Considering that genetic polymorphisms are probably involved in COVID-19 severity and there are differences between the frequencies of these polymorphisms across different populations and ethnicities, we investigated the association between the rs1799752/ACE1, rs2285666/ACE2, rs12329760/TMPRSS2, rs2109069/DPP9, rs2304256/TYK2, rs1990760/IFIH1, rs2236757/IFNAR2, rs368234815/IFNL4, and rs3775291/TLR3 polymorphisms and COVID-19 severity and mortality in a Brazilian population. The gene discussed is TLR3; the disease is COVID-19.