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The SARS‐CoV‐2 virus causes COVID‐19, an infection capable of causing severe disease and death but which can also be asymptomatic or oligosymptomatic. We investigated whether ABO blood group or secretor status was associated with COVID‐19 severity. We investigated secretor status because expression of ABO glycans on secreted proteins and non‐erythroid cells are controlled by a fucosyltransferase (FUT2), and inactivating FUT2 mutations result in a non‐secretor phenotype which protects against some viral infections. Data combined from healthcare records and our own laboratory tests (n = 275) of hospitalized SARS‐CoV‐2 polymerase chain reaction positive patients confirmed higher than expected numbers of blood group A individuals compared to O (RR = 1.24, CI 95% [1.05, 1.47], p = 0.0111). There was also a significant association between group A and COVID‐19‐related cardiovascular complications (RR = 2.56, CI 95% [1.43, 4.55], p = 0.0011) which is independent of gender. Molecular analysis revealed that group A non‐secretors are significantly less likely to be hospitalized than secretors. Testing of convalescent plasma donors, among whom the majority displayed COVID‐19 symptoms and only a small minority required hospitalization, group A non‐secretors were slightly over‐represented. Our findings showed that group A non‐secretors are not resistant to infection by SARS‐CoV‐2, but are more likely to experience a less severe form of associated disease.

The SARS-CoV-2 virus causes COVID-19, an infection capable of causing severe disease and death but which may also be asymptomatic or oligosymptomatic in many individuals. While several risk factors, including age, have been described, the mechanisms of this variation are poorly understood. Several studies have described associations between blood group and COVID-19 severity, while others do not. Expression of ABO glycans on secreted proteins and non-erythroid cells is controlled by a fucosyltransferase (FUT2). Inactivating mutations result in a non-secretor phenotype which is known to protect against some viral infections. We investigated whether ABO or secretor status was associated with COVID-19 severity. Data combined from healthcare records and laboratory tests (n=275) of SARS-CoV-2 PCR positive patients hospitalised with COVID-19, confirmed higher than expected numbers of blood group A individuals compared to O (RR=1.24, CI 95% [1.05,1.47], P=0.0111). There was also a significant association between group A and COVID-19-related cardiovascular complications (RR=2.56, CI 95% [1.43,4.55], P=0.0011) which is independent of gender. Molecular analysis of phenotype revealed that group A patients who are non-secretors are significantly less likely to be hospitalised than secretors. In a larger cohort of 1000 convalescent plasma donors, among whom the majority displayed COVID-19 symptoms and only a small minority required hospitalisation, group A non-secretors were slightly over-represented. Our findings indicate that group A non-secretors are not resistant to infection by SARS-CoV-2, but they are likely to experience a less severe form of its associated disease.Key PointsBlood group type A is associated with an increased risk of cardiovascular complications in COVID-19 patients.FUT2 “non-secretor” status reduces the risk of severe COVID-19 outcomes in patients with blood group A.