Seroepidemiological study of factors affecting anti-spike IgG antibody titers after a two-dose mRNA COVID-19 vaccination in 3744 healthy Japanese volunteers

Several factors related to anti-spike(S) IgG antibody titers after mRNA COVID-19 vaccination have been elucidated, but the magnitude of the effects of each factor has not been fully understood. This cross-sectional study assessed anti-S and anti-nucleocapsid (N) antibody titers on 3744 healthy volunteers (median age, 36 years; IQR, 24–49 years; females, 59.0%) who received two doses of mRNA-1273 or BNT162b2 vaccine and completed a survey questionnaire. Multiple regression was conducted to identify factors associated with antibody titers. All but one participant tested positive for anti-S antibodies (99.97%). The following factors were independently and significantly associated with high antibody titer: < 3 months from vaccination (ratio of means 4.41); mRNA-1273 vaccine (1.90, vs BNT162b2); anti-N antibody positivity (1.62); age (10’s: 1.50, 20’s: 1.37, 30’s: 1.26, 40’s: 1.16, 50’s: 1.15, vs ≧60’s); female (1.07); immunosuppressive therapy (0.54); current smoking (0.85); and current drinking (0.96). The largest impact on anti-S IgG antibody titers was found in elapsed time after vaccination, followed by vaccine brand, immunosuppressants, previous SARS-CoV-2 infection (anti-N antibody positive), and age. Although the influence of adverse reactions after the vaccine, gender, smoking, and drinking was relatively small, they were independently related factors.