The TMPRSS2 rs75603675 genotype (OR = 0.586), dyslipidemia (OR = 2.289), sex (OR = 0.586), and the Charlson Comorbidity Index (OR = 1.126) were identified as the main predictors of COVID-19 severity in 817 patients who attended Hospital Universitario de La Princesa during March and April 2020. Here, TMPRSS2 is linked to COVID-19.