Human genetic and immunological determinants of critical COVID-19 pneumonia.
Nature
; 603(7902): 587-598, 2022 03.
Artículo
en Inglés
| MEDLINE | ID: covidwho-1655590
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, IFNß 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.
Texto completo:
Disponible
Colección:
Bases de datos internacionales
Base de datos:
MEDLINE
Asunto principal:
Interferón Tipo I
/
COVID-19
Tipo de estudio:
Estudio pronóstico
Límite:
Humanos
Idioma:
Inglés
Revista:
Nature
Año:
2022
Tipo del documento:
Artículo
País de afiliación:
S41586-022-04447-0
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