The Skinny on Fat and Covid-19
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.
Some hospitals are pioneers in ditching plastic, turning green
This is part 2 of a three part series on a new generation of doctors leading the charge to make the health care industry more sustainable - for the benefit of their patients and the planet. Read part 1 here and part 3 here.
After graduating from her studies as an engineer, Nora Stroetzel ticked off the top item on her bucket list and traveled the world for a year. She loved remote places like the Indonesian rain forest she reached only by hiking for several days on foot, mountain villages in the Himalayas, and diving at reefs that were only accessible by local fishing boats.
“But no matter how far from civilization I ventured, one thing was already there: plastic,” Stroetzel says. “Plastic that would stay there for centuries, on 12,000 foot peaks and on beaches several hundred miles from the nearest city.” She saw “wild orangutans that could be lured by rustling plastic and hermit crabs that used plastic lids as dwellings instead of shells.”
While traveling she started volunteering for beach cleanups and helped build a recycling station in Indonesia. But the pivotal moment for her came after she returned to her hometown Kiel in Germany. “At the dentist, they gave me a plastic cup to rinse my mouth. I used it for maybe ten seconds before it was tossed out,” Stroetzel says. “That made me really angry.”
She decided to research alternatives for plastic in the medical sector and learned that cups could be reused and easily disinfected. All dentists routinely disinfect their tools anyway and, Stroetzel reasoned, it wouldn’t be too hard to extend that practice to cups.
It's a good example for how often plastic is used unnecessarily in medical practice, she says. The health care sector is the fifth biggest source of pollution and trash in industrialized countries. In the U.S., hospitals generate an estimated 6,000 tons of waste per day, including an average of 400 grams of plastic per patient per day, and this sector produces 8.5 percent of greenhouse gas emissions nationwide.
“Sustainable alternatives exist,” Stroetzel says, “but you have to painstakingly look for them; they are often not offered by the big manufacturers, and all of this takes way too much time [that] medical staff simply does not have during their hectic days.”
When Stroetzel spoke with medical staff in Germany, she found they were often frustrated by all of this waste, especially as they took care to avoid single-use plastic at home. Doctors in other countries share this frustration. In a recent poll, nine out of ten doctors in Germany said they’re aware of the urgency to find sustainable solutions in the health industry but don’t know how to achieve this goal.
After a year of researching more sustainable alternatives, Stroetzel founded a social enterprise startup called POP, short for Practice Without Plastic, together with IT expert Nicolai Niethe, to offer well-researched solutions. “Sustainable alternatives exist,” she says, “but you have to painstakingly look for them; they are often not offered by the big manufacturers, and all of this takes way too much time [that] medical staff simply does not have during their hectic days.”
In addition to reusable dentist cups, other good options for the heath care sector include washable N95 face masks and gloves made from nitrile, which waste less water and energy in their production. But Stroetzel admits that truly making a medical facility more sustainable is a complex task. “This includes negotiating with manufacturers who often package medical materials in double and triple layers of extra plastic.”
While initiatives such as Stroetzel’s provide much needed information, other experts reason that a wholesale rethinking of healthcare is needed. Voluntary action won’t be enough, and government should set the right example. Kari Nadeau, a Stanford physician who has spent 30 years researching the effects of environmental pollution on the immune system, and Kenneth Kizer, the former undersecretary for health in the U.S. Department of Veterans Affairs, wrote in JAMA last year that the medical industry and federal agencies that provide health care should be required to measure and make public their carbon footprints. “Government health systems do not disclose these data (and very rarely do private health care organizations), unlike more than 90% of the Standard & Poor’s top 500 companies and many nongovernment entities," they explained. "This could constitute a substantial step toward better equipping health professionals to confront climate change and other planetary health problems.”
Compared to the U.K., the U.S. healthcare industry lags behind in terms of measuring and managing its carbon footprint, and hospitals are the second highest energy user of any sector in the U.S.
Kizer and Nadeau look to the U.K. National Health Service (NHS), which created a Sustainable Development Unit in 2008 and began that year to conduct assessments of the NHS’s carbon footprint. The NHS also identified its biggest culprits: Of the 2019 footprint, with emissions totaling 25 megatons of carbon dioxide equivalent, 62 percent came from the supply chain, 24 percent from the direct delivery of care, 10 percent from staff commute and patient and visitor travel, and 4 percent from private health and care services commissioned by the NHS. From 1990 to 2019, the NHS has reduced its emission of carbon dioxide equivalents by 26 percent, mostly due to the switch to renewable energy for heat and power. Meanwhile, the NHS has encouraged health clinics in the U.K. to install wind generators or photovoltaics that convert light to electricity -- relatively quick ways to decarbonize buildings in the health sector.
Compared to the U.K., the U.S. healthcare industry lags behind in terms of measuring and managing its carbon footprint, and hospitals are the second highest energy user of any sector in the U.S. “We are already seeing patients with symptoms from climate change, such as worsened respiratory symptoms from increased wildfires and poor air quality in California,” write Thomas B. Newman, a pediatrist at the University of California, San Francisco, and UCSF clinical research coordinator Daisy Valdivieso. “Because of the enormous health threat posed by climate change, health professionals should mobilize support for climate mitigation and adaptation efforts.” They believe “the most direct place to start is to approach the low-lying fruit: reducing healthcare waste and overuse.”
In addition to resulting in waste, the plastic in hospitals ultimately harms patients, who may be even more vulnerable to the effects due to their health conditions. Microplastics have been detected in most humans, and on average, a human ingests five grams of microplastic per week. Newman and Valdivieso refer to the American Board of Internal Medicine's Choosing Wisely program as one of many initiatives that identify and publicize options for “safely doing less” as a strategy to reduce unnecessary healthcare practices, and in turn, reduce cost, resource use, and ultimately reduce medical harm.
A few U.S. clinics are pioneers in transitioning to clean energy sources. In Wisconsin, the nonprofit Gundersen Health network became the first hospital to cut its reliance on petroleum by switching to locally produced green energy in 2015, and it saved $1.2 million per year in the process. Kaiser Permanente eliminated its 800,000 ton carbon footprint through energy efficiency and purchasing carbon offsets, reaching a balance between carbon emissions and removing carbon from the atmosphere in 2020, the first U.S. health system to do so.
Cleveland Clinic has pledged to join Kaiser in becoming carbon neutral by 2027. Realizing that 80 percent of its 2008 carbon emissions came from electricity consumption, the Clinic started switching to renewable energy and installing solar panels, and it has invested in researching recyclable products and packaging. The Clinic’s sustainability report outlines several strategies for producing less waste, such as reusing cases for sterilizing instruments, cutting back on materials that can’t be recycled, and putting pressure on vendors to reduce product packaging.
The Charité Berlin, Europe’s biggest university hospital, has also announced its goal to become carbon neutral. Its sustainability managers have begun to identify the biggest carbon culprits in its operations. “We’ve already reduced CO2 emissions by 21 percent since 2016,” says Simon Batt-Nauerz, the director of infrastructure and sustainability.
The hospital still emits 100,000 tons of CO2 every year, as much as a city with 10,000 residents, but it’s making progress through ride share and bicycle programs for its staff of 20,000 employees, who can get their bikes repaired for free in one of the Charité-operated bike workshops. Another program targets doctors’ and nurses’ scrubs, which cause more than 200 tons of CO2 during manufacturing and cleaning. The staff is currently testing lighter, more sustainable scrubs made from recycled cellulose that is grown regionally and requires 80 percent less land use and 30 percent less water.
The Charité hospital in Berlin still emits 100,000 tons of CO2 every year, but it’s making progress through ride share and bicycle programs for its staff of 20,000 employees.
Wiebke Peitz | Specific to Charité
Anesthesiologist Susanne Koch spearheads sustainability efforts in anesthesiology at the Charité. She says that up to a third of hospital waste comes from surgery rooms. To reduce medical waste, she recommends what she calls the 5 Rs: Reduce, Reuse, Recycle, Rethink, Research. “In medicine, people don’t question the use of plastic because of safety concerns,” she says. “Nobody wants to be sued because something is reused. However, it is possible to reduce plastic and other materials safely.”
For instance, she says, typical surgery kits are single-use and contain more supplies than are actually needed, and the entire kit is routinely thrown out after the surgery. “Up to 20 percent of materials in a surgery room aren’t used but will be discarded,” Koch says. One solution could be smaller kits, she explains, and another would be to recycle the plastic. Another example is breathing tubes. “When they became scarce during the pandemic, studies showed that they can be used seven days instead of 24 hours without increased bacteria load when we change the filters regularly,” Koch says, and wonders, “What else can we reuse?”
In the Netherlands, TU Delft researchers Tim Horeman and Bart van Straten designed a method to melt down the blue polypropylene wrapping paper that keeps medical instruments sterile, so that the material can be turned it into new medical devices. Currently, more than a million kilos of the blue paper are used in Dutch hospitals every year. A growing number of Dutch hospitals are adopting this approach.
Another common practice that’s ripe for improvement is the use of a certain plastic, called PVC, in hospital equipment such as blood bags, tubes and masks. Because of its toxic components, PVC is almost never recycled in the U.S., but University of Michigan researchers Danielle Fagnani and Anne McNeil have discovered a chemical process that can break it down into material that could be incorporated back into production. This could be a step toward a circular economy “that accounts for resource inputs and emissions throughout a product’s life cycle, including extraction of raw materials, manufacturing, transport, use and reuse, and disposal,” as medical experts have proposed. “It’s a failure of humanity to have created these amazing materials which have improved our lives in many ways, but at the same time to be so shortsighted that we didn’t think about what to do with the waste,” McNeil said in a press release.
Susanne Koch puts it more succinctly: “What’s the point if we save patients while killing the planet?”
The Friday Five: A surprising health benefit for people who have kids
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
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Here are the promising studies covered in this week's Friday Five:
- Kids stressing you out? They could be protecting your health.
- A new device unlocks the heart's secrets
- Super-ager gene transplants
- Surgeons could 3D print your organs before operations
- A skull cap looks into the brain like an fMRI