Is SARS-CoV-2 Hiding in Your Fat Cells?
Studies by Stanford Medicine researchers show that SARS-CoV-2 can infect human adipose tissue. This phenomenon has been seen in laboratory experiments performed on adipose tissue excised from patients undergoing bariatric and cardiac surgery, then infected with SARS-CoV-2 in experimental dishes. It was further confirmed in autopsy samples from deceased COVID-19 patients.
Obesity is a well-established independent risk factor for SARS-CoV-2 infection, as well as severe illness and death in infected patients. The reasons for this increased vulnerability range from impaired breathing due to the pressure of extra body weight to altered immune responses in obese people.
But new research provides a more direct reason: SARS-CoV-2, the virus that causes COVID-19, can directly infect adipose tissue. It initiates a cycle of viral replication within fat cells, causing a marked inflammation in the immune cells hanging in the adipose tissue. To do.
This is a potential cause for concern as 2 out of 3 adults in America are overweight and more than 4 out of 10 are obese. “
Tracey McLaughlin, MD, Professor of Endocrinology
The findings are described in a study published online on Sept. 22. Science Translational MedicineMcLaughlin and Catherine Blish, MD, PhD, Professor of Infectious Diseases, are senior authors of this study. First author is former postdoctoral researcher Giovanny Martínez-Colón, Ph.D. and graduate student Kalani Ratnasiri.
Relationship between fat and COVID-19
Obesity is medically defined as having a body mass index (weight in kilograms divided by height in meters squared) of 30 or higher. A person with a BMI greater than or equal to 25 is defined as OverweightObese people are up to 10 times more likely to die from COVID-19, McLaughlin said, but the increased risk of bad outcomes from SARS-CoV-2 infection starts with a BMI as low as 24.
“Adipose tissue susceptibility to SARS-CoV-2 infection may play a role in making obesity a risk factor for COVID-19,” said Blish, George E. and Lucy Becker Professor of Medicine. rice field. “Infected adipose tissue excretes the exact inflammatory chemicals found in the blood of critically ill COVID-19 patients. High levels of infected fat contribute to the overall inflammatory profile of critically ill COVID-19 patients. It is reasonable to speculate that it may be
Scientists obtained samples of adipose tissue from various parts of the body of 22 patients undergoing bariatric or cardiothoracic surgery at Stanford Medicine’s Bariatric Surgery and Cardiothoracic Surgery Clinic. Then, in a secure facility, the researchers infected the samples with her SARS-CoV-2-containing solution, or her SARS-CoV-2-free solution as a control. Rigorous experiments have shown that viruses can infect fat cells, replicate, exit the cells, and cause new infections in other cells.
Adipose tissue contains not only adipocytes, but also a variety of immune cells, including a type of immune cell called macrophages. These cells (whose name derives from two Greek words for “gluttony”) perform a variety of tasks, from tissue repair and general trash cleanup, to vicious attacks on recognized pathogens. perform actions. In the process, it can cause considerable collateral damage to normal tissue.
Researchers identified a subset of macrophages in adipose tissue that were infected with SARS-CoV-2, but only for a moment. His SARS-CoV-2 infection of these macrophages fails. No executable virus descendants are produced. However, it causes major mood changes in macrophages.
“Once infected, these macrophages not only cause inflammation themselves, but also induce inflammation in neighboring uninfected ‘bystander cells’, as well as calling out more inflammatory immune cells.” secretes,” Blish said.
Adipose tissue surrounds our heart, intestines, kidneys and pancreas and can be adversely affected by tissue inflammation. -In CoV-2-infected adipose tissue samples, we found that infection can cause inflammation.
Genetic material encoding SARS-CoV-2 was almost always present in adipose tissue in different body regions of eight patients who died of COVID-19. Examining tissues from two of her other deceased COVID-19 patients showed infiltration of inflammatory immune cells adjacent to infected adipocytes in the epicardial fat.
“This was a big concern for us because the epicardial fat is right next to the myocardium and there is no physical barrier separating them,” McLaughlin said. “So inflammation can directly affect the heart muscle and coronary arteries.”
Curiously, ACE2 — the cell surface molecule implicated as the primary receptor for SARS-CoV-2 — appeared to play little or no role in the virus’ ability to infect adipocytes.
How SARS-CoV-2 enters adipocytes and adipose tissue macrophages remains a mystery. A major established mode of entry occurs when the virus associates with a protein called ACE2 that is present on the cell surface of many body tissues. ACE2 performs an important and legitimate function, but the virus doesn’t care what ACE2 does for a living. This cell surface protein is viewed as a simple docking station.
This was of great irony for McLaughlin and Blish, who began their studies after seeing reports suggesting that ACE2 might be present in adipose tissue, although they did not prove it. (No one claimed to have seen the protein itself, Blish added.)
But the researchers surprisingly found that ACE2 was virtually absent in cells present in adipose tissue.
“Since we were unable to detect functional proteins in adipose tissue, it is highly unlikely that the virus entered through ACE2,” Blish said.
This means new drugs may be needed to clear SARS-CoV-2 from adipose tissue. For example, monoclonal antibody therapies licensed against COVID-19 typically work by interfering with the ACE2/SARS-CoV-2 interaction.
The potential for adipose tissue to act as a reservoir in which SARS-CoV-2 can hide also raises the possibility that it contributes to the persistent post-infection symptoms collectively known as COVID over the long term. This is the hypothesis McLaughlin and Blish are beginning to explore.
Researchers from the University of Tübingen, the University of Basel, the Beth Israel Deaconess Medical Center in Boston, and the Canton Hospital Baselland in Liestal, Switzerland, contributed to this work.
This study was funded by the National Institutes of Health (grant 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, and Chan Zuckerberg. it was done. Biohub, National Science Foundation, Bill and Melinda Gates Foundation.