Abstract and Introduction
Despite extensive technological advances in recent years, objective and continuous assessment of physiologic measures after vaccination is rarely performed. We conducted a prospective observational study to evaluate short-term self-reported and physiologic reactions to the booster BNT162b2 mRNA (Pfizer-BioNTech, https://www.pfizer.com) vaccine dose. A total of 1,609 participants were equipped with smartwatches and completed daily questionnaires through a dedicated mobile application. The extent of systemic reactions reported after the booster dose was similar to that of the second dose and considerably greater than that of the first dose. Analyses of objective heart rate and heart rate variability measures recorded by smartwatches further supported this finding. Subjective and objective reactions after the booster dose were more apparent in younger participants and in participants who did not have underlying medical conditions. Our findings further support the safety of the booster dose from subjective and objective perspectives and underscore the need for integrating wearables in clinical trials.
The severe acute respiratory syndrome coronavirus 2 Delta variant (also termed variant B.1.617.2) was discovered in October 2020 in India and was designated as a variant of concern by the World Health Organization in May 2021.[1–3] Since its discovery, it has spread worldwide and has rapidly become the most dominant variant in many countries.[4–7] Although the BNT162b2 COVID-19 vaccine (Pfizer-BioNTech, https://www.pfizer.com) is highly effective against the Alpha variant, recent studies show that the effectiveness of the Pfizer-BioNTech vaccines is notably lower against the Delta variant: 88% compared with 93.7% against the Alpha variant.[9–12] Moreover, recent evidence shows that fully vaccinated persons infected with the virus can easily transmit it because their peak viral burden is similar to that observed for unvaccinated persons.[7,10] In Israel, the Delta variant has accelerated coronavirus disease (COVID-19) infection and hospitalization; numbers doubled every 10 days during July 1–August 9, 2021,[7,13] despite the high coverage of the BNT162b2 vaccine in Israel during this period, which was >75% coverage with 2 Pfizer doses in the eligible population (persons ≥12 years of age).
The rapid increase in hospitalizations associated with the Delta-driven COVID-19 resurgence and the imminent risk for hospital overcrowding led the Israeli government to initialize on July 30, 2021, an unparalleled, proactive, national third (booster) vaccine shot campaign, offering the BNT162b2 mRNA COVID-19 vaccine to persons >60 years of age. On August 13, 2021, the booster campaign was expanded to include persons >50 years of age and reached 63% third-dose coverage among the eligible population within only 26 days.[7,14–16] Two weeks later, on August 29, 2021, the campaign was expanded to include all persons ≥16 years of age, requiring only that 5 months had passed since the receipt of the second dose. This effort reached 40% third-dose coverage among the eligible population <50 years of age within 16 days.[13,17]
Limited information is available on the safety of a BNT162b2 third dose.[18,19] Such a booster vaccine has yet to be authorized by the US Food and Drug Administration (FDA) for the general population. Although recent evidence shows that a third BNT162b2 dose for immunocompromised persons has a favorable safety profile,[19,21] the safety of a third (booster) dose in the general population has not yet been fully established.
Clinical trial guidelines for assessing the safety of vaccines, including the FDA criteria, are primarily based on subjective, self-reported questionnaires. Despite the extensive advances in recent years, objective, continuous assessment of physiologic measures postvaccination is rarely performed. Two recent pioneering studies demonstrated the use of wearable devices to monitor short-term physiologic changes after the first and second doses of the BNT162b2 mRNA vaccine. The first study used a chest-patch sensor to monitor changes in 13 different cardiovascular and hemodynamic vitals in a cohort of 160 persons up to 3 days postvaccination. The second study used a consumer-grade smartwatch to evaluate changes in heart rate variability (HRV), resting heart rate, and respiration rate in a cohort of 19 persons. Both studies found major changes in several physiologic measures in the first days after vaccination.
We evaluated the short-term effects of a third BNT162b2 mRNA COVID-19 vaccine dose on self-reported and physiologic indicators on a relatively large sample. Specifically, we tested 2,912 participants; of these persons, 1,609 participants received ≥1 doses of the BNT162b2 vaccine after entering the study. Participants were equipped with Garmin (https://www.garmin.com) Vivosmart 4 smart fitness trackers and completed daily questionnaires by using a dedicated mobile application for 37 days, starting 7 days before vaccination. The mobile application collected daily self-reported questionnaires on local and systemic reactions, as well as various well-being indicators. The smartwatch continuously monitored several physiologic measures, including heart rate, HRV, and blood oxygen saturation level (SpO2). Our analysis of comprehensive data for each participant examined the safety of a third (booster) vaccine dose from a subjective perspective (self-reported questionnaire) and an objective perspective (smartwatch data).
Emerging Infectious Diseases. 2022;28(7):1375-1383. © 2022 Centers for Disease Control and Prevention (CDC)