ACIP Update to the Evidence to Recommendations for a 2nd COVID-19 Booster Dose in Adults Ages 50 Years and Older and Immunocompromised Individuals

About

The Evidence to Recommendations (EtR) frameworks describe information considered in moving from evidence to ACIP vaccine recommendations.

Summary

Question:

Do the balance of benefits and risks warrant an update to the COVID-19 vaccine policy, allowing adults ages ≥50 years and persons with moderate to severe immunocompromised ages ≥12 years to receive a second booster of an mRNA COVID-19 vaccine?

Population:

  • People ages 50 years and older who received an initial COVID-19 booster dose (regardless of which vaccine was used) at least 4 months ago
  • People ages 12 years and older who are moderately or severely immunocompromised who received an initial COVID-19 booster dose (regardless of which vaccine was used) at least 4 months ago
  • People ages 18 years and older who received both a primary dose and a booster dose of J&J/Janssen COVID-19 vaccine at least 4 months ago

Intervention:

A second booster using an mRNA COVID-19 vaccine in the following populations:

  • People ages 50 years and older who received an initial COVID-19 booster dose (regardless of which vaccine was used) at least 4 months ago
  • People ages 12 years and older who are moderately or severely immunocompromised who received an initial COVID-19 booster dose (regardless of which vaccine was used) at least 4 months ago
  • People ages 18 years and older who received both a primary dose and an initial booster dose of J&J/Janssen COVID-19 vaccine at least 4 months ago

Background

The emergence of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), has led to a global pandemic with substantial societal and economic impacts on individual persons and communities. In the United States, more than 80 million cases and more than 986,000 COVID-19-associated deaths have been reported as of April 17, 2022. Persons of all ages are at risk for infection and severe disease. However, the risk for severe illness from COVID-19 is higher in people ages ≥50 years and those who are immunocompromised.

Three COVID-19 vaccines are currently approved under a Biologics License Application or authorized under an Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) and recommended for primary vaccination by the Advisory Committee on Immunization Practices (ACIP): the two-dose mRNA-based Pfizer-BioNTech/Comirnaty and Moderna COVID-19 vaccines and the single-dose adenovirus vector-based Janssen (Johnson & Johnson) COVID-19 vaccine.

On August 12, 2021, the FDA amended the EUAs for Pfizer-BioNTech (persons aged ≥12 years) and Moderna (persons aged ≥18 years) COVID-19 vaccines to authorize an additional dose for certain immunocompromised persons. Due to insufficient data, the EUA amendment for an additional dose did not apply to Janssen COVID-19 vaccine or to individuals who received Janssen COVID-19 vaccine as a primary series. Previous data on the use of additional doses of COVID-19 vaccine is linked here: ACIP Evidence to Recommendations for Use of an Additional COVID-19 Vaccine Dose in Immunocompromised People | Advisory Committee on Immunization Practices (ACIP) | CDC.

Additionally, during September-October, 2021, the FDA amended the COVID-19 vaccine EUAs to allow for booster doses of Pfizer-BioNTech, Moderna, or Janssen COVID-19 vaccines in persons who completed primary vaccination with these vaccines, as well as use of each of the available COVID-19 vaccines as a heterologous (or “mix and match”) booster dose in eligible individuals following completion of primary vaccination with a different COVID-19 vaccine. Previous data on the use of booster doses of COVID-19 vaccine is linked here: ACIP Evidence to Recommendations for Use of COVID-19 Vaccine Booster Doses | Advisory Committee on Immunization Practices (ACIP) | CDC.

On March 29, 2022, the FDA amended the COVID-19 vaccine EUAs to authorize a second booster dose of either the Pfizer-BioNTech or the Moderna COVID-19 vaccines for individuals 50 years of age and older as well as certain immunocompromised individuals 12 years of age and older at least 4 months after receipt of a first booster dose of any authorized or approved COVID-19 vaccine.

Following FDA’s regulatory action on March 29, 2022, CDC updated its COVID-19 vaccination guidance to allow certain immunocompromised individuals and people over the age of 50 who received an initial booster dose at least 4 months ago to be eligible for another mRNA booster to increase their protection against severe disease from COVID-19. Separately, and in addition, based on newly published data, adults who received a primary vaccine and booster dose of Johnson & Johnson’s COVID-19 vaccine at least 4 months ago may now receive a second booster dose using an mRNA COVID-19 vaccine.

Additional background information supporting the ACIP recommendation on the use of additional or booster doses of COVID-19 vaccine can be found in the relevant publication of the recommendation referenced on the ACIP website.

Updates to the EtR framework are presented below to address the evidence supporting a second booster.

Public Health Problem

Criteria Evidence Additional Information
Is the problem of public health importance? General COVID-19 information
The current 7-day average of COVID-19 cases is approximately 4% of the peak seen during the Omicron surge, with COVID-19 related hospitalization admissions and deaths continuing to decline from this surge. As of April 17, 2022, there have been over 80 million total cases and 986,000 deaths reported in the United States.1,2
Adults ages 50 years and older and SARS-CoV-2 infection
However, throughout the pandemic, adults 50 years of age and older have displayed higher hospitalization rates than younger age groups.3 In immunocompetent adults, receipt of a booster dose has been shown to increase protection against infection, hospitalization, and death compared to unvaccinated adults and adults that only received the primary series, remaining high 4-6 months after the additional dose.4
Immunocompromised people and SARS-CoV-2 infection
Vaccination provides some protection against severe outcomes in immunocompromised individuals, but more rapid waning is observed after a third dose in immunocompromised individuals compared to those that are immunocompetent.7,8
 Vaccination:
As of April 18, 2022, more than 218 million people in the United States are fully vaccinated against COVID-19 and 99.5 million people have received a booster dose.5
Variants of Concern:
As of April 16, 2022, the Omicron variant is the dominant circulating variant in the United States and is more than twice as contagious as previous variants.6

Benefits and Harms

Criteria Evidence Additional Information
How substantial are the desirable anticipated effects? In an open-label, non-randomized study among healthcare workers in Israel, an increased immune response, lower rate of infection and severe illness was observed after a fourth dose when compared to a third dose.1 An analysis of the potential benefits of a booster dose, using the epidemiologic data in the U.S., demonstrated incremental benefits in hospitalizations, ICU admissions, and deaths prevented per million series completed following each subsequent booster dose, suggesting that the greatest benefit is achieved from receipt of the primary series and first booster dose but additional benefits may be achieved through receipt of a second booster dose. There are no efficacy or effectiveness studies of COVID-19 prevention following a 4th dose in immunocompromised persons.
How substantial are the undesirable anticipated effects? The risk of myocarditis/pericarditis was identified after COVID-19 vaccine booster doses in individuals ages 12 years and older. Among those ages 12–39 years, cases of mostly myocarditis and myopericarditis with onset <7 days after the 1st booster were observed. However, the risk of myocarditis and myopericarditis was less than that seen after the 2nd dose in the primary series. Among those ages 40 years and older, mostly pericarditis cases were observed, and the small, elevated risk was more spread out in the 3 weeks after the 1st booster.2 Theoretical risks of immune tolerance and imprinting have been identified, but current data suggests these are not of concern at this time3,4,5, however data will be closely monitored.
Do the desirable effects outweigh the undesirable effects? The Work Group concluded that the potential desirable effects of an additional mRNA COVID-19 vaccine dose outweigh the undesirable effects, including theoretical risks.

Values and Acceptability

Criteria Evidence Additional Information
Does the target population feel that the desirable effects are large relative to undesirable effects? A new survey by STAT and The Harris Poll, which polled 2,028 U.S. adults between March 25th and 27th, finds 6 in 10 Americans have already decided they will get another booster if it’s recommended for them. Just under one-quarter of U.S. adults indicated they will only receive a second booster shot if a new variant arises or there is a surge in COVID-19 cases in their area; and 18% have no plans to get a booster at all. Additionally, 73% of baby boomers – those 57 years and older – plan to get a booster, if recommended, compared with 48% of Gen Z’ers, who are between 18 and 24 years old. Among those polled, 54% of Black, non-Hispanic respondents and 43% of Hispanic individuals would get another booster, compared with 73% of Asian, non-Hispanic individuals and 65% of White, non-Hispanic respondents.1

An ongoing survey by the CDC and University of Iowa/RAND Corporation was designed to assess attitudes and intentions for additional COVID-19 vaccine doses among 1,412 “boosted” U.S. adults aged 50 years and older. The purposes of conducting this survey were to:

  1. Assess vaccination intentions for a 2nd COVID-19 vaccine booster in the next 4 months among boosted, U.S. adults aged 50 years and over
  2. Assess barriers toward receiving a 2nd COVID-19 vaccine booster
  3. Assess vaccination intentions for receiving another COVID-19 vaccine now and in the Fall2

In relation to vaccination intentions for a 2nd COVID-19 vaccine booster, 82% of survey respondents “definitely” or “probably” will get a 2nd booster dose in the next 4 months; and 68% of respondents intending to get a 2nd booster reported they would get the currently available booster.2

In reference to vaccination intentions for receiving another COVID-19 vaccine now and in the Fall, 70% of respondents said they would get a COVID-19 booster now and again in the Fall. However, 10% of respondents said they would get a COVID-19 booster either now or in the Fall, but not both. The emergence of new variants, preventing the spread to others, and increased severity of cases were among the top reasons for receiving another booster. Additionally, a strong healthcare provider recommendation was influential in the decision to receive another COVID-19 vaccine booster.2
Is there important uncertainty about or variability in how much people value the main outcomes? Regarding vaccination intentions for a 2nd COVID-19 vaccine booster, 19% of respondents intending to get a 2nd booster reported they would wait for a new booster that protects against variants. Beliefs related to another dose of the currently available vaccines not providing additional protection was the primary reason given for not wanting a 2nd COVID-19 booster, with 31% of respondents indicating they have enough protection from previous doses. Furthermore, 24.1% are waiting for a new booster and 18.4% feel that boosters are not effective. Conclusively, 86% of respondents “definitely” or “probably” would get a 2nd booster dose if a new COVID vaccine that protects against variants became available.2

Feasibility and Implementation

Criteria Evidence Additional Information
Is the intervention feasible to implement? Among people who are fully vaccinated, approximately 52% of people ages 50-64 years and 67% of people ages 65 years and older have received a COVID-19 vaccine booster dose. At the time of authorization, approximately 30 million people were eligible (at least 4 months after their previous dose), which was nearly 10 million eligible individuals ages 50-64 years and around 20 million individuals ages 65 years and older. Based on timing of recommendations, people with immunocompromised conditions would not be eligible for a second booster (5th total dose) until May 13, 2022, at the earliest.
The number of people reportedly getting vaccinated has nearly tripled since authorization of second booster doses, to an average of 447,000 per day in the week ending April 8th, compared with 160,000 per day in the week ending March 29th.2,3 As of April 19, 2022, approximately 1.1 million second COVID-19 vaccine booster doses have been given in adults ages 50-64 years and 3.2 million second booster doses have been given in adults ages 65 years and older since authorization.4

Equity

Criteria Evidence Additional Information
What would be the impact of the intervention on health equity? There are noted disparities in booster vaccination trends by race or ethnicity among fully vaccinated people in the United States. Individuals who identified as Multiracial, Asian, and White persons have higher uptake of booster doses (72.3%, 68.5%, and 59%, respectively). However, there is a gap in uptake among people from some racial and ethnic groups including Native Hawaiian or Other Pacific Islander, American Indian/Alaska Native, Black, and Hispanic or Latino populations (47%, 45.1%, 44.4% and 41.8%, respectively).1 Consequently, while the gaps for vaccine uptake were closed for primary series, disparities still remain with uptake for booster doses.
Racial and ethnic minority groups, ages 65 years and older, are under-represented in the population, both overall and among COVID-19-associated hospitalizations.2,3 Whereas, COVID-19-associated hospitalizations among adults ages 50-64 years are more consistent with the underlying population.3 Moreover, underlying medical conditions that increase the risk for COVID-19 are more prevalent in racial and ethnic minority groups.4 A second booster recommendation for adults ages 50 years and older may prevent COVID-19 among persons from racial and ethnic minority groups and persons with underlying medical conditions.

Work Group Interpretation Summary

In relation to adults ages 50 years and older, the risk of COVID-19 increases with age; so, a 2nd booster (4th total dose) for older adults can help ensure those at risk are protected from severe disease. The current vaccine effectiveness data shows limited waning for immunocompetent adults after receiving a 3rd dose; and currently, there are lower COVID-19 case counts and hospitalization rates. Nevertheless, there may be additional recommendations for COVID-19 vaccines in the future. Altogether, the Work Group supported recommendation that adults ages 50 years and older may receive a 2nd COVID-19 vaccine booster dose.

Pertaining to immunocompromised individuals ages 12 years and older, the earliest eligibility for a 2nd booster (5th dose) based on timing of previous recommendations would be mid-May. The currently available vaccine effectiveness data is from the 3rd dose in the primary series, which shows waning; however, there’s no vaccine effectiveness data that’s currently available for the recommended 1st booster (4th dose). Currently, there are lower COVID-19 case counts and hospitalization rates; however, immunocompromised individuals are likely to remain at higher risk for severe outcomes. Therefore, it is important that immunocompromised individuals receive all doses of the primary series (including additional doses) and the 1st booster dose. All things considered, the Work Group supported recommendation that immunocompromised individuals ages 12 years and older may receive a 2nd COVID-19 vaccine booster dose.

The current recommendations that individuals may receive a COVID-19 vaccine 2nd booster reflect current conditions in the pandemic including:

  • Wide availability of COVID-19 vaccines
  • High protection against severe disease from the primary series and first booster dose
  • Low rates of COVID-19 cases and hospitalizations
  • Use of antivirals and monoclonal antibodies for SARS-CoV-2

As the 2nd booster is already authorized and available, recommendations can rapidly adjust if COVID-19 epidemiology changes in the future. The current recommendation allows for flexibility, giving patients and providers access to the vaccine dose and the ability to decide based on individual factors and timing.

For more information, the Interim Clinical Considerations guidance on who should receive a 2nd COVID-19 vaccine booster dose is linked here: Interim Clinical Considerations for Use of COVID-19 Vaccines | CDC.

Draft recommendation: ACIP and CDC recommendations

Those 50 and older and those who are 12 and older and immunocompromised should get a second booster dose.

References

Problem

  1. CDC COVID Data Tracker. https://covid.cdc.gov/covid-data-tracker/#trends_dailycases Accessed April 19, 2022
  2. CDC COVID Data Tracker. https://covid.cdc.gov/covid-data-tracker/#trends_dailydeaths Accessed April 13, 2022
  3. CDC COVID Data Tracker: COVID-NET. https://covid.cdc.gov/covid-data-tracker/#covidnet-hospitalization-network Accessed April 19, 2022
  4. CDC COVID Data Tracker. https://covid.cdc.gov/covid-data-tracker/#rates-by-vaccine-status Accessed April 19, 2022
  5. CDC COVID Data Tracker. https://covid.cdc.gov/covid-data-tracker/#vaccinations_vacc-total-admin-rate-total Accessed April 19, 2022
  6. CDC COVID Data Tracker. https://covid.cdc.gov/covid-data-tracker/#variant-proportions Accessed April 19, 2022
  7. Preliminary unpublished data, based on methods described here: https://www.bmj.com/content/376/bmj-2021-069761
  8. Link-Gelles, R. COVID-19 Vaccine Effectiveness during Omicron. Presentation to ACIP. April 20, 2022. www.cdc.gov/vaccines/acip/meetings/downloads/slides-2022-04-20/02-COVID-Link-Gelles-508.pdf

Benefits and harms

  1. Bar-On, Y. M., et al. (2022). "Protection by a Fourth Dose of BNT162b2 against Omicron in Israel." New England Journal of Medicine.
  2. Klein, N & Shimabukuro, T. Safety update of 1st boost mRNA COVID-19 vaccination. Presentation to ACIP. April 20, 2022. www.cdc.gov/acip/media/pdfs/2024/09/03-COVID-Klein-Shimabukuro-508.pdf
  3. Regev-Yochay, G., et al. (2022). "Efficacy of a Fourth Dose of Covid-19 mRNA Vaccine against Omicron." New England Journal of Medicine 386(14): 1377-1380.
  4. Gagne, M., et al. (2022). "mRNA-1273 or mRNA-Omicron boost in vaccinated macaques elicits comparable B cell expansion, neutralizing antibodies and protection against Omicron." https://www.biorxiv.org/content/10.1101/2022.02.03.479037v1.full.pdf
  5. Research Square. (2022). Safety, Immunogenicity and Antibody Persistence of a Bivalent Beta-Containing Booster Vaccine. https://assets.researchsquare.com/files/rs-1555201/v1_covered.pdf?c=1650045900

Values and Acceptability

  1. STAT+. STAT-Harris Poll: Most Americans would get a COVID-19 booster shot if recommended. https://www.statnews.com/pharmalot/2022/04/06/covid19-vaccine-mask-booster-harris-poll/. Accessed April 12, 2022
  2. CDC and University of Iowa/RAND survey, unpublished

Feasibility and Implementation

  1. Data Source: CDC IZ Data Lake. 3/28/2022
  2. SEAN COVID-19 Survey Summary: April 15, 2022. https://www.langerresearch.com/wp-content/uploads/SEAN-COVID-19-Survey-Summary_4-15-22.pdf. Accessed April 15, 2022
  3. CDC COVID Data Tracker. Trends in Number of COVID-19 Vaccinations in the US. https://covid.cdc.gov/covid-data-tracker/#vaccination-trends_vacctrends-total-daily. Accessed April 15, 2022
  4. Data Source: IZDL All Admin

Equity

  1. CDC COVID Data Tracker. Trends in Demographic Characteristics of People Receiving COVID-19 Vaccinations in the United States. https://covid.cdc.gov/covid-data-tracker/#vaccination-demographics-trends. Accessed April 19, 2022
  2. United States Census Bureau. The Population 65 Years and Older in the United States. https://www.census.gov/library/publications/2018/acs/acs-38.html Issued October 2018
  3. Data Source: COVID-NET
  4. Presented to ACIP September 22, 2020, www.cdc.gov/vaccines/acip/meetings/downloads/slides-2020-09/COVID-07-Dooling-508.pdf. Source: National Center for Health Statistics, National Health Interview Survey, 2018

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Content Source:
National Center for Immunization and Respiratory Diseases (NCIRD)