A Blog by Jonathan Low


Apr 11, 2021

Why the Debate Over Whether To Delay 2nd Covid Shots Has Become More Urgent

There is growing concern that new, more easily transmissable Covid variants may increase vulnerability. Some argue that following the UK's one-dose regimen which delays the second dose for weeks, will help inhibit the spread by giving partially vaccinated people a better chance. 

Others are concerned that partial vaccinations will lead to the rise of spread from more lethal variants which have opportunistically adapted to the weaker protection. Though it appears the US is unlikely to shift its two dose strategy at this point, that could change if new infections remain stubbornly high despite growing numbers of vaccinated people. JL

Carl Zimmer reports in the New York Times:

Proponents of delaying doses point to mounting evidence suggesting a first dose can provide potent protection. Two weeks after a single dose of either Moderna or Pfizer-BioNTech, risk of infection dropped 80%. And that first-dose protection is persistent for at least 12 weeks. “There are fewer infected people in which variants can arise.” Britain’s campaign to get first doses into more people played a role in the 95% drop in cases. Opponents argue delaying doses will leave the country vulnerable to variants - those already circulating, as well as new ones that evolve inside the bodies of partially vaccinated people who are not able to fight off an infection.

The prospect of a fourth wave of the coronavirus, with new cases climbing sharply in the Upper Midwest, has reignited a debate among vaccine experts over how long to wait between the first and second doses. Extending that period would swiftly increase the number of people with the partial protection of a single shot, but some experts fear it could also give rise to dangerous new variants.

In the United States, two-dose vaccines are spaced three to four weeks apart, matching what was tested in clinical trials. But in Britain, health authorities have delayed doses by up to 12 weeks in order to reach more people more quickly. And in Canada, which has precious few vaccines to go around, a government advisory committee recommended on Wednesday that second doses be delayed even longer, up to four months.

Some health experts think the United States should follow suit. Dr. Ezekiel J. Emanuel, a co-director of the Healthcare Transformation Institute at the University of Pennsylvania, has proposed that for the next few weeks, all U.S. vaccines should go to people receiving their first dose.

“That should be enough to quell the fourth surge, especially in places like Michigan, like Minnesota,” he said in an interview. Dr. Emanuel and his colleagues published the proposal in an op-ed on Thursday in USA Today.

But opponents, including health advisers to the Biden administration, argue that delaying doses is a bad idea. They warn it will leave the country vulnerable to variants — those already circulating, as well as new ones that could evolve inside the bodies of partially vaccinated people who are not able to swiftly fight off an infection.

“It’s a very dangerous proposal to leave the second dose to a later date,” said Dr. Luciana Borio, the former acting chief scientist of the Food and Drug Administration. Dr. Anthony S. Fauci, the nation’s top infectious-disease expert, agreed. “Let’s go with what we know is the optimal degree of protection,” he said.

The seeds of the debate were planted in December, when clinical trials gave scientists their first good look at how well the vaccines worked. In the clinical trial for the Pfizer-BioNTech vaccines, for example, volunteers enjoyed robust protection from Covid-19 two weeks after the second dose. But just 10 days after the first dose, researchers could see that the volunteers were getting sick less often than those who got the placebo. In the same month, Britain experienced a surge of cases caused by a new, highly transmissible variant called B.1.1.7. Once the British government authorized two vaccines — from Pfizer-BioNTech and AstraZeneca — it decided to fight the variant by delaying the second doses of both formulations by 12 weeks.
That policy has allowed Britain to get first doses into an impressive number of arms. As of Thursday, 48 percent of the British population has received at least one dose. By contrast, the United States has delivered at least one dose to just 33 percent of Americans.

In January, some researchers lobbied for the United States to follow Britain’s example.

“I think right now, in advance of this surge, we need to get as many one doses in as many people over 65 as we possibly can to reduce a serious illness and deaths that are going to occur over the weeks ahead,” Michael T. Osterholm of the University of Minnesota said on Jan. 31 on NBC’s “Meet the Press.”

But the government stayed the course, arguing that it would be unwise to veer off into the unknown in the middle of a pandemic. Although the clinical trials did show some early protection from the first dose, no one knew how well that partial protection would last.

“When you’re talking about doing something that may have real harm, you need empirical data to back that,” said Dr. Céline R. Gounder, an infectious-disease specialist at Bellevue Hospital Center and a member of Mr. Biden’s coronavirus advisory board. “I don’t think you can logic your way out of this.”

But in recent weeks, proponents of delaying doses have been able to point to mounting evidence suggesting that a first dose can provide potent protection that lasts for a number of weeks.

The Centers for Disease Control and Prevention reported that two weeks after a single dose of either the Moderna or the Pfizer-BioNTech vaccine, a person’s risk of coronavirus infection dropped by 80 percent. And researchers in Britain have found that first-dose protection is persistent for at least 12 weeks.

Dr. Emanuel argued that Britain’s campaign to get first doses into more people had played a role in the 95 percent drop in cases since their peak in January. “It’s been pretty stunning,” Dr. Emanuel said.

He points to data like this as further evidence that the United States should stretch out vaccinations. He and his colleagues estimate that if the country had used a 12-week schedule from the start of its rollout, an additional 47 million people would have gotten at least one dose by April 5.

Sarah E. Cobey, an epidemiologist and evolutionary biologist at the University of Chicago, said she thought that the United States had lost a precious opportunity to save many lives with such a strategy. “We’ve missed a window, and people have died,” she said.

But even now, Dr. Emanuel said, it’s worth delaying doses. The United States is giving out roughly three million vaccines a day, but nearly half are going to people who have already received one shot. The nation’s entire supply, he argued, should instead be going to first-timers.

If that happened, it would take two or three weeks for the United States to catch up with Britain, according to his team’s calculations. The extra protection would not just save the lives of the vaccinated but would help reduce transmission of the virus to people yet to get any protection.

Still, some scientists say it’s premature to credit the delayed vaccination schedule for Britain’s drop in cases.

“They’ve done a few other things, like shut down,” Dr. Fauci said.

“I think the real test will be whether we see a rebound in cases now that the U.K. is reopening,” Dr. Gounder said.

Instead of experimenting with vaccination schedules, critics say it would be wiser to get serious about basic preventive measures like wearing masks. “It’s crucial that we don’t just reopen into a big national party,” Dr. Borio said.

She and others are also worried by recent studies that show that a single dose of Moderna or Pfizer-BioNTech does not work as well against certain variants, such as B.1.351, which was first found in South Africa.

“Relying on one dose of Moderna or Pfizer to stop variants like B.1.351 is like using a BB gun to stop a charging rhino,” said John P. Moore, a virologist at Weill Cornell Medicine.

Dr. Moore said he also worried that delaying doses could promote the spread of new variants that can better resist vaccines. As coronaviruses replicate inside the bodies of some vaccinated people, they may acquire mutations that allow them to evade the antibodies generated by the vaccine.

But Dr. Cobey, who studies the evolution of viruses, said she wasn’t worried about delayed doses breeding more variants. “I would put my money on it having the opposite effect,” she said.

Last week, she and her colleagues published a commentary in Nature Reviews Immunology in defense of delaying doses. Getting more people vaccinated — even with moderately less protection — could translate into a bigger brake on the spread of the virus in a community than if fewer people had stronger protection, they said. And that decline wouldn’t just mean more lives were saved. Variants would also have a lower chance of emerging and spreading.

“There are fewer infected people in which variants can arise,” she said.

Dr. Adam S. Lauring, a virologist at the University of Michigan who was not involved in the commentary, said he felt that Dr. Cobey and her colleagues had made a compelling case. “The arguments in that piece really resonate with me,” he said.

Although it seems unlikely that the United States will shift course, its neighbor to the north has embraced a delayed strategy to cope with a booming pandemic and a short supply of vaccines.

Dr. Catherine Hankins, a public health specialist at McGill University in Montreal and a member of Canada’s Covid-19 Immunity Task Force, endorsed that decision, based on the emerging evidence about single doses. And she said she thought that other countries facing even worse shortfalls should consider it as well.

“I will be advocating at the global level that countries take a close look at Canada’s strategy and think seriously about it,” Dr. Haskins said.


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