AUTHOR=Matic Sanja , Milovanovic Dragan , Mijailovic Zeljko , Djurdjevic Predrag , Stefanovic Srdjan , Todorovic Danijela , Vitosevic Katarina , Canovic Vanja , Popovic Suzana , Dimitrijevic Nevena Milivojevic , Zivanovic Marko , Seklic Dragana , Aleksic Sanja , Djordjevic Nemanja , Vukic Milena , Vukovic Nenad , Filipovic Nenad , Baskic Dejan , Djordjevic Natasa TITLE=ACE2 and TMPRSS2 genetic polymorphisms as potential predictors of COVID−19 severity and outcome in females JOURNAL=Frontiers in Medicine VOLUME=Volume 11 - 2024 YEAR=2024 URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1493815 DOI=10.3389/fmed.2024.1493815 ISSN=2296-858X ABSTRACT=IntroductionACE2 and TMPRSS2 represent the major gateways for SARS-CoV-2 cell entry. The presence of functional ACE2 and TMPRSS2 genetic polymorphisms that affect gene expression may affect the risk of severe form of COVID-19 and its fatal outcome.Material and patientsThis observational study enrolled 178 hospitalized patients diagnosed with SARS-CoV-2 infection at the University Clinical Centre of Kragujevac, Serbia. Demographic, clinical, and laboratory data were gathered at admission. Genotyping for single nucleotide polymorphisms of ACE2 (rs2106809 and rs2074192) and TMPRSS2 (rs2070788 and rs4818239) was performed using the Real-Time PCR method with TaqMan assays.ResultsControlling for other factors of influence, such as CCI, N/L ratio, LDH level, and pO2, we showed that females with TMPRSS2 rs2070788 A/A genotype were less likely to develop severe COVID-19 (odds ratio [OR] [95% confidence interval (95% CI)]: 0.030 [0.001; 0.862]). Additionally, the likelihood of dying of SARS-CoV-2 infection was lower in female carriers of at least one ACE2 rs2106809 C allele (OR [95% CI]: 0.004 [0.000; 0.981]).ConclusionOur findings indicate TMPRSS2 rs2070788 and ACE2 rs2106809 polymorphisms as independent predictors of severity and outcome of COVID-19 in females.