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When is the fourth dose? why for whom?


EIn various parts of the world, the incidence of Covid-19 has stabilized thanks to the vaccination schedule and the first booster dose, which has been applied to just over 20% of the population to date, according to Our World in Data. However, uncertainties about new variants and the reduced coverage of the first dose have led many to wonder when and when a second booster dose may be needed.

The truth is that little is known, since some studies have analyzed its effectiveness and safety. Even so, owning one is still beyond the reach of the average person, especially for people over the age of 50 or 60, who are more likely to be protected after 5 to 8 months after the first dose.

This is the case in the United States, where the Food and Drug Administration (FDA) authorized a few weeks ago (March 29) the implementation of the second booster dose of Pfizer / BioNTech and Moderna vaccines, once at least four months have passed. after receiving the first recall of any vaccine. The application is only a recommendation for a specific population: over 50 years old; over 18 years of age with a certain group of immuno-depression (when they have a weak immune system); and those over the age of 12 who have had a solid organ transplant or whose immune system is severely compromised.

Israel is another country where health authorities have decided to implement the second dose of the recall to people over 60 from January 2022. Several articles prepared by researchers in this country show that while the young population does not have many advantages, for the older population this second reinforcement could be “a lifeline”.

Although such authorizations have been made on the basis of preliminary studies or peer-reviewed articles, experiments may provide clues to other nations to assess the available scientific evidence and decide whether or not to apply it.

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Possible reduction in mortality

As with the first doses of the basic regimen, the protection conferred by the first booster dose is likely to decrease over time. Until now, exactly how much and at what rate is unknown, so it is difficult to know exactly when this dose would be needed.

However, there are some preliminary results that show that this second dose could offer remarkable benefits, especially in older adults. For example, in a peer-reviewed report, an Israeli research group selected 563,465 participants, with an average age of 73 and comorbidities such as diabetes, obesity and high blood pressure. 58% received the second booster dose and assessed how many of them died of Covid-19 compared to those who received only one.

They found that “death due to Covid-19 occurred in 92 people receiving the second booster dose and 232 in those receiving one”, which “demonstrated a substantial reduction in mortality due to Covid-19 due to the second booster dose of “The second dose of the recall is a rescue,” Ronen Arbel, one of the authors, told Israeli media.

But for the younger population, the second dose of booster, or the fourth dose, as it is called in some places, is not effective. In another peer-reviewed article published in the New England Journal of Medicine, another group of researchers in Israel looked at the effects of the second booster dose on 1,050 healthy young health workers four months after the second booster dose. The results show “marginal benefits” and state that the maximum immunogenicity of messenger RNA vaccines (such as those in Pfizer and Moderna) is achieved after three doses, so that the second booster is not so necessary in this population.

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Increased antibodies

One of the criteria to consider in assessing whether a second booster dose is needed is the level of antibody given. Even groups in Israel that tested health workers monitored how many neutralized antibodies were increased in the population that received the second dose of the booster.

And of all the measures taken, the second booster dose achieved an increase in antibodies by a factor of 9 to 10 for both brands of vaccines, meaning that after the new booster neutralized antibodies were slightly higher than those obtained after the first recall. Meanwhile, in the control group the number of antibodies continued to decrease. In addition, since they found “the fourth dose does not lead to major adverse effects”, they concluded that at least in the studies it is safe.

Increase efficiency

One of the most recent articles on the evolution of vaccine efficacy over time (in this case, that of Pfizer / BioNtech, Astra Zeneca and Moderna) was published in The Lancet Infectious Diseases a few days ago by a UK research group .

They used a app where data were recorded on more than 620 thousand participants and monitored for a positive Covid-19 test for eight months following the baseline vaccination schedule and booster doses (May to November 2021).

They found that the effectiveness of the three vaccines decreased after five months of application of the second dose, but that in the case of those who received the first booster dose, the effectiveness of the vaccine was offset by up to 92.5% in the case of. Pfizer with 88.8% for those who got a different booster, either from Astra Zeneca or Moderna. What is interesting is that they noticed a greater decrease in the effectiveness of the population over 55 years and also among those who had some comorbidities, which may be an indicator that the older population is one that would be more ask for the second reminder.

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If you’re not a population at risk, you can wait

Despite the fact that the CDC has authorized the fourth dose for the at-risk population in the United States, some days ago the same agency clarified that you should not insist on taking a fourth dose, especially if you are not part of the at-risk population. .

For example, for those who are newly infected, it is not necessary to take the fourth dose at this time. “If you’ve had Omicron recently, this is probably a natural boost for you. So you don’t need a reminder anymore … and you can wait two to four months for a new dose, “said CDC director Rochelle Walensky.

Another reason is that both infections and hospitalizations can continue to fall in many places, so there is no urgency to have a new vaccine. And finally, Walensky says, the second reminder is not imperative because you just don’t know what’s coming. “We will meet to assess what kind of vaccine will be needed, how we prepare for the future.”

Therefore, although there are some beneficial signs for people with immune or advanced age morbidity, there is still no evidence to confirm that the second dose of booster is necessary for the rest of the population. And as the type of vaccine or booster that will require the next few months is not known, it is probably the best decision that the healthy population can make is simply waiting.

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