This is why some people are more likely to die from COVID

Why are some people more susceptible to COVID-19?  (Getty)

Why are some people more susceptible to COVID-19? (Getty)

Why do some people have mild – or no – symptoms when infected with COVID-19, while others quickly contract serious illness and even death?

A new study published in the journal Nature may have shed light on the question.

The researchers showed that mice with gene variants previously linked to Alzheimer’s disease were at greater risk of dying when infected with COVID.

Retrospective analysis suggests that patients with the same gene variants were more likely to die from COVID during the pandemic.

About 3% of the world’s population possesses these gene variants – so the findings could have implications for hundreds of millions of individuals worldwide.

Sohail Tavazoie, the Leon Hess professor at Rockefeller University, said: “It is clear that age, gender, and certain conditions such as diabetes increase the risk of adverse outcomes, but these factors do not fully explain the spectrum of COVID outcomes.”

“This is the first time we’ve seen such a common genetic variant linked to COVID death.”

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In previous work, Tavazoie’s lab studied a gene called APOE that plays a role in cancer metastasis.

Most people have a form called APOE3, but 40% of the population has at least one copy of the APOE2 or APOE4 variant.

Individuals with APOE2 or APOE4 produce proteins that are one or two amino acids different from APOE3 protein.

As the pandemic progressed, Tavazoie and Ostendorf began to question whether APOE variants could also influence COVID results.

“We had only looked at non-infectious diseases,” he says. “But what if APOE variants also make people vulnerable to an infectious agent, such as SARS-CoV-2? Can they trigger different immune responses against a virus?”

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To find out, Tavazoie and colleagues first exposed more than 300 mice designed to carry human APOE to a mouse-modified version of SARS-CoV-2.

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,” said Ostendorf, lead author of the study. “A difference in just one or two amino acids in the APOE gene was enough to cause major differences in the survival of mice exhibiting COVID.”

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

At the cellular level, the researchers found that APOE3 appeared to reduce the amount of virus entering the cell, while animals with the other variants had less potent immune responses to the virus.

“Overall, these results suggest that the APOE genotype influences COVID outcomes in two ways,” Ostendorf says, “by modulating the immune response and by preventing SARS-CoV-2 from infecting cells.”

The lab then turned to retrospective studies in humans. In an analysis of 13,000 patients in the UK Biobank, the researchers found that individuals with two copies of APOE4 or APOE2 were more likely to die from COVID than those with two copies of APOE3.

About 3% of people have two copies of APOE2 or APOE4, representing an estimated 230 million people worldwide.

Tavazoie says: “We have taken the first step. But to be clinically useful, these results need to be assessed in prospective human trials that test individuals for their APOE genotypes and take into account the availability of vaccination, something that was not available early on.” in the pandemic and would improve COVID results across APOE genotypes.”

If future studies confirm a link between APOE and COVID results, clinicians may recommend that individuals with APOE4 or APOE2 be prioritized for vaccinations, boosters, and antiviral therapies.

Screening for APOE is fairly routine and inexpensive.

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