Second dose of Covid vaccines: is it possible to administer it beyond the established times?

Britain has moved it three to 12 weeks with a decision of its scientific committee of last December 31st. Denmark has also decided to extend the period between the administration of the first and second vaccine doses, lengthening it up to six weeks. The objective of this forcing with respect to the indications provided by the producers and developers, until now Pfizer-BioNTech (for whose vaccine the booster must be carried out after 21 days) and Moderna (after 28 days), is to cover the largest possible number of citizens with the first dose, which however provides from the 12th / 14th day a variable immunity percentage, in one credible range of effectiveness between 29.5 and 62.4% for the Pfizer vaccine (for the Moderna, however, the experimentation does not allow to establish that interval).

As known, the regulatory authorities set the threshold value of 50% as the minimum level for the emergency use of the vaccine, so that in many cases the first dose will not even be sufficient to reach the minimum efficacy envisaged by international bodies. But it is still a value above zero and given the disastrous epidemiological situation in which many countries find themselves, in some cases it was decided to extend the recall period also to make up for the intermittent supplies of the American giants, whose findings are the only ones so far authorized by the European Medicines Agency. All of course dividing the scientific community: there are those who endorse the choice of even very long delays, those who limit themselves to emphasizing that a week or a little more than 21 (or 28 days) of the recall does not constitute a problem and those, like the Italian technical-scientific committee and the Tricolor Medicines Agency, intends strictly follow the instructions provided by Pfizer and Moderna, the only ones corroborated by scientific trials. Indeed, every other interval of administration has not been investigated. And according to some experts like Antonio Cassone, member of the American Academy of Microbiology, “delaying the second dose, the one that ensures the necessary high efficacy of the vaccine, makes us risk total loss of the little protection obtainable with the first dose”.

On the contrary, he replied in the past few hours Armando Genazzani, Italian representative to the CHMP of the European Medicines Agency, the committee that deals with medicinal products for human use and responsible for the authorization of vaccines, “if we are talking about a delay of a few days, one or two weeks, there is no problem. However, it would be better to keep the interval fixed, also for an organizational reason, but if it happens that someone has to delay, they will have no problem, we know it from the data ». In short, a more nuanced position: if logistically it serves to buy time, a week is not a drama. Different speech, however, quadruple the window as has been done in the United Kingdom for all vaccines, including that developed by AstraZeneca and the University of Oxford. The WHO also returned to the point explaining that you must follow the periods indicated but also that we need to be “open to this type of decisions that some countries have taken on the basis of their epidemiological situation”. Well go up to a couple of weeks more, then, but nothing has been said about prolonged postponements. Also Center for disease control and prevention Americans are essentially in this position of slight flexibility.

Basically, if studies show marked protection from Covid-19 after the first dose and a reinforcement after the second – the one that these days are beginning to be given to the first vaccinated in December, even if counting on Pfizer supplies less conspicuous than those established in the contracts – such as to boost effectiveness over 90%, they say nothing about the postponement beyond 21 days (or 28 for Moderna) of the recall. Nothing even says the EMA, which does not touch the point by referring the question exclusively to indications provided by manufacturers and drawn up on the basis of the results of clinical tests conducted on tens of thousands of volunteers in different parts of the world in recent months, and still ongoing. In short, the only indication is this and obviously concerns the different aspects of the vaccine within that time window: not only the effectiveness but also the safety.

Other solutions will come for which only one dose will be enough, such as the vaccine Janssen, a subsidiary of Johnson & Johnson, which we should have available in March. The point, for those tested in double doses, is that after the first dose the data on the stimulation of memory lymphocytes (especially B lymphocytes) are scarce. And many other aspects remain ahead of a sufficient critical threshold of information. Not to mention thepsychological effect: it would give people the false perception that after the first dose they can be immune and safe. When, based on the few data we have, It is not so. Instead of buying time, we would actually waste it. Transparency should also be demonstrated with the recipients of a so to speak delayed second dose, given all these points of doubt.

L’Aifa and our Cts, as mentioned, prefer instead follow the main road and strictly adhere to the deadlines of 21 and 28 days. As you can read on the website ofItalian drug agency «Published studies tell us that one dose is sufficient to cause the desired immune response within two weeks and that this response is strongly enhanced by the second dose. We don’t know how long immunity lasts after a first dose. A population vaccinated with only one dose sees its risk of getting sick with Covid only halved. The Center for Disease Control in the United States stated that for both mRNA vaccines (Pfizer / BioNTech and Moderna) “The second dose should be administered as close as possible to the recommended interval”, that is 21 days and 28 days respectively. A similar indication was given by the World Health Organization. Therefore, the AIFA CSV deems it necessary to follow the current indications for the administration of two doses for the vaccines approved so far ».