8 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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- Zuber J.
- 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
Double all-optical encryption of M-QAM signals based on spectrally sliced encoding keys
- Publication venue
- IEEE
- Publication date
- 01/07/2015
- Field of study
Full text linkAll-optical narrowband spectral slicing encryption with super-Gaussian filters
- Publication venue
- IEEE
- Publication date
- 01/08/2014
- Field of study
Full text linkA new all-optical cryptography technique applied to WDM-compatible DPSK signals
- Author
- Publication venue
- IEEE
- Publication date
- 01/06/2013
- Field of study
Full text linkTransmission of encrypted optical signals in a metropolitan WDM-compatible TON with differential phase-shift keying modulation
- Author
- Publication venue
- IEEE
- Publication date
- 01/08/2013
- Field of study
Full text linkAll-optical cryptography through spectral amplitude and delay encoding
- Publication venue
- 'FapUNIFESP (SciELO)'
- Publication date
- Field of study
No full textAll-optical data encryption is a promising technology that could lead communication systems to an unprecedented degree of security. In this paper we use computer simulations to systematically investigate a new all-optical cryptography technique that is bit-rate independent and transparent to modulation formats. Encryption encompasses signal spectral slicing followed by two encoding stages that impose different attenuations and delays to each of the spectral slices. We analyze the quality of the encoded signal by evaluating its bit error rate (BER) performance. Results indicate that such BER may achieve 45 and 28%, respectively, for input non-return-to-zero on-off keying (NRZ-OOK) and differential quadrature phase-shift keying (DQPSK) signals. At the receiver side, results suggest that signals may be properly decoded after propagation distances that are compatible with those utilized in metropolitan area networks. The robustness of the technique against waveform analysis and brute force attacks is also approached
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 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
- 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
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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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- 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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- 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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- 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
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- Oziel Johanna
- Ozkaya-Parlakay Aslinur
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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.
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- Pouletty Marie S.
- Pourcelot Annegaelle
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- Pourshahnazari Persia
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- Preckel Bennedikt
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- Prins Jan M.
- Provoost Marie-Julie
- Puel Anne
- 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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- 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
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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
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- Sukumar Gauthaman
- Szwebel Tali-Anne
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- Sánchez-Ramón Silvia
- Sözeri Betül
- Taccone Fabio
- Tacconelli Evelina
- Taffame Kossi
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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
