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Study finds one in four patients hospitalized for COVID-19 with metabolic syndrome developed ARDS.

Researchers looked at data from 26 countries, 181 hospitals. Inflammatory processes believed to be mechanism at work.

Josh Denson portrait, August 2020
Dr. Joshua Denson, pulmonary and critical care medicine physician at Tulane University School of Medicine, is the lead author of a new study linking ARDS with metabolic syndrome in hospitalized COVID-19 patients.
Photo courtesy of Tulane University

ROCHESTER, Minn. — Persons with metabolic syndrome who are hospitalized for COVID-19 have a one in four chance of getting Acute Respiratory Distress Syndrome (ARDS), a condition generally requiring mechanical ventilation.

That's the takeaway from a global study published Wednesday in JAMA Network Open , the largest investigation yet of COVID-19 hospitalization data and the metabolically unhealthy, often insulin-resistant syndrome believed by many to connect the major forms of chronic disease in wealthy nations.

The study, a joint effort between Mayo Clinic and the Society of Critical Care Medicine, drew on hospitalization records collected between February, 2020 and February, 2021 for 46,000 patients at 181 hospitals in 26 countries.

The study found that for each factor in the metabolic syndrome cluster — a constellation including high blood pressure, dyslipidemia, diabetes and mild obesity — chances of ARDS rose.

All persons hospitalized with COVID-19 carried a 10% risk of ARDS, but adding a second component of metabolic syndrome increased that risk to 15%, while a third raised the risk of ARDS to 20%. Those with all four components of metabolic syndrome held 25% risk of getting ARDS.

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'Underlying conditions' could all be related

The study suggested the so-called "underlying conditions" frequently named as risk factors for severe outcomes with COVID-19 could reflect the shared risk of metabolic syndrome.

"It's not exactly just obesity, or just diabetes, or abnormal cholesterol ... these diagnoses, they travel together," said lead author Dr. Joshua Denson, a pulmonary specialist at Tulane University. Denson believes the data "solidifies what people thought may not have been such a strong link between these disorders."

Metabolic syndrome is common. One in five Americans between 20 and 40, one in three overall and nearly one-half of those over 60 are believed to have the phenotype.

Denson said the threshold for the components of metabolic syndrome is low.

"They think they are healthy," he says. "But they are a little bit obese, have a little of early diabetes, if not actual diabetes, and then they have a little bit of high blood pressure ... It's been tough for me to hear people talk about the different risk factors and say well 'they had co-morbid conditions.'"

"Usually it's what a lot of people in our country don't consider co-morbid conditions. If you told everyone in our country with a BMI of 31 that they had a co-morbid condition, they'd laugh at you."

ARDS is the highest severity development for patients with COVID-19.

"Once someone's diagnosed with ARDS," Denson says, "all we have to offer them is that we are going to put them on a ventilator and turn them on their stomach. That's really the only therapy we have to offer."

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The mechanism causing metabolic syndrome patients to deteriorate during COVID-19 hospitalization is believed to be underlying inflammation, he says, a process exacerbating the body's natural response to infection.

"I've got one guy, he has all four of these criteria (and) he has been sick with COVID for over two weeks ... The reason he's so sick isn't from the virus, it's his body's inflammation causing his lungs to give up."

The timeline is a slow burn. It creeps up on you ... Some patients get better around day five to seven, and then they get worse again. That seems to be this patient population.
Dr. Joshua Denson

But the worsening of COVID-19 with metabolic syndrome happens slowly, Denson says, reflecting a secondary process.

"You start off feeling fine," he says. "You get a little cold."

"Then about a week later, that's when, if you're unlucky, you start getting short of breath and pneumonia components."

"The timeline is a slow burn. It creeps up on you ... Some patients get better around day five to seven, and then they get worse again. That seems to be this patient population."

Denson says the study should be seen as a wake-up call to get vaccinated, even if you believe you are unaffected.

"If you have these risk factors and you're young, you should be worried, and you should definitely be vaccinated and boosted. We don't know what omicron's going to do with patients who have metabolic disease and the vaccine. That's yet to be determined."

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Kashyap Rahul
Dr. Rahul Kashyap
Contributed / Mayo Clinic

Coauthor Dr. Rahul Kashyap of Mayo Clinic says the finding reflects the importance of a Mayo Clinic and Society of Critical Care medicine partnership "to actually capture and harmonize" de-identified data from medical records "to answer questions that could not be answered through one-hospital data or a few hospitals data."

"We should take these findings seriously," he said. "The patients who are in this category should be careful to know the components of metabolic syndrome put them in higher risk compared to others who are others who are infected.

"Those who are not vaccinated should go ahead and get vaccinated to protect themselves, knowing they have added risk compared to other people who are vaccinated or not vaccinated."

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