Transient nasal anti-interferon autoantibodies predict better outcomes in COVID-19 infection 4226

Abstract Description Pre-existing anti-interferon alpha (anti-IFN-α) autoantibodies in blood are associated with susceptibility to life-threatening COVID-19. However, it is unclear whether anti-IFN-α autoantibodies in the airways, the initial site of infection, can also determine disease outcomes. We developed a multiparameter technology, FlowBEAT, to quantify the isotype and subclass of antibodies against SARS-CoV-2 and IFN-α along with cytokines associated with IFN response, including CXCL10. We applied FlowBEAT to longitudinal samples collected from the airways and blood of 125 donors spanning mild to severe COVID-19. Nasal IgA1 anti-IFN-α autoantibodies were induced post-infection onset in > 70% of mild and moderate cases and were associated with robust anti-SARS-CoV-2 immunity in the nose, less systemic inflammation, lesser symptoms, and efficient recovery. Notably, only patients who produced nasal IFN-α developed nasal anti-IFN-α, which waned with disease recovery. In contrast, systemic IgG1 anti-IFN-α autoantibodies appeared later and only in a subset of patients with elevated systemic inflammation and worsening symptoms. Thus, our findings suggest that anti-IFN-α autoantibodies may serve a homeostatic function to regulate host IFN-α after viral infection in the respiratory mucosa. Finally, we show that FlowBEAT can be used as a predictive diagnostic test to inform personalized treatment options early during infection and help determine disease susceptibility beyond standard comorbidities. Funding Sources Supported by NIH/NIAD R21AI167032; NIH R01AI123126-05S1; NCI U54 CA260563 Emory SeroNet; COVID Fast Grant from Emergent Ventures at the Mercatus Center, George Mason University; Program for Breakthrough Biomedical Research Award. American Society of Hematology Graduate Hematology Award; Van Auken Private Fndn; David Henke; Pamela and Edward Taft. Topic Categories Mucosal and Regional Immunology (MUC)