Abstract
The world is dealing with one of the worst pandemics ever. SARS-CoV-2 is the etiological agent of COVID-19 that has already spread to more than 200 countries. However, infectivity, severity, and mortality rates do not affect all countries equally. Here we consider 140 HLA alleles and extensively investigate the landscape of 3,723 potential HLA-I A and B restricted SARS-CoV-2-derived antigens and how 37 countries in the world are predicted to respond to those peptides considering their HLA-I distribution frequencies. The clustering of HLA-A and HLA-B allele frequencies partially separates most countries with the lowest number of deaths per million inhabitants from the other countries. We further correlated the patterns of in silico predicted population coverage and epidemiological data. The number of deaths per million inhabitants correlates to the predicted antigen coverage of S and N derived peptides and its module is influenced if a given set of frequent or rare HLA alleles are analyzed in a given population. Moreover, we highlighted a potential risk group carrying HLAs associated with an elevated number of deaths per million inhabitants. In addition, we identified three potential antigens bearing at least one amino acid of the four-length insertion that differentiates SARS-CoV-2 from previous coronavirus strains. We believe these data can contribute to the search for peptides with the potential to be used in vaccine strategies considering the role of herd immunity to hamper the spread of the disease. Importantly, to the best of our knowledge, this work is the first to use a populational approach in association with COVID-19 outcome.
Highlights
Since December 2019, the world has been facing one of the worst pandemics of all times caused by a novel Betacoronavirus (Severe Acute Respiratory Syndrome Coronavirus 2—SARS-CoV-2)
To assess the landscape of peptides potentially presented by Histocompatibility Leukocyte Antigen (HLA)-I alleles occurring in the global population and how this diversity is associated with the disease outcome, we selected a list of countries hit by the pandemic with known HLAs genetic frequencies
Considering the ratio value, we evaluate the spectrum of S and N derived peptides that simultaneously bind to a collection of HLA alleles, determining if the ratio between the coverage for S/N proteins is more associated with the number of deaths rather than the coverage of each protein separately
Summary
Since December 2019, the world has been facing one of the worst pandemics of all times caused by a novel Betacoronavirus (Severe Acute Respiratory Syndrome Coronavirus 2—SARS-CoV-2). Some studies predicting HLArestricted peptides derived from SARS-CoV-2 are already available [12, 13] These characteristics must be taken into account when considering epitope-based vaccines since target epitopes must be able to bind to the HLA molecule and prove to be immunogenic to promote a functional response [14]. We evaluated how different populations potentially present HLA class I restricted SARS-CoV-2 peptides and their association with the local epidemic progression features across different countries This strategy led us to a set of peptides derived from virus S and N proteins, which showed distinct correlations with disease outcomes. These results may prove critical in guiding efforts towards the development of vaccine candidates, as well as determine high-risk groups based on HLA alleles
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