Evidence of Induction and Sustained Expression of Autoantibodies Six Months After SARS-CoV-2 Infection

Autoantibodies are commonly present during acute COVID-19. If these antibodies are pre-existing, induced post-infection, and/or maintained months into convalescence is unclear. Also, if autoantibody trajectories post-infection differ between inpatient and outpatient subjects is unknown. We measured the expression of 17 autoantibodies linked to autoimmune connective tissue diseases from five subject groups: (1) pre-pandemic, (2) SARS-CoV-2+ inpatient, (3) SARS-CoV-2+ outpatient, (4) scleroderma, and (5) systemic lupus erythematosus. Autoantibody levels from SARS-CoV-2+ subjects were followed over time from initial symptom onset for an average of six months. Cross-sectional analysis revealed that six of the 17 autoantibodies measured were higher on average in inpatient and/or outpatient SARS-CoV-2 subjects six months after symptom onset compared with prepandemic controls. Autoantibody trajectories over time from longitudinal sample sets were differentially scored based on expression changes and two key findings were revealed: (1) a ‘newly induced and sustained’ expression pattern was found for at least one autoantibody in 18% of the outpatient and 63% of the inpatient subjects, indicating initiation and durable expression of new, self-reactive memory immune reponses post-infection; and (2) 64% and 83% of positively scored autoantibodies from the inpatient and outpatient groups, respectively, exhibited an ‘always positive’ pattern beginning from the initial days of symptom onset, suggesting pre-existing self-reactive immunity as a putative driver of symptomatic COVID-19 after viral exposure. As positivity to individual autoantibodies precedes presentation of clinical autoimmune disease, SARS-CoV-2 may create a potent “fertile field” of self-reactive immune cells that will spur autoimmune disease with a future immune trigger.