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Can the second dose of a COVID-19 vaccine be delayed? It's complicated


A couple of weeks after the first dose of vaccine, people are well protected against severe COVID-19, new data suggest. With the demand for shots far exceeding supply, this has sparked a debate among scientists and policymakers: Is it okay to stop giving the second dose?

Delaying the dose could lead to more people receiving their first shots and stopping the spread of the coronavirus, advocates say. Opponents say there is not enough data to show whether that one-time protection is durable enough. And they worry that the time change could now confuse people, undermine confidence, and cause more widespread hesitation to take the vaccine.

Here’s a closer look at the issues involved.

Dosage data

In clinical trials, the second dose of the Pfizer / BioNTech vaccine was administered 21 days after the first. Moderna's second shot followed the first shot after 28 days. Both vaccines were effective between 94 and 95 percent after two doses (SN: 12/18/20).

AstraZeneca and Oxford University separated doses of their vaccine four to 12 weeks apart in four separate trials. The effectiveness of this vaccine ranged from 62 percent to about 90 percent depending on the schedules and dosage amounts (SN: 23/11/20).

The U.S. Food and Drug Administration has issued an emergency permit for Pfizer and Moderna vaccines to be administered at the same time tested in the trials. (The AstraZeneca vaccine is not yet approved for use in the United States.)

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The UK has taken a different approach, deciding in late December to delay the administration of coronavirus vaccines for 12 weeks after the initial dose. The goal: to stretch the supply of vaccines to cover as many people as possible. The decision attracted criticism. After all, scientists said, the effectiveness of time against coronavirus has never been proven.

But now some new data seems to justify the decision to delay.

A reanalysis of Pfizer clinical trial data found that the mRNA vaccine is 92.6 percent effective from two weeks after the first shot, two Canadian researchers wrote in a letter to the publisher published Feb. 17 in New England Journal of Medicine. This is similar to the 92.1 percent effectiveness that Moderna reported after a shot of its mRNA vaccine.

Pfizer initially calculated that the effectiveness of the first shot was 52.4 percent, but that it included cases that arose in the first two weeks after vaccination when immunity was still boosted. Those early cases are not fair proof of the effectiveness of a vaccine, says Danuta Skowronski, head of epidemiology for influenza and emerging respiratory pathogens at the British Columbia Center for Disease Control in Vancouver. It takes a couple of weeks to build antibodies and train immune cells to attack a virus. The new estimate is similar to the evaluation of Public Health England data.

See how the effectiveness of the first shot developed both in the real world and when real-world problems caused wrinkles in the trials:

Among health workers at Sheba Medical Center in Israel, infection rates fell by 75 percent between 15 and 28 days after the first dose of the Pfizer vaccine compared to unvaccinated health workers, researchers reported on Feb. 18 in the Lancet. . And rates of cases with symptoms have dropped by 85 percent. Among nearly 600,000 people who received the Pfizer vaccine through Israel’s largest health care system, the vaccine was 46 percent effective in preventing infections, 62 percent in preventing serious disease, and 72 percent in Researchers reported on February 24 in the New England Journal of Medicine which predicted death two or more weeks after the first dose. In Scotland, the Pfizer vaccine was 85% effective in preventing hospitalizations 28 to 34 days after the first shot, according to the researcher on 19 February. a prepress in Lancet. That study also found that the AstraZeneca vaccine was 94% effective in keeping people out of the hospital a month off the first shot. These preliminary data have not yet been thoroughly examined by other scientists. And when delays in manufacturing the second dose of the AstraZeneca vaccine in trials in the UK, Brazil and South Africa were delayed, efficacy increased. When people received the second shot less than six weeks from the first, the effectiveness of the vaccine was about 55 percent, but the wait of 12 weeks or more to give the booster shot produced 81 percent effectiveness, according to the researchers reported Feb. 19 in the Lancet. The researchers found that antibody levels in the study participants did not drop in the three months following the first shot, suggesting that the first shot provides lasting protection against the coronavirus.

Arguing the delay

Those numbers justify temporarily postponing second doses to ensure more people get their first vaccines, says Robert Wachter, who heads the Department of Medicine at the University of California, San Francisco.

“It’s not a difficult math question,” he says. “You’ll save a lot more life, on the order of tens of thousands more lives, by giving those extra doses of vaccine to people for their first shot, protecting them from zero to 85 percent, than using the same ability (to) give people the his second shot and getting them from 85 to 95 (percent effectiveness) ".

The real driving force behind the proposals to delay the second shots is that there is not enough vaccine to turn around. It’s about putting punches in as many arms as possible, Skowronski says.

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Postponing the second dose does not mean canceling it, she says. It is only a delay that could allow for a more widespread distribution of the vaccine, especially to people at high risk of hospitalization and death from COVID-19.

Although no one knows how long the protection of a single shot will last, immunity does not disappear overnight. That saves time, she says.

“We should be making sure that as many people as possible, by whatever means possible, get the first dose before folding and trying to refill with a second dose,” Skowronski says. "Every second dose we administer is essentially depriving another person of the substantial protection they could have obtained from the vaccine as a first dose."

Arguing against the delay

Yes, the data in general suggests that the first doses work pretty well, but scientists don’t know how long that protection is, says virologist Onyema Ogbuagu. It may not be so much of a problem in countries like Israel and the UK, which have vaccinated people fairly quickly. But in the United States, the vaccine launch has been creeping in and out, Ogbuagu says. Because of that slow progress, "he could be six or 10 months into the vaccination and the first people he vaccinated would be vulnerable again."

The second shot should make the immunity last longer. “The role of the second dose is definitely an advantage,” he says. "Optimizes efficiency and durability." Ogbuagu, who oversees COVID-19 clinical trials at Yale School of Medicine, participated in the Pfizer vaccine efficacy test.

The first phase I and II safety trials also tested people’s immune responses to mRNA vaccines. These data have shown that antibody levels after the first shot are respectable, but often do not come close to the matching levels seen in people who have recovered from COVID-19, Ogbuagu says. “But the pattern after the second dose is so amazing, antibody levels just skyrocket,” often surpassing the levels of recovered patients, he says.

He also notes that the dosing data from the AstraZeneca trial came from an unplanned part of the study and other unknowns may be influencing the outcome. A new clinical trial mixing Pfizer and AstraZeneca vaccines will test the order in which vaccines should be taken. and whether a four- or 12-week interval between doses produces better efficacy. That trial will produce more reliable data on which to base a decision on shooting schedules. For now, "we have to deal with the unknowns," he says, "and I think the benefits of giving that second shot outweigh that of giving the first and expecting the best."

There is another big concern: even at best, some people are forced to get sick after getting vaccinated. Vaccines are not perfect and some new variants of coronavirus can bypass the antibodies generated by the blows. Some researchers are concerned that delaying a second dose may help produce new variants (SN: 14/01/21).

And if infections occur while not being tested with untested dosing intervals, it could undermine public confidence in the shots, worries Nicole Lurie, a strategic advisor to the Coalition for Epidemic Preparedness Innovations, an organization that funds vaccine development.

It may feed a narrative that health officials have not fully followed science as promised, Lurie says. If public confidence erodes to the point that people reject vaccines, "then in the long run, it's hurting the nation."

It’s okay to provide a small space for people to get the second shot when circumstances (like winter storms in Texas or other problems) prevent them from getting it on time, she says. But sticking to the schedule as closely as possible should be the policy.

She and Wachter set out their counterarguments on the dose delay on Feb. 17 in the New England Journal of Medicine. And while they’ve come to different conclusions, they don’t necessarily disagree on the challenges, including the concern that some people interpret the data to mean they don’t need any background. Watcher says, "We have to decide if the uncertainty is too great to do which, for me, makes a lot of sense."

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