Longitudinal analysis reveals elevation then sustained higher expression of autoantibodies for six months after SARS-CoV-2 infection

High autoantibody levels are found in individuals hospitalized for COVID-19. The temporal trajectories and levels of these autoantibodies months into convalescence after SARS-CoV-2 infection are unclear. It is also unknown if the composite autoantibody signatures of convalescent SARS-CoV-2-infected individuals resemble those with diagnosed autoimmune diseases. We measured the circulating levels of 17 autoantibodies associated with autoimmune connective tissue diseases from SARS-CoV-2 hospitalized and outpatient participants, as well as from individuals with scleroderma (SSc), systemic lupus erythematosus (SLE), and uninfected pre-pandemic controls. Seven of the 17 autoantibodies measured were higher in hospitalized and/or outpatient SARS-CoV-2 individuals an average of six months after symptom onset compared with controls, with multivariate analyses revealing links between SARS-CoV-2 infection and positivity of SSB-La, Sm, Proteinase 3, Myleoperoxidase, Jo-1, and Ku reactive IgG six months post-symptom onset. Autoantibody levels from SARS-CoV-2 infected individuals were followed over time from initial symptom onset for an average of six months, and different temporal autoantibody trajectories were classified. A negative, then positive expression pattern was found for at least one autoantibody in 18% of the outpatient and 53% of the hospitalized participants, indicating initiation and durable expression of self-reactive immune responses post-infection, particularly with severe acute illness. Analysis of individual participant autoantibody expression patterns revealed similar patterns between pre-pandemic and convalescent SARS-CoV-2 infected groups that are distinct from participants with both the SSc and SLE. As autoantibody positivity can occur years prior to autoimmune disease onset, the possibility that SARS-CoV-2-associated autoantibodies are a herald of future autoimmune disorders requires further investigation. One Sentence SummaryAutoantibody levels rise after acute SARS-CoV-2 infection and remain elevated for at least six months after symptom onset in participants with mild or severe COVID-19.