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.