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• Posted March 22, 2023

'Muted' Immune Response May Explain Why COVID Is Tougher for Obese People

Obesity is a well-known risk factor for severe COVID-19, and researchers think they've uncovered a possible reason why.

Obese folks appear to have a blunted inflammatory response to COVID, leaving their immune systems less capable of fighting it, according to a recent study.

The findings were a surprise to researchers, given that severe COVID often has been tied to an overactive immune response that produces damaging levels of inflammation in humans.

People who are obese already have higher levels of inflammatory biochemicals in their blood, so it was suspected that COVID's damaging inflammation would be even worse, noted researcher Menna Clatworthy, a clinician scientist at the University of Cambridge in the United Kingdom.

"During the pandemic, the majority of younger patients I saw on the COVID wards were obese,"Clatworthy said in a university news release. "Given what we know about obesity, if you'd asked me why this was the case, I would have said that it was most likely due to excessive inflammation. What we found was the absolute opposite."

For this study, Clatworthy and her colleagues analyzed blood and lung samples taken from 13 obese patients with severe COVID who required mechanical ventilation and intensive care.

They compared those samples against 20 COVID patients who weren't obese and didn't require ventilation.

The researchers found the obese patients had underactive immune and inflammatory responses in their lungs.

In particular, lung cells and immune cells had lower levels of activity on genes responsible for producing interferons (which help control immune system response) and tumor necrosis factor (which causes inflammation).

"This was really surprising and unexpected,"Clatworthy said. "Across every cell type we looked at, we found that that the genes responsible for the classical antiviral response were less active. They were completely muted."

The team then replicated these findings in nasal immune cells from obese children with COVID, researchers said.

This is important because the nose is one of the entry points for the virus, and a powerful immune response there could ward off a severe infection, the researchers explained.

The hunger hormone leptin could be one reason why obese folks have a limited immune response to COVID, the researchers said.

Leptin also plays a role in immune response, directly stimulating immune cells. In people of normal weight, leptin levels increase in response to infection.

But obese people already have chronically high levels of leptin, and it's possible that they're not able to produce sufficient additional leptin to respond to infection, Clatworthy said. If that's the case, it would lead to inadequate stimulation of their immune cells.

The study was published recently in the American Journal of Respiratory and Critical Care Medicine.

These results suggest that the anti-inflammatory drugs used to dampen an overactive immune response in COVID patients might not be appropriate for obese patients, said co-researcher Dr. Andrew Conway Morris, of the University of Cambridge.

"What we've shown is that not all patients are the same, so we might need to tailor treatments,"Morris said. "Obese subjects might need less anti-inflammatory treatments and potentially more help for their immune system."

More information

The U.S. Centers for Disease Control and Prevention has more on obesity and COVID-19.

SOURCE: University of Cambridge, news release, March 20, 2023