ABSTRACT
Background: To date, globally considered, the literature suggests that AIRD may be at higher risk of infection and death due to COVID19 compared to the general population. Vaccination against SARS-CoV-2 reduces the risk of hospitalization and mortality. However, immunological alteration associated with Autoimmune Infam-matory Rheumatic Diseases (AIRD) and immunosuppressive medications may impair the response to vaccination. Emerging data suggest that immunosuppres-sive treatment may negatively impact the response to anti-SARS-CoV-2 vaccines in the AIRD population;data are robust for some treatments, more controversial for others. Identifying patients at higher risk of lack of protection is essential for shielding them and for adapting therapeutic protocol and vaccination timing. Objectives: In the light of the current COVID19 epidemic and the availability of effective vaccines, this study aims to identify predictors of non-response to anti-SARS-CoV-2 vaccines in patients affected by AIRD. Methods: An observational cross-sectional study was conducted evaluating the serological response and the persistence of antibodies at eight weeks in IRD patient cohort and non-IRD control. IRD and age and sex-matched controls volunteer among the health professionals (CTRL) who underwent vaccination with two doses of BNT162b2 were recruited for this study. Anti-Trimeric Spike protein antibodies were assayed eight ± one week after the second vaccine dose. Uni-variate and logistic regression analyses were performed to identify predictors of non-response and low antibody titers. Results: Samples were obtained from 237 IRD patients (m/f 73/164, mean age 5 7, CI 95% [56-59]): 4 autoinfammatory diseases (AI), 62 connective tissue diseases (CTD), 86 rheumatoid arthritis (RA), 71 spondylarthritis (SpA) and 14 vasculitis (Vsc). 232 CTRL were recruited (m/f 71/161, mean age 5 7, CI 95% [56-58]). Globally, IRD had a lower seroconversion rate (88.6% vs 99.6%, CI 95% OR [1.61-5.73], p<0.0001) and lower antibody titer compared to controls (median (IQR) 403 (131.5-1012) vs 1160 (702.5-1675), p<0.0001). After logistic regression, age, corticosteroid (CCS), Abatacept (ABA), and Mycophenolate Mofetil (MMF) use were predictors of non-response. The antibody titers eight weeks after the second dose of vaccine were lower in AIRD compared to controls, median (IQR) 403 (131.5-1012) vs 1160 (702.5-1675), p<0.0001 with no difference between sexes and age groups. CTD, RA and SpA had lower antibodies levels. However, the logistic regression model identifed treatment with MMF, ABA, CCS, Methotrexate (MTX), Rituximab (RTX), Janus Kinase inhibitors (JAKi) and TNF inhibitors (TNFi) as independent predictors of serum titer. ABA, RTX, MMF, and MTX had the strongest effect size. Conclusion: The response to anti-SARS-CoV-2 vaccines is often impaired in AIRD patients under treatment and may pose them at higher risk of severe COVID-19. Although this work focused on serological response, most of the treatment the impaired vaccine response are known to act on T cells, possibly also influencing the cellular response. Evidence-based protocols are required to time vaccination and treatment to improve immunization of AIRD patients.