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A New York City police officer in Manhattan.Credit...Benjamin Norman for The New York Times

One of the most aggressive vaccine mandates in the nation is set to take effect Friday evening in New York City, and it is expected to bring a flurry of last-minute legal wrangling, protests and possibly force some city services to be curtailed.

Similar mandates in Texas, Florida and other municipalities have been met with a barrage of court challenges and opposition from lawmakers.

Though some of New York City’s more than 300,000 employees were already covered by earlier mandates, Mayor Bill de Blasio announced last week that “all city workers” needed to get at least one vaccine dose by 5 p.m. Friday, or they would face unpaid leave.

Most city workers have been vaccinated, but about 46,000 had not been as of last week, officials said. The highest percentage of unvaccinated employees is in the city’s Department of Corrections, where only half of the workers had been vaccinated.

More than a quarter of employees in other crucial departments — emergency medical services, fire, police and sanitation — remained unvaccinated as of last week.

Mr. de Blasio’s announcement of the mandates was met with protests and lawsuits.

On Monday, thousands of people, including police officers, firefighters and sanitation workers, marched across the Brooklyn Bridge, holding large American flags and chanting that they would not comply.

The city’s largest police union, the Police Benevolent Association, filed a lawsuit on Monday to halt the mandate, but a New York State judge on Wednesday denied the request.

The police union said it would appeal, and has previously instructed members on how to undermine City Hall edicts. Patrick J. Lynch, the president of the police union, said in a statement, “Today’s ruling sets the city up for a real crisis.”

Andrew Ansbro, the president of the Uniformed Firefighters Association, said recently that he had ordered his unvaccinated members to report to work and defy the mandate, Reuters reported. But the city’s fire commissioner said he expects about a 20 percent staffing reduction at firehouses and in ambulances because of the mandate, Gothamist reported.

Workers who do not show proof of vaccination by 5 p.m. Friday will be put on unpaid leave as of Monday. Requests for medical or religious exemptions were due on Wednesday, and workers who applied for those exemptions will be permitted to work if they undergo weekly testing while their cases are considered.

Because of a severe staffing shortage on Rikers Island, the city made an exception for uniformed corrections officers, giving them until Dec. 1 to get their first dose. The city’s health care workers and education department employees were already required to be vaccinated under earlier mandates.

Mr. de Blasio said Wednesday the city had been preparing for the possibility of staff shortages and predicted that almost all workers would ultimately get vaccinated rather than lose their paychecks.

“These are agencies that have been preparing for months,” Mr. de Blasio said. “Every one of the commissioners has been absolutely confident that they can make the adjustments and every one of the commissioners has adamantly wanted us to move forward with a vaccine mandate. So, I feel ready.”

A large clinical trial has found that a common and inexpensive antidepressant lowered the odds that high-risk Covid-19 patients would be hospitalized. The results, published on Wednesday, could open the door to new guidelines for the drug’s use both in the United States and globally.

The drug, fluvoxamine, has been safely prescribed for nearly 30 years as a treatment for obsessive-compulsive disorder. But when the coronavirus started spreading, researchers were drawn to the medication because of its ability to reduce inflammation, potentially allowing it to quell the body’s overwhelming response to a coronavirus infection.

Several smaller studies of fluvoxamine earlier in the pandemic showed promising results, but none was as large or persuasive as the one published on Wednesday by a group of researchers in Canada, the United States and Brazil, outside scientists said. Among nearly 1,500 Covid patients in Brazil given either fluvoxamine or a placebo, the drug reduced the need for hospitalization or prolonged medical observation by one-third, the study found. It was published in The Lancet Global Health.

Some patients struggled to tolerate the drug and stopped taking it, the study said, raising a question among outside scientists about whether they had yet identified the ideal dose. But among those who had largely followed doctors’ orders, the benefits were even more striking. In those patients, the drug reduced the need for hospitalization by two-thirds and slashed the risk of dying: One Covid patient given fluvoxamine died, compared with 12 given a placebo.

“That’s really good,” said Dr. David Boulware, an infectious disease scientist at the University of Minnesota who worked on a smaller, real-world study of the drug in Covid patients in California. Plus, he added, “it’s not a shiny new, expensive drug. The nice thing about this is it has a known safety profile.”

Beyond proper dosing, the study left other questions unresolved, scientists said. Penny Ward, a visiting professor in pharmaceutical medicine at King’s College London, noted that part of the drug’s benefit appeared to come from reducing the need for extended medical observation, which the study tracked alongside hospital admissions. And most patients in the study were unvaccinated, Professor Ward said, so it’s unclear how well the drug would work in the vaccinated.

The new study, coming nearly a year after smaller trials of the drug, was a reminder of the difficulty that many researchers have had running large tests of Covid treatments. The Biden administration has made more funding available for such trials, scientists said, but enrolling enough patients has only gotten more difficult: Most high-risk Americans are vaccinated, and vaccine-averse people may be less likely to participate in trials.

Because fluvoxamine is already approved for treating O.C.D., doctors can already prescribe it “off label” for Covid. But Dr. Boulware said that prescriptions of the drug had increased only slightly during the pandemic, unlike other repurposed drugs with far less scientific support, like hydroxychloroquine and ivermectin.

“It hasn’t really gotten any cult following,” he said.

Federal treatment guidelines say that larger trials are necessary to evaluate the use of fluvoxamine for Covid, and scientists said they expected those recommendations to change on the basis of the new study.

The new findings are also expected to boost the popularity of the drug in less wealthy countries: A 10-day course of the drug costs about $4.

Some American adults with weakened immune systems who received a third dose of either the Pfizer-BioNTech or Moderna coronavirus vaccine authorized just for them will become eligible for a fourth shot as a booster next year, according to updated guidelines from the Centers for Disease Control and Prevention.

“In such situations, people who are moderately and severely immunocompromised may receive a total of four vaccine doses,” with the fourth coming at least six months after the third, the C.D.C.’s guidelines said.

In August, federal regulators cleared a third dose of the Pfizer-BioNTech and Moderna vaccines for some immunocompromised recipients of those vaccines, instructing them to get it at least 28 days after their second shot. Federal agencies said that studies have shown that those people may not be adequately protected by just two shots.

The earliest that immunocompromised people who received that third mRNA vaccine shot can get a fourth shot as a booster would be February. The agency said that people could select that booster from any of the three coronavirus vaccines available in the United States.

The C.D.C. also recommends that moderately and severely immunocompromised adults who received Johnson & Johnson’s one-dose vaccine get another dose of any one of the three vaccine brands, at least two months after their initial shot.

The agency updated its guidelines on Monday, adding the possibility of a booster dose for many immunocompromised people, including those undergoing chemotherapy, recovering from a solid organ transplant or facing certain other medical issues, like infection with H.I.V.

The new recommendations also specified that a fourth dose of Moderna’s vaccine should be half the size of a normal dose.

Many health officials and experts in the United States and other countries have made a distinction between additional shots for immunocompromised people, who may not have mounted a strong immune response after their initial doses, and broader booster programs intended to shore up other peoples’ immunity, which can wane against infection naturally over time.

The World Health Organization has supported additional doses for people with weakened immune systems while calling for a global moratorium until the end of the year on booster programs for otherwise healthy people, so that more doses can be allocated to lower-income countries with low rates of vaccination.

The call for a moratorium has not stopped countries like Israel, the United States and Germany from moving ahead with booster programs.

Gov. Kay Ivey of Alabama issued an executive order this week directing state agencies to not cooperate, whenever possible, with federal vaccine mandates, describing the Biden administration’s actions as an “overreach.”

The governor’s directive comes as some Republican governors across the country, playing to their conservative bases, have taken actions aimed at countering President Biden’s attempt to raise the country’s overall vaccination rate through expansive mandates.

The White House has issued an order requiring all federal employees, workers for federal contractors, and people who work for health care companies receiving Medicare and Medicaid to be vaccinated. The administration also has plans to ask companies with more than 100 workers to adopt vaccine mandates or weekly testing.

The federal mandates, along with masks in schools, are unpopular among conservatives, many of whom see them as an infringement on personal freedoms, and Republican elected officials in some states have sought to capitalize on that sentiment.

“Alabamians are overwhelmingly opposed to these outrageous Biden mandates, and I stand with them,” Ms. Ivey said in a statement.

In Texas, the Republican governor, Greg Abbott, issued a broad executive order that bars virtually any coronavirus vaccine mandate in the state. And in Florida, Gov. Ron DeSantis, who is seen as a possible G.O.P. presidential contender, has adamantly opposed any measures that would require vaccines or masks, saying they infringe on personal liberties.

Ms. Ivey’s order says state agencies should prepare to assist with a lawsuit that the Alabama attorney general is expected to file challenging the federal mandate.

Legal experts say the federal government has broad authority to address the public health crisis created by the pandemic, and Mr. Biden has predicted that his health orders will survive legal challenges.

Beyond political symbolism, the impact of Ms. Ivey’s order is unclear. It directs state agencies not to punish businesses and people who do not comply with the federal vaccine mandate. It also states that if an agency is required to enforce the federal mandate, employees should inform those businesses or individuals that the state “does not approve, condone or otherwise endorse” such mandates.

“The federal government’s outrageous overreach has simply given us no other option but to begin taking action, which is why I am issuing this executive order to fight these egregious Covid-19 vaccine mandates,” Ms. Ivey said in a statement.

Ms. Ivey has walked a fine line on the issue of vaccinations. During the summer, she expressed frustration over unvaccinated people’s refusal to get a shot, saying that it was “time to start blaming the unvaccinated folks, not the regular folks.”

“It’s the unvaccinated folks that are letting us down,” she told reporters in July.

Still, Ms. Ivey said that she is “adamantly” opposed to issuing her own vaccine mandate in the state, adding that she believed the way to increase vaccination rates was through “persuasion.”

Pregnant and breastfeeding women respond to the first dose of the coronavirus vaccines more slowly than other women, and mount a less potent defense against the virus, according to a new study. After the second dose, however, their response looks almost normal.

The results, published this month in the journal Science Translational Medicine, suggest that pregnant and breastfeeding women remain susceptible to the virus for longer after vaccination. The study underscores the importance of giving these women the second dose in time, and monitoring them closely in the meantime for signs of infection.

During pregnancy, the immune system is modified to tolerate the fetus — effectively a foreign entity — leaving pregnant women particularly susceptible to pathogens like the coronavirus. Because of this, pregnant women are more likely to become severely ill and to die from Covid than other women of the same age.

Earlier research had suggested that pregnancy might also dampen the response to vaccines. But the initial trials of Covid vaccines did not include pregnant and breastfeeding women because of safety concerns, so there has been limited information about how well they respond to the inoculations.

The researchers analyzed the antibodies produced by 84 pregnant women, 31 breastfeeding women and 16 nonpregnant women of the same ages, immunized with the coronavirus vaccines made by Pfizer-BioNTech or Moderna.

After the first dose, pregnant and breastfeeding women had fewer antibodies than other women of the same age. And the antibodies were less effective at recruiting other parts of the immune system to fight the virus.

Two to six weeks after the second dose, pregnant and breastfeeding women had about as many antibodies as other women their age, consistent with results from other studies, and the qualitative differences also narrowed.

Breastfeeding women boosted their response more effectively than pregnant women after the second dose, and the quality of their immune response more closely resembled that of nonpregnant women.

The women in the study were immunized at different times during pregnancy. Future studies should analyze the optimal time during pregnancy to deliver the vaccines, the researchers said.

An experiment in Ukraine that pursued an aggressive campaign to vaccinate most inhabitants of one small town has yielded the expected results: very low infection rates and no hospitalizations for Covid-19.

In April, when Ukraine was still short on vaccines, only certain categories of the population, like teachers and doctors, were allowed to get vaccinations. But the Health Ministry made an exception for the town of Morshyn, in western Ukraine, allowing local health authorities to attempt to vaccinate all 6,000 residents.

Morshyn was chosen partly because its economy, which depends on tourism to resorts and spas, had essentially shut down because of the pandemic, and because it was thought people would be receptive to vaccination so they could resume working.

The plan was to give 70 percent of the town a first dose of vaccine in one month. But despite the economic incentive, distrust in vaccines was an obstacle. Nationwide, 56 percent of Ukrainians still say they will not be vaccinated.

Morshyn’s authorities went on the offensive.

“We realized that we need to call each person individually,” Dr. Henadiy Yukshynsky, the town’s chief doctor, said in an interview with local media. “We created five special teams that called people and explained to everyone the need for vaccination.”

The local authorities posted billboards, set up tents with information tables inside, made videos for social networks and the news media, and created handouts advocating vaccination.

In the end, it took two months to vaccinate 72 percent of the town’s residents, far more than Ukraine’s nationwide rate of 16 percent, which is the lowest in Europe.

Across the country, infections and hospitalizations are soaring, with an average of 21,364 new cases a day over the past week. The death rate in Ukraine is higher now than during the first wave of Covid-19, with an average of 538 deaths per day. Panic is beginning to take hold, and more areas of the country have been designated “red zones” and placed under partial lockdown.

But life in Morshyn goes on as usual. It has no patients hospitalized with Covid-19 and only 19 cases of the virus, 15 of them in people who were not vaccinated.

The health minister of Australia announced on Wednesday that fully vaccinated residents would finally be allowed to travel abroad starting on Nov. 1, a year and a half after borders were closed to most ingoing and outgoing travel.

“Fully vaccinated Australians will not require an exemption to depart Australia,” Greg Hunt, the country’s health minister, told reporters in Canberra. He added that they would also be able to return without restrictions.

The eased restrictions will be the first stage in Australia’s plan to reopen its international borders since slamming them shut on March 20, 2020, separating families and leaving thousands of Australians stranded overseas.

The second stage, Mr. Hunt said, will allow students and critical workers to enter the country and, eventually, see borders fully reopened to tourists and other visitors.

“It’s exciting,” said Kelsey May, 25, an Australian who returned home from Britain in March of 2020, and has been separated from her partner since. But, Ms. May added: “We’ve been told so many things over the past 18 months that haven’t come to fruition. We just want to see what happens.”

On Monday, the health authorities also approved Pfizer-BioNTech vaccine booster shots for those 18 and older. They said the decision would make the country among the most highly vaccinated places in the world.

Nationwide, 62 percent of eligible Australians have had two doses of the vaccine, and 74 percent have had one dose.

But Canberra, the capital, announced it had become the first jurisdiction in the country to fully vaccinate more than 90 percent of eligible residents age 12 and older.

Merck has granted a royalty-free license for its promising Covid-19 pill to a United Nations-backed nonprofit group in a deal that would allow the drug to be manufactured and sold cheaply in the poorest nations, where vaccines for the coronavirus are in devastatingly short supply.

The agreement with the organization, Medicines Patent Pool — which works to make medical treatment and technologies globally accessible — will allow companies in 105 countries, mostly in Africa and Asia, to sublicense the formulation for the antiviral pill, called molnupiravir, and begin making it.

Merck reported this month that the drug halved the rate of hospitalizations and deaths in high-risk Covid patients in a large clinical trial. Affluent nations, including the United States, have rushed to negotiate deals to buy the drug, tying up large portions of the supply even before it has been approved by regulators and raising concerns that poor countries would be shut out of access to the medicine, much as they have been for vaccines.

Treatment-access advocates welcomed the new deal, which was announced Wednesday morning, calling it an unusual step for a major Western pharmaceutical company.

“The Merck license is a very good and meaningful protection for people living in countries where more than half of the world’s population lives,” said James Love, who leads Knowledge Ecology International, a nonprofit research organization. “It will make a difference.”

Charles Gore, director of the Medicines Patent Pool, said: “This is the first transparent public health license for a Covid medicine, and really importantly, it is for something that could be used outside of hospitals, and which is potentially going to be very cheap.”

Molnupiravir was developed by Merck and Ridgeback Biotherapeutics of Miami, based on a molecule first studied at Emory University in Atlanta. All three organizations are party to this deal, which will not require a fee from any sublicensing company.

Sandee Babb, 54, of Grand Rapids, Mich., has seen nearly two dozen doctors over the past year to figure out what is causing a range of symptoms, including cardiac arrhythmia, a chronic cough, shortness of breath and joint pain, which have kept her from returning to her job as a teacher and librarian.

She could not get a coronavirus test when she first got sick in March 2020. But a September progress note from her doctor said her symptoms “could be consistent with long-haul type syndrome.”

After months documenting her condition, she submitted her unemployment application in August and is not sure when she will get an answer. “If it doesn’t come through, then I’m really stuck,” she said. “Where do I go from here?”

The Biden administration has said people with the condition known as “long Covid” could qualify for federal disability protection