Gene variant identified linked to asymptomatic COVID-19

A genetic variant that might provide some protection against severe COVID-19 disease has been identified in a new study led by researchers from Newcastle University.

The scientists compared the genomic information of 69 people with mild or asymptomatic SARS-CoV-2 infections with 49 people that suffered severe COVID-19 after contracting SARS-CoV-2. They found that the gene variant HLA-DRB1*04:01 was present three times more often in asymptomatic virus carriers, suggesting that expression of this gene might lead to partial protection from severe disease.

'This is an important finding as it may explain why some people catch COVID-19 but don't get sick… It could lead us to a genetic test which may indicate who we need to prioritise for future vaccinations.' said Dr Carlos Echevarria from Newcastle University and co-author of the study, 'At a population level, this is important to us to know because when we have lots of people who are resistant, so they catch COVID-19 but don't show symptoms, then they risk spreading the virus while asymptomatic.'

However, while the study did not look into biological mechanisms, it is known that HLA-DRB1*04:01 is a human leukocyte antigen (HLA), meaning it plays a role in the human immune response. As part of the HLA complex, it contributes to differentiating between proteins of the body and 'foreign' viral or bacterial proteins. Different HLA gene variants have already been linked to susceptibility to malaria, dengue, Middle East respiratory syndrome (MERS), severe acute respiratory syndrome (SARS) and other infectious diseases.

Additionally, the HLA-DRB1*04:01 gene variant is known to be associated with latitude and longitude, which means that more people in the North and West of Europe will carry the gene. This suggests that these people are more likely to be asymptomatic spreaders of SARS-CoV-2 infection.

As this study focused only on patients from North East England, the scientists highlight that more research across the UK and worldwide will be needed and might potentially identify further variants affecting disease manifestation.

Professor Martin Hibberd, a professor of emerging infectious disease from the London School of Hygiene and Tropical Medicine, who was not involved in the study 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… which could be achieved by replication of the study findings in larger cohorts.'

Previously, Neanderthal variants have been discovered that triple the risk of developing severe COVID-19 (see BioNews 1066), and, in stark contrast, Neanderthal variants that significantly reduce the risk of developing severe COVID-19 (see BioNews 1084).

The HLA genotype study was published in the journal HLA.