Publisher Health

Great uncertainty surrounds the origins of SARS-CoV-2. Early on, some suggested a link between COVID-19 and a seafood market in Wuhan, China. Other theories are now circulating, though the origins of the virus are still unknown.
In response, governments have pushed for the closing of so-called “wet markets” around the world, but this is not an effective policy solution, Princeton University researchers report.
A widespread shuttering of all wet markets could have the unintended consequences of disrupting critical food supply chains, stimulating an unregulated black market for animal products, and stoking xenophobia and anti-Asian sentiment. Furthermore, the majority of these informal markets — which specialize in fresh meat, seafood, and other perishable items in open-air settings — pose little risk to human health or biodiversity.
Instead, policymakers should target the most high-risk aspects of markets to prevent disruptions to local food supply chains while reducing human health and biodiversity dangers, the researchers argue in the journal The Lancet Planetary Health. Markets selling live animals, especially live wild animals, pose the most outsized risks to human health and biodiversity, the researchers conclude.
“The usage of the term ‘wet market’ is laced with negative undertones, especially in light of COVID-19. I believe this is driven, in part, by a misunderstanding of what these markets actually are and the ways they can meaningfully differ from other markets and from each other. Given this confusion, the term is slowly being replaced in the academic and popular literature by more specific terminology,” said study lead author Bing Lin, a second-year Ph.D. student in the Program in Science, Technology, and Environmental Policy at the Princeton School of Public and International Affairs. “Our research injects some clarity on what wet markets are, and adds precision to how their risks can be considered and classified.”
“In the wake of the COVID-19 pandemic, many nations temporarily shut down their wet markets, but that’s not going to last — eventually some will be opened up while others will be more closely regulated or closed altogether,” said study co-author David S. Wilcove, professor of ecology and evolutionary biology and public affairs and the High Meadows Environmental Institute and a core faculty member at Princeton’s Center for Policy Research on Energy and the Environment. “Our work presents a way to tell which ones are worth focusing on for tighter regulation or closure.”
Lin and Wilcove began with a definition of wet markets, which sell consumption-oriented, perishable goods in a non-supermarket setting. These markets were named after their frequently wet floors, a result of regular washing to keep food stalls clean and the melting of ice to keep foods fresh. Wildlife markets, on the other hand, sell non-domesticated wild animals, and live-animal markets sell live animals. The Huanan Seafood Wholesale Market — considered a possible source of the COVID-19 pandemic — was a wet market, a live-animal market, and a wildlife market all in one.

The British have suffered for their fashion for centuries according to a new study suggesting that a vogue for shoes with a pointed tip led to a sharp increase in hallux valgus of the big toe — often called bunions — in the late medieval period.
Researchers investigating remains in Cambridge, UK, found that those buried in the town centre, particularly in plots for wealthier citizens and clergy, were much more likely to have had bunions — suggesting rich urbanites paid a higher price for their footwear in more ways than one.
A University of Cambridge team also discovered that older medieval people with hallux valgus were significantly more likely to have sustained a broken bone from a probable fall compared to those of a similar age with normal feet.
Hallux valgus is a minor deformity in which the largest toe becomes angled outward and a bony protrusion forms at its base, on the inside of the foot.
While various factors can predispose someone to bunions, from genetics to muscle imbalance, by far the most common contemporary cause is constrictive boots and shoes. The condition is often associated with wearing high heels.
Archaeologists analysed 177 skeletons from cemeteries in and around the city of Cambridge and found that only 6% of individuals buried between 11th and 13th centuries had evidence of the affliction. However, 27% of those dating from the 14th and 15th centuries had been hobbled by longstanding hallux valgus.

Flush the taps, focus on indoor air quality and consider getting creative about staff schedules.For the last 15 months, many American offices sat essentially empty. Conference rooms and cubicles went unused, elevators uncalled, files untouched. Whiteboards became time capsules. Succulents had to fend for themselves.But over the coming weeks, many of these workplaces will creak slowly back to life. By September, roughly half of Manhattan’s one million office workers are likely to return to their desks, at least part time, according to a recent survey by the Partnership for New York City.Although the risk of contracting Covid-19 has fallen significantly in the United States — especially for those who are fully vaccinated — it has not disappeared entirely, and many workers remain nervous about returning to their desks. (Many others, of course, never had the luxury of working remotely in the first place.)“If you’re still feeling uncomfortable or anxious, that’s totally understandable,” said Joseph Allen, an expert on healthy buildings who teaches at Harvard’s T.H. Chan School of Public Health. “This pandemic has affected all of us in profound ways, and people are going to be ready to re-enter life again or re-enter interacting with people at different times.”But scientists have learned a lot about the virus over the past year, and there are some clear, evidence-based steps that employers can take to protect their workers — and that workers can take to protect themselves. Some of these strategies are likely to pay dividends that outlast the current crisis.“I think it’s important for us as a community, but also individual employers, to think about these questions in relation to not just this week and this month,” said Alex Huffman, an aerosol scientist at the University of Denver. “How do we make decisions now that benefit the safety and health of our work spaces well into the future?”A neglected plant in the offices of The New York Times last summer.Chris Maggio for The New York TimesAddress the risks of closuresAlthough Covid-19 is the headline health concern, long-term building closures can present risks of their own. Plumbing systems that sit unused, for instance, can be colonized by Legionella pneumophila, bacteria that can cause a type of pneumonia known as Legionnaires’ disease.“Long periods with stagnant, lukewarm water in pipes — the exact conditions in many under-occupied buildings right now — create ideal conditions for growth of Legionella,” Dr. Allen said.Some schools have already reported finding the bacteria in their water. In buildings with lead pipes or fixtures, high levels of the toxic metal can also accumulate in stagnant water. Employers can reduce both risks by thoroughly flushing their taps, or turning on the water and letting it run, before reopening.“We know that flushing water during periods of inactivity usually reduces lead levels and also potentially bacteria that may form,” said Jennifer Hoponick Redmon, a senior environmental health scientist at RTI International, a nonprofit research organization based in North Carolina. She added: “A general rule of thumb is 15 minutes to one hour of flushing for long-term closures, such as for Covid-19.”The Centers for Disease Control and Prevention also recommends that companies check for mold growth and pest infestations before reopening.Upgrade ventilation and filtrationA MERV 13 HVAC filter being installed last summer at a gym in Islip, N.Y.Al Bello/Getty ImagesBecause the coronavirus is thought to spread primarily through tiny, airborne droplets, employers should upgrade their ventilation and filtration systems before bringing workers back, experts said.“One thing you can do before you go back to work is simply ask them what they’ve done,” Dr. Allen said. “And if you hear things like, ‘Yes, we’re meeting code,’ then that’s a flag that something’s not right. They should be going above and beyond the bare minimum ventilation and filtration rates.”Although the ideal ventilation rate varies, in general, employers should maximize the amount of fresh air coming in from outdoors, he said. In a relatively small space — say, the size of a typical school classroom — employers should aim for four to six air changes per hour, meaning that the air inside the space is being completely refreshed every 10 to 15 minutes. Opening windows can also improve air flow.High-quality air filters, like those that are rated as MERV 13 or higher, can trap a majority of airborne viral particles. Some commercial buildings are not equipped for these heavy-duty filters; in those offices, portable air purifiers, equipped with HEPA filters, can be effective, experts said.“These types of portable units can do a great job of taking particles out of the room,” Dr. Huffman said. “And the next level is even a desktop level HEPA filter, where you have a really small unit that provides clean air into your direct breathing zone.”These personal units may be particularly helpful in poorly ventilated offices, although experts stressed that employers, not employees, should bear the burden of improving indoor air quality.Be wary of chemical disinfectionExperts warn against installing air-cleaning devices or adding chemical disinfectants to the air. And in most ordinary workplaces, wiping down one’s desk with bleach is likely to do more harm than good.Tamir Kalifa for The New York TimesWhile ventilation and filtration are crucial, employers and building managers should stay away from foggers, fumigators, ionizers, ozone generators or other “air cleaning” devices that promise to neutralize the coronavirus by adding chemical disinfectants to the air. “These are all really terrible ideas of things to do to indoor air,” said Delphine Farmer, an atmospheric chemist at Colorado State University.The compounds that these products emit — which may include hydrogen peroxide, bleach-like solutions or ozone — can be toxic, inflaming the lungs, causing asthma attacks and leading to other kinds of respiratory or cardiovascular problems. And there is not rigorous, real-world evidence that these devices actually reduce disease transmission, Dr. Farmer said.“A lot of employers are now — and school districts and building managers are now — thinking that they have solved the problem by using those devices,” Dr. Farmer said. “So then they are not increasing ventilation rates or adding other filters. And so that means that people think that they’re safer than they actually are.”Surfaces pose minimal risk for coronavirus transmission, and disinfectants needlessly applied to them can also wind up in the air and can be toxic when inhaled. So in most ordinary workplaces, wiping down your desk with bleach is likely to do more harm than good, Dr. Farmer said. (Some specific workplaces — such as hospitals, laboratories or industrial kitchens — may still require disinfection, experts noted.)Nor is there any particular need for special antimicrobial wipes or cleansers, which may fuel the emergence of antibiotic resistant bacteria and wipe out communities of benign or beneficial microbes. “As tempting as it may be to try to sterilize everything, it’s never going to happen, and there may be some real serious consequences,” said Erica Hartmann, an environmental microbiologist at Northwestern University.Don’t depend on desk shieldsIn the early months of the pandemic, plastic barriers sprang up in schools, stores, restaurants, offices and other shared spaces. “They can be great to stop the bigger droplets — really they’re big sneeze guards,” Dr. Huffman said.But the smallest, lightest particles can simply float over and around them. These barriers “may not provide enough benefit to justify their costs,” said Martin Bazant, a chemical engineer at the Massachusetts Institute of Technology. They may even raise the risk of disease transmission, by encouraging riskier behavior or impeding air flow.There are some environments in which these kinds of barriers may still make sense. “It can be a really good idea for people who would otherwise have very close face-to-face contact, like grocery store workers at cash registers,” Dr. Farmer said. “But past that, in offices where you’re sitting for a lengthy period of time, there is no benefit to putting yourself in a plexiglass cage.”There are some environments in which plastic barriers may make sense, experts said, but offices where workers spend a lengthy amount of time are not among them.Alex Welsh for The New York TimesCarefully consider staffing plansSocial distancing may still have some benefits; if an employee is exhaling infectious virus, people sitting directly in that person’s breathing zone will quite likely be exposed to the highest doses. “If you were sitting at a shared table space, two feet away from someone, then there could be some potential value to moving away a little bit further,” Dr. Huffman said.But aerosols can stay aloft for hours and travel far beyond six feet, so moving desks farther apart is likely to have diminishing returns. “Strict distancing orders, such as the six-foot rule, do little to protect against long-range airborne transmission,” Dr. Bazant said, “and may provide a false sense of security in poorly ventilated spaces.”In offices in which most people are vaccinated and local case rates are low, the benefits of distancing are probably minimal, scientists said. Higher-risk workplaces may want to consider de-densification, or reducing the number of people — any one of whom might be infectious — who are present at the same time. “That, to me, has been the biggest benefit of this social distancing indoors,” Dr. Farmer said. “It’s just having fewer potential sources of SARS-CoV-2 in a room.”Companies could allow a subset of employees to work at home indefinitely or on alternating days or weeks. They could also consider “cohorting,” or creating separate teams of workers that do not have in-person interactions with those who are not on their team.Creating these kinds of cohorts could also make it easier to respond if someone does contract the virus, allowing the affected team to quarantine without having to shut down an entire workplace. “When we think about reopening, we need to think about what do we do when, inevitably, we see a case?” said Justin Lessler, an infectious disease epidemiologist at Johns Hopkins University. “There are creative ways to lessen the impact.”In offices in which most people are vaccinated and local case rates are low, the benefits of distancing are probably minimal, scientists said. But higher-risk workplaces may want to consider de-densification.Leah Millis/ReutersGo back to basicsRegular hand-washing, which can reduce the spread of all kinds of pathogens, is always a good idea. “The messaging at the beginning of the pandemic about washing your hands and washing your hands for at least 20 seconds — that is totally valid and still really important,” Dr. Hartmann said.And when your office itself needs cleaning, a mild detergent will generally do the trick, she added: “Soap and water is great.”Masks, too, remain effective. “If you’re someone who’s vaccinated and still feeling anxious about going back to work, the best thing to do is continue to wear a mask for the first couple of weeks until you feel more comfortable,” Dr. Allen said.Scientists recommended that unvaccinated workers continue to wear masks in the office. But for those who are eligible, the most effective risk reduction strategy is obvious, Dr. Allen said: “The No. 1 thing is to get vaccinated.”

Boris Johnson has announced that the UK will donate at least 100 million vaccine doses to other countries within the next year. The first doses will be delivered within a few weeks. Speaking before the G7 summit, Mr Johnson said it was a “colossal number of doses.” President Biden has promised half a billion doses of Pfizer vaccines. Vaccines Minister Nadhim Zahawi said pharmaceutical companies are increasing production around the world.

Pediatricians are urging U.S. parents to get their children caught up on routine vaccinations, following a decline in the number of inoculations for diseases like measles as the pandemic forced restrictions, including shelter-at-home orders, last year.New data from 10 jurisdictions that closely monitor immunizations confirm that the number of administered vaccine doses plunged between March and May of last year, especially among older children, the Centers for Disease Control and Prevention reported on Thursday.Though vaccinations rebounded between June 2020 and September 2020, approaching pre-pandemic levels, the increase was not enough to make up for the earlier drop, the study found.Vaccinations are required for attendance at most schools, camps and day care centers, but the authors of the C.D.C. study warned that the lag nonetheless “might pose a serious public health threat that would result in vaccine-preventable disease outbreaks.”They expressed concern that the transition to remote learning during the pandemic may have hobbled enforcement of vaccination requirements, noting that even temporary declines in immunization can compromise herd immunity.In 2018-2019, a measles outbreak occurred in Rockland County, N.Y., and nearby counties after measles vaccination coverage in area schools dropped to 77 percent, below the 93 percent to 95 percent figure needed to sustain herd immunity. “Pediatric outbreaks of vaccine-preventable diseases have the potential to derail efforts to reopen schools” in the fall, the researchers added.Parents should plan ahead and schedule appointments now so that their children can be protected, said Dr. Yvonne Maldonado, who chairs the committee on infectious diseases at the American Academy of Pediatrics.“We should start thinking about it,” Dr. Maldonado said in a phone interview. “People forget. We have regular pertussis outbreaks every four or five years, and are just waiting to see another one.”“We’re probably going to start seeing more infections, because kids are going to get back together and there’s going to be less masking and social distancing,” she added.The C.D.C. analyzed data from nine states and New York City. In eight of the jurisdictions, some form of stay-at-home order was issued last spring.The number of administered doses of diphtheria, tetanus and pertussis vaccines (DTaP) dropped 15.7 percent among children under age 2, and 60 percent among those aged 2 to 6 in the spring of last year, compared with the same period in 2018 and 2019.Doses of measles, mumps and rubella vaccine (MMR) declined by 22.4 percent among 1-year-olds, and 63 percent among those aged 2 to 8.HPV vaccine administration declined by more than 63 percent among youngsters aged 9 to 17, compared with the same period in 2018 and 2019; and doses of Tdap (tetanus, diphtheria and pertussis) decreased by over 60 percent.

Researchers have studied human kidney cells in the lab to examine the effects of COVID-19 on kidney health. The findings appear in an upcoming issue of JASN.
Many individuals who develop COVID-19 also experience kidney damage, but it’s unclear if this is a direct result of viral infection or a consequence of another condition or the body’s response to the infection. To investigate, a team led by Benjamin Dekel, MD, PhD (Sheba Medical Center, in Israel) cultivated human kidney cells in lab dishes and infected them with the virus that causes COVID-19.
The researchers found that although the virus that causes COVID-19 could enter, infect, and replicate in human adult kidney cells, this did not typically lead to cell death. Prior to infection, the cells contained high levels of interferon signaling molecules, and the infection stimulated an inflammatory response that increased these molecules. In contrast, infection of kidney cells deficient in such molecules resulted in cell death, suggesting a protective effect.
The cells in these experiments were grown as a three-dimensional spheroid that imitates the healthy kidney or as a two-dimensional layer that mimics the cells of an acutely injured kidney. Cells that mimicked an acutely injured kidney were more prone to infection and additional injury but not cell death.
“The data indicate that it is unlikely that the virus is a primary cause of acute kidney injury seen in COVID-19 patients. It implies that if such injury takes place in the kidney by any cause, the virus might jump on the wagon to intensify it. Therefore, if we’re able to limit the common scenario of acute kidney injury in the first place, then there might be the possibility to minimize potential damage caused by the virus,” Dr. Dekel explained.
Study co-authors from the Sheba Medical Center and the Israel Institute for Biological Research include Dorit Omer, PhD, Oren Pleniceanu, MD, PhD, Yehudit Gnatek, MSc, Michael Namestnikov, Osnat Cohen-Zontag, PhD, Sanja Goldberg, PhD, Yehudit Eden Friedman, MD, Nehemya Friedman, PhD, Michal Mandelboim, PhD, Einat B. Vitner, PhD, Hagit Achdout, PhD, Roy Avraham, PhD, Eran Zahavy, PhD, Tomer Israely, PhD, and Haim Mayan, MD.
Disclosures: Dr. Dekel is a co-founder and shareholder at KidneyCure Ltd.
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Materials provided by American Society of Nephrology. Note: Content may be edited for style and length.

Have you ever been cut off in traffic by another driver, leaving you still seething miles later? Or been interrupted by a colleague in a meeting, and found yourself replaying the event in your head even after you’ve left work for the day? Minor rude events like this happen frequently, and you may be surprised by the magnitude of the effects they have on our decision-making and functioning. In fact, recent research co-authored by management professor Trevor Foulk at the University of Maryland’s Robert H. Smith School of Business suggests that in certain situations, incidental rudeness like this can be deadly.
In “Trapped by A First Hypothesis: How Rudeness Leads to Anchoring” forthcoming in the Journal of Applied Psychology, Foulk and co-authors Binyamin Cooper of Carnegie Mellon University, Christopher R. Giordano and Amir Erez of the University of Florida, Heather Reed of Envision Physician Services, and Kent B. Berg of Thomas Jefferson University Hospital looked at how experiencing rudeness amplifies the “anchoring bias.” The anchoring bias is the tendency to get fixated on one piece of information when making a decision (even if that piece of information is irrelevant).
For example, if someone asks, “Do you think the Mississippi River is shorter or longer than 500 miles?,” that suggestion of 500 miles can become an anchor that can influence how long you think the Mississippi River is. When it happens, it’s difficult to stray very far from that initial suggestion, says Foulk.
The anchoring bias can happen in a lot of different situations, but it’s very common in medical diagnoses and negotiations. “If you go into the doctor and say ‘I think I’m having a heart attack,’ that can become an anchor and the doctor may get fixated on that diagnosis, even if you’re just having indigestion,” Foulk explains. “If doctors don’t move off anchors enough, they’ll start treating the wrong thing.”
Because anchoring can happen in many scenarios, Foulk and his co-authors wanted to study more about the phenomenon and what factors exacerbate or mitigate it. They have been studying rudeness in the workplace for years and knew from previous studies that when people experience rudeness, it takes up a lot of their psychological resources and narrows their mindset. They suspected this might play a role in the anchoring effect.
To test their theory, the researchers ran a medical simulation with anesthesiology residents. The residents had to diagnose and treat the patient, and right before the simulation started, the participants were given an (incorrect) suggestion about the patient’s condition. This suggestion served as the anchor, but then throughout the exercise, the simulator provided feedback that the ailment was not the suggested diagnosis, but instead something else.

Medulloblastoma is a rare but devastating childhood brain cancer. This cancer can spread through the spinal fluid and be deposited elsewhere in the brain or spine. Radiation therapy to the whole brain and spine followed by an extra radiation dose to the back of the brain prevents this spread and has been the standard of care. However, the radiation used to treat such tumors takes a toll on the brain, damaging cognitive function, especially in younger patients whose brains are just beginning to develop.
A national study led by Washington University School of Medicine in St. Louis and St. Jude Children’s Research Hospital suggests that children with what is called “average risk medulloblastoma” can receive a radiation “boost” to a smaller volume of the brain at the end of a six-week course of radiation treatment and still maintain the same disease control as those receiving radiation to a larger area. But the researchers also found that the dose of the preventive radiation treatments given to the whole brain and spine over the six-week regimen cannot be reduced without reducing survival. Further, the researchers showed that patients’ cancers responded differently to therapy depending on the biology of the tumors, setting the stage for future clinical trials of more targeted treatments.
Children with average risk medulloblastoma have five-year survival rates of 75% to 90%. In contrast, children with what’s called “high risk medulloblastoma” have five-year survival rates of 50% to 75%. Other factors — such as a child’s age and whether the tumor has spread — help determine the risk category. For this study, the researchers focused on patients with average risk medulloblastoma.
The findings appears online June 10 in the Journal of Clinical Oncology.
“Medulloblastoma is a devastating disease,” said first and corresponding author Jeff M. Michalski, MD, the Carlos A. Perez Distinguished Professor of Radiation Oncology at Washington University. “It is a malignant brain tumor that develops in the cerebellum, the back lower part of the brain that is important for coordinating movement, speech and balance. The radiation treatment for this tumor also can be challenging, especially in younger children whose brains are actively developing in these areas. There’s a balance between effectively treating the tumor without damaging children’s abilities to move, think and learn.”
Children with average risk medulloblastoma typically undergo surgery to remove as much of the tumor as possible. They also receive chemotherapy and radiation therapy to prevent the spread of the tumor to other parts of the brain and spine through the cerebrospinal fluid.

A new Cleveland Clinic-led study has identified mechanisms by which COVID-19 can lead to Alzheimer’s disease-like dementia. The findings, published in Alzheimer’s Research & Therapy, indicate an overlap between COVID-19 and brain changes common in Alzheimer’s, and may help inform risk management and therapeutic strategies for COVID-19-associated cognitive impairment.
Reports of neurological complications in COVID-19 patients and “long-hauler” patients whose symptoms persist after the infection clears are becoming more common, suggesting that SARS-CoV-2 (the virus that causes COVID-19) may have lasting effects on brain function. However, it is not yet well understood how the virus leads to neurological issues.
“While some studies suggest that SARS-CoV-2 infects brain cells directly, others found no evidence of the virus in the brain,” says Feixiong Cheng, Ph.D., assistant staff in Cleveland Clinic’s Genomic Medicine Institute and lead author on the study. “Identifying how COVID-19 and neurological problems are linked will be critical for developing effective preventive and therapeutic strategies to address the surge in neurocognitive impairments that we expect to see in the near future.”
In the study, the researchers harnessed artificial intelligence using existing datasets of patients with Alzheimer’s and COVID-19. They measured the proximity between SARS-CoV-2 host genes/proteins and those associated with several neurological diseases where closer proximity suggests related or shared disease pathways. The researchers also analyzed the genetic factors that enabled SARS-COV-2 to infect brain tissues and cells.
While researchers found little evidence that the virus targets the brain directly, they discovered close network relationships between the virus and genes/proteins associated with several neurological diseases, most notably Alzheimer’s, pointing to pathways by which COVID-19 could lead to AD-like dementia. To explore this further, they investigated potential associations between COVID-19 and neuroinflammation and brain microvascular injury, which are both hallmarks of Alzheimer’s.
“We discovered that SARS-CoV-2 infection significantly altered Alzheimer’s markers implicated in brain inflammation and that certain viral entry factors are highly expressed in cells in the blood-brain barrier,” explained Dr. Cheng. “These findings indicate that the virus may impact several genes or pathways involved in neuroinflammation and brain microvascular injury, which could lead to Alzehimer’s disease-like cognitive impairment.”
The researchers also found that individuals with the allele APOE E4/E4, the greatest genetic risk factor for Alzheimer’s, had decreased expression of antiviral defense genes, which could make these patients more susceptible to COVID-19.
“Ultimately, we hope to have paved the way for research that leads to testable and measurable biomarkers that can identify patients at the highest risk for neurological complications with COVID-19,” said Dr. Cheng.
Dr. Cheng and his team are now working to identify actionable biomarkers and new therapeutic targets for COVID-19-associated neurological issues in COVID long-haulers using cutting-edge network medicine and artificial intelligence technologies.
Yadi Zhou, Ph.D.; Jielin Xu, Ph.D., and Yuan Hou, Ph.D., are co-first authors on the study. The study was supported by the National Institute on Aging, the National Heart, Lung, and Blood Institute; the National Institute of Neurological Disorders and Stroke, and Cleveland Clinic’s VeloSano Pilot Program.
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Metformin is a widely prescribed blood sugar-lowering drug. It is often used as an early therapy (in combination with diet and lifestyle changes) for type 2 diabetes, which afflicts more than 34 million Americans.
Metformin works by lowering glucose production in the liver, reducing blood sugar levels that, in turn, improve the body’s response to insulin. But scientists have also noted that metformin possesses anti-inflammatory properties, though the basis for this activity was not known.
In a study published online June 8, 2021 in the journal Immunity, a multi-institution team led by researchers at University of California San Diego School of Medicine identified the molecular mechanism for the anti-inflammatory activity of metformin and, in mouse studies, found that metformin prevents pulmonary or lung inflammation in animals infected with SARS-CoV-2, the virus that causes COVID-19.
Over the past year, several retrospective clinical studies had reported that metformin use by diabetic and obese patients prior to hospital admission for COVID-19 correlated to reduced severity and mortality. Both diabetes and obesity are recognized risk factors for COVID-19, and are linked to more severe outcomes. Notably, other drugs used to control blood sugar levels do not appear to produce a similar effect.
But while these clinical studies suggested metformin’s anti-inflammatory activity, rather than lowering of blood glucose, could be responsible for reduced COVID-19 severity and mortality, none of the studies offered an explanation or prompted large, randomized clinical trials needed for obtaining conclusive answers.
“The clinical studies were plagued by confounders that made conclusions hard to reach. There was some skepticism in their findings,” said corresponding study author Michael Karin, PhD, Distinguished Professor of Pharmacology and Pathology and Ben and Wanda Hildyard Chair for Mitochondrial and Metabolic Diseases at UC San Diego School of Medicine. “And because metformin is an out-of-patent, low-cost drug, there is little impetus to conduct large-scale trials, which are quite expensive.”
Karin, with co-senior author Elsa Sanchez-Lopez, PhD, an assistant professor at the Department of Orthopedic Surgery, postdoctoral fellow Hongxu Xian, PhD, and others, turned their focus to a mouse model of acute respiratory distress syndrome (ARDS), a life-threatening condition in which fluids leak into the lungs, making breathing difficult and restricting oxygen supply to essential organs.