SARS-CoV-2 utilizes the angiotensin-converting enzyme 2 (ACE2) receptor and transmembrane serine protease (TMPRSS2) to infect human lung cells. Previous studies have suggested that different host ACE2 and TMPRSS2 genetic backgrounds might contribute to differences in the rate of SARS-CoV-2 infection or COVID-19 severity. Recent studies have also shown that variants in 15 genes related to type I interferon immunity to influenza virus might predispose patients toward life-threatening COVID-19 pneumonia. Other genes (SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6, XCR1, IL6, CTSL, ABO, and FURIN) and HLA alleles have also been implicated in the response to infection with SARS-CoV-2. Currently, Brazil has recorded the third-highest number of COVID-19 cases worldwide. We aimed to investigate the genetic variation present in COVID-19-related genes in the Brazilian population. We analyzed 27 candidate genes and HLA alleles in 954 admixed Brazilian exomes. We used the information available in two public databases (http://www.bipmed.org and http://abraom.ib.usp.br/) and additional exomes from individuals born in southeast Brazil, the region of the country with the highest number of COVID-19 patients. Variant allele frequencies were compared with the 1000 Genomes Project phase 3 (1KGP) and gnomAD databases. We detected 395 nonsynonymous variants; of these, 325 were also found in the 1KGP and/or gnomAD. Six of these variants were previously reported to influence the rate of infection or clinical prognosis of COVID-19. The remaining 70 variants were identified exclusively in the Brazilian sample, with a mean allele frequency of 0.0025. In silico analysis revealed that seven of these variants are predicted to affect protein function. Furthermore, we identified HLA alleles previously associated with the COVID-19 response at loci DQB1 and DRB1. Our results showed genetic variability common to other populations and rare and ultrarare variants exclusively found in the Brazilian population. These findings might lead to differences in the rate of infection or response to infection by SARS-CoV-2 and should be further investigated in patients with this disease.

SARS-CoV-2 利用血管紧张素转换酶 2 (ACE2) 受体和跨膜丝氨酸蛋白酶 (TMPRSS2) 感染人肺细胞。先前的研究表明，不同的宿主ACE2和TMPRSS2遗传背景可能导致 SARS-CoV-2 感染率或 COVID-19 严重程度的差异。最近的研究还表明，与对流感病毒的 I 型干扰素免疫相关的 15 个基因的变异可能使患者易患危及生命的 COVID-19 肺炎。其他基因（SLC6A20、LZTFL1、CCR9、FYCO1、CXCR6、XCR1、IL6、CTSL、ABO和FURIN）和HLA等位基因也与对 SARS-CoV-2 感染的反应有关。目前，巴西的 COVID-19 病例数在全球排名第三。我们旨在调查巴西人群中 COVID-19 相关基因中存在的遗传变异。我们分析了 27 个候选基因和HLA954 个混合的巴西外显子组中的等位基因。我们使用了两个公共数据库（http://www.bipmed.org 和 http://abraom.ib.usp.br/）中可用的信息，以及来自巴西东南部出生的个体的其他外显子组，该地区是巴西COVID-19 患者人数最多。将变异等位基因频率与 1000 Genomes Project 第 3 阶段 (1KGP) 和 gnomAD 数据库进行了比较。我们检测到 395 个非同义变体；其中，1KGP 和/或 gnomAD 中也发现了 325 个。据报道，其中六种变体会影响 COVID-19 的感染率或临床预后。其余 70 个变体仅在巴西样本中鉴定，平均等位基因频率为 0.0025。计算机分析显示，其中七种变体预计会影响蛋白质功能。此外，我们确定了先前与基因座DQB1和DRB1处的 COVID-19 反应相关的HLA等位基因。我们的结果显示了其他人群共有的遗传变异性，以及仅在巴西人群中发现的稀有和超稀有变异。这些发现可能导致感染率或对 SARS-CoV-2 感染的反应存在差异，应在患有这种疾病的患者中进一步研究。