Can the COVID-19 Vaccine's Most Troubling Side Effect Be Easily Prevented?

Why are teenage boys most liable to suffer from myocarditis after being vaccinated against COVID? Does the heart inflammation have anything to do with the way the shot is administered? New studies are trying to answer these questions, or at least to generate a more transparent discussion about the side effects

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A boy in Portugal receiving his second dose of the Pfizer vaccine, last month.
A boy in Portugal receiving his second dose of the Pfizer vaccine, last month. Credit: Pedro Nunes / Reuters
Smadar Reisfeld
Smadar Reisfeld
Smadar Reisfeld
Smadar Reisfeld

Last weekend, the Health Ministry’s Facebook page carried a “Fake News Warning” in glaring red font. The warning referred to a post by Dr. Yoav Yehezkelli, an internist and a member of the “Public Emergency Council for the COVID19 Crisis,” who a few hours earlier had attacked the ministry over insufficient research into the side effects of COVID vaccinations.

Like previous posts about side effects, this one by the Health Ministry also drew thousands of angry responses. Another ministry post, maintaining that reports on side effects were being monitored and examined regularly, triggered a storm when surfers claimed that the ministry had deleted thousands of responses from people who had reported side effects. The ministry retorted that only posts containing obscenities had been deleted, and in response surfers posted screenshots of “clean” responses that had been removed.

The agitated public discourse on the vaccinations has developed a centrifugal force that is flinging the participants as far as possible from one another. It is making them cling to their positions far beyond the circumscribed zone in which one can ask questions and make comments without being considered a complete heretic or, alternately, a blind follower.

At this stage the debate seems to be bipolar. At one pole are those who personally know 10 people who died within minutes of being vaccinated, and who are convinced that an organized whitewashing conspiracy effort is underway with the aim of controlling the public. At the other pole are those who roll their eyes and dismiss the question of side effects as one of boring trivialities that only hysterics or those with vested interests make a fuss about.

The time has come for a saner, more balanced discourse that also addresses complexity. The possibility of achieving this may have arrived at last. Last week, two large-scale studies by two groups of Israeli scientists were published in the New England Journal of Medicine – one by the Health Ministry, the other by the Clalit health maintenance organization – which examined the possible connection between vaccination against COVID-19 and myocarditis (heart inflammation). Their findings were quite similar, but because the Health Ministry study was more comprehensive (in fact it is the most comprehensive in the world, because it’s the only one that included everyone vaccinated in a single country), and because its follow-up of those who were vaccinated was more prolonged and it also distinguished between recipients of the first and second jabs – I will refer to the data it contains.

Among all those who received the second shot – 5,671,471 people through May 31, 2021 – 142 cases of myocarditis were found. The ratio, then, is 1:40,000 vaccinees. The question is whether this is a low value or a high one. One way to read the findings is: “Only 142 out of five million vaccinated Israelis suffered heart inflammation.” That approach, which was how Haaretz headlined the story, “diminishes” the figure. Or, one could “augment” the number – for example, by adding a worrisome exclamation mark: “More than 140 of those vaccinated developed myocarditis!” Either way, the result requires substantive clarification.

“In trying to determine whether a connection exists between heart inflammation and vaccination, we adopted several approaches,” says Prof. Dror Mevorach, who is the first signatory on the NEJM article reporting on the study, and the head of the committee established by the Health Ministry to examine the subject. “Among other criteria, we compared the frequency [of myocarditis] in those vaccinated with those not vaccinated, and we discovered that the number of cases was twice as high. We also examined the pattern of its appearance, and we saw that in 90 percent of the cases, it manifested three to four days after the second shot. We concluded that there is a connection between the two phenomena.

“But equally important was to look at the data up-close,” Mevorach continues. “It turns out that the frequencies are not distributed equally among the population. The inflammation appears far more in men than in women, and the highest risk is for male adolescents aged 16 to 19. In that group, the likelihood of contracting myocarditis in the wake of two vaccine doses is 1:6,637 vaccinees.”

Again the question arises about the ratio. Is it high? Low? Relative to what? One could also ask other important questions, such as what caused the inflammation to occur precisely in these people? Is myocarditis a reversible condition? Can it be prevented? And perhaps even whether it is possible to base practical conclusions on the finding.

Prof. Dror Mevorach. “It’s important to remember that most of those who develop myocarditis in the wake of the vaccination recover within a few days.” Credit: Emil Salman

An article that might suggest a possible direction for answers appeared this past summer in the journal Clinical Infectious Diseases, which is published by the Infectious Diseases Society of America. Scientists injected the vaccine (Pfizer’s mRNA) into two groups of mice. One group received it in the muscle, the other intravenously – that is, in the bloodstream. Each mouse received two doses, the second two weeks after the first. The results were fascinating: All the mice that received the vaccine into the bloodstream developed symptoms of heart muscle inflammation, but not a single mouse that received the doses into the muscle!

Changes in the heart tissue were documented in the mice that received the vaccine in the blood. The spike protein was found in some cells, and a rise was recorded in the level of cykotines, the materials that invite the invasion of the vaccine cells that are responsible for the inflammation. All these changes lasted for two weeks after the first dose and were very much aggravated in the wake of the second dose.

“That is also the picture we saw in our study of humans,” says Prof. Mevorach, of Hadassah University Hospital, Ein Karem. “The absolute majority of the cases of inflammation appeared after the second shot.” (Because the Health Ministry’s study concluded before the start of the large-scale operation to administer the third dose, no data about it appears in the study.)

But what is the connection between the experiment on the mice and the vaccination procedure for people? After all, everyone who was vaccinated remembers very well that the inoculation was given in the deltoid muscle of the arm, and not in the vein. Those are also the instructions of Pfizer (and of Moderna). But does that really happen? The researchers who studied the mice raise the possibility that in a small proportion of the human injections, the syringe may have by chance encountered blood vessels in the muscle and injected the vaccine into the bloodstream instead of the muscle. Thus, they surmise, instead of the mRNA situating itself in the muscle cell and doing its work, it was transported via the blood and reached the heart. But is that the case?

“It’s definitely a relevant hypothesis,” Mevorach says, “and along with it we are examining other hypotheses regarding a factor that might explain at least some of the cases in which the inflammation developed.”

A chance injection into blood vessels in the muscle is a tempting explanation for the appearance of a side effect in general, but naturally not every tempting explanation is the right one. Often, when a good argument is encountered, there’s a tendency to choose the appropriate facts and ignore challenging questions. This one, for example: The deltoid is a large muscle that contains few blood vessels, and if so, what is the probability of the needle encountering one of them?

In connection with myocarditis, it’s important to remember that most of those who develop it in the wake of the vaccination recover within a few days.

Prof. Mevorach

The question becomes even more acute in light of the fact that heart inflammation has been found to surge precisely after the second dose of the vaccine. What is the probability that in both jabs – the first and the second – the needle will penetrate blood vessels by chance? The experiment with the mice actually answers the second question. The researchers found that it was sufficient for the first dose to have been injected into the blood for the mice to develop heart inflammation after the second dose. It made no difference whether the second jab was into the blood or the muscle. What can be inferred for humans is that it’s possible that the accidental injection of the first dose into blood vessels is sufficient to produce myocarditis in the wake of the second dose.

Is there any way to know whether the needle accidentally penetrated blood vessels? It turns out that until a few years ago, the vaccination protocol referred exactly to this matter. In the past, individual vaccinations were given in two stages. In the first, the needle was inserted into the tissue, and then withdrawn a bit by lightly pulling out the plunger of the syringe and seeing whether any blood was drawn. If it was, that meant the needle had entered a blood vessel, in which case it was pulled out and inserted elsewhere. If the pumping turned up nothing, the procedure continued: The plunger was pushed in fully, and the material was injected into the muscle.

A few years ago, the recommendations and guidelines of both the U.S. Centers for Disease Control and Prevention and the World Health Organization were revised: They no longer require the cautionary stage of withdrawing the plunger. In fact, the 2020 directives emphasize specifically that drawing it out is not required, and a call to an instructor in a nursing school in Israel made it clear that this procedure is no longer followed here, either. It’s difficult to track down the reasons that led to the revision in the protocol, but it apparently stemmed from an effort to reduce the pain (vaccination that includes extraction is more painful in the place of the injection) and from the thinking that the chance of encountering blood vessels is very low.

And again the question arises: What is “low”? Low in a way that can explain, even partially, the “low” frequency of the appearance of heart inflammation? Perhaps consideration should be given to reverting to the original vaccination protocol, which was in practice before the anti-COVID vaccination was developed.

A healthcare worker prepares doses of the coronavirus disease (COVID-19) vaccine.Credit: CALLAGHAN O'HARE/ REUTERS

Sports and testosterone

Another interesting phenomenon that might shed light on the mechanism responsible for the occurrence of myocarditis is that condition’s particularly high frequency among males aged 16 to 19. Why does that happen? One characteristic of teens of that age is heightened participation in sports. If so, it’s possible that their developed deltoid muscles are nourished by a large number of blood vessels, which constitute a larger target for the syringe’s errant needle.

“That hypothesis supplements another hypothesis that we’re checking, which is also related to an intensified occupation with sports among this group,” says Mevorach. “Because engaging in sports heightens the blood flow to the muscle, it’s possible that such activity, if engaged in shortly before the inoculation, increases the possibility of the vaccine entering the blood and causing undesirable phenomena.”

The professor's research team is also examining other possible mechanisms, such as that sex hormones play a part in the appearance of the myocarditis. High levels of testosterone might have something to do with the higher risk among men, or alternately, it’s possible that women are protected by estrogen. In addition, he says, “there is always the possibility of a prior genetic tendency that sets apart the individuals who were affected, and it’s very possible that not one but several reasons created the picture we are seeing.”

Now that you have probed the side effects more thoroughly – heart inflammation is perhaps only one example – does that go some way toward dampening enthusiasm for the third dose or for vaccinating children?

Mevorach: “To begin with, in connection with myocarditis, it’s important to remember that most of those who develop it in the wake of the vaccination recover within a few days. To date, there does not appear to be a prolonged impact, though we have to complete a long-term study. Second, data always has to be read in accordance with the alternatives. In general, when I evaluate the possible dangers of infection by the coronavirus, as compared with the possible dangers from vaccinations, I think that vaccination is preferable, including for children.

“For example, massive data from the United States shows that among every 3,000 to 4,000 children, ages 3 to 15, who were infected by the virus, a ‘multisystem inflammatory syndrome’ develops, which is far more serious than myocarditis and could even be fatal. So vaccination is still the better step, and I recommend it as of now.

“At the same time, what is most important in my opinion is transparency: Those who are getting vaccinated – or, if they are under 18, their parents – must be given all the information, clearly presented, so that they can weigh possibilities against risks and make an educated decision. In the end, it’s a decision by each person about himself. They can rely on my recommendation, but also on other considerations and values. That’s fine. I respect every decision,” Mevorach concludes.

There’s no doubt that what’s most important is transparency. In conversations I've held with people, among them many physicians (all of them from the mainstream), a strong feeling arose that there is under-reporting of side effects. Not because of an evil conspiracy hatched by the establishment, but more because of tardiness, snags and lack of clarity. If a doctor saw a patient who contracted facialis (facial-nerve paralysis) and had been vaccinated in the days or weeks prior to that, can she determine that there is a causal connection between the two events? Contrary to popular opinion, that form of paralysis can also appear in regular times, with no connection to a vaccination. And what about the disruption of women’s menstrual cycle?

To establish a causal connection between two phenomena, a great deal of data – clear, detailed, precise – needs to be collected and then subjected to statistical analysis, which can differentiate between elusive gut feelings and valid facts. And therein lies the problem. Whereas the data about myocarditis was compiled actively by researchers, the compilation of most of the other data is dependent on their goodwill and the ability of the physician and the vaccinees to report.

The form that physicians are required to fill out when they encounter a patient who is experiencing a disorder, and who is also a recent vaccinee, is very complicated and unclear. Some physicians tend to bypass it. The website that invites people to report anonymously about disorders they experienced cannot be considered reliable, because it doesn’t allow researchers to get in touch with the person and to check the details with them. The fact that no intensive, systematic effort is being undertaken (again, not necessarily deliberately) is frustrating people, angering them and leading to dangerous and automatic antagonism.

According to a senior figure in the Health Ministry’s unit that deals with epidemics, the ministry is working on making the reporting of physicians and patients accessible, in order to facilitate a free and reliable flow of reports about side effects.

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