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Population Difference in Allele Frequency of HLA-C*05 and Its Correlation with COVID-19 Mortality

Atsushi Sakuraba1, Haider Haider1, Toshiro Sato2,3

  • 1Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medicine, Chicago, IL 60637, USA.

Viruses
|November 25, 2020
PubMed

Insights

Human leukocyte antigen (HLA) class I, specifically HLA-C*05, is linked to COVID-19 mortality. Genetic variations in innate immunity may explain differing country death rates, warranting further study.

Area of Science:

  • Immunogenetics
  • Viral Pathogenesis
  • Epidemiology

Background:

  • Coronavirus disease 2019 (COVID-19) exhibits significant global mortality disparities.
  • Human leukocyte antigen (HLA) class I is crucial for viral infection susceptibility.
  • Investigating the role of HLA class I in COVID-19 mortality differences is essential.

Purpose of the Study:

  • To examine the association between human leukocyte antigen (HLA) class I allele frequencies and COVID-19 mortality rates across countries.
  • To explore the correlation between HLA-C*05, its natural killer (NK) cell receptor KIR2DS4fl, and differential COVID-19 mortality.

Main Methods:

  • Collected HLA allele frequency data for 74 countries from public databases.
  • Utilized linear and multivariable regression to assess associations between HLA allele frequencies and COVID-19 mortality.
  • Analyzed the interaction of HLA-C*05 with KIR2DS4fl and its relation to historical pandemic mortality patterns.

Main Results:

  • HLA-A*01, -B*07, -B*08, -B*44, and -C*05 showed initial associations with COVID-19 mortality risk.
  • HLA-C*05 remained the only statistically significant factor after multivariable regression (p=0.000027).
  • A 1% increase in HLA-C*05 frequency correlated with 44 additional deaths per million, linked to NK cell hyperactivation.

Conclusions:

  • The allele frequency of HLA-C*05 and its interaction with KIR2DS4fl strongly correlate with COVID-19 mortality.
  • Host genetic variations in innate immunity likely contribute to observed international differences in COVID-19 mortality.
  • Further research with patient samples is recommended to validate these findings.
Abstract

Keywords:
COVID-19HLAgeneglobalinnate immunitymortalityselection

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