New York, Sep 21 (IANS): In a significant find, a Nature study has linked a gene called 'APOE' with Covid-related deaths, and a retrospective analysis suggests that three per cent people on Earth (at least 230 million) have copies of this particular gene and may be at the Covid-induced death risk.

It may be the most baffling quirk of Covid: What manifests as minor, flu-like symptoms in some individuals spirals into severe disease, disability, and even death in others.

The researchers have now demonstrated that mice with gene variants previously linked to Alzheimer's disease were at greater risk of dying when infected with Covid.

Since three percent of the world population possesses these gene variants, the findings may have implications for hundreds of millions of individuals globally, the researchers noted. Roughly three percent of individuals have two copies of APOE2 or APOE4, representing an estimated 230 million people worldwide.

More than 6.5 million people have lost their lives across the globe due to Covid.

"It is clear that age, sex, and certain preconditions such as diabetes increase the risk of detrimental outcomes, but these factors don't fully explain the spectrum of Covid outcomes," said Sohail Tavazoie, the Leon Hess Professor at The Rockefeller University in New York.

"This is the first time that we've seen such a common genetic variant associated with COVID mortality," Tavazoie added.

Most people have a form called APOE3, but 40 per cent 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.

One or two amino acids make a difference. Individuals with APOE4 are at greater risk of developing Alzheimer's and atherosclerosis, and Tavazoie and Benjamin Ostendorf, a postdoctoral fellow, has, in his lab, demonstrated that APOE4 and APOE2 impact the immune response against melanoma.

As the pandemic progressed, Tavazoie and Ostendorf began to wonder whether APOE variants might impact Covid outcomes, too.

To find out, Tavazoie and colleagues first exposed more than 300 mice engineered to carry human APOE to a mouse-adapted version of SARS-CoV-2 produced by colleagues Hans-Heinrich Hoffmann and Charles M. Rice.

They found that mice with APOE4 and APOE2 were more likely to die than those with the more common APOE3 allele.

"The results were striking. A difference in just one or two amino acids in the APOE gene was sufficient to cause major differences in the survival of mice exhibiting Covid," said Ostendorf, lead author on the study.

Mice with APOE2 and APOE4 also had more virus replicating in their lungs, and more signs of inflammation and tissue damage.

"Taken together, these results suggest that the APOE genotype impacts COVID outcomes in two ways - by modulating the immune response and by preventing SARS-CoV-2 from infecting cells," Ostendorf said.

Tavazoie emphasised that there is no evidence that the 40 percent of individuals carrying only one of these alleles are at increased risk.

"Vaccination changes the picture," he added.

If future studies do confirm a link between APOE and Covid outcomes, clinicians might recommend that individuals with APOE4 or APOE2 be prioritised for vaccinations, boosters, and antiviral therapies.