Covid-19: before everyone vaccinates, 5 mysteries to solve

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SCIENCE – Like the settling plan, there will be several stages for the coronavirus vaccination plan. In any case, this is what the High Authority for Health (HAS) recommended on Monday 30 November. In its 58-page report that should serve as the basis for the government’s strategy, it unveils five progressive steps to offer the vaccine as a priority to the most vulnerable to Covid-19, and then gradually expand, depending on the availability of laboratory doses ( which should not exceed a few million doses at the start of the campaign). But not only.

Because the HAS clearly explains that this “very optimistic” scenario is based on a dream situation: that the various vaccines currently being tested in large-scale clinical trials (phase 3) are finalized and that the results are positive. In fact, there are still many unknowns in the equation, despite enthusiastic announcements from Pfizer, Moderna or AstraZeneca.

First, the results of these studies need to be published and analyzed, which should be done in a few weeks. But this will not be the end of the scientific study on the effect of these vaccines. “When vaccination is implemented, we will obviously have pharmacovigilance monitoring, but also effectiveness. This is extremely important and this information will be provided to us when we start using the vaccines, ”explains Daniel Floret, vice president of the technical committee on vaccination at HAS.

Because the current clinical studies, if they allow to guarantee a good risk / benefit ratio, will not be enough. There are elements that these studies cannot analyze and that will be monitored during the first waves of vaccination. New more specific tests will also be launched. Here are the gray areas that still exist and on which the launch of vaccinations and future campaigns should provide answers, before vaccinating the entire population.

1. Is the vaccine safe for everyone?

If the preliminary results of the phase 3 trials are confirmed, the authorized vaccines will be considered “safe”. But it is possible to miss very rare effects, because they affect a very small percentage of people or only a very specific part of the population. “Only large-scale trials will allow us to study the efficacy of the vaccine on severe forms” on certain specific populations, specifies the HAS report.

On very old people in nursing homes, “they are little studied in ongoing trials, but the risks of vaccination should not be exaggerated,” believes Élisabeth Bouvet, chair of the HAS vaccination technical committee. “We can hardly give a global answer at this stage, but we can think on the contrary that these people will be protected”, he specifies.

In short: the risk of death for an elderly person who contracts Covid-19, especially in nursing homes, is much higher than the low risk of a possible unexpected side effect.

2. Should we vaccinate people who are already infected?

The role of a vaccine is to make our body believe that a virus is attacking us so that it defends itself (particularly by creating antibodies) and creates resistance to stop being infected in the future. So the question arises: should we vaccinate people who have already been affected by Covid-19 disease and can they be immune?

“Protected people are protected, but not in the same way depending on the form of the disease, and we don’t know how long they are protected”, explains Élisabeth Bouvet. Indeed, we are still in the dark about the question of immunity: how long do our antibodies protect us? Do we develop it even after an asymptomatic form of Covid?

Most importantly, there may be a hidden risk. It has in fact been shown that some viruses are able to infect an organism using the constant part of the antibody, which therefore facilitates its contamination. The best known example is that of dengue, where a second infection is more likely to lead to severe forms. Similar studies have been conducted on Sars and Mers, two other coronaviruses that are dangerous to humans.

“Studies are underway to find out if there would be a problem vaccinating someone who has already had an infection,” explains Élisabeth Bouvet. But there is no evidence of the risk here. So it is not, in principle, about depriving an elderly person of the vaccine because he had an asymptomatic form of Covid-19 a few months earlier. Once again, the benefit / risk ratio will need to be assessed. “These questions have been analyzed and we will offer a clear answer before Phase 1” of the vaccination coverage plan arrives, he says.

The HAS specifies in its report that if the first tests excluded people who had already been infected with the coronavirus, “secondary analyzes relating to all subjects, regardless of their infectious state compared to 2 are instead expected in some tests”.

3. Who to vaccinate with which vaccine?

Currently, the laboratories have released partial and not very detailed data on their Phase 3 clinical trials. But once the details are obtained, it will be possible for the HAS and the European Medicines Agency to verify the efficacy and risk of each. vaccine depending on the target population.

“If it turns out that RNA vaccines, for example, are more effective than inactivated vaccines in the elderly, we would say they should be used on the elderly rather,” explains Daniel Floret. “If in the phase 3 trials and in the follow-up we see that there are undesirable effects in this or that population category, this will also be taken into account,” he adds.

4. Can minors be vaccinated?

The HAS predicts that the first vaccines will not be authorized for children under 18, which would be logical: “the clinical trials that were set up first targeted the most affected people,” specifies Daniel Floret. And therefore not the youngest, who are known to develop few severe forms of Covid-19.

However, their role in the broadcast is debated. And it’s also known that teenagers are also likely to have and transmit the coronavirus. They are only at little risk of developing a severe form. So if we want to eradicate the epidemic with a vaccine, we will have to vaccinate the little ones.

Specifically, “the various laboratories developing vaccines intend in a second phase to introduce children who could benefit from a marketing authorization in a second phase,” says Daniel Floret. Pfizer, for example, began testing its vaccine on some young people since late October. It remains to be seen whether the younger one’s vaccination has any interest.

5. Can the vaccine eradicate the coronavirus?

The final two stages of the HAS plan to vaccinate the entire adult population. The goal here is no longer to prevent serious forms, but to eradicate the coronavirus. This is the ultimate goal of a vaccine: to immunize enough people so that the virus can no longer spread and disappear.

But for this to happen, the vaccine doesn’t simply have to interfere with the disease. It must completely prevent taking it and thus possibly spreading the coronavirus. However, today, it is not known whether the vaccines tested have an effect on transmission. What researchers are looking at in clinical trials right now is the occurrence of significant symptoms.

“Covid disease affects the lung, except that the virus penetrates through the upper airways. So a vaccine that blocks the disease by preventing it in the lungs doesn’t necessarily block it in the upper airways, ”explains Daniel Floret. Clearly, even with the vaccine, this scenario is possible: you may get the impression that you have a simple cold when you contract the coronavirus and therefore risk infecting someone else.

For the moment we are totally unaware of this point. These data will be available later when laboratories analyze mice from Phase 3 clinical trials in more detail. “If some vaccines are found to have an effect in blocking transmission of the virus, they will be recommended. preferential for people who are more likely to transmit the disease, “recalls Daniel Floret.

But, even in the best of cases, this question will not arise for months, when we have enough doses not just to vaccinate vulnerable populations. At that point, let’s hope science has cleared up these mysteries that still surround vaccines.

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