PMID- 36574143 OWN - NLM STAT- MEDLINE DCOM- 20230322 LR - 20230328 IS - 2092-9293 (Electronic) IS - 1976-9571 (Print) IS - 1976-9571 (Linking) VI - 45 IP - 4 DP - 2023 Apr TI - Targeted capture enrichment and sequencing identifies HLA variants associated with the severity of COVID-19. PG - 451-456 LID - 10.1007/s13258-022-01358-2 [doi] AB - 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. CI - (c) 2022. The Author(s) under exclusive licence to The Genetics Society of Korea. FAU - Liu, Chuanmiao AU - Liu C AD - Department of Infectious Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu Medical College, Bengbu, China. AD - National Clinical Research Center for Infectious Diseases, First Affiliated Hospital of Bengbu Medical College, Bengbu Medical College, Bengbu, China. FAU - Zhang, Li AU - Zhang L AD - Department of Infectious Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu Medical College, Bengbu, China. AD - National Clinical Research Center for Infectious Diseases, First Affiliated Hospital of Bengbu Medical College, Bengbu Medical College, Bengbu, China. FAU - Chen, Jiasheng AU - Chen J AD - Department of Infectious Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu Medical College, Bengbu, China. AD - National Clinical Research Center for Infectious Diseases, First Affiliated Hospital of Bengbu Medical College, Bengbu Medical College, Bengbu, China. FAU - Gao, Yu AU - Gao Y AUID- ORCID: 0000-0002-4210-7338 AD - School of Life Science, Bengbu Medical College, Bengbu, China. gaoyu@bbmc.edu.cn. AD - Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Bengbu, China. gaoyu@bbmc.edu.cn. AD - School of Life Science, Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, No. 2600 Donghai Road, Bengbu, 233030, China. gaoyu@bbmc.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221227 PL - Korea (South) TA - Genes Genomics JT - Genes & genomics JID - 101481027 RN - 0 (HLA-DRB3 Chains) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (HLA Antigens) SB - IM MH - Humans MH - *COVID-19/genetics MH - HLA-DRB3 Chains/genetics MH - SARS-CoV-2 MH - Histocompatibility Antigens Class I/genetics MH - HLA Antigens/genetics PMC - PMC9793816 OTO - NOTNLM OT - Allele frequency OT - Coronavirus disease 2019 (COVID-19) OT - Disease association OT - HLA-DRB3 OT - HLA-K OT - Human leukocyte antigen (HLA) COIS- The authors declare that there are no conflicts of interest. EDAT- 2022/12/28 06:00 MHDA- 2023/03/23 06:00 PMCR- 2022/12/27 CRDT- 2022/12/27 11:18 PHST- 2021/09/09 00:00 [received] PHST- 2022/12/20 00:00 [accepted] PHST- 2022/12/28 06:00 [pubmed] PHST- 2023/03/23 06:00 [medline] PHST- 2022/12/27 11:18 [entrez] PHST- 2022/12/27 00:00 [pmc-release] AID - 10.1007/s13258-022-01358-2 [pii] AID - 1358 [pii] AID - 10.1007/s13258-022-01358-2 [doi] PST - ppublish SO - Genes Genomics. 2023 Apr;45(4):451-456. doi: 10.1007/s13258-022-01358-2. Epub 2022 Dec 27.