Genetic link discovered explaining why some people who get COVID-19 don’t get sick
The first evidence of a genetic link as to why some people who get 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 HLA-DRB1 * 04: 01 gene is found three times more often in asymptomatic people. This suggests that people with this gene have some level of protection against severe Covid.
The study, funded by Innovate UK, the UK’s innovation agency, compared asymptomatic people to patients in the same community who developed severe Covid but had no underlying disease, and is published in the HLA newspaper.
The study team believe this is the first clear evidence of genetic resistance, as this study compared severely affected people with an asymptomatic COVID cluster and used next-generation sequencing to focus in detail and large scale on HLA genes which are clustered on chromosome 6. Other studies have scanned the entire genome but this approach is less efficient 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 the variation in different populations means that significant variation can be overlooked. For example, different alleles or versions of the same gene could have opposite effects on the immune response. This study was much more targeted and compared symptomatic to asymptomatic in the same population revealing the âprotectiveâ qualities of the allele.
The identified human leukocyte antigen gene, HLA-DRB1 * 04: 01, is known to correlate directly 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 will be more likely to remain asymptomatic but still transmit the disease to susceptible populations.
Dr Carlos Echevarria of the Institute for Translational and Clinical Research at Newcastle University, who also works as a respiratory consultant at the Newcastle Hospitals NHS Foundation Trust and is a co-author of the article, says: âIt is an important finding because it may explain why some people get the Covid but don’t get sick.
“This could lead us to a genetic test that could indicate who we should prioritize for future vaccinations.”
âAt the population level, it is important that we know this because when we have a lot of resistant people, then they catch Covid but do not show symptoms, then they risk spreading the virus while being asymptomatic. “
The effect of geolocation related genes is an accepted scientific concept and it is well known that HLA genes develop over generations in response to pathogenic pathogens.
Study author David Langton, whose company ExplantLab helped fund the study with an Innovate UK research award, added: âSome of the most interesting findings were the relationship between longitude and latitude. and the frequency of the HLA gene. It has long been known that the incidence of multiple sclerosis increases with increasing latitude. This has been attributed in part to reduced UV exposure and therefore lower vitamin D levels. However, we did not know that one of the main risk genes for MS, namely DRB1 * 15:01, was directly correlated with latitude.
âIt highlights the complex interplay between environment, genetics and disease. We know that some HLA genes are sensitive to vitamin D and that low levels of vitamin D are a risk factor for severe COVID and we are continuing our work in this area. “
The study used samples from 49 patients with severe Covid who had been hospitalized for respiratory failure, samples from an asymptomatic group of 69 hospital workers who had tested positive in routine blood antibody blood tests and a control group of a study on the relationship between HLA genotypes and the outcome of joint replacement surgery.
The research used next-generation sequencing machines to thoroughly study different versions, or alleles, of HLA genes, which was combined with a variety of expertise and modeling. Work was limited to samples from north-east England during the first lockdown, this variation reduced in study groups, but further studies will be needed in the UK and other populations as there may be different copies of the HLA genes offering resistance in other populations.
Reference: “The influence of the HLA genotype on the severity of COVID-19[female[feminine 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 the University of Newcastle, the Newcastle Hospitals NHS Foundation Trust, the Northumbria Healthcare NHS Foundation Trust as well as the James Cook University Hospital and the North Tees and Hartlepool Hospitals NHS Foundation Trust.
Co-author Professor Sir John Burn, Professor of Clinical Genetics at Newcastle University, said: âSARS Cov-2 is one of the greatest threats humanity has faced. The more we understand why some people get sick, the better we will be able to defend ourselves against this virus and others like it in the future. “