Effectiveness of COVID-19 vaccines: the battle of the numbers

Paris | Efficiency of 94.5%, 95% or 70% “on average” with a paradoxically better result from a lower dose: the race for the vaccine against COVID-19 is also a battle of numbers, as spectacular as difficult for the general public to interpret.

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How do we measure effectiveness?

Some of the volunteers in each trial were given the vaccine and others a placebo, so they could compare.

The volunteers lead normal lives during the test. Over time, some will naturally catch COVID-19. If the vaccine is effective, the number of sick people will be lower among participants who have been vaccinated than among those who have received the placebo.

Theoretically, a vaccine is 100% effective if no patient identified in the trial belongs to the group of vaccinated volunteers.

The results recently announced by several competing teams relate to the last stage of their clinical trial, phase 3, for which tens of thousands of volunteers have been recruited.

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These results were unveiled as soon as a predefined number of COVID-19 patients was reached among the volunteers: 95 for the American laboratory Moderna (November 16), 170 for the American-German alliance Pfizer / BioNTech (November 18 ) and 131 for the European AstraZeneca / University of Oxford project on Monday.

What results?

Pfizer / BioNTech claims an efficacy of 95%: of its 170 patients, 8 were from the vaccinated group and 162 from the placebo group. Ditto or almost for Moderna, with 94.5% efficiency (5 patients in the vaccinated group, 90 in the placebo group).

Pfizer measured the effectiveness of its vaccine one week after the second and final injection, and Moderna two weeks after.

For their part, AstraZeneca and the University of Oxford on Monday announced an average efficiency of 70%, calculated from the results of two different protocols.

Efficacy is 90% for volunteers who first received a half dose and then a full dose a month later. It goes down to 62% for another group, which was however more vaccinated, with two full doses a month apart. A paradox which is only apparent, according to specialists.

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“We all expected that two full doses would result in the best response. (But) it seems that a lower initial dose allows the immune system to be better primed to prepare it to give a better response ”, explained one of the researchers in charge of the project, Andrew Pollard, at a conference of hurry.

This could be because a lower starting dose “mimics what happens during a real infection better,” according to her colleague Sarah Gilbert.

Another hypothesis: it could also come from the technology used by this vaccine. AstraZeneca and the University of Oxford have in fact relied on the technique of the “viral vector”: we use another virus (here, a chimpanzee adenovirus) that we modify so that it carries genetic material capable of transporting into our cells. to fight Covid-19.

According to several experts who commented on these results, too strong a first dose of the vaccine could actually cause the immune system to fight off the virus used as a transporter, contrary to the desired effect. This point will have to be clarified in the rest of the tests.

Finally, the Russians at the Gamaleia Institute assured on November 11 that their vaccine was 92% effective. But they are based on a very small number of patients (only 20).

Which one is the most effective?

Impossible to say at the moment, especially since all these results were announced only by press releases, without detailed scientific publication.

However, despite apparently lower efficacy figures, experts believe the AstraZeneca / Oxford vaccine could have an added benefit.

“Unlike other trials, the Oxford / AstraZeneca team tested all participants weekly for asymptomatic infections,” commented Prof. Eleanor Riley (University of Edinburgh), quoted by the UK Science Media Center. .

Indeed, one of the main questions is whether these vaccines block the transmission of the virus, in addition to reducing the severity of the disease in those who have received them.

“We have early indications that this vaccine may reduce transmission of the virus, as a decrease in asymptomatic infections has been observed,” Oxford University said in a statement.

All these data are however only preliminary.

“The differences in efficacy are based on the analysis of 100 to 200 patients out of a total of 30,000 to 50,000 volunteers for each vaccine, and these figures can therefore experience large variations thereafter,” warned another expert , Dr Julian Tang (University of Leicester), cited by Science Media Center.

Effective, but on whom?

Many other questions remain unanswered.

First, it is not known how long these vaccines protect.

Then, it is not known whether their action is identical in the populations most at risk, starting with the elderly. They are much more likely to have a severe form of Covid-19, so it is essential that a vaccine is effective in this population group.

Pfizer / BioNTech said its vaccine’s efficacy was “over 94%” for those over 65. But for lack of publication in a scientific journal, we do not know the details.

AstraZeneca and the University of Oxford, on November 19, published results in the prestigious medical journal The Lancet: they show that their vaccine provokes in the oldest subjects (over 56 years) an immune response identical to that that it triggers in the youngest (18 to 55 years old).

However, these published results do not relate to phase 3, but to the previous step, phase 2: the total number of volunteers is much smaller (560 against 23,000) and they are not representative of the population. general.

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