Persistence of SARS-CoV-2 neutralizing antibodies and anti-Omicron IgG induced by BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic disease: an explanatory study in Japan

BACKGROUND: Autoimmune inflammatory rheumatic disease (AIRD) patients are at high risk of the coronavirus disease 2019 (COVID-19), but the medium-term effects of immunosuppressants on vaccine efficacy are unknown. We investigated the duration of humoral responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild-type and Omicron variant in AIRD patients administered with two doses of the BNT162b2 (Pfizer–BioNTech) vaccine. METHODS: Serum-neutralizing antibody (NAb) and anti-receptor-binding domain (RBD)/spike antibody levels were measured. Short- and medium-term effects of immunosuppressants were analyzed pre-vaccination (Term 1) and 14–42 days (Term 2) and 100–200 days (Term 3) after the second vaccination. FINDINGS: From Feb 1, 2021, to Feb 28, 2022, 439 AIRD patients and 146 healthy controls were investigated. The seropositivity rate and log(10)-NAb titers were significantly lower in AIRD patients than in controls at Terms 2 and 3. In rheumatoid arthritis patients, tumor necrosis factor-α inhibitors (TNFis) at Term 3, and older age, glucocorticoids, and abatacept at Terms 2 and 3 were risk factors for reduced responses. Anti-Omicron RBD/spike IgG levels strongly correlated with NAb titers. INTERPRETATION: Glucocorticoids, TNFis, and abatacept treatments negatively affect the longevity of humoral responses to SARS-CoV-2, including Omicron, after two vaccine doses. These findings may inform the timing of additional vaccination for AIRD patients. FUNDING: Cloud Funding of Peace Winds Japan; 10.13039/501100009033Center of Innovation Program from the 10.13039/501100001700Ministry of Education, Culture, Sports, Science and Technology of Japan; 10.13039/501100001691Japan Society for the Promotion of Science KAKENHI; 10.13039/100009619Japan Agency for Medical Research and Development; 10.13039/100020408Kansai Economic Federation; Mitsubishi Zaidan; and Research Grant from 10.13039/100009619Japan Agency for Medical Research and Development—10.13039/501100003382Core Research for Evolutional Science and Technology.