Why Are People with Obesity More Vulnerable to COVID?

It was clear relatively early in the pandemic that a handful of risk factors dramatically impacted the severity of COVID-19. Among them were advanced age and obesity. Both appeared to reduce the body’s ability to fight off the infection, leaving people more prone to acute illness, hospitalization and death.

As we age, our immune system weakens, rendering us more susceptible to illness. The pandemic has highlighted the fact that obesity can trigger and exacerbate similar immunologic changes even in younger individuals.

“The biggest risk factor for about every disease is age,” says Kenneth Walsh, a professor of biochemistry and molecular genetics at the University of Virginia School of Medicine. “A lot of that might be due to the process known as ‘inflammaging.’ When you get to the bottom of lots of diseases, they have an underlying inflammatory component to them.”

Over the decades the immune system becomes “corrupted,” Walsh says, making it underactive, overactive or a combination of the two. Obesity seems to accelerate this process.

In a healthy body, adipose tissue plays a positive role, serving as reservoir of energy in times of food scarcity. Fat tissue is also full of immune system cells. And in lean, healthy individuals, it secretes factors that are anti-inflammatory and protective.

If, however, the fat tissue becomes unhealthy, as often happens in people with obesity, it can become dysfunctional and secrete hormones and other chemical signals that promote chronic low-grade inflammation. This constant simmering state—often present in elderly as well as people with obesity—is not the same as normal inflammation, which is self-limiting and part of the body’s response to infection, damaged cells and other threats. Chronic inflammation raises the risk of a number of conditions, including autoimmune diseases, certain cancers and ailments of the heart, pancreas, lungs, stomach and reproductive system. It may also be the reason a high body mass index (BMI) is associated with poorer outcomes from infectious diseases, including COVID-19.

Researchers are still working out the mechanisms by which this inflammation occurs. One hypothesis is that when fat cells become overloaded with nutrients, the resulting intercellular stress can trigger an “inflammatory cascade.”

“One way to think about it is: with obesity, people store a lot of substances in the fat cells, but they also begin to release more than normal as they grow,” says Andrew Greenberg, director of the obesity laboratory at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University. “These circulate into the blood and bind to immune cells in the liver and muscle. And this leads to the release of inflammatory factors.”

Another possibility is that when fat tissue builds up, it become hypoxic, or lacking in oxygen. This, too, can activate inflammatory pathways.

A third pathway concerns the infiltration of immune cells called macrophages in adipose tissue. In addition, Walsh says, when engorged fat cells begin to die, “the body has trouble ridding itself of this tissue. This contributes to a lot of toxicity and sets off a cascade where all sorts of bad things happen.”

Poor diet can also play a role in increasing inflammation. According to a 2019 paper in the journal Nutrients, the Western diet, which is high in sugar and bad fats and low in complex carbohydrates, fiber and healthy micronutrients, is in itself a risk factor for “metaflammation,” or chronic metabolic inflammation, particularly in people who are overweight. Among the probable mechanisms is that poor diet alters the composition of the intestinal microbiome, encouraging the production of microbial toxins, including lipopolysaccharide (LPS). Obesity can increase the gut’s permeability to those toxins, also known as gut leakiness, allowing them to be released into the bloodstream. When the body senses extra LPS, it induces an inflammatory response from immune cells.

While diet can be harmful and inflammatory, good nutrition can help reduce some of the damage caused by obesity-related issues. Some nutrients, including omega-3 fatty acids, can work to diminish inflammation. One eating plan thought to combat chronic disease is the Mediterranean diet, which is rich in fruits and vegetables, nuts, fish and healthy fats. This diet is thought to provide people with a host of protective compounds, including omega-3s and polyphenols, plant-based compounds with antioxidant properties.

Greenberg says more research is needed to determine whether supplements, including fish oil, fiber, prebiotics and probiotics, can work to reduce inflammation, boost immunity and reverse chronic conditions associated with obesity, such as diabetes. The most tried-and-true approach, though not an easy one, is weight loss, he says. And a small amount can make a difference. “They don’t have to be at their ideal body weight,” Greenberg says. “Even losing 5 to 10 percent of a person’s weight really helps improve their metabolic profile.”

Exercise, even in modest amounts, can also help reduce inflammation. According to a 2017 study published in Brain, Behavior, and Immunity, a 20-minute session of treadmill walking can stimulate an anti-inflammatory response.

Impaired immune function is just one reason obesity raises the risks of COVID-19. Type 2 diabetes, which so often accompanies obesity, also complicates COVID, as does restricted breathing (another consequence of a high BMI). A healthy diet, weight management and exercise help fortify the body in the best of times, and they are even more critical during a pandemic.

This article is part of an editorially independent Springer Nature collection that was produced with financial support from Lonza.



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