The virus which causes COVID-19 (SARS-CoV-2) has been particularly cryptic in its strike pattern. There is a wide variation in expression and severity of symptoms from person to person; with some people experiencing nothing more than a dry cough, and others bedbound in intensive care. In working out why this is the case, researchers are turning to data from biobanks in the hope of uncovering a genetic factor which may be at play.
UK Biobank has crept into the news recently as one of many facilities around the world analysing and releasing such data to support research on COVID-19. Biobanks are large stores of biological material, donated by volunteers, with the purpose of creating a big pool of data. This data includes genetic, lifestyle and health information representative of the wider population, within which significant patterns of the virus’ transmission may be unearthed.
Biobanks could help to decode the mystery behind who gets sick and why, through the exploration of the role our genes play in response to infection. The most searched for clues when scouring gene data from biobanks are genetic biomarkers; certain sequences of DNA found more frequently among sufferers of a specific disease. The idea being that this correlation may indicate a causal relationship.
Previous successes which stemmed from biobank data include the linking of loss-of-function mutations with type 2 diabetes, asthma and coronary heart disease. Once such a mutation is identified, developing a drug which targets the gene or its pathway becomes the next mission for the pharmaceutical frontline. However, these biomarkers can also be used to identify and prioritise certain patients who require preventative treatment more urgently.
The UK biobank, among others, has made available its coronavirus-related data for examination of both genetic and non-genetic factors. The emerging worldwide network of researchers and their data may provide certain clues as to why some people with no underlying health conditions may be affected by the virus so severely.
Here are the three of the more prominent theories of person to person differences responsible for COVID-19’s irregularity of impact.
1 It may be the case that there exists an underlying mutation in the human gene for an enzyme called ACE2. The spike (S) protein in the virus enables its entry into target cells. Once primed and close to the cell, SARS-CoV-2 uses a human enzyme known as angiotensin-converting enzyme 2 (ACE2) to hotwire the entry system and break in, take over the cell’s protein production line, and begin synthesising copies of the virus.
2 The next potential genetic target to have made it into my top 3 was discovered back in the 2002 pandemic of another coronavirus – SARS-Cov. Certain immune system genes, known as human leukocyte antigen genes, are involved with the recognition of an invading pathogen. On April 17th, a paper published in the American Journal of Virology showed that variability in these genes may be affecting people’s vulnerability to the virus. This information would be hugely beneficial for deciding which members of the public should be prioritised for treatment when it is developed.
3 Alternatively, and dubiously, a new factor of interest has cropped up among news reports. A group of researchers in China have published a non-peer-reviewed scientific paper alleging a relationship between blood type and susceptibility to the virus. The association was made that people with blood group A had a higher incidence of COVID-19, and those with blood group O showed resistance.
Whilst this association is yet to be confirmed, it may be an interesting avenue of research. There are many potential benefits of this discovery, such as avoiding false positive results when trialling a vaccine – you wouldn’t want a vaccine to seem effective, only to find years later that all the members of the trial group were blood group O. However, it should be said that as the association was published in a pre-print it be taken with a pinch of salt, and that more work in this area is due to be carried out.
A lot of information is coming to light regarding predispositions to the virus. Biobanks have played an essential role in shedding this light, and will hopefully continue to do so in aid of developing the big guns – a COVID-19 vaccine. A lot of funding which goes towards the fight against the virus is focussed on the immediate treatment of sufferers, to alleviate their current state. Biobanks, however, are helping fight the battle in a different manner with the longer term goal of eradicating this villainous strain of the spiky coronavirus for good.
Written by Marlon Jasielczuk – Lando and edited by Ailie McWhinnie.