MHC Haplotyping of SARS-CoV-2 patients: HLA subtypes are not associated with the presence and severity of Covid-19  in the Israeli population

Abstract

HLA haplotypes were found to be associated with increased risk for viral infections or disease severity in various diseases, including SARS. Several genetic variants are associated with Covid-19 severity. However, no clear association between HLA and Covid-19 incidence or severity has been reported. We conducted a large scale HLA analysis of Israeli individuals who tested positive for SARS-CoV-2 infection by PCR. Overall, 72,912 individuals with known HLA haplotypes were included in the study, of whom 6,413 (8.8%) were found to have SARS-CoV-2 by PCR. a Total of 20,937 subjects were of Ashkenazi origin (at least 2/4 grandparents). One hundred eighty-one patients (2.8% of the infected) were hospitalized due to the disease. None of the 66 most common HLA loci (within the five HLA subgroups; A, B, C, DQB1, DRB1) was found to be associated with SARS-CoV-2 infection or hospitalization. Similarly, no association was detected in the Ashkenazi Jewish subset. Moreover, no association was found between heterozygosity in any of the HLA loci and either infection or hospitalization.We conclude that HLA haplotypes are not a major risk/protecting factor among the Israeli population for SARS-CoV-2 infection or severity.

Detailed stratified GWAS analysis for severe COVID-19 in four European populations

“…Our hypothesis-driven analysis of associations in the HLA, as well as COVID-19 specific PepWAS analyses yielded no significant results, indicating no major role for HLA variability in mediating the severity of COVID-19 in our cohorts. These results are in line with a recent, and the so-far largest, HLA analysis from Shachar et al 40 Interestingly, we observed statistical association of the Y-haplogroup R with COVID-19 disease and mortality, however none of the results remain significant after correction for multiple testing. To gain more knowledge regarding the potential role of the Y-chromosome haplogroups in the COVID-19 pandemic, larger study samples are necessary as well as studies following the pandemic over time investigating whether the associations weaken or strengthen for different haplogroups.…”

“…These results are in line with a recent, and so-far the largest, HLA analysis from Shachar et al . (40) Within our analysis of Y-chromosome haplogroups, none of the results remain significant after correction for multiple testing, though single haplogroups showed trends for association ( Supplementary Text ) and larger study samples are necessary to obtain reliable conclusions. For individual haplogroups, we observed different frequencies between batches that may also arise from different versions of the same genotyping platform.…”

Japan COVID-19 Task Force: a nation-wide consortium to elucidate host genetics of COVID-19 pandemic in Japan

“…Given their critical impact on immune responses and contribution to host genetics of various infectious diseases, 26,27 HLA gene variants have been investigated for their possible role in the response to COVID-19 infection with controversial discussions 28,29 . To address this issue, we applied in silico imputation of both classical and non-classical HLA variants using the HLA reference panel of Japanese ( n = 1,118) 30,31 .…”

Polymorphism of the HLA system and weak antibody response to BNT162b2 mRNA vaccine

“…Among the first entered into use, the RNA-based vaccines demonstrated to be suitable for the dual challenge of efficacy and the need of a large-scale timely production; in addition, since nucleotide-based vaccines (DNA and RNA) induce cells to synthetize the viral protein by themselves starting from genetic information, a stronger humoral and cellular immunity is expected after vaccination 1,2 in comparison with peptide-based. In this perspective, the polymorphism of the HLA system may affect the number and the binding affinity of SARS-CoV-2 peptides derived from the nucleic acid coding for the Spike protein and their presentation within the molecules of HLA class I and II after vaccination; nonetheless, although the HLA system has been extensively studied since the beginning of the pandemic across most populations (with contrasting results), [3][4][5][6][7][8][9] there are no reported studies on the HLA polymorphism and the antibody response after RNA-based vaccination. Similarly, in silico prediction analyses describe the expected affinity and repertoire of viral peptidome presentation by specific HLA alleles or haplotypes, [10][11][12] giving insights into viral clearance and suggesting the existence of high-risk HLA types that are more susceptible to be associated with severe or even fatal COVID-19.…”