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.

Keywords: BNT162b2 mRNA-based vaccine; COVID-19; Immunosuppression.

Fig. 1

Study participant enrollment flow chart. SARDS, systemic autoimmune rheumatic diseases

Fig. 2

Serology results according to study group. A In the SARDS group 25.3% were seronegative (orange) compared to 2.3% in the control group, P value 0.001. B Comparing serology results regarding the use of immunosuppressive or immunomodulatory drugs. In the SARDS group 69.6% in the treated group were seropositive (blue) compared to 96.8% among untreated participants (healthy and rheumatic patients), P value < 0.0001. SARDS, systemic autoimmune rheumatic diseases; SARDS-T, SARDs patients treated with any immunosuppressive or immunomodulatory drugs

Fig. 3

Immunogenicity of the vaccine according to the use of immunosuppressive and immunomodulatory drugs. Prednisone, MMF, and mabthera were in negative correlation to seropositivity (p = 0.007, 0.044, 0.004, respectively). MTX, methotrexate; HCQ, hydroxychloroquine; SSZ, sulfasalazine; LEFL, leflunomide; COLCH, colchicine; MMF, mycophenolate mofetil; TNF-i, tumor necrosis factor inhibitors; IL6i, interleukin 6 inhibitors; JAKi, janus kinase inhibitors; MAB, mabthera; BELIM, belimumab; PRED, prednisone