Autoimmune anti-DNA antibodies predict disease severity in COVID-19 patients

Gomes, C.; Zuniga, M.; Crotty, K. A.; Qian, K.; Hsu Lin, L.; Argyropoulos, K.; Li, H.; Cotzia, P.; Rodriguez, A.

Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to severe disease and death, however the mechanisms of pathogenesis in these patients remain poorly understood. High levels of autoimmune antibodies have been observed frequently in coronavirus disease (COVID-19) patients but their specific contribution to disease severity and clinical manifestations remain unknown. We performed a retrospective study of 115 COVID-19 hospitalized patients with different degrees of severity to analyze the generation of autoimmune antibodies to common antigens: a lysate of erythrocytes, the lipid phosphatidylserine (PS) and DNA. The statistical relation of autoantibody levels to death, disease severity and specific pathologies was determined using high-throughput data analysis of 118 clinical parameters for all patients. High levels of IgG autoantibodies against erythrocyte lysates were observed in a large percentage (up to 41%) of patients with COVID-19 compared to uninfected controls. Anti-DNA antibodies determined upon hospital admission were high in 16% of patients and correlated strongly with later development of severe disease, showing a positive predictive value of 89.5% and accounting for 22% of total severe cases. Statistical analysis identified strong correlations between anti-DNA antibodies and markers of cell injury, coagulation, neutrophil levels and erythrocyte size. Anti-DNA autoantibodies may play an important role in the pathogenesis of COVID-19 and could be developed as a predictive biomarker for disease severity and specific clinical manifestations.