The influence of HLA genotype on the severity of COVID‐19 infection

  1. David J. Langton
  2. Stephen C. Bourke
  3. Benedicte A. Lie
  4. Gabrielle Reiff
  5. Shonali Natu
  6. Rebecca Darlay
  7. John Burn
  8. Carlos Echevarria

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Abstract

The impact of COVID‐19 varies markedly, not only between individual patients but also between different populations. We hypothesised that differences in 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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  1. Version published to 10.1111/tan.14284
  2. ScreenIT

    SciScore for 10.1101/2020.12.31.20249081: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Blood antibody testing was carried out using the Medicines and Healthcare Regulatory Agency (MHRA) approved Abbott (Ilinois, United States) or Roche tests (Basel, Switzerland) which detect immunoglobulin (Ig) G antibodies to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).
    Ig) G
    suggested: None
    Software and Algorithms
    SentencesResources
    DNA was the quantified using the Thermo Fisher Qubit dsDNA BR Assay kit and standardised to 25ng/ul.
    Thermo Fisher Qubit
    suggested: (Thermo Fisher Qubit fluorimeter, RRID:SCR_018095)
    Haplotypes were estimated for DRB1-DQA1-DQB1 also in UNPHASED.
    UNPHASED
    suggested: (UNPHASED, RRID:SCR_009056)

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • No funding statement was detected.
    • No protocol registration statement was detected.

    About SciScore

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  3. Version published to 10.1101/2020.12.31.20249081 on medRxiv