Study supports safety of fourth BNT162b2 mRNA vaccine

A study from Israel validated the safety of the fourth BNT162b2 mRNA COVID-19 vaccine (ie, second booster) using data from a retrospective and a prospective cohort.

“[Both] analyses support the safety of the second booster, with our findings reflecting physicians’ diagnoses and patients’ objective physiologic measures and subjective reactions,” said the researchers.

“The absence of sufficient vaccine safety information is one of the key contributors to vaccine hesitancy,” they noted. This knowledge gap should be filled to raise confidence in boosters, they stressed, as this gap “has thus far been filled by non-scientific, somewhat speculative theories.”

 

Prospective analysis

In this cohort, 1,785 participants received the first booster while 699 got the second (median age 62 years). They were provided with smartwatches to track heart rate (HR) data and daily questionnaires to report vaccine reactions. [Lancet Respir Med 2022;S2213-2600(22)00407-6]

HR rose substantially during the first 3 days after the second booster administration compared with baseline (Kruskal-Wallis test, statistic: 120.792; p<0.0001), peaking at day 2 (mean difference, 1.61 beats per minute [bpm]). On day 6 post vaccine, HR returned to baseline level (0.94 bpm; p=0.62).

Evidence suggests that even a minor long-lasting increase in HR is tied to an increased mortality risk. [Open Hear 2019;6:e000856; PLoS One 2020;15:e0233898] “However, … the daily mean difference of HR values returned to baseline levels by the sixth day after vaccination, so we do not expect an increased risk by this temporal change,” the researchers noted.

Two-thirds of second booster recipients did not report any new signs or symptoms after receiving their second booster. The most frequently reported reactions of fatigue, headache, muscle pain, cold, and sore throat eventually waned in almost all recipients within 3 days of receiving their shot.

Of note is the age (>50 years) of most second booster recipients. [corona.health.gov.il/en/vaccine-for-covid; www.cdc.gov/media/releases/2022/s0519-covid-booster-acip.html, accessed January 30, 2023] “This age group is characterized by a higher rate of underlying medical conditions and might be more sensitive to changes caused by vaccine reactions. Thus, if guidelines are changed to include all individuals aged ≥18 years, our findings might not be generalizable.”

 

Retrospective analysis

The retrospective analysis was based on medical records of participants who received the first (n=94,169) and second (n=17,814; median age 69 years) boosters. The researchers compared the frequency of 25 potential adverse events (AEs) 42 days prior to the first and second boosters against AEs 42 days post vaccination.

There was no significant positive risk difference attributable to the second booster for any AE evaluated. Risk differences for pericarditis, Bell’s Palsy, and myocardial infarction were –2.25, –1.68, and 2.25, respectively. There were no events of myocarditis pre or post vaccination.

“[This analysis] suggested that none of the 25 events examined was associated with the second booster dose,” said the researchers. The absence of myocarditis or pericarditis should quell certain concerns, they added, as myocarditis following COVID-19 mRNA vaccine is one of the primary drivers of vaccine reluctance. [Public Health 2021;194:245-251]

 

Provides safety assurance

One limitation that should be taken into context is the non-medical-grade smartwatches used in the prospective analysis. The exact algorithms of these watches were also not completely disclosed. Also, it was quite tedious for participants to wear the watch consistently, not to mention the twice-weekly task of filling in questionnaires for 2 years.

The prospective analysis was also more of a convenient sampling as participants were recruited by social media ads and word-of-mouth. The retrospective analysis sample, albeit large, may not be sufficient to distinguish rare severe events.

“[Nonetheless,] we believe this study provides safety assurances to the global population who are eligible to receive an additional COVID-19 booster inoculation,” the researchers said. “These assurances can help increase the number of high-risk individuals who opt to receive this booster vaccine and thereby prevent severe outcomes associated with COVID-19.”