On 27 December 2020, the vaccination campaign was officially launched. Because the number of vaccinated people was small at first, it was difficult to classify such reports. In the meantime, millions of people have been immunised: Time to take stock.

The vaccinations have not only prevented hospital admissions and deaths, but also made a large part of social life possible again, write US authors in the scientific journal "Jama". In order for people to trust the vaccines, it is important to clearly communicate "the major benefits and minor risks", but also to monitor the safety of the vaccines, the experts of the health authority CDC emphasise.

Germany has "monitored suspected cases of vaccine side effects and complications with the highest priority from the beginning, also recognised very rare side effects at an early stage, and initiated measures to minimise the risk", write the heads of the Paul Ehrlich Institute (PEI) and the Federal Institute for Drugs and Medical Devices (BfArM), Klaus Cichutek and Karl Broich, in their review one year after the start of vaccinations.

According to the German Society for Immunology (DGfI), typical complaints after a vaccination are pain at the injection site, fatigue and headache, muscle pain, chills and fever. "These reactions are an expression of the desired confrontation of the immune system with the vaccine and usually subside completely after a few days," writes the Robert Koch Institute (RKI).

The PEI, which is responsible for the safety of vaccines, regularly publishes so-called safety reports on the Covid 19 vaccines. The most recent one dates from 23 December and refers to over 123 million vaccinations administered nationwide by the end of November. Reported by then were 1.6 suspected cases per 1,000 doses - equivalent to 0.16 percent. Considering only the severe reactions, the reporting rate is 0.2 suspected cases per 1,000 vaccine doses - 0.02 percent.

The Medicines Act defines "serious" as side effects that are fatal or life-threatening, require inpatient treatment or lead to permanent damage. According to the Infection Protection Act, serious side effects must be reported if they "go beyond the usual level of a vaccination reaction“.

As "very rare risks of Covid-19 vaccines", the latest PEI safety report lists: Allergies (anaphylactic reactions), heart muscle inflammation (myocarditis) and pericarditis, the nerve inflammation Guillain-Barré syndrome, and blood clots (thrombosis-with-thrombocytopenia syndrome, TTS).

In general, the PEI points out that "adverse reactions are reported in temporal, but not necessarily in causal connection with a vaccination. Only studies could prove whether a reaction is actually a consequence of the vaccination. The PEI works with probabilities: It compares how often an adverse reaction is reported and puts this in relation to how often this statistically occurs in a comparable unvaccinated population. "According to current knowledge, serious adverse reactions are very rare and do not change the positive risk-benefit ratio of the vaccines," emphasises the latest safety report.

"Myocarditis is a relevant side effect," says the chairman of the board of the German Heart Foundation, Thomas Voigtländer. But that should not be a reason to decide against a Covid-19 vaccination, he adds: "Those who don't get vaccinated against Covid-19 run a much higher risk due to the dangers of severe Covid-19 disease.“

Myocarditis or pericarditis as vaccine reactions are very rare, he said. "We are talking about just under five cases related to 100,000 vaccinations." Moreover, they are usually mild and heal in almost all cases. The suspicious reports mainly concerned the two mRNA vaccines and predominantly male adolescents. According to the safety report, 15 deaths were mentioned in connection with the Covid 19 vaccination. In three of these, the PEI considers a causal connection to be possible; in the other cases, the authority does not assume this "on the basis of the current data situation“.

In spring, reports of very rare thromboses caused a stir - the thrombosis-with-thrombocytopenia syndrome (TTS). These blood clots often occur in unusual places, such as the brain: affected people have a reduced number of platelets at the same time. "This condition is a rare but potentially dangerous side effect of vector-based Sars-CoV-2 vaccines," stresses the Society for Thrombosis and Haemostasis Research (GTH).

The reports mainly concerned the vector vaccines from AstraZeneca and Johnson & Johnson. Women were affected more often than average. According to the safety report, 43 deaths from TTS were linked to the vaccinations. According to the PEI, 29 of them fulfil the special criteria for a TTS: Accordingly, they concern the preparations of AstraZeneca and Johnson & Johnson. AstraZeneca is no longer used in Germany, Johnson & Johnson plays a minor role.

Anaphylactic reactions occurred with all four licensed vaccines, but they were also very rare. The reporting rate was less than one case per 100,000 vaccine doses by the end of November. It is slightly higher in females than males and higher for the first vaccine dose than for subsequent vaccines.

Guillain-Barré syndrome (GBS) is a very rare autoimmune disease of the nervous system. According to the safety report, the reporting rate after vaccination with one of the two vector vaccines was lower than one report per 100,000 vaccine doses.

"There are two possibilities of what is meant by the term "long-term consequences"," writes the PEI. "Something that occurs only after a long time, or something that lasts over a long period of time." That very rare vaccination complications last over a long period of time is "the absolute exception", the authority writes.

"Concerned citizens understand long-term effects - often called late effects - to mean side effects that occur after a delay of many months or years after vaccination," it continues. "These concerns are unjustified. We are not aware of such very late-onset side effects of vaccines.“

According to the latest safety report, suspected deaths following vaccination were reported 1,919 times. But only in 78 individual cases did the PEI "assess the causal relationship with vaccination as possible or probable". A comparison of the number of reported deaths with the statistically expected number of deaths in the same period "did not reveal a risk signal for any of the four Covid 19 vaccines used in Germany so far", writes the PEI.

A side effect is an effect that occurs in addition to the intended main effect of a drug. Alternatively, the terms "adverse reaction" and "complication" are also used.

Side effects of medicines or vaccines are listed in the package insert, the specialist information for doctors and the manufacturer's product information. For this, a causal relationship must be known or at least plausible.

"Unforeseen side effects" are reactions that have not been observed before and are not yet described in the expert information.

"Serious side effects" are reactions that are fatal or life-threatening, require hospitalisation or lead to permanent or serious damage.

"Rare side effects" are only seen when a very large number of people have been given the product. The number of people taking part in phase 3 trials of a new drug is often too small to see side effects that occur, for example, once per million people. The term says nothing about the severity of the side effects. It ranges from harmless side effects such as fatigue to risks whose harm exceeds the benefit of the drug.

(Original text: Sandra Trauner, dpa; Translation: Mareike Graepel)