Self-Reported and Physiologic Reactions to Third BNT162b2 mRNA COVID-19 (Booster) Vaccine Dose

Abstract

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.

Keywords: BNT162b2; COVID-19; SARS-CoV-2; adverse effects; booster vaccine; coronavirus disease; coronaviruses; heart rate variability; mRNA; physiologic reactions; respiratory infections; self-reported reactions; severe acute respiratory syndrome coronavirus 2; smartwatch; third COVID-19 dose; vaccine; viruses; wearables; zoonoses.

Figure 1

Reactions reported by participants through a mobile application for self-reported and physiologic reactions to BNT162b2 (Pfizer, https://www.pfizer.com) mRNA coronavirus disease vaccine doses. Error bars indicate 90% CIs.

Figure 2

Changes in subjective well-being indicators reported by participants through a mobile application for self-reported and physiologic reactions to BNT162b2 (Pfizer, https://www.pfizer.com) mRNA coronavirus disease vaccine doses. Mean difference compared with baseline levels are shown for the well-being indicators of mood level (A), stress level (B), sport duration (C), and sleep quality (D). Mood level, stress level, and sleep quality were reported on a 1–5 Likert scale. Sport duration was measured in minutes. Error bars indicate 90% CIs. Horizontal dashed lines indicate no change compared with baseline levels.

Figure 3

Changes in objective physiologic indicators measured through smartwatch for self-reported and physiologic reactions to BNT162b2 (Pfizer, https://www.pfizer.com) mRNA coronavirus disease vaccine doses. Mean difference are shown for smartwatch-recorded heart rate (A‒C), HRV-based stress (D‒F), and SpO₂ (G‒I) after the first, second, and third dose compared with their baseline levels. Mean values are indicated by solid lines; 90% CIs are indicated as shaded regions. Horizontal dashed line indicates no change compared with baseline levels, and vertical lines indicate 24-hour periods. HRV, heart-related variability; SpO₂, blood oxygen saturation level.

Figure 4

Self-reported and objective reactions following the third vaccine dose, stratified by age, sex, and underlying medical condition for self-reported and physiologic reactions to third BNT162b2 (Pfizer, https://www.pfizer.com) mRNA coronavirus disease vaccine doses. Reactions reported by participants through the mobile application (A, C, E) and objective heart rate and heart rate variability measured through a smartwatch (B, D, F) are shown, stratified by age (A, B), sex (C, D), and underlying medical condition (E, F). Bars indicate percentage of participants with a reported or recorded reaction; error bars indicate 90% CIs.