Evidence for safety of Pfizer-BioNTech’s COVID-19 vaccine booster dose

Researchers in the United States and Israel have conducted a study demonstrating the safety of administering a third (booster) dose of Pfizer-BioNTech’s BNT162b2 vaccine to protect against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 ) – the agent that causes coronavirus disease 2019 (COVID-19).

Study: Self-reported and physiological reactions to the third BNT162b2 mRNA COVID-19 (booster) vaccine dose. Image Credit: guteksk7/ Shutterstock

Findings from the study of more than 1,500 individuals who had received at least one dose of the vaccine showed that local and systemic reactions following a third dose were very similar to those observed following the second dose, which has already been shown to be safe in clinical trials.

Furthermore, the changes observed following a third dose, including self-reported reactions and objective physiological indicators, returned to their baseline levels within three days, says the team from Tel Aviv University, Stanford University in California, and Maccabi Healthcare Services in Tel Aviv.

“Our work further supports the safety of a third COVID-19 BNT162b2 (booster) vaccine dose from both a subjective and an objective perspective,” writes Erez Shmueli and colleagues.

A pre-print version of the research paper is available on the medRxiv* server while the article undergoes peer review.

Israeli government initiated a booster shot campaign

Although the BNT162b2 vaccine developed by Pfizer-BioNTech has exhibited high efficacy (93.7%) against the B.1.1.7 (alpha) variant of SARS-CoV-2, recent studies have shown a reduced efficacy (88%) against the more recently emerged delta (B.1.617.2) variant of concern.

On July 30^th, 2021, the Israeli government initiated an unparalleled, pro-active, national campaign, offering a third (booster) vaccine shot of BNT162b2 to all individuals aged over 60 years.

On August 13^th, the campaign was expanded to include those aged over 50 years. By August 29^th, it was extended to anyone in the general population who had received a second dose more than five months previously.

However, “limited information is available on the safety of a BNT162b2 third dose, with such a booster vaccine yet to be authorized by the US Food and Drug Administration for the general population,” say the researchers.

“While recent evidence shows that a third BNT162b2 dose in immunocompromised individuals has a favorable safety profile, a formal clinical trial for assessing the safety of a third (booster) dose in the general population has not yet been fully established.”

What did the researchers do?

Erez Shmueli and colleagues set out to evaluate the self-reported and physiological reactions to a third dose of the BNT162b2 vaccine.

The team followed a large cohort of 2,848 prospective study participants, among whom 1,503 participants (aged 19 to 88 years) had received at least one dose of the BNT162b2 vaccine between December 20^th, 2020 September 6^th, 2021.

Of these 1,503 participants, 1,231 had received a third vaccine dose.

Each participant received a dedicated mobile application that collected daily self-reported questionnaires on local and systemic reactions and well-being indicators over 21 days, starting seven days before vaccination (baseline levels).

Participants were also equipped with a fitness tracker (smartwatch) that continuously monitored several physiological measures, including heart rate and heart rate variability.

What did the study find?

Self-reported local and systemic changes following a booster vaccine dose were similar to those reported following the second dose.

The types of reactions that were most frequently reported (fatigue, muscle pain, headache, fever, and chills) returned to baseline levels among nearly all participants within three days.

“Notably, these trends are consistent with those reported in the first and second dose BNT162b2 mRNA vaccine clinical trial,” says the team.

According to the self-reported well-being indicators, participants experienced a significant reduction in mood levels, sleep quality, sport duration, and a notable increase in stress levels, compared with baseline levels, during the first two days following the booster vaccine.

Again, these changes faded within three days, and a similar trend was observed following the second dose.

Analysis of the objective physiological measurements collected by the smartwatch revealed a considerable increase in both heart rate and heart rate variability in the first two days following receipt of the third dose. These measurements also returned to baseline levels within three days.

All trends observed were consistent irrespective of age, gender, or any underlying medical conditions.

What did the team conclude?

The team says the study supports the short-term safety of a third BNT162b2 booster vaccine dose and mitigates, in part, the concerns regarding its short-term effects.

“Our analysis of the comprehensive data on each participant examines the safety of a third (booster) vaccine dose from both a subjective perspective (patient questionnaire) and an objective perspective (smartwatch data),” writes Shmueli and colleagues.

The researchers also say the medical and scientific communities may benefit significantly from the largely unbiased data generated by wearable digital health technologies.

“Our findings could also be of interest to public health officials and other stakeholders, as it is important that objective measures are given attention in the critical evaluation of clinical trials,” concludes the team.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Sally Robertson

Sally first developed an interest in medical communications when she took on the role of Journal Development Editor for BioMed Central (BMC), after having graduated with a degree in biomedical science from Greenwich University.