Two new observational studies detail Pfizer/BioNTech COVID-19 vaccine protection among US children and adolescents amid the Omicron variant surge, one finding 71% efficacy against infection after a third dose in 12- to 15-year-olds, and the second showing lower risks of infection and hospitalization in vaccinated youth aged 5 to 17 in New York state. The studies were published late last week in JAMA.
Three doses more effective than 2 in teens
In the first study, researchers from the US Centers for Disease Control and Prevention analyzed data from 74,208 drive-thru polymerase chain reaction (PCR) COVID-19 test results from children aged 5 to 11 years, and 47,744 tests from aged 12 to 15 from Dec 26, 2021, to Feb 21, 2022. The tests were conducted by a single pharmacy chain at 6,897 sites in 49 states; Washington, DC; and Puerto Rico.
The researchers compared the effectiveness of two Pfizer COVID-19 vaccine doses at least 2 weeks before testing with no vaccination in children, and two or three doses 2 or more weeks earlier in adolescents. Overall, the study involved 30,888 positive tests and 43,209 negative tests from children aged 5 to 11 and 22,273 positive tests and 25,471 negative tests from 12- to 15-year-olds. Median age was 10 years, 50.2% were girls, 70.1% were White, and 25.7% were Hispanic or Latino.
Among the younger age-group, 78.4% of test results were from unvaccinated children, and 21.3% were from two-dose recipients. In test results from those aged 12 to 15 years, 51.9% were from unvaccinated participants, 46.2% from two-dose recipients, and 1.9% from those who received a third dose.
Two to 4 weeks after the second dose in children, the adjusted odds ratio (OR) of symptomatic infection was 0.40 (95% confidence interval [CI], 0.35 to 0.45), and estimated vaccine effectiveness (VE) was 60.1% [95% CI, 54.7% to 64.8%]). Among adolescents, the OR was 0.40 (95% CI, 0.29 to 0.56), and estimated VE was 59.5% [95% CI, 44.3% to 70.6%]).
In the second month after the second dose among children, the OR was 0.71 (95% CI, 0.67 to 0.76), and estimated VE was 28.9% (95% CI, 24.5% to 33.1%). Among adolescents, the OR was 0.83 (95% CI, 0.76 to 0.92), and estimated VE was 16.6% (95% CI, 8.1% to 24.3%). The OR 2 to 6.5 weeks after the booster dose in adolescents was 0.29 (95% CI, 0.24 to 0.35), and estimated VE was 71.1% (95% CI, 65.5% to 75.7%).
"Among children and adolescents, estimated VE for 2 doses of BNT162b2 [Pfizer] against symptomatic infection was modest and decreased rapidly," the authors wrote. "Among adolescents, the estimated effectiveness increased after a booster dose."
Sustained protection against hospitalization
A research team from the New York State Department of Health used four state COVID-19 databases to evaluate infections and hospitalizations among vaccinated children aged 5 to 11 years (two doses) and adolescents aged 12 to 17 (two or three doses) who had completed the series at least 14 days earlier, and those who were unvaccinated from Nov 29, 2021, to Jan 30, 2022.
A total of 365,502 children 5 to 11 years old (average age, 8.3 years) were fully vaccinated, and another 997,554 (average age, 7.8 years) were unvaccinated. Among adolescents, 852,384 (average age, 14.6 years) were fully vaccinated, and 208,145 (average age, 14.6 years) were unvaccinated.
Over the study period, 140,680 COVID-19 infections and 414 hospitalizations occurred in the younger age-group, while there were 154,555 infections and 671 hospitalizations in older participants.
Among adolescents, the unvaccinated versus vaccinated incident rate ratios (IRRs) against infection fell from 6.7 (95% CI, 6.2 to 7.2) on Nov 29 to 2.9 (95% CI, 2.8 to 3.0) by Dec 13 and then to 2.0 (95% CI, 1.9 to 2.2) by Jan 24. Omicron made up 19% of sequences in the first period and greater than 99% in the later period.
Among 5- to 11-year-olds, the IRR against infection in unvaccinated versus fully vaccinated children was 3.1 (95% CI, 2.7 to 3.6) the week of Dec 13, falling to 1.1 (95% CI, 1.1 to 1.2) by Jan 24. Hospitalizations were higher in unvaccinated than in fully vaccinated participants by Jan 24, with an IRR of 1.9 (95% CI, 0.9 to 4.8) in the younger age-group, compared with 3.7 (95% CI, 2.1-6 to 5) in the older age-group.
Within 13 or fewer days of full vaccination, the IRR for infection for unvaccinated versus vaccinated 5- to 11-year-olds was 2.9 (95% CI, 2.7 to 3.1) and was 2.3 (95% CI, 1.9 to 2.7) and 1.1 (95% CI, 1.1 to 1.2) at 28 to 34 days. At the same time points, the IRRs among 12- to 17-year-olds were 4.3 (95% CI, 1.1-1.2) and 2.3 (95% CI, 1.9-2.7) at 28 to 34 days.
The risks of infection and hospitalization were higher for unvaccinated than vaccinated participants in both age-groups, although the risk declined as Omicron circulated more widely. Protection declined over time since vaccination.
"These results complement recent findings of reduced vaccine effectiveness for adolescents against the Delta variant and the dual effects of the variant and waning protection against infection, with sustained protection against hospitalizations," the researchers wrote. "These findings support efforts to increase vaccination coverage in children and adolescents and review dosing strategies for children aged 5 to 11 years."
Time to review doses for 5- to 11-year-olds?
In a commentary on both studies, Sophie Katz, MD, MPH, and Kathryn Edwards, MD, both of Vanderbilt University, asked whether the appropriate doses of COVID-19 for children have been chosen.
"During the pivotal clinical trials submitted to the US Food and Drug Administration (FDA) for the EUA [emergency use authorization], the immune responses observed in adolescents at the 30-µg [microgram] dose were nearly 2-fold higher than the immune responses observed in adults 16 to 32 years of age," they wrote. "Receipt of the 10-µg dose in children 5 to 11 years old was comparable to the immune responses in adults, but less than the immune responses to the 30-µg dose for adolescents."
But Katz and Edwards pointed out that while children can have severe COVID-19 infections, they generally are milder than in adults, and a previous study published on a preprint server suggested that 75% of US children have already been infected. "An acceptable balance between safety and effectiveness of pediatric vaccines is paramount, particularly because many children will likely have preexisting natural immunity," they wrote.
"The encouraging message should be that although vaccine protection for children and adolescents was lower in the Omicron era than with previous variants and that such protection wanes rapidly, vaccine effectiveness against hospitalization remains high and booster doses confer additional protection," they concluded.