July 14, 2020 -- Stephen O’Rahilly recently spent a week in a hospital, sick with COVID-19 and struggling to breathe.
“My lungs were quite badly affected,” says O’Rahilly, 62, who spent almost a week getting extra oxygen in what’s known as a high-intensity care unit in the U.K.
The experience got him thinking: While about 80% of cases of COVID-19 can be treated at home, why do some people, including him, wind up with more severe infections?
Besides his age, O’Rahilly knew he had another strike against him when it comes to COVID-19 infection: his weight. His BMI, or body mass index, is over 30.
O’Rahilly, who directs the MRC Metabolic Diseases Unit at Cambridge University, is considered one of the world’s leading obesity researchers. He was knighted in 2013 by Queen Elizabeth II for his work, which includes the discovery of a genetic condition that robs the body of the hormone leptin, which controls appetite and weight.
Obesity a Known COVID Risk
It has become clearer that people who are obese are one of the groups at highest risk from the disease, regardless of their age. The CDC recently refined its risk categories for COVID-19, stating that obesity was as big a risk for COVID as having a suppressed immune system or chronic lung or kidney disease. The agency also lowered the bar for where that risk starts -- from a BMI of 40 to a BMI of 30. Roughly 40% of Americans have a BMI over 30.
The CDC’s change in BMI risk comes after a British study of more than 17 million people found that people living with severe obesity were about twice as likely to die from COVID-19 as people who were not obese. That was true even after other things like their age and sex were taken into account. The study also found that risk rises with the degree of obesity. The bigger a person, the higher their risk of a COVID-19 death.
During the 2009 H1N1 influenza pandemic, there was a strong link between obesity and bad outcomes for patients. People with obesity were at a higher risk of dying during flu pandemics in the 1950s and 1960s, too.
Markers Hint to Reason
So why is that? Some people say that being heavier just makes it harder to breathe, especially when you’re sick.
“On the radio, you heard people making really facile comments about big tummies and pressing on the diaphragm and bad for ventilation and rather simplistic thoughts about why obesity might be associated with bad outcomes, and I wondered about that,” O’Rahilly says, “and I thought it was a bit unlikely.”
Instead, he thinks the risk comes from the fact that fat makes and regulates hormones.
For example, people who are obese make more of something called “complement” proteins. These proteins can trigger out-of-control blood clotting, which is a problem in patients with severe COVID-19.
People with obesity also have lower blood levels of a hormone called adiponectin. Recent studies in mice show that adiponectin protects the lungs. O’Rahilly thinks that if you have lower levels to begin with, you may be more likely to have lung inflammation during an infection like COVID-19.
Adiponectin also helps keep blood vessels clean and open.
A Mixture of Problems
So if the insides of your blood vessels are sticky, and a virus causes your immune system to go haywire and create more blood clots, that sets the stage for blockages. These blockages can cause heart attacks, strokes, and lung damage -- all problems seen in COVID-19 patients.
To compound the problem, people with obesity appear to have more ACE2 receptors on their cells than others. ACE2 receptors are the doors the virus uses to infect cells and then make more copies of itself.
A recent study found that fat tissue has more ACE2 receptors than lung cells do. More ACE2 may mean more virus in the body, says Carl Lavie, MD, medical director of cardiac rehabilitation and prevention at Ochsner Health in New Orleans.
Lavie recently published a paper on obesity and COVID-19 in Mayo Clinic Proceedings.
On top of all that, there’s insulin resistance, which is more common in people who are obese and may turn up the ACE2 receptors even further.
Insulin is a hormone that’s critical for maintaining blood sugar levels. In obesity and some other conditions, cells of the body stop responding as well to insulin’s message to use sugar as energy and take it out of the blood and instead it stores it as fat. In response, the pancreas tries to turn up the volume by cranking out more insulin. The problem is that insulin doesn’t just impact blood sugar levels.
“One of the things it affects is the ACE2 receptor that this virus binds to,” says Francis Finucane, MD a consultant endocrinologist at Galway University Hospital in Galway, Ireland.
“If you’re insulin-resistant, you’ve got more receptors for those spike proteins on your cell surfaces, say, for example on your lung cells,” he says.
“We think that would make it easier for viruses to get into those lung cells, and that more viruses would get in, and that would create a worse COVID infection, and that would account for at least some of the variation in the severity of the disease,” Finucane says.
He says researchers are planning studies that will try to prove some of these theories.
Role of Insulin
His team is going to try to measure insulin resistance in COVID-19 patients through blood tests, then look at how sick they are.
Finucane admits that may not show anything. Illness can make people insulin-resistant. So they might be measuring an effect of the infection, and not a cause.
A different team of researchers in the U.K. is taking a different approach. They’re going to mine data on tens of thousands of patients to see if genes for insulin resistance are tied to COVID-19 severity or survival.
Learning the root causes can help doctors develop strategies to help protect obese patients. For example, there are ways to improve insulin sensitivity relatively quickly through diet, physical activity, and drugs.
“I’m being facetious here, but we may need to outlaw chocolate and sugar-sweetened beverage to reduce the population risk from COVID-19,” Finucane says.