See what is known about the fourth dose of Covid vaccine

The Sars-CoV-2 virus has changed with the omicron variant, which is more transmissible and capable of partially escaping the antibodies produced by vaccination.

As a result, many people became infected even when vaccinated. The so-called vaccine leaks were already known for other strains of the virus less frequently, but now appear in greater numbers with the new wave of Covid around the world.

Fortunately, vaccines retain their protection against severe cases, hospitalizations, and deaths, and most symptoms in people who have already been boosted are mild, with no need for hospitalization.

However, in some cases, even individuals who have received all three doses are hospitalized, and that is why health authorities and governments are evaluating the application of a fourth dose of the immunizers.

The first country to adopt a fourth dose was Israel on 3 January. In the United States, it is already recommended for immunosuppressed people over 5 years of age.

The Brazilian Ministry of Health also approved the fourth application for immunosuppressed people over 12 years of age, such as transplant recipients, living with HIV, undergoing cancer treatment, undergoing hemodialysis or using immunosuppressive drugs.

On February 9, São Paulo governor João Doria (PSDB) made an announcement saying that the entire population would receive a fourth dose in the state, but backtracked and said the state was, in fact, evaluating the possibility. On the same day, Health Minister Marcelo Queiroga said that there is still no forecast for a fourth dose and that the priority is to strengthen the population.

What do the studies say about the need and effectiveness of a fourth dose?

So far, there is not enough evidence to prove the need for a fourth dose of the vaccines in an unrestricted manner.

In Israel, a Pfizer booster study showed that there is an increase in the amount of antibodies in the blood after the fourth dose similar to that seen at the peak with the third dose, but it did not prevent infections. The research evaluated 274 health professionals who received three doses of mRNA immunizers (Pfizer or Moderna) plus one dose of Pfizer.

According to another study from Israel, the fourth dose of Covid did not prevent the omicron infection, but the short booster period (only one month) may not have been enough to stop the virus from entering.

On the other hand, science has already shown that vaccines induce a type of protective cellular response, which is memory, responding quickly when there is contact with the real virus.

“This cellular protection, although not measured, it is there, so even when there is a decay of neutralizing antibodies, we know that the individual vaccinated with three doses is protected”, says the immunologist and professor at the Federal University of Health Sciences in Porto. Alegre, Cristina Bonorino.

For her, the third dose is necessary, but talking about a fourth injection is still too early.

Which countries have already adopted a fourth dose and for which people is it indicated?

To date, few countries have included the fourth dose for their population. They are: Israel, for all health professionals and people over 60 years old; Canada, for the population over 18 years of age three months after taking the last injection; Denmark, for individuals at higher risk and over 60 years of age; Chile, which began vaccinating its population aged 55 and over in February; and, more recently, Sweden, for seniors over 80, and South Korea, for health workers and vulnerable people.

Other countries, such as the United Kingdom, the United States and Brazil itself recommend the fourth dose only for immunosuppressed individuals: over 18 years of age in the United Kingdom, over 5 years of age in the United States, and over 12 years of age in Brazil.

What do we know about the safety profile of the fourth dose?

In general, the adverse effects that occur with booster doses of the vaccine are mild, and it is expected that the same will be observed with the application of the fourth dose. In the Israel study of 274 volunteers, the main adverse events were local (80%), disappearing within two days.

Studies also show that the frequency of post-vaccination adverse events decreases with boosters. This does not mean that they should be neglected, says pediatrician and director of the Brazilian Society of Immunizations (SBIm), Renato Kfouri.

“It is important to highlight that with more than 11 billion doses of vaccines against Covid applied worldwide, serious side effects are very rare. [de segurança], which we do not yet know. That’s why you need to investigate,” he says.

Does the effectiveness of vaccines decrease over time? What changes with the omicron variant?

The studies carried out so far show that two doses of the vaccines or a single dose of Janssen, against the omicron, have reduced efficacy.

According to a survey by the US Centers for Disease Control and Prevention (CDC), the effectiveness of the booster dose drops after four months. Even with the drop, protection remains high, around 78%, says the agency.

A national survey carried out in the United Kingdom pointed out that, in the context of the omicron, the booster dose provides 20 times greater protection for hospitalization and death compared to individuals with only two doses. The age cut was above 50 years.

“This is data that shows that for people over 50, immediately after a booster, vaccine protection is recovered from 59% to 95%, that is, the third dose is essential”, explains Julio Croda, researcher from Fiocruz.

However, Croda assesses that the elderly in Brazil, who received the booster mostly in September or October 2021, need a fourth dose precisely because of this decrease in protection.

Recently, research indicated that a Pfizer booster six months later in people with two doses of Coronavac regains effectiveness from 72.5% to 97.3% against severe cases. The research did not include the period of omicron circulation.

There are still elderly people, mainly in the state of SP, who were vaccinated with two doses of Coronavac and a booster also of Coronavac, for whom there is no protection data after four months.

“For this group, a fourth dose is urgent, because they are already at greater risk and have not received booster protection with Pfizer”, says infectious disease specialist Rosana Richtmann, who is part of the federal government’s advisory committee for vaccines.

For her, the priority at the moment is to rescue people who are already ready for reinforcements and have not done so.

Croda agrees with the recommendation, but says that campaigns should not be exclusive. “We should not fall into the same mistake of the past of thinking that it is necessary to first complete the third dose before starting the fourth, because the elderly over 80 are at very high risk for hospitalizations and deaths”, he evaluates.

Will we have an annual Covid vaccination like the flu or will we get boosters every four months?

We still don’t know how long the Covid pandemic will last, but experts believe that the Sars-CoV-2 coronavirus will become an endemic virus, like the influenza virus. Scientists are already working, however, for a combined flu and coronavirus vaccine.

“We need better vaccines and this year we should have news, including vaccines that have a longer duration of protection or are more effective in neutralizing the virus in the nose, such as nasal spray vaccines”, says infectologist and professor at Unicamp Raquel Stucchi.

Until then, however, it is necessary to accelerate the vaccination of people with an incomplete schedule, says Stucchi. “The discourse of many people today is that they will not take the booster because the idea of ​​giving successive boosters causes distrust, and we need to improve communication by reaffirming the importance of vaccines and, especially, the booster dose.”​