Laboratory Findings and Biomarkers in Long COVID: What Do We Know So Far? Insights into Epidemiology, Pathogenesis, Therapeutic Perspectives and Challenges International Journal of Molecular Sciences
Abstract Long COVID (LC) encompasses a constellation of long-term symptoms experienced by at least 10% of people after the initial SARS-CoV-2 infection, and so far it has affected about 65 million people. The etiology of LC remains unclear; however, many pathophysiological pathways may be involved, including viral persistence; a chronic, low-grade inflammatory response; immune dysregulation and a defective immune response; the reactivation of latent viruses; autoimmunity; persistent endothelial dysfunction and coagulopathy; gut dysbiosis; hormonal and metabolic dysregulation; mitochondrial dysfunction; and autonomic nervous system dysfunction. There are no specific tests for the diagnosis of LC, and clinical features including laboratory findings and biomarkers may not specifically relate to LC. Therefore, it is of paramount importance to develop and validate biomarkers that can be employed for the prediction, diagnosis and prognosis of LC and its therapeutic response, although this effort may be hampered by challenges pertaining to the non-specific nature of the majority of clinical manifestations in the LC spectrum, small sample sizes of relevant studies and other methodological issues. Promising candidate biomarkers that are found in some patients are markers of systemic inflammation, including acute phase proteins, cytokines and chemokines; biomarkers reflecting SARS-CoV-2 persistence, the reactivation of herpesviruses and immune dysregulation; biomarkers of endotheliopathy, coagulation and fibrinolysis; microbiota alterations; diverse proteins and metabolites; hormonal and metabolic biomarkers; and cerebrospinal fluid biomarkers. At present, there are only two reviews summarizing relevant biomarkers; however, they do not cover the entire umbrella of current biomarkers, their link to etiopathogenetic mechanisms or the diagnostic work-up in a comprehensive manner. Herein, we aim to appraise and synopsize the available evidence on the typical laboratory manifestations and candidate biomarkers of LC, their classification based on pathogenetic mechanisms and the main LC symptomatology in the frame of the epidemiological and clinical aspects of the syndrome and furthermore assess limitations and challenges as well as potential implications in candidate therapeutic interventions. Keywords: biomarkers, COVID-19, epidemiology, laboratory, long COVID, pathogenesis, post-acute sequelae of SARS-CoV infection (PASC), post-COVID, post-COVID syndrome (PCS)
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Dimitrios Tsilingiris, Natalia G Vallianou, Irene Karampela et al.. Laboratory Findings and Biomarkers in Long COVID: What Do We Know So Far? Insights into Epidemiology, Pathogenesis, Therapeutic Perspectives and Challenges. International Journal of Molecular Sciences. (2023). https://doi.org/10.3390/ijms241310458 Dimitrios Tsilingiris, Natalia G Vallianou, Irene Karampela, Gerasimos Socrates Christodoulatos, Georgios Papavasileiou, Dimitra Petropoulou, Faidon Magkos, Maria Dalamaga
1First Department of Internal Medicine, University Hospital of Alexandroupolis, Democritus University of Thrace, Dragana, 68100 Alexandroupolis, Greece; [email protected] 2Department of Internal Medicine, Evangelismos General Hospital, 45-47 Ipsilantou Street, 10676 Athens, Greece; [email protected] 32nd Department of Critical Care, Medical School, University of Athens, Attikon General University Hospital, 1 Rimini Street, 12462 Athens, Greece; [email protected] 4Department of Microbiology, Sismanogleio General Hospital, 1 Sismanogleiou Street, 15126 Athens, Greece; [email protected] 5Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527 Athens, Greece; [email protected] (G.P.); [email protected] (D.P.) 6Department of Nutrition, Exercise, and Sports, University of Copenhagen, DK-2200 Frederiksberg, Denmark; [email protected] 