The Advisory Committee on Immunization Practices’ Recommendation ..

Recommendations for Use of Moderna COVID-19 Vaccine

During June 2020–February 2022, ACIP convened 23 public meetings to review data on the epidemiology of COVID-19 and considerations for use of all COVID-19 vaccines, including the Moderna COVID-19 vaccine (4). The ACIP COVID-19 Vaccines Work Group, which includes experts in infectious diseases, vaccinology, vaccine safety, public health, and ethics, held meetings each week to review COVID-19 epidemiologic and surveillance data on vaccine efficacy, effectiveness, and safety and implementation considerations. After a systematic review of published and unpublished scientific evidence for benefits and harms^¶ of Moderna COVID-19 vaccination, the Work Group used a modified GRADE approach to assess the certainty of evidence for outcomes related to the vaccine, rated on a scale of type 1 to type 4 (type 1 = high certainty, type 2 = moderate certainty, type 3 = low certainty, and type 4 = very low certainty). Within the EtR Framework, ACIP considered the importance of COVID-19 as a public health problem, benefits and harms (as informed by the GRADE evidence assessment), patients’ values and preferences, issues of resource use, acceptability to stakeholders, feasibility of implementation, and anticipated impact on health equity. Work Group conclusions regarding the evidence for the Moderna COVID-19 vaccine were presented to ACIP at a public meeting on February 4, 2022.**

The body of scientific evidence for potential benefits and harms of the Moderna COVID-19 vaccine was guided by one large randomized, double-blind, placebo-controlled Phase III clinical trial (5,6), one Phase II clinical trial (7), one small Phase I clinical trial (8,9), 26 observational vaccine effectiveness studies, and two postauthorization vaccine safety monitoring systems: the Vaccine Adverse Events Reporting System (VAERS) and the Vaccine Safety Datalink (VSD). VAERS is a national passive surveillance vaccine safety monitoring system managed by CDC and FDA. VSD covers nine participating integrated health care organizations serving approximately 12 million persons and identifies possible adverse events after vaccination, using detailed clinical and demographic data available in near real time from electronic medical records. Updated findings from the ongoing Phase III clinical trial were based on 30,420 enrolled participants contributing approximately 11,000 person-years of data, with a median follow-up of 5 months during September 4, 2020–March 26, 2021 (ending with the date placebo recipients were offered crossover to receive study vaccine). Pooled effectiveness estimates were calculated when multiple observational studies reported data on a specific outcome; the study periods for the observational studies included in the pooled estimates ranged from 1 to 10 months (median = 5 months).

The estimated efficacy of the Moderna COVID-19 vaccine in the Phase III clinical trial was based on outcomes that occurred ≥14 days after receipt of the second dose. The demographic characteristics of participants, including age and race (5), have remained consistent since initial enrollment. Efficacy in preventing symptomatic, laboratory-confirmed COVID-19 in persons aged ≥18 years without evidence of previous SARS-CoV-2 infection was 92.7% (Table 1). One hospitalization occurred among the vaccinated group and 24 hospitalizations among the placebo group, yielding an estimated vaccine efficacy of 95.9% against COVID-19–associated hospitalization. No COVID-19–associated deaths occurred among study participants in the vaccinated group, and three occurred in the placebo group resulting in a vaccine efficacy of 100% against COVID-19–associated deaths. Efficacy in preventing asymptomatic SARS-CoV-2 infection was 57.4%. Observational data were available for all beneficial outcomes assessed: the pooled vaccine effectiveness estimates were 89.2% for prevention of symptomatic, laboratory-confirmed COVID-19 (11 studies); 94.8% against COVID-19–associated hospitalizations (15 studies), 93.8% against COVID-19–associated death (five studies), and 69.8% against asymptomatic SARS-CoV-2 infection (three studies). Most of the follow-up time occurred before B.1.1.529 (Omicron) became the predominant circulating SARS-CoV-2 variant. From the GRADE evidence assessment, the level of certainty for the benefits of Moderna COVID-19 vaccination among persons aged ≥18 years was type 1 (high certainty) for the prevention of symptomatic SARS-CoV-2 infection, type 1 (high certainty) for the prevention of asymptomatic SARS-CoV-2 infection, type 2 (moderate certainty) for prevention of COVID-19–associated hospitalization, and type 2 (moderate certainty) for the prevention of COVID-19–associated death.

In the Phase III clinical trial, severe local and systemic adverse reactions (i.e., reactogenicity) in the 7 days after vaccination (grade 3 or higher,^†† defined as adverse reactions interfering with daily activity) were more likely to occur among vaccine recipients (21.3%) than placebo recipients (4.5%) (relative risk = 5.03; 95% CI = 4.65–5.45) (Table 2). Among vaccine recipients, the most common grade 3 symptoms were fatigue, headache, joint pain, muscle pain, and injection-site pain. Overall, reactions categorized as grade 3 or higher were more likely to be reported after the second dose than after the first dose. The frequency of serious adverse events^§§ was 1.7% among vaccine recipients and 1.9% among placebo recipients. Based on data from VAERS and VSD, two rare but clinically serious adverse events after vaccination were detected: anaphylaxis and myocarditis or myopericarditis.^¶¶ Based on VSD data, 5.1 cases of anaphylaxis per 1 million doses of Moderna COVID-19 vaccine administered among persons aged ≥18 years were observed (10). Myocarditis or pericarditis were more common among vaccine recipients who were younger and male, and occurred more frequently after the second vaccine dose; 65.7 cases per 1 million doses of Moderna COVID-19 vaccine administered were observed from analysis of VSD chart-reviewed myocarditis and myopericarditis cases that met CDC case definitions (11) among men aged 18–39 years after dose 2 and occurring within a 0–7-day risk interval after vaccination. Although VAERS data are subject to the limitations of a passive surveillance system,*** the elevated number of observed versus expected myocarditis and myopericarditis cases during the 0–7-day risk interval after receipt of the second Moderna vaccine dose is generally consistent with the findings from VSD. The level of certainty from the GRADE evidence assessment regarding potential harms after vaccination was type 2 (moderate certainty) for serious adverse events and type 1 (high certainty) for reactogenicity. GRADE was last completed for Moderna COVID-19 primary vaccination in December 2020 (1); since that time, additional data became available on all prespecified outcomes of interest, resulting in a higher level of certainty in the estimates for the benefit of vaccination in prevention of asymptomatic infection and death (the GRADE evidence profile is available at https://www.cdc.gov/vaccines/acip/recs/grade/bla-covid-19-moderna-vaccine.html). Overall, the benefits for the Moderna COVID-19 vaccine outweigh any observed vaccine-associated risks (Table 1) (Table 2).

Data reviewed within the EtR Framework support the use of the Moderna COVID-19 vaccine. The Work Group concluded that COVID-19 remains an important public health problem and that the desirable effects of disease prevention through vaccination with Moderna COVID-19 vaccine in persons aged ≥18 years are large and outweigh the potential harms. With 204 million doses of Moderna COVID-19 vaccine administered to date (2), the Work Group determined that the vaccine is acceptable to vaccine providers and that implementation of vaccination is feasible. The Work Group also acknowledged that vaccine-eligible persons aged ≥18 years probably considered the desirable effects of vaccination to be favorable compared with the undesirable effects; however, there is likely important variability in vaccine acceptance within this age group, especially among those who are currently unvaccinated. Despite having recommendations for the Moderna COVID-19 vaccine for >1 year, data indicate vaccine coverage varies by geography, race/ethnicity, sexual orientation, and gender identity (12–14). Because these disparities remained even after the Pfizer COVID-19 vaccine had received standard authorization, the Work Group concluded that changing from an interim to a standard ACIP recommendation alone for the Moderna COVID-19 vaccine would probably have minimal impact on health equity (the evidence used to inform the EtR is available at https://www.cdc.gov/vaccines/acip/recs/grade/bla-covid-19-moderna-etr.html).