Anaphylaxis appears rare with COVID-19 vaccine, alternative dosing strategies considered

The CDC's monitoring system found low rates of anaphylaxis after a first dose of the Pfizer-BioNTech COVID-19 vaccine, peer-reviewed data were published on the Moderna vaccine, and single-dose vaccine strategies were considered.

The CDC released new data last week showing that anaphylaxis is rare after the first dose of the Pfizer-BioNTech COVID-19 vaccine. Monitoring by the Vaccine Adverse Event Reporting System detected 21 cases of anaphylaxis after administration of a reported 1,893,360 first vaccine doses from Dec. 14 to 23, 2020, for a rate of 11.1 cases per million doses, according to a report published by MMWR on Jan. 6. Most of the reactions (71%) occurred within 15 minutes of vaccination, and no deaths from anaphylaxis were recorded, the report said. Locations administering the COVID-19 vaccine should adhere to CDC guidance, the report said, including ensuring that supplies are available to manage anaphylaxis, screening potential vaccine recipients to identify those with contraindications and precautions, observing recipients for the recommended period based on history of allergic reactions, ensuring that clinicians can recognize anaphylaxis signs and symptoms early, and treating suspected anaphylaxis with epinephrine immediately. The CDC's guidance on COVID-19 vaccine administration was updated on Jan. 6 to include clarification on the four-day grace period for administration of a second vaccine dose, updated recommendations regarding vaccine coadministration, clarification on passive antibody therapy and vaccine administration, and updated information on management of anaphylaxis.

Peer-reviewed data on the Moderna vaccine for COVID-19 were published Dec. 30, 2020, by the New England Journal of Medicine. The data had previously been shared with the FDA and were the basis for the agency's emergency use authorization for the vaccine on Dec. 18.

In the observer-blinded phase 3 trial conducted at 99 centers in the United States, 30,420 volunteers were randomly assigned to receive two doses of either vaccine (n=15,210) or placebo (n=15,210), with more than 96% receiving both injections. One hundred eighty-five participants in the placebo group and 11 participants in the vaccine group developed confirmed symptomatic COVID-19 illness (56.5 per 1,000 person-years [95% CI, 48.7 to 65.3] vs. 3.3 per 1,000 person-years [95% CI, 1.7 to 6.0]). The vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001).

Serious adverse events were rare, and no safety concerns were noted. Thirty cases of severe COVID-19 illness developed, all in the placebo group. Fewer cases of symptomatic SARS-CoV-2 infection occurred after a single vaccine dose, a finding that the authors called “encouraging.” However, they noted that their trial was not designed to evaluate the efficacy of a single vaccine dose and said that more evaluation is warranted.

Recent articles published on Jan. 5 by Annals of Internal Medicine discussed alternate administration schedules for COVID-19 vaccines. In one study, published as a research letter, the authors used a previously published model of a COVID-19 vaccination program to quantify the “speed-versus-efficacy tradeoff” by comparing the likely performance of one- and two-dose vaccine candidates over a six-month horizon. They found that in their model, a single-dose vaccine that conferred lifetime protection needed to attain an efficacy of 55% to avert as many infections as a two-dose vaccine with 95% efficacy, whereas a single-dose vaccine whose protection duration was uncertain would need to attain 75% efficacy. Similar mortality outcomes could be achieved at single-dose efficacy levels of 40% for lifetime protection and 60% for uncertain protection, the authors estimated.

In another study published as a research letter, researchers used a decision analytic cohort model to estimate direct benefits of vaccination against COVID-19 under alternative strategies for dose allocation: a fixed strategy based on the current U.S. model of two doses, timed about one month apart, and a flexible strategy that would reserve 10% of the supply for second doses during the first three weeks, 90% during each of the next three weeks, and 50% thereafter. According to their estimates, an additional 23% to 29% of COVID-19 cases would be averted with the flexible versus the fixed strategy. The two key determinants of an optimal strategy were the number of highly protected individuals at the end of the simulation and the stability of the vaccine supply, the authors noted. “We find that under most plausible scenarios, a more balanced approach that withholds fewer doses during early distribution in order to vaccinate more people as soon as possible could substantially increase the benefits of vaccines, while enabling most recipients to receive second doses on schedule,” they wrote.

In addition, an Ideas and Opinions article outlined a public health strategy for maximizing the health gains of every COVID-19 vaccine dose and said that use of a single dose of both the Pfizer-BioNTech and Moderna vaccines should be considered, while an accompanying editorial noted that the COVID-19 vaccine rollout faces supply, administration, and demand constraints that may not be addressed and may be exacerbated by alternative dosing schedules.

“There are no short cuts to inspiring trust among those at greatest risk, developing and implementing an effective vaccination program, and monitoring for safety and effectiveness over time,” the editorialist wrote. “Models of alternative strategies—particularly those that make large assumptions about vaccine efficacy in the absence of reliable data—should not drive policy without a full consideration of the challenges of implementation and potential unintended effects.” While considering alternative approaches is worthwhile, the editorialist said, the current priority should be increasing the related evidence base through clinical testing and observational studies.