In focus: The safety of licensed Covid-19 vaccines
The top priority in the development of Covid 19 vaccines from the outset was tolerability and safety. Fortunately, the very first vaccines proved to be well tolerated. However, the safety review does not end with the approval of the vaccines, but continues thereafter. How this is done is explained here.
During development, the tolerability of each vaccine was first tested in animal studies and then (if the results were good) in all subsequent clinical trials with volunteers. All Covid-19 vaccines that have been approved in the EU to date or for which EU approval is pending have shown good tolerability in this context: although many study participants experienced the usual vaccination reactions (pain at the injection site, fatigue or somewhat elevated body temperature in the initial period after vaccination, etc.), they did not experience any problematic side effects.
The longest stage in covid-19 vaccine development is testing with volunteers. There is much to consider in this process. How these vaccines are tested is described in detail here.
Because the phase III trials were conducted with a very large number of participants (approx. 20,000 to 45,000) and about half of them received injections with the real vaccine, the tolerability was or is already broadly assured at the time of approval. Nevertheless, even in studies of this magnitude, side effects do not occur very rarely - i.e., in less than one in ten thousand vaccinated persons.
Experiences in the application
As with all medications administered as shots or infusions, in very rare cases Covid-19 vaccines can cause an immediate violent immune reaction called anaphylaxis. Fortunately, vaccinators know how to treat this reaction with common medications. Therefore, as a precautionary measure, it is sufficient not to let those who have been vaccinated go home immediately, but to continue to observe them for at least another quarter of an hour. Only people who have had an anaphylactic reaction to the first injection should not receive the second dose (which is otherwise due after three or four weeks).
The review of vaccine safety in the ongoing vaccination effort was explained by vfa research spokesman Dr. Rolf Hömke in a Deutsche Welle TV segment on Jan. 22, 2021:
(© Deutsche Welle)
Many people, many medical events: This is the backdrop against which vaccination campaigns play out
If there were only healthy people and nothing else in medicine but SARS-CoV-2 and the vaccinations against it, then it would be comparatively easy to identify what side effects of a vaccine are and what are not. For then every medical event in the weeks after a vaccination - from headache to heart attack or death - could only be due to the vaccination or an infection that occurred in the meantime. But unfortunately it is not that simple: In any randomly assembled larger group of people, quite a few medical events occur in the course of a month - completely without vaccination or infection: Migraine attacks, heart attacks, initial diagnoses of cancer or diabetes, thromboses, hemorrhages, and much more. In order to be able to determine whether a vaccination poses a health risk or not, the drug authorities analyzed anonymized medical records many years ago and then determined how often events of this type occur for different age groups and according to gender. They therefore also know how many people in a particular age group die on average within a month.
On the basis of such evaluations it is obvious that it cannot be otherwise than that in the case of mass vaccinations some vaccinated persons have to be medically treated hours, days or weeks after the vaccination or even die without this having anything to do with the vaccination. Only an increased rate of such events would be a clear alarm signal.
Thus, whenever it is suspected that observed cases of illness may be related to a previous vaccination (as is currently being discussed for thrombosis and bleeding with a Covid 19 vaccine), drug authorities investigate in two directions:
- A comparison will be made to see if the rate of these disease cases is higher among the vaccinated than among the unvaccinated.
- It will also be investigated among the affected individuals themselves to see if there is evidence of a causal relationship.
As a rule, such investigations show that the vaccine did not increase the risk and that there was only a coincidental coincidence in time between some vaccinations and medical emergencies.
However, if a previously unknown serious vaccine side effect were to be detected in this way, the drug authorities would immediately initiate countermeasures with the manufacturer. This could be the recall of a production batch if the side effects only occurred in that batch, or the exclusion of certain groups of people who are already at high risk for the side effect in question.
For Germany, the responsible drug agency, the Paul Ehrlich Institute (PEI), reports weekly on its website on reported medical events after Corona vaccination.
Ongoing safety monitoring
But safety monitoring of approved Covid 19 vaccines (known in the trade as pharmacovigilance) is not limited to evaluating reports that physicians or affected individuals submit to authorities on their own.
Overall, drug regulators and vaccine manufacturers around the world are tackling it in three ways:
- Follow-up of participants from phase III trials:
Participants in the trials that are the basis of regulatory approvals continue to be regularly monitored for potential side effects after efficacy has been determined - typically for two years.
- Study of cohorts of vaccinated:
Among the vaccinated, many countries recruit people who are willing to provide information about their health status and possible vaccine reactions in the days after vaccination and for six months and a full year afterward. Such a group of people is called a "cohort." Participants in the German cohort submit their information confidentially to the competent drug authority, the Paul Ehrlich Institute, using the App SaveVac 2.0.
- And only third: the spontaneous reports of vaccinated:
All reports of suspected cases of adverse reactions that vaccinated on their own initiative ("spontaneously") are collected. All vaccinated persons are called upon to report. They can report, for example, via their physician or pharmacist or the reporting portal of the drug authorities www.nebenwirkungen.bund.de (more here). In this regard, the vaccinated individual does not have to provide his or her own evidence that the negative physical reaction experienced is truly a vaccine side effect. Rather, any reaction that someone suspects may be a side effect can be reported. The reports go into the European database EudraVigilance and are screened by experts from the national regulatory authorities together with the European Medicines Agency (EMA) to determine whether the reported medical events could really be a vaccine consequence or occurred purely by chance shortly after vaccination.
Of course, not only vaccinated, but also their relatives can report potential side effects and also members of the health professions, such as doctors and pharmacists, are required by professional code to report suspected cases of side effects.
International cooperation on safety surveillance and security measures
The SARs are not just collected by each country or the EU on its own. They are pooled from around the world as part of the World Health Organization's (WHO) activities so that a previously unknown adverse reaction requiring countermeasures can be identified as quickly as possible, and risk mitigation measures can also be applied globally. This makes sense, given that Covid vaccines are already used in more than 40 countries.
In addition to monitoring the safety of the Covid 19 vaccines, the international collaborations are, of course, also about gaining knowledge.
Tolerability to pregnant women and unborn children
As part of the clinical trials, all manufacturers and their collaborating medical institutions have taken care to ensure that no pregnant women participate in the studies. This is the normal procedure with any new drug, whether or not scientists suspect a risk to mother or child.
Nevertheless, unknowing pregnancies have occasionally been discovered among participants. These pregnancies are closely monitored and their outcome documented. In addition, the mothers and newborn children are examined. So far, there has been no indication of a problem, and a company has now been able to begin a clinical trial involving pregnant women. Outside of such studies, however, Covid vaccines should currently be considered only after a precise medical risk assessment for the individual pregnant woman, according to the regulatory agency.