The Skinny on Fat and Covid-19

The Skinny on Fat and Covid-19

Researchers at Stanford have found that the virus that causes Covid-19 can infect fat cells, which could help explain why obesity is linked to worse outcomes for those who catch Covid-19.

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Obesity is a risk factor for worse outcomes for a variety of medical conditions ranging from cancer to Covid-19. Most experts attribute it simply to underlying low-grade inflammation and added weight that make breathing more difficult.

Now researchers have found a more direct reason: SARS-CoV-2, the virus that causes Covid-19, can infect adipocytes, more commonly known as fat cells, and macrophages, immune cells that are part of the broader matrix of cells that support fat tissue. Stanford University researchers Catherine Blish and Tracey McLaughlin are senior authors of the study.


Most of us think of fat as the spare tire that can accumulate around the middle as we age, but fat also is present closer to most internal organs. McLaughlin's research has focused on epicardial fat, “which sits right on top of the heart with no physical barrier at all,” she says. So if that fat got infected and inflamed, it might directly affect the heart.” That could help explain cardiovascular problems associated with Covid-19 infections.

Looking at tissue taken from autopsy, there was evidence of SARS-CoV-2 virus inside the fat cells as well as surrounding inflammation. In fat cells and immune cells harvested from health humans, infection in the laboratory drove "an inflammatory response, particularly in the macrophages…They secreted proteins that are typically seen in a cytokine storm” where the immune response runs amok with potential life-threatening consequences. This suggests to McLaughlin “that there could be a regional and even a systemic inflammatory response following infection in fat.”

It is easy to see how the airborne SARS-CoV-2 virus infects the nose and lungs, but how does it get into fat tissue? That is a mystery and the source of ample speculation.

The macrophages studied by McLaughlin and Blish were spewing out inflammatory proteins, While the the virus within them was replicating, the new viral particles were not able to replicate within those cells. It was a different story in the fat cells. “When [the virus] gets into the fat cells, it not only replicates, it's a productive infection, which means the resulting viral particles can infect another cell,” including microphages, McLaughlin explains. It seems to be a symbiotic tango of the virus between the two cell types that keeps the cycle going.

It is easy to see how the airborne SARS-CoV-2 virus infects the nose and lungs, but how does it get into fat tissue? That is a mystery and the source of ample speculation.

Macrophages are mobile; they engulf and carry invading pathogens to lymphoid tissue in the lymph nodes, tonsils and elsewhere in the body to alert T cells of the immune system to the pathogen. Perhaps some of them also carry the virus through the bloodstream to more distant tissue.

ACE2 receptors are the means by which SARS-CoV-2 latches on to and enters most cells. They are not thought to be common on fat cells, so initially most researchers thought it unlikely they would become infected.

However, while some cell receptors always sit on the surface of the cell, other receptors are expressed on the surface only under certain conditions. Philipp Scherer, a professor of internal medicine and director of the Touchstone Diabetes Center at the University of Texas Southwestern Medical Center, suggests that, in people who have obesity, “There might be higher levels of dysfunctional [fat cells] that facilitate entry of the virus,” either through transiently expressed ACE2 or other receptors. Inflammatory proteins generated by macrophages might contribute to this process.

Another hypothesis is that viral RNA might be smuggled into fat cells as cargo in small bits of material called extracellular vesicles, or EVs, that can travel between cells. Other researchers have shown that when EVs express ACE2 receptors, they can act as decoys for SARS-CoV-2, where the virus binds to them rather than a cell. These scientists are working to create drugs that mimic this decoy effect as an approach to therapy.

Do fat cells play a role in Long Covid? “Fat cells are a great place to hide. You have all the energy you need and fat cells turn over very slowly; they have a half-life of ten years,” says Scherer. Observational studies suggest that acute Covid-19 can trigger the onset of diabetes especially in people who are overweight, and that patients taking medicines to regulate their diabetes “were actually quite protective” against acute Covid-19. Scherer has funding to study the risks and benefits of those drugs in animal models of Long Covid.

McLaughlin says there are two areas of potential concern with fat tissue and Long Covid. One is that this tissue might serve as a “big reservoir where the virus continues to replicate and is sent out” to other parts of the body. The second is that inflammation due to infected fat cells and macrophages can result in fibrosis or scar tissue forming around organs, inhibiting their function. Once scar tissue forms, the tissue damage becomes more difficult to repair.

Current Covid-19 treatments work by stopping the virus from entering cells through the ACE2 receptor, so they likely would have no effect on virus that uses a different mechanism. That means another approach will have to be developed to complement the treatments we already have. So the best advice McLaughlin can offer today is to keep current on vaccinations and boosters and lose weight to reduce the risk associated with obesity.

Bob Roehr
Bob Roehr is a biomedical journalist based in Washington, DC. Over the last twenty-five years he has written extensively for The BMJ, Scientific American, PNAS, Proto, and myriad other publications. He is primarily interested in HIV, infectious disease, immunology, and how growing knowledge of the microbiome is changing our understanding of health and disease. He is working on a book about the ways the body can at least partially control HIV and how that has influenced (or not) the search for a treatment and cure.
Why we need to get serious about ending aging

With the population of older people projected to grow dramatically, and the cost of healthcare with it, the future welfare of the country may depend on solving aging, writes philosopher Ingemar Patrick Linden.

Photo by Alessio Lin on Unsplash

It is widely acknowledged that even a small advance in anti-aging science could yield benefits in terms of healthy years that the traditional paradigm of targeting specific diseases is not likely to produce. A more youthful population would also be less vulnerable to epidemics. Approximately 93 percent of all COVID-19 deaths reported in the U.S. occurred among those aged 50 or older. The potential economic benefits would be tremendous. A more youthful population would consume less medical resources and be able to work longer. A recent study published in Nature estimates that a slowdown in aging that increases life expectancy by one year would save $38 trillion per year for the U.S. alone.

A societal effort to understand, slow down, arrest or even reverse aging of at least the size of our response to COVID-19 would therefore be a rational commitment. In fact, given that America’s older population is projected to grow dramatically, and the cost of healthcare with it, it is not an overstatement to say that the future welfare of the country may depend on solving aging.

This year, the kingdom of Saudi Arabia has announced that it will spend up to 1 billion dollars per year on science with the potential to slow down the aging process. We have also seen important investments from billionaires like Google co-founder Larry Page, Amazon founder Jeff Bezos, business magnate Larry Ellison, and PayPal co-founder Peter Thiel.

The U.S. government, however, is lagging: The National Institutes of Health spent less than one percent of its $43 billion budget for the fiscal year of 2021 on the National Institute on Aging’s Division of Aging Biology. When you visit the division’s webpage you find that their mission statement carefully omits any mention of the possibility of slowing down the aging process.

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Ingemar Patrick Linden
Driven by a passion to probe the fundamental questions we are confronted with, Dr. INGEMAR PATRICK LINDEN has been on a journey of discovery taking him from Lund University in Sweden, to UCL in London, to University of California, to New York, where he has taught philosophy for almost a decade. Death. It does not get more fundamental than that. One of the ideas that has remained a firm conviction of the author’s since childhood is that we do not have enough time. We are but the beginnings of complete humans, fragments of what we could be. It was the realization that not all share this view, in fact, surveys show that most do not, that inspired, and necessitated, the writing of THE CASE AGAINST DEATH.
Could a tiny fern change the world — again?

A worker tends to a rural farm in Hanoi, Vietnam, where technology is making it easier to harvest an ancient fern called Azolla. Some scientists and farmers view Azolla as a solution to our modern-day agricultural and environmental challenges.

Pham Gia Minh

More than 50 million years ago, the Arctic Ocean was the opposite of a frigid wasteland. It was a gigantic lake surrounded by lush greenery brimming with flora and fauna, thanks to the humidity and warm temperatures. Giant tortoises, alligators, rhinoceros-like animals, primates, and tapirs roamed through nearby forests in the Arctic.

This greenhouse utopia abruptly changed in the early Eocene period, when the Arctic Ocean became landlocked. A channel that connected the Arctic to the greater oceans got blocked. This provided a tiny fern called Azolla the perfect opportunity to colonize the layer of freshwater that formed on the surface of the Arctic Ocean. The floating plants rapidly covered the water body in thick layers that resembled green blankets.

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Anuradha Varanasi
Anuradha Varanasi is a freelance science journalist based in Mumbai, India. She has an MA in Science Journalism from Columbia University in the City of New York. Her stories on environmental health, biomedical research, and climate change have been published in Forbes, UnDark, Popular Science, and Inverse. You can follow her on Twitter @AnuradhaVaranas