9 research outputs found
Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
- Author
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- Zuccaro V.
- Zwinderman A. H.
- Publication venue
- Publication date
- 01/01/2023
- Field of study
Get PDFBackground: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old
Coût global de prise en charge des patients atteints de cancer du rein métastatique (CAPRI)
- Publication venue
- Elsevier BV
- Publication date
- 01/11/2012
- Field of study
Full text linkImpact de la publication du STROBE sur la qualité du reporting des études observationnelles (REPODERM study) : évaluation avant-après versus séries chronologiques
- Author
- Publication venue
- Elsevier BV
- Publication date
- 01/02/2014
- Field of study
Full text linkIdentification de quatre phénotypes d’hidradénite suppurée à partir d’une série consécutive de 618 patients : méthode de classification non hiérarchique des k-means (Créteil, France)
- Publication venue
- Elsevier BV
- Publication date
- 01/04/2011
- Field of study
Full text linkCorrélation phénotype/génotype dans la neurofibromatose 1 : apport d’une classification phénotypique sans hypothèse a priori
- Author
- Publication venue
- Elsevier BV
- Publication date
- 01/12/2015
- Field of study
Full text linkCombination Therapy with Clindamycin and Rifampicin for Hidradenitis Suppurativa: A Series of 116 Consecutive Patients
- Author
- Publication venue
- S. Karger AG
- Publication date
- 01/01/2009
- Field of study
Full text link<i>Background:</i> Antibiotics are frequently used to treat hidradenitis suppurativa (HS); however, few data on their efficacy are available. <i>Objective:</i> To evaluate the efficacy of a combination of systemic clindamycin (300 mg twice daily) and rifampicin (600 mg daily) in the treatment of patients with severe HS. <i>Methods:</i> Patients (n = 116) who received this combination were studied retrospectively. The main outcome measure was the severity of the disease, assessed by the Sartorius score, before and after 10 weeks of treatment. <i>Results:</i> The Sartorius score dramatically improved at the end of treatment (median = 29, interquartile range = 14.5, vs. median = 14.5, interquartile range = 11; p < 0.001), as did other parameters of severity as well as the quality of life score. Eight patients (6.9%) stopped the treatment because of side effects. <i>Conclusion:</i> The combination of clindamycin and rifampicin is effective in the treatment of severe HS.</jats:p
Trois phénotypes de neurofibromatose 1 : analyse en classe latente à partir d’une population d’étude de 1351 patients
- Author
- Publication venue
- Elsevier BV
- Publication date
- 01/12/2014
- Field of study
Full text linkRare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
- Author
- Abad Jorge
- Abad Sebastien
- Abassi Radhiya
- Abdelhadi Nour Mekki
- Abdellaoui Abdelrafie
- Abdelmalek Abdelkrim
- Abdoul Hendy
- Abel Laurent
- Abel Laurent
- Abel Laurent
- Abel Laurent
- Abergel Helene
- Abeud Fariza
- Abgrall Sophie
- Abisror Noemie
- Abolhassani Hassan
- Abou Tayoun Ahmad
- Accordino Giulia
- Achille Cristian
- Adechian Marylise
- Aderdour Nordine
- Admane Hakeem Farid
- Adnet Frederic
- Afritt Sara
- Agostini Helene
- Agra Juan José Cáceres
- Aguilar Claire
- Aguilera-Albesa Sergio
- Aguiló-Cucurull Aina
- Agut Sophie
- Aiello Tommaso Francesco
- Aiuti Alessandro
- Ajeenthiravasan Gokula
- Akcan Özge Metin
- Al-Muhsen Saleh
- Al-Muhsen Saleh Zaid
- Al-Mulla Fahd
- Alauzy Virginie
- Alavi Darazam Ilad
- Alavoine Loubna
- Alba Camille
- Albisures Jonathan Antonio Roblero
- Alby-Laurent Fanny
- Aldave Juan C.
- Algera Anne Geke
- Aliberti Anna
- Alkan Gulsum
- AlKhater Suzan A.
- Allard Lucie
- Allardet-Servent Jerome
- Allende Luis M.
- Alonso-Arias Rebeca
- Alosaimi Mohammed Faraj
- Alshahrani Mohammed S.
- Alsina Laia
- Alsohime Fahad M.
- Alvarez Josep Trenado
- Alyanakian Marie-Alexandra
- Alyanakian Marie-Alexandra
- Amam Sabrina
- Amara Yasmina Ould
- Amat Karine
- Amoura Zahir
- Amrouche Lucile
- Amsterdam UMC Covid-19 Biobank [missing]
- Anderson Mark S.
- Andreakos Evangelos
- Andrejak Claire
- Andronikof Marc
- Anglicheau Dany
- Angoulvant François
- Anguel Nadia
- Annane Djillali
- Antolí Arnau
- Aounzou Mohammed
- Aparicio Caroline
- Appelman Brent
- Aratus Gladys
- Arias Andrés A.
- Arias Andrés Augusto
- Arlet Jean-Benoit
- Arquero Miguel Fernandez
- Arranz María Jesús
- Arrestier Romain
- Arzoine Jeremy
- Asano Takaki
- Aslangul Elisabeth
- Assefi Mona
- Aubart Mélodie
- Aubry Adeline
- Audiffred Laetitia
- Audureau Etienne
- Auger Christelle Nathalie
- Auguet Teresa
- Auregan Jean-Charles
- Avramenko Iryna
- Awotar Celine
- Aytekin Gokhan
- Aytekin Gökhan
- Aytekin Selma Erol
- Azan Delphine
- Azemar Laurene
- Azot Axelle
- Azzouguen Billal
- Bachelet Delphine
- Badsi Aïda
- Baghdadi Jamila El
- Bahram Seiamak
- Bajolle Fanny
- Bakouboula Prissile
- Balcerowiak Coline
- Baldanti Fausto
- Balde Fanta
- Baldivia Elodie
- Baldolli Aurélie
- Ballester Maite
- Bangamingo Eliane-Flore
- Baptiste Amandine
- Baran-Marszak Fanny
- Barau Caroline
- Barget Nathalie
- Baris-Feldman Hagit
- Baronnet Flore
- Barrou Benoit
- Barthelemy Romain
- Bartoli Marie
- Barzaghi Federica
- Basmaci Romain
- Basso Sabrina
- Bastard Paul
- Baudel Jean-Luc
- Baudry Camille
- Baudry Elodie
- Bauters FreUZGent001994324141802000568191973982159689FF187EC0-F0ED-11E1-A9DE-61C894A0A6B4
- Bax Diane
- Bayhan Gulsum Iclal
- Beaugerie Laurent
- Behilill Sylvie
- Behillil Sylvie
- Belamri Adel
- Belaube Nicolas
- Belilita Rhida
- Bellani Giacomo
- Bellassen Pierre
- Belmokhtar Rawan
- Belot Alexandre
- Belot Alexandre
- Beltran Isabel
- Beluze Marine
- Benainous Ruben
- Benallaoua Mourad
- Benamouzig Robert
- Benbara Amélie
- Benhida Jaouad
- Benkerrou Dehbia
- Benkhelouf Anis
- Benlagha Jihene
- Benmostafa Chahinez
- Benothmane Skander
- Bentifraouine Miassa
- Berard Laurence
- Beretta Ilaria
- Bergman Peter
- Berkell Matilda
- Bernier Quentin
- Bertholon Frédérique
- Berti Enora
- Bertier Astrid
- Berton Laure
- Bessis Simon
- Bettini Laura Rachele
- Beudel Martijn
- Beurton Alexandra
- Bezrodnik Liliana
- Bhavsar Krishna
- Bianco Celine
- Bianquis Clara
- Bidar Frank
- Biggs Catherine M.
- Bilbao Agurtzane
- Biondi Andrea
- Bizien Lucy
- Blanchard-Rohner Geraldine
- Blanche Philippe
- Blanco Ignacio
- Blandinières Adeline
- Blayau Clarisse
- Bleibtreu Alexandre
- Bleibtreu Alexandre
- Blin Emmanuelle
- Bloch-Queyrat Coralie
- Bloomfield Marketa
- Blázquez-Gamero Daniel
- Bogaard Harm Jan
- Bogunovic Dusan
- Boissier Marie-Christophe
- Boisson Bertrand
- Boisson-Dupuis Stephanie
- Boland Anne
- Bolivar-Prados Mireia
- Bollens Diane
- Bolze Alexandre
- Bolzoni Marion
- Bomers Marije
- Bompard Rudy pierre
- Bondarenko Anastasiia
- Bondarenko Anastasiia
- Bondesan Simone
- Bonnet Nicolas
- Bonnouvrier Justine
- Bonta Peter
- Borghesi Alessandro
- Borie Raphael
- Borrero Blanca Amador
- Borrero Blanca Amador
- Bos Lieuwe
- Bosteels CedricUZGent0000801514038020020805839741893007650000-0003-3230-087910CBF714-F0EE-11E1-A9DE-61C894A0A6B4
- Botdhlo-Nevers Elisabeth
- Botelho-Nevers Elisabeth
- Botha Shirmonecrystal
- Botta Michela
- Bouadma Lila
- Boucenna Wissam
- Bouchama Fatiha
- Bouchaud Olivier
- Bouchez Sabelline
- Bouchghoul Hanane
- Boudjebla Taoueslylia
- Boudjema Noel
- Bouffard Catherine
- Bougle Adrien
- Bouguerra Meriem
- Bouiller Kévin
- Boulanger Cécile
- Bouras Leila
- Bourcier Agnes
- Bourgeon Marilou
- Bourrier Anne
- Bouscambert Maude
- Bouscarat Fabrice
- Bousfiha Ahmed A.
- Bousfiha Ahmed A.
- Bousquet Aurore
- Boutolleau David
- Bouvattier Claire
- Bouvry Diane
- Bouziri Nesrine
- Bouzrara Ons
- Boyarchuk Oksana
- Bozdemir Şefika Elmas
- Bravais Juliette
- Bribier Sarah
- Briones M. Luisa
- Brodin Petter
- Brouwer Matthijs C.
- Brugier Delphine
- Bruneau Léa
- Brunel Melanie
- Brunner Marie-Eve
- Bruno Raffaele
- Bryceson Yenan
- Bryceson Yenan T.
- Bueno Maria Rita P.
- Bugiani Marianna
- Bui Eida
- Buis David T. P.
- Buisson Anne
- Bukhari Huda
- Bukreyeva Iryna
- Bulle Esther
- Burdet Charles
- Bureau Côme
- Bureau Serge
- Bustamante Carlos D.
- Bustamante Jacinta
- Bustos Ingrid G.
- Butte Manish J.
- Cabrera-Marante Oscar
- Cadranel Jacques
- Cailhol Johann
- Calin Ruxandra
- Canavaggio Pauline
- Cancella Marta
- Cantin Delphine
- Cao Albert
- Capra Ruggero
- Carapito Raphael
- Carbillon Lionel
- Carcel Sheila
- Carelli Valerio
- Carlier Nicolas
- Carrabba Maria
- Carrera Paola
- Casanova Jean-Laurent
- Casanova Jean-Laurent
- Casari Giorgio
- Casasnovas Carlos
- Caseris Marion
- Cassaniti Irene
- Cassard Clementine
- Castelle Martin
- Castelli Francesco
- Castor Guylaine
- Castro Mateus V.
- Catherinot Emilie
- Cauchy Marion
- Cazzaniga Marina
- Celik Jale Bengi
- Cervantes-Gonzalez Minerva
- Ceschi Alessandro
- Cha Olivier
- Chachoua Abla
- Chahine Abir
- Chaigne Benjamin
- Chair Anissa
- Chakravorty Samya
- Chaldebas Matthieu
- Challal Salima
- Chalumeau Martin
- Chalumeau Nathalie Costedoat
- Champion Karine
- Charbit Bruno
- Chariot Patrick
- Charpentier Charlotte
- Chas Julie
- Chauveau Simon
- Chauvin Anthony
- Chauvin Clement
- Chavarot Nathalie
- Chaïbi Khalil
- Chebbout Kamélia
- Cheng Matthew P.
- Cherai Mustapha
- Cherubini Ilaria
- Chevalier Amelie
- Chiarabini Thibault
- Chinet Thierry
- Chirouze Catherine
- Chirouze Catherine
- Chocron Richard
- Choinier Pascaline
- Chommeloux Juliette
- Choquet Christophe
- Choupeaux Laure
- Chousterman Benjamin
- Christelle Kouakam
- Christodoulou John
- Ciocan Dragosmarius
- Citerio Giuseppe
- Clarke Ada
- Clavere Gaëlle
- Clavier Florian
- Clavé Père
- Clement Karine
- Clerc Sebastien
- Cloherty Osoul Chouchane Alex
- Clotet Bonaventura
- Cobat Aurélie
- Codina Anna
- Coelho Alexandra
- Cohen Adrien
- Cohen Fleur
- Cohen Yves
- Cohen Yves
- Coilly Audrey
- Colboc Hester
- Colin Pauline
- Collet Magalie
- Colobran Roger
- Comarmond Chloé
- Comarmond Cloé
- Combacon Emeline
- Combe Caroline Lascoux
- Combes Alain
- Combes Alain
- Comoli Patrizia
- Comparon Celine
- Condino-Neto Antonio
- Constantin Jean-Michel
- Constantinescu Stefan N.
- Contro Ernesto
- Cooper Megan A.
- Cordel Hugues
- Cordier Anne-Gael
- Corsico Angelo G.
- Costantini Adrien
- Couffignal Camille
- Couffignal Camille
- Couffin-Cadiergues Sandrine
- Couffin-Cadiergues Sandrine
- Coupeau Doriane
- CoV-Contact Cohort [missing]
- COVID Clinicians [missing]
- COVID Human Genetic Effort [missing]
- COVID-STORM Clinicians [missing]
- COVIDeF Study Group [missing]
- Covill Laura E.
- Coşkuner Taner
- Creange Alain
- Cuadros Esmeralda Nuñez
- Cvetkovski Aleksandar
- Cyrus Cyril
- Da Silveira Charlène
- Dalgard Clifton L.
- Dalmau David
- Danielson Jeffrey J.
- Danion François
- Darley David Ross
- Das Vincent
- Dauby Nicolas
- Dauger Stéphane
- De Bouille Jeanne Goupil
- de Brabander Justin
- de Bree Godelieve
- de Bruin Sanne
- De Castro Nathalie
- De Chambrun Marc Pineton
- de Chambrun Marc Pineton
- de Diego Rebeca Pérez
- De Farcy Pauline Mary
- de Jong Menno D.
- De Munter Paul
- de Pontual Loic
- de Rotte Maurits C. F. J.
- De Rycke Yann
- de Vera Martín Castillo
- de Vries Heder
- Debray Marie-Pierre
- Dechanet Aline
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- Deconinck Lauren
- Dehban Amin
- Del Pozo Lucie
- del Prado Maria Yolanda Ruiz
- Delannoy Quentin
- Delay Mathieu
- Deleris Robin
- Deleuze Jean-François
- Delforge Juliette
- Delmonte Ottavia M.
- Delphine Laëtitia
- Delplancq Geoffroy
- Demar Magalie
- Demare Noemie
- Demeret Sophie
- Demerville Lauren
- Demirkol Yasemin Kendir
- Demoule Alexandre
- Demoule Alexandre
- Deniau Aurore
- Deplanque Dominique
- Deplanque Dominique
- Depret François
- Derolez Sophie
- Derradji Ouda
- Derridj Nawal
- Desai Murkesh
- Descamps Diane
- Descamps Diane
- Descamps Vincent
- Deschamps Lydia
- Desconclois Celine
- Desguerre Isabelle
- Desille-Dugast Mireille
- Desmarets Maxime
- Desnos Cyrielle
- Desongins Karine
- Desvallée Mathilde
- Devouge Eglantine Ferrand
- Dhote Robin
- Di Sabatino Antonio
- Diallo Alpha
- Diallo Benjamin
- Didier Morgane
- Diehl Jean-Luc
- Diemer Myriam
- Diez Stephane
- Dijkstra Mirjam
- Diouf Alphonsine
- Djadi-Prat Juliette
- Djebara Siham
- Djebra Naoual
- Djietcheu Minette
- Djillali Hadjer
- Djossou Félix
- Djouadi Nouara
- Dobbelaere Stephanie
- Dobbs Kerry
- Domínguez-Garrido Elena
- Dongelmans Dave A.
- Donneger Severine
- Dorival Céline
- Dos Santos Catarina
- Dournon Nathalie
- Dres Martin
- Droctove Laura
- Drogrey Marie
- Drolet Beth A.
- Dropy Margot
- Drouet Elodie
- Dubos François
- Dubosq Valérie
- Dubost Clément
- Dubreucq Evelyne
- Dubus Estelle
- Duchemann Boris
- Duchenoy Thibault
- Dudoignon Emmanuel
- Dufau Romain
- Dujardin Romein W. G.
- Dumas Florence
- Duran Clara
- Durand Anne Bourgarit
- Duron Emmanuelle
- Durrbach Antoine
- Duval Xavier
- Duval Xavier
- Duvivier Claudine
- D’Angio’ Mariella
- d’Ortenzio Eric
- Ebstein Nathan
- Ecobichon Jean-Luc
- Ekwall Olov
- El Zein Loubna
- Elabbadi Alexandre
- Elbers Paul
- Elharrar Brigitte
- Elie Caroline
- Elnagdy Marwa H.
- Eloy Philippine
- Elrufaai Marwa Bachir
- Emiroglu Melike
- Endo Akifumi
- Enouf Vincent
- Enouf Vincent
- Erdeniz Emine Hafize
- Ernotte Gabriel
- Esling Anne
- Esperou Hélène
- Espinosa-Padilla Sara
- Esposito-Farese Marina
- Espérou Hélène
- Etienne Manuel
- Etienne Martin
- Euvrard Romain
- Eyer Xavier
- Fabio Giovanna
- Faivre Laurence
- Falck Antonin
- Fartoukh Muriel
- Fartoukh Muriel sarah
- Faure Morgane
- Fayali Takoua
- Feldman Hagit Baris
- Feldman Hagit Baris
- Fellay Jacques
- Fermaut Marion
- Ferrer Ricard
- Ferreres Jose
- Fiorentino Alessio
- Fiorentino Arianna
- Fleuren Lucas
- Fliss Souha
- Flores Carlos
- Florkin Benoit
- Foti Giuseppe
- Fouchard Julie
- Fournier Benjamin
- Fournier Marie-Céline
- Franco Jose Luis
- Franco José Luis
- Francois Bruno
- Francois Hélène
- French COVID Cohort Study Group [missing]
- Freynet Olivia
- Frezouls Wahiba
- Frigout Yvann
- Froidure Antoine
- Fromont Isaure
- Fuentes Axelle
- Fumadó Victoria
- Fung Kitty S. C.
- Furet Thomas
- Fusco Francesca
- Gagneux-Brunon Amandine
- Gagro Alenka
- Galand Joris
- Garnier Marc
- Garçon Pierre
- Gatineau Audrey Giraud
- Gaubert Agnes
- Gaudry Stéphane
- Gaugain Samuel
- Gault Nathalie
- Gaussem Pascale
- Gauthier Damien
- Gautier Maxime
- Gaymard Alexandre
- Gayretli Zeynep
- Geijtenbeek Suzanne Geerlings Theo
- Georgin-Lavialle Sophie
- Geromin Daniela
- Gervais Adrian
- Ghalayini Mohamed
- Ghaleh Bijan
- Ghezal Myriam
- Ghosn Jade
- Gibelin Aude
- Gigante Tristan
- Gil-Herrera Juana
- Gilardin Laurent
- Gilg Morgane
- Gimeno Linda
- Girard Benoit
- Girbes Armand
- Girona-Alarcón Mònica
- Gissot Valérie
- Goas Carole L. E.
- Godínez Karen Alejandra Cifuentes
- Goffard Jean-Christophe
- Gomes Doryan
- Gomes-Pires Elisabete
- Gonzales Nacho
- Gonzalez-Granado Luis I.
- González-Montelongo Rafaela
- Goorhuis Bram
- Gorochov Guy
- Gouge Anne
- Gouja Amel
- Goulet Helene
- Goupil Sylvain
- Gras Julien
- Greffe Segolene
- Gregersen Peter K.
- Grimaldi Lamiae
- Grobusch Martin P.
- Guedeney Paul
- Guedj Jérémie
- Guerder Antoine
- Guidet Bertrand
- Guillo Matthias
- Gulczynski Mariechristelle
- Gumucio Victor Daniel
- Gunst Jan
- Gut Marta
- Gysembergh-Houal Anne
- Gérardin Patrick
- Gülhan Belgin
- Hadjadj Jérôme
- Hadjam Tassadit
- Haerynck FilomeenGE35UZGent0019901101968020016542880000-0001-9161-73614054C2A2-2240-11E3-BD2F-D1D610BDE39D
- Hafkamp Florianne
- Hagens Laura
- Hagin David
- Haguenauer Didier
- Halwani Rabih
- Hamann Jorg
- Hammal Soumeya
- Hammarström Lennart
- Hammoudi Nadjib
- Hancerli Selda
- Hanitsch Leif Gunnar
- Hanon Olivier
- Hariyan Tetyana
- Harris Vanessa
- Harrois Anarole
- Hatipoglu Nevin
- Hatipoğlu Nevin
- Hausfater Pierre
- Hautem Coraline
- Heath James R.
- Heijmans Catherine
- Hekimian Guillaume
- Heming Nicholas
- Hemke Robert
- Hendou Samia
- Henrickson Sarah E.
- Heppekcan Deniz
- Hermine Olivier
- Hernandez-Brito Elisa
- Heunks Sabine M. Hermans Leo
- Ho Po-ki
- Ho Sylvie
- Hoctin Alexandre
- Hoffmann Isabelle
- Holanda-Peña María Soledad
- Hollmann Markus
- Horcajada Juan P.
- Horn Janneke
- Hoste EricGE35UZGent0019824231508020000737940000-0001-9301-8055F8813B06-F0ED-11E1-A9DE-61C894A0A6B4
- Hoste LeviGE35UZGent0000907296558020033105640000-0001-9733-1049240309EE-F0EE-11E1-A9DE-61C894A0A6B4
- Houas Ikram
- Houhou Nadhira
- Houllier Marie
- Hovius Joppe W.
- Hraiech Sami
- Hsieh Elena W. Y.
- Hulot Jean-Sébastien
- Humbert Linda
- Hung Ivan F. N.
- Huot Benjamin
- Hupalo Daniel N.
- Huscenot Tessa
- Husebye Eystein
- Iglesias Alejandro D.
- Ikherbane Ghilas
- Imai Kohsuke
- Imarazene Meriem
- Imberti Luisa
- Ingiliz Patrick
- Iratni Lina
- Itan Yuval
- Jaafoura Salma
- Jamme Matthieu
- Jarvis Erich D.
- Jaureguiberry Stephane
- Jean-Marc Jean-Francois
- Jeulin Hélène
- Jeyarajasingham Deleena
- Jimeno Marie-Thérèse
- Jordan Iolanda
- Jouanguy Emmanuelle
- Jouany Pauline
- Jouis Veronique
- Jourdaine Clement
- Kaci Marc Ait
- Kafif Ouifiya
- Kafif Ouifiya
- Kafif Ouifiya
- Kaguelidou Florentia
- Kahn-Kirby Amanda
- Kali Sabrina
- Kallala Rim
- Kara Yalcin Burak
- Karahan Aydın
- Karamitros Timokratis
- Karbuz Adem
- Kasapcopur Ozgur
- Kashimada Kenichi
- Katsahian Sandrine
- Kayani Sandrine Dautheville Guibal El
- Keles Sevgi
- Kelesyan Lilit
- Keo Vixra
- Kermanach Nathalie Saidenberg
- Ketz Flora
- Khalifa Jihane El
- Khalil Antoine
- Khamis Warda
- Khan Coralie
- Khan Taj Ali
- Khelili Enfel
- Khellaf Mehdi
- Kido Yasutoshi
- Kılıç Ahmet Osman
- Kisand Kai
- Kizil Can
- Klocperk Adam
- Koning Rutger
- Kounis Ilias
- Koutsoukou Antonia
- Kpalma Gaelle
- Krause Jessica
- Król Zbigniew J.
- Ksouri Hatem
- Ku Cheng-Lung
- Kuentz Paul
- Kwan Arthur M. C.
- Kwan Yat Wah M.
- Kwok Janette S. Y.
- Kyheng Christèle
- Labbe Vincent
- Lack Justin
- Lacombe Karine
- Lacorte Jean-Marc
- Lafont Anne Gaelle
- Lafont Emmanuel
- Lagha Lynda
- Lagier Jean-Christophe
- Laine Fabrice
- Lam David S. Y.
- Lamarre Yannie Cuvillier
- Lambrecht BartGE35UZGent8010009682390000-0003-4376-6834F946B58E-F0ED-11E1-A9DE-61C894A0A6B4
- Lamhaut Lionel
- Lampropoulou Vicky
- Lancelot Aymeric
- Landman Cecilia
- Lanternier Fanny
- Lanternier Fanny
- Laouénan Cédric
- Larcheveque Cecile
- Laribi Samira
- Larmurier Isabelle Nion
- Lasa Maria Pilar Etxart
- Lassel Ludovic
- Lau Yu-Lung
- Laverdant Benjamin
- Lavergne Christophe
- Lavillegrand Jean-Rémi
- Laviolle Bruno
- Lazureanu Pompilia
- Le Bourgeois Fleur
- Le Guennec Loïc
- Le Hingrat Quentin
- Le Mestre Soizic
- Le Nagard Hervé
- Le Minh
- Leberre Lamia
- Leblanc Claire
- Leboyer Marion
- Lecomte Francois
- Lecorre Marine
- Leenhardt Romain
- Lefebvre Bénédicte
- Lefebvre Marylou
- Lefévre Benjamin
- Legendre Paul
- Leger Anne
- Legrand Karine
- Legros Laurence
- Legrosse Justyna
- Lehacaut Jonathan
- Lehuunghia Sébastien
- Lemarec Julien
- Leo Yee-Sin
- Leon-Lopez Rafael
- Leporrier-Ext Jeremie
- Leprieur Bénédicte Giroux
- Lermine Alban
- Lescure François-Xavier
- Lesein Manon
- Lesur Hubert
- Letrou Sophie
- Letrou Sophie
- Leung Daniel
- Levin Michael
- Levy Albert
- Levy Michael
- Levy Vincent
- Levy Yves
- Li Zhi
- Lien Olivia Tran Dinh Thanh
- Lifton Richard P.
- Lilleri Daniele
- Lim Endry H. T.
- Lima Breno Melo
- Lima Edson Jose Adrian Bolanos
- Lina Bruno
- Lina Bruno
- Ling Yun
- Lingas Guillaume
- Linglart Agnes
- Llovich Alex Serra
- Lomazzi Sandra
- Lopes Amanda
- Lopes Edwige
- Lopez Rafael Leon
- Lopez Vanessa
- Lopinto Julien
- Lorenzo-Salazar José M.
- Lortholary Olivier
- Louadah Badr
- Louapre Céline
- Loze Bénédicte
- Lubetzki Catherine
- Lucarelli Aude
- Lucas Carrie L.
- Lucas Marie-Laure
- Lucasamichi Axelle
- Lucet Jean Christophe
- Lucet Jean-Christophe
- Lung Kwok-Cheung
- Luong Liem Binh
- Luyt Charles-Edouard
- Lye David C.
- Lévy Romain
- López-Collazo Eduardo
- Magazimama-Ext Arouna
- Magnone Cinthia
- Maillot Adrien
- Maingret David
- Malhotra Surbi
- Malvy Denis
- Malvy Denis
- Mambert Marina
- Mameri Lakhdar
- Manchon Pauline
- Maniatis Tom
- Manivet Philippe
- Manry Jeremy
- Mansouri Cylia
- Mansouri Davood
- Marcault Estelle
- Marchal Astrid
- Marchioni Enrico
- Marey Jonathan
- Marin Nathalie
- Marioli Carola
- Marjani Majid
- Marois Clémence
- Marques Laura
- Martin Olivier
- Martin-Nalda Andrea
- Martineau Lou
- Martinez Antonio Morales
- Martinez-Lopez Cannelle
- Martinez-Picado Javier
- Martyniuck Pierre
- Martín-Nalda Andrea
- Marzana Iciar
- Marzouk Nessrine
- Maródi László
- Masmoudi Rafik
- Mata-Martínez Carmen
- Mathian Alexis
- Matos Larissa R. B.
- Matthews Gail V.
- Mattiaccio Alessandro
- Matuozzo Daniela
- Mayaux Julien
- McLaughlin-Garcia Raquel
- Mebazaa Alexandre
- Mechai Frédéric
- Mecozzi Fabio
- Medina Yeray Novoa
- Mediouni Chamseddine
- Meersseman Philippe
- Megarbane Bruno
- Meghadecha Mohamed
- Mejean Élodie
- Mekinian Arsene
- Mekni Rania
- Mekontso-Dessap Armand
- Meliti Thinhinan Sabrina
- Melián Abián Montesdeoca
- Melki Isabelle
- Meloni Federica
- Meng Paris
- Mentre France
- Mentré France
- Merbah Soraya
- Mergeay-Fabre Mayka
- Meritet Jean-François
- Merlani Paolo
- Messani Fadhila
- Messaoudi Yasmine
- Metin Akcan Ozge
- Meunier Alexandre
- Mewasing Baboo-Irwinsingh
- Meyts Isabelle
- Meyts Isabelle
- Meyts Isabelle
- Meziane Amina
- Meziane Lydia
- Mezidi Mehdi
- Michelot-Burger Carole
- Migaud Maria-Claire
- Migeotte Isabelle
- Mignot Françoise
- Milisavljevic Baptiste
- Milla Sonia Ayllon
- Millereux Maude
- Million Matthieu
- Milner Joshua D.
- Minka Fadi Hillary
- Mirault Tristan
- Mircher Clotilde
- Mironska Kristina
- Mirsaeidi Mehdi
- Miyara Makoto
- Mizoguchi Yoko
- Modi Bhavi P.
- Mogensen Trine H.
- Moine Pierre
- Mojoli Francesco
- Molina Jean-Michel
- Moncomble Elsa
- Monnory Fatima-Zohra Djamouri
- Montagne Samatha
- Montegnies-Boulet Anaïs
- Monti Alexandra
- Montlahuc Claire
- Montout Anne-Lise
- Moores Alexandre
- Morandeira Francisco
- Morange Pierre-Emmanuel
- Morbieu Caroline
- Mordacq Cléemence
- Morelle Guillaume
- Morio Tomohiro
- Mortelette Helene
- Mouly Stéphane
- Mouly Stéphane J.
- Mouquet Hugo
- Mullaert Jimmy
- Muzaffar Rosita
- Muñoz-Barrera Adrián
- Mège Jean-Louis
- Nacerddine Cherifa Iness
- Nadal Marine
- Nadif Hajer
- Nadji Seyed Alireza
- Naesens LeslieUGentUZGent0000802646688020030372470000-0003-1715-0665118A0826-F0EE-11E1-A9DE-61C894A0A6B4
- Nafati Cyril
- Nagashima Shintaro
- Nakagama Yu
- Narvaez Rafael Usubillaga
- Nassarmadji Kladoum
- Natella Pierre
- Ndingamondze Sandrine
- Neant Nadège
- Nellen Jeaninne
- Neraal Stefan
- Neven Bénédicte
- Neves João Farela
- Ng Lisa F. P.
- Ng Lisa F. P.
- Ng Yuk-Yung
- Nguyen Caroline
- Nguyen Duc
- Nguyen Duc
- NIAID-USUHS COVID Study Group [missing]
- Nicolas Leturque
- Nielly hubert
- Nlomenyengue Luc
- Noel Nicolas
- Noret Marion
- Nossent Esther J.
- Notarangelo Luigi D.
- Notarangelo Luigi D.
- Nouroudine Mariama
- Novelli Antonio
- Novelli Giuseppe
- Nseir Saad
- Nunes Hilario
- Nussbaum Robert
- N’Guyen Bao
- Ocejo-Vinyals J. Gonzalo
- Okada Satoshi
- Okamoto Keisuke
- Oler Andrew J.
- Omar Edris
- Orchestra Working Group [missing]
- Oualha Mehdi
- Ouazene Zineb
- Ouedrani Amani
- Ouedraogo Elise
- Ouelaa Wassila
- Oufella Hafid Ait
- Oukhedouma Anissa
- Oya Herve
- Ozcelik Tayfun
- Oziel Johanna
- Ozkaya-Parlakay Aslinur
- O’Farrelly Cliona
- Padilla Thomas
- Pagani Michele
- Paillaud Elena
- Paiva Solenne
- Palabiyik Figen
- Pan-Hammarström Qiang
- Papadaki Maria
- Papadopoulos Aurélie
- Parfait Beatrice
- Paris Christophe
- Parize Perrine
- Parizot Christophe
- Parizot Christophe
- Parola Philippe
- Parrot Antoine
- Pascreau Tiffany
- Paul Christelle
- Paul Stéphane
- Paulus Frederique
- Pavot Arthur
- Payet Christine
- Paz-Artal Estela
- Peaudecerf Laetitia
- Pedraza Sigifredo
- Peiffer-Smadja Nathan
- Pellecer Nancy Carolina González
- Pellegrini Silvia
- Pene Frédéric
- Pepin Marion
- Pereira Jesus Marquez
- Pernet Julie
- Pernin Claire
- Perpoint Thomas
- Perreau Pauline
- Pesci Alberto
- Peters Edgar
- Petit Mylène
- Petrov-Sanchez Ventzislava
- Peyrony Olivier
- Peytavin Gilles
- Pham Huong
- Philippe Aurélien
- Philippot Quentin
- Picod Adrien
- Picone Olivier
- Pietri Marie-Pierre
- Pietri Olivia
- Pina-Fuentes Dan A. I.
- Pinson Michelle
- Pintado Claire
- Pippucci Tommaso
- Piquard Valentine
- Piquard Valentine
- Piquard Valentine
- Piralla Antonio
- Pires Christine
- Pistone Thierry
- Planas Anna M.
- Planas-Serra Laura
- Planquette Benjamin
- Pleguezuelo Daniel E.
- Ploin Dominique
- Poirier Sandrine
- Poissy Julien
- Pomel Anne-Laure
- Poncelet Géraldine
- Pons Stéphanie
- Ponscarme Diane
- Poulakou Garyphallia
- Pouletty Marie S.
- Pourcelot Annegaelle
- Pourcher Valérie
- Pourshahnazari Persia
- Pouvaret Anne
- Prando Carolina
- Preckel Bennedikt
- Prever Florian
- Previlon Miresta
- Prevost Margot
- Prins Jan M.
- Provoost Marie-Julie
- Puel Anne
- Pueyo David Martínez
- Pujol Aurora
- Puéchal Oriane
- Pérez-Fernández Xosé Luis
- Qiu-Chen Jia Li
- Quaresima Virginia
- Quemeneur Cyril
- Quentric Paul
- Quintana-Murci Lluis
- Quintin Caroline
- Quiros-Roldan Eugenia
- Raasveld Jorinde
- Rabaud Christian
- Rafat Cédric
- Ramaswamy Sathishkumar
- Rambaud Thomas
- Rami Agathe
- Ramos Miquel Alfonso
- Ranque Brigitte
- Raoult Didier
- Raoult Violette
- Raphael Maurice
- Raphalen Jean Herle
- Rastoin Anna
- Raux Mathieu
- Rebai Amani
- Rebillat Anne-Sophie
- Reby Michael
- Redin Claire
- Regent Alexis
- Regrag Asma
- Reijnders Tom
- Renia Laurent
- Resche-Rigon Matthieu
- Resmini Léa
- Resnick Igor
- Ressaire Quentin
- Reyes Luis Felipe
- Ricart Pilar
- Richard Christian
- Richard Jean-Christophe
- Richard Lucie
- Richard Mariecaroline
- Rigo-Bonnin Raúl
- rivet Nadia
- Rivière Jacques G.
- Robert Maxence
- Rocamora-Blanch Gemma
- Rodero Mathieu P.
- Rodrigo Carlos
- Rodriguez Luis Antonio
- Rodriguez-Gallego Carlos
- Rodriguez-Palmero Agustí
- Rodríguez-Gallego Carlos
- Rohaut Benjamin
- Rojas Julian
- Rolland-Debord Camille
- Romero Carolina Soledad
- Ropers Jacques
- Roque-Afonso Anne-Marie
- Rosa-Calatrava Manuel
- Rosenberger John
- Rossi Camillo
- Rossignol Bénédicte
- Rossignol Patrick
- Rosso Charlotte
- Rothenbuhler Anya
- Roufai Layidé
- Rousseaux Mélanie
- Rousseaux Nabila
- Roux Damien
- Roux Lorène
- Roux Swasti
- Rouzaud Claire
- Rovere-Querini Patrizia
- Rovina Nikoletta
- Roy Carine
- Rozenberg Flore
- Rozes Antoine
- Rubenstein Emma
- Ruch Yvon
- Ruiz Montse
- Ruiz-Rodriguez Juan Carlos
- Sabate Jean-Marc
- Sabater-Riera Joan
- Sabet Sheila
- Sacleux Sophie-Caroline
- Saied Wafa Ibn
- Saks Kai
- Salagianni Maria
- Saliba Faouzi
- Salmon Dominique
- Sanchez Oliver
- Sancho-Shimizu Vanessa
- Savale Laurent
- Savary Guillaume
- Sberro Rebecca
- Scemla Anne
- Schidlowski Laire
- Schinkel Michiel
- Schlemmer Frederic
- Schluter Agatha
- Schlüter Agatha
- Schmidt Julien
- Schmidt Matthieu
- Schneider Marion
- Schrauwen Femke A. P.
- Schuetz Catharina
- Schultz Marcus J.
- Schuurmans Alex
- Schuurmans Jaap
- Schwartz Mathieu
- Schweitzer Cyril E.
- Scolari Francesco
- Sedfi Saïd
- Sediva Anna
- Sediva Anna
- Seeleuthner Yoann
- Sefir-Kribel Samia
- Seijo Luis
- Seksik Philippe
- Sellier Pierre
- Selves Agathe
- Sembach Nicole
- Semerano Luca
- Seminario Analia Gisela
- Senat Marie-Victoire
- Sene Damien
- Sene Damien
- Seng Piseth
- Senoglu Sevtap
- Seppänen Mikko
- Seppänen Mikko R. J.
- Seri Marco
- Serris Alexandra
- Sese Lucile
- Sghiouar Naima
- Shahrooei Mohammad
- Shcherbina Anna
- Shcherbina Anna
- Sigaloff Kim
- Sigaux Johanna
- Siguier Martin
- Siguret Virginie
- Silvain Johanne
- Simon Noémie
- Simon Tabassome
- Siouti Eleni
- Skandri Lina Innes
- Slabbynck Hans
- Slaby Ondrej
- Slim Marleen A.
- Slimani Miassa
- Smadja David M.
- Smeele Patrick
- Smit Marry
- Smith Nikaia
- Snauwaert Aurélie
- Snow Andrew L.
- Snow Andrew L.
- Sobh Ali
- Sokol Harry
- Solanich Xavier
- Soler Catherine
- Soler-Palacin Pere
- Soler-Palacín Pere
- Soler-Palacín Pere
- Soliman Heithem
- Solis Blanca Garcia
- Soltani Nisrine
- Solé-Violán Jordi
- Sottini Alessandra
- Soyer Benjamin
- Sozeri Betul
- Spaan András N.
- Steg Gabriel
- Stella Giulia Maria
- Stepanovskiy Yuriy
- Stijnis Cornelis S.
- Stilma Willemke
- Stoclin Annabelle
- Su Helen C.
- Su Helen C.
- Su Richa
- Suarez Lydia
- Sukumar Gauthaman
- Szwebel Tali-Anne
- Sánchez-Montalvá Adrián
- Sánchez-Ramón Silvia
- Sözeri Betül
- Taccone Fabio
- Tacconelli Evelina
- Taffame Kossi
- Talouarn Estelle
- Tancevski Ivan
- Tandjaoui-Lambiotte Yacine
- Tangye Stuart G.
- Tantet Claire
- Tardivon Coralie
- Tardy Bernard
- Tateo Mariagrazia
- Taupin Jean-Luc
- Tavernier SimonWE140020014667758020006635750000-0003-2514-56550109AD1C-F0EE-11E1-A9DE-61C894A0A6B4
- Tellier Marie-Capucine
- Tello Loreto Vidaur
- Terrier Benjamin
- Terrier Olivier
- Teunissen Charlotte
- Theodose Igor
- Thiebaud Pierre clement
- Thiery Guillaume
- Thomas Caroline
- Thoral Patrick
- Thorball Christian
- Thorn Karolina
- Thumerelle Caroline
- Thy Michael
- Tiercelet Kelly
- Timsit Jean-François
- Tipu Imran
- Tisserand Julie
- Tolstrup Martin
- Tomasoni Gabriele
- Tomczak Carole
- Tompkins Miranda F.
- Torelino Krystel
- Touam-Ext Fatima
- Toubiana Julie
- Toumi Lilia
- Toury Gustave
- Toy-Miou Mireille
- Trandinh Alexy
- Treluyer Jean-Marc
- Tresoldi Cristina
- Triantafyllia Vasiliki
- Trinque Baptiste
- Trouillet-Assant Sophie
- Troya Jesus
- Troya Jesús
- Truchot Jennifer
- Tsang Owen T. Y.
- Tserel Liina
- Tso Eugene Y. K.
- Tsonas Anissa M.
- Tual Christelle
- Tubach Florence
- Tubiana Sarah
- Tucci Alessandra
- Tuinman Pieter R.
- Tunesi Simone
- Turpin Agathe
- Turpin Matthieu
- Turvey Stuart E.
- Téoulé François
- Uddin Furkan
- Uddin Mohammed J.
- Urbina Tomas
- Ursini Matilde Valeria
- Utsumi Takanori
- Uzunhan Yurdagul
- Uzunhan Yurdagul
- Vabres Pierre
- Vacher Yannick
- Vaittinadaayar Prabakar
- Valencia-Ramos Juan
- Valent Arnaud
- Valentian Maelle
- Valin Nadia
- Vallet Hélène
- Valsecchi Maria Grazia
- van Agtmael Michiel
- van Baarle Frank
- Van Braeckel EvaGE35UZGent0019990642098020000443910000-0002-7242-0747F85E6FEA-F0ED-11E1-A9DE-61C894A0A6B4
- van de Beek Diederik
- van de Beek Diederik
- van de Beek Diederik
- Van Den Rym Ana Maria
- van der Poll Tom
- van der Valk Marc
- Van Der Werf Sylvie
- van der Werf Sylvie
- van Mourik Niels
- Van Praet JensGE510019991971778020000575290000-0002-7125-7001F8703A72-F0ED-11E1-A9DE-61C894A0A6B4
- van Vugt Michèle
- Vanderlinden Dimitri
- Vandernoot Isabelle
- Vanel Noémie
- Vaz Marina
- Vazquezibarra Miguel-Alejandro
- Vedie Benoit
- Veelo Denise
- Vega Clara Campos
- Veislinger Aurélie
- Velez-Santamaria Valentina
- Veliz Silvia Patricia Zuniga
- Velly Laetitia
- Verstuyft Celine
- Viallette Cedric
- Vicaut Eric
- Vidaud Michel
- Vidigal Mateus C.
- Viel Sébastien
- Vignali Valérie
- Vignes Dorothee
- Vilaire-Meunier Marie E.
- Villain Cédric
- Villar-García Judit
- Vimpere Damien
- Vincent Audrey
- Vinh Donald C.
- Virlouvet Myriam
- Visseaux Benoit
- Visseaux Benoit
- Vlaar Alexander P. J.
- Voiriot Guillaume
- Voiriot Guillaume
- Voisot Lena
- Volleman Carolien
- Volokha Alla
- von Bernuth Horst
- Vught Lonneke A.
- Vuotto Fanny
- Waucquier Nawal
- Wauters Els
- Wauters Joost
- Weiss Emmanuel
- Weiss Nicolas
- Wiedemann Aurélie
- Wiersinga W. Joost
- Wilkerson Matthew D.
- Winchenne Anaïs
- Wouters Dorien
- Wu Alan K. L.
- Wu Tak-Chiu
- Yahşi Aysun
- Yasar Kadriye Kart
- Yazdanpanah Yazdan
- Yazdanpanah Yazdan
- Yesilbas Osman
- Yildiz Mehmet
- Yordanov Youri
- Youkou Christy Gaëlla Kotokpo
- Young Barnaby E.
- Yüksek Saliha Kanık
- Yükselmiş Ufuk
- Zafrani Lara
- Zaidan Mohamad
- Zaidi Wissem
- Zak Cathia
- Zarhrate-Ghoul Aida
- Zatout Ouassila
- Zatz Mayana
- Zatz Mayana
- Zatz Mayana
- Zawadzki Pawel
- Zecca Marco
- Zeino Suzanne
- Zeitouni Michel
- Zemirli Naïma
- Zerah Lorene
- Zhang Peng
- Zhang Qian0002114872788020038650809740070091702cbd7cfa-2ba8-11ec-a073-a297246d27bb
- Zhang Shen-Ying
- Zhang Xijun
- Zhang Yu
- Zia Ounsa
- Ziol Marianne
- Zolario Oceane
- Zuber Julien
- Zuccaro Valentina
- Zwinderman A. H.
- Íñigo-Campos Antonio
- Öz Şadiye Kübra Tüter
- Özkan Esra Akyüz
- Özçelik Tayfun
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2023
- Field of study
No full textBackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.A
Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
- Author
- Abad Jorge
- Abad Sebastien
- Abassi Radhiya
- Abdelhadi Nour Mekki
- Abdellaoui Abdelrafie
- Abdelmalek Abdelkrim
- Abdoul Hendy
- Abel Laurent
- Abel Laurent
- Abel Laurent
- Abel Laurent
- Abergel Helene
- Abeud Fariza
- Abgrall Sophie
- Abisror Noemie
- Abolhassani Hassan
- Abou Tayoun Ahmad
- Accordino Giulia
- Achille Cristian
- Adechian Marylise
- Aderdour Nordine
- Admane Hakeem Farid
- Adnet Frederic
- Afritt Sara
- Agostini Helene
- Agra Juan José Cáceres
- Aguilar Claire
- Aguilera-Albesa Sergio
- Aguiló-Cucurull Aina
- Agut Sophie
- Aiello Tommaso Francesco
- Aiuti Alessandro
- Ajeenthiravasan Gokula
- Akcan Özge Metin
- Al-Muhsen Saleh
- Al-Muhsen Saleh Zaid
- Al-Mulla Fahd
- Alauzy Virginie
- Alavi Darazam Ilad
- Alavoine Loubna
- Alba Camille
- Albisures Jonathan Antonio Roblero
- Alby-Laurent Fanny
- Aldave Juan C.
- Algera Anne Geke
- Aliberti Anna
- Alkan Gulsum
- AlKhater Suzan A.
- Allard Lucie
- Allardet-Servent Jerome
- Allende Luis M.
- Alonso-Arias Rebeca
- Alosaimi Mohammed Faraj
- Alshahrani Mohammed S.
- Alsina Laia
- Alsohime Fahad M.
- Alvarez Josep Trenado
- Alyanakian Marie-Alexandra
- Alyanakian Marie-Alexandra
- Amam Sabrina
- Amara Yasmina Ould
- Amat Karine
- Amoura Zahir
- Amrouche Lucile
- Amsterdam UMC Covid-19 Biobank [missing]
- Anderson Mark S.
- Andreakos Evangelos
- Andrejak Claire
- Andronikof Marc
- Anglicheau Dany
- Angoulvant François
- Anguel Nadia
- Annane Djillali
- Antolí Arnau
- Aounzou Mohammed
- Aparicio Caroline
- Appelman Brent
- Aratus Gladys
- Arias Andrés A.
- Arias Andrés Augusto
- Arlet Jean-Benoit
- Arquero Miguel Fernandez
- Arranz María Jesús
- Arrestier Romain
- Arzoine Jeremy
- Asano Takaki
- Aslangul Elisabeth
- Assefi Mona
- Aubart Mélodie
- Aubry Adeline
- Audiffred Laetitia
- Audureau Etienne
- Auger Christelle Nathalie
- Auguet Teresa
- Auregan Jean-Charles
- Avramenko Iryna
- Awotar Celine
- Aytekin Gokhan
- Aytekin Gökhan
- Aytekin Selma Erol
- Azan Delphine
- Azemar Laurene
- Azot Axelle
- Azzouguen Billal
- Bachelet Delphine
- Badsi Aïda
- Baghdadi Jamila El
- Bahram Seiamak
- Bajolle Fanny
- Bakouboula Prissile
- Balcerowiak Coline
- Baldanti Fausto
- Balde Fanta
- Baldivia Elodie
- Baldolli Aurélie
- Ballester Maite
- Bangamingo Eliane-Flore
- Baptiste Amandine
- Baran-Marszak Fanny
- Barau Caroline
- Barget Nathalie
- Baris-Feldman Hagit
- Baronnet Flore
- Barrou Benoit
- Barthelemy Romain
- Bartoli Marie
- Barzaghi Federica
- Basmaci Romain
- Basso Sabrina
- Bastard Paul
- Baudel Jean-Luc
- Baudry Camille
- Baudry Elodie
- Bauters Fre
- Bax Diane
- Bayhan Gulsum Iclal
- Beaugerie Laurent
- Behilill Sylvie
- Behillil Sylvie
- Belamri Adel
- Belaube Nicolas
- Belilita Rhida
- Bellani Giacomo
- Bellassen Pierre
- Belmokhtar Rawan
- Belot Alexandre
- Belot Alexandre
- Beltran Isabel
- Beluze Marine
- Benainous Ruben
- Benallaoua Mourad
- Benamouzig Robert
- Benbara Amélie
- Benhida Jaouad
- Benkerrou Dehbia
- Benkhelouf Anis
- Benlagha Jihene
- Benmostafa Chahinez
- Benothmane Skander
- Bentifraouine Miassa
- Berard Laurence
- Beretta Ilaria
- Bergman Peter
- Berkell Matilda
- Bernier Quentin
- Bertholon Frédérique
- Berti Enora
- Bertier Astrid
- Berton Laure
- Bessis Simon
- Bettini Laura Rachele
- Beudel Martijn
- Beurton Alexandra
- Bezrodnik Liliana
- Bhavsar Krishna
- Bianco Celine
- Bianquis Clara
- Bidar Frank
- Biggs Catherine M.
- Bilbao Agurtzane
- Biondi Andrea
- Bizien Lucy
- Blanchard-Rohner Geraldine
- Blanche Philippe
- Blanco Ignacio
- Blandinières Adeline
- Blayau Clarisse
- Bleibtreu Alexandre
- Bleibtreu Alexandre
- Blin Emmanuelle
- Bloch-Queyrat Coralie
- Bloomfield Marketa
- Blázquez-Gamero Daniel
- Bogaard Harm Jan
- Bogunovic Dusan
- Boissier Marie-Christophe
- Boisson Bertrand
- Boisson-Dupuis Stephanie
- Boland Anne
- Bolivar-Prados Mireia
- Bollens Diane
- Bolze Alexandre
- Bolzoni Marion
- Bomers Marije
- Bompard Rudy pierre
- Bondarenko Anastasiia
- Bondarenko Anastasiia
- Bondesan Simone
- Bonnet Nicolas
- Bonnouvrier Justine
- Bonta Peter
- Borghesi Alessandro
- Borie Raphael
- Borrero Blanca Amador
- Borrero Blanca Amador
- Bos Lieuwe
- Bosteels Cedric
- Botdhlo-Nevers Elisabeth
- Botelho-Nevers Elisabeth
- Botha Shirmonecrystal
- Botta Michela
- Bouadma Lila
- Boucenna Wissam
- Bouchama Fatiha
- Bouchaud Olivier
- Bouchez Sabelline
- Bouchghoul Hanane
- Boudjebla Taoueslylia
- Boudjema Noel
- Bouffard Catherine
- Bougle Adrien
- Bouguerra Meriem
- Bouiller Kévin
- Boulanger Cécile
- Bouras Leila
- Bourcier Agnes
- Bourgeon Marilou
- Bourrier Anne
- Bouscambert Maude
- Bouscarat Fabrice
- Bousfiha Ahmed A.
- Bousfiha Ahmed A.
- Bousquet Aurore
- Boutolleau David
- Bouvattier Claire
- Bouvry Diane
- Bouziri Nesrine
- Bouzrara Ons
- Boyarchuk Oksana
- Bozdemir Şefika Elmas
- Bravais Juliette
- Bribier Sarah
- Briones M. Luisa
- Brodin Petter
- Brouwer Matthijs C.
- Brugier Delphine
- Bruneau Léa
- Brunel Melanie
- Brunner Marie-Eve
- Bruno Raffaele
- Bryceson Yenan
- Bryceson Yenan T.
- Bueno Maria Rita P.
- Bugiani Marianna
- Bui Eida
- Buis David T. P.
- Buisson Anne
- Bukhari Huda
- Bukreyeva Iryna
- Bulle Esther
- Burdet Charles
- Bureau Côme
- Bureau Serge
- Bustamante Carlos D.
- Bustamante Jacinta
- Bustos Ingrid G.
- Butte Manish J.
- Cabrera-Marante Oscar
- Cadranel Jacques
- Cailhol Johann
- Calin Ruxandra
- Canavaggio Pauline
- Cancella Marta
- Cantin Delphine
- Cao Albert
- Capra Ruggero
- Carapito Raphael
- Carbillon Lionel
- Carcel Sheila
- Carelli Valerio
- Carlier Nicolas
- Carrabba Maria
- Carrera Paola
- Casanova Jean-Laurent
- Casanova Jean-Laurent
- Casari Giorgio
- Casasnovas Carlos
- Caseris Marion
- Cassaniti Irene
- Cassard Clementine
- Castelle Martin
- Castelli Francesco
- Castor Guylaine
- Castro Mateus V.
- Catherinot Emilie
- Cauchy Marion
- Cazzaniga Marina
- Celik Jale Bengi
- Cervantes-Gonzalez Minerva
- Ceschi Alessandro
- Cha Olivier
- Chachoua Abla
- Chahine Abir
- Chaigne Benjamin
- Chair Anissa
- Chakravorty Samya
- Chaldebas Matthieu
- Challal Salima
- Chalumeau Martin
- Chalumeau Nathalie Costedoat
- Champion Karine
- Charbit Bruno
- Chariot Patrick
- Charpentier Charlotte
- Chas Julie
- Chauveau Simon
- Chauvin Anthony
- Chauvin Clement
- Chavarot Nathalie
- Chaïbi Khalil
- Chebbout Kamélia
- Cheng Matthew P.
- Cherai Mustapha
- Cherubini Ilaria
- Chevalier Amelie
- Chiarabini Thibault
- Chinet Thierry
- Chirouze Catherine
- Chirouze Catherine
- Chocron Richard
- Choinier Pascaline
- Chommeloux Juliette
- Choquet Christophe
- Choupeaux Laure
- Chousterman Benjamin
- Christelle Kouakam
- Christodoulou John
- Ciocan Dragosmarius
- Citerio Giuseppe
- Clarke Ada
- Clavere Gaëlle
- Clavier Florian
- Clavé Père
- Clement Karine
- Clerc Sebastien
- Cloherty Osoul Chouchane Alex
- Clotet Bonaventura
- Cobat Aurélie
- Codina Anna
- Coelho Alexandra
- Cohen Adrien
- Cohen Fleur
- Cohen Yves
- Cohen Yves
- Coilly Audrey
- Colboc Hester
- Colin Pauline
- Collet Magalie
- Colobran Roger
- Comarmond Chloé
- Comarmond Cloé
- Combacon Emeline
- Combe Caroline Lascoux
- Combes Alain
- Combes Alain
- Comoli Patrizia
- Comparon Celine
- Condino-Neto Antonio
- Constantin Jean-Michel
- Constantinescu Stefan N.
- Contro Ernesto
- Cooper Megan A.
- Cordel Hugues
- Cordier Anne-Gael
- Corsico Angelo G.
- Costantini Adrien
- Couffignal Camille
- Couffignal Camille
- Couffin-Cadiergues Sandrine
- Couffin-Cadiergues Sandrine
- Coupeau Doriane
- CoV-Contact Cohort [missing]
- COVID Clinicians [missing]
- COVID Human Genetic Effort [missing]
- COVID-STORM Clinicians [missing]
- COVIDeF Study Group [missing]
- Covill Laura E.
- Coşkuner Taner
- Creange Alain
- Cuadros Esmeralda Nuñez
- Cvetkovski Aleksandar
- Cyrus Cyril
- Da Silveira Charlène
- Dalgard Clifton L.
- Dalmau David
- Danielson Jeffrey J.
- Danion François
- Darley David Ross
- Das Vincent
- Dauby Nicolas
- Dauger Stéphane
- De Bouille Jeanne Goupil
- de Brabander Justin
- de Bree Godelieve
- de Bruin Sanne
- De Castro Nathalie
- De Chambrun Marc Pineton
- de Chambrun Marc Pineton
- de Diego Rebeca Pérez
- De Farcy Pauline Mary
- de Jong Menno D.
- De Munter Paul
- de Pontual Loic
- de Rotte Maurits C. F. J.
- De Rycke Yann
- de Vera Martín Castillo
- de Vries Heder
- Debray Marie-Pierre
- Dechanet Aline
- Declercq Jozefien
- Deconinck Lauren
- Dehban Amin
- Del Pozo Lucie
- del Prado Maria Yolanda Ruiz
- Delannoy Quentin
- Delay Mathieu
- Deleris Robin
- Deleuze Jean-François
- Delforge Juliette
- Delmonte Ottavia M.
- Delphine Laëtitia
- Delplancq Geoffroy
- Demar Magalie
- Demare Noemie
- Demeret Sophie
- Demerville Lauren
- Demirkol Yasemin Kendir
- Demoule Alexandre
- Demoule Alexandre
- Deniau Aurore
- Deplanque Dominique
- Deplanque Dominique
- Depret François
- Derolez Sophie
- Derradji Ouda
- Derridj Nawal
- Desai Murkesh
- Descamps Diane
- Descamps Diane
- Descamps Vincent
- Deschamps Lydia
- Desconclois Celine
- Desguerre Isabelle
- Desille-Dugast Mireille
- Desmarets Maxime
- Desnos Cyrielle
- Desongins Karine
- Desvallée Mathilde
- Devouge Eglantine Ferrand
- Dhote Robin
- Di Sabatino Antonio
- Diallo Alpha
- Diallo Benjamin
- Didier Morgane
- Diehl Jean-Luc
- Diemer Myriam
- Diez Stephane
- Dijkstra Mirjam
- Diouf Alphonsine
- Djadi-Prat Juliette
- Djebara Siham
- Djebra Naoual
- Djietcheu Minette
- Djillali Hadjer
- Djossou Félix
- Djouadi Nouara
- Dobbelaere Stephanie
- Dobbs Kerry
- Domínguez-Garrido Elena
- Dongelmans Dave A.
- Donneger Severine
- Dorival Céline
- Dos Santos Catarina
- Dournon Nathalie
- Dres Martin
- Droctove Laura
- Drogrey Marie
- Drolet Beth A.
- Dropy Margot
- Drouet Elodie
- Dubos François
- Dubosq Valérie
- Dubost Clément
- Dubreucq Evelyne
- Dubus Estelle
- Duchemann Boris
- Duchenoy Thibault
- Dudoignon Emmanuel
- Dufau Romain
- Dujardin Romein W. G.
- Dumas Florence
- Duran Clara
- Durand Anne Bourgarit
- Duron Emmanuelle
- Durrbach Antoine
- Duval Xavier
- Duval Xavier
- Duvivier Claudine
- D’Angio’ Mariella
- d’Ortenzio Eric
- Ebstein Nathan
- Ecobichon Jean-Luc
- Ekwall Olov
- El Zein Loubna
- Elabbadi Alexandre
- Elbers Paul
- Elharrar Brigitte
- Elie Caroline
- Elnagdy Marwa H.
- Eloy Philippine
- Elrufaai Marwa Bachir
- Emiroglu Melike
- Endo Akifumi
- Enouf Vincent
- Enouf Vincent
- Erdeniz Emine Hafize
- Ernotte Gabriel
- Esling Anne
- Esperou Hélène
- Espinosa-Padilla Sara
- Esposito-Farese Marina
- Espérou Hélène
- Etienne Manuel
- Etienne Martin
- Euvrard Romain
- Eyer Xavier
- Fabio Giovanna
- Faivre Laurence
- Falck Antonin
- Fartoukh Muriel
- Fartoukh Muriel sarah
- Faure Morgane
- Fayali Takoua
- Feldman Hagit Baris
- Feldman Hagit Baris
- Fellay Jacques
- Fermaut Marion
- Ferrer Ricard
- Ferreres Jose
- Fiorentino Alessio
- Fiorentino Arianna
- Fleuren Lucas
- Fliss Souha
- Flores Carlos
- Florkin Benoit
- Foti Giuseppe
- Fouchard Julie
- Fournier Benjamin
- Fournier Marie-Céline
- Franco Jose Luis
- Franco José Luis
- Francois Bruno
- Francois Hélène
- French COVID Cohort Study Group [missing]
- Freynet Olivia
- Frezouls Wahiba
- Frigout Yvann
- Froidure Antoine
- Fromont Isaure
- Fuentes Axelle
- Fumadó Victoria
- Fung Kitty S. C.
- Furet Thomas
- Fusco Francesca
- Gagneux-Brunon Amandine
- Gagro Alenka
- Galand Joris
- Garnier Marc
- Garçon Pierre
- Gatineau Audrey Giraud
- Gaubert Agnes
- Gaudry Stéphane
- Gaugain Samuel
- Gault Nathalie
- Gaussem Pascale
- Gauthier Damien
- Gautier Maxime
- Gaymard Alexandre
- Gayretli Zeynep
- Geijtenbeek Suzanne Geerlings Theo
- Georgin-Lavialle Sophie
- Geromin Daniela
- Gervais Adrian
- Ghalayini Mohamed
- Ghaleh Bijan
- Ghezal Myriam
- Ghosn Jade
- Gibelin Aude
- Gigante Tristan
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- Gilardin Laurent
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- Gimeno Linda
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- Girona-Alarcón Mònica
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- Goas Carole L. E.
- Godínez Karen Alejandra Cifuentes
- Goffard Jean-Christophe
- Gomes Doryan
- Gomes-Pires Elisabete
- Gonzales Nacho
- Gonzalez-Granado Luis I.
- González-Montelongo Rafaela
- Goorhuis Bram
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- Gras Julien
- Greffe Segolene
- Gregersen Peter K.
- Grimaldi Lamiae
- Grobusch Martin P.
- Guedeney Paul
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- Guerder Antoine
- Guidet Bertrand
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- Hatipoğlu Nevin
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- Hautem Coraline
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- Heijmans Catherine
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- Heming Nicholas
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- Minka Fadi Hillary
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- Modi Bhavi P.
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- Mouly Stéphane J.
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- Nadji Seyed Alireza
- Naesens Leslie
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- Nagashima Shintaro
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- Narvaez Rafael Usubillaga
- Nassarmadji Kladoum
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- Neant Nadège
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- Neves João Farela
- Ng Lisa F. P.
- Ng Lisa F. P.
- Ng Yuk-Yung
- Nguyen Caroline
- Nguyen Duc
- Nguyen Duc
- NIAID-USUHS COVID Study Group [missing]
- Nicolas Leturque
- Nielly hubert
- Nlomenyengue Luc
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- Nossent Esther J.
- Notarangelo Luigi D.
- Notarangelo Luigi D.
- Nouroudine Mariama
- Novelli Antonio
- Novelli Giuseppe
- Nseir Saad
- Nunes Hilario
- Nussbaum Robert
- N’Guyen Bao
- Ocejo-Vinyals J. Gonzalo
- Okada Satoshi
- Okamoto Keisuke
- Oler Andrew J.
- Omar Edris
- Orchestra Working Group [missing]
- Oualha Mehdi
- Ouazene Zineb
- Ouedrani Amani
- Ouedraogo Elise
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- Oufella Hafid Ait
- Oukhedouma Anissa
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- Ozcelik Tayfun
- Oziel Johanna
- Ozkaya-Parlakay Aslinur
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- Paillaud Elena
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- Parfait Beatrice
- Paris Christophe
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- Paul Stéphane
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- Pham Huong
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- Pietri Olivia
- Pina-Fuentes Dan A. I.
- Pinson Michelle
- Pintado Claire
- Pippucci Tommaso
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- Piquard Valentine
- Piquard Valentine
- Piralla Antonio
- Pires Christine
- Pistone Thierry
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- Planas-Serra Laura
- Planquette Benjamin
- Pleguezuelo Daniel E.
- Ploin Dominique
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- Poissy Julien
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- Pouletty Marie S.
- Pourcelot Annegaelle
- Pourcher Valérie
- Pourshahnazari Persia
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- Preckel Bennedikt
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- Provoost Marie-Julie
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- Pueyo David Martínez
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- Pérez-Fernández Xosé Luis
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- rivet Nadia
- Rivière Jacques G.
- Robert Maxence
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- Rodero Mathieu P.
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- Schrauwen Femke A. P.
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- Schultz Marcus J.
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- Seppänen Mikko R. J.
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- Slaby Ondrej
- Slim Marleen A.
- Slimani Miassa
- Smadja David M.
- Smeele Patrick
- Smit Marry
- Smith Nikaia
- Snauwaert Aurélie
- Snow Andrew L.
- Snow Andrew L.
- Sobh Ali
- Sokol Harry
- Solanich Xavier
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- Soyer Benjamin
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- Stijnis Cornelis S.
- Stilma Willemke
- Stoclin Annabelle
- Su Helen C.
- Su Helen C.
- Su Richa
- Suarez Lydia
- Sukumar Gauthaman
- Szwebel Tali-Anne
- Sánchez-Montalvá Adrián
- Sánchez-Ramón Silvia
- Sözeri Betül
- Taccone Fabio
- Tacconelli Evelina
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- Tandjaoui-Lambiotte Yacine
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- Tantet Claire
- Tardivon Coralie
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- Taupin Jean-Luc
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- Thy Michael
- Tiercelet Kelly
- Timsit Jean-François
- Tipu Imran
- Tisserand Julie
- Tolstrup Martin
- Tomasoni Gabriele
- Tomczak Carole
- Tompkins Miranda F.
- Torelino Krystel
- Touam-Ext Fatima
- Toubiana Julie
- Toumi Lilia
- Toury Gustave
- Toy-Miou Mireille
- Trandinh Alexy
- Treluyer Jean-Marc
- Tresoldi Cristina
- Triantafyllia Vasiliki
- Trinque Baptiste
- Trouillet-Assant Sophie
- Troya Jesus
- Troya Jesús
- Truchot Jennifer
- Tsang Owen T. Y.
- Tserel Liina
- Tso Eugene Y. K.
- Tsonas Anissa M.
- Tual Christelle
- Tubach Florence
- Tubiana Sarah
- Tucci Alessandra
- Tuinman Pieter R.
- Tunesi Simone
- Turpin Agathe
- Turpin Matthieu
- Turvey Stuart E.
- Téoulé François
- Uddin Furkan
- Uddin Mohammed J.
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- Ursini Matilde Valeria
- Utsumi Takanori
- Uzunhan Yurdagul
- Uzunhan Yurdagul
- Vabres Pierre
- Vacher Yannick
- Vaittinadaayar Prabakar
- Valencia-Ramos Juan
- Valent Arnaud
- Valentian Maelle
- Valin Nadia
- Vallet Hélène
- Valsecchi Maria Grazia
- van Agtmael Michiel
- van Baarle Frank
- Van Braeckel Eva
- van de Beek Diederik
- van de Beek Diederik
- van de Beek Diederik
- Van Den Rym Ana Maria
- van der Poll Tom
- van der Valk Marc
- Van Der Werf Sylvie
- van der Werf Sylvie
- van Mourik Niels
- Van Praet Jens
- van Vugt Michèle
- Vanderlinden Dimitri
- Vandernoot Isabelle
- Vanel Noémie
- Vaz Marina
- Vazquezibarra Miguel-Alejandro
- Vedie Benoit
- Veelo Denise
- Vega Clara Campos
- Veislinger Aurélie
- Velez-Santamaria Valentina
- Veliz Silvia Patricia Zuniga
- Velly Laetitia
- Verstuyft Celine
- Viallette Cedric
- Vicaut Eric
- Vidaud Michel
- Vidigal Mateus C.
- Viel Sébastien
- Vignali Valérie
- Vignes Dorothee
- Vilaire-Meunier Marie E.
- Villain Cédric
- Villar-García Judit
- Vimpere Damien
- Vincent Audrey
- Vinh Donald C.
- Virlouvet Myriam
- Visseaux Benoit
- Visseaux Benoit
- Vlaar Alexander P. J.
- Voiriot Guillaume
- Voiriot Guillaume
- Voisot Lena
- Volleman Carolien
- Volokha Alla
- von Bernuth Horst
- Vught Lonneke A.
- Vuotto Fanny
- Waucquier Nawal
- Wauters Els
- Wauters Joost
- Weiss Emmanuel
- Weiss Nicolas
- Wiedemann Aurélie
- Wiersinga W. Joost
- Wilkerson Matthew D.
- Winchenne Anaïs
- Wouters Dorien
- Wu Alan K. L.
- Wu Tak-Chiu
- Yahşi Aysun
- Yasar Kadriye Kart
- Yazdanpanah Yazdan
- Yazdanpanah Yazdan
- Yesilbas Osman
- Yildiz Mehmet
- Yordanov Youri
- Youkou Christy Gaëlla Kotokpo
- Young Barnaby E.
- Yüksek Saliha Kanık
- Yükselmiş Ufuk
- Zafrani Lara
- Zaidan Mohamad
- Zaidi Wissem
- Zak Cathia
- Zarhrate-Ghoul Aida
- Zatout Ouassila
- Zatz Mayana
- Zatz Mayana
- Zatz Mayana
- Zawadzki Pawel
- Zecca Marco
- Zeino Suzanne
- Zeitouni Michel
- Zemirli Naïma
- Zerah Lorene
- Zhang Peng
- Zhang Qian
- Zhang Shen-Ying
- Zhang Xijun
- Zhang Yu
- Zia Ounsa
- Ziol Marianne
- Zolario Oceane
- Zuber Julien
- Zuccaro Valentina
- Zwinderman A. H.
- Íñigo-Campos Antonio
- Öz Şadiye Kübra Tüter
- Özkan Esra Akyüz
- Özçelik Tayfun
- Publication venue
- Springer Science and Business Media LLC
- Publication date
- 01/01/2023
- Field of study
No full textBackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old
