June 4, 2021

expert reaction to study looking at the gene HLA-DRB1*04:01 in people with asymptomatic SARS-CoV-2 infection or severe COVID-19 disease

A study published in the HLA journal looks at the influence of the HLA genotype on the severity of COVID-19 infection.

(Clarifying comment from one of the study authors (not a third-party comment):

Prof Sir John Burn, Professor of Clinical Genetics, Newcastle University, said:

“Genomic studies seeking evidence of disease causation due to HLA tissue types are difficult because of the very large number of alleles at the multiple genes in the Major Histocompatibility Complex.  This study compared extreme Covid19 phenotypes using next gen sequencing of the system.  The study cannot alone  be definitive given the challenge of multiple testing but is highly suggestive and biological plausible.

“The failure of Genome Wide Association Studies to identify an HLA influence does not exclude a significant influence on severity of specific alleles, given the complexity of the system. A useful analogy is the difference between satellite imagery and well equipped ground surveillance.

“We look forward to replication HLA studies in view of the value for further understanding disease mechanism.”)

Prof Martin Hibberd, Professor of Emerging Infectious Disease, London School of Hygiene & Tropical Medicine, said:

“While this paper raises some interesting ideas, the findings need to be replicated before firm conclusions can be made.  For this type of investigation, typically thousands of subjects need to be investigated to reach robust significance levels.  There have now been a number of studies of sufficient scale, that have been able to show good evidence of gene involvement such as blood group type, but not yet HLA involvement.  I think for these novel findings we need more evidence, which could be achieved by replication of the study findings in larger cohorts.”

‘The influence of HLA genotype on the severity of COVID-19 infection’ by David J. Langton et al. was published in the HLA journal.

DOI: 10.1111/tan.14284

All our previous output on this subject can be seen at this weblink:

www.sciencemediacentre.org/tag/covid-19

Declared interests

None received.