Lewis a⁻b⁻ histo-blood group antigen phenotype is predictive of severe COVID-19 in the black South African population group

Several risk factors have been associated with SARS-CoV-2 infections and severity of COVID-19 disease it causes. This study investigated whether variations in histo-blood group antigen (HBGA) expression can predispose individuals to SARS-CoV-2 infections and severity of the disease. Nasopharyngeal swabs, randomly selected from SARS-CoV-2 positive and SARS-CoV-2 negative individuals, were tested for Lewis and H-type 1 HBGA phenotypes by ELISA using monoclonal antibodies specific to Lewis a, Lewis b and H type 1 antigens. The most common Lewis HBGA phenotype among all study participants was Lewis a⁻b⁺ (46%), followed by Lewis a⁻b⁻ (24%), Lewis a⁺b⁻ and Lewis a⁺b⁺ (15% each), while 55% of the study participants were H-type 1. Although SARS-CoV-2 negative individuals had a lower likelihood of having a Lewis a⁻b⁻ phenotype compared to their SARS-CoV-2 positives counterparts (OR: 0.53, 95% C.I: 0.255–1.113), it did not reach statistical significance (P = 0.055). The frequency of Lewis a⁺b⁺, Lewis a⁺B⁻, Lewis a⁻b⁺, H type 1 positive and H type 1 negative were consistent between SARS-CoV-2 positive and SARS-CoV-2 negative individuals. When stratified according to severity of the disease, individuals with Lewis a⁺b⁻ phenotype had a higher likelihood of developing mild COVID-19 symptoms (OR: 3.27, 95% CI; 0.9604–11.1), but was not statistically significant (P = 0.055), while Lewis a⁻b⁻ phenotype was predictive of severe COVID-19 symptoms (OR: 4.3, 95% CI: 1.274–14.81), P = 0.016. In conclusion, individuals with Lewis a⁻b⁻ phenotype were less likely to be infected by SARS-CoV-2, but when infected, they were at risk of severe COVID-19.