Do COVID-19 or its vaccines cause autoimmunity?

Over 20 million people in the US are affected by long COVID syndrome, also called post-acute sequelae of SARS-CoV-2 infection (PASC), occurring in ~30% of infected individuals irrespective of SARS-CoV-2 vaccination status. We follow patients with neurologic symptoms of PASC (Neuro-PASC) at our clinic and we frequently observe musculoskeletal (MSK) and neurologic manifestations in this cohort. MSK symptoms including muscle, joint, and nerve pain often lasting for months to years after acute infection. Several characteristics of Neuro-PASC suggest a contribution of autoimmunity to its pathogenesis, including the increased ratio of women to men affected, the presence of autoantibodies against type I interferons (IFNs), and pre-existing autoimmune disease as a comorbidity correlated with increased Neuro-PASC incidence. Autoantibodies against nuclear antigens implicated in rheumatic diseases are also frequently found in COVID convalescents, with sex-specific differences indicating different autoimmune phenotypes in men and women. Up to 62% of Neuro-PASC patients report pain, fatigue, and myalgia/arthralgia, symptoms shared by those with autoimmune diseases. However, it remains unknown if viral proteins that activate T cells also induce cross-reactivity to autoimmune antigens in these patients. The overall objective of this proposal is to determine how T cell responses after COVID-19 may contribute to the etiology or pathogenesis of autoimmunity in Neuro-PASC. The central hypothesis is that T cell responses directed against common autoantigens implicated in rheumatic diseases are increased in a large subset of Neuro-PASC patients with elevated markers of inflammation or autoimmunity, and that SARS-CoV-2 vaccination may enhance T cell autoreactivity in Neuro-PASC patients. Our research group is uniquely positioned to conduct these studies as we comprise the research arm of the Neuro-COVID-19 clinic at Northwestern Memorial Hospital headed by Dr. Igor Koralnik which has evaluated >1500 patients and recruited hundreds of participants into research studies since May, 2020.