The Intersection of COVID-19 and Autoimmunity: What is Our Current Understanding?

Abstract

Viral infections have historically had a complex relationship with autoimmune diseases. For patients with preexisting autoimmune disorders, often complicated by immunosuppressive therapies, there are numerous potential effects of COVID-19, a disease of complex immunobiology, including the potential for an altered natural history of COVID-19 when infected. In addition, individuals without recognized autoimmune disease may be vulnerable to virally induced autoimmunity in the forms of autoantibody formation, as well as the development of clinical immune-mediated inflammatory diseases. Until quite recently in the pandemic, this relationship between COVID-19 and autoimmune diseases has been relatively underexplored; yet such investigation offers potential insights into immunopathogenesis as well as for the development of new immune-based therapeutics. Our review examines this relationship through exploration of a series of questions with relevance to both immunopathogenic mechanisms as well as some clinical implications.

Keywords: Autoantibodies; Autoimmunity; COVID-19; DMARDs; Immune-mediated inflammatory disease; MIS-C; SARS-CoV-2.

Figure 1.

The evolving immune landscape of COVID-19: Baseline characteristics implicated in disease course, and immune-mediated sequelae. The clinical course of COVID-19 infection may be influenced by the immunologic milieu and the immune-based therapies of patients with pre-existing IMIDs who become infected (left). In addition, the infection itself may influence the clinical course of patients with IMIDs (ie, induce flares) or the development of autoimmune laboratory phenomenon and/or new IMIDs as well as potentially contributing to some post COVID-19 sequelae such as long COVID-19 symptomatology (right). Abbreviations: IMID, immune-mediated inflammatory disease; MIS-C, multisystem inflammatory syndrome in children.

Figure 2.

Summary of the 3 phases of COVID-19 immune response and disease progression over time. Immune response against SARS-CoV-2 infection proceeds through 3 general phases. Phase 1 is that of asymptomatic innate immune activation initiated by entry of SARS-CoV-2 into host cells of the upper respiratory track with triggering of innate immunity including the interferon response. The virus appears to antagonize initial viral detection and interferon by yet unknown mechanisms [33]. Failing to contain the infection Phase 2 is marked by activation of adaptive immune response with production of specific IgM followed by IgG antibodies as well as T-cell activation including CD4 and CD8 responses but not marked by hyperinflammation. Clinical resolution generally occurs over 10-14 days in the majority of patients. In a minority of patients often accompanied by one or more of numerous comorbid conditions (shown on left) or genetic risk factors [34], which largely remain poorly defined, a third phase ensues characterized by hyperinflammation, lymphopenia, immunothrombosis, and end organ damage especially in the lungs in about 15%-20% of patients.