Why does SARS-CoV-2 hit in different ways? Host genetic factors can influence the acquisition or the course of COVID-19

Abstract

The identification of high-risk factors for the infection by SARS-CoV-2 and the negative outcome of COVID-19 is crucial. The genetic background of the host might account for individual responses to SARS-CoV-2 infection besides age and comorbidities. A list of candidate polymorphisms is needed to drive targeted screens, given the existence of frequent polymorphisms in the general population. We carried out text mining in the scientific literature to draw up a list of genes referable to the term “SARS-CoV*“. We looked for frequent mutations that are likely to affect protein function in these genes. Ten genes, mostly involved in innate immunity, and thirteen common variants were identified, for some of these the involvement in COVID-19 is supported by publicly available epidemiological data. We looked for available data on the population distribution of these variants and we demonstrated that the prevalence of five of them, Arg52Cys (rs5030737), Gly54Asp (rs1800450) and Gly57Glu (rs1800451) in MBL2 , Ala59Thr (rs25680) in CD27 , and Val197Met (rs12329760) in TMPRSS2 , correlates with the number of cases and/or deaths of COVID-19 observed in different countries. The association of the TMPRSS2 variant provides epidemiological evidence of the usefulness of transmembrane protease serine 2 inhibitors for the cure of COVID-19. The identified genetic variants represent a basis for the design of a cost-effective assay for population screening of genetic risk factors in the COVID-19 pandemic.

Polymorphisms and mutations of ACE2 and TMPRSS2 genes are associated with COVID-19: a systematic review

“…In the Italian COVID-19 patient population, the predominant mutation p.V197M showed a detrimental effect on proteases but was found beneficial to patients (rs12329760). Variations prove to be more abundant in individuals bearing concurrent disease who do not require hospitalization or oxygen therapy than in individuals who do require oxygen therapy, ventilation, or intubation [ 39 , 40 ]. According to a German study, the ACE2 rs2285666, GG genotype, or G allele proved to be related, with a nearly twofold greater risk of SARS-CoV-2 infection and a threefold increased risk of serious disease or death, due to COVID-19 [ 41 ].…”

Investigation of MBL2 and NOS3 functional gene variants in suspected COVID-19 PCR (–) patients

“…In a recent review [ 24 ], three frequent missense mutations in MBL2 were tested: Gly54Asp (rs1800450), Arg52Cys (rs5030737) and Gly57Glu (rs1800451) . This study highlights that Gly54Asp (rs1800450) is significantly associated with susceptibility to SARS-CoV infection, but not with disease severity [ 21 , 24 ].…”

“…In a recent review [ 24 ], three frequent missense mutations in MBL2 were tested: Gly54Asp (rs1800450), Arg52Cys (rs5030737) and Gly57Glu (rs1800451) . This study highlights that Gly54Asp (rs1800450) is significantly associated with susceptibility to SARS-CoV infection, but not with disease severity [ 21 , 24 ]. The allele frequency per population of Arg52Cys (rs5030737) was positively correlated with the number of cases per country of COVID-19, but not with the mortality [ 24 , 25 ].…”

“…This study highlights that Gly54Asp (rs1800450) is significantly associated with susceptibility to SARS-CoV infection, but not with disease severity [ 21 , 24 ]. The allele frequency per population of Arg52Cys (rs5030737) was positively correlated with the number of cases per country of COVID-19, but not with the mortality [ 24 , 25 ]. Allele frequency per population of Gly54Asp (rs1800450) was positively correlated with both number of cases and mortality [ 21 , 24 ].…”

“…The allele frequency per population of Arg52Cys (rs5030737) was positively correlated with the number of cases per country of COVID-19, but not with the mortality [ 24 , 25 ]. Allele frequency per population of Gly54Asp (rs1800450) was positively correlated with both number of cases and mortality [ 21 , 24 ]. The results of this review also support the hypothesis that MBL2 plays a protective role and that its inactivation is a risk factor for SARS-CoV-2 infection and that immune response plays a role in the course of the disease.…”