Autoimmunity and autoinflammation in COVID-19: molecular mechanisms and therapeutic strategies

Abstract

As of May 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 150 million people worldwide. The mechanisms of immune dysregulation in resulting coronavirus disease 2019 (COVID-19) have not yet been fully elucidated. There is growing evidence to suggest a connection between SARS-CoV-2 infection and the development of autoinflammatory and autoimmune responses. This article will investigate how immune dysregulation in COVID-19 contributes to autoinflammation and autoimmune disease, and discuss the therapeutic implications. The viral infection provokes hyperinflammation by shifting innate and adaptive immune responses towards a proinflammatory state, while suppressing immune regulation. Immune dysregulation and molecular mimicry by SARS-CoV-2 have the potential to break down immunological tolerance, stimulate cross-reactive immune responses, and induce lasting autoimmune disease. Promising immunomodulatory therapies include treatment with type I and III interferons, antibodies against the virus or inflammatory immune pathways, corticosteroids, cell therapies, immune checkpoint inhibitors, and superantigen therapy. Contextualized by the current research, this article will also address the emerging cases of vaccine-induced thrombotic thrombocytopenia (VITT): a life-threatening autoimmune disease elicited by certain SARS-CoV-2 viral vector vaccines. This review exposes the necessity for longitudinal studies investigating the prevalence and persistence of autoinflammatory damage and autoimmune disease following SARS-CoV-2 infection.