| Summary: | SARS-CoV-2 uses the ACE2 receptor and the cellular protease TMPRSS2 for entry into target cells. The present study aimed to establish if the TMPRSS2 polymorphisms are associated with COVID-19 disease. The study included 609 patients with COVID-19 confirmed by RT-PCR test and 291 individuals negative for the SARS-CoV-2 infection confirmed by RT-PCR test and without antibodies anti-SARS-CoV-2. Four TMPRSS2 polymorphisms (rs12329760, rs2298659, rs456298, and rs462574) were determined using the 5′exonuclease TaqMan assays. Under different inheritance models, the rs2298659 (<i>p</i><sub>codominant2</sub> = 0.018, <i>p</i><sub>recessive</sub> = 0.006, <i>p</i><sub>additive</sub> = 0.019), rs456298 (<i>p</i><sub>codominant1</sub> = 0.014, <i>p</i><sub>codominant2</sub> = 0.004; <i>p</i><sub>dominant</sub> = 0.009, <i>p</i><sub>recessive</sub> = 0.004, <i>p</i><sub>additive</sub> = 0.0009), and rs462574 (<i>p</i><sub>codominant1</sub> = 0.017, <i>p</i><sub>codominant2</sub> = 0.004, <i>p</i><sub>dominant</sub> = 0.041, <i>p</i><sub>recessive</sub> = 0.002, <i>p</i><sub>additive</sub> = 0.003) polymorphisms were associated with high risk of developing COVID-19. Two risks (<i>ATGC</i> and <i>GAAC</i>) and two protectives (<i>GAGC</i> and <i>GAGT</i>) haplotypes were detected. High levels of lactic acid dehydrogenase (LDH) were observed in patients with the rs462574<i>AA</i> and rs456298<i>TT</i> genotypes (<i>p</i> = 0.005 and <i>p</i> = 0.020, respectively), whereas, high heart rate was present in patients with the rs462574<i>AA</i> genotype (<i>p</i> = 0.028). Our data suggest that the rs2298659, rs456298, and rs462574 polymorphisms independently and as haplotypes are associated with the risk of COVID-19. The rs456298 and rs462574 genotypes are related to high levels of LDH and heart rate.
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