Class I HLA allele predicted antigenic coverages for Spike and Nucleocapsid proteins are associated with deaths related to COVID-19
Authors: Pretti Marco Antônio M. , Galvani Rômulo G. , Vieira Gustavo Fioravanti , Bonomo Adriana , Bonamino Martín H. , Boroni Mariana 
Published: June 2020

AbstractThe 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 3 potential antigens bearing at least one amino acid of the 4-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.ImportanceThe emergence of COVID-19 outbreak caused by a novel coronavirus opens up an imminent need to better understand how our immune system responds to this new virus and to develop ways to control its spread. Our results suggest why some countries show a higher number of deaths due to COVID-19 while other countries do not. SARS-CoV-2 expresses 10 proteins that could be used as targets for vaccine development. By using a comprehensive bioinformatic screening of potential epitopes derived from the SARS-CoV-2 sequences, we identified potential antigens for 148 HLA-I alleles distributed world-wide. These peptides are likely to have a high affinity for HLA class I molecules and may induce critical immune responses. Our results suggest that different coverages for S and N derived peptides is associated with deaths related to COVID-19 in distinct populations. Of note, frequent and rare HLA alleles influence the effects we observed. We explored these associations regarding potential antigens derived from each viral protein to enumerate a set of protective HLA alleles. Moreover, we explored the novel insertion in the SARS-CoV-2 protein S genome to map 3 potential antigens bearing this new region, and a set of peptides presented by those protective HLA alleles, of interest for vaccine strategies. Finally, we propose that vaccine development strategies should consider the inverse relationships of proteins S and N in view of the associations with the number of deaths.