Population-Predicted MHC Class II Epitope Presentation of SARS-CoV-2 Structural Proteins Correlates to the Case Fatality Rates of COVID-19 in Different Countries

Abstract

We observed substantial differences in predicted Major Histocompatibility Complex II (MHCII) epitope presentation of SARS-CoV-2 proteins for different populations but only minor differences in predicted MHCI epitope presentation. A comparison of this predicted epitope MHC-coverage revealed for the early phase of infection spread (till day 15 after reaching 128 observed infection cases) highly significant negative correlations with the case fatality rate. Specifically, this was observed in different populations for MHC class II presentation of the viral spike protein (p-value: 0.0733 for linear regression), the envelope protein (p-value: 0.023), and the membrane protein (p-value: 0.00053), indicating that the high case fatality rates of COVID-19 observed in some countries seem to be related with poor MHC class II presentation and hence weak adaptive immune response against these viral envelope proteins. Our results highlight the general importance of the SARS-CoV-2 structural proteins in immunological control in early infection spread looking at a global census in various countries and taking case fatality rate into account. Other factors such as health system and control measures become more important after the early spread. Our study should encourage further studies on MHCII alleles as potential risk factors in COVID-19 including assessment of local populations and specific allele distributions.

Allelic variation in Class I HLA determines pre-existing memory responses to SARS-CoV-2 that shape the CD8+ T cell repertoire upon viral exposure

“…The interplay between HLA-restricted epitope presentation and available TCR repertoire shapes the cellular response to SARS-CoV-2. There are few limited studies suggesting an influence of HLA genotype on COVID-19 severity (27,(41)(42)(43). Large-scale, high-resolution HLA mapping, consistent with what we have done for select HLAs in this work, may help identify relationships between HLA genotype and protection against severe disease, ideally uncovering mechanism.…”

Distribution of HLA-DRB1 alleles in BRICS countries with a high tuberculosis burden: a systematic review and meta-analysis

“…Likewise, an insufficient number of studies have analyzed HLA class I alleles. Liang et al reported that a significant overlap can occur between HLA class I and class II alleles regarding their specificity to epitopes of the same antigen 17 . However, it is not clear whether a significant overlap is recognized within the same individual.…”

“…One limitation of this study was the lack of sufficient articles to explore more specific allelic frequencies within all 13 HLA-DRB1 allelic groups. The affinity of the alleles within each allelic group for a given epitope can vary considerably 17 . However, for most HLA-DRB1 allelic groups, one or a few alleles are responsible for a high proportion of their occurrence 17 , and there are tools available to address this issue in vaccine design 30 .…”

“…The affinity of the alleles within each allelic group for a given epitope can vary considerably 17 . However, for most HLA-DRB1 allelic groups, one or a few alleles are responsible for a high proportion of their occurrence 17 , and there are tools available to address this issue in vaccine design 30 .…”

“…Among these, promising candidates include epitope-based vaccines that use HLA class II peptide ligands recognized by T cells to generate effective cellular immunity and protection. The impact of HLA class II binding efficiency to relevant epitopes in the immune response against infection at a population level has recently been addressed 17 . To provide high coverage in endemic settings, the present study performed a series of systematic reviews, followed by a meta-analysis, to identify the most relevant HLA alleles for targeting by effective epitopes in the BRICS populations.…”