Genetic Link Discovered Explaining Why Some People Who Catch COVID-19 Don’t Become Sick

Gene protection for COVID-19 identified.

The first evidence of a genetic link explaining why some people who contract Covid-19 don’t get sick has been discovered.

A scientific and medical team led by the University of Newcastle, UK, has shown that the gene, HLA-DRB1*04:01, is found three times more often in people who have no symptoms. This suggests that people with this gene have some degree of protection against severe Covid.

The study, funded by Innovate UK, the British innovation agency, compared asymptomatic people with patients from the same community who developed severe Covid but had no underlying diseases, and is published in the HLA journal.

dr. Carlos Echevarria, University of Newcastle, UK. Credit: Newcastle University, UK

The research team believes this is the first clear evidence of genetic resistance, as this study compared severely affected humans to an asymptomatic COVID group and used next-generation sequencing to focus on the HLA genes in detail and at scale. packed together on chromosome 6. studies have scanned the whole genome, but that approach is less effective in the tissue typing complex.

Genome-wide studies can be compared to a satellite image. The high density and complexity of the histocompatibility complex and variation in different populations means that significant variation can be overlooked. For example, different alleles or versions of the same gene can have opposite effects on the immune response. This study was much more focused, comparing symptomatic with asymptomatic in the same population, revealing the allele’s “protective” properties.

The identified human leukocyte antigen gene, HLA-DRB1*04:01, is known to be directly correlated with latitude and longitude. This means that more people in Northern and Western Europe are likely to have this gene.

This suggests that populations of European descent are more likely to remain asymptomatic, yet transmit the disease to susceptible populations.

dr. Carlos Echevarria of the Translational and Clinical Research Institute, Newcastle University, who also works as a Respiratory Consultant in the Newcastle Hospitals NHS Foundation Trust and co-authored the paper, says: “This is an important finding as it may explain why some people get Covid but don’t get sick.

David Langton, ExplantLab and author of the study. Credit: ExplantLab

“It could lead us to a genetic test that can indicate who to prioritize for future vaccinations.”

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

The effect of genes being linked to geolocation is an accepted scientific concept and it is well known that HLA genes evolve over generations in response to disease-causing pathogens.

Study author David Langton, whose company ExplantLab helped fund the study through an Innovate UK research award, added: “Some of the most interesting findings were the relationships between latitude and longitude and HLA gene frequency. It has long been known that the incidence of multiple sclerosis increases with increasing latitude. This is partly due to reduced UV exposure and thus lower vitamin D levels. However, we were not aware that one of the main risk genes for MS, DRB1*15:01, is directly related to latitude.

“This highlights the complex interaction between environment, genetics and disease. We know that 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.”

The study used samples from 49 patients with severe Covid who had been hospitalized with respiratory failure, samples from an asymptomatic group of 69 hospital workers who tested positive through routine blood antibody testing, and a control group from a study investigating the relationship between HLA genotypes. and the results of joint replacement surgery.

The research used next-generation sequencing machines to in-depth study the different versions, or alleles, of the HLA genes, combined with a variety of expertise and modeling. The work was limited to samples from North East England during the initial shutdown, this reduced variation across the study groups, but more studies will be needed in the UK and other populations as there may be several copies of the HLA genes conferring resistance in other populations.

Reference: “The influence of the HLA genotype on the severity of COVID-19 infection: by David J. Langton, Stephen C. Bourke, Benedicte A. Lie, Gabrielle Reiff, Shonali Natu, Rebecca Darlay, John Burn and Carlos Echevarria, April 25, 2021, HLA.
DOI: 10.1111 / tan.14284

The work was a collaboration between Newcastle University, Newcastle Hospitals NHS Foundation Trust, Northumbria Healthcare NHS Foundation Trust and James Cook University Hospital and North Tees and Hartlepool Hospitals NHS Foundation Trust.

Co-author, Professor Sir John Burn, Professor of Clinical Genetics at Newcastle University, said: “SARS Cov-2 is one of the greatest threats facing humanity. The more we understand why some people get sick, the better we can defend ourselves against this virus and others who like it in the future.”