With a seductive number, AstraZeneca study fueled hopes that eclipsed its data

A new paper released this week suggested that a vaccine developed by AstraZeneca and Oxford University not only protected clinical trial participants from developing disease, but also may significantly reduce transmission of the virus that causes the disease.

In the recent burst of data on Covid-19 vaccines, that suggestion stood out. The question of whether Covid-19 vaccines reduce transmission has been a critical and unanswered one, creating uncertainty over whether people who have been vaccinated will still be able to be infected by and transmit onward SARS-Cov-2, the virus that causes Covid, to those who have not yet been vaccinated. 

Media reports seized on a reference in the paper from Oxford researchers that a single dose of the vaccine cut positive test results by 67%, pointing to it as the first evidence that a vaccine could prevent transmission of the virus. But the paper, which has not yet been peer-reviewed, does not prove or even claim that — although it hints at the possibility.

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Instead, it showed that fewer people were carrying the virus as a result of being vaccinated. Fewer people carrying virus, the researchers argued, would equate to a reduction in the amount of virus circulating in a community. 

“These data indicate that [the AstraZeneca vaccine], used in the authorised schedules, may have a substantial impact on transmission by reducing the number of infected individuals in the population,” the authors wrote.

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If a person tests negative, Andrew Pollard, one of the study authors and a professor of pediatric infection and immunity at the University of Oxford, told STAT via email, “then it is a reasonable assumption that they cannot transmit.”

But it is a big and unjustified leap, outside experts agree, from that suggestion to proof of decreased transmission from people who are vaccinated.

“The study showed a decrease in [viral] shedding, not ‘transmission,’” said Carlos del Rio, a professor of infectious diseases at the Emory University School of Medicine. “The bottom line is, no, one cannot draw a conclusion or straight line.”

Kathleen Neuzil, director of the Center for Vaccine Development at the University of Maryland School of Medicine, concurred.

“There are too many, in my view, moving variables to make too much of one single result here,” she said. “The trend, though, is consistent and in the right direction.”

The researchers studying the Oxford-AstraZeneca vaccine did not set out to look at whether people who have gotten the vaccine are less likely to transmit the SARS-2 virus. They did, however, ask every volunteer in the one of their studies, conducted in the U.K., to weekly swirl a swab inside their nostrils of their nose to test for infection, using polymerase chain reaction, or PCR. None of the other big vaccine studies took that step as part of their protocols.

What they found was that while a single dose of the two-dose vaccine cut positive test results by 67% — the figure many media reports seized on — two doses reduced the positive tests by a lesser amount, 49.5%. 

That decline is hard to explain, and the Oxford paper does not attempt to do so.

“Biologically how do we explain that? Does that signal that those numbers can not be directly compared?” asked Natalie Dean, a biostatistician focused on vaccines at the University of Florida, who noted that booster doses typically improve a vaccine’s performance, not erode it. “You just have certain expectations and that one is hard to understand. How would efficacy go down after receiving a booster?”

More research is needed on the AstraZeneca vaccine, said del Rio, adding that the current studies, first reported on in December, do not answer many important questions. Differing perspectives about the study — a compilation of four differently designed studies — have divided the world, as the U.K., much of Europe, and India have approved the vaccine, while the U.S. and Switzerland are waiting for more information.

A large U.S. study is being conducted with the U.S. government, similar to the ones conducted by Moderna and Johnson & Johnson. Results may come as soon as the end of February.

“I just keep telling my volunteers that the U.S. study is the one that’s going to be the definitive study to tell us how this vaccine works against severe, hospitalized Covid and symptomatic Covid,” said Anna Durbin a vaccine researcher at Johns Hopkins Bloomberg School of Public Health who is involved in the U.S. trial of the AstraZeneca vaccine.

Unfortunately, in a pandemic, there is nothing more difficult than waiting.

Source: STAT