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Safety of the Fourth COVID-19 BNT162b2 mRNA (Second Booster) Vaccine
45 Pages Posted: 24 Jun 2022More...
Background: COVID-19 remains a global concern due to vaccine protection waning and the emergence of immune-evasive variants. While the effectiveness of a second booster vaccine dose (i.e., fourth inoculation) is well proven, its safety has yet to be fully understood. This lack of sufficient vaccine safety information is one of the key contributors to vaccine hesitancy.
Methods: To evaluate the safety of the second BNT162b2 mRNA COVID-19 booster vaccine, we analyzed its short-term effects and compared them to those of the first booster by utilizing data from (1) a prospective cohort of 2,019 participants and (2) a retrospective cohort of 250,000 random members of the second-largest healthcare organization in Israel. Participants from the prospective cohort received smartwatches, downloaded a dedicated mobile application, and granted access to their medical records. The smartwatches continuously monitored several physiological measures, including heart rate and stress-based heart rate variability. The mobile application collected daily self-reported questionnaires on local and systemic reactions. Medical records of the retrospective cohort were accessed to examine the occurrence of 30 potential adverse events. In both cohorts, we evaluated the risk differences between the pre- and post-vaccination periods in a pairwise fashion.
Findings: The prospective cohort includes 1,789 participants who received the first booster and 615 who received the second booster. We found substantial changes from baseline levels in the 72 hours following the second booster in both self-reported questionnaires and physiological reactions measured by the smartwatches. However, no significant difference was observed between the reactions to the first and second booster. We also found that participants who reported more severe reactions to the first booster tended to likewise report more severe reactions to the second booster. The retrospective cohort includes 94,169 participants who received the first booster and 17,075 who received the second booster. We observed no positive association between the second booster vaccination and any of the adverse events tested, including myocarditis and pericarditis.
Interpretation: Both our prospective and retrospective analyses support the safety of the second booster, with our findings reflecting patients’ objective and subjective responses.
Funding Information: This research was supported by the European Research Council (ERC) project #949850 and the Israel Science Foundation (ISF), grant No. 3409/19, within the Israel Precision Medicine Partnership program.
Declaration of Interests: The authors declare no competing interests.
Ethics Approval Statement: All the subjects in the prospective study were advised, both orally and in writing, as to the nature of the study and then gave a written informed consent to participate. The entire study (prospective and retrospective parts) was approved by Maccabi Healthcare Service's Helsinki institutional review board, protocol number 0122-20-MHS.
Keywords: COVID-19 vaccine, second COVID-19 booster vaccine, BNT162b2, adverse effects, wearable sensors
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