The intersection of COVID-19 and autoimmunity
Jason S. Knight, … , Julia Y. Wang, William J. McCune
Jason S. Knight, … , Julia Y. Wang, William J. McCune
Published October 28, 2021
Citation Information: J Clin Invest. 2021;131(24):e154886. https://doi.org/10.1172/JCI154886.
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Review

The intersection of COVID-19 and autoimmunity

Abstract

Acute COVID-19, caused by SARS-CoV-2, is characterized by diverse clinical presentations, ranging from asymptomatic infection to fatal respiratory failure, and often associated with varied longer-term sequelae. Over the past 18 months, it has become apparent that inappropriate immune responses contribute to the pathogenesis of severe COVID-19. Researchers working at the intersection of COVID-19 and autoimmunity recently gathered at an American Autoimmune Related Diseases Association Noel R. Rose Colloquium to address the current state of knowledge regarding two important questions: Does established autoimmunity predispose to severe COVID-19? And, at the same time, can SARS-CoV-2 infection trigger de novo autoimmunity? Indeed, work to date has demonstrated that 10% to 15% of patients with critical COVID-19 pneumonia exhibit autoantibodies against type I interferons, suggesting that preexisting autoimmunity underlies severe disease in some patients. Other studies have identified functional autoantibodies following infection with SARS-CoV-2, such as those that promote thrombosis or antagonize cytokine signaling. These autoantibodies may arise from a predominantly extrafollicular B cell response that is more prone to generating autoantibody-secreting B cells. This Review highlights the current understanding, evolving concepts, and unanswered questions provided by this unique opportunity to determine mechanisms by which a viral infection can be exacerbated by, and even trigger, autoimmunity. The potential role of autoimmunity in post-acute sequelae of COVID-19 is also discussed.

Authors

Jason S. Knight, Roberto Caricchio, Jean-Laurent Casanova, Alexis J. Combes, Betty Diamond, Sharon E. Fox, David A. Hanauer, Judith A. James, Yogendra Kanthi, Virginia Ladd, Puja Mehta, Aaron M. Ring, Ignacio Sanz, Carlo Selmi, Russell P. Tracy, Paul J. Utz, Catriona A. Wagner, Julia Y. Wang, William J. McCune

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Figure 3

Potential mechanisms of de novo autoimmunity in COVID-19.

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Potential mechanisms of de novo autoimmunity in COVID-19. Naive B cells ...
Naive B cells can be activated via both the germinal center and the extrafollicular pathway. The extrafollicular pathway lacks some tolerance checkpoints that prevent the activation and maturation of autoreactive B cells and is, therefore, more prone to generating autoantibodies. Patients with severe COVID-19 exhibit higher levels of extrafollicular B cells lacking IgD, CD27, CXCR5, and CD21 (known as double-negative [DN2] cells) and plasma cells. They may also lack germinal centers. Red arrows indicate increased or reduced levels in patients with severe COVID-19 compared with patients with mild COVID-19.