HomeHealthMedicineStanford Medicine study shows SARS-CoV-2 can infect human fat tissue

Stanford Medicine study shows SARS-CoV-2 can infect human fat tissue

Does SARS-CoV-2 Hide In Your Fat Cells?

A study by researchers at Stanford Medicine shows that SARS-CoV-2 can infect human adipose tissue. This phenomenon was observed in laboratory experiments performed on adipose tissue excised from patients undergoing bariatric and cardiac surgery and later contaminated with SARS-CoV-2 in a laboratory dish. It was further confirmed in autopsy samples from deceased COVID-19 patients.

Obesity is an established, independent risk factor for SARS-CoV-2 infection and for the progression of the patient, once infected, to serious illness and death. The reasons for this increased vulnerability range from decreased breathing due to the pressure of extra weight, to altered immune response in obese people.

But the new study gives a more direct reason: SARS-CoV-2, the virus that causes COVID-19, can directly infect adipose tissue (what most of us just call “fat”). That, in turn, triggers a cycle of viral replication in the existing fat cells, or adipocytes, and causes marked inflammation in immune cells that hang out in adipose tissue. The inflammation converts even uninfected “bystander” cells in the tissue into an inflammatory state.

With 2 in 3 American adults overweight and more than 4 in 10 obese, this is a potential cause for concern.”

Tracey McLaughlin, MD, professor of endocrinology

The findings are detailed in a study published online Sept. 22 Science Translational Medicine. McLaughlin and Catherine Blish, MD, PhD, professor of infectious diseases, are the senior authors of the study. Lead authorship is shared by former postdoctoral scientist Giovanny Martínez-Colón, PhD, and graduate student Kalani Ratnasiri.

The thick-COVID-19 connection

Obesity is medically defined as a body mass index (weight in kilograms divided by the square of height in meters) of 30 or more. Someone with a BMI of 25 or higher is defined as overweight. Obese individuals are up to 10 times more likely to die from COVID-19, McLaughlin said, but an increased risk of poor outcomes from SARS-CoV-2 infection starts at BMIs as low as 24.

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“The susceptibility of adipose tissue to SARS-CoV-2 infection may play a role in making obesity a risk factor for COVID-19,” said Blish, the professor of medicine for George E. and Lucy Becker. “Infected adipose tissue pumps out exactly the inflammatory chemicals you see in the blood of severe COVID-19 patients. It is reasonable to conclude that having a lot of infected fat can contribute to the overall inflammatory profile of critically ill COVID-19 patients. “

The scientists obtained samples of adipose tissue from various locations in the body of 22 patients undergoing bariatric or cardiothoracic surgery at the Stanford Medicine Bariatric Surgery and Cardiothoracic Surgery clinic. The researchers then infected the samples in a secure facility with a solution containing SARS-CoV-2 or, as a control, a SARS-CoV-2-free solution. Rigorous experiments showed that the virus can infect and multiply in fat cells, leave the cells and cause new infections in other cells.

Adipose tissue contains not only fat cells but also a wide variety of immune cells, including a type called macrophages. These cells (whose name is derived from two Greek words meaning “big eaters”) perform a number of actions ranging from tissue repair and general disposal of waste to fierce attacks on observed pathogens -; sometimes causing significant collateral damage to normal tissue in the process.

The researchers identified a subset of macrophages in adipose tissue that become infected with SARS-CoV-2, although only fleeting. SARS-CoV-2 infection of these macrophages fails: it does not produce viable viral progeny. But it does cause a major mood change in the macrophages.

“Once infected, these macrophages not only become inflamed on their own, but also secrete substances that trigger more inflammatory immune cells, in addition to inducing inflammation in uninfected neighboring ‘bystander cells,'” Blish said.

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Adipose tissue surrounds our hearts, gut, kidneys, and pancreas, which can be adversely affected by tissue inflammation. Ominously, the scientists found an infection that could cause inflammation in virtually every SARS-CoV-2 infected adipose tissue sample they collected and analyzed.

Genetic material encoding SARS-CoV-2 was almost always present in adipose tissue from various body parts of eight patients who had died from COVID-19. When examining tissue from two other deceased COVID-19 patients, the team saw an infiltration of inflammatory immune cells alongside infected fat cells in epicardial fat.

“This was a big concern for us because epicardial fat is right next to the heart muscle, with no physical barrier separating them,” McLaughlin said. “So any inflammation there can directly affect the heart muscle or coronary arteries.”

Missing ACE2

Strangely enough, ACE2 -; the cell surface molecule implicated as the cardinal receptor for SARS-CoV-2 -; was found to play little or no role in the virus’ ability to infect fat cells.

The method by which SARS-CoV-2 gains access to fat cells and macrophages in adipose tissue remains mysterious. The established primary mode of entry occurs when the virus binds to a protein called ACE2 that resides on cell surfaces in numerous body tissues. While ACE2 performs important, legitimate functions, the virus doesn’t care what ACE2 does for a living -; it considers this cell surface protein merely as a docking station.

This was the epitome of irony for McLaughlin and Blish, who started the investigation because they had seen reports suggesting, though not proven, that ACE2 could be present in adipose tissue. (No one had claimed to have seen the protein themselves, Blish added.)

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But the researchers were surprised to find that ACE2 was virtually nonexistent on cells in adipose tissue.

“The virus is highly unlikely to enter via ACE2, because we were unable to detect the functional protein in adipose tissue,” Blish said.

This means that new drugs may be needed to clear SARS-CoV-2 from adipose tissue. For example, monoclonal antibody therapies approved for COVID-19 generally work by interfering with the ACE2/SARS-CoV-2 interaction.

The potential of adipose tissue to serve as a reservoir for SARS-CoV-2 to hide also raises the possibility that it could contribute to the lingering symptoms after infection collectively termed long-term COVID, a hypothesis McLaughlin and Blish are beginning to support. to research.

Researchers from the University of Tübingen, University of Basel, Beth Israel Deaconess Medical Center in Boston and Cantonal Hospital Baselland in Liestal, Switzerland contributed to the work.

The study was funded by the National Institutes of Health (grants R21AI159024, 5T32 AI007502, and T32 DK007217), the American Diabetes Association, the Stanford University Innovative Medicines Accelerator, the Botnar Research Center for Child Health, the Swiss National Science Foundation, the Chan Zuckerberg Biohub, the National Science Foundation and the Bill and Melinda Gates Foundation.



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