DNA Providing New Clues to Why COVID-19 Hits People Differently

Since the beginning of the pandemic, the mercurial nature of the coronavirus has been on display. Some people get mild, cold-like illnesses or even have no symptoms when infected, while other people become severely ill and may die from COVID-19, the journal JAMA Oncology reported.

What determines that fate is complicated and somewhat mysterious. Researchers are looking at a wide variety of factors that may play a role — everything from demographics to preexisting conditions to vaccination status and even genetic clues.

Researchers know that older people are more likely to have severe complications of the disease. The unvaccinated, too, have an increased risk of hospitalization and death compared with people who have gotten their COVID shots.

Unvaccinated people age 50 and older were 12 times as likely to die from COVID-19 as vaccinated people who had gotten two or more booster shots, August data from the U.S. Centers for Disease Control and Prevention indicate. For instance, among the unvaccinated there were 5.46 deaths per 100,000 people on August 28, compared with 0.49 per 100,000 for those with two-plus boosters.

Even among the vaxxed the number of shots counts. That same month, people 50 and older who got their first two shots and only one booster were nearly three times as likely to die (1.27 deaths per 100,000) as their peers who got two or more boosters.

A litany of health conditions, including heart disease, kidney disease, chronic obstructive pulmonary disease (COPD), diabetes and obesity, increase the risk of bad outcomes from COVID-19 at any age. Yet some types of asthma may protect against the disease (SN: 5/2/22).

Cancer patients are among the most vulnerable to COVID-19. But even among cancer patients, some people are more vulnerable than others.

Cancer patients who are immunosuppressed, either because of problems with their immune systems or because they are taking immune-dampening drugs, are more likely to get severe COVID-19, die or develop cytokine storm — a whirlwind of immune chemicals that can set off tissue- and organ-damaging inflammation, researchers report. The effect was worse for immunosuppressed people who were getting immunotherapy for cancer, compared with people getting other chemotherapies or no treatment.

That means cancer patients with weakened immune systems “should be very careful and adopt strict measures to prevent them from catching COVID-19,” says study coauthor Chris Labaki, a cancer researcher at Dana-Farber Cancer Institute in Boston.

“Wear masks as much as possible, clean everything, including washing your hands. Maybe don’t go to crowded public places where the chance of catching COVID-19 might be higher.” People who have cancer patients in their lives may also want to take more care to avoid the coronavirus, he says.

But young and otherwise healthy people may get really sick, be hospitalized or even die from COVID-19 too. It’s hard to predict who might succumb, but researchers are searching for genetic clues.

Some studies have found that versions of genes inherited from Neandertals may protect against COVID-19, while other genetic heirlooms passed down from Neandertals can up the risk of severe disease (SN: 2/17/21; SN: 10/2/20).

A massive international study examining DNA from more than 28,000 COVID-19 patients and almost 600,000 people who hadn’t been infected (to the best of their knowledge) confirmed that inheritance from Neandertals is involved in COVID-19 susceptibility.

The study also confirmed a previous finding that people with type O blood may have some protection against getting infected with the coronavirus (SN: 7/8/21). Exactly what accounts for the protection is still not known.

People with rare variants in a gene called toll-like receptor 7, or TLR7, are 5.3 times more likely to get severe COVID-19 than those who don’t have the variants, the team also reported November 3 in PLOS Genetics. Biologically, the link makes sense. TLR7’s protein is involved in signaling the immune system that a virus has invaded. Part of its duties include marshaling interferons, immune system chemicals that are some of the first responders to viral infections (SN: 8/6/20). Interferons warn cells to raise their antiviral defenses and help to kill infected cells.

A gene called TYK2 is involved in producing some interferons. Genetic variants in that gene raise the risk of developing lupus, but may protect against coronavirus infection, researchers report in a separate study also published November 3 in PLOS Genetics. While riling up interferons may fend off the coronavirus, when there is no virus to combat, the immune system may damage the body with friendly fire, producing lupus or other autoimmune diseases. Such genetic trade-offs are common (SN: 10/19/22).

Evidence links many other genes to COVID-19 outcomes, multiple large studies have found. Some of those findings may hint at drugs that could better treat the disease.

But the problem with all of these studies is that they can’t tell any individual what their chances are of a bad outcome from catching COVID-19. For instance, the DNA testing company 23andMe tells me that I have less than 2 percent Neandertal DNA (SN: 5/22/18). I don’t know whether that includes the variants that would make me more susceptible to severe disease or the ones that protect against infection. What if I got both? And how does that play with my blood type and all the other genetic variants I may carry?

Then you have to factor in your age, your health, your environment. Let’s face it, that last one is probably the most important. For instance, if you have a job that exposes you to multiple people, you’re at higher risk of getting COVID-19 than someone who works from home.

There’s nothing you can do about the genetic hand you’re dealt (at least not until gene editing is perfected). Many experts I talk to say that improving indoor air in public buildings is what is really needed to avoid infection. That’s also out of most people’s hands. But there are still things you can do to lessen your risk. Labaki’s advice to cancer patients — mask, avoid crowds, wash your hands — plus staying up-to-date on vaccinations is good for everyone.

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