Autoimmune responses associated with SARS-CoV-2 infection

PROJECT SUMMARY Current research focuses on three important aspects of COVID-19 pandemic - therapy, vaccine and diagnostics. Directing UPMC's Clinical Immune Diagnostic Laboratory, we understand the urgent need to initiate clinical research that will allow us to assess and analyze potential deferred health outcomes in a population of recovered COVID-19 patients. Although a robust immune response is associated with clinical recovery of most SARS-CoV- 2 infected patients, when a protective immune response is impaired or delayed, virus will propagate, and massive destruction of the affected tissues will occur. Extensive tissue damage and release of autoantigens, especially if associated with disproportionate systemic inflammation and cytokine storm, has been shown to dysregulate peripheral immune tolerance and facilitate initiation of autoimmune pathways. Our working hypothesis that COVID-19 recovered individuals are under increased risk of developing antibodies to self-antigen(s) is a high- risk hypothesis with important clinical implications that will lay the groundwork for future mechanistic studies. To test our hypothesis, we propose to: Determine if increased autoantibodies are associated with prior SARS-CoV- 2 infection by measuring prevalence of autoantibodies in patients with a history of COVID-19 infection. If our hypothesis is confirmed, our data will provide the first evidence for the need to follow COVID-19 recovered patients for the appearance of autoimmune antibodies and increased risk of systemic and tissue-specific autoimmune diseases.