Anti-Covid-19 vaccine: what to think about the 3rd dose?

The High Authority for Health has just made a favorable opinion concerning the injection of a third dose of vaccine anti-covid-19 in people over 65 years old. If the European Medicines Agency gives its fire green, a recall campaign could take place this fall in France, together with the influenza vaccination.

Why a third dose?

Where does this apparent need for a third dose come from? It would seem that it is the situation in Israel which motivates the health authorities, given the increase in the number of cases of reinfection despite a large part of the vaccinated population. However, these epidemiological analyzes constituting an argument in favor of the third dose are far from unanimous in the scientific community, mainly because they are riddled with confounding factors.

For Professor Antoine Flahault, epidemiologist and director of the Institut de Santé Globale, “ it seems that the variant Delta does not greatly affect vaccine efficacy against severe forms of Covid linked to the new variant. This very good news comes from the recent Israeli experience which estimates the effectiveness of the Pfizer-BioNTech vaccine above 85% in those over 50 and above 90% in those under 50 to prevent serious cases leading to hospitalization. Efficacy against transmission and mild infections may be somewhat lowered against the Delta variant ”.

Another argument also comes up, that of the drop in antibodies. In fact, in the current immunological paradigm, most of the protection we have against a pathogenic resides in our amount of antibodies circulating in the blood. But this argument comes up against a common problem in medicine: the compatibility Come in biological markers and clinical status.

What evidence of effectiveness?

Believe in what the sciences say and in the progress they offer us is something commendable. Certainly, it is better to place your trust in statements scientifically corroborated by rigorous methods than in the first theory that comes along and devoid of experimental correlates. In science, it is generally admitted that experience has the power to reveal to us the real (even though it does not have the logical force to decide between theories). And what is happening now is that the relevance, safety and efficacy of this third dose are based only on theoretical grounds or on biological measures. No controlled trial has evaluated these three fundamental parameters on what interests us most, namely the risk of developing a severe form of the disease.

Judging the effectiveness of a treatment on intermediate measures is not new in medicine. ” This is something that is well known in medical science. It is easier to carry out studies on intermediate endpoints than on clinical events. We did it for thehemoglobin glycated in the context of diabetes or LDL-cholesterol for cardiovascular illnesses. The efficacy is valid on the biological marker and we realize years later that this does not change anything in terms of clinical events such as the risk of death or hospitalization ”, details Florian Zores, cardiologist in Strasbourg. In reality, the whole question is to know to what extent one can extrapolate an efficacy on a biological marker to a clinical efficacy.

On the issue of vaccines, Florian Zores suggests that this is probably not the worry major : ” There is probably a correlation between the level of antibodies and the protection conferred by the vaccine. The real question is the clinical gain compared to a two-dose vaccination schedule, especially in younger people. If the third dose reduces the probability of having a severe form by 0.01% (the figures are fictitious and are used by way of illustration to understand the reasoning, editor’s note) in young populations, but at the same time it increases the risk of myocarditis 5 or 10%, is it reasonable to consider this third dose? “ concludes the cardiologist.

Is this really the best strategy against a global pandemic?

The best strategy against the emergence of variants is to stop the circulation of virus. Indeed, like all viruses, SARS-CoV-2 mutates, although more slowly than most of its congeners thanks to a enzyme correcting his mistakes replication. But, by infecting immunocompromised patients or a considerable number of people, the likelihood that part of his genetic code changes over time increases. Taking into account the fact that only 1.4% of the population of developing countries have a complete vaccination schedule, would it not be better to work on making logistical communications possible to make access to vaccines easier everywhere? in the world, in order to limit the circulation of the virus and therefore its probability of mutating?

Antoine Flahault is, for the moment, unfavorable to this third dose: ” Political leaders are grappling with the pandemic, and in rich countries they will feel like they are “do something” for their people with this 3^e dose, and hope to avoid further containment, but without, of course, any evidence about it. First, let’s vaccinate all eligible populations around the world, starting at home. First, let’s maintain the lowest level of community transmission. First, let’s make schools, transport and all enclosed places safe ”.