A perspective on pathogenesis of post-COVID syndrome

In 2023, the World Health Organization declared the COVID-19 pandemic caused by SARS-CoV-2 officially over. The infection has now transitioned into seasonal respiratory viral infections. However, one of the major health concerns persisting beyond the pandemic is post-COVID syndrome — a condition characterized by the persistence of COVID-19 symptoms or the emergence of new symptoms three months after the initial illness. The common mechanisms underlying post-COVID syndrome include immune dysregulation, viral persistence, chronic systemic inflammation, autoimmune manifestations, thrombosis, vascular endothelial dysfunction, myocarditis, myocardial infarction, ischemic heart disease, and pulmonary fibrosis. A significant autoimmune feature of post-COVID syndrome is the high prevalence of autoantibodies, including those targeting interferons, which can neutralize the biological activity of these protective cytokines. The combined effects of these mechanisms lead to a wide range of complications affecting multiple organ systems, including neurological and neuropsychiatric disorders. The exact pathophysiological mechanisms of post-COVID syndrome and their causal relationships remain to be fully understood. This is necessary to build on accumulated experience, be fully prepared for future infectious challenges, and prevent further casualties. This review examines the clinical manifestations and pathogenesis of post-COVID syndrome.