A Gene Called APOE Could be Tied to COVID-19 Severity

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To put it mildly, COVID-19 is a puzzle. For the past three years, we’ve seen a variety of different symptoms, severities, and outcomes on an individual basis. It is known that COVID can be affected by factors such as age, gender, and certain medical conditions. However, there are other factors that can influence how COVID affects a person. New research published in NatureThis suggests that there may be another reason why certain people are more affected by COVID than others.

The APOE gene could be to blame

Scientists have struggled to identify who is most at risk of dying from COVID. Recent research by The Rockefeller University suggests that the APOE gene may be a key player in COVID cases.

In their study, researchers found that mice with gene variants previously linked to Alzheimer’s disease were at greater risk of dying when infected with COVID. In their retrospective analysis, it was suggested that human COVID patients with those same genetic mutations—which are found in 3% of the world’s population, or approximately 240 million people—were more likely to have died during the pandemic.

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“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,”Sohail Tavazoie is the Leon Hess Professor at The Rockefeller University. Telled Futurity. “This is the first time that we’ve seen such a common genetic variant associated with COVID mortality.”

The Difference Between APOE Varants

Tavazoie’s lab had previously studied the APOE gene, which plays a role in cancer metastasis. It’s known to regulate tumor-fighting immune responses and suppress the spread of melanoma.

While most people are carriers of APOE3 (the APOE3 gene), 40% of us have at least one copy each of the APOE2 and APOE4 variants. Individuals with these variants (also called alleles) produce proteins that differ by just one or two amino acids compared to APOE3—and according to Tavazoie’s research, that difference has a massive impact.

Those with the APOE4 variation are at greater risk for Alzheimer’s, which is what prompted Tavazoie and his team to wonder if APOE variants could possibly affect COVID outcomes, too.

“We had looked only at non-infectious diseases,”He said. “But what if APOE variants also made people vulnerable to an infectious agent, like SARS-CoV-2? Could they cause different immune responses against a virus?”

APOE, COVID-19 Severity

Tavazoie and the team tested more than 300 mice that were engineered to carry human APOE. They also had higher levels of virus replication in their lungs and more tissue damage.

“The results were striking,”Benjamin Ostendorf was the lead author of the study. Futurity. “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.”

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The researchers analyzed 13,000 COVID patients from the UK Biobank and compared their study results. They found that people with two copies of APOE4 were more likely than those with APOE2.

What the Research Says

Tavazoie clearly states that there is no evidence that 40% of those who have one of these alleles are at higher risk. The vaccine has also shown that the vaccine may have reduced the risk for the 3% who are carrying two APOE2 and APOE4 alleles.

He explained that the data in the UK Biobank is from the entire pandemic, and it’s possible that those who died early on may have been protected against dire outcomes if they’d been vaccinated. However, he wants to see more research about the connection between APOE-specific COVID outcomes.

“We want to better understand the function of APOE by studying how it shapes the behavior of cells in these disparate contexts of cancer, dementia, and now viral infection,” Tavazoie said.

Although this research might help us to understand COVID better, human trials that take into account vaccination are needed in order for the results of the study to be clinically applicable. If future research confirms that there is a link between APOE results and COVID outcomes, this could aid in prioritizing people for vaccines, boosters, or antiviral treatments.

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