Interestingly, a recent study shows that the ε4 carriers (ε3/ε4 or ε4/ε4) have lowest plasma levels of APOE among all APOE genotypes.26 Low protein levels and compact structural feature of APOE4 may act synergistically to cause a decreased inhibitory effect on SARS-CoV-2 viral load, and thereby resulting in increased inflammation and disease severity in COVID-19 patients with APOE ε4 genotype, compared to those with APOE ε3 genotype. This evidence concerns the gene APOE and COVID-19.