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Review
. 2023 May 26:12:e86014.
doi: 10.7554/eLife.86014.

Immune mechanisms underlying COVID-19 pathology and post-acute sequelae of SARS-CoV-2 infection (PASC)

Sindhu Mohandas  1 , Prasanna Jagannathan  2 , Timothy J Henrich  3 , Zaki A Sherif  4 , Christian Bime  5 , Erin Quinlan  6 , Michael A Portman  7 , Marila Gennaro  8 , Jalees Rehman  9 ; RECOVER Mechanistic Pathways Task Force
Collaborators, Affiliations
Review

Immune mechanisms underlying COVID-19 pathology and post-acute sequelae of SARS-CoV-2 infection (PASC)

Sindhu Mohandas et al. 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.

Keywords: COVID-19; PASC; adaptive immunity; immunology; immunopathology; inflammation; innate immunity.

PubMed Disclaimer

Conflict of interest statement

SM, PJ, TH, ZS, CB, MP, MG, JR No competing interests declared, EQ is employed by the NIH which funded the RECOVER trial

Figures

Figure 1.
Figure 1.. A simplified overview of responses of the immune system to the SARS-CoV-2 virus, over various time courses that lead to severe COVID-19 and long COVID (PASC) in some patients.
The innate immune response serves as the initial line of defense against the virus, involving the activation of immune cells such as monocytes, natural killer (NK) cells, dendritic cells, and macrophages. These cells release cytokines and chemokines to recruit other immune cells, such as T cells and neutrophils, to the site of infection. Later in the course of the infection, the adaptive immune cells including B plasma cells release antibodies. However, the overreactive immune responses trigger inflammatory conditions that are sustained in PASC due to dysregulation of the immune system. The diagram was created using the Biorender.com software.
See this image and copyright information in PMC

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