While many nations (including Russia and the United States) are actively encouraging citizens to revaccinate, scientists are still questioning the need for the booster, and the WHO is calling for the vaccine not to be wasted on those already vaccinated, with so many more people who are yet to receive a single dose.
Molecular biologist Irina Yakutenko delves into the scientific debate over whether boosters are needed at all and whether it's worth rushing to revaccinate after as few as six months.
Two aspects inevitably come up in the discussions about supplemental vaccination against COVID-19: personal (how good my protection will be) and public (whether it will be possible to develop collective immunity that will protect, among others, those who for some reason cannot be vaccinated, and will prevent the spread of the virus).
The personal aspect
During the pandemic, it turned out the public was terribly disappointed that anti-coronavirus vaccines did not protect against infection. The belief that a person will never develop symptoms of the disease after immunization stems from experience with vaccines against «childhood» diseases such as measles, polio, or mumps. But strictly speaking, we don't know for sure if they guarantee one hundred percent sterilizing immunity: the pathogens that cause these diseases are almost non-existent in Western countries, so the chance of a vaccinee encountering one and testing his or her protection is slim. And even if such an encounter occurs, we don't know exactly what events will unfold in the vaccinee's body. It may well be that the virus will penetrate sensitive cells and begin to multiply, but the vaccine-trained immune system will quickly notice the invasion and destroy the enemy. As a result, the likelihood of developing symptoms depends on both the vaccine and the properties of the pathogen and how it interacts with the immune system. Some viruses can manifest themselves in the early stages of infection, others need to run rampant before the infected person senses that something is wrong.
But in terms of personal safety, it doesn't matter if you get infected or not. What matters is whether your symptoms are so severe that you may end up in hospital, in the intensive care unit on a ventilator, or dead. A positive test, as well as a cough, fever, or momentary loss of taste (although this symptom is much less common with the delta strain than with its predecessors) does not in itself indicate that the vaccine is ineffective. A minor ailment can be uncomfortable, but not seriously threatening to your health – after all, you're not overly afraid of the common cold, are you? And statistics from various countries show that in many regions with high rates of vaccination, even with relatively high rates of new infections, the percentage of hospitalizations and deaths is not increasing.
In other words, with such a notion of efficacy, one round of existing vaccinations seems quite sufficient at this time. A good illustration of this thesis is a paper whose authors studied an outbreak of delta strain-induced covid in a Texas federal prison. Penitentiaries in America rival nursing homes in the number of infections and deaths since the pandemic began: in both cases people live in crowded environments, many of them subject to risk factors for developing a severe form of the disease. After anti-coronavirus vaccines were developed, the U.S. prison population was largely vaccinated. In the prison referred to in the study, 79% of prisoners were fully immunized. An outbreak of covid began at the prison in early July and the virus was eventually detected in 172 of 233 inmates (79%). 70% of vaccinated inmates and 93% of unvaccinated inmates were infected. Four inmates were admitted to hospital, three of them being unvaccinated. One of the hospitalized unvaccinated inmates died. Of course, prison is an artificial situation, and in normal life people do not interact with so many of the same people so closely and for so long. Nevertheless, this spontaneous experiment shows that although vaccinated people can become infected, the vaccines reliably protect them from a severe course of the disease.
A «natural» experiment in an American prison showed: vaccinated people can become infected, but vaccines reliably protect them from a severe course of the disease
Even more illustrative data were obtained by medical doctors from St. Petersburg who analyzed the proportion of vaccinated and unvaccinated patients among those with coronavirus brought in by ambulances to tomography centers (in St. Petersburg the network of such centers works as a primary filter, reducing the load on hospital emergency rooms). Among those who eventually required inpatient treatment (495 out of 13,894 people), vaccinated people accounted for 3.4%, i.e., 17 people. In other words, 96.4% of those with a severe form of coronavirus were unvaccinated or partially vaccinated. In St. Petersburg, the Sputnik vaccine was used almost exclusively, so those figures can be roughly considered as indicators of the actual effectiveness of the vaccine. As in the Texan paper, the delta strain was the primary strain at the time of the study.
Indeed, experience with many other types of vaccination indicates that a booster dose is likely to promote longer term protection. By presenting the immune system with the enemy once again, we give it an opportunity to refine the information about the enemy, tweak the antibodies, making them even more accurate, and perhaps help solidify the long-term immune memory of the pathogen. Initial data from Israel, where the third dose has been given to people at risk and all residents over 60 since early July, clearly indicate that at least the neutralizing antibody levels increase dramatically after the booster. But similarly, we know from experience that increasing the interval between the first and subsequent vaccinations often contributes to better immune protection. For coronavirus, there are of course no reliable data on the effect of the interval between the main course and the booster, but when the pause between the first and second doses of AstraZeneca and Pfizer/BioNTech vaccines was extended, volunteers produced noticeably more neutralizing antibodies. So, even if a coronavirus vaccination booster is needed, it's probably worth postponing it for maximum effect.
It may well be worth postponing the revaccination for maximum effect
Another important personal aspect is that booster vaccination is highly likely to increase the frequency of side effects. Experts warn about this, particularly, in a sensational article printed in The Lancet. Many media outlets were presenting this work as almost an anti-booster manifesto, but in reality, despite a great deal of reasonable argument, the text is rife with misstatements and insinuations. Nevertheless, the suggestion of increased incidence of adverse reactions has substance. However, to properly assess the risk/benefit ratio of the booster dose, it should be remembered that serious adverse reactions to the vaccination are rare or very rare.
The Paul Ehrlich Institute in Germany, in its recent report, collected all reported cases of adverse effects after vaccinations between the end of December 2020 and the end of August 2021. Myocarditis and pericarditis, i.e., inflammation of the heart muscle and pericardial sac, respectively, temporarily associated with covid vaccination, were reported at an average incidence of 1.5 per 100 000 doses for men and 0.5 per 100 000 doses for women. The vast majority of patients recovered without consequences, but in a few people the complication led to death - namely, 13 deaths per 100 million doses. Given that most of those vaccinated received two doses, one can roughly estimate the rate of deaths from myocarditis or pericarditis potentially associated with vaccination as 13 per 50 million complete courses of a vaccine.
Based on a slightly smaller but still solid statistic of 2 million vaccinated people in the US, the incidence of myocarditis, presumably related to vaccination, was 0.001% and the incidence of pericarditis was 0.0018%. There were no fatalities or even any serious cases in this sample. In comparison, the risk of myocarditis is 5,000 times higher with covid than after vaccination, the risk of pericarditis is 883 times higher.
While the countries of the Golden Billion agonize over whether to vaccinate, on average as little as 2% of the population in Africa has been vaccinated
Exactly what percentage should have immunity to the pathogen depends on the contagiousness of the virus. Say, if a person infected with pathogen A transmits it to an average of 18 other people, then in order to stop the number of new infections from increasing, at least 17 of those 18, i.e., 94.4%, must be protected. If one person infected with pathogen B infects, on average, three other people, two out of three, i.e., 67%, must have pre-existing immunity to stop an outbreak. The above figures are not random: the contagiousness of pathogen A equals that of measles and the contagiousness of pathogen B equals the presumed contagiousness of coronavirus prior to the emergence of the alpha and delta strains. Accordingly, to prevent spontaneous measles outbreaks, at least 94% of the population would need to be vaccinated (and the evidence supports these calculations).
At least two-thirds of the population would need to be vaccinated to stop the spread of older strains of SARS-CoV-2. The alpha and even more so delta variants are much more contagious (roughly, the alpha variant outperforms its predecessors by a factor of two in this area, while the delta is twice as infectious as alpha), i.e. for a collective immunity effect to manifest, about 85-90% of the population must be vaccinated (however, in certain groups local effects may be observed with a smaller percentage of those immunized).
For collective immunity, about 85-90% of the population should be vaccinated
In Europe, one of the globe's most vaccinated regions, the average percentage of those vaccinated oscillates around 60-65%. In such circumstances, primary vaccination of those who are not yet immune will be the key to facilitating the quickest possible recovery from the pandemic, rather than boosting the already reliable individual protection by administering a third dose.
Initial data from Israel on the effect of the booster dose indicate that protection against infection increases immediately after the third vaccination, but so far scientists have evaluated the effect for only one month after the third vaccination. It is not yet clear for how long this effect will last, and there is reason to believe it will soon begin to diminish. The fact is that the main weapon against the spread of the virus in the upper respiratory tract, and thus against its transmission, is local immunity, implemented by a special group of antibodies called type A immunoglobulins (IgA). IgA synthesis is rather poorly stimulated by intramuscular vaccines, meaning that even with high levels of systemic type G antibodies, the virus will be able to penetrate past the first line of defense. Intranasal vaccines should better stimulate local immunity, but there are none yet for covid (although several are in development), while the intranasal flu vaccine has shown very modest results.
And another aspect of public safety. While the countries of the Golden Billion agonize over whether to vaccinate, on average as little as 2% of the population in Africa has been vaccinated. There is nothing particularly surprising about this fact in itself; we are used to Africa being poor and disorderly. But unlike poverty, covid is contagious and easily transmitted; moreover, it is in countries where the virus is spreading unchecked that new potentially dangerous strains are likely to emerge. In such regions, there are many over-infected people whose immunity cannot completely suppress the multiplication of the virus, but can destroy the weakest variants, thus facilitating the selection of the strains that are better equipped to evade immunity. On the other hand, there are many non-immune people in those countries, in whose bodies such select pathogens can multiply and evolve, producing even more insidious offspring. So, supplying Africa, Bangladesh or India with vaccines is not so much an act of humanitarian aid, but primarily a concern for our own future and an attempt to reduce the risk of new pandemics that will require new vaccinations.
Supplying poor countries with vaccines is not an act of humanitarian aid, but a concern for our own future
In fact, research shows that there may be even more suitable conditions for viral evolution - namely at the threshold of collective immunity, if there are no restrictions. In such a situation, the selection pressure on the virus is maximized, while the opportunities to spread and try new ways of adapting are still high. But we are still a long way from that situation.
Thus, the initiation of booster vaccination with insufficient primary coverage resembles the situation from the joke when a driver who has run a red light stops twice at the green light to prevent an accident. A third dose would probably yield a short-term effect in reducing transmission and would temporarily provide additional protection. But only giving the vaccine to those who have not yet been vaccinated can change the situation globally.
A third dose may have a short-term effect, but only giving the vaccine to those who have not yet been vaccinated can change the situation globally
All of the abovementioned considerations apply to Western Europe, the USA, Israel and other countries that use WHO-approved vaccines. That's because for these vaccines we have reliable data on their degree of protection, the percentage of breakthrough infections, the severity of disease in those who developed symptoms despite vaccination. None of these vaccines are available in Russia, nor are there adequate statistics on the available drugs. Therefore, the arguments in favor of booster shots are even more shaky here, and any recommendations on whether or not to boost vaccination can only be based on general considerations.
In Russia, the average vaccination rate is somewhere around 30%; about the same number of people apparently got over covid and recovered. Unlike in many Western countries, there are no restrictions in the country, or they are not observed, so the prevalence of the virus is high - about a thousand deaths a day according to official statistics alone confirm this. Accordingly, the risk of encountering and being exposed to a high dose of the virus - the pathogen's concentration in the upper respiratory tract stays at its peak much longer in unvaccinated individuals than in vaccinees - is quite high for everyone. Data on protection against the virus, which more or less meet international standards, are available only for the Sputnik vaccine, and they show that it affords good protection against a severe course of the disease involving hospitalization. Therefore, people who are at risk and perhaps those who are constantly exposed to the virus, e.g., health care workers, should be concerned about additional protection.
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