HLA-B*44 and C*01 Prevalence Correlates with Covid19 Spreading across Italy

Int J Mol Sci. 2020 Jul 23;21(15):5205. doi: 10.3390/ijms21155205.

Abstract

The spread of COVID-19 is showing huge, unexplained, differences between northern and southern Italy. We hypothesized that the regional prevalence of specific class I human leukocyte antigen (HLA) alleles, which shape the anti-viral immune response, might partly underlie these differences. Through an ecological approach, we analyzed whether a set of HLA alleles (A, B, C), known to be involved in the immune response against infections, correlates with COVID-19 incidence. COVID-19 data were provided by the National Civil Protection Department, whereas HLA allele prevalence was retrieved through the Italian Bone-Marrow Donors Registry. Among all the alleles, HLA-A*25, B*08, B*44, B*15:01, B*51, C*01, and C*03 showed a positive log-linear correlation with COVID-19 incidence rate fixed on 9 April 2020 in proximity of the national outbreak peak (Pearson's coefficients between 0.50 and 0.70, p-value < 0.0001), whereas HLA-B*14, B*18, and B*49 showed an inverse log-linear correlation (Pearson's coefficients between -0.47 and -0.59, p-value < 0.0001). When alleles were examined simultaneously using a multiple regression model to control for confounding factors, HLA-B*44 and C*01 were still positively and independently associated with COVID-19: a growth rate of 16% (95%CI: 0.1-35%) per 1% point increase in B*44 prevalence; and of 19% (95%CI: 1-41%) per 1% point increase in C*01 prevalence. Our epidemiologic analysis, despite the limits of the ecological approach, is strongly suggestive of a permissive role of HLA-C*01 and B*44 towards SARS-CoV-2 infection, which warrants further investigation in case-control studies. This study opens a new potential avenue for the identification of sub-populations at risk, which could provide Health Services with a tool to define more targeted clinical management strategies and priorities in vaccination campaigns.

Keywords: COVID-19; HLA class I; SARS-Cov2; coronavirus; viral infection susceptibility.

Publication types

  • Observational Study

MeSH terms

  • Coronavirus Infections / epidemiology*
  • Coronavirus Infections / genetics*
  • Coronavirus Infections / immunology
  • Gene Frequency
  • HLA-B44 Antigen / genetics*
  • HLA-C Antigens / genetics*
  • Humans
  • Italy / epidemiology
  • Pandemics
  • Pneumonia, Viral / epidemiology*
  • Pneumonia, Viral / genetics*
  • Pneumonia, Viral / immunology
  • Prevalence
  • Registries
  • Regression Analysis

Substances

  • HLA-B44 Antigen
  • HLA-C Antigens

Supplementary concepts

  • COVID-19