Gene protection for COVID-19 identified

#COVID19 #immunology #coronavirus #MHC #HLA

The first evidence of a genetic link explaining why some people who catch COVID-19 don't become sick has been discovered.

A scientific and medical team led by Newcastle University, UK, have demonstrated that the gene, HLA-DRB1*04:01, is found three times as often in people who are asymptomatic. This suggests that people with this gene have some level of protection from severe COVID.

The study, funded by Innovate UK, the UK's innovation agency, compared asymptomatic people to patients from the same community who developed severe COVID but had no underlying illnesses, and is published today in the HLA journal.

The study team believe this is the first clear evidence of genetic resistance because this study compared severely affected people with an asymptomatic COVID group and used next generation sequencing to focus in detail and at scale on the HLA genes which are packed together on chromosome 6. Other studies have scanned the whole genome but that approach is less effective in the tissue typing complex.

Genome wide studies can be likened to a satellite image. The high density and complexity of the histocompatibility complex and variation in different populations means 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 focused and compared symptomatic to asymptomatic in the same population revealing the "protective" qualities of the allele.

It is known that the human leukocyte antigen gene identified, HLA-DRB1*04:01, is directly correlated to latitude and longitude. This means more people in the North and West of 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 from the Translational and Clinical Research Institute, Newcastle University who also works as a Respiratory Consultant in the Newcastle Hospitals NHS Foundation Trust and is a co-author of the paper says: "This is an important finding as it may explain why some people catch COVID but don't get sick.

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