Ostendorf, B.N. et al. Nature (2022) https://doi.org/10.1038/s41586-022-05344-2

While most COVID-19 cases only have mild or no symptoms, some patients develop serious illness. Therefore, there is a pressing need to identify the factors that predispose patients to severe COVID-19. A new study links APOE2 and APOE4 variants to adverse outcomes in SARS-CoV-2 infection.

To assess the effect of APOE variation on SARS-CoV-2 infection, the researchers infected mice in which the murine Apoe gene was replaced with one of the three human APOE alleles (APOE2, APOE3 and APOE4 knock-in mice) with a mouse-adapted strain of SARS-CoV-2. Compared with APOE3 mice, APOE2 and APOE4 mice exhibited rapid disease progression, poor survival outcomes, elevated viral loads and blunted adaptive immune responses early after infection. The study also shows that the APOE genotype was associated with survival in SARS-CoV-2 infected patients in the UK Biobank.