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=8

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=<p><bold>Introduction:</bold> Severe respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the androgen receptor (AR), through ACE2 receptor and TMPRSS2, to enter nasal and upper airways epithelial cells. Genetic analyses revealed that <italic>HSD3B1</italic> 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 <italic>HSD3B1</italic> polymorphism status and its potential association with clinical outcomes in hospitalized patients with COVID-19 in Southern Switzerland.</p><p><bold>Materials and Methods:</bold> The cohort included 400 patients hospitalized for COVID-19 during the first wave between February and May 2020 in two different hospitals of Canton Ticino. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue blocks, and <italic>HSD3B1</italic> gene polymorphism was evaluated by Sanger sequencing. Statistical associations were verified using different test.</p><p><bold>Results:</bold><italic>HSD3B1</italic> polymorphic variants were not associated with a single classical factor related to worse clinical prognosis in hospitalized patients with SARS-CoV-2. However, in specific subgroups, <italic>HSD3B1</italic> variants played a clinical role: intensive care unit admission was more probable in patients with P1245C diabetes compared with P1245A individuals without this comorbidity and death was more associated with hypertensive P1245A&gt;C cases than patients with P1245A diabetes without hypertension.</p><p><bold>Discussion:</bold> This is the first study showing that <italic>HSD3B1</italic> gene status may influence the severity of SARS-CoV-2 infection. If confirmed, our results could lead to the introduction of <italic>HSD3B1</italic> gene status analysis in patients infected with SARS-CoV-2 to predict clinical outcome.</p>