Fig. 1.

The roles of SARS-CoV-2 entry mechanism-related genes in COVID-19. There are some entry mechanisms for SARS-CoV-2 in the host genome which their diversity could affect the severity of the COVID-19. Accordingly, ACE2 is the most known virus entry receptor which undergoes some alterations; some of which such as K31R, N33I, N51S, M26V, K68E, and F72V are associated with less susceptibility to the virus, while E23K, T27A, H378R, Q102P, and N64K reduce susceptibility. Similarly, some SNPs in TMPRSS2 include rs75603675, rs61735792, rs61735794, rs112657409, rs11910678, rs77675406, and rs713400 have an association with more severe disease; however, p.V197M (rs12329760) can destabilize TMPRSS2, and as a result, attenuate the interaction of ACE2 and spike protein. The presence of SNPs such as rs20540199, rs769062069 in the FURIN gene have roles in disease mortality. Patients carrying rs3788979 and rs13015258 in the DPP4 genome, as well as those with rs12610495 in the DPP9 genome, show higher inflammatory responses in lung tissue. Also, the higher risk of COVID-19 mortality could be associated with the ε4 variant of the APOE that enhances the trafficking of ACE2 toward the cell surface.