PMID- 33500568
OWN - NLM
STAT- MEDLINE
DCOM- 20210512
LR  - 20220531
IS  - 1530-0366 (Electronic)
IS  - 1098-3600 (Print)
IS  - 1098-3600 (Linking)
VI  - 23
IP  - 5
DP  - 2021 May
TI  - Deletion of the NKG2C receptor encoding KLRC2 gene and HLA-E variants are risk 
      factors for severe COVID-19.
PG  - 963-967
LID - 10.1038/s41436-020-01077-7 [doi]
AB  - PURPOSE: Host genetic variants may contribute to severity of COVID-19. NKG2C(+) 
      NK cells are potent antiviral effector cells, potentially limiting the extent of 
      SARS-CoV-2 infections. NKG2C is an activating NK cell receptor encoded by the 
      KLRC2 gene, which binds to HLA-E on infected cells leading to NK cell activation. 
      Heterozygous or homozygous KLRC2 deletion (KLRC2(del)) may naturally occur and is 
      associated with a significantly lower or absent NKG2C expression level. In 
      addition, HLA-E*0101/0103 genetic variants occur, caused by a single-nucleotide 
      polymorphism. We therefore investigated whether the severity of COVID-19 is 
      associated with these genetic variants. METHODS: We investigated the distribution 
      of KLRC2 deletion and HLA-E*0101/0103 allelic variants in a study cohort of 361 
      patients with either mild (N = 92) or severe (N = 269) COVID-19. RESULTS: 
      Especially the KLRC2(del), and at a lower degree the HLA-E*0101, allele were 
      significantly overrepresented in hospitalized patients (p = 0.0006 and p = 0.01), 
      particularly in patients requiring intensive care (p < 0.0001 and p = 0.01), 
      compared with patients with mild symptoms. Both genetic variants were independent 
      risk factors for severe COVID-19. CONCLUSION: Our data show that these genetic 
      variants in the NKG2C/HLA-E axis have a significant impact on the development of 
      severe SARS-CoV-2 infections, and may help to identify patients at high-risk for 
      severe COVID-19.
FAU - Vietzen, Hannes
AU  - Vietzen H
AD  - Center for Virology, Medical University of Vienna, Vienna, Austria.
FAU - Zoufaly, Alexander
AU  - Zoufaly A
AD  - Department of Medicine IV, Kaiser Franz Josef Hospital, Vienna, Austria.
FAU - Traugott, Marianna
AU  - Traugott M
AD  - Department of Medicine IV, Kaiser Franz Josef Hospital, Vienna, Austria.
FAU - Aberle, Judith
AU  - Aberle J
AD  - Center for Virology, Medical University of Vienna, Vienna, Austria.
FAU - Aberle, Stephan W
AU  - Aberle SW
AD  - Center for Virology, Medical University of Vienna, Vienna, Austria.
FAU - Puchhammer-Stockl, Elisabeth
AU  - Puchhammer-Stockl E
AUID- ORCID: 0000-0002-0673-8335
AD  - Center for Virology, Medical University of Vienna, Vienna, Austria. 
      elisabeth.puchhammer@meduniwien.ac.at.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210126
PL  - United States
TA  - Genet Med
JT  - Genetics in medicine : official journal of the American College of Medical 
      Genetics
JID - 9815831
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (KLRC2 protein, human)
RN  - 0 (NK Cell Lectin-Like Receptor Subfamily C)
SB  - IM
MH  - *COVID-19
MH  - Histocompatibility Antigens Class II
MH  - Humans
MH  - *NK Cell Lectin-Like Receptor Subfamily C/genetics
MH  - Risk Factors
MH  - SARS-CoV-2
PMC - PMC7835668
EDAT- 2021/01/28 06:00
MHDA- 2021/05/13 06:00
PMCR- 2021/09/05
CRDT- 2021/01/27 05:50
PHST- 2020/09/02 00:00 [received]
PHST- 2020/12/15 00:00 [accepted]
PHST- 2021/01/28 06:00 [pubmed]
PHST- 2021/05/13 06:00 [medline]
PHST- 2021/01/27 05:50 [entrez]
PHST- 2021/09/05 00:00 [pmc-release]
AID - S1098-3600(21)01448-9 [pii]
AID - 10.1038/s41436-020-01077-7 [doi]
PST - ppublish
SO  - Genet Med. 2021 May;23(5):963-967. doi: 10.1038/s41436-020-01077-7. Epub 2021 Jan 
      26.