Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children
Author:
Bastard Paul1234ORCID, Gervais Adrian12ORCID, Taniguchi Maki5ORCID, Saare Liisa6ORCID, Särekannu Karita7ORCID, Le Voyer Tom12ORCID, Philippot Quentin12ORCID, Rosain Jérémie12ORCID, Bizien Lucy12ORCID, Asano Takaki5ORCID, Garcia-Prat Marina8ORCID, Parra-Martínez Alba8ORCID, Migaud Mélanie12ORCID, Tsumura Miyuki5ORCID, Conti Francesca910ORCID, Belot Alexandre11121314ORCID, Rivière Jacques G.8ORCID, Morio Tomohiro15ORCID, Tanaka Junko16ORCID, Javouhey Etienne17ORCID, Haerynck Filomeen18ORCID, Duvlis Sotirija1920ORCID, Ozcelik Tayfun21ORCID, Keles Sevgi22ORCID, Tandjaoui-Lambiotte Yacine232425ORCID, Escoda Simon26ORCID, Husain Maya26ORCID, Pan-Hammarström Qiang27ORCID, Hammarström Lennart27ORCID, Ahlijah Gloria1ORCID, Abi Haidar Anthony1ORCID, Soudee Camille1ORCID, Arseguel Vincent1, Abolhassani Hassan2728ORCID, Sahanic Sabina29ORCID, Tancevski Ivan29ORCID, Nukui Yoko30ORCID, Hayakawa Seiichi5ORCID, Chrousos George P.31ORCID, Michos Athanasios3132ORCID, Tatsi Elizabeth-Barbara3132ORCID, Filippatos Filippos3132ORCID, Rodriguez-Palmero Agusti333435ORCID, Troya Jesus36ORCID, Tipu Imran37ORCID, Meyts Isabelle3839ORCID, Roussel Lucie4041ORCID, Ostrowski Sisse Rye42ORCID, Schidlowski Laire43ORCID, Prando Carolina43ORCID, Condino-Neto Antonio44ORCID, Cheikh Nathalie45ORCID, Bousfiha Ahmed A.46ORCID, El Bakkouri Jalila47ORCID, Aguilera-Albesa Sergio, AlKhater Suzan A., Alkan Gulsum, Castagnoli Riccardo, Cyrus Cyril, Elmas Bozdemir Sefika, Emiroglu Melike, Gulhan Belgin, Erdeniz Emine Hafize, Hatipoglu Nevin, Bayhan Gülsün Iclal, Jabandziev Petr, Kanik Yuksek Saliha, Karbuz Adem, Tüter Öz Şadiye Kübra, Marseglia Gian Luigi, Metin Akcan Ozge, Kılıç Ahmet Osman, Ozkaya Parlakay Aslinur, Papadaki Maria, Slaba Katerina, Sevketoglu Esra, Valencia-Ramos Juan, Yahşi Aysun, Aguilera Guirao Antonio, Álvarez Escudero Julián, Antela López Antonio, Barbeito Castiñeiras Gema, Bello Paderne Xabier, Ben García Miriam, Carral García María Victoria, Cebey López Miriam, Coira Nieto Amparo, Conde Pájaro Mónica, Costa Alcalde José Javier, Currás Tuala María José, Dacosta Urbieta Ana Isabel, Díaz Esteban Blanca, Domínguez Santalla María Jesús, Fernández Pérez Cristina, Fernández Villaverde Juan, Galbán Rodríguez Cristóbal, García Allut José Luis, García Vicente Luisa, Giráldez Vázquez Elena, Gómez Carballa Alberto, Gómez Rial José, González Barcala Francisco Javier, Guerra Liñares Beatriz, Leboráns Iglesias Pilar, Lence Massa Beatriz, Lendoiro Fuentes Marta, López Franco Montserrat, López Lago Ana, Martinón-Torres Federico, Salas Antonio, Navarro De la Cruz Daniel, Núñez Masid Eloína, Ortolá Devesa Juan Bautista, Pardo Seco Jacobo, Pazo Núñez María, Pérez del Molino Bernal Marisa, Pérez Freixo Hugo, Piñeiro Rodríguez Lidia, Pischedda Sara, Portela Romero Manuel, Pose Reino Antonio, Prada Hervella Gloria María, Queiro Verdes Teresa, Redondo Collazo Lorenzo, Regueiro Casuso Patricia, Rey García Susana, Rey Vázquez Sara, Riveiro Blanco Vanessa, Rivero Calle Irene, Rivero Velasco Carmen, Rodríguez Núñez Nuria, Rodríguez-Tenreiro Sánchez Carmen, Saborido Paz Eva, Sadiki Orayyou José Miguel, Saito Villanueva Carla, Serén Fernández Sonia, Souto Sanmartín Pablo, Taboada Muñiz Manuel, Trastoy Pena Rocío, Treviño Castellano Mercedes, Valdés Cuadrado Luis, Varela García Pablo, Vilas Iglesias María Soledad, Viz Lasheras Sandra, Ferreiro-Iglesias Rocio, Bastón-Rey Iria, Calviño-Suárez Cristina, Abel Laurent, Aiuti Alessandro, Al-Muhsen Saleh, Al-Mulla Fahd, Amara Ali, Anderson Mark S., Andreakos Evangelos, Arias Andrés A., Arkin Lisa M., Baris Feldman Hagit, Bastard Paul, Belot Alexandre, Biggs Catherine M., Bogunovic Dusan, Bolze Alexandre, Bondarenko Anastasiia, Bousfiha Ahmed A., Brodin Petter, Bryceson Yenan, Butte Manish J., Casanova Jean-Laurent, Casari Giorgio, Christodoulou John, Cobat Aurélie, Colobran Roger, Condino-Neto Antonio, Constantinescu Stefan N., Cooper Megan A., Dalgard Clifton L., Desai Murkesh, Drolet Beth A., Duval Xavier, El Baghdadi Jamila, Eloy Philippine, Espinosa-Padilla Sara, Fellay Jacques, Flores Carlos, Franco José Luis, Froidure Antoine, Gorochov Guy, Gregersen Peter K., Grimbacher Bodo, Haerynck Filomeen, Hagin David, Halwani Rabih, Hammarström Lennart, Heath James R., Hsieh Elena W.Y., Husebye Eystein, Imai Kohsuke, Itan Yuval, Jarvis Erich D., Jouanguy Emmanuelle, Kaja Elżbieta, Karamitros Timokratis, Kisand Kai, Ku Cheng-Lung, Lau Yu-Lung, Ling Yun, Lucas Carrie L., Mansouri Davood, Maródi László, Mentré France, Meyts Isabelle, Milner Joshua D., Mironska Kristina, Mogensen Trine H., Morio Tomohiro, Ng Lisa F.P., Notarangelo Luigi D., Novelli Antonio, Novelli Giuseppe, O’Farrelly Cliona, Okada Satoshi, Okamoto Keisuke, Ozcelik Tayfun, Pan-Hammarström Qiang, Pape Jean W., Perez de Diego Rebeca, Perez-Tur Jordi, Perlin David S., Pesole Graziano, Planas Anna M., Prando Carolina, Pujol Aurora, Puel Anne, Quintana-Murci Lluis, Ramaswamy Sathishkumar, Renia Laurent, Resnick Igor, Rodríguez-Gallego Carlos, Sancho-Shimizu Vanessa, Sediva Anna, Seppänen Mikko R.J., Shahrooei Mohammed, Shcherbina Anna, Slaby Ondrej, Snow Andrew L., Soler-Palacín Pere, Soumelis Vassili, Spaan András N., Su Helen C., Tancevski Ivan, Tangye Stuart G., Abou Tayoun Ahmad, Temel Şehime Gülsün, Thorball Christian, Tiberghien Pierre, Trouillet-Assant Sophie, Turvey Stuart E., Furkan Uddin K.M., Uddin Mohammed J., van de Beek Diederik, Vinh Donald C., von Bernuth Horst, Wauters Joost, Zatz Mayana, Zawadzki Pawel, Zhang Qian, Zhang Shen-Ying, Peterson Pärt7ORCID, Pujol Aurora48ORCID, Lévy Romain124ORCID, Quartier Pierre24ORCID, Vinh Donald C.4041ORCID, Boisson Bertrand123ORCID, Béziat Vivien123ORCID, Zhang Shen-Ying123ORCID, Borghesi Alessandro49ORCID, Pession Andrea9ORCID, Andreakos Evangelos50ORCID, Marr Nico51ORCID, Mentis Alexios-Fotios A.31ORCID, Mogensen Trine H.5253ORCID, Rodríguez-Gallego Carlos545556ORCID, Soler-Palacin Pere8ORCID, Colobran Roger57ORCID, Tillmann Vallo6ORCID, Neven Bénédicte24ORCID, Trouillet-Assant Sophie13145859ORCID, Brodin Petter6061ORCID, Abel Laurent123ORCID, Jouanguy Emmanuelle123ORCID, Zhang Qian123ORCID, Martinón-Torres Federico626364ORCID, Salas Antonio6465ORCID, Gómez-Carballa Alberto636465ORCID, Gonzalez-Granado Luis I.66ORCID, Kisand Kai7ORCID, Okada Satoshi5ORCID, Puel Anne123ORCID, Cobat Aurélie123ORCID, Casanova Jean-Laurent1236768ORCID, , ,
Affiliation:
1. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children 1 , Paris, France 2. University Paris Cité, Imagine Institute 2 , Paris, France 3. St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University 3 , New York, NY, USA 4. Pediatric Hematology-Immunology and Rheumatology Unit, Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris (AP-HP) 4 , Paris, France 5. Graduate School of Biomedical and Health Sciences, Hiroshima University 5 Dept. of Pediatrics, , Hiroshima, Japan 6. Institute of Clinical Medicine, University of Tartu 6 Dept. of Pediatrics, , Tartu, Estonia 7. Institute of Biomedicine and Translational Medicine, University of Tartu 7 Molecular Pathology, , Tartu, Estonia 8. Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d’Hebron, Vall d’Hebron Research Institute, Vall d’Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona (UAB) 8 , Barcelona, Spain 9. Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna 9 , Bologna, Italy 10. University of Bologna 10 Dept. of Medical and Surgical Sciences, Alma Mater Studiorum, , Bologna, Italy 11. National Reference Center for Rheumatic, and Autoimmune and Systemic Diseases in Children 11 , Lyon, France 12. Immunopathology Federation LIFE, Hospices Civils de Lyon 12 , Lyon, France 13. Hospices Civils de Lyon 13 , Lyon, France 14. International Center of Research in Infectiology, Lyon University, International Center of Research in Infectiology, Lyon University, INSERM U1111, CNRS UMR 5308, ENS, UCBL 14 , Lyon, France 15. Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU) 15 Dept. of Pediatrics and Developmental Biology, , Tokyo, Japan 16. Graduate School of Biomedical and Health Sciences, Hiroshima University 16 Dept. of Epidemiology, Infectious Disease Control and Prevention, , Hiroshima, Japan 17. Pediatric Intensive Care Unit, Hospices Civils de Lyon, Hopital Femme Mère Enfant 17 , Lyon, France 18. Center for Primary Immunodeficiency Ghent, Jeffrey Modell Diagnosis and Research Center, Ghent University Hospital 18 Dept. of Paediatric Immunology and Pulmonology, , Ghent, Belgium 19. Faculty of Medical Sciences, University “Goce Delchev” 19 , Stip, Republic of Northern Macedonia 20. Institute of Public Health of the Republic of North Macedonia 20 , Skopje, North Macedonia 21. Bilkent University 21 Dept. of Molecular Biology and Genetics, , Ankara, Turkey 22. Meram Medical Faculty, Necmettin Erbakan University 22 , Konya, Turkey 23. 23Pulmonology and Infectious Disease Department, Saint Denis Hospital, Saint Denis, France 24. 24INSERM UMR 1137 IAME, Paris, France 25. 25INSERM UMR 1272 Hypoxia and Lung, Bobigny, France 26. Saint-Denis Hospital 26 Pediatric Dept., , Saint-Denis, France 27. Karolinska Institutet 27 Division of Immunology, Dept. of Medical Biochemistry and Biophysics, , Stockholm, Sweden 28. Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences 28 , Tehran, Iran 29. Medical University of Innsbruck 29 Dept. of Internal Medicine II, , Innsbruck, Austria 30. Medical Hospital, TMDU 30 Dept. of Infection Control and Prevention, , Tokyo, Japan 31. University Research Institute of Maternal and Child Health and Precision Medicine, National and Kapodistrian University of Athens 31 , Athens, Greece 32. National and Kapodistrian University of Athens 32 First Dept. of Pediatics, , Athens, Greece 33. Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat 33 , Barcelona, Spain 34. Dept. of Pediatrics, Germans Trias i Pujol University Hospital, UAB 34 , Barcelona, Spain 35. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) 35 , Madrid, Spain 36. Infanta Leonor University Hospital 36 Dept. of Internal Medicine, , Madrid, Spain 37. University of Management and Technology 37 , Lahore, Pakistan 38. Laboratory of Inborn Errors of Immunity, Microbiology and Transplantation, KU Leuven 38 Dept. of Immunology, , Leuven, Belgium 39. Jeffrey Modell Diagnostic and Research Network Center, University Hospitals Leuven 39 Dept. of Pediatrics, , Leuven, Belgium 40. McGill University Health Centre 40 Dept. of Medicine, Division of Infectious Diseases, , Montréal, Canada 41. Infectious Disease Susceptibility Program, Research Institute–McGill University Health Centre 41 , Montréal, Canada 42. Rigshospitalet, Copenhagen University Hospital 42 Dept. of Clinical Immunology, , Copenhagen, Denmark 43. Faculdades Pequeno Príncipe, Instituto de Pesquisa Pelé Pequeno Príncipe 43 , Curitiba, Brazil 44. Institute of Biomedical Sciences, University of São Paulo 44 Dept. of Immunology, , São Paulo, Brazil 45. Pediatric Hematology Unit, University Hospital of Besançon 45 , Besançon, France 46. Hassan II University 46 Dept. of Pediatric Infectious Disease and Clinical Immunology, CHU Ibn Rushd and LICIA, Laboratoire d’Immunologie Clinique, Inflammation et Allergie, Faculty of Medicine and Pharmacy, , Casablanca, Morocco 47. Laboratory of Immunology, CHU Ibn Rushd and LICIA, Laboratoire d’Immunologie Clinique, Inflammation et Allergie, Faculty of Medicine and Pharmacy, Hassan II University 47 , Casablanca, Morocco 48. Neurometabolic Diseases Laboratory, IDIBELL-Hospital Duran i Reynals, CIBERER U759, and Catalan Institution of Research and Advanced Studies 48 , Barcelona, Spain 49. Neonatal Intensive Care Unit, Fondazione IRCCS Policlinico San Matteo 49 , Pavia, Italy 50. Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens 50 , Athens, Greece 51. Research Branch, Sidra Medicine 51 , Doha, Qatar 52. Aarhus University Hospital 52 Dept. of Infectious Diseases, , Skejby, Denmark 53. Aarhus University 53 Dept. of Biomedicine, , Aarhus, Denmark 54. Hospital Universitario de Gran Canaria Dr Negrín, Canarian Health System 54 , Las Palmas, Spain 55. University Fernando Pessoa Canarias 55 Dept. of Clinical Sciences, , Las Palmas de Gran Canaria, Spain 56. School of Medicine, University of Las Palmas de Gran Canaria 56 Dept. of Medical and Surgical Sciences, , Las Palmas de Gran Canaria, Spain 57. Hospital Universitari Vall d’Hebron, Vall d’Hebron Research Institute, Vall d’Hebron Barcelona Hospital Campus, UAB 57 Immunology Division, Genetics Dept., , Barcelona, Spain 58. Joint Research Unit, Hospices Civils de Lyon-bio Mérieux, Hospices Civils de Lyon, Lyon Sud Hospital 58 , Pierre-Bénite, France 59. International Center of Research in Infectiology, Lyon University, INSERM U1111, CNRS UMR 5308, ENS, UCBL 59 , Lyon, France 60. Karolinska Institutet 60 Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, , Solna, Sweden 61. 61Department of Immunology and Inflammation, Imperial College London, London, UK 62. Hospital Clínico Universitario de Santiago, Servizo Galego de Saude (SERGAS) 62 Translational Pediatrics and Infectious Diseases, Pediatrics Dept., , Santiago de Compostela, Spain 63. GENVIP Research Group, Instituto de Investigación Sanitaria de Santiago (IDIS), Universidad de Santiago de Compostela 63 , Galicia, Spain 64. Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Instituto de Salud Carlos III 64 , Madrid, Spain 65. Facultade de Medicina, Unidade de Xenética, Instituto de Ciencias Forenses, Universidade de Santiago de Compostela, and GenPoB Research Group, IDIS, SERGAS 65 , Galicia, Spain 66. Immunodeficiencies Unit, Hospital 12 de octubre, Research Institute Hospital 12 octubre 66 , Madrid, Spain 67. Howard Hughes Medical Institute 67 , New York, NY, USA 68. Necker Hospital for Sick Children, AP-HP 68 Dept. of Pediatrics, , Paris, France
Abstract
We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-α2 in 10 patients: IFN-α2 only in three, IFN-α2 plus IFN-ω in five, and IFN-α2, IFN-ω plus IFN-β in two; IFN-ω only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-α2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-ω in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-α2 only (OR [95% CI] = 67.6 [5.7–9,196.6]) than for auto-Abs neutralizing IFN-ω only (OR [95% CI] = 2.6 [1.2–5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6–35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1–9.6]) of IFN-ω and/or IFN-α2.
Publisher
Rockefeller University Press
Subject
Immunology,Immunology and Allergy
Cited by
1 articles.
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