Impact of comorbidities on the serological response to COVID-19 vaccination in Taiwan

Abstract Background/Aims Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the best policies to control COVID-19 pandemic. The serological response to COVID-19 vaccination in Taiwanese patients with different comorbidities is elusive. Methods Uninfected subjects who received 3 doses of mRNA vaccines (BNT162b2 [Pfizer-BioNTech, BNT] and mRNA-1273 [Moderna]), viral vector-based vaccines (ChAdOx1-S (AZD1222, AZ) or protein subunit vaccines (Medigen COVID-19 vaccine) were prospectively enrolled. The SARS-CoV-2-IgG spike antibody level was determined within three months after the 3rd dose of vaccination. The Charlson Comorbidity Index (CCI) was applied to determine the association between vaccine titers and underlying comorbidities. Results A total of 824 subjects were enrolled in the current study. The proportions of CCI scores of 0-1, 2-3 and >4 were 52.8% (n=435), 31.3% (n=258) and 15.9% (n=131), respectively. The most commonly used vaccination combination was AZ-AZ-Moderna (39.2%), followed by Moderna-Moderna-Moderna (27.8%). The mean vaccination titer was 3.11 log BAU/mL after a median of 48 days after the 3rd dose. Factors associated with potentially effective neutralization capacity included an age ≥60 years (odds ratio [OR]/95% confidence interval [CI], 0.49/0.34–0.72; P <0.001), female gender (OR/CI, 1.78/1.26–2.53; P =0.001), Moderna-based vaccination (compared to AZ-based vaccination; OR/CI, 6.49/3.90–10.82; P <0.001) and a CCI score ≥4 (OR/CI, 0.55/0.35–0.85; P =0.01). There was a decreasing trend in antibody titers with increasing CCI scores (trend P<0.001). Linear regression analysis revealed that AZ-based vaccination (β: 0.341, CI: 0.144, 0.21, P<0.001) and higher CCI scores (β: -0.055, CI: -0.096, -0.014, P=0.009) independently correlated with low IgG spike antibody levels. Conclusions Subjects with more comorbidities had a poor response to 3 doses of COVID-19 vaccination.