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‘The Last of Us’ Come Alive: Fungi Are Adapting to Warmer Temperatures

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Dangerous fungal infections are on the rise, and a growing body of research suggests warmer temperatures might be a culprit.

The human body’s average temperature of 98.6 degrees Fahrenheit has long been too hot for most fungi to thrive, infectious-disease specialists say. But as temperatures have risen globally, some fungi might be adapting to endure more heat stress, including conditions within the human body, research suggests. Climate change might also be creating conditions for some disease-causing fungi to expand their geographical range, research shows. 

“As fungi are exposed to more consistent elevated temperatures, there’s a real possibility that certain fungi that were previously harmless suddenly become potential pathogens,” said

Peter Pappas,

an infectious-disease specialist at the University of Alabama at Birmingham. 

Deaths from fungal infections are increasing, due in part to growing populations of people with weakened immune systems who are more vulnerable to severe fungal disease, public-health experts said. At least 7,000 people died in the U.S. from fungal infections in 2021, the Centers for Disease Control and Prevention said, up from hundreds of people each year around 1970. There are few effective and nontoxic medications to treat such infections, they said. 

Photos: What We Know About Deadly Fungal Infections

In the video game and HBO show “The Last of Us,” a fungus infects people en masse and turns them into monstrous creatures. The fungus is based on a real genus, Ophiocordyceps, that includes species that infect insects, disabling and killing them.

There have been no known Ophiocordyceps infections in people, infectious-disease experts said, but they said the rising temperatures that facilitated the spread of the killer fungi in the show may be pushing other fungi to better adapt to human hosts and expand into new geographical ranges. 

A January study in the journal Proceedings of the National Academy of Sciences showed that higher temperatures may prompt some disease-causing fungi to evolve faster to survive. 

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Researchers at Duke University grew 800 generations of a type of Cryptococcus, a group of fungi that can cause severe disease in people, in conditions of either 86 degrees Fahrenheit or 98.6 degrees Fahrenheit. The researchers used DNA sequencing to track changes in the fungi’s genome with a focus on “jumping genes”—DNA sequences that can move from one location on the genome to another.

Asiya Gusa, a study co-author and postdoctoral researcher in Duke’s Molecular Genetics and Microbiology Department, said movement of such genes can result in mutations and alter gene expression. In fungi, Dr. Gusa said, the movement of the genes could play a role in allowing fungi to adapt to stressors including heat. 

Dr. Gusa and her colleagues found that the rate of movement of “jumping genes” was five times higher in the Cryptococcus raised in the warmer temperature. 

Cryptococcus infections can be deadly, particularly in immunocompromised people. At least 110,000 people die globally each year from brain infections caused by Cryptococcus fungi, the Centers for Disease Control and Prevention said. 

Candida auris, a highly deadly fungus that has been reported in about half of U.S. states, also appears to have adapted to warmer temperatures, infectious-disease specialists said. 

“Fungi isn’t transmitted from person to person, but through fungal spores in the air,” Dr. Gusa said. “They’re in our homes, they’re everywhere.”

An analysis published last year in the journal Clinical Infectious Diseases said some potentially deadly fungi found in the soil, including Coccidioides and Histoplasma, have significantly expanded their geographical range in the U.S. since the 1950s. Andrej Spec, a co-author of the analysis and an associate professor of medicine at Washington University School of Medicine in St. Louis, said warming temperatures, as well as other environmental alterations associated with climate change, could have played a role in this spread. 

Cases of Coccidioidomycosis or Valley fever, a disease caused by Coccidioides, were once mostly limited to the Southwest, Dr. Spec said. Now people are being diagnosed in significant numbers in most states. Histoplasma infections, once common only in the Midwest, have been reported in 94% of states, the analysis said. Histoplasma is also spread through bat droppings and climate change has been linked to changing bat migration patterns, Dr. Spec said.

The World Health Organization has identified Cryptococcus, Coccidioides, Histoplasma and Candida auris as being among the fungal pathogens of greatest threat to people. 

“We keep saying these fungi are rare, but this must be the most common rare disease because they’re now everywhere,” Dr. Spec said.

Write to Dominique Mosbergen at dominique.mosbergen@wsj.com

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For Future Viral Threats, Health Officials Look to Sewage

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When the virologist Kirsten St. George learned last summer that a paralyzed patient in New York’s Rockland County had tested positive for polio, she turned her attention to the state’s sewers.

Polio is particularly stealthy because most infected people never develop symptoms but can still spread the virus. A wastewater-surveillance network established during the Covid-19 pandemic helped officials at the New York State Department of Health’s Wadsworth Center track polio’s spread in several counties.

New York is now expanding wastewater monitoring and starting to look for flu, RSV, hepatitis A, norovirus and antibiotic-resistant genes in parts of the state, as health officials across the U.S. consider wastewater as a more permanent public-health tool for watching a variety of threats.

“Are we on the brink of another outbreak, if it’s rising? Is it just sort of holding steady?” asked Dr. St. George, Wadsworth’s director of virology. “These are all important public health questions.”   

Dr. Kirsten St. George of the Wadsworth Center is looking for clues in the state’s sewage.
An analysis conducted at the Wadsworth Center indicates the presence of the hepatitis A virus.

Dr. Kirsten St. George of the Wadsworth Center, which is starting to track the spread of pathogens including the hepatitis A virus.

For decades, researchers around the world used wastewater primarily to track poliovirus, which spreads through contact with an infected person’s feces. At the onset of the pandemic, scientists found that the Covid-19 virus’s genetic material could be detected in sewage. That meant sewage might help track other respiratory viruses, too.

Researchers built surveillance networks around the country to track Covid-19 and monitor for variants. 

Now they are starting to leverage that system to search for other pathogens they had wanted to track through the sewers for years including norovirus and antibiotic-resistant microbes, said Amy Kirby, program lead of wastewater surveillance at the Centers for Disease Control and Prevention. 

“Once you have this system, it’s much easier to activate it for a new pathogen,” Dr. Kirby said.

Sewage samples from treatment plants are sent to labs, where genetic material that can come from hundreds of thousands of people is isolated. Researchers usually test samples for pathogens with the PCR technology used in a Covid-19 lab test administered at the doctor’s office.  

Health officials use the data to track changing concentrations of a virus, which can help them monitor the spread of pathogens including flu and RSV for which many people might not be tested. The technique has yielded early evidence of Covid-19 outbreaks and helped officials tailor public messaging and decide where to open testing sites.

Biobot Analytics Inc., which works with the CDC to monitor Covid-19 and the renamed mpox, started tracking opioids in wastewater before the pandemic. It has collected data on substances including fentanyl in more than 100 counties across 47 states. Officials in Cary, N.C., used that data to encourage people to dispose of drugs properly and to distribute more overdose-reversal drugs, Biobot said.

Not everything can be tracked through sewage, and there isn’t a standard national system for collecting data and comparing readings from site to site. Privacy can be a concern in smaller communities or when tracking illicit substances, researchers said, though wastewater data is processed as an anonymous group sample. And some communities that collect wastewater data aren’t using it to guide public-health policy, researchers said. 

The wastewater treatment plant in Schenectady, N.Y., is participating in the study of sewage.
Workers at the Schenectady treatment plant collect samples and ship them for analysis.
Analysis of the wastewater samples is conducted at the Wadsworth Center in Albany, N.Y.

The wastewater treatment plant in Schenectady, N.Y., where workers collect samples and ship them for analysis at the Wadsworth Center in Albany, N.Y.

The National Academies of Sciences, Engineering, and Medicine said in a report Thursday that the U.S. should invest more in the CDC’s wastewater-surveillance network and expand its reach. The report recommended that the CDC should have an open process for picking which pathogens to track and establish an ethics committee, among other steps.  

“We’re at a critical juncture where it has gone from being a grass-roots effort to a more nationally recognized tool,” said Megan Diamond, head of the Rockefeller Foundation’s wastewater-surveillance program, who wasn’t involved with the report.

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After a polio case was confirmed in New York in July, health officials reviewed stored wastewater samples and found poliovirus in wastewater from several counties, including as far back as spring. Health officials urged people who weren’t vaccinated against polio to get the shots and alerted doctors.

The CDC extended poliovirus wastewater testing to a handful of counties with low vaccination rates or potential connections to New York’s polio case.

“What you might expect a virus to do when it starts circulating is exactly what we saw in the wastewater,” said Dan Lang, deputy director of New York’s Center for Environmental Health and head of the state’s wastewater-monitoring program.

No samples tested positive for poliovirus by the end of November, but it was detected again in Orange County last month. Health officials are planning to analyze past samples from additional counties for traces of the virus before deciding whether to widen poliovirus wastewater monitoring when the weather warms and the virus can spread more readily. 

“We’re worried about a big sort of roaring back,” said Dr. Eli Rosenberg, a lead epidemiologist who coordinates New York’s polio response. “We’re using this time now to prepare.”

Poliovirus was found in Orange County, N.Y., last month.

Write to Brianna Abbott at brianna.abbott@wsj.com

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Mystery of Smell Loss After Covid-19 Might Be Solved

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The nose knows why some people still can’t smell long after recovering from Covid-19.

A haywire immune response in the olfactory system was found to explain why some people still can’t smell long after symptoms of the disease have abated, according to a small, peer-reviewed study published Wednesday in the journal Science Translational Medicine. In some cases, the immune or inflammatory response was detected in patients with smell loss up to 16 months after recovery from Covid-19.

Compared with people who can smell normally, patients with long-term smell loss had fewer olfactory sensory neurons, cells in the nose responsible for detecting smells and sending that information to the brain. Patients with lingering loss of smell had an average of 75% fewer of the neurons compared with healthy people, said

Brad Goldstein,

a study co-author and sinus surgeon at Duke University.

“We think the reduction of sensory neurons is almost definitely related to the inflammation,” Dr. Goldstein said.

Loss of smell is a common Covid-19 symptom, though its prevalence varies widely depending on factors including which variant caused the infection, head and neck specialists said.

Most Covid-19 patients who experience smell loss regain the sense within weeks of infection. But the symptom can stick around for a year or longer for up to 7% of patients, a February analysis said.

Dr. Goldstein said he and his colleagues sought to identify what was damaged or altered in people with long-term smell loss. “If we don’t know what’s broken, it’s hard to tell how to fix it,” he said.

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They took samples from the nose tissue of nine patients who couldn’t smell long after Covid-19 infections and compared them with cells from healthy people. Patients with persistent smell loss had more T-cells, a type of white blood cell that plays a critical part in immune response, in their noses, the study said. The T-cells were making interferon-gamma, a substance linked to inflammation, Dr. Goldstein said, and support cells appeared to be reacting to it.

The support cells protect and nourish olfactory sensory neurons. Without them, the olfactory sensory neurons can’t survive. Research has shown that the virus that causes Covid-19 doesn’t infect olfactory sensory neurons directly, but that it can attack such support cells.

Patients with smell loss also had fewer of a certain type of anti-inflammatory cell and more of a particular inflammatory cell than healthy people, said the study of 24 patients. The healthy group included two people who had recovered from Covid-19 but didn’t have long-term smell loss.

Covid-19 researchers said the study bolstered evidence that inflammation could be a culprit in long-Covid symptoms. An April study in the journal JAMA Neurology found inflammation among deceased Covid-19 patients in the olfactory bulb, the part of the brain responsible for receiving and processing information from olfactory sensory neurons in the nose.

Neuroinflammation could be a contributor to loss of smell and other neurological symptoms related to long-Covid such as brain fog, said

Cheng-Ying Ho,

a co-author of the April study and an associate professor of pathology at Johns Hopkins University School of Medicine.

Dr. Ho, who wasn’t involved in the new study, said inflammation that starts in the nasal cavity could extend to the brain. She said that the new study was compelling but that its small sample size necessitated further work in more patients. Because the vaccination status of participants wasn’t collected, she said it wasn’t clear whether getting the shots played a role in the olfactory system’s inflammatory response. 

In a survey published last year of more than 400 patients with smell loss, more than 40% reported depressive symptoms and almost 90% reported enjoying food less.

“People might think smell loss is not really an important Covid symptom compared with severe symptoms such as pneumonia, but it can really bother some patients,” Dr. Ho said. 

Researchers said regions of the brain linked to the sense of smell are closely associated with brain regions that control memory and emotion.  

Sandeep Robert Datta,

a co-author of the new study and a professor of neurobiology at Harvard Medical School, said he and others are conducting more research into the reasons for smell loss following Covid-19 infection smell loss. The research could lead to potential targets for treatment. There are no effective treatments for long-term smell loss, Dr. Datta said.

“Smell gives you a sense of place. It can be very disorienting without it,” Dr. Datta said.

Write to Dominique Mosbergen at dominique.mosbergen@wsj.com

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Why You Can’t Find Wegovy, the Weight-Loss Drug

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Novo Nordisk

NVO 0.61%

A/S flubbed the launch of its buzzy new weight-loss drug Wegovy, missing out on hundreds of millions of dollars in sales and squandering a head start before a rival could begin selling a competing product.

Wegovy is among a new class of drugs that health regulators have approved to cut the weight of people who are obese, a goal long sought by doctors and patients. Their weight-dropping potential became a viral sensation on social media. Elon Musk tweeted about Wegovy in October. And a related drug for diabetes, Ozempic, is a hot topic in Hollywood among celebrities seeking to stay thin, according to doctors.

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Yet Denmark-based Novo underestimated how big demand for the drug would be, and wasn’t ready to make enough to fill the prescriptions that flooded in after U.S. approval last year. Then a contract manufacturer halted production to address inspection issues.

“We should have forecasted better, which we did not,” Novo Chief Executive

Lars Fruergaard Jørgensen

said. “Had we forecasted that, we would have built a different supply chain.”

The missteps have proven costly for Novo, which was forced to ration Wegovy to patients who already had started taking it. The company has recorded around $700 million in sales to date, well short of the $2 billion in 2021 and 2022 sales that some analysts had projected before supply issues hit.

Novo Nordisk Chief Executive Lars Fruergaard Jørgensen admits the drug company misjudged how popular Wegovy would be.



Photo:

Carsten Snejbjerg/Bloomberg News

Amber Blaylock, a music teacher from Springfield, Mo., said she has been trying to get Wegovy to help her reduce weight since hearing about the drug on TikTok and YouTube. She asked her doctor in September to prescribe it, but hasn’t been able to find it. 

“Frustrated and impatient for sure,” said Ms. Blaylock, 29 years old.

To turn things around, Mr. Jørgensen said Novo has increased its capacity to make Wegovy and plans a “relaunch” early next year, which should fulfill all orders.

Novo, however, lost valuable time establishing a beachhead in the lucrative obesity-drug market before rival

Eli Lilly

LLY 1.20%

& Co. can enter. Lilly is expected to launch a similar, competing drug named Mounjaro late next year or in early 2024.

The market for anti-obesity drugs, now worth $2.4 billion worldwide, could reach $50 billion in 2030, Morgan Stanley estimates.

“Novo has left the door open for Lilly,” said BMO Capital Markets analyst Evan David Seigerman. 

Mr. Jørgensen said the company can regain lost ground because of high demand for Wegovy and the large potential for what is still a mostly untapped market. He said he was unconcerned with the looming competition with Lilly’s drug, because there is room for both products.

“We disappointed physicians and patients in the first round,” he said. “The company wants to be better prepared for the second round.” Novo lists Wegovy at $1,349 a month. Some commercial insurers cover the drug.  

Wegovy works by imitating a hormone called GLP-1, which occurs naturally in the body and suppresses appetite, among other effects. 

Novo developed GLP-1 drugs to treat diabetes. In 2017, the company began selling semaglutide, the active ingredient in Wegovy, under the brand name Ozempic to treat diabetes. 

During the drug’s development, Novo found that weight loss was a side effect, prompting the company to probe using semaglutide to treat obesity. A key trial found that Wegovy helped people with a high body-mass index shed up to 15% of their weight, surpassing the results for older obesity drugs like Novo’s Saxenda. 

Saxenda and other older weight-loss drugs had sold modestly, partly due to their limited weight loss, as well as some unpleasant side effects and the refusal of many health insurers to pay up. 

Novo worked with Catalent to fill its Wegovy weight-loss drug into syringes.



Photo:

yara nardi/Reuters

Given the experience, Novo figured Wegovy sales would increase gradually. To augment its own production, Novo contracted with a single manufacturer,

Catalent Inc.,

to fill the drug into syringes. Novo said it thought it would have time to add manufacturing capacity to meet a gradual increase in demand.

Wegovy may be superior to older drugs, but “we thought it would still be a journey to open up the market,” Mr. Jørgensen said. 

When Novo started selling Wegovy in the U.S. in June last year, however, demand took off. Doctors with large followings on social media touted Wegovy as groundbreaking, while users posted photos holding injection pens and shared their progress losing weight. 

“Demand for these new agents has been unlike anything I’ve ever seen in my time in medicine,” said Dr. Michael Albert, a physician specializing in weight-loss treatment at telehealth provider Accomplish Health who has consulted for Novo. Many of his patients began asking about Wegovy, he said, after they heard about it in Facebook groups or on TikTok.

It took only five weeks for doctors to write new prescriptions for Wegovy at the same weekly volume that Saxenda took four years to reach, according to Mr. Jørgensen. “It’s a completely different ballgame that we’re in,” said Ambre Brown Morley, the company’s vice president of media and digital global communication. 

Within weeks, supplies were strained. Novo warned that patients might experience delays in receiving their prescriptions. Then in December 2021, Catalent temporarily stopped deliveries and manufacturing at its plant after Food and Drug Administration inspections found faulty air filters and damaged equipment.

To date, Novo has recorded around $700 million in Wegovy sales compared with the $2 billion in 2021 and 2022 sales that some analysts had projected before supply issues emerged.



Photo:

JACOB GRONHOLT-PEDERSEN/REUTERS

Many people who couldn’t get Wegovy for weight loss have sought prescriptions for Novo’s Ozempic and Lilly’s Mounjaro, according to analysts, even though the FDA hasn’t approved the latter two drugs for such use. Ozempic sales increased so much that certain doses are in short supply through at least January, the FDA said.

Lilly is studying Mounjaro, its GLP-1-containing drug for diabetes, for weight loss. 

Novo and Lilly said they don’t promote their diabetes drugs for the “off-label” use treating obesity.

A Catalent spokesman said the company is still making improvements to the plant and working with customers to limit the impact of supply constraints on patients. The company restarted filling Wegovy syringes at the facility in the spring. 

Novo has been amassing a sufficient inventory before the Wegovy relaunch, Mr. Jørgensen said. When Wegovy relaunches, he said, insurance coverage will be broader than when the drug first went on sale. 

Write to Peter Loftus at Peter.Loftus@wsj.com and Denise Roland at denise.roland@wsj.com

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Flu, RSV and Covid-19 Add to Crunch on Pediatric Hospitals

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Flu activity continued to rise across the U.S. in the past week, adding to a crunch on emergency departments and pediatric hospitals from an early surge in respiratory viruses.

Flu has caused an estimated 4.4 million illnesses, 38,000 hospitalizations and 2,100 deaths so far this season including seven pediatric deaths, the Centers for Disease Control and Prevention said Friday. The highest flu hospitalization rates are among adults ages 65 and older, followed by children under the age of 5, the CDC said.

Pediatric hospitals across the U.S. have been under strain for weeks from a rush of patients with RSV and other respiratory viruses. RSV amounts to a cold in most people, but the virus can be dangerous for younger children and older adults, especially those with other health concerns. 

“You have flu that is starting to surge in other areas where they’re trying to deal with the RSV surge, and you also have Covid,” said Tina Tan, vice president of the Infectious Diseases Society of America. “It’s one after the other after the other.” 

RSV cases appear to be plateauing or declining in parts of the U.S., doctors said. Within the CDC’s RSV-surveillance network of 12 states, the hospitalization rate for RSV remains higher than the most recent prepandemic peak.  

Some 76% of pediatric inpatient beds are occupied across the U.S. and occupancy of pediatric intensive-care beds is just above 80%, according to the Department of Health and Human Services. That’s up from 65% of pediatric beds and 70% pediatric ICU beds occupied in early August.   

States including Massachusetts, Nevada, Pennsylvania and Texas have more than 90% of their pediatric intensive-care beds occupied, the data show. The data doesn’t specify why patients are in the hospital. 

Researchers say the coronavirus is having a persistent effect, keeping millions out of work and reducing the productivity and hours of millions more.



Photo:

Neeta Satam for The Wall Street Journal

“We really maxed out all the space we have,” said Kristina Deeter, physician-in-chief at Renown Children’s Hospital in Reno, Nev., and specialty medical officer for pediatric critical care at

Pediatrix Medical Group.

Pediatric patients at Renown Children’s are backed up into the waiting room, some teenagers have been sent to the adult floor and a list of kids from nearby emergency departments are waiting for a bed, she said. 

Other respiratory viruses, including Covid-19, and high demand from pediatric mental-health patients are contributing to the strain at pediatric hospitals, doctors said. Nursing shortages and a decrease in pediatric beds have compounded the crunch. 

From 2008 to 2018, the number of pediatric inpatient beds in the U.S. decreased by 12%, according to a 2021 study in the journal Pediatrics. Declines in rural areas were steeper than average, and pediatric specialty care has been increasingly concentrated at large children’s hospitals. The pandemic exacerbated those trends, doctors said. 

“When we combine that decrease in beds with a surge in the need for those beds, I certainly think we feel it,” said Anna Cushing, lead author on the study and a pediatric emergency medicine physician at Children’s Hospital Los Angeles. Children’s Hospital Los Angeles hasn’t had space to accept all the transfer patients looking for a bed, said chief medical officer James Stein.

At Rady Children’s Hospital-San Diego, emergency department wait times have fluctuated between two and six hours. In October, the hospital started sending administrative staff to volunteer there, freeing up the regular workers to focus on the sickest patients. 

The staffers give kids blankets and alert a triage nurse if patients get sicker, said Nicholas Holmes, chief operating officer at Rady Children’s. A trained pediatric urologist, Dr. Holmes said he worked in the emergency room several times last week. 

“Handing out a coloring book and giving a kid a Popsicle, it helps them feel a little bit better,” Dr. Holmes said.  

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People should wash their hands, stay home if they’re sick, consider wearing masks indoors and while traveling and get vaccinated against Covid-19 and the flu, doctors and health officials said. They said people should be particularly conscious of risks to infants and older adults during Thanksgiving gatherings. 

There are no specific treatments for RSV, but over-the-counter medication can help with fever and patients should stay hydrated. Parents should consult pediatricians if a child is having trouble breathing, having trouble staying hydrated or appears lethargic, doctors said. 

The American Academy of Pediatrics said eligible high-risk infants could receive more than the standard five consecutive doses of the monoclonal antibody palivizumab to protect them during this unusually early and long RSV season. Hospital referrals should be reserved for children who need a higher level of care, to avoid overcrowding and extended wait times, the academy said. 

—Jon Kamp contributed to this article.

Write to Brianna Abbott at brianna.abbott@wsj.com

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Marijuana May Hurt Smokers More than Cigarettes Alone

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Marijuana might do more damage to smokers than cigarettes alone.

A study published Tuesday in the journal Radiology demonstrated higher rates of conditions including emphysema and airway inflammation among people who smoke marijuana than among nonsmokers and people who smoked only tobacco. Nearly half of the 56 marijuana smokers whose chest scans were reviewed for the study had mucus plugging their airways, a condition that was less common among the other 90 participants who didn’t smoke marijuana.

“There is a public perception that marijuana is safe and people think that it’s safer than cigarettes,” said Giselle Revah, a radiologist who helped conduct the study at the Ottawa Hospital in Ontario. “This study raises concerns that might not be true.”

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One-fifth of Canadians over 15 years old reported using marijuana in the past three months, according to a 2020 survey of some 16,000 people conducted by Canada’s national statistical office. About 18% of Americans reported using marijuana at least once in 2020 in the U.S. Substance Abuse and Mental Health Services Administration’s National Survey of Drug Use and Health, including about one in three young adults age 18 to 25. The surveys didn’t ask how marijuana was consumed. About one-fourth of people over 12 years old believed there was great harm from smoking marijuana once or twice a week, according to the survey.

Previous studies have found that marijuana is more likely than tobacco to be smoked unfiltered and that smokers tend to inhale more smoke and hold it in their lungs longer. Bong smoke contains tiny pollutants that can linger indoors for up to 12 hours, a study published in March in JAMA Network Open showed.

Among the 56 marijuana smokers in the Ottawa study, 50 also smoked tobacco. The tobacco-only smokers were patients whose chest scans were performed as part of a high-risk lung-cancer screening program that included people age 50 and above who had smoked for several years.

Marijuana’s illicit status long discouraged substantial research into the long-term effects of its use, said Albert Rizzo, chief medical officer for the American Lung Association, who wasn’t involved in the study. Inhaling any heated substance can irritate airways, among other health dangers, he said.

“There could be an additive effect if you smoke cigarettes as well as marijuana,” Dr. Rizzo said.

The study authors found bronchial thickening in 64% of marijuana smokers versus 42% of tobacco-only smokers and a condition that leads to excess mucus buildup in 23% of marijuana smokers versus 6% of tobacco-only smokers.

Age-matched marijuana smokers had higher rates of emphysema (93%) than tobacco-only smokers (67%), and the emphysema, which appears in imaging as small holes in lung tissue, was more prevalent in the marijuana smokers, the study found.

Write to Julie Wernau at julie.wernau@wsj.com

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RSV Hospitalizations Surge, Babies Hit Hardest

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High rates of hospitalization with RSV are hitting the youngest children especially hard, part of an unseasonably early surge in respiratory infections.

Some 3.0 people for every 100,000 were hospitalized with respiratory syncytial virus the week ended Nov. 5, according to federal data from 12 states. The rate is the highest since the winter just before the pandemic, when some 2.7 people per 100,000 were hospitalized in January 2020. The hospitalization rate declined from 3.4 hospitalizations per 100,000 in the week ended Oct. 29.

Babies under six months old have the highest RSV-related hospitalization rate, data from the Centers for Disease Control and Prevention show, at 145 hospitalizations per 100,000 infants. Infants six to 12 months old were hospitalized at a rate of 63 for every 100,000 children that age. For adults, the hospitalization rate is 0.6 per 100,000 people.

RSV is a common virus that most children encounter by their second birthday. Reinfections can occur at any age. Most people experience mild, cold-like symptoms and recover in a week or two. But RSV can be serious for some infants and older adults, causing bronchitis and pneumonia.

Younger children tend to be at higher risk, in part because their airways are smaller and get more easily clogged when they are inflamed, said Dana Free, a travel nurse with a company called Trustaff, working in a pediatric intensive-care unit in Danville, Pa.

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“If you think of it as a straw, and that’s your normal breathing, that’s fine,” Ms. Free said. “You coat it in congestion, essentially snot and mucus, you’re making that airway much smaller.”

Emergency rooms and pediatric hospitals across the U.S. have reported strain due to increased cases of RSV and other common respiratory viruses. Some recent closures of pediatric units have compounded the issue, doctors said, and staff are stretched thin.

Some hospitals in the Northeast are postponing elective surgeries or sending older children to adult hospitals, said Connecticut Department of Public Health Commissioner Manisha Juthani. Those strategies aren’t as effective for pediatric care because fewer children have elective surgeries than adults and hospitalization rates among older children are lower, she said.

Children’s Hospital New Orleans is getting calls from doctors in Mississippi, Alabama and Texas looking for beds for patients, said pediatric infectious disease specialist Mark Kline. “You’re talking about kids who have critical illness because they’re in respiratory failure,” Dr. Kline said. “They’re not occasional calls. It’s every day.”

Schools in states including Kentucky and Ohio temporarily suspended classes or switched to remote learning at least one day this week because students and staff were out sick.

RSV usually spreads from the fall through winter, peaking sometime between late December and mid-February. But with the onset of the Covid-19 pandemic, RSV cases practically disappeared, likely because of Covid-19 mitigation measures including masking that appear to have restricted the spread of a range of viruses.

RSV came back in the summer of 2021, unusual for that time of year, eventually reaching a hospitalization rate of 1.3 per 100,000 people in mid-December. The virus continued circulating this year throughout the spring and summer and surged in recent weeks.

Physicians are reporting high numbers of respiratory illnesses like RSV and the flu earlier than the typical winter peak. WSJ’s Brianna Abbott explains what the early surge means for the coming winter months. Photo illustration: Kaitlyn Wang

“RSV has done something similar in the previous two seasons where it started early, but nothing to this extent and nothing as widespread as now,” said William Schaffner, medical director at the National Foundation for Infectious Diseases.

Many younger infants might not have been exposed to RSV, in part because of Covid-19 mitigation efforts that kept other viruses in check, doctors said. Mitigation measures have largely been dropped at places including schools and daycare centers, and the relative lack of exposure compared with prior seasons created a wider pool of susceptible people, some public-health experts said.

“This increased number of cases is to be expected, given the number of individuals that are susceptible to the virus at this time,” José Romero, director for the National Center for Immunization and Respiratory Diseases at the CDC, said last week. There aren’t any indications at this time that the cases are more severe, Dr. Romero said.

There aren’t any specific RSV treatments, but some over-the-counter medications can help manage pain and fever, and patients should stay hydrated, doctors said. Most adults and infants without other health conditions don’t need to be hospitalized, the CDC said.

People should seek medical attention if they have trouble breathing, aren’t drinking enough fluids or have worsening symptoms, the CDC said. Some might need additional oxygen, fluids or a breathing tube. Hospitalization tends to last a few days.

Among children under the age of 5, an estimated 100 to 300 RSV-related deaths occur each year in the U.S. while some 6,000 to 10,000 deaths occur among adults 65 and older, according to the CDC. The RSV-hospitalization rate for people 65 and older is per 100,000 people, according to CDC data.

The CDC said it doesn’t have real-time death data because RSV reporting isn’t mandatory.

Areas including the Southeast and South-Central parts of the U.S. last week recorded declines in the proportion of tests positive for RSV, Dr. Romero said. In Connecticut, children’s hospitals reported a stable or slightly lower number of children admitted to the hospital compared with the week prior, the state health department’s Dr. Juthani said.

“I’m hoping that we’ve somewhat plateaued in the Connecticut area,” Dr. Juthani said. “The downside is that flu is taking off.”

Doctors and health officials said they are watching how flu and Covid-19 might collide with RSV trends this winter.  

“We likely have not peaked,” said Amanda Castel, an infectious-disease epidemiologist at the George Washington University Milken Institute School of Public Health.

Write to Brianna Abbott at brianna.abbott@wsj.com

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Health

Pig’s Heart Took Longer to Generate a Beat in Transplant Patient

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A genetically modified pig heart transplanted into a severely ill person took longer to generate a heartbeat than those of typical pig or human hearts, research showed, another potential challenge for doctors aiming to conduct clinical trials of pig-organ transplants.

Doctors took daily electrocardiograms of

David Bennett,

a 57-year-old handyman and father of two who received a gene-edited pig heart in an experimental surgery at the University of Maryland Medical Center in Baltimore in January. Mr. Bennett died in March from heart failure, but doctors still aren’t sure why the pig heart thickened and lost its pumping ability.

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Doctors involved in the groundbreaking surgery have been studying data from Mr. Bennett’s case, which is being closely watched in the wider transplant community. Researchers reported in May that a common pig virus was detected in the pig heart transplanted into Mr. Bennett. They said there is no evidence the virus infected Mr. Bennett, but its presence in the pig heart could have caused inflammation that contributed to the cascade of events that led to his death from heart failure.

Researchers analyzed Mr. Bennett’s EKG data as part of efforts to understand his decline after the transplant, direct future research and determine a possible path toward opening clinical trials. Widely used tests that measure electrical signals that cause the heart to beat, EKGs can help diagnose heart attacks, irregular heart rhythms and other possible abnormalities.

Researchers reported unexpected findings in two aspects of Mr. Bennett’s EKG data: the time it takes electricity to travel from the top to the bottom chamber of the heart and across the bottom chambers, which pumps blood through the heart, and the time it takes the lower chambers of the heart to go through a full electrical cycle, which is associated with a heartbeat.



The surfaces of pig cells contain a sugar molecule that triggers the human immune system to attack the organs. Scientists are using the gene editing tool Crispr to overcome this obstacle.

Here’s one approach:

…and then insert the edited DNA into a pig egg cell whose nucleus has been removed. The egg cell is then transferred to the uterus of a sow. The sow gives birth to pigs whose cells—including those in their organs— contain the edited genes.

Crispr acts like scissors cutting DNA at a specific place

scientists edit troublesome genes in pig DNA…

…and sometimes add human genes…

ORGAN OPTIONS

Researchers are trying various techniques that might allow transplantation of gene-edited pig hearts, kidneys and livers into humans. Recent studies on pig organ transplantation in baboons and people have focused mainly on hearts and kidneys.

HEART TO HEART

Pig and human hearts have similarities—but also some differences.

Pigs can be bred to have hearts of similar size as human hearts.

Pig and human hearts each have four pumping chambers—two small ones known as atria and two large ones known as ventricles.

The wall of tissue separating the ventricles is thicker in pig hearts than in human hearts.

Pig and human hearts each are attached to a large artery known as the aorta as well as to a large vein known as the vena cava.

A pig’s inferior (lower) vena cava joins a pig heart’s right atrium at an angle. The vein is longer in pigs than in humans.

EASING ORGAN REJECTION

The surfaces of pig cells contain a sugar molecule that triggers the human immune system to attack the organs. Scientists are using the gene editing tool Crispr to overcome this obstacle. Here’s one approach:

Crispr acts like scissors cutting DNA at a specific place.

Scientists edit troublesome genes in pig DNA…

…and sometimes add human genes…

…and then insert the edited DNA into a pig egg cell whose nucleus has been removed. The egg cell is then transferred to the uterus of a sow. The sow gives birth to pigs whose cells—including those in their organs—contain the edited genes.

ORGAN OPTIONS

Researchers are trying various techniques that might allow transplantation of gene-edited pig

hearts, kidneys and livers into humans. Recent studies on pig organ transplantation in baboons and people have focused mainly on hearts and kidneys.

HEART TO HEART

Pig and human hearts have similarities—but also some differences.

Pigs can be bred to have hearts of similar size as human hearts.

Pig and human hearts each have four pumping chambers—two small ones known as atria and two large ones known as ventricles.

The wall of tissue separating the ventricles is thicker in pig hearts than in human hearts.

Pig and human hearts each are attached to a large artery known as the aorta as well as to a large vein known as the vena cava.

A pig’s inferior (lower) vena cava joins a pig heart’s right atrium at an angle. The vein is longer in pigs than in humans.

EASING ORGAN REJECTION

The surfaces of pig cells contain a sugar molecule that triggers the human immune system to attack the organs. Scientists are using the gene editing tool Crispr to overcome this obstacle. Here’s one approach:

Crispr acts like scissors cutting DNA at a specific place.

Scientists edit troublesome genes in pig DNA…

…and sometimes add human genes…

…and then insert the edited DNA into a pig egg cell whose nucleus has been removed. The egg cell is then transferred to the uterus of a sow. The sow gives birth to pigs whose cells— including those in their organs—contain the edited genes.

ORGAN OPTIONS

Researchers are trying various techniques that might allow transplantation of gene-edited pig

hearts, kidneys and livers into humans. Recent studies on pig organ transplantation in baboons and people have focused mainly on hearts and kidneys.

HEART TO HEART

Pig and human hearts have similarities—but also some differences.

Pigs can be bred to have hearts of similar size as human hearts.

Pig and human hearts each have four pumping chambers—two small ones known as atria and two large ones known as ventricles.

The wall of tissue separating the ventricles is thicker in pig hearts than in human hearts.

Pig and human hearts each are attached to a large artery known as the aorta as well as to a large vein known as the vena cava.

A pig’s inferior (lower) vena cava joins a pig heart’s right atrium at an angle. The vein is longer in pigs than in humans.

The time intervals are typically shorter in pig hearts that are in pigs. But they took longer in the gene-modified pig heart inside a human. The time for the electricity to travel through the heart’s electrical system and generate a heartbeat also took longer than what is typical for human hearts, said

Timm Dickfeld,

a professor of medicine and director of electrophysiology research at the University of Maryland Medical Center, who was the leader of the EKG study.

What that might mean in the future for doctors caring for patients with gene-modified pig heart transplants is uncertain, said

Paul Wang,

director of the Stanford Cardiac Arrhythmia Service and a professor of medicine and bioengineering at Stanford University, who examined the data but wasn’t involved in the study.

“It has only been done once,” Dr. Wang said. “It needs to be done many more times for us to understand what these differences mean.”

The EKG data haven’t been published or undergone an outside vetting process. They are being presented by the Maryland team at an American Heart Association annual meeting starting Nov. 5. The Maryland team said they are studying the significance of the findings and hope to gather more data in future studies.

The fact that the electrical signals traveled through Mr. Bennett’s heart more slowly than expected “did not appear to be associated with a pathological outcome,” said

Bartley Griffith,

co-director of the cardiac xenotransplantation program at the University of Maryland School of Medicine, who performed Mr. Bennett’s transplant surgery.

Dr. Griffith added that if Mr. Bennett had survived longer and the time intervals became even slower, a pacemaker might eventually have become necessary.

Researchers have tried for decades to develop the transplantation of organs between different species, or xenotransplantation, to address a chronic shortage of organs. More than 3,500 people are on the waiting list in the U.S. for a heart transplant, according to a 2022 update from the American Heart Association.

Megan Sykes,

director of the Columbia Center for Translational Immunology in New York, said that although pigs are similar to humans in organ size and physiology, the EKG data illustrate that there are differences that may only emerge after doing transplants into humans.

“We have reached the point where we need human studies as well as animal studies,” Dr. Sykes said.

The Maryland team and other groups have met with the Food and Drug Administration recently to discuss how to start small clinical trials of genetically modified pig organs. The FDA has requested additional data from the Maryland team in baboons, said

Muhammad Mohiuddin,

the scientific program director of cardiac xenotransplantation at the University of Maryland School of Medicine. Dr. Mohiuddin said they plan to gather additional EKG data as part of the research.

Write to Amy Dockser Marcus at amy.marcus@wsj.com

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Business

Americans Take Ketamine at Home for Depression With Little Oversight

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Startups are prescribing ketamine online to treat serious mental-health conditions, raising concern among psychiatrists about the safety of taking the mind-altering anesthetic without medical supervision, sometimes at high doses that raise risks of side effects.

Ketamine is approved by the Food and Drug Administration to anesthetize people and animals and has been used safely in hospitals for decades. The out-of-body, hallucinogenic sensations it produces made it popular as a party drug known as Special K. Some doctors prescribe ketamine off-label to treat patients with conditions including severe depression, suicidal thoughts and post-traumatic stress disorder.

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Is there enough support available for people taking ketamine at home because of mental-health concerns? Join the conversation below.

Generic ketamine isn’t approved for those conditions. Studies have shown it can rapidly alleviate symptoms of severe depression when other treatments have failed.

There is less data on ketamine’s effectiveness for other conditions including anxiety and PTSD, and little data on its long-term use.

The FDA has approved a chemically related version of the drug, called esketamine, from

Johnson & Johnson

for treatment-resistant depression with suicidal thoughts.

Clinics that are certified to administer J&J’s nasal spray must monitor patients for two hours afterward.

People taking generic ketamine at home aren’t subject to the same oversight.

Clinics specializing in ketamine treatment for depression and other mood disorders have popped up across the U.S. in recent years. WSJ visits a clinic to learn why some entrepreneurs are betting that demand for ketamine will continue to rise. Photo illustration: Laura Kammermann

Mindbloom Inc., Nue Life Health PBC and Wondermed LLC are among around a dozen companies now selling ketamine tablets or lozenges online, making use of relaxed restrictions on the prescription of controlled substances during the pandemic.

The companies work with clinicians who prescribe ketamine to patients based on a questionnaire and virtual evaluation. The generic ketamine pills or lozenges are mailed to patients’ homes. The companies say they instruct people to take the medication with someone nearby, among other safety measures.

Taking ketamine at home without medical supervision increases risks of patients falling and hurting themselves or taking more of the drug than prescribed, doctors said. Ketamine can be addictive, and patients might not get the help they need if they have a distressing experience while taking the drug, psychiatrists said.

“Places that are doing virtual ketamine are negotiating a compromise between accessibility and safety,” said Dr.

Benjamin Yudkoff,

medical director of the ketamine and esketamine program at Brigham and Women’s Faulkner Hospital in Boston.

Ketamine increases heart rate and blood pressure, raising the risk of rare complications including stroke or heart attack at the higher doses that some telehealth patients have been prescribed, medical experts said.

“Giving any drug like that has the potential to cause general anesthesia at home in a completely unmonitored environment,” said Dr.

Michael Champeau,

president of the American Society of Anesthesiologists.

The companies said prescribing ketamine-assisted therapy at home can help fill a need for people who don’t respond to existing medications or can’t reach or afford treatment in person. Ketamine blocks a receptor in brain cells important for brain adaptability, which researchers say might help facilitate changes in mood and mind-set.

Ketamine was prescribed for Leon New Valentine, who said it alleviated symptoms of treatment-resistant depression and PTSD.



Photo:

Tara Pixley for The Wall Street Journal

Mindbloom and Nue Life cited peer-reviewed research they published suggesting that many patients reported feeling better after taking ketamine and that few reported problems related to taking the drug.

Mindbloom, Nue Life and Wondermed said they decline to treat people who have symptoms that are too severe or histories of conditions such as substance-use disorder, psychosis or uncontrolled hypertension. Nue Life said it sometimes consults with a patient’s doctor before prescribing ketamine, and Mindbloom said it often asks for medical records. Wondermed said patients can choose to have their doctors work with the company during treatment.

“‘Places that are doing virtual ketamine are negotiating a compromise between accessibility and safety.’”


— Dr. Benjamin Yudkoff, Brigham and Women’s Faulkner Hospital

Nue Life said it starts patients at around 125 milligrams and prescribes at most 750 milligrams for a dose. Wondermed said it prescribes patients between 100 milligrams and 400 milligrams for a dose. Mindbloom said that it starts patients at around 400 milligrams and that some patients graduate to doses of around 1,000 milligrams.

Doses of around 1,000 milligrams heighten risks for severe side effects including rare seizures, hemorrhages or strokes, said

Ari Aal,

a psychiatrist in Boulder, Colo., who prescribes ketamine at lower doses to patients who take it under supervision at his clinic.

“That’s way too much of a dose to be doing at home and probably at all, and way too much without a practitioner watching you,” Dr. Aal said.

Mindbloom and Wondermed said they provide blood-pressure monitors for patients to use before and during treatment. Nue Life said it instructs patients with controlled hypertension to monitor their blood pressure.

A ketamine kit provided by Mindbloom for Courtney Gable.



Photo:

Courtney Gable

Timothy Mitchell,

a 40-year-old patient advocate from Ballston Lake, N.Y., said Mindbloom started him on an 800-milligram dose last year. He said he is undergoing his third course of a six-dose regimen with Mindbloom at 1,200 milligrams a dose. The treatment helped quiet suicidal thoughts, he said.

Wondermed said it charges $399 for a month of ketamine tablets or lozenges and telemedicine treatment. Mindbloom said it charges around $1,000 for around three months of ketamine and telemedicine care. Nue Life said it charges as much as $2,999 for ketamine tablets and telemedicine treatment over four months. Health insurers usually don’t reimburse people for the off-label treatments.

Amanda Itzkoff,

a psychiatrist and chief executive of Curated Mental Health, which administers ketamine in clinics, said she declined to be on Mindbloom’s advisory board in part because she was concerned that at-home use might not include enough patient supervision.

Making a comparison with a crackdown on psychedelic-drug research decades ago, she said that if companies recklessly prescribe ketamine for home use, they could set back adoption of a valuable treatment. “We could blow it again,” Dr. Itzkoff said.

A spokesman said that Mindbloom ended its relationship with Dr. Itzkoff and that she didn’t raise safety concerns. Mindbloom’s medical director, Dr.

Leonardo Vando,

said striking the right balance between expanding access to ketamine and safe prescribing practices is critical to Mindbloom.

Courtney Gable,

47, said her husband checked on her when she took ketamine that Mindbloom prescribed for her this year to treat chronic pain and depression. The 400-milligram dose was higher than initial doses prescribed at a clinic where she works in Philadelphia, she said.

“There’s a safety net, but the spaces between the net are a little wider,” Ms. Gable said.

Leon New Valentine,

a 32-year-old actor and videogame model in Los Angeles, was prescribed 100 milligrams of ketamine online last year by Peak Health Global Inc., and took the medication with someone nearby. Mx. Valentine, who uses they as a pronoun, said they graduated to 150-milligram doses and took that alone. Ketamine alleviated symptoms of treatment-resistant depression and PTSD, Mx. Valentine said.

“Things are joyful again even though I’m in pain,” Mx. Valentine said. Peak said it would close in November because it expects rules allowing controlled substances to be prescribed remotely to be tightened soon.

Write to Brianna Abbott at brianna.abbott@wsj.com and Daniela Hernandez at daniela.hernandez@wsj.com

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Health

Monkeypox Outbreak Leaves Risks, Questions in Its Wake

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As a global outbreak of monkeypox loses steam, disease researchers said they need a better understanding of how the virus spreads, and how well vaccination protects against it to predict whether it could come roaring back.

A global outbreak that gained momentum in May spread the virus much farther than it had been found previously. The virus might have reached new animal hosts, increasing the risk of future outbreaks, said epidemiologists and infectious-disease specialists. The extent to which vaccination has protected the most at-risk people from catching monkeypox is unknown.

“We can’t get lulled into this sense that monkeypox has disappeared,” said Jason Kindrachuk, an assistant professor at the University of Manitoba with a focus on emerging viruses.

Case numbers have been steadily declining since early August. Daily reported cases in the U.S. have fallen to around 40, from a peak of around 440. In Ontario, once a hot spot, health officials in the Canadian province said they are considering whether to declare the outbreak over.

The slowdown is attributed to a combination of a buildup of immunity and behavioral change, disease researchers said. The exact role each played hasn’t been determined. “They are working together in many cases,” said

David Heymann,

professor of infectious-disease epidemiology at the London School of Hygiene and Tropical Medicine.

Dozens of countries bet that Jynneos, a vaccine made by Denmark’s

Bavarian Nordic

A/S that had sat in stockpiles as a biodefense against a possible reintroduction of smallpox, could curb the spread of monkeypox, which is part of the same virus family. Studies on smallpox vaccines in Africa had found that they were around 85% effective at preventing monkeypox, but no such studies had been undertaken with Jynneos.

Early evidence from Jynneos’s use during the outbreak suggests the bet paid off. A recent study from the Centers for Disease Control and Prevention found that among men ages 18 to 49 in the U.S. who were eligible for Jynneos, case rates among the unvaccinated were 14 times higher than for those who had received at least one dose at least two weeks earlier. As of Oct. 18, around 647,400 people in the U.S. had received at least one dose of Jynneos, according to the CDC.

Immunity doesn’t fully explain the drop in cases, disease experts said. In the U.K., new cases started to fall before a vaccination campaign gained momentum, said Jake Dunning, senior researcher at the University of Oxford’s Pandemic Sciences Institute.

Early evidence indicates that use of the Jynneos vaccine has helped contain monkeypox.



Photo:

patrick t. fallon/Agence France-Presse/Getty Images

“Vaccine probably helped to bring things down and keep it as one curve, rather than more of a roller coaster,” he said.

Also driving down cases, disease experts said, was a reduction in sexual contact by men at the highest risk of catching monkeypox. In an August survey of around 800 men who have sex with men in the U.S., around half reported taking at least one measure in response to the monkeypox outbreak to limit their number of sexual contacts. Those measures included reducing one-time sexual encounters and cutting down the number of sex partners. A U.K. report published in September found that rates of two sexually transmitted diseases that also disproportionately affect men who have sex with men fell in August, suggesting that behavior change contributed to the decline in monkeypox.

Uncertainty regarding the precise roles played by immunity and behavior change mean that it is impossible to predict the trajectory of the virus, disease experts said. “If there’s a significant proportion that is attributed to behavior change, if that behavior change is not sustainable, will we see increases again?” said Anne Rimoin, professor of epidemiology at the University of California, Los Angeles, who has been researching monkeypox in the Democratic Republic of Congo for many years.

Even if the virus fades in some places, it is likely to be reintroduced through international travel because it is present in so many countries, said Emma Thomson, a professor of infectious disease at the University of Glasgow.

Testing sewage to track viruses has drawn renewed interest after recent outbreaks of monkeypox and polio. WSJ visited a wastewater facility to find out how the testing works. Photo illustration: Ryan Trefes

It hasn’t been determined whether the virus made its way into any new animal populations during the global outbreak. While monkeypox is mainly associated with forest-dwelling rodents in western and central Africa, it has been detected in other animals. An Italian greyhound in Paris caught monkeypox in June, likely from one of its owners, according to a case report in the Lancet.

“More human infections may arise because of that,” Geoffrey Smith, an expert on poxviruses at the University of Cambridge, said of potential animal reservoirs.

In 2003, around 50 people in the U.S. caught monkeypox from pet prairie dogs that had contracted the virus after sharing caging and bedding with small animals imported from western Africa. None of those cases went on to infect other people.

The global outbreak has prompted fresh calls for more research. A U.K. government-backed science funding group this week provided 2 million pounds, the equivalent of $2.2 million, for monkeypox research to 25 scientists spanning 12 universities. The researchers said their work would include detailed genomic sequencing, studies into the immune response to vaccination, developing new therapies and investigating the potential for animals to spread monkeypox.

Scientists said they want more research into monkeypox in central Africa, where a more-severe strain of the virus known as clade I circulates, to reduce transmission in countries there and to lower the risk of its sparking a more widespread outbreak. Dr. Dunning said that a global outbreak arising from the milder clade II virus raised the possibility that it could happen with clade I.

“That would be even more concerning,” he said.

Write to Denise Roland at denise.roland@wsj.com

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