COVID-19: a 4th dose of vaccine, now or later?

Quebec’s Ministry of Health and Social Services (MSSS) announced in early May that all people under the age of 60 can now receive a second booster dose of an RNA vaccine against COVID-19 (Pfizer or Moderna ) if they wish, if more than three months have passed after their first reminder. However, the D^r Luc Boileau, acting national director of public health, clearly explained that this booster dose is not recommended for people aged 60 and under. A position that echoes the most recent opinion on this subject from the Committee on Immunization of Quebec (CIQ), which had recommended to the government not to offer a new dose to this group of the population before September or October. « The CIQ stands by this recommendation and does not plan to produce a new opinion in the short term », specifies the D^D Caroline Quach-Thanh, committee member. The federal immunization committee also does not recommend a new booster for those under 60. So what to do? Here’s what you need to know.

Why this recall is not recommended

Three elements justify the committee’s decision.

First, the evidence that this booster is really beneficial in reducing the risk of serious illness and mortality is non-existent for this population group. The only study published so far, in April, was carried out in Israel with around 200 health care workers (that’s not a lot!) who received a fourth dose of Moderna for half of them, and Pfizer for others. Researchers didn’t assess protection against the severe forms of the disease that cause hospitalizations and deaths — since none of the people studied were found to have three or four doses .

During this study, conducted in the midst of the Omicron wave, 25% of people who had their first booster more than four months ago were infected, compared to 20.7% in the group who received a second Moderna booster and 18, 3% for those who have had that of Pfizer. We agree that it does not make a huge difference.

Then, as the study clearly shows, we must also remember that a person under the age of 60 without immunodeficiency is very unlikely to be seriously ill in the six months following their first booster dose, underlines immunologist Alain Lamarre, from the National Institute for Scientific Research (INRS).

Finally, wanting to quickly improve its protection against simple infections is not very useful at a time when the virus is not very present. However, the number of new COVID-related hospitalizations during the sixth wave, a good indicator of the circulation of the virus, peaked a month ago and should soon fall back to its level of late spring 2021. Even if we are preparing to remove the masks indoors, except in hospitals and public transport, it is unlikely that we will see a resurgence of the epidemic.

Who could still — perhaps — benefit

The MSSS decision aims to give everyone under 60 a choice based on their situation, even if the benefit is not clearly demonstrated or significant. According to experts, those who could benefit the most from this new recall are:

• relatives of immunosuppressed people;
• people who received their first booster more than six months ago and who plan to travel to a country where the virus is more active, such as Australia, since even a mild infection abroad could force a delay in returning ;
• people who, while not immunocompromised, are in very poor health and may be at increased risk of becoming seriously ill with the virus, for example those who are morbidly obese and have severe lung problems.

In any case, it must however be understood that this fourth injection will not automatically dispense with a new dose in the fall. It’s also unclear if it changes anything to the risk of developing long-lasting COVID after an infection.

Who benefits for sure?

In March and April, both committees strongly advised a second booster for people who are at much higher risk of hospitalization or death from COVID, and who are also more likely to be protected with a shorter dose. vaccine due to immunosenescence, the aging process of the immune system. These people may already have had a second booster dose for several weeks, and it is still worth it for them. It’s about :

• residents of collective living environments that house a high proportion of elderly and vulnerable people, such as CHSLDs and private seniors’ residences;
• of all people over the age of 80;
• people with severe or moderate immunodeficiency;
• vulnerable people living in remote or isolated communities.

Too many doses, is it risky?

There is a good chance that a new dose of vaccine will be advised this fall even for people who would receive one now, since, if we rely on previous years, the virus could circulate more intensely at the end of the beautiful days, and even more so in winter, and that the protection against serious diseases ends up decreasing after a while.

“In theory, close and repeated doses of the same vaccine could in the long run reduce the immune response it elicits,” explains Alain Lamarre. This is also the principle behind desensitization for allergies, which consists of repeatedly stimulating the immune system with small doses of allergen to gradually cause it to react less. “But with the COVID vaccines, we continue to see a good rise in antibodies after four or even five doses, so there is no need to worry about it for the moment”, estimates the immunologist.

A new wave before the fall?

Receiving a new dose of vaccine now could be justified if there were fears that a new wave would surge within weeks. In South Africa, cases are on the rise, driven by the new BA.4 and BA.5 subvariants, which are said to be somewhat more contagious than BA.2, but not more severe, according to reports. knows so far.

Could these new strains, like during the Omicron wave, soon generate another wave in Europe that we would then see arriving here? Unlikely, according to the D^r Gaston De Serres, epidemiologist at the INSPQ, because of the high number of recent infections by Omicron and BA.2 in Quebec, which has increased population immunity, and the arrival of sunny days, less conducive to contagion . “South Africa is entering winter, and unlike Europe and Canada, it has not had a recent BA.2 wave that would protect well against these new variants,” adds Caroline Quach-Thanh. “We still have to watch carefully what is happening in Europe and in the evolution of the virus, because we can still have surprises”, believes for his part Alain Lamarre.

If a radically new variant were to come out of nowhere soon, which cannot be completely ruled out, there is nothing to say, however, that a fourth dose of the current vaccine would change anything in the situation of a person under 60 years old already triple vaccinated.

What vaccine in the fall?

Very clever who can say now which variant will circulate this fall, if it will cause a new wave of importance, which vaccines will be offered at that time and who will need another booster dose. “We will give new recommendations to the government just before the summer, then adapt according to the evolution of the situation. One thing is certain, we will have to be able to be very responsive both in our recommendations and in the deployment of vaccination in the field”, warns Gaston De Serres.

As soon as Omicron appeared, Pfizer and Moderna announced the start of trials for a vaccine aimed at Omicron, but it may not be the one they will favor. It is indeed possible that a vaccine directed against this single variant induces, through natural selection, the return of older, more virulent variants (such as Alpha or Delta) which continue to circulate imperceptibly. And we don’t want that!

The two pharmaceutical companies have therefore also undertaken to test a so-called “bivalent” vaccine, comprising both the RNA which codes for the surface protein of the original strain, like the current vaccines, and Omicron’s own RNA. They are very discreet about their progress. Will this new formula be ready before the fall? The last public statement from Albert Bourla, CEO of Pfizer, implied that it is not at all safe.

In addition to efficacy against a particular variant, the duration of immunity also risks becoming a major criterion of choice for future vaccines, because immunization campaigns are very expensive and the support of the population decreases with each new dose. It is possible that a dose of a different vaccine, such as those from Medicago or AstraZeneca, given after doses of RNA vaccines, will broaden the protection and lengthen its duration, but this is not proven and there are unlikely to be before this summer.

Obviously, from the industrial point of view, it is preferable to take as many doses as possible. But in the end, immunization committees and governments will decide, and there is strong pressure on pharmaceutical companies to offer the booster doses that best combine efficacy and duration of protection. The competition between them is fiercer than ever.