PARIS ― With cases of COVID-19 climbing across Europe, new restrictions and vaccine measures are being put into place across the continent. France has now announced that boosters are available for everyone over 18 years of age, 5 months after they receive their second dose. Elderly people have until mid-December to get their boosters or risk losing their pass sanitaire, the French COVID passport. Those over 18 have until mid-January.
A number of questions remain: Does everyone need a third dose, regardless of age or immune status? How do we envision a long-term vaccination strategy when hospitals are still so strained? Are we moving toward more personalized vaccination?
Medscape’s French Edition spoke with infectious disease specialist Benjamin Davido, MD, from Raymond-Poincaré Hospital in Garches, Paris, for his thoughts on these questions and more.
Medscape: The third dose of the COVID vaccine is now suggested for everyone over 18 in France. What do you think of this measure?
Davido: I think it’s quite logical. The vaccine booster is justified because, as we have seen in recent studies, the third dose allows individuals to regain increased neutralizing antibody immunity against the Delta variant. You will recall the transmissibility study published in Nature Medicine that showed that when someone receives two vaccine doses, the risk of becoming infected and thus transmitting the virus during the first 2 months is very low. But beyond those 2 months, the benefit is lost with the Delta variant. We also know that after 6 to 7 months, infection rates return to the levels seen in unvaccinated individuals. This is not at all surprising. Historically, we know that humans are not expected to have a lot of immunity, even natural immunity, against most seasonal coronaviruses.
So should everyone get a third dose? Yes, but the reality is that we have to prioritize vaccination. We have to vaccinate the frailest individuals first, those who are most at risk of requiring hospitalization. And then there are healthcare workers, for whom exposure factors, rather than age, are taken into consideration. If we repeat a booster regimen, we should follow the same schedule as for the first vaccination and adhere to the interval of at least 6 months after the last dose. Moreover, a three-dose vaccine with boosters is not at all unusual; a perfect example is the hepatitis B vaccine (M0, M1, M6).
Medscape: Was it necessary to threaten people with suspending their pass sanitaire, especially elderly people, right before Christmas?
Davido: People over 65 years of age are the most inclined to be vaccinated. And in France, more than 85% of individuals over 12 years of age are vaccinated. The difficulties initially encountered during the vaccination campaign were due to fear of adverse reactions, which we now know more about. Getting a booster is very easy, and I think a priori people will be quite inclined to get the booster, regardless of their age range.
But if we propose this strategy on a punitive basis, heavy-handedly linking it to the pass sanitaire, it may create tension. We could quite simply explain to the French people that the first vaccinations went very well, that they allowed the restrictions to be lifted, and that a booster dose will help prevent a new wave. Who is going to say “no” to this common sense?
Medscape: What about the risk for myocarditis with a third dose in the youngest age groups?
Davido: Initially, there were a lot of questions — which, by the way, were completely legitimate — about the safety of the mRNA vaccines. Now we have answers. There is, in fact, a low risk for myocarditis in people under 30 years of age with the Moderna vaccine that is well described, and this is why half doses of this vaccine have been recommended for subsequent boosters. To my knowledge, there have not been any fatal cases of myocarditis associated with the vaccines.
Moreover, young people are ten times more likely to develop myocarditis from the infection than from the Pfizer vaccine, which is why, in France, the Pfizer vaccine is recommended for this age category.
Moreover, young people are ten times more likely to develop myocarditis from the infection than from the Pfizer vaccine, which is why, in France, the Pfizer vaccine is recommended for this age category. We need to reassure the public with full transparency and we also need to follow the protocols: individuals must be monitored and not engage in strenuous activities for 2 weeks after the vaccination. This especially applies to young people, whom we know are more inclined to participate in sports, which could increase the risk for myocarditis and increase the risk for a diagnosis being missed because the symptoms are thought to be due to exertion.
Medscape: Do you think that young people have been sufficiently informed about the necessary precautions? Pediatricians, in particular, do not seem to have been listened to regarding vaccination.
Davido: Actually, I think that this has not been communicated very well. And pediatricians probably have not been listened to because it was feared that these messages would slow down the vaccination momentum. But this adverse event, which is a special situation, was observed and now things are clear, which we can be glad about.
The Pfizer vaccine is being given to people under 30 years of age and a half dose of the Moderna vaccine for everyone else.
Medscape: Do you recommend a heterologous vaccination instead?
Davido: Yes, I think that a half dose of the Moderna vaccine as a booster after vaccination with the Pfizer vaccine is beneficial. Several studies have shown that the Moderna vaccine is more immunogenic, which probably also explains the adverse reactions that have been identified.
Medscape: In this context of heterologous vaccination, do you think other vaccines could be available soon?
Davido: I have been waiting for several months to see what the results will be for the Novavax vaccine. The data from the clinical trials show that it is relatively effective. Again, we know that heterologous vaccinations are more effective. The RNA vaccines have performed well but create little immune memory and very little mucosal immunity.
It will be interesting to see how these antigen vaccines behave with respect to immune memory.
In any case, we are going to need vaccines that are much easier to store to vaccinate regions such as Africa, which have been somewhat selfishly neglected. We seem to have forgotten that the best way to fight COVID is to eliminate the reservoir and make vaccination universal.
There are also the so-called “2.0” mRNA vaccines, including recombinant vaccines against the Beta and Gamma strains, which should arrive by next fall.
We have a lot of ammunition and many solutions to use against this new coronavirus. We mustn’t lose sight of the fact that they are all good as long as they control the spread of the virus and prevent hospital units from being saturated again.
As for transmission, although the third dose seems to restore a certain degree of effectiveness with respect to reducing transmission, mucosal vaccines could find their place in the management of the pandemic, probably in 2023. They have the advantage of being administered as nasal sprays and are therefore very beneficial because they are highly reproducible, making them excellent candidates for vaccinating young children. This should fill us with optimism. We have a lot of ammunition and many solutions to use against this new coronavirus. We mustn’t lose sight of the fact that they are all good as long as they control the spread of the virus and prevent hospital units from being saturated again.
Medscape: How do you envision the situation in the weeks to come, and particularly the holidays at the end of the year?
Davido: I think that in terms of hospitalizations, the fifth wave will be greatly diminished by vaccination. The real challenge will be the combination of COVID, flu, and other viruses which can quickly overwhelm hospitals and make restriction measures necessary. Because, whereas we saw mainly COVID patients and very few other diagnoses in the hospital last year, this winter we will have to screen for COVID along with the other illnesses.
Overall, I think that we are going to find ourselves in a vigilance situation, that is, a situation with no restrictions but with activities that are controlled and monitored with the pass sanitaire. We will be on our guard, but I don’t think the situation is going to explode. The corollary is the effectiveness of the third-dose campaign. It’s a marathon and the hardest thing will be to get over the hurdle of January, February, and March in 2022.
Medscape: It has now been a year and a half since the first wave of the epidemic, which inundated French hospitals. Do you think that healthcare workers have been heard and that they will have the resources to cope with another “COVID” winter?
Davido: The resources are not always available; healthcare workers feel as if they are emptying the ocean with buckets. But the situation at the hospital was already very tough, even before COVID, and it’s getting worse for many reasons. During the first wave, “scaffolding” was erected to support the hospital. Currently, the teams have none of that energy left, and I often hear my colleagues say that they can’t take more than 2 months in a COVID unit. I don’t see how we will be able to profoundly reform the hospital system in France until we have gotten past this epidemic.
Healthcare workers feel as if they are emptying the ocean with buckets. We won’t be able to profoundly reform the hospital system until we have gotten past this epidemic.
Medscape: Can it be said that this was a missed opportunity?
Davido: Yes, for sure. During the first wave, I felt like something exceptional was happening. The profession was very highly valued. Promises were made, but it turned out to be just smoke and mirrors, because, after all, this cannot be done quickly. And each recurring wave weakens the hospital a little bit more. I’m seeing back-to-back departures…. The nursing teams have never changed so much.
Medscape: Can a more personalized vaccination strategy be considered, by assessing, for example, the immune status of candidates for the third dose?
Davido: It’s true that many people were thought to be protected because they had received both of their doses or because they had recovered from the disease. But actually, we are realizing that people respond with different antibody levels, depending, in particular, on whether or not they have had the disease. The literature even talks about patients with “super immunity,” because there will inevitably be people who are doubly vaccinated who will also “get COVID.” In my opinion, this is how the epidemic will be stopped: people will have enough acquired protection from vaccination for them to get sick “without realizing it,” and especially without the healthcare system having to take care of them.
It will be very useful to work more effectively on the need for boosters, apart from age group. In fact, a study published in the Journal of Infection by a team from Toulouse shows that below 140 BAU (binding antibody units)/mL, you are virtually no longer protected against the coronavirus, and above 1600 BAU/mL, you are almost 100% protected. We are beginning to see more and more publications that are trying to assign a value ― admittedly a rough one because there is a big difference between 140 and 1600 ― to what might be strong or weak immunity to the disease. And the numbers are of course going to be subject to change, depending on the variants.
Larger studies should also be conducted to determine what the mean level of antibodies to the virus typically was in populations in places where the epidemic has resurged and where it has not.
Medscape: If the studies confirm this, might à la carte vaccination based on age, immunity, etc., be considered?
Davido: Yes, and I will go even further than that. With the French pass sanitaire, there should be the possibility of doing away with the certificate of recovery, which is meaningless, and instead indicate antibody level. The French High Authority of Health (HAS) now recommends that individuals previously infected with SARS-CoV-2 should receive one dose only and no subsequent booster. If someone has an adequate immune profile, they don’t need to be vaccinated; they could have an “unlimited” pass similar to someone who has had, to use another disease as an example, severe measles and will never be vaccinated for that disease. The more the epidemic progresses, the higher the likelihood of having come into contact with the disease. In fact, a study recently published in the Lancet shows that sick individuals who have had one vaccine dose have cellular immunity fivefold higher than those who have been vaccinated with two doses, which is surprising.
If someone has an adequate immune profile, they don’t need to be vaccinated; they could have an ‘unlimited’ pass similar to someone who has had, to use another disease as an example, severe measles and will never be vaccinated for that disease.
Medscape: What about medical confidentiality if immune status is included in the pass sanitaire, especially for people who have an immunodeficiency?
Davido: I’m not concerned about that. I wouldn’t be upset if we were able to tell people who have an antibody level of 1600 BAU/mL in a serology test performed less than 6 months earlier that they are protected, rather than making them get a booster dose. In addition, lately I have been asked more and more often for options regarding people who have extremely high serology test results (e.g., antibody levels higher than this threshold because they have had a severe case of COVID) but who are also eligible for the third dose and are asking serious questions because they are afraid of losing their pass sanitaire. Obviously, they can get vaccinated with a booster dose, but in the medium and long term, we need to think about permanent and à la carte measures, because each person has their own medical history. In Europe, does everyone need three vaccine doses, a serology test, PCR tests, QR codes, etc.? Currently, each country has a different strategy, which is a problem. Furthermore, this may be what will “save” that confidentiality right now. When you enter the United States, for example, you are not scanned. This is the opposite of what we experience on a daily basis in France. Until we have considered a universal protection policy, or we have done seroprevalence surveys, we will still have to ask all of these questions.
Medscape: Why do you think routine serologic screening has not been implemented yet? Is it a matter of cost?
Davido: A serology test costs 25 euros. But that’s also the price of one dose.
Actually, it is still a bit too soon. Some people asked the question at the start of the vaccination campaign, but it didn’t make much sense because, statistically, few people had been in contact with the virus. Now the virus affects one in three people. So just as free routine screening for everyone was implemented, we could consider redistributing this money to a 25 euro serology test.
Remember that in the study published in Nature Medicine, 18 to 24 months of immunity was observed in people who developed the disease. So some people are going to receive the third dose when they don’t need it, or at least not right away…. This is unfortunate because that dose could be redistributed to other candidates or to other countries.
Medscape: According to the Centers for Disease Control and Prevention, vaccination confers greater immunity than the disease does. What do you think?
Davido: I didn’t understand that report, especially since we know that vaccine immunity lasts 6 to 7 months. Perhaps it was poorly worded and it refers to vaccination administered in people who have already gotten the virus.
Natural immunity is higher, but I’m not saying that everyone needs to become infected, which would be risky both individually and collectively for the hospital. I’m simply referring to the natural history of infectious diseases. We are all going to come into contact with the virus at some point, and the solution may be to gain time with boosters to increase the duration of protection, then come into contact with the virus and finally achieve this herd immunity that we are told is unattainable…but no one can say that for certain.
Medscape: If vaccination allows us to gain time, how can we envision the booster-dose strategy over the long term?
Davido: We accept that the booster schedule is annual. This year, the virus is spreading again, especially in Europe, and people are concerned, they want to protect themselves. But in 2 years, it’s hard to see people getting boosters every 6 months for a disease that is gaining ground. Hence, the need to conduct studies that would compare immunity levels from year to year (e.g., 2021 vs 2022) to better understand how our serologic response and our immune response are evolving. If you get the virus twice, is that equivalent to a vaccine booster? We don’t know yet. Not to mention, serology is just one part of immunity; there is also cellular immunity, especially immune memory.
However, if you are young and have had a mild form, you will have few or no antibodies. In addition, although you might not get a serious form, you are contributing to spreading the virus, which is exactly what prompted vaccination for all.
But how are young people going to react to boosters and to their hypothetical individual benefit? I really don’t know. Even though I am advocating for universal vaccination, I fear that, as we go forward in the epidemic, we will see that the systematization of “x doses for everyone” doesn’t work in the long term. In the meantime, we expect that the spread of the virus across the entire globe will finally allow us to “catch our breath.”
This article originally appeared in the French edition of Medscape. The interview has been updated to take into account changes in French policy that were made after the original publication.