Human genetic and immunological determinants of critical COVID-19 pneumonia

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Zhang Q., Bastard P., Cobat A., Casanova J.

NATURE, cilt.603, sa.7902, ss.587-598, 2022 (SCI-Expanded, Scopus) identifier identifier identifier

  • Yayın Türü: Makale / Derleme
  • Cilt numarası: 603 Sayı: 7902
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1038/s41586-022-04447-0
  • Dergi Adı: NATURE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, International Bibliography of Social Sciences, Aerospace Database, Agricultural & Environmental Science Database, Animal Behavior Abstracts, Applied Science & Technology Source, Aqualine, Aquatic Science & Fisheries Abstracts (ASFA), Art Source, Artic & Antarctic Regions, BIOSIS, CAB Abstracts, Chemical Abstracts Core, Communication Abstracts, EBSCO Education Source, EMBASE, Environment Index, Food Science & Technology Abstracts, Gender Studies Database, Geobase, INSPEC, MEDLINE, Metadex, MLA - Modern Language Association Database, Pollution Abstracts, Psycinfo, Public Affairs Index, Veterinary Science Database, zbMATH, DIALNET, Civil Engineering Abstracts
  • Sayfa Sayıları: ss.587-598
  • Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
  • Ondokuz Mayıs Üniversitesi Adresli: Hayır

Özet

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 IFN alpha, IFN beta and/or IFN omega, 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.