DNA testing could improve outcomes for patients with COVID-19, according to preliminary research posted on bioRxiv. By posting preprints on bioRxiv, authors are able to make their findings immediately available to the scientific community and receive feedback on draft manuscripts before they are submitted to journals. At this time, information on COVID-19 research needs to be shared rapidly and openly to inform the global public health response and to help save lives.
In his preprint, Dr Bill Gibson, a Professor in the Department of Medical Genetics at the University of British Columbia, USA, has highlighted the potential benefits of testing COVID-19 patients for genetic variants of ACE2. ACE2 is the protein identified as the key point of entry for the new coronavirus into human cells. By searching genetic databases, Dr Gibson and his team identified several variants already present in the human population that could affect how the virus binds the protein and enters the cell. Finding out whether such variants do influence the severity of the disease could help clinicians make more informed treatment decisions during the pandemic.
Could genetic variants influence the course of COVID-19?
There is, as yet, no direct laboratory evidence that different genetic variants are influencing the course of this disease; however, many countries have observed startling differences in the COVID-19 death rates between men and women. In the UK and USA, men with COVID-19 are dying at twice the rate as women with the disease.
This could be partly explained by the fact that the gene for ACE2 lies on the X chromosome, meaning males only have a single version of the gene. If the copy they inherited makes them more susceptible to the virus, then their cells will only express that more susceptible version. Because females carry two copies of the gene, any viral susceptibility coming from one variant would be mitigated by the ACE2 protein made from their second ACE2 allele.
There are many other factors that will influence the severity of COVID-19, says Dr Gibson. His preliminary analysis shows that 1 or 2% of Ashkenazi Jewish individuals and around 1% of non-Finnish Europeans carry one of these ACE2 variants, but they are rarer in other populations and almost absent in East Asians.
“Some portion of this difference between men and women in COVID-19 morbidity and mortality may be genetic, we just don’t know how much”, he said.
The quickest way to find these variants is to examine the ACE2 gene in unusual cases of COVID-19, taking what is known as the ‘extreme phenotypes’ approach. For example, children are less likely to come down with severe disease after being exposed to COVID-19. Therefore, any child with unusually severe COVID-19 (requiring ICU care, for example), could, in principle, have this gene sequenced where resources allow, suggests Dr Gibson. However, we would need to add up the data from many, many children and adults before we could be sure that rare ACE2 variants truly affect disease severity, he said.
“What we have right now is a model, and hopefully a useful one. In some places around the world doctors are already making difficult decisions about who to treat and how: a genetic test such as this could arm clinicians with the knowledge they need to intervene earlier in certain cases, and thereby save more lives.”
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