In December 2019, a novel coronavirus (SARS-CoV-2) emerged, causing coronavirus disease-19 (COVID-19). Italy experienced a severe wave of the pandemic. SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as a host receptor. This study analyzed whole-exome sequencing data from 6930 Italian individuals to identify ACE2 variants. Several variants potentially impacting protein stability were found, including three common missense changes (p.(Asn720Asp), p.(Lys26Arg), and p.(Gly211Arg)) and rare variants (p.(Leu351Val) and p.(Pro389His)). Comparison of ACE2 data between 131 COVID-19 patients and 258 controls showed significantly higher allelic variability in controls (P<0.029). These findings suggest a role for ACE2 genetic background in COVID-19 susceptibility and severity.

Elisa Benetti, Rossella Tita, Ottavia Spiga, Andrea Ciolfi, Giovanni Birolo, Alessandro Bruselles, Gabriella Doddato, Annarita Giliberti, Caterina Marconi, Francesco Musacchia, Tommaso Pippucci, Annalaura Torella, Alfonso Trezza, Floriana Valentino, Margherita Baldassarri, Alfredo Brusco, Rosanna Asselta, Mirella Bruttini, Simone Furini, Marco Seri, Vincenzo Nigro, Giuseppe Matullo, Marco Tartaglia, Francesca Mari, GEN-COVID Multicenter Study, Alessandra Renieri, Anna Maria Pinto