Background: 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. Methods: 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). Results: 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 (p < 0.05), reflecting distinct immune signatures. Conclusions: 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.

Patients with antibody deficiency disorders, such as primary immunodeficiency (PID) or secondary immunodeficiency (SID) to B-cell lymphoproliferative disorder (B-CLPD), are two groups vulnerable to developing the severe or chronic form of coronavirus disease caused by SARS-CoV-2 (COVID-19). The data on adaptive immune responses against SARS-CoV-2 are well described in healthy donors, but still limited in patients with antibody deficiency of a different cause. Herein, we analyzed spike-specific IFN-γ and anti-spike IgG antibody responses at 3 to 6 months after exposure to SARS-CoV-2 derived from vaccination and/or infection in two cohorts of immunodeficient patients (PID vs. SID) compared to healthy controls (HCs). Pre-vaccine anti-SARS-CoV-2 cellular responses before vaccine administration were measured in 10 PID patients. Baseline cellular responses were detectable in 4 out of 10 PID patients who had COVID-19 prior to vaccination, perceiving an increase in cellular responses after two-dose vaccination (p < 0.001). Adequate specific cellular responses were observed in 18 out of 20 (90%) PID patients, in 14 out of 20 (70%) SID patients and in 74 out of 81 (96%) HCs after vaccination (and natural infection in some cases). Specific IFN-γ response was significantly higher in HC with respect to PID (1908.5 mUI/mL vs. 1694.1 mUI/mL; p = 0.005). Whereas all SID and HC patients mounted a specific humoral immune response, only 80% of PID patients showed positive anti-SARS-CoV-2 IgG. The titer of anti-SARS-CoV-2 IgG was significantly lower in SID compared with HC patients (p = 0.040), without significant differences between PID and HC patients (p = 0.123) and between PID and SID patients (p =0.683). High proportions of PID and SID patients showed adequate specific cellular responses to receptor binding domain (RBD) neoantigen, with a divergence between the two arms of the adaptive immune response in PID and SID patients. We also focused on the correlation of protection of positive SARS-CoV-2 cellular response to omicron exposure: 27 out of 81 (33.3%) HCs referred COVID-19 detected by PCR or antigen test, 24 with a mild course, 1 with moderate symptoms and the remaining 2 with bilateral pneumonia that were treated in an outpatient basis. Our results might support the relevance of these immunological studies to determine the correlation of protection with severe disease and for deciding the need for additional boosters on a personalized basis. Follow-up studies are required to evaluate the duration and variability in the immune response to COVID-19 vaccination or infection.

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.