Researchers in the UK are closing in on a possible genetic defense against COVID-19. The findings could help explain why some people can catch the virus without getting sick.

A team of researchers led by members at the Newcastle University, UK, reports that the gene HLA-DRB1*04:01 likely confers its bearers some sort of protection against the coronavirus, or at least, from its more severe symptoms. This conclusion was drawn from the observation that the gene is found, on average, three times as often in asymptomatic patients compared to symptomatic ones.

The study worked with patients from the same communities in the UK in order to limit the influence of other factors such as environment, location, and socioeconomic status.

Genetically insulated

According to the authors, this is the first clear evidence of genetic resistance against COVID-19. While previous research has worked with whole genomes, that approach is far less effective than focusing on individual genes, as the current paper does. A genome-wide view can miss important tidbits of information, quite like watching the forest means you don’t focus on individual trees. The current research focused on comparing symptomatic to asymptomatic members of the same community to make it easier to spot how individual genes or alleles (variations of the same gene) can help protect us from COVID-19.

HLA-DRB1*04:01, a human leukocyte antigen gene, was identified as a prime candidate in this regard. The finding is based on samples taken from 49 patients with severe COVID-19 symptoms — who had been hospitalized with respiratory failure, — 69 hospital workers who had tested positive for the virus but were asymptomatic, and a control group.

These samples were analyzed so that the team could study the different HLA alleles present in the general population of North East England during the first lockdown. The asymptomatic patients, on average, were three times as likely to have the HLA-DRB1*04:01 allele in their genomes than symptomatic patients (16.7% vs. 5.1% after adjustment for age and sex).

From previous research, we know that the incidence of the HLA-DRB1*04:01 allele in the general population is directly correlated to latitude and longitude. People in the North and West of Europe are more likely to have this allele. Sadly, this also means that these areas will have a harder time keeping the virus under control.

“This is an important finding as it may explain why some people catch Covid but don’t get sick,” explains Dr. Carlos Echevarria from the Translational and Clinical Research Institute, Newcastle University, a Respiratory Consultant in the Newcastle Hospitals NHS Foundation Trust, and co-author of the paper. “It could lead us to a genetic test which may indicate who we need to prioritize for future vaccinations.”

“At a population level, this is important for us to know because when we have lots of people who are resistant, so they catch Covid but don’t show symptoms, then they risk spreading the virus while asymptomatic.”

Populations of European descent, the authors add, are most likely to remain asymptomatic but still carry and transmit the disease to individuals that do not enjoy the same levels of genetic protection. The fact that there is a link between gene expression and geolocation is a well-established scientific concept. Genes are selected for by the unique sets of demands placed on different groups by their environment, so people living in different areas will evolve different types of genetic defences. The HLA gene is no different: they develop over generations as a response to pathogens.

“Some of the most interesting findings were the relationships between longitude and latitude and HLA gene frequency,” adds co-author David Langton, whose company ExplantLab helped fund the study. “It has long been known that the incidence of multiple sclerosis increases with increasing latitude. This has been put down in part to reduced UV exposure and therefore lower vitamin D levels. We weren’t aware, however, that one of the main risk genes for MS, that is DRB1*15:01, directly correlates to latitude.”

“This highlights the complex interaction between environment, genetics and disease. We know some HLA genes are vitamin D responsive, and that low vitamin D levels are a risk factor for severe COVID and we are doing further work in this area.”

Still, the team notes that more studies will be needed (both in the UK and other areas) as there may be different copies of the HLA genes providing resistance in other populations.

The paper “The influence of HLA genotype on the severity of COVID‐19 infection” has been published in the journal HLA.