Scientists, including Fauci, are facing off over whether to delay 2nd vaccine doses. Here’s why the risk of more mutations from delaying shots may ultimately be worth it.

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Dr. Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, preparing to receive his first dose of a COVID-19 vaccine at the National Institutes of Health on December 22 in Bethesda, Maryland. Patrick Semansky-Pool/Getty Images
  • Experts are split on whether to delay the second dose of COVID-19 vaccines to immunize more people.
  • Prioritising first doses means more vulnerable people get some protection, which could save lives.
  • The risk of more coronavirus mutations could be the price we pay.
  • Visit the Business section of Insider for more stories.

Experts are split on whether governments should delay the second doses of coronavirus vaccines to ensure that more people get a first shot.

Countries must decide what to do with their limited vaccine stock: Do they immunize more people with a first dose of a two-dose shot, which doesn’t give any of them full protection against the coronavirus, or do they hold back doses so that more people complete the vaccine course? Central to the debate is how to minimise the risk from coronavirus variants that are more contagious than the original virus and threaten to make vaccines less effective.

So far, most authorised COVID-19 shots in the world are two-dose vaccines. Some experts, including Dr. Anthony Fauci, the leading infectious-disease expert in the US, fear that delaying second doses risks variants spreading faster. This is because a weaker immune response, from one dose instead of the full two, could nurture variants with mutations that help them survive, they say.

Variants are a significant concern — but for now a theoretical one, as it has not yet been demonstrated that delaying second shots promotes variants.

On the other hand, the 2.4 million deaths worldwide from COVID-19 are proof that the risk from coronavirus is deadly and immediate. Getting people some immunity from the first shot might therefore be a better focus, and some experts are arguing to immunize as many people as possible.

UK delays 2nd doses by up to 12 weeks

The UK government pioneered the strategy of delaying the second COVID-19 vaccine dose on December 31, hoping to give some immunity to as many people as possible amid surging numbers of hospitalizations caused by a more contagious variant, called B.1.1.7.

Brits can get the second dose of the COVID-19 vaccines authorised in the country — one from Pfizer and BioNTech, the other from AstraZeneca and Oxford University — up to 12 weeks after the first dose. The second dose must be the same vaccine.

Dr. Michael Osterholm, a former COVID-19 advisor for President Joe Biden, has said the US should follow a similar model, prioritising the first dose and delaying the second. He says this would “reduce serious illness and death” that could occur in the weeks ahead from coronavirus variants.

In Israel, which is rapidly vaccinating its population, a single shot of Pfizer’s vaccine was found to be 85% effective at protecting against symptomatic COVID-19 15 to 28 days after the first shot, according to a study published in The Lancet.

The B.1.1.7 variant, first found the UK, has spread to the US, and the Centres for Disease Control and Prevention predicts it will become the most common coronavirus variant there by March.

Michael Osterholm
Dr. Michael Osterholm, the director of the Centre for Infectious Disease Research and Policy at the University of Minnesota, during an appearance on NBC News’ ‘Meet the Press’ on October 18. Meet the Press/NBC

The CDC has recommended that the second dose of the COVID-19 shots authorised in the US should be given at the intervals tested in trials.

One, from Pfizer and BioNTech, was tested with the doses 21 days apart, while the other, developed by Moderna, was tested 28 days apart. Both were roughly 95% effective at preventing symptomatic COVID-19 in late-stage trials.

But in “exceptional circumstances,” such as when people have forgotten which dose they have received, the CDC says second shots can be given up to six weeks after the first dose.

The World Health Organisation has also recommended a six-week gap “in exceptional circumstances,” such as a vaccine shortage.WHO said there was some clinical data that the Pfizer-BioNTech vaccine provided some protection against COVID-19 for up to six weeks from the first dose, so the guidance gives countries leeway to maximise the number of people benefiting from the first vaccine dose.

Many experts oppose delaying 2nd doses

But Fauci, who is President Joe Biden’s chief medical advisor, has said scientific data favoured prioritising both doses over a single shot. Fauci also said in January that delaying second doses could “immunologically select” for virus variants. “It may not be the case, but it gets risky,” he said, without elaborating.

South Africa’s most senior vaccine expert, Barry Schoub, said on January 7 that the fact coronavirus variants, including one found in South Africa, were more transmissible “would be a motivation to go for the double dose as much as you can.” The variant spreading in South Africa has been shown in lab studies to evade antibodies — a part of the human immune system — but researchers have suggested that higher levels of antibodies can still fight against it.

Lawrence Young, a virologist at the University of Warwick, told Insider that the longer you leave it between doses, “the more people are likely to get infected.”

“They might not get sick, but they could develop vaccine-resistant strains and drive further evolution of the virus,” he said.

Nicole Lurie, professor of medicine and public health offical said in the New England Journal of Medicine that delaying the second dose could risk public confidence in COVID-19 vaccines if people get infected after having one dose.

“If these breakthrough cases appear to occur more frequently before the second, delayed dose, confidence will be further compromised, ultimately delaying the end of the pandemic and social and economic recovery,” she said.

However, the risks from delaying are uncertain

The UK’s top scientist on January 5 called this a “real worry but quite a small real worry.” Chris Whitty, the UK’s chief medical officer, said it was a “balance of risk” between getting more people immunized versus encouraging further mutations.

Jonathan Stoye, an eminent virologist at the Francis Crick Institute, told Insider there was a “danger” of more mutations happening with delaying the second dose — but the magnitude of the danger is unclear. It is not a question of the number of mutations but the types of mutations, Stoye said. “We get a lot of mutations anyway,” he said.

The British approach of delaying the second dose could be especially advantageous for the COVID-19 vaccine developed by AstraZeneca and Oxford, which uses an inactivated chimpanzee virus to stimulate an immune response, because trials have indicated a longer gap could even produce a better immune response.

Delaying the second dose of messenger-RNA-based COVID-19 vaccines, which use a genetic code to produce an immune response, is more controversial because mRNA vaccines use groundbreaking technology, so we don’t know how well they work when the second dose is delayed. Moderna’s and Pfizer-BioNTech’s shots are mRNA-based. A small study in Israel, which came with caveats, has shown a single dose of the Pfizer-BioNTech shot was less effective than hoped.

Both Stoye and Young told Insider that, overall, they agreed with Whitty that the risk of mutations was a tradeoff.

Stoye said the UK’s approach wasn’t foolish, as long as people got their second doses.

Young emphasised the importance of protecting vulnerable people from getting sick and dying. “Even if they’re getting partial immunity,” he said, “that should be enough.”

This article was updated on February 19 with new information about the efficacy of a single shot.