The largest COVID-19 safety study to date was published online earlier this month in the journal Vaccine. The study, which was spearheaded by the Global Vaccine Data Network and funded by the CDC, included data on over 99 million vaccinated individuals across 10 sites in eight countries.
Sensational headlines immediately began cropping up across news sites:
At first glance, these stories appear to be reporting something new and different about the COVID vaccines. But when we step back, we realize this information is not new at all. The study is simply confirming what we’ve known for years now: there is a small risk of adverse events from the COVID vaccines but the benefits still far outweigh any risks.
Monitoring the Safety of the COVID-19 Vaccines
The COVID-19 vaccines were introduced globally in 2020, accompanied by the most intensive vaccine safety monitoring program the world has ever seen. After 3 years of administration, data show that for the vast majority of the 13.6 billion doses administered globally, recipients experienced either no vaccine reactions or reactions that were mild and self-limiting (fever, chills, tiredness, headache, etc.).
Anytime a medicine or a vaccine is approved and introduced into wider use, rare adverse events are found in the population that would be impossible to find in clinical trials. The U.S. government constantly monitors different databases like the Vaccine Adverse Event Reporting System (VAERS) for rare adverse events and potential safety signals that may arise, and then analyzes whether the number of events among vaccinated individuals is greater than what would be seen normally in the population. While some rare side effects of the COVID-19 vaccines have been shown to occur more frequently than in the background rate of the population, the number of these events represents a tiny percentage of the billions of people overall who received the vaccines.
Before this new study was published, healthcare professionals like yourself and the public were already aware of safety signals of a few very rare adverse events detected in databases (i.e. rare allergic reactions, myocarditis and pericarditis mostly detected in young men after mRNA and Novavax vaccines, or rare but serious cases of thrombosis with thrombocytopenia syndrome [TTS] after the Johnson & Johnson and AstraZeneca vaccines). Even though TTS cases linked to the J&J vaccine were extremely rare, use of this product was quickly paused and eventually deprioritized as a result, proof that the safety surveillance system is very sensitive to detect the rarest events, and that the system does work to make vaccines safer.
Digging Deeper Into the Vaccine Safety Study
The purpose of the study was to get more precise estimates of the risk of adverse events following COVID-19 across several countries. Three vaccines were examined in the study: two were mRNA vaccines (Pfizer/BioNTech and Moderna) and the other was AstraZeneca’s viral vector vaccine, which was never authorized in the U.S. but is the same vaccine type as the J&J shot.
It is important to note that the results of this study are not odds ratios or relative risks (which would be comparing vaccinated to unvaccinated people), but instead the study methodology examined the observed versus expected (OE) ratios: observed post-vaccination rates from a pre-specified list of adverse events to the expected rates, or the historical, background rate of the same events calculated from the same populations during 2015-2019, before the vaccines were available. Any event where the lowest end of the observed rate range was estimated to be at least more than 1.5 times the expected/background rate (using the lower bound of the confidence interval) was flagged as a potential safety signal. Because there is no direct comparison, studies like these are not used for causality assessment, but only for detecting potential safety signals.
So, what did the study find?
Despite headlines that may have suggested there was some kind of bombshell finding in this study, the main, statistically significant findings from this study really only served to confirm safety signals that already had been found in other databases around the world. The following are the events that were identified as safety signals:
- Guillain-Barré syndrome (OE 2.49, 95% CI 2.15-2.87) following the first dose of AstraZeneca’s viral vector vaccine
- Cerebral venous sinus thrombosis (OE 3.23, 95% CI 2.51-4.09) following the first AstraZeneca dose (these are the TTS blood clots also linked to the J&J shot)
- Acute disseminated encephalomyelitis (OE 3.78, 95% CI 1.52-7.78) following the first dose of Moderna’s mRNA vaccine — this was not found in a more rigorous follow-up study done by this same group
- Myocarditis and pericarditis following Pfizer and Moderna’s mRNA vaccines and AstraZeneca’s viral vector vaccine were >1.5
All of the other findings of lower magnitude from the study were deemed to be “hypothesis generating” and should be followed-up on with more rigorous designs.
This was the conclusion from the authors: “This multi-country analysis confirmed pre-established safety signals for myocarditis, pericarditis, Guillain-Barré syndrome, and cerebral venous sinus thrombosis. Other potential safety signals that require further investigation were identified.”
Don’t Let the Headlines Halt Prevention Efforts
The bottom line is that no medication or vaccine is 100% effective or 100% safe, and everything has risks and benefits. But any risks from medications and vaccines need to be balanced against the risks of the disease you are trying to prevent. For example, the risk of myocarditis/pericarditis from COVID-19 is six to 11 times higher and is associated with a more severe clinical presentation than the risk from the COVID-19 vaccine.
COVID-19 has killed over a million people in the U.S. and has led to permanent disability in many others. The vaccines are very safe overall, and the benefit of the vaccine still definitely outweighs the risks. Fear mongering headlines serve only to harm, not help, public health.
Katrine Wallace, PhD, is an epidemiologist and adjunct assistant professor in the Division of Epidemiology and Biostatistics & Division of Community Health Sciences in the School of Public Health at the University of Illinois at Chicago.
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