Human genetic and immunological determinants of critical COVID-19 pneumonia.

Zhang Q, Bastard P, Cobat A, Casanova JL, Karbuz A, Gervais A, Tayoun AA, Aiuti A, Belot A, Bolze A, Gaudet A, Bondarenko A, Liu Z, Spaan AN, Guennoun A, Arias AA, Planas AM, Sediva A, Shcherbina A, Neehus AL, Puel A, Froidure A, Novelli A, Parlakay AÖ, Pujol A, Yahşi A, Gülhan B, Bigio B, Boisson B, Drolet BA, Franco CAA, Flores C, Rodríguez-Gallego C, Prando C, Biggs CM, Luyt CE, Dalgard CL, O'Farrelly C, Matuozzo D, Dalmau D, Perlin DS, Mansouri D, van de Beek D, Vinh DC, Dominguez-Garrido E, Hsieh EWY, Erdeniz EH, Jouanguy E, Şevketoglu E, Talouarn E, Quiros-Roldan E, Andreakos E, Husebye E, Alsohime F, Haerynck F, Casari G, Novelli G, Aytekin G, Morelle G, Alkan G, Bayhan GI, Feldman HB, Su HC, von Bernuth H, Resnick I, Bustos I, Meyts I, Migeotte I, Tancevski I, Bustamante J, Fellay J, El Baghdadi J, Martinez-Picado J, Casanova JL, Rosain J, Manry J, Chen J, Christodoulou J, Bohlen J, Franco JL, Li J, Anaya JM, Rojas J, Ye J, Uddin KMF, Yasar KK, Kisand K, Okamoto K, Chaïbi K, Mironska K, Maródi L, Abel L, Renia L, Lorenzo L, Hammarström L, Ng LFP, Quintana-Murci L, Erazo LV, Notarangelo LD, Reyes LF, Allende LM, Imberti L, Renkilaraj MRLM, Moncada-Velez M, Materna M, Anderson MS, Gut M, Chbihi M, Ogishi M, Emiroglu M, Seppänen MRJ, Uddin MJ, Shahrooei M, Alexander N, Hatipoglu N, Marr N, Akçay N, Boyarchuk O, Slaby O, Akcan OM, Zhang P, Soler-Palacín P, Gregersen PK, Brodin P, Garçon P, Morange PE, Pan-Hammarström Q, Zhou Q, Philippot Q, Halwani R, de Diego RP, Levy R, Yang R, Öz ŞKT, Muhsen SA, Kanık-Yüksek S, Espinosa-Padilla S, Ramaswamy S, Okada S, Bozdemir SE, Aytekin SE, Karabela ŞN, Keles S, Senoglu S, Zhang SY, Duvlis S, Constantinescu SN, Boisson-Dupuis S, Turvey SE, Tangye SG, Asano T, Ozcelik T, Le Voyer T, Maniatis T, Morio T, Mogensen TH, Sancho-Shimizu V, Beziat V, Solanich X, Bryceson Y, Lau YL, Itan Y.

Source :

Nature

2022 Mar 1

Pmid / DOI:

PMID: 35090163

Abstract

SARS-CoV-2 infection is benign in most individuals but, in around 10% of cases, it triggers hypoxaemic COVID-19 pneumonia, which leads to critical illness in around 3% of cases. The ensuing risk of death (approximately 1% across age and gender) doubles every five years from childhood onwards and is around 1.5 times greater in men than in women. Here we review the molecular and cellular determinants of critical COVID-19 pneumonia. Inborn errors of type I interferons (IFNs), including autosomal TLR3 and X-chromosome-linked TLR7 deficiencies, are found in around 1-5% of patients with critical pneumonia under 60 years old, and a lower proportion in older patients. Pre-existing auto-antibodies neutralizing IFNα, IFNβ and/or IFNω, which are more common in men than in women, are found in approximately 15-20% of patients with critical pneumonia over 70 years old, and a lower proportion in younger patients. Thus, at least 15% of cases of critical COVID-19 pneumonia can be explained. The TLR3- and TLR7-dependent production of type I IFNs by respiratory epithelial cells and plasmacytoid dendritic cells, respectively, is essential for host defence against SARS-CoV-2. In ways that can depend on age and sex, insufficient type I IFN immunity in the respiratory tract during the first few days of infection may account for the spread of the virus, leading to pulmonary and systemic inflammation.

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