SARS-CoV-2 Vaccine Safety: Why We Shouldn’t Lower Our Guard

Vaccines against the SARS-CoV-2 virus have been shown to be highly effective in preventing severe forms of Covid-19 disease, whether they are adenoviral vector vaccines (AstraZeneca and Johnson & Johnson) or messenger RNA vaccines (BioNTech / Pfizer and Modern).

So far in years they have been administered 8.5 billion doses worldwide and the available data indicates that its safety is excellent too. In fact, the most common reactions (injection site pain, fever, muscle aches, headaches, etc.) resolve quickly and are similar to those seen with other vaccines.

Consequently, the benefit-risk balance of Covid-19 vaccination is unquestionably positive, and leads to maximizing vaccination coverage as far as possible.

However, vaccination campaigns meet opposition or doubts from some people. Among the various reasons given, the fear that certain undesirable effects have not yet been identified is predominant. This concern is fueled by isolated observations whose cause-effect relationship cannot be established by conventional pharmacovigilance programs.

The objective of this article is to encourage the development of studies specifically designed to identify or rule out very rare complications. It will be essential to communicate the information that is collected in a transparent way, so that opponents of vaccination do not have a monopoly on these issues.

Rare adverse events that have attracted attention

The first serious complication to come to light was atypical thrombosis after administration of the AstraZeneca vaccine in young women. The consequences of this thrombosis can be dramatic, especially when affects brain vessels.

At first, responsibility for vaccination was ruled out on the grounds that the incidence of thrombosis was similar in vaccinated and unvaccinated populations. It took some insightful physicians, impressed by the analogy with a rare complication of heparin (an anticoagulant) treatment, to identify the biomarkers of these atypical thromboses to see the evidence. This evidence was confirmed by specific epidemiological studies that estimated the risk in 2 cases per 100,000 doses under 50 years.

On the recommendation of regulatory agencies, health authorities in many countries have adapted the strategies for the use of adenoviral vector vaccines based on age, in order to minimize the risk of complication. In France, adenoviral vector vaccines have been reserved for people over 55 years of age.

Inflammation of the heart (myocarditis) or its envelope (pericarditis), seen occasionally in the days following messenger RNA vaccine injection, is another rare complication that has led to modification of Covid-19 vaccine strategies. It occurs most often in young men, and the risk is higher after the second dose of Moderna vaccine (about 13 cases per 100,000 doses).

It is the exemplary organization of the Israeli health system that has highlighted this serious complication. Fortunately, the vast majority of cases have a favorable outcome.

The approximately five-fold increase in risk with the Moderna vaccine appears to be related to the amount of RNA present, which is more than three times greater in this vaccine than in the Pfizer / BioNTech product. This has led to [Alta Autoridad Sanitaria francesa] to discourage the use of the Moderna vaccine in people under 30 years, in addition to administering only half a dose of this vaccine when it is used as a booster.

At this time, we cannot exclude that other rare adverse events may occur following the administration of SARS-CoV-2 vaccines. The challenge is determining what they are, especially if their rarity can cause them to slip through the cracks in pharmacovigilance systems.

Reappearance of lymphomas

The observation by our team of the development of a lymphoma after administration of a booster vaccine from Pfizer (a tumor of the lymphatic system, which occurs at the expense of B and T lymphocytes) leads us to consider in particular the possible consequences of the hyperstimulation of the immune system induced by RNA vaccines. This is related to its action on a particular population of lymphocytes, the follicular T cells.

Messenger RNA vaccines are, in fact, much more powerful in this regard than vaccines based on conventional technologies. The question is whether this hyperstimulation is not, in some cases, a double-edged sword.

In the case of lymphoproliferative diseases, our observation is not isolated. Three other cases of recurrence of lymphomas have been published after vaccination against SARS-CoV-2, one after the Pfizer vaccine, the two others after the AstraZeneca vaccine.

In the field of immuno-inflammatory diseases, a recent article also draws attention to 13 cases of glomerulonephritis (damage to the glomerulus, a functional unit of the kidney) that occurred or worsened after vaccination.

We suggest that special attention is also paid to children at high risk of developing Diabetes type 1 (insulin dependent). They have activated follicular T cells in large numbers, even before the level of glucose in their blood rises. Therefore, it is prudent to ensure that mRNA vaccines do not further stimulate these cells, which could accelerate the onset of diabetes.

Continue to improve pharmacovigilance systems

Existing pharmacovigilance systems are highly unlikely to detect whether vaccination against SARS-CoV-2 accelerates the course of the above-mentioned diseases. Not because inappropriate expedited procedures are handled, but because the traditional method of establishing vaccine liability in a given disease event is based on comparing its frequency in vaccinated and unvaccinated populations as a whole.

Studies targeting at-risk populations based on a credible mechanistic hypothesis are much better suited to prove or disprove rare complications.

Whatever the results of these investigations, they should not overshadow the overall very favorable benefit-risk ratio of messenger RNA vaccines. But they do invite adaptation of vaccination strategies for patients with certain conditions that put them at specific risk.

Michel Goldman, President of the I3h institute, Free University of Brussels (ULB)

This article was originally published on The Conversation. read the original.

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