There are a few arguments in favor of a beneficial role of adaptation to hypoxia in SARS-CoV-2 infection which could support the Arias-Reyes hypothesis (Arias-Reyes et al., 2020): 1) hypoxic activation of the hypoxia-inducible factor (HIF)-1α was reported to inhibit epithelial cells attaching to SARS-CoV-2 by modulating the expression of ACE2 and heparan sulfate (Prieto-Fernandez et al., 2021; Wing et al., 2021) and, 2) an association of rs11549465 (C1772T) variant of HIF-1α with COVID-19 susceptibility was described (Das et al., 2021). This evidence concerns the gene ACE2 and COVID-19.