Genetic Variability in Immune System May Affect Susceptibility to COVID-19

A study published in the Journal of Virology suggested that individual genetic variation could explain the differences in immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19).

The study results showed that genetic variability across the 3 major histocompatibility complex (MHC) class I Genes – human leukocyte antigen (HLA) A, B, and C – may affect an individual’s susceptibility to and severity of COVID-19.

Previous studies have shown that HLA alleles, which are significant segments of the viral antigen presentation pathway, are responsible to providing differential susceptibility and severity of viruses in individuals. 

The silico analysis incorporated viral peptide-MHC class I binding affinity across 145 HLA -A, -B, and -C genotypes for all SARS-CoV-2 peptides. The study additionally evaluated the potential for cross-protective immunity due to past exposure to 4 common human coronaviruses.

Findings included that HLA-B*46:01 had the fewest predicted binding peptides for SARS-CoV-2. This suggests that individuals who have this allele could express particular vulnerability to COVID-19, as they were previously shown to be for SARS. On the other end, the study found that HLA-B*15:03 expressed the greatest capacity to present highly conserved SARS-CoV-2 peptides shared among common human coronaviruses, meaning that the allele has the potential to enable cross-protective T-cell based immunity.

The study furthermore reported the global distributions of HLA types with potential epidemiological implications within the scope of the COVID-19 pandemic. Evaluation of the data found that, in general, there is no correlation between the HLA allelic frequency in the population and the allelic capacity to bind SARS-CoV or SARS-CoV-2 peptides.

Limitations of the study include the fact that it is an entirely in silico study, and researchers were unable to obtain individual-level HLA typing and clinical results for real-world COVID-19 populations.

“This study…introduces the relationship between coronavirus sequence conservation and MHC class I antigen presentation,” the study authors wrote.

“We show that individual HLA, haplotype, and full genotype variability likely influence the capacity to respond to SARS-CoV-2 infection, and we note certain alleles in particular (eg HLA-B*46:01) that could be associated with more severe infection, as previously shown with SARS-CoV. Indeed, we further compare SARS-CoV and SARS-CoV-2 peptide presentation and note a high degree of similarity between the two across HLA types.”

“Finally, this is the first study to report global distributions of HLA types and haplotypes with potential epidemiological ramifications in the setting of the current pandemic,” the authors concluded.

References:

1. Nguyen A, David JK, Maden SK, et al. Human leukocyte antigen susceptibility map for SARS-CoV-2. American Society for Microbiology. 2020; doi:10.1128/JVI.00510-20