A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death
Authors: Minnai Francesca , Biscarini Filippo , Esposito Martina , Dragani Tommaso A. , Bujanda Luis , Rahmouni Souad , Alarcón-Riquelme Marta E. , Bernardo David , Carnero-Montoro Elena , Buti Maria , Zeberg Hugo , Asselta Rosanna , Romero-Gómez Manuel ,   GEN-COVID Multicenter Study, Mari Francesca , Daga Sergio , Meloni Ilaria , Brunelli Giulia , Lista Mirjam , Maffeo Debora , Pasquinelli Elena , Antolini Enrica , Basso Simona Letizia , Minetto Samantha , Rollo Giulia , Rina Angela , Rozza Martina , Tita Rossella , Mencarelli Maria Antonietta , Rizzo Caterina Lo , Pinto Anna Maria , Ariani Francesca , Montagnani Francesca , Tumbarello Mario , Rancan Ilaria , Fabbiani Massimiliano , Cameli Paolo , Bennett David , Anedda Federico , Marcantonio Simona , Scolletta Sabino , Franchi Federico , Mazzei Maria Antonietta , Guerrini Susanna , Conticini Edoardo , Cantarini Luca , Frediani Bruno , Tacconi Danilo , Raffaelli Chiara Spertilli , Emiliozzi Arianna , Feri Marco , Donati Alice , Scala Raffaele , Guidelli Luca , Spargi Genni , Corridi Marta , Nencioni Cesira , Croci Leonardo , Caldarelli Gian Piero , Romani Davide , Piacentini Paolo , Bandini Maria , Desanctis Elena , Cappelli Silvia , Canaccini Anna , Verzuri Agnese , Anemoli Valentina , Ognibene Agostino , Lorubbio Maria , Pancrazzi Alessandro , Vaghi Massimo , Monforte Antonella D.’Arminio , Miraglia Federica Gaia , Mondelli Mario U. , Mantovani Stefania , Bruno Raffaele , Vecchia Marco , Maffezzoni Marcello , Martinelli Enrico , Girardis Massimo , Busani Stefano , Venturelli Sophie , Cossarizza Andrea , Antinori Andrea , Vergori Alessandra , Rusconi Stefano , Siano Matteo , Gabrieli Arianna , Riva Agostino , Francisci Daniela , Schiaroli Elisabetta , Pallotto Carlo , Parisi Saverio Giuseppe , Basso Monica , Panese Sandro , Baratti Stefano , Scotton Pier Giorgio , Andretta Francesca , Giobbia Mario , Scaggiante Renzo , Gatti Francesca , Castelli Francesco , Quiros-Roldan Eugenia , Antoni Melania Degli , Zanella Isabella , Monica Matteo della , Piscopo Carmelo , Capasso Mario , Russo Roberta , Andolfo Immacolata , Iolascon Achille , Fiorentino Giuseppe , Carella Massimo , Castori Marco , Merla Giuseppe , Squeo Gabriella Maria , Aucella Filippo , Raggi Pamela , Perna Rita , Bassetti Matteo , Di Biagio Antonio , Sanguinetti Maurizio , Masucci Luca , Guarnaccia Alessandra , Valente Serafina , Di Florio Alex , Mandalà Marco , Giorli Alessia , Salerni Lorenzo , Zucchi Patrizia , Parravicini Pierpaolo , Menatti Elisabetta , Trotta Tullio , Giannattasio Ferdinando , Coiro Gabriella , Lacerenza Gianluca , Mussini Cristina , Tavecchia Luisa , Crotti Lia , Parati Gianfranco , Menè Roberto , Sanarico Maurizio , Gori Marco , Raimondi Francesco , Stella Alessandra , Biscarini Filippo , Bachetti Tiziana , La Rovere Maria Teresa , Bussotti Maurizio , Ludovisi Serena , Capitani Katia , Dei Simona , Ravaglia Sabrina , Giliberti Annarita , Gori Giulia , Artuso Rosangela , Andreucci Elena , Perrella Antonio , Bianchi Francesco , Bergomi Paola , Catena Emanuele , Colombo Riccardo , Luchi Sauro , Morelli Giovanna , Petrocelli Paola , Iacopini Sarah , Modica Sara , Baroni Silvia , Micheli Giulia , Falcone Marco , Urso Donato , Tiseo Giusy , Matucci Tommaso , Pulcinelli Alice , Grassi Davide , Ferri Claudio , Marinangeli Franco , Brancati Francesco , Vincenti Antonella , Borgo Valentina , Lombardi Stefania , Lenzi Mirco , Di Pietro Massimo Antonio , Attala Letizia , Costa Cecilia , Gabbuti Andrea , Bellucci Alessio , Colaneri Marta , Casprini Patrizia , Pomara Cristoforo , Esposito Massimiliano , Leoncini Roberto , Cirianni Michele , Galasso Lucrezia , Bellini Marco Antonio , Gabbi Chiara , Picchiotti Nicola , Furini Simone , Pelo Elisabetta , Minuti Barbara , Gerundino Francesca , Lazzeri Chiara , Vecchi Arianna , Bianchi Leila , Venturini Elisabetta , Montagnani Carlotta , Chiappini Elena , Beltrami Cristina , Galli Luisa , Fernandez-Cadenas Israel , Fallerini Chiara , Zguro Kristina , Croci Susanna , Baldassarri Margherita , Bruttini Mirella , Furini Simone , Renieri Alessandra , Colombo Francesca 
Published: February 2024

The clinical manifestations of SARS-CoV-2 infection vary widely among patients, from asymptomatic to life-threatening. Host genetics is one of the factors that contributes to this variability as previously reported by the COVID-19 Host Genetics Initiative (HGI), which identified sixteen loci associated with COVID-19 severity. Herein, we investigated the genetic determinants of COVID-19 mortality, by performing a case-only genome-wide survival analysis, 60 days after infection, of 3904 COVID-19 patients from the GEN-COVID and other European series (EGAS00001005304 study of the COVID-19 HGI). Using imputed genotype data, we carried out a survival analysis using the Cox model adjusted for age, age2, sex, series, time of infection, and the first ten principal components. We observed a genome-wide significant (P-value < 5.0 × 10−8) association of the rs117011822 variant, on chromosome 11, of rs7208524 on chromosome 17, approaching the genome-wide threshold (P-value = 5.19 × 10−8). A total of 113 variants were associated with survival atP-value < 1.0 × 10−5and most of them regulated the expression of genes involved in immune response (e.g., CD300 and KLR genes), or in lung repair and function (e.g., FGF19 and CDH13). Overall, our results suggest that germline variants may modulate COVID-19 risk of death, possibly through the regulation of gene expression in immune response and lung function pathways.