Does ABO blood group influence antibody response to SARS‐CoV‐2 vaccination?

In two recent studies published in Vox Sanguinis, de Freitas Dutra et al. and Bloch et al. investigated whether ABO blood group was associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibody response following natural infection in convalescent plasma donors [1, 2]. de Freitas Dutra et al. found lower infection prevalence, and neutralizing and anti-nucleocapsid antibody titres among blood types O and B compared to A and AB [1]. Bloch et al. also found significant differences in neutralizing antibody titres according to ABO blood groups [2].

The impact of ABO blood group on SARS-CoV-2 infection risk and disease severity has been investigated by several studies. Results of a recent systematic review and meta-analysis suggest that non-O blood groups are associated with a significantly increased probability of SARS-CoV-2 infection compared to individuals with blood group O [3]. It has been proposed that anti-A antibodies in blood group O individuals could interfere in the interaction between SARS-CoV-2 and its receptor, decreasing the susceptibility to infection of blood group O individuals [3].

The antibody titre before SARS-CoV-2 vaccination has been identified as a significant predictor of postvaccination response [4]; we conducted a cross-sectional study to investigate whether ABO blood group influences antibody response to SARS-CoV-2 vaccination. Participants were enrolled among medical students of the University of Turin, in Northern Italy, undergoing vaccination with Pfizer/BNT162b2 SARS-CoV-2 mRNA vaccine. The study was approved by the University's bioethical committee (protocol number 280344). Serum samples were obtained from participants 2 weeks after completing a full vaccination cycle (two doses, 21 days apart), in June 2021. Informed consent was obtained prior to the collection of data and specimens. SARS-CoV-2 anti-S antibodies were assayed using the EUROIMMUN QuantiVac ELISA kit (EUROIMMUN Medizinische Labordiagnostika AG, Lübeck, Germany). This method detects IgG antibodies against the S1 domain of the spike protein including the receptor-binding domain (RBD). Results were expressed in relative units, RU/ml. Due to non-normal distribution (Shapiro–Wilk test), the Kruskal–Wallis test was conducted to evaluate possible differences between ABO blood groups. All analyses were conducted using SPSS version 27.0 (IBM, Armonk, NY).

In total, 85 medical students were enrolled, of which 57.6% (n = 49) were female and 42.4% (n = 36) were male. Only 5.88% (n = 5) had a previous COVID-19 infection confirmed by reverse-transcription polymerase chain reaction (RT-PCR) testing. The overall mean anti-S IgG titre was 1497.64 RU/ml (SD 937.28 RU/ml). Table 1 reports anti-S IgG titres stratified by blood groups. As shown in Figure 1, no significant differences in antibody levels among ABO blood groups were identified in our sample (p 0.771 at Kruskal-Wallis test).

TABLE 1. Anti-spike IgG antibody titres following full vaccination cycle with Pfizer/BNT162b2 SARS-CoV-2 mRNA vaccine, stratified by ABO blood groups, in a sample of medical students of the University of Turin, Italy, June 2021 (N = 85) Blood group N (%) Median (IQR), RU/ml O 35 (41.18) 1240.80 (788.56–2009.28) A 28 (32.94) 1254.80 (817.68–1553.36) B 14 (16.47) 1212.84 (676.56–1789.44) AB 8 (9.41) 1299.16 (1203.52–2129.4) Abbreviations: IQR, interquartile range; RU, relative units. image Box plots representing anti-spike IgG antibody titres following full vaccination cycle with Pfizer/BNT162b2 SARS-CoV-2 mRNA vaccine, stratified by ABO blood groups, in a sample of medical students of the University of Turin, Italy, June 2021 (N = 85). RU, relative units [Colour figure can be viewed at wileyonlinelibrary.com]

Despite limitations due to our small sample, which only included medical students from a single University, our results do not support an influence of ABO blood group on vaccine response, and could be useful to inform vaccine strategy.

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