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Association between the HLA genotype and the severity of COVID-19 infection among South Asians.

ABSTRACT: Regional variations are found in the incidence and severity of the COVID-19 infection. Human leukocyte antigen (HLA) polymorphism is one of the genetic factors that might have an impact on the outcome of the disease. This study explored the association between the HLA genotype and the severity of COVID-19 among patients from South Asia. Blood samples from 95 Asians (Bangladeshis, Indians, and Pakistanis) with COVID-19 were collected. The patients were divided according to the severity of their infection: mild (N = 64), severe (N = 31), and fatal (N = 20). DNA was extracted from all samples, and HLA genotyping was performed for both class I (A, B, and C) and class II (DRB1, DQA1, and DQB1) using the PCR-rSSO (polymerase chain reaction-reverse sequence-specific oligonucleotide) molecular method. The frequency of HLA-B*51 was significantly higher among patients in the fatal group than among those in the mild infection group (15% vs. 4.7%, p = 0.027). Additionally, the frequency of HLA-B*35 was significantly higher in the mild infection group than in the fatal group (21.1% vs. 7.5%, p = 0.050 [a borderline p-value]). In terms of HLA class II, DRB1*13 was significantly observed in the fatal group than in the mild infection group (17.5% vs. 11.3%, p = 0.049). However, the p-value for all alleles became insignificant after a statistical correction for the p-values (p_c = 0.216, p_c = 0.4, and p_c = 0.49, respectively). Compared with all published data, this study highlights that the association between the HLA system and the COVID-19 outcome might be ethnic-dependent. Genetic variation between populations must be examined on a wider scale to assess infection prognosis and vaccine effectiveness.

SUBMITTER: Naemi FMA

PROVIDER: S-EPMC8251353 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The impact of COVID-19 varies markedly, not only between individual patients but also between different populations. We hypothesised that differences in human leukocyte antigen (HLA) genes might influence this variation. Using next generation sequencing, we analysed the class I and class II classical HLA genes of 147 individuals of European descent experiencing variable clinical outcomes following COVID-19 infection. Forty-nine of these patients were admitted to hospital with severe respiratory disease. They had no significant pre-existing comorbidities. We compared the results to those obtained from a group of 69 asymptomatic hospital workers who evidence of COVID exposure based on blood antibody testing. Allele frequencies in both the severe and asymptomatic groups were compared to local and national healthy controls with adjustments made for age and sex. With the inclusion of hospital staff who had reported localised symptoms only (limited to loss of smell/taste, n = 13) or systemic symptoms not requiring hospital treatment (n = 16), we carried out ordinal logistic regression modelling to determine the relative influence of age, BMI, sex and the presence of specific HLA genes on symptomatology. We found a significant difference in the allele frequency of HLA-DRB1*04:01 in the severe patient compared to the asymptomatic staff group (5.1% vs. 16.7%, P = .003 after adjustment for age and sex). There was a significantly lower frequency of the haplotype DQA1*01:01-DQB1*05:01-DRB1*01:01 in the asymptomatic group compared to the background population (P = .007). Ordinal logistic regression modelling confirmed the significant influence of DRB1*04:01 on the clinical severity of COVID-19 observed in the cohorts. These alleles are found in greater frequencies in the North Western European population. This regional study provides evidence that HLA genotype influences clinical outcome in COVID-19 infection. Validation studies must take account of the complex genetic architecture of the immune system across different geographies and ethnicities.

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Association between the HLA genotype and the severity of COVID-19 infection among South Asians.

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