Stanford Medicine scientists’ findings could explain why obese people have a higher risk of SARS-CoV-2 infection and are more likely to progress to severe disease and die of infection.
SARS-CoV-2 (small red entities), the virus that causes COVID-19, can infect fat tissue, which contains many cell types: fat cells are yellow, macrophages purple, and other immune cells blue. Photo by biorender.com
Is SARS-CoV-2 hiding in your fat cells?
A study by Stanford Medicine investigators shows that SARS-CoV-2 can infect human fat tissue. This phenomenon was seen in laboratory experiments conducted on fat tissue excised from patients undergoing bariatric and cardiac surgeries, and later infected in a laboratory dish with SARS-CoV-2. It was further confirmed in autopsy samples from deceased COVID-19 patients.
Obesity is an established, independent risk factor for SARS-CoV-2 infection as well as for the patients’ progression, once infected, to severe disease and death. Reasons offered for this increased vulnerability range from impaired breathing resulting from the pressure of extra weight to altered immune responsiveness in obese people.
But the new study provides a more direct reason: SARS-CoV-2, the virus that causes COVID-19, can directly infect adipose tissue (which most of us refer to as just plain “fat”). That, in turn, cooks up a cycle of viral replication within resident fat cells, or adipocytes, and causes pronounced inflammation in immune cells that hang out in fat tissue. The inflammation converts even uninfected “bystander” cells within the tissue into an inflammatory state.
“With 2 of every 3 American adults overweight and more than 4 in 10 of them obese, this is a potential cause for concern,” said Tracey McLaughlin, MD, professor of endocrinology.
The findings are described in a study published online Sept. 22 in Science Translation Medicine. McLaughlin and Catherine Blish, MD, PhD, professor of infectious diseases, are the study’s senior authors. Lead authorship is shared by former postdoctoral scholar Giovanny Martínez-Colón, PhD, and graduate student Kalani Ratnasiri.
Obesity is defined medically as having a body mass index (weight in kilograms divided by the square of height in meters) of 30 or greater. Someone with a BMI of 25 or greater is defined as being overweight. Obese individuals are up to 10 times as likely to die from COVID-19, McLaughlin said, but increased risk for poor outcomes of SARS-CoV-2 infection begins at BMIs as low as 24.
Catherine Blish and Tracey McLaughlin Stanford Medicine archives
“Fat tissue’s susceptibility to SARS-CoV-2 infection may be playing a role in making obesity a COVID-19 risk factor,” said Blish, who is the George E. and Lucy Becker Professor in Medicine. “Infected fat tissue pumps out precisely the inflammatory chemicals you see in the blood of severe COVID patients. It’s reasonable to infer that having a lot of infected fat could contribute to the overall inflammatory profile of severely ill COVID-19 patients.”
The scientists obtained samples of fat tissue from various locations in the bodies of 22 patients undergoing bariatric or cardiothoracic surgery at the Stanford Medicine Bariatric Surgery and Cardiothoracic Surgery clinic.
Then, in a secure facility, the researchers infected the samples with a solution containing SARS-CoV-2 or, as a control, a SARS-CoV-2-free solution. Rigorous experiments showed that the virus could infect and replicate in fat cells, exit the cells and cause new infections in other cells.
Fat tissue contains not only fat cells but also a wide variety of immune cells, including a type called macrophages. These cells (whose name derives from two Greek words meaning “big eaters”) carry out a number of actions ranging from tissue repair and general garbage cleanup to fierce attacks on perceived pathogens — sometimes producing substantial collateral damage to normal tissue in the process.
The researchers identified a subset of macrophages in fat tissue that become infected by SARS-CoV-2, although only fleetingly. SARS-CoV-2 infection of these macrophages is abortive: It produces no viable viral progeny. But it does induce a major mood change in the macrophages.
“Once infected, these macrophages not only become inflamed themselves but also secrete substances that call in more inflammatory immune cells, in addition to inducing inflammation in uninfected neighboring ‘bystander cells,’” Blish said.
Fat tissue surrounds our hearts, guts, kidneys and pancreases, which can be adversely affected by tissue inflammation. Ominously, the scientists found infection capable of driving inflammation in virtually every SARS-CoV-2-infected fat-tissue sample they collected and analyzed.