Influence of HLA-A, -B, -DR Polymorphisms on the Severity of COVID-19: A Case-Control Study in the Iranian Population

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Abstract

Background:

As an emerging pandemic disease, COVID-19 encompasses a spectrum of clinical diagnoses, from the common cold to severe respiratory syndrome. Considering the shreds of evidence demonstrating the relationship between human leukocyte antigen (HLA) allele diversity and infectious disease susceptibility, this study was conducted to determine the association of HLA alleles with COVID-19 severity in Iranian subjects.

Methods:

In this case-control study, a total of 200 unrelated individuals (consisting of 100 people with severe COVID-19 and an average age of 55.54 as the case group, and 100 patients with mild COVID-19 with an average age of 48.97 as the control group) were recruited, and HLA typing (Locus A, B, and DR) was performed using the Olerup sequence-specific oligonucleotide (SSO) HLA-typing kit.

Results:

Our results showed that HLA-A*11 and HLA-DRB1*14 alleles were more frequently observed in severe COVID-19 cases, while HLA-B*52 was more common in mild cases, which was in agreement with some previous studies.

Conclusion:

Our results confirmed the evidence for the association of HLA alleles with COVID-19 outcomes. We found that HLA-A*11 and HLA-DRB1*14 alleles may be susceptibility factors for severe COVID-19, while HLA-B*52 may be a protective factor. These findings provide new insight into the pathogenesis of COVID-19 and help patient management.

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Most cited references 26

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Genomewide Association Study of Severe Covid-19 with Respiratory Failure

David Ellinghaus, Frauke Degenhardt, Luis Bujanda … (2020)

Abstract Background There is considerable variation in disease behavior among patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19). Genomewide association analysis may allow for the identification of potential genetic factors involved in the development of Covid-19. Methods We conducted a genomewide association study involving 1980 patients with Covid-19 and severe disease (defined as respiratory failure) at seven hospitals in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe. After quality control and the exclusion of population outliers, 835 patients and 1255 control participants from Italy and 775 patients and 950 control participants from Spain were included in the final analysis. In total, we analyzed 8,582,968 single-nucleotide polymorphisms and conducted a meta-analysis of the two case–control panels. Results We detected cross-replicating associations with rs11385942 at locus 3p21.31 and with rs657152 at locus 9q34.2, which were significant at the genomewide level (P<5×10−8) in the meta-analysis of the two case–control panels (odds ratio, 1.77; 95% confidence interval [CI], 1.48 to 2.11; P=1.15×10−10; and odds ratio, 1.32; 95% CI, 1.20 to 1.47; P=4.95×10−8, respectively). At locus 3p21.31, the association signal spanned the genes SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6 and XCR1. The association signal at locus 9q34.2 coincided with the ABO blood group locus; in this cohort, a blood-group–specific analysis showed a higher risk in blood group A than in other blood groups (odds ratio, 1.45; 95% CI, 1.20 to 1.75; P=1.48×10−4) and a protective effect in blood group O as compared with other blood groups (odds ratio, 0.65; 95% CI, 0.53 to 0.79; P=1.06×10−5). Conclusions We identified a 3p21.31 gene cluster as a genetic susceptibility locus in patients with Covid-19 with respiratory failure and confirmed a potential involvement of the ABO blood-group system. (Funded by Stein Erik Hagen and others.)

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COVID-19 and Multi-Organ Response

Sevim Zaim, Jun Heng Chong, Vissagan Sankaranarayanan … (2020)

Since the outbreak and rapid spread of COVID-19 starting late December 2019, it has been apparent that disease prognosis has largely been influenced by multi-organ involvement. Comorbidities such as cardiovascular diseases have been the most common risk factors for severity and mortality. The hyperinflammatory response of the body, coupled with the plausible direct effects of SARS-CoV-2 on body-wide organs via ACE2, has been associated with complications of the disease. Acute respiratory distress syndrome, heart failure, renal failure, liver damage, shock and multi-organ failure have precipitated death. Acknowledging the comorbidities and potential organ injuries throughout the course of COVID-19 is therefore crucial in the clinical management of patients. This paper aims to add onto the ever-emerging landscape of medical knowledge on COVID-19, encapsulating its multi-organ impact.

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Human Leukocyte Antigen Susceptibility Map for Severe Acute Respiratory Syndrome Coronavirus 2

Austin Nguyen, Julianne David, Sean Maden … (2020)

Individual genetic variation may help to explain different immune responses to a virus across a population. In particular, understanding how variation in HLA may affect the course of COVID-19 could help identify individuals at higher risk from the disease. HLA typing can be fast and inexpensive. Pairing HLA typing with COVID-19 testing where feasible could improve assessment of severity of viral disease in the population. Following the development of a vaccine against SARS-CoV-2, the virus that causes COVID-19, individuals with high-risk HLA types could be prioritized for vaccination.

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Author and article information

Contributors

Parisa Mashayekhi:

ORCID: https://orcid.org/0000-0002-6373-3266

Role: Formal analysisRole: Funding acquisitionRole: InvestigationRole: Project administrationRole: ValidationRole: Writing – original draft

Mir Davood Omrani:

ORCID: https://orcid.org/0000-0002-0673-9717

Role: ConceptualizationRole: Funding acquisitionRole: SupervisionRole: ValidationRole: Writing – review & editing

Zeynab Yassin:

ORCID: https://orcid.org/0000-0002-1915-6596

Role: Resources

Ali Dehghanifard: Role: MethodologyRole: Validation

Leila Ashouri: Role: Resources

Sara Sadat Aghabozorg Afjeh:

ORCID: https://orcid.org/0000-0002-6352-9310

Role: Formal analysisRole: Software

Zahra Shabanzadeh: Role: Data curationRole: Visualization

Journal

Journal ID (nlm-ta): Arch Iran Med

Journal ID (iso-abbrev): Arch Iran Med

Journal ID (publisher-id): Arch Iran Med

Journal ID (publisher-id): AIM

Title: Archives of Iranian medicine

Publisher: Academy of Medical Sciences of I.R. Iran

ISSN (Print): 1029-2977

ISSN (Electronic): 1735-3947

Publication date (Print): May 2023

Publication date (Electronic): 01 May 2023

Volume: 26

Issue: 5

Pages: 261-266

Affiliations

¹Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran

²Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

³Antimicrobial resistance Research Center, Institute Of Immunology And Infectious Disease, Iran University of Medical Sciences, Tehran, Iran

⁴Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Author notes

[* ] Corresponding Author: Mir Davood Omrani, Email: davood_omrani@ 123456yahoo.co.uk

Author information

Parisa Mashayekhi https://orcid.org/0000-0002-6373-3266

Mir Davood Omrani https://orcid.org/0000-0002-0673-9717

Zeynab Yassin https://orcid.org/0000-0002-1915-6596

Sara Sadat Aghabozorg Afjeh https://orcid.org/0000-0002-6352-9310

Article

DOI: 10.34172/aim.2023.40

PMC ID: 10685865

PubMed ID: 38301089

SO-VID: 3ab53372-1c91-46b2-93e5-d9b554a55b18

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 05 November 2022

Date accepted : 12 March 2023

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Tables: 5, References: 27

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Influence of HLA-A, -B, -DR Polymorphisms on the Severity of COVID-19: A Case-Control Study in the Iranian Population

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Abstract

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Novel Coronavirus Disease COVID-19

Most cited references 26

Genomewide Association Study of Severe Covid-19 with Respiratory Failure

COVID-19 and Multi-Organ Response

Human Leukocyte Antigen Susceptibility Map for Severe Acute Respiratory Syndrome Coronavirus 2

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