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. 2021 Aug;41(6):1154-1161.
doi: 10.1007/s10875-021-01071-x. Epub 2021 May 29.

MHC Haplotyping of SARS-CoV-2 Patients: HLA Subtypes Are Not Associated with the Presence and Severity of COVID-19 in the Israeli Population

Shay Ben Shachar  1   2   3 , Noam Barda  2   4 , Sigal Manor  5 , Sapir Israeli  6 , Noa Dagan  2   4 , Shai Carmi  7 , Ran Balicer  2 , Bracha Zisser  5 , Yoram Louzoun  8
Affiliations

MHC Haplotyping of SARS-CoV-2 Patients: HLA Subtypes Are Not Associated with the Presence and Severity of COVID-19 in the Israeli Population

Shay Ben Shachar et al. J Clin Immunol. 2021 Aug.

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. Studies have proposed associations, based on a very small sample and a large number of tested HLA alleles, but 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 6413 (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 in the general Israeli population. 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. Our results suggest that if any HLA association exists with the disease it is very weak, and of limited effect on the pandemic.

Keywords: Ashkenazi; HLA; Israel; SARS-CoV-2; association; hospitalization.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Odds ratio (OR) as a function of HLA allele. In all figures, the dot represents the odds ratio, and the interval represents the 95% confidence intervals (Bonferroni correction). The left plot is for SARS-CoV-2 infection and the right plot is for hospitalization. We trim error bars at 3 for better visualization. The analysis presented here is for the full population. One can see that no HLA allele is significantly associated
Fig. 2
Fig. 2
Odds ratio (OR) as a function of HLA allele in the Ashkenazi population. In all figures, the dot represents the odds ratio, and the interval represents the 95% confidence intervals (Bonferroni correction). The left plot is for SARS-CoV-2 infection and the right plot is for hospitalization. We trim error bars at 3 for better visualization. The analysis presented here is for the Ashkenazi population. One can see that no HLA allele is significantly associated
Fig. 3
Fig. 3
Effect of homozygosity on either infection or hospitalization in the entire studied population or the Ashkenazi population. Again no significant association was found. Homozygosity at a given locus is defined as having the same low-resolution allele in this locus
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