Host Genetic Risk Factors Associated with COVID-19 Susceptibility and Severity in Vietnamese

Abstract

Since the emergence and rapid transmission of SARS-CoV-2, numerous scientific reports have searched for the association of host genetic variants with COVID-19, but the data are mostly acquired from Europe. In the current work, we explored the link between host genes (SARS-CoV-2 entry and immune system related to COVID-19 sensitivity/severity) and ABO blood types with COVID-19 from whole-exome data of 200 COVID-19 patients and 100 controls in Vietnam. The O blood type was found to be a protective factor that weakens the worst outcomes of infected individuals. For SARS-CoV-2 susceptibility, rs2229207 (TC genotype, allele C) and rs17860118 (allele T) of IFNAR2 increased the risk of infection, but rs139940581 (CT genotype, allele T) of SLC6A20 reduced virus sensitivity. For COVID-19 progress, the frequencies of rs4622692 (TG genotype) and rs1048610 (TC genotype) of ADAM17 were significantly higher in the moderate group than in the severe/fatal group. The variant rs12329760 (AA genotype) of TMPRSS2 was significantly associated with asymptomatic/mild symptoms. Additionally, rs2304255 (CT genotype, allele T) of TYK2 and rs2277735 (AG genotype) of DPP9 were associated with severe/fatal outcomes. Studies on different populations will give better insights into the pathogenesis, which is ethnic-dependent, and thus decipher the genetic factor's contribution to mechanisms that predispose people to being more vulnerable to COVID-19.

Keywords: ABO blood type; COVID-19; SARS-CoV-2; host genetic variants; whole-exome sequencing.

Figure 1

Demographic characteristics of the studied cohort. SARS-CoV-2-infected subjects were positive with quantitative RT-PCR tests. The clinical manifestations were classified into three categories: asymptomatic/mild (grey, 69 patients, 34.5%), moderate (orange, 67 patients, 33.5%), severe/fatal (green, 64 patients, 32%).

Figure 2

Frequency distribution of IFNAR2 and SLC6A20 genotypes and alleles studied cohort. (a) For IFNAR2 rs12229207, COVID-19 patients carrying TT genotype showed significantly higher frequencies than the controls, while the frequency of the CT genotype was significantly higher in the controls compared with the patient’s group; (b) for both IFNAR2 rs12229207 and rs17860118, the mutant alleles were significantly higher in the infected individuals compared to the controls; (c) for SLC6A20 rs139940581, there was a significantly higher frequency of infected individuals carrying CT genotype and allele T compared with those observed in the controls.

Figure 3

Genotype and allele frequency of ADAM17, TMPRSS2, TYK2, and DPP9 in COVID-19 patients. (a) For ADAM17, the frequency of TG genotype of rs4622692 and TC genotype of rs1048610 in the moderate group were significantly higher than in the severe/fatal group, (b) for TMPRSS2 rs12329760, the frequency of AA genotype in asymptomatic/mild cases was significantly higher than that in severe/fatal cases, (c) for TYK2 rs2304255, CT genotype and allele T in severe/fatal cases were significantly higher than those in the asymptomatic/mild cases, (d) for DPP9 rs2277735, heterozygous AG genotype showed a significantly higher frequency in moderate and severe/fatal groups compared with that in the asymptomatic/mild group.