Increased Risk of Myositis-Specific and Myositis-Associated Autoantibodies after COVID-19 pandemic and Vaccination: A Spanish Multicenter Collaborative Study

Emerging evidence suggests that the severe-acute-respiratory-syndrome-related coronavirus (SARS- CoV-2) infection and anti-SARS-CoV-2 vaccines may trigger autoimmune responses in genetically predisposed individuals. Idiopathic inflammatory myopathies (IIMs) are a group of diseases with a broad spectrum of clinical manifestations featured by the presence of myositis autoantibodies (MAs). The diagnosis of IIM is challenging due to the limitations of current classification criteria and diagnostic assays. We conducted a multicenter observational study, whose main goal was to describe the incidence of IIM following exposure to SARS-CoV-2 infection and/or its specific vaccination, and to compare the rates of both. A total of 788 patients belonging to 11 different Spanish referral centers were analyzed, with a cumulative count of 1,209 MAs measured by line blot immunoassays (LIA). The study identified distinct patterns in the frequency of aminoacyl-tRNA synthetase (ARS) antibodies compared to pre-pandemic periods. Notably, the most prevalent ARS antibody identified associated to IIM was anti-PL-7 (14.85%), whereas anti-Jo1, traditionally the most frequent antibody documented, had a frequency of 7.23% in our cohort. Anti- MDA5, the most commonly described antibody in the literature associated with the SARS-CoV-2 infection, was identified in 11.68% of our patients. Our cohort displayed positive antinuclear antibodies (ANA) result in 61% of patients, which suggests an underlying autoimmune background. The most prevalent final diagnoses were anti- synthetase syndrome (ASSD) or IIM-non-ASSD (21.31% of total cases) and other systemic autoimmune diseases (SAID) with 13.57% of cases. 91.13% of patients received at least one dose of a messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccine, with a median of three doses per patient. It is noteworthy that patients with prior SARS-CoV-2 infection or heterologous vaccination demonstrated a higher frequency of multiple autoantibody positivity (p<0.05), which could reflect different humoral and cellular immune signatures. This collaborative work enhances our understanding of IIM and may facilitate the optimization of care through the implementation of standardized approaches. Further investigation is required to fully characterize the autoimmune risks and phenotypes following a diagnosis of SARS-CoV-2 infection or vaccination.Emerging evidence suggests that the severe-acute-respiratory-syndrome-related coronavirus (SARS- CoV-2) infection and anti-SARS-CoV-2 vaccines may trigger autoimmune responses in genetically predisposed individuals. Idiopathic inflammatory myopathies (IIMs) are a group of diseases with a broad spectrum of clinical manifestations featured by the presence of myositis autoantibodies (MAs). The diagnosis of IIM is challenging due to the limitations of current classification criteria and diagnostic assays. We conducted a multicenter observational study, whose main goal was to describe the incidence of IIM following exposure to SARS-CoV-2 infection and/or its specific vaccination, and to compare the rates of both. A total of 788 patients belonging to 11 different Spanish referral centers were analyzed, with a cumulative count of 1,209 MAs measured by line blot immunoassays (LIA). The study identified distinct patterns in the frequency of aminoacyl-tRNA synthetase (ARS) antibodies compared to pre-pandemic periods. Notably, the most prevalent ARS antibody identified associated to IIM was anti-PL-7 (14.85%), whereas anti-Jo1, traditionally the most frequent antibody documented, had a frequency of 7.23% in our cohort. Anti- MDA5, the most commonly described antibody in the literature associated with the SARS-CoV-2 infection, was identified in 11.68% of our patients. Our cohort displayed positive antinuclear antibodies (ANA) result in 61% of patients, which suggests an underlying autoimmune background. The most prevalent final diagnoses were anti- synthetase syndrome (ASSD) or IIM-non-ASSD (21.31% of total cases) and other systemic autoimmune diseases (SAID) with 13.57% of cases. 91.13% of patients received at least one dose of a messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccine, with a median of three doses per patient. It is noteworthy that patients with prior SARS-CoV-2 infection or heterologous vaccination demonstrated a higher frequency of multiple autoantibody positivity (p<0.05), which could reflect different humoral and cellular immune signatures. This collaborative work enhances our understanding of IIM and may facilitate the optimization of care through the implementation of standardized approaches. Further investigation is required to fully characterize the autoimmune risks and phenotypes following a diagnosis of SARS-CoV-2 infection or vaccination.

myositis autoantibodies; idiopathic inflammatory myopathies; anti-synthetase syndrome; anti-aminoacyl-tRNA synthetase autoantibodies; line blot immunoassays; coronavirus disease 2019; SARS-CoV-2 infection; COVID-19 vaccine