Originally published by our sister publication, Infectious Disease Special Edition

The White House Coronavirus Task Force is calling for boosters of the messenger RNA (mRNA) vaccines because data show that immunity wanes over time. The Advisory Committee for Immunization Practices (ACIP) discussed the need for a booster dose of COVID-19 mRNA vaccine at its recent meeting, but is not ready to make a recommendation.

Sara Oliver, MD, MSPH, from the CDC, outlined a risk-based booster dose strategy for COVID-19 vaccines that would target people at risk for severe disease and individuals who are critical to the public health system. Dr. Oliver presented a preliminary framework to identify who might need a booster the most, including people ages 65 years and older, residents in long-term care facilities and health care workers.

Data show the vaccines remain effective at preventing hospitalization and severe disease but are less effective at preventing infection or mild symptomatic illness, and stopping transmission, especially in light of the delta variant.

Dr. Oliver pointed out another issue: Health care workers with mild COVID-19 illness are required to call out sick, and these job absences burden the health care system.

However, several ACIP members disagreed about the need for booster shots, saying vaccinating the unvaccinated population should remain the priority.

Grace Lee, MD, of Stanford University, in California, argued that it didn’t have to be an either/or situation. She said it makes sense to prevent severe disease, hospitalization and death by vaccinating those who were unvaccinated as well as providing booster doses in populations vulnerable to severe illness and death.

Currently, booster doses of vaccine are only authorized for immunocompromised individuals. Dr. Oliver said policy on booster doses requires continued evaluation of effectiveness, monitoring the impact of both time and variants, and the ability of booster doses to improve protection.

The panel also met to discuss Comirnaty, the Pfizer-BioNTech mRNA vaccine. Despite rare adverse events, the ACIP is recommending the vaccine for people 16 years of age and older. This is the first COVID-19 vaccine to receive full FDA approval, rather than to be given under an emergency use authorization.

The 14-member ACIP agreed that the benefits far outweighed the risks of the vaccine. After a review of nine studies, the panel concluded that the Pfizer-BioNTech vaccine prevented COVID-19 infection with symptoms roughly 90% to 92% of the time, at least for the first four months after the second dose. 

According to Julia Gargano, PhD, of the CDC, there is a high level of evidence that the Pfizer-BioNTech COVID-19 vaccine is effective in preventing symptomatic COVID-19 and moderate evidence that the vaccine prevents COVID-19 hospitalization and prevents death due to COVID-19. Two cohort studies showed benefit of vaccination for preventing asymptomatic infections, but the magnitude was inconsistent. In the randomized controlled trials, serious adverse events were balanced between vaccine and placebo arms, and in post-authorization safety monitoring, myocarditis and anaphylaxis were rare but more common following vaccination. In terms of reactogenicity, severe reactions within seven days were more common in vaccinated individuals and any grade 3 or higher reaction was reported by 10.7% of vaccinated versus 2.3% of the placebo group.
Most of the meeting was taken up by presentations that discussed the safety of the vaccine, particularly concerns about anaphylaxis and myocarditis. The rate of anaphylaxis was estimated at five cases for every 1 million shots. While cases of myocarditis and pericarditis were more common in patients getting the vaccine than in those who did not get the vaccine, they were less common than in those with COVID-19 infection. Patients with SARS-CoV-2 infection had 16 to 18 times higher risk for myocarditis than patients without SARS-CoV-2. The risk for myocarditis in individuals after SARS-CoV-2 infection was six to 34 times higher than in those who received the mRNA vaccine.

  • Younger men are more at risk for myocarditis from mRNA vaccines, but these harms were dwarfed by the potential benefits. While every 1 million doses of the vaccine given to 18- to 24-year-old males would be expected to cause 39 cases of myocarditis over 120 days, the vaccine would prevent 75,200 COVID-19 cases, 1,000 hospitalizations, 230 ICU admissions and two deaths from COVID-19. 
  • While every 1 million doses of the vaccine given to 18- to 24-year-old females would be expected to cause three cases of myocarditis over 120 days, the vaccine would prevent 107,000 COVID-19 cases, 3,000 hospitalizations, 240 ICU admissions and 21 deaths from COVID-19. 
  • While every 1 million doses of the vaccine given to 25- to 29-year-old men would be expected to cause 12 cases of myocarditis over 120 days, the vaccine would prevent 76,600 COVID-19 cases, 2,200 hospitalizations, 490 ICU admissions and 44 deaths. 
  • While every 1 million doses of the vaccine given to 25- to 29-year-old females would be expected to cause 1 case of myocarditis over 120 days, the vaccine would prevent 105,000 COVID-19 cases, 4,100 hospitalizations, 240 ICU admissions and 16 deaths. 

Since the risk for myocarditis from the vaccine wanes over time, the risk?benefit profile improves with longer follow-up, the panel was told.

Amanda Cohn, MD, of the CDC, said the vaccine-associated myocarditis is substantially less harmful than myocarditis caused by other types of infections or vaccines. This sentiment was echoed by several clinicians and panel members. So far, the average hospital length of stay for vaccine-associated myocarditis is one to two days, and vaccine-associated myocarditis has not resulted in any deaths. (However, the New Zealand Ministry of Health reported on Aug 30 that the COVID-19 Vaccine Independent Safety Monitoring Board (CV-ISMB) is reviewing the death of a woman following her Pfizer-BioNtech vaccination. The CV-ISMB said the woman’s death was due to myocarditis. Although the cause of death has not yet been determined, the CV-ISMB considered that the myocarditis “was probably due to vaccination,” according to the New Zealand health department. The CV-ISMB noted that there were concurrent medical issues that may have influenced the outcome following vaccination. Almost 3.7 million doses of vaccine have been distributed in New Zealand by Sept. 2.)

Whereas the emergency use authorization relied on one phase 2/3 clinical trial with a median of two months of follow-up data, the recent full approval is based on at least six months of data from trials in addition to a plethora of observational studies and extremely high-quality, real-world evidence, according to Kathleen Dooling, MD, of the CDC.

The sources reported no relevant financial disclosures.

--Kate O’Rourke