In a recent pre-print study posted to Research Square* whilst under review for publication in Molecular Biology reports, researchers evaluated the association between human leukocyte antigens (Hla) alleles and severity of coronavirus disease 2019 (COVID-19).
COVID-19 has profoundly impacted many lives across the globe. While the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection led to severe disease with many hospitalizations and deaths, patients diagnosed with mild infection recovered at home with conservative treatment. The diverse clinical presentation of the viral infection warrants an understanding of the genetic constitution of the patients. This would enable the prediction of the patient’s response to infection and help devise treatment measures accordingly.
The Hla system essentially contributes to the host immune response by the regulation of inflammatory mediators such as cytokines and chemokines that are responsible for the clinical manifestation of COVID-19. This system comprises three classes of genes (Class I, III, and II), among which Hla-C, A, and B haplotypes of Class I genes and Hla-DQ, DP, and DR haplotypes of Class II genes provide resistance to the host against viral dissemination. Polymorphisms in alleles could increase susceptibility and affect the clinical outcome of SARS-CoV-2 infections.
Although previous studies have investigated the role of the Hla system in COVID-19 severity, the findings have been varied, probably due to the effect of geographical differences on the genetic polymorphisms.
About the study
In the present prospective study, the researchers investigated the association between HLA haplotypes of Class II and I genes and COVID-19 severity. They assessed whether the alleles could predict the risk of severe SARS-CoV-2 infection.
A total of 59 Turkish COVID-19 patients diagnosed by reverse-transcriptase polymerase chain reaction (RT-PCR) from August 2020 to August 2021 were included in this study. Out of the 59 patients, 30 required intensive care unit (ICU) admission and were classified under the severe group (SG). These patients had dyspnea, oxygen saturation equal to or lesser than 93%, respiratory frequency equal to or greater than 30 breaths/minute, 50% ratios of partial pressures in arteries and inspired oxygen fraction within one to two days, septic shock, respiratory failure, or multiorgan failure or dysfunction. The non-severe group (NSG) comprised 29 participants who required follow-up examination in the clinics. Both the study groups were compared with a group of 30 healthy controls (HC).
Demographics, comorbidities, laboratory, and clinical findings of the participants were obtained. Blood was collected from all participants, post which their deoxyribonucleic acid (DNA) was isolated and used for Hla typing at a Turkish hospital laboratory. The sequence-specific oligonucleotide (SSOP) technique was employed for HLA tissue typing. Major histocompatibility complex (MHC) Hla haplotypes B, A, C of Class I genes and HLA haplotypes DQB1, DRB1, and DQA1 of Class II genes from each parent of an individual are matched for Hla typing and all three groups were comparatively assessed.
Results and discussion
Significant age differences were observed between the SG and HC groups with an average age of 41 years in SG. Mortality, as well as comorbidities such as cardiovascular disease and hypertension, were substantially more among SG participants. These findings indicate that advanced age and comorbidities increase the risk of severe COVID-19.
In the parent-1 Hla group, A*32, A*26, B*41, DRB1*14, DRB1*8, C*14, and C*16 alleles were present in SG whereas the presence of B*52, C*5, B*27, and aDQB1*4 alleles was noted in both study groups but not in HC.
Additionally, both NSG and SG groups demonstrated B*37, A*68, B*58, DQB1*4, C*14, and DRB1*16 alleles from parent-2 Hla groups. These alleles are known to enhance COVID-19 susceptibility. Parent-2 HLA groups B*15, A*1, B*54, and DQB1*4 were exclusively present in HC, indicative of their protective activity against COVID-19.
The study findings showed that the A*32 Hla allele was associated with severe COVID-19 since this allele was the only one identified in parents 1 and 2 in SG. This finding indicates that the Hla-A*32 allele has a prognostic value in COVID-19 severity. However, future studies with large gene databases and bigger sample sizes must be conducted to decipher the genetic diversity in the Hla system based on regional differences. This would enhance knowledge on the varying allele distribution and frequencies and enable better prediction of severe SARS-CoV-2 infection.
Treatment strategies could be tailored based on the Hla risk assessment for the administration of the most appropriate therapeutic regimens to patients. This would lead to a reduction in the morbidity and mortality of COVID-19.
Research Square publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.