In November 2021, just as the Omicron surge was in its infancy in the United States, Pfizer/BioNTech received authorization by both the FDA and CDC for emergency use of the low-dose Covid-19 vaccine for children age 5 to 11 years. The reduced dose of 10 micrograms per vaccine, given as a two-vaccine regimen three weeks apart, is one third the dose of the 30 micrograms given as two doses three weeks apart, followed by a booster dose five or more months later, in individuals ages 12 years and up. Initial data from vaccine trials in 5- to 11-year-olds showed favorable safety profiles with excellent antibody response in a prospective trial of nearly 5,000 children. But the vaccine, as was the case for the adult vaccine, was designed based on both the earliest coronavirus variants, as well as the delta variant. In addition, safety profiles, with emphasis on reducing severe reactions such as myocarditis, were paramount, in order to protect children from any side effects, even mild ones. The vaccine for 5- to 11-year-olds showed excellent efficacy, meaning great response in the clinical trials, but the question of effectiveness, in other words how well it works in the real world, were yet to be determined. And then came Omicron.
While data on the vaccine clinical trial participants was extremely promising, new data on this age group’s response to the Omicron variant was quite different. A preprint article released this past week looked at the real-world effectiveness of the vaccine during the peak of the Omicron surge. The New York State Department of Health analyzed Covid-19 infection rates in 5- to 17-year-olds between December 13, 2021 and January 30, 2022, when New York state saw the highest number of new coronavirus infections and hospitalizations in two years. The study authorws divided the group into two cohorts— 12- to 17-year-olds, where vaccines were 30 micrograms per dose, as was the dose for adults, and 5- to 11-year-olds, who received 10 micrograms per dose. They looked at both new Covid-19 infections as well as new Covid-19-related hospitalizations.
Looking at over 850,000 fully vaccinated 12- to 17-year-olds in New York State, the vaccine effectiveness against infection declined from 66% to 51% during the study period of the Omicron surge. Effectiveness of the vaccine preventing hospitalization in this age group declined from 85% to 73% during this same time period. Overall, while effectiveness in preventing infection was significantly reduced, 73% reduction in hospitalization remained promising.
However, the real-time results in the 5- to 11-year-olds was not what was seen in the efficacy trials. The New York State Department of Health looked at over 365,000 fully vaccinated 5- to 11-year-olds during the Omicron surge in New York. Effectiveness in preventing infection dropped from 68% to a dismal 12%. Prevention of hospitalization dropped from 100% to 48% during that same six-week period. However, a big caveat to all of these dramatic-looking percentage drops is that the absolute number of hospitalizations were relatively low for all vaccinated children ages 5- to 17-years-old, so although the percent drops seem significant, one must recognize that even with these data points, the overall number of vaccinated children hospitalized or with severe illness due to Covid-19, even the Omicron variant, remained quite low.
As was the case for the Covid-19 vaccine trials in 2- 4-year-olds, which showed low efficacy for antibodies from the reduced dose of 3 micrograms, or one-tenth of the adult dose, it may be that the 10-microgram dose in some of the 5- to 11-year-olds was too low. A striking finding in the preprint report was that during the week of January 24-30, 2022, there was a 67% effectiveness in the vaccine for 12-year-olds, but only an 11% effectiveness for 11-year-olds, who received one third the dose of children born just one year prior to them. There is likely very little difference in the immune systems between 11- and 12-year-olds, which may lead to studies of a higher dose in older school-aged children. In addition, extending the interval between first and second doses from three weeks to eight weeks may minimize adverse reactions to the second dose, as well as improve immunologic response and extend protection against infection.
While the results of the New York State data are disheartening, they continued to show the vaccine’s effectiveness in reducing severe illness and hospitalization from Omicron infections. Continued assessment of age-appropriate dosing and intervals are critical moving forward, especially as many other Covid-19 mitigation measures are being lifted throughout the U.S.