Article (Scientific journals)
Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality.
Nakanishi, Tomoko; Pigazzini, Sara; Degenhardt, Frauke et al.
2021In Journal of Clinical Investigation, Online ahead of print.
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Abstract :
[en] BACKGROUND: There is considerable variability in COVID-19 outcomes amongst younger adults-and some of this variation may be due to genetic predisposition. We characterized the clinical implications of the major genetic risk factor for COVID-19 severity, and its age-dependent effect, using individual-level data in a large international multi-centre consortium. METHOD: The major common COVID-19 genetic risk factor is a chromosome 3 locus, tagged by the marker rs10490770. We combined individual level data for 13,424 COVID-19 positive patients (N=6,689 hospitalized) from 17 cohorts in nine countries to assess the association of this genetic marker with mortality, COVID-19-related complications and laboratory values. We next examined if the magnitude of these associations varied by age and were independent from known clinical COVID-19 risk factors. FINDINGS: We found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (hazard ratio [HR] 1·4, 95% confidence interval [CI] 1·2-1·6) and COVID-19 related mortality (HR 1·5, 95%CI 1·3-1·8). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (odds ratio [OR] 2·0, 95%CI 1·6-2·6), venous thromboembolism (OR 1·7, 95%CI 1·2-2·4), and hepatic injury (OR 1·6, 95%CI 1·2-2·0). Risk allele carriers ≤ 60 years had higher odds of death or severe respiratory failure (OR 2·6, 95%CI 1·8-3·9) compared to those > 60 years OR 1·5 (95%CI 1·3-1·9, interaction p-value=0·04). Amongst individuals ≤ 60 years who died or experienced severe respiratory COVID-19 outcome, we found that 31·8% (95%CI 27·6-36·2) were risk variant carriers, compared to 13·9% (95%CI 12·6-15·2%) of those not experiencing these outcomes. Prediction of death or severe respiratory failure among those ≤ 60 years improved when including the risk allele (AUC 0·82 vs 0·84, p=0·016) and the prediction ability of rs10490770 risk allele was similar to, or better than, most established clinical risk factors. INTERPRETATION: The major common COVID-19 risk locus on chromosome 3 is associated with increased risks of morbidity and mortality-and these are more pronounced amongst individuals ≤ 60 years. The effect on COVID-19 severity was similar to, or larger than most established risk factors, suggesting potential implications for clinical risk management. FUNDING: Funding was obtained by each of the participating cohorts individually.
Disciplines :
Immunology & infectious disease
Author, co-author :
Nakanishi, Tomoko
Pigazzini, Sara
Degenhardt, Frauke
Cordioli, Mattia
Butler-Laporte, Guillaume
Maya-Miles, Douglas
Nafría-Jiménez, Beatriz
Bouysran, Youssef
Niemi, Mari
Palom, Adriana
Ellinghaus, David
Khan, Atlas
Martínez-Bueno, Manuel
Rolker, Selina
Amitano, Sara
Tato, Luisa Roade
Fava, Francesca
Spinner, Christoph D.
Prati, Daniele
Bernardo, David
Garcia, Federico
DARCIS, Gilles ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service des maladies infectieuses - médecine interne
Fernández-Cadenas, Israel
Holter, Jan Cato
Banales, Jesus
Frithiof, Robert
Kiryluk, Krzysztof
Duga, Stefano
Asselta, Rosanna
Pereira, Alexandre C.
Romero-Gómez, Manuel
Bujanda, Luis
Hov, Johannes R.
Migeotte, Isabelle
Renieri, Alessandra
Planas, Anna M.
Ludwig, Kerstin U.
Buti, Maria
Rahmouni, Souad  ;  Université de Liège - ULiège > GIGA Medical Genomics - Unit of Animal Genomics
Alarcón-Riquelme, Marta E.
Schulte, Eva C.
Franke, Andre
Karlsen, Tom H.
Valenti, Luca
Zeberg, Hugo
Richards, J. Brent
Ganna, Andrea
Georges, Michel  ;  Université de Liège - ULiège > Dpt. de gestion vétérinaire des Ressources Animales (DRA) > Génomique animale
Moutschen, Michel  ;  Université de Liège - ULiège > Département des sciences cliniques > Immunopath. - Maladies infect. et médec. interne gén.
Misset, Benoît ;  Université de Liège - ULiège > Département des sciences cliniques > Soins intensifs
GUIOT, Julien  ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de pneumologie - allergologie
Parzibut, Gilles ;  Centre Hospitalier Universitaire de Liège - CHU > Autres Services Médicaux > Service des soins intensifs
MEURIS, Christelle ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service des maladies infectieuses - médecine interne
THYS, Marie ;  Centre Hospitalier Universitaire de Liège - CHU > Département de gestion des systèmes d'informations (GSI) > Secteur exploitation des données
JACQUES, Jessica ;  Centre Hospitalier Universitaire de Liège - CHU > Département de gestion des systèmes d'informations (GSI) > Secteur exploitation des données
LEONARD, Philippe ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Clinique de médecine des voyageurs
FRIPPIAT, Frédéric  ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service des maladies infectieuses - médecine interne
GIOT, Jean-Baptiste ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service des maladies infectieuses - médecine interne
SAUVAGE, Anne-Sophie ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service des maladies infectieuses - médecine interne
VON FRENCKELL, Christian ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de rhumatologie
LAMBERMONT, Bernard  ;  Centre Hospitalier Universitaire de Liège - CHU > Autres Services Médicaux > Service des soins intensifs
MALAISE, Olivier ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de rhumatologie
BOVY, Christophe ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de néphrologie
BOUQUEGNEAU, Antoine  ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de néphrologie
consortium, COVID-HGI
More authors (55 more) Less
Language :
English
Title :
Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality.
Publication date :
October 2021
Journal title :
Journal of Clinical Investigation
ISSN :
0021-9738
eISSN :
1558-8238
Publisher :
American Society for Clinical Investigation, United States - Michigan
Volume :
Online ahead of print.
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 26 May 2021

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