Autoantibody production is enhanced after mild SARS-CoV-2 infection despite vaccination in individuals with and without long COVID

Long COVID patients who experienced severe acute SARS-CoV-2 infection can present with humoral autoimmunity. However, whether mild SARS-CoV-2 infection increases autoantibody responses and whether vaccination can decrease autoimmunity in long COVID patients is unknown. Here, we demonstrate that mild SARS-CoV-2 infection increases autoantibodies associated with systemic lupus erythematosus (SLE) and inflammatory myopathies in long COVID patients with persistent neurologic symptoms to a greater extent than COVID convalescent controls at 8 months post-infection. Furthermore, high titers of SLE-associated autoantibodies in long COVID patients are associated with impaired cognitive performance and greater symptom severity, and subsequent vaccination/booster does not decrease autoantibody titers. In summary, we found that mild SARS-CoV-2 infection can induce persistent humoral autoimmunity in both long COVID patients and healthy COVID convalescents, suggesting that a reappraisal of vaccination and mitigation strategies is warranted.