AUTHOR=Epistolio Samantha , Ramelli Giulia , Ottaviano Margaret , Crupi Emanuele , Marandino Laura , Biggiogero Maira , Maida Pier Andrea , Ruinelli Lorenzo , Vogl Ursula , Mangan Dylan , Pascale Mariarosa , Cantù Marco , Ceschi Alessandro , Bernasconi Enos , Mazzucchelli Luca , Catapano Carlo , Alimonti Andrea , Garzoni Christian , Gillessen Sommer Silke , Stefanini Federico Mattia , Franzetti-Pellanda Alessandra , Frattini Milo , Pereira Mestre Ricardo 

TITLE=P1245 Polymorphic Variants of HSD3B1 Gene Confer Different Outcome in Specific Subgroups of Patients Infected With SARS-CoV-2

JOURNAL=Frontiers in Medicine

VOLUME=Volume 8 - 2021

YEAR=2022

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.793728

DOI=10.3389/fmed.2021.793728

ISSN=2296-858X

ABSTRACT=Introduction
SARS-CoV-2 uses the androgen receptor, through ACE2 receptor and TMPRSS2, to enter nasal and upper airways epithelial cells. Genetic analyses revealed that HSD3B1 P1245C polymorphic variant increases dihydrotestosterone production and upregulation of TMPRSS2 with respect to P1245A variant, thus possibly influencing SARS-CoV-2 infection. Our aim was to characterize the HSD3B1 polymorphism status and its potential association with clinical outcomes in hospitalized COVID-19 patients in Southern Switzerland.

Materials and Methods
The cohort included 400 patients hospitalized for COVID-19 during the first wave between February and May 2020 in two different hospital of Canton Ticino. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue blocks and HSD3B1 gene polymorphism was evaluated by Sanger sequencing. Statistical associations were verified using different test. 

Results
HSD3B1 polymorphic variants were not associated with a single classical factor related to worse clinical prognosis in SARS-CoV-2 hospitalized patients. However, in specific subgroups, HSD3B1 variants played a clinical role: intensive care unit admission was more probable in P1245C diabetic patients compared to P1245A individuals without this comorbidity and death was more associated with hypertensive P1245A>C cases than P1245A patients without hypertension.

Discussion
This is the first study showing that HSD3B1 gene status may influence the severity of SARS-CoV-2 infection. If confirmed, our results could lead to the introduction of HSD3B1 gene status analysis in SARS-CoV-2 infected patients in order to predict clinical outcome.