COVID-19 Science Update released: November 19, 2021 Edition 114

PEER-REVIEWED

Evaluation of the BNT162b2 COVID-19 vaccine in children 5 to 11 years of age.external icon Walter et al. NEJM (November 9, 2021).

Key findings:

• In children aged 5-11 years, BNT162b2 (Comirnaty, Pfizer/BioNTech) vaccine efficacy for prevention of COVID-19 was 90.7% (95% CI 67.4%-98.3%) (Figure).
• SARS-CoV-2 neutralizing antibody titers 1 month after dose 2 among 5-11-year-olds (10 µg dose) were similar to those among 16-25-year-olds who received 30 µg doses (geometric mean ratio was 1.04, 95% CI 0.93-1.18).
• BNT162b2 10 µg doses had a favorable safety profile among 5-11-year-olds (Figure).
  • No serious vaccine-related adverse events were noted.

Methods: Ongoing phase 2-3 safety, immunogenicity, and efficacy trial of BNT162b2 vaccination in healthy children aged 5-11 years. Children were randomly assigned to receive either two 10 µg doses of BNT162b2 21 days apart or placebo; 1,517 received BNT162b2 and 751 received placebo. Vaccine efficacy was assessed ≥7 days after dose 2. Immune responses 1 month after dose 2 were immunologically bridged to those of 16-25-year-old participants from the pivotal trialexternal icon of 2 BNT162b2 30 µg doses. Limitations: Short duration of follow up (median 2.3 months); study likely under-powered to detect rare adverse events.

Implications: Two 10 µg doses of BNT162b2 vaccine were safe, immunogenic, and efficacious in children 5-11 years of age.

Note: Adapted from Walter et al. Panel A shows the cumulative incidence of the 1^st occurrence of COVID-19 afterBNT162b2 dose 1or placebo. Each symbol represents cases of COVID-19 on a given day. Panel B shows systemic events reported within 7 days after vaccine dose 1 (n = 1,511) and dose 2 (n = 1,501) and placebo (dose 1, n = 748 or 749; dose 2, n = 740 or 741 [number of children reporting at least 1 "yes" or "no" for the event after each dose]). Bar colors refer to adverse event severity: mild, moderate, severe, grade 4. Numbers above bars are percentage of participants in each group. I bars represent 95% CIs. From the New England Journal of Medicine, Walter et al., Evaluation of the BNT162b2 COVID-19 vaccine in children 5 to 11 years of age. November 9, 2021, online ahead of print. Copyright © 2021 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.

Distinct SARS-CoV-2 antibody reactivity patterns elicited by natural infection and mRNA vaccinationexternal icon . Assis et al. NPJ Vaccines (November 4, 2021).

Key findings:

• Specimens from mRNA-vaccinated healthcare workers demonstrated higher antibody levels to the SARS-CoV-2 spike protein S1 and receptor binding domains (RBD) than specimens from a community sample of unvaccinated seropositive persons (Figure).
  • When exposed to RBD domains from the Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), and wild-type lineages, higher anti-RBD antibody titers were observed in plasma from vaccinated persons than in plasma from people who recovered from confirmed COVID-19 (Figure).
• Specimens from mRNA-vaccinated healthcare workers had greater anti-RBD reactivity than specimens from unvaccinated hospitalized COVID-19 patients who required ICU care.

Methods: Samples were obtained from 2 ongoing COVID-19 longitudinal serological surveys of Orange County, CA residents (July and December 2020) and healthcare workers (May and December 2020-March 2021) and a hospital biorepository of samples from 93 hospitalized patients. IgG levels were determined using a multiplex antigen microarray containing antigens from SARS-CoV-2. Limitations: Unclear severity and timing of participants' infections and timing of vaccination; SARS-CoV-2 exposure may have differed between groups; specimens collected during pre-Delta period.

Implications: mRNA vaccination appears to induce a broader antibody response than SARS-CoV-2 infection.

Figure:

Note: Adapted from Assis et al. Natural exposure (from Santa Ana cohort, December 2020) vs.mRNA vaccination(from February/March 2021 cohort) antibody reactivity against (a) SARS-CoV-2 antigens, and (b) RBD from Alpha, Beta, Delta, and Mink variants, and wild-type (WT) virus. Mean fluorescence intensity (MFI) signals for antibodies are plotted. The boxes represent the 1^st quartile, median, and 3^rd quartile and the whiskers extend 1.5 times the interquartile range (IQR). Wilcoxon test was performed for pairwise comparisons and p values <0.01 were considered significant and represented as **. Licensed under CC BY 4.0.

PREPRINTS (NOT PEER-REVIEWED)

Three doses of COVID-19 mRNA vaccination are safe based on adverse events reported in electronic health records.external icon Niesen et al. medRxiv (November 9, 2021).

Key findings:

• Reports of severe adverse events after a 3^rd dose of a COVID-19 mRNA vaccine were rare.
  • Pericarditis, anaphylaxis, myocarditis, and cerebral venous sinus thrombosis after dose 3 were reported for ≤0.01% of vaccinated persons (similar to the occurrence after dose 2) (Figure).
• Fatigue, lymphadenopathy, nausea, and headache were reported slightly more often after dose 3 than dose 2 (Figure).

Methods: Retrospective study of patients vaccinated with 3 doses of BNT162b2 (Comirnaty, Pfizer/BioNTech, n = 38,094) or mRNA-1273 (Moderna, n = 9,905), December 1, 2020-October 17, 2021. Electronic health records were used to identify adverse events in the 2 weeks prior to the 1^st dose and 2 weeks following the 1^st, 2^nd, and 3^rd doses. Limitations: Limited to signs/symptoms included in electronic health records; persons who experienced post-vaccine adverse events might be less likely to get subsequent doses; results may not be generalizable.

Implications: The risk of severe adverse events after a 3^rd dose of COVID-19 mRNA vaccine is low and comparable to the risk after a 2^nd dose.

Figure:

Note: Adapted from Niesen et al. Prevalence of vaccine-associated adverse events in 3-dose vaccinated individuals during the 14-day period before 1^st dose, after 1^st dose, after 2^nd dose, and after 3^rd dose in (a) individuals that received 3 doses of BNT162b2, and (b) individuals that received 3 doses of mRNA-1273. Error bars indicate 95% confidence intervals, and asterisks indicate adverse events with significant (two-tailed p-value <0.05) difference in prevalence after the 3^rd dose, compared with before the 1^st dose (blue asterisk) or after the 2nd dose (orange asterisk). Used by permission of authors.

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