In a highly unusual move, CDC Director Rochelle Walensky, MD, MPH, overruled her own vaccine advisory committee when they became mired in a far-ranging debate about COVID-19 booster shots that led to an end-of-the day vote not to recommend them for healthcare workers (HCWs).

The surprising 9-6 “no” vote by the Advisory Committee on Immunization Practices (ACIP) rejected a generally worded “occupational” risk recommendation for many reasons, including the fact that many HCWs actually acquire SARS-CoV-2 in the community. That would seem to be supported in part by the breakthrough infections after the CDC temporarily canceled mask recommendations for the vaccinated.

The contentious meeting was held Sept. 23. Walensky overruled the panel on the occupational booster question in an email statement sent at 12:27 a.m. Sept. 24. The rapidity and decisiveness of that revocation has been rarely seen between the CDC and its advisory committees.

The occupational rationale is not supported by evidence as HCWs are protecting themselves with personal protective equipment (PPE) and other measures at work, noted ACIP member Beth Bell, MD, MPH, clinical professor of global health at the University of Washington.

“I don’t believe [the recommendation] is scientifically correct,” Bell said at the meeting. “Perhaps a case could be made for healthcare workers to reduce the incidence of infections they get because of exposure in the community, and therefore reduce absenteeism among vaccinated healthcare workers.”

That might be strictly true given the protective measures taken in hospitals, but there always is the risk of a breach in protocol, an unanticipated direct exposure, or something potentially more widespread like not using a negative pressure room to perform an aerosol-generating procedure on a COVID-19 patient.

ACIP members also argued vaccinated workers would remain protected against serious infection, which was the original intent of the vaccines. This raises a question that demands a coherent answer and some consensus from public health officials: Does immunity to the delta variant wane after two doses of mRNA vaccine? A recent CDC study of HCWs — which has not been highly touted and was advised to be “interpreted with caution” — offered this relatively straightforward conclusion: “The vaccine efficacy point estimates declined from 91% before predominance of the SARS-CoV-2 delta variant to 66% since the SARS-CoV-2 delta variant became predominant.”1

The vaccines were thought to be waning when the Biden administration announced an ambitious plan to boost the public at large in August. In contrast, ACIP members expressed concern about loose wording in the “occupational” recommendation that would negate the purpose of designating groups and let everybody receive a booster pell-mell.

“We might as well as just say, ‘Give it to everybody 18 and over,” said ACIP member Pablo Sanchez, MD, principal investigator in the Center for Perinatal Research at The Research Institute and a professor of pediatrics at The Ohio State University. “We have a really effective vaccine, and this is like saying it is not working — and it is working. Certainly, some high-risk individuals do have waning immunity with time, but I am concerned about this.”

At this point, the narrative was going off track, particularly since the FDA approved a similar recommendation only a day before the ACIP meeting.

ACIP chair Grace Lee, MD, MPH, professor of pediatrics at Stanford University School of Medicine, was cool under pressure, reminding the committee the risk-benefit calculation for the recommendation is “individualized,” meaning those at risk of occupational exposures who are fully vaccinated can choose to get the booster — or not. It is a choice. On the other hand, the benefit in passing the recommendation would be providing greater “access” to the booster, which in turn opens a wider path to equity, she emphasized.

Although CDC officials reminded ACIP the recommendation will be accompanied by education and close follow-up for myocarditis — a rare side effect seen primarily in young men — one ACIP member said the effect of the booster could actually increase risk for this population by prompting a strong antibody response.

“If an 18-year-old is anxious about myocarditis, we are not providing anything in the benefit department, but we are providing risk,” said ACIP member Sarah Long, MD, professor of pediatrics at Drexel University College of Medicine.

In any case, many ACIP members thought the original occupational recommendation was written too broadly, open-ended, and would be difficult to explain. Other members argued it was necessary to maintain the healthcare workforce and preserve morale amid massive burnout and a national nursing shortage.

Still, many ACIP members seemed unenthusiastic about the boosters, citing competing pandemic priorities — including immunizing children — and frustration at focusing on those already vaccinated when so many are not. The tipping point probably came when one member called the recommendation a “solution looking for a problem.”

The meeting ended shortly after the measure was rejected, but the CDC moved quickly to head off a public relations debacle that could have read something like this: “Healthcare workers, who held the line when there was no vaccine, have been denied the full measure of immunity amid a nursing shortage, chronic burnout, and the highly transmissible delta variant.” Not a good look, and the reversal happened quickly.

CDC, FDA Booster Recommendations

Here is the CDC occupational recommendation as reissued and approved by Walensky:

“People aged 18-64 years who are at increased risk for COVID-19 exposure and transmission because of occupational or institutional setting may receive a booster shot of Pfizer-BioNTech’s COVID-19 vaccine at least six months after their Pfizer-BioNTech primary series, based on their individual benefits and risks.”2

This is the original wording of the measure voted down by ACIP:

“A single Pfizer-BioNTech COVID-19 vaccine booster dose is recommended based on individual benefit and risk for persons age 18-64 who are in an occupational or institutional setting where the burden of COVID-19 infection and risk of transmission are high, at least six months after the primary the series under the FDA’s emergency authorization act.”

A key difference is the word “recommended” is deleted in the final CDC version, which instead emphasizes those in the category “may” get the booster. Still, Lee was right: It was a choice based on individual benefit-risk, and the revision made that point clearer.

The other recommendations approved by ACIP are as follows:

  • People age 65 years and older and residents in long-term care settings should receive a booster shot of Pfizer-BioNTech vaccine six months after completion of the first series;
  • People age 50-64 years with underlying medical conditions should receive a Pfizer-BioNTech booster shot at least six months after completion of the first series;
  • People age 18-49 years with underlying medical conditions may receive a Pfizer-BioNTech booster shot at least six months after completion of the first series, based on their individual benefits and risks.2

The FDA finalized similar recommendations after its Sept. 17 meeting of the Vaccines and Related Biological Products Advisory Committee. One exception is the ACIP panel lowered the age range for those at high risk to age 50 years, in a nod to health disparities among minorities and ethnic populations. Walensky’s statement said the agencies are in alignment, but there is much more to be done because the FDA only issued an emergency use authorization (EUA) for a Pfizer-BioNTech booster.

The FDA recommended boosters for individuals:

  • age 65 years and older;
  • age 18-64 years of age at high risk of severe COVID-19 infection;
  • age 18-64 years whose frequent institutional or occupational exposure to SARS-CoV-2 places them at high risk of serious complications of COVID-19.3

In an initial vote, the FDA decided vaccine efficacy was still sufficient in immune-competent people in the general population, dashing President Biden’s hopes of a large national rollout of booster shots. A lack of overall data and the concern for myocarditis side effects in young people were among the reasons cited before the 16-2 vote against broad booster shots.

In comments to fellow FDA committee members, Paul Offit, MD, a vaccine expert at the Children’s Hospital of Philadelphia, summed up the situation this way: “The stated goal of this vaccine for people like Rochelle Walensky and others has been to protect against serious illness,” he said. “The data presented show that the vaccine still does exactly that. It is also clear, however, that the third dose of mRNA vaccine increases the titer of virus-specific neutralizing antibodies and will likely decrease the incidence of asymptomatic or symptomatic infection, which is associated with contagiousness. So then the question becomes, ‘What will the impact of that be on the arc of the pandemic?’ It may not be all that much. Certainly, we all agree that if we really want to impact this pandemic, we need to vaccinate the unvaccinated.”

The FDA said the most common booster side effects among clinical trial participants were pain, redness, and swelling at the injection site. Also reported were fatigue, headache, muscle or joint pain, and chills. “Of note, swollen lymph nodes in the underarm were observed more frequently following the booster dose than after the primary two-dose series,” the FDA reported.3

In terms of efficacy, the FDA studied real-world data from the United States and international sources, including the United Kingdom and Israel. “The immune responses of approximately 200 participants 18 through 55 years of age who received a single booster dose approximately six months after their second dose … demonstrated a booster response,” the FDA said.3

A Voice in the Wilderness

The FDA did not detail the degree of that response, but it was previously described in enthusiastic terms by Anthony Fauci, MD, director of the NIH’s National Institute for Allergy and Infectious Diseases. This is what makes the ACIP vote and reversal one of the more surprising glitches that have occurred throughout the pandemic response.

Only a month or so before the ACIP vote on occupational boosters, Fauci said at a White House briefing that “the booster mRNA immunization increases antibody titers by at least tenfold.” He also emphasized evidence of waning immunity of the vaccines to the SARS-CoV-2 delta variant.4 Who would not want a super-boost of immunity, HCW or not? But that message did not seem to resonate in any significant way in the ACIP meeting, and certainly was not presented as a compelling argument to protect HCWs in the final, controversial vote.

In making the claim, Fauci cited a study in preprint. “Two weeks after the booster vaccinations, titers against the wild-type original strain, B.1.351, and P.1 variants increased to levels similar to or higher than peak titers after the primary series vaccinations,” the researchers concluded.5 The research did not appear to test against the delta variant, but Fauci found the findings compelling, citing data from a Pfizer-BioNTech booster study that showed a dramatic increase in antibody titer to delta.6

Although his was a voice in the wilderness during the ACIP discussions, Fauci’s contention was recently vindicated by an Israeli study. In a large study involving more than 2 million patients, researchers found the booster dose after the initial two-shot series reduced the incidence of COVID-19 infection more than tenfold compared to those who were vaccinated at least five months previously but not boosted.

“Our findings can be understood through the following example,” the authors explained.7 “Suppose, first, that the combined effect of waning immunity and the increased prevalence of the delta variant decreases the efficacy of a vaccine that had been administered six months earlier to approximately 50% relative to the susceptibility in an unvaccinated person, as recent reports have suggested. Then, suppose that, as suggested by our results, the booster dose reduces the rate of infection for such vaccine recipients by a factor of 10. This would mean that the susceptibility of a person who receives a booster dose would decrease to approximately 5% (i.e., 50% divided by 10) relative to that in an unvaccinated person and would bring the vaccine efficacy among booster recipients to approximately 95%, a value similar to the original vaccine efficacy reported against the alpha variant.”

In retrospect, it appears there was a major disconnect between the Biden administration and the CDC and FDA on boosters. The Biden plan was to begin Sept. 20. The Department of Health and Human Services issued an announcement supporting the plan, specifically stating those who were vaccinated earliest — “including many healthcare workers”8 — would be eligible for boosters.

However, this was before the FDA and CDC held meetings on boosters. The president seemed to concede in a Sept. 9 speech on vaccine mandates that the administration got out ahead of the federal agencies.

“The decision of which booster shots to give, when to start them, and who will give them, will be left completely to the scientists at the FDA and the CDC,” Biden said in his address.9

They did, but to what effect? Was it politics trumped by science, some bruised egos whose input was ignored, or just another day in chaotic pandemic response, with too few singing from the same hymnal? If more non-boosted vaccinated people start experiencing breakthrough infections, particularly if they are serious, there may be some hastily called meetings at these federal agencies.

REFERENCES

  1. Fowlkes A, Gaglani M, Groover K, et al. Effectiveness of COVID-19 vaccines in preventing SARS-CoV-2 infection among frontline workers before and during B.1.617.2 (delta) variant predominance — eight U.S. locations, December 2020-August 2021. MMWR Morb Mortal Wkly Rep 2021;70:1167-1169.
  2. Centers for Disease Control and Prevention. Who is eligible for a COVID-19 vaccine booster shot? Sept. 30, 2021.
  3. Food and Drug Administration. FDA authorizes booster dose of Pfizer-BioNTech COVID-19 vaccine for certain populations. Sept. 22, 2021.
  4. The White House. Press briefing by White House COVID-19 Response Team and public health officials. Aug. 18, 2021.
  5. Wu K, Choi A, Koch M, et al. Preliminary analysis on the safety and immunogenicity of a SARS-COV-2 variant booster. medRxiv 2021.05.05.21256716. doi: 10.1101/2021.05.05.21256716. [Preprint].
  6. Watch Dr. Fauci reveal reasons for Covid-19 Booster (W.H. press briefing). CNET Highlights. Aug 18, 2021.
  7. Bar-on YM, Goldberg Y, Mandel M, et al. Protection of BNT162b2 vaccine booster against COVID-19 in Israel. N Engl J Med 2021 Sep 15;NEJMoa2114255. doi: 10.1056/NEJMoa2114255. [Online ahead of print].
  8. Department of Health and Human Services. Joint statement from HHS public health and medical experts on COVID-19 booster shots. Aug.18, 2021.
  9. Weise E. Who will be able to get a COVID-19 booster shot and when? That’s still in limbo. USA Today. Sept. 13, 2021.