Immune mechanisms underlying COVID-19 pathology and post-acute sequelae of SARS-CoV-2 infection (PASC)
Mohandas, S; Jagannathan, P; Henrich, TJ; et al., eLife
Published
May 2023
Journal
eLife
Abstract
With a global tally of more than 500 million cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections to date, there are growing concerns about the post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Recent studies suggest that exaggerated immune responses are key determinants of the severity and outcomes of the initial SARS-CoV-2 infection as well as subsequent PASC. The complexity of the innate and adaptive immune responses in the acute and post-acute period requires in-depth mechanistic analyses to identify specific molecular signals as well as specific immune cell populations which promote PASC pathogenesis. In this review, we examine the current literature on mechanisms of immune dysregulation in severe COVID-19 and the limited emerging data on the immunopathology of PASC. While the acute and post-acute phases may share some parallel mechanisms of immunopathology, it is likely that PASC immunopathology is quite distinct and heterogeneous, thus requiring large-scale longitudinal analyses in patients with and without PASC after an acute SARS-CoV-2 infection. By outlining the knowledge gaps in the immunopathology of PASC, we hope to provide avenues for novel research directions that will ultimately lead to precision therapies which restore healthy immune function in PASC patients.
Authors
Sindhu Mohandas, Prasanna Jagannathan, Timothy J Henrich, Zaki A Sherif, Christian Bime, Erin Quinlan, Michael A Portman, Marila Gennaro, Jalees Rehman; RECOVER Mechanistic Pathways Task Force
Keywords
COVID-19; PASC; adaptive immunity; immunology; immunopathology; inflammation; innate immunity
Short Summary
People who had COVID-19 may develop Long COVID, which is when someone may experience various health issues after having COVID. Many of these problems are due to a strong reaction to the SARS-CoV-2 virus by the immune system (the body’s defense system that fights infections). This reaction can happen a long time after the virus is no longer in the body.
A healthy immune system can tell the difference between our body’s healthy cells and the harmful ones that can make us sick. However, an overactive immune system can make mistakes and cause harm because it may attack healthy organs and tissues. The immune system response to diseases like COVID is complex and different for each person.
It is important to understand how the immune system works after having COVID for many different people, and this may require large, long-term studies. This paper reviews researchers’ current knowledge and the gaps in their understanding about the immune response after a COVID infection and how that may lead to both short-term and long-term problems.