Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were launched in December 2020. Vaccination of patients with rheumatic diseases is recommended, as they are considered at higher risk of severe COVID-19 than the general population. Patients with rheumatic disease have largely been excluded from vaccine phase 3 trials. This study explores the safety and reactogenicity of BNT162b2 among patients with rheumatic diseases. Patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), median age 58.8 years, 285 subjects in total, were vaccinated twice with the BNT162b2 (Pfizer/BioNTech). Questionnaires on reactogenicity matching the original phase 3 study were answered seven days after completed vaccination. The majority of SLE and RA patients experienced either local (78.0%) or systemic reactions (80.1%). Only 1.8% experienced a grade-4 reaction. Compared to the original study, we found more frequent fatigue [Odds ratio (OR) 2.2 (1.7-2.8)], headache 2)], muscle pain 3)], and joint pain ] in patients. In contrast, the use of antipyretics was less frequent [OR 0.5 (0.3-0.6)]. Patients with SLE and RA experience reactogenicity to the Pfizer-BioNTech BNT162b2 COVID-19 vaccine. Reactogenicity was more frequent in patients, however, not more severe compared with healthy controls.

Objectives Patients with chronic rheumatic diseases (CRD), such as Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA), require special attention during the COVID‐19 pandemic, as they are considered at risk of severe infections. We assessed the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) antibodies in patients with SLE and RA and patient behavior, disease‐related symptoms, and mental health. Methods More than 900 participants were included: 405 patients with RA or SLE (CRD‐patients) and 513 blood donors. All participants had blood SARS‐CoV‐2 total antibodies measured (sensitivity 96.7%, specificity 99.5%) and answered a questionnaire concerning behavior, anxiety, and symptoms of depression (PHQ‐9). The CRD patients were further asked about physical activity, adherence to medication, and disease‐related symptoms. Results CRD‐patients had a significant lower seroprevalence of SARS‐CoV‐2 antibodies (n=1/365, 0.3%) compared to blood donors (n=10/513, 1.9%) (p=0.03). Almost 60% of patients were unable to exercise as usual, increased pain was experienced by 34% of patients and increased disease activity by 24%. Almost 10% of patients reduced or discontinued their immunosuppressive treatments at their own initiative. Symptoms of moderate depression were present in 19% of patients compared to 6,8% blood donors (p<0.001). Conclusions Low seroprevalence in patients with CRDs indicates successful mitigation of exposure to SARS‐CoV‐2. However, this appears to occur at the expense of physical activity, experience of increased pain, disease activity, and symptoms of depression. There is a need for care providers to be aware of these negative side‐effects and for further studies to investigate the possible long‐term consequences.

Objective We aimed to investigate if patients with rheumatic diseases treated with rituximab raise a serological response towards the COVID-19 mRNA vaccines and to elucidate the influence of time since the last dose RTX before vaccination on this response. Methods We identified and included 201 patients with rheumatic diseases followed at the out-patient clinic at the Department of Rheumatology, Aarhus University Hospital, who had been treated with RTX in the period 2017-2021 and who had finished their two-dose vaccination with a COVID-19 mRNA vaccine. Total antibodies against SARS-CoV2 spike protein were measured on all patients and 44 blood donors as a reference. Results We observed a time-dependent increase in antibody response as the interval from the last RTX treatment to vaccination increased. Only 17.3% of patients developed a detectable antibody response after receiving their vaccination 6 months or less after their previous RTX treatment. Positive antibody response increased to 66.7% in patients who had RTX 9-12 months before vaccination. All blood donors (100%) had detectable antibodies after vaccination. Conclusion Patients with rheumatic diseases treated with rituximab have a severely impaired serological response towards the COVID-19 mRNA vaccine. Our data suggest that the current recommendations of a 6 months interval between rituximab treatment and vaccination should be revised.

Objectives To investigate the effect of either a booster vaccine (one dose) or revaccination (two doses three weeks apart) on the antibody response to the COVID-19 mRNA vaccines in patients with rheumatic disease (RD) treated with Rituximab (RTX), who had not produced vaccine-reactive antibodies after the initial two vaccine doses. Further, to examine if B cell levels in peripheral blood predicted seroconversion. Methods We included 91 RTX-treated RD patients previously vaccinated against COVID-19. Patients were offered revaccination or a single booster vaccination with an mRNA vaccine. Serum total antibodies against SARS-CoV-2 spike protein were measured before and six weeks after the last vaccine dose. B-cells (CD19+CD45+) were measured by flow cytometry at inclusion. Results Of RD patients with undetectable SARS-CoV-2 antibody levels before inclusion, seroconversion was seen in 38% six weeks after the booster dose and 32% after revaccination. Patients receiving revaccination had significantly higher antibody levels than patients receiving a booster dose (p&lt; 0.001). In both univariate and multivariate logistic regression analysis, only B-cells higher than 10/µL before boost or revaccination were associated with seroconversion (p= 0.009 and p= 0.01, respectively). Seroconversion was independent of age, gender, diagnosis, cumulative RTX dose, RTX treatment time, and time since last RTX treatment. Conclusion Continuously impaired humoral response to mRNA vaccines was found in most RTX treated patients after a booster dose or revaccination. Seroconversion was observed in approximately one-third of the patients. Measurable B-cells before boosting or revaccination was the strongest predictor of antibody response after boost or revaccination.