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Human Genetic and Immunological Determinants of Critical Covid-19 Pneumonia Publisher Pubmed



Zhang Q1, 2, 3, 16, 19, 25, 36, 127 ; Bastard P1, 2, 3, 4, 16, 19, 25, 36, 127 ; Karbuz A6 ; Gervais A7, 8, 26, 27, 38 ; Tayoun AA9 ; Aiuti A10 ; Belot A11 ; Bolze A12 ; Gaudet A13, 14 ; Bondarenko A15 ; Liu Z1, 16, 19, 25, 36, 127 ; Spaan AN1, 16, 17, 19, 25, 36, 127 ; Guennoun A18 ; Arias AA1, 16, 19, 20, 21, 25, 36, 93, 127 Show All Authors
Authors
  1. Zhang Q1, 2, 3, 16, 19, 25, 36, 127
  2. Bastard P1, 2, 3, 4, 16, 19, 25, 36, 127
  3. Karbuz A6
  4. Gervais A7, 8, 26, 27, 38
  5. Tayoun AA9
  6. Aiuti A10
  7. Belot A11
  8. Bolze A12
  9. Gaudet A13, 14
  10. Bondarenko A15
  11. Liu Z1, 16, 19, 25, 36, 127
  12. Spaan AN1, 16, 17, 19, 25, 36, 127
  13. Guennoun A18
  14. Arias AA1, 16, 19, 20, 21, 25, 36, 93, 127
  15. Planas AM22
  16. Sediva A23
  17. Shcherbina A24
  18. Neehus AL7, 8, 26, 27, 38
  19. Puel A1, 7, 8, 16, 19, 25, 26, 27, 36, 38, 127
  20. Froidure A28, 29
  21. Novelli A30
  22. Parlakay AO31
  23. Pujol A32, 33, 34
  24. Yahsi A35
  25. Gulhan B35
  26. Bigio B1, 16, 19, 25, 36, 127
  27. Boisson B1, 7, 8, 16, 19, 25, 26, 27, 36, 38, 127
  28. Drolet BA37
  29. Franco CAA7, 26, 38, 39
  30. Flores C40, 41, 42
  31. Rodriguezgallego C43, 44
  32. Prando C45
  33. Biggs CM46
  34. Luyt CE47
  35. Dalgard CL48
  36. Ofarrelly C49
  37. Matuozzo D7, 8, 26, 27, 38
  38. Dalmau D50, 51, 52
  39. Perlin DS53
  40. Mansouri D54
  41. Van De Beek D55
  42. Vinh DC56, 57
  43. Dominguezgarrido E58
  44. Hsieh EWY59
  45. Erdeniz EH60
  46. Jouanguy E1, 7, 8, 16, 19, 25, 26, 27, 36, 38, 127
  47. Sevketoglu E61
  48. Talouarn E7, 8, 26, 27, 38
  49. Quirosroldan E62
  50. Andreakos E63
  51. Husebye E64
  52. Alsohime F65
  53. Haerynck F66
  54. Casari G67
  55. Novelli G68
  56. Aytekin G69
  57. Morelle G70
  58. Alkan G71
  59. Bayhan GI31
  60. Feldman HB72
  61. Su HC73
  62. Von Bernuth H74, 75, 76
  63. Resnick I77
  64. Bustos I78
  65. Meyts I79, 80, 81
  66. Migeotte I82
  67. Tancevski I83
  68. Bustamante J1, 7, 8, 16, 19, 25, 26, 27, 36, 38, 127
  69. Fellay J84, 85
  70. El Baghdadi J86
  71. Martinezpicado J87
  72. Casanova JL1, 2, 3, 4, 5, 16, 19, 25, 36, 88, 89, 127
  73. Rosain J7, 8, 26, 27, 38
  74. Manry J7, 8, 26, 27, 38
  75. Chen J1, 16, 19, 25, 36, 127
  76. Christodoulou J90
  77. Bohlen J7, 8, 26, 27, 38
  78. Franco JL91
  79. Li J1, 16, 19, 25, 36, 127
  80. Anaya JM92
  81. Rojas J20, 93
  82. Ye J94
  83. Uddin KMF95
  84. Yasar KK96
  85. Kisand K97
  86. Okamoto K98
  87. Chaibi K99
  88. Mironska K100
  89. Marodi L101
  90. Abel L7, 8, 26, 27, 38
  91. Renia L102, 103
  92. Lorenzo L7, 8, 26, 27, 38
  93. Hammarstrom L104
  94. Ng LFP102, 103
  95. Quintanamurci L105, 106
  96. Erazo LV7, 26, 38, 39
  97. Notarangelo LD73
  98. Reyes LF107
  99. Allende LM108
  100. Imberti L109
  101. Renkilaraj MRLM7, 8, 26, 27, 38
  102. Moncadavelez M1, 16, 19, 25, 36, 127
  103. Materna M7, 8, 26, 27, 38
  104. Anderson MS110
  105. Gut M111
  106. Chbihi M7, 8, 26, 27, 38
  107. Ogishi M1, 16, 19, 25, 36, 127
  108. Emiroglu M73
  109. Seppanen MRJ112, 113
  110. Uddin MJ114, 115
  111. Shahrooei M116, 117
  112. Alexander N1, 16, 19, 25, 36, 127
  113. Hatipoglu N118
  114. Marr N1, 16, 19, 25, 36, 127
  115. Akcay N61
  116. Boyarchuk O119
  117. Slaby O120
  118. Akcan OM121
  119. Zhang P1, 16, 19, 25, 36, 127
  120. Solerpalacin P122
  121. Gregersen PK123
  122. Brodin P124
  123. Garcon P125
  124. Morange PE126
  125. Panhammarstrom Q104
  126. Zhou Q1, 16, 19, 25, 36, 127, 128
  127. Philippot Q7, 8, 26, 27, 38
  128. Halwani R129
  129. De Diego RP130
  130. Levy R7, 8, 26, 27, 38
  131. Yang R1, 16, 19, 25, 36, 127
  132. Oz SKT71
  133. Muhsen SA65
  134. Kanikyuksek S35
  135. Espinosapadilla S131
  136. Ramaswamy S9
  137. Okada S132
  138. Bozdemir SE133
  139. Aytekin SE121
  140. Karabela SN96
  141. Keles S134
  142. Senoglu S96
  143. Zhang SY1, 7, 8, 16, 19, 25, 26, 27, 36, 38, 127
  144. Duvlis S135
  145. Constantinescu SN136
  146. Boissondupuis S1, 7, 8, 16, 19, 25, 26, 27, 36, 38, 127
  147. Turvey SE137
  148. Tangye SG138, 139
  149. Asano T1, 16, 19, 25, 36, 127
  150. Ozcelik T140
  151. Le Voyer T7, 8, 26, 27, 38
  152. Maniatis T94
  153. Morio T141
  154. Mogensen TH142
  155. Sanchoshimizu V143, 144
  156. Beziat V1, 7, 8, 16, 19, 25, 26, 27, 36, 38, 127
  157. Solanich X145
  158. Bryceson Y146
  159. Lau YL147
  160. Itan Y148, 149
  161. Cobat A1, 2, 3, 16, 19, 25, 36, 127
Show Affiliations
Authors Affiliations
  1. 1. St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, United States
  2. 2. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, U1163, Necker Hospital for Sick Children, Paris, France
  3. 3. University of Paris, Imagine Institute, Paris, France
  4. 4. Department of Pediatrics, Necker Hospital for Sick Children, Paris, France
  5. 5. Howard Hughes Medical Institute, Paris, France
  6. 6. Cemil Tascioglu City Hospital, Istanbul, Turkey
  7. 7. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
  8. 8. Imagine Institute, University of Paris, Paris, France
  9. 9. Al Jalila Children’s Hospital, Dubai, United Arab Emirates
  10. 10. San Raffaele Telethon Institute for Gene Therapy, IRCCS Ospedale San Raffaele, and Vita Salute San Raffaele University, Milan, Italy
  11. 11. Hospices Civils de Lyon, Lyon, France
  12. 12. Helix, San Mateo, CA, United States
  13. 13. Department of Intensive Care Medicine, Critical Care Center, CHU Lille, Lille, France
  14. 14. Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR9017-CIIL-Centre d’Infection et d’Immunite deLille, Lille, France
  15. 15. Shupyk National Medical Academy for Postgraduate Education, Kiev, Ukraine
  16. 16. St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, United States
  17. 17. Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, Netherlands
  18. 18. Sidra Medicine, Doha, Qatar
  19. 19. St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, United States
  20. 20. Primary Immunodeficiencies Group, Department of Microbiology and Parasitology, School of Medicine, University of Antioquia, Medellin, Colombia
  21. 21. School of Microbiology, University of Antioquia, Medellin, Colombia
  22. 22. IIBB-CSIC, IDIBAPS, Barcelona, Spain
  23. 23. Department of Immunology, Second Faculty of Medicine Charles University, University Hospital in Motol, Prague, Czech Republic
  24. 24. Department of Immunology, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation
  25. 25. St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, United States
  26. 26. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
  27. 27. Imagine Institute, University of Paris, Paris, France
  28. 28. Pulmonology Department, Cliniques Universitaires Saint-Luc, Brussels, Belgium
  29. 29. Institut de Recherche Experimentale et Clinique (IREC), Universite Catholique de Louvain, Brussels, Belgium
  30. 30. Laboratory of Medical Genetics, IRCCS Bambino Gesu Children’s Hospital, Rome, Italy
  31. 31. Ankara City Hospital, Yildirim Beyazit University, Ankara, Turkey
  32. 32. Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
  33. 33. Catalan Institution of Research and Advanced Studies, ICREA, Barcelona, Spain
  34. 34. Center for Biomedical Research on Rare Diseases (CIBERER), ISCIII, Barcelona, Spain
  35. 35. Ankara City Hospital, Ankara, Turkey
  36. 36. St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, United States
  37. 37. School of Medicine and Public Health, University of Wisconsin, Madison, WI, United States
  38. 38. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
  39. 39. Grupo de Inmunodeficiencias Primarias, Departamento de Microbiologia y Parasitologia, Facultad de Medicina, Universidad de Antioquia UDEA, Medellin, Colombia
  40. 40. Research Unit, Hospital Universitario Nuestra Senora de Candelaria, Santa Cruz de Tenerife, Spain
  41. 41. CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain
  42. 42. Genomics Division, Instituto Tecnologico y de Energias. Renovables (ITER), Santa Cruz de Tenerife, Spain
  43. 43. Department of Immunology, University Hospital of Gran Canaria Dr Negrin, Canarian Health System, Las Palmas de Gran Canaria, Spain
  44. 44. Department of Clinical Sciences, University Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain
  45. 45. Faculdades Pequeno Principe, Instituto de Pesquisa Pele Pequeno Principe, Curitiba, Brazil
  46. 46. Department of Pediatrics, BC Children’s and St. Paul’s Hospitals, University of British Columbia, Vancouver, BC, Canada
  47. 47. Groupe Hospitalier Pitie-Salpetriere, Paris, France
  48. 48. Department of Anatomy, Physiology & Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, United States
  49. 49. Comparative Immunology Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland
  50. 50. Hospital Universitari Mutua Terrassa, Terrasa, Spain
  51. 51. Fundacio Docencia i Recerca Mutua Terrassa, Terrasa, Spain
  52. 52. Universitat de Barcelona, Barcelona, Spain
  53. 53. Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, United States
  54. 54. Department of Clinical Immunology and Infectious Diseases, National Research Institute of Tuberculosis and Lung Diseases, The Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Masih Daneshvari Hospital, Shahid Beheshti, University of Medical Sciences, Tehran, Iran
  55. 55. Department of Neurology, Amsterdam Neuroscience, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands
  56. 56. Department of Medicine, Division of Infectious Diseases, McGill University Health Centre, Montreal, QC, Canada
  57. 57. Infectious Disease Susceptibility Program, Research Institute, McGill University Health Centre, Montreal, Quebec, Canada
  58. 58. Fundacion Rioja Salud, Logrono, Spain
  59. 59. Departments of Pediatrics, Immunology and Microbiology, University of Colorado, School of Medicine, Aurora, CO, United States
  60. 60. Ondokuz Mayis University, Samsun, Turkey
  61. 61. Pediatric Intensive Care Unit, University of Health Sciences, Bakirkoy Dr Sadi Konuk Research and Training Hospital, Istanbul, Turkey
  62. 62. Universita degli Studi di Brescia, Brescia, Italy
  63. 63. Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece
  64. 64. Department of Medicine, Haukeland University Hospital, Bergen, Norway
  65. 65. Immunology research lab, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia
  66. 66. Department of Paediatric Immunology and Pulmonology, Centre for Primary Immunodeficiency Ghent (CPIG), PID Research Laboratory, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Ghent, Belgium
  67. 67. Clinical Genomics, IRCCS San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy
  68. 68. Department of Biomedicine and Prevention, Tor Vergata University of Rome, Rome, Italy
  69. 69. Konya City Hospital, Konya, Turkey
  70. 70. CHU Kremlin-Bicetre, Paris, France
  71. 71. Department of Pediatrics, Division of Pediatric Infectious Diseases, Faculty of Medicine, Selcuk University, Konya, Turkey
  72. 72. The Genetics Institute, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
  73. 73. National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
  74. 74. Department of Pediatric Pneumology, Immunology and Intensive Care, Charite Universitatsmedizin, Berlin University Hospital Center, Berlin, Germany
  75. 75. Department of Immunology, Labor Berlin, Berlin, Germany
  76. 76. Berlin Institutes of Health (BIH), Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Germany
  77. 77. University Hospital St Marina, Varna, Bulgaria
  78. 78. Universidad de La Sabana, Chia, Colombia
  79. 79. Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium
  80. 80. Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
  81. 81. Laboratory for Inborn Errors of Immunity, KU Leuven, Leuven, Belgium
  82. 82. Center of Human Genetics, Universite Libre de Bruxelles (ULB), Brussels, Belgium
  83. 83. Department of Internal Medicine II, Medical University of Innsbruck, Innsbruck, Austria
  84. 84. School of Life Sciences, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland
  85. 85. Precision Medicine Unit, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
  86. 86. Genetics Unit, Military Hospital Mohamed V, Rabat, Morocco
  87. 87. IrsiCaixa, IGTP, CIBERINFEC, UVic-UCC, ICREA, Barcelona, Spain
  88. 88. The Rockefeller University & Howard Hughes Medical Institute, New York, NY, United States
  89. 89. Necker Hospital for Sick Children & INSERM, Paris, France
  90. 90. Murdoch Children’s Research Institute and Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia
  91. 91. Group of Primary Immunodeficiencies, University of Antioquia, Medellin, Colombia
  92. 92. Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogota, Colombia
  93. 93. Primary Immunodeficiencies Group, Department of Microbiology and Parasitology, School of Medicine, University of Antioquia, Medellin, Colombia
  94. 94. Zukerman Mind Brain Behavior Institute, Columbia University, New York, NY, United States
  95. 95. Centre for Precision Therapeutics, Genetics & Genomic Medicine Centre, NeuroGen Children’s Healthcare, Holy Family Red Crescent Medical College, Dhaka, Bangladesh
  96. 96. Department of Infectious Diseases and Clinical Microbiology, Bakirkoy Dr Sadi Konuk Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
  97. 97. Molecular Pathology, Department of Biomedicine, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia
  98. 98. Tokyo Medical and Dental University, Tokyo, Japan
  99. 99. Centre Hospitalier Universitaire Avicenne, Bobigny, France
  100. 100. University Clinic for Children’s Diseases, Department of Pediatric Immunology, Medical Faculty, University St Cyril and Methodij, Skopje, North Macedonia
  101. 101. Primary Immunodeficiency Clinical Unit and Laboratory, Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, Budapest, Hungary
  102. 102. A*STAR Infectious Disease Labs, Agency for Science, Technology and Research, Singapore, Singapore
  103. 103. Lee Kong Chian School of Medicine, Nanyang Technology University, Singapore, Singapore
  104. 104. Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
  105. 105. Human Evolutionary Genetics Unit, CNRS U2000, Institut Pasteur, Paris, France
  106. 106. Human Genomics and Evolution, College de France, Paris, France
  107. 107. Universidad de La Sabana, Bogota, Colombia
  108. 108. Hospital Universitario 12 de Octubre, Madrid, Spain
  109. 109. ASST Spedali Civili di Brescia, Brescia, Italy
  110. 110. Diabetes Center, University of California San Francisco, San Francisco, CA, United States
  111. 111. Centre Nacional d’Analisi Genomica (CNAG-CRG), Barcelona, Spain
  112. 112. Adult Immunodeficiency Unit, Infectious Diseases, Inflammation Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
  113. 113. Rare Diseases Center and Pediatric Research Center, Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
  114. 114. College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
  115. 115. Cellular Intelligence (Ci) Lab, GenomeArc, Toronto, ON, Canada
  116. 116. Specialized Immunology Laboratory of Dr Shahrooei, Ahvaz, Iran
  117. 117. Department of Microbiology and Immunology, Clinical and Diagnostic Immunology, KU Leuven, Leuven, Belgium
  118. 118. Pediatric Infectious Diseases Unit, Bakirkoy Dr Sadi Konuk Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
  119. 119. I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine
  120. 120. Central European Institute of Technology & Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
  121. 121. Necmettin Erbakan University, Konya, Turkey
  122. 122. Pediatric Infectious Diseases and Immunodeficiencies Unit, Vall d’Hebron Barcelona Hospital, Catalonia, Barcelona, Spain
  123. 123. Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, United States
  124. 124. SciLifeLab, Department Of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden
  125. 125. GHEF Marne-la-Vallee, Jossigny, France
  126. 126. Assistance Publique des Hopitaux de Marseille, Marseille, France
  127. 127. St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, United States
  128. 128. Clinical Allergy and Immunology, Children’s Hospital of Fudan University, Shanghai, China
  129. 129. Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
  130. 130. Institute of Biomedical Research of IdiPAZ, University Hospital La Paz, Madrid, Spain
  131. 131. Instituto Nacional de Pediatria, Mexico City, Mexico
  132. 132. Department of Pediatrics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
  133. 133. Bursa City Hospital, Bursa, Turkey
  134. 134. Necmettin Erbakan University Meram Medical Faculty, Konya, Turkey
  135. 135. Faculty of Medical Sciences, University Goce Delcev, Stip, North Macedonia
  136. 136. de Duve Institute and Ludwig Cancer Research, Brussels, Belgium
  137. 137. BC Children’s Hospital, The University of British Columbia, Vancouver, BC, Canada
  138. 138. Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
  139. 139. St Vincent’s Clinical School, Faculty of Medicine, UNSW Sydney, Syndey, NSW, Australia
  140. 140. Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey
  141. 141. Tokyo Medical & Dental University Hospital, Tokyo, Japan
  142. 142. Department of Biomedicine, Aarhus University, Aarhus, Denmark
  143. 143. Department of Paediatric Infectious Diseases and Virology, Imperial College London, London, United Kingdom
  144. 144. Centre for Paediatrics and Child Health, Faculty of Medicine, Imperial College London, London, United Kingdom
  145. 145. Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain
  146. 146. Department of Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden
  147. 147. Department of Paediatrics & Adolescent Medicine, The University of Hong Kong, Hong Kong
  148. 148. Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
  149. 149. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States

Source: Nature Published:2022


Abstract

SARS-CoV-2 infection is benign in most individuals but, in around 10% of cases, it triggers hypoxaemic COVID-19 pneumonia, which leads to critical illness in around 3% of cases. The ensuing risk of death (approximately 1% across age and gender) doubles every five years from childhood onwards and is around 1.5 times greater in men than in women. Here we review the molecular and cellular determinants of critical COVID-19 pneumonia. Inborn errors of type I interferons (IFNs), including autosomal TLR3 and X-chromosome-linked TLR7 deficiencies, are found in around 1–5% of patients with critical pneumonia under 60 years old, and a lower proportion in older patients. Pre-existing auto-antibodies neutralizing IFNα, IFNβ and/or IFNω, which are more common in men than in women, are found in approximately 15–20% of patients with critical pneumonia over 70 years old, and a lower proportion in younger patients. Thus, at least 15% of cases of critical COVID-19 pneumonia can be explained. The TLR3- and TLR7-dependent production of type I IFNs by respiratory epithelial cells and plasmacytoid dendritic cells, respectively, is essential for host defence against SARS-CoV-2. In ways that can depend on age and sex, insufficient type I IFN immunity in the respiratory tract during the first few days of infection may account for the spread of the virus, leading to pulmonary and systemic inflammation. © 2022, Springer Nature Limited.
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