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Targeted capture enrichment and sequencing identifies HLA variants associated with the severity of COVID-19
Chuanmiao Liu1,2, Li Zhang1,2, Jiasheng Chen1,2
1Department of Infectious Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu Medical College, Bengbu, China.
Insights
Human leukocyte antigen (HLA) variations are linked to COVID-19 severity. Specific HLA alleles, including HLA-DRB3*01:01, were significantly associated with disease progression in a study of COVID-19 patients.
Area of Science:
- Immunogenetics
- Infectious Disease Epidemiology
Background:
- The COVID-19 pandemic highlights the need to understand severe disease pathogenesis.
- Human Leukocyte Antigen (HLA) gene polymorphisms play a crucial role in immune responses.
- The potential influence of HLA variants on COVID-19 outcomes remains largely unexplored.
Purpose of the Study:
- To investigate the association between individual Human Leukocyte Antigen (HLA) variations and the severity of Coronavirus disease 2019 (COVID-19).
- To test the hypothesis that HLA polymorphisms may alter COVID-19 disease course.
Main Methods:
- Targeted capture enrichment and sequencing of HLA genes in 16 COVID-19 patients (severe vs. mild cases).
- HLA typing performed using contig comparison against the IPD-IMGT/HLA Database.
- Statistical analysis to identify significant associations between HLA alleles and disease severity.
Main Results:
- 139 four-digit resolution HLA alleles were identified.
- The HLA-DRB3*01:01 allele showed a significant association with COVID-19 severity (OR=27.64, P=0.0064).
- HLA-K*01:01 and HLA-K*01:02 alleles were also associated with COVID-19 severity, potentially as risk and protective factors, respectively.
Conclusions:
- Three non-classical HLA alleles (HLA-DRB3*01:01, HLA-K*01:01, HLA-K*01:02) are associated with COVID-19 severity.
- These findings contribute to understanding the role of HLA gene polymorphisms in COVID-19 development and progression.
Background:
Coronavirus disease 2019 (COVID-19) is currently a global pandemic. The pathogenesis of severe COVID-19 has been widely investigated, but it is still unclear. Human leukocyte antigen (HLA) plays a central role in immune response, and its variants might be related to COVID-19 progression and severity.
Objective:
To investigate the hypothesis that individual HLA variations could alter the course of COVID-19 and might be associated with the severity of COVID-19.
Methods:
In this study, we conducted an HLA targeted capture enrichment and sequencing of severe COVID-19 patients matched to mild cases. A total of 16 COVID-19 patients, confirmed by SARS-CoV-2 viral RNA polymerase-chain-reaction (PCR) test and chest computed tomography (CT) scan, were enrolled in this study. The HLA targeted capture enrichment and sequencing were conducted. HLA typing was performed by comparing contigs with IPD-IMGT/HLA Database.
Results:
In this study, 139 four-digit resolution HLA alleles were acquired. The results showed that HLA-DRB3*01:01 allele was significantly associated with the severity of COVID-19 (odds ratio [OR] = 27.64, 95% confidence interval [CI] = 1.35-560.50, P = 0.0064). And HLA-K*01:01 might be a potential risk factor for COVID-19 severity (OR = 0.11, 95% CI = 0.017-0.66, P = 0.019), but HLA-K*01:02 might be a protective factor (OR = 7.50, 95% CI = 1.48-37.92, P = 0.019).
Conclusion:
Three non-classical HLA alleles, including HLA-DRB3*01:01, HLA-K*01:01, HLA-K*01:02 were identified to be associated with the severity of COVID-19 by comparing mild and severe patients. The current findings would be helpful for exploring the influence of HLA gene polymorphisms on the development and severity of COVID-19.
