Barbara Sibley’s four New York restaurants had already weathered the city’s initial Covid-19 wave, the prevaccine surge last winter and this summer’s Delta spike when last weekend it finally happened: Fearing an outbreak and struggling with staffing after one of her workers got sick with Covid, she temporarily shut down one of her locations.
That was only the start of Ms. Sibley’s worries. She also had to weigh how long the employee, who was fully vaccinated, should isolate before returning to the job. And the messaging from public health experts was not clear-cut.
In the early days of the pandemic the Centers for Disease Control and Prevention recommended that most people who tested positive for the coronavirus isolate for 14 days. It later reduced its recommended isolation period to 10 days. But these policies were based on data from unvaccinated individuals and were implemented before the widespread availability of rapid tests. An increasing number of health and policy professionals now suggest that vaccinated people can end their isolation after five to seven days, so long as they are not symptomatic and they test negative.
On Thursday, the C.D.C. reduced, in some circumstances, the number of days it recommends that health care workers who test positive for the coronavirus isolate themselves, but it did not address other businesses.
said on Friday that fully vaccinated critical workers could return to work five days after testing positive, so long as they have no symptoms or their symptoms are resolving and they have had no fever for 72 hours. Those workers will also have to wear a mask, she said.
Omicron has intensified staffing shortages across industries, and the spike in cases has disrupted travel during the holidays, stranding thousands of customers and underscoring the economic toll of employees needing to isolate. Already, some economists are warning about the potential impact that shutdowns can have on consumer spending.
Delta Air Lines asked the C.D.C. on Tuesday to cut isolation time to five days for fully vaccinated people, warning that the current 10-day period may “significantly impact” operations. It was followed by JetBlue and Airlines for America, a trade group that represents eight airlines.
eliminated weekly testing for vaccinated players who are asymptomatic, with its chief medical officer saying the pandemic had reached a stage in which it’s unnecessary for vaccinated players to sit out if they feel healthy.
canceled performances through Christmas. CityMD, the privately owned urgent care clinic, temporarily shut 19 sites in New York and New Jersey because of staffing shortages. At least a dozen New York restaurants have temporarily closed in response to positive tests.
“I think lots of companies are looking at a lot of disruption in the next month and trying to put in policies right now, because they know their employees are going to get infected in very high numbers,” said Dr. Jha.
The United States might take direction from policy shifts abroad. Britain said on Wednesday that it was reducing to seven from 10 the days that people must isolate after showing Covid-19 symptoms.
After the British government lifted nearly all its pandemic restrictions in July, hundreds of thousands of workers were pinged by the National Health Service’s track-and-trace app and told to isolate because they had been exposed to the coronavirus. Businesses complained of being short-staffed, and economists said the “pingdemic” may have slowed economic growth in July.
In the United States, new tools to help manage through the pandemic are on the way.
The Food and Drug Administration this week authorized two pills to treat Covid, from Pfizer and Merck. Those treatments have been shown to stave off severe disease and have potential to reduce transmission of the virus, though supply of both pills, especially Pfizer’s, will be limited in the next few months.
President Biden said on Tuesday that he planned to invoke the Defense Production Act to buy and give away 500 million rapid antigen tests, a crucial tool in detecting transmissibility, though those tests will not be available for weeks or longer.
If a combination of the antiviral pills and rapid tests is able to get individuals back to work faster, “that’s a big economic point,” said Dr. Eric Topol, a professor of molecular medicine at Scripps Research.
Molly Moon Neitzel, who owns an ice cream business in Seattle with just over 100 employees, said she had kept guidelines for isolation conservative.
“I’m on the side of protecting people over getting them back to work right now,” she said, adding that if it were summer and her business were busier, she might consider a shorter isolation period. “It’s the slowest time of the year for an ice cream company, so that is in my favor.”
Some public health experts worry that if the C.D.C. shortens its guidelines on isolating, employers could pressure workers to get back before they’re fully recovered.
“What I don’t want to see happen is for this to be used as an excuse to force people to come back while they are unwell,” Dr. Ranney of Brown said.
And even with clearer guidelines, putting policies in place can be tricky. While some experts suggest different isolation rules for vaccinated and unvaccinated employees, some companies do not yet have a system for tracking which of their workers have gotten a vaccine. The question of whether the C.D.C. will change its definition of fully vaccinated to include booster shots adds another layer of complexity.
It’s not just sick employees who may have to stay home: Companies are also grappling with whether vaccinated workers should quarantine after exposure to someone with Covid-19, which C.D.C. guidelines do not require.
“It becomes a challenge for employers to choose between providing a safer environment and keeping staff intact, or going with the C.D.C. guidance,” said Karen Burke, an adviser at the Society for Human Resource Management.
But almost two years into the pandemic, that’s the position that employers continue to find themselves in, amid an ever-flowing cascade of new data, guidelines and considerations.
“Every moment, you’re making life or death decisions,” Ms. Sibley said. “That’s not what we signed up for.”
Moderna’s market value has nearly tripled this year to more than $120 billion. Two of its founders, as well as an early investor, this month made Forbes magazine’s list of the 400 richest people in the United States.
As the coronavirus spread in early 2020, Moderna raced to design its vaccine — which uses a new technology known as messenger RNA — and to plan a safety study. To manufacture the doses for that trial, the company received $900,000 from the nonprofit Coalition for Epidemic Preparedness Innovations.
The nonprofit group said Moderna had agreed to its “equitable access principles.” That meant, according to the coalition, that the vaccine would be “first available to populations when and where they are needed and at prices that are affordable to the populations at risk, especially low- and middle-income countries or to public sector entities that procure on their behalf.”
Moderna agreed in May to provide up to 34 million vaccine doses this year, plus up to 466 million doses in 2022, to Covax, the struggling United Nations-backed program to vaccinate the world’s poor. The company has not yet shipped any of those doses, according to a Covax spokesman, although Covax has distributed tens of millions of Moderna doses donated by the United States.
Mr. Bancel said that many more doses would have gone to Covax this year had the two parties reached a supply deal in 2020. Aurélia Nguyen, a Covax official, denied that, saying, “It became clear early on that the best we could expect was minimal doses in 2021.”
Late last year, the Tunisian government was hoping to order Moderna doses. Dr. Hechmi Louzir, who led Tunisia’s vaccine procurement efforts, didn’t know how to contact Moderna to begin talks and asked the U.S. Embassy in Tunisia for help, he said. Officials there contacted Moderna, he said, but nothing came of it.
“We were very interested in Moderna,” Dr. Louzir said. “We tried.”
Johnson & Johnson’s Covid vaccine was supposed to be one of Africa’s most important weapons against the coronavirus.
The New Jersey-based company agreed to sell enough of its inexpensive single-shot vaccine to eventually inoculate a third of the continent’s residents. And the vaccine would be produced in part by a South African manufacturer, raising hopes that those doses would quickly go to Africans.
That has not happened.
South Africa is still waiting to receive the overwhelming majority of the 31 million vaccine doses it ordered from Johnson & Johnson. It has administered only about two million Johnson & Johnson shots. That is a key reason that fewer than 7 percent of South Africans are fully vaccinated — and that the country was devastated by the Delta variant.
At the same time, Johnson & Johnson has been exporting millions of doses that were bottled and packaged in South Africa for distribution in Europe, according to executives at Johnson & Johnson and the South African manufacturer, Aspen Pharmacare, as well as South African government export records reviewed by The New York Times.
donated by the United States. But about four million of the country’s 60 million residents are fully vaccinated.
That left the population vulnerable when a third wave of cases crested over the country. At times in recent months, scores of Covid-19 patients at Helen Joseph Hospital in Johannesburg were waiting in the emergency department for a bed, and the hospital’s infrastructure struggled to sustain the huge volumes of oxygen being piped into patients’ lungs, said Dr. Jeremy Nel, an infectious-disease doctor there.
“The third wave, in terms of the amount of death we saw, was the most heartbreaking, because it was the most avoidable,” Dr. Nel said. “You see people by the dozens dying, all of whom are eligible for a vaccine and would’ve been among the first to get it.”
a United Nations-backed clearinghouse for vaccines that has fallen behind on deliveries. South Africa was slow to enter negotiations with manufacturers for its own doses. In January, a group of vaccine experts warned that the government’s “lack of foresight” could cause “the greatest man-made failure to protect the population since the AIDS pandemic.”
announced in November. Aspen’s facility in Gqeberha, on South Africa’s southern coast, was the first site in Africa to produce Covid vaccines. (Other companies subsequently announced plans to produce vaccines on the continent.)
Understand the State of Vaccine and Mask Mandates in the U.S.
Mask rules. The Centers for Disease Control and Prevention in July recommended that all Americans, regardless of vaccination status, wear masks in indoor public places within areas experiencing outbreaks, a reversal of the guidance it offered in May. See where the C.D.C. guidance would apply, and where states have instituted their own mask policies. The battle over masks has become contentious in some states, with some local leaders defying state bans.
Vaccine rules . . . and businesses.Private companies are increasingly mandating coronavirus vaccines for employees, with varying approaches. Such mandates are legally allowed and have been upheld in court challenges.
College and universities. More than 400 colleges and universities are requiring students to be vaccinated against Covid-19. Almost all are in states that voted for President Biden.
Schools. On Aug. 11, California announced that it would require teachers and staff of both public and private schools to be vaccinated or face regular testing, the first state in the nation to do so. A survey released in August found that many American parents of school-age children are opposed to mandated vaccines for students, but were more supportive of mask mandates for students, teachers and staff members who do not have their shots.
Hospitals and medical centers. Many hospitals and major health systems are requiring employees to get a Covid-19 vaccine, citing rising caseloads fueled by the Delta variant and stubbornly low vaccination rates in their communities, even within their work force.
New York. On Aug. 3, Mayor Bill de Blasio of New York announced that proof of vaccination would be required of workers and customers for indoor dining, gyms, performances and other indoor situations, becoming the first U.S. city to require vaccines for a broad range of activities. City hospital workers must also get a vaccine or be subjected to weekly testing. Similar rules are in place for New York State employees.
At the federal level. The Pentagon announced that it would seek to make coronavirus vaccinations mandatory for the country’s 1.3 million active-duty troops “no later” than the middle of September. President Biden announced that all civilian federal employees would have to be vaccinated against the coronavirus or submit to regular testing, social distancing, mask requirements and restrictions on most travel.
South African officials hailed Aspen’s involvement as indispensable.
Aspen “belongs to us as South Africans, and it is making lifesaving vaccines,” South Africa’s president, Cyril Ramaphosa, said during a visit to Aspen’s plant in March. He said he had pushed Johnson & Johnson to prioritize the doses made there for Africans.
“I want them now,” Mr. Ramaphosa added. “I’ve come to fetch our vaccines.”
results of a clinical trial suggested that the vaccine from AstraZeneca offered little protection from mild or moderate infections caused by the Beta variant that was circulating in South Africa.
Weeks later, Johnson & Johnson and the government signed a contract for 11 million doses. South Africa ordered another 20 million doses in April. That would be enough to vaccinate about half the country.
South Africa agreed to pay $10 per dose for the 11 million shots, according to the contract. That was the same price that the United Statespaid and slightly more than the $8.50 that the European Commission agreed to pay.The South African contract prohibited the government from banning exports of the vaccine, citing the need for doses to “move freely across national borders.”
introduced export controls this year to conserve scarce supplies. India halted exports produced by the Serum Institute, which was supposed to be a major vaccine supplier to poor countries. In the United States, officials said they didn’t ban exports, but they didn’t need to. The combination of the extensive vaccine production on American soil and the high prices the U.S. government was willing to pay meant that companies made the delivery of shots for Americans a priority.
Other benefits for Johnson & Johnson were embedded in the South African contract.
While such contracts typically protect companies from lawsuits brought by individuals, this one shielded Johnson & Johnson from suits by a wider range of parties, including the government. It also imposed an unusually high burden on potential litigants to show that any injuries caused by the vaccine were the direct result of company representatives engaging in deliberate misconduct or failing to follow manufacturing best practices.
“The upshot is that you have moved almost all of the risk of something being wrong with the vaccine to the government,” said Sam Halabi, a health law expert at Georgetown University who reviewed sections of the South African contract at the request of The Times.
Mr. Halabi said the contract’s terms appeared more favorable to the pharmaceutical company than other Covid vaccine contracts he had seen. South African officials have said Pfizer, too, sought aggressive legal protections.
The contract said Johnson & Johnson would aim to deliver 2.8 million doses to South Africa by the end of June, another 4.1 million doses by the end of September and another 4.1 million doses by the end of December. (The government expects the 20 million additional doses to be delivered by the end of this year, Mr. Maja said.)
The company has so far fallen far short of those goals. As of the end of June, South Africa had received only about 1.5 million of the doses from its order. The small number of doses that have been delivered to the African Union were on schedule.
The difficulties in procuring doses have revealed the limits of fill-and-finish sites, which leave countries dependent on vaccines from places like the European Union or the United States, said Dr. Salim Abdool Karim, who until March was co-chairman of South Africa’s ministerial advisory committee on Covid.
“Ultimately,” he said, “the solution to our problem has to be in making our own vaccines.”
Lynsey Chutel and Choe Sang-Hun contributed reporting.
In delivering vaccines, pharmaceutical companies aided by monumental government investments have given humanity a miraculous shot at liberation from the worst pandemic in a century.
But wealthy countries have captured an overwhelming share of the benefit. Only 0.3 percent of the vaccine doses administered globally have been given in the 29 poorest countries, home to about 9 percent of the world’s population.
Vaccine manufacturers assert that a fix is already at hand as they aggressively expand production lines and contract with counterparts around the world to yield billions of additional doses. Each month, 400 million to 500 million doses of the vaccines from Moderna, Pfizer and Johnson & Johnson are now being produced, according to an American official with knowledge of global supply.
But the world is nowhere close to having enough. About 11 billion shots are needed to vaccinate 70 percent of the world’s population, the rough threshold needed for herd immunity, researchers at Duke University estimate. Yet, so far, only a small fraction of that has been produced. While global production is difficult to measure, the analytics firm Airfinity estimates the total so far at 1.7 billion doses.
dangerous new variants emerge, requiring booster shots and reformulated vaccines, demand could dramatically increase, intensifying the imperative for every country to lock up supply for its own people.
The only way around the zero-sum competition for doses is to greatly expand the global supply of vaccines. On that point, nearly everyone agrees.
But what is the fastest way to make that happen? On that question, divisions remain stark, undermining collective efforts to end the pandemic.
Some health experts argue that the only way to avert catastrophe is to force drug giants to relax their grip on their secrets and enlist many more manufacturers in making vaccines. In place of the existing arrangement — in which drug companies set up partnerships on their terms, while setting the prices of their vaccines — world leaders could compel or persuade the industry to cooperate with more companies to yield additional doses at rates affordable to poor countries.
Those advocating such intervention have focused on two primary approaches: waiving patents to allow many more manufacturers to copy existing vaccines, and requiring the pharmaceutical companies to transfer their technology — that is, help other manufacturers learn to replicate their products.
more than 100 countries in asking the W.T.O. to partially set aside vaccine patents.
But the European Union has signaled its intent to oppose waivers and support only voluntary tech transfers, essentially taking the same position as the pharmaceutical industry, whose aggressive lobbying has heavily shaped the rules in its favor.
Some experts warn that revoking intellectual property rules could disrupt the industry, slowing its efforts to deliver vaccines — like reorganizing the fire department amid an inferno.
“We need them to scale up and deliver,” said Simon J. Evenett, an expert on trade and economic development at the University of St. Gallen in Switzerland. “We have this huge production ramp up. Nothing should get in the way to threaten it.”
Others counter that trusting the pharmaceutical industry to provide the world with vaccines helped create the current chasm between vaccine haves and have-nots.
The world should not put poorer countries “in this position of essentially having to go begging, or waiting for donations of small amounts of vaccine,” said Dr. Chris Beyrer, senior scientific liaison to the Covid-19 Prevention Network. “The model of charity is, I think, an unacceptable model.”
halting vaccine exports a month ago. Now, as a wave of death ravages the largely unvaccinated Indian population, the government is drawing fire at home for having let go of doses.
poses universal risks by allowing variants to take hold, forcing the world into an endless cycle of pharmaceutical catch-up.
“It needs to be global leaders functioning as a unit, to say that vaccine is a form of global security,” said Dr. Rebecca Weintraub, a global health expert at Harvard Medical School. She suggested that the G7, the group of leading economies, could lead such a campaign and finance it when the members convene in England next month.
Pfizer expects to sell $26 billion worth of Covid vaccines this year; Moderna forecasts that its sales of Covid vaccines will exceed $19 billion for 2021.
History also challenges industry claims that blanket global patent rights are a requirement for the creation of new medicines. Until the mid-1990s, drug makers could patent their products only in the wealthiest markets, while negotiating licenses that allowed companies in other parts of the world to make generic versions.
Even in that era, drug companies continued to innovate. And they continued to prosper even with the later waivers on H.I.V. drugs.
“At the time, it rattled a lot of people, like ‘How could you do that? It’s going to destroy the pharmaceutical industry,’” recalled Dr. Anthony S. Fauci, President Biden’s chief medical adviser for the pandemic. “It didn’t destroy them at all. They continue to make billions of dollars.”
Leaders in the wealthiest Western nations have endorsed more equitable distribution of vaccines for this latest scourge. But the imperative to ensure ample supplies for their own nations has won out as the virus killed hundreds of thousands of their own people, devastated economies, and sowed despair.
The drug companies have also promised more support for poorer nations. AstraZeneca’s vaccine has been the primary supply for Covax, and the company says it has sold its doses at a nonprofit price.
stumbled, falling short of production targets. And producing the new class of mRNA vaccines, like those from Pfizer-BioNTech and Moderna, is complicated.
Where pharmaceutical companies have struck deals with partners, the pace of production has frequently disappointed.
“Even with voluntary licensing and technology transfer, it’s not easy to make complex vaccines,” said Dr. Krishna Udayakumar, director of the Duke Global Health Innovation Center.
Much of the global capacity for vaccine manufacturing is already being used to produce other lifesaving inoculations, he added.
But other health experts accuse major pharmaceutical companies of exaggerating the manufacturing challenges to protect their monopoly power, and implying that developing countries lack the acumen to master sophisticated techniques is “an offensive and a racist notion,” said Matthew Kavanagh, director of the Global Health Policy and Politics Initiative at Georgetown University.
With no clear path forward, Ms. Okonjo-Iweala, the W.T.O. director-general, expressed hope that the Indian and South African patent-waiver proposal can be a starting point for dialogue.
“I believe we can come to a pragmatic outcome,” she said. “The disparity is just too much.”
Peter S. Goodman reported from London, Apoorva Mandavilli from New York, Rebecca Robbins from Bellingham, Wash., and Matina Stevis-Gridneff from Brussels. Noah Weiland contributed reporting from New York.
The vaccines produced similar responses in all three groups of women, eliciting both antibody and T-cell responses against the coronavirus, the scientists found. Of particular note, experts said, was the fact that the shots produced high levels of neutralizing antibodies, which can prevent the virus from entering cells, in both pregnant and nonpregnant women.
“Clearly, the vaccines were working in these people,” said Akiko Iwasaki, an immunologist at Yale University who was not involved in the research. “These levels are expected to be quite protective.”
The researchers also found neutralizing antibodies in the breast milk of vaccinated mothers and in umbilical cord blood collected from infants at delivery. “Vaccination of pregnant people and lactating people actually leads to transfer of some immunity to their newborns and lactating infants,” said Dr. Ai-ris Y. Collier, a physician-scientist at Beth Israel who is the first author of the paper.
The results are “really encouraging,” Dr. Iwasaki said. “There is this added benefit of conferring protective antibodies to the newborn and the fetus, which is all the more reason to get vaccinated.”
The scientists also measured the women’s immune responses to two variants of concern: B.1.1.7, which was first identified in Britain, and B.1.351, which was first identified in South Africa. All three groups of women produced antibody and T-cell responses to both variants after vaccination, although their antibody responses were weaker against the variants, especially B.1.351, than against the original strain of the virus, according to the study.
“These women developed immune responses to the variants, although the asterisk is that the antibody responses were reduced several-fold,” said Dr. Dan Barouch, a study author and virologist at Beth Israel.(Dr. Barouch and his colleagues developed the Johnson & Johnson vaccine, which was not included in this study.)
“Overall, it’s good news,” he added. “And it increases the data that suggests that there is a substantial benefit for pregnant women to be vaccinated.”
Not all teenagers long for the vaccine. Many hate getting shots. Others say that because young people often get milder cases of Covid, why risk a new vaccine?
Patsy Stinchfield, a nurse practitioner who oversees vaccination for Children’s Minnesota, has stark evidence that some cases in young people can be serious. Not only have more children with Covid been admitted to the hospital recently, but its intensive care unit also has Covid patients who are 13, 15, 16 and 17 years old.
The F.D.A.’s new authorization means all those patients would be eligible for the shots, she noted. “If you can prevent your child ending up in the I.C.U. with a safe vaccine, why wouldn’t you ?” she said.
Mr. Quesnel, the East Hartford, Conn., superintendent, said the most powerful message for reaching older adolescents would probably appeal just as much to younger ones. Rather than focusing on the fact that the shot will protect them, he said, they seize on the idea that it will keep them from having to quarantine if they are exposed.
“They’re not so afraid of the health care dangers from Covid but the social losses that come along with it,” he said, adding that 60 percent of his district’s seniors, or about 300 students, got their first dose at a mass vaccination site run by Community Health Center on April 26. “Some of our greatest leverage right now is that social component — ‘You won’t be quarantined.’”
Michael Jackson of North Port, Fla., can’t wait for his 14-year-old son, Devin, to get the vaccine. During the past year, he said, his son’s beloved Little League games went on hiatus and the family had to suspend their regular Sunday suppers with grandparents And Devin, an eighth grader, had to quarantine three times after being exposed to Covid.
Millions of Americans are not getting the second doses of their Covid-19 vaccines, and their ranks are growing.
More than five million people, or nearly 8 percent of those who got a first shot of the Pfizer or Moderna vaccines, have missed their second doses, according to the most recent data from the Centers for Disease Control and Prevention. That is more than double the rate among people who got inoculated in the first several weeks of the nationwide vaccine campaign.
Even as the country wrestles with the problem of millions of people who are wary about getting vaccinated at all, local health authorities are confronting an emerging challenge of ensuring that those who do get inoculated are doing so fully.
The reasons vary for why people are missing their second shots. In interviews, some said they feared the side effects, which can include flulike symptoms. Others said they felt that they were sufficiently protected with a single shot.
Walgreens, one of the biggest vaccine providers, sent some people who got a first shot of the Pfizer or Moderna vaccine to get their second doses at pharmacies that only had the other vaccine on hand.
Several Walgreens customers said in interviews that they scrambled, in some cases with help from pharmacy staff, to find somewhere to get the correct second dose. Others, presumably, simply gave up.
voted to recommend lifting a pause on the Johnson & Johnson Covid vaccine and adding a label about an exceedingly uncommon but potentially dangerous blood clotting disorder.
Federal health officials are expected to formally recommend that states lift the pause.
Administration of the vaccine ground to a halt recently after reports emerged of a rare blood clotting disorder in six women who had received the vaccine.
The overall risk of developing the disorder is extremely low. Women between 30 and 39 appear to be at greatest risk, with 11.8 cases per million doses given. There have been seven cases per million doses among women between 18 and 49.
Nearly eight million doses of the vaccine have now been administered. Among men and women who are 50 or over, there has been less than one case per million doses.
Johnson & Johnson had also decided to delay the rollout of its vaccine in Europe amid similar concerns, but it later decided to resume its campaign after the European Union’s drug regulator said a warning label should be added. South Africa, devastated by a more contagious virus variant that emerged there, also suspended use of the vaccine but later moved forward with it.
In Arkansas and Illinois, health officials have directed teams to call, text or send letters to people to remind them to get their second shots. In Pennsylvania, officials are trying to ensure that college students can get their second shots after they leave campus for the summer. South Carolina has allocated several thousand doses specifically for people who are overdue for their second shot.
recommended restarting use of the vaccine, but the combination of the safety scare and ongoing production problems is likely to make that vaccine a viable option for fewer people.
The C.D.C.’s count of missed second doses is through April 9. It covers only people who got a first Moderna dose by March 7 or a first Pfizer dose by March 14.
Roughly three-quarters of adults come back for their second dose of the vaccine that protects against shingles.
In some cases, problems with shipments or scheduling may be playing a role in people missing their second doses. Some vaccine providers have had to cancel appointments because they did not receive expected vaccine deliveries. People have also reported having their second-dose appointments canceled or showing up only to find out that there were no doses available of the brand they needed.
Some people can be flexible about being rebooked. But that’s harder for people who lack access to reliable transportation or who have jobs with strictly scheduled hours, said Elena Cyrus, an infectious disease epidemiologist at the University of Central Florida.
Walgreens booked some customers for their second appointments at places that didn’t have the same vaccine that they had received for their initial doses. The company said it fixed the problem in late March.
come under fire for, until recently, scheduling second doses of the Pfizer vaccine four weeks after the first shot, rather than the three-week gap recommended by the C.D.C. Pharmacists have been besieged by customers complaining, including about their inability to book vaccine appointments online.
In other cases, though, access to vaccines is not the sole barrier; people’s attitudes contribute, too.
Basith Syed, a 24-year-old consultant in Chicago, nabbed a leftover Moderna vaccine at a Walgreens in mid-February. But when the time came for his second shot, he was busy at work and preparing for his wedding. After the first shot, he had spent two days feeling drained. He didn’t want to risk a repeat, and he felt confident that a single dose would protect him.
C.D.C. says there is limited data on the vaccine’s effectiveness when shots are separated by more than six weeks, although some countries, including Britain and Canada, are giving shots with a gap of up to three or four months.
Mr. Syed’s experience is part of a broader shift in Illinois. When vaccines were mostly being given to health care workers, residents of long-term care facilities and people over 65, almost everyone was getting their second shots. In recent weeks, though, the number dipped below 90 percent, though it has since rebounded slightly, according to the Illinois Department of Public Health.
In Arkansas, about 84,000 people have missed their second shots, representing 11 percent of those eligible for those shots, said Dr. Jennifer Dillaha, the state epidemiologist. Workers recently began calling people who are due or overdue for their second shots.
College students pose a particular challenge. Many recently became eligible to be vaccinated and are getting their first shots, but they will have left campus by the time they are due for their second doses.
In Pennsylvania, health officials have instructed vaccine providers to give second doses to college students even if they did not receive their first doses from that location.
Some vaccine providers have put on special clinics for people who need a second dose. In South Carolina, the health system Tidelands Health started a program specifically for people who received their first Pfizer doses more than 23 days earlier but hadn’t been able to find a second shot. The state health department sent the health system 2,340 doses for the effort.
Demand has been strong, and Tidelands only has a few hundred doses left. The majority of takers have been people who “were having difficulty navigating all the various scheduling systems and providers,” said Gayle Resetar, the health system’s chief operating officer.
In many cases, vaccine providers had canceled second-dose appointments because of bad winter weather. “It was up to the individual to reschedule themselves on a web portal or web platform, and that just became difficult for people,” Ms. Resetar said.
There are rare cases in which people are supposed to forgo the second shot, such as if they had an allergic reaction after their first shot.
Zvi Ish-Shalom, a religious studies professor from Boulder, Colo., had planned to get fully vaccinated. Then, an hour after his first shot of the Moderna vaccine, he developed a headache that hasn’t gone away more than a month later.
There is no way to know for sure whether the vaccine triggered the headache. But after weighing what he saw as the risks and benefits of a second dose, Dr. Ish-Shalom reached a decision about how to proceed.
“At this point in time, I feel very clear and very comfortable, given all the various elements of this equation, to forgo the second shot,” he said.
For weeks, New Yorkers have witnessed the alarming rise of a homegrown variant of the coronavirus that has kept the number of cases in the city stubbornly high. City officials have repeatedly warned that the variant may be more contagious and may dodge the immune response.
On that second point, at least, they can now breathe easier: Both the Pfizer-BioNTech and Moderna vaccines will effectively prevent serious illness and death from the variant, two independent studies suggest.
Antibodies stimulated by those vaccines are only slightly less potent at controlling the variant than the original form of the virus, both studies found.
“We’re not seeing big differences,” said Michel Nussenzweig, an immunologist at Rockefeller University in New York and a member of the team that published one of the studies on Thursday.
possible explanation: Antibodies from vaccinated people are distributed across a broader range of parts of the virus, so no single mutation has a big impact on their effectiveness — making vaccines a better bet against variants than immunity from natural infection.
The variant first identified in New York, known to scientists as B.1.526, raced through the city after its initial discovery in November. It accounted for one in four diagnosed cases by November and nearly half of cases as of April 13. The variant that brought Britain to a standstill, B.1.1.7, is also circulating widely in New York. Together, the two add up to more than 70 percent of coronavirus cases in the city.
second study, Dr. Landau’s team found that the Pfizer and Moderna vaccines are only marginally less protective against the variant that devastated Britain and against forms of the variant discovered in New York that don’t contain the Eek mutation.
Several laboratory studies have shown that antibodies induced by the Pfizer and Moderna vaccines are slightly less powerful against a third variant, one identified in South Africa, which also contains Eek. Other vaccines fared worse. South Africa suspended use of the AstraZeneca vaccine after clinical trials showed that the vaccine did not prevent mild or moderate illness from the variant that was circulating there.
“It already started out as a lower level in terms of the immunity that it generated,” Dr. Nussenzweig said of the AstraZeneca vaccine. Referring to the Pfizer and Moderna shots, he said, “We’re so lucky in this country to have these vaccines compared to the rest of the world.”
Florian Krammer, an immunologist at the Icahn School of Medicine at Mount Sinai who was not involved in either of the new studies, said he was more concerned about other countries’ vaccine programs than about the variants themselves.
“I am less concerned about variants than I was two months ago,” he said, but added: “I’m worried about countries that don’t have enough vaccine and that don’t have that vaccine rollout. I’m not worried anymore about the U.S., honestly.”
Dr. Landau’s team also tested monoclonal antibodies used to treat Covid-19 against the variants. They found that the cocktail of monoclonal antibodies made by Regeneron worked as well against the variant discovered in New York as against the original virus.
The studies are reassuring, but they indicate that the Eek mutation is one to watch, said Jesse Bloom, an evolutionary biologist at the Fred Hutchinson Cancer Research Center in Seattle.
“This could certainly be a step toward the virus becoming somewhat more resistant to infection- and vaccine-mediated immunity,” Dr. Bloom said. “I don’t think it’s something that people need to immediately become alarmed about, but it definitely impresses us as important.”
Dr. Bloom led the analysis comparing vaccine-induced antibodies with those produced by natural infection. He found that the most powerful antibodies bind to multiple sites in a key part of the virus. Even if a mutation affects the binding in one site in this region, antibodies that target the remaining sites would still be protective.
Antibodies induced by the vaccine cover many more sites across this region than those from natural infection — and so are less likely to be affected by a mutation in any one site.
The study looked only at antibodies stimulated by the Moderna vaccine, but the results are likely to be the same for the Pfizer-BioNTech vaccine, he added.
“This could potentially be a good thing as the virus is creating mutations,” Dr. Bloom said.
Walgreens’s system currently allows people to rebook their second-dose appointment, but they can do so only the day before the appointment.
“I’m not happy about it,” Ms. DeTurris Poust said. “It gives me one extra week of not being protected, so it means there’s one more week that I’m worried about catching it from someone, or giving it to someone.”
Some public health experts said they were not concerned that Walgreens has been scheduling doses with a four-week gap.
“It’s a week difference. Everybody’s going to need to put it in their contexts and their risk factors, but I think this is a very reasonable approach” from Walgreens, said Dr. Katherine Poehling, a pediatrician at Wake Forest School of Medicine who sits on the C.D.C. advisory panel that recommended that Pfizer doses be given roughly three weeks apart.
But other experts said they were troubled.
“It is not the role of a private, for-profit company to make public health decisions that should be determined by guidelines issued by a public health authority,” said Lawrence Gostin, a global health law professor at Georgetown University.
Dima Qato, a pharmacist and associate professor at the University of Southern California School of Pharmacy, said she was concerned about how the public perceives inconsistent messages about spacing doses of the same vaccine.
“As we’re trying to build trust in this pandemic, I think this may push us back,” Dr. Qato said.
Walgreens is not the only vaccine provider that has been giving second shots slightly later than recommended. Others around the country have been doing so for months, especially in the early days of the rollout when vaccine supply was constrained and sites had little clarity about which vaccines and how many doses they would be receiving in subsequent weeks, said Tinglong Dai, who studies health care operations at Johns Hopkins University.
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.
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.
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.
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.
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.”
