COVID-19 Vaccine Safety Assessed in Largest Real-World Study

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A study published in The New England Journal of Medicine is the largest real-world assessment of a COVID-19 vaccine safety.

Earlier this week, the Pfizer vaccine became the first COVID-19 vaccine to receive full FDA approval. Over the years, several clinical trials and real-world studies have assessed the vaccine’s efficacy. However, reports of its high efficacy have also been accompanied by rare adverse reactions in vaccinated individuals. Moreover, previous studies that examined the vaccine’s safety, evaluated it in a vaccination setting. The real-world numbers, outside of a clinical trial setting, remain unknown. The lack of information on vaccine safety further adds to vaccine hesitancy.

Now researchers from the Clalit Research Institute and Harvard University have conducted an analysis of the Pfizer vaccine’s safety. The study, conducted in Israel, is the largest real-world assessment of COVID-19 vaccine safety. The analysis included health record data from over 2 million individuals in Israel. Results of the analysis are available in The New England Journal of Medicine.

To date, one of the main drivers of vaccine hesitancy has been a lack of information regarding potential side effects of the vaccine. This careful epidemiological study provides reliable information on vaccine safety, which we hope will be helpful to those who have not yet decided about vaccination.

Professor Ben Reis, study co-author

The team conducted two separate analyses: a comparison of adverse events between vaccinated and unvaccinated individuals, and between unvaccinated people infected with SARS-CoV-2 and unvaccinated noninfected people.

Risk Higher in Unvaccinated Individuals

They examined the health records for 25 potential side-effects, ranging from mild to severe. Only 4 showed a strong association with the vaccine: lymphadenopathy, herpes zoster infection, appendicitis, and myocarditis.

Myocarditis, a rare inflammation of the heart muscles, had 2.7 excess cases per 100,000 vaccinated individuals. They mostly occurred in males aged 20 to 34 years. However, coronavirus-infected unvaccinated individuals had higher rates of the disease. Although researchers also found an association with a small number of other adverse events, unvaccinated individuals with SARS-CoV-2 reported higher and more serious adverse events. Reports of cardiac arrhythmias, kidney damage, deep-vein thrombosis, and stroke were much higher among the unvaccinated patients.

This study sheds light for the first time on the significant side effects of the coronavirus vaccine. Since this is a more comprehensive analysis based on electronic medical records, these are more reliable assessments than those published to date which have relied on voluntary active reporting systems.

Doron Netzer, Chief Medical Officer of Clalit’s Community Health Division.

The results of the real-world study confirmed the Pfizer vaccine’s safety profile as reported in previous clinical trials. They further proved that the risk of adverse events is significantly higher in those infected with coronavirus or unvaccinated, compared to vaccinated individuals. Thus, revealing that the benefits of the vaccine outweigh the risk.


Noam Barda et al, Safety of the BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting, New England Journal of Medicine (2021). DOI: 10.1056/NEJMoa2110475


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