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Has the Era of Overzealous Cleaning Finally Come to an End?

This week, the C.D.C. acknowledged what scientists have been saying for months: The risk of catching the coronavirus from surfaces is low.

When the coronavirus began to spread in the United States last spring, many experts warned of the danger posed by surfaces. Researchers reported that the virus could survive for days on plastic or stainless steel, and the Centers for Disease Control and Prevention advised that if someone touched one of these contaminated surfaces — and then touched their eyes, nose or mouth — they could become infected.

Americans responded in kind, wiping down groceries, quarantining mail and clearing drugstore shelves of Clorox wipes. Facebook closed two of its offices for a “deep cleaning.” New York’s Metropolitan Transportation Authority began disinfecting subway cars every night.

But the era of “hygiene theater” may have come to an unofficial end this week, when the C.D.C. updated its surface cleaning guidelines and noted that the risk of contracting the virus from touching a contaminated surface was less than 1 in 10,000.

“People can be affected with the virus that causes Covid-19 through contact with contaminated surfaces and objects,” Dr. Rochelle Walensky, the director of the C.D.C., said at a White House briefing on Monday. “However, evidence has demonstrated that the risk by this route of infection of transmission is actually low.”

The admission is long overdue, scientists say.

“Finally,” said Linsey Marr, an expert on airborne viruses at Virginia Tech. “We’ve known this for a long time and yet people are still focusing so much on surface cleaning.” She added, “There’s really no evidence that anyone has ever gotten Covid-19 by touching a contaminated surface.”

During the early days of the pandemic, many experts believed that the virus spread primarily through large respiratory droplets. These droplets are too heavy to travel long distances through the air but can fall onto objects and surfaces.

In this context, a focus on scrubbing down every surface seemed to make sense. “Surface cleaning is more familiar,” Dr. Marr said. “We know how to do it. You can see people doing it, you see the clean surface. And so I think it makes people feel safer.”

A “sanitization specialist” at an Applebee’s Grill and Bar in Westbury, N.Y., wiping down a used pen last year. Restaurants and other businesses have highlighted extra cleaning in their marketing since the pandemic began.
A “sanitization specialist” at an Applebee’s Grill and Bar in Westbury, N.Y., wiping down a used pen last year. Restaurants and other businesses have highlighted extra cleaning in their marketing since the pandemic began.Hiroko Masuike/The New York Times

But over the last year, it has become increasingly clear that the virus spreads primarily through the air — in both large and small droplets, which can remain aloft longer — and that scouring door handles and subway seats does little to keep people safe.

“The scientific basis for all this concern about surfaces is very slim — slim to none,” said Emanuel Goldman, a microbiologist at Rutgers University, who wrote last summer that the risk of surface transmission had been overblown. “This is a virus you get by breathing. It’s not a virus you get by touching.”

The C.D.C. has previously acknowledged that surfaces are not the primary way that the virus spreads. But the agency’s statements this week went farther.

“The most important part of this update is that they’re clearly communicating to the public the correct, low risk from surfaces, which is not a message that has been clearly communicated for the past year,” said Joseph Allen, a building safety expert at the Harvard T.H. Chan School of Public Health.

Catching the virus from surfaces remains theoretically possible, he noted. But it requires many things to go wrong: a lot of fresh, infectious viral particles to be deposited on a surface, and then for a relatively large quantity of them to be quickly transferred to someone’s hand and then to their face. “Presence on a surface does not equal risk,” Dr. Allen said.

In most cases, cleaning with simple soap and water — in addition to hand-washing and mask-wearing — is enough to keep the odds of surface transmission low, the C.D.C.’s updated cleaning guidelines say. In most everyday scenarios and environments, people do not need to use chemical disinfectants, the agency notes.

“What this does very usefully, I think, is tell us what we don’t need to do,” said Donald Milton, an aerosol scientist at the University of Maryland. “Doing a lot of spraying and misting of chemicals isn’t helpful.”

Still, the guidelines do suggest that if someone who has Covid-19 has been in a particular space within the last day, the area should be both cleaned and disinfected.

“Disinfection is only recommended in indoor settings — schools and homes — where there has been a suspected or confirmed case of Covid-19 within the last 24 hours,” Dr. Walensky said during the White House briefing. “Also, in most cases, fogging, fumigation and wide-area or electrostatic spraying is not recommended as a primary method of disinfection and has several safety risks to consider.”

And the new cleaning guidelines do not apply to health care facilities, which may require more intensive cleaning and disinfection.

Saskia Popescu, an infectious disease epidemiologist at George Mason University, said that she was happy to see the new guidance, which “reflects our evolving data on transmission throughout the pandemic.”

But she noted that it remained important to continue doing some regular cleaning — and maintaining good hand-washing practices — to reduce the risk of contracting not just the coronavirus but any other pathogens that might be lingering on a particular surface.

Dr. Allen said that the school and business officials he has spoken with this week expressed relief over the updated guidelines, which will allow them to pull back on some of their intensive cleaning regimens. “This frees up a lot of organizations to spend that money better,” he said.

Schools, businesses and other institutions that want to keep people safe should shift their attention from surfaces to air quality, he said, and invest in improved ventilation and filtration.

“This should be the end of deep cleaning,” Dr. Allen said, noting that the misplaced focus on surfaces has had real costs. “It has led to closed playgrounds, it has led to taking nets off basketball courts, it has led to quarantining books in the library. It has led to entire missed school days for deep cleaning. It has led to not being able to share a pencil. So that’s all that hygiene theater, and it’s a direct result of not properly classifying surface transmission as low risk.”

Roni Caryn Rabin contributed reporting

Many Children With MIS-C Had No Covid-19 Symptoms

Pediatricians should be vigilant, experts said, after the release of the largest U.S. study of the syndrome, MIS-C, that can strike young people weeks after their coronavirus infection.

Many children and teenagers who developed the mysterious inflammatory syndrome that can emerge several weeks after contracting the coronavirus never had classic Covid-19 symptoms at the time of their infection, according to the largest study so far of cases in the United States.

The study, led by researchers from the Centers for Disease Control and Prevention, found that in over 1,000 cases in which information about whether they got sick from their initial Covid-19 illness was available, 75 percent of the patients did not experience such symptoms. But two to five weeks later, they became sick enough to be hospitalized for the condition, called Multisystem Inflammatory Syndrome in Children (MIS-C), which can affect multiple organs, especially the heart.

Published Tuesday in JAMA Pediatrics, the study said that “most MIS-C illnesses are believed to result from asymptomatic or mild Covid-19” followed by a hyper-inflammatory response that appears to occur when the patients’ bodies have produced their maximum level of antibodies to the virus. Experts do not yet know why some young people, and a smaller number of adults, respond this way.

“It means primary-care pediatricians need to have a high index of suspicion for this because Covid is so prevalent in the society and children often have asymptomatic disease as their initial Covid infection,” said Dr. Jennifer Blumenthal, a pediatric intensivist and pediatric infectious disease specialist at Boston Children’s Hospital, who was not involved in the study.

The researchers evaluated 1,733 of the 2,090 cases of the syndrome in people age 20 and younger that had been reported to the C.D.C. as of January.

The findings show that although the syndrome is rare, it can be serious. The C.D.C’s data only included patients who were hospitalized. Over 90 percent of those young people experienced symptoms involving at least four organ systems and 58 percent needed treatment in intensive care units.

Many experienced significant heart issues: over half developed low blood pressure, 37 percent developed cardiogenic shock and 31 percent experienced cardiac dysfunction involving their heart’s inability to pump adequately. The study said that a significantly higher percentage of patients who had not had Covid-19 symptoms experienced those heart problems, compared with those who had initial coronavirus symptoms. A greater percentage of initially asymptomatic patients also ended up in intensive care.

“Even the kids with severe MIS-C, who were in the I.C.U. — the vast majority of them did not have a preceding illness that they recognized,” said Dr. Roberta DeBiasi, chief of infectious diseases at Children’s National Hospital in Washington, D.C., who was not involved in the research.

The study provided the most detailed demographic and geographic picture of the syndrome to date. About 34 percent of the patients were Black and 37 percent were Hispanic, reflecting the way that the coronavirus has disproportionately affected members of those communities. As the pandemic went on, the authors wrote, the proportion of patients who were white increased, comprising 20 percent of all cases. People of Asian heritage comprised just over 1 percent of patients.

Overall, nearly 58 percent of the patients were male, but the proportion was not the same across all ages. The youngest group — newborn to age 4 — had roughly equal numbers of boys and girls, and the male-to-female ratio increased in the older groups until it was more than two-to-one male to female in the 18-to-20 group.

The vast majority of patients (nearly 86 percent) were younger than 15. The study found that those under 5 had the lowest risk of serious heart complications and were less likely to need intensive care. Patients 10 and older were significantly more likely to develop issues like shock, low blood pressure and myocarditis (inflammation of the heart muscle).

“I think that’s similar to what we saw with Covid, that the older kids seemed to have more severe disease,” Dr. DeBiasi said. “And that’s because what makes people really sick from the Covid is the inflammatory aspect of it, so maybe these older kids, for whatever reasons, make more inflammation, whether that’s in primary Covid or MIS-C.”

Still, significant numbers of the youngest patients developed heart problems. In the newborn-to-4 age group, 36 percent had low blood pressure, 25 percent had shock and 44 percent were treated in the I.C.U.

Patients of all ages in the study had about the same occurrence of some of the less-common heart issues linked to the syndrome, including coronary aneurysms and fluid buildup. Children 14 and under were more likely to have rash and red eyes, while those older than 14 were more likely to have chest pain, shortness of breath and cough. Abdominal pain and vomiting afflicted about two-thirds of all patients.

There were 24 deaths recorded, spread across all age groups. There was no information in the study about whether patients had underlying medical conditions, but doctors and researchers have reported that young people with MIS-C were often previously healthy and significantly more likely to be healthy than the relatively small number of young people who become seriously ill from initial Covid infections.

Of the 1,075 patients for whom information about initial Covid illness was available, only 265 had symptoms at that time. They were more likely to be older — their median age was 11, while the median age of those with asymptomatic Covid infections was 8. But that could be because “younger children can’t express their concerns as well,” said Dr. Blumenthal, who co-wrote an editorial about the study.

“We don’t necessarily know if there’s actually less symptomatology in the very young population, ” she said.

Similarly unclear are the reasons behind the study’s finding that in the first wave of MIS-C, from March 1 to July 1, 2020, young people were more prone to a few of the most serious heart complications. Dr. DeBiasi said that did not match the experience of her hospital, where “the kids were sicker in the second wave.”

The study documented two waves of MIS-C cases that followed surges in overall coronavirus cases by about a month or more. “The most recent third peak of the Covid-19 pandemic appears to be leading to another MIS-C peak perhaps involving urban and rural communities,” the authors wrote.

The study found that most of the states where the rate of MIS-C cases per population was highest were in the Northeast, which had the first surge of cases, and the South. By contrast, most states with high per-population rates of children with Covid-19 but low rates of MIS-C were in the Midwest and West. While the concentration of cases spread from large cities to smaller towns over time, it wasn’t as pronounced as the overall pandemic trends, the authors said.

Dr. Blumenthal said that geographic pattern could reflect that the “understanding of the complications of the disease” hadn’t caught up to its prevalence in different regions or that many states with lower rates of MIS-C have less ethnically diverse populations. “It could also be something about Covid itself, although we don’t know that,” she said. “Right now, we don’t know anything about how the variants necessarily affect children.”

The study represented only the strictest criteria for MIS-C, excluding about 350 reported cases that met the C.D.C. definition of the syndrome but had a negative antibody test or primarily involved respiratory symptoms. Dr. DeBiasi said there are also many probable MIS-C cases that are not reported to the C.D.C. because they don’t meet all the official criteria.

“These probable MIS-C kids, in real life that’s a big chunk of kids,” she said. In addition, while the focus so far has been on serious cases, “there’s another whole group of kids that may actually have mild MIS-C.”

If a community has experienced a recent coronavirus surge, then “just because the kid says, ‘I never had Covid or my parents never had it,’ that doesn’t mean the kid in front of you doesn’t have MIS-C,” Dr. DeBiasi said. “If your city has Covid, then get ready.”

Many Children With Serious Inflammatory Syndrome Had No Covid Symptoms

Pediatricians should be vigilant, experts said, after the release of the largest U.S. study of the syndrome, MIS-C, that can strike young people weeks after their coronavirus infection.

Many children and teenagers who developed the mysterious inflammatory syndrome that can emerge several weeks after contracting the coronavirus never had classic Covid-19 symptoms at the time of their infection, according to the largest study so far of cases in the United States.

The study, led by researchers from the Centers for Disease Control and Prevention, found that in over 1,000 cases in which information about whether they got sick from their initial Covid-19 illness was available, 75 percent of the patients did not experience such symptoms. But two to five weeks later, they became sick enough to be hospitalized for the condition, called Multisystem Inflammatory Syndrome in Children (MIS-C), which can affect multiple organs, especially the heart.

Published Tuesday in JAMA Pediatrics, the study said that “most MIS-C illnesses are believed to result from asymptomatic or mild Covid-19” followed by a hyper-inflammatory response that appears to occur when the patients’ bodies have produced their maximum level of antibodies to the virus. Experts do not yet know why some young people, and a smaller number of adults, respond this way.

“It means primary-care pediatricians need to have a high index of suspicion for this because Covid is so prevalent in the society and children often have asymptomatic disease as their initial Covid infection,” said Dr. Jennifer Blumenthal, a pediatric intensivist and pediatric infectious disease specialist at Boston Children’s Hospital, who was not involved in the study.

The researchers evaluated 1,733 of the 2,090 cases of the syndrome in people age 20 and younger that had been reported to the C.D.C. as of January.

The findings show that although the syndrome is rare, it can be serious. The C.D.C’s data only included patients who were hospitalized. Over 90 percent of those young people experienced symptoms involving at least four organ systems and 58 percent needed treatment in intensive care units.

Many experienced significant heart issues: over half developed low blood pressure, 37 percent developed cardiogenic shock and 31 percent experienced cardiac dysfunction involving their heart’s inability to pump adequately. The study said that a significantly higher percentage of patients who had not had Covid-19 symptoms experienced those heart problems, compared with those who had initial coronavirus symptoms. A greater percentage of initially asymptomatic patients also ended up in intensive care.

“Even the kids with severe MIS-C, who were in the I.C.U. — the vast majority of them did not have a preceding illness that they recognized,” said Dr. Roberta DeBiasi, chief of infectious diseases at Children’s National Hospital in Washington, D.C., who was not involved in the research.

The study provided the most detailed demographic and geographic picture of the syndrome to date. About 34 percent of the patients were Black and 37 percent were Hispanic, reflecting the way that the coronavirus has disproportionately affected members of those communities. As the pandemic went on, the authors wrote, the proportion of patients who were white increased, comprising 20 percent of all cases. People of Asian heritage comprised just over 1 percent of patients.

Overall, nearly 58 percent of the patients were male, but the proportion was not the same across all ages. The youngest group — newborn to age 4 — had roughly equal numbers of boys and girls, and the male-to-female ratio increased in the older groups until it was more than two-to-one male to female in the 18-to-20 group.

The vast majority of patients (nearly 86 percent) were younger than 15. The study found that those under 5 had the lowest risk of serious heart complications and were less likely to need intensive care. Patients 10 and older were significantly more likely to develop issues like shock, low blood pressure and myocarditis (inflammation of the heart muscle).

“I think that’s similar to what we saw with Covid, that the older kids seemed to have more severe disease,” Dr. DeBiasi said. “And that’s because what makes people really sick from the Covid is the inflammatory aspect of it, so maybe these older kids, for whatever reasons, make more inflammation, whether that’s in primary Covid or MIS-C.”

Still, significant numbers of the youngest patients developed heart problems. In the newborn-to-4 age group, 36 percent had low blood pressure, 25 percent had shock and 44 percent were treated in the I.C.U.

Patients of all ages in the study had about the same occurrence of some of the less-common heart issues linked to the syndrome, including coronary aneurysms and fluid buildup. Children 14 and under were more likely to have rash and red eyes, while those older than 14 were more likely to have chest pain, shortness of breath and cough. Abdominal pain and vomiting afflicted about two-thirds of all patients.

There were 24 deaths recorded, spread across all age groups. There was no information in the study about whether patients had underlying medical conditions, but doctors and researchers have reported that young people with MIS-C were often previously healthy and significantly more likely to be healthy than the relatively small number of young people who become seriously ill from initial Covid infections.

Of the 1,075 patients for whom information about initial Covid illness was available, only 265 had symptoms at that time. They were more likely to be older — their median age was 11, while the median age of those with asymptomatic Covid infections was 8. But that could be because “younger children can’t express their concerns as well,” said Dr. Blumenthal, who co-wrote an editorial about the study.

“We don’t necessarily know if there’s actually less symptomatology in the very young population, ” she said.

Similarly unclear are the reasons behind the study’s finding that in the first wave of MIS-C, from March 1 to July 1, 2020, young people were more prone to a few of the most serious heart complications. Dr. DeBiasi said that did not match the experience of her hospital, where “the kids were sicker in the second wave.”

The study documented two waves of MIS-C cases that followed surges in overall coronavirus cases by about a month or more. “The most recent third peak of the Covid-19 pandemic appears to be leading to another MIS-C peak perhaps involving urban and rural communities,” the authors wrote.

The study found that most of the states where the rate of MIS-C cases per population was highest were in the Northeast, which had the first surge of cases, and the South. By contrast, most states with high per-population rates of children with Covid-19 but low rates of MIS-C were in the Midwest and West. While the concentration of cases spread from large cities to smaller towns over time, it wasn’t as pronounced as the overall pandemic trends, the authors said.

Dr. Blumenthal said that geographic pattern could reflect that the “understanding of the complications of the disease” hadn’t caught up to its prevalence in different regions or that many states with lower rates of MIS-C have less ethnically diverse populations. “It could also be something about Covid itself, although we don’t know that,” she said. “Right now, we don’t know anything about how the variants necessarily affect children.”

The study represented only the strictest criteria for MIS-C, excluding about 350 reported cases that met the C.D.C. definition of the syndrome but had a negative antibody test or primarily involved respiratory symptoms. Dr. DeBiasi said there are also many probable MIS-C cases that are not reported to the C.D.C. because they don’t meet all the official criteria.

“These probable MIS-C kids, in real life that’s a big chunk of kids,” she said. In addition, while the focus so far has been on serious cases, “there’s another whole group of kids that may actually have mild MIS-C.”

If a community has experienced a recent coronavirus surge, then “just because the kid says, ‘I never had Covid or my parents never had it,’ that doesn’t mean the kid in front of you doesn’t have MIS-C,” Dr. DeBiasi said. “If your city has Covid, then get ready.”

Researchers Are Hatching a Low-Cost Covid-19 Vaccine

A new formulation entering clinical trials in Brazil, Mexico, Thailand and Vietnam could change how the world fights the pandemic.

A new vaccine for Covid-19 that is entering clinical trials in Brazil, Mexico, Thailand and Vietnam could change how the world fights the pandemic. The vaccine, called NVD-HXP-S, is the first in clinical trials to use a new molecular design that is widely expected to create more potent antibodies than the current generation of vaccines. And the new vaccine could be far easier to make.

Existing vaccines from companies like Pfizer and Johnson & Johnson must be produced in specialized factories using hard-to-acquire ingredients. In contrast, the new vaccine can be mass-produced in chicken eggs — the same eggs that produce billions of influenza vaccines every year in factories around the world.

If NVD-HXP-S proves safe and effective, flu vaccine manufacturers could potentially produce well over a billion doses of it a year. Low- and middle-income countries currently struggling to obtain vaccines from wealthier countries may be able to make NVD-HXP-S for themselves or acquire it at low cost from neighbors.

“That’s staggering — it would be a game-changer,” said Andrea Taylor, assistant director of the Duke Global Health Innovation Center.

First, however, clinical trials must establish that NVD-HXP-S actually works in people. The first phase of clinical trials will conclude in July, and the final phase will take several months more. But experiments with vaccinated animals have raised hopes for the vaccine’s prospects.

“It’s a home run for protection,” said Dr. Bruce Innes of the PATH Center for Vaccine Innovation and Access, which has coordinated the development of NVD-HXP-S. “I think it’s a world-class vaccine.”

2P to the rescue

The molecular structure of HexaPro, a modified version of the SARS-CoV-2 spike protein, with its six key alterations shown as red and blue spheres.
The molecular structure of HexaPro, a modified version of the SARS-CoV-2 spike protein, with its six key alterations shown as red and blue spheres.University of Texas at Austin

Vaccines work by acquainting the immune system with a virus well enough to prompt a defense against it. Some vaccines contain entire viruses that have been killed; others contain just a single protein from the virus. Still others contain genetic instructions that our cells can use to make the viral protein.

Once exposed to a virus, or part of it, the immune system can learn to make antibodies that attack it. Immune cells can also learn to recognize infected cells and destroy them.

In the case of the coronavirus, the best target for the immune system is the protein that covers its surface like a crown. The protein, known as spike, latches onto cells and then allows the virus to fuse to them.

But simply injecting coronavirus spike proteins into people is not the best way to vaccinate them. That’s because spike proteins sometimes assume the wrong shape, and prompt the immune system to make the wrong antibodies.

Jason McLellan, a structural biologist at the University of Texas at Austin. His research on coronavirus spike proteins aided the development of the Pfizer, Moderna, Johnson & Johnson and Novavax vaccines.Ilana Panich-Linsman for The New York Times

This insight emerged long before the Covid-19 pandemic. In 2015, another coronavirus appeared, causing a deadly form of pneumonia called MERS. Jason McLellan, a structural biologist then at the Geisel School of Medicine at Dartmouth, and his colleagues set out to make a vaccine against it.

They wanted to use the spike protein as a target. But they had to reckon with the fact that the spike protein is a shape-shifter. As the protein prepares to fuse to a cell, it contorts from a tulip-like shape into something more akin to a javelin.

Scientists call these two shapes the prefusion and postfusion forms of the spike. Antibodies against the prefusion shape work powerfully against the coronavirus, but postfusion antibodies don’t stop it.

Dr. McLellan and his colleagues used standard techniques to make a MERS vaccine but ended up with a lot of postfusion spikes, useless for their purposes. Then they discovered a way to keep the protein locked in a tulip-like prefusion shape. All they had to do was change two of more than 1,000 building blocks in the protein into a compound called proline.

The resulting spike — called 2P, for the two new proline molecules it contained — was far more likely to assume the desired tulip shape. The researchers injected the 2P spikes into mice and found that the animals could easily fight off infections of the MERS coronavirus.

The team filed a patent for its modified spike, but the world took little notice of the invention. MERS, although deadly, is not very contagious and proved to be a relatively minor threat; fewer than 1,000 people have died of MERS since it first emerged in humans.

But in late 2019 a new coronavirus, SARS-CoV-2, emerged and began ravaging the world. Dr. McLellan and his colleagues swung into action, designing a 2P spike unique to SARS-CoV-2. In a matter of days, Moderna used that information to design a vaccine for Covid-19; it contained a genetic molecule called RNA with the instructions for making the 2P spike.

Other companies soon followed suit, adopting 2P spikes for their own vaccine designs and starting clinical trials. All three of the vaccines that have been authorized so far in the United States — from Johnson & Johnson, Moderna and Pfizer-BioNTech — use the 2P spike.

Other vaccine makers are using it as well. Novavax has had strong results with the 2P spike in clinical trials and is expected to apply to the Food and Drug Administration for emergency use authorization in the next few weeks. Sanofi is also testing a 2P spike vaccine and expects to finish clinical trials later this year.

Two prolines are good; six are better

Dr. McLellan’s ability to find lifesaving clues in the structure of proteins has earned him deep admiration in the vaccine world. “This guy is a genius,” said Harry Kleanthous, a senior program officer at the Bill & Melinda Gates Foundation. “He should be proud of this huge thing he’s done for humanity.”

But once Dr. McLellan and his colleagues handed off the 2P spike to vaccine makers, he turned back to the protein for a closer look. If swapping just two prolines improved a vaccine, surely additional tweaks could improve it even more.

“It made sense to try to have a better vaccine,” said Dr. McLellan, who is now an associate professor at the University of Texas at Austin.

In March, he joined forces with two fellow University of Texas biologists, Ilya Finkelstein and Jennifer Maynard. Their three labs created 100 new spikes, each with an altered building block. With funding from the Gates Foundation, they tested each one and then combined the promising changes in new spikes. Eventually, they created a single protein that met their aspirations.

The winner contained the two prolines in the 2P spike, plus four additional prolines found elsewhere in the protein. Dr. McLellan called the new spike HexaPro, in honor of its total of six prolines.

The structure of HexaPro was even more stable than 2P, the team found. It was also resilient, better able to withstand heat and damaging chemicals. Dr. McLellan hoped that its rugged design would make it potent in a vaccine.

Dr. McLellan also hoped that HexaPro-based vaccines would reach more of the world — especially low- and middle-income countries, which so far have received only a fraction of the total distribution of first-wave vaccines.

“The share of the vaccines they’ve received so far is terrible,” Dr. McLellan said.

To that end, the University of Texas set up a licensing arrangement for HexaPro that allows companies and labs in 80 low- and middle-income countries to use the protein in their vaccines without paying royalties.

Meanwhile, Dr. Innes and his colleagues at PATH were looking for a way to increase the production of Covid-19 vaccines. They wanted a vaccine that less wealthy nations could make on their own.

With a little help from eggs

The first wave of authorized Covid-19 vaccines require specialized, costly ingredients to make. Moderna’s RNA-based vaccine, for instance, needs genetic building blocks called nucleotides, as well as a custom-made fatty acid to build a bubble around them. Those ingredients must be assembled into vaccines in purpose-built factories.

The way influenza vaccines are made is a study in contrast. Many countries have huge factories for making cheap flu shots, with influenza viruses injected into chicken eggs. The eggs produce an abundance of new copies of the viruses. Factory workers then extract the viruses, weaken or kill them and then put them into vaccines.

The PATH team wondered if scientists could make a Covid-19 vaccine that could be grown cheaply in chicken eggs. That way, the same factories that make flu shots could make Covid-19 shots as well.

In New York, a team of scientists at the Icahn School of Medicine at Mount Sinai knew how to make just such a vaccine, using a bird virus called Newcastle disease virus that is harmless in humans.

For years, scientists had been experimenting with Newcastle disease virus to create vaccines for a range of diseases. To develop an Ebola vaccine, for example, researchers added an Ebola gene to the Newcastle disease virus’s own set of genes.

The scientists then inserted the engineered virus into chicken eggs. Because it is a bird virus, it multiplied quickly in the eggs. The researchers ended up with Newcastle disease viruses coated with Ebola proteins.

At Mount Sinai, the researchers set out to do the same thing, using coronavirus spike proteins instead of Ebola proteins. When they learned about Dr. McLellan’s new HexaPro version, they added that to the Newcastle disease viruses. The viruses bristled with spike proteins, many of which had the desired prefusion shape. In a nod to both the Newcastle disease virus and the HexaPro spike, they called it NDV-HXP-S.

PATH arranged for thousands of doses of NDV-HXP-S to be produced in a Vietnamese factory that normally makes influenza vaccines in chicken eggs. In October, the factory sent the vaccines to New York to be tested. The Mount Sinai researchers found that NDV-HXP-S conferred powerful protection in mice and hamsters.

“I can honestly say I can protect every hamster, every mouse in the world against SARS-CoV-2,” Dr. Peter Palese, the leader of the research, said. “But the jury’s still out about what it does in humans.”

The potency of the vaccine brought an extra benefit: The researchers needed fewer viruses for an effective dose. A single egg may yield five to 10 doses of NDV-HXP-S, compared to one or two doses of influenza vaccines.

“We are very excited about this, because we think it’s a way of making a cheap vaccine,” Dr. Palese said.

A nurse administering the NDV-HXP-S  vaccine to a volunteer at Mahidol University in Bangkok during the country’s first human trial.Government Pharmaceutical Organization of Thailand, via Agence France-Presse — Getty Images

PATH then connected the Mount Sinai team with influenza vaccine makers. On March 15, Vietnam’s Institute of Vaccines and Medical Biologicals announced the start of a clinical trial of NDV-HXP-S. A week later, Thailand’s Government Pharmaceutical Organization followed suit. On March 26, Brazil’s Butantan Institute said it would ask for authorization to begin its own clinical trials of NDV-HXP-S.

Meanwhile, the Mount Sinai team has also licensed the vaccine to the Mexican vaccine maker Avi-Mex as an intranasal spray. The company will start clinical trials to see if the vaccine is even more potent in that form.

To the nations involved, the prospect of making the vaccines entirely on their own was appealing. “This vaccine production is produced by Thai people for Thai people,” Thailand’s health minister, Anutin Charnvirakul, said at the announcement in Bangkok.

From left, Dimas Covas, director of the Butantan Institute in Brazil; João Doria, governor of the state of São Paulo; and Jean Gorinchteyn, the state health secretary, announcing the ButanVac Covid-19 vaccine candidate against in São Paulo on March 26. Miguel Schincariol/Agence France-Presse — Getty Images

In Brazil, the Butantan Institute trumpeted its version of NDV-HXP-S as “the Brazilian vaccine,” one that would be “produced entirely in Brazil, without depending on imports.”

Ms. Taylor, of the Duke Global Health Innovation Center, was sympathetic. “I could understand why that would really be such an attractive prospect,” she said. “They’ve been at the mercy of global supply chains.”

Madhavi Sunder, an expert on intellectual property at Georgetown Law School, cautioned that NDV-HXP-S would not immediately help countries like Brazil as they grappled with the current wave of Covid-19 infections. “We’re not talking 16 billion doses in 2020,” she said.

Instead, the strategy will be important for long-term vaccine production — not just for Covid-19 but for other pandemics that may come in the future. “It sounds super promising,” she said.

In the meantime, Dr. McLellan has returned to the molecular drawing board to try to make a third version of their spike that is even better than HexaPro.

“There’s really no end to this process,” he said. “The number of permutations is almost infinite. At some point, you’d have to say, ‘This is the next generation.’”

Researchers Are Hatching a Low-Cost Coronavirus Vaccine

A new formulation entering clinical trials in Brazil, Mexico, Thailand and Vietnam could change how the world fights the pandemic.

A new vaccine for Covid-19 that is entering clinical trials in Brazil, Mexico, Thailand and Vietnam could change how the world fights the pandemic. The vaccine, called NVD-HXP-S, is the first in clinical trials to use a new molecular design that is widely expected to create more potent antibodies than the current generation of vaccines. And the new vaccine could be far easier to make.

Existing vaccines from companies like Pfizer and Johnson & Johnson must be produced in specialized factories using hard-to-acquire ingredients. In contrast, the new vaccine can be mass-produced in chicken eggs — the same eggs that produce billions of influenza vaccines every year in factories around the world.

If NVD-HXP-S proves safe and effective, flu vaccine manufacturers could potentially produce well over a billion doses of it a year. Low- and middle-income countries currently struggling to obtain vaccines from wealthier countries may be able to make NVD-HXP-S for themselves or acquire it at low cost from neighbors.

“That’s staggering — it would be a game-changer,” said Andrea Taylor, assistant director of the Duke Global Health Innovation Center.

First, however, clinical trials must establish that NVD-HXP-S actually works in people. The first phase of clinical trials will conclude in July, and the final phase will take several months more. But experiments with vaccinated animals have raised hopes for the vaccine’s prospects.

“It’s a home run for protection,” said Dr. Bruce Innes of the PATH Center for Vaccine Innovation and Access, which has coordinated the development of NVD-HXP-S. “I think it’s a world-class vaccine.”

2P to the rescue

The molecular structure of HexaPro, a modified version of the SARS-CoV-2 spike protein, with its six key alterations shown as red and blue spheres.
The molecular structure of HexaPro, a modified version of the SARS-CoV-2 spike protein, with its six key alterations shown as red and blue spheres.University of Texas at Austin

Vaccines work by acquainting the immune system with a virus well enough to prompt a defense against it. Some vaccines contain entire viruses that have been killed; others contain just a single protein from the virus. Still others contain genetic instructions that our cells can use to make the viral protein.

Once exposed to a virus, or part of it, the immune system can learn to make antibodies that attack it. Immune cells can also learn to recognize infected cells and destroy them.

In the case of the coronavirus, the best target for the immune system is the protein that covers its surface like a crown. The protein, known as spike, latches onto cells and then allows the virus to fuse to them.

But simply injecting coronavirus spike proteins into people is not the best way to vaccinate them. That’s because spike proteins sometimes assume the wrong shape, and prompt the immune system to make the wrong antibodies.

Jason McLellan, a structural biologist at the University of Texas at Austin. His research on coronavirus spike proteins aided the development of the Pfizer, Moderna, Johnson & Johnson and Novavax vaccines.Ilana Panich-Linsman for The New York Times

This insight emerged long before the Covid-19 pandemic. In 2015, another coronavirus appeared, causing a deadly form of pneumonia called MERS. Jason McLellan, a structural biologist then at the Geisel School of Medicine at Dartmouth, and his colleagues set out to make a vaccine against it.

They wanted to use the spike protein as a target. But they had to reckon with the fact that the spike protein is a shape-shifter. As the protein prepares to fuse to a cell, it contorts from a tulip-like shape into something more akin to a javelin.

Scientists call these two shapes the prefusion and postfusion forms of the spike. Antibodies against the prefusion shape work powerfully against the coronavirus, but postfusion antibodies don’t stop it.

Dr. McLellan and his colleagues used standard techniques to make a MERS vaccine but ended up with a lot of postfusion spikes, useless for their purposes. Then they discovered a way to keep the protein locked in a tulip-like prefusion shape. All they had to do was change two of more than 1,000 building blocks in the protein into a compound called proline.

The resulting spike — called 2P, for the two new proline molecules it contained — was far more likely to assume the desired tulip shape. The researchers injected the 2P spikes into mice and found that the animals could easily fight off infections of the MERS coronavirus.

The team filed a patent for its modified spike, but the world took little notice of the invention. MERS, although deadly, is not very contagious and proved to be a relatively minor threat; fewer than 1,000 people have died of MERS since it first emerged in humans.

But in late 2019 a new coronavirus, SARS-CoV-2, emerged and began ravaging the world. Dr. McLellan and his colleagues swung into action, designing a 2P spike unique to SARS-CoV-2. In a matter of days, Moderna used that information to design a vaccine for Covid-19; it contained a genetic molecule called RNA with the instructions for making the 2P spike.

Other companies soon followed suit, adopting 2P spikes for their own vaccine designs and starting clinical trials. All three of the vaccines that have been authorized so far in the United States — from Johnson & Johnson, Moderna and Pfizer-BioNTech — use the 2P spike.

Other vaccine makers are using it as well. Novavax has had strong results with the 2P spike in clinical trials and is expected to apply to the Food and Drug Administration for emergency use authorization in the next few weeks. Sanofi is also testing a 2P spike vaccine and expects to finish clinical trials later this year.

Two prolines are good; six are better

Dr. McLellan’s ability to find lifesaving clues in the structure of proteins has earned him deep admiration in the vaccine world. “This guy is a genius,” said Harry Kleanthous, a senior program officer at the Bill & Melinda Gates Foundation. “He should be proud of this huge thing he’s done for humanity.”

But once Dr. McLellan and his colleagues handed off the 2P spike to vaccine makers, he turned back to the protein for a closer look. If swapping just two prolines improved a vaccine, surely additional tweaks could improve it even more.

“It made sense to try to have a better vaccine,” said Dr. McLellan, who is now an associate professor at the University of Texas at Austin.

In March, he joined forces with two fellow University of Texas biologists, Ilya Finkelstein and Jennifer Maynard. Their three labs created 100 new spikes, each with an altered building block. With funding from the Gates Foundation, they tested each one and then combined the promising changes in new spikes. Eventually, they created a single protein that met their aspirations.

The winner contained the two prolines in the 2P spike, plus four additional prolines found elsewhere in the protein. Dr. McLellan called the new spike HexaPro, in honor of its total of six prolines.

The structure of HexaPro was even more stable than 2P, the team found. It was also resilient, better able to withstand heat and damaging chemicals. Dr. McLellan hoped that its rugged design would make it potent in a vaccine.

Dr. McLellan also hoped that HexaPro-based vaccines would reach more of the world — especially low- and middle-income countries, which so far have received only a fraction of the total distribution of first-wave vaccines.

“The share of the vaccines they’ve received so far is terrible,” Dr. McLellan said.

To that end, the University of Texas set up a licensing arrangement for HexaPro that allows companies and labs in 80 low- and middle-income countries to use the protein in their vaccines without paying royalties.

Meanwhile, Dr. Innes and his colleagues at PATH were looking for a way to increase the production of Covid-19 vaccines. They wanted a vaccine that less wealthy nations could make on their own.

With a little help from eggs

The first wave of authorized Covid-19 vaccines require specialized, costly ingredients to make. Moderna’s RNA-based vaccine, for instance, needs genetic building blocks called nucleotides, as well as a custom-made fatty acid to build a bubble around them. Those ingredients must be assembled into vaccines in purpose-built factories.

The way influenza vaccines are made is a study in contrast. Many countries have huge factories for making cheap flu shots, with influenza viruses injected into chicken eggs. The eggs produce an abundance of new copies of the viruses. Factory workers then extract the viruses, weaken or kill them and then put them into vaccines.

The PATH team wondered if scientists could make a Covid-19 vaccine that could be grown cheaply in chicken eggs. That way, the same factories that make flu shots could make Covid-19 shots as well.

In New York, a team of scientists at the Icahn School of Medicine at Mount Sinai knew how to make just such a vaccine, using a bird virus called Newcastle disease virus that is harmless in humans.

For years, scientists had been experimenting with Newcastle disease virus to create vaccines for a range of diseases. To develop an Ebola vaccine, for example, researchers added an Ebola gene to the Newcastle disease virus’s own set of genes.

The scientists then inserted the engineered virus into chicken eggs. Because it is a bird virus, it multiplied quickly in the eggs. The researchers ended up with Newcastle disease viruses coated with Ebola proteins.

At Mount Sinai, the researchers set out to do the same thing, using coronavirus spike proteins instead of Ebola proteins. When they learned about Dr. McLellan’s new HexaPro version, they added that to the Newcastle disease viruses. The viruses bristled with spike proteins, many of which had the desired prefusion shape. In a nod to both the Newcastle disease virus and the HexaPro spike, they called it NDV-HXP-S.

PATH arranged for thousands of doses of NDV-HXP-S to be produced in a Vietnamese factory that normally makes influenza vaccines in chicken eggs. In October, the factory sent the vaccines to New York to be tested. The Mount Sinai researchers found that NDV-HXP-S conferred powerful protection in mice and hamsters.

“I can honestly say I can protect every hamster, every mouse in the world against SARS-CoV-2,” Dr. Peter Palese, the leader of the research, said. “But the jury’s still out about what it does in humans.”

The potency of the vaccine brought an extra benefit: The researchers needed fewer viruses for an effective dose. A single egg may yield five to 10 doses of NDV-HXP-S, compared to one or two doses of influenza vaccines.

“We are very excited about this, because we think it’s a way of making a cheap vaccine,” Dr. Palese said.

A nurse administering the NDV-HXP-S  vaccine to a volunteer at Mahidol University in Bangkok during the country’s first human trial.Government Pharmaceutical Organization of Thailand, via Agence France-Presse — Getty Images

PATH then connected the Mount Sinai team with influenza vaccine makers. On March 15, Vietnam’s Institute of Vaccines and Medical Biologicals announced the start of a clinical trial of NDV-HXP-S. A week later, Thailand’s Government Pharmaceutical Organization followed suit. On March 26, Brazil’s Butantan Institute said it would ask for authorization to begin its own clinical trials of NDV-HXP-S.

Meanwhile, the Mount Sinai team has also licensed the vaccine to the Mexican vaccine maker Avi-Mex as an intranasal spray. The company will start clinical trials to see if the vaccine is even more potent in that form.

To the nations involved, the prospect of making the vaccines entirely on their own was appealing. “This vaccine production is produced by Thai people for Thai people,” Thailand’s health minister, Anutin Charnvirakul, said at the announcement in Bangkok.

From left, Dimas Covas, director of the Butantan Institute in Brazil; João Doria, governor of the state of São Paulo; and Jean Gorinchteyn, the state health secretary, announcing the ButanVac Covid-19 vaccine candidate against in São Paulo on March 26. Miguel Schincariol/Agence France-Presse — Getty Images

In Brazil, the Butantan Institute trumpeted its version of NDV-HXP-S as “the Brazilian vaccine,” one that would be “produced entirely in Brazil, without depending on imports.”

Ms. Taylor, of the Duke Global Health Innovation Center, was sympathetic. “I could understand why that would really be such an attractive prospect,” she said. “They’ve been at the mercy of global supply chains.”

Madhavi Sunder, an expert on intellectual property at Georgetown Law School, cautioned that NDV-HXP-S would not immediately help countries like Brazil as they grappled with the current wave of Covid-19 infections. “We’re not talking 16 billion doses in 2020,” she said.

Instead, the strategy will be important for long-term vaccine production — not just for Covid-19 but for other pandemics that may come in the future. “It sounds super promising,” she said.

In the meantime, Dr. McLellan has returned to the molecular drawing board to try to make a third version of their spike that is even better than HexaPro.

“There’s really no end to this process,” he said. “The number of permutations is almost infinite. At some point, you’d have to say, ‘This is the next generation.’”

Can Vaccinated People Spread the Virus? We Don’t Know, Scientists Say.

Researchers pushed back after the C.D.C. director asserted that vaccinated people “do not carry the virus.”

The Centers for Disease Control and Prevention on Thursday walked back controversial comments made by its director, Dr. Rochelle P. Walensky, suggesting that people who are vaccinated against the coronavirus never become infected or transmit the virus to others.

The assertion called into question the precautions that the agency had urged vaccinated people to take just last month, like wearing masks and gathering only under limited circumstances with unvaccinated people.

“Dr. Walensky spoke broadly during this interview,” an agency spokesman told The Times. “It’s possible that some people who are fully vaccinated could get Covid-19. The evidence isn’t clear whether they can spread the virus to others. We are continuing to evaluate the evidence.”

The agency was responding in part to criticism from scientists who noted that current research was far from sufficient to claim that vaccinated people cannot spread the virus.

The data suggest that “it’s much harder for vaccinated people to get infected, but don’t think for one second that they cannot get infected,” said Paul Duprex, director of the Center for Vaccine Research at the University of Pittsburgh.

In a television interview with MSNBC’s Rachel Maddow, Dr. Walensky referred to data published by the C.D.C. showing that one dose of the Moderna or Pfizer-BioNTech vaccine was 80 percent effective at preventing infection, and two doses were 90 percent effective.

That certainly suggested that transmission from vaccinated people might be unlikely, but Dr. Walensky’s comments hinted that protection was complete. “Our data from the C.D.C. today suggests that vaccinated people do not carry the virus, don’t get sick,” she said. “And that it’s not just in the clinical trials, it’s also in real-world data.”

Dr. Walensky went on to emphasize the importance of continuing to wear masks and maintain precautions, even for vaccinated people. Still, the brief comment was widely interpreted as saying that the vaccines offered complete protection against infection or transmission.

In a pandemic that regularly spawns scientific misunderstanding, experts said they were sympathetic to Dr. Walensky and her obvious desire for Americans to continue to take precautions. It was only Monday that she said rising caseloads had left her with a sense of “impending doom.”

“If Dr. Walensky had said most vaccinated people do not carry virus, we would not be having this discussion,” said John Moore, a virologist at Weill Cornell Medicine in New York.

“What we know is the vaccines are very substantially effective against infection — there’s more and more data on that — but nothing is 100 percent,” he added. “It is an important public health message that needs to be gotten right.”

Misinterpretation could disrupt the agency’s urgent pleas for immunization, some experts said. As of Wednesday, 30 percent of Americans had received at least one dose of a vaccine and 17 percent were fully immunized.

“There cannot be any daylight between what the research shows — really impressive but incomplete protection — and how it is described,” said Dr. Peter Bach, director of the Center for Health Policy and Outcomes at Memorial Sloan Kettering Cancer Center in New York.

“This opens the door to the skeptics who think the government is sugarcoating the science,” Dr. Bach said, “and completely undermines any remaining argument why people should keep wearing masks after being vaccinated.”

All of the coronavirus vaccines are spectacularly successful at preventing serious disease and death from Covid-19, but how well they prevent infection has been less clear.

Clinical trials of the vaccines were designed only to assess whether the vaccines prevent serious illness and death. The research from the C.D.C. on Monday brought the welcome conclusion that the vaccines are also extremely effective at preventing infection.

The study enrolled 3,950 health care workers, emergency responders and others at high risk of infection. The participants swabbed their noses each week and sent the samples in for testing, which allowed federal researchers to track all infections, symptomatic or not. Two weeks after vaccination, the vast majority of vaccinated people remained virus-free, the study found.

Follow-up data from clinical trials support that finding. In results released by Pfizer and BioNTech on Wednesday, for example, 77 people who received the vaccine had a coronavirus infection, compared with 850 people who got a placebo.

“Clearly, some vaccinated people do get infected,” Dr. Duprex said. “We’re stopping symptoms, we’re keeping people out of hospitals. But we’re not making them completely resistant to an infection.”

The number of vaccinated people who become infected is likely to be higher among those receiving vaccines made by Johnson & Johnson and AstraZeneca, which have a lower efficacy, experts said. (Still, those vaccines are worth taking, because they uniformly prevent serious illness and death.)

Infection rates may also be higher among people exposed to a virus variant that can sidestep the immune system.

Cases across the country are once again on the upswing, threatening a new surge. Dr. Walensky’s comment came just a day after she made an emotional appeal to the American public to continue taking precautions.

“I am asking you to just hold on a little longer, to get vaccinated when you can, so that all of those people that we all love will still be here when this pandemic ends,” she said.

Given the rising numbers, it’s especially important that immunized people continue to protect those who have not yet been immunized against the virus, experts said.

“Vaccinated people should not be throwing away their masks at this point,” Dr. Moore said. “This pandemic is not over.”

Virus Variants Can Infect Mice, Scientists Report

Infected rodents pose no immediate danger to humans, but the research suggests that mutations are helping the coronavirus expand its range of potential hosts.

Bats, humans, monkeys, minks, big cats and big apes — the coronavirus can make a home in many different animals. But now the list of potential hosts has expanded to include mice, according to an unnerving new study.

Infected rodents pose no immediate risk to people, even in cities like London and New York, where they are ubiquitous and unwelcome occupants of subway stations, basements and backyards.

Still, the finding is worrying. Along with previous work, it suggests that new mutations are giving the virus the ability to replicate in a wider array of animal species, experts said.

“The virus is changing, and unfortunately it’s changing pretty fast,” said Timothy Sheahan, a virologist at the University of North Carolina at Chapel Hill, who was not involved in the new study.

In the study, the researchers introduced the virus into the nasal passages of laboratory mice. The form of the virus first identified in Wuhan, China, cannot infect laboratory mice, nor can B.1.1.7, a variant that has been spreading across much of Europe, the researchers found.

But B.1.351 and P1, the variants discovered in South Africa and Brazil, can replicate in rodents, said Dr. Xavier Montagutelli, a veterinarian and mouse geneticist at the Pasteur Institute in Paris, who led the study. The research, posted online earlier this month, has not yet been reviewed for publication in a scientific journal.

The results indicate only that infection in mice is possible, Dr. Montagutelli said. Mice caught in the wild have not been found to be infected with the coronavirus, and so far, the virus does not seem to be able to jump from humans to mice, from mice to humans, or from mice to mice.

“What our results emphasize is that it is necessary to regularly assess the range of species that the virus can infect, especially with the emergence of new variants,” Dr. Montagutelli said.

The coronavirus is thought to have emerged from bats, with perhaps another animal acting as an intermediate host, and scientists worry that the virus may return to what they describe as an animal “reservoir.”

Apart from potentially devastating those animal populations, a coronavirus spreading in another species may then acquire dangerous mutations, returning to humans in a form the current vaccines weren’t designed to fend off.

A mink looks out from its cage at a farm in Denmark, where mink populations were hit hard by the coronavirus.
A mink looks out from its cage at a farm in Denmark, where mink populations were hit hard by the coronavirus.Mads Claus Rasmussen/Agence France-Presse — Getty Images

Minks are the only animals known to be able to catch the coronavirus from humans and pass it back. In early November, Denmark culled 17 million farmed mink to prevent the virus from evolving into dangerous new variants in the animals.

More recently, researchers found that B.1.1.7 infections in domesticated cats and dogs can cause the pets to develop heart problems similar to those seen in people with Covid-19.

To establish a successful infection, the coronavirus must bind to a protein on the surface of animal cells, gain entry into the cells, and exploit their machinery to make copies of itself. The virus must also evade the immune system’s early attempts at thwarting the infection.

Given all those requirements, it is “quite extraordinary” that the coronavirus can infect so many species, said Vincent Munster, a virologist at the National Institute of Allergy and Infectious Diseases. “Typically, viruses have a more curtailed host range.”

Mice are a known reservoir for hantavirus, which causes a rare and deadly disease in people. Even though the coronavirus variants don’t seem to be able to jump from mice to people, there is potential for them to spread among rodents, evolve into new variants, and then infect people again, Dr. Munster said.

The variants may also threaten endangered species like black-footed ferrets. “This virus seems to be able to surprise us more than anything else, or any other previous virus,” Dr. Munster said. “We have to err on the side of caution.”

Dr. Sheahan said he was more concerned about transmission to people from farm animals and pets than from mice.

“You’re not catching wild mice in your house and snuggling — getting all up in their face and sharing the same airspace, like maybe with your cat or your dog,” he said. “I’d be more worried about wild or domestic animals with which we have a more intimate relationship.”

But he and other experts said the results emphasized the need to closely monitor the rapid changes in the virus.

“It’s like a moving target — it’s crazy,” he added. “There’s nothing we can do about it, other than try and get people vaccinated really fast.”

The Pfizer-BioNTech Vaccine Is Said to Be Powerfully Protective in Adolescents

A clinical trial found no infections among vaccinated children ages 12 to 15, the companies said, and there were no serious side effects. The data have not yet been reviewed by independent experts.

The Pfizer-BioNTech coronavirus vaccine is extremely effective in adolescents 12 to 15 years old, perhaps even more so than in adults, the companies reported on Wednesday. No infections were found among children who received the vaccine in a recent clinical trial, the drug makers said; the children produced strong antibody responses and experienced no serious side effects.

The findings, if they hold up, may speed a return to normalcy for millions of American families. Depending on regulatory approval, vaccinations could begin before the start of the next academic year for middle school and high school students, and for elementary school children not long after.

The companies announced the results in a news release that did not include detailed data from the trial, which has not yet been peer-reviewed nor published in a scientific journal. Still, the news drew praise and excitement from experts.

“Oh my god, I’m so happy to see this — this is amazing,” said Akiko Iwasaki, an immunologist at Yale University. If the vaccines’s performance in adults was A-plus, the results in children were “A-plus-plus.”

The good news arrives even as the country records another rise in infections and health officials renew calls for Americans to heed precautions and get vaccinated. On Monday, Dr. Rochelle Walensky, director of the Centers for Disease Control and Prevention, said that rising cases had left her with sense of “impending doom,” while President Biden called on state and local officials to reinstate mask mandates.

Vaccination efforts are accelerating throughout the nation. As of Tuesday, 29 percent of adults had received at least one dose of a coronavirus vaccine, and 16 percent had been fully inoculated, according to the C.D.C.

But the country cannot hope to reach herd immunity — the point at which immunity becomes so widespread that the coronavirus slows its crawl through the population — without also inoculating the youngest Americans, some experts say. Children under 18 account for about 23 percent of the population in the United States.

“The sooner that we can get vaccines into as many people as possible, regardless of their age, the sooner we will be able to really feel like we’re ending this pandemic for good,” said Angela Rasmussen, a virologist affiliated with Georgetown University in Washington.

Data from Israel suggest that vaccinating adults alone can significantly decrease the number of cases, but “long term, to hit the herd immunity threshold, we will have to vaccinate children,” she said.

The trial included 2,260 adolescents ages 12 to 15. The children received two doses of the vaccine three weeks apart — the same amounts and schedule used for adults — or a placebo of saltwater.

The researchers recorded 18 cases of coronavirus infection in the placebo group, and none among the children who received the vaccine. Still, the low number of infections makes it difficult to be too specific about the vaccine’s efficacy in the population at large, Dr. Rasmussen said.

“But obviously, it looks good for the vaccine if there were zero Covid cases among the vaccinated people,” she added.

The adolescents who got the vaccine produced much higher levels of antibodies on average, compared with participants 16 to 25 years of age in an earlier trial. The children experienced the same minor side effects as older participants, although the companies declined to be more specific.

Dr. Iwasaki said she had expected antibody levels in adolescents to be comparable to those in young adults. “But they’re getting even better levels from the vaccines,” she said. “That’s really incredible.”

She and other experts cautioned that the vaccine might be less effective in children, and adults, against some of the variants that have begun circulating in the United States.

Pfizer and BioNTech have begun a clinical trial of the vaccine in children under 12 and started inoculations of children ages 5 to 11 just last week. Company scientists plan to start testing the vaccine next week in even younger children, ages 2 to 5, followed by trials in children ages 6 months to 2 years.

Results from that three-phase trial are expected in the second half of the year, and the companies hope to make the vaccine available for children under 12 early next year.

“We share the urgency to expand the use of our vaccine to additional populations and are encouraged by the clinical trial data from adolescents between the ages of 12 and 15,” Albert Bourla, Pfizer’s chairman and chief executive officer, said in a statement.

Moderna has also been testing its vaccine in children. Results from a trial in adolescents ages 12 to 17 are expected in the next few weeks and in children 6 months to 12 years old in the second half of this year.

AstraZeneca started testing its vaccine in children 6 months and older last month, and Johnson & Johnson has said it will wait for results from trials in older children before testing its vaccine in children under 12.

Some parents have said they are reluctant to immunize their children because the risk posed by the virus is low. Children make up fewer than 1 percent of deaths from Covid-19, but about 2 percent of children who get the illness require hospital care.

The new results may not sway all of those parents, but they may reassure parents who have been wary of the vaccines, said Jennifer Nuzzo, an epidemiologist at the Johns Hopkins Center for Health Security.

“While I don’t think we have to wait until children are vaccinated to fully reopen schools, being able to vaccinate children may help some families feel safer about returning to school,” she said.

Pfizer and BioNTech plan to request from the Food and Drug Administration an amendment to the emergency use authorization for their vaccine, in hopes of beginning immunizations of older children before the start of the next school year. The companies also are planning to submit their data for peer review and publication in a scientific journal.

They will monitor the participants for two years after the second dose to assess the vaccine’s long-term safety and efficacy. Side effects of vaccines are usually apparent within the first six weeks, said Dr. Kristin Oliver, a pediatrician and vaccine expert at Mount Sinai Hospital in New York. “Still, it’s good to know that safety monitoring is going to continue,” she said.

The C.D.C. recommends that people avoid getting other vaccines for two weeks before and after receiving the two doses of the coronavirus vaccine.

But children receive more vaccines in the few weeks before the school year than at any other time, Dr. Oliver noted, so pediatricians and parents should aim to get those other immunizations done earlier than usual.

The coronavirus vaccines should ideally be given by pediatricians who have deep experience in immunizing children, Dr. Oliver added. “Now is the time to start planning how that rollout is going to take place in this age group,” she said.

Getting One Vaccine Is Good. How About Mix-and-Match?

Researchers are exploring the possible benefits of pairing doses from two different Covid-19 vaccines.

In January, Britain made a change to its vaccine guidelines that shocked many health experts: If the second dose of one vaccine wasn’t available, patients could be given a different one.

The new rule was based on sheer guesswork; there was no scientific data at the time demonstrating that mixing two coronavirus vaccines was safe and effective. But that may change soon.

In February, researchers at the University of Oxford began a trial in which volunteers received a dose of the Pfizer-BioNTech vaccine followed by a dose of AstraZeneca’s formulation, or vice versa. This month, the researchers will start analyzing the blood of the subjects to see how well the mix-and-match approach works.

As growing numbers of vaccines are being authorized, researchers are testing other combinations. A few are in clinical trials, while others are being tested in animals for now.

Mixing vaccines might do more than just help overcome supply bottlenecks. Some researchers suspect that a pair of different vaccines might work better than two doses of the same one.

“I think we’re on the cusp of some interesting data,” said Adam Wheatley, an immunologist at the University of Melbourne in Australia.

The concept of mixing vaccines — sometimes called a heterologous prime-boost — is not new to our pandemic era. For decades, researchers have investigated the approach, hoping to find potent combinations against a range of viruses, such as influenza, H.I.V. and Ebola.

But scientists had little to show for all that research. It was easy enough to demonstrate that two vaccines may work well together in a mouse. But running full-blown clinical trials on a combination of vaccines is a tall order.

“For a single company to develop two parallel arms of a vaccine is twice the work and twice the cost,” Dr. Wheatley said.

Some of the early successes for heterologous prime-boosts came in the search for vaccines for Ebola. Many researchers focused their efforts on presenting the immune system with a protein found on the surface of the Ebola virus.

The gene for that protein was inserted into a different, harmless virus. When people received an injection of the vaccine, the harmless virus entered their cells; the cells then read the instructions in the Ebola gene and mass-produced Ebola’s surface protein. The immune system encountered the Ebola protein and made antibodies against it. And those antibodies protected the vaccinated people if they became infected with a full-blown Ebola virus.

This type of vaccine, called a viral vector vaccine, came with a big risk: The recipients might develop immunity to the viral vector after just the first dose. When the second dose arrived, their immune systems could swiftly wipe out the viral vector before it delivered its payload.

A number of vaccine makers decided to sidestep this potential threat by using different viruses for each dose. That way, the viral vectors in the second dose would be as new to the immune system as the first was. In 2017, for example, researchers at the Gamaleya Research Institute in Russia created an Ebola vaccine whose first dose contained a virus called an adenovirus. The second shot used another virus, called vesicular stomatitis virus.

When the Covid-19 pandemic began last year, the Gamaleya researchers used a similar strategy to create vaccines against the new coronavirus. The first dose used the same adenovirus as in their Ebola vaccine, called Ad5. The second dose contained a different human adenovirus, Ad26. The researches inserted a gene into both viruses for the protein on the surface of the coronavirus, called spike.

Studies revealed that the vaccine, now known as Sputnik V, provided a strong defense against Covid-19. In clinical trials, the researchers found that it had an efficacy of 91.6 percent. Sputnik V is now in use in Russia and 56 other countries.

Recently, the Gamaleya institute joined forces with AstraZeneca, which makes its own Covid-19 vaccine. AstraZeneca’s consists of two doses of a chimpanzee adenovirus called ChAdOx1. Last week, the company reported that its vaccine had an efficacy of 76 percent.

The Gamaleya and AstraZeneca teams want to see how well their vaccines work together. They have registered a pair of clinical trials in which volunteers will receive a dose of AstraZeneca’s ChAdOx1 and another of Sputnik V’s Ad26.

A spokesman for AstraZeneca said that one trial in Azerbaijan is underway, and a second, in Russia, is still under review by the country’s ministry of health.

Dr. Jakob Cramer, the head of clinical development at CEPI, a vaccine development organization, said that vaccines using viral vectors were not the only kind that might benefit from mixing. In fact, certain combinations might provoke a different, more effective immune response than a single type of vaccine. “Immunologically, there are several arguments in favor of exploring heterologous priming,” Dr. Kramer said.

Another kind of Covid-19 vaccine being tested contains the actual spike protein, rather than genetic instructions for it. Some of the vaccines contain the entire protein; others contain just a fragment of it. Currently, there are 29 protein-based vaccines for Covid-19 in clinical trials, although none have been authorized yet.

Dr. Wheatley and his colleagues have been testing protein-based vaccines in mice. They injected the full spike protein into the animals as a first dose. For the second dose, they injected only the tip of the spike, a region known as the receptor-binding domain, or R.B.D.

Dr. Wheatley and his colleagues found that the mixture worked better than two doses of the spike or of the R.B.D.

The researchers suspect that the first dose produces a broad range of antibodies that can stick to spots along the length of the spike protein, and that the second dose delivers a big supply of particularly potent antibodies to the tip of the spike. Together, the assortment of antibodies does a better job of stopping the coronavirus.

“You’re able to basically take that initial immunity that was elicited to that spike vaccine, and then really focus it down onto that R.B.D.,” Dr. Wheatley said.

Other combinations of vaccines may bring benefits of their own. Some vaccines, especially protein-based ones, do a good job of generating antibodies. Others, such as viral vectors, are better at training immune cells. A viral vector followed by a protein boost might offer the best of both worlds.

John Moore, a virologist at Weill Cornell Medicine, cautioned that there was no guarantee that clinical trials would reveal a benefit to mixing vaccines. In the search for an H.I.V. vaccine, researchers tried combining viral vectors and protein boost without success, he noted. Still, Dr. Moore said, the story might turn out differently for coronavirus vaccines.

“I’d like to see these studies done,” he said. “Doing it in the Covid space is completely rational, but may not be necessary.”

Some researchers are investigating heterologous vaccines not to find a superior mixture, but simply to open up more options for countries desperate to vaccinate their populations. Last week, India held back exports of vaccines to other countries as it grappled with a surge of Covid-19. For countries that were counting on those vaccines, a safe alternative for second doses could save lives.

After Britain was criticized in January for suggesting that vaccines could be mixed, researchers at the University of Oxford set out to put the idea to a formal test. In a trial called Com-Cov, they recruited 830 volunteers to test the two vaccines authorized by the British government: AstraZeneca’s adenovirus-based vaccine and the vaccine by Pfizer-BioNTech.

Pfizer-BioNTech’s vaccine uses a fundamentally different technology to produce spike proteins in the body. It contains tiny bubbles with genetic molecules called RNA. Once the bubbles fuse to cells, the cells use the RNA to make spike proteins.

One group of volunteers is receiving a Pfizer-BioNTech shot followed by AstraZeneca, while another will receive them in the reverse order. The other volunteers are receiving the standard two-dose version of the vaccines.

Later this month, the Oxford team will draw blood from the volunteers, examining their antibodies and immune cells to see whether the heterologous prime-boost creates an immune response roughly as strong as two doses of each of the authorized vaccines.

If more vaccines are authorized in Britain, the Com-Cov team may add them to the trial. Dr. Matthew Snape, who is leading the Com-COV trial, hopes it will be useful not just to his own country but to others that will be trying to vaccinate their citizens over the next few years.

“It might be that actually this flexibility becomes essential in the future,” he said.

Dr. Cramer said CEPI is planning to support additional heterologous prime-boost studies. There are plenty of possible studies to run. Worldwide, 13 vaccines are now in use against Covid-19, with 67 more in clinical trials.

“In the current situation, we have a quite a luxurious position of having so many advanced, effective vaccines,” Dr. Wheatley said.

As the number of authorized vaccines grows, the possible combinations in which they can be used will explode. Recently, researchers at China’s National Institutes for Food and Drug Control scaled up their research on heterologous prime-boosts by trying out four different vaccines that have either been authorized in China or are in late-stage clinical trials there — vaccines based on adenoviruses, proteins, RNA and coronaviruses that have been inactivated with chemicals.

The researchers injected mice with a first dose of one vaccine, then a second dose of another. Some of the combinations caused the mice to produce stronger immune responses than mice that received the same vaccine for both doses.

Whether scientists carry out more experiments on other vaccines will depend on the willingness of the vaccine manufacturers. “You’re requiring quite large pharmaceutical companies to play nice together,” Dr. Wheatley said.

Dr. Bernard Moss, a virologist at the National Institute of Allergy and Infectious Diseases, suspects that a number of companies will be willing to let their vaccines be tested in combinations. “It’s always better to be a part of something that is going to be used,” he said, “than to wholly own something that isn’t.”

One Vaccine Is Good. How About Mixing Two?

Researchers are exploring the possible benefits of combining doses from two different Covid-19 vaccines.

In January, Britain made a change to its vaccine guidelines that shocked many health experts: If the second dose of one vaccine wasn’t available, patients could be given a different one.

The new rule was based on sheer guesswork; there was no scientific data at the time demonstrating that mixing two coronavirus vaccines was safe and effective. But that may change soon.

In February, researchers at the University of Oxford began a trial in which volunteers received a dose of the Pfizer-BioNTech vaccine followed by a dose of AstraZeneca’s formulation, or vice versa. This month, the researchers will start analyzing the blood of the subjects to see how well the mix-and-match approach works.

As a growing number of vaccines are being authorized, researchers are testing other combinations. A few are in clinical trials, while others are being tested in animals for now.

Mixing vaccines might do more than just help overcome supply bottlenecks. Some researchers suspect that a pair of different vaccines might work better than two doses of the same one.

“I think we’re on the cusp of some interesting data,” said Adam Wheatley, an immunologist at the University of Melbourne in Australia.

The concept of mixing vaccines — sometimes called a heterologous prime-boost — is not new to our pandemic era. For decades, researchers have investigated the approach, hoping to find potent combinations against a range of viruses, such as influenza, H.I.V. and Ebola.

But scientists had little to show for all that research. It was easy enough to demonstrate that two vaccines may work well together in a mouse. But running full-blown clinical trials on a combination of vaccines is a tall order.

“For a single company to develop two parallel arms of a vaccine is twice the work and twice the cost,” Dr. Wheatley said.

Some of the early successes for heterologous prime-boosts came in the search for vaccines for Ebola. Many researchers focused their efforts on presenting the immune system with a protein found on the surface of the Ebola virus.

The gene for that protein was inserted into a different, harmless virus. When people received an injection of the vaccine, the harmless virus entered their cells; the cells then read the instructions in the Ebola gene and mass-produced Ebola’s surface protein. The immune system encountered the Ebola protein and made antibodies against it. And those antibodies protected the vaccinated people if they became infected with a full-blown Ebola virus.

This type of vaccine, called a viral vector vaccine, came with a big risk: The recipients might develop immunity to the viral vector after just the first dose. When the second dose arrived, their immune systems could swiftly wipe out the viral vector before it delivered its payload.

A number of vaccine makers decided to sidestep this potential threat by using different viruses for each dose. That way, the viral vectors in the second dose would be as new to the immune system as the first was. In 2017, for example, researchers at the Gamaleya Research Institute in Russia created an Ebola vaccine whose first dose contained a virus called an adenovirus. The second shot used another virus, called vesicular stomatitis virus.

When the Covid-19 pandemic began last year, the Gamaleya researchers used a similar strategy to create vaccines against the new coronavirus. The first dose used the same adenovirus as in their Ebola vaccine, called Ad5. The second dose contained a different human adenovirus, Ad26. The researches inserted a gene into both viruses for the protein on the surface of the coronavirus, called spike.

Studies revealed that the vaccine, now known as Sputnik V, provided a strong defense against Covid-19. In clinical trials, the researchers found that it had an efficacy of 91.6 percent. Sputnik V is now in use in Russia and 56 other countries.

Recently, the Gamaleya institute joined forces with AstraZeneca, which makes its own Covid-19 vaccine. AstraZeneca’s consists of two doses of a chimpanzee adenovirus called ChAdOx1. Last week, the company reported that its vaccine had an efficacy of 76 percent.

The Gamaleya and AstraZeneca teams want to see how well their vaccines work together. They have registered a pair of clinical trials in which volunteers will receive a dose of AstraZeneca’s ChAdOx1 and another of Sputnik V’s Ad26.

A spokesman for AstraZeneca said that one trial in Azerbaijan is underway, and a second, in Russia, is still under review by the country’s ministry of health.

Dr. Jakob Cramer, the head of clinical development at CEPI, a vaccine development organization, said that vaccines using viral vectors were not the only kind that might benefit from mixing. In fact, certain combinations might provoke a different, more effective immune response than a single type of vaccine. “Immunologically, there are several arguments in favor of exploring heterologous priming,” Dr. Kramer said.

Another kind of Covid-19 vaccine being tested contains the actual spike protein, rather than genetic instructions for it. Some of the vaccines contain the entire protein; others contain just a fragment of it. Currently, there are 29 protein-based vaccines for Covid-19 in clinical trials, although none have been authorized yet.

Dr. Wheatley and his colleagues have been testing protein-based vaccines in mice. They injected the full spike protein into the animals as a first dose. For the second dose, they injected only the tip of the spike, a region known as the receptor-binding domain, or R.B.D.

Dr. Wheatley and his colleagues found that the mixture worked better than two doses of the spike or of the R.B.D.

The researchers suspect that the first dose produces a broad range of antibodies that can stick to spots along the length of the spike protein, and that the second dose delivers a big supply of particularly potent antibodies to the tip of the spike. Together, the assortment of antibodies does a better job of stopping the coronavirus.

“You’re able to basically take that initial immunity that was elicited to that spike vaccine, and then really focus it down onto that R.B.D.,” Dr. Wheatley said.

Other combinations of vaccines may bring benefits of their own. Some vaccines, especially protein-based ones, do a good job of generating antibodies. Others, such as viral vectors, are better at training immune cells. A viral vector followed by a protein boost might offer the best of both worlds.

John Moore, a virologist at Weill Cornell Medicine, cautioned that there was no guarantee that clinical trials would reveal a benefit to mixing vaccines. In the search for an H.I.V. vaccine, researchers tried combining viral vectors and protein boost without success, he noted. Still, Dr. Moore said, the story might turn out differently for coronavirus vaccines.

“I’d like to see these studies done,” he said. “Doing it in the Covid space is completely rational, but may not be necessary.”

Some researchers are investigating heterologous vaccines not to find a superior mixture, but simply to open up more options for countries desperate to vaccinate their populations. Last week, India held back exports of vaccines to other countries as it grappled with a surge of Covid-19. For countries that were counting on those vaccines, a safe alternative for second doses could save lives.

After Britain was criticized in January for suggesting that vaccines could be mixed, researchers at the University of Oxford set out to put the idea to a formal test. In a trial called Com-Cov, they recruited 830 volunteers to test the two vaccines authorized by the British government: AstraZeneca’s adenovirus-based vaccine and the vaccine by Pfizer-BioNTech.

Pfizer-BioNTech’s vaccine uses a fundamentally different technology to produce spike proteins in the body. It contains tiny bubbles with genetic molecules called RNA. Once the bubbles fuse to cells, the cells use the RNA to make spike proteins.

One group of volunteers is receiving a Pfizer-BioNTech shot followed by AstraZeneca, while another will receive them in the reverse order. The other volunteers are receiving the standard two-dose version of the vaccines.

Later this month, the Oxford team will draw blood from the volunteers, examining their antibodies and immune cells to see whether the heterologous prime-boost creates an immune response roughly as strong as two doses of each of the authorized vaccines.

If more vaccines are authorized in Britain, the Com-Cov team may add them to the trial. Dr. Matthew Snape, who is leading the Com-COV trial, hopes it will be useful not just to his own country but to others that will be trying to vaccinate their citizens over the next few years.

“It might be that actually this flexibility becomes essential in the future,” he said.

Dr. Cramer said CEPI is planning to support additional heterologous prime-boost studies. There are plenty of possible studies to run. Worldwide, 13 vaccines are now in use against Covid-19, with 67 more in clinical trials.

“In the current situation, we have a quite a luxurious position of having so many advanced, effective vaccines,” Dr. Wheatley said.

As the number of authorized vaccines grows, the possible combinations in which they can be used will explode. Recently, researchers at China’s National Institutes for Food and Drug Control scaled up their research on heterologous prime-boosts by trying out four different vaccines that have either been authorized in China or are in late-stage clinical trials there — vaccines based on adenoviruses, proteins, RNA and coronaviruses that have been inactivated with chemicals.

The researchers injected mice with a first dose of one vaccine, then a second dose of another. Some of the combinations caused the mice to produce stronger immune responses than mice that received the same vaccine for both doses.

Whether scientists carry out more experiments on other vaccines will depend on the willingness of the vaccine manufacturers. “You’re requiring quite large pharmaceutical companies to play nice together,” Dr. Wheatley said.

Dr. Bernard Moss, a virologist at the National Institute of Allergy and Infectious Diseases, suspects that a number of companies will be willing to let their vaccines be tested in combinations. “It’s always better to be a part of something that is going to be used,” he said, “than to wholly own something that isn’t.”

A Nursing Home’s Mission to Vaccinate Its Hesitant Staff

Almost all of the residents at Forest Hills of D.C. got their initial Covid-19 shots in January. But nearly half of the staff there had declined. Would an effort to change their minds succeed?

WASHINGTON — The Covid-19 vaccine had finally come to Forest Hills of D.C., a nursing home in a prosperous neighborhood of the nation’s capital, but there was a problem. Though nearly all of the home’s residents agreed to get the shots, nearly half its 200 staff members declined.

Tina Sandri, the chief executive, vowed not to let those numbers stand.

Over the next two months, rounding out the most bruising year of her long career in elder care, Ms. Sandri tried everything. She bombarded employees with text messages containing facts about the science behind the vaccines. She assigned a popular young worker to try to sway reluctant colleagues as an “influencer.” She set up a giant screen to show a television special that the Black actor and director Tyler Perry made to fight vaccine hesitancy — on a continuous loop, no less. Most of all, she worked to understand their concerns.

“You really have to listen to each person’s story and address it from that standpoint, so they feel, ‘This is a workplace that cares about me,’” she said.

Three months after the nation’s health care workers were among the first Americans to be eligible for the lifesaving new vaccines, long-term care facilities across the country continue to face a similar daunting challenge. The federal program that sent vaccinators from Walgreens and CVS into tens of thousands of nursing homes and assisted living residences has by one measure been strikingly successful, inoculating nearly all of the vulnerable residents of the facilities. Deaths in nursing homes have plummeted since the program began in late December.

But reaching the mostly low-wage employees of the facilities has proved far more difficult. A poll by The Washington Post and Kaiser Family Foundation conducted from Feb. 11 to March 7 found that half of the workers at nursing homes had yet to get even a first shot, and only 15 percent of that group said they definitely planned to.

At Forest Hills, the workers who turned down the vaccine during the center’s first vaccination event in early January included nurses, certified nursing assistants, members of the kitchen and activities staffs, and a security officer. Most were Black, reflecting the overall makeup of the home’s work force; many were immigrants from African countries, such as Nigeria, Liberia and Cameroon.

Ms. Sandri’s goal was to persuade — not pressure — them. But she found there was not one unifying story behind their refusal, and no straightforward message that helped to convince them.

She ruled out some tactics deployed by other nursing homes, including offering gift cards, bonuses or extra vacation days to employees who agreed to get the vaccine; Ms. Sandri considered those incentives inappropriate and called them “bribes.”

“We’re doing this because we care,” she said. “To dilute that message with other things is almost patronizing to people’s intellect.”

The vaccinators from Walgreens would come back twice more — in early February and early March — and Ms. Sandri had dozens of minds to change. By her count, there were still 92 employees who needed the shot.

Tina Sandri, right, chief executive of Forest Hills of D.C., receiving her vaccine shot. She wanted the first day of vaccinations to feel like a party, she said.
Tina Sandri, right, chief executive of Forest Hills of D.C., receiving her vaccine shot. She wanted the first day of vaccinations to feel like a party, she said.
Mariah Proctor, a security guard at Forest Hills, said her mother had said to her about the vaccine: “You don’t know the ingredients. You know nothing.”

January

Ms. Sandri, 57, a yoga and outdoors enthusiast whose manner is at once bustling and soothing, had arrived at Forest Hills only in May, replacing a predecessor who left after the coronavirus had taken hold.

Three residents at Forest Hills had died from the virus and 17 others had become ill, along with 45 members of the staff — a less devastating toll than at many other nursing homes, but still an ordeal. Another resident would die in February, after a flurry of cases over the holiday period.

For the first vaccination event, on Jan. 4, Ms. Sandri laid out snacks, took lots of pictures and played upbeat music — “the cookout kind!” — aiming to create a partylike atmosphere that could help people feel the hope and promise of getting immunized.

When Mariah Proctor, a security guard, arrived for her shift that day, she encountered the festive buzz — and the persistent question between colleagues: “Are you getting it?”

Her answer was no. A conversation with her mother, who she said had never taken her for vaccinations for fear of putting anything besides healthy food in her children’s bodies, had cemented her decision.

Ms. Proctor, 24, said her mother had told her: “You don’t even know what that is. You don’t know the ingredients. You know nothing.”

After the disappointing vaccination turnout that first day, and with morale dipping and emotions fragile as the pandemic wore on, Ms. Sandri changed her approach. She had been holding “huddles” with different departments to explain the science of the vaccines, but now, instead of continuing to load people with facts, she focused on asking them: What information do you need? What is your concern?

Miles Lee has been serving as an influencer of sorts at Forest Hills, talking to his co-workers about their feelings or offering to look up information for them about the vaccine.
Ms. Sandri reviewing the “Heroes of Hope” wall depicting staff members who have been vaccinated.

February

Ms. Proctor was taking a break from her shift with Deborah Childs, a colleague from the payroll department who had also refused the vaccine, when the vaccinators from Walgreens came back on a snowy day in early February.

This time, Ms. Childs agreed to get the vaccine.

“I looked up the company and, you know, I found out that they’ve been doing research on mRNA for over 10 years, so that made me feel a little bit better,” she said, referring to the molecule that is the active ingredient in the Moderna vaccine that Walgreens is offering.

She was still a little scared, especially after reading about a doctor in Miami who had developed a rare blood disorder days after getting the Pfizer shot and died two weeks later. Still, she said: “I’m ready to get back to my life. And I know that this is probably one of the ways that we’re going to get back to being normal.”

Ms. Proctor was wavering. “My emotions are everywhere,” she said. She had been watching co-workers who had received their shots and asking them how they felt. “I would say that I am educating myself a little more now, versus just saying, ‘I don’t want to do it,’” she said.

Yet, she ended up refusing the shot again that day.

She wasn’t afraid of needles — she had multiple tattoos, she said, laughing. So what was holding her back?

“Having a bad reaction, or not being able to adjust to it at all,” she said.

She had also heard some frightening things — even though she suspected they weren’t true. “I heard someone say the first couple of people who took it for the trial died,” she said. “I’m not going to believe those things, but you do keep them in the back of your head and it makes you scared.”

Still, Ms. Sandri’s efforts seemed to be paying off. Forty-eight more workers decided to get their first shot that day.

For those who remained unvaccinated, Ms. Sandri had four weeks to change their minds.

March

Janice Johnson, director of nursing and infection prevention at Forest Hills, checking on staff members on vaccination day.
Staff members waiting their turn for the shot.

Across the country, vaccine hesitancy was receding — a Pew poll conducted in late February found that 30 percent of Americans said they would probably or definitely not get vaccinated, down from the 39 percent who said the same in November. The poll also found that far more Black Americans were willing to get the vaccine than they were before, but Ms. Sandri did not find that to be true among the African immigrants on her staff.

For them, the half-hour Tyler Perry video that had been playing on repeat on a giant screen in the multipurpose room did not seemed to resonate.

Ms. Sandri, who is of Chinese descent, began to understand. “I’m Asian, but I’m not Japanese or Thai or Indian, and they are very different people,” she said. “Until we understand cultural sensitivities beyond the major skin color groups, we’re not going to be successful at reaching herd immunity levels with some of those subsets.”

She started planning to have her director of maintenance, an African immigrant who has been vaccinated, to talk to reluctant peers about his experience and their concerns, and to find leaders of local African churches who might be willing to do the same.

She also doubled down on what she believed was working best: listening to and addressing the concerns of her employees one by one — what she called a “time-intensive, conversation-intensive, case-by-case uphill climb.”

The key, she said, was to tailor her message to what would resonate most with each person.

“For analytical people, we provided data on number of cases, number of people in trials, percent of people who experience an immune response,” she said. “For relationship-based thinkers, we asked if they had any vulnerable friends or family members, and how having or not having the vaccine might impact the relationship.”

Still, as the date of the third vaccination event approached in early March, Ms. Proctor was tired — of the pandemic and the long loss of freedoms, but also of hearing every day at work about the importance of getting the shot. Ms. Sandri, whose office was just around the corner, stopped by frequently to chat and gently raise the benefits of being vaccinated.

“It feels a little — almost like peer pressure,” Ms. Proctor said.

At times, she envied people who worked outside health care, suspecting they were not being barraged with information about the vaccine in quite the same way. Yet, she had come to appreciate that the vaccine was a commodity that most people her age — and most people in general — did not have access to yet. Getting vaccinated, she told herself, could help protect her sister who lived with her. It would also protect her when she returned to her second job — bartending — and made long-delayed trips to Puerto Rico and Jamaica later in the year.

By March 8, the day of the final event at Forest Hills, she was close to talking herself into rolling up her sleeve. At Ms. Sandri’s urging, she had watched the Tyler Perry special and an online town-hall-style forum for workers at nursing homes about the vaccine, organized by the Black Coalition Against Covid-19.

“It gave me a little more confidence,” she said. “I don’t know anyone in my immediate circle that took the vaccine yet, and it just makes me feel like if no one else has done it, then maybe I should.”

Despite working to convince herself of the vaccine’s benefits over recent days, Ms. Procter grew concerned as she was about to get vaccinated. Ms. Sandri was there to reassure Ms. Proctor before her shot.
Ms. Childs, who was at first hesitant about getting the vaccine, received her second dose this month. “I’m ready to get back to my life,” she said. “And I know that this is probably one of the ways that we’re going to get back to being normal.”

The final tally

Fifteen minutes before her shift ended, Ms. Proctor made her way to the home’s all-purpose room — normally the sight of bingo games and movie nights — and took off her jacket. Scanning the consent form with its daunting questions — Have you ever had a severe allergic reaction to something? Do you have a bleeding disorder or weakened immune system? — made her feel “leery,” she said.

Still, she got the shot. As she lingered in an easy chair afterward, Ms. Sandri fluttered in to check on her, gently touching her bare arm.

“I don’t have any thoughts, really, besides wondering how I’m going to feel — that’s my main concern,” Ms. Proctor said. By the end of the day, 18 more co-workers, along with Ms. Proctor, had joined the ranks of the partly or fully vaccinated. They now make up 79 percent of the staff at Forest Hills.

“I’m ready to do cartwheels down the hallway,” Ms. Sandri said, noting that Forest Hills had surpassed the goal set by the American Health Care Association, a trade group, to vaccinate 75 percent of the nation’s nursing home work force by the end of June.

With the federal program ending soon, the city’s health department had agreed to provide doses for anyone in nursing homes who still needed them.

“Everyone’s fears are real, whether or not they are grounded in science or in something they believe right now,” Ms. Sandri said, recounting what she had learned from her staff over the past few months. “Beliefs change with time or new knowledge, so we have to ride it out. Listen hard, don’t judge and let them move at their own pace.”

Kenny Holston contributed reporting.

Getting to Yes: A Nursing Home’s Mission to Vaccinate Its Hesitant Staff

Almost all of the residents at Forest Hills of D.C. got their initial Covid-19 shots in January. But nearly half of the staff there had declined. Would an effort to change their minds succeed?

WASHINGTON — The Covid-19 vaccine had finally come to Forest Hills of D.C., a nursing home in a prosperous neighborhood of the nation’s capital, but there was a problem. Though nearly all of the home’s residents agreed to get the shots, nearly half its 200 staff members declined.

Tina Sandri, the chief executive, vowed not to let those numbers stand.

Over the next two months, rounding out the most bruising year of her long career in elder care, Ms. Sandri tried everything. She bombarded employees with text messages containing facts about the science behind the vaccines. She assigned a popular young worker to try to sway reluctant colleagues as an “influencer.” She set up a giant screen to show a television special that the Black actor and director Tyler Perry made to fight vaccine hesitancy — on a continuous loop, no less. Most of all, she worked to understand their concerns.

“You really have to listen to each person’s story and address it from that standpoint, so they feel, ‘This is a workplace that cares about me,’” she said.

Three months after the nation’s health care workers were among the first Americans to be eligible for the lifesaving new vaccines, long-term care facilities across the country continue to face a similar daunting challenge. The federal program that sent vaccinators from Walgreens and CVS into tens of thousands of nursing homes and assisted living residences has by one measure been strikingly successful, inoculating nearly all of the vulnerable residents of the facilities. Deaths in nursing homes have plummeted since the program began in late December.

But reaching the mostly low-wage employees of the facilities has proved far more difficult. A poll by The Washington Post and Kaiser Family Foundation conducted from Feb. 11 to March 7 found that half of the workers at nursing homes had yet to get even a first shot, and only 15 percent of that group said they definitely planned to.

At Forest Hills, the workers who turned down the vaccine during the center’s first vaccination event in early January included nurses, certified nursing assistants, members of the kitchen and activities staffs, and a security officer. Most were Black, reflecting the overall makeup of the home’s work force; many were immigrants from African countries, such as Nigeria, Liberia and Cameroon.

Ms. Sandri’s goal was to persuade — not pressure — them. But she found there was not one unifying story behind their refusal, and no straightforward message that helped to convince them.

She ruled out some tactics deployed by other nursing homes, including offering gift cards, bonuses or extra vacation days to employees who agreed to get the vaccine; Ms. Sandri considered those incentives inappropriate and called them “bribes.”

“We’re doing this because we care,” she said. “To dilute that message with other things is almost patronizing to people’s intellect.”

The vaccinators from Walgreens would come back twice more — in early February and early March — and Ms. Sandri had dozens of minds to change. By her count, there were still 92 employees who needed the shot.

Tina Sandri, right, chief executive of Forest Hills of D.C., receiving her vaccine shot. She wanted the first day of vaccinations to feel like a party, she said.
Tina Sandri, right, chief executive of Forest Hills of D.C., receiving her vaccine shot. She wanted the first day of vaccinations to feel like a party, she said.
Mariah Proctor, a security guard at Forest Hills, said her mother had said to her about the vaccine: “You don’t know the ingredients. You know nothing.”

January

Ms. Sandri, 57, a yoga and outdoors enthusiast whose manner is at once bustling and soothing, had arrived at Forest Hills only in May, replacing a predecessor who left after the coronavirus had taken hold.

Three residents at Forest Hills had died from the virus and 17 others had become ill, along with 45 members of the staff — a less devastating toll than at many other nursing homes, but still an ordeal. Another resident would die in February, after a flurry of cases over the holiday period.

For the first vaccination event, on Jan. 4, Ms. Sandri laid out snacks, took lots of pictures and played upbeat music — “the cookout kind!” — aiming to create a partylike atmosphere that could help people feel the hope and promise of getting immunized.

When Mariah Proctor, a security guard, arrived for her shift that day, she encountered the festive buzz — and the persistent question between colleagues: “Are you getting it?”

Her answer was no. A conversation with her mother, who she said had never taken her for vaccinations for fear of putting anything besides healthy food in her children’s bodies, had cemented her decision.

Ms. Proctor, 24, said her mother had told her: “You don’t even know what that is. You don’t know the ingredients. You know nothing.”

After the disappointing vaccination turnout that first day, and with morale dipping and emotions fragile as the pandemic wore on, Ms. Sandri changed her approach. She had been holding “huddles” with different departments to explain the science of the vaccines, but now, instead of continuing to load people with facts, she focused on asking them: What information do you need? What is your concern?

Miles Lee has been serving as an influencer of sorts at Forest Hills, talking to his co-workers about their feelings or offering to look up information for them about the vaccine.
Ms. Sandri reviewing the “Heroes of Hope” wall depicting staff members who have been vaccinated.

February

Ms. Proctor was taking a break from her shift with Deborah Childs, a colleague from the payroll department who had also refused the vaccine, when the vaccinators from Walgreens came back on a snowy day in early February.

This time, Ms. Childs agreed to get the vaccine.

“I looked up the company and, you know, I found out that they’ve been doing research on mRNA for over 10 years, so that made me feel a little bit better,” she said, referring to the molecule that is the active ingredient in the Moderna vaccine that Walgreens is offering.

She was still a little scared, especially after reading about a doctor in Miami who had developed a rare blood disorder days after getting the Pfizer shot and died two weeks later. Still, she said: “I’m ready to get back to my life. And I know that this is probably one of the ways that we’re going to get back to being normal.”

Ms. Proctor was wavering. “My emotions are everywhere,” she said. She had been watching co-workers who had received their shots and asking them how they felt. “I would say that I am educating myself a little more now, versus just saying, ‘I don’t want to do it,’” she said.

Yet, she ended up refusing the shot again that day.

She wasn’t afraid of needles — she had multiple tattoos, she said, laughing. So what was holding her back?

“Having a bad reaction, or not being able to adjust to it at all,” she said.

She had also heard some frightening things — even though she suspected they weren’t true. “I heard someone say the first couple of people who took it for the trial died,” she said. “I’m not going to believe those things, but you do keep them in the back of your head and it makes you scared.”

Still, Ms. Sandri’s efforts seemed to be paying off. Forty-eight more workers decided to get their first shot that day.

For those who remained unvaccinated, Ms. Sandri had four weeks to change their minds.

March

Janice Johnson, director of nursing and infection prevention at Forest Hills, checking on staff members on vaccination day.
Staff members waiting their turn for the shot.

Across the country, vaccine hesitancy was receding — a Pew poll conducted in late February found that 30 percent of Americans said they would probably or definitely not get vaccinated, down from the 39 percent who said the same in November. The poll also found that far more Black Americans were willing to get the vaccine than they were before, but Ms. Sandri did not find that to be true among the African immigrants on her staff.

For them, the half-hour Tyler Perry video that had been playing on repeat on a giant screen in the multipurpose room did not seemed to resonate.

Ms. Sandri, who is of Chinese descent, began to understand. “I’m Asian, but I’m not Japanese or Thai or Indian, and they are very different people,” she said. “Until we understand cultural sensitivities beyond the major skin color groups, we’re not going to be successful at reaching herd immunity levels with some of those subsets.”

She started planning to have her director of maintenance, an African immigrant whohas been vaccinated, to talk to reluctant peers about his experience and their concerns, and to find leaders of local African churches who might be willing to do the same.

She also doubled down on what she believed was working best: listening to and addressing the concerns of her employees one by one — what she called a “time-intensive, conversation-intensive, case-by-case uphill climb.”

The key, she said, was to tailor her message to what would resonate most with each person.

“For analytical people, we provided data on number of cases, number of people in trials, percent of people who experience an immune response,” she said. “For relationship-based thinkers, we asked if they had any vulnerable friends or family members, and how having or not having the vaccine might impact the relationship.”

Still, as the date of the third vaccination event approached in early March, Ms. Proctor was tired — of the pandemic and the long loss of freedoms, but also of hearing every day at work about the importance of getting the shot. Ms. Sandri, whose office was just around the corner, stopped by frequently to chat and gently raise the benefits of being vaccinated.

“It feels a little — almost like peer pressure,” Ms. Proctor said.

At times, she envied people who worked outside health care, suspecting they were not being barraged with information about the vaccine in quite the same way. Yet, she had come to appreciate that the vaccine was a commodity that most people her age — and most people in general — did not have access to yet. Getting vaccinated, she told herself, could help protect her sister who lived with her. It would also protect her when she returned to her second job — bartending — and made long-delayed trips to Puerto Rico and Jamaica later in the year.

By March 8, the day of the final event at Forest Hills, she was close to talking herself into rolling up her sleeve. At Ms. Sandri’s urging, she had watched the Tyler Perry special and an online town-hall-style forum for workers at nursing homes about the vaccine, organized by the Black Coalition Against Covid-19.

“It gave me a little more confidence,” she said. “I don’t know anyone in my immediate circle that took the vaccine yet, and it just makes me feel like if no one else has done it, then maybe I should.”

Despite working to convince herself of the vaccine’s benefits over recent days, Ms. Procter grew concerned as she was about to get vaccinated. Ms. Sandri was there to reassure Ms. Proctor before her shot.
Ms. Childs, who was at first hesitant about getting the vaccine, received her second dose this month. “I’m ready to get back to my life,” she said. “And I know that this is probably one of the ways that we’re going to get back to being normal.”

The final tally

Fifteen minutes before her shift ended, Ms. Proctor made her way to the home’s all-purpose room — normally the sight of bingo games and movie nights — and took off her jacket. Scanning the consent form with its daunting questions — Have you ever had a severe allergic reaction to something? Do you have a bleeding disorder or weakened immune system? — made her feel “leery,” she said.

Still, she got the shot. As she lingered in an easy chair afterward, Ms. Sandri fluttered in to check on her, gently touching her bare arm.

“I don’t have any thoughts, really, besides wondering how I’m going to feel — that’s my main concern,” Ms. Proctor said. By the end of the day, 18 more co-workers, along with Ms. Proctor, had joined the ranks of the partly or fully vaccinated. They now make up 79 percent of the staff at Forest Hills.

“I’m ready to do cartwheels down the hallway,” Ms. Sandri said, noting that Forest Hills had surpassed the goal set by the American Health Care Association, a trade group, to vaccinate 75 percent of the nation’s nursing home work force by the end of June.

With the federal program ending soon, the city’s health department had agreed to provide doses for anyone in nursing homes who still needed them.

“Everyone’s fears are real, whether or not they are grounded in science or in something they believe right now,” Ms. Sandri said, recounting what she had learned from her staff over the past few months. “Beliefs change with time or new knowledge, so we have to ride it out. Listen hard, don’t judge and let them move at their own pace.”

Kenny Holston contributed reporting.

Pfizer Begins Testing Its Vaccine in Young Children

Other drug makers have begun similar trials of their Covid-19 vaccines. If they work in children younger than 12 as expected, it will be easier for the U.S. to reach herd immunity.

Pfizer has begun testing its Covid-19 vaccine in children under 12, a significant step in turning back the pandemic. The trial’s first participants, a pair of 9-year-old twin girls, were immunized at Duke University in North Carolina on Wednesday.

Results from the trial are expected in the second half of the year, and the company hopes to vaccinate younger children early next year, said Sharon Castillo, a spokeswoman for the pharmaceutical company.

Moderna also is beginning a trial of its vaccine in children six months to 12 years of age. Both companies have been testing their vaccines in children 12 and older, and expect those results in the next few weeks.

AstraZeneca last month began testing its vaccine in children six months and older, and Johnson & Johnson has said it plans to extend trials of its vaccine to young children after assessing its performance in older children.

Immunizing children will help schools to reopen as well as help to end the pandemic, said Dr. Emily Erbelding, an infectious diseases physician at the National Institutes of Health who oversees testing of Covid-19 vaccines in special populations.

An estimated 80 percent of the population may need to be vaccinated for the United States to reach herd immunity, the threshold at which the coronavirus runs out of people to infect. Some adults may refuse to be vaccinated, and others may not produce a robust immune response.

Children under 18 account for about 23 percent of the population in the United States, so even if a vast majority of adults opt for vaccines, “herd immunity might be hard to achieve without children being vaccinated,” Dr. Erbelding said.

Pfizer had initially said it would wait for data from older children before starting trials of its vaccine in children under 12. But “we were encouraged by the data from the 12 to 15 group,” said Ms. Castillo, who did not elaborate on the results so far.

Scientists will test three doses of the Pfizer vaccine — 10, 20 and 30 micrograms — in 144 children. Each dose will be assessed first in children 5 through 11 years of age, then in children ages 2 through 4 years, and finally in the youngest group, six months to 2 years.

After determining the most effective dose, the company will test the vaccine in 4,500 children. About two-thirds of the participants will be randomly selected to receive two doses 21 days apart; the remaining will get two placebo shots of saline. The researchers will assess the children’s immune response in blood drawn seven days after the second dose.

“It sounds like a good plan, and it’s exciting that another Covid-19 vaccine is moving forward with trials in children,” said Dr. Kristin Oliver, a pediatrician and vaccine expert at Mount Sinai Hospital in New York.

Dr. Oliver said about half of the parents she sees in practice are eagerly waiting for vaccines, and even to volunteer their children for clinical trials, while the rest are skeptical because comparatively few children become seriously ill from coronavirus infection.

Both groups of parents will benefit from knowing exactly how safe and effective the vaccines are in children, she said.

Children represent 13 percent of all reported cases in the United States. More than 3.3 million children have tested positive for the virus, at least 13,000 have been hospitalized and at least 260 have died, noted Dr. Yvonne Maldonado, who represents the American Academy of Pediatrics on the federal Advisory Committee on Immunization Practices.

The figures do not fully capture the damage to children’s health. “We don’t know what the long-term effects of Covid infection are going to be,” Dr. Maldonado said.

Other vaccines have helped to control many horrific childhood diseases that can cause long-term complications, she added: “For some of us who’ve seen that, we don’t want to go back to those days.”

Children often react more strongly to vaccines than adults do, and infants and toddlers in particular can experience high fevers. Any side effects are likely to appear soon after the shot, within the first week and certainly within the first few weeks, experts have said.

Some vaccines are tested only in animals before being assessed in children, and have to be monitored carefully for side effects.

“But this is a little different, because we’ve already had experience with tens of millions of people with these vaccines,” Dr. Maldonado said. “So there’s a higher degree of confidence now in giving this vaccine to kids.”

Some experts suggested that the Food and Drug Administration may require up to six months of safety data from studies of children before authorizing the Covid-19 vaccines. But a spokeswoman said the agency did not expect six months of safety data to support the vaccines’ authorization.

The Pfizer-BioNTech vaccine is authorized for children 16 through 18 years old, and the authorization for that age group was based on just two months of safety data, she said.

Parents will want to know how the companies and the F.D.A. plan to monitor and disclose side effects from the vaccines, and how long they will continue to follow trial participants after the vaccines’ authorization, Dr. Oliver said.

“I think everyone has learned throughout this,” she said. “The more transparent you can be, the better.”

Why It Pays to Think Outside the Box on Coronavirus Tests

Universities and other institutions looking to protect themselves from Covid-19 may benefit from sharing their testing resources with the wider community, a new study suggests.

Last year, when the National Football League decided to stage its season in the midst of the coronavirus pandemic, it went all-in on testing. The league tested all players and personnel before they reported for summer training camp, and continued near-daily testing in the months that followed. Between Aug. 1 and the Super Bowl in early February, the N.F.L. administered almost one million tests to players and staff.

Many other organizations have sought safety in mass testing. The University of Illinois is testing its students, faculty and staff twice a week and has conducted more than 1.6 million tests since July. Major corporations, from Amazon to Tyson Foods, have rolled out extensive testing programs for their own employees.

Now, a new analysis suggests that schools, businesses and other organizations that want to keep themselves safe should think beyond strictly themselves. By dedicating a substantial proportion of their tests to people in the surrounding community, institutions could reduce the number of Covid-19 cases among their members by as much as 25 percent, researchers report in a new paper, which has not yet been published in a scientific journal.

“It’s natural in an outbreak for people to become self-serving, self-focused,” said Dr. Pardis Sabeti, a computational biologist at Harvard University and the Broad Institute who lead the analysis. But, she added, “If you’ve been in enough outbreaks you just understand that testing in a box doesn’t makes sense. These things are communicable, and they’re coming in from the community.”

The study has “really profound implications, especially if others can replicate it,” said David O’Connor, a virologist at the University of Wisconsin, Madison, who was not involved in the analysis but reviewed a draft of the paper. As the pandemic enters its second year, he said, “We want to start using more sophisticated modeling and probably economic theory to inform what an optimal testing program would look like.”

Dr. Sabeti is an epidemic veteran, part of teams that responded to an Ebola outbreak in West Africa in 2014 and a mumps outbreak in the Boston area a few years later. When the coronavirus closed down the country last spring, many colleges and universities sought her advice on how to safely reopen.

At a time when testing resources were in short supply, many of these institutions were proposing intensive, expensive testing regimens focused entirely on their own members. Again and again, Dr. Sabeti suggested that universities think more broadly, and allocate some of their tests to people who might be friends, family members or neighbors of their students and employees.

“The metaphor I often used on the calls was to say, ‘You’re in a drought in a place with a lot of forest fires, and you have a shortage of fire alarms,’” she recalled. “‘And if you run out and buy every fire alarm and install it in your own house, you’ll be able to pick up a fire the moment it hits your house, but at that point it’s burning to the ground.’”

Still, convincing university officials to divert precious testing resources away from their own institutions was a hard sell, Dr. Sabeti said, especially without data on the effectiveness of the approach. So she and her colleagues decided to gather some.

“Fundamentally, the paper is about the intersection of kindness and success — how being generous with one’s resources actually is the most effective” strategy, said one of the study’s authors.
“Fundamentally, the paper is about the intersection of kindness and success — how being generous with one’s resources actually is the most effective” strategy, said one of the study’s authors.Pete Kiehart for The New York Times

They developed an epidemiological model to simulate how a virus might spread through a midsize university, like Colorado Mesa University, one of the schools Dr. Sabeti’s team has been advising. (Several C.M.U. officials and researchers are co-authors of the paper.)

Using real-world data from C.M.U., the researchers created a baseline scenario in which 1 percent of people at the school, and 6 percent of those in the surrounding county, were infected by the coronavirus, and the university was testing 12 percent of its members every day. The team assumed that they had a complete list of each university member’s close off-campus contacts, and that if someone tested positive for the virus, they and their contacts would quarantine until they were no longer infectious.

Under these conditions, the researchers found, if the university used all of its tests on its own members, it would have roughly 200 Covid-19 cases after 40 days. But if instead it parceled out some of those tests, using them on community members who were close contacts of students and staff, the number of cases dropped by one-quarter.

“The optimal proportion of tests to use outside the institution on those targeted, first-degree contacts came out to be about 45 percent,” said Ivan Specht, an undergraduate researcher in Dr. Sabeti’s lab and a co-author of the paper. In short, institutions could reduce their caseloads by one-fourth if they used almost half their tests on people just outside their direct membership. That percentage “is remarkably high considering that most institutions use zero percent of their tests outside of themselves,” Mr. Specht noted.

The researchers then tweaked the model’s parameters in various ways: What if the virus were more prevalent? What if students and staff did not report all their contacts? What if they were better about mask-wearing and social distancing? What if the university deployed more tests, or fewer?

Unsurprisingly, the more testing the university did, and the more information it had about its members’ close contacts, the fewer Covid-19 cases there were. But in virtually every scenario, sharing at least some tests with the broader community led to fewer cases than hoarding them.

“The surprising thing is just how robust that finding is in the face of some pretty plausible variations,” said A. David Paltiel, a professor of health policy and management at Yale School of Public Health, who was not involved in the study.

Still, he noted, there were plenty of scenarios that the model didn’t test, and the paper still needs to undergo a thorough peer review.

Its predictions should also be tested in the real world, Dr. O’Connor said: “It needs to be explored and tested head-to-head with other allocation methods.”

But if the findings hold up, it would suggest that schools and other institutions that are trying to reopen safely should think beyond their own walls when they develop testing programs. “Even if your goal is only to protect the students in your care, you will still be doing the maximum to protect those students by taking care of the people in the surrounding community,” Dr. Paltiel said. “That’s a pretty strong argument.”

Some universities are beginning to adopt this outlook. C.M.U. now offers free tests to all of its students’ self-reported contacts, whether or not they are affiliated with the university, and runs a testing site that is open to local residents, said Amy Bronson, a co-chair of the university’s Covid-19 task force and an author of the paper.

And in November, the University of California, Davis, began offering free coronavirus tests to anyone who lives or works in the city. The Healthy Davis Together program, a partnership with the city, has since administered more than 450,000 tests and identified more than 1,000 people with the virus, said Brad Pollock, an epidemiologist at U.C. Davis who directs the project.

“A virus does not respect geographic boundaries,” Dr. Pollock said. “It is ludicrous to think that you can get control of an acute infectious respiratory disease like Covid-19, in a city like Davis that hosts a very large university, without coordinated public health measures that connect both the university and the community.”

There are barriers to the more altruistic approach, including internal political pressure to use testing resources in house and concerns about legal liability. But the researchers hope that their model convinces at least some institutions to rethink their strategy, not only during this epidemic but also in future ones.

“An outbreak is an opportunity to buy a lot of community good will, or to burn a lot of community good will,” Dr. Sabeti said. “We could have spent an entire year building up that relationship between organizations and institutions and their communities. And we would have done all that hard work together, as opposed to everybody turning inward.”

Why It Pays to Think Outside the Box on Coronavirus Tests

Universities and other institutions looking to protect themselves from Covid-19 may benefit from sharing their testing resources with the wider community, a new study suggests.

Last year, when the National Football League decided to stage its season in the midst of the coronavirus pandemic, it went all-in on testing. The league tested all players and personnel before they reported for summer training camp, and continued near-daily testing in the months that followed. Between Aug. 1 and the Super Bowl in early February, the N.F.L. administered almost one million tests to players and staff.

Many other organizations have sought safety in mass testing. The University of Illinois is testing its students, faculty and staff twice a week and has conducted more than 1.6 million tests since July. Major corporations, from Amazon to Tyson Foods, have rolled out extensive testing programs for their own employees.

Now, a new analysis suggests that schools, businesses and other organizations that want to keep themselves safe should think beyond strictly themselves. By dedicating a substantial proportion of their tests to people in the surrounding community, institutions could reduce the number of Covid-19 cases among their members by as much as 25 percent, researchers report in a new paper, which has not yet been published in a scientific journal.

“It’s natural in an outbreak for people to become self-serving, self-focused,” said Dr. Pardis Sabeti, a computational biologist at Harvard University and the Broad Institute who lead the analysis. But, she added, “If you’ve been in enough outbreaks you just understand that testing in a box doesn’t makes sense. These things are communicable, and they’re coming in from the community.”

The study has “really profound implications, especially if others can replicate it,” said David O’Connor, a virologist at the University of Wisconsin, Madison, who was not involved in the analysis but reviewed a draft of the paper. As the pandemic enters its second year, he said, “We want to start using more sophisticated modeling and probably economic theory to inform what an optimal testing program would look like.”

Dr. Sabeti is an epidemic veteran, part of teams that responded to an Ebola outbreak in West Africa in 2014 and a mumps outbreak in the Boston area a few years later. When the coronavirus closed down the country last spring, many colleges and universities sought her advice on how to safely reopen.

At a time when testing resources were in short supply, many of these institutions were proposing intensive, expensive testing regimens focused entirely on their own members. Again and again, Dr. Sabeti suggested that universities think more broadly, and allocate some of their tests to people who might be friends, family members or neighbors of their students and employees.

“The metaphor I often used on the calls was to say, ‘You’re in a drought in a place with a lot of forest fires, and you have a shortage of fire alarms,’” she recalled. “‘And if you run out and buy every fire alarm and install it in your own house, you’ll be able to pick up a fire the moment it hits your house, but at that point it’s burning to the ground.’”

Still, convincing university officials to divert precious testing resources away from their own institutions was a hard sell, Dr. Sabeti said, especially without data on the effectiveness of the approach. So she and her colleagues decided to gather some.

“Fundamentally, the paper is about the intersection of kindness and success — how being generous with one’s resources actually is the most effective” strategy, said Kian Sani, one of the study’s authors.
“Fundamentally, the paper is about the intersection of kindness and success — how being generous with one’s resources actually is the most effective” strategy, said Kian Sani, one of the study’s authors.Pete Kiehart for The New York Times

They developed an epidemiological model to simulate how a virus might spread through a midsize university, like Colorado Mesa University, one of the schools Dr. Sabeti’s team has been advising. (Several C.M.U. officials and researchers are co-authors of the paper.)

Using real-world data from C.M.U., the researchers created a baseline scenario in which 1 percent of people at the school, and 6 percent of those in the surrounding county, were infected by the coronavirus, and the university was testing 12 percent of its members every day. The team assumed that they had a complete list of each university member’s close off-campus contacts, and that if someone tested positive for the virus, they and their contacts would quarantine until they were no longer infectious.

Under these conditions, the researchers found, if the university used all of its tests on its own members, it would have roughly 200 Covid-19 cases after 40 days. But if instead it parceled out some of those tests, using them on community members who were close contacts of students and staff, the number of cases dropped by one-quarter.

“The optimal proportion of tests to use outside the institution on those targeted, first-degree contacts came out to be about 45 percent,” said Ivan Specht, an undergraduate researcher in Dr. Sabeti’s lab and a co-author of the paper. In short, institutions could reduce their caseloads by one-fourth if they used almost half their tests on people just outside their direct membership. That percentage “is remarkably high considering that most institutions use zero percent of their tests outside of themselves,” Mr. Specht noted.

The researchers then tweaked the model’s parameters in various ways: What if the virus were more prevalent? What if students and staff did not report all their contacts? What if they were better about mask-wearing and social distancing? What if the university deployed more tests, or fewer?

Unsurprisingly, the more testing the university did, and the more information it had about its members’ close contacts, the fewer Covid-19 cases there were. But in virtually every scenario, sharing at least some tests with the broader community led to fewer cases than hoarding them.

“The surprising thing is just how robust that finding is in the face of some pretty plausible variations,” said A. David Paltiel, a professor of health policy and management at Yale School of Public Health, who was not involved in the study.

Still, he noted, there were plenty of scenarios that the model didn’t test, and the paper still needs to undergo a thorough peer review.

Its predictions should also be tested in the real world, Dr. O’Connor said: “It needs to be explored and tested head-to-head with other allocation methods.”

But if the findings hold up, it would suggest that schools and other institutions that are trying to reopen safely should think beyond their own walls when they develop testing programs. “Even if your goal is only to protect the students in your care, you will still be doing the maximum to protect those students by taking care of the people in the surrounding community,” Dr. Paltiel said. “That’s a pretty strong argument.”

Some universities are beginning to adopt this outlook. C.M.U. now offers free tests to all of its students’ self-reported contacts, whether or not they are affiliated with the university, and runs a testing site that is open to local residents, said Amy Bronson, a co-chair of the university’s Covid-19 task force and an author of the paper.

And in November, the University of California, Davis, began offering free coronavirus tests to anyone who lives or works in the city. The Healthy Davis Together program, a partnership with the city, has since administered more than 450,000 tests and identified more than 1,000 people with the virus, said Brad Pollock, an epidemiologist at U.C. Davis who directs the project.

“A virus does not respect geographic boundaries,” Dr. Pollock said. “It is ludicrous to think that you can get control of an acute infectious respiratory disease like Covid-19, in a city like Davis that hosts a very large university, without coordinated public health measures that connect both the university and the community.”

There are barriers to the more altruistic approach, including internal political pressure to use testing resources in house and concerns about legal liability. But the researchers hope that their model convinces at least some institutions to rethink their strategy, not only during this epidemic but also in future ones.

“An outbreak is an opportunity to buy a lot of community good will, or to burn a lot of community good will,” Dr. Sabeti said. “We could have spent an entire year building up that relationship between organizations and institutions and their communities. And we would have done all that hard work together, as opposed to everybody turning inward.”

First Covid, Then Psychosis: ‘The Most Terrifying Thing I’ve Ever Experienced’

Ivan Agerton pulled his wife, Emily, into their bedroom closet, telling her not to bring her cellphone.

“I believe people are following me,” he said, his eyes flaring with fear.

He described the paranoid delusions haunting him: that people in cars driving into their suburban Seattle cul-de-sac were spying on him, that a SWAT officer was crouching in a bush in their yard.

It was a drastic change for the 49-year-old Mr. Agerton, a usually unflappable former marine and risk-taking documentary photographer whose most recent adventure involved exploring the Red Sea for two months in a submarine. He was accustomed to stress and said that neither he nor his family had previously experienced mental health issues.

But in mid-December, after a mild case of Covid-19, he was seized by a kind of psychosis that turned life into a nightmare. He couldn’t sleep, worried he had somehow done something wrong, suspected ordinary people of sinister motives and eventually was hospitalized in a psychiatric ward twice.

“Like a light switch — it happened this fast — this intense paranoia hit me,” Mr. Agerton said in interviews over two months. “It was really single-handedly the most terrifying thing I’ve ever experienced in my life.”

Mr. Agerton’s experience reflects a phenomenon doctors are increasingly reporting: psychotic symptoms emerging weeks after coronavirus infection in some people with no previous mental illness.

Doctors say such symptoms may be one manifestation of brain-related aftereffects of Covid-19. Along with more common issues like brain fog, memory loss and neurological problems, “new onset” psychosis may result from an immune response, vascular issues or inflammation from the disease process, experts hypothesize. Sporadic cases have occurred with other viruses, and while such extreme symptoms are likely to affect only a small proportion of Covid survivors, cases have emerged worldwide.

Much about the condition remains mysterious. Some patients feel urges to harm others or themselves. Others, like Mr. Agerton, have no violent impulses but become almost obsessively paranoid. Some need weeks of hospitalization with doctors trying different medications, while others improve faster. Some patients relapse.

Mr. Agerton spent about a week in a psychiatric ward in December, missing Christmas with his wife and three children. By mid-January, he seemed to have recovered and his doctor planned to taper his antipsychotic medication. In February, however, “the paranoia came screaming back,” Mr. Agerton said in an interview a day before being hospitalized a second time.

“I have all these questions,” said Dr. Veronika Zantop, a psychiatrist who has treated Mr. Agerton since his first hospitalization and who confirmed that he had no previous mental health issues. Among them: “Is this temporary? You know, how long does the risk continue?”

Paranoid delusions more commonly accompany schizophrenia in late adolescence or dementia in older adults, but so far, post-Covid psychosis has mostly afflicted patients in their 30s, 40s and 50s.

One of Mr. Agerton’s tattoos, the state of Nevada, where he grew up. A former Marine who works as a documentary photographer, Mr. Agerton said neither he nor his family had any history of mental illness.
One of Mr. Agerton’s tattoos, the state of Nevada, where he grew up. A former Marine who works as a documentary photographer, Mr. Agerton said neither he nor his family had any history of mental illness.Jovelle Tamayo for The New York Times

Another notable difference: Some post-Covid patients have realized something was wrong, while typical psychosis patients often “don’t have insight into their symptoms,” Dr. Zantop said.

With Mr. Agerton, she said, “It’s almost like he had a split self where he was able to say, ‘My brain is telling me that the police are after me.’ And then he was also able to say, ‘I know that’s not true on some level, but it feels like reality to me.’”

After a December New York Times article about post-Covid psychosis, several people reached out to say they, or someone they knew, had experienced it. Mr. Agerton said he wanted to share his experience to help others by raising awareness of the condition.

Mr. Agerton tested positive for the coronavirus in late November after returning from the Red Sea. Because the expedition team followed strict precautions, he assumes he became infected while flying home. With a low fever, mild respiratory symptoms and a loss of smell, he isolated in a bedroom at home on Bainbridge Island near Seattle for 10 days, protecting Ms. Agerton, 46, and their children, ages 5, 11 and 16.

Then, on Dec. 17, an ordinary spam call on his cellphone triggered a cascade of paranoia linked to technology, surveillance and government agents.

“I started having these auditory hallucinations,” he said. He would jump to the window at night, imagining voices outside. Fearing that families looking at their neighborhood’s Christmas lights were conducting espionage, he would grab the family’s Australian shepherd, Duke, and walk outside “to get eyeballs on the people in the car,” he said. Then, he would become convinced that police scanners were broadcasting his dog walking and every other move he made.

“I couldn’t control myself,” he said, adding “I was just thinking ‘I’m losing my mind.’”

After two mostly sleepless days of keeping it to himself, he confided in his wife, who was stunned. “To have your person that is great in a crisis experiencing a crisis was for me just total helplessness and fear,” she said.

He asked her to place the family’s phones in airplane mode and worried their house was bugged. He became “out-of-his-skin anxious” about an ambulance siren, said Ms. Agerton, who drove him around looking for it. “Probably every 30 minutes, he needed to make the rounds outside and see what was out there.”

She took him shopping, thinking “something as mindless as Costco would kind of help it be just a normal day,” but said he feared shoppers were plainclothes agents. “It was really torture for him.”

That evening, she called a friend, a nurse with mental health experience.

“You need to get to the emergency department right now,” the friend urged, adding, “lock up any guns,’” Ms. Agerton said.

Although Mr. Agerton had no suicidal or homicidal thoughts, his wife added an extra locking mechanism to a safe containing a pistol. “That he could harm himself or me or the kids hadn’t even occurred to me, but that’s an entirely different element of fear and protection that starts to surge through you,” she said.

Emergency room doctors ruled out a brain tumor and sent him home with sleeping pills. But after he slept, “the delusions picked right back up where he said good night to them the night before,” his wife said. “It was progressively worse. It was something new every 10 minutes.”

Ms. Agerton, a health care administrator and part-time graduate student studying organizational leadership, desperately sought psychiatric help for him. Finally, her nurse friend found space at the Swedish Medical Center in Seattle.

On the ferry to Seattle, Mr. Agerton imagined a FedEx truck driver was hacking their cellphones. At the hospital, a wrong-number call to the phone in his room rattled him. “It was this snowball effect,” he recalled.

“When he came to us, he was very psychotic,” said Dr. Zantop, who focuses on intersections between medical, neurological and psychiatric issues at the Swedish center. “He was having a really hard time functioning with these constant thoughts that he’s about to get picked up by the police or thrown into jail.”

He asked his wife to inform two photographer friends, explaining his absence from their text group.

“Ivan is a very self-aware, in-control-with-chaos guy,” said one, Vincent Laforet, who contacted anyone who might help, including the firm leading the Red Sea expedition, OceanX. “When that type of person reaches out to you through his wife, it’s almost like sending out an S.O.S. broadcast of ‘I’m losing control.’”

Vincent Pieribone, OceanX’s vice chairman and a Yale neuroscience professor, spoke with Mr. Agerton’s doctors. He said it was crucial that Mr. Agerton recognized he was in trouble and was not ashamed to seek help.

An M.R.I. and other tests found no identifiable problems, said Dr. Zantop, who dove into researching Covid-linked cases.

At first, Mr. Agerton wept and stared outside at a parking structure “where I thought guys were watching me,” he said. His photographer’s eye was discomfited by hospital lighting he said was “out of a bad movie.”

On Christmas, he spoke to his family by phone. “It was really sad,” his wife said.

He worried how their children would process his situation. He hoped doctors wouldn’t blame stress or danger from his job, which he loves.

“Part of me was thinking, ‘This is who I am and my career is over, my life is over,’” he said, his voice breaking.

Dr. Zantop said an antipsychotic medication, as well as information and assurances, including that security guards weren’t after him, helped him “kind of calm down.”

He also immersed himself in books about Napoleon and the Lost Boys of Sudan, although, he said, “I’d have to reread paragraphs two, three, four times.”

Recently, Mr. Agerton said he felt better, with most of the paranoia gone and his sense of smell is beginning to return. He hopes that signals lasting improvement. Jovelle Tamayo for The New York Times

Shortly before New Year’s Day, he returned home. Five days later, he estimated he was 85 percent recovered, except for “little twinges” like thinking a neighbor’s air vent was a submarine periscope.

Dr. Zantop found that Mr. Agerton was doing well. In mid-January, after his 50th birthday, he said he felt “100 percent.” But a month later, a headline about a police raid reignited the symptoms. He felt less anxiety than before, he said, but “my paranoia was overwhelming my rational mind,” making it “harder this time.”

He worried, “they were coming after me and I would lose my family,” he said. “It’s not real, but it feels so real, and it’s frightening and it’s lonely.”

Dr. Zantop said Mr. Agerton interrupted a telemedicine session that week to run outside and check an unfamiliar car’s license plate, and he expressed suspicion of helicopters flying over the house and a man with a backpack walking by.

“I was surprised that it came back, honestly,” she said.

She increased his antipsychotic, and added an anti-anxiety medication and two antioxidant supplements, but outpatient treatment wasn’t helping enough, she said.

Ms. Agerton said her husband’s paranoia seemed exacerbated by his being in their house, which they’d begun renting shortly before his first psychotic episode, so he associated it with that trauma. During his second hospitalization, he told her he felt safe. They plan to move when their lease ends.

In the hospital, Dr. Zantop prescribed different antipsychotic and anti-anxiety medications. Six days later he had improved enough to return home.

Recently, Mr. Agerton said he felt considerably better, with 90 percent of the paranoia gone. His sense of smell is beginning to return. He hopes that signals lasting improvement.

It’s unclear how long he will need medication and when he will be able to resume his adventurous work.

“There’s this fear of how long is this going to happen,” he said. “How long am I going to live with this?”

How Much Weight Did We Gain During Lockdowns? 2 Pounds a Month, Study Hints

Many Americans know they’ve put on weight during the pandemic, but it’s been difficult for experts to detail the scope of the problem.

Soon after the pandemic started over a year ago, Americans started joking about the dreaded “quarantine 15,” worried they might gain weight while shut in homes with stockpiles of food, glued to computer screens and binge-watching Netflix.

The concern is real, but assessing the problem’s scope has been a challenge. Surveys that simply ask people about their weight are notoriously unreliable, and many medical visits have been virtual.

Now a very small study using objective measures — weight measurements from Bluetooth-connected smart scales — suggests that adults under shelter-in-place orders gained more than half a pound every 10 days.

That translates to nearly two pounds a month, said Dr. Gregory M. Marcus, senior author of the research letter, published on Monday in the peer-reviewed JAMA Network Open. Americans who kept up their lockdown habits could easily have gained 20 pounds over the course of a year, he added.

“We know that weight gain is a public health problem in the U.S. already, so anything making it worse is definitely concerning, and shelter-in-place orders are so ubiquitous that the sheer number of people affected by this makes it extremely relevant,” said Dr. Marcus, a cardiologist and professor of medicine at University of California, San Francisco.

While it is almost impossible to make generalizations based on the study — which included fewer than 300 people scattered across the United States — all participants were tracking their weight regularly.

Many of these people were losing weight before shelter-in-place orders were issued in their states, Dr. Marcus noted. “It’s reasonable to assume these individuals are more engaged with their health in general, and more disciplined and on top of things,” he said. “That suggests we could be underestimating — that this is the tip of the iceberg.”

Excess weight has been linked to a greater risk of developing more severe Covid-19 disease, and the United States already has among the highest rates of overweight and obesity in the world. Some 42 percent of American adults over age 20 have obesity, as defined by body mass index, while another 32 percent of Americans are simply overweight.

The risk of severe illness has been documented among young adults who are overweight or obese, as well. Many states are prioritizing people who are overweight or obese for vaccination, along with those who have other chronic conditions like diabetes or hypertension.

The new study analyzed data obtained from 269 participants who were involved in an ongoing cardiology study, the Health eHeart Study. They volunteered to report weight measurements from Bluetooth-connected smart scales and weighed themselves regularly; the researchers gathered 7,444 weight measurements over a four-month period, an average of 28 weight measurements from each participant.

The group was not nationally representative, by any means, so the results are not generalizable: About three-quarters were white, and just 3.5 percent identified as Black or African-American; about 3 percent identified as Asian-American. The average age was 51, and they were split almost evenly among men and women.

The participants were from 37 states and the District of Columbia. The researchers analyzed weight measurements taken between Feb. 1, 2020, and June 1, 2020, in order to look at weight changes both before and after shelter-in-place orders were issued for each state.

While the participants mostly had been losing pounds before the orders were issued, their weights rose steadily at a rate of about six-tenths of a pound every 10 days after the orders were issued, regardless of where they were in the country and regardless of chronic medical conditions.

The lockdowns have certainly had an effect on dietary patterns, on what people eat and how often they eat. But the restrictions also curtailed the humdrum physical activity that is part and parcel of daily living, the researchers said.

“If you think about people commuting, even running to the subway or bus stop, or stepping in at the post office to mail a letter, or stopping at the store — we burn a lot of calories in non-exercise activities of daily living,” said Leanne Redman, a professor of clinical physiology at the Pennington Biomedical Research Center, part of Louisiana State University.

Her research had found that people were eating a healthier diet during the initial days of the shutdown but were more sedentary.

An earlier study by U.C.S.F. researchers looked at daily step counts, as tracked by smartphones, among nearly half a million people in nearly 200 countries. The number of steps people took declined by 27 percent a month after the World Health Organization declared the pandemic.

The concern about exercise also extends to children, who are known to pack on unhealthy pounds during the summer recess months when they are not in school. The risk is even greater for Hispanic and Black children than for white children, said Andrew G. Rundle, an associate professor of epidemiology at Columbia University’s Mailman School of Public Health, author of a recent paper that expressed concern that school closings would exacerbate existing racial health disparities.

“We argued that being out of school, which we thought would go on for six months and has gone on longer, was going to be like the summer recess but even worse, because everyone would be loading up on shelf-stable calorie-laden food, and staying indoors and not going out,” he said. “Everything that makes the summer dangerous for kids would be magnified by the lockdown.”

Coronavirus Reinfections Are Rare, Danish Researchers Report

People over 65 are more likely to experience a second bout with the virus, according to a large study of medical records.

The vast majority of people who recover from Covid-19 remain shielded from the virus for at least six months, researchers reported on Wednesday in a large study from Denmark.

Prior infection with the coronavirus reduced the chances of a second bout by about 80 percent in people under 65, but only by about half in those older than 65. But those results, published in the journal Lancet, were tempered by many caveats.

The number of infected older people in the study was small. The researchers did not have any information beyond the test results, so it’s possible that only people who were mildly ill the first time became infected again and that the second infections were largely symptom-free.

Scientists have said that reinfections are likely to be asymptomatic or mild because the immune system will suppress the virus before it can do much damage. The researchers also did not assess the possibility of reinfection with newer variants of the virus.

Still, the study suggests that immunity to a natural infection is unpredictable and uneven, and it underscores the importance of vaccinating everyone — especially older people, experts said.

“You can certainly not rely on a past infection as protecting you from being ill again, and possibly quite ill if you are in the elderly segment,” said Steen Ethelberg, an epidemiologist at Statens Serum Institut, Denmark’s public health agency.

Because people over 65 are at highest risk of severe disease and death, he said, “they are the ones we are most eager to protect.”

Rigorous estimates of second infections have generally been rare because many people worldwide did not initially have access to testing, and laboratories require genetic sequences from both rounds of testing to confirm a reinfection.

But the findings are consistent with those from experiments in a wide variety of settings: sailors on a fishing trawler in Seattle, Marine Corps recruits in South Carolina, health care workers in Britain and patients at clinics in the United States.

The new study’s design and size benefited from Denmark’s free and abundant testing for the coronavirus. Nearly 70 percent of the country’s population was tested for the virus in 2020.

The researchers looked at the results from 11,068 people who tested positive for the coronavirus during the first wave in Denmark between March and May 2020. During the second wave, from September to December, 72 of those people, or 0.65 percent, again tested positive, compared with 3.27 percent of people who became infected for the first time.

That translates to a 80 percent protection from the virus in those who had been infected before. The protection fell to 47 percent for those over 65. The team also analyzed test results from nearly 2.5 million people throughout the epidemic, some longer than seven months after the first infection, and found similar results.

“It was really nice to see that there was no difference in protection from reinfection over time,” said Marion Pepper, an immunologist at the University of Washington in Seattle.

She and other experts noted that while 80 percent might not seem superb, protection from symptomatic illness was likely to be higher. The analysis included anyone who was tested, regardless of symptoms.

“A lot of these will be asymptomatic infections, and a lot of these will likely be people who have a blip of virus,” noted Florian Krammer, an immunologist at the Icahn School of Medicine at Mount Sinai in New York. “Eighty percent risk reduction against asymptomatic infection is great.”

The findings indicate that people who have recovered from Covid-19 should get at least one dose of a coronavirus vaccine to boost the level of protection, Dr. Krammer added. Most people produce robust immune response to a natural infection, “but there’s a lot of variability,” he said. Following vaccination, “we don’t see variability — we see very high responses in basically everybody, with very few exceptions.”

Experts were less convinced by the results in people over 65, saying the findings would have been more robust if the analysis had included more people from that age group.

“I wish it had actually been broken down into specific decades over 65,” Dr. Pepper said. “It would be nice to know whether the majority of people who were getting reinfected were over 80.”

The immune system grows progressively weaker with age, and people over 80 typically mount weak responses to infection with a virus. The lower protection in older people seen in the study is consistent with those observations, said Akiko Iwasaki, an immunologist at Yale University.

“I think we kind of tend to forget how the vaccines have been pretty amazing in offering protection in this age group, because you can see that natural infection doesn’t confer the same kind of protection,” she said. “This really does emphasize the need to cover older people with the vaccine, even if they have had Covid first.”

Some Long Covid-19 Patients Feel Better After Vaccine Doses

It is too soon to tell whether the shots have a broad beneficial effect on patients with continuing issues, but scientists are intrigued and beginning to study the phenomenon.

Judy Dodd began struggling with long Covid symptoms last spring — shortness of breath, headaches, exhaustion. Then she got the vaccine.

After her first Pfizer-BioNTech shot in late January, she felt so physically miserable that she had to be persuaded to get the second. For three days after that one, she also felt awful. But the fourth day, everything changed.

“I woke up and it was like ‘Oh what a beautiful morning,’” said Ms. Dodd, a middle-school teacher who is also an actor and director. “It was like I’d been directing ‘Sweeney Todd’ for months, and now I’m directing Oklahoma.”

Ms. Dodd, who continues to feel good, is among a number of people who are reporting that the post-Covid symptoms they’ve experienced for months have begun improving, sometimes significantly, after they got the vaccine. It’s a phenomenon that doctors and scientists are watching closely, but as with much about the yearlong coronavirus pandemic, there are many uncertainties.

Scientists are only beginning to study any potential effect of vaccines on long Covid symptoms. Anecdotes run the gamut: Besides those who report feeling better after the shots, many people say they have experienced no change and a small number say they feel worse.

Reports from doctors vary too. Dr. Daniel Griffin, an infectious disease physician at Columbia University, said about 40 percent of the long Covid patients he’s been treating cite symptom improvement after the vaccine. “They notice, ‘Hey, over the days, I’m feeling better. The fatigue isn’t so bad, maybe smell is coming back,’” Dr. Griffin said.

Other doctors say it is too early to know.

“Too few of our participants have been vaccinated so far to really be able to provide insight into this question,” said Dr. Michael Peluso, an infectious disease specialist working on a study of long-term Covid patients at University of California, San Francisco. “I’ve heard anecdotes as well, but I’ve seen too little data so far.”

This month, a small study by British researchers that has not yet been peer reviewed found that eight months after people were hospitalized for Covid-19, those who were vaccinated experienced improvement in more long Covid symptoms than those who weren’t yet vaccinated. The 44 vaccinated patients in the study were older and had more underlying medical conditions, since people with those characteristics qualified for vaccines earlier.

One month after vaccination, those patients reported improvement in 23 percent of their long Covid symptoms like joint pain and breathing, while 5.6 percent of their symptoms had worsened. The 22 unvaccinated people questioned at that time said 15 percent of their symptoms were better, while 14 percent of their symptoms were worse. There was no difference in response between people who received the Pfizer-BioNTech and Oxford-AstraZeneca vaccines.

Additional information comes from two surveys of several hundred people with long Covid symptoms, many of whom were never hospitalized for the disease.

Jim Golen, a former hospice nurse in Saginaw, Minn. He said his long Covid symptoms have gotten worse since his vaccination, but he’s still glad he got the vaccine.
Jim Golen, a former hospice nurse in Saginaw, Minn. He said his long Covid symptoms have gotten worse since his vaccination, but he’s still glad he got the vaccine.Tim Gruber for The New York Times

One survey of 345 people, mostly women and mostly in the U.K., found that two weeks or more after their second vaccine dose, 93 felt slightly better and 18 felt back to normal — a total of 32 percent reporting improved long Covid symptoms.

In that survey, by Gez Medinger, a London-based filmmaker who has experienced post-Covid symptoms, 61 people, just under 18 percent, felt worse, most of them reporting only a slight decline in their condition. Nearly half — 172 people — reported feeling no different.

Another survey, by Survivor Corps, a group of over 150,000 Covid survivors, found that as of March 17, 225 of 577 respondents reported some improvement, while 270 felt no change and 82 felt worse.

Jim Golen, 55, of Saginaw, Minn., feels some long Covid symptoms have worsened since his vaccination. Mr. Golen, a former hospice nurse who also has a small farm, had experienced months of difficulty, including blood clots in his lungs, chest pain, brain fog, insomnia and shortness of breath with any exertion. Late last year, after seeing several doctors, “I was finally starting to get better,” he said.

Since receiving the second dose of the Pfizer vaccine in mid-January, he said, his chest burning and shortness of breath have returned with a vengeance, especially if he taxes himself with activities like collecting sap from the maple trees on his farm. Nonetheless, Mr. Golen said he was “very happy” to be vaccinated, emphasizing that the effects of Covid were worse and preventing it is crucial.

Some people shared stories of stark symptom improvements that took them by surprise.

Laura Gross, 72, of Fort Lee, N.J. rattled off a lengthy list of debilitating long Covid symptoms she’d experienced since April, including exhaustion, joint pain, muscle aches and a “zizzy-dizzy-weaky thing that was like an internal headachy all-over-body vibration.”

Her cognitive fuzziness and forgetfulness were so intense that “brain fog barely describes it,” she said. “It’s more like brain cyclone.”

She also felt uncharacteristically “hopeless, sad, lonely, unmotivated,” she said.

Three days after her first Moderna shot in late January, everything changed. “It was like a revelation,” she said. The brain fog cleared completely, muscle aches were gone, joint pains were less intense and she suddenly had much more energy. It felt, she said, “like the old me.”

That continued after the second dose. “It’s like my cells went kerflooey last year when they met Covid,” she said, and the “vaccine said, ‘Wait, you dopes, that isn’t how you fight this, do it this way.’”

Recently, she walked briskly for 23 minutes and even “ran a little bit because I was so happy,” she said. “I’m a very happy little chappy.”

Laura Gross of Fort Lee, N.J., said brain fog is inadequate in describing her symptoms: “It’s more like brain cyclone,” she said. She reports feeling much better since being vaccinated.Nancy Borowick for The New York Times

Scientists say that understanding whether vaccines help some long Covid patients but not others could help unravel the underlying causes of different symptoms and potential ways to treat them.

“They might be different disease processes and you manage them differently,” said Dr. Adam Lauring, a virologist and infectious disease physician at the University of Michigan. “It might be that there’s a subset of people who have a certain type of long Covid, who respond well to vaccines, but there might be other people who have a different subtype that we haven’t quite defined yet.”

Akiko Iwasaki, an immunologist at Yale, said that a vaccine, by generating antibodies to the coronavirus’s spike protein, could potentially eliminate vestiges of the virus or remnants of viral RNA that may linger in some patients.

If this is occurring, she said, it could suggest that the vaccine “might be like a permanent cure” for those patients.

Dr. Iwasaki said the vaccine might also help people whose long Covid symptoms may be caused by a post-viral response resembling an autoimmune disease if “the vaccine stimulates innate immune responses that dampen these kinds of autoreactive responses,” she said. But based on experiences of people with other autoimmune diseases, that relief would “not be very long-lasting and they would kind of revert back” to having symptoms like fatigue, she said.

Dr. Eric Topol, a professor of molecular medicine at the Scripps Research Institute in San Diego, said he is starting a study to measure physiological information like heart rate, respiratory rate, temperature and markers of immune system response in people with long Covid before they receive a vaccine and weeks afterward.

It’s plausible that “you have your immune system revved up when you’re fighting a reservoir” of virus or RNA remnants, he said, “and that could be an explanation of why you’re in overdrive with your heart rate.” He wants to see if these biological indicators improve post-vaccine.

“We’d really like objective metrics that show that you not just feel better,” Dr. Topol said. “You could feel better from the placebo effect, but it’s unlikely your heart rate’s going to go from 100 to 60 because of a placebo effect. And if we keep seeing that pattern, that would be like Eureka.”

He added, “I think there’s probably something there, but I just don’t know what is the magnitude, how many people are going to benefit.”

There are many other questions: Are there specific characteristics, like age, gender, type or duration of symptoms, that might make some long Covid patients more likely to feel better? Would a vaccine be less effective for people with more complex conditions: people whose symptoms are driven by multiple biological pathways (perhaps both an RNA remnant and autoimmune activation) or whose symptoms have changed or fluctuated over time? Are certain types of vaccines more likely to produce benefit?

“It was awful thinking it may never get better, like ‘Is this my new normal, am I now damaged this way?’” recalled Bridget Hayward of her symptoms, which she says have eased since her vaccination.Alyssa Schukar for The New York Times

Bridget Hayward, 51, an operating room nurse in Alexandria, Va., said that after contracting Covid a year ago, her body ached from her hands to her hips and she became so brain-fogged that instead of asking for a scalpel, she would say “Give me that sharp thing we cut with.”

Almost daily, she would briefly pass out while bending down to fix a patient’s intravenous line or plug in the cord of a hospital bed.

“It was horrifying,” she said. “It was awful thinking it may never get better, like ‘Is this my new normal, am I now damaged this way?’”

After several months, her worst symptoms improved, but she still tired easily, felt hot even in cool weather, and found it too taxing to do some ordinary tasks, she said.

One day after her first dose of the Pfizer vaccine in late December, “it was like click, everything is fine,” she said. Her body temperature has normalized and “it felt like a darkness lifted.”

While “it’s not 100 percent every day,” she said she has so much energy now that “I’m not just getting from A to B, I’m like leaping up.”

One recent day, she did several long-overdue errands. “This may not sound like much but it is a 180-turnaround from three months ago,” she said. “I’m back!”

Kim Leighton, 64, of Vancouver, Wash., has had a similar experience. She was hospitalized last March and had long Covid symptoms that included mini blackouts, shortness of breath, getting lost in her own neighborhood, depression and fatigue.

“It really has been hell,” she said.

When she started feeling better in late January, she didn’t even think to connect it to the vaccine, but later realized her stark improvement had started four days after receiving her first Moderna shot. She is delighted that she can now take walks in downtown Portland and has the desire to reconnect with friends.

“Every day, I feel like I’m feeling stronger,” Ms. Leighton said. “All the stuff I had to let go of, I’m trying to get it back.”

Ms. Dodd, like several others, said she wasn’t taking her improvement for granted. “I’m still sort of wary of what’s around the corner, this disease is so unpredictable,” she said.

But, she added, “even if, God forbid, I have a relapse, to have this time now when I feel better, it’s really amazing.”

Some Long Covid Patients Feel Better After Getting the Vaccine

It is too soon to tell whether the shots have a broad beneficial effect on patients with continuing issues, but scientists are intrigued and beginning to study the phenomenon.

Judy Dodd began struggling with long Covid symptoms last spring — shortness of breath, headaches, exhaustion. Then she got the vaccine.

After her first Pfizer-BioNTech shot in late January, she felt so physically miserable that she had to be persuaded to get the second. For three days after that one, she also felt awful. But the fourth day, everything changed.

“I woke up and it was like ‘Oh what a beautiful morning,’” said Ms. Dodd, a middle-school teacher who is also an actor and director. “It was like I’d been directing ‘Sweeney Todd’ for months, and now I’m directing Oklahoma.”

Ms. Dodd, who continues to feel good, is among a number of people who are reporting that the post-Covid symptoms they’ve experienced for months have begun improving, sometimes significantly, after they got the vaccine. It’s a phenomenon that doctors and scientists are watching closely, but as with much about the yearlong coronavirus pandemic, there are many uncertainties.

Scientists are only beginning to study any potential effect of vaccines on long Covid symptoms. Anecdotes run the gamut: Besides those who report feeling better after the shots, many people say they have experienced no change and a small number say they feel worse.

Reports from doctors vary too. Dr. Daniel Griffin, an infectious disease physician at Columbia University, said about 40 percent of the long Covid patients he’s been treating cite symptom improvement after the vaccine. “They notice, ‘Hey, over the days, I’m feeling better. The fatigue isn’t so bad, maybe smell is coming back,’” Dr. Griffin said.

Other doctors say it is too early to know.

“Too few of our participants have been vaccinated so far to really be able to provide insight into this question,” said Dr. Michael Peluso, an infectious disease specialist working on a study of long-term Covid patients at University of California, San Francisco. “I’ve heard anecdotes as well, but I’ve seen too little data so far.”

This month, a small study by British researchers that has not yet been peer reviewed found that eight months after people were hospitalized for Covid-19, those who were vaccinated experienced improvement in more long Covid symptoms than those who weren’t yet vaccinated. The 44 vaccinated patients in the study were older and had more underlying medical conditions, since people with those characteristics qualified for vaccines earlier.

One month after vaccination, those patients reported improvement in 23 percent of their long Covid symptoms like joint pain and breathing, while 5.6 percent of their symptoms had worsened. The 22 unvaccinated people questioned at that time said 15 percent of their symptoms were better, while 14 percent of their symptoms were worse. There was no difference in response between people who received the Pfizer-BioNTech and Oxford-AstraZeneca vaccines.

Additional information comes from two surveys of several hundred people with long Covid symptoms, many of whom were never hospitalized for the disease.

Jim Golen, a former hospice nurse in Saginaw, Minn. He said his long Covid symptoms have gotten worse since his vaccination, but he’s still glad he got the vaccine.
Jim Golen, a former hospice nurse in Saginaw, Minn. He said his long Covid symptoms have gotten worse since his vaccination, but he’s still glad he got the vaccine.Tim Gruber for The New York Times

One survey of 345 people, mostly women and mostly in the U.K., found that two weeks or more after their second vaccine dose, 93 felt slightly better and 18 felt back to normal — a total of 32 percent reporting improved long Covid symptoms.

In that survey, by Gez Medinger, a London-based filmmaker who has experienced post-Covid symptoms, 61 people, just under 18 percent, felt worse, most of them reporting only a slight decline in their condition. Nearly half — 172 people — reported feeling no different.

Another survey, by Survivor Corps, a group of over 150,000 Covid survivors, found that as of March 16, 207 of 508 respondents reported some improvement, while 231 felt no change and 70 felt worse.

Jim Golen, 55, of Saginaw, Minn., feels some long Covid symptoms have worsened since his vaccination. Mr. Golen, a former hospice nurse who also has a small farm, had experienced months of difficulty, including blood clots in his lungs, chest pain, brain fog, insomnia and shortness of breath with any exertion. Late last year, after seeing several doctors, “I was finally starting to get better,” he said.

Since receiving the second dose of the Pfizer vaccine in mid-January, he said, his chest burning and shortness of breath have returned with a vengeance, especially if he taxes himself with activities like collecting sap from the maple trees on his farm. Nonetheless, Mr. Golen said he was “very happy” to be vaccinated, emphasizing that the effects of Covid were worse and preventing it is crucial.

Some people shared stories of stark symptom improvements that took them by surprise.

Laura Gross, 72, of Fort Lee, N.J. rattled off a lengthy list of debilitating long Covid symptoms she’d experienced since April, including exhaustion, joint pain, muscle aches and a “zizzy-dizzy-weaky thing that was like an internal headachy all-over-body vibration.”

Her cognitive fuzziness and forgetfulness were so intense that “brain fog barely describes it,” she said. “It’s more like brain cyclone.”

She also felt uncharacteristically “hopeless, sad, lonely, unmotivated,” she said.

Three days after her first Moderna shot in late January, everything changed. “It was like a revelation,” she said. The brain fog cleared completely, muscle aches were gone, joint pains were less intense and she suddenly had much more energy. It felt, she said, “like the old me.”

That continued after the second dose. “It’s like my cells went kerflooey last year when they met Covid,” she said, and the “vaccine said, ‘Wait, you dopes, that isn’t how you fight this, do it this way.’”

Recently, she walked briskly for 23 minutes and even “ran a little bit because I was so happy,” she said. “I’m a very happy little chappy.”

Laura Gross of Fort Lee, N.J., said brain fog is inadequate in describing her symptoms: “It’s more like brain cyclone,” she said. She reports feeling much better since being vaccinated.Nancy Borowick for The New York Times

Scientists say that understanding whether vaccines help some long Covid patients but not others could help unravel the underlying causes of different symptoms and potential ways to treat them.

“They might be different disease processes and you manage them differently,” said Dr. Adam Lauring, a virologist and infectious disease physician at the University of Michigan. “It might be that there’s a subset of people who have a certain type of long Covid, who respond well to vaccines, but there might be other people who have a different subtype that we haven’t quite defined yet.”

Akiko Iwasaki, an immunologist at Yale, said that a vaccine, by generating antibodies to the coronavirus’s spike protein, could potentially eliminate vestiges of the virus or remnants of viral RNA that may linger in some patients.

If this is occurring, she said, it could suggest that the vaccine “might be like a permanent cure” for those patients.

Dr. Iwasaki said the vaccine might also help people whose long Covid symptoms may be caused by a post-viral response resembling an autoimmune disease if “the vaccine stimulates innate immune responses that dampen these kinds of autoreactive responses,” she said. But based on experiences of people with other autoimmune diseases, that relief would “not be very long-lasting and they would kind of revert back” to having symptoms like fatigue, she said.

Dr. Eric Topol, a professor of molecular medicine at the Scripps Research Institute in San Diego, said he is starting a study to measure physiological information like heart rate, respiratory rate, temperature and markers of immune system response in people with long Covid before they receive a vaccine and weeks afterward.

It’s plausible that “you have your immune system revved up when you’re fighting a reservoir” of virus or RNA remnants, he said, “and that could be an explanation of why you’re in overdrive with your heart rate.” He wants to see if these biological indicators improve post-vaccine.

“We’d really like objective metrics that show that you not just feel better,” Dr. Topol said. “You could feel better from the placebo effect, but it’s unlikely your heart rate’s going to go from 100 to 60 because of a placebo effect. And if we keep seeing that pattern, that would be like Eureka.”

He added, “I think there’s probably something there, but I just don’t know what is the magnitude, how many people are going to benefit.”

There are many other questions: Are there specific characteristics, like age, gender, type or duration of symptoms, that might make some long Covid patients more likely to feel better? Would a vaccine be less effective for people with more complex conditions: people whose symptoms are driven by multiple biological pathways (perhaps both an RNA remnant and autoimmune activation) or whose symptoms have changed or fluctuated over time? Are certain types of vaccines more likely to produce benefit?

“It was awful thinking it may never get better, like ‘Is this my new normal, am I now damaged this way?’” recalled Bridget Hayward of her symptoms, which she says have eased since her vaccination.Alyssa Schukar for The New York Times

Bridget Hayward, 51, an operating room nurse in Alexandria, Va., said that after contracting Covid a year ago, her body ached from her hands to her hips and she became so brain-fogged that instead of asking for a scalpel, she would say “Give me that sharp thing we cut with.”

Almost daily, she would briefly pass out while bending down to fix a patient’s intravenous line or plug in the cord of a hospital bed.

“It was horrifying,” she said. “It was awful thinking it may never get better, like ‘Is this my new normal, am I now damaged this way?’”

After several months, her worst symptoms improved, but she still tired easily, felt hot even in cool weather, and found it too taxing to do some ordinary tasks, she said.

One day after her first dose of the Pfizer vaccine in late December, “it was like click, everything is fine,” she said. Her body temperature has normalized and “it felt like a darkness lifted.”

While “it’s not 100 percent every day,” she said she has so much energy now that “I’m not just getting from A to B, I’m like leaping up.”

One recent day, she did several long-overdue errands. “This may not sound like much but it is a 180-turnaround from three months ago,” she said. “I’m back!”

Kim Leighton, 64, of Vancouver, Wash., has had a similar experience. She was hospitalized last March and had long Covid symptoms that included mini blackouts, shortness of breath, getting lost in her own neighborhood, depression and fatigue.

“It really has been hell,” she said.

When she started feeling better in late January, she didn’t even think to connect it to the vaccine, but later realized her stark improvement had started four days after receiving her first Moderna shot. She is delighted that she can now take walks in downtown Portland and has the desire to reconnect with friends.

“Every day, I feel like I’m feeling stronger,” Ms. Leighton said. “All the stuff I had to let go of, I’m trying to get it back.”

Ms. Dodd, like several others, said she wasn’t taking her improvement for granted. “I’m still sort of wary of what’s around the corner, this disease is so unpredictable,” she said.

But, she added, “even if, God forbid, I have a relapse, to have this time now when I feel better, it’s really amazing.”

Three Feet or Six? Distancing Guideline for Schools Stirs Debate

Some public health officials say it’s time for the C.D.C. to loosen its social distancing guidelines for classrooms, but the idea has detractors.

The Centers for Disease Control and Prevention is clear and consistent in its social distancing recommendation: To reduce the risk of contracting the coronavirus, people should remain at least six feet away from others who are not in their households. The guideline holds whether you are eating in a restaurant, lifting weights at a gym or learning long division in a fourth-grade classroom.

The guideline has been especially consequential for schools, many of which have not fully reopened because they do not have enough space to keep students six feet apart.

Now, spurred by a better understanding of how the virus spreads and a growing concern about the harms of keeping children out of school, some public health experts are calling on the agency to reduce the recommended distance in schools from six feet to three.

“It never struck me that six feet was particularly sensical in the context of mitigation,” said Dr. Ashish Jha, dean of the Brown University School of Public Health. “I wish the C.D.C. would just come out and say this is not a major issue.”

On Sunday, Dr. Anthony S. Fauci, the director of the National Institute of Allergy and Infectious Diseases, said on CNN that the C.D.C. was reviewing the matter.

The idea remains contentious, in part because few studies have directly compared different distancing strategies. But the issue also boils down to a devilishly difficult and often personal question: How safe is safe enough?

“There’s no magic threshold for any distance,” said Dr. Benjamin Linas, a specialist in infectious diseases at Boston University. “There’s risk at six feet, there’s risk at three feet, there’s risk at nine feet. There’s risk always.” He added, “The question is just how much of a risk? And what do you give up in exchange?”

The origins of six feet

The American Academy of Pediatrics recommends three to six feet of social distancing in schools, while the World Health Organization recommends just one meter, or 3.3 feet.
The American Academy of Pediatrics recommends three to six feet of social distancing in schools, while the World Health Organization recommends just one meter, or 3.3 feet.Pete Kiehart for The New York Times

The origin of the six-foot distancing recommendation is something of a mystery. “It’s almost like it was pulled out of thin air,” said Linsey Marr, an expert on viral transmission at Virginia Tech University.

When the virus first emerged, many experts believed that it was transmitted primarily through large respiratory droplets, which are relatively heavy. Old scientific studies, some dating back more than a century, suggested that these droplets tend not to travel more than three to six feet. This observation, as well as an abundance of caution, may have spurred the C.D.C. to make its six foot suggestion, Dr. Marr said.

But that recommendation was not universal. The American Academy of Pediatrics recommends three to six feet of social distancing in schools, but the World Health Organization recommends just one meter, or 3.3 feet.

And over the last year, scientists have learned that respiratory droplets are not the primary mode of coronavirus transmission. Instead, the virus spreads mostly through tiny airborne droplets known as aerosols, which can travel longer distances and flow through rooms in unpredictable ways.

Data also suggests that schools appear to be relatively low-risk environments; children under 10 seem to transmit the virus less readily than adults.

In recent months, there have been hints that six feet of distancing may not be necessary in school settings. Case rates have generally been low even in schools with looser distancing policies. “We know lots of schools have opened up to less than six feet and have not seen big outbreaks,” said Dr. Jha.

In a 2020 analysis of observational studies in a variety of settings, researchers found that physical distancing of at least one meter substantially reduced transmission rates of several different coronaviruses, including the one that causes Covid-19. But they found some evidence to suggest that a two meter guideline “might be more effective.”

“One of the really important data points that has been missing is a direct head-to-head comparison of places that had implemented three feet of distance versus six feet of distance,” said Dr. Elissa Perkins, the director of emergency medicine infectious disease management at Boston University School of Medicine.

A natural experiment

A hand sanitizer station in a Catholic school in Boston in January.Allison Dinner/Reuters

Dr. Perkins and her colleagues recently conducted such a comparison by taking advantage of a natural experiment in Massachusetts. Last summer, the state’s education department issued guidelines recommending three to six feet of distancing in schools that were planning to reopen in the fall. As a result, school policies varied: Some districts imposed strict, six-foot distancing, whereas others required just three. (The state required all staff members, as well as students in second grade and above, to wear masks.)

The researchers found that the social distancing strategy had no statistically significant effect on Covid-19 case rates, the team reported in the journal Clinical Infectious Diseases last week. The study also found that Covid-19 rates were lower in schools than in the surrounding communities.

The authors say the findings provide reassurance that schools can loosen their distancing requirements and still be safe, provided they take other precautions, like enforcing universal mask wearing.

“Masking still appears to be effective,” said lead investigator Dr. Westyn Branch-Elliman, an infectious diseases specialist at the VA Boston Healthcare System. “And so, provided we have universal masking mandates, I think it’s very reasonable to move to a three-foot recommendation.”

Not everyone finds the study so convincing. A. Marm Kilpatrick, an infectious disease researcher at the University of California, Santa Cruz, said that the school-district data was too noisy to draw firm conclusions from. “It doesn’t really allow you to get, I think, an answer that you can feel really confident in,” he said.

The study’s authors acknowledged that they could not rule out the possibility that increased distancing provided a small benefit.

With aerosol transmission, safety generally increases with distance; the farther the aerosols travel, the more they diluted become. “It’s like being close to a smoker,” Dr. Marr said. “The closer you are, the more you’re going to breathe in.”

And distance aside, the more people there are in a room, the higher the odds that one of them will be infected with the coronavirus. A six-foot rule helps reduce that risk, said Donald Milton, an aerosol expert at the University of Maryland: “If people are six feet apart, you can’t pack them in. And so, it’s safer just because it’s less dense.”

Masks and good ventilation do a lot to reduce the risk. With these measures in place, the difference between three and six feet was likely to be relatively small, scientists said. And if Covid-19 is not very prevalent in the surrounding community, the absolute risk of contracting the virus in schools is likely to remain low, as long as these protections are in place.

“We can always do things to reduce our risks further,” Dr. Marr said. “But at some point, you reach diminishing returns, and you have to think about the costs of trying to achieve those additional risk reductions.”

Debate and diminishing risks

“Provided we have universal masking mandates, I think it’s very reasonable to move to a three-foot recommendation,” said one infectious disease specialist.Rosem Morton for The New York Times

Some experts say that a small increase in risk is outweighed by the benefits of fully reopening schools. “Trying to follow the six-foot guideline should not prevent us from getting kids back to school full time with masks, with at least three-foot distancing,” Dr. Marr said.

Others said it was too soon to loosen the C.D.C. guidelines. “Ultimately, I think there could be a place for this changing guidance,” Saskia Popescu, an infectious disease epidemiologist at George Mason University, said in an email. “But it’s not now, when we are struggling to vaccinate people, we’re still seeing over 60,000 cases a day and we’re trying to not reverse the progress we’ve made.”

Even proponents of changing the guideline say that any shift to looser distancing will have to be done carefully, and in combination with other precautionary measures. “If you’re in an area where there’s not a strong tendency to rely on masks, I don’t think it would be wise to extrapolate our data to that environment,” Dr. Perkins said.

Moreover, officials risk muddying the public health messaging if they establish different standards for schools than for other shared spaces. “I’ve evolved on this,” Dr. Linas said. “Last summer I felt like, ‘How are we going to explain to people that it’s six feet everywhere except for schools? That seems not consistent and problematic.’”

But schools are unique, he said. They are relatively controlled environments that can enforce certain safety measures, and they have unique benefits for society. “The benefits of school are different than the benefits of movie theaters or restaurants,” he said. “So I’d be willing to assume a little bit more risk just to keep them open.”

Virus Variants Likely Evolved Inside People With Weak Immune Systems

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Virus Variants Likely Evolved Inside People With Weak Immune Systems

Growing evidence suggests that people with cancer and other conditions that challenge their immune systems may be incubators of mutant viruses.

A Covid patient in the I.C.U. of Sarasota Memorial Hospital in Florida last month.
A Covid patient in the I.C.U. of Sarasota Memorial Hospital in Florida last month.Credit…Shannon Stapleton/Reuters
Apoorva Mandavilli

  • March 15, 2021, 3:23 p.m. ET

The version of the coronavirus that surfaced in Britain late last year was shocking for many reasons. It came just as vaccines had offered a glimpse of the end of the pandemic, threatening to dash those hopes. It was far more contagious than earlier variants, leading to a swift increase in hospitalizations. And perhaps most surprising to scientists: It had amassed a large constellation of mutations seemingly overnight.

A coronavirus typically gains mutations on a slow-but-steady pace of about two per month. But this variant, called B.1.1.7, had acquired 23 mutations that were not on the virus first identified in China. And 17 of those had developed all at once, sometime after it diverged from its most recent ancestor.

Experts said there’s only one good hypothesis for how this happened: At some point the virus must have infected someone with a weak immune system, allowing it to adapt and evolve for months inside the person’s body before being transmitted to others. “It appears to be the most likely explanation,” said Dr. Ravindra Gupta, a virologist at the University of Cambridge.

If true, the idea has implications for vaccination programs, particularly in countries that have not yet begun to immunize their populations. People with compromised immune systems — such as cancer patients — should be among the first to be vaccinated, said Dr. Adam Lauring, a virologist and infectious disease physician at the University of Michigan. The faster that group is protected, the lower the risk that their bodies turn into incubators for the world’s next supercharged mutant.

“We should give the best shot we can, both literally and figuratively, to protect this population,” Dr. Lauring said.

That might be complicated, he added. For the same reason that these people don’t mount a strong immune response to the virus, vaccines might not work well in them. So they may need to be treated with cocktails of monoclonal antibodies as well, he said.

Like other viruses, the coronavirus collects mutations every time it replicates. The overwhelming majority of those genetic glitches are insignificant and transient. In most people, an active infection lasts only about a week, not long enough for the virus to acquire more than one noteworthy mutation, if any.

Mutations that make the coronavirus more contagious or enable it to dodge the immune system are extremely rare, researchers reported in a study published last week in the journal Science. “But if they do occur, and if they can get transmitted, then it’s open season,” said Katrina Lythgoe, an evolutionary biologist at the University of Oxford who led the study.

Over a period of months to years, the virus may string together several such mutations. Scientists can observe this slow evolution using a molecular “clock” that captures the changes over time. But in a person with a weak immune system, this timeline can be greatly accelerated.

Multiple studies have shown that in some people who are immunocompromised, the virus can persist for more than eight months, ample time and opportunity to keep evolving.

“If we look at several time points through that course of infection, and we look at the virus population in that patient, we see — every time — different variants popping up with a large turnover rate,” said Vincent Munster, a virologist at the National Institute of Allergy and Infectious Diseases who led one of the studies.

Coronavirus Variants and Mutations

Tracking recent mutations, variants and lineages.

If one of these variants that has gained important mutations is transmitted to someone else, it may spread quickly through the population and seem to have emerged out of nowhere — as in the case of the variant that walloped Britain, and perhaps others identified in South Africa and Brazil.

“That’s a pretty decent hypothesis that they’ve come from people with persistent infection,” Dr. Lythgoe said of the variants. “By keeping infection rates low, you’re going to reduce the number of immunocompromised people who are infected and reduce the chance that they occur.”

“Immunocompromised” is a nebulous term encompassing a wide range of conditions — from diabetes and rheumatoid arthritis to leukemia and lymphoma — and experts disagreed on which conditions may lead to variants.

Some say the list should include older people, as well as those who take medications that suppress the immune system and anyone who does not produce a robust set of antibodies.

“We learned from the vaccines that antibodies matter,” said Paul Duprex, director of the Center for Vaccine Research at the University of Pittsburgh. “It’s very important to keep an eye on people who are immune-suppressed, who don’t have fully functional immune systems.”

Dr. Lauring said he was most worried about people with blood-related cancers like leukemia, but did not have strong concerns about those taking drugs like Humira or Enbrel, which are used to treat rheumatoid arthritis.

“It’s a different kind of immunosuppression that I’m not sure would lead to this, but no one knows for sure,” he said.

Some people with weak immune systems have been known to transmit other viruses over long periods, Dr. Lauring noted. One man in England has shed poliovirus for at least 28 years. Others have had persistent infections with norovirus or influenza.

“We’ve been dealing with this for a long time,” he said. “But just like everything with Covid, we’re dealing with it on a big scale.”

He and the other experts emphasized that regardless of the risks, it is important not to stigmatize or blame people who have compromised immune systems. Instead, they said, the focus should be on limiting their exposure to the virus.

“Let’s get the vaccines into people, let’s do good distancing, let’s do good masking,” Dr. Duprex said. “Everything that we can do to stop the virus spreading is really very important.”

Pandemic Raises Concerns About Childhood Lead Poisoning

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Pandemic Raises Concerns About Childhood Lead Poisoning

Lead screenings for children plummeted last spring, and stay-at-home orders may have increased household exposure to the toxic metal.

A worker scraping off lead paint. The C.D.C. estimates that more than 20 million housing units in the United States contain lead-based paint, which was essentially banned in 1978.
A worker scraping off lead paint. The C.D.C. estimates that more than 20 million housing units in the United States contain lead-based paint, which was essentially banned in 1978.Credit…Jamie Hooper/Alamy

  • March 11, 2021, 5:00 a.m. ET

Over the past half-century, public health officials have made enormous progress in protecting American children from lead poisoning and the irreversible neurological damage it can cause. Since the 1970s, the percentage of children with high levels of lead in their blood has plummeted.

But in 2020, a new health threat, the coronavirus, endangered these hard-earned gains.

When Covid-19 cases spiked last spring, lockdowns and day care closures confined young children to their homes, where lead exposure can be particularly high. The growing national emergency also delayed lead-removal efforts and disrupted routine childhood lead screenings, leaving health officials unable to identify and treat many children living in lead-laden homes.

Last month, the Centers for Disease Control and Prevention estimated that in the early months of the pandemic, roughly 10,000 children with elevated levels of lead in their blood may have gone undetected.

“Hundreds of thousands of children have missed their essential tests for lead,” said Joseph Courtney, a senior epidemiologist at the C.D.C.’s lead poisoning prevention and environmental health tracking branch, who conducted the analysis. “And it’s something that has potentially permanent lifetime effects.”

There is no safe level of exposure to lead, which can disrupt neurological and cognitive development, causing learning disabilities, behavioral problems and developmental delays.

The C.D.C. estimates that more than 20 million housing units in the United States contain lead-based paint, which was banned in 1978. When the paint flakes, cracks or peels, the lead mixes with dust, which children can ingest or inhale. Young children, whose brains are still developing, are at particular risk.

“The main route of exposure for most children is lead-contaminated dust, from paint getting on their hands or their toys,” said David Jacobs, chief scientist at the National Center for Healthy Housing. “And then normal child behavior at this age is, everything goes in the mouth.”

For that reason, many states recommend or require that children of certain ages have their blood tested for lead. (Federal guidelines require that all children who are enrolled in Medicaid receive blood lead level tests at ages one and two.) Doctors typically perform these tests as part of a child’s regular checkup.

But when the pandemic hit last March, government officials issued stay-at-home orders, and many medical offices closed. Others started conducting appointments virtually. “You can’t do a blood lead test by telemedicine,” said Dr. Stephanie Yendell, senior epidemiology supervisor at the Minnesota Department of Public Health. “You can’t get a blood sample by video call.”

That month in Minnesota, the number of tests for blood lead level fell to 70 percent of what it had been the previous year, Dr. Yendell said. “And then in April, we bottomed out at 43 percent compared to the year before.”

In New York City, which was hit by an early wave of Covid-19 cases, childhood lead screenings declined by 88 percent last April.

Anecdotal reports of these declines soon made their way to the C.D.C., which asked state and local health officials to share their lead screening data so the agency could conduct a more formal analysis. Thirty-four health departments — representing 32 states, plus New York City and Washington, D.C. — ultimately did so.

Paint is the most common cause of childhood lead poisoning, but lead pipes also pose a threat; the longer that water sits stagnant in such pipes, the more lead leeches into it.
Paint is the most common cause of childhood lead poisoning, but lead pipes also pose a threat; the longer that water sits stagnant in such pipes, the more lead leeches into it.Credit…Julio Cortez/Associated Press

Every one of those departments reported a drop-off in testing last spring, Dr. Courtney and his colleagues found. Over the first five months of 2020, roughly 500,000 fewer children had their blood lead levels tested in these districts compared with the same period of 2019. The decline was especially steep in March, April and May, when testing levels fell 50 percent compared to the previous year.

That kind of decline has no precedent, Dr. Courtney said: “There’s nothing like it before.”

Roughly 2 percent of American children have elevated blood lead levels, Dr. Courtney said. If that percentage holds for the children who missed their screenings last year, it would mean that nearly 10,000 of them had significant lead exposures. “And there were 18 states that we didn’t receive data from that probably would have added to that total,” he noted. “So that’s a conservative estimate.”

There is also reason to suspect that lead poisoning is even more prevalent among the children who missed their blood tests last year, experts said. Children of color, and those who live in low-income neighborhoods, are particularly likely to be exposed to lead. Those same communities have been among the hardest hit by the coronavirus and may have faced the biggest obstacles in receiving pediatric checkups last year.

“We’re afraid that the kids who are being missed are probably the kids at higher risk,” Dr. Courtney said. Some states reported that the dip in lead screenings was especially pronounced among children who were on Medicaid, he added.

For lead-poisoned children, the consequences could be devastating. Although there is no way to reverse lead poisoning, nutritional supplements and educational services can help mitigate the harms. Children who miss their lead screenings may not receive these essential interventions.

Moreover, in many cases, it takes an elevated blood lead level to trigger lead removal or remediation efforts. “If you don’t test, you don’t find,” said Dr. Morri Markowitz, director of the lead poisoning treatment and prevention program at the Children’s Hospital at Montefiore, in New York City. “If you don’t find, you don’t intervene, and the kid continues to be exposed, continues potentially to be ingesting lead.” He added: “And then it can progress, and by the time you check, things will have gotten worse.”

Even as lead testing rates were falling last spring, the amount of time that children were spending in their homes, where lead exposure is most likely, was rising. The pandemic, and the financial hardships that accompanied it, may also have prompted some families and property owners to postpone essential building repairs and maintenance tasks.

“I’m very concerned that we potentially may have more children who have been exposed if they’ve been in homes with peeling, chipping paint,” said Dr. Joneigh Khaldun, the chief medical executive for the state of Michigan and chief deputy director for health in the Michigan Department of Health and Human Services. “We just don’t even know it.”

Widespread building closures have created other risks. Although paint is the most common cause of childhood lead poisoning, lead pipes also pose a threat. The longer that water sits stagnant in such pipes, the more lead leeches into it; schools and day care centers that shut down last year could find their water dangerously contaminated when they reopen.

“There’s likely to be high lead levels in some taps,” said Jennifer Hoponick Redmon, a senior environmental health scientist at RTI International, a nonprofit research organization based in North Carolina. “Water needs to be flushed at schools and child care centers — and really, all places that are closed — before people start using the water again for drinking and cooking.”

There is some evidence that lead poisoning rates may have risen slightly last year. Health officials in Massachusetts said they detected a 3 percent increase in the prevalence of lead poisoning among young children between mid-March and mid-August 2020. “While this may seem like a small increase, it is concerning, as we normally see rates of lead poisoning decline each year,” said Jan Sullivan, acting director of the Bureau of Environmental Health at the Massachusetts Department of Public Health.

And in New York City, preliminary data suggests that the share of young children with elevated blood lead levels was essentially flat over the first three-quarters of 2020, after years of steady declines.But not all health departments have found these patterns, and many are still analyzing their data from last year. Of course, if the children who face the biggest lead hazards are the ones who skipped their screenings , a rise in lead poisoning may not show up in the testing data, experts said.

Early evidence suggests that blood lead testing did begin to rebound in the second half of 2020. “But it still fell below the levels of previous years and did not nearly make up for the number of children missed earlier in the year,” Dr. Courtney said.

In Michigan, where childhood lead testing was about one-third lower in 2020 than in 2019, health officials are now trying to make up lost ground. They are organizing mobile lead testing events, to be held across the state, and planning a major media campaign.

“We’re going to put some money behind it, have some commercials and a real intentional focus on making sure people are aware of the risk of lead and that they know how and where to get tested,” said Dr. Khaldun. “We are really focused on making sure we don’t have other unintended consequences of the pandemic.”

Severe Obesity Raises Risk of Covid-19 Hospitalization and Death, Study Finds

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Severe Obesity Raises Risk of Covid-19 Hospitalization and Death, Study Finds

A large new study has confirmed an association between obesity and patient outcomes among people who contract the coronavirus.

A Covid-19 patient in the intensive care unit at Sharp Coronado Hospital in Southern California in January.
A Covid-19 patient in the intensive care unit at Sharp Coronado Hospital in Southern California in January.Credit…Etienne Laurent/EPA, via Shutterstock

  • March 8, 2021, 6:56 p.m. ET

Over the past year, many scientific teams around the world have reported that obese people who contract the coronavirus are especially likely to become dangerously ill.

Now, a large new study, of nearly 150,000 adults at more than 200 hospitals across the United States, paints a more detailed picture of the connection between weight and Covid-19 outcomes.

The study, performed by a team of researchers as the Centers for Disease Control and Prevention, has confirmed that obesity significantly increases the risk for hospitalization and death among those who contract the virus. And among those who are obese, the risk increases as a patient’s body mass index, or B.M.I., a ratio of weight to height, increases. Patients with a B.M.I. of 45 or higher, which corresponds to severe obesity, were 33 percent more likely to be hospitalized and 61 percent more likely to die than those who were at a healthy weight, the researchers found.

“The findings of the study highlight the serious clinical public health implications of elevated B.M.I., and they suggest the continued need for intensive management of Covid-19 illness, especially among patients affected by severe obesity,” said the lead author, Lyudmyla Kompaniyets, a health economist at the Division of Nutrition, Physical Activity and Obesity at the C.D.C.

But the relationship between weight and outcomes is nuanced. Covid-19 patients who were underweight were also more likely to be hospitalized than those who were at a healthy weight, although they were not more likely to be admitted to the intensive care unit or to die.

Dr. Kompaniyets and her colleagues used a database of Covid-19 cases to identify 148,494 adults who received a diagnosis of the disease at American hospitals from last March to December. They calculated the B.M.I. of each patient and looked for correlations between B.M.I. and a variety of serious outcomes, including hospitalization, I.C.U. admission, mechanical ventilation and death.

They found that obesity, which is defined as a B.M.I. of 30 or higher, increased the risk of both hospitalization and death. Patients with a B.M.I. of 30 to 34.9 were just 7 percent more likely to be hospitalized and 8 percent more likely to die than people who were at a healthy weight, but the risks increased sharply as B.M.I. rose.

Providing evidence for this kind of “dose response” relationship makes the study particularly compelling, said Dr. Anne Dixon, the director of pulmonary and critical care medicine at the University of Vermont Medical Center, who was not involved in the research. “What it shows is the more severe your obesity, the worse the effect is. And the fact that goes up stepwise with increasing levels of obesity, I think, adds sort of biological plausibility to the relationship between obesity and the outcome.”

The connection between obesity and poor outcomes was strongest among patients under 65, but it held even for older adults. Previous, smaller studies have not found strong links between obesity and severity of Covid-19 in older adults.

“Potentially because they had more power from this large sample size, they’ve demonstrated that obesity remains an important risk factor for death in older adults as well,” said Dr. Michaela R. Anderson, an expert in pulmonary and critical care medicine at Columbia University Medical Center, who was not involved in the study. “It’s a beautifully done study with a massive population.”

Dr. Kompaniyets and her colleagues also documented a linear relationship between B.M.I. and the likelihood of needing mechanical ventilation; the higher the B.M.I., the more likely a patient was to require such intervention, which is invasive and can come with serious complications.

The study also found that patients who were underweight, with a B.M.I. below 18.5, were 20 percent more likely to be hospitalized than those who had a healthy weight. The reasons are not entirely clear, but may stem from the fact that some of these patients were malnourished or frail or had other diseases.

The B.M.I. range associated with the best outcomes, the researchers found, was near the dividing line between what is considered healthy and overweight, consistent with some prior research suggesting that a few extra pounds might help protect people when they contract an infectious disease.

“Exactly why that association exists is currently unknown,” said Dr. Alyson Goodman, a pediatrician and medical epidemiologist at the C.D.C. and a co-author of the study. One possibility is that having a bit of extra fat may provide much needed energy reserves over the course of a long illness.

The findings highlight the importance of carefully managing the care of patients who are severely obese and of ensuring that people who are obese have access to vaccines and other preventive measures.

“This just provides further evidence for the recommendation to vaccinate those with a high B.M.I. as early as feasible,” said Sara Y. Tartof, an infectious disease epidemiologist at the Department of Research & Evaluation at Kaiser Permanente, who was not involved in the study.

Women Report Worse Side Effects After a Covid Vaccine

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Women Report Worse Side Effects After a Covid Vaccine

Men and women tend to respond differently to many kinds of vaccines. That’s probably because of a mix of factors, including hormones, genes and the dosing of the shots.

C.D.C. researchers analyzed safety data from 13.7 million Covid-19 vaccinations, finding 79.1 percent of reported side effects came from women, though only 61.2 percent of the vaccines had been administered to women.
C.D.C. researchers analyzed safety data from 13.7 million Covid-19 vaccinations, finding 79.1 percent of reported side effects came from women, though only 61.2 percent of the vaccines had been administered to women.Credit…Mike Kai Chen for The New York Times

  • March 8, 2021, 11:44 a.m. ET

On the morning that Shelly Kendeffy received her second dose of the Moderna Covid-19 vaccine, she felt fine. By afternoon, she noticed a sore arm and body aches, and by evening, it felt like the flu.

“My teeth were chattering, but I was sweating — like soaked, but frozen,” said Ms. Kendeffy, 44, a medical technician in State College, Pa.

The next day, she went to work and surveyed her colleagues — eight men and seven women — about their vaccine experiences. Six of the women had body aches, chills and fatigue. The one woman who didn’t have flu symptoms was up much of the night vomiting.

The eight men gave drastically different reports. One had mild arm pain, a headache and body aches. Two described mild fatigue and a bit of achiness. One got a headache. And four had no symptoms at all.

“I work with some very tough women,” Ms. Kendeffy said. But “clearly, us women suffered a severity of the side effects.” She felt better after 24 hours, and is thrilled she got the vaccine. “I wouldn’t change a thing, because it sure beats the alternative,” she said. “But I also didn’t know what to expect.”

The differences Ms. Kendeffy observed among her co-workers are playing out across the country. In a study published last month, researchers from the Centers for Disease Control and Prevention analyzed safety data from the first 13.7 million Covid-19 vaccine doses given to Americans. Among the side effects reported to the agency, 79.1 percent came from women, even though only 61.2 percent of the vaccines had been administered to women.

Nearly all of the rare anaphylactic reactions to Covid-19 vaccines have occurred among women, too. C.D.C. researchers reported that all 19 of the individuals who had experienced such a reaction to the Moderna vaccine have been female, and that women made up 44 of the 47 who have had anaphylactic reactions to the Pfizer vaccine.

“I am not at all surprised,” said Sabra Klein, a microbiologist and immunologist at the Johns Hopkins Bloomberg School of Public Health. “This sex difference is completely consistent with past reports of other vaccines.”

In a 2013 study, scientists with the C.D.C. and other institutions found that four times as many women as men between the ages of 20 and 59 reported allergic reactions after receiving the 2009 pandemic flu vaccine, even though more men than women got those shots. Another study found that between 1990 and 2016, women accounted for 80 percent of all adult anaphylactic reactions to vaccines.

In general, women “have more reactions to a variety of vaccines,” said Julianne Gee, a medical officer in the C.D.C.’s Immunization Safety Office. That includes influenza vaccines given to adults, as well as some given in infancy, such as the hepatitis B and measles, mumps and rubella (M.M.R.) vaccines.

The news isn’t all bad for women, though. Side effects are usually mild and short-lived. And these physical reactions are a sign that a vaccine is working — that “you are mounting a very robust immune response, and you will likely be protected as a result,” Dr. Klein said.

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But why do these sex differences happen? Part of the answer could be behavioral. It’s possible that women are more likely than men to report side effects even when their symptoms are the same, said Rosemary Morgan, an international health researcher at the Johns Hopkins Bloomberg School of Public Health. There’s no vaccine-specific research to support this claim, but men are less likely than women to see doctors when they are sick, so they may also be less likely to report side effects, she said.

Still, there’s no question that biology plays an important role. “The female immune response is distinct, in many ways, from the male immune response,” said Eleanor Fish, an immunologist at the University of Toronto.

Research has shown that, compared with their male counterparts, women and girls produce more — sometimes twice as many — infection-fighting antibodies in response to the vaccines for influenza, M.M.R., yellow fever, rabies, and hepatitis A and B. They often mount stronger responses from immune fighters called T cells, too, Ms. Gee noted. These differences are often most robust among younger adults, which “suggests a biological effect, possibly associated with reproductive hormones,” she said.

Sex hormones including estrogen, progesterone and testosterone can bind to the surface of immune cells and influence how they work. Exposure to estrogen causes immune cells to produce more antibodies in response to the flu vaccine, for example.

And testosterone, Dr. Klein said, “is kind of beautifully immunosuppressive.” The flu vaccine tends to be less protective in men with lots of testosterone compared with men with less of the sex hormone. Among other things, testosterone suppresses the body’s production of immune chemicals known as cytokines.

Genetic differences between men and women may also influence immunity. Many immune-related genes are on the X chromosome, of which women have two copies and men have only one. Historically, immunologists believed that only one X chromosome in women was turned on, and that the other was inactivated. But research now shows that 15 percent of genes escape this inactivation and are more highly expressed in women.

These robust immune responses help to explain why 80 percent of autoimmune diseases afflict women. “Women have greater immunity, whether it’s to ourselves, whether it’s to a vaccine antigen, whether it’s to a virus,” Dr. Klein said.

The size of a vaccine dose may also be important. Studies have shown that women absorb and metabolize drugs differently than men do, often needing lower doses for the same effect. But until the 1990s, drug and vaccine clinical trials largely excluded women. “The drug dosages that are recommended are historically based on clinical trials that involve male participants,” Dr. Morgan said.

Clinical trials today do include women. But in the trials for the new Covid vaccines, side effects were not sufficiently separated and analyzed by sex, Dr. Klein said. And they did not test whether lower doses might be just as effective for women but cause fewer side effects.

Until they do, Dr. Klein said, health care providers should talk to women about vaccine side effects so they are not scared by them. “I think that there is value to preparing women that they may experience more adverse reactions,” she said. “That is normal, and likely reflective of their immune system working.”

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