Lack of association between APOE genotypes and COVID‐19 in a black South African cohort

COVID-19 and its long-term consequences remain a major global health challenge, with host genetic factors contributing to inter-individual variation in susceptibility. Apolipoprotein E ( APOE ) genotypes, particularly those including the ε4 allele, have been associated with an increased risk of COVID-19 infection in Europeans, but evidence from continental Africans remains limited. We investigated the association between APOE genotypes (ε2/ε2, ε2/ε3, ε2/ε4, ε3/ε3, ε3/ε4 and ε4/ε4) and COVID-19 positivity in 921 Bantu-speaking South Africans. COVID-19 positivity was determined serologically, while APOE genotypes were identified using TaqMan™ SNP genotyping of rs429358 and rs7412. Associations were assessed using multinomial logistic regression across unadjusted, partially adjusted (age, sex, education), and fully adjusted models (age, sex, education, wealth index, hypertension, diabetes, episodic memory, HIV), with ε3/ε3 as the reference. The most frequent genotype was ε3/ε3 (36%), followed by ε3/ε4 (29%) and ε2/ε3 (19%). None of the genotypes were significantly associated with COVID-19 positivity. In fully adjusted models, females had higher risk than males (OR = 1.54, 95% CI 1.13–2.12), this effect was also shown in sensitivity analyses using imputed covariates. In contrast to European studies, APOE genotypes were not associated with COVID-19 positivity in this cohort, highlighting the importance of ancestrally diverse genomic research. Larger African cohorts are needed to explore sex-specific effects and ancestry-dependent modifiers of APOE in COVID-19 susceptibility.