Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths - Sorbonne Université Access content directly
Journal Articles Science Immunology Year : 2021

Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths

Paul Bastard (1) , Adrian Gervais (1) , Tom Le Voyer (1) , Jeremie Rosain (1) , Quentin Philippot (1) , Jérémy Manry (1) , Eleftherios Michailidis , Hans-Heinrich Hoffmann , Shohei Eto , Marina Garcia-Prat , Lucy Bizien , Alba Parra-Martinez , Rui Yang , Liis Haljasmagi , Melanie Migaud , Karita Sarekannu , Julia Maslovskaja , Nicolas de Prost (2) , Yacine Tandjaoui-Lambiotte (3) , Charles-Edouard Luyt (4, 5) , Blanca Amador-Borrero (6) , Alexandre Gaudet (7, 8) , Julien Poissy (7, 8) , Pascal Morel (9, 10) , Pascale Richard (9) , Fabrice Cognasse (11, 12) , Jesus Troya (13) , Sophie Trouillet-Assant (13, 14) , Alexandre Belot (14, 13) , Kahina Saker (14, 13) , Pierre Garcon (15) , Jacques G. Riviere , Jean-Christophe Lagier (16, 17) , Stephanie Gentile (18, 19) , Lindsey B. Rosen , Elana Shaw , Tomohiro Morio , Junko Tanaka , David Dalmau , Pierre-Louis Tharaux (20) , Damien Sene (6) , Alain Stepanian (6, 21) , Bruno Megarbane (22, 23) , Vasiliki Triantafyllia , Arnaud Fekkar (1, 4) , James R. Heath , Jose Luis Franco , Juan-Manuel Anaya , Jordi Sole-Violan , Luisa Imberti , Andrea Biondi , Paolo Bonfanti , Riccardo Castagnoli , Ottavia M. Delmonte , Yu Zhang , Andrew L. Snow , Steven M. Holland , Catherine Biggs , Marcela Moncada-Velez , Andres Augusto Arias , Lazaro Lorenzo (1) , Soraya Boucherit (1) , Boubacar Coulibaly (1) , Dany Anglicheau (24) , Anna M. Planas , Filomeen Haerynck , Sotirija Duvlis , Robert L. Nussbaum , Tayfun Ozcelik , Seygi Keles , Ahmed A. Bousfiha , Jalila El Bakkouri , Carolina Ramirez-Santana , Stéphane Paul (25, 14) , Qiang Pan-Hammarstrom , Lennart Hammarstrom , Annabelle Dupont (26) , Alina Kurolap , Christine N. Metz , Alessandro Aiuti , Giorgio Casari , Vito Lampasona , Fabio Ciceri , Lucile A. Barreiros , Elena Dominguez-Garrido , Mateus Vidigal , Mayana Zatz , Diederik van de Beek , Sabina Sahanic , Ivan Tancevski , Yurii Stepanovskyy , Oksana Boyarchuk , Yoko Nukui , Miyuki Tsumura , Loreto Vidaur , Stuart G. Tangye , Sonia Burrel (27) , Darragh Duffy (28) , Lluis Quintana-Murci (29, 30) , Adam Klocperk , Nelli Y. Kann , Anna Shcherbina , Yu-Lung Lau , Daniel Leung , Matthieu Coulongeat (31) , Julien Marlet (32, 31) , Rutger Koning , Luis Felipe Reyes , Angelique Chauvineau-Grenier (33) , Fabienne Venet (34, 35) , Guillaume Monneret (34, 35) , Michel C. Nussenzweig , Romain Arrestier , Idris Boudhabhay , Hagit Baris-Feldman , David Hagin , Joost Wauters , Isabelle Meyts , Adam H. Dyer , Sean P. Kennelly , Nollaig M. Bourke , Rabih Halwani , Narjes Saheb Sharif-Askari , Karim Dorgham (36) , Jerome Sallette , Souad Mehlal Sedkaoui , Suzan Alkhater , Raul Rigo-Bonnin , Francisco Morandeira , Lucie Roussel , Donald C. Vinh , Sisse Rye Ostrowski , Antonio Condino-Neto , Carolina Prando , Anastasiia Bonradenko , Andras N. Spaan , Laurent Gilardin (37, 38) , Jacques Fellay , Stanislas Lyonnet (1) , Kaya Bilguvar , Richard P. Lifton , Shrikant Mane , Hgid Lab , Covid Clinicians , Covid-Storm Clinicians , Niaid Immune Response To Covid Group , Nh-Covair Study Group , Chge Danish , Study Danish Blood Donor , Hospital St. James'S , Sars Cov2 Interest Group , Covid Cohort Study Group French , Covid-Group Imagine , Consortium Milieu Interieur , V. Contact Cohort Co , U. M. C. Covid Amsterdam , Investigators Biobank , Covid Human Genetic Effort , Constances Cohort , C. Dijon Study , Health-Care Cerba , Group Etablissement Du Sang Study , Mark S. Anderson , Bertrand Boisson , Vivien Beziat , Shen-Ying Zhang , Evangelos Vandreakos , Olivier Hermine , Aurora Pujol , Part Peterson , Trine H. Mogensen , Lee Rowen , James Mond , Stephanie Debette (39) , Xavier de Lamballerie (40, 17) , Xavier Duval (41) , France Mentré (41, 42) , Marie Zins (43) , Pere Soler-Palacin , Roger Colobran , Guy Gorochov , Xavier Solanich , Sophie Susen (26) , Javier Martinez-Picado , Didier Raoult (16, 17) , Marc Vasse , Peter K. Gregersen , Lorenzo Piemonti , Carlos Rodriguez-Gallego , Luigi D. Notarangelo , Helen C. Su , Kai Kisand , Satoshi Okada , Anne Puel , Emmanuelle Jouanguy , Charles M. Rice , Pierre Tiberghien , Qian Zhang , Aurelie Cobat , Laurent Abel , Jean-Laurent Casanova , Jean-Christophe Richard (44, 45) , Mathieu P Rodero (46) , Sylvie van Der Werf (47) , Claire Andréjak (48, 49, 50)
1 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
2 CARMAS - Groupe de recherche clinique CARMAS (Cardiovascular and Respiratory Manifestations of Acute lung injury and Sepsis)
3 Hôpital Avicenne [AP-HP]
4 CHU Pitié-Salpêtrière [AP-HP]
5 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases
6 Hôpital Lariboisière-Fernand-Widal [APHP]
7 CIIL - Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204
8 Hôpital Roger Salengro [Lille]
9 EFS - Etablissement Français du Sang [La Plaine Saint-Denis]
10 RIGHT - Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098)
11 SAINBIOSE - Santé Ingénierie Biologie Saint-Etienne
12 EFS - Etablissement français du sang - Auvergne-Rhône-Alpes
13 HCL - Hospices Civils de Lyon
14 CIRI - Centre International de Recherche en Infectiologie
15 GHEF - Grand Hôpital de l'Est Francilien
16 MEPHI - Microbes évolution phylogénie et infections
17 IHU Marseille - Institut Hospitalier Universitaire Méditerranée Infection
18 APHM - Assistance Publique - Hôpitaux de Marseille
19 CEReSS - Centre d'études et de recherche sur les services de santé et la qualité de vie
20 PARCC (UMR_S 970/ U970) - Paris-Centre de Recherche Cardiovasculaire
21 (EA_3518) - Recherche clinique appliquée à l'hématologie
22 Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière]
23 OPTeN (UMR_S 1144 / U1144) - Optimisation thérapeutique en Neuropsychopharmacologie
24 INEM - UM 111 (UMR 8253 / U1151) - Institut Necker Enfants-Malades
25 CIC-EC 1408 - Centre d'Investigation Clinique - Epidémiologie Clinique [CHU Saint-Etienne]
26 RNMCD - Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U 1011
27 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
28 Immunologie Translationnelle - Translational Immunology lab
29 Génétique Evolutive Humaine - Human Evolutionary Genetics
30 Collège de France - Chaire Génomique humaine et évolution
31 CHU Trousseau [Tours]
32 MAVIVHe - Morphogénèse et antigénicité du VIH, des Virus des Hépatites et Emergents
33 Hôpital Robert Ballanger [Aulnay-sous-Bois]
34 Hôpital Edouard Herriot [CHU - HCL]
35 PI3 - Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression
36 CIMI - Centre d'Immunologie et des Maladies Infectieuses
37 Hôpital Jean Verdier [AP-HP]
38 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers
39 BPH - Bordeaux population health
40 UVE - Unité des Virus Emergents
41 CIC 1425 - Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique
42 IAME (UMR_S_1137 / U1137) - Infection, Anti-microbiens, Modélisation, Evolution
43 CONSTANCES - Cohortes épidémiologiques en population
44 CREATIS - Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé
45 MYRIAD - Modeling & analysis for medical imaging and Diagnosis
46 LCBPT - UMR 8601 - Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques
47 IP - Institut Pasteur [Paris]
48 AGIR - Agents infectieux, résistance et chimiothérapie - UR UPJV 4294
49 CHU Amiens-Picardie
50 French COVID cohort study group
Eleftherios Michailidis
Hans-Heinrich Hoffmann
Shohei Eto
Marina Garcia-Prat
Lucy Bizien
Alba Parra-Martinez
  • Function : Author
Rui Yang
Liis Haljasmagi
  • Function : Author
Melanie Migaud
  • Function : Author
Karita Sarekannu
  • Function : Author
Julia Maslovskaja
Yacine Tandjaoui-Lambiotte
Jesus Troya
Jacques G. Riviere
  • Function : Author
Lindsey B. Rosen
  • Function : Author
Elana Shaw
Tomohiro Morio
Junko Tanaka
  • Function : Author
David Dalmau
Vasiliki Triantafyllia
James R. Heath
  • Function : Author
Jose Luis Franco
Juan-Manuel Anaya
Jordi Sole-Violan
  • Function : Author
Luisa Imberti
Andrea Biondi
  • Function : Author
Paolo Bonfanti
Riccardo Castagnoli
Ottavia M. Delmonte
  • Function : Author
Yu Zhang
  • Function : Author
Andrew L. Snow
  • Function : Author
Steven M. Holland
  • Function : Author
Catherine Biggs
Marcela Moncada-Velez
Andres Augusto Arias
Dany Anglicheau
Anna M. Planas
  • Function : Author
Filomeen Haerynck
Sotirija Duvlis
Robert L. Nussbaum
  • Function : Author
Tayfun Ozcelik
Seygi Keles
  • Function : Author
Ahmed A. Bousfiha
  • Function : Author
Jalila El Bakkouri
Carolina Ramirez-Santana
Qiang Pan-Hammarstrom
Lennart Hammarstrom
  • Function : Author
Alina Kurolap
Christine N. Metz
  • Function : Author
Alessandro Aiuti
Giorgio Casari
Vito Lampasona
Fabio Ciceri
Lucile A. Barreiros
  • Function : Author
Elena Dominguez-Garrido
Mateus Vidigal
Mayana Zatz
Diederik van de Beek
Sabina Sahanic
  • Function : Author
Ivan Tancevski
  • Function : Author
Yurii Stepanovskyy
Oksana Boyarchuk
Yoko Nukui
Miyuki Tsumura
  • Function : Author
Loreto Vidaur
Stuart G. Tangye
  • Function : Author
Adam Klocperk
Nelli Y. Kann
  • Function : Author
Anna Shcherbina
Yu-Lung Lau
Daniel Leung
Matthieu Coulongeat
Rutger Koning
Luis Felipe Reyes
Michel C. Nussenzweig
  • Function : Author
Romain Arrestier
  • Function : Author
Idris Boudhabhay
  • Function : Author
Hagit Baris-Feldman
David Hagin
Joost Wauters
Isabelle Meyts
Adam H. Dyer
  • Function : Author
Sean P. Kennelly
  • Function : Author
Nollaig M. Bourke
  • Function : Author
Rabih Halwani
Narjes Saheb Sharif-Askari
Jerome Sallette
  • Function : Author
Souad Mehlal Sedkaoui
  • Function : Author
Suzan Alkhater
Raul Rigo-Bonnin
  • Function : Author
Francisco Morandeira
  • Function : Author
Lucie Roussel
Donald C. Vinh
  • Function : Author
Sisse Rye Ostrowski
Antonio Condino-Neto
Carolina Prando
Anastasiia Bonradenko
  • Function : Author
Andras N. Spaan
  • Function : Author
Jacques Fellay
Kaya Bilguvar
Richard P. Lifton
  • Function : Author
Shrikant Mane
Hgid Lab
  • Function : Author
Covid Clinicians
  • Function : Author
Covid-Storm Clinicians
  • Function : Author
Nh-Covair Study Group
  • Function : Author
Chge Danish
  • Function : Author
Study Danish Blood Donor
  • Function : Author
Hospital St. James'S
  • Function : Author
Sars Cov2 Interest Group
  • Function : Author
Covid-Group Imagine
  • Function : Author
Consortium Milieu Interieur
  • Function : Author
V. Contact Cohort Co
  • Function : Author
U. M. C. Covid Amsterdam
  • Function : Author
Investigators Biobank
  • Function : Author
Covid Human Genetic Effort
  • Function : Author
Constances Cohort
  • Function : Author
C. Dijon Study
  • Function : Author
Health-Care Cerba
  • Function : Author
Mark S. Anderson
  • Function : Author
Bertrand Boisson
Vivien Beziat
  • Function : Author
Shen-Ying Zhang
Evangelos Vandreakos
  • Function : Author
Olivier Hermine
Aurora Pujol
Part Peterson
  • Function : Author
Trine H. Mogensen
  • Function : Author
Lee Rowen
  • Function : Author
James Mond
  • Function : Author
Stephanie Debette
Marie Zins
Pere Soler-Palacin
Roger Colobran
Guy Gorochov
Xavier Solanich
Javier Martinez-Picado
Marc Vasse
  • Function : Author
Peter K. Gregersen
  • Function : Author
Lorenzo Piemonti
Carlos Rodriguez-Gallego
Luigi D. Notarangelo
  • Function : Author
Helen C. Su
  • Function : Author
Kai Kisand
Satoshi Okada
Anne Puel
Emmanuelle Jouanguy
Charles M. Rice
  • Function : Author
Pierre Tiberghien
Qian Zhang
Aurelie Cobat
  • Function : Author
Laurent Abel
Jean-Laurent Casanova
Sylvie van Der Werf

Abstract

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients > 80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1,124 deceased patients (aged 20 days-99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of subjects carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals <70 years, 2.3% between 70 and 80 years, and 6.3% >80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over-80s, and total fatal COVID-19 cases.
Fichier principal
Vignette du fichier
BPH_SI_2021_Bastard.pdf (4.36 Mo) Télécharger le fichier
Origin Files produced by the author(s)

Dates and versions

hal-03358792 , version 1 (29-09-2021)

Licence

Identifiers

Cite

Paul Bastard, Adrian Gervais, Tom Le Voyer, Jeremie Rosain, Quentin Philippot, et al.. Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths. Science Immunology, 2021, 6 (62), pp.eabl4340. ⟨10.1126/sciimmunol.abl4340⟩. ⟨hal-03358792⟩
342 View
165 Download

Altmetric

Share

Gmail Mastodon Facebook X LinkedIn More