Human genetic and immunological determinants of critical COVID-19 pneumonia

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F22%3A10440028" target="_blank" >RIV/00064203:_____/22:10440028 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11130/22:10440028
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=YbrslJh6.s" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=YbrslJh6.s</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41586-022-04447-0" target="_blank" >10.1038/s41586-022-04447-0</a>

Result language
angličtina
Original language name
Human genetic and immunological determinants of critical COVID-19 pneumonia
Original language description
SARS-CoV-2 infection is benign in most individuals but, in ~10% of cases, it triggers hypoxemic COVID-19 pneumonia, which becomes critical in ~3% of cases. The ensuing risk of death (~1%) doubles every five years from childhood onward and is ~1.5 times greater in men than in women. What are the molecular and cellular determinants of critical COVID-19 pneumonia? Inborn errors of type I IFNs, including autosomal TLR3 and X-linked TLR7 deficiencies, are found in ~1-5% of patients with critical pneumonia under 60 years old, and a lower proportion in older patients. Pre-existing autoantibodies neutralizing IFN-α, -β, and/or -ω, which are more common in men than in women, are found in ~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 apparently 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 defense 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.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30101 - Human genetics

Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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