The pathophysiology of postacute sequelae of COVID-19 (PASC): Possible role for persistent inflammation

As the SARS-CoV-2-induced pandemic wanes, a substantial number of patients with acute Corona Virus-induced disease (COVID-19 continue to have symptoms for a prolonged time after initial infection. These patients are said to have postacute sequelae of COVID (PASC) or “long COVID”. The underlying pathophysiology of this syndrome is poorly understood and likely quite heterogeneous. The role of persistent, possibly deviant inflammation as a major factor in comorbidity is suspected. OBJECTIVE: To review data that address the relative importance of inflammation in the pathophysiology spectrum of PASC and to address how this would impact diagnosis and approach to therapy in patients identified as having such inflammatory abnormalities. METHODS: A review of public databases, including PubMed, MeSH, NLM catalog, and clinical trial databases such as clinicaltrials.gov. RESULTS: The literature supports a prominent role for various forms and types of inflammation in the pathophysiologic spectrum of PASC. Such inflammation can be persistent ant CoV-2-specific responses, new onset autoimmune responses, or a loss of normal immunoregulation resulting in widespread, sustained inflammatory pathologies that can affect both broad constitutional symptoms (such as fatigue, neurocognitive dysfunction, and anxiety/depression) and organ-specific dysfunction and/or failure. CONCLUSIONS: PASC is a significant clinical entity with similarities to and differences from other postviral syndromes. Significant research efforts are ongoing to better understand specific aberrant inflammatory pathways present in individual patients for the purpose of developing and implementing effective therapies and ultimately prophylaxis strategies to prevent the progression of COVID-19 as well as likely future viral illnesses and pandemics.