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HLA
. 2022 Jan 23.
doi: 10.1111/tan.14560. Online ahead of print.
Association of HLA gene polymorphism with susceptibility, severity, and mortality of COVID-19: A systematic review
Paroma Deb 1 , Kaniz-E- Zannat 2 , Shiny Talukder 3 , Amirul Huda Bhuiyan 1 , Md Shariful Alam Jilani 4 5 , K M Saif-Ur-Rahman 6 7
Affiliations
- PMID: 35067002
- DOI: 10.1111/tan.14560
Abstract
Human Leukocyte Antigen (HLA) is crucial for appropriate immune responses in several viral infections, as well as in Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2). The unpredictable nature of Coronavirus Disease 19 (COVID 19), observed in both inter-individual and inter-population level, raises the question, to what extent the HLA, as part of host genetic factors, contribute to disease susceptibility and prognosis. We aimed to identify significant HLAs, those were investigated till now, for their association with COVID 19. Three databases were searched (PubMed, Cochrane library, and Web of Science) and articles published between Jan'2020 to May'2021 were included for in-depth analysis. Two separate teams including four observers independently extracted the summary data, with discrepancies resolved by consensus. This study is registered with PROSPERO (CRD42021251670). Of 1278 studies identified, 36 articles were included consisting of 794,571 participants. Countries from the European region appeared in the highest number of studies and vice versa for countries from South East Asia. Among 117 significantly altered alleles, eighty-five (72.65%) were found to have a positive correlation with COVID 19 and thirty-two (27.35%) alleles were observed having a negative correlation. HLA A*02 is the most investigated allele (n=18) and showed contradictory results. Non-classical HLA E was explored by only one study and it showed that E*01:01 is associated with severity. Both in silico and wet lab data were considered and contrasting results were found from two approaches. Although several HLAs depicted significant association, nothing conclusive could be drawn because of heterogeneity in study designs, HLA typing methods, etc. This systematic review shows that, though HLAs play role in COVID 19 susceptibility, severity, and mortality, more uniformly designed, interrelated studies with the inclusion of global data, for use in evidence-based medicine are needed. This article is protected by copyright. All rights reserved.
Keywords: COVID-19; Genetic susceptibility; HLA polymorphism; SARS CoV-2; Systematic review.