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Record W3195130348 · doi:10.1126/sciimmunol.abl4340

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

2021· article· en· W3195130348 on OpenAlexafffund
Paul Bastard, Adrian Gervais, Jérémie Rosain, Quentin Philippot, Jérémy Manry, Eleftherios Michailidis, Hans-Heinrich Hoffmann, Shohei Eto, Marina García-Prat, Lucy Bizien, Alba Parra-Martínez, Rui Yang, Liis Haljasmägi, Mélanie Migaud, Karita Särekannu, Julia Maslovskaja, Nicolas de Prost, Yacine Tandjaoui-Lambiotte, Charles‐Édouard Luyt, Blanca Amador-Borrero, Alexandre Gaudet, Julien Poissy, Pascal Morel, Pascale Richard, Fabrice Cognasse, Jesús Troya, Sophie Trouillet‐Assant, Alexandre Bélot, Kahina Saker, Pierre Garçon, Jacques G. Rivière, Jean‐Christophe Lagier, Stéphanie Gentile, Lindsey B. Rosen, Elana Shaw, Tomohiro Morio, Junko Tanaka, David Dalmau, Pierre‐Louis Tharaux, D. Sène, Alain Stépanian, Bruno Mégarbane, Vasiliki Triantafyllia, Arnaud Fekkar, James R. Heath, José Luis Franco, Juan‐Manuel Anaya, Jordi Solé‐Violán, Luisa Imberti, Andrea Biondi, Paolo Bonfanti, Riccardo Castagnoli, Ottavia M. Delmonte, Yu Zhang, Andrew L. Snow, Steven M. Holland, Catherine M. Biggs, Marcela Moncada‐Vélez, Andrés A. Arias, Lazaro Lorenzo, Soraya Boucherit, Boubacar Coulibaly, Dany Anglicheau, Anna M. Planas, Filomeen Haerynck, Sotiriјa Duvlis, Robert L. Nussbaum, Tayfun Özçelık, Sevgi Keleş, Ahmed Aziz Bousfiha, Jalila El Bakkouri, Carolina Ramı́rez-Santana, Stéphane Paul, Qiang Pan‐Hammarström, Lennart Hammarström, Annabelle Dupont, Alina Kurolap, Christine N. Metz, Alessandro Aiuti, Giorgio Casari, Vito Lampasona, Fabio Ciceri, Lucila Akune Barreiros, Elena Domínguez‐Garrido, Mateus Vidigal, Mayana Zatz, Diederik van de Beek, Sabina Sahanic, Ivan Tancevski, Yuriy Stepanovskyy, Oksana Boyarchuk, Yoko Nukui, Miyuki Tsumura, Loreto Vidaur, Stuart G. Tangye, Sonia Burrel, Darragh Duffy, Lluís Quintana‐Murci, Adam Klocperk, Nelli Y. Kann, Anna Shcherbina, YL Lau, Daniel Leung, Matthieu Coulongeat, Julien Marlet, Rutger Koning, Luis Felipe Reyes, Angélique Chauvineau‐Grenier, Fabienne Venet, Guillaume Monneret, Michel C. Nussenzweig, Romain Arrestier, Idris Boudhabhay, Hagit Baris Feldman, David Hagin, Joost Wauters, Isabelle Meyts, Adam H. Dyer, Seán Kennelly, Nollaig M. Bourke, Rabih Halwani, Narjes Saheb Sharif‐Askari, Karim Dorgham, Jérôme Sallette, Souad Mehlal Sedkaoui, Suzan A. AlKhater, Raül Rigo‐Bonnin, Francisco Morandeira, Lucie Roussel, Donald C. Vinh, Sisse Rye Ostrowski, Antônio Condino‐Neto, Carolina Prando, Анастасія Бондаренко, András N. Spaan, Laurent Gilardin, Jacques Fellay, Stanislas Lyonnet, Kaya Bilgüvar, Richard P. Lifton, Shrikant Mane, Mark S. Anderson, Bertrand Boisson, Vivien Béziat, Shen‐Ying Zhang, Evangelos Andreakos, Olivier Hermine, Aurora Pujol, Pärt Peterson, Trine H. Mogensen, Lee Rowen, James Mond, Stéphanie Debette, Xavier de Lamballerie, Xavier Duval, France Mentré, Marie Zins, Pere Soler‐Palacín, Roger Colobrán, Guy Gorochov, Xavier Solanich, Sophie Susen, Javier Martínez‐Picado, Didier Raoult, Marc Vasse, Peter K. Gregersen, Lorenzo Piemonti, Carlos Rodríguez‐Gallego, Luigi D. Notarangelo, Helen C. Su, Kai Kisand, Satoshi Okada, Anne Puel, Emmanuelle Jouanguy, Charles M. Rice, Pierre Tiberghien, Qian Zhang, Aurélie Cobat, Laurent Abel, Jean‐Laurent Casanova

Bibliographic record

VenueScience Immunology · 2021
Typearticle
Languageen
FieldMedicine
TopicSARS-CoV-2 and COVID-19 Research
Canadian institutionsMcGill University Health CentreBC Children's HospitalUniversity of British Columbia
FundersNIH Clinical CenterNational Institute of Dental and Craniofacial ResearchNational Institute of Allergy and Infectious DiseasesNational Cancer InstituteNational Human Genome Research InstituteAgencia Estatal de InvestigaciónEuropean Regional Development FundInstituto de Salud Carlos IIIBiomedical Advanced Research and Development AuthorityNational Institutes of HealthSorbonne UniversitéInstituto Colombiano de Crédito Educativo y Estudios Técnicos en el ExteriorIpsenHellenic Foundation for Research and InnovationVlaamse regeringRegione LombardiaAgentura Pro Zdravotnický Výzkum České RepublikyUniformed Services University of the Health SciencesMutuelle Générale de l'Education NationaleMedical Research CouncilTartu ÜlikoolUniversità degli Studi di BresciaKaradeniz Teknik ÜniversitesiUniversité de BordeauxUniversità degli Studi di PaviaHoward Hughes Medical InstituteMeath FoundationNHLBI Division of Intramural ResearchUniversity of Hong KongAl Jalila FoundationUniversitair Ziekenhuis GentUniversiteit GentShahid Beheshti University of Medical SciencesCSL BehringChang Gung UniversityFonds Wetenschappelijk OnderzoekUniversità degli Studi di Milano-BicoccaUniversity of New South WalesKU LeuvenFondation pour la Recherche MédicaleSemmelweis EgyetemEesti TeadusagentuurUniversidade de São PauloEuropean CommissionFundação de Amparo à Pesquisa do Estado de São PauloUniversity of SharjahJeffrey Modell FoundationNational Health and Medical Research CouncilFondation du SouffleFisher Center for Alzheimer's Research FoundationAssistance publique-Hôpitaux de ParisAgence Nationale de la RechercheInstitut des maladies génétiques ImagineFudan UniversityNovo Nordisk FondenCelldex TherapeuticsMinistero della SaluteInstitut National de la Santé et de la Recherche MédicaleDepartamento Administrativo de Ciencia, Tecnología e Innovación (COLCIENCIAS)Japan Agency for Medical Research and DevelopmentCroucher FoundationMichael Smith Health Research BCGeorgia Clinical and Translational Science AllianceYale UniversityNational Center for Advancing Translational SciencesMercatus Center, George Mason UniversityDa VolterraJPB FoundationUniversité de BourgogneChang Gung Medical FoundationFondation de FranceSanofiIrving Medical Center, Columbia UniversityFondazione IRCCS Policlinico San MatteoFondation Bettencourt SchuellerGeorge Mason UniversityMinisterio de Ciencia e InnovaciónSt. Giles Foundation
KeywordsAutoantibodyCoronavirus disease 2019 (COVID-19)Virology2019-20 coronavirus outbreakSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)ImmunologyCoronavirus InfectionsNeutralizing antibodyBiologyAntibodyMedicineDiseaseOutbreakInternal medicineInfectious disease (medical specialty)

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.014

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0040.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.057
GPT teacher head0.396
Teacher spread0.339 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations631
Published2021
Admission routes2
Has abstractyes

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