ABSTRACT
Background: Vaccination against COVID19 is the most important prevention tool against the current pandemic. However, since the approval of anti-COVID19 mRNA vaccines by EMA, safety and tolerability in patients with rheumatic musculoskeletal diseases has always been a much-discussed topic, given their novel, unprecedented mechanism of action and the concern for potential disease fares. Objectives: To assess the safety and type of adverse events after two doses of BNT162b2 anti-SARS-CoV-2 vaccine in patients affected by rheumatologic diseases. Methods: 241 patients who received two doses of BNT162b2 were invited to take part to a follow-up live visit 2 months after completion of the primary vaccination cycle. Data regarding age, sex, diagnosis, treatment and adverse events after vaccination were collected for each patient during the visit. Pearson chi-square and Fisher exact tests were used to compare the distribution of each type of adverse event between male and female and among Rheumatoid Arthritis, Spondyloarthritis and Connective Tissue Disease patients. Results: Mean age of recruited patients was 57 years (IQR 49-65) and F:M ratio was 2.49:1 (172 F/69 M). Number and percentage of individuals for each disease category were represented as follows: Rheumatoid Arthritis 87 (36,10%), Spondyloarthritides 72 (29,88%), Connective Tissue Diseases 65 (26,97%), Autoinfammatory Diseases 4 (1,66%), Vasculitides 13 (5,39%). 42 subjects (17,42%) reported no adverse events, whereas local reactions such as pain and swelling at injection site were the most commonly reported side effect, (154 subjects, 63,9%, Table 1). Constitutional symptoms, comprising fatigue, muscle and joint pain, fever, chills and headache, were described in 54,77% of the interviews (132 subjects, Table 1). No patient experienced severe allergic reactions after vaccination. Statistical comparison among disease categories showed no differences in the distribution of adverse events. When analysing for sex, joint pain appeared to be reported signifcantly more frequently in male patients (p=0.002), while chills were more present in female patients (p=0.033). None of the interviewed subjects reported any sign or symptom relatable to disease fares. Conclusion: Vaccination with two doses of BNT162b2 was safe and generally well tolerated. No reports of signs or symptoms of disease reactivation were found in our cohort.
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.
ABSTRACT
Background: The new coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) is a source of concern for the management of patients suffering from rheumatic and musculoskeletal diseases (RMDs) treated with immunomodulatory therapies (1). Objectives: We aimed to analyze the prevalence of SARS-CoV-2 infection in patients with RMDs living in Italy. Methods: During the first wave (March-May 2020) and during the second wave (October-December 2020) of COVID-19, we conducted a survey to investigate the incidence of SARS-CoV-2 infection in patients with RMDs followed at the Rheumatology Unit of the University of Campania, Italy. The demographic data, medication use, the frequency of respiratory symptoms and the incidence of COVID-19 confirmed by nasopharyngeal swab were collected with questionnaires administered by phone. The prevalence of COVID-19 of our cohort was compared to that of the general population (2). Results: During the first wave, we collected data from 900 patients with RMDs (Table 1): 320 patients with rheumatoid arthritis (RA), 295 patients with spondyloarthropathies (SpA), 283 patients with systemic lupus erythematosus (SLE), 2 patients with vasculitis. 546 (60%) were treated with bDMARD/tsDMARDs. Overall, a total of 11/900 (1%) cases were tested for COVID-19 due to compatible symptoms. 2 (0.2%) adult patients treated with bDMARDs were registered as swab test positive by PCR for COVID-19. 2 patients without confirmed COVID-19 developed pneumonia that required admission to hospital. No deaths occurred among the patients with confirmed COVID-19. During the second wave, data were collected from 470 patients who accepted to take part of the study (Table 1). 49 presented with symptoms that were compatible with COVID-19. 139 patients were tested whereas 30 patients (6%) had a swab confirmation of SARS-CoV-2 infection. Among them, 16 (53%) were treated with bDMARDs and a patient was treated with tofacitinib. we found no increase in COVID-19 prevalence in patients treated with bDMARD/tsDMARDs (p≥0.05). A patient with SLE developed pneumonia that required admission to hospital and died. Lacking distinct prevalence data between first and second waves, we found no differences in total COVID-19 prevalence between general population living in Campania (215.752/5.802.000;3.7%) and patients with RMDs (32/900;3.5%). However, we had a significant increase in COVID-19 prevalence in our cohort during the second wave compared to the first. Nevertheless, no increase in mortality or hospitalization was recorded, confirming the safety of immunomodulatory therapies in patients with RMDs. Conclusion: In this cohort of patients with RMDs in a geographical region with a high prevalence of COVID-19, the risk of SARS-CoV-2 infection does not appear different from that observed in the general population.