skirrow, PM},
title = {Appropriate Screening Tests to Assess Post-COVID-19 Cognitive Dysfunction in Aeromedical Settings.},
journal = {Aerospace medicine and human performance},
volume = {96},
number = {5},
pages = {414-424},
doi = {10.3357/AMHP.6500.2025},
pmid = {40643301},
issn = {2375-6322},
mesh = {Humans ; *COVID-19/complications/psychology ; *Cognitive Dysfunction/diagnosis/etiology ; *Pilots/psychology ; *Aerospace Medicine ; *Neuropsychological Tests ; SARS-CoV-2 ; Mass Screening ; },
abstract = {INTRODUCTION: Post-COVID-19, 10-20% of individuals may experience long-term symptoms (some having cognitive deficits), even after mild or nonsymptomatic infection. A sufficiently sensitive screening test of cognitive function, based on the typical cognitive effects of COVID-19 and skills considered most relevant to pilot performance, would be highly beneficial to be used alongside other performance checks. This study aimed to identify appropriate screening tests for post-COVID-19 cognitive dysfunction.

METHODS: Initially, a systematic search and narrative review identified 13 screening tools that are likely to be effective in screening pilots for post-COVID-19 neurocognitive impairment. Following a more in-depth evaluation of the identified tools, five tests including the Trail Making Test, Symbol Digit Modalities Test, Stroop Color Word Test, Psychomotor Vigilance Test, and Paced Auditory Serial Addition Test were chosen for a Delphi evaluation exercise. A two-round modified Delphi process was undertaken with international aviation medicine and psychology experts to obtain a consensus on which of the identified tests would be appropriate to screen for cognitive dysfunction in pilots.

RESULTS: Based on evaluation of literature review findings and Delphi consultation with subject matter experts, the Trail Making Test and Symbol Digit Modalities Test were identified as quick and suitable screening tests likely to detect post-COVID-19 cognitive dysfunction.

DISCUSSION: These tools are objective, have good utility, are available in multiple versions, and assess cognitive abilities relevant to pilot performance. Their use for screening in aeromedical examinations would be further supported by confirming their ability to reliably detect neurocognitive impacts associated with COVID-19. Beka SG, Griffiths RF, Myers JA, Skirrow PM. Appropriate screening tests to assess post-COVID-19 cognitive dysfunction in aeromedical settings. Aerosp Med Hum Perform. 2025; 96(5):414-424.},
}

Humans
*COVID-19/complications/psychology
*Cognitive Dysfunction/diagnosis/etiology
*Pilots/psychology
*Aerospace Medicine
*Neuropsychological Tests
SARS-CoV-2
Mass Screening

@article {pmid40640033,
year = {2025},
author = {Giunta, S and Giuliani, A and Sabbatinelli, J and Olivieri, F},
title = {A multidimensional immunological perspective on long COVID.},
journal = {Cytokine & growth factor reviews},
volume = {84},
number = {},
pages = {1-11},
doi = {10.1016/j.cytogfr.2025.07.001},
pmid = {40640033},
issn = {1879-0305},
mesh = {Humans ; *COVID-19/immunology/complications ; *SARS-CoV-2/immunology ; Inflammation/immunology ; Cytokines/immunology ; Post-Acute COVID-19 Syndrome ; Autoantibodies/immunology/blood ; },
abstract = {Long COVID is a chronic condition that arises after SARS-CoV-2 infection and is characterized by persistent and often debilitating symptoms, such as fatigue, cognitive dysfunction ("brain fog"), dyspnea, and autonomic disturbances. Increasing evidence suggests that Long COVID shares key immunopathological mechanisms with autoimmune diseases, primarily sustained immune dysregulation. In individuals with genetic or immunological susceptibility, SARS-CoV-2 infection can trigger the production of autoantibodies targeting cytokines, membrane receptors, and components of the autonomic nervous system (ANS), thereby disrupting neuroimmune homeostasis. This immune imbalance may impair anti-inflammatory regulatory pathways, such as the cholinergic anti-inflammatory pathway (CAP), and may contribute to a chronic state of inflammation and autoimmunity. One proposed contributor to this process is inflammaging - a chronic, low-grade inflammation associated with aging - which may not only predispose individuals to Long COVID but may also be amplified by the persistent immune activation seen in this condition. In this perspective, we propose a conceptual framework in which inflammaging, immune-tolerance breakdown, and autonomic dysfunctions interact to sustain the pathophysiology of Long COVID. We discuss emerging biomarkers across these axes, including inflammatory cytokines, circulating autoantibodies, immune cell phenotypes, epigenetic modifications, and heart rate variability. Advances in inflammaging-related biomarkers and biological clocks may support early identification of individuals at higher risk for persistent immune and autonomic dysregulation, ultimately informing more precise diagnostic and therapeutic strategies for Long COVID.},
}

Humans
*COVID-19/immunology/complications
*SARS-CoV-2/immunology
Inflammation/immunology
Cytokines/immunology
Post-Acute COVID-19 Syndrome
Autoantibodies/immunology/blood

@article {pmid40597822,
year = {2025},
author = {Münte, C and Glattacker, M and Müller, S and Zülke, AE and Heinze, M and Riedel-Heller, SG and Pieper, D and Jacke, C and Deckert, S and Neumann, A},
title = {Long COVID in people with mental health disorders: a scoping review.},
journal = {BMC psychiatry},
volume = {25},
number = {1},
pages = {669},
pmid = {40597822},
issn = {1471-244X},
mesh = {Humans ; *COVID-19/complications/psychology ; *Mental Disorders/psychology/epidemiology/complications/therapy ; *Post-Acute COVID-19 Syndrome/complications/epidemiology/psychology ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Long COVID, Post COVID Syndrome or PASC (post-acute sequelae of COVID-19), according to the World Health Organization (WHO), is defined as the continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation. The term Long COVID will be used throughout this review. Little is known about individuals with pre-existing mental health conditions experiencing Long COVID. This scoping review aims to provide an overview of these individuals, focusing on: 1) the course of mental disorders, 2) care needs, 3) utilization of healthcare services, and 4) psychosocial aspects, as outlined by the International Classification of Functioning (ICF).

METHODS: This review followed the JBI (Joanna Briggs Institute) methodology for scoping reviews and the PRISMA extension for scoping reviews. We included reports focusing on individuals with at least one pre-existing mental health diagnosis and Long COVID. Full-text reports in English or German were included, with no geographical limitations. Literature searches were conducted in PubMed, Embase, and PsycINFO on November 1, 2023, for records published between January 2020 and October 2023. Six reviewers participated in the screening process in pairs, independently conducting study selection and data extraction. Conflicts were resolved by consensus. Citation tracking was performed, and data were summarized narratively in tables.

RESULTS: From 4256 initial hits and citation tracking, 8 reports were included. The studies were heterogeneous, including chart reviews, case reports, cross-sectional, and longitudinal studies. Evidence on the impact of Long COVID on pre-existing mental health conditions was inconsistent. Most findings focused on the course of mental health disorders, ranging from symptom worsening to new symptoms of anxiety, depression, or insomnia. Evidence on mental health care needs, service utilization, and psychosocial aspects was limited.

CONCLUSION: Limited evidence suggests that individuals with pre-existing mental health disorders who experience Long COVID may be at an increased risk of worsening mental health. However, critical aspects such as care needs, service utilization, and psychosocial factors remain under-researched, highlighting the need for further studies on mental health care for Long COVID.

REVIEW REGISTRATION: Open Science Framework https://osf.io/tqexa .

CLINICAL TRIAL NUMBER: Not applicable.},
}

Humans
*COVID-19/complications/psychology
*Mental Disorders/psychology/epidemiology/complications/therapy
*Post-Acute COVID-19 Syndrome/complications/epidemiology/psychology
SARS-CoV-2

@article {pmid40589858,
year = {2025},
author = {Saikarthik, J and Saraswathi, I and Padhi, BK and Shamim, MA and Alzerwi, N and Alarifi, A and Gandhi, AP},
title = {Structural and functional neuroimaging of hippocampus to study adult neurogenesis in long COVID-19 patients with neuropsychiatric symptoms: a scoping review.},
journal = {PeerJ},
volume = {13},
number = {},
pages = {e19575},
pmid = {40589858},
issn = {2167-8359},
mesh = {Humans ; *COVID-19/complications/diagnostic imaging/physiopathology ; *Hippocampus/diagnostic imaging/physiopathology/pathology ; *Neurogenesis/physiology ; SARS-CoV-2 ; Adult ; *Functional Neuroimaging ; *Mental Disorders/diagnostic imaging/physiopathology ; Neuroimaging ; Magnetic Resonance Imaging ; },
abstract = {BACKGROUND: Worsening of neuropsychiatric and neurodegenerative disorders occurs in COVID-19. Impaired adult neurogenesis is linked to most of the neuropsychiatric symptoms and disorders.

AIM: The current scoping review identified and mapped the available evidence on adult neurogenesis in long COVID-19, at a global level following the JBI methodology for scoping reviews and followed the framework by Arksey and O'Malley.

METHOD: Original studies focusing on structural and functional neuroimaging of the hippocampus to study adult neurogenesis in long COVID-19 were included in the review. Studies published in English language with no restriction on the time of publication were searched using the specified search strategy in PubMed, Web of Science, Embase, and SCOPUS. Articles obtained from the database search were collated and uploaded into the Nested Knowledge AutoLit semi-automated systematic review platform for data extraction.

RESULTS: The current review provides evidence of the potential alterations in adult neurogenesis in long COVID-19 and its potential link to neuropsychiatric sequelae of long COVID-19, with further research required to validate this assertion.

CONCLUSION: This review proposes conceptual and methodological approaches for future investigations to address existing limitations and elucidate the precise role of adult neurogenesis in the pathophysiology and treatment of long COVID-19.},
}

Humans
*COVID-19/complications/diagnostic imaging/physiopathology
*Hippocampus/diagnostic imaging/physiopathology/pathology
*Neurogenesis/physiology
SARS-CoV-2
Adult
*Functional Neuroimaging
*Mental Disorders/diagnostic imaging/physiopathology
Neuroimaging
Magnetic Resonance Imaging

@article {pmid40583757,
year = {2025},
author = {Cornwell, WK and Levine, BD and Baptiste, D and Bhave, N and Desai, S and Dineen, E and Durstenfeld, M and Edward, J and Huang, M and Jacobsen, R and Kim, JH and Spatz, E and , },
title = {Exercise Intolerance and Response to Training in Patients With Postacute Sequelae of SARS-CoV2 (Long COVID): A Scientific Statement From the American Heart Association.},
journal = {Circulation},
volume = {152},
number = {5},
pages = {e50-e62},
doi = {10.1161/CIR.0000000000001348},
pmid = {40583757},
issn = {1524-4539},
mesh = {Humans ; *COVID-19/physiopathology/complications/therapy ; *Exercise Tolerance ; American Heart Association ; United States ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Exercise Therapy/methods ; Cardiovascular Deconditioning ; Quality of Life ; Exercise ; },
abstract = {The postacute sequelae of SARS-CoV-2, also known as Long COVID, may affect 10% to 25% of individuals diagnosed with SARS-CoV-2. More than 100 symptoms have been reported among patients with Long COVID, but almost all patients report severe fatigue, orthostatic intolerance, shortness of breath, and reductions in exercise tolerance. Emerging data suggest that cardiovascular deconditioning plays a major role in the development of this syndrome and that reductions in functional capacity among patients with Long COVID are comparable to reductions seen among individuals with cardiovascular deconditioning resulting from bed rest. Concern has been raised about the use of exercise training as part of the management strategy for patients with Long COVID. However, exercise training appropriately tailored to the patient with cardiovascular deconditioning may be an effective strategy to facilitate improvement in symptoms. This American Heart Association scientific statement provides a concise yet comprehensive overview of mechanisms contributing to development of Long COVID and methods by which exercise training may be applied to this unique patient population to alleviate symptoms and improve quality of life. In addition, methods of reintroducing exercise and return to play among athletes affected by COVID-19 are discussed.},
}

Humans
*COVID-19/physiopathology/complications/therapy
*Exercise Tolerance
American Heart Association
United States
SARS-CoV-2
Post-Acute COVID-19 Syndrome
*Exercise Therapy/methods
Cardiovascular Deconditioning
Quality of Life
Exercise

@article {pmid40582622,
year = {2025},
author = {Xu, K and He, W and Yu, B and Wang, JJ and Wu, J and Wang, DW},
title = {Unveiling the silent threat: COVID-19 and myocardial injury.},
journal = {Pharmacology & therapeutics},
volume = {273},
number = {},
pages = {108904},
doi = {10.1016/j.pharmthera.2025.108904},
pmid = {40582622},
issn = {1879-016X},
abstract = {Since COVID-19 firstly appeared in 2019 December, it has been defined as an infectious disease mainly performing lung symptoms, which contracted more attention. However, more and more findings indicate myocardial injury appears in considerable proportion of COVID-19 patients (30 % - 50 %) not only but also major cause leading to the death in patients, many of whom may be even without severe respiratory symptoms. Meanwhile myocarditis after injecting vaccines has been paid more attention to globally which always performs uncontrollable inflammation and lead to death. Now myocardial injury has been a main complication in patients with long COVID-19, which is worthy of attention. Furthermore, myocardial injury or myocarditis is detectable and treatable. In order to abstract attention to myocardial injury associated with COVID-19 and provide more evidence and experience for patients who still suffer myocardial injury from COVID-19 vaccines or long COVID-19, the review comprehensively summarized previous researches from pathogenesis, clinical symptoms, diagnosis and treatment and emphasized the crucial role of RASS inhibitors especially ARBs.},
}

@article {pmid40575972,
year = {2025},
author = {Zhu, T and Li, X and Gao, S and Cui, R and Wang, J and Deng, Q},
title = {Successful salvage therapy of ruxolitinib on interstitial pneumonia after long COVID or post-COVID-19 syndrome with follicular lymphoma: two case reports and literature review.},
journal = {Chinese clinical oncology},
volume = {14},
number = {3},
pages = {35},
doi = {10.21037/cco-24-106},
pmid = {40575972},
issn = {2304-3873},
mesh = {Humans ; Nitriles ; *Pyrazoles/therapeutic use ; *COVID-19/complications ; Pyrimidines ; *Lymphoma, Follicular/complications/drug therapy ; *Salvage Therapy/methods ; Male ; SARS-CoV-2 ; Middle Aged ; Female ; *Lung Diseases, Interstitial/drug therapy/etiology ; COVID-19 Drug Treatment ; Aged ; Methylprednisolone/therapeutic use ; },
abstract = {BACKGROUND: Immunocompromised patients with B lymphocyte deficiency and hypogammaglobulinemia after anti-CD19 chimeric antigen receptor (CAR) T cell therapy for relapsed/refractory follicular lymphoma (FL) are at high risk of severe coronavirus disease 2019 (COVID-19) infection.

CASE DESCRIPTION: In our study, two patients with refractory FL had persistent COVID-19 infection after their anti-CD19 CAR T cell therapy. The patients were diagnosed with post-COVID-19 syndrome or COVID-19 with interstitial inflammation and persistent hypoxemia. The patients received molnupiravir and Paxlovid, along with methylprednisolone therapy when their interleukin (IL)-6 levels were high. No response was observed in interstitial inflammation, persistent hypoxemia, or persistent positive expression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, the level of IL-6 decreased after these therapies. These two patients subsequently received low-dose ruxolitinib (5 mg, twice daily) as salvage therapy in combination with a gradually reduced dosage of methylprednisolone. After 1-2 months of ruxolitinib therapy, persistent hypoxemia was relieved, and interstitial inflammation was significantly absorbed. At the same time, the SARS-CoV-2 detection was found to be negative.

CONCLUSIONS: Ruxolitinib might be a safe and effective alternative salvage therapy for patients with COVID-19 having interstitial inflammation and persistent hypoxemia without high cytokine levels and no response to corticosteroids.},
}

Humans
Nitriles
*Pyrazoles/therapeutic use
*COVID-19/complications
Pyrimidines
*Lymphoma, Follicular/complications/drug therapy
*Salvage Therapy/methods
Male
SARS-CoV-2
Middle Aged
Female
*Lung Diseases, Interstitial/drug therapy/etiology
COVID-19 Drug Treatment
Aged
Methylprednisolone/therapeutic use

@article {pmid40566540,
year = {2025},
author = {Koutsiaris, AG and Karakousis, K},
title = {Long COVID Mechanisms, Microvascular Effects, and Evaluation Based on Incidence.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {6},
pages = {},
pmid = {40566540},
issn = {2075-1729},
abstract = {Since the initial reports of Long COVID symptoms, numerous pathophysiological mechanisms have been proposed to explain them; nevertheless, no consensus has been reached. Some of these mechanisms are directly linked to microcirculation, while others are related indirectly. Those with a direct connection involve the respiratory system (such as pulmonary embolism), the cardiovascular system (including cardiac arrest, heart failure, myocardial inflammation, stroke, endothelial dysfunction, and microangiopathy), hematological conditions (like coagulopathy, deep vein thrombosis, microclots, and endothelial irregularities), and brain function. However, few of these mechanisms are grounded in quantitative data and fundamental physiological principles. Furthermore, diagnostic and therapeutic methods remain inadequate. This report provides a brief overview of these processes, focusing primarily on quantitative data, recently proposed mechanisms, and advances in microcirculation, with a special emphasis on the tissue blood supply reduction (TBSR or SR in short) mechanism. Then, the SR pathophysiological mechanism is assessed based on the total incidence rate of the Long COVID symptoms that can be directly attributed to this mechanism. The proposed SR mechanism can account for seven principal Long COVID symptoms with a total normalized incidence of 76%.},
}

@article {pmid40566294,
year = {2025},
author = {Rocha, DM and Pedroso, AO and Menegueti, MG and Silveira, RCCP and Sousa, LRM and Gir, E and Reis, RK},
title = {Predictors of Anxiety, Depression, and Stress in Long COVID: Systematic Review of Prevalence.},
journal = {International journal of environmental research and public health},
volume = {22},
number = {6},
pages = {},
pmid = {40566294},
issn = {1660-4601},
support = {88881.657963/2021-01//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; },
mesh = {Humans ; *COVID-19/psychology/epidemiology/complications ; *Anxiety/epidemiology/etiology ; *Depression/epidemiology/etiology ; Prevalence ; *Stress, Psychological/epidemiology/etiology ; Aged ; SARS-CoV-2 ; Adult ; },
abstract = {Anxiety, depression, and stress are prevalent psychosocial manifestations in Long COVID, and understanding their global impact can guide safe, effective, and evidence-based interventions. This study reviewed the literature to analyze the prevalence indicators and predictors of anxiety, depression, or stress experienced by adults and older adults with Long COVID. This systematic prevalence review was conducted using the databases MEDLINE via PubMed[®], CINAHL-EBSCO, Web of Science, Scopus, EMBASE, LILACS, and BDENF. Observational studies that assessed anxiety, depression, or perceived stress in adults and older adults with Long COVID were included, with no restrictions on time or language. Two reviewers independently conducted the selection process. Full texts were analyzed for their eligibility potential. Methodological quality was assessed using the JBI Critical Appraisal Checklist for Studies. Ten observational studies with moderate methodological quality were included. Anxiety and depression were the most prevalent psychosocial symptoms in Long COVID, reported in mild, moderate, and severe cases of COVID-19 infection. Prevalence rates reached up to 47.8% for anxiety, 37.3% for depression, and 23% for stress. The combined analysis revealed a pooled prevalence of 15.3% (95% CI: 10.8% to 20.2%). Being female, having pre-existing mental disorders or associated clinical comorbidities, experiencing severe infection in the acute phase, and receiving intensive care were predictors of greater mental burden. The experience of anxiety, depression, and stress in prolonged COVID-19 was reported in countries with different income levels and was disproportionately experienced, especially by women and individuals with associated clinical conditions or psychopathological comorbidities.},
}

Humans
*COVID-19/psychology/epidemiology/complications
*Anxiety/epidemiology/etiology
*Depression/epidemiology/etiology
Prevalence
*Stress, Psychological/epidemiology/etiology
Aged
SARS-CoV-2
Adult

@article {pmid40564201,
year = {2025},
author = {Hemat Jouy, S and Tonchev, H and Mostafa, SM and Mahmoud, AM},
title = {Post-COVID Metabolic Fallout: A Growing Threat of New-Onset and Exacerbated Diabetes.},
journal = {Biomedicines},
volume = {13},
number = {6},
pages = {},
pmid = {40564201},
issn = {2227-9059},
support = {R00 HL140049/HL/NHLBI NIH HHS/United States ; R01 HL161386/HL/NHLBI NIH HHS/United States ; 1R00HL140049-03/NH/NIH HHS/United States ; 1R01HL161386-04/NH/NIH HHS/United States ; },
abstract = {Emerging evidence highlights the profound and lasting impact of severe illnesses such as COVID-19, particularly among individuals with underlying comorbidities. Patients with pre-existing conditions like diabetes mellitus (DM) are disproportionately affected, facing heightened risks of both disease exacerbation and the onset of new complications. Notably, the convergence of advanced age and DM has been consistently associated with poor COVID-19 outcomes. However, the long-term metabolic consequences of SARS-CoV-2 infection, especially its role in disrupting glucose homeostasis and potentially triggering or worsening DM, remain incompletely understood. This review synthesizes current clinical and experimental findings to clarify the bidirectional relationship between COVID-19 and diabetes. We critically examine literature reporting deterioration of glycemic control, onset of hyperglycemia in previously non-diabetic individuals, and worsening of metabolic parameters in diabetic patients after infection. Furthermore, we explore proposed mechanistic pathways, including pancreatic β-cell dysfunction, systemic inflammation, and immune-mediated damage, that may underpin the development or progression of DM in the post-COVID setting. Collectively, this work underscores the urgent need for continued research and clinical vigilance in managing metabolic health in COVID-19 survivors.},
}

@article {pmid40563736,
year = {2025},
author = {Doskas, T and Vavougios, GD and Kormas, C and Kokkotis, C and Tsiptsios, D and Spiliopoulos, KC and Tsiakiri, A and Christidi, F and Aravidou, T and Dekavallas, L and Kazis, D and Dardiotis, E and Vadikolias, K},
title = {Neurocognitive Impairment After COVID-19: Mechanisms, Phenotypes, and Links to Alzheimer's Disease.},
journal = {Brain sciences},
volume = {15},
number = {6},
pages = {},
pmid = {40563736},
issn = {2076-3425},
abstract = {BACKGROUND/OBJECTIVES: SARS-CoV-2 can affect the central nervous system directly or indirectly. AD shares several similarities with long COVID cognitive impairment on a molecular and imaging level, as well as common risk factors. The objective of this review is to evaluate the incidence of post-acute COVID-19 cognitive impairment. Secondarily, we aim to determine if neuroinflammation in COVID-19 survivors may be associated with the onset of neurological disease, with a focus on Alzheimer's disease (AD).

METHODS: literature search up to March 2025 on the prevalence of cognitive deficits in COVID-19 survivors, underlying pathophysiology and associations with neurological disorders.

RESULTS: a wide array of neuropsychiatric manifestations is associated with COVID-19; executive function, memory, and attention are the most frequently reported neurocognitive deficits, regardless of COVID-19 severity. There are associations between the risks for cognitive deficits post-infection with the age of the patients and the severity of the disease. Increasing evidence suggests that neurocognitive deficits are associated with the onset of neurological and neuropsychiatric disease in COVID-19 survivors.

CONCLUSIONS: clinicians caring for COVID-19 survivors should actively investigate neurocognitive sequelae, particularly for patients with increased risk for cognitive deficits.},
}

@article {pmid40552782,
year = {2025},
author = {Xu, Y and Xu, JW and Wu, Y and Rong, LJ and Ye, L and Franco, OH and Chien, CW and Feng, XR and Chen, JY and Tung, TH},
title = {Prevalence and prognosis of sarcopenia in acute COVID-19 and long COVID: a systematic review and meta-analysis.},
journal = {Annals of medicine},
volume = {57},
number = {1},
pages = {2519678},
doi = {10.1080/07853890.2025.2519678},
pmid = {40552782},
issn = {1365-2060},
mesh = {Humans ; *Sarcopenia/epidemiology ; *COVID-19/complications/epidemiology/mortality ; Prevalence ; Prognosis ; SARS-CoV-2 ; Length of Stay/statistics & numerical data ; Hospitalization/statistics & numerical data ; },
abstract = {BACKGROUND: A comprehensive investigation delineating the prevalence of sarcopenia across different infection phases, from acute COVID-19 to long COVID, is lacking. Meanwhile, the relationship between sarcopenia and adverse outcomes among COVID-19 patients remains inconsistent.

MATERIALS AND METHODS: A systematic search of MEDLINE/PubMed, Embase, Cochrane Library, Web of Science, and Scopus, before 22nd February 2025, was conducted to identify studies assessing sarcopenia prevalence in acute COVID-19 and long COVID. Random effects meta-analyses were performed to estimate the pooled prevalence of sarcopenia for acute COVID-19 and long COVID patients. Subgroup analyses stratified by assessment tool, region, income, hospitalization status, and age were performed. The associations between sarcopenia and COVID-19-related clinical outcomes were further quantified.

RESULTS: A total of 39 studies with 6,982 individuals were included. The pooled prevalence of sarcopenia was 48.7% (95% confidence interval (CI): 39.6-57.9%) in acute COVID-19 and 23.5% (95% CI: 12.7-39.4%) in long COVID. In acute COVID-19 patients, sarcopenia was not significantly associated with length of stay (mean difference = 2.215, 95% CI: -0.004 to 4.433), mechanical ventilation (Odds ratio (OR) = 1.80, 95% CI: 0.84-3.85), admission to the intensive care unit (OR = 1.05, 95% CI: 0.63-1.77), or mortality (OR = 1.41, 95% CI: 0.86-2.32), but was significantly associated with tracheostomy (OR = 2.48, 95% CI: 1.28-4.82).

CONCLUSION: In conclusion, our findings indicate that sarcopenia is highly prevalent in acute COVID-19 and persists in a substantial proportion of long COVID patients, suggesting prolonged muscle loss beyond the acute phase. Future well-designed studies are needed to further investigate the association between sarcopenia and short-term and long-term prognostic outcomes in both acute and long COVID patients.},
}

Humans
*Sarcopenia/epidemiology
*COVID-19/complications/epidemiology/mortality
Prevalence
Prognosis
SARS-CoV-2
Length of Stay/statistics & numerical data
Hospitalization/statistics & numerical data

@article {pmid40543387,
year = {2025},
author = {Beuren, T and Ferrari, F and Franzoni, LT and Goulart, CDL and Val, F and Cipriano, G and Stein, R},
title = {Exploring the interplay between host genetics and acute and long COVID: A narrative review.},
journal = {Clinics (Sao Paulo, Brazil)},
volume = {80},
number = {},
pages = {100708},
pmid = {40543387},
issn = {1980-5322},
abstract = {Over the past four years, pivotal discoveries have deepened the understanding of the relationship between genetic factors and SARS-CoV-2 infection. Numerous genes associated with severe COVID-19 suggest a potential genetic predisposition, which may help explain why some individuals develop more serious illnesses. Emerging evidence highlights the role of genes involved in pulmonary immunity, such as Forkhead box Protein P4 (FOXP4), whose increased expression in lung tissue has been linked to more severe disease. Other genes - Transmembrane Protease Serine-2 (TMPRSS2), Leucine Zipper Transcription Factor Like-1 (LZTFL1), Solute Carrier family 6 member 20 (SLC6A20), Tyrosine Kinase-2 (TYK2), Angiotensin-Converting Enzyme (ACE), and FYVE and Coiled-Coil Domain-Containing-1 (FYCO1) - have also been implicated in COVID-19 severity. In contrast, certain genetic variants - such as the T-allele of rs12329760 in the TMPRSS2 gene and rs35705950-T in the Mucin-5B (MUC5B) gene - may confer protection against severe disease. Overall, the evidence suggests that genetic factors can influence both susceptibility to and protection from severe COVID-19, although these associations are likely shaped by complex interactions with environmental, behavioral, and other biological factors. This review summarizes current knowledge on genetic determinants linked to COVID-19 outcomes.},
}

@article {pmid40540167,
year = {2025},
author = {Lang, SM and Schiffl, H},
title = {Long-term renal consequences of COVID-19. Emerging evidence and unanswered questions.},
journal = {International urology and nephrology},
volume = {},
number = {},
pages = {},
pmid = {40540167},
issn = {1573-2584},
abstract = {PURPOSE: COVID-19 infection is associated with a high burden of acute or acute on chronic kidney injury (AKI), particularly in critically ill patients. Given the large numbers of COVID-19 survivors, characterization of long-term adverse kidney effects of COVID-19 have important implications for post-COVID-19 care.

METHODS: This narrative review provides a summary of epidemiologic evidence for post-COVID kidney disorders.

RESULTS: Precise post-COVID renal data are scarce. The true burden of long-COVID chronic kidney disease (CKD) remains unknown owing to under-recognition, under-diagnosis, clinical heterogeneity of patients, incomplete follow-up, and temporal trends in critical COVID-19 disease across waves of the pandemic. Collectively, the few well-designed studies assessing the impact of long-COVID on kidney health found that the overwhelming majority of patients with normal renal function at admission and without AKI during acute COVID-19 disease preserved kidney function. Post-infection kidney function trajectories of patients who experience a loss of renal function vary. Kidney function may decline gradually even in non-hospitalized patients, hospitalized patients may experience a rapid loss of kidney function 6-12 months after COVID-19 diagnosis or hospital discharge resulting from AKI during the acute phase of the disease. End-stage renal disease may occur after non-recovery from AKI and rapid progression of pre-existing CKD. Multiple mechanisms may trigger post-COVID CKD including maladaptive repair after AKI, or progression of renal lesions of systemic co-morbidities, persistence of the virus and dysregulation of inflammatory cytokines.

CONCLUSIONS: The COVID-19 pandemic has significantly impacted and may continue to have an impact on kidney health. Patients at risk have a higher propensity to develop critical COVID-19 disease. Post-COVID-19 care must pay close attention to renal function in patients discharged from hospital.},
}

@article {pmid40534826,
year = {2025},
author = {Souissi, A and Prieto-González, P and Ben Saad, H},
title = {Widespread pain syndrome in long COVID-19: melatonin as an adjuvant treatment.},
journal = {Frontiers in pain research (Lausanne, Switzerland)},
volume = {6},
number = {},
pages = {1609095},
pmid = {40534826},
issn = {2673-561X},
abstract = {Long coronavirus disease 2019 (LC19) represents a complex global health challenge. Survivors frequently report persistent problems like widespread pain syndrome (WPS), cognitive dysfunction, cardiovascular complications, and sleep disturbances. These health problems, which are worsened by oxidative stress and inflammaging, open the prospect of treatment strategies targeting these mechanisms. Melatonin is a potential option for treating LC19 problems because of its anti-inflammatory, antioxidant, and pain-modulating properties. Melatonin targets shared pathological pathways, offering a promising approach to reducing inflammation, oxidative stress, and neuroendocrine dysfunction. The present mini-review explores the therapeutic potential of melatonin in the treatment of LC19, focusing on its effects on WPS and inflammation.},
}

@article {pmid40531392,
year = {2025},
author = {da Silva, MD and da Silva, TS and Mendes, CG and Valbão, MCM and Badu-Tawiah, AK and Laurindo, LF and Barbalho, SM and Direito, R and Miglino, MA},
title = {Advances in Understanding Long COVID: Pathophysiological Mechanisms and the Role of Omics Technologies in Biomarker Identification.},
journal = {Molecular diagnosis & therapy},
volume = {},
number = {},
pages = {},
pmid = {40531392},
issn = {1179-2000},
support = {200177/2022-2//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; },
abstract = {Long coronavirus disease (COVID) is a multisystem condition that affects a significant proportion of individuals following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with persistent symptoms ranging from fatigue and cognitive dysfunction to cardiovascular disorders. It is estimated that 30-60% of infected individuals experience symptoms lasting more than 12 weeks. Despite advances in understanding acute infection, the pathophysiological mechanisms underlying long COVID remain unclear. Current hypotheses suggest that viral persistence, immune dysfunction, and metabolic alterations play central roles. Omics approaches, including metabolomics, proteomics, and lipidomics, have played a crucial role in investigating molecular changes, identifying biomarkers, and refining therapeutic strategies. This review discusses recent advances in understanding long COVID, addressing its mechanisms, risk factors, the impact of viral variants, and the role of vaccination, with an emphasis on the importance of omics technologies in elucidating this condition.},
}

@article {pmid40529374,
year = {2025},
author = {Trautmann, A},
title = {Core features and inherent diversity of post-acute infection syndromes.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1509131},
pmid = {40529374},
issn = {1664-3224},
mesh = {Humans ; Post-Acute COVID-19 Syndrome ; Animals ; Fatigue/etiology ; *Infections/immunology/complications ; Critical Illness ; },
abstract = {Post-acute infection syndromes (PAIS), i.e., long-lasting pathologies subsequent to infections that do not properly resolve, have both a common core and a broad diversity of manifestations. PAIS include a group of core symptoms (pathological fatigue, cognitive problems, sleep disorders and pain) accompanied by a large set of diverse symptoms. Core and diverse additional symptoms, which can persist for years, exhibiting periods of relapses and remissions, usually start suddenly after an apparently common infection. PAIS display highly variable clinical features depending on the nature of the initial pathogen, and to an even larger extent, on the diversity of preexisting individual terrains in which PAIS are rooted. In a first part, I discuss biological issues related to the persistence of microbial antigens, dysregulated immune responses, reactivation of latent viruses, different potential self-sustained inflammatory loops, mitochondrial dysfunction, metabolic disorders in the tryptophan- kynurenin pathway (TKP) with impact on serotonin, and consequences of a dysfunctional bidirectional microbiota-gut-brain axis. The second part deals with the nervous system dependence of PAIS. I rely on the concept of interoception, the process by which the brain senses, integrates and interprets signals originating from within the body, and sends feebacks aimed at maintaining homeostasis. Interoception is central for understanding the origin of fatigue, dysautonomia, dysfunctioning of the hypothalamus-pituitary-adrenal (HPA) axis, and its relation with stress, inflammation or depression. I propose that all individual predispositions leading to self-sustained vicious circles constitute building blocks that can self-assemble in many possible ways, to give rise to both core and diverse features of PAIS. A useful discrimination between different PAIS subtypes should be obtained with a composite profiling including biomarkers, questionnaires and functional tests so as to take into account PAIS multidimensionality.},
}

Humans
Post-Acute COVID-19 Syndrome
Animals
Fatigue/etiology
*Infections/immunology/complications
Critical Illness

@article {pmid40514644,
year = {2025},
author = {Elboraay, T and Ebada, MA and Elsayed, M and Aboeldahab, HA and Salamah, HM and Rageh, O and Elmallahy, M and AboElfarh, HE and Mansour, LS and Nabil, Y and Eltawab, AKA and Atwan, H and Alkanj, S},
title = {Long-term neurological and cognitive impact of COVID-19: a systematic review and meta-analysis in over 4 million patients.},
journal = {BMC neurology},
volume = {25},
number = {1},
pages = {250},
pmid = {40514644},
issn = {1471-2377},
mesh = {Humans ; *COVID-19/complications/psychology/epidemiology ; *Nervous System Diseases/epidemiology/etiology ; *Cognitive Dysfunction/epidemiology/etiology ; Prevalence ; Fatigue/epidemiology ; },
abstract = {BACKGROUND: Neuropsychiatric symptoms emerged early in the COVID-19 pandemic as a key feature of the virus, with research confirming a range of neuropsychiatric manifestations linked to acute SARS-CoV-2 infection. However, the persistence of neurological symptoms in the post-acute and chronic phases remains unclear. This meta-analysis assesses the long-term neurological effects of COVID-19 in recovered patients, providing insights for mental health service planning.

METHODS: A comprehensive literature search was conducted across five electronic databases: PubMed, Scopus, Web of Science, EBSCO, and CENTRAL, up to March 22, 2024. Studies evaluating the prevalence of long-term neurological symptoms in COVID-19 survivors with at least six months of follow-up were included. Pooled prevalence estimates, subgroup analyses, and meta-regression were performed, and publication bias was assessed.

RESULTS: The prevalence rates for the different symptoms were as follows: fatigue 43.3% (95% CI [36.1-50.9%]), memory disorders 27.8% (95% CI [20.1-37.1%]), cognitive impairment 27.1% (95% CI [20.4-34.9%]), sleep disorders 24.4% (95% CI [18.1-32.1%]), concentration impairment 23.8% (95% CI [17.2-31.9%]), headache 20.3% (95% CI [15-26.9%]), dizziness 16% (95% CI [9.5-25.7%]), stress 15.9% (95% CI [10.2-24%]), depression 14.0% (95% CI [10.1-19.2%]), anxiety 13.2% (95% CI [9.6-17.9%]), and migraine 13% (95% CI [2.2-49.8%]). Significant heterogeneity was observed across all symptoms. Meta-regression analysis showed higher stress, fatigue, and headache in females, and increased stress and concentration impairment with higher BMI.

CONCLUSIONS: Neurological symptoms are common and persistent in COVID-19 survivors. This meta-analysis highlights the significant burden these symptoms place on individuals, emphasizing the need for well-resourced multidisciplinary healthcare services to support post-COVID recovery.

REGISTRATION AND PROTOCOL: This meta-analysis was registered in PROSPERO with registration number CRD42024576237.},
}

Humans
*COVID-19/complications/psychology/epidemiology
*Nervous System Diseases/epidemiology/etiology
*Cognitive Dysfunction/epidemiology/etiology
Prevalence
Fatigue/epidemiology

@article {pmid40512228,
year = {2025},
author = {Goldenberg, DL},
title = {The pivotal role of central sensitization in long COVID, fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome.},
journal = {Expert review of neurotherapeutics},
volume = {25},
number = {8},
pages = {973-989},
doi = {10.1080/14737175.2025.2516097},
pmid = {40512228},
issn = {1744-8360},
mesh = {Humans ; *Fatigue Syndrome, Chronic/physiopathology/therapy ; *Fibromyalgia/physiopathology/therapy ; *COVID-19/physiopathology/complications/therapy ; *Central Nervous System Sensitization/physiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; },
abstract = {INTRODUCTION: Long COVID is a condition characterized by persistent unexplained symptoms following COVID-19 infection. These symptoms are not related to another disease or organ damage and are similar to those in fibromyalgia and myslgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

AREAS COVERED: The similar clinical and pathophysiological features and management of long COVID, fibromyalgia and ME/CFS are explored from the unifying framework of central sensitivity syndromes. The article is based on a literature search utilizing PubMed for content published between 2021 and 1 May 2025, using search terms: long COVID, long COVID syndrome, post-COVID-19, post-acute SARS-CoV-2, fibromyalgia, ME/CFS, post-exertional malaise and central sensitization.

EXPERT OPINION: Once long COVID is redefined to exclude patients with well-defined organ disease, it fits best as a model of central sensitization. Long COVID is a single syndrome, rather than many distinct diseases. Optimal management of long COVID and similar central sensitivity syndromes should include personalized care with a primary care led-multidisciplinary team.},
}

Humans
*Fatigue Syndrome, Chronic/physiopathology/therapy
*Fibromyalgia/physiopathology/therapy
*COVID-19/physiopathology/complications/therapy
*Central Nervous System Sensitization/physiology
Post-Acute COVID-19 Syndrome
SARS-CoV-2

@article {pmid40507911,
year = {2025},
author = {Popa, E and Popa, AE and Poroch, M and Poroch, V and Ungureanu, MI and Slanina, AM and Bacusca, A and Coman, EA},
title = {The Molecular Mechanisms of Cognitive Dysfunction in Long COVID: A Narrative Review.},
journal = {International journal of molecular sciences},
volume = {26},
number = {11},
pages = {},
pmid = {40507911},
issn = {1422-0067},
mesh = {Humans ; *COVID-19/complications/metabolism ; *Cognitive Dysfunction/etiology/metabolism/virology ; SARS-CoV-2 ; Biomarkers/metabolism ; Blood-Brain Barrier/metabolism ; },
abstract = {Cognitive dysfunction represents one of the most persistent and disabling features of Long COVID, yet its molecular underpinnings remain incompletely understood. This narrative review synthesizes current evidence on the pathophysiological mechanisms linking SARS-CoV-2 infection to long-term neurocognitive sequelae. Key processes include persistent neuroinflammation, blood-brain barrier (BBB) disruption, endothelial dysfunction, immune dysregulation, and neuroendocrine imbalance. Microglial activation and cytokine release (e.g., IL-6, TNF-α) promote synaptic dysfunction and neuronal injury, while activation of inflammasomes such as NLRP3 amplifies CNS inflammation. Vascular abnormalities, including microthrombosis and BBB leakage, facilitate the infiltration of peripheral immune cells and neurotoxic mediators. Hypothalamic-pituitary-adrenal axis dysfunction and reduced vagal tone further exacerbate systemic inflammation and autonomic imbalance. Biomarkers such as GFAP, NFL, IL-6, and S100B have been associated with both neuroinflammation and cognitive symptoms. Notably, transcriptomic signatures in Long COVID overlap with those observed in Alzheimer's disease, highlighting shared pathways involving tau dysregulation, oxidative stress, and glial reactivity. Understanding these mechanisms is critical for identifying at-risk individuals and developing targeted therapeutic strategies. This review underscores the need for longitudinal research and integrative biomarker analysis to elucidate the molecular trajectory of cognitive impairment in Long COVID.},
}

Humans
*COVID-19/complications/metabolism
*Cognitive Dysfunction/etiology/metabolism/virology
SARS-CoV-2
Biomarkers/metabolism
Blood-Brain Barrier/metabolism

@article {pmid40507071,
year = {2025},
author = {Bigman, G and Rusu, ME and Shelawala, N and Sorkin, JD and Beamer, BA and Ryan, AS},
title = {A Comprehensive Scoping Review on Diet and Nutrition in Relation to Long COVID-19 Symptoms and Recovery.},
journal = {Nutrients},
volume = {17},
number = {11},
pages = {},
pmid = {40507071},
issn = {2072-6643},
support = {IK6 RX003977/RX/RRD VA/United States ; K01 AG078545/AG/NIA NIH HHS/United States ; P30 AG028747/AG/NIA NIH HHS/United States ; R01 AG051752/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/complications/physiopathology/diet therapy ; *Nutritional Status ; *Diet ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Adult ; },
abstract = {Background/Objectives: Long COVID-19 is characterized by persistent symptoms lasting three months or more following SARS-CoV-2 infection. Nutrition has emerged as a modifiable factor influencing recovery trajectories and symptom burden; however, existing evidence remains fragmented across diverse study designs and populations. This scoping review synthesized global evidence on the role of diet and nutrition in managing long COVID-19 symptoms and supporting recovery. Methods: Following PRISMA-ScR and Joanna Briggs Institute guidelines for scoping reviews, we searched major biomedical databases for studies published between 2020 and 2025. Eligible studies examined dietary intake, nutritional status, or nutrition-related interventions in adults with long COVID-19. Results: After duplicates were removed, 1808 records were screened, resulting in 50 studies that met the inclusion criteria-27 intervention studies and 23 observational studies. Nutritional exposures included micronutrients (e.g., vitamins D, K2), amino acids (e.g., L-arginine), multinutrient formulations, microbiota-targeted therapies (e.g., probiotics, synbiotics), nutritional status, diet quality, and whole-diet patterns (e.g., the Mediterranean diet). Approximately 76% of studies reported improvements in long COVID-19-related symptoms such as fatigue, mood disturbances, physical function, and markers of inflammation. Conclusions: Diet and nutrition may support long COVID-19 recovery by targeting inflammation and the gut microbiome to alleviate symptoms and improve functional outcomes. Well-powered trials of whole-diet approaches, combined with targeted supplementation, are needed to confirm their potential as scalable, accessible tools for post-COVID-19 recovery and management.},
}

Humans
*COVID-19/complications/physiopathology/diet therapy
*Nutritional Status
*Diet
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Adult

@article {pmid40496528,
year = {2024},
author = {Akbari, B and Wang, JM and Baghaei-Yazdi, N and Lahooti, H and Sherman, JH},
title = {Systems Thinking, Causal Loop Diagram, and Systems Dynamic in Public Health Challenges: Navigating Long COVID Syndrome and Sense of Smell in LGBTQIA+ Communities.},
journal = {Public health challenges},
volume = {3},
number = {3},
pages = {e70004},
pmid = {40496528},
issn = {2769-2450},
abstract = {BACKGROUND: The coronavirus pandemic has profoundly affected global health, economic stability, and environmental sustainability. Despite these challenges, significant gaps in data remain, particularly in effectively assessing and engaging diverse communities such as color, LGBTQIA+ individuals, and low-income groups. This shortage of comprehensive research limits our capacity to undertake sensitive studies, specifically in dealing with the complexities of long COVID, which some individuals continue to suffer from after their initial recovery.

OBJECTIVE: This review delves into the ongoing repercussions of long-term COVID-19, a postinfectious syndrome marked by neurological symptoms such as cognitive deficits and sensory impairments, which may last well beyond the acute phase of the illness. These symptoms frequently overlap with mental health issues (e.g., anxiety and depression), which can aggravate the socioeconomic challenges faced by vulnerable populations, especially within the LGBTQA+ communities.

METHODS: To tackle these complex interactions, we have introduced a novel public health framework: model-based systems thinking (MBST), which incorporates System Dynamics and causal loop diagrams (CLD).

RESULTS AND DISCUSSION: The articles were selected on the basis of their discussion of COVID-19-associated anosmia, exploration of olfactory dysfunction alongside neurocognitive disorders, and the challenges experienced in LGBQA+ communities. This approach offers a robust framework for dissecting the intricate ties between socioeconomic factors, health outcomes, and the extended recovery trajectories associated with long-term COVID-19, with a particular focus on olfactory dysfunction. We also explore strategies to make our models more accessible to healthcare providers and the LGBTQA+ communities, encouraging its broader adoption.

CONCLUSION: Long COVID's impact on public health and marginalized communities highlights the urgent need for adopting systems thinking models. Additionally, this article calls for a concerted effort from all experts to foster multidisciplinary, team-based research and implement effective support measures for COVID-19 survivors across all communities, mainly focusing on the scientific, social, and behavioral challenges LGBTQIA+ and low-income individuals face.},
}

@article {pmid40492581,
year = {2025},
author = {Vlaming-van Eijk, LE and Tang, G and Bourgonje, AR and den Dunnen, WFA and Hillebrands, JL and van Goor, H},
title = {Post-COVID-19 condition: clinical phenotypes, pathophysiological mechanisms, pathology, and management strategies.},
journal = {The Journal of pathology},
volume = {266},
number = {4-5},
pages = {369-389},
pmid = {40492581},
issn = {1096-9896},
mesh = {Humans ; *COVID-19/complications/therapy/physiopathology/pathology ; Phenotype ; SARS-CoV-2 ; Risk Factors ; Post-Acute COVID-19 Syndrome ; },
abstract = {Post-COVID-19 condition (PCC), also known as long COVID, is a complex multiple organ system condition that can develop and persist for months after acute COVID-19. PCC encompasses a wide range of symptoms, resulting in heterogeneous clinical manifestations. These manifestations likely arise from diverse underlying pathophysiological mechanisms, which, in turn, are influenced by risk factors such as age, sex, and comorbidities. To this end, characterising clinical phenotypes of PCC is essential for deepening our understanding of its (potentially) distinct pathophysiological mechanisms and for advancing diagnostic and patient-tailored management strategies. PCC is thought to result from a complex interaction of various pathophysiological mechanisms, leading to functional and structural pathological alterations across multiple organ systems. Investigating these alterations is critical to improving our currently incomplete understanding of PCC's complex pathophysiology. This review provides an overview of the main clinical phenotypes of PCC, characterises these phenotypes by examining symptoms and signs, as well as the associated risk factors. The main hypothesised pathophysiological mechanisms are discussed by outlining the current knowledge on PCC pathology, focussing on the most commonly affected organ systems. Current PCC management includes supportive care such as physiotherapy and the repurposing of existing drugs primarily targeting persistence of SARS-CoV-2 (e.g. antivirals, monoclonal antibodies) and immune dysfunction (e.g. antiinflammatory drugs, immunomodulators). To date, prevention of SARS-CoV-2 infection remains critical, which can be achieved through effective public health measures and vaccination strategies. Finally, this review highlights current knowledge gaps and proposes future research directions to advance the understanding and treatment of PCC. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.},
}

Humans
*COVID-19/complications/therapy/physiopathology/pathology
Phenotype
SARS-CoV-2
Risk Factors
Post-Acute COVID-19 Syndrome

@article {pmid40481619,
year = {2025},
author = {Linton, J and Carmichael, J and Newlands, F and Puri, A and Fox-Smith, L and Pinto Pereira, SM and Coughtrey, A and Shafran, R and Stephenson, T},
title = {Pre-Pandemic Prevalence of Post COVID-19 Condition Symptoms in Adolescents.},
journal = {Acta paediatrica (Oslo, Norway : 1992)},
volume = {114},
number = {9},
pages = {2116-2123},
pmid = {40481619},
issn = {1651-2227},
support = {COV-LT-0022//UK Research and Innovation/ ; 183885//Beryl Alexander Charity PhD Studentship/ ; MR/Y009398/1//UK Medical Research Council Senior Non-clinical Fellowship/ ; //NIHR Great Ormond Street Hospital Biomedical Research Centre/ ; },
mesh = {Humans ; Adolescent ; *COVID-19/complications/epidemiology ; Prevalence ; Child ; Young Adult ; *Adolescent Health ; },
abstract = {AIM: The emergence of post COVID-19 condition (PCC) within adolescents has been characterised by a wide range of symptoms, raising concerns for young people's health and quality of life. However, many symptoms are non-specific and there is considerable variation in symptom reporting. It is essential to understand how rates of these symptoms compare to the pre-pandemic health of adolescents.

METHODS: A systematic search of academic literature and websites, using traditional and automated search systems, was undertaken to identify symptoms described in adolescents aged 10-19 years in the 30 years up to and including 2019. Studies were reviewed and symptom prevalence data extracted.

RESULTS: Twenty-five sources (n = 483 097 participants) met the inclusion criteria, including longitudinal and cross-sectional study designs. The description and prevalence of symptoms varied widely, but there was a high pre-pandemic median prevalence of cough (13.6%), headache (30.0%), and fatigue (20.5%). These high prevalences highlight a gap in understanding of pre-pandemic adolescent health and the need for comprehensive, serial symptom profiling.

CONCLUSION: These findings provide a baseline of adolescent symptomatology prior to the emergence of PCC and provide important context for interpreting ongoing COVID symptoms. Data on PCC in adolescents should consider pre-pandemic symptom prevalence.},
}

Humans
Adolescent
*COVID-19/complications/epidemiology
Prevalence
Child
Young Adult
*Adolescent Health

@article {pmid40476637,
year = {2025},
author = {Rahmati, M and Udeh, R and Kang, J and Dolja-Gore, X and McEvoy, M and Kazemi, A and Soysal, P and Smith, L and Kenna, T and Fond, G and Boussat, B and Nguyen, DC and Do, H and Tran, BX and Veronese, N and Yon, DK and Boyer, L},
title = {Long-Term Sequelae of COVID-19: A Systematic Review and Meta-Analysis of Symptoms 3 Years Post-SARS-CoV-2 Infection.},
journal = {Journal of medical virology},
volume = {97},
number = {6},
pages = {e70429},
pmid = {40476637},
issn = {1096-9071},
support = {//The authors received no specific funding for this work./ ; },
mesh = {Humans ; *COVID-19/complications/epidemiology/physiopathology ; Fatigue/epidemiology ; Dyspnea/epidemiology ; SARS-CoV-2 ; Prevalence ; Sleep Wake Disorders/epidemiology ; Post-Acute COVID-19 Syndrome ; Survivors ; },
abstract = {The symptoms of long COVID are well-documented. However, the long-term effects beyond 2 years remain poorly understood due to a lack of data. This systematic review and meta-analysis examined the prevalence of persistent symptoms in COVID-19 survivors 3 years following initial SARS-CoV-2 infection. PubMed, MEDLINE (Ovid), CENTRAL, Web of Science, Scopus, and Embase were searched from inception of the databases up to July 20, 2024, by two independent researchers for articles reporting on the prevalence of persistent symptoms 3 years' post-infection of people who survived COVID-19 infection. We employed a random-effect model for the pooled analysis, and the meta-analytical effect size was prevalence for the applicable end-points, I[2] statistics, and quality assessment of included studies using the Newcastle-Ottawa Scale. Eleven articles were included after the literature search yielded 223 potentially relevant articles. We found that among patients with long COVID, fatigue, sleep disturbances, and dyspnea were the most common symptoms. Pooled analysis showed that the proportion of individuals experiencing at least one persistent symptom 3 years post-COVID-19 is 20% (95% confidence interval [CI]: 8-43). The prevalence of persistent symptoms was dyspnea (12%; 95% CI: 10-15), fatigue (11%; 95% CI: 6-20), insomnia (11%; 95% CI: 2-37), loss of smell (7%; 95% CI: 5-8), loss of taste (7%; 95% CI: 3-16), and anxiety (6%; 95% CI: 1-32). Prevalence of other findings include impaired diffusion capacity (42%; 95% CI: 34-50) and impaired forced expiratory volume in 1 s (10%; 95% CI: 8-12). Our findings confirm the persistence of unresolved symptoms 3 years post-COVID-19 infection, with implications for future research, healthcare policy, and patient care.},
}

Humans
*COVID-19/complications/epidemiology/physiopathology
Fatigue/epidemiology
Dyspnea/epidemiology
SARS-CoV-2
Prevalence
Sleep Wake Disorders/epidemiology
Post-Acute COVID-19 Syndrome
Survivors

@article {pmid40474772,
year = {2025},
author = {Gupta, G and Buonsenso, D and Wood, J and Mohandas, S and Warburton, D},
title = {Mechanistic Insights Into Long Covid: Viral Persistence, Immune Dysregulation, and Multi-Organ Dysfunction.},
journal = {Comprehensive Physiology},
volume = {15},
number = {3},
pages = {e70019},
doi = {10.1002/cph4.70019},
pmid = {40474772},
issn = {2040-4603},
mesh = {Humans ; *COVID-19/immunology/complications/virology/physiopathology ; *SARS-CoV-2/physiology ; *Multiple Organ Failure/immunology/virology/etiology ; Post-Acute COVID-19 Syndrome ; Animals ; },
abstract = {Long Covid is a post-viral syndrome characterized by persistent symptoms targeting multiple organ systems after initial SARS-CoV-2 infection. Current literature suggests that the mechanisms causing Long Covid involve viral persistence, immune dysregulation, systemic inflammation, endothelial dysfunction, and metabolic disturbances. By forming reservoirs in the tissues of various organs, SARS-CoV-2 may evade immunological clearances while triggering immune responses and contributing to chronic symptoms through cytokine imbalances, T-cell exhaustion, and systemic inflammation. These symptoms parallel other post-viral syndromes such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), suggesting similar mechanisms of pathology. The coronavirus has also been linked to neuroinflammation and endothelial dysfunction causing cognitive symptoms and cardiovascular complications. Furthermore, its ability to lower energy production links it to post-exertion malaise (PEM) and muscle pain. These symptoms may result from iron dysregulation and persistent oxidative stress due to Covid-impaired mitochondrial function. This review synthesizes current data on the mechanisms that drive Long Covid pathogenesis and explores potential therapeutic strategies to mitigate viral persistence, immune dysfunction, and metabolic disturbances. It is critical to understand these interactions to develop targeted interventions that address the long-term sequelae of SARS-CoV-2 infection and improve patient outcomes.},
}

Humans
*COVID-19/immunology/complications/virology/physiopathology
*SARS-CoV-2/physiology
*Multiple Organ Failure/immunology/virology/etiology
Post-Acute COVID-19 Syndrome
Animals

@article {pmid40470564,
year = {2025},
author = {Iannuccelli, C and Favretti, M and Dolcini, G and Di Carlo, M and Pellegrino, G and Bazzichi, L and Atzeni, F and Lucini, D and Varassi, G and Leoni, MLG and Fornasari, DMM and Conti, F and Salaffi, F and Sarzi-Puttini, P and Di Franco, M},
title = {Fibromyalgia: one year in review 2025.},
journal = {Clinical and experimental rheumatology},
volume = {43},
number = {6},
pages = {957-969},
doi = {10.55563/clinexprheumatol/buhd2z},
pmid = {40470564},
issn = {0392-856X},
mesh = {Humans ; *Fibromyalgia/therapy/physiopathology/diagnosis/epidemiology/psychology ; Quality of Life ; COVID-19/epidemiology ; },
abstract = {Fibromyalgia (FM) is a chronic syndrome characterised by widespread pain, high prevalence, and a significant impact on quality of life. Despite extensive research, its pathogenesis and treatment remain only partially understood, driving continued investigation throughout 2024. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system has been linked to chronic stress responses and neuroinflammation, with neuroimaging and preclinical studies confirming altered pain and stress processing. Low-grade inflammation and metabolic disturbances, including cytokine imbalance and increased adipose tissue infiltration, further exacerbate symptoms. Alterations in the gut microbiota contribute to immune and emotional dysregulation. MRI studies continue to reveal brain changes that differentiate FM from other chronic pain disorders. Multi-omics approaches, including transcriptomic and metabolomic analyses, show promise as diagnostic biomarkers. Mitochondrial dysfunction also emerges as a key factor, since impaired energy metabolism seems to correlate with symptom severity. From a clinical perspective, recent studies have explored under-recognised aspects of FM, such as sexual and cognitive dysfunction, the role of gender, environmental exposures, and the disease's impact on relationships and family life. The differential diagnosis of FM and long COVID has ignited discussion about potential shared mechanisms. Conversely, residual pain in inflammatory diseases remains insufficiently addressed. Therapeutically, non-pharmacological strategies, particularly physical activity and psychosocial interventions, remain fundamental. Emerging areas such as non-invasive neuromodulation, psychedelic therapies, and the integration of technologies like virtual reality and artificial intelligence are opening new frontiers in treatment, patient care, and research. These advances underscore the multifactorial nature of FM and the need for personalised, interdisciplinary approaches.},
}

Humans
*Fibromyalgia/therapy/physiopathology/diagnosis/epidemiology/psychology
Quality of Life
COVID-19/epidemiology

@article {pmid40465774,
year = {2025},
author = {Salmam, I and Dubé, MO and Zahouani, I and Ramos, A and Desmeules, F and Best, KL and Roy, JS},
title = {The impact of long COVID on physical and cardiorespiratory parameters: A systematic review.},
journal = {PloS one},
volume = {20},
number = {6},
pages = {e0318707},
pmid = {40465774},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/physiopathology/complications ; SARS-CoV-2 ; Respiratory Function Tests ; Adult ; Exercise Tolerance ; },
abstract = {BACKGROUND: Since the emergence of COVID-19, millions worldwide have continued to experience persistent symptoms months after infection. Among these, physical and cardiorespiratory impairments are frequently reported, but remain poorly understood. This systematic review aimed to identify and synthesize evidence regarding physical and cardiorespiratory impairments in individuals with long COVID, defined as symptoms persisting for at least three months post-infection.

METHODS AND FINDINGS: A structured search was conducted across the MEDLINE, Embase, CINAHL, and Web of Science databases to identify cross-sectional and longitudinal cohort studies on physical and cardiorespiratory deficits in adults with long COVID. Twenty-two studies involving 3,041 adults with long COVID were included. Critical appraisal using the JBI-APT indicated that most studies had clear inclusion criteria (17/22), well-defined study populations (17/22), and valid exposure measurements (16/22), though confounding factors were often unaddressed (9/22 unclear or not reported). Findings indicate that while adults with long COVID displayed normal pulmonary function at rest, including Forced Vital Capacity (FVC), Forced Expiratory Volume (FEV1), Total Lung Capacity (TLC), and resting Arterial oxygen saturation (SpO2), significant impairments in exercise capacity were identified. Notably, all studies assessing the 6-minute walk test (6MWT) reported reduced distances, consistently falling below the 50th percentile of normative values. Additionally, VO₂peak was decreased in most studies (7/10), falling below 80% of the predicted value, indicating impaired aerobic capacity. Lower Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) values were observed in three out of six studies, with values below 75% of predicted, suggesting impaired gas exchange efficiency during exertion.

CONCLUSION: Despite preserved resting lung function, these findings highlight significant physical deconditioning in Long COVID adults, with substantial reduction in exercise capacity. Routine assessments should include more sensitive measures, such as the 6MWT and VO₂peak, to detect subtle exercise limitations, even in patients with normal resting SpO₂, to better inform rehabilitation interventions.},
}

Humans
*COVID-19/physiopathology/complications
SARS-CoV-2
Respiratory Function Tests
Adult
Exercise Tolerance

@article {pmid40464778,
year = {2025},
author = {Leite Barbosa, N and Rangel Agra Oliveira, T and Nóbrega, LD and Araújo, TTF and Dos Santos Bezerra, SR and Oliveira, GM and Do Nascimento, RM and de Miranda Silva Nogueira, PA and Tomaz, AF and Do Nascimento Sales Figueiredo Fernandes, AT},
title = {Prevalence and characteristics of respiratory and cardiovascular sequelae in post-COVID-19 syndromes: a scoping review.},
journal = {Expert review of respiratory medicine},
volume = {},
number = {},
pages = {1-19},
doi = {10.1080/17476348.2025.2515992},
pmid = {40464778},
issn = {1747-6356},
abstract = {INTRODUCTION: Post acute and Long COVID-19 are public health issues, marked by persistent respiratory and cardiovascular symptoms such as dyspnea and palpitations. These complications often extend beyond the acute phase, affecting even individuals with mild or moderate COVID-19. This article reviews the clinical impact of long COVID-19 and emphasizes the need for a multidisciplinary approach to management.

AREAS COVERED: A comprehensive literature search was conducted through PubMed, Medline, CINAHL, SciELO, and LILACS to identify studies published up to 28 October 2024, reporting on respiratory and cardiovascular sequelae in long COVID-19. This review examines the prevalence and characteristics of persistent symptoms such as dyspnea, cough, and palpitations, as well as the associated risk factors and assessment methods.

EXPERT OPINION: Long COVID-19 represents a significant healthcare challenge, underscoring the need for standardized protocols for diagnosis and treatment. A multidisciplinary approach is crucial to address the diverse symptoms of affected patients. Future research should focus on understanding the underlying pathophysiology, and developing targeted therapeutic strategies to improve patient outcomes.},
}

@article {pmid40453253,
year = {2025},
author = {Boorle, NVLD and Kurra, NC and Gandrakota, N and Modi, K and Sudireddy, K and Irfan, SA and Jain, A and Parikh, PA and Jillella, D},
title = {Central Nervous System Manifestations of Long COVID: A Systematic Review.},
journal = {Cureus},
volume = {17},
number = {4},
pages = {e83247},
pmid = {40453253},
issn = {2168-8184},
abstract = {Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been one of the most widespread and devastating global pandemics, impacting hundreds of millions of people worldwide. After the cessation of active infection, the disease continues to have a disabling impact due to the persistence of fatigue, brain fog, anxiety, and depression - among the most common symptoms. This study explores the progression of neurological symptoms over 12 months and beyond following an initial diagnosis of COVID-19. Through an electronic search of eligible studies from PubMed, the Cochrane Trial Register, and Google Scholar, 10 studies were included for qualitative analysis. The systematic review highlights the similarities and differences in findings across the included studies. Olfactory dysfunction was prevalent in 0.9%-51% of individuals, and taste impairment was observed in 1.1%-21.3%. At 12 months, anxiety was more prevalent (3.5%-29%) than depression (3.5%-26%). Fatigue was the predominant neurocognitive complaint in 56% of individuals with severe COVID-19. Nearly half of individuals reported sleep difficulties. Memory impairment, followed by headaches and dizziness, also constitutes neurocognitive symptoms reported at 12 months. Our study found that there is a significant neurological burden one year following the diagnosis of COVID-19. Further studies exploring the pathological mechanisms of long-term COVID-19 are necessary to better delineate the mechanisms behind several long-term neurological manifestations of COVID-19.},
}

@article {pmid40447142,
year = {2025},
author = {Vreeman, ECA and Pillay, J and Burgess, JK},
title = {Post-COVID pulmonary sequelae: Mechanisms and potential targets to reduce persistent fibrosis.},
journal = {Pharmacology & therapeutics},
volume = {272},
number = {},
pages = {108891},
doi = {10.1016/j.pharmthera.2025.108891},
pmid = {40447142},
issn = {1879-016X},
mesh = {Humans ; *COVID-19/complications ; *Pulmonary Fibrosis/etiology/drug therapy/virology ; SARS-CoV-2 ; Lung/pathology ; },
abstract = {After the severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) pandemic, the emergence of long-term sequelae post-infection poses a new healthcare challenge. Following initial infection with SARS-CoV-2, approximately 1 in 10 people experience post-acute sequelae of COVID-19 (PASC), also known as long COVID. PASC can affect the entire body, with the airways and lungs being a primary target of the initial viral infection. Many post-COVID symptoms have been associated with fibrotic lung lesions and diminished respiratory function. The reversibility, persistence, or progression of post-COVID-19 pulmonary fibrosis is still a topic of debate. We aimed to compare current findings and examined similar viral infections from the past, to increase understanding of prevalence, persistence and possible pharmacological targets of post-COVID-19 pulmonary fibrosis. Recent studies have documented PASC symptoms persisting up to 3 years post-recovery, and lung impairments present after 15 years after infection with the similar SARS-CoV virus in 2003. These findings suggest the potential for long-term pulmonary fibrosis following SARS-CoV-2 infection, highlighting the need for new anti-fibrotic treatments capable of reversing pulmonary fibrosis. Besides the approved anti-fibrotics, pirfenidone and nintedanib, other promising treatments include histone deacetylase inhibitors, angiotensin receptor blockers and mesenchymal stem cells. The pathophysiological mechanisms underlying post-COVID-19 pulmonary fibrosis are still incompletely understood, necessitating future research to clarify the development of persistent post-COVID-19 pulmonary fibrosis following SARS-CoV-2 infection. Given the widespread transmission of SARS-CoV-2, even a low prevalence of persistent post-COVID-19 pulmonary fibrosis would represent a significant public health concern for which therapeutic strategies are essential to identify.},
}

Humans
*COVID-19/complications
*Pulmonary Fibrosis/etiology/drug therapy/virology
SARS-CoV-2
Lung/pathology

@article {pmid40438846,
year = {2025},
author = {Idris Fadul, AA and Osman Mohamed, AA and Mohammed Ahmed, AAS and Elmobark, S and Merghani Hammour, AS and Elgaleel Khir Elsiad, NMN and Mohammed Elhaj, EA},
title = {Post-coronavirus Disease 2019 (COVID-19) Cardiovascular Manifestations: A Systematic Review of Long-Term Risks and Outcomes.},
journal = {Cureus},
volume = {17},
number = {4},
pages = {e83083},
pmid = {40438846},
issn = {2168-8184},
abstract = {Emerging evidence suggests that coronavirus disease 2019 (COVID-19) survivors face increased risks of cardiovascular complications, but the long-term risks, underlying mechanisms, and clinical implications remain incompletely characterized. This systematic review synthesizes current evidence on post-COVID-19 cardiovascular manifestations, evaluating their incidence, pathophysiology, and outcomes. A comprehensive literature search was conducted across PubMed/MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Fifteen observational studies (cohort, case-control, cross-sectional) meeting predefined eligibility criteria, confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, cardiovascular outcomes assessed ≥4 weeks post-infection, sample sizes >10, and peer-reviewed publication, were included. The risk of bias was assessed using the Newcastle-Ottawa Scale. The multinational studies (United States, Europe, Asia, South America) involved diverse populations (n=80-8,126,462), with follow-up durations ranging from three to 24 months. Mechanisms such as endothelial dysfunction, myocardial inflammation, and autonomic dysregulation were consistently supported across studies via imaging (e.g., cardiac MRI) and biomarkers (e.g., troponin, C-reactive protein (CRP)). Persistent arrhythmias and subclinical myocardial injury were directly demonstrated in 40-60% of patients. Worse outcomes were associated with hospitalization during acute infection, preexisting cardiovascular disease, and metabolic syndrome. Heterogeneity in follow-up durations may limit the detection of very-late-onset complications, though risks remained elevated across all intervals. Individualized management strategies should include cardiovascular imaging (echocardiography, MRI), biomarker profiling, and tailored pharmacotherapy (anti-inflammatory agents, anticoagulants). The ethical rationale for randomized trials is now strengthened by the clear evidence of long-term risks; ongoing trials are testing targeted anti-inflammatory and anticoagulant regimens. These findings underscore the necessity of systematic cardiovascular surveillance and risk-stratified care for COVID-19 survivors. Future research should prioritize extended follow-up studies and randomized controlled trials (RCTs) to optimize interventions for this growing population.},
}

@article {pmid40436612,
year = {2025},
author = {Daynes, E and Barker, RE and Jones, AV and Walsh, JA and Nolan, CM and Man, WD and Singh, SJ and Greening, NJ and Houchen-Wolloff, L and Evans, RA},
title = {Determining the minimum important differences for field walking tests in adults with long-term conditions: a systematic review and meta-analysis.},
journal = {European respiratory review : an official journal of the European Respiratory Society},
volume = {34},
number = {176},
pages = {},
pmid = {40436612},
issn = {1600-0617},
support = {/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; *Walk Test ; *Exercise Tolerance ; Time Factors ; Predictive Value of Tests ; Male ; Female ; *Minimal Clinically Important Difference ; Reproducibility of Results ; Adult ; Middle Aged ; *Lung/physiopathology ; *Walking ; Aged ; *Respiratory Tract Diseases/diagnosis/physiopathology/therapy ; *Heart Diseases/diagnosis/physiopathology ; Prognosis ; *Exercise Test ; *Nervous System Diseases/diagnosis/physiopathology ; Chronic Disease ; },
abstract = {IMPORTANCE: The minimum important difference (MID) for field walking tests aims to improve interpretation of outcomes, but the volume and heterogeneity of MIDs for these tests is challenging. We aimed to determine the MID for the 6-min walk distance (6MWD), incremental shuttle walk test (ISWT) and endurance shuttle walk test (ESWT) in adults with long-term conditions.

METHODS: This systematic review included studies that generated a MID using an anchor-based approach in patients with long-term conditions for the 6MWD, ISWT or ESWT field walking tests. Studies were screened and data extracted by independent reviewers. Meta-analyses were performed using RevMan.

RESULTS: 42 studies were included in the analyses, involving n=13 949 participants. Of these, 12 studies involving exercise as an intervention were included in the meta-analyses to produce MIDs, presented as mean (95% confidence interval). The MID for the 6MWD was 25 m (24-26 m) for respiratory conditions, 23 m (8-37 m) for cardiac conditions and 37 m (26-49 m) for neurological/musculoskeletal conditions. The MID for the ISWT was 48 m (39-57 m) for respiratory conditions and 70 m (55-85 m) for cardiac conditions. The MID for ESWT in COPD was 159 s (94-224 s). The pooled MID across conditions within exercise interventions was 26 m (22-40 m) for the 6MWD and 53 m (44-62 m) for the ISWT, with reasonable heterogeneity (I[2]=48% and I[2]=47%, respectively).

CONCLUSION: We propose new MIDs for exercise interventions using anchor-based methodology in long‑term conditions for the 6MWD, ISWT and ESWT. These can be used internationally for meta‑analyses where studies have used different field walking tests, to optimise trial sample size calculations, and for clinical service benchmarking.},
}

Humans
*Walk Test
*Exercise Tolerance
Time Factors
Predictive Value of Tests
Male
Female
*Minimal Clinically Important Difference
Reproducibility of Results
Adult
Middle Aged
*Lung/physiopathology
*Walking
Aged
*Respiratory Tract Diseases/diagnosis/physiopathology/therapy
*Heart Diseases/diagnosis/physiopathology
Prognosis
*Exercise Test
*Nervous System Diseases/diagnosis/physiopathology
Chronic Disease

@article {pmid40435383,
year = {2025},
author = {Nairn, B and Tsakanikas, V and Gordon, B and Karapintzou, E and Kaski, D and Fotiadis, DI and Bamiou, DE},
title = {Smart Wearable Technologies for Balance Rehabilitation in Older Adults at Risk of Falls: Scoping Review and Comparative Analysis.},
journal = {JMIR rehabilitation and assistive technologies},
volume = {12},
number = {},
pages = {e69589},
pmid = {40435383},
issn = {2369-2529},
abstract = {BACKGROUND: Falls among older adults are a significant public health concern, often leading to severe injuries, decreased quality of life, and substantial health care costs. Smart wearable technologies for balance rehabilitation present a promising avenue for addressing the falls epidemic, capable of providing detailed objective movement data, engaging visuals, and real-time feedback. With the recent and rapid evolution of innovative technologies, including artificial intelligence (AI), augmented reality (AR) or virtual reality (VR), and motion tracking, there is a need to evaluate the market to identify the most effective and accessible smart balance systems currently available.

OBJECTIVE: This study aims to evaluate the current landscape of smart wearable technology systems for balance rehabilitation in older adults at risk of falls. In addition, it aims to compare market-available systems to the telerehabilitation of balance clinical and economic decision support system (TeleRehab DSS), a recently developed smart balance system.

METHODS: A scoping review and strengths, weaknesses, opportunities, and threats (SWOT) analysis was completed, exploring the landscape of smart balance systems in older adults at risk of falls. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines, electronic databases PubMed, MEDLINE, and Cochrane were systematically searched for articles in English from July 1, 2014, to July 1, 2024. Gray literature searches of relevant institutions and web pages were also conducted. The database search and commercial systems were then compared against the TeleRehab DSS in a SWOT analysis.

RESULTS: The scoping review yielded 17 systems that met the inclusion criteria; 10 investigational systems and 7 commercially available systems. Out of 10 studies, only 1 reported the use of intelligent learning or AI, 8 studies reported the use of motion tracking, and 9 studies used virtual reality. Of the studies incorporating motion tracking, 3 provided feedback as either visual or auditory. All but 2 studies reported the use of gamification, and 7 studies incorporated balance exercises. In total, 2 studies reported remote delivery, with 5 being clinician-supervised and 4 providing a clinician report. The SWOT analysis of TeleRehab DSS against the 7 market-available smart balance systems revealed several unique advantages, including personalized therapy with AI-DSS, AR for real-world interaction, enhanced clinician involvement, and comprehensive data analytics.

CONCLUSIONS: The findings from this scoping review highlight the rapid evolution of smart balance systems, yet significant gaps remain in AI integration, remote accessibility, and clinician-driven data analytics. Despite limitations such as cost, accessibility, and user training requirements, TeleRehab DSS emerges as a significant innovation, addressing many of these gaps through AI-driven personalization, AR for real-world interaction, and real-time clinician monitoring. These features position it as a next-generation solution that aligns closely with the evolving needs of patients and clinicians. The results of this review provide valuable insights for future research, supporting the need for further validation studies and the development of more intelligent and accessible balance rehabilitation technologies.},
}

@article {pmid40431734,
year = {2025},
author = {Kim, DH and Kim, JH and Jeon, MT and Kim, KS and Kim, DG and Choi, IS},
title = {The Role of TDP-43 in SARS-CoV-2-Related Neurodegenerative Changes.},
journal = {Viruses},
volume = {17},
number = {5},
pages = {},
pmid = {40431734},
issn = {1999-4915},
support = {25-BR-02-03//Korea Brain Research Institute/ ; },
mesh = {Humans ; *DNA-Binding Proteins/metabolism/genetics ; *COVID-19/complications/metabolism/virology/pathology ; *SARS-CoV-2/physiology ; *Neurodegenerative Diseases/metabolism/virology/pathology/etiology ; Virus Replication ; Animals ; },
abstract = {The coronavirus disease 2019 (COVID-19) pandemic has been linked to long-term neurological effects with multifaceted complications of neurodegenerative diseases. Several studies have found that pathological changes in transactive response DNA-binding protein of 43 kDa (TDP-43) are involved in these cases. This review explores the causal interactions between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and TDP-43 from multiple perspectives. Some viral proteins of SARS-CoV-2 have been shown to induce pathological changes in TDP-43 through its cleavage, aggregation, and mislocalization. SARS-CoV-2 infection can cause liquid-liquid phase separation and stress granule formation, which accelerate the condensation of TDP-43, resulting in host RNA metabolism disruption. TDP-43 has been proposed to interact with SARS-CoV-2 RNA, though its role in viral replication remains to be fully elucidated. This interaction potentially facilitates viral replication, while viral-induced oxidative stress and protease activity accelerate TDP-43 pathology. Evidence from both clinical and experimental studies indicates that SARS-CoV-2 infection may contribute to long-term neurological sequelae, including amyotrophic lateral sclerosis-like and frontotemporal dementia-like features, as well as increased phosphorylated TDP-43 deposition in the central nervous system. Biomarker studies further support the link between TDP-43 dysregulation and neurological complications of long-term effects of COVID-19 (long COVID). In this review, we presented a novel integrative framework of TDP-43 pathology, bridging a gap between SARS-CoV-2 infection and mechanisms of neurodegeneration. These findings underscore the need for further research to clarify the TDP-43-related neurodegeneration underlying SARS-CoV-2 infection and to develop therapeutic strategies aimed at mitigating long-term neurological effects in patients with long COVID.},
}

Humans
*DNA-Binding Proteins/metabolism/genetics
*COVID-19/complications/metabolism/virology/pathology
*SARS-CoV-2/physiology
*Neurodegenerative Diseases/metabolism/virology/pathology/etiology
Virus Replication
Animals

@article {pmid40431631,
year = {2025},
author = {de Melo, BP and da Silva, JAM and Rodrigues, MA and Palmeira, JDF and Amato, AA and Argañaraz, GA and Argañaraz, ER},
title = {SARS-CoV-2 Spike Protein and Long COVID-Part 2: Understanding the Impact of Spike Protein and Cellular Receptor Interactions on the Pathophysiology of Long COVID Syndrome.},
journal = {Viruses},
volume = {17},
number = {5},
pages = {},
pmid = {40431631},
issn = {1999-4915},
mesh = {*Spike Glycoprotein, Coronavirus/metabolism/genetics ; Humans ; *COVID-19/virology/physiopathology/complications/metabolism ; *SARS-CoV-2/metabolism/genetics/physiology ; *Receptors, Virus/metabolism ; Protein Binding ; Post-Acute COVID-19 Syndrome ; },
abstract = {SARS-CoV-2 infection has had a significant impact on global health through both acute illness, referred to as coronavirus disease 2019 (COVID-19), and chronic conditions (long COVID or post-acute sequelae of COVID-19, PASC). Despite substantial advancements in preventing severe COVID-19 cases through vaccination, the rise in the prevalence of long COVID syndrome and a notable degree of genomic mutation, primarily in the S protein, underscores the necessity for a deeper understanding of the underlying pathophysiological mechanisms related to the S protein of SARS-CoV-2. In this review, the latest part of this series, we investigate the potential pathophysiological molecular mechanisms triggered by the interaction between the spike protein and cellular receptors. Therefore, this review aims to provide a differential and focused view on the mechanisms potentially activated by the binding of the spike protein to canonical and non-canonical receptors for SARS-CoV-2, together with their possible interactions and effects on the pathogenesis of long COVID.},
}

*Spike Glycoprotein, Coronavirus/metabolism/genetics
Humans
*COVID-19/virology/physiopathology/complications/metabolism
*SARS-CoV-2/metabolism/genetics/physiology
*Receptors, Virus/metabolism
Protein Binding
Post-Acute COVID-19 Syndrome