Early clues regarding the pathogenesis of long-COVID

Abstract

Intense investigation into the predictors and determinants of post-acute sequelae of SARS-CoV-2 infection (PASC), including 'long COVID', is underway. Recent studies provide clues to the mechanisms that might drive this condition, with the goal of identifying host or virus factors that can be intervened upon to prevent or reverse PASC.

Keywords: SARS-CoV-2; immunology; long COVID; post-acute COVID syndrome (PACS); post-acute sequelae of SARS-CoV-2 (PASC).

Figure 1

Predictors and proposed pathophysiologic mechanisms of long coronavirus disease (COVID). Studies to date have identified certain factors that predict whether an individual with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection will fully recover or develop post-acute sequelae, including the persistent symptoms that characterize long COVID. Shown here are several mechanisms with evidence supported by recent studies of individuals with post-acute sequelae of SARS-CoV-2 infection (PASC) [1,4., 5., 6., 7., 8., 9., 10.]. These include tissue persistence of viral antigen, systemic and tissue-localized inflammatory responses, reactivation of human herpesviruses (e.g., Epstein-Barr virus), alterations in the gut microbiome, issues related to clotting, and the interplay between SARS-CoV-2-specific and autoreactive immunity. Some individuals with long COVID will spontaneously recover over time, possibly due to resolution of these factors and/or evolving immune status. The confirmation of these mechanisms in individuals with PASC may lead to therapeutics targeting the pathophysiology of this condition, with the goal of allowing more individuals to achieve full recovery. Figure created with BioRender.com