Impact of ABO Blood System on Immunogenicity and Vaccine Efficacy of COVID‐19 Booster Vaccination—A Population‐Based Study of 3066 Individuals

Background ABO blood group has been associated with SARS‐CoV‐2 susceptibility. Little data exist regarding the impact of ABO and Rhesus (Rh[D]) type on breakthrough infections and antibody responses following SARS‐CoV‐2 booster vaccination. Methods This multicenter, population‐based cohort study includes individuals ≥ 18 years who received a booster vaccination against SARS‐CoV‐2. Antibody levels against SARS‐CoV‐2 receptor binding domain (RBD) and neutralizing antibodies against wild‐type (WT) virus and Omicron variant were assessed at baseline, after 4 weeks and after 6 months. At 6 months follow‐up, self‐reported ABO and Rh(D) type, time to, and severity of breakthrough infections were collected. Results In total, 3066 participants (mean age 49 [35–59], 62% female) were included in multivariable regression models, showing no association of anti‐RBD and neutralizing antibodies against wild‐type and Omicron variant with ABO or Rh(D) 4 weeks after booster vaccination. Time‐dependent Cox regression analysis showed significantly lower rates of breakthrough infections in patients with AB (hazard ratio [HR] 0.67 [0.50–0.90]; p = 0.008) compared to O, even after adjustment for relevant covariates and a trend for blood group B (HR 0.82 [0.66–1.01]; p = 0.06) compared to O; there were no associations between Rh(D) and breakthrough infection rates or between observed (asymptomatic to moderate) COVID‐19 symptom severity and ABO or Rh(D) blood group. Conclusions ABO or Rh(D) blood group was not associated with COVID‐19 severity or antibody responses following SARS‐CoV‐2 vaccination. Breakthrough infections were least common in blood groups AB and B. Although our data do not support previously discussed protective effects of anti‐A/B/Rh(D) agglutinins, differences in ABO group appear relevant for Omicron transmission.