Immunogenicity and safety of the mRNA-based BNT162b2 vaccine in systemic autoimmune rheumatic diseases patients

Abstract

Background The COVID-19 outbreak has led to the rapid development and administration of the COVID-19 vaccines worldwide. Data about the immunogenicity and adverse effects of the vaccine on patients with systemic autoimmune rheumatic diseases (SARDs) is emerging. Aim To evaluate Pfizer/BioNTech (BNT162b2) mRNA-based vaccine second-dose immunogenicity and safety, and the relation between them, in patients with SARDs. Methods A total of one hundred forty tow adults who received two doses of the BNT162b2 vaccine were included in the study. The SARDs group included Ninety-nine patients and the control group (forty-three participants) comprised a mixture of healthy participants and patients who were seen at the rheumatology clinic for non-SARDs. Anti-SARS-CoV-2 IgG antibodies against the Spike protein were evaluated using a SARS-CoV-2 IgG immunoassay. A level of > 150 AU/mL was considered positive. An adverse effects questionnaire was given to the participants upon their first visit to the clinic after their BNT162b2 vaccination. Results Of the 142 participants, 116 were seropositive (81.7%) and 26 (18.3%) were seronegative. Of the seronegative participants, 96.2% were SARDs patients. The proportion of seropositivity in the SARDs patients treated with any immunosuppressant was significantly lower (69.9%) compared to the control group and SARDs patients not receiving immunosuppressants (96.8%). A significant negative correlation between seronegativity and treatment with rituximab, mycophenolate mofetil (MMF), and prednisone was found in the SARDs group (p = 0.004, 0.044, 0.007 respectively). No fever was observed following the BNT162b2 vaccine in seronegative patients, and the frequency of musculoskeletal adverse effects upon the second dose of the BNT162b2 vaccine was significantly higher in seropositive compared to seronegative patients and in the control group compared to the SARDs patients (p = 0.045, p = 0.02 respectively). Conclusion A decline in the immunogenicity to the second dose of BNT162b2 mRNA is seen in patients with SARDs, especially in patients treated with rituximab, MMF, and prednisone. Adverse effects of the vaccine including fever and musculoskeletal symptoms might be a signal for the acquisition of immunity in those patients. Key Points• BNT162b2 mRNA vaccine is less immunogenic in SARDs patients compared to the control group.• Rituximab, prednisone, and mycophenolate mofetil significantly reduced immunogenicity to the vaccine.• There is a correlation between immunogenicity and adverse effects of the vaccine.

The impact of immunotherapies on COVID-19 case fatality rates during the US vaccination campaign: a multidisciplinary open data analysis using FDA Adverse Event Reporting System and Our World in Data

“…We found that although the CFR decreases in the general population with increasing vaccination coverage, this effect is not observed in patients treated with CD20-targeting drugs or patients treated with glucocorticoids. This is in line with studies showing impaired humoral and cellular vaccination responses in patients under anti-CD20 treatment ( Moor et al, 2021 ; Pri-Paz Basson et al, 2022 ; Wu et al, 2022 ) and studies showing that glucocorticoids impair the immunogenicity of the COVID-19 vaccine ( Bugatti et al, 2021 ; Pri-Paz Basson et al, 2022 ). In contrast, in accordance with previous studies that found that the respective treatments do not significantly impair COVID-19 vaccination efficacy, we observed a decrease in CFRs for patients under anti-TNFα ( Dimopoulou et al, 2022 ; Pri-Paz Basson et al, 2022 ; Venerito et al, 2022 ), JAK inhibitor ( Winthrop et al, 2016 ; Mortezavi et al, 2021 ; Pri-Paz Basson et al, 2022 ), or thalidomide analog ( Jenner et al, 2021 ) treatment.…”

“…This is in line with studies showing impaired humoral and cellular vaccination responses in patients under anti-CD20 treatment ( Moor et al, 2021 ; Pri-Paz Basson et al, 2022 ; Wu et al, 2022 ) and studies showing that glucocorticoids impair the immunogenicity of the COVID-19 vaccine ( Bugatti et al, 2021 ; Pri-Paz Basson et al, 2022 ). In contrast, in accordance with previous studies that found that the respective treatments do not significantly impair COVID-19 vaccination efficacy, we observed a decrease in CFRs for patients under anti-TNFα ( Dimopoulou et al, 2022 ; Pri-Paz Basson et al, 2022 ; Venerito et al, 2022 ), JAK inhibitor ( Winthrop et al, 2016 ; Mortezavi et al, 2021 ; Pri-Paz Basson et al, 2022 ), or thalidomide analog ( Jenner et al, 2021 ) treatment. For the thalidomide analogs group (median patient age 68 years, IQR 61–76 years) the evolution of the CFR over the course of the vaccination campaign is similar to what we observed for patients ≥65 years old in the general population (FAERS COVID-19 dataset, irrespective of treatment).…”

Integration of Cellular and Humoral Immune Responses as an Immunomonitoring Tool for SARS-CoV-2 Vaccination in Healthy and Fragile Subjects

“…Literature evidence reported an impaired immune proficiency, especially in the humoral arm, in the presence of autoimmune diseases under treatment [ 57 , 58 , 59 ]. Our analysis included a low number of individuals characterized by these clinical conditions; thus, we might not reach final conclusions in this regard.…”

Steroid treatment suppresses the CD4+ T-cell response to the third dose of mRNA COVID-19 vaccine in systemic autoimmune rheumatic disease patients

“…More studies focusing on the effect of steroids on regulatory cytokine expression and T-cells in the context of mRNA vaccines might contribute to a better understanding of the role of steroids in inhibiting the cellular response to mRNA vaccine. Further, studies show that anti-B cell therapy and glucocorticoid treatment were found to reduce the humoral response to two doses of the BNT162b2 vaccine 4 , 22 . However, the third dose of the vaccine was shown to increase the antibody titers also in immunosuppressed patients 23 , 24 .…”