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Association of HLA Class I Genotype with Mortality in Patients with Diabetes Mellitus and COVID-19

M Yu Shkurnikov1,2, D A Averinskaya3, A G Komarov4

  • 1Faculty of Biology and Biotechnology, HSE University, Moscow, Russia. mshkurnikov@hse.ru.

Doklady. Biochemistry and Biophysics
|February 14, 2023
PubMed

Insights

Diabetes mellitus (DM) significantly increases COVID-19 mortality. This study links poor COVID-19 outcomes in DM patients to specific major histocompatibility complex class I (MHC-I) genotypes with low binding affinity to SARS-CoV-2 peptides.

Area of Science:

  • Immunogenetics
  • Infectious Disease Epidemiology
  • Metabolic Disorders

Background:

  • Diabetes mellitus (DM) is a known risk factor, increasing COVID-19 mortality fivefold.
  • DM complications like micro-/macroangiopathies and organ failure contribute to COVID-19 lethality.
  • Viral infections, including SARS-CoV-2, modulate immune responses, affecting T cell activity and insulin resistance.

Purpose of the Study:

  • To investigate the association between major histocompatibility complex class I (MHC-I) genotype and COVID-19 outcomes in patients with diabetes mellitus (DM).
  • To explore the role of genetic factors in COVID-19 severity among diabetic individuals under 60.

Main Methods:

  • Genotyping of major histocompatibility complex class I (MHC-I) molecules in 222 patients with DM.
  • Analysis of the correlation between specific MHC-I genotypes and COVID-19 mortality.
  • Assessment of MHC-I molecule affinity for SARS-CoV-2 peptides.

Main Results:

  • Lethal COVID-19 outcomes in diabetic patients were significantly associated with their MHC-I genotype.
  • Specifically, low affinity between individual MHC-I molecules and SARS-CoV-2 peptides correlated with increased mortality.
  • The study highlights the importance of MHC-I in T cell recognition of infected cells.

Conclusions:

  • The MHC-I genotype plays a critical role in determining COVID-19 prognosis for patients with diabetes mellitus.
  • Low-affinity interactions between MHC-I and viral peptides represent a potential mechanism for increased COVID-19 lethality in DM.
  • Understanding these genetic associations could inform personalized risk assessment and treatment strategies.

Keywords:
COVID-19HLAMHC-Idiabetes mellitus

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