'Obesity should not be dismissed': Excess weight drives inflammation, hypoventilation behind COVID-19 complications
New data on underlying conditions among people hospitalized with COVID-19 reveal that the novel coronavirus is disproportionately affecting people with obesity, who are far more likely to experience severe complications compared with people without excess weight. Some of the most severe complications of COVID-19 — namely, acute respiratory failure or acute respiratory distress syndrome — can be driven by conditions already present in a person with obesity, such as chronic, low-grade inflammation and hypoventilation.
“Individuals with obesity can have hypoventilation at baseline, and that increases with the degree of obesity,” Ania Jastreboff, MD, PhD, DABOM, assistant professor of medicine and pediatrics (endocrinology and metabolism), director of weight management and obesity prevention at the Yale Stress Center, Yale University School of Medicine, and vice chair of The Obesity Society Clinical Committee, told Healio. “Individuals with obesity can have lower operating lung volumes. Some may have obesity hypoventilation syndrome. If an individual is not ventilating their body adequately at baseline, and you add on top of this COVID-19 infection with acute respiratory distress syndrome, individuals with obesity are already at a physiologic disadvantage in terms of their respiratory status as they work to fight the virus off.”
Obesity as risk factor
In an analysis of underlying conditions and symptoms among adults hospitalized with COVID-19 across 14 states from March 1-30, researchers reported that approximately 90% of hospitalized patients had one or more underlying conditions. The most common condition was hypertension (49.7%), followed by obesity (48.3%) and diabetes (28.3%). The results were published in the April 17 issue of the CDC’s Morbidity and Mortality Weekly Report.
In a retrospective analysis of 3,615 patients with COVID-19 who presented to a large academic hospital system in New York City, Jennifer Lighter, MD, assistant professor in the department of pediatrics at NYU Grossman School of Medicine, and colleagues observed that 775 (21% ) had a BMI between 30 kg/m² and 34 kg/m², and an additional 595 (16%) had a BMI of at least 35 kg/m².
Within the cohort, those aged younger than 60 years with a BMI between 30 kg/m² and 34 kg/m² were twice as likely to be admitted to acute care vs. those with a BMI of 30 kg/m² or less (95% CI, 1.6-2.6) and were 1.8 times more likely to be admitted to critical care (95% CI, 1.2-2.7). Similarly, patients with COVID-19 with a BMI of at least 35 kg/m² were 2.2 times more likely to be admitted to acute care (95% CI, 1.7-2.9) and 3.6 times more likely to be admitted to critical care (95% CI, 2.5-5.3). The findings were published in April in Clinical Infectious Disease.
People with COVID-19 and obesity are also more likely to require invasive mechanical ventilation vs. patients with normal weight. In a retrospective analysis of hospitalized patients in France published in Obesity, researchers found that the proportion of people with COVID-19 who required invasive mechanical ventilation increased across BMI categories. The greatest need for ventilation was observed among people with a BMI of at least 35 kg/m², who had an OR of 7.36 (95% CI, 1.63-33.14) compared with people with a BMI of 25 kg/m² or less.
“Obesity should not be dismissed,” Jastreboff said. “A higher percentage of individuals with obesity are being admitted with COVID-19 than not. That has been demonstrated in New York City, especially among adults aged 60 years and younger.”
Mechanisms at play
Experts said there are several factors that may predispose individuals with excess weight to worse outcomes or complications with COVID-19.
“Obesity is often accompanied by pulmonary diseases, such as obstructive sleep apnea, and other conditions, like type 2 diabetes, which are also independent risk factors for worse complications,” Steven B. Heymsfield, MD, FTOS, professor in the department of metabolism and body composition at Pennington Biomedical Research Center, Louisiana State University, told Healio. “There is some evidence that people with obesity have impaired immune function and are more susceptible to viral infections, such as influenza.”
People with obesity also have a mild, chronic inflammatory state, which can cause the body to mount an excessive immune response to any infection, such as COVID-19, Heymsfield said.
“People with obesity have a chronic inflammatory state,” Heymsfield said. “That sets the stage for this likely susceptibility to COVID-19 complications, like the need for ventilation. The ‘cytokine storm,’ which has been discussed extensively, may be facilitated by this inflammatory state in people with obesity. There have been underlying mechanisms proposed for this, metabolic pathways, particularly in diabetes.”
Differences in symptoms, treatment
People with obesity who may have COVID-19 have different medical needs that can complicate care before they even present to a hospital, Jastreboff said.
“When treating individuals with obesity, consider the resources we have for them,” Jastreboff said. “They may need different hospital beds. They need different settings on ventilators. People with obesity may be more hesitant to come into the hospital because they have faced the lifelong stigma of having obesity. These things all affect care.”
Additionally, disorders of respiratory function — such as obesity hypoventilation syndrome — as well as issues maintaining normal blood oxygenation are likely present for many with obesity who are not even aware of it, Heymsfield said.
“People with obesity may not be symptomatic from their lung disease compared with someone who is not obese,” Heymsfield said. “A person could have blood oxygen levels drop to an almost fatal level and not be aware of it until they drop dead. There have been cases where this has happened, and people do not seem to recognize that.”
There are also technical issues that require adjustments with a patient who has COVID-19 and obesity, Jastreboff said.
“Let’s say you’re turning someone prone to help them oxygenate better into their lungs. It is much more difficult to do that with someone who has severe obesity, simply because of the mechanics,” Jastreboff said. “The measures we take helping people so they don’t require mechanical ventilation, like turning them prone, may not work as well in individuals with obesity both because of mechanics and difference in lung function at baseline.”
Differences in adverse events after treatment are also an issue for people with obesity, according to experts. Steroid treatment for cytokine storm, for example, could bring unintended consequences for a person with obesity who may already have prediabetes or type 2 diabetes.
“High-dose steroids are an important tool in treating cytokine storm. Anyone may develop hyperglycemia in the setting of high-dose steroids, but this is much more likely in individual with obesity,” Jastreboff said. “Individuals with obesity, especially if they already have glycemic perturbations, can have higher glucose levels. We don’t know yet how that contributes to outcomes.”
There are other unknowns when treating people with obesity, including dose titration during COVID-19 treatment.
“We don’t know whether the dose of medication for someone with a BMI in the lean range is the same dose needed for someone with obesity,” Jastreboff said. “Do they need higher or different doses of anticoagulation or other medications used to treat COVID-19?”
Heymsfield said it is important to interpret the flood of new COVID-19 data with caution.
“As I’m watching the data come through, I see extremely variable numbers of people with obesity positive for COVID-19,” Heymsfield said. “In New Orleans, it was 70%, and then the next day it was 20%. We don’t know how any of that compares with populations in other areas. We need good data on this. I do not doubt that people with obesity are at greater risk for COVID-19 complications, but there is a lot of noise here that we will have to consider over time.”
Jastreboff said the statistics underscore the need for better obesity treatment overall.
“If we treat obesity in the same way we treat other chronic diseases, we can decrease risk for our patients, whether it is for COVID-19 or any other disease,” Jastreboff said. “This crisis brings to the forefront that it is absolutely critical to care for patients with obesity and to treat obesity as a disease in and of itself.” – by Regina Schaffer
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Disclosures: Jastreboff reports consulting fees for Novo Nordisk and Rhythm Pharmaceuticals. Heymsfield reports no relevant financial disclosures.