Vaccination status of the groups.

Within a few years after the pandemic outbreak, several of evidence have found to suggest that the genetic factors influence the severity and mortality rate of COVID-19. In particular, the identification of genetic markers that increase the risk of severe or critical COVID-19 is important for public health management during the pandemic. By August 2021, 88.9% of Mongolian population had been vaccinated. Therefore, we conducted this study to compare the polymorphisms of candidate genes by selecting people who developed mild or severe COVID-19 within this vaccinated population. A total of 90 patients with severe COVID-19, 95 patients with mild COVID-19, and 90 asymptomatic patients were participated in present cross-sectional study. rs4646994, rs4240157, rs41423247, rs56149945, rs10052957, rs12329760, rs4303795, rs75603675 and rs17854725 polymorphisms of the ACE, ACE2, NR3C1 and TMPRSS2 genes were genotyped. Genotyping performed by real-time PCR, RFLP and allele-specific PCR methods. Odds ratio, 95% confidence interval, p value were calculated using logistic regression analysis. SNP-SNP interaction were explored using multi-dimensional reduction analysis. P values for multivariate model was corrected by Bonferroni correction. Totally 10 polymorphisms of above-mentioned genes were genotyped among the groups. Only A/C genotype frequencies of rs75603675 were significantly different between groups. Compared with mild COVID-19 group, the participants who carrying A/C genotype of rs75603675 had 3.58-fold (95% CI, 1.38–9.29, p = 0.009) higher risk for severe COVID-19. In addition, the synergistic interaction (RERI = 2.573; AP = 0.934; S = 8.352) was observed between D/D or I/D genotype of rs4646994 and A/C genotype of rs75603675, which combination (OR=4.88, 95% CI, 1.38–18.01, p = 0.014, Power = 91.1%) was associated with increased risk of severe COVID-19 after Bonferroni correction. Our result suggesting that the combination of rs4646994 of the ACE gene and rs75603675 of the TMPRSS2 gene is associated with increased risk of severe COVID-19.

新冠疫情暴发后的数年内，多项研究证据表明遗传因素会影响新型冠状病毒肺炎（COVID-19）的病情严重程度与病死率。尤为关键的是，在疫情期间，识别可增加重症或危重型COVID-19发病风险的遗传标记物，对于公共卫生管理具有重要意义。截至2021年8月，蒙古国人群的新冠疫苗接种率已达88.9%。为此，本研究选取该接种人群中确诊轻型或重型COVID-19的受试者，对候选基因的多态性展开对比分析。本横断面研究共纳入90例重型COVID-19患者、95例轻型COVID-19患者以及90例无症状感染者。本研究对血管紧张素转换酶（ACE）、血管紧张素转换酶2（ACE2）、核受体亚家族3C成员1（NR3C1）及跨膜丝氨酸蛋白酶2（TMPRSS2）基因的rs4646994、rs4240157、rs41423247、rs56149945、rs10052957、rs12329760、rs4303795、rs75603675及rs17854725位点进行了基因分型。基因分型采用实时荧光定量PCR（real-time PCR）、限制性片段长度多态性（RFLP）及等位基因特异性PCR（allele-specific PCR）技术完成。采用logistic回归分析计算比值比（OR）、95%置信区间（95% CI）及P值；借助多维度降维分析探究单核苷酸多态性（SNP）位点间的交互作用。多变量模型的P值采用Bonferroni校正法进行校正。本研究共对上述基因的10个多态性位点进行了分组基因分型。仅rs75603675位点的A/C基因型频率在各组间存在显著差异。与轻型COVID-19组相比，携带rs75603675位点A/C基因型的受试者发生重型COVID-19的风险升高3.58倍（95% CI：1.38~9.29，P=0.009）。此外，rs4646994位点的D/D或I/D基因型与rs75603675位点的A/C基因型之间存在协同交互作用（相对超额风险交互效应RERI=2.573；归因比例AP=0.934；协同指数S=8.352）；经Bonferroni校正后，该基因型组合（OR=4.88，95% CI：1.38~18.01，P=0.014，检验效能Power=91.1%）与重型COVID-19的发病风险升高显著相关。本研究结果表明，ACE基因rs4646994位点与TMPRSS2基因rs75603675位点的基因型组合，与重型COVID-19的发病风险升高显著相关。