Mortality in COVID-19 disease patients: Correlating the association of major histocompatibility complex (MHC) with severe acute respiratory syndrome 2 (SARS-CoV-2) variants

Abstract

Genetic factors such as the HLA type of patients may play a role in regard to disease severity and clinical outcome of patients with COVID-19. Taking the data deposited in the GISAID database, we made predictions using the IEDB analysis resource (TepiTool) to gauge how variants in the SARS-CoV-2 genome may change peptide binding to the most frequent MHC-class I and -II alleles in Africa, Asia and Europe. We caracterized how a single mutation in the wildtype sequence of of SARS-CoV-2 could influence the peptide binding of SARS-CoV-2 variants to MHC class II, but not to MHC class I alleles. Assuming the ORF8 (L84S) mutation is biologically significant, selective pressure from MHC class II alleles may select for viral varients and subsequently shape the quality and quantity of cellular immune responses aginast SARS-CoV-2. MHC 4-digit typing along with viral sequence analysis should be considered in studies examining clinical outcomes in patients with COVID-19.

Keywords: Autoimmunity; COVID-19; Cross-reactivity; Cytokines; Disease association; Epitope; HLA; MHC; MHC binding; Peptides; SARS; SARS-CoV-2; T-cells; Viral variants.