Laboratory Findings and Biomarkers in Long COVID: What Do We Know So Far? Insights into Epidemiology, Pathogenesis, Therapeutic Perspectives and Challenges

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.

Children and Young People with Long COVID—Comparing Those Seen in Post-COVID Services with a Non-Hospitalised National Cohort: A Descriptive Study

“…There are many possible explanations for this, including increased viral load. Although no specific biomarkers have yet been established that differentiate Long COVID from other disease entities, it is hoped that sensitive and reliable diagnostic biomarkers will emerge which may further help identify which children are in need of clinical interventions [33]. Monitoring young people reporting multiple symptoms during infection may also enable early intervention and support.…”

Potential Beneficial Effects of Naringin and Naringenin on Long COVID—A Review of the Literature

“…This review addresses the pathogenesis and statistical status of eleven complications of long COVID and specifically addresses the therapeutic potential of naringin and naringenin in long COVID ( Table 1 ). The clinical symptoms and biomarkers of long COVID have been widely reported, and long COVID can indeed have serious long-term effects on human health [ 260 , 261 ]. There are no definitive medications that directly treat multiple long COVID complications [ 262 ], and the treatment approach for long COVID is still based solely on clinical symptoms and the use of nutraceuticals and probiotics to improve symptoms [ 263 ].…”

Autoimmunity and long COVID in children

“…In general, long COVID symptoms are found in at least 10–20% of individuals who have had a SARS-CoV-2 infection [ 1 ]. This means that more than 80 million people may experience long COVID symptoms, which not only have a substantial impact on healthcare but also may carry significant social and economic consequences [ 2 ].…”

“…Several hypotheses about the pathogenetic mechanisms of long COVID have been proposed and summarized [ 2 , 9 , 11 ]. Immune system dysfunction is one of the leading hypotheses in the development of long COVID.…”