Increased Risk of Myositis-Specific and Myositis-Associated Autoantibodies After COVID-19 Pandemic and Vaccination: A Spanish Multicenter Collaborative Study.

: Emerging evidence suggests that SARS-CoV-2 infection and vaccines may trigger autoimmune responses in predisposed individuals. Idiopathic inflammatory myopathies (IIMs) are diseases with diverse clinical manifestations, often associated with myositis autoantibodies (MAs). Diagnosing IIM is challenging due to limitations in classification criteria and diagnostic assays. This study aimed to describe the incidence of IIM following SARS-CoV-2 infection or vaccination and compare rates between exposures. : A multicenter observational study was conducted with 788 patients from 11 Spanish referral centers. A total of 1209 autoantibodies including myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs), were analyzed using line blot immunoassay (LIA). : The study identified distinct patterns in aminoacyl-tRNA synthetase (ARS) antibody frequencies compared to pre-pandemic periods. Anti-PL-7 was the most prevalent ARS antibody (14.85%), while anti-Jo-1 was less frequent (7.23%). Anti-MDA5, commonly linked to SARS-CoV-2 infection, was detected in 11.68%. ANA positivity was observed in 60.66%, suggesting an autoimmune background. The most frequent diagnoses were anti-synthetase syndrome (ASSD) or IIM-non-ASSD (21.31%), followed by other systemic autoimmune diseases (SAIDs) (13.57%). Among the cohort, 91.13% received at least one dose of a messenger RNA (mRNA) COVID-19 vaccine, with a median of three doses per patient. Patients with prior SARS-CoV-2 infection or heterologous vaccination showed a higher frequency of multiple autoantibody positivity ( < 0.05), reflecting distinct immune signatures. : This study provides valuable insights into the autoimmune risks and phenotypes associated with SARS-CoV-2 infection and vaccination, establishing a basis for further research on IIM and its link to MSAs and MAAs.