“I’m just worried that, if we say yes, that the states are going to mandate administration of this vaccine to children in order to go to school, and I do not agree with that.”—H. Cody Meissner, Professor of Pediatrics, Tufts University School of Medicine, and a member of the Vaccines and Related Biological Products Advisory Committee of the U.S. Food and Drug Administration, before a vote on October 26 whether to recommend extending the Emergency Use Authorization of Pfizer Inc.’s Covid-19 vaccine to children1
They said yes.
The Ad-Com had been confronted by the FDA with a yes-or-no, up-or-down question. “No” would have denied the vaccine to all kids aged 5 through 11, including kids at exceptional risk, such as those who are immunodeficient, obese, suffering from pulmonary disorders, or dependent on tube feeding. Hence a “yes” that was nearly unanimous.2
The FDA extended the EUA the next day.
If a statement was wanted to acknowledge that the need for this vaccine varies across the pediatric population, it would then have to come from the Centers for Disease Control and Prevention. But the next week here was Rochelle Walensky, the CDC Director: “We are now expanding vaccine recommendations to more than 28 million children in the United States.”3
Not much nuance there. Twenty-eight million would be … everybody—all kids 5-11.
Are mandates next?
Peter Marks, who heads the FDA unit overseeing vaccine reviews, had given the Ad-Com this assurance: “There are certain governors who already announced they would not do a mandate until there is an approval as opposed to an Emergency Use Authorization.”
There would be good reason for Dr. Marks to skirt vaccine politics. Amid the frantic pan-vaxxing push of the Biden administration, the FDA had received 143,499 comments from a public deeply divided over this vaccine so new to medical science. Yet the issue isn’t mandates ahead of a formal vaccine approval by the FDA. It’s what governors will do afterward. Gavin Newsom in California has already announced that every school kid in the state will have to get the jab.4 Kathy Hochul in New York says she is “going to keep all options on the table for sure.”5
Is it still okay to ask, What’s the emergency? What’s the emergency, at least, for kids in good health? The incidence of severe Covid illness in children is nothing like that in adults. The death rate in healthy children is so low as to be difficult to measure.6
Consider how Pfizer had to design this latest trial if the company was to meet the tight deadline encouraged by Covid fear and trembling. The trial enrolled 4,647 children.7 Given a population of that modest size, given the need for speed, there was little chance of demonstrating a reduction in severe disease, especially as most of the kids were healthy. The odds would have been different had the trial focused on kids at high risk, but it didn’t.
How many kids, then, in either the vaccine or the placebo group, died of Covid? Zero. How many came down with severe illness? Zero. In an earlier Pfizer study of older kids, aged 12 through 15, how many died or suffered severe illness? Zero and zero.8
Hence a focus on antibodies induced by the vaccine. That was the primary endpoint (the primary test of efficacy) for the 5-11 group. Understand that the FDA stated in its briefing memo to the Ad-Com that “ … no specific neutralizing antibody titer,” titer signifying antibody level, “has been established to predict protection against Covid-19 …” There was a way forward, though: immunobridging.
Follow along: If antibody production in the 5-11 group, which group might be called A, adequately approximated that in a group aged 16 through 25, or B, then it was inferred that the benefit of the vaccine to A would be like that already shown in B.
Next: The benefit to be inferred did not have to be shown in B specifically, but rather across a larger group of which B was part, this last group, C, being a mostly adult population in which Pfizer conducted its first efficacy trial last year and in which a benefit was demonstrated, namely, a significant reduction in mild-to-moderate disease.9
Got that? C to B to A: A double inference. Let’s not quibble. It met the endpoint.
Supplemental data relative to a “descriptive” secondary endpoint did indicate a benefit even if the numbers as of the data cutoff for the Ad-Com meeting weren’t quite large enough to reach statistical significance. In the placebo group, 16 kids, or about 2.1%, experienced mild-to-moderate symptoms; in the vaccine group, 3 kids, or about 0.2%—a relative reduction of nearly 91%. All kids with fevers reported as Covid symptoms were in the placebo group, though fever was notably more common as a side effect in the vaccine group. Again, let’s not quibble.
For the issue is less benefit and short-term side effects than longer-term risk. Heart inflammation (myocarditis and pericarditis) is now by consensus deemed real if rare—and complicated by the realization that it can result from infection. This trial was too small to evaluate the risk either way. So the FDA statistically modeled six scenarios: deaths spared, depending on the scenario, ranged from none to three over six months for every million vaccinated children; hospitalizations went down in five of the scenarios and up in one.
Models are, as the FDA says, “sensitive” to inputs. One big input that was lacking: natural immunity conferred by infection.10 According to a CDC estimate, 42 percent of kids 5 through 11 had been infected as of early in the summer of 2021. Another input that might shatter any current model would be more therapeutic options, including a drug for which Pfizer will soon seek an EUA. In any event, a model won’t count for much in the public mind if ever a fully vaccinated and boosted NBA player collapses on the court in cardiac distress.
Pfizer calls its vaccine “the shot of a lifetime.”11 Shots, in the plural, would seem apropos. If the protection of even two shots is as short-lived in children as in adults, one shot will follow the next for years. How many shots will a child of five be getting by the end of adolescence, to say nothing of throughout a lifetime? The prospect of repeated dosing heightens anxiety over potential if still speculative ill effects not limited to heart inflammation.12
Time may tell whether vaxxing kids does anything to slow the spread of infection and thus disease (or acquired immunity), but it is already clear that vaccinated adults can become infected, carry substantial viral loads, and transmit infection.13 Vaccination as a mantle of virtue is wearing thin. Surely there is no virtue in putting young children at risk to shield their elders. Whatever the risk, whatever the benefit, who is to make the call on vaccination other than parents?
Michael Nelson, who directs the Asthma, Allergy, and Clinical Immunology Division at the University of Virginia, remarked that he personally had been deluged with emails ahead of the Ad-Com meeting. His “yes” vote was not the only one that bore a caveat: “I see this as an access and personal-choice and equity question,” he said, “and not a mandate for all in this age group.”
For now, parents have a choice. They may have to fight to keep it.
1All references to data presented at the Ad-Com meeting or remarks made there can be found in documents or the video that the FDA has posted to its website: https://www.fda.gov/advisory-committees/advisory-committee-calendar/vaccines-and-related-biological-products-advisory-committee-october-26-2021-meeting-announcement
2The vote was 17-0, with one abstention.
3The announcement as carried on CBS Miami, Nov. 4, 2021. The CDC’s own advisory panel, the Advisory Committee on Immunization Practices, had just voted 14-0 in favor of the vaccine.
4Press release, Office of Governor Gavin Newsom, Oct. 1, 2021
5WYNT, Channel 13, New York, Oct. 24, 2021
6Mortality and hospitalization data for the 5-11 population, before accounting for any lag in reporting, as presented by the CDC at the Ad-Com meeting: Covid deaths, 94 (Jan. 1, 2020 to Oct. 16, 2021); Covid hospitalizations, meaning anyone admitted to a hospital within two weeks of a positive Covid test ordered by a healthcare professional, 30 per 100,000, 68% of them associated with underlying medical conditions (March 1, 2020-Oct. 2, 2021). One study found the three conditions most closely associated with severe disease in hospitalized children to be obesity, chronic metabolic disease, and feeding-tube dependence (March 2020 to August 2021). The 5-11 population is about 28 million.
7The trial comprised two cohorts. In the first, 2,268 subjects were enrolled to study both efficacy and safety, and the safety follow-up for 95% of the subjects was at least two months; in the second, a safety study, 2,379 subjects were enrolled, and the median follow-up was 2.4 weeks.
8The trial in the 12-15 group, which enrolled 2,260 subjects, has also resulted in an EUA. It, too, relied primarily on immunobridging, though the FDA said the trial provided “compelling direct evidence of clinical benefit in addition to the immunobridging data.” In the placebo group, 16 subjects experienced mild-to-moderate Covid symptoms; in the vaccine group, none.
9The first and largest of the efficacy trials enrolled about 44,000 subjects aged 16 and up, nearly all of them adults, about one in five aged 65 and older. The reduction in mild-to-moderate symptoms was statistically significant (incidence: 0.88% in the placebo group and 0.044% in the vaccine group; relative-risk reduction, 95%). The number of severe cases was small, but the FDA said the split in cases between the placebo and vaccine groups “does suggest protection” from severe disease. No one died of Covid in either group. It is for use in this group, 16 and up, that the vaccine has the usual product approval beyond an EUA, and it is that approval which has triggered government and private-sector mandates.
10How to determine infection rates can be controversial. Some weeks ago, the regular data reports issued by the UK Health Security Agency indicated that, as protection from vaccines waned, infection rates (cases per 100,000) had grown higher among the fully vaccinated than the unvaccinated for all age groups 30 and older. The Office of Statistics Regulation protested, saying the Agency relied on the wrong population figures and failed to account for varying inter-group behaviors. The Agency has since attached ever lengthening caveats to the data and, specifically for Pfizer’s vaccine, raised its confidence in 75-85% protection from infection from “low” to “medium.” The Agency and the Office agree that hospitalization and mortality are substantially higher among the unvaccinated. (“COVID-19 vaccine surveillance report,” weeks 40 through 44, UK Health Security Agency; Daily Mail, Nov. 2, 2021.)
11See pfizer.com. “SHOT OF A LIFETIME-How Pfizer and BioNTech Developed and Manufactured a COVID-19 Vaccine in Record Time.” Pfizer has projected worldwide delivery of 2.3 billion doses in 2021 and sales of $36 billion.
12”We are part of a group of clinicians, scientists, and patient advocates who have lodged a formal ‘Citizen Petition’ with the United States Food and Drug Administration (FDA), asking the agency to delay any consideration of a ‘full approval’ of a covid-19 vaccine. The message of our petition is ‘slow down and get the science right—there is no legitimate reason to hurry to grant a license to a coronavirus vaccine.’ We believe the existing evidence base—both pre- and post-authorization—is simply not mature enough at this point to adequately judge whether clinical benefits outweigh the risks in all populations.” In addition to longer clinical studies, the petitioners asked for “complete proper biodistribution studies … to better understand the implications of mRNA translation in distant tissues.” (Why we petitioned the FDA to refrain from fully approving any covid-19 vaccine this year, British Medical Journal, June 8, 2021.)
13“Vaccination reduced the risk of delta variant infection and accelerates viral clearance. Nevertheless, fully vaccinated individuals with breakthrough infections have peak viral load similar to unvaccinated cases and can efficiently transmit infection in household settings, including to fully vaccinated contacts.” (Community transmission and viral load kinetics of the SARS-CoV-2 delta [B.1.617.2] variant and unvaccinated individuals in the UK: a prospective, longitudinal, cohort study, The Lancet Infectious Diseases, October 29, 2021.)