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

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

Eric de Sousa et al. Int J Infect Dis. 2020 Sep.

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.

Copyright © 2020. Published by Elsevier Ltd.

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Figures

Figure 1
Figure 1

Distribution of the SARS-CoV-2 ORF8 S residue at position 84. 11970 SARS-CoV-2 sequences deposited in the GISAID database by April 27th, 2020. 87% have the Leucine amino acid at position 84 and 13% exhibit Serine. In the countries that submitted more than 100 sequences where the proportion is different: in China, 38% SARS-CoV-2 sequences account for ORF8 (S84L), in Spain 43%, in the USA 32% and in Canada 31%.

Figure 2
Figure 2

Frequency of HLA-DRB1*04:01 that allows binding of the ORF8 variant epitope. Based on previous studies (Solberg et al., 2008), the allele frequency of HLA-DRB1*04:01 is around 0.03 in Spain, around 0.1 in Caucasians in the USA, but around 0.02 in other ethnicities in the USA, around 0.01 in China, and 0.008 in Canada.

Figure 3
Figure 3

Frequency of HLA-DRB1*09:01. Based on previous studies (Solberg et al., 2008) for HLA-DRB1*09:01, the allele frequency is around 0.008 in Spain, approximately 0.1 in Asians in the USA, but around 0.01 in other ethnicities in the USA, and approximately 0.07 in Canada.

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