Human genetic and immunological determinants of critical COVID-19 pneumonia

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/00216208:11130/22:10440028

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Human genetic and immunological determinants of critical COVID-19 pneumonia

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Human genetic and immunological determinants of critical COVID-19 pneumonia

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30101 - Human genetics

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Nature

ISSN

0028-0836

e-ISSN

—

Svazek periodika

603

Číslo periodika v rámci svazku

7902

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

12

Strana od-do

587-598

Kód UT WoS článku

000769826700001

EID výsledku v databázi Scopus

2-s2.0-85124267100