The Pfizer vaccine will likely be available to children ages 5 to 11 next week, but many parents are hesitant about getting their kids vaccinated. Chart via the KFF COVID-19 Vaccine Monitor.
Last week, the Food and Drug Administration (FDA) recommended Pfizer’s COVID-19 vaccine for children ages 5 to 11, under an Emergency Use Authorization. The agency’s vaccine advisory committee met on Tuesday to discuss Pfizer’s application and voted overwhelmingly in favor; the FDA followed this up with an EUA announcement on Friday.
This coming week, the process continues: CDC’s own vaccine advisory committee will discuss and vote on vaccinating kids in the 5-11 age group, and then the agency will make an official decision. If all goes well—and all is expected to go well—younger kids will be able to get their vaccines in time for Thanksgiving.
Many of the parents I know have been eagerly awaiting this authorization, but the sentiment is far from universal. COVID-19 vaccinations for kids are incredibly controversial, more so than vaccinations for adults. The public comment section of the FDA advisory committee meeting—in which basically anyone can apply to share their thoughts—was full of anti-vaxxers, many of them sharing misinformation. Even some experts on the FDA advisory committee were not fully convinced that vaccines are needed for all young kids, though all but one eventually voted in favor.
Now, let me be clear: there are definite benefits to vaccinating younger children. While kids are less likely to have severe COVID-19 cases than adults, the disease has still been devastating for many children. Almost 100 kids in the 5 to 11 age range have died of COVID-19, making this disease one of the top 10 causes of death for this group over the past year and a half.
Plus, children who get infected with the coronavirus are at risk for Long COVID and MIS-C, two conditions with long-lasting ramifications. There have been about 5,200 MIS-C cases thus far—and the majority of these cases have occurred in Black and Hispanic/Latino children. Minority children are also at much higher risk for COVID-19 hospitalization.
This impt 🧵from today's FDA advisory meeting on Pfizer vaccine for 5-11s.
1) CDC seroprevalence studies show infections in kids are underreported. Kids are as likely as adults to be infected.
2) Black, Hispanic, and AI/AN children have the highest risk of hospitalization. https://t.co/BvwxIuO5g6
Vaccination can prevent children from severe ramifications of a potential COVID-19 case, as well as from the mild infections that lead to missed school and other disruptions. But the FDA committee had to carefully weigh this benefit against potential side effects from vaccination, namely myocarditis—a type of heart inflammation.
The U.S. system for tracking vaccine side effects has identified a small number of myocarditis cases in children ages 12 to 15 after their second shots of Pfizer or Moderna vaccines. For the meeting this past Tuesday, the FDA presented some models weighing potential myocarditis cases in young kids against vaccination benefits; the models showed that, in almost every scenario, the number of severe COVID-19 cases prevented by vaccination is higher than the myocarditis cases.
It’s worth noting: in Pfizer’s clinical trial for the 5 to 11 age group, no child had a severe adverse reaction to the vaccine. But the Pfizer researchers did observe five medical events that were unrelated to vaccination—including one kid who swallowed a penny.
Some of the FDA advisory committee members suggested that perhaps vaccines would be most beneficial for children with underlying medical conditions, who are more susceptible to severe COVID-19. But the committee ultimately voted in favor of vaccines for all kids in the 5 to 11 age group, allowing parents to consult their pediatricians and pursue vaccination if they deem it necessary.
Polling data suggest that many parents don’t currently deem it necessary, though. The latest survey from the Kaiser Family Foundation found that just 27% of parents with kids in the 5 to 11 age range plan to get their kids vaccinated immediately, once shots are available. 33% intend to “wait and see,” 5% will only pursue vaccination if it’s required by the child’s school, and 30% say “definitely not.”
Public health experts, pediatricians, and others in the science communication world have a lot of work ahead of us to convey the importance of vaccinating kids—and dispel misinformation.
This week, the FDA’s vaccine advisory committee had a two-day meeting to discuss booster shots for Moderna’s and Johnson & Johnson’s COVID-19 vaccines. From the outside, these meetings may have appeared fairly straightforward: the committee voted unanimously to recommend booster shots for both vaccines.
But in fact, the discussions on both days were wide-reaching and full of questions, touching on the many continued gaps in our knowledge about the need for additional vaccine doses. The FDA committee continues to make decisions based on rather limited data, as do other top U.S. officials. Case in point: on Thursday, the committee was asked to consider data from Israel’s booster shot campaign—which is utilizing Pfizer vaccines—as evidence for Moderna boosters in the U.S.
In the Moderna vote on Thursday afternoon, committee member Dr. Patrick Moore, a virologist at the University of Pittsburgh, said that he voted “on gut feeling rather than really truly serious data.” The comment exemplified how much we still don’t know regarding the need for boosters, thanks in large part to the CDC’s failure to comprehensively track breakthrough cases in the U.S.
Um. Am I the only person who is seriously bothered to hear a VRBPAC committee member say he voted "on gut feeling rather than really truly serious data"?
Still, there are a few major facts that we have learned since the FDA and CDC discussions on Pfizer boosters that took place a couple of weeks ago. Here’s my summary of what we’ve learned—and what we still don’t know.
What we’ve learned since the Pfizer discussion:
Israel’s booster rollout continues to align with falling case numbers. On Thursday, representatives from the Israeli national health agency presented data on their booster shot rollout—which, again, is using Pfizer vaccines. The vast majority of seniors in Israel have now received a third dose, and over 50% of other age groups have as well. According to the Israeli scientists, this booster rollout both decreased the risk of severe COVID-19 disease for older adults and helped to curb the country’s Delta-induced case wave, causing even unvaccinated adults to have a decreased risk of COVID-19.
In Israel, severe cases among both vaccinated and unvaccinated adults decreased after the country provided third Pfizer doses to its residents. Screenshot taken from Thursday’s VRBPAC meeting.
You can read more about Israel’s booster campaign in this paper, published in the New England Journal of Medicine in early October. It’s worth noting, however, that Delta is known to spur both case increases and decreases in cycles that can be somewhat unpredictable—and may not be exactly linked to vaccination. So, I personally take the Israeli claims that boosters stopped their case wave with a grain of salt.
Spain and Italy have finished this wave and Israel is almost done; the UK and Germany are on the rise, and the US is headed down. Delta isn't correlated with % vaccinated. Israel argues it is boosters, but causality is not assignable. The rise and fall of COVID is complex. pic.twitter.com/UVwcoFJIuP
Decreased vaccine effectiveness against infection may be tied more to Delta and behavioral factors than “waning antibodies.” This week, the New York State Department of Health (DOH) announced results from a large study of vaccine effectiveness which is, from what I’ve seen, the first of its kind in the U.S. The New York DOH used state databases on COVID-19 vaccinations, tests, and hospitalizations to examine vaccine effectiveness against both infection and hospitalization in summer 2021, when Delta spread rapidly through the state.
They found that vaccine effectiveness against infection did decline over the summer. But the declines occurred similarly for all age groups, vaccine types, and vaccine timing (i.e. which month the New Yorkers in the study received their vaccines)—suggesting that the decline in effectiveness was not tied to waning immune system protection. Rather, the effectiveness decline correlated well with Delta’s rise in the state. It also correlated with reduced safety behaviors, like the lifting of New York’s indoor mask mandate and the reopening of various businesses.
Vaccine effectiveness against hospitalization declined for older adults, but remained at very high levels for New Yorkers under age 65, the study found. Here’s what lead author Dr. Eli Rosenberg said in a statement:
The findings of our study support the need for boosters in older people in particular, and we encourage them to seek out a booster shot from their health care provider, pharmacy or mass vaccination site. We saw limited evidence of decline in effectiveness against severe disease for people ages 18 to 64 years old. While we did observe early declines in effectiveness against infections for this age group, this appears to have leveled off when the Delta variant became the predominant strain in New York. Together, this suggests that ongoing waning protection may be less of a current concern for adults younger than 65 years.
I was surprised that this study didn’t come up in the FDA advisory committee meetings this week, and will be curious to see if it’s cited in future booster shot discussions. The study does align, however, with the committee’s decision against recommending booster shots for all adults over age 18 who received Moderna vaccines.
Johnson & Johnson vaccine recipients appear to need boosters more than mRNA vaccine recipients. On Friday, presentations from both J&J representatives and FDA scientists made a clear case for giving J&J vaccine recipients a second dose of this adenovirus vaccine. In one 30,000-patient study, patients who received a second J&J shot two months after their first shot saw their vaccine efficacy (against symptomatic infection) rise from 74% to 94%.
Interestingly, unlike the Pfizer and Moderna vaccines, a J&J shot’s ability to protect against coronavirus infection appears relatively stable over time. However, a booster shot can make this vaccine more effective—especially against variants. Despite arguments from J&J representatives that their vaccine’s second dose should come six months after the first dose, the FDA advisory committee voted to recommend second J&J shots just two months after the first dose, for all adults over age 18.
It’s worth noting that this vaccine regimen might effectively change J&J’s product from a one-shot vaccine to a two-shot vaccine. STAT’s Helen Branswell and Matthew Herper go into the situation more in their liveblog.
Mixing and matching vaccines is a strong strategy for boosting immunity, especially if one of the vaccines involved uses mRNA technology. This week, the National Institutes of Health (NIH) released a highly anticipated study (posted as a preprint) on mix-and-match vaccine regimens. The NIH researchers essentially tested every possible booster combination among the three vaccines that have been authorized in the U.S. Before and after vaccination, the researchers took blood samples and tested for antibodies that would protect against the coronavirus.
In short, the NIH study found that all three vaccines—Pfizer, Moderna, and J&J—will provide a clear antibody boost to people who have received any other vaccine. But the mRNA vaccines (Pfizer and Moderna) provide bigger benefits, both in the form of higher baseline antibody levels (after two shots) and a higher boost. The best combination was a J&J vaccine initially, followed by a Moderna booster, Dr. Katelyn Jetelina notes in a Your Local Epidemiologist summary of the study.
Every vaccine provided a “boost” of protective antibodies to recipients of every other vaccine. Figure from the NIH preprint. mrna-1273 refers to the Moderna vaccine, Ad26.COV2.S refers to the J&J vaccine, and BNT162b2 refers to the Pfizer vaccine.
The booster regimens also appeared to be safe, with limited side effects. But this was a relatively small study, including about 450 people. In their discussion on Friday afternoon, the FDA advisory committee members said that they would be very likely to authorize mix-and-match vaccine regimens after seeing more safety data.
Moderna and J&J boosters appear to be safe, with similar side effects to second shots. Safety data from Moderna’s and J&J’s clinical trials of their booster shots, along with data from the NIH mix-and-match study, indicate that the additional doses cause similar side effects to first and second doses. After a booster, most recipients had a sore arm, fatigue, and other relatively minor side effects.
And here’s what we still don’t know:
Which medical conditions, occupations, and other settings confer higher breakthrough case risk? I wrote about this issue in detail in September. The U.S. continues to have little-to-no data on breakthrough case risk by specific population group, whether that’s groups of people with a specific medical condition or occupation. This data gap persists, even though U.S. researchers have some avenues for breakthrough risk analysis at their disposal (see: this post from last week).
This lack of data came up in FDA advisory committee discussions on Thursday. An FDA representative was unable to cite any evidence that people in specific occupational settings are at a higher risk for breakthrough cases.
Question from Cody Meisner again about data that shows people in certain occupational settings more vulnerbale to severe covid?
Are there any rare vaccine side effects that may occur after breakthrough doses? When I covered the FDA advisory committee meeting on Pfizer boosters, I noted that Pfizer’s clinical trial of these shots included just 306 participants—providing the committee members with very limited data on rare adverse events, like myocarditis. Well, Moderna’s clinical trial of its booster shots was even smaller: just 171 people. J&J had a larger clinical trial, including over 9,000 people.
These trials and the NIH mix-and-match study indicated that booster shots cause similar side effects to first and second shots, as I noted above. But few clinical trials are large enough to catch very rare (yet more serious) side effects like myocarditis and blood clots. (In J&J’s case, blood clots occur roughly twice for every million doses administered.) Federal officials will carefully watch for any side effects that show up when the U.S.’s booster rollout begins for Moderna and J&J.
How do antibody levels correlate to protection against COVID-19, and what other aspects of the immune system are involved? The NIH mix-and-match study focused on measuring antibody levels in vaccine recipients’ blood, as did other booster shot trials. While it may sound impressive to say, for example, “J&J recipients had a 76-fold increase in neutralizing antibodies after receiving a Moderna booster,” we don’t actually know how this corresponds to protection against COVID-19 infection, severe disease, and death.
Some experts—including a couple of those on the FDA advisory committee—have said that discussions focusing on antibodies distract from other types of immunity, like the memory cells that retain information about a virus long after antibody levels have fallen. More research is needed to tie various immune system measurements to real-world protection against the coronavirus.
What needs to happen at the FDA for mix-and-match vaccination to be authorized? One challenge now facing the FDA is, the federal agency has clear evidence that mix-and-match vaccine regimens are effective—but it does not have a traditional regulatory pathway to follow in authorizing these regimens. Typically, a company applies for FDA authorization of its specific product. And right now, no vaccine company wants to apply for authorization of a regimen that would involve people getting a different product from the one that brings this company profit.
So, how will the FDA move forward? There are a couple of options, like the CDC approving mix-and-match boosters directly. See this article for more info.
Finally: I can’t end this post without acknowledging that, as we discuss booster shots in the U.S., millions of people in low-income countries have yet to even receive their first doses. Many countries in Africa have under 1% of their populations vaccinated, according to the Bloomberg tracker. While the Biden administration has pledged to donate doses abroad, boosters take up airtime in expert discussions and in the media—including in this publication. Boosters distract from discussions of what it will take to vaccinate the world, which is our true way out of the pandemic.
Some good global vaccine news this week: it looks like vaccine cocktails may be a promising option.
A clinical trial based in Spain of around 600 participants (aged 18-59) reported encouraging results regarding mix-and-match vaccines (or “heterologous prime-and-boost,” if you want the jargon) meaning one shot of one vaccine and the second shot of another. In this study, the first dose given was AstraZeneca, and the second was Pfizer.
The study found that protective IgG antibodies were 30-40 times higher in the treatment group than the control group (those who had only received the first dose of the AstraZeneca vaccine). Neutralizing antibodies were also seven times higher after the Pfizer dose compared to the control, while usually they double in number after the second AstraZeneca shot.
As some people familiar with Covid vaccines may note, these vaccines use two different mechanisms to stimulate the immune system: the AstraZeneca shot uses an adenovirus vector modified with the SARS-CoV-2 spike protein while the Pfizer vaccine uses messenger RNA to coax cells into making the spike protein themselves. This early success demonstrates that vaccines with different mechanisms can be combined to induce a strong immune response.
In the wake of the AstraZeneca blood clot news, it’s reasonable to expect that some may be hesitant to get the second shot if they have received the first AstraZeneca shot. Some authorities have advised people who have gotten the first dose of AstraZeneca to get an alternative for the second shot. Having an alternative that hasn’t been linked to blood clots might persuade those hesitant to get the second AstraZeneca shot to complete a vaccination regimen, especially if it might stimulate even more of an immune response than the regular AstraZeneca regimen.
There’s currently another heterologous prime-and-boost trial in place in the United Kingdom with a slightly more complicated experimental setup (the four groups were AstraZeneca for both shots, Pfizer for both shots, Pfizer for the first and AstraZeneca for the second, or vice versa), with all participants over 50.
This study hasn’t reported results regarding immune responses yet, but they have reported some preliminary reactogenicity results. On May 12, researchers reported that mild side effects like fever or fatigue were more common in people who had received mixed vaccines. However, there were no severe side effects, and the mild ones subsided after a few days. The Spanish study did not find this, and instead found that mild side effects were about as common as they were with a regular vaccine regimen.
The UK study is expected to report immune response data soon, so it’ll be interesting to see if it matches the results found by the Spanish study. We’ll keep you updated when those results come out.
Following the end of the federal public health emergency in May, the CDC has lost its authority to collect vaccination data from all state and local health agencies that keep immunization records. As a result, the CDC is no longer providing comprehensive vaccination numbers on its COVID-19 dashboards. But we still have some information about this year’s vaccination campaign, thanks to continued CDC efforts as well as reporting by other health agencies and research organizations.
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