Can the protection be among us? Previous viral contacts and prevalent HLA alleles could be avoiding an even more disseminated COVID-19 pandemic.

Antonio, E. C.; Meireles, M. R.; Bragatte, M. A. S.; Vieira, G. F.

Background: COVID-19 is bringing scenes of sci-fi movies into real life, and it seems to be far from over. Infected individuals exhibit variable severity, with no relation between the number of cases and mortality, suggesting the involvement of the populational genetic constitution and previous cross-reactive immune contacts in the individuals' disease outcome. Methods: A clustering approach was conducted to investigate the involvement of human MHC alleles with individuals' outcomes. HLA frequencies from affected countries were used to fuel the Hierarchical Clusterization Analysis. The formed groups were compared regarding their death rates. To prospect the T cell targets in SARS-CoV-2, and by consequence, the epitopes that are conferring cross-protection in the current pandemic, we modeled 3D structures of HLA-A*02:01 presenting immunogenic epitopes from SAR-CoV-1, recovered from Immune Epitope Database. These pMHC structures were also compared with models containing the corresponding SARS-CoV-2 epitope, with alphacoronavirus sequences, and with a panel of immunogenic pMHC structures contained in CrossTope. Findings: The combined use of HLA-B*07, HLA-B*44, HLA-DRB1*03, and HLADRB1*04 allowed the clustering of affected countries presenting similar death rates, based only on their allele frequencies. SARS-CoV HLA-A*02:01 epitopes were structurally investigated. It reveals molecular conservation between SARS-CoV-1 and SARS-CoV-2 peptides, enabling the use of formerly SARS-CoV-1 experimental epitopes to inspect actual targets that are conferring cross-protection. Alpha-CoVs and, impressively, viruses involved in human infections share fingerprints of immunogenicity with SARS-CoV peptides. Interpretation: Wide-scale HLA genotyping in COVID-19 patients shall improve prognosis prediction. Structural identification of previous triggers paves the way for herd immunity examination and wide spectrum vaccine development. Funding: This work was supported by the National Council for Scientific and Technological Development (CNPq) and National Council for the Improvement of Higher Education (CAPES) for their support