PMID- 33928374
OWN - NLM
STAT- MEDLINE
DCOM- 20210722
LR  - 20210722
IS  - 1537-6613 (Electronic)
IS  - 0022-1899 (Print)
IS  - 0022-1899 (Linking)
VI  - 224
IP  - 2
DP  - 2021 Jul 15
TI  - Activating Killer-Cell Immunoglobulin-Like Receptors Are Associated With the 
      Severity of Coronavirus Disease 2019.
PG  - 229-240
LID - 10.1093/infdis/jiab228 [doi]
LID - jiab228
AB  - BACKGROUND: Etiopathogenesis of the clinical variability of the coronavirus 
      disease 2019 (COVID-19) remains mostly unknown. In this study, we investigate the 
      role of killer cell immunoglobulin-like receptor (KIR)/human leukocyte antigen 
      class-I (HLA-I) interactions in the susceptibility and severity of COVID-19. 
      METHODS: We performed KIR and HLA-I genotyping and natural killer cell (NKc) 
      receptors immunophenotyping in 201 symptomatic patients and 210 noninfected 
      controls. RESULTS: The NKcs with a distinctive immunophenotype, suggestive of 
      recent activation (KIR2DS4low CD16low CD226low CD56high TIGIThigh NKG2Ahigh), 
      expanded in patients with severe COVID-19. This was associated with a higher 
      frequency of the functional A-telomeric activating KIR2DS4 in severe versus mild 
      and/or moderate patients and controls (83.7%, 55.7% and 36.2%, P < 7.7 x 10-9). 
      In patients with mild and/or moderate infection, HLA-B*15:01 was associated with 
      higher frequencies of activating B-telomeric KIR3DS1 compared with patients with 
      other HLA-B*15 subtypes and noninfected controls (90.9%, 42.9%, and 47.3%; 
      P < .002; Pc = 0.022). This strongly suggests that HLA-B*15:01 specifically 
      presenting severe acute respiratory syndrome coronavirus 2 peptides could form a 
      neoligand interacting with KIR3DS1. Likewise, a putative neoligand for KIR2DS4 
      could arise from other HLA-I molecules presenting severe acute respiratory 
      syndrome coronavirus 2 peptides expressed on infected an/or activated lung 
      antigen-presenting cells. CONCLUSIONS: Our results support a crucial role of NKcs 
      in the clinical variability of COVID-19 with specific KIR/ligand interactions 
      associated with disease severity.
CI  - (c) The Author(s) 2021. Published by Oxford University Press for the Infectious 
      Diseases Society of America. All rights reserved. For permissions, e-mail: 
      journals.permissions@oup.com.
FAU - Bernal, Enrique
AU  - Bernal E
AD  - Infectious Disease Unit, Reina Sofia University Hospital and the Instituto 
      Murciano de Investigacion Biosanitaria (IMIB), Murcia, Spain.
FAU - Gimeno, Lourdes
AU  - Gimeno L
AD  - Immunology Service, Hospital Clinico Universitario Virgen de la Arrixaca (HCUVA) 
      and Instituto Murciano de Investigacion Biosanitaria (IMIB), Murcia, Spain.
AD  - Human Anatomy Department, University of Murcia, Murcia, Spain.
FAU - Alcaraz, Maria J
AU  - Alcaraz MJ
AD  - Infectious Disease Unit, Reina Sofia University Hospital and the Instituto 
      Murciano de Investigacion Biosanitaria (IMIB), Murcia, Spain.
FAU - Quadeer, Ahmed A
AU  - Quadeer AA
AD  - Department of Electronic and Computer Engineering, The Hong Kong University of 
      Science and Technology, Hong Kong, China.
FAU - Moreno, Marta
AU  - Moreno M
AD  - Internal Medicine Service, Hospital Universitario Morales Meseguer, Murcia, 
      Spain.
FAU - Martinez-Sanchez, Maria V
AU  - Martinez-Sanchez MV
AD  - Immunology Service, Hospital Clinico Universitario Virgen de la Arrixaca (HCUVA) 
      and Instituto Murciano de Investigacion Biosanitaria (IMIB), Murcia, Spain.
FAU - Campillo, Jose A
AU  - Campillo JA
AD  - Immunology Service, Hospital Clinico Universitario Virgen de la Arrixaca (HCUVA) 
      and Instituto Murciano de Investigacion Biosanitaria (IMIB), Murcia, Spain.
FAU - Gomez, Jose M
AU  - Gomez JM
AD  - Internal Medicine Service, Hospital Universitario Morales Meseguer, Murcia, 
      Spain.
FAU - Pelaez, Ana
AU  - Pelaez A
AD  - Internal Medicine Service, Hospital Rafael Mendez, Lorca, Spain.
FAU - Garcia, Elisa
AU  - Garcia E
AD  - Infectious Disesase Unit, Hospital Clinico Universitario Virgen de la Arrixaca 
      (HCUVA) and Instituto Murciano de Investigacion Biosanitaria (IMIB), Murcia, 
      Spain.
FAU - Herranz, Maite
AU  - Herranz M
AD  - Internal Medicine Service, Hospital Universitario Morales Meseguer, Murcia, 
      Spain.
FAU - Hernandez-Olivo, Marta
AU  - Hernandez-Olivo M
AD  - Pheumology Service, Hospital Universitario Santa Lucia, Murcia, Spain.
FAU - Martinez-Alfaro, Elisa
AU  - Martinez-Alfaro E
AD  - Internal Medicine Service, Hospital General de Albacete, Albacete, Spain.
FAU - Alcaraz, Antonia
AU  - Alcaraz A
AD  - Infectious Disease Unit, Reina Sofia University Hospital and the Instituto 
      Murciano de Investigacion Biosanitaria (IMIB), Murcia, Spain.
FAU - Munoz, Angeles
AU  - Munoz A
AD  - Infectious Disease Unit, Reina Sofia University Hospital and the Instituto 
      Murciano de Investigacion Biosanitaria (IMIB), Murcia, Spain.
FAU - Cano, Alfredo
AU  - Cano A
AD  - Infectious Disease Unit, Reina Sofia University Hospital and the Instituto 
      Murciano de Investigacion Biosanitaria (IMIB), Murcia, Spain.
FAU - McKay, Matthew R
AU  - McKay MR
AD  - Department of Electronic and Computer Engineering, The Hong Kong University of 
      Science and Technology, Hong Kong, China.
AD  - Department of Chemical and Biological Engineering, The Hong Kong University of 
      Science and Technology, Hong Kong, China.
FAU - Muro, Manuel
AU  - Muro M
AD  - Immunology Service, Hospital Clinico Universitario Virgen de la Arrixaca (HCUVA) 
      and Instituto Murciano de Investigacion Biosanitaria (IMIB), Murcia, Spain.
FAU - Minguela, Alfredo
AU  - Minguela A
AD  - Immunology Service, Hospital Clinico Universitario Virgen de la Arrixaca (HCUVA) 
      and Instituto Murciano de Investigacion Biosanitaria (IMIB), Murcia, Spain.
LA  - eng
GR  - COV20/00377/MINECO-Instituto de Salud Carlos III/
GR  - European Regional Development Fund/
GR  - A way to make Europe/
GR  - Murcian Association for the Investigation and Study of Infection Diseases/
GR  - Asociacion Pablo Ugarte/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Infect Dis
JT  - The Journal of infectious diseases
JID - 0413675
RN  - 0 (HLA Antigens)
RN  - 0 (Receptors, KIR)
SB  - IM
MH  - Aged
MH  - COVID-19/*genetics/immunology/pathology
MH  - Cross-Sectional Studies
MH  - Female
MH  - Genetic Predisposition to Disease/*genetics
MH  - Genotype
MH  - HLA Antigens/genetics/metabolism
MH  - Humans
MH  - Immunophenotyping
MH  - Killer Cells, Natural/metabolism
MH  - Male
MH  - Middle Aged
MH  - Prospective Studies
MH  - Receptors, KIR/*genetics/metabolism
MH  - SARS-CoV-2
MH  - Severity of Illness Index
PMC - PMC8135764
OTO - NOTNLM
OT  - COVID-19 severity
OT  - HLA class-I
OT  - NK cells
OT  - SARS-Cov-2
OT  - activating KIR receptors
EDAT- 2021/05/01 06:00
MHDA- 2021/07/23 06:00
PMCR- 2021/05/20
CRDT- 2021/04/30 07:02
PHST- 2021/01/08 00:00 [received]
PHST- 2021/04/23 00:00 [accepted]
PHST- 2021/05/01 06:00 [pubmed]
PHST- 2021/07/23 06:00 [medline]
PHST- 2021/04/30 07:02 [entrez]
PHST- 2021/05/20 00:00 [pmc-release]
AID - 6259338 [pii]
AID - jiab228 [pii]
AID - 10.1093/infdis/jiab228 [doi]
PST - ppublish
SO  - J Infect Dis. 2021 Jul 15;224(2):229-240. doi: 10.1093/infdis/jiab228.