@article {pmid41444262,
year = {2025},
author = {Wilson, JE and Gurdasani, D and Helbok, R and Ozturk, S and Fraser, DD and Filipović, SR and Peluso, MJ and Iwasaki, A and Yasuda, CL and Bocci, T and Priori, A and Altmann, D and Alwan, NA and Wesley Ely, E},
title = {COVID-19-associated neurological and psychological manifestations.},
journal = {Nature reviews. Disease primers},
volume = {11},
number = {1},
pages = {91},
pmid = {41444262},
issn = {2056-676X},
mesh = {Humans ; *COVID-19/complications/psychology/physiopathology/epidemiology ; *Nervous System Diseases/etiology/virology ; *Mental Disorders/etiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Anxiety/etiology ; Depression/etiology ; },
abstract = {Long COVID is an infection-associated chronic condition that typically occurs within 3 months of acute COVID-19 infection in which symptoms are intermittently or continuously present for at least 3 months. Long COVID is estimated to affect between 80 and 400 million people globally, with an incidence of 5-20% in the community and up to 50% among hospitalized patients following acute SARS-CoV-2 infection. Common neuropsychiatric and mental health symptoms of long COVID include memory deficits, executive dysfunction, anxiety, depression, recurring headaches, sleep disturbances, neuropathies, problems with taste and smell, and dizziness that accompanies erratic heart rates and severe post-exertional malaise. Underlying pathophysiological mechanisms includes SARS-CoV-2 viral persistence, herpesvirus reactivation, microbiota dysbiosis, autoimmunity, clotting and endothelial abnormalities, and chronic immune activation. Owing to the variability in the clinical presentation, management must be tailored based on a patient's presenting symptoms.},
}

Humans
*COVID-19/complications/psychology/physiopathology/epidemiology
*Nervous System Diseases/etiology/virology
*Mental Disorders/etiology
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Anxiety/etiology
Depression/etiology

@article {pmid41440526,
year = {2025},
author = {László, SA and Ianoși, ES and Văsieșiu, AM and Szathmáry, M and Ianoși, MB and Rachiș, DL and Nistor, G and Jimborean, G},
title = {COVID-19 and Lung Cancer Interactions: A Literature Review.},
journal = {Medical sciences (Basel, Switzerland)},
volume = {13},
number = {4},
pages = {},
doi = {10.3390/medsci13040295},
pmid = {41440526},
issn = {2076-3271},
mesh = {Humans ; *COVID-19/epidemiology/complications/virology ; *Lung Neoplasms/epidemiology/diagnosis/virology ; SARS-CoV-2 ; Incidence ; Pandemics ; },
abstract = {This review aims to discuss the apparent reduction in pulmonary cancer incidence in the general population during and shortly after the COVID-19 pandemic from a biological and pathophysiological mechanistic point of view. While the epidemiological evidence points to a disruption in the early- and mid-stage diagnostic process, which causes a shift to late-stage lung cancer discovery with no impact on its actual prevalence, an alternative hypothesis based on the intersection of viral and cancer biology could have a real effect on lung carcinogenesis as an independent phenomenon. By weaving together population-level trends, mechanistic insights, and translational oncology, we discuss whether the pandemic-associated decline in lung cancer diagnoses reflects primarily a temporary diagnostic artifact or whether it also reveals biologically relevant intersections between SARS-CoV-2 and pulmonary oncogenesis. The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has exerted profound and multifaceted effects on global healthcare systems, altering patterns of disease detection, management, and outcomes across nearly all medical disciplines. These disruptions generated what has been termed a "diagnostic deficit", producing a backlog of undetected cancers that have only partially been recovered in subsequent years. This phenomenon, sometimes described as a "COVID-19 debt" in oncology, is thought to contribute to excess late-stage diagnoses and potentially worse medium-term survival outcomes. Beyond the disruption of medical systems, the pandemic also raised a more speculative but biologically intriguing question: could SARS-CoV-2 infection itself, through direct or indirect mechanisms, influence lung cancer biology? Our review aims to critically synthesize the evidence across seven domains to address this dual hypothesis. (1) We examine the observed effects of the pandemic on cancer incidence, highlighting global registry and health-system data; (2) we review SARS-CoV-2 infection biology, including viral entry, replication, protein functions, and treatment implications; (3) we summarize the pathogenesis of lung cancer; (4) we explore the role of immune checkpoints in tumor immune evasion, followed by (5) analyses of immune dysregulation in acute infection and (6) in long COVID; and (7) finally, we evaluate proposed oncogenic mechanisms of SARS-CoV-2, integrating molecular virology with cancer immunology. We conclude that the "diagnostic deficit" phenomenon was a reality during and immediately post-pandemic. However, a definitive answer to the questions related to the impact of the infection as an independent phenomenon would require advanced research information covering the biology of the viral infection and lung cancer oncogenesis: processes that are not currently implemented in routine clinical laboratory investigations.},
}

Humans
*COVID-19/epidemiology/complications/virology
*Lung Neoplasms/epidemiology/diagnosis/virology
SARS-CoV-2
Incidence
Pandemics

@article {pmid41439932,
year = {2025},
author = {Zuñiga-Jimenez, CT and Rojas-Esguerra, DF and Muñoz-Martinez, AP and Mendoza-Guzman, DC and Daza-Arana, JE},
title = {Musculoskeletal Sequelae of Post-COVID-19 Syndrome: A Systematic Review.},
journal = {Diseases (Basel, Switzerland)},
volume = {13},
number = {12},
pages = {},
doi = {10.3390/diseases13120391},
pmid = {41439932},
issn = {2079-9721},
abstract = {Background/Objectives: COVID-19 infection is a respiratory illness that affects multiple body systems, including the musculoskeletal system. In August 2024, Colombia reported 6 million infections and a 2.2% mortality rate related to COVID-19. Post-COVID-19 syndrome (PCS) is a chronic condition occurring after the acute infection, typically characterized by fatigue, weakness, pain, and sarcopenia, impacting the patient's quality of life (QoL). This systematic review aimed to identify musculoskeletal sequelae, including peripheral muscle strength, fatigue, and QoL, in patients with PCS. Methods: We searched the PubMed, Scopus, and Web of Science databases for cross-sectional, case-control, and cohort studies focusing on musculoskeletal sequelae in patients with COVID-19 infection published between 2020 and 2025. Study quality and risk of bias were assessed using the MINORS and the ROBINS-E scales, respectively. Results: Thirteen studies (n = 5657 patients) met the eligibility criteria. Seventy-six percent of studies indicated muscle weakness as the most common sequela, primarily in older adults and individuals with comorbidities (obesity, diabetes, and chronic obstructive pulmonary disease). General fatigue (reported in 76% of the studies) significantly influenced patients' daily lives, whereas 90% of patients reported some level of deterioration in their QoL, primarily regarding mental health, bodily pain, and physical performance. Conclusions: Patients with PCS who required mechanical ventilation showed reduced muscle strength and poor physical performance, especially older adults. Inactive individuals had worse musculoskeletal sequelae, while physical activity was associated with better strength levels. Although QoL improved after 12 months, the combination of aerobic exercise with adequate nutrition is essential to promote muscle recovery, reduce fatigue, and improve overall functional capacity in post-COVID-19 patients.},
}

@article {pmid41438927,
year = {2025},
author = {Cheng, AL and Barker, R and von Nordheim, D and McQueen, A},
title = {Long COVID: What is it? Who has it? What Are Treatment Resources in Missouri?.},
journal = {Missouri medicine},
volume = {122},
number = {6},
pages = {488-494},
pmid = {41438927},
issn = {0026-6620},
mesh = {Humans ; Missouri/epidemiology ; *COVID-19/epidemiology/complications/therapy ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {As we pass the five-year mark since the COVID-19 pandemic hit, the prevalence of persistent (and often disabling) symptoms from the SARS-CoV-2 virus is estimated to be on par with the prevalence of heart disease. Yet, these Long COVID symptoms can masquerade as other conditions and/or normal aging, so it is believed that Long COVID is under-diagnosed and, as a result, under-treated. Although there is not yet a true cure for Long COVID, many patients benefit substantially from rehabilitation strategies, medications, and social support resources that are available in Missouri. The purpose of this article is to review the definition and epidemiology of Long COVID, provide practical guidance for Long COVID assessment and management especially in the primary care setting, and increase awareness of regional resources for people in Missouri who are living with Long COVID and for the clinicians who are caring for them.},
}

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

@article {pmid41425584,
year = {2025},
author = {Ruiz-Pablos, M and Paiva, B and Zabaleta, A},
title = {The origin of autoimmune diseases: is there a role for ancestral HLA-II haplotypes in immune hyperactivity.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1710571},
pmid = {41425584},
issn = {1664-3224},
mesh = {Humans ; *Autoimmune Diseases/immunology/genetics/etiology ; *Haplotypes ; Genetic Predisposition to Disease ; Autoimmunity ; *Histocompatibility Antigens Class II/genetics/immunology ; Animals ; },
abstract = {The prevalence of autoimmune diseases in contemporary human populations poses a challenge for both medicine and evolutionary biology. This review explores how the ancestral human leukocyte antigen class II (HLA-II) haplotypes DR2-DQ6, DR4-DQ8 and DR3-DQ2 could play a central role in susceptibility to these diseases. We propose that these haplotypes, selected in historical contexts of high infectious pressure, may have been maintained because of their ability to elicit strong T-cell responses against pathogens; however, that antigenic promiscuity may be associated with an increased tendency toward immune hyperreactivity in modern environments. This hyperreactivity, involving proinflammatory cytokines including interferon-gamma (IFN-γ), could contribute to the breakdown of tolerance and the emergence of autoimmunity and related clinical phenomena (e.g., Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome and post-vaccination syndromes), although the evidence for the latter remains limited. Finally, we discuss how chronic infections, immunotherapies, vaccination, obesity and chronic physical stressors may exacerbate this susceptibility and consider the therapeutic implications of integrating HLA-II profiling into clinical practice.},
}

Humans
*Autoimmune Diseases/immunology/genetics/etiology
*Haplotypes
Genetic Predisposition to Disease
Autoimmunity
*Histocompatibility Antigens Class II/genetics/immunology
Animals

@article {pmid41421320,
year = {2025},
author = {Soares, L and Davis, H and Spier, E and Walker, T and Davenport, T and Putrino, D and Peluso, M and Vogel, JM},
title = {Recommended long COVID outcome measures and their implications for clinical trial design, with a focus on post-exertional malaise.},
journal = {EBioMedicine},
volume = {123},
number = {},
pages = {106083},
doi = {10.1016/j.ebiom.2025.106083},
pmid = {41421320},
issn = {2352-3964},
abstract = {Long COVID has created a worldwide public health crisis and has no approved treatments or validated biomarkers. We summarize the current challenges and considerations of outcome selection in Long COVID trials, along with recommendations for current trial design and future endpoint validation, with a focus on post-exertional malaise (PEM). We make five overarching recommendations for Long COVID clinical trials: 1) thorough characterisation of baseline disease; 2) collection of longitudinal data; 3) design of a placebo arm to enable comparison of treatment effect relative to the disease natural history; 4) accounting for, and when feasible, measuring PEM; 5) balancing severity, duration, and relevant phenotypes across trial arms and within subgroups to be analysed. We present a list of outcomes that may be considered for Long COVID clinical trials, with a focus on PEM. Crucially, the field of Long COVID clinical trials urgently needs funding and research effort investment to develop and validate outcomes concomitantly with clinical trial research.},
}

@article {pmid41415584,
year = {2025},
author = {Kvandova, M and Balis, P and Kalocayova, B and Vlkovicova, J and Dobrodenkova, S and Puzserova, A},
title = {Cardiovascular damage and comorbidities related to long COVID: pathomechanisms, prevention, and therapy.},
journal = {Frontiers in cardiovascular medicine},
volume = {12},
number = {},
pages = {1671951},
pmid = {41415584},
issn = {2297-055X},
abstract = {Long COVID (LC) is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-associated chronic condition and is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems, including cardiovascular. Extensive literature supports an association between SARS-CoV-2 infection and cardiovascular complications and increased cardiovascular risk after infection. The cardiovascular sequelae after SARS-CoV-2 infection have not yet been comprehensively characterized. A growing body of evidence suggests that endothelial dysfunction is a central mechanism in COVID-19 and has also been identified as a key pathogenic mechanism in LC. Although considerable progress has been made in characterizing the epidemiology, clinical course, and biology of LC, many questions remain unanswered. The incomplete understanding of the pathomechanisms of LC has hampered the development of targeted therapies to date. Further research and data are needed to develop effective therapeutic and preventive tools. Based on current literature this review aims to provide an up-to-date overview of the pathomechanisms affecting the cardiovascular system and the potential role of selected micronutrients, vitamins and minerals, and flavonoids as preventive and therapeutic strategies in LC.},
}

@article {pmid40387694,
year = {2026},
author = {Weix, NM and Shake, HM and Duran Saavedra, AF and Clingan, HE and Hernandez, VC and Johnson, GM and Hansen, AD and Collins, DM and Pryor, LE and Kitchens, R and Armstead, A and Hilton, C},
title = {Cognitive Interventions and Rehabilitation to Address Long-COVID Symptoms: A Systematic Review.},
journal = {OTJR : occupation, participation and health},
volume = {46},
number = {1},
pages = {74-95},
pmid = {40387694},
issn = {1938-2383},
mesh = {Humans ; *COVID-19/rehabilitation/complications/psychology ; *Cognitive Behavioral Therapy/methods ; *Occupational Therapy/methods ; SARS-CoV-2 ; *Cognitive Dysfunction/rehabilitation ; Quality of Life ; },
abstract = {Long COVID symptoms include cognitive and physical deficits impacting one's functional performance and quality of life. Limited evidence examines the use of cognitive interventions provided by occupational therapists in treating long COVID symptoms among adults. This systematic review summarizes existing studies on cognitive interventions and rehabilitation to treat long COVID symptoms and discusses their potential use within the scope of occupational therapy practice. We identified literature from 2021 to 2023 through searches of MEDLINE, CINAHL, PsycINFO, Cochrane Trials, and Scopus databases. Nineteen articles met inclusion criteria and were categorized into five types of intervention: (a) cognitive training, (b) cognitive behavioral therapy, (c) neurostimulation, (d) neurostimulation combined with cognitive training, and (e) multi-component rehabilitation programs. Strong evidence supports cognitive training, moderate supports cognitive behavioral training and low-level evidence supports other interventions provided by occupational therapists to target long COVID cognitive symptoms in adults.},
}

Humans
*COVID-19/rehabilitation/complications/psychology
*Cognitive Behavioral Therapy/methods
*Occupational Therapy/methods
SARS-CoV-2
*Cognitive Dysfunction/rehabilitation
Quality of Life

@article {pmid41407606,
year = {2025},
author = {Ouksel, H},
title = {[Long covid pulmonary rehabilitation].},
journal = {Revue des maladies respiratoires},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.rmr.2025.12.001},
pmid = {41407606},
issn = {1776-2588},
abstract = {While the SARS-CoV-2 pandemic has left a lasting impression, the long-term effects of this virus, such as persistent symptoms or long COVID, remain unclear. However, recommendations from learned societies for improving these symptoms exist and are being applied by a number of respiratory rehabilitation centers. In this paper, we provide a summary of the specificities of long COVID care in the context of respiratory rehabilitation, particularly as regards respiratory symptoms, fatigue, cognitive disorders, and cardiovascular symptoms and, more specifically, vegetative dysautonomia. The key elements of support are Therapeutic Patient Education (TPE) and activity management and fractionated exercise (PACING). While the effects of respiratory rehabilitation are highly promising, with potential improvement in symptoms and exercise capacity, the level of evidence remains low to moderate. Structured and coordinated multidisciplinary work is of paramount importance as a means of providing for these individuals the best possible support on their road to recovery. Further studies are needed to improve the level of evidence on the effectiveness of rehabilitation in cases of long COVID.},
}

@article {pmid41407484,
year = {2025},
author = {Wilson, JC and Liu, KY and Mittelman, E and Bareke, P and Shleifer, E and Howard, R},
title = {Brain fog with long covid and chemotherapy: systematic review and meta-analysis.},
journal = {BMJ mental health},
volume = {28},
number = {1},
pages = {},
doi = {10.1136/bmjment-2025-301969},
pmid = {41407484},
issn = {2755-9734},
mesh = {Humans ; *COVID-19/complications/psychology ; *Antineoplastic Agents/adverse effects ; *Neoplasms/drug therapy ; SARS-CoV-2 ; *Cognitive Dysfunction/etiology ; },
abstract = {QUESTION: What are the cognitive, functional and affective characteristics of brain fog in individuals with long covid and following chemotherapy, and how are these features assessed across studies?

STUDY SELECTION AND ANALYSIS: In March 2024, we conducted a systematic review and meta-analysis of peer-reviewed studies assessing cognition, function or mood in adults (≥18 years) with brain fog after COVID-19 or chemotherapy. PubMed, Embase and Web of Science were searched systematically according to eligibility criteria to March 2024, with an update in May 2025. Random-effects meta-analyses using the 'dmetar' package (V.0.0.9000) in R V.4.3.1 were performed for studies comparing individuals with and without brain fog. Bias was assessed using the National Institutes of Health Study Quality Assessment Tools.

FINDINGS: Of 3077 records screened, 65 studies met inclusion criteria: 40 investigated brain fog in long covid and 25 in chemotherapy populations. Considerable variation in assessment tools was observed. Montreal Cognitive Assessment was the most common cognitive test in long covid studies; Functional Assessment of Cancer Therapy-Cognitive Function was most used in chemotherapy studies. Nine long covid studies were eligible for meta-analysis. Compared with controls, individuals with brain fog had significantly lower cognitive performance (Hedge's g=-0.63, 95% CI -1.15 to -0.12), higher fatigue (Hedge's g=2.64, 95% CI 0.41 to 4.86) and more depressive symptoms (Hedge's g=1.48, 95% CI 0.40 to 2.55). Heterogeneity was high (I[2]>70%). No chemotherapy studies were appropriate for meta-analysis, preventing direct comparison of brain fog features between long covid and chemotherapy groups.

CONCLUSIONS: Brain fog in long covid and chemotherapy populations is associated with cognitive complaints, fatigue and mood disturbance, though assessment methods differ widely. To improve comparability and clinical understanding, we propose adoption of consistent tools and definitions in future studies. This will be a crucial step in generating findings that can be meaningfully compared across populations.

PROSPERO REGISTRATION NUMBER: CRD42024520549.},
}

Humans
*COVID-19/complications/psychology
*Antineoplastic Agents/adverse effects
*Neoplasms/drug therapy
SARS-CoV-2
*Cognitive Dysfunction/etiology

@article {pmid34170086,
year = {2021},
author = {Richter, D and Guasti, L and Koehler, F and Squizzato, A and Nistri, S and Christodorescu, R and Dievart, F and Gaudio, G and Asteggiano, R and Ferrini, M},
title = {Late phase of COVID-19 pandemic in General Cardiology. A position paper of the ESC Council for Cardiology Practice.},
journal = {ESC heart failure},
volume = {8},
number = {5},
pages = {3483-3494},
pmid = {34170086},
issn = {2055-5822},
mesh = {*COVID-19/complications ; *Cardiology ; Humans ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {Cardiovascular (CV) engagement in coronavirus disease 2019 (COVID-19) is a huge determinant of prognosis during the acute phase of the disease. However, little is known about the potential chronic implications of the late phase of COVID-19 and about the appropriate approach to these patients. Heart failure, type 1 and type 2 myocardial infarction, arrhythmias, myocarditis, pulmonary fibrosis, and thrombosis have been shown to be related to severe acute respiratory syndrome coronavirus 2 infection, and a 'long COVID-19' illness has been recognized with fatigue, chest pain, and dyspnoea among the most frequent symptoms reported after discharge from hospital. This paper focuses on some open questions that cardiologists are going to face during the next months in a general cardiology outpatient clinic, in particular how to evaluate a 'post-COVID' patient during follow-up of CV complications of the acute phase and how to manage new CV symptoms that could be the consequence, at least in part, of heart/vessels and/or lung involvement of the previous virus infection. Present symptoms and signs, history of previous CV disease (both preceding COVID-19 and occurring during viral infection), and specific laboratory and imaging measurements during the acute phase may be of interest in focusing on how to approach the clinical evaluation of a post-COVID patient and how to integrate in our standard of care the new information on COVID-19, possibly in a multidisciplinary view. Dealing with the increased COVID-associated CV risk burden and becoming acquainted with potential new e-cardiology approaches aimed at integrating the cardiology practice are relevant new challenges brought by severe acute respiratory syndrome coronavirus 2 infection and its sequelae.},
}

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

@article {pmid41394882,
year = {2025},
author = {Padilla-Blanco, M and García-García, T and Grigas, J and López-Ayllón, BD and Garrido, JJ and Oliva, MA and Montoya, M},
title = {Hidden players of COVID-19: the evolving roles of SARS-CoV-2 accessory proteins.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1726698},
pmid = {41394882},
issn = {1664-3224},
mesh = {Humans ; *SARS-CoV-2/immunology/genetics ; *COVID-19/immunology/virology ; Host-Pathogen Interactions/immunology ; Interferon Type I/immunology/metabolism ; Animals ; *Viral Regulatory and Accessory Proteins/immunology/genetics/metabolism ; Viral Proteins/immunology ; },
abstract = {SARS-CoV-2 accessory proteins (APs), particularly ORF3a and ORF9b, have emerged as key modulators of host-pathogen interaction and potential contributors to long COVID. Of the 13 predicted APs, only nine are expressed during infection - termed Infection-related APs - while the remaining are classified as Putative APs. Despite this distinction, extensive gene overlap among APs underscores the remarkable adaptability of SARS-CoV-2 viral genome. This review delves into the diverse roles of the original Wuhan APs and their Omicron counterparts in shaping host immunity, with an emphasis on their ability to suppress type I interferon (IFN-I) signalling, modulate cellular metabolism, and trigger inflammatory/apoptotic pathways. By integrating immunopathological insights with evolutionary dynamics and structural perspectives, this review provides a comprehensive understanding of the mechanism underlying Omicron's reduced pathogenicity and highlights promising, yet unexplored, therapeutic targets within the SARS-CoV-2 accessory proteome.},
}

Humans
*SARS-CoV-2/immunology/genetics
*COVID-19/immunology/virology
Host-Pathogen Interactions/immunology
Interferon Type I/immunology/metabolism
Animals
*Viral Regulatory and Accessory Proteins/immunology/genetics/metabolism
Viral Proteins/immunology

@article {pmid41394849,
year = {2025},
author = {Gabig-Cimińska, M},
title = {Dysregulated TFEB-autophagy-lysosome pathway links acute COVID-19 immunopathology to Long COVID sequelae.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1708364},
pmid = {41394849},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology/pathology/complications ; *Lysosomes/immunology/metabolism ; *Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism/immunology ; *Autophagy/immunology ; *SARS-CoV-2/immunology ; Animals ; Signal Transduction/immunology ; Immunity, Innate ; },
abstract = {SARS-CoV-2 disrupts cellular homeostasis, including the autophagy-lysosome pathway (ALP), a critical component of innate immunity and viral clearance. By subverting autophagy, SARS-CoV-2 proteins such as ORF3a, ORF7a, and NSP6 inhibit autophagosome-lysosome (APG-L) fusion, generating "incomplete autophagy" that permits viral persistence and drives hyperinflammation. Transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy, has emerged as a central player in the host response to coronavirus infection. TFEB orchestrates the expression of genes required for lysosomal function and autophagic flux while also shaping immune processes, including cytokine production, interferon-stimulated gene expression, and inflammasome clearance. This mini review synthesizes current knowledge on the TFEB-ALP axis in COVID-19 pathogenesis, highlighting its influence on acute immunopathology and its potential contribution to post-acute sequelae (Long COVID). Restoring TFEB activity and autophagic flux may counteract SARS-CoV-2 evasion strategies and restrain aberrant inflammatory responses. Harnessing the TFEB-autophagy pathway as a host-directed therapeutic strategy could help rebalance immune homeostasis, limit tissue damage during acute infection, and mitigate persistent inflammatory sequelae in Long COVID.},
}

Humans
*COVID-19/immunology/pathology/complications
*Lysosomes/immunology/metabolism
*Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism/immunology
*Autophagy/immunology
*SARS-CoV-2/immunology
Animals
Signal Transduction/immunology
Immunity, Innate

@article {pmid41384659,
year = {2025},
author = {Bessalah, S and Sinha, D and Yuan, X and Paul, S and Longet, S},
title = {[Long COVID: therapeutic challenges and opportunities in the face of persistent sequelae].},
journal = {Medecine sciences : M/S},
volume = {41},
number = {11},
pages = {869-876},
doi = {10.1051/medsci/2025185},
pmid = {41384659},
issn = {1958-5381},
mesh = {Humans ; *COVID-19/complications/therapy/epidemiology ; *SARS-CoV-2/physiology ; Post-Acute COVID-19 Syndrome ; Pandemics ; COVID-19 Drug Treatment ; Antiviral Agents/therapeutic use ; Chronic Disease ; },
abstract = {The COVID-19 pandemic, caused by SARS-CoV-2, has not only led to a global health and economic crisis but also renewed attention to a clinical phenomenon of persistent symptoms after viral infection. This phenomenon is defined as long COVID or post-COVID-19 syndrome. Approximately one in eight patients experience persistent symptoms of varying intensity after the acute phase of the infection. This phenomenon, combined with the virus's high transmissibility and rapid mutation rate, poses a major public health challenge. This review examines various therapeutic approaches currently under consideration for treating long COVID, and explores future prospects in this field.},
}

Humans
*COVID-19/complications/therapy/epidemiology
*SARS-CoV-2/physiology
Post-Acute COVID-19 Syndrome
Pandemics
COVID-19 Drug Treatment
Antiviral Agents/therapeutic use
Chronic Disease

@article {pmid38619233,
year = {2024},
author = {Tomasiewicz, K and Woron, J and Kobayashi, A and Krasinski, Z and Rydzewska, G and Szymanski, FM},
title = {Post-COVID-19 syndrome in everyday clinical practice: interdisciplinary expert position statement endorsed by the Polish Society of Civilization Diseases.},
journal = {Polish archives of internal medicine},
volume = {134},
number = {5},
pages = {},
doi = {10.20452/pamw.16728},
pmid = {38619233},
issn = {1897-9483},
mesh = {Humans ; *COVID-19/complications/therapy ; Poland ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; },
abstract = {Post-COVID-19 syndrome, also known as long COVID-19 syndrome, is a complex set of symptoms that persist for weeks or months after recovery from an acute phase of COVID-19. These symptoms can affect various body systems, including the respiratory, nervous, cardiovascular, and digestive systems. The most common complaints are fatigue, shortness of breath, joint pain, taste and smell disorders, as well as problems with memory and concentration. Pathogenesis of post-COVID-19 syndrome is complicated and not fully understood, but it is likely related to an overactive immune system, disturbances in the intestinal microbiome, and cell and tissue damage caused by the virus. Incorporating a multidisciplinary approach to treating and rehabilitating patients and further research into this syndrome's underlying mechanisms and therapy are crucial for understanding and effectively treating this complex and multifaceted condition.},
}

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

@article {pmid36272444,
year = {2023},
author = {Sacks-Zimmerman, A and Bergquist, TF and Farr, EM and Cornwell, MA and Kanellopoulos, D},
title = {Rehabilitation of Neuropsychiatric Symptoms in Patients With Long COVID: Position Statement.},
journal = {Archives of physical medicine and rehabilitation},
volume = {104},
number = {2},
pages = {350-354},
pmid = {36272444},
issn = {1532-821X},
mesh = {Adult ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Quality of Life ; *Mental Disorders ; Chronic Disease ; },
abstract = {Long COVID, a term used to describe ongoing symptoms after COVID-19 infection, parallels the course of other postviral syndromes. Neuropsychiatric symptoms of long COVID can be persistent and interfere with quality of life and functioning. Within the biopsychosocial framework of chronic illness, rehabilitation professionals can address the neuropsychiatric sequelae of long COVID. However, current practice models are not designed to address concurrent psychiatric and cognitive symptoms in adults living with long COVID. Thus, we present a biopsychosocial framework for long COVID and provide treatment strategies based on evidence from current literature of postviral chronic illness. These recommendations will guide rehabilitation professionals in identifying common neuropsychiatric symptoms in long COVID that can be targeted for intervention and addressing these symptoms via integrative interventions taking into account the biopsychosocial presentation of long COVID symptoms.},
}

Adult
Humans
Post-Acute COVID-19 Syndrome
*COVID-19
Quality of Life
*Mental Disorders
Chronic Disease

@article {pmid35460319,
year = {2022},
author = {Rakusa, M and Öztürk, S and Moro, E and Helbok, R and Bassetti, CL and Beghi, E and Bereczki, D and Bodini, B and Di Liberto, G and Jenkins, TM and Macerollo, A and Maia, LF and Martinelli-Boneschi, F and Pisani, A and Priori, A and Sauerbier, A and Soffietti, R and Taba, P and von Oertzen, TJ and Zedde, M and Crean, M and Burlica, A and Cavallieri, F and Sellner, J and , },
title = {COVID-19 vaccination hesitancy among people with chronic neurological disorders: A position paper.},
journal = {European journal of neurology},
volume = {29},
number = {8},
pages = {2163-2172},
pmid = {35460319},
issn = {1468-1331},
mesh = {*COVID-19/complications/prevention & control ; *COVID-19 Vaccines/administration & dosage ; Humans ; *Nervous System Diseases ; Pandemics ; SARS-CoV-2 ; Vaccination/psychology ; *Vaccination Hesitancy ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND AND PURPOSE: Health risks associated with SARS-CoV-2 infection are undisputed. Moreover, the capability of vaccination to prevent symptomatic, severe, and fatal COVID-19 is recognized. There is also early evidence that vaccination can reduce the chance for long COVID-19. Nonetheless, the willingness to get vaccinated and receive booster shots remains subpar among people with neurologic disorders. Vaccine scepticism not only jeopardizes collective efforts to end the COVID-19 pandemic but puts individual lives at risk, as some chronic neurologic diseases are associated with a higher risk for an unfavorable COVID-19 course.

METHODS: In this position paper, the NeuroCOVID-19 Task Force of the European Academy of Neurology (EAN) summarizes the current knowledge on the prognosis of COVID-19 among patients with neurologic disease, elucidates potential barriers to vaccination coverage, and formulates strategies to overcome vaccination hesitancy. A survey among the Task Force members on the phenomenon of vaccination hesitancy among people with neurologic disease supports the lines of argumentation.

RESULTS: The study revealed that people with multiple sclerosis and other nervous system autoimmune disorders are most skeptical of SARS-CoV-2 vaccination. The prevailing concerns included the chance of worsening the pre-existing neurological condition, vaccination-related adverse events, and drug interaction.

CONCLUSIONS: The EAN NeuroCOVID-19 Task Force reinforces the key role of neurologists as advocates of COVID-19 vaccination. Neurologists need to argue in the interest of their patients about the overwhelming individual and global benefits of COVID-19 vaccination. Moreover, they need to keep on eye on this vulnerable patient group, its concerns, and the emergence of potential safety signals.},
}

*COVID-19/complications/prevention & control
*COVID-19 Vaccines/administration & dosage
Humans
*Nervous System Diseases
Pandemics
SARS-CoV-2
Vaccination/psychology
*Vaccination Hesitancy
Post-Acute COVID-19 Syndrome

@article {pmid41379191,
year = {2025},
author = {La Scaléa, ACR and Uehara, SCDSA},
title = {Pain in Long COVID: A scoping review of clinical characteristics and patterns of manifestation.},
journal = {Revista latino-americana de enfermagem},
volume = {33},
number = {},
pages = {e4777},
doi = {10.1590/1518-8345.7836.4777},
pmid = {41379191},
issn = {1518-8345},
mesh = {Humans ; *COVID-19/complications ; Female ; *Pain/etiology/diagnosis/epidemiology ; Male ; Pain Measurement ; SARS-CoV-2 ; },
abstract = {to map the available scientific evidence on the clinical characteristics and patterns of pain manifestation (location, frequency, duration, intensity, and quality) in individuals with Long COVID. a scoping review of publications from March 2020 to June 2024, indexed across four databases. Study selection was conducted by two independent, blinded reviewers. Data were extracted using a standardized instrument and analyzed descriptively. nineteen studies were included, indicating that pain affects individuals across all age groups, with higher prevalence among women, primarily involving the head, neck, shoulder, lower back, and hip. Pain frequency ranged from daily to monthly episodes, with duration exceeding one year in some cases. Intensity varied from mild to severe, and pain characteristics were diverse, with descriptors including burning, pressure, colicky, and throbbing pain. the clinical characteristics and patterns of pain manifestation in Long COVID are diverse. However, there is a paucity of studies providing detailed analyses of pain features and the influence of individual variables. These findings should guide future research and clinical practice toward a more comprehensive and contextualized assessment of pain in Long COVID.},
}

Humans
*COVID-19/complications
Female
*Pain/etiology/diagnosis/epidemiology
Male
Pain Measurement
SARS-CoV-2

@article {pmid41368891,
year = {2025},
author = {Pinero, S and Li, X and Zhang, J and Winter, M and Lee, SH and Nguyen, T and Liu, L and Li, J and Le, TD},
title = {Omics-based computational approaches for biomarker identification, prediction, and treatment of Long COVID.},
journal = {Critical reviews in clinical laboratory sciences},
volume = {},
number = {},
pages = {1-27},
doi = {10.1080/10408363.2025.2583083},
pmid = {41368891},
issn = {1549-781X},
abstract = {Long COVID, or post-acute sequelae of COVID-19 (PASC), is a major global health problem, with cumulative estimates suggesting that around 400 million people worldwide have been affected. It is characterized by persistent or new symptoms such as fatigue, cognitive impairment, and breathlessness lasting beyond four weeks after acute infection. Diverse clinical manifestations, chronic course, and incompletely understood pathophysiology-including hypotheses involving viral persistence, immune dysregulation, autoimmunity, endothelial dysfunction, and metabolic reprogramming-impede the development of diagnostic criteria, biomarkers, and targeted therapies. We conducted a critical review of 101 Long COVID omics studies, focusing on the computational methods used and their methodological quality. Using standardized criteria, we evaluated study design, statistical rigor, reproducibility, and clinical relevance across genomics, epigenomics, transcriptomics, proteomics, metabolomics, and multiomics integration, and mapped these findings onto regulatory and translational frameworks. Despite substantial methodological heterogeneity, convergent biological signals emerged. Genomic studies implicate risk loci in immune and cardiopulmonary pathways. Epigenomic analyses identify differentially methylated regions in immune and circadian genes. Transcriptomic studies reveal persistent dysregulation of innate immune and coagulation pathways, as well as reproducible molecular endotypes. Proteomic studies consistently show abnormalities in the complement cascade and coagulation, with a small panel of complement proteins showing highly reproducible changes across independent cohorts. Metabolomic studies demonstrate sustained mitochondrial dysfunction and altered cellular bioenergetics for up to two years after infection. Multiomics integration supports at least two major endotypes, characterized by predominant inflammatory versus metabolic dysregulation, and provides a basis for patient stratification and computational treatment discovery. Machine learning models frequently achieve high classification performance, but are rarely externally validated. Critical limitations restrict clinical translation. Most studies are underpowered relative to analytical complexity, use heterogeneous case definitions and controls, and report platform-specific signatures with limited overlap. External validation, preregistered analysis plans, and regulatory-aligned assay development are uncommon. To date, no regulatory-approved diagnostic assay or evidence-based therapeutic intervention has directly emerged from these computational findings. Future progress requires harmonized phenotyping protocols, adequately powered longitudinal cohorts with external validation, integration of spatial omics and explainable artificial intelligence, and early engagement with regulatory and health-technology assessment pathways. This review provides a critical assessment and a translational roadmap, outlining how methodologically robust computational omics can be advanced toward clinically actionable tools for Long COVID.},
}

@article {pmid39449339,
year = {2025},
author = {Qian, CY and Hu, SN and Liu, HD and Liu, JJ},
title = {Potential Mechanisms of COVID-19 Related Nervous System Damage and Effects on Female Fertility.},
journal = {Current medicinal chemistry},
volume = {32},
number = {42},
pages = {9555-9569},
pmid = {39449339},
issn = {1875-533X},
support = {JCYJ20190806153207263//Natural Science Foundation of Shenzhen Science and Technology Innovation Commission/ ; 82200315//National Natural Science Foundation/ ; 2021A1515111145//Guangdong Basic and Applied Basic Research Foundation/ ; SZSM201412012//Sanming Project of Medicine in Shenzhen/ ; SYWGSJCYJ202301//Major scientific research project of Shenzhen People's Hospital/ ; },
mesh = {Humans ; *COVID-19/complications/physiopathology/pathology ; Female ; SARS-CoV-2 ; *Infertility, Female/etiology ; *Nervous System Diseases ; *Fertility ; Autonomic Nervous System/physiopathology ; },
abstract = {Signs and symptoms that persist or worsen beyond the "acute COVID-19" stage are referred to as long-COVID. These patients are more likely to suffer from multiple organ failure, readmission, and mortality. According to a recent theory, long-lasting COVID-19 symptoms may be caused by abnormal autonomic nervous system (ANS) activity, such as hypovolemia, brain stem involvement, and autoimmune reactions. Furthermore, COVID-19 can also cause impaired fertility in women, which may also be related to inflammation and immune responses. Currently, few treatments are available for long-COVID symptoms. This article reviews the major effects of COVID-19 on the nervous system and female fertility, as well as offers potential treatment approaches.},
}

Humans
*COVID-19/complications/physiopathology/pathology
Female
SARS-CoV-2
*Infertility, Female/etiology
*Nervous System Diseases
*Fertility
Autonomic Nervous System/physiopathology

@article {pmid38285646,
year = {2026},
author = {McMaster, MW and Dey, S and Fishkin, T and Wang, A and Frishman, WH and Aronow, WS},
title = {The Impact of Long COVID-19 on the Cardiovascular System.},
journal = {Cardiology in review},
volume = {34},
number = {1},
pages = {11-18},
doi = {10.1097/CRD.0000000000000654},
pmid = {38285646},
issn = {1538-4683},
mesh = {Humans ; *COVID-19/complications/physiopathology ; *Cardiovascular Diseases/physiopathology/etiology/virology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {Long coronavirus disease (COVID) is the development or persistence of symptoms after an acute SARS-CoV-2 (COVID-19) infection. Fewer patients are developing acute COVID-19 infections, but patients with long COVID continue to have alarming long-term sequelae. Many cardiac magnetic resonance imaging studies show significant changes in cardiac structure after a COVID-19 infection, suggestive of an increased burden of many cardiovascular diseases, notably myocarditis. The pathophysiology of COVID-19 requires viral binding to angiotensin-converting enzyme 2 protein receptors throughout the body, which are upregulated by inflammation. Consequently, the numerous preexisting conditions that worsen or prolong inflammation enhance this binding and have differing effects on patients based on their unique immune systems. These pathophysiological changes drive long COVID cardiac sequelae such as inappropriate sinus tachycardia, postural orthostatic tachycardia, and other types of orthostatic intolerance. Increased screening for long COVID and low-risk interventions such as exercise regimens could alleviate the suffering endured by patients with long COVID. Many studies such as the Researching COVID to Enhance Recovery Initiative (RECOVER) trials at the National Institutes of Health are exploring potential treatments for long COVID patients.},
}

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

@article {pmid41350176,
year = {2025},
author = {Miller, CM and Moen, JK and Iwasaki, A},
title = {The lingering shadow of epidemics: post-acute sequelae across history.},
journal = {Trends in immunology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.it.2025.10.010},
pmid = {41350176},
issn = {1471-4981},
abstract = {The SARS-CoV-2 pandemic has drawn global attention to post-acute infection syndromes (PAIS), with millions affected by post-acute sequelae of COVID-19 (PASC, or Long COVID). While Long COVID is newly defined, PAIS have been described for over a century following epidemic infections. Multiple pathogens - including influenza, Epstein-Barr virus, and Borrelia burgdorferi, among others - can precipitate persistent, poorly understood symptoms. Chronic illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have long been linked to infectious triggers. This recurring association highlights critical knowledge gaps and underscores the need for systematic investigation. Unlike prior pandemics, the current era offers advanced technologies and analytic tools to address these gaps. Defining the biology of Long COVID may yield broader insights into host-pathogen interactions and mechanisms of chronic illness.},
}

@article {pmid41349462,
year = {2025},
author = {Eksteen, C and Asja, LC and Rass, A and Riedemann, J and Engelbrecht, AM},
title = {Post COVID-19 pandemic Inflammatory Insights into Cancer: Consequences for immunotherapy.},
journal = {Cytokine & growth factor reviews},
volume = {87},
number = {},
pages = {10-18},
doi = {10.1016/j.cytogfr.2025.12.002},
pmid = {41349462},
issn = {1879-0305},
abstract = {The COVID-19 pandemic has reshaped the landscape of global health, revealing novel interactions between infectious diseases and chronic conditions such as cancer. Beyond acute infection, growing evidence suggests that persistent exposure to SARS-CoV-2 spike protein, whether through infection or vaccination, may sustain inflammatory pathways that contribute to tumour progression and immune modulation. This review explores the overlap between post-COVID inflammation, particularly in Long-COVID syndromes and the tumour microenvironment (TME), focusing on key mediators such as IL-6, TNF-α, IL-1β, and NF-κB. We revisit the concept of the cytokine storm in the context of persistent inflammation, spike protein immunogenicity and immune exhaustion, proposing a model in which chronic inflammatory signalling may disrupt tumour immune surveillance, reawaken dormant cancer cells and compromise the efficacy of immunotherapies. Comparative analysis with other cancer types highlights shared pathways of oncogenic inflammation. Lastly, we outline emerging therapeutic strategies to mitigate these effects, including cytokine-targeted interventions and immunomodulatory screening in post-COVID cancer patients. These post-pandemic insights call for urgent translational research to ensure effective and safe cancer immunotherapy in the evolving inflammatory landscape.},
}

@article {pmid41349247,
year = {2025},
author = {Halma, M and Varon, J},
title = {Metabolic modulation as a therapeutic strategy for post-acute vaccination syndrome (PACVS): A review of pathomechanisms and existing therapeutic components.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {193},
number = {},
pages = {118864},
doi = {10.1016/j.biopha.2025.118864},
pmid = {41349247},
issn = {1950-6007},
abstract = {Post-Acute Vaccination Syndrome (PACVS) is a post-vaccination disorder marked by persistent fatigue, cognitive impairment, and exercise intolerance. Current research identifies interconnected pathophysiological processes, including persisting spike protein, mitochondrial dysfunction, decreased tissue oxygenation, and impaired metabolism. Emerging treatments rely on metabolic regulation and therapeutic agents promoting mitochondrial and vascular function. These therapies stimulate cellular energy generation, reduce oxidative stress, and regulate inflammatory pathways. This review examines metabolic and mitochondrial mechanisms underlying PACVS, evaluates existing therapeutic strategies targeting these pathways, and synthesizes current evidence for future research and clinical management.},
}

@article {pmid41346576,
year = {2025},
author = {Guimarães, GN and Brunetti, NS and De Lima, DG and Proenca-Modena, JL and Farias, AS},
title = {Vaccination and COVID-19: impact on long-COVID.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1686572},
pmid = {41346576},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology/prevention & control ; *COVID-19 Vaccines/immunology/administration & dosage ; *SARS-CoV-2/immunology ; *Vaccination ; Post-Acute COVID-19 Syndrome ; },
abstract = {Long- and post-COVID-19 syndromes have emerged as a significant global health challenge, with millions of individuals experiencing persistent or the development of new symptoms after a long period of an initial SARS-CoV-2 infection. These symptoms are multisystemic and may indicate changes in the respiratory, neurological, cardiovascular and gastrointestinal systems, in addition to prolonged fatigue. Vaccination has played a crucial role in reducing severe disease and mortality, but the impact of the different vaccine combinations on the development and resolution of Long COVID remains a topic of debate. This review synthesizes current evidence on how different vaccine platforms, dosing strategies and booster doses influence the immunological response, protection, incidence, severity, and persistence of Long COVID symptoms. We discuss key immunological mechanisms by which vaccination may modulate and protect post-COVID syndrome outcomes, including its effects on viral clearance, immune response reprogramming, inflammation, and autoimmunity, seeking to combat misinformation and concepts spread by fake news. The review also highlights controversies and research gaps, such as variability in vaccine response among different populations and the role in the selection of more transmissible and virulent SARS-CoV-2 variants, as well as the potential differences between vaccine-induced and infection-induced immunity, and the role of pre-existing immune conditions in this scenario.},
}

Humans
*COVID-19/immunology/prevention & control
*COVID-19 Vaccines/immunology/administration & dosage
*SARS-CoV-2/immunology
*Vaccination
Post-Acute COVID-19 Syndrome

@article {pmid36154545,
year = {2022},
author = {Hadda, V and Suri, TM and Iyer, H and Jain, A and Mittal, S and Madan, K and Mohan, A and Seith Bhalla, A and Sindhwani, G and Dutt, N and Venkatnarayan, K and Nath, A and Dhooria, S and Kumar, R and Marwah, V and Karmakar, S and Chaudhry, D and Ayub, II and Dwivedi, DP and Tiwari, P and Koul, P and Behera, AK and Saxena, P and Sengupta, A and Mohapatra, PR and Goyal, A and Christopher, DJ and Guleria, R},
title = {A Delphi consensus statement for the management of post-COVID interstitial lung disease.},
journal = {Expert review of respiratory medicine},
volume = {16},
number = {9},
pages = {983-995},
doi = {10.1080/17476348.2022.2128770},
pmid = {36154545},
issn = {1747-6356},
mesh = {Humans ; Delphi Technique ; *COVID-19/complications ; *Lung Diseases, Interstitial/diagnosis/epidemiology/etiology ; Consensus ; Lung/diagnostic imaging ; },
abstract = {INTRODUCTION: As millions of people worldwide recover from COVID-19, a substantial proportion continue to have persistent symptoms, pulmonary function abnormalities, and radiological findings suggestive of post-COVID interstitial lung disease (ILD). To date, there is limited scientific evidence on the management of post-COVID ILD, necessitating a consensus-based approach.

AREAS COVERED: A panel of experts in pulmonology and thoracic radiology was constituted. Key questions regarding the management of post-COVID ILD were identified. A search was performed on PubMed and EMBASE and updated till 1 March 2022. The relevant literature regarding the epidemiology, pathophysiology, diagnosis and treatment of post-COVID ILD was summarized. Subsequently, suggestions regarding the management of these patients were framed, and a consensus was obtained using the Delphi approach. Those suggestions which were approved by over 80% of the panelists were accepted. The final document was approved by all panel members.

EXPERT OPINION: Dedicated facilities should be established for the care of patients with post-COVID ILD. Symptom screening, pulmonary function testing, and thoracic imaging have a role in the diagnosis. The pharmacologic and non-pharmacologic options for the management of post-COVID ILD are discussed. Further research into the pathophysiology and management of post-COVID ILD will improve our understanding of this condition.},
}

Humans
Delphi Technique
*COVID-19/complications
*Lung Diseases, Interstitial/diagnosis/epidemiology/etiology
Consensus
Lung/diagnostic imaging

@article {pmid35266533,
year = {2022},
author = {Rienks, R and Holdsworth, D and Davos, CH and Halle, M and Bennett, A and Parati, G and Guettler, N and Nicol, ED},
title = {Cardiopulmonary assessment prior to returning to high-hazard occupations post-symptomatic COVID-19 infection: a position statement of the Aviation and Occupational Cardiology Task Force of the European Association of Preventive Cardiology.},
journal = {European journal of preventive cardiology},
volume = {29},
number = {13},
pages = {1724-1730},
pmid = {35266533},
issn = {2047-4881},
mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Occupations ; *Cardiology ; *Aviation ; Post-Acute COVID-19 Syndrome ; },
abstract = {This article provides an overview of the recommendations of the Aviation and Occupational Cardiology Task Force of the European Association of Preventive Cardiology on returning individuals to work in high-hazard occupations (such as flying, diving, and workplaces that are remote from healthcare facilities) following symptomatic Coronavirus Disease 2019 (COVID-19) infection. This process requires exclusion of significant underlying cardiopulmonary disease and this consensus statement (from experts across the field) outlines the appropriate screening and investigative processes that should be undertaken. The recommended response is based on simple screening in primary healthcare to determine those at risk, followed by first line investigations, including an exercise capacity assessment, to identify the small proportion of individuals who may have circulatory, pulmonary, or mixed disease. These individuals can then receive more advanced, targeted investigations. This statement provides a pragmatic, evidence-based approach for those (in all occupations) to assess employee health and capacity prior to a return to work following severe disease, or while continuing to experience significant post-COVID-19 symptoms (so-called 'long-COVID' or post-COVID-19 syndrome).},
}

Humans
*COVID-19
SARS-CoV-2
Occupations
*Cardiology
*Aviation
Post-Acute COVID-19 Syndrome

@article {pmid41318861,
year = {2025},
author = {Yadav, JP and Yadav, S and Dubey, NK and Yadav, IP and Pathak, P and Verma, A},
title = {Lingering echoes of SARS-CoV-2: mechanistic insights and management of long COVID syndrome.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {41318861},
issn = {1568-5608},
abstract = {Throughout the world-wide COVID-19 pandemic, there has arisen a significant and a sustained public-health issue, whereby a significant proportion of individuals report persistent symptoms, well beyond the acute period of infection. The non-united array of chronic, multisystemic events, such as fatigue, cognitive deficit, respiratory dysfunction, cardiovascular abnormalities, and neuropsychiatric disorders characterize this sequela, which is referred to as LCS. LCS is much more than the starting viral insult, as it causes long-term complications that impact various organ systems. The current review questions the pathophysiological mechanisms of LCS, including scrutinizing the importance of the dysregulation of immunity, the persistence of viral reservoirs, endothelial dysfunction, autonomic imbalance, and mitochondrial injury. We highlight the heterogeneity of the syndrome and the associated diagnostic and treatment difficulties. In addition, we stress the urgency of powerful biomarkers that will be used to diagnose LCS as early as possible and monitor it over time. Present treatment strategies, including pharmacologic therapy (immunomodulators, anticoagulants, antiviral medications, etc.) and non-pharmacologic treatment (rehabilitative programs, etc.) are discussed against the backdrop of recent clinical findings. This review incorporates the recent literature and presents a review of potential treatment options that alleviate symptoms and improve the quality of life of LCS patients. Finally, this integrated synthesis can be used by both clinicians and researchers to gain practical information on the diagnosis, treatment, and future treatment directions of LCS.},
}

@article {pmid41308689,
year = {2025},
author = {Amdal, CD and Falk, RS and Alanya, A and Schlichting, M and Roychoudhury, S and Bhatnagar, V and Wintner, LM and Regnault, A and Ingelgård, A and Coens, C and le Cessie, S and Holzner, B and Chang, J and Taphoorn, M and Cislo, P and Giesinger, JM and Cappelleri, JC and Pawar, V and Ten Seldam, S and Papadopoulos, EJ and Calvert, MJ and Joseph, KL and Bottomley, A and Griebsch, I and Arraras, JI and Astrup, GL and Basch, E and Belančić, A and Brundage, M and Campbell, A and Rerhou Rantell, K and Cocks, K and Cherny, N and Eremenco, S and Ferrer, M and Fiero, MH and Gerlinger, C and Goetghebeur, E and Grouven, U and Lauer, A and Aiyegbusi, OL and Machingura, A and Mizusawa, J and Molenberghs, G and Aa Petersen, M and Reijneveld, JC and Ringash, J and Rumpold, G and Rutherford, C and Quinten, C and Sail, K and Sasseville, M and Sauerbrei, W and Schiel, A and Smith, AW and Snyder, C and Velikova, G and Wang, XS and Bjordal, K and Pe, M and , },
title = {SISAQOL-IMI consensus-based guidelines to design, analyse, interpret, and present patient-reported outcomes in cancer clinical trials.},
journal = {The Lancet. Oncology},
volume = {26},
number = {12},
pages = {e683-e693},
doi = {10.1016/S1470-2045(25)00520-0},
pmid = {41308689},
issn = {1474-5488},
mesh = {Humans ; *Patient Reported Outcome Measures ; *Neoplasms/therapy/drug therapy ; Consensus ; Quality of Life ; *Research Design/standards ; *Clinical Trials as Topic/standards ; Randomized Controlled Trials as Topic/standards ; },
abstract = {Standardising the implementation of patient-reported outcomes (PROs) in clinical trials is crucial for evaluating the benefits and risks of cancer treatments. The Setting International Standards in Analysing Patient-Reported Outcomes and Quality of Life Endpoints in Cancer Clinical Trials-Innovative Medicines Initiative (SISAQOL-IMI) has developed 146 consensus-based recommendations for designing, analysing, interpreting, and presenting PROs in cancer clinical trials. This initiative, undertaken from 2021 to 2025, involved experts, including statisticians, PRO measurement experts, clinicians, and patient representatives from 41 organisations representing regulatory agencies, academia, the pharmaceutical industry, health-technology assessment bodies, and patient advocates. SISAQOL-IMI provides guidance on the implementation of PROs in randomised controlled trials and single-arm trials, terminology, definitions and the selection of PRO score interpretation thresholds, and for visualising PRO results for different audiences. To facilitate the implementation of these standards, in addition to this Policy Review, four key outputs are available: an interactive table, a guidebook, plain language materials, and a glossary.},
}

Humans
*Patient Reported Outcome Measures
*Neoplasms/therapy/drug therapy
Consensus
Quality of Life
*Research Design/standards
*Clinical Trials as Topic/standards
Randomized Controlled Trials as Topic/standards

@article {pmid41305454,
year = {2025},
author = {Miftahof, J and Bernauer, B and Tan, CS},
title = {Neurological Manifestations of SARS-CoV-2.},
journal = {Viruses},
volume = {17},
number = {11},
pages = {},
doi = {10.3390/v17111432},
pmid = {41305454},
issn = {1999-4915},
mesh = {Humans ; *COVID-19/complications/pathology/virology ; Animals ; *SARS-CoV-2/pathogenicity ; Disease Models, Animal ; Brain/virology/pathology ; *Nervous System Diseases/virology/pathology/etiology ; Central Nervous System/virology/pathology ; },
abstract = {Neurocognitive symptoms have emerged as notable sequelae of SARS-CoV-2 infection (COVID-19). Although primarily a respiratory virus, SARS-CoV-2 has been associated with central nervous system (CNS) changes observed in both clinical and experimental settings. To better understand these effects and their pathological mechanisms, we conducted a systematic literature search of published studies and employed a qualitative, analytical approach to identify and synthesize key findings from peer-reviewed studies, including large-scale retrospective clinical cohorts, human autopsy reports, animal models (murine, non-human primate), and in vitro brain organoid systems. While viral components were detected in post mortem central nervous system tissues, COVID-19 neuropathology appears to stem primarily from immune-mediated inflammation and vascular injury rather than direct CNS infection. Persistent glial activation and BBB disruption may underlie the long-term neurological symptoms reported in long COVID-19. Although animal models offer mechanistic insight, species-specific differences necessitate cautious extrapolation to human pathology. Further investigation into the chronic effects of SARS-CoV-2 on the brain is essential to guide long-term clinical management and therapeutic development.},
}

Humans
*COVID-19/complications/pathology/virology
Animals
*SARS-CoV-2/pathogenicity
Disease Models, Animal
Brain/virology/pathology
*Nervous System Diseases/virology/pathology/etiology
Central Nervous System/virology/pathology

@article {pmid41305428,
year = {2025},
author = {Chiang, KC and Chiu, CEN and Altaf, M and Cheng, MTK and Gupta, RK},
title = {Mechanisms of Cell-Cell Fusion in SARS-CoV-2: An Evolving Strategy for Transmission and Immune Evasion.},
journal = {Viruses},
volume = {17},
number = {11},
pages = {},
doi = {10.3390/v17111405},
pmid = {41305428},
issn = {1999-4915},
mesh = {Humans ; *SARS-CoV-2/immunology/physiology/pathogenicity/genetics ; *COVID-19/transmission/immunology/virology ; *Immune Evasion ; Cell Fusion ; *Virus Internalization ; Giant Cells/virology ; Animals ; Antibodies, Neutralizing/immunology ; },
abstract = {Early studies on the evolution of SARS-CoV-2 revealed mutations that favored host transmission of the virus and more efficient viral entry. However, cell-free virus spread is vulnerable to host-neutralizing antibodies. As population immunity developed, mutations that confer escape from neutralization were selected. Notably, cell syncytia formation wherein an infected cell fuses with a noninfected cell is a more efficient route of transmission that bypasses humoral immunity. Cell syncytia formation has been implicated in the pathogenicity of SARS-CoV-2 infection whilst compromising host transmission due to impaired whole virion release. Therefore, understanding the mechanisms of virus-mediated cell-cell fusion will aid in identifying and targeting more pathogenic strains of SARS-CoV-2. Whilst the general kinetics of cell-cell fusion have been known for decades, the specific mechanisms by which SARS-CoV-2 induces fusion are beginning to be elucidated. This is partially due to emergence of more reliable, high throughput methods of quantifying and comparing fusion efficiency in experimental models. Moreover, the ongoing inflammatory response and emerging health burden of long COVID may point to cell-cell fusion in the pathogenesis. In this review, we synthesize current understanding of SARS-CoV-2-mediated cell-cell fusion and its consequences on immune escape, viral persistence, and the innate immune response.},
}

Humans
*SARS-CoV-2/immunology/physiology/pathogenicity/genetics
*COVID-19/transmission/immunology/virology
*Immune Evasion
Cell Fusion
*Virus Internalization
Giant Cells/virology
Animals
Antibodies, Neutralizing/immunology

@article {pmid41304256,
year = {2025},
author = {Mateescu, DM and Ilie, AC and Cotet, I and Guse, C and Muresan, CO and Pah, AM and Badalica-Petrescu, M and Iurciuc, S and Craciun, ML and Avram, A and Margan, MM and Enache, A},
title = {Gut Microbiome Dysbiosis in COVID-19: A Systematic Review and Meta-Analysis of Diversity Indices, Taxa Alterations, and Mortality Risk.},
journal = {Microorganisms},
volume = {13},
number = {11},
pages = {},
doi = {10.3390/microorganisms13112570},
pmid = {41304256},
issn = {2076-2607},
support = {"Victor Babes" University of Medicine and Pharmacy Timisoara//"Victor Babes" University of Medicine and Pharmacy Timisoara/ ; },
abstract = {COVID-19 is associated with gut microbiome alterations that may influence disease outcomes through immune and inflammatory pathways. This systematic review and meta-analysis evaluated global evidence on gut dysbiosis in COVID-19. We searched PubMed/MEDLINE, Embase, Web of Science, Scopus, and Cochrane Library up to 5 October 2025 (PROSPERO CRD420251160970). Alpha-diversity indices and microbial taxa log-fold changes (logFC) were analyzed using random-effects models. The pooled standardized mean difference (SMD) for the Shannon index was -0.69 (95% CI -0.84 to -0.54; I[2] = 42%), confirming reduced microbial diversity. Faecalibacterium prausnitzii showed a significant pooled depletion (logFC = -1.24; 95% CI -1.68 to -0.80; k = 10; I[2] = 74%), while Enterococcus spp. was increased (logFC = 1.45; 95% CI 1.12-1.78). Egger's test did not suggest publication bias (p = 0.32). Gut dysbiosis was consistently associated with reduced microbial diversity and enrichment of pathogenic taxa, correlating with increased disease severity and mortality (HR = 1.67). These findings highlight the potential of microbiome profiling as a prognostic tool in COVID-19, although clinical translation requires further validation.},
}

@article {pmid41304215,
year = {2025},
author = {Arruda, ISA and Cavalcante, CDS and Rubens, RS and Castro, LNPF and Nóbrega, YKM and Dalmolin, TV},
title = {Changes in the Gut Microbiota of Patients After SARS-CoV-2 Infection: What Do We Know?.},
journal = {Microorganisms},
volume = {13},
number = {11},
pages = {},
doi = {10.3390/microorganisms13112529},
pmid = {41304215},
issn = {2076-2607},
support = {DPI/BCE nº 01/2025//University of Brasilia/ ; FAPDF nº 09/2023//Fundação de Apoio à Pesquisa do Distrito Federal/ ; },
abstract = {COVID-19 can cause long-term symptoms, such as a post-infection syndrome, known as Long-COVID. Among the symptoms present during this period, the most reported are gastrointestinal symptoms. This study discusses the effects of changes in the gut microbiota of post-COVID-19 patients. SARS-CoV-2 infection is associated with significant alterations in gut microbial composition, disturbing its homeostasis and promoting a reduction in the abundance of beneficial symbiotic bacteria and an increase in the abundance of opportunistic pathogens. Furthermore, the composition of the gut microbiota may play a role in the prognosis of patients with post-COVID-19 infection. The microbiota of the intestinal tract and the respiratory tract influence each other; therefore, the gut-lung axis has attracted increasing interest in understanding COVID-19. Moreover, the brain-gut axis has been studied, since there have been reports of anxiety and depression along with post-COVID-19 gastrointestinal symptoms. Treatments options for intestinal dysbiosis in Long-COVID patients include probiotics, prebiotics, and fecal microbiota transplantation. These treatments may serve as an approach to improve gastrointestinal symptoms during Long-COVID, increasing microbiome diversity, strengthening the integrity of intestinal barrier functions, and consequently influencing the treatment of COVID-19.},
}

@article {pmid41303176,
year = {2025},
author = {Olarinde, F and Nunes-Silva, A and Sanchez-Ramirez, DC and Molgat-Seon, Y and Villar, R},
title = {Using Active Standing Orthostatic Stress Test to Assess Physiological Responses in Individuals with Long COVID: A Systematic Review.},
journal = {Journal of clinical medicine},
volume = {14},
number = {22},
pages = {},
doi = {10.3390/jcm14228139},
pmid = {41303176},
issn = {2077-0383},
abstract = {Background/Objectives: Individuals experiencing long COVID (LC) frequently report orthostatic intolerance symptoms, which may be linked to autonomic and cardiovascular dysfunction. The active standing test provides a simple, clinically relevant means to assess these impairments. This systematic review aims to determine the use of the active standing orthostatic stress test in evaluating cardiovascular, autonomic, and respiratory responses in people experiencing LC. Methods: A systematic search, according to PRISMA guidelines, was conducted in PubMed, MEDLINE, EMBASE, CINAHL, and Scopus for articles published between 2020 and 2025. This study was registered in PROSPERO CRD-42024615872. Studies were included if they used the active standing test, enrolled adults (≥18 years), included both long COVID and healthy control groups, used continuous beat-to-beat measurements, and reported physiological outcomes. Risk of bias was assessed using the nine-point Newcastle-Ottawa Scale. Results: Three studies (216 participants experiencing LC and 186 controls) met the inclusion criteria. Across studies, LC individuals consistently exhibited elevated heart rate in both supine and standing positions. However, blood pressure findings were more variable: only one study reported 13% of participants met orthostatic hypotension criteria, while another found significant increases in diastolic blood pressure during standing. Long COVID groups also showed reduced heart rate variability compared to controls. Conclusions: Individuals experiencing LC show elevated heart rate and impaired autonomic function during active standing, with subgroup-specific blood pressure changes. These alterations may contribute to dizziness, fatigue, and reduced activity tolerance. Incorporating active standing into clinical assessment could aid early identification of autonomic dysfunction and inform rehabilitation strategies, though more research is urgently needed.},
}

@article {pmid41302566,
year = {2025},
author = {Sui, SX and Yu, L},
title = {Patient and Professional Perspectives on Long COVID: A Systematic Literature Review and Meta-Synthesis.},
journal = {International journal of environmental research and public health},
volume = {22},
number = {11},
pages = {},
doi = {10.3390/ijerph22111620},
pmid = {41302566},
issn = {1660-4601},
mesh = {Humans ; *COVID-19/psychology ; *Health Personnel/psychology ; SARS-CoV-2 ; Qualitative Research ; },
abstract = {BACKGROUND: Post-COVID-19 condition ('long COVID') involves fluctuating symptoms across multiple organ systems and disability or functional loss, which may be episodic, continuous, or permanent. Qualitative research is essential to capture lived experiences and explain how social and health system contexts may influence improvement, recovery, and service use. We synthesised perspectives from people living with long COVID and healthcare professionals to inform service design and policy.

METHODS: We conducted a systematic review and qualitative meta-synthesis. MEDLINE, Embase, PsycINFO, CINAHL, Scopus, and Web of Science were searched for studies published between 1 January 2020 and 19 August 2025. Eligible studies reported qualitative data from adults with long COVID (≥12 weeks after acute infection) and/or healthcare professionals in any setting. We excluded non-qualitative, non-primary, or non-English reports. Two reviewers independently screened, extracted, and appraised studies using the Critical Appraisal Skills Programme checklist. Data were synthesised thematically. The protocol was registered with the Open Science Framework.

FINDINGS: Of 1544 records screened, 49 studies met the inclusion criteria: 41 involving patients, two involving professionals, and six involving both. Eight patient themes (including symptom burden, identity disruption and stigma) and four professional themes (including recognition, care coordination and holistic care models) were identified. Recognition emerged as a cross-cutting mechanism: validation and consistent pacing guidance facilitated engagement and safer activity, whereas invalidation and inconsistent advice were associated with distress, avoidance, and disengagement. Trajectories showed gradual expansion of multidisciplinary care models, but major capacity and equity gaps persisted. Most studies had low methodological concerns, although heterogeneity in populations and settings was substantial.

INTERPRETATION: Long COVID is a chronic, biological condition that also intersects with social and psychological dimensions, and may present with episodic, continuous, or progressive trajectories. Healthcare services must prioritise early validation, provide consistent pacing and relapse prevention guidance, expand access to multidisciplinary and peer-supported rehabilitation, integrate mental healthcare, strengthen coordinated pathways, and support graded return to work. Explicit attention to equity is required to avoid widening disparities.},
}

Humans
*COVID-19/psychology
*Health Personnel/psychology
SARS-CoV-2
Qualitative Research

@article {pmid41301889,
year = {2025},
author = {Ivanovska, M and Homadi, MS and Angelova, G and Taskov, H and Murdjeva, M},
title = {Differential Characteristics and Comparison Between Long-COVID Syndrome and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).},
journal = {Biomedicines},
volume = {13},
number = {11},
pages = {},
doi = {10.3390/biomedicines13112797},
pmid = {41301889},
issn = {2227-9059},
abstract = {Long-COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome are disabling diseases characterised by ongoing fatigue, post-exertional malaise, cognitive impairment, and autonomic dysfunction. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome typically follows viral infections, whereas Long-COVID exclusively follows SARS-CoV-2 infection, with overlapping but distinct features. This review uses comprehensive searches of online databases to compare their clinical presentations, pathophysiologies, and treatments. Both Long-COVID and ME/CFS appear to involve multifactorial mechanisms, including viral persistence, immune dysregulation, endothelial dysfunction, and autoimmunity, though their relative contributions remain uncertain. Symptom management strategies are consistent, however. Cognitive behaviour therapy has been successful, and there are minimal drug treatments. Graded exercise therapy occupies a contested place, recommending individualised pacing and multidisciplinary rehabilitation. Common and exclusive mechanisms must be identified to formulate valuable therapies. A more significant body of research focusing on immune dysfunction as a pathogenic mechanism for advancing the disease and enabling more effective therapies and diagnostics is needed.},
}

@article {pmid41285857,
year = {2025},
author = {Green, R and Marjenberg, Z and Lip, GYH and Banerjee, A and Wisnivesky, J and Delaney, BC and Peluso, MJ and Wynberg, E and Abduljawad, S},
title = {A systematic review and meta-analysis of the impact of vaccination on prevention of long COVID.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {10326},
pmid = {41285857},
issn = {2041-1723},
mesh = {Humans ; *COVID-19/prevention & control/immunology/virology/epidemiology ; *COVID-19 Vaccines/administration & dosage/immunology ; Immunization, Secondary ; *SARS-CoV-2/immunology ; *Vaccination ; Odds Ratio ; },
abstract = {Long COVID affects millions worldwide and its prevention is a critical public health strategy. While prior analyses show primary vaccination prevents long COVID in subsequent infections, the effect of booster vaccination on long COVID after Omicron infections is unclear. This systematic review identifies 31 observational studies, of which 11 are suitable for pairwise meta-analyses. The pooled odds ratio (OR) of long COVID in those vaccinated (any dose) versus unvaccinated is 0.77 (95% confidence interval [CI] 0.70-0.85; p < 0.0001; 10 studies). ORs were also lower for primary course vaccination versus unvaccinated (OR 0.81; 95% CI 0.79-0.83; p < 0.0001; 3 studies), booster vaccination versus unvaccinated (OR 0.74; 95% CI 0.63-0.86; p = 0.0001; 4 studies), and booster vaccination versus primary course vaccination (OR 77; 95% CI 0.65-0.92; p = 0.0044; 3 studies). These findings indicate that booster vaccination can provide additional protection against long COVID, highlighting the importance of seasonal vaccination against new SARS-CoV-2 variants. They should, however, be interpreted cautiously, given the small number of studies and the low quality of evidence.},
}

Humans
*COVID-19/prevention & control/immunology/virology/epidemiology
*COVID-19 Vaccines/administration & dosage/immunology
Immunization, Secondary
*SARS-CoV-2/immunology
*Vaccination
Odds Ratio

@article {pmid41272382,
year = {2025},
author = {Dornas, W and Reis, JP and Belilo, TE and Vaz, LG and Nasser, HH and de Souza Maia, ML and Figueiredo, A and Tcherniacovski, AG and Montenegro, LCC and Yang, X and C Santiago, H},
title = {Persistent inflammatory cytokine signature in long Covid-19 patients: a meta-analysis.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {41272382},
issn = {1568-5608},
abstract = {Post-acute sequelae of Covid-19 (PASC) refer to persistent symptoms lasting weeks to months after acute SARS-CoV-2 infection. However, identifying biological mechanisms, potential therapeutic targets, and modifiable environmental risk factors remains necessary. Here, we analyzed cytokine levels in patients with PASC through a systematic literature search of the PubMed/MEDLINE, Web of Science, and Scopus databases, including articles published up to December 2024. A total of 33 studies (comprising 3294 patients) were included, addressing the long-term sequelae following acute Covid-19 infection. Levels of IL-6, IL-2, MCP-1/CCL2, TNF-α, IFN-γ, and IP-10/CXCL10 were higher in Covid-19 patients with PASC compared to those without PASC, suggesting an inflammatory basis for the persistence of symptoms. Conversely, little or no difference was observed for IL-1β, IL-7, IL-10, IL-4, IL-17A, IL-8, and IL-1α. To assess the duration of the sustained inflammatory response post-infection, cytokine measurements were categorized as < 6 months or ≥ 6 months after diagnosis. IL-6, MCP-1/CCL2, TNF-α, and IFN-γ remained elevated in both time windows, while IL-1β, IL-8, IP-10/CXCL10, IL-2, and IL-10 showed increased levels beyond 6 months post-Covid-19 diagnosis. Our findings indicate that persistent elevation of inflammatory cytokine is associated with PASC, contributing to a better understanding of the immune pathology underlying chronic dysfunction related to Covid-19.},
}

@article {pmid41271803,
year = {2025},
author = {Bansal, A},
title = {Economic burden of long COVID: macroeconomic, cost-of-illness and microeconomic impacts.},
journal = {NPJ primary care respiratory medicine},
volume = {35},
number = {1},
pages = {53},
pmid = {41271803},
issn = {2055-1010},
mesh = {Humans ; *COVID-19/economics/epidemiology ; *Cost of Illness ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Global Health ; Unemployment ; },
abstract = {Long COVID, defined by symptoms persisting three months post-SARS-CoV-2 infection, presents a significant global health and economic challenge, with global prevalence estimated at 36% (ranging from 1-92%). This brief communication consolidates current knowledge on its economic impacts, including macroeconomic, cost-of-illness, and microeconomic impacts, which are estimated at an average annual burden of $1 trillion globally and $9000 per patient in the USA, with some individuals covering substantial out-of-pocket expenses. Annual lost earnings in the USA alone are estimated at approximately $170 billion. Long COVID was associated with increased unemployment, financial distress, and work impairment for up to three years post-infection. This paper highlights discrepancies in impact estimation methodologies and calls for standardised metrics especially in emerging economies. Key research gaps include the absence of comprehensive longitudinal studies on individual and aggregated economic burden, specific long COVID phenotypes and biomarkers, and cost-effectiveness evaluations of interventions.},
}

Humans
*COVID-19/economics/epidemiology
*Cost of Illness
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Global Health
Unemployment

@article {pmid41268373,
year = {2025},
author = {Calleja-Conde, J and Echeverry-Alzate, V and Sánchez-Diez, S and Giné, E and Bühler, KM},
title = {Severe alcohol use and COVID-19: implications for physical and mental health.},
journal = {Frontiers in psychiatry},
volume = {16},
number = {},
pages = {1640207},
pmid = {41268373},
issn = {1664-0640},
abstract = {The COVID-19 pandemic has revealed and intensified the vulnerability of individuals with pre-existing medical and behavioral conditions, notably those related to substance use. Among these, chronic alcohol consumption represents a clinically significant, yet often under-addressed, vulnerability factor that may exacerbate both the acute severity and long-term consequences of SARS-CoV-2 infection. This narrative review examines the biological and clinical intersections between alcohol use and COVID-19, focusing on shared mechanisms of immune dysfunction, neuroinflammation, and disruption of the gut-brain axis. We synthesize current findings showing that both conditions compromise innate and adaptive immune responses, alter cytokine signaling, and weaken mucosal and blood-brain barriers. These changes contribute to cognitive and emotional dysregulation and may increase the risk of persistent neuropsychiatric symptoms, including those observed in Long COVID. In addition, we discuss how chronic alcohol use may alter host susceptibility to infection and affect the immune response to vaccination, with implications for treatment outcomes and recovery. Our findings highlight the need to integrate alcohol use disorder into COVID-19 risk assessments, clinical management, and long-term mental health care planning. A multidisciplinary approach is essential to address the overlapping biological pathways that link alcohol-related vulnerability to COVID-19 outcomes.},
}

@article {pmid41262872,
year = {2025},
author = {Lv, X and Ji, L and Cao, W and Xue, Y and Dai, H and Zhang, S},
title = {Revisiting lung cancer immunotherapy in the era of long COVID: mechanistic insights and therapeutic implications.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1657691},
pmid = {41262872},
issn = {2235-2988},
mesh = {Humans ; *COVID-19/immunology/complications ; *Immunotherapy/methods ; *Lung Neoplasms/therapy/immunology ; SARS-CoV-2/immunology ; Tumor Microenvironment/immunology ; Immune Checkpoint Inhibitors/therapeutic use ; },
abstract = {In the post-COVID-19 era, understanding the long-term impact of Long COVID on the immune system is essential for deciphering its influence on lung cancer pathogenesis and immunotherapeutic efficacy. This review comprehensively examines how persistent COVID-19 sequelae-manifested as chronic inflammation, pulmonary fibrosis, cytokine dysregulation, and T-cell exhaustion can reshape the lung cancer microenvironment. In addition, the emerging roles of memory B cells and altered neutrophil function in promoting tumorigenesis are discussed. Importantly, we analyze recent clinical evidence suggesting that COVID-19 vaccination may enhance the efficacy of immune checkpoint inhibitors, potentially by modulating host immunity. By integrating mechanistic insights with clinical observations, this review aims to illuminate the challenges and opportunities at the intersection of Long COVID and lung cancer treatment, thereby fostering the development of personalized therapeutic strategies in the post-pandemic era.},
}

Humans
*COVID-19/immunology/complications
*Immunotherapy/methods
*Lung Neoplasms/therapy/immunology
SARS-CoV-2/immunology
Tumor Microenvironment/immunology
Immune Checkpoint Inhibitors/therapeutic use

@article {pmid41247781,
year = {2025},
author = {Henrich, TJ and Montgomery, CP and Graf, J and Ismali, N and Mohandas, S and Suthar, MS and Brim, H and Coffin, JM and Pagaria, A and Guzmán Rivera, J and Vudali, U and Keim, P and Zhong, G and McGrath, R and Edwards, B and García-Sastre, A and Gennaro, ML},
title = {The role of co-infection in the pathogenesis of acute SARS-CoV-2 infection and development of post-acute sequelae: A perspective.},
journal = {eLife},
volume = {14},
number = {},
pages = {},
doi = {10.7554/eLife.106308},
pmid = {41247781},
issn = {2050-084X},
mesh = {Humans ; *COVID-19/complications/pathology/virology ; *Coinfection/virology ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Bacterial Infections/complications ; },
abstract = {A major health challenge resulting from the COVID-19 pandemic is the manifestation of post-acute sequelae of SARS-CoV-2 (PASC). PASC (or long COVID) is a collective term used for clinical symptoms, various pathologies, and life-quality-changing functional impairment that persist for months to years after the initial SARS-CoV-2 infection. The mechanisms underlying PASC are not understood, although advances have been made in identifying factors that may contribute to long-term pathology. Recent data have emerged, showing an association between SARS-CoV-2 viral persistence and non-SARS-CoV-2 infections (pre-existing, viral reactivation, or new infections) in facilitating or mediating PASC. However, the heterogeneous nature and timing of co-infections have made it challenging to understand, interpret, and contextualize their contribution to PASC. Here, we summarize the impact of potential viral, bacterial, and fungal infections on SARS-CoV-2 pathogenesis, with a focus on their possible roles in the development of PASC. We also provide a framework to understand the mechanisms of PASC and inform basic, translational, and clinical research initiatives, including RECOVER, a large and ongoing research initiative to understand, treat, and prevent long COVID.},
}

Humans
*COVID-19/complications/pathology/virology
*Coinfection/virology
*SARS-CoV-2
Post-Acute COVID-19 Syndrome
Bacterial Infections/complications

@article {pmid41244103,
year = {2025},
author = {Yue, Y and Han, X and Chen, Q and Dai, L and Ai, Q and Zhang, Z and Ma, F and Gao, J},
title = {The effect of pulmonary rehabilitation for post-acute sequelae of SARS-CoV-2 infection in patients: a systematic review and meta-analysis.},
journal = {Frontiers in rehabilitation sciences},
volume = {6},
number = {},
pages = {1634351},
doi = {10.3389/fresc.2025.1634351},
pmid = {41244103},
issn = {2673-6861},
abstract = {BACKGROUND: Post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID, are characterized by persistent symptoms such as fatigue, dyspnea, and reduced functional capacity. Pulmonary rehabilitation (PR) is recommended for chronic respiratory conditions, but its effectiveness in PASC, particularly across different delivery modes, remains uncertain.

OBJECTIVE: To assess the impact of PR, including telerehabilitation and in-person modalities, on physical function, dyspnea, pulmonary function, fatigue, and quality of life in patients with PASC.

METHODS: We conducted a systematic search of PubMed, Embase, the Cochrane Library, and Web of Science from inception to March 25 for controlled clinical trials assessing the effects of PR in PASC patients. Two independent reviewers performed study selection and data extraction. The risk of bias was assessed using the Cochrane Risk of Bias Tool, and data were analyzed using Review Manager (RevMan) 5.4.1. Effect sizes were reported as mean differences (MD) or standardized mean differences (SMD) with 95% confidence intervals (CI).

RESULTS: Ten randomized controlled trials involving 673 participants were included. Most studies were judged to have a moderate risk of bias. Compared with usual care, PR significantly improved six-minute walk distance (MD: 76.85 meters; 95% CI: 57.35-96.36; p < 0.001), maximal inspiratory pressure (MD: 17.63 cmH₂O; 95% CI: 4.50-30.76; p = 0.009), fatigue (SMD: -1.15; 95% CI: -1.83 to -0.48; p < 0.001), and quality of life (SMD: 1.73; 95% CI: 0.56-2.91; p = 0.004). No statistically significant improvement was found for dyspnea (MD: -0.41; 95% CI: -1.51 to -0.68; p = 0.46). Subgroup analyses showed no significant differences between telerehabilitation and in-person PR across all outcomes, including exercise capacity (p = 0.84), dyspnea (p = 0.86), fatigue (p = 0.93), and quality of life (p = 0.44).

CONCLUSIONS: PR improves physical and functional outcomes in patients with PASC. Telerehabilitation offers a clinically equivalent alternative to in-person PR, supporting its broader implementation.},
}

@article {pmid41241149,
year = {2025},
author = {Park, WH},
title = {The Mitochondrial Nexus: Dysfunction, Inhibition, and Therapeutic Frontiers in Lung Disease.},
journal = {Respiratory medicine},
volume = {},
number = {},
pages = {108506},
doi = {10.1016/j.rmed.2025.108506},
pmid = {41241149},
issn = {1532-3064},
abstract = {Mitochondria are increasingly recognized as central arbiters of cellular fate, placing them at the nexus of pulmonary health and disease. Beyond their canonical role in adenosine triphosphate (ATP) synthesis, these organelles are critical hubs for redox signaling, metabolic homeostasis, and programmed cell death. Mitochondrial dysfunction-a multifaceted condition characterized by impaired bioenergetics, excessive reactive oxygen species (ROS) production, aberrant dynamics, and defective quality control via mitophagy-is a unifying pathogenic feature in chronic lung diseases, including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and pulmonary arterial hypertension (PAH). This dysfunction is also a critical determinant of severity in acute conditions like acute lung injury (ALI) and COVID-19 and is a key mechanistic driver of Long COVID. This review synthesizes the core mechanisms of mitochondrial impairment, delineates their specific contributions to this spectrum of pulmonary pathologies, and discusses the burgeoning field of mitochondria-targeted therapeutics. Strategies ranging from targeted antioxidants and metabolic modulators to novel regenerative approaches like mitochondrial transplantation are highlighted, with an expanded discussion on their limitations, challenges, and clinical implications. By framing mitochondrial integrity as a critical determinant of pulmonary disease, we underscore a pivotal axis for future diagnostic and therapeutic innovation.},
}

@article {pmid41235245,
year = {2025},
author = {Chen-Camaño, R and DeAntonio, R and López-Vergès, S},
title = {T-cell exhaustion in COVID-19: what do we know?.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1678149},
pmid = {41235245},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology ; *SARS-CoV-2/immunology ; *T-Lymphocytes/immunology ; T-Cell Exhaustion ; },
abstract = {T-cell exhaustion is a terminal state of immune dysfunction characterized by impaired proliferation and effector functions, diminished cytokine secretion, and sustained expression of inhibitory receptors. In coronavirus disease 2019 (COVID-19), increasing evidence links exhausted T-cell phenotypes with poor clinical outcomes, including severe disease, delayed viral clearance, and persistent symptoms associated with Long COVID. Exhaustion results from prolonged antigenic stimulation and inflammatory signals and is marked by transcriptional reprogramming, metabolic and epigenetic dysregulation, and co-expression of inhibitory receptors such as programmed cell death protein-1 (PD-1), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Notably, exhausted phenotypes in COVID-19 frequently coexist with hyperactivation, raising the unresolved question of whether inhibitory receptor expression reflects transient activation or irreversible dysfunction. Emerging therapeutic strategies to reverse these dysfunctional states include immune checkpoint inhibitors, cytokine modulation, metabolic interventions, and epigenetic therapies, although their clinical translation remains at an early stage. Critical research gaps include the scarcity of longitudinal data, incomplete profiling of T-cell subsets across disease stages during COVID-19 and Long COVID-19, and contradictory evidence of vaccine-induced exhaustion with limited understanding of its consequences. This non-systematic literature review synthesizes current advances in COVID-19 immunopathology and therapeutic strategies, underscoring that understanding T-cell exhaustion is crucial to improving outcomes and shaping next-generation immunotherapies and vaccines.},
}

Humans
*COVID-19/immunology
*SARS-CoV-2/immunology
*T-Lymphocytes/immunology
T-Cell Exhaustion

@article {pmid41235244,
year = {2025},
author = {Wang, D and Zhang, F},
title = {CKD-related impairment in humoral and cellular immune response and potential correlation with long COVID-19: a systematic review.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1690298},
pmid = {41235244},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology/prevention & control ; *Immunity, Humoral ; *Renal Insufficiency, Chronic/immunology/therapy ; *Immunity, Cellular ; *SARS-CoV-2/immunology ; *COVID-19 Vaccines/immunology ; Antibodies, Viral/blood/immunology ; Vaccination ; },
abstract = {INTRODUCTION: Patients with chronic kidney disease (CKD) are at high risk of morbidity and mortality from SARS-CoV-2 infection (COVID-19). However, their immune response to vaccination may vary among individuals. The purpose of this review was to identify characteristics of alterations in humoral and cellular immune responses to the vaccination, and to provide insights into their immune dysfunctions for a better care of acute COVID-19 and prevention of long COVID-19.

METHODS: PubMed, Embase, Scopus, Web of science and Cochrane Central were systematically searched. Eligible publications included clinical studies reporting immune response to COVID-19 vaccination in CKD patients without dialysis or KT, CKD patients undergoing dialysis, as well as CKD patients with KT. Demographics, measurements and results of their humoral and cellular response were evaluated, and the quality of studies were assessed using the Joanna Briggs Institute (JBI) critical appraisal tool and the Newcastle-Ottawa quality assessment scale (NOS).

RESULTS: A total of 31 eligible studies were identified. A decreased proportion of patients with KT showed anti-S IgG positivity after the 2[nd] (67%) and 3[rd] (56.6%) dose of vaccination. Similarly, a decreased proportion of these patients presented S-specific T-cell response after the 2[nd] (17.7%) and 3[rd] (12.9%) dose. Though lower anti-S IgG titers in patients with CKD or on dialysis, as well as T-cell response in patients on dialysis were reported to be lower after the 2[nd] or 3[rd] dose of vaccination, conflicting results were reported by other studies. Limited studies on correlated change between humoral and cellular immune response revealed a low rate of co-presence of the two in patients with dialysis, though antibody level was correlated with rate of cellular response, while no such correlation was revealed in patients with KT.

CONCLUSION: The study provides crucial information on features of humoral and cellular immune responses to COVID-19 vaccinations in CKD patients, and suggests possible directions for strategy of management such as antibody monitoring, additional booster dose or immunomodulatory therapies not only for acute COVID-19 but also for long COVID-19.},
}

Humans
*COVID-19/immunology/prevention & control
*Immunity, Humoral
*Renal Insufficiency, Chronic/immunology/therapy
*Immunity, Cellular
*SARS-CoV-2/immunology
*COVID-19 Vaccines/immunology
Antibodies, Viral/blood/immunology
Vaccination

@article {pmid41151241,
year = {2025},
author = {Raijmakers, RPH and Lund Berven, L and Keijmel, SP and Rodrigo, C and Wyller, VBB and Katz, BZ and Buchwald, D and Evans, RA and Gérardin, P and Knoop, H and Prins, M and Stavem, K and Stiansen-Sonerud, T and Taylor, R and Valencia Arroyo, BM and Wensaas, KA and Selvakumar, JP and van den Wijngaard, C and Lloyd, AR and Sandler, CX},
title = {Immunological associations in post-infective fatigue syndromes including Long COVID-a systematic review and meta-analysis.},
journal = {EBioMedicine},
volume = {121},
number = {},
pages = {105970},
pmid = {41151241},
issn = {2352-3964},
support = {R01 AI105781/AI/NIAID NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/complications/immunology ; SARS-CoV-2 ; Biomarkers ; *Fatigue/immunology/etiology ; },
abstract = {BACKGROUND: The pathophysiology of post-infective fatigue syndromes (PIFS), including Long COVID, is unknown. This systematic review and meta-analysis aimed to investigate if PIFS is associated with persistent immune activation.

METHODS: PubMed, EMBASE, and Web of Science were searched for terms related to infection, fatigue, persistent symptoms, and immunological markers.

POPULATION: adults and adolescents; Exposure: documented acute infection; Comparator: those who developed PIFS vs. recovered controls from the same exposure; and Outcomes: immunological biomarkers. Studies which documented acute infection, applied diagnostic criteria for PIFS, and assayed circulating immunologic markers were eligible.

FINDINGS: From 14,985 studies screened, 30 articles were included (n = 5102 participants; 833 PIFS/PIFS-like cases, n = 4269 recovered control participants) with many studies excluded by inadequate quality in eligibility criteria. The meta-analysis (11 studies; n = 413 PIFS cases, analysed with random-effects models) showed PIFS cases had increased: white cell counts at 3-6 months (Cohen's d: 0.41, 95% CI 0.09-0.74); and circulating levels of RANTES and TNFα at 6-12 months (Cohen's d: 0.45 [95% CI 0.16-0.73] and 0.30 [95% CI 0.04-0.57], respectively) compared to controls recovered from the same exposure.

INTERPRETATION: These findings provide cautious support for persistent immune activation in PIFS, but warrant further replication. Future studies should include better documentation of acute infection and PIFS case characterisation.

FUNDING: ARL is supported by a National Health and Medical Research Council Practitioner Fellowship (Grant 1041897). CXS is supported by a Cancer Institute New South Wales Early Career Fellowship (2021/ECF1310). BZK is supported by the National Institute of Allergy and Infectious Diseases (AI 105781). RAE is supported by the National Institute for Health and Care.},
}

Humans
*COVID-19/complications/immunology
SARS-CoV-2
Biomarkers
*Fatigue/immunology/etiology

@article {pmid41226731,
year = {2025},
author = {Varghese, S and Al-Hassani, I and Al-Aani, U and Rob, NJ and Al-Mannai, S and Jaguri, A and Yousif, RA and Al-Mulla, A and Palayangal, FF and Laws, S and Al-Ali, D and Zakaria, D},
title = {Long-Term Complications of Multisystem Inflammatory Syndrome in Children and Adults Post-COVID-19: A Systematic Review.},
journal = {International journal of molecular sciences},
volume = {26},
number = {21},
pages = {},
doi = {10.3390/ijms262110695},
pmid = {41226731},
issn = {1422-0067},
mesh = {Humans ; *COVID-19/complications ; *Systemic Inflammatory Response Syndrome/complications/therapy/etiology ; Child ; Adult ; SARS-CoV-2 ; },
abstract = {The SARS-CoV-2 pandemic has posed global medical challenges due to its ability to affect multiple organ systems. Among the post-COVID-19 complications, multisystem inflammatory syndrome has emerged as a severe condition affecting both children (MIS-C) and adults (MIS-A). This review aims to compile and analyze published data to investigate clinical characteristics, laboratory findings, and outcomes of MIS post-COVID-19. A comprehensive search of various databases was conducted to identify studies reporting MIS-related complications in pediatric and adult populations post-COVID-19 infection. Screening, data extraction, and cross-checking were performed by two independent reviewers. Only 64 studies met our inclusion criteria, and compiled results revealed that cardiac complications were the predominant manifestation followed by gastrointestinal, hematologic, neurological, and mucocutaneous involvement. Laboratory findings consistently demonstrated elevated inflammatory markers including CRP, ferritin, D-dimer, and IL-6. Most patients required hospitalization, and many needed intensive care; treatment typically involved IVIG, corticosteroids, and biologic therapies. While most patients recovered, a subset experienced persistent complications. These findings highlight the importance of early recognition, multidisciplinary management, and structured follow-up for MIS. Future research is warranted to clarify the underlying mechanisms, risk factors, and long-term outcomes associated with MIS in post-COVID-19 patients.},
}

Humans
*COVID-19/complications
*Systemic Inflammatory Response Syndrome/complications/therapy/etiology
Child
Adult
SARS-CoV-2

@article {pmid41226415,
year = {2025},
author = {Zolotarenko, AD and Poghosyan, HM and Sheptiy, VV and Bruskin, SA},
title = {COVID-19 Hijacking of the Host Epigenome: Mechanisms, Biomarkers and Long-Term Consequences.},
journal = {International journal of molecular sciences},
volume = {26},
number = {21},
pages = {},
doi = {10.3390/ijms262110372},
pmid = {41226415},
issn = {1422-0067},
support = {123120500032-9//Ministry of Science and Higher Education of the Russian Federation/ ; },
mesh = {Humans ; *COVID-19/genetics/virology/immunology/pathology ; *SARS-CoV-2/physiology ; *Epigenesis, Genetic ; *Epigenome ; Biomarkers/metabolism ; Immunity, Innate ; *Host-Pathogen Interactions/genetics ; MicroRNAs/genetics ; DNA Methylation ; },
abstract = {The epigenetics of COVID-19 is a rapidly expanding field that reveals how the SARS-CoV-2 virus initiates alterations in the host's genome, influencing the susceptibility to infection, the disease severity, and long-term consequences, known as "long COVID." In this review, we describe the mechanisms utilized by the virus to manipulate the host epigenome, suppressing antiviral responses and creating a favorable environment for viral replication. We also highlight virus-induced epigenetic changes across diverse cell populations that contribute to COVID-19 pathogenesis. Notably, the virus reprograms hematopoietic stem and progenitor cells, leading to long-lasting alterations in innate immunity, a phenomenon known as "trained immunity." These epigenetic modifications are maintained in differentiated daughter cells and may explain the persistent inflammation and other symptoms of long COVID. Furthermore, we discuss emerging epigenetic biomarkers of disease severity, including methylation signatures in genes such as AIM2, HLA-C, and PARP9, as well as dysregulated miRNA profiles. Understanding this complex interplay between the virus and the host's epigenetic landscape is crucial for developing new therapeutic approaches that target specific epigenetic modifications to suppress pathological processes and improve clinical outcomes for COVID-19 patients.},
}

Humans
*COVID-19/genetics/virology/immunology/pathology
*SARS-CoV-2/physiology
*Epigenesis, Genetic
*Epigenome
Biomarkers/metabolism
Immunity, Innate
*Host-Pathogen Interactions/genetics
MicroRNAs/genetics
DNA Methylation

@article {pmid41223394,
year = {2025},
author = {Zamora, FV and Santos, ACFF and Zamora, AV and Galvao, LKCS and Pimenta, NDS and Salles, JPCEA and Carneiro, VB and Starling, CEF},
title = {Hyperbaric Oxygen Treatment for Long-COVID syndrome: A Systematic Review of Current Evidence on Cognitive Decline.},
journal = {Undersea & hyperbaric medicine : journal of the Undersea and Hyperbaric Medical Society, Inc},
volume = {52},
number = {3},
pages = {327-335},
pmid = {41223394},
issn = {1066-2936},
mesh = {Humans ; *Hyperbaric Oxygenation/methods ; *Cognitive Dysfunction/therapy/etiology ; *COVID-19/complications ; Executive Function ; Post-Acute COVID-19 Syndrome ; Attention ; Randomized Controlled Trials as Topic ; Fatigue/therapy ; },
abstract = {INTRODUCTION: There is no established specific treatment for long-COVID syndrome (LCS), yet hyperbaric oxygen (HBO2) treatment has been studied as a potential option. Therefore, we conducted a systematic review to evaluate the benefits of HBO2 treatment in LCS patients.

METHODS: We systematically searched PubMed, Embase, and Cochrane databases until April 2024. Risk of bias and GRADE quality assessment were evaluated. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) with ID CRD42024530421.

RESULTS: Seven studies from seven countries, divided into RCTs and observational studies, included 199 participants. HBO₂ treatment protocols included breathing 100% oxygen at 2.0 ATA until 2.5 ATA; the number of sessions varied from ten to 60 depending on the patient's comorbidities and symptoms. Memory, executive function, attention, fatigue, and pain level improved with HBO2 treatment. The intervention had minimal side effects, and none were serious.

CONCLUSION: HBO₂ treatment might be a potential option and safe treatment in LCS patients. However, further research should be focused on evaluating its efficacy in a larger number of patients through randomized studies.},
}

Humans
*Hyperbaric Oxygenation/methods
*Cognitive Dysfunction/therapy/etiology
*COVID-19/complications
Executive Function
Post-Acute COVID-19 Syndrome
Attention
Randomized Controlled Trials as Topic
Fatigue/therapy

@article {pmid41218870,
year = {2025},
author = {He, XY and Li, XH and Tong, ZH},
title = {[Cognitive impairment in long COVID: advances in pathological mechanisms and exercise rehabilitation interventions].},
journal = {Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases},
volume = {48},
number = {11},
pages = {1087-1095},
doi = {10.3760/cma.j.cn112147-20250610-00315},
pmid = {41218870},
issn = {1001-0939},
support = {2023YFC0872500//National Key Research and Development Program/ ; Ggyfz202503//Reform and Development Program of Beijing Institute of Respiratory Medicine/ ; },
mesh = {Humans ; *COVID-19/complications/psychology ; *Cognitive Dysfunction/rehabilitation/etiology ; *Exercise Therapy ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Quality of Life ; },
abstract = {Since the outbreak of the novel coronavirus (COVID-19) pandemic, long-term effects of the virus, known as long-COVID, has emerged. It is a chronic syndrome following infection. It is estimated that around 20% of COVID-19 survivors worldwide experience cognitive dysfunction. This is characterized by impairments in executive function, attention, memory, and other cognitive domains, and can have a significant impact on quality of life and social functioning. This article systematically reviewed recent studies and summarized the potential pathological mechanisms underlying cognitive dysfunction in long COVID, including neuroinflammation, glial cell dysregulation, involvement of the olfactory pathway and limbic system, autoimmunity and viral reactivation, cerebrovascular and blood-brain barrier damage, as well as abnormalities in neurotrophic factors and synaptic plasticity. Additionally, it explored the effects of exercise rehabilitation and multidimensional comprehensive rehabilitation strategies. The aim was to provide theoretical and scientific foundations for optimizing intervention programs for cognitive dysfunction in long COVID and for formulating clinical guidelines and public health policies.},
}

Humans
*COVID-19/complications/psychology
*Cognitive Dysfunction/rehabilitation/etiology
*Exercise Therapy
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Quality of Life

@article {pmid40294910,
year = {2025},
author = {Sessford, JD and Dodwell, A and Elms, K and Gill, M and Premnazeer, M and Scali, O and Roque, M and Cameron, JI},
title = {Factors associated with mental health outcomes among family caregivers to adults with COVID: a scoping review.},
journal = {Disability and rehabilitation},
volume = {47},
number = {23},
pages = {5983-6000},
doi = {10.1080/09638288.2025.2494223},
pmid = {40294910},
issn = {1464-5165},
mesh = {Humans ; *Caregivers/psychology ; *COVID-19/psychology ; *Mental Health ; Adaptation, Psychological ; Adult ; Risk Factors ; SARS-CoV-2 ; Social Support ; },
abstract = {PURPOSE: Family caregivers (FCGs) are essential to the health and wellbeing of people affected by COVID. Protecting mental health of FCGs is essential to sustaining their caregiving role. The objective of this scoping review was to synthesise identified risks factors and protective factors for mental health of FCGs to adults with COVID.

MATERIALS AND METHODS: Using the Joanna Briggs Institute (JBI) methodology, the search was conducted across Medline, CINAHL, and PsycINFO. Original studies conducted since the pandemic began were included. The population was adult FCGs to adults with COVID, and studies reported mental health outcomes and related factors.

RESULTS: Of 3474 identified articles, 22 met inclusion criteria (14 quantitative, seven qualitative, one mixed-methods, 18/22 conducted in Iran). Across all study designs, risk factors included limited support, financial burden, family challenges, unpredictable nature of COVID, inexperience, isolation, and unpleasant experiences. Protective factors included accessing support services, self-reinforcement, coping strategies, professional help, and online intervention.

CONCLUSIONS: Quantitative and qualitative research identified common mental health risk factors and protective factors for FCGs to adults with COVID. These factors may inform development of supports and services for FCGs to people with COVID, such as online interventions. Studies did not distinguish acute versus long COVID.},
}

Humans
*Caregivers/psychology
*COVID-19/psychology
*Mental Health
Adaptation, Psychological
Adult
Risk Factors
SARS-CoV-2
Social Support

@article {pmid41223978,
year = {2025},
author = {Spanoghe, M and Antonacci, T and Schneider, N and Molmans, THJ},
title = {Viewpoint | linking long Covid and AD(H)D through neuroimmune dysfunction: A translational framework proposal for precision medicine.},
journal = {Brain, behavior, and immunity},
volume = {},
number = {},
pages = {106181},
doi = {10.1016/j.bbi.2025.106181},
pmid = {41223978},
issn = {1090-2139},
}

@article {pmid39710927,
year = {2025},
author = {Heidari, F and Farahighasreaboonasr, F and Hassan, ZM and Fazeli, P and Hosseini, M and Ebtekar, M},
title = {Annual SZ: An Alternative Immunotherapy for COVID-19 and Long COVID.},
journal = {Infectious disorders drug targets},
volume = {25},
number = {5},
pages = {e18715265323116},
pmid = {39710927},
issn = {2212-3989},
mesh = {Humans ; COVID-19/immunology ; *COVID-19 Drug Treatment ; Antibodies, Monoclonal, Humanized/therapeutic use ; Adenosine Monophosphate/analogs & derivatives/therapeutic use ; SARS-CoV-2/drug effects ; *Antiviral Agents/therapeutic use ; Dexamethasone/therapeutic use ; Alanine/analogs & derivatives/therapeutic use ; *Immunotherapy/methods ; Cytokine Release Syndrome/drug therapy ; },
abstract = {Since the outbreak of coronavirus disease 2019 (COVID-19) in late 2019 and early 2020, the identification of drugs to control severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its symptoms has been a pressing focus of research. Cytokine storm and acute respiratory distress syndrome (ARDS) are the leading causes of mortality following infection. In this review, we discuss immune pathogenesis and four medications, including Remdesivir, Tocilizumab, Dexamethasone, and Annual SZ for COVID-19. A comparison of the effectiveness and therapeutic usage of drugs as reported in clinical trials and reports was made at different disease levels as well. Clinical studies indicate that Annual SZ with mild side effects was more affordable and might be more effective than other medications. Additionally, Annual SZ was capable of reducing the levels of pro-inflammatory cytokines as well as viral attachment and RNA replication.},
}

Humans
COVID-19/immunology
*COVID-19 Drug Treatment
Antibodies, Monoclonal, Humanized/therapeutic use
Adenosine Monophosphate/analogs & derivatives/therapeutic use
SARS-CoV-2/drug effects
*Antiviral Agents/therapeutic use
Dexamethasone/therapeutic use
Alanine/analogs & derivatives/therapeutic use
*Immunotherapy/methods
Cytokine Release Syndrome/drug therapy

@article {pmid41212631,
year = {2025},
author = {Goodfellow, H and Blandford, A and Bradbury, K and Gomes, M and Hamilton, F and Henley, W and Stevenson, F and Fernandez-Reyes, D and Hurst, J and Heightman, M and Pfeffer, P and Ricketts, W and Singh, R and Hylton, H and Linke, S and Bindman, J and Robson, C and Walker, S and Ismaila, H},
title = {Development and implementation of a digital health intervention in routine care for long COVID patients: a comprehensive synopsis.},
journal = {Health and social care delivery research},
volume = {13},
number = {39},
pages = {1-27},
doi = {10.3310/GJHG0331},
pmid = {41212631},
issn = {2755-0079},
abstract = {BACKGROUND: By July 2020, large numbers of post-COVID patients were experiencing symptoms for weeks or months, but traditional National Health Service models of rehabilitation service delivery could not meet demand.

OBJECTIVES: Design and deploy a digital health intervention to provide digitally delivered, remotely supported rehabilitation to long COVID patients on complicated and evolving pathways.

METHODS: The multidisciplinary team combined established research methods based on engineering and computer science (considering safety, stability and user requirements) with those based on biomedical and health service research (considering effectiveness and population impact). Qualitative data comprised recordings of meetings between study team members and clinicians and semistructured interviews with clinician and patient users. Quantitative data comprised referral, registration and usage rates; demographic and clinical characteristics of patients; and patient-reported outcome measures.

RESULTS: We created a modifiable digital health intervention, 'Living With COVID Recovery[TM] developed by Living With Ltd', London, UK, that continues to be used by National Health Service trusts. The digital health intervention included integration into a clinical pathway, a clinician-facing dashboard, two-way messaging and a patient-facing app with information and evidence-based treatments. We aimed to register 1000 users. By study completion on 20 December 2022, there were 9781 patients invited, of whom 7679 (78.5%) had registered, at 33 National Health Service clinics.

LIMITATIONS: Data came from patients at long COVID clinics, however data were unlikely to be representative of people with long COVID. We could not observe clinics under lockdown and had limited access to patient digital health intervention users or to people not engaging with the digital health intervention. Patient user data were incomplete, with inconsistent patient-reported outcome measure and other questionnaire data completion and no data on initial severity of disease, vaccination status, comorbidities or other individual circumstances.

CONCLUSIONS: Long COVID can be extremely debilitating, comparable to stage IV lung cancer in relation to fatigue and health-related quality of life. Care and rehabilitation should address the management of fatigue and reflect the impact of social disadvantage on symptom severity. With sufficient resources, a digital health intervention can be developed quickly and effectively using agile methodology and bringing together a genuinely multidisciplinary team, including, importantly, an industry partner. Digital health intervention product design and deployment are both important in getting National Health Service trusts, healthcare professionals and patients to engage with a digital health intervention. Projects should work closely with all user groups. Lockdown and the unmet need of a new patient group encouraged those who might otherwise have been reluctant to try a digital health intervention. Many patients and clinics accepted this digital remote support, which helped patients feel cared for while reducing strain on health services. This may encourage acceptance of other digital health intervention, although medical record integration remains a deterrent to clinics.

FUTURE WORK: This research focused on the development, deployment and evaluation of a digitally enabled rehabilitation programme for long COVID. Clinical effectiveness will be assessed within the Symptoms, Trajectory, Inequalities and Management: Understanding Long-COVID to Address and Transform Existing Integrated Care Pathways (UCL, London, UK) study.

FUNDING: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme as award number NIHR132243.},
}

@article {pmid41194817,
year = {2025},
author = {Dimitrakopoulou, A and Sarantaki, A and Nanou, CI and Georgakopoulou, VE and Taskou, C and Chouli, M and Diamanti, A},
title = {Long COVID-Related Fatigue During Pregnancy: A Systematic Review.},
journal = {Cureus},
volume = {17},
number = {10},
pages = {e93877},
pmid = {41194817},
issn = {2168-8184},
abstract = {Long sequelae of COVID-19 (Long COVID), or post-acute sequelae of SARS-CoV-2 infection, encompasses a wide range of persistent symptoms, with fatigue emerging as one of the most prevalent and disabling. Pregnant individuals may be uniquely susceptible to post-viral fatigue due to immunological and physiological adaptations during gestation. This review consolidates existing data regarding the prevalence, risk factors, and clinical implications of Long COVID-associated fatigue in pregnant individuals. A narrative review was conducted of studies examining fatigue among pregnant individuals with confirmed SARS-CoV-2 infection. Key outcomes included fatigue prevalence, symptom persistence, associated risk or protective factors, and comparisons with non-pregnant populations. Across both the acute and post-acute stages of COVID-19, fatigue emerged as a consistently common symptom. Its prevalence and persistence varied significantly across studies, partly due to heterogeneity in assessment tools and follow-up durations. Severe acute illness, hospitalization, obesity, and smoking during pregnancy were linked to a higher risk of prolonged fatigue, whereas anosmia appeared to act as a potential protective factor. In contrast, comorbidities such as hypertension, diabetes, and lung disease were not significantly linked to fatigue risk. No consistent associations were found with maternal age or alcohol use. Long COVID-related fatigue presents a substantial burden in pregnancy, with implications for maternal health, quality of life, and postpartum recovery. Early recognition, individualized care strategies, and public health interventions targeting modifiable risk factors are essential to support this vulnerable population. Ongoing research is essential to uncover underlying mechanisms and guide evidence-based clinical management.},
}

@article {pmid41189723,
year = {2025},
author = {Fineberg, D and Moreau, A and Schneider-Futschik, EK and Armstrong, CW},
title = {A Perspective on the Role of Metformin in Treating Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID.},
journal = {ACS pharmacology & translational science},
volume = {8},
number = {10},
pages = {3411-3431},
pmid = {41189723},
issn = {2575-9108},
abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID (LC) are increasingly recognized as debilitating postinfectious conditions that impact both individuals and society. Recent research highlights the potential of metformin, an antidiabetic agent, as a treatment for these syndromes by targeting their underlying mechanisms. This review assesses the effectiveness of metformin in ME/CFS and LC, which involve complex dysfunctions related to cytokines, glycolysis, ATP generation, oxidative stress, gastrointestinal microbiomes, and vascular endothelial function. Metformin, traditionally known for its antihyperglycemic properties may offer broader therapeutic benefits by influencing these pathological pathways. It works by inhibiting complexes I and IV of the electron transport chain, which reduces the strain on malfunctioning complex V and decreases the production of harmful free radicals. Additionally, metformin's impact on mTOR signaling could improve energy metabolism in ME/CFS and LC by downregulating an overactive but underperforming protein, thereby alleviating symptoms. Beyond the impact on cellular metabolism, metformin has shown to have anti-inflammatory, vascular, gastrointestinal, neuroprotective and epigenetic effects. We explore this impact of metformin and the potential role it could play to help people with ME/CFS. While metformin shows promise, it is unlikely to be a stand-alone solution. Instead, it may be part of a broader treatment strategy that includes other therapies targeting neurocognitive and autonomic impairments.},
}

@article {pmid41178423,
year = {2025},
author = {Limami, Y and Wahnou, H and Ndayambaje, M and Hba, S and Chgari, O and Ammara, M and El Kebbaj, R and Naya, A and Oudghiri, M and Duval, RE},
title = {SARS-CoV-2: A Liver Brief.},
journal = {WIREs mechanisms of disease},
volume = {17},
number = {6},
pages = {e70005},
doi = {10.1002/wsbm.70005},
pmid = {41178423},
issn = {2692-9368},
mesh = {Humans ; *COVID-19/complications/virology/pathology/immunology ; *SARS-CoV-2/pathogenicity ; *Liver Diseases/virology/pathology ; *Liver/virology/pathology/immunology/metabolism ; Angiotensin-Converting Enzyme 2/metabolism ; Virus Internalization ; },
abstract = {The Coronavirus Disease 2019 (COVID-19) pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has revealed the virus's ability to induce multi-organ damage, including significant liver injury. The molecular mechanisms of liver dysfunction in COVID-19 patients are explored, focusing on direct viral infection, immune-mediated damage, and the gut-liver axis. SARS-CoV-2 enters liver cells through the Angiotensin-Converting Enzyme 2 (ACE2) and Transmembrane Serine Protease 2 (TMPRSS2) receptors, but alternative pathways, such as CD209/Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN) and AXL receptors, can also contribute to viral entry. Additionally, immune responses, particularly the cytokine storm, exacerbate liver inflammation, leading to hepatocyte damage. Pre-existing liver conditions, such as metabolic-associated fatty liver disease (MAFLD), alcohol-related liver disease (ALD), and liver fibrosis, heighten the risk of severe outcomes in COVID-19 patients. Post-COVID-19 liver complications, including fibrosis progression and persistent liver damage, have been reported, with emerging evidence suggesting chronic inflammation, viral persistence, and autoimmune reactions as potential contributors. Furthermore, Drug-Induced Liver Injury (DILI) from COVID-19 treatments remains a concern, highlighting the need for careful management. Consequently, understanding the interplay between SARS-CoV-2 and the liver is critical for improving patient outcomes and developing targeted therapies to mitigate liver-related complications in both acute and Long COVID-19 phases. This article is categorized under: Infectious Diseases > Molecular and Cellular Physiology.},
}

Humans
*COVID-19/complications/virology/pathology/immunology
*SARS-CoV-2/pathogenicity
*Liver Diseases/virology/pathology
*Liver/virology/pathology/immunology/metabolism
Angiotensin-Converting Enzyme 2/metabolism
Virus Internalization

@article {pmid40590080,
year = {2025},
author = {Goh, DY and Lam, WC and Zhong, LLD},
title = {Effect of interventions for the management of sleep disturbances in patients with long COVID: a systematic review and meta-analysis of randomized controlled trials.},
journal = {Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine},
volume = {21},
number = {11},
pages = {1993-2005},
doi = {10.5664/jcsm.11782},
pmid = {40590080},
issn = {1550-9397},
mesh = {Humans ; *COVID-19/complications ; *Sleep Wake Disorders/therapy/etiology ; Randomized Controlled Trials as Topic ; Quality of Life ; SARS-CoV-2 ; },
abstract = {STUDY OBJECTIVES: Long COVID presents with symptoms that persist for weeks or months postinfection, with sleep disturbances that significantly affect quality of life. The diverse approaches to managing sleep disturbances highlight the need for comparing treatment effectiveness to improve patient outcomes. This study systematically reviews and conducts a meta-analysis of randomized controlled trials to assess the effectiveness of current interventions for sleep disturbances in patients with long COVID and explores the underlying mechanisms and promising treatments.

METHODS: Relevant studies were identified through a comprehensive literature search across Embase, Web of Science, PubMed, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Data databases. The included studies focused on interventions aimed at managing patients with long COVID with sleep disturbances. Data extraction and analysis were performed, followed by a meta-analysis of comparable studies. The quality of evidence was assessed using the Cochrane Risk of Bias Tool (RoB 2.0) and the Grading of Recommendations, Assessment, Development, and Evaluation system.

RESULTS: Out of 3,352 retrieved studies, 14 were included in the systematic review and 2 in the meta-analysis. Interventions were categorized as pharmacological and nonpharmacological. Whereas most studies indicated improved sleep quality measured by standardized scales, some did not demonstrate significant benefits. The quality of evidence varied from low to moderate.

CONCLUSIONS: The results suggest that sleep disturbances in patients with long COVID result from a complex interplay of physiological, psychological, and neurological factors. Both pharmacological and nonpharmacological interventions show potential in managing these disturbances, with nonpharmacological approaches showing particular promise. To establish more robust evidence, more high-quality, large-scale randomized controlled trials are necessary in future research.

CITATION: Goh DY, Lam WC, Zhong LLD. Effect of interventions for the management of sleep disturbances in patients with long COVID: a systematic review and meta-analysis of randomized controlled trials. J Clin Sleep Med. 2025;21(11):1993-2005.},
}

Humans
*COVID-19/complications
*Sleep Wake Disorders/therapy/etiology
Randomized Controlled Trials as Topic
Quality of Life
SARS-CoV-2

@article {pmid41171518,
year = {2025},
author = {Mallouli, SZ and Munblit, D and Iakovleva, E and Winkler, AS and Fornari, A and Helbok, R and Struhal, W and Beretta, S and De Groote, W and Curatoli, C and Lanza, M and Ericka, F and Crivelli, L and Giussani, G and Wasay, M and Chakroun Walha, O and Safi, F and Leonardi, M and Allegri, R and Guekht, A and Triki, CC},
title = {Persistent neurological sequelae in children and adolescents after SARS-CoV-2: a scoping review.},
journal = {Infection},
volume = {},
number = {},
pages = {},
pmid = {41171518},
issn = {1439-0973},
abstract = {OBJECTIVES: For the past five years, COVID-19 has not only been a priority for health planning but also a hotspot for clinical research. Yet, the weight of the worldwide COVID-19 pandemic arises from the critical phase consequences due to the onset of acute disease, associated containment measures, and documented ongoing disabling symptoms. Investigating the global longitudinal effects on children and adolescents will inform future health directives tailored to this population's needs. This review aimed to report the spectrum of persistent neurological sequelae in children and adolescents following SARS-CoV-2 infection.

METHODS: Hence, we conducted a scoping review following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). We included the peer-reviewed articles from PubMed, Google Scholar, Web of Science, Cochrane Library, and WHO COVID database to identify relevant literature on long-COVID-19 neurological signs/symptoms among children and adolescents. The search covered the period between September 2020 and September 2024.

RESULTS: The results of our analysis of 33 studies found long-COVID-19-related neurological signs/symptoms were predominantly: pain and sensory problems (N = 74,612/91,543; 81.5%), followed by sleep disturbances (N = 14,630/91,543; 15.9%), and cognitive difficulties (N = 2274/91,543; 2.4%). The global prevalence of long COVID-19 neurological signs/symptoms was estimated between 0.4% (20/5032; 95% CI = 2.1-3%) and 34% (27/79) based on data obtained through online questionnaire; while it varied between 1.8% (4/215) and 83.14% (74/89; 95%CI =   -  0.12; 0.30) based on patient assessment. Long-COVID-19-related neurological signs/symptoms were more common in the 11-16 age group. Children with immunocompetent profiles were at higher risk of developing long-COVID-19-related neurological signs/symptoms.

CONCLUSION: Our results demonstrate a considerable burden of COVID-19-related persistent neurological signs/symptoms in children and adolescents, which should be taken into consideration in healthcare decision-making.},
}

@article {pmid41168795,
year = {2025},
author = {Gartmann, J and Sturm, C and Bökel, A},
title = {Physiotherapy interventions in post- and long-COVID-19: a scoping review of the literature up to February 2023.},
journal = {BMC health services research},
volume = {25},
number = {1},
pages = {1425},
pmid = {41168795},
issn = {1472-6963},
}

@article {pmid41164170,
year = {2025},
author = {Raveendran, VV and AlQattan, S and AlMutairy, E},
title = {A review on clinical implications of S100 proteins in lung diseases.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1618772},
pmid = {41164170},
issn = {2296-858X},
abstract = {The S100 family of proteins plays a pivotal role in the pathogenesis of lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, pulmonary arterial hypertension (PAH), pulmonary fibrosis, lung cancers, acute lung injury, acute respiratory distress syndrome, COVID-19, and lung transplantation. This review comprehensively examines the contributions of S100 proteins to the progression of these disorders, focusing on their potential as diagnostic and prognostic biomarkers, as well as therapeutic targets. S100A protein-mediated key molecular mechanisms that influence inflammation, airway remodeling, fibrosis, and tumorigenesis in the lungs are discussed. The importance of their normal function is evident from the observation that simultaneous mutations in S100A3 and S100A13 predispose individuals to early-onset pulmonary fibrosis, underscoring their critical role in lung health. Furthermore, sustained S100 protein elevation is explored in the context of long COVID, shedding light on its role in chronic inflammation. These proteins act as damage-associated molecular patterns (DAMPs), activating immune pathways via receptors like TLR4 and RAGE, thereby driving inflammation and immune cell recruitment. Notably, in lung transplantation, elevated levels of S100A8, S100A9, and S100A12 serve as early biomarkers of graft rejection and complications such as graft-vs.-host disease, which indicates their role in mediating immune responses and transplant outcomes. While promising, the clinical application of S100 proteins faces challenges, including disease-specific variability and the need for robust validation across diverse populations. This narrative review underscores the dual potential of S100 proteins as biomarkers and therapeutic targets in respiratory medicine while emphasizing the importance of overcoming current limitations through targeted research and clinical trials.},
}

@article {pmid41161981,
year = {2025},
author = {Vishnu, P and Aboulafia, DM},
title = {Hemostatic Disorders Following Severe Acute Respiratory Syndrome Coronavirus 2 Infection, COVID-19 Vaccination, and Long-COVID Syndrome: Current Evidence and Controversies in Clinical Practice.},
journal = {Clinics in laboratory medicine},
volume = {45},
number = {4},
pages = {643-655},
doi = {10.1016/j.cll.2025.07.008},
pmid = {41161981},
issn = {1557-9832},
mesh = {Humans ; *COVID-19/complications/prevention & control ; *COVID-19 Vaccines/adverse effects ; *Hemostatic Disorders/etiology ; SARS-CoV-2 ; *Vaccination/adverse effects ; },
abstract = {The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented profound global health challenges. Beyond acute illness, a substantial proportion of individuals experience persistent symptoms including fatigue, brain fog, and post-exertional malaise, collectively known as Long-COVID. Among the complications associated with SARS-CoV-2 infection and vaccination, hemostatic disorders ranging from mild platelet dysfunction to severe thromboembolic events, and rare but serious coagulation-related adverse effects, such as vaccine-induced immune thrombotic thrombocytopenia, have emerged as a significant concern. Herein we provide an overview of current information and controversies surrounding hemostatic complications in SARS-CoV-2 infection and COVID-19 vaccination.},
}

Humans
*COVID-19/complications/prevention & control
*COVID-19 Vaccines/adverse effects
*Hemostatic Disorders/etiology
SARS-CoV-2
*Vaccination/adverse effects

@article {pmid41160239,
year = {2025},
author = {Krassnig, K and Bauer, R and Glasl, S and Haubenberger, P and Evanzin, HJ and Schneider, K and Margotti, D},
title = {[Herbal treatment options for post-viral symptoms and long COVID].},
journal = {Wiener medizinische Wochenschrift (1946)},
volume = {},
number = {},
pages = {},
pmid = {41160239},
issn = {1563-258X},
abstract = {BACKGROUND: Long COVID and post-viral symptom complexes have become a significant focus in medical practice. There is an urgent need to provide evidence-based treatment options to those patients. The aim of the literature review was to summarize herbal medicinal products as a treatment option for post-viral conditions, particularly long COVID.

METHODS: A working group of the Austrian Society for Phytotherapy conducted a narrative review between 2022 and 2024, based on external literature from the PubMed, PubPharm and Scopus databases and clinical experience from practice. The review identified the most relevant medicinal plants and their preparations for the most common symptom complexes of long COVID.

RESULTS: A total of 98 publications and 24 monographs were included in the literature review. The symptom complexes (+ relevant phytopharmaceuticals) include neurological complaints, such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) (Ginseng radix, Panax quinquefolii radix, Eleutherocci radix, Rhodiolae rhizoma et radix, Schisandrae fructus), nootropics (Ginkgo folium, Lavandulae flos), irritations of the respiratory tract (Liquiritiae radix, Nigellae semen, Eucalypti folium), gastrointestinal complaints (Gentianae radix, Centauri herba, Artemisii herba, Galangae rhizoma, Zingiberis rhizoma, Boswellia serrata, Curcuma longae rhizoma), circulatory weakness (Crataegi folium cum flore, Rosmarini folium, Salviae officinalis folium) and loss of smell (Rosae flos, Citri pericarpium, Caryophylli flos, Eucalypti folium). External evidence and clinical experience in medical practice show that many important symptoms of post-viral conditions can be successfully treated with herbal preparations.

CONCLUSION: Phytopharmaceuticals can provide evidence-based support for the therapeutic portfolio for viral diseases and their consequences in current and future viral epidemics.},
}

@article {pmid41158347,
year = {2025},
author = {Xie, K and Zhang, P and Li, Y and Xia, L},
title = {The post-COVID-19 pulmonary sequelae: manifestations, mechanisms and treatment strategies.},
journal = {Journal of thoracic disease},
volume = {17},
number = {9},
pages = {7414-7429},
pmid = {41158347},
issn = {2072-1439},
abstract = {Recent studies have increasingly demonstrated that coronavirus disease 2019 (COVID-19) patients may develop long-term sequelae of varying severity, collectively referred to as long COVID or post-COVID-19 condition. Pulmonary sequelae are particularly common, which significantly impair patients' quality of life. The mechanisms underlying post-COVID-19 pulmonary sequelae are complex and multifactorial, and their management is still at an exploratory stage. This review explores the manifestations, underlying mechanisms, and potential treatment approaches for post-COVID-19 pulmonary sequelae. Fatigue, dyspnea, myalgia, and sleep disturbances are the most commonly reported symptoms following COVID-19 infection, while anxiety and depression are also prevalent. Respiratory symptoms include dyspnoea, persistent cough, hypoxia, and reduced exercise capacity. Impaired lung diffusion capacity is the most frequently observed pulmonary function abnormality, and residual abnormalities on chest computed tomography (CT) commonly include ground-glass opacities (GGO) and fibrotic-like changes. Air trapping is also an important CT finding and has been reported to associated with impaired lung diffusion function. The potential mechanisms may include pulmonary fibrosis, chronic inflammation, immune dysregulation, coagulation abnormalities and thrombosis, and persistent viral infection. Current treatment strategies encompass vaccination, pulmonary rehabilitation, and pharmacological interventions such as antifibrotic, anti-inflammatory, and anticoagulant therapies. A comprehensive understanding of the recovery trajectory and the mechanisms underlying post-COVID-19 pulmonary sequelae is crucial for improving patient outcomes.},
}

@article {pmid41157587,
year = {2025},
author = {Heath, AM and Li, D},
title = {Symptomatology of Long COVID Associated with Inherited and Acquired Thrombophilic Conditions: A Systematic Review.},
journal = {Viruses},
volume = {17},
number = {10},
pages = {},
doi = {10.3390/v17101315},
pmid = {41157587},
issn = {1999-4915},
mesh = {Humans ; *COVID-19/complications ; *Thrombophilia/complications ; SARS-CoV-2 ; },
abstract = {Thrombophilic conditions, conditions where blood has a tendency to form thrombi due to abnormal coagulatory processes, can affect the trajectory of diseases such as Post-Acute Sequelae of SARS-CoV-2 Infection, better known as Long COVID (LC), by worsening symptoms and complicating outlooks. As a comorbidity in pro-coagulatory diseases such as COVID-19 and LC, patients with thrombophilic conditions may experience worse symptoms than their peers, due to this elevated level of hypercoagulation. A 15-week literature review through the public PubMed database was conducted to investigate the severity, mechanisms, and symptom profiles of thrombophilic patients with LC. Papers were only included if samples included participants with pre-existing tendencies for hypercoagulable states, and confirmation of SARS-CoV-2 infection via a Polymerase Chain Reaction test. Each paper included in this review was analyzed by topic and assessed for eligibility against the Joanna Briggs Institute's Critical Appraisal tool. Each paper was also assessed for biases. Results from the 6 papers included in this review showed that LC could be predicted following COVID-19 illness by a hypercoagulable blood profile, indicating that LC may be linked to chronic hypercoagulation and inflammation post-infection. Additionally, symptoms linked to microthrombi formation, such as hair loss, arrhythmia, and dizziness, were exhibited more frequently in patients with thrombophilia and/or thrombophilic conditions, indicating that those with thrombophilic conditions may exhibit unique LC symptom profiles compared to healthy controls. This paper's research is preliminary and thus is limited in the strength of its findings; However, further research into LC and its interactions with co-morbidities like thrombophilic conditions would aid in the development of better treatment plans for patients, such as the usage of anticoagulants or screening for hypercoagulable blood profiles post-COVID-19 to assess patient risk.},
}

Humans
*COVID-19/complications
*Thrombophilia/complications
SARS-CoV-2

@article {pmid41157582,
year = {2025},
author = {Prakash, S and Karan, S and Lekbach, Y and Tifrea, DF and Figueroa, CJ and Ulmer, JB and Young, JF and Glenn, G and Gil, D and Jones, TM and Redfield, RR and BenMohamed, L},
title = {Insights into Persistent SARS-CoV-2 Reservoirs in Chronic Long COVID.},
journal = {Viruses},
volume = {17},
number = {10},
pages = {},
doi = {10.3390/v17101310},
pmid = {41157582},
issn = {1999-4915},
support = {AI158060//National Institute of Allergy and Infectious Diseases/ ; },
mesh = {Humans ; *COVID-19/virology/immunology/complications ; *SARS-CoV-2/physiology/genetics ; Animals ; Chronic Disease ; Post-Acute COVID-19 Syndrome ; RNA, Viral ; Disease Reservoirs/virology ; *Persistent Infection/virology ; },
abstract = {Long COVID (LC), also known as post-acute sequelae of COVID-19 infection (PASC), is a heterogeneous and debilitating chronic disease that currently affects 10 to 20 million people in the U.S. and over 420 million people globally. With no approved treatments, the long-term global health and economic impact of chronic LC remains high and growing. LC affects children, adolescents, and healthy adults and is characterized by over 200 diverse symptoms that persist for months to years after the acute COVID-19 infection is resolved. These symptoms target twelve major organ systems, causing dyspnea, vascular damage, cognitive impairments ("brain fog"), physical and mental fatigue, anxiety, and depression. This heterogeneity of LC symptoms, along with the lack of specific biomarkers and diagnostic tests, presents a significant challenge to the development of LC treatments. While several biological abnormalities have emerged as potential drivers of LC, a causative factor in a large subset of patients with LC, involves reservoirs of virus and/or viral RNA (vRNA) that persist months to years in multiple organs driving chronic inflammation, respiratory, muscular, cognitive, and cardiovascular damages, and provide continuous viral antigenic stimuli that overstimulate and exhaust CD4[+] and CD8[+] T cells. In this review, we (i) shed light on persisting virus and vRNA reservoirs detected, either directly (from biopsy, blood, stool, and autopsy samples) or indirectly through virus-specific B and T cell responses, in patients with LC and their association with the chronic symptomatology of LC; (ii) explore potential mechanisms of inflammation, immune evasion, and immune overstimulation in LC; (iii) review animal models of virus reservoirs in LC; (iv) discuss potential T cell immunotherapeutic strategies to reduce or eliminate persistent virus reservoirs, which would mitigate chronic inflammation and alleviate symptom severity in patients with LC.},
}

Humans
*COVID-19/virology/immunology/complications
*SARS-CoV-2/physiology/genetics
Animals
Chronic Disease
Post-Acute COVID-19 Syndrome
RNA, Viral
Disease Reservoirs/virology
*Persistent Infection/virology

@article {pmid41157147,
year = {2025},
author = {Jach, ME and Sajnaga, E and Bumbul, M and Serefko, A and Borowicz, KK and Golczyk, H and Kieliszek, M and Wiater, A},
title = {The Role of Probiotics and Their Postbiotic Metabolites in Post-COVID-19 Syndrome.},
journal = {Molecules (Basel, Switzerland)},
volume = {30},
number = {20},
pages = {},
doi = {10.3390/molecules30204130},
pmid = {41157147},
issn = {1420-3049},
mesh = {*Probiotics/therapeutic use/pharmacology ; Humans ; *COVID-19/complications ; Gastrointestinal Microbiome/drug effects ; SARS-CoV-2 ; Dysbiosis ; Fatty Acids, Volatile/metabolism ; },
abstract = {Post-COVID-19 syndrome, also known as long-COVID, is characterized by a wide spectrum of persistent symptoms involving multiple body organs and systems, including fatigue, gastrointestinal disorders, and neurocognitive dysfunction. Emerging evidence suggests that gut microbiota dysbiosis and disruption of the gut-brain axis play a central role in the pathophysiology of this condition. Probiotics and their metabolites (postbiotics) have gained increasing attention as potential therapeutic agents given their immunomodulatory, anti-inflammatory, and antiviral properties. In this review, we discuss the current understanding of the antiviral mechanisms of probiotics, including reinforcement of intestinal epithelial barrier function, direct virus inhibition, receptor competition, and immune system modulation. Special emphasis is placed on short-chain fatty acids (SCFAs), lactic acid, hydrogen peroxide, and bacteriocins as key factors that contribute to these effects. SCFAs appear to be essential postbiotic compounds during post-COVID recovery. We also highlight recent clinical trials involving specific probiotic species, such as Lactiplantibacillus plantarum, Lacticaseibacillus rhamnosus, and Bifidobacterium longum, and their potential role in alleviating long-term COVID symptoms. Although the current results are promising, further research is needed to clarify the most effective strains, dosages, and mechanisms of action in post-COVID therapeutic strategies.},
}

*Probiotics/therapeutic use/pharmacology
Humans
*COVID-19/complications
Gastrointestinal Microbiome/drug effects
SARS-CoV-2
Dysbiosis
Fatty Acids, Volatile/metabolism

@article {pmid41156656,
year = {2025},
author = {Delpino, MV and Quarleri, J},
title = {Mitochondrial Dysfunction in Aging, HIV, and Long COVID: Mechanisms and Therapeutic Opportunities.},
journal = {Pathogens (Basel, Switzerland)},
volume = {14},
number = {10},
pages = {},
doi = {10.3390/pathogens14101045},
pmid = {41156656},
issn = {2076-0817},
mesh = {Humans ; *Aging/metabolism ; *HIV Infections/metabolism/therapy/pathology ; *Mitochondria/metabolism/pathology ; *COVID-19/metabolism/therapy/pathology ; DNA, Mitochondrial/genetics ; *Mitochondrial Diseases/therapy ; Oxidative Stress ; SARS-CoV-2 ; Mitophagy ; },
abstract = {We hypothesize that a unified mitochondrial perspective on aging, HIV, and long COVID reveals shared pathogenic mechanisms and specific therapeutic vulnerabilities that are overlooked when these conditions are treated independently. Mitochondrial dysfunction is increasingly recognized as a common factor driving aging, HIV, and long COVID. Shared mechanisms-including oxidative stress, impaired mitophagy and dynamics, mtDNA damage, and metabolic reprogramming-contribute to ongoing energy failure and chronic inflammation. Recent advancements highlight new therapeutic strategies such as mitochondrial transfer, transplantation, and genome-level correction of mtDNA variants, with early preclinical and clinical studies providing proof-of-concept. This review summarizes current evidence on mitochondrial changes across aging and post-viral syndromes, examines emerging organelle-based therapies, and discusses key challenges related to safety, durability, and translation.},
}

Humans
*Aging/metabolism
*HIV Infections/metabolism/therapy/pathology
*Mitochondria/metabolism/pathology
*COVID-19/metabolism/therapy/pathology
DNA, Mitochondrial/genetics
*Mitochondrial Diseases/therapy
Oxidative Stress
SARS-CoV-2
Mitophagy

@article {pmid41155411,
year = {2025},
author = {Caliman-Sturdza, OA and Hamamah, S and Iatcu, OC and Lobiuc, A and Bosancu, A and Covasa, M},
title = {Microbiome and Long COVID-19: Current Evidence and Insights.},
journal = {International journal of molecular sciences},
volume = {26},
number = {20},
pages = {},
doi = {10.3390/ijms262010120},
pmid = {41155411},
issn = {1422-0067},
support = {760073/23.05.2023, code 285/30.11.2022, within Pillar III, Component C9, Investment 8.//Romania's National Recovery and Resilience Plan/ ; 760073/23.05.2023, code 285/30.11.2022, within Pillar III, Component C9, Investment 8.//Romania's National Recovery and Resilience Plan/ ; },
mesh = {Humans ; *COVID-19/microbiology/complications ; *Gastrointestinal Microbiome ; SARS-CoV-2 ; Dysbiosis/microbiology ; Post-Acute COVID-19 Syndrome ; Probiotics/therapeutic use ; *Microbiota ; },
abstract = {Long COVID, also referred to as post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by persistent multi-systemic symptoms such as fatigue, cognitive impairment, and respiratory dysfunction. Accumulating evidence indicates that gut and oral microbiota play an important role in its pathogenesis. Patients with long COVID consistently exhibit reduced microbial diversity, depletion of beneficial short-chain fatty acid (SCFA)-producing species such as Faecalibacterium prausnitzii and Bifidobacterium spp. and enrichment of proinflammatory taxa including Ruminococcus gnavus, Bacteroides vulgatus, and Veillonella. These alterations may disrupt intestinal barrier integrity, sustain low-grade systemic inflammation, and influence host immune and neuroendocrine pathways through the gut-brain and gut-lung axes. Distinct microbial signatures have also been associated with symptom clusters, including neuropsychiatric, respiratory, and gastrointestinal manifestations. Proposed mechanisms linking dysbiosis to long COVID include impaired SCFA metabolism, tryptophan depletion, microbial translocation, and interactions with host immune and inflammatory responses, including autoantibody formation and viral antigen persistence. Preliminary interventional studies using probiotics, synbiotics, and fecal microbiota transplantation suggest that microbiome-targeted therapies may alleviate symptoms, although evidence remains limited and heterogeneous. This review synthesizes current literature on the role of gut and oral microbiota in long COVID, highlights emerging microbial biomarkers, and discusses therapeutic implications. While causality remains to be firmly established, restoring microbial balance represents a promising avenue for diagnosis, prevention, and management of long COVID.},
}

Humans
*COVID-19/microbiology/complications
*Gastrointestinal Microbiome
SARS-CoV-2
Dysbiosis/microbiology
Post-Acute COVID-19 Syndrome
Probiotics/therapeutic use
*Microbiota

@article {pmid41155179,
year = {2025},
author = {Refrigeri, M and Tola, A and Mogavero, R and Pietracupa, MM and Gionta, G and Scatena, R},
title = {Mechanisms of Mitochondrial Impairment by SARS-CoV-2 Proteins: A Nexus of Pathogenesis with Significant Biochemical and Clinical Implications.},
journal = {International journal of molecular sciences},
volume = {26},
number = {20},
pages = {},
doi = {10.3390/ijms26209885},
pmid = {41155179},
issn = {1422-0067},
mesh = {Humans ; *Mitochondria/metabolism/virology/pathology ; *COVID-19/metabolism/virology/pathology ; *SARS-CoV-2/metabolism/pathogenicity ; Reactive Oxygen Species/metabolism ; Host-Pathogen Interactions ; Immunity, Innate ; },
abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) closely interacts with host cellular mechanisms, with mitochondria playing a crucial role in this process. As essential organelles that control cellular energy production, apoptosis, reactive oxygen species (ROS) metabolism, and innate immune responses, mitochondria are vital to the development of COVID-19. However, the exact molecular interactions between mitochondria and SARS-CoV-2 remain under active investigation. Gaining a comprehensive understanding of mitochondrial involvement in SARS-CoV-2 infection is therefore essential for uncovering complex disease mechanisms, identifying prognostic biomarkers, and developing effective treatments. Ultimately, exploring these virus-host interactions may provide new insights into the fundamental and complex aspects of mitochondrial physiology and pathophysiology.},
}

Humans
*Mitochondria/metabolism/virology/pathology
*COVID-19/metabolism/virology/pathology
*SARS-CoV-2/metabolism/pathogenicity
Reactive Oxygen Species/metabolism
Host-Pathogen Interactions
Immunity, Innate

@article {pmid41146789,
year = {2025},
author = {Dudek, A and Bursy, M and Szkudlarek, W and Linkiewicz, J and Fabiszewski, Z and Starosta, P},
title = {Chronic Cardiovascular Disorders Associated With COVID-19: A Literature Review.},
journal = {Cureus},
volume = {17},
number = {9},
pages = {e93271},
pmid = {41146789},
issn = {2168-8184},
abstract = {The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, is now widely recognized for causing several long-term effects known as post-COVID-19 syndrome (PCS) or long COVID (LC). This presents a growing challenge for healthcare systems worldwide. This narrative review summarizes original peer-reviewed studies indexed in PubMed and published between January 2020 and August 2025. It focuses on adult populations unless stated otherwise. We included studies that provided primary clinical or imaging data on chronic cardiovascular outcomes after confirmed SARS-CoV-2 infection. We excluded case reports, pediatric-only cohorts, and non-peer-reviewed sources. Among the various cardiovascular issues related to LC, we focused on heart fibrosis (HF), postural orthostatic tachycardia syndrome (POTS), new-onset hypertension (HT), and coagulopathy. These conditions consistently show up in the reports and are significant in terms of illness, potential long-term disability, and public health impact. Although these issues are distinct in their underlying causes, they share common mechanisms. These include ongoing inflammation of the endothelium, disruption of the renin-angiotensin-aldosterone system (RAAS), immune-related tissue damage, and an ongoing state that promotes blood clots. These processes can lead to measurable myocardial fibrosis that cardiac magnetic resonance imaging can detect, autonomic dysfunction often seen as POTS, a greater risk of developing hypertension shortly after infection, and a long-term rise in thromboembolic events due to increased clotting and resistant microclots. Current management is mostly focused on relief of symptoms and involves a team approach. It uses repurposed medications and tailored physical rehabilitation since no specific cure is available yet. Promising but still experimental methods, such as endothelial-protective agents like sulodexide and targeting inflammatory pathways, need thorough testing. There are significant gaps in our understanding of the long-term risk of hypertension, the natural progression of fibrosis, and the best treatment for POTS. This highlights urgent needs for future research. Beyond caring for individual patients, these ongoing cardiovascular problems raise important public health concerns. They include higher healthcare use, long-term disability, and economic costs. This situation requires increased clinical attention and proactive cardiovascular monitoring for those recovering from COVID-19.},
}

@article {pmid41145456,
year = {2025},
author = {Sujith, S and Gatzke, N},
title = {An overview of clinical presentation and management of long COVID.},
journal = {The Nurse practitioner},
volume = {50},
number = {11},
pages = {38-42},
doi = {10.1097/01.NPR.0000000000000374},
pmid = {41145456},
issn = {1538-8662},
mesh = {Humans ; *COVID-19/nursing/complications/therapy ; Risk Factors ; Nurse Practitioners ; SARS-CoV-2 ; },
abstract = {The COVID-19 pandemic has been the 21st century's most significant public health emergency. In addition to the acute symptoms of COVID-19, many individuals are facing long-term health issues related to the infection. The terms "long COVID," "postacute sequelae of SARS-CoV-2 infection," "postacute COVID syndrome," and "long-haul COVID-19" refer to long-term consequences of SARS-CoV-2 infection. Symptoms may persist for weeks or months, reducing quality of life. Health practitioners must stay updated and take proactive measures to manage long COVID effectively. This manuscript provides an overview of risk factors, diagnostic tools, and management strategies, which serve as a resource for understanding and managing long COVID.},
}

Humans
*COVID-19/nursing/complications/therapy
Risk Factors
Nurse Practitioners
SARS-CoV-2

@article {pmid40329717,
year = {2025},
author = {Parwani, S and Upreti, S and Mishra, CK and Tripathi, A and Chakraborty, S and Tiwari, S},
title = {Navigating the COVID-19 Treatment Landscape: Efficacy and Side-Effects of Current Therapies against SARS-CoV-2.},
journal = {Current HIV research},
volume = {23},
number = {3},
pages = {145-160},
doi = {10.2174/011570162X338375250414114957},
pmid = {40329717},
issn = {1873-4251},
mesh = {Humans ; COVID-19/immunology ; *SARS-CoV-2/drug effects ; *Antiviral Agents/therapeutic use/adverse effects ; *COVID-19 Drug Treatment ; COVID-19 Vaccines/immunology ; *HIV Infections/complications/immunology/drug therapy ; Drug Repositioning ; },
abstract = {Coronavirus Disease 2019 (COVID-19), caused by the highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 in Wuhan, China. Designated as an epidemic by the World Health Organization (WHO) on January 30, 2020, the virus quickly escalated to a global emergency, officially declared a pandemic in March 2020. With over 6 million recorded deaths and more than 200 identified symptoms in diverse individuals, the impact of COVID-19 is substantial. COVID-19 poses a greater risk to individuals with advanced HIV, while those with well-managed HIV are not at increased risk. Although COVID-19 vaccines are generally effective for people with HIV, some may experience reduced vaccine effectiveness and breakthrough infections due to suboptimal immune responses. Long COVID, affecting at least 65 million individuals, adds a layer of complexity. The virus's rapid mutation has led to diverse symptomatology, prompting adjustments in treatment guidelines. This review comprehensively examines repurposed antiviral drug candidates against COVID-19, explores immune responses across different age groups, delves into the mechanisms of COVID-19 vaccines, and discusses potential immunosuppressants. Additionally, the focus extends to Intravenous Immunoglobulin (IVIG), steroids, and anti-cytokine therapy as promising avenues to address cytokine release syndrome (CRS), a critical condition in COVID-19 patients.},
}

Humans
COVID-19/immunology
*SARS-CoV-2/drug effects
*Antiviral Agents/therapeutic use/adverse effects
*COVID-19 Drug Treatment
COVID-19 Vaccines/immunology
*HIV Infections/complications/immunology/drug therapy
Drug Repositioning

@article {pmid41117273,
year = {2025},
author = {Oba, S and Hosoya, T and Iwai, H and Yasuda, S},
title = {Long COVID: mechanisms of disease, multisystem sequelae, and prospects for treatment.},
journal = {Immunological medicine},
volume = {},
number = {},
pages = {1-24},
doi = {10.1080/25785826.2025.2570902},
pmid = {41117273},
issn = {2578-5826},
abstract = {Long COVID has emerged as a significant global health issue, affecting individuals across a wide spectrum of initial disease severity. While its definition and prevalence vary across studies, persistent symptoms such as fatigue, cognitive dysfunction, respiratory difficulties, and cardiovascular complications have been widely reported. Multiple pathophysiological mechanisms have been proposed, including incomplete viral clearance, reactivation of latent viruses, immune dysregulation, autoimmunity, endothelial dysfunction, microbiome alterations, and mitochondrial impairment. These interconnected processes are thought to contribute to chronic inflammation and multi-organ disease. To date, there are no established therapies for Long COVID, and management primarily focuses on symptomatic relief and rehabilitation. Vaccination has been shown to reduce the incidence of Long COVID, and emerging strategies, including antiviral agents, immune-modulating therapies, microbiome restoration, and mitochondria-targeted interventions, are under investigation. This review summarizes the current understanding of the epidemiology, pathophysiology, organ-specific manifestations, and potential therapeutic approaches for Long COVID, aiming to provide insights into future research directions and clinical management strategies.},
}

@article {pmid40676931,
year = {2025},
author = {Abdul-Azees, PA and Marinkovic, M and Singh, BB and Dean, DD and Chen, XD and Goldberg, MP and Restrepo, MI and Loomer, PM and Yeh, CK},
title = {The Impact of Aging Oral Health on Long COVID-19.},
journal = {Journal of dental research},
volume = {104},
number = {12},
pages = {1294-1303},
doi = {10.1177/00220345251349805},
pmid = {40676931},
issn = {1544-0591},
mesh = {Humans ; *COVID-19/complications/immunology ; *Oral Health ; *Aging/physiology/immunology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Mouth Diseases/virology ; },
abstract = {At least 10% of individuals infected with SARS-CoV-2 develop a variety of multisystem symptoms lasting more than 12 wk known as postacute sequelae of COVID-19 (PASC) or "long COVID." While the precise pathogenesis of PASC remains unclear, immune dysregulation is widely recognized as a key factor. Moreover, PASC disproportionately affects older individuals who are prone to age-related immune system decline, which further exacerbates the risk and severity of PASC. The oral cavity, a primary site for initial SARS-CoV-2 infection, may contribute to the development and persistence of PASC. Emerging evidence suggests that changes in age-related oral health, such as periodontitis, salivary gland (SG) dysfunction, and gustatory and olfactory impairments, may create an environment conducive to forming an oral reservoir of intact virus or viral antigens, which may contribute to the chronicity of PASC. Alternatively, the pathogenesis of PASC may increase the risk of a wide range of oral health issues, such as dental diseases, dry mouth, and sensory dysfunction (e.g., taste and smell) that are frequently reported by patients with PASC. This review highlights how aging facilitates oral SARS-CoV-2 infection, co-infection with other viruses may drive PASC in aging patients, aging and PASC dysregulate the oral microbiome, SARS-CoV-2 infection promotes molecular mechanisms involved in oral tissue aging, aging oral health affects susceptibility to developing PASC, and inflammation associated with PASC exacerbates dysregulation of metabolic/enzymatic pathways of aging oral mucosa and diseases of the periodontal apparatus, SGs, and taste. It underscores the urgent need to comprehensively address the interplay between aging oral health and PASC, which will help mitigate long-term complications and improve overall health outcomes for affected individuals.},
}

Humans
*COVID-19/complications/immunology
*Oral Health
*Aging/physiology/immunology
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Mouth Diseases/virology

@article {pmid41108594,
year = {2025},
author = {Akbar, N and Phadke, S and Mehelay, S and Pullattayil, AK and Fakolade, A and Busse, M},
title = {Considerations of race and ethnicity within rehabilitation studies for post COVID-19 condition: A scoping review.},
journal = {PM & R : the journal of injury, function, and rehabilitation},
volume = {},
number = {},
pages = {},
doi = {10.1002/pmrj.70027},
pmid = {41108594},
issn = {1934-1563},
abstract = {Post COVID-19 condition (PCC) or long COVID disproportionately affects racial and ethnic minority communities. There are a growing number of rehabilitation studies for PCC, however, it has yet to be determined whether existing studies take race and ethnicity into account in their study designs and whether existing rehabilitative approaches are equally effective across diverse racial and ethnic groups. The objective of this study was to describe the extent to which rehabilitation studies of PCC consider race and ethnicity in defining eligibility criteria, planning recruitment strategies, designing intervention delivery and adherence promoting approaches, selecting outcome measures, and reporting results. Of the 4845 studies screened, 23 met eligibility criteria and were included in this review. The most common reason for exclusion was a lack of mention of race or ethnicity anywhere within the article. Among the 23 studies included, 13 studies provided data on the race and/or ethnicity characteristics of their sample, with 88% of participants across all of these studies being White. Less than 25% of studies described the incorporation of race and/or ethnicity in their recruitment strategies (n = 3, 13%) or data analysis (n = 5, 22%). Greater racial and ethnic diversity is needed within rehabilitation studies for PCC as there is currently a significant underrepresentation of racial and ethnic minorities in existing studies. Overall, more PCC rehabilitation studies need to incorporate race and ethnicity into their study designs as it is not well understood whether existing rehabilitation strategies are equally effective across different racial and ethnic groups.},
}

@article {pmid41104805,
year = {2025},
author = {Luo, S and Lai, LY and Zhu, R and Gao, Y and Zhao, Z},
title = {Prevalence and duration of common symptoms in people with long COVID: a systematic review and meta-analysis.},
journal = {Journal of global health},
volume = {15},
number = {},
pages = {04282},
doi = {10.7189/jogh.15.04282},
pmid = {41104805},
issn = {2047-2986},
mesh = {Humans ; *COVID-19/epidemiology/complications ; Prevalence ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Time Factors ; Fatigue/epidemiology ; },
abstract = {BACKGROUND: During the COVID-19 pandemic, an increasing number of patients have reported persistent symptoms after recovery, a phenomenon known as long COVID. These symptoms may persist for weeks or months, affecting the patient's daily life and health. To systematically understand the long-term impact of long COVID, this study conducted a systematic review and meta-analysis. This study aims to determine the long-term effects of long COVID by identifying, evaluating and summarising the incidence and duration of persistent symptoms after the acute phase of COVID-19.

METHOD: We searched PubMed, Embase, and medRxiv up to August 2021 for articles and preprints presenting original research on the symptoms of long COVID. Following title/abstract and full-text screening, based on the PICOS framework, we excluded articles that did not clearly report on diagnoses, reported on symptoms lasting less than four weeks, lacked epidemiological data, or did not provide complete data. We assessed the bias of included studies using the Newcastle-Ottawa Scale. For effects reported in more than two studies, we performed meta-analysis of prevalence, and also counted the duration of each symptom.

RESULTS: We included 19 observational studies in the meta-analysis, through which we determined the incidence and duration of five common long COVID symptoms, including cognitive/memory/attention disorders (36%, unreported duration), fatigue (34%, 5.5 months), mental health problems (including anxiety and depression, 31%, 3.5-3.8 months), and dyspnoea (24%, 6.52 months) and chest pain (23%, 2 months).

CONCLUSIONS: The symptoms of long COVID usually persist after the acute phase of COVID-19. The clustering of long COVID symptoms provides a direction for studying the aetiology, diagnosis, and management of post-COVID conditions. Our findings provide important baseline data for the prevention and treatment of long COVID.},
}

Humans
*COVID-19/epidemiology/complications
Prevalence
Post-Acute COVID-19 Syndrome
SARS-CoV-2
Time Factors
Fatigue/epidemiology

@article {pmid41094377,
year = {2025},
author = {Arab, Z and Shayanfar, N and Mojaver, MR and Khormali, M and Boskabady, MH and Niazmand, S},
title = {Cardiopulmonary crosstalk in Long COVID: a systematic review of emerging evidence.},
journal = {BMC cardiovascular disorders},
volume = {25},
number = {1},
pages = {742},
pmid = {41094377},
issn = {1471-2261},
mesh = {Humans ; *COVID-19/physiopathology/complications ; Renin-Angiotensin System ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Endothelium, Vascular/physiopathology ; *Pulmonary Fibrosis/physiopathology ; },
abstract = {BACKGROUND: Long COVID is a complex, multisystem syndrome with significant cardiopulmonary implications. Persistent inflammation, endothelial dysfunction, and microvascular injury contribute to prolonged symptoms such as dyspnea, chest pain, and exercise intolerance. Despite growing recognition of these complications, the underlying mechanisms of cardiopulmonary interactions remain poorly understood.

METHODS: A comprehensive literature search was conducted on PubMed, Scopus, Google Scholar, and Web of Science covering studies from 2019 to 2025. Keywords included "Long COVID", "cardiopulmonary interaction", "pulmonary fibrosis", "myocardial inflammation", and "endothelial dysfunction". A total of 102 articles were included, comprising 65 original research studies and 37 review articles.

RESULTS: Pulmonary sequelae, such as fibrotic remodeling, persistent hypoxia, and microthrombosis, impose significant strain on the cardiovascular system, exacerbating myocardial inflammation, arrhythmias, and endothelial dysfunction. Shared mechanisms, such as oxidative stress, immune dysregulation, and neurohumoral activation, create a vicious cycle of sustained cardiopulmonary impairment. The disruption of the renin-angiotensin-aldosterone system (RAAS) further contributes to systemic vascular dysregulation.

CONCLUSION: A deeper understanding of cardiopulmonary interactions in Long COVID is essential for developing effective management strategies. Targeting inflammatory pathways, restoring endothelial function, and addressing autonomic instability may provide therapeutic benefits. As the long-term impact of this syndrome continues to evolve, further research is needed to refine treatment approaches and mitigate its burden on global health.},
}

Humans
*COVID-19/physiopathology/complications
Renin-Angiotensin System
Post-Acute COVID-19 Syndrome
SARS-CoV-2
*Endothelium, Vascular/physiopathology
*Pulmonary Fibrosis/physiopathology

@article {pmid41091675,
year = {2025},
author = {Nagra, G and Ezeugwu, VE and Bostick, GP and Branton, E and Dennett, L and Drake, K and Durand-Moreau, Q and Guptill, C and Hall, M and Ho, C and Hung, P and Khan, A and Lam, GY and Nowrouzi-Kia, B and Gross, DP},
title = {Return-to-work for people living with long COVID: A scoping review of interventions and recommendations.},
journal = {PloS one},
volume = {20},
number = {10},
pages = {e0321891},
doi = {10.1371/journal.pone.0321891},
pmid = {41091675},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/rehabilitation/epidemiology ; *Return to Work ; SARS-CoV-2/isolation & purification ; },
abstract = {INTRODUCTION: Long COVID is characterized by the presence of new onset or persistent symptoms 3 months after a suspected or confirmed history of SARS-CoV-2 infection. It is a complex and multi-faceted condition that affects people in different ways. Long COVID affects individuals' labour market participation. While some cannot work, others may return to work (RTW) in a limited capacity. Determining what rehabilitation or related strategies are safe and effective for facilitating RTW is necessary.

OBJECTIVES: To synthesize evidence on RTW interventions for people living with Long COVID and to identify 'promising' interventions for enhancing work ability and RTW.

METHODS: We followed Arksey & O'Malley's methodology and the PRISMA extension for scoping reviews. Five electronic bibliographic databases and grey literature were searched. The literature search included various study designs, such as randomized controlled trials (RCT), quasi-experimental designs, and observational studies as well as clinical practice guidelines (CPGs). Two reviewers conducted screening and data extraction, with disagreements resolved through consensus. Intervention studies were categorized as promising (statistically significant RTW outcomes or ≥ 50% RTW), somewhat promising (20% to < 50% RTW), not promising (non-statistically significant RTW outcomes or < 20% RTW), or uncertain (did not specify proportion of RTW).

RESULTS: Twelve CPGs and nineteen intervention studies were identified. Of the intervention studies, 5 were cohort studies, 3 quasi-experimental studies, 4 observational, 2 interventional, 3 RCTs, and 2 case reports. Promising interventions included multimodal and interdisciplinary work-focused rehabilitation, multidisciplinary inpatient and outpatient rehabilitation, psychoeducation, pacing, and breathing strategies, shifting focus from symptom monitoring to optimizing functional outcomes, enhanced external counterpulsation inflatable pressure to improve blood flow, and constraint-induced cognitive therapy.

CONCLUSION: Many uncertainties remain regarding which RTW interventions are effective or the optimal characteristics of these interventions.},
}

Humans
*COVID-19/rehabilitation/epidemiology
*Return to Work
SARS-CoV-2/isolation & purification

@article {pmid41089587,
year = {2025},
author = {Albazee, E and Alajmi, SA and Alkandari, AM and Aladwani, AN and Alenezi, YY and Alsaeed, MA and Uqlah, B and Abu-Zaid, A},
title = {Platelet-Rich Plasma for COVID-19-Related Olfactory Dysfunction: A Systematic Review and Meta-analysis of Randomized Controlled Trials.},
journal = {Cureus},
volume = {17},
number = {10},
pages = {e94386},
pmid = {41089587},
issn = {2168-8184},
abstract = {A notable rise in olfactory dysfunction (OD) prevalence has been observed since the COVID-19 pandemic. COVID-19-related OD is associated with several consequences, especially deteriorated quality of life. Hence, several treatment options have been investigated, with platelet-rich plasma (PRP) showing promising results. A systematic review and meta-analysis summarizing randomized controlled trial (RCT) evidence were retrieved from PubMed, Google Scholar, Scopus, and Web of Science up to June 2025. The risk of bias was assessed using the Cochrane Risk of Bias 2 assessment tool. Data were analyzed using Stata MP version 18 (StataCorp LLC, College Station, TX), pooling dichotomous outcomes as relative risks (RRs) and continuous outcomes as standardized mean differences (SMDs), each with 95% confidence intervals (CIs). Four RCTs, including 198 participants, were included in our meta-analysis. PRP significantly improved objective olfactory scores (SMD = 1.86, 95% CI (0.14, 3.57), p = 0.03) and subjective olfactory scores (SMD = 0.92, 95% CI (0.32, 1.51), p < 0.001). Additionally, PRP significantly increased the response rate (RR = 1.79, 95% CI (1.14, 2.81), p = 0.01). PRP was generally well-tolerated across the included trials, with no major adverse events reported. Two RCTs showed an overall low risk of bias, one trial showed some concerns, and another showed a high risk of bias. With uncertain evidence, PRP may improve both objective and subjective smell function and clinical outcomes in people with long COVID-related OD. PRP treatment was reported to be safe, with minor, temporary side effects primarily related to the procedure. Although initial results are promising, the small number of RCTs requires a cautious approach to interpretation.},
}

@article {pmid41089328,
year = {2025},
author = {Blitshteyn, S and Funez-dePagnier, G and Szombathy, A and Hutchinson, M},
title = {Immunotherapies for postural orthostatic tachycardia syndrome, other common autonomic disorders, and Long COVID: current state and future direction.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1647203},
pmid = {41089328},
issn = {2235-2988},
mesh = {Humans ; *Postural Orthostatic Tachycardia Syndrome/therapy/immunology ; *COVID-19/therapy/immunology/complications ; *Immunotherapy/methods/trends ; *Autonomic Nervous System Diseases/therapy/immunology ; Immunoglobulins, Intravenous/therapeutic use ; SARS-CoV-2 ; Plasmapheresis ; Adrenal Cortex Hormones/therapeutic use ; Post-Acute COVID-19 Syndrome ; },
abstract = {Postural orthostatic tachycardia syndrome (POTS), neurocardiogenic syncope, and orthostatic hypotension are the most common autonomic disorders encountered in clinical practice. The autoimmune etiology and association of these conditions with systemic autoimmune and inflammatory disorders, autonomic neuropathy, and post-acute infectious syndromes, including Long COVID, suggest that immunotherapies should be considered as a therapeutic option, at least in a subset of patients. However, the treatment of common autonomic disorders has traditionally included pharmacologic and non-pharmacologic symptomatic therapies as the standard approach. Unfortunately, these symptomatic therapies have been of limited or insufficient efficacy to meaningfully improve functional status or result in recovery, especially in patients with severe symptoms. Case reports, case series, and clinical experience suggest that intravenous and subcutaneous immunoglobulin, as well as other immunologic therapies (such as plasmapheresis, corticosteroids, and rituximab), may be effective in some patients with severe POTS and other common autonomic disorders who are refractory to standard therapies. In this narrative review, we summarize the literature available on the topic of immunotherapies for POTS, other common autonomic disorders, and Long COVID. We also highlight the need for large, multicenter, placebo-controlled trials of immunoglobulin, plasmapheresis, intermittent corticosteroids, and other repurposed immunotherapies in patients with common autonomic disorders who have significant functional impairment.},
}

Humans
*Postural Orthostatic Tachycardia Syndrome/therapy/immunology
*COVID-19/therapy/immunology/complications
*Immunotherapy/methods/trends
*Autonomic Nervous System Diseases/therapy/immunology
Immunoglobulins, Intravenous/therapeutic use
SARS-CoV-2
Plasmapheresis
Adrenal Cortex Hormones/therapeutic use
Post-Acute COVID-19 Syndrome

@article {pmid41087378,
year = {2025},
author = {Yonker, LM and Dredge, D and Munro, A and Di Chiara, C and Cotugno, N and Buonsenso, D},
title = {The second-order effects that the COVID-19 pandemic has had on pediatric populations.},
journal = {Expert review of anti-infective therapy},
volume = {},
number = {},
pages = {},
doi = {10.1080/14787210.2025.2575044},
pmid = {41087378},
issn = {1744-8336},
abstract = {INTRODUCTION: There is growing recognition that SARS-CoV-2 can have long-term health consequences that persist beyond acute infection. While the long-term health impact of SARS-CoV-2 is evident in adults and the elderly, the impact on children and adolescents remains under recognized. In this paper, we navigate the second-order post-acute effects that the COVID-19 has had on the pediatric populations, with the exception of mental health implication of social restrictions, out of the scope of this review.

AREAS COVERED: We outline common scenarios related with SARS-CoV-2 infection encountered in pediatric clinical practice, such as in the Multisystem inflammatory syndrome (MIS-C), Long Covid, neurological and autoimmune complications of Covid-19, immunological impact of the viral infection, as well as epidemiological and public health consequences associated with the implementation of non-pharmacological interventions.

EXPERT OPINION: SARS-CoV-2 has had several second-order effects on child health, from a biological, epidemiological, and public health perspective, highlighting the complexity of dealing with new infections and the urgent need to implement multidisciplinary interventions that support the health of people at single person and societal level. Funding on modern surveillance system, preventing strategies and research to better understand and cure post-acute complications of viral infections should be a priority of every funding agency.},
}

@article {pmid41082082,
year = {2025},
author = {Wasim, R},
title = {From infection to intervention: post-acute sequelae of SARS-CoV-2 infection and cardiovascular risk.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {41082082},
issn = {1568-5608},
abstract = {COVID is now a worldwide epidemic of non-communicable diseases. The symptoms, which impact several organs, might last for hours, weeks, or even months after the SARS-CoV-2 infection has ended. Electrocardiogram abnormalities (ECG), postural orthostatic tachycardia, and supraventricular or ventricular arrhythmias are among the common signs of long COVID-19. According to data, certain patient groups have persistent, post-infectious perimyocarditis, which may lead to left or right ventricular failure, arterial wall inflammation, or microthrombosis. This information has been made available by cardiac and vasculature imaging, and it may be used to develop efficient treatment plans for the cardiovascular symptoms of long COVID. Long COVID requires a greater understanding of the cellular and molecular processes. There are a variety of approaches that have been put forward, some of which include direct impacts on the heart and others that involve microthrombotic damage to the arteries or heart. When evaluated 3 months after SARS-CoV-2 infection, the currently employed circulating biomarkers, such as coagulation and inflammatory markers, do not serve as a highly predictive predictor for the existence or outcome of long COVID. However, further study is required to better understand the underlying processes and particular biomarkers for future COVID preventive methods.},
}

@article {pmid41076807,
year = {2025},
author = {Domingo, JL},
title = {Differentiating COVID-19 vaccine-related adverse events from long COVID: A comprehensive review of clinical manifestations, pathophysiology, and diagnostic approaches.},
journal = {Vaccine},
volume = {66},
number = {},
pages = {127842},
doi = {10.1016/j.vaccine.2025.127842},
pmid = {41076807},
issn = {1873-2518},
abstract = {The global deployment of COVID-19 vaccines has introduced diagnostic challenges due to overlapping symptoms with long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), prompting a comprehensive review of vaccine safety profiles, long COVID manifestations, and evidence-based differentiation strategies. Through a literature search (PubMed, Scopus, Web of Science) from December 2020 to June 2025, including peer-reviewed studies, clinical trials, and cohort studies, the present review reports that COVID-19 vaccines maintain robust safety, with rare adverse events like myocarditis and thrombosis with thrombocytopenia syndrome, while long COVID affects 10-40 % of SARS-CoV-2 survivors, presenting symptoms such as fatigue, cognitive dysfunction, and dyspnea. Differentiation between these conditions relies on careful analysis of the timing of symptom onset, detailed symptom characterization, and the use of advanced diagnostic tools. Systematic clinical assessment is essential for accurate diagnosis, which is critical for appropriate patient management, maintaining public confidence in vaccination, and guiding future research. Further studies are needed to validate diagnostic biomarkers, develop targeted therapies, and monitor long-term outcomes, with standardized global registries and interdisciplinary collaboration identified as key priorities for improving care and advancing the field.},
}

@article {pmid41073921,
year = {2025},
author = {Takamatsu, N and Kuga, H},
title = {Applicability and adaptation of cognitive behavior therapy for long COVID neuropsychiatric symptoms: a review with insights from ME/CFS.},
journal = {BMC infectious diseases},
volume = {25},
number = {1},
pages = {1275},
pmid = {41073921},
issn = {1471-2334},
support = {JP23K02953//Japan Society for the Promotion of Science/ ; },
}

@article {pmid41073313,
year = {2025},
author = {Wang, MC and Liu, X and Hu, K},
title = {[Intermittent hypoxia exposure in the rehabilitation of long COVID patients].},
journal = {Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases},
volume = {48},
number = {10},
pages = {961-964},
doi = {10.3760/cma.j.cn112147-20250601-00295},
pmid = {41073313},
issn = {1001-0939},
support = {JCRCYG-2022-012//Interdisciplinary Innovative Talents Foundation from Renmin Hospital of Wuhan University/ ; },
mesh = {Humans ; *COVID-19/rehabilitation ; *Hypoxia/rehabilitation ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Fatigue ; },
abstract = {Patients recovering from COVID-19 infection often experience "Long COVID", which is characterized by symptoms such as fatigue, reduced exercise capacity or dyspnea, and cognitive dysfunction. These symptoms negatively impact their quality of life. Currently, there is a lack of widely recognized therapeutic approaches or specific pharmacological interventions for managing these conditions. During intermittent hypoxic exposure (IHE), participants are alternated to hypoxic and normoxic exposure, which induced beneficial adaptive responses in the body. Emerging evidence suggests that IHE can alleviate symptoms of Long COVID through mechanisms such as improving ventilatory function, enhancing cardiopulmonary endurance, modulating immune responses, and reducing inflammation. These effects contribute to an improved quality of life and more holistic recovery, highlighting the promising potential of IHE in managing long COVID.},
}

Humans
*COVID-19/rehabilitation
*Hypoxia/rehabilitation
Quality of Life
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Fatigue

@article {pmid41065846,
year = {2025},
author = {Chang, CC and Li, YH and Chen, HH and Sun, SF},
title = {Clinical applications and molecular mechanisms for intravenous laser blood irradiation: a systematic review.},
journal = {Lasers in medical science},
volume = {40},
number = {1},
pages = {416},
pmid = {41065846},
issn = {1435-604X},
support = {TSGH-D-110120//Tri-Service General Hospital/ ; VTA114-V3-1-2//Taipei, Taichung, Kaohsiung Veterans General Hospital, Tri-Service General Hospital, Academia Sinica Joint Research Program/ ; VTA114-V3-1-1//Taipei, Taichung, Kaohsiung Veterans General Hospital, Tri-Service General Hospital, Academia Sinica Joint Research Program/ ; KAFGH-ZY-A-113016//Zuoying Armed Forces General Hospital/ ; KSVGH-114-102//Kaohsiung Veterans General Hospital/ ; },
mesh = {Humans ; *Low-Level Light Therapy/methods ; Cardiovascular Diseases/radiotherapy ; *Blood/radiation effects ; Musculoskeletal Diseases/radiotherapy ; COVID-19 ; Nervous System Diseases/radiotherapy ; },
abstract = {Intravenous Laser Irradiation of Blood (ILIB) is a therapeutic approach that utilizes low-level laser energy to irradiate blood, showing potential clinical value in treating various diseases in recent years. This systematic review aims to comprehensively examine the basic principles, technological developments, biological effects, and clinical applications of ILIB, while analyzing the level of evidence and limitations of existing research. Through searching relevant literature in databases such as PubMed, this study collected research on ILIB applications in musculoskeletal diseases, respiratory diseases, cardiovascular diseases, and neurological disorders. Results indicate that ILIB exhibits multiple biological effects, including improved blood rheological properties, enhanced erythrocyte oxygen-carrying capacity, immune regulation, and reduction of inflammatory responses and oxidative stress. Clinical studies suggest that ILIB has positive therapeutic effects on musculoskeletal pain, sleep disorders, pulmonary diseases, and long COVID-related cognitive impairments. However, existing research still has limitations such as small sample sizes, lack of large-scale randomized controlled trials, and non-standardized dosage parameters. Future research should focus on developing standardized treatment protocols, exploring mechanisms of action in depth, and strategies for combining with conventional therapies to further establish ILIB's position in clinical practice.},
}

Humans
*Low-Level Light Therapy/methods
Cardiovascular Diseases/radiotherapy
*Blood/radiation effects
Musculoskeletal Diseases/radiotherapy
COVID-19
Nervous System Diseases/radiotherapy

@article {pmid41062170,
year = {2025},
author = {Houweling, L and Rots, I and Bloemsma, LD and van Vorstenbosch, R and Del Motto, S and Vermeulen, RCH and Maitland-Van der Zee, AH and Golebski, K and Downward, GS},
title = {Impact of air pollution on COVID-19 severity: a systematic review of underlying biological mechanisms.},
journal = {European respiratory review : an official journal of the European Respiratory Society},
volume = {34},
number = {178},
pages = {},
doi = {10.1183/16000617.0070-2025},
pmid = {41062170},
issn = {1600-0617},
mesh = {Humans ; *COVID-19/epidemiology/immunology/virology ; *Air Pollution/adverse effects ; Severity of Illness Index ; SARS-CoV-2 ; Particulate Matter/adverse effects ; *Air Pollutants/adverse effects ; },
abstract = {BACKGROUND: Our recent systematic review highlighted key associations between ambient air pollution (AAP) exposure and COVID-19 severity. This systematic review aims to summarise toxicological studies on the biological mechanisms underlying these associations.

METHODS: On 17 July 2025, PubMed, Embase, Scopus and Web of Science were searched for in vitro, in vivo and in silico studies that examined the biological mechanisms of AAP exposure on COVID-19 health outcomes. Two independent reviewers engaged in the selection and data extraction process. The methodological quality of the included studies was assessed with the Toxicological Data Reliability Assessment Tool. The Integrated Network and Dynamical Reasoning Assembler (INDRA) was used to provide visual biomechanistic summaries of the included studies by creating knowledge graphs of the described mechanisms.

RESULTS: A total of 18 studies were included in this review. Findings consistently indicated that AAP exposure can worsen COVID-19 severity through two key mechanisms 1) increased expression of viral entry factors (e.g. angiotensin-converting enzyme 2 and transmembrane serine protease 2), facilitating infection, and 2) immune dysregulation, resulting in increased inflammation and oxidative stress. These key mechanisms were also identified in the INDRA networks. While studies commonly focused on particulate matter (n=15), similar effects were seen with ultrafine particles and ozone.

CONCLUSION: These findings highlight the impact of AAP exposure on COVID-19 health outcomes on the molecular level. The findings of this review illustrate the urgent need for air quality improvements to help shape public health strategies to reduce and prevent future health impacts caused by AAP exposure.},
}

Humans
*COVID-19/epidemiology/immunology/virology
*Air Pollution/adverse effects
Severity of Illness Index
SARS-CoV-2
Particulate Matter/adverse effects
*Air Pollutants/adverse effects

@article {pmid41062137,
year = {2025},
author = {Daniels, S and Wei, H and McElvenny, DM and van Tongeren, M and Bramwell, D and Coleman, A and Forde, D and Wiggans, R},
title = {Return to work with long COVID: a rapid review of support and challenges.},
journal = {BMJ open},
volume = {15},
number = {10},
pages = {e101698},
doi = {10.1136/bmjopen-2025-101698},
pmid = {41062137},
issn = {2044-6055},
mesh = {Humans ; *Return to Work ; *COVID-19/rehabilitation ; SARS-CoV-2 ; Workplace ; },
abstract = {OBJECTIVES: To explore existing evidence for the provision of support for return to work (RTW) in long COVID (LC) patients and the barriers and facilitators to taking up this support.

DESIGN: A rapid review reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The study was preregistered in PROSPERO (ID: CRD42023478126).

DATA SOURCES: Searches were completed in June 2024 across major databases including MEDLINE, Embase, PsycINFO, evidence-based medicine reviews, Web of Science and Google Scholar.

ELIGIBILITY CRITERIA: Included studies focused on people with LC (PwLC) symptoms lasting over 12 weeks and addressed either: (1) non-workplace- or workplace-based support for RTW and/or (2) barriers and facilitators to RTW in this population.

DATA EXTRACTION AND SYNTHESIS: A quality assessment was conducted using the JBI Systematic Reviews critical appraisal tool. The data were summarised in tabular format and a narrative synthesis.

RESULTS: Twenty-five studies were included. While many studies demonstrated rigorous methodologies and low risk of bias levels, some had high and medium risk levels. Non-workplace-based support was mostly measured quantitatively and included interdisciplinary healthcare programmes, clinical interventions and rehabilitation programmes focusing on pacing and breathing strategies. Compensation and insurance schemes were important funders of these interventions.Workplace-based support was mostly measured qualitatively. Barriers to the provision of support at organisational level included lack of understanding of LC symptoms, insufficient workplace guidance and educational gaps among managers. Individual barriers included threat of income loss, remote working and disconnection from the workplace. Facilitators for support included recognition and validation of LC and its symptoms, and eligibility for disability benefits associated with work.

CONCLUSIONS: RTW is an important outcome of health-related absence and should be systematically recorded in studies of PwLC. The heterogeneity and unpredictability of LC symptoms create challenges for supporting working age populations. Further research is crucial to better understand the specific RTW needs for PwLC and address potential barriers and facilitators to workplace-based support, particularly through interventions, organisational practices and employ-led policies that enable sustained RTW. Consistent guidelines on LC's definition and disability status may facilitate the provision of support and the development of interventions.

PROSPERO REGISTRATION NUMBER: CRD42023478126.},
}

Humans
*Return to Work
*COVID-19/rehabilitation
SARS-CoV-2
Workplace

@article {pmid41057923,
year = {2025},
author = {Gidey, K and Niriayo, YL and Asgedom, SW and Lubetkin, E},
title = {Health-related quality of life in COVID-19 patients: a systematic review and meta-analysis of EQ-5D studies.},
journal = {Health and quality of life outcomes},
volume = {23},
number = {1},
pages = {97},
pmid = {41057923},
issn = {1477-7525},
support = {1627-RA//EuroQol Research Foundation/ ; 1627-RA//EuroQol Research Foundation/ ; 1627-RA//EuroQol Research Foundation/ ; 1627-RA//EuroQol Research Foundation/ ; },
abstract = {BACKGROUND: COVID-19 has affected millions globally, with a significant proportion experiencing long-COVID and impaired health-related quality of life (HRQoL). This systematic review and meta-analysis aimed to synthesize the existing literature on HRQoL in COVID-19 patients.

METHODS: We conducted a systematic search of PubMed, Embase, Web of Science, Scopus, and the Cochrane Library for studies published between December 2019 and March 2025. Eligible studies were peer-reviewed and assessed HRQoL in COVID-19 patients using the EQ-5D instrument. Study quality and risk of bias were evaluated using the Newcastle-Ottawa Scale. Pooled health utility values were estimated using a random-effects model, and heterogeneity was assessed via I[2] statistics. Predictors of poor HRQoL were qualitatively narrated.

RESULTS: Out of 3539 references, 187 studies with 116,525 participants were analyzed. The majority (80.2%) used the EQ-5D-5 L version. The pooled mean EQ-5D utility score was 0.76 (95% CI 0.74-0.79, I[2] = 99.9%) while the mean EQ-5D Visual Analogue Scale (VAS) score was 70.76 (95% CI 68.48-73.04; I[2] = 99.7%). Pain/discomfort and anxiety/depression were the most affected domains, reported by 51% and 46% of patients, respectively. Subgroup analysis showed significant differences in HRQoL based on national income status (p = 0.038) and geographic region (p < 0.001). Common predictors of lower HRQoL included older age, female gender, disease severity, comorbidities, and post-COVID-19 symptoms.

CONCLUSION: This systematic review demonstrates a substantial reduction in HRQoL among COVID-19 patients compared to the general population. The pooled utility values of COVID-19 contribute to understanding patients' HRQoL and can assist in calculating Quality-Adjusted Life Years. This provides essential data for future economic evaluations and informs health policy decisions.},
}

@article {pmid41057797,
year = {2025},
author = {Bessaguet, C and Bonilla, A and Polin, C and Lacroix, A and Cartz-Piver, L},
title = {A systematic review to find link between past psychiatric history and development of long covid.},
journal = {BMC psychiatry},
volume = {25},
number = {1},
pages = {942},
pmid = {41057797},
issn = {1471-244X},
abstract = {BACKGROUND: Covid-19 is a pandemic acute infectious disease that emerged in 2019. It is estimated that 10-20% will develop persistent symptoms, known as long Covid or post-Covid syndrome. The risk factors for the development of this syndrome are still being studied. Psychosocial factors are known to increase the duration and severity of respiratory infections.

AIMS: (i) to review current knowledge of the link between past psychiatric history and the development of long Covid; (ii) to obtain information on the psychological experience of the initial infection; (iii) to establish a link between the presence of psychiatric symptoms during the acute phase and the development of long Covid.

METHOD: We conducted a systematic review according to PRISMA standards using the Pubmed, Science Direct and Scopus databases. We included observational studies of adult subjects with long Covid whose psychiatric and/or addictive histories were searched.

RESULTS: A total of 36 articles were included in our review. Depression and anxiety appear to be risk factors for the development of long Covid. There is no consensus on the contribution of smoking to the onset of the syndrome. The negative psychological experience of the acute infection favours the persistence of symptoms. Psychological symptoms during the acute phase, studied in only one of our articles, seem to contribute to the persistence of concentration and attention problems.

CONCLUSION: Psychological comorbidities pre-existing COVID-19 infection, in particular depression and anxiety, as well as a poor psychological experience of the acute phase, may favour the development of long Covid.

TRIAL REGISTRATION NUMBER: PROSPERO registration number CRD42023391720.},
}

@article {pmid41056092,
year = {2025},
author = {Newby, MJ and Haracz, K and Lane, SJ and Tona, J},
title = {Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and Occupational Performance: A Scoping Review.},
journal = {The American journal of occupational therapy : official publication of the American Occupational Therapy Association},
volume = {79},
number = {6},
pages = {},
doi = {10.5014/ajot.2025.051238},
pmid = {41056092},
issn = {0272-9490},
mesh = {Humans ; *Occupational Therapy/methods ; Child ; *Obsessive-Compulsive Disorder/rehabilitation ; *Activities of Daily Living ; Social Participation ; Autoimmune Diseases ; },
abstract = {IMPORTANCE: Pediatric acute-onset neuropsychiatric syndrome (PANS) is a neuroimmune condition that significantly affects children's occupational performance across multiple domains. However, occupational performance is often overlooked in current PANS clinical frameworks, despite its critical role in daily functioning and well-being.

OBJECTIVE: To synthesize evidence on the occupational performance challenges experienced by children with PANS, the tools used to assess these challenges, and occupational therapy interventions used with these children.

DATA SOURCES: MEDLINE, CINAHL, Cochrane Library, PsycINFO, SCOPUS, ERIC, and EMBASE were searched from their inception through May 17, 2024.

Peer-reviewed studies addressing PANS and occupational performance were included, with data categorized using the Occupational Therapy Practice Framework, 4th Edition.

FINDINGS: Of 3,431 records, 40 studies met inclusion criteria. Occupational performance challenges centered on communication, nutrition, education, rest/sleep, social participation, and toileting, with limited data on bathing, dressing, personal hygiene, and play and leisure. Assessments emphasized client factors, rarely using occupation-based tools. Only 2 studies mentioned occupational therapy interventions.

CONCLUSIONS AND RELEVANCE: PANS has a pervasive impact on children's occupational performance, highlighting the urgent need to prioritize it within clinical frameworks. Future research should focus on occupation-based intervention studies and assessments to enhance outcomes for children with PANS. Plain-Language Summary: Pediatric acute-onset neuropsychiatric syndrome (PANS) causes sudden, severe symptoms, such as obsessive-compulsive behaviors, eating difficulties, sensory and motor changes, and developmental regression, which significantly disrupt children's ability to perform daily activities. This study included 40 research articles addressing what is known about the impact of PANS on children's daily functioning and the role of occupational therapy in managing challenges. Results showed that most studies focused on communication, nutrition, education, sleep, social, and toileting challenges, but few addressed other daily tasks like bathing, dressing, personal hygiene, and play or leisure. Despite identified challenges, only two studies mentioned occupational therapy interventions, highlighting a major gap in the evidence. Assessments focused mainly on a child's skills and challenges, rather than looking at how the child participates in everyday activities. The findings highlight the need to better understand the challenges children with PANS face in their everyday activities and to provide practical strategies to help them succeed. Positionality Statement: Newby is a pediatric occupational therapist and researcher with both professional and personal experience of PANS. Her clinical work with children diagnosed with PANS, along with personal experience supporting a family member with this condition, has deepened her interest in the episodic fluctuations in occupational performance that occur during periods of exacerbation and remission. Haracz is an occupational therapist, academic, and researcher with a focus on mental health and the intersection between physical and psychological well-being. Lane is an occupational therapist, academic, and researcher who specializes in the neuroscience of developmental conditions and how sensory processing differences affect children's engagement in daily occupations. Tona is an occupational therapist and educational psychologist whose interest in neuroinflammatory disorders emerged following a family member's diagnosis with PANS. Her research explores the characteristics of PANS, treatment access, caregiver burden, and the role of occupational therapy in improving participation in both PANS and long-COVID populations.},
}

Humans
*Occupational Therapy/methods
Child
*Obsessive-Compulsive Disorder/rehabilitation
*Activities of Daily Living
Social Participation
Autoimmune Diseases

@article {pmid41049923,
year = {2025},
author = {Pedraza, A and Bonnice, S and Won, MN and Kesselman, MM and Demory Beckler, M},
title = {Impact of COVID-19 on the Gut Microbiome: A Review.},
journal = {Cureus},
volume = {17},
number = {9},
pages = {e91470},
pmid = {41049923},
issn = {2168-8184},
abstract = {Coronavirus Disease 2019 (COVID-19) has resulted in over 6 million deaths worldwide in fewer than four years and is a result of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The protein that mediates SARS-CoV-2 host cell entry is the angiotensin-converting enzyme 2 (ACE2), which is highly expressed on the membrane of gastrointestinal (GI) cells. Consequently, infection can lead to direct damage to the GI tract and gut dysbiosis, which is associated with an imbalance of microbiota, inflammation, and other systemic infections and diseases. In this review, we will focus on the impact of COVID-19 on the GI system. We will examine the pathophysiology of gut dysbiosis in COVID-19 patients, as well as emphasize the significance of probiotics in addressing this condition. Additionally, we will identify key areas of interest that warrant further investigation.},
}

@article {pmid41049897,
year = {2025},
author = {Castellano, B and Castellano, C and Sobczak, A and Khanna, D},
title = {Long-Term Manifestations of COVID-19: A Review.},
journal = {Cureus},
volume = {17},
number = {9},
pages = {e91492},
pmid = {41049897},
issn = {2168-8184},
abstract = {Although most coronavirus disease 2019 (COVID-19) cases resolve within a few weeks after the onset of infection, a considerable number of patients still suffer from prolonged or recurrent symptoms evident after weeks or months post-COVID-19 recovery. This paper analyzed the current literature related to long-term manifestations of COVID-19 and aimed to identify the common symptoms reported four weeks or more after the initial onset of the disease. COVID-19 has been shown to have lasting systemic effects on an array of organ systems, such as the lungs, heart, brain, and gastrointestinal systems. Common symptoms include, but are not limited to, fatigue, brain fog, respiratory difficulties, and loss of taste and smell. The impact of COVID-19 on multiple organ systems is thought to be associated with its ability to bind angiotensin-converting enzyme 2 (ACE2) receptors throughout the body and promote cytokine release. This study provides insight into common long-term manifestations of COVID-19. Future studies should look at how long COVID-19 syndrome affects various subpopulations differently.},
}

@article {pmid41048263,
year = {2025},
author = {Verma, A and Naidu, SV and Sulthana, H and Ullah, A and Shabil, M and Sah, R and Mehta, R and Jan, A and Ain, NU and Rahim, A and Abu Nahla, U},
title = {Musculoskeletal manifestations in post-acute sequelae of SARS-CoV-2 infection: a systematic review and meta-analysis.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1662953},
pmid = {41048263},
issn = {2296-2565},
mesh = {Humans ; *COVID-19/complications/epidemiology ; *Musculoskeletal Diseases/epidemiology/etiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Prevalence ; Incidence ; Myalgia/epidemiology ; },
abstract = {BACKGROUND: The COVID-19 pandemic has highlighted a spectrum of long-term sequelae, with musculoskeletal symptoms being a substantial component of Post-Acute Sequelae of SARS-CoV-2 infection (PASC). This systematic review and meta-analysis aimed to evaluate the incidence and nature of musculoskeletal manifestations in individuals recovering from COVID-19.

METHODS: A systematic search across PubMed, Embase, and Web of Science was performed up to February 15, 2024, to identify studies reporting on musculoskeletal symptoms post-COVID-19. Observational studies which reported any musculoskeletal symptoms of PASC were included. Data were pooled using a random-effects model to calculate the incidence of symptoms, with subgroup analyses based on time since infection. Statistical analysis were conducted in R software (V 4.3).

RESULTS: Sixty-four studies were included, demonstrating a pooled prevalence of muscle pain at 28% (95% CI: 22%-35%), which increased to 25.9% (95% CI: 20.7%-31.7%) at 12 months post-infection. Joint pain showed a pooled prevalence of 14.8% (95% CI: 10.6%-20.2%), with no significant temporal change. Muscle weakness was observed in 12.9% (95% CI: 4.2%-32.9%) of patients. Notable heterogeneity was observed across studies (I [2] > 89% for all symptoms).

CONCLUSION: Musculoskeletal symptoms are prevalent in individuals with PASC, with muscle pain being the most common. The findings highlight the need for comprehensive clinical management and continuous research to create targeted treatments and revise care protocols as the pandemic evolves.},
}

Humans
*COVID-19/complications/epidemiology
*Musculoskeletal Diseases/epidemiology/etiology
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Prevalence
Incidence
Myalgia/epidemiology

@article {pmid41038267,
year = {2025},
author = {Thomas, D and Yang, PC and Wu, JC and Sayed, N},
title = {Decoding long COVID-associated cardiovascular dysfunction: Mechanisms, models, and new approach methodologies.},
journal = {Journal of molecular and cellular cardiology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.yjmcc.2025.09.008},
pmid = {41038267},
issn = {1095-8584},
abstract = {The COVID-19 pandemic has revealed that the impact of SARS-CoV-2 infection extends well beyond the acute phase, with long-term sequelae affecting multiple organ systems, most notably, the cardiovascular system. Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by persistent symptoms such as fatigue, dyspnea, chest pain, and palpitations, which can last for months or even years after initial recovery. Increasing evidence implicates immune dysregulation, endothelial dysfunction, persistent viral antigens, and coagulopathy as central drivers of cardiovascular complications. Mechanistic studies demonstrate that direct viral infection of cardiac and vascular cells, along with autoantibody formation and cytokine-mediated injury, contribute to myocardial inflammation, fibrosis, and arrhythmias. Sex-based immunological differences and underlying comorbidities further influence individual susceptibility and disease trajectory. Large-scale epidemiological studies have confirmed significantly increased risks of pericarditis, cardiomyopathy, dysrhythmias, and heart failure among COVID-19 survivors. In parallel, the emergence of advanced preclinical platforms, including patient-derived induced pluripotent stem cell (iPSC)-based cardiac organoids, engineered heart tissues, and organ-on-a-chip systems has enabled mechanistic dissection of Long COVID pathophysiology. These human-relevant models, when integrated with clinical datasets and artificial intelligence (AI)-driven analytics, offer powerful tools for biomarker discovery, risk stratification, and precision therapeutic development. This review synthesizes the current understanding of cardiovascular involvement in Long COVID, highlights key mechanistic insights from both clinical and preclinical studies, and outlines future directions for diagnostic and therapeutic innovation.},
}

@article {pmid40660830,
year = {2025},
author = {Pagliano, P and Salzano, F and D'Amore, C and Spera, A and Conti, V and Folliero, V and Franci, G and Ascione, T},
title = {How do drug discovery scientists address the unmet need of long COVID syndrome therapeutics and what more can be done?.},
journal = {Expert opinion on drug discovery},
volume = {20},
number = {10},
pages = {1251-1265},
doi = {10.1080/17460441.2025.2534056},
pmid = {40660830},
issn = {1746-045X},
mesh = {Humans ; *COVID-19/complications/physiopathology ; Post-Acute COVID-19 Syndrome ; *Drug Discovery/methods ; *COVID-19 Drug Treatment ; *Antiviral Agents/pharmacology/therapeutic use/administration & dosage ; COVID-19 Vaccines/administration & dosage ; SARS-CoV-2 ; },
abstract = {INTRODUCTION: Long COVID (LC), also known as post-acute COVID-19 syndrome (PASC), has emerged as a significant public health concern characterized by persistent symptoms following SARS-CoV-2 infection. This condition affects regardless of initial illness severity and can significantly impair daily functioning. Understanding the implications of LC is crucial, given that approximately 6.9 % of adults reported related symptoms in 2022, with increased prevalence among women and individuals of Hispanic descent. The pathogenesis of LC is multifactorial, involving mechanisms such as endothelial dysfunction, chronic inflammation, immune dysregulation, and potential viral persistence. The clinical manifestations include fatigue, cognitive impairment, musculoskeletal pain, and sleep disturbances. Current research emphasizes the importance of early antiviral interventions and vaccines to mitigate the risk of developing LC. Despite promising therapies like anti-inflammatory agents and metabolic enhancers, the lack of established biomarkers complicates diagnosis and treatment.

AREAS COVERED: The authors provide an overview of the pathogenesis of LC and briefly review the currently available therapy. The authors then give their perspectives on how best future drug discovery efforts can be utilized to address the current demand for novel LC therapeutics to reduce the burden of this public health problem.

EXPERT OPINION: Progress has been made in understanding the pathophysiology and potential treatment options, as well as in establishing reliable biomarkers for potential tailored strategies. Future research should prioritize both pharmacological and non-pharmacological interventions to enhance patient outcomes and quality of life. Addressing these challenges is essential for developing comprehensive care protocols for individuals affected by LC.},
}

Humans
*COVID-19/complications/physiopathology
Post-Acute COVID-19 Syndrome
*Drug Discovery/methods
*COVID-19 Drug Treatment
*Antiviral Agents/pharmacology/therapeutic use/administration & dosage
COVID-19 Vaccines/administration & dosage
SARS-CoV-2

@article {pmid41030634,
year = {2025},
author = {Johnson, BL},
title = {"In-Flu-Enza and Out-Flew Hair:" Post-Epidemic Health and the Importance of the History of Epidemics.},
journal = {The Yale journal of biology and medicine},
volume = {98},
number = {3},
pages = {341-348},
pmid = {41030634},
issn = {1551-4056},
mesh = {Humans ; *COVID-19/epidemiology/history ; History, 20th Century ; *Influenza, Human/epidemiology/history ; SARS-CoV-2 ; *Epidemics/history ; Pandemics/history ; History, 21st Century ; Influenza Pandemic, 1918-1919/history ; },
abstract = {When COVID-19 survivors reported ongoing symptoms or new health concerns following their infections in 2020 and early 2021, many medical practitioners and health agencies questioned the connection between novel viruses and long-term health impacts. Medical historians studying epidemics understand the connection between viral infection and health complications emerging immediately or years or decades later. In this essay, I explore the similarities between the medical fallout of the 1918 influenza and COVID-19 pandemics. Despite the differences between the viruses, these novel strains produced similar medium- and long-term health difficulties, including cardiovascular dysfunction and crushing fatigue. As I demonstrate, a significant difference between these two pandemics is in the response by medical practitioners. Following influenza, practitioners expected new and worsening health issues and took their patients' complaints seriously, offering support through food delivery, convalescent care, specialist oversight, and in-home nursing. Early in the COVID-19 pandemic, many practitioners characterized ongoing or new symptoms as anxiety. Patients led efforts to recognize Long COVID as an authentic medical condition, and today, physicians around the country refer their patients to Long COVID clinics. The value of medical history is apparent in this comparison-if practitioners understand how historical epidemics impacted various populations, they expect that in the epidemic aftermath or the period following an acute epidemic crisis, not all patients get well. Including the history of epidemics in public health education, continuing education programming, and even medical school curricula can resist epidemic erasure and empower medical practitioners to expect the unexpected.},
}

Humans
*COVID-19/epidemiology/history
History, 20th Century
*Influenza, Human/epidemiology/history
SARS-CoV-2
*Epidemics/history
Pandemics/history
History, 21st Century
Influenza Pandemic, 1918-1919/history

@article {pmid41011507,
year = {2025},
author = {Maddaloni, L and Bugani, G and Fracella, M and Bitossi, C and D'Auria, A and Aloisi, F and Azri, A and Santinelli, L and Ben M'Hadheb, M and Pierangeli, A and Frasca, F and Scagnolari, C},
title = {Pattern Recognition Receptors (PRRs) Expression and Activation in COVID-19 and Long COVID: From SARS-CoV-2 Escape Mechanisms to Emerging PRR-Targeted Immunotherapies.},
journal = {Microorganisms},
volume = {13},
number = {9},
pages = {},
doi = {10.3390/microorganisms13092176},
pmid = {41011507},
issn = {2076-2607},
support = {RM124190A260C1F0//Sapienza University of Rome/ ; },
abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is recognized by pattern recognition receptors (PRRs), which play a vital role in triggering innate immune responses such as the production of type I and III interferons (IFNs). While modest PRR activation helps to defend against SARS-CoV-2, excessive or sustained activation can cause harmful inflammation and contribute to severe Coronavirus Disease 2019 (COVID-19). Altered expression of Toll-like receptors (TLRs), which are among the most important members of the PRR family members, particularly TLRs 2, 3, 4, 7, 8 and 9, has been strongly linked to COVID-19 severity. Furthermore, retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5), collectively known as RLRs (RIG-I-like receptors), act as sensors that detect SARS-CoV-2 RNA. The expression of these receptors, as well as that of different DNA sensors, varies in patients infected with SARS-CoV-2. Changes in PRR expression, particularly that of TLRs, cyclic GMP-AMP synthase (cGAS), and the stimulator of interferon genes (STING), have also been shown to play a role in the development and persistence of long COVID (LC). However, SARS-CoV-2 has evolved strategies to evade PRR recognition and subsequent signaling pathway activation, contributing to the IFN response dysregulation observed in SARS-CoV-2-infected patients. Nevertheless, PRR agonists and antagonists remain promising therapeutic targets for SARS-CoV-2 infection. This review aims to describe the PRRs involved in recognizing SARS-CoV-2, explore their expression during SARS-CoV-2 infection, and examine their role in determining the severity of both COVID-19 and long-term manifestations of the disease. It also describes the strategies developed by SARS-CoV-2 to evade PRR recognition and activation. Moreover, given the considerable interest in modulating PRR activity as a novel immunotherapy approach, this review will provide a description of PRR agonists and antagonists that have been investigated as antiviral strategies against SARS-CoV-2. This review aims to explore the complex interplay between PRRs and SARS-CoV-2 in depth, considering its implications for prognostic biomarkers, targeted therapeutic strategies and the mechanistic understanding of long LC. Additionally, it outlines future perspectives that could help to address knowledge gaps in PRR-mediated responses during SARS-CoV-2 infection.},
}