New-Onset IgG Autoantibodies in Hospitalized Patients with COVID-19

Chang, S. E.; Feng, A.; Meng, W.; Apostolidis, S.; Mack, E.; Artandi, M.; Barman, L.; Bennett, K.; Chakraborty, S.; Chang, I.; Cheung, P.; Chinthrajah, S.; Dhingra, S.; Do, E.; Finck, A.; Gaano, A.; Gessner, R.; Giannini, H. M.; Gonzalez, J.; Greib, S.; Guendisch, M.; Hsu, A. R.; Kuo, A.; Manohar, M.; Mao, R.; Neeli, I.; Neubauer, A.; Oniyide, O.; Powell, A. E.; Puri, R.; Renz, H.; Schapiro, J. M.; Weidenbacher, P. A.; Wittman, R.; Ahuja, N.; Chung, H.-R.; Jagannathan, P.; James, J.; Kim, P. S.; Meyer, N. J.; Nadeau, K. C.; Radic, M.; Robinson, W. H.; Singh, U.; Wang, T. T.; Wherry, E. J.; Ske,

Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), is associated with a wide range of clinical manifestations, including autoimmune features and autoantibody production. We developed three different protein arrays to measure hallmark IgG autoantibodies associated with Connective Tissue Diseases (CTDs), Anti-Cytokine Antibodies (ACA), and anti-viral antibody responses in 147 hospitalized COVID-19 patients in three different centers. Autoantibodies were identified in approximately 50% of patients, but in <15% of healthy controls. When present, autoantibodies largely targeted autoantigens associated with rare disorders such as myositis, systemic sclerosis and CTD overlap syndromes. Anti-nuclear antibodies (ANA) were observed in ~25% of patients. Patients with autoantibodies tended to demonstrate one or a few specificities whereas ACA were even more prevalent, and patients often had antibodies to multiple cytokines. Rare patients were identified with IgG antibodies against angiotensin converting enzyme-2 (ACE-2). A subset of autoantibodies and ACA developed de novo following SARS-CoV-2 infection while others were transient. Autoantibodies tracked with longitudinal development of IgG antibodies that recognized SARS-CoV-2 structural proteins such as S1, S2, M, N and a subset of non-structural proteins, but not proteins from influenza, seasonal coronaviruses or other pathogenic viruses. COVID-19 patients with one or more autoantibodies tended to have higher levels of antibodies against SARS-CoV-2 Nonstructural Protein 1 (NSP1) and Methyltransferase (ME). We conclude that SARS-CoV-2 causes development of new-onset IgG autoantibodies in a significant proportion of hospitalized COVID-19 patients and are positively correlated with immune responses to SARS-CoV-2 proteins.