Why do some people become seriously ill with COVID-19, or suffer fatalities, while for others the condition manifests as a ‘cold-like’ set of symptoms? The answer could lie with genetics.
Researchers from Rockefeller University have identified a common gene variant linked to COVID-19 mortality. It is estimated that three percent of the world’s population possesses these gene variants, hence the findings carry potential implications for hundreds of millions of people.
The researchers set out to identify the genetic underpinnings of COVID-19, using an animal model. It was found that mice with gene variants previously linked to Alzheimer’s disease were at greater risk of dying when infected with the SARS CoV-2 virus.
The information was used to construct a retrospective review of individuals who had the same gene variant. It was established that these patients s were more likely to have died of COVID -19throughout the pandemic.
While there are other factors that affect the seriousness of a COVID-19 infection, such as sex, age, and pre-conditions like diabetes, these factors alone cannot account for mortality. The other important factor isa common genetic variant.
A gene called APOE, one that plays a role in cancer metastasis, is the critical key. After demonstrating that the gene suppresses the spread of melanoma and regulates anti-tumour immune responses, the researchers began looking at its different forms (alleles).
Most humans have a form called APOE3. However, 40 percent of the population carries at least one copy of the APOE2 or APOE4 variant. Individuals with APOE2 or APOE4 produce proteins that differ from APOE3 protein by one or two amino acids.
When it comes to understanding COVID-19, one or two amino acids make a difference. To demonstrate this, the researchers exposed more than 300 mice engineered to carry human APOE to a mouse-adapted version of SARS-CoV-2. It was discovered that mice with APOE4 and APOE2 were more likely to die than those with the more common APOE3 allele.
The reason for the deaths was because mice with APOE2 and APOE4 possessed more of the virus replicating in their lungs, together with more signs of inflammation and tissue damage.
The data suggests that the APOE genotype impacts COVID outcomes in two ways: By modulating the immune response and by preventing SARS-CoV-2 from infecting cells.
The comparison with patients established that individuals with two copies of either APOE4 or APOE2 were more likely to have died of COVID-19 than those with two copies of APOE3.
The research appears in the journal Nature, titled “Common human genetic variants of APOE impact murine COVID-19 mortality.”