ACIP Evidence to Recommendations (EtR) for Use of an Updated (Monovalent XBB Containing) COVID-19 Vaccine Under an Emergency Use Authorization

About

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

Summary

Question: Should 2023 – 2024 (monovalent, XBB containing) COVID-19 vaccines authorized under EUA or approved by BLA be recommended for use in persons ≥6 months of age?

Population: People 6 months of age and older

Intervention:

  • A single dose of a 2023 – 2024 COVID-19 vaccine for everyone ages 5 years and older
  • A multi-dose initial series with at least one dose of the 2023 – 2024 COVID-19 vaccine for children ages 6 months – 4 years (2 doses of Moderna or 3 doses of Pfizer-BioNTech mRNA COVID-19 vaccine)
  • A 3-dose initial series with a least one dose of the 2023 – 2024 COVID-19 vaccine (may receive 1 or more additional 2023 – 2024 COVID-19 vaccine doses) for people who are moderately or severely immunocompromised

Background

The emergence of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), in late 2019 has led to a global pandemic with dramatic societal and economic impact on individual persons and communities. In the United States, more than 18 million hospitalizations and more than 3 million COVID-19-associated deaths have been reported by the end of 2022.1 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 aged ≥65 years and those with chronic medical conditions. Additionally, there is a disproportionate burden of COVID-19 infections and deaths among racial and ethnic minority communities. Non-Hispanic Black, Hispanic/Latino (Hispanic) and American Indian/Alaska Native persons have experienced higher rates of disease, hospitalization and death compared with non-Hispanic White persons. This is likely related to inequities in social determinants of health that put racial and ethnic minority groups at increased risk for COVID-19, including overrepresentation among essential workers who have higher risk of exposure to COVID-19, lower incomes, reduced access to healthcare, or higher rates of comorbid conditions.

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): 1) the 2-or 3-dose monovalent mRNA Pfizer-BioNTech/Comirnaty COVID-19 vaccine; 2) the 2-or 3-dose monovalent mRNA Moderna/Spikevax COVID-19 vaccine, and 3) the 2-dose, adjuvanted protein subunit-based Novavax COVID-19 vaccine.

During September – October 2021, the FDA amended the COVID-19 vaccine EUAs to allow for booster doses of Pfizer-BioNTech and Moderna 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 COVID-19 vaccine booster doses is linked here: EtR for Use of COVID-19 Vaccine Booster Doses | CDC.

Furthermore, 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 vaccine 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.

Additionally, on August 31, 2022, the FDA amended the Emergency Use Authorization (EUA) of the Moderna COVID-19 vaccine and the Pfizer-BioNTech COVID-19 vaccine to authorize bivalent formulations of the vaccines for use as a single booster dose at least two months following primary or booster vaccination. Following FDA’s regulatory action, CDC updated its COVID-19 vaccination guidance on September 1, 2022, for use of updated COVID-19 boosters from Pfizer-BioNTech for people ages 12 years and older and from Moderna for people ages 18 years and older to better protect against the most recently circulating COVID-19 variant.

Once more, on October 12, 2022, the FDA amended the Emergency Use Authorization (EUA) of the Moderna COVID-19 vaccine and the Pfizer-BioNTech COVID-19 vaccine to authorize bivalent formulations of the vaccines for use as a single booster dose in younger age groups. The bivalent booster is authorized for administration at least 2 months following completion of primary or booster vaccination in children down to 6 years of age for the Moderna COVID-19 vaccine and down to 5 years of age for the Pfizer-BioNTech COVID-19 vaccine. Subsequent to FDA’s regulatory action, CDC expanded the use of updated (bivalent) COVID-19 vaccines to children ages 5 through 11 years.

On September 11, 2023, the FDA took action approving and authorizing for emergency use updated COVID-19 vaccines manufactured by Moderna and Pfizer-BioNTech formulated to more closely target currently circulating variants and to provide better protection against serious consequences of COVID-19, including hospitalization and death. Following FDA’s regulatory action, CDC updated its COVID-19 vaccination guidance on September 12, 2023, recommending everyone 6 months and older get an updated COVID-19 vaccine to protect against the potentially serious outcomes of COVID-19 illness this fall and winter.

Additional background information supporting the interim ACIP recommendation on the use of 2023 – 2024 COVID-19 vaccines can be found in the relevant publication of the recommendation referenced on the ACIP website.

1 Meagan C. Fitzpatrick et al., “Two Years of U.S. COVID-19 Vaccines Have Prevented Millions of Hospitalizations and Deaths,” To the Point (blog), Commonwealth Fund, Dec. 13, 2022. https://doi.org/10.26099/whsf-fp90

Public Health Problem

Criteria Work Group Judgements Evidence Additional Information
Is the problem of public health importance? Yes Hospitalization rates are highest in infants and older adults; and despite some recent upticks, hospitalization rates overall are currently lower than they have been at previous points in the pandemic.1 The number of COVID-19 new hospital admissions by week from the National Healthcare Safety Network (NHSN), show that rates correspond to over 17,000 new hospital admissions a week.2 Additionally, annual hospitalizations per 100,000 population for other pediatric vaccine preventable diseases prior to their vaccine recommendation, compared to COVID-19, show that hospitalization burden is similar or greater for COVID-19 compared to other vaccine preventable diseases.3,4,5,6
Burden projections from the COVID-19 scenario modeling hub were assessed as well. The COVID-19 scenario modeling hub is a multi-team effort aimed at creating and modeling planning scenarios of the mid- to long-term COVID-19 situation. The policy scenarios are developed in close collaboration with government agencies and other stakeholders, and project anticipated hospitalizations and deaths due to COVID-19. For this round, there were 6 scenarios focusing on 3 vaccine recommendation scenarios and 2 different rates of immune escape. The 3 recommendation scenarios were no vaccine recommendation vs. recommendation for 65 years and older vs. a universal recommendation. Additionally, there was a low immune escape vs. a high immune escape scenario. The teams assumed that vaccines were reformulated to target strains circulating on June 15th of each year and that vaccines were made available from September 1st. The reformulated vaccines were assumed to have 65% vaccine effectiveness against symptomatic infection with the strain targeted by reformulation. Vaccine uptake was based on first booster uptake and teams were required to project a minimum of 2 years into the future. Eight teams provided national level projections. Based on the ensemble projections, weekly hospitalizations are likely to increase this winter and stay within last year’s range.7
It is known that underlying conditions put people at higher risk for severe COVID-19 outcomes, and that the percent of the population that have underlying conditions differ dramatically by age. To evaluate the burden among those without underlying conditions, the percent hospitalized for COVID-19 that have no underlying conditions by age group, the percent of those with no underlying conditions admitted to the ICU and the percent of those admitted to ICU with no underlying conditions were assessed. In each of these categories, those without underlying conditions are progressing to severe illness.8
In relation to provisional COVID-19 deaths by week in the United States, similar to hospitalizations, weekly deaths have been dropping since last winter and are currently at their lowest point.9 Despite COVID-19 deaths being at their lowest point, the number of annual deaths is still very large. There have already been over 400 deaths in those ages 20 – 44 years and thousands of deaths in older age groups from January 1 – July 22, 2023.10 Moreover, pertaining to the pediatric age group, a population which is less likely to have underlying conditions and has had the lowest hospitalization rates overall, there has been 26 deaths in those less than a year old, 18 deaths in those 1 – 4 years old and 36 deaths in those 5 – 19 years old, so far this year. In 2022, each of these groups had more than 100 deaths.11
When considering the underlying condition status of pediatric COVID-19 deaths using data from COVID-NET, it was determined that COVID-19 deaths were rare among the pediatric population with no underlying conditions, with about 1% of hospitalizations in this population progressing to death. However, when considering pediatric COVID-19 deaths as a whole, 50% of those 17 years or younger who died of COVID-19 had no underlying medical conditions.12
When comparing COVID-19 deaths to the number of deaths seen for other pediatric vaccine preventable diseases prior to vaccine introduction, there were many more COVID-19 deaths compared to these other vaccine preventable diseases in 2022.13,14,15,16,17,18 Additionally, when compared to the number of pediatric influenza deaths, the number of COVID and flu deaths have been similar so far this year; and in previous years of the pandemic, COVID-19 deaths surpassed that of flu.11

Benefits and Harms

Criteria Work Group Judgements Evidence Additional Information
How substantial are the desirable anticipated effects? Large Published assessments of previous vaccine formulations VE and safety were evaluated using GRADE. The pooled vaccine effectiveness estimates from the observational studies demonstrated that the updated (i.e., bivalent) COVID-19 vaccine reduced medically attended (emergency department/urgent care) COVID-19 in adolescents and adults (pooled vaccine effectiveness: 50%, 95% CI 50–56%; based on 2 studies).1,2 The pooled vaccine effectiveness against hospitalization due to COVID-19 was 48% (95% CI 30–61%), based on 4 studies.2,3,4,5 The pooled vaccine effectiveness for prevention of death due to COVID-19 was 61% (95% CI 41–74%), based on two studies.2,3 For infants and children benefits were indirectly inferred from adolescents and adults.
Pertaining to estimated COVID-19 hospitalizations prevented over 6 months for every million mRNA COVID-19 doses among those ages 50 years and younger, benefits of COVID-19 vaccination are anticipated in all age groups. Among those ages 6 months – 4 years, it is estimated that 103 to 476 hospitalizations per million doses would be prevented over 6 months. Anticipated benefits are lowest in  5 – 11 and 12-17-year-olds, still with an estimated 16-19 hospitalizations prevented per million doses at lowest COVID-19 incidence.
In addition to hospitalizations prevented, it has been calculated that 5 – 19 ICU admissions and 0 – 1 deaths are anticipated to be prevented per million doses in 12-17-year-olds, over 6 months. For both males and females these benefits compare with 0 myocarditis cases in over 55,000 bivalent doses administered in VSD for each age group.11
Manufacturer provided clinical and preclinical data on updated (XBB.1.5-containing) COVID-19 vaccines. Data from Moderna, Pfizer-BioNTech, and Novavax show that monovalent XBB-containing COVID-19 vaccines increase the immune response against the currently circulating XBB-sublineage variants.
Additionally, a universal vaccine recommendation is projected to prevent about 400,000 hospitalizations and 40,000 deaths over the next 2 years compared with no recommendation, regardless of level of immune escape. Furthermore, compared with only vaccinating those 65 years and older, a universal vaccine recommendation is projected to prevent about 200,000 more hospitalizations and 15,000 more deaths over the next 2 years.12
 For the outcome of post-COVID conditions, there were no studies that met the IVAC inclusion criteria. However, data not captured in the systematic review indicate that COVID-19 vaccine provides some protection against post-COVID conditions.
Regarding Novavax vaccine effectiveness and safety, due to lower uptake of Novavax COVID-19 vaccine, no post-authorization vaccine effectiveness estimates from the prior COVID-19 vaccine formulation are available.7
How substantial are the undesirable anticipated effects? Small Observational data on specified serious adverse events (myocarditis/pericarditis and anaphylaxis) were reviewed. Analyses from the Vaccine Safety Datalink (VSD) found that myocarditis/pericarditis and anaphylaxis are rare and have been associated with vaccination (GRADE Appendix 3).6
Severe reactogenicity (Grade ≥3 local or systemic reactions) was assessed using pooled clinical trial data following any original monovalent primary series dose. Severe reactogenicity occurred more often in the vaccine than placebo arm among both infants and children and adolescents and adults (GRADE Table 4a/4b).6
There are limited data to inform myocarditis risk following an updated mRNA dose. Myocarditis rates following booster doses in adolescent and young adult males are lower than rates following primary series, but estimates are limited by fewer numbers of doses for both the bivalent boosters and the previous monovalent boosters administered in VSD,8 which limits the precision for this rare outcome. Additionally, myocarditis risk is lower with longer time between doses. Rates of myocarditis were lower with an extended interval between dose 1 and dose 2 for the primary series.9 A longer interval between updated doses may also impact myocarditis rates. Studies have shown that most individuals with myocarditis/pericarditis have fully recovered at follow up;10 and in a study done earlier in the pandemic, the risk of adverse cardiac outcomes was notably higher (1.8 – 5.6 times higher) after SARS-CoV-2 infection than after mRNA COVID-19 vaccination among males ages 12-17 years.11
 In relation to Novavax, available data from the Vaccine Adverse Event Reporting System or VAERS are consistent with those from preauthorization clinical trials. Most VAERS reports were classified as nonserious. The most commonly reported adverse events included dizziness, fatigue, and headache. No new safety concerns were identified.7
Do the desirable effects outweigh the undesirable effects? Favors intervention The Work Group decided that the desirable effects of the COVID-19 vaccine outweigh the undesirable effects

Values

Criteria Work Group Judgements Evidence Additional Information
Does the target population feel that the desirable effects are large relative to undesirable effects? Moderate Americans’ perception of whether “the coronavirus situation” is getting better or worse has fluctuated throughout the pandemic, generally following changes in the U.S. infection rate. Over the last year, more Americans have consistently said the coronavirus situation is getting better rather than worse. As of February 2023, 62% said the situation was getting better and 30% said it was staying the same, while just 8% said it was worsening.1
Is there important uncertainty about or variability in how much people value the main outcomes? Probably important uncertainty or variability Despite feeling that the COVID-19 situation was getting better, as of August 2023, 30% of US adults report feeling very or moderately concerned about getting COVID-19.2 Additionally, people still report concern about serious COVID-19 illness in their family. In March, 50% of people reported being very or somewhat concerned about a family member becoming seriously ill from COVID.3

Acceptability

Criteria Work Group Judgements Evidence Additional Information
Is the intervention acceptable to key stakeholders? Yes, Probably yes, Varies As of August 2023, 42% of survey respondents report that they definitely will or probably will get the new, updated COVID-19 vaccine.1 Based on data from bivalent vaccine uptake and intent, vaccination intent is highly related to receipt of previous COVID-19 vaccine doses. Those that had a past COVID-19 vaccination were more likely to have received a bivalent vaccine dose, while the majority of the unvaccinated reported that they probably or definitely will not get a bivalent vaccine.2 When looking at the top concerns or issues regarding the bivalent vaccine, among those who reported that they probably or definitely will not get the vaccine, regardless of past vaccination status, the most commonly reported concern was unknown serious side effects.2
Pertaining to confidence in vaccine safety for the COVID-19 vaccine, influenza vaccine and other routine vaccines, confidence in vaccine safety is higher for influenza and other routine adult vaccines than for the COVID-19 vaccine, with only about half of survey respondents reporting that the COVID-19 vaccine is completely or very safe.2
In relation to vaccine recommendation by a healthcare provider, among those eligible for each vaccine (i.e., flu, shingles, pneumonia, tetanus, and COVID-19), a lower percentage were recommended the COVID-19 vaccine compared to other vaccines. Additionally, those who received a provider recommendation were more likely to receive the recommended vaccine across all vaccines.2
Moreover, data from the Fall 2022 DocStyles survey were analyzed to examine the prevalence of COVID-19 vaccination attitudes and practices among health care providers (HCPs) caring for women of reproductive age, and to assess whether providers recommended and offered or administered COVID-19 vaccines to their pregnant patients. Overall, 82.9% of providers reported recommending COVID-19 vaccination to women of reproductive age, and 54.7% offered or administered the vaccine in their practice. Among HCPs who cared for pregnant patients, obstetrician-gynecologists were more likely to recommend COVID-19 vaccination to pregnant patients (94.2%) than were family practitioners/internists (82.1%). HCPs were more likely to offer or administer COVID-19 vaccination onsite to pregnant patients if they also offered or administered influenza and Tdap vaccines.3

Feasibility

Criteria Work Group Judgements Evidence Additional Information
Is the intervention feasible to implement? Yes Vaccines with a monovalent XBB.1.5 composition will be the first COVID-19 vaccines to be available directly from the manufacturers as part of the commercial market, rather than through the United States Government (USG). The public will continue to be directed to Vaccines.gov to find providers offering COVID-19 vaccine. While providers will no longer be required to report inventory to Vaccines.gov after vaccines transition to being available on the commercial market, they will continue to be encouraged to report voluntarily. Providers are also strongly encouraged to report the minimum age (in months and years) for whom a location can administer vaccine. The CDC will continue its efforts to make sure that all people have access to COVID-19 countermeasures and know where to find product now and in the future.1
In relation to feasibility of vaccine implementation, inclusion of COVID-19 vaccines in the Vaccines for Children (VFC) program will likely result in more pediatricians stocking the vaccine. There will be single dose vial presentations and smaller minimum order quantities, which directly addresses concerns from health care providers (HCPs), likely to reduce wastage, eases logistics and helps with storage capacity limitations. Vial presentations and order quantities are listed below:
  • Moderna, 12+ years: single dose vial (10-pack) and manufacturer-prefilled syringes (10-pack)
  • Moderna, 6 months – 11 years: single dose vial (10-pack)
  • Novavax, 12+ years: 5-dose multi-dose vial (2 vials per carton)
  • Pfizer, 12+ years: single dose vial (10-pack), limited quantity of manufacturer-prefilled syringes (10-pack)
  • Pfizer, 5 – 11 years: single dose vial (10-pack)
  • Pfizer, 6 months – 4 years: 3-dose multi-dose vial (10-pack)

Preparation is the same or simpler than it was before:

  • Moderna preparation is the same (no dilution)
  • Novavax preparation is the same (no dilution)
  • Pfizer preparation is simplified (currently 2 presentations require dilution; for 2023 – 2024 COVID-19 vaccine, ONLY little peds formulation requires dilution)

Storage and handling will be the same as it is now:

  • Moderna: Frozen until expiration; 30 days at refrigerator storage
  • Novavax: Stable at 2-8°C (refrigerator storage); 9-month shelf life; use within 12 hours of first puncture
  • Pfizer: Ultra-cold storage until expiration; 10 weeks at refrigerator storage (Ultra-cold storage continues to be a challenge, as most provider offices do not have a unit)

Additionally, the dose volume for Pfizer is simplified (all doses are 0.3mL) and Moderna now only has two presentations, reducing the change for errors.2

Regarding barriers, there are now three seasonal vaccines and preventative products for respiratory diseases to manage, which entails more seasonal vaccines to manage, limited storage space and more vaccines, and more opportunities for vaccine administration errors. Additionally, providers have to adapt to new cap/label colors:
  • Moderna: 6 months – 11 years is blue cap/green label; 12+ years is blue cap/blue label
  • Novavax: 12+ years is blue
  • Pfizer: 6 months – 4 years is yellow; 5 – 11 years is blue; 12+ years is gray

Furthermore, Moderna, Novavax and Pfizer all have products with blue caps, introducing opportunity for error.2

Resource Use

Criteria Work Group Judgements Evidence Additional Information
Is the intervention a reasonable and efficient allocation of resources? Yes The incremental cost-effectiveness ratios for COVID-19 vaccines showed that the cost per QALY was $155,588 in 18–49-year-olds, $25,787 in 50–64-year-olds, and is cost saving in ≥65 years.1 Cost-effectiveness estimates in those ages ≥50 years were robust to input changes across plausible ranges. Cost-effectiveness estimates in those 18 – 49 years were sensitive to changes in inputs. If vaccine effectiveness or hospitalization rates are higher than anticipated, the cost effectiveness estimates would be more favorable. Cost-effectiveness estimates are not yet available for pediatric populations.

Health Equity Questions and Evidence Reviewed

CDC is committed to COVID-19 vaccine equity, which is when everyone has fair and just access to COVID-19 vaccination.1 The Evidence to Recommendations Framework (EtR), through which ACIP considers all evidence regarding the potential use of a vaccine to guide its recommendations, includes an Equity Domain. However, the impact of the intervention on health equity was not clear through the current EtRs to date. Therefore, processes were put in place to restructure the Equity domain of the Evidence to Recommendations Framework.

In April – August 2022, a subset of the COVID-19 ACIP Work Group engaged in a critical review of the Equity Domain and gathered extensive input and feedback on strategies to adjust the domain through the following mechanisms: a thorough review of use of the Equity domain (April 2022), a one-time consultation with health equity experts (May 2022), an iterative review of possible adjustment strategies with experts (June – August 2022), presentation to leadership and membership of the National Medical Association and presentation to the Structural & Social Determinants of Health Workgroup of the Office of Minority Health and Health Equity (August 2022). Through this process, it became clear that consideration of equity is integral to every aspect of production, study, authorization, and recommendation of COVID-19 vaccines.

The need for a systematic, reliable, and action-oriented review of evidence toward enhanced equity was also made clear: structural problems require structural solutions. Adjustment of structure is required for meaningful change; and adjustment of the EtR Framework to enable systematic and reliable review of evidence toward actionable recommendations to enhance equity may facilitate meaningful change. Therefore, we proposed a change to restructure the Equity Domain as a consideration across each EtR Domain. We recommend the systematic, reliable inclusion of data to speak to the Equity considerations in each domain, both to demonstrate the data and encourage actions needed to enhance equity as relevant to each domain. Therefore, we will remove the voting question on Equity and enhance attention to equity across all domains. We do not recommend voting on these Equity questions, but rather using them to ensure consideration of equity through every step of the process of production, study, authorization, and recommendation of COVID-19 vaccines. For that reason, while the Work Group reviewed data to support the recommendation, they did not determine their judgement for any of the Equity Domain Questions. This newly proposed structure will be depicted in this Evidence to Recommendations (EtR) Framework.

1 COVID-19 Vaccine Equity for Racial and Ethnic Minority Groups | CDC Archive

Evidence to Recommendations (EtR) Domain Domain Equity Question Evidence Reviewed
Public Health Problem Does the problem impact all populations equally? Age-adjusted COVID-19-associated hospitalization rates by race and ethnicity show that cumulative hospitalization rates remain highest in American Indian/Alaska Native and Black persons.19 In relation to the risk ratio of death, invasive mechanical ventilation, and admission to intensive care unit by the number of underlying medical conditions among adults hospitalized with COVID-19, the risk for all outcomes increases with the number of underlying medical conditions.20
Pertaining to the prevalence of a subset of conditions, including chronic obstructive pulmonary disease (COPD), heart conditions, diabetes mellitus, chronic kidney disease (CKD), and obesity (defined as body mass index [BMI] of ≥30 kg per m2) with the strongest and most consistent evidence of association with increased risk for severe COVID-19-asosciated illness, the prevalence of underlying conditions is not uniform across the United States, with the highest prevalence in the southeastern US. It is also worth noting that the prevalence of this subset of high-risk conditions is high overall.21
Finally, regarding the number of chronic conditions by age among Asian, Black, Hispanic, and White adults in the National Health Interview Survey, the percentage with multiple underlying conditions increases with age and varies by race and ethnicity.22
Benefits and Harms Are the desirable and undesirable anticipated effects demonstrated across all populations equally? There is no evidence to suggest that COVID-19 vaccine effectiveness varies substantially by race/ethnicity.13,14 Differences in vaccine hesitancy/uptake, crowding, access to care, and prior infection could impact vaccine effectiveness and these factors may also differ by race and ethnicity. There is also no evidence to suggest that COVID-19 vaccine safety profiles vary by race and ethnicity; however, risk has been shown to differ by age and sex, as risk for myocarditis is highest in adolescent and young adult males. Benefits and harms for the U.S. population are best assessed when clinical trial and study populations are optimally representative of the U.S. population.
Values Is there important variability in how patients or populations value the outcome? There are differences in the level of concern about getting COVID-19 by race and ethnicity, with White, non-Hispanic persons having the highest percentage reporting that they are not at all concerned about getting COVID-19, while Black-non-Hispanic persons had the highest percentage reporting that they were very concerned. When considering the level of concern by urbanicity, those living in urban areas reported more concern over getting COVID-19 than those who reside in rural or suburban areas. Finally, when considered by income, concern about getting COVID-19 decreased as income increased.2
Acceptability Is the intervention equally acceptable across all populations? In relation to COVID-19 vaccine safety confidence by race and ethnicity, there is some variability with White, non-Hispanic populations having the largest percentage at either end of the spectrum, with 23% reporting that they feel the vaccine is completely safe and 23% who reportedly feel it is not safe at all. Whereas other racial and ethnic groups have larger percentages that fall in the middle. Regarding the perceptions of COVID-19 vaccine safety by income, those with higher income repot higher levels of confidence in the safety of COVID-19 vaccines. There are also differences by urbanicity, with 30% of people living in rural areas reporting that they feel the vaccine is not at all safe.1
Pertaining to the intent to get the new, updated COVID-19 vaccine by age, vaccine intent increases by age, with those ages 65 years and older being the most likely to report intent to vaccinate.1 The intent to get the new, updated COVID-19 vaccine mirrors the uptake with the updated (bivalent) booster doses, with older adults having much higher coverage than younger adults and children.3 Furthermore, the intent to get the new, updated COVID-19 vaccine varies some, but not substantially by race and ethnicity.1 However, there continues to be disparities in receipt of COVID-19 vaccination by race and ethnicity, particularly receipt of an updated (bivalent) booster dose.4
As seen in the overall population, healthcare provider recommendation is important across racial and ethnic groups, as those who received a provider recommendation were more likely to receive a COVID-19 vaccine.2
Additionally, the percent of pregnant people ages 18 – 49 years who are up to date with COVID-19 vaccines by race and ethnicity is low overall. There are also disparities by race and ethnicity, with Black and Hispanic pregnant persons having the lowest vaccine uptake.5
Feasibility Is the intervention equally feasible to implement across all populations? There are disparities in the percentage of US adults without health insurance, as American Indian and Alaska Native and Hispanic or Latino populations have the highest rates among those who are uninsured by race and ethnicity.3
CDC will provide access to COVID-19 vaccines for uninsured individuals once COVID-19 vaccines become available.1 Uninsured children will be able to receive COVID-19 vaccines through the existing Vaccines for Children (VFC) program.1 The VFC program offers vaccines at no cost to eligible children through a national network of participating health care providers.4 Adults who are uninsured or underinsured will be able to receive no-cost COVID-19 vaccines through the temporary Bridge Access Program for COVID-19 Vaccines. This program consists of two components:
  • Public health infrastructure: through state immunization programs, State and local health departments and HRSA-supported health centers will provide no-cost COVID-19 vaccines to adults who are uninsured or underinsured.
  • Participating retail pharmacies: CVS, Walgreens and eTrueNorth will continue to provide no-cost COVID-19 vaccines to adults who are uninsured or underinsured.5

CDC’s Bridge Access Program for COVID-19 Vaccines and COVID-19 vaccine implementation plans are intentionally designed to overcome barriers to access and availability, which includes a design for maximized proximity to no-cost COVID-19 vaccines among populations of people who are uninsured or underinsured. CDC and HHS continue to invest in health systems and programs that support vaccine access and outreach in underserved communities, such as HRSA-Supported Health Centers, Rural Health Clinics, and State and local health departments. These networks can be leveraged for access to COVID-19 vaccines as well as other needed medicines.6

Resource Use Is the intervention a reasonable and efficient allocation of resources across all populations? COVID-19 vaccination is most cost-effective in older adults in which disease burden is highest compared to younger adults. COVID-19 vaccination is likely more cost-effective in populations with risk factors, such as underlying conditions, which increase their probability due to COVID-19. Additional work is ongoing to evaluate cost-effectiveness in the pediatric populations.

Work Group Interpretation Summary

The burden of COVID-19 varies by age and underlying condition status with those ages ≥65 years and those with multiple underlying medical conditions having the highest risk of severe outcomes due to COVID-19. COVID-19 burden is currently lower than at previous points in the pandemic; however, there are still thousands of hospitalizations and hundreds of deaths each week. Children and adults ages 5 – 49 years had the lowest hospitalization rates overall; however, severe outcomes occur in this age group, including in people with no underlying medical conditions. Although hospitalization rates are currently low, rates have increased in recent weeks, and it is anticipated that rates will further increase as the respiratory virus season approaches. The majority of the U.S. population has some level of immunity due to infection, vaccination, or both. Vaccine and infection-induced immunity wane and new variants have emerged, suggesting that susceptibility remains and may increase over time. Racial and ethnic minority groups have been disproportionately affected by COVID-19 as well.

Monovalent XBB containing COVID-19 vaccines increase the immune response against the currently circulating variants. Last year’s updated vaccine was effective at preventing medically attended COVID-19, hospitalization due to COVID-19 and death due to COVID-19. COVID-19 vaccines have a high degree of safety, and it is unlikely that updating the formulation would increase adverse event rates. Benefits are anticipated in all age groups; however, benefits of COVID-19 vaccines vary by age, and incidence of COVID-19 hospitalizations. Additionally, benefits outweigh risks in age groups for which there is a risk of myocarditis. Modeling projects more hospitalization and deaths averted when updated doses are universally recommended compared to no recommendation or recommended only for persons ages ≥65 years.

The Work Group considered non-universal policy options, with considerable discussion around the magnitude of benefits in the young, healthy population. As part of these deliberations, the Work Group requested additional data on severe illness due to COVID-19 in those with and without underlying medical conditions. There was no group that clearly had no risk of severe illness. The vast majority of the US population has an underlying condition that would qualify under a risk-based recommendation, as prevalence of overweight and obesity alone is >70% of adults.1 However, a risk-based recommendation would not allow access to COVID-19 vaccines for all that wanted them. Shared clinical decision making could create barriers to vaccination and may not effectively target those at highest risk. COVID-19 epidemiology remains uncertain and non-universal recommendations would need to be quickly revisited if there was an increase in burden. Still, substantial COVID-19 disease burden and simple, stable recommendations may increase vaccine coverage over time. The Work Group emphasized that COVID-19 recommendations should be reviewed on an ongoing basis as more is learned about COVID-19 seasonality and disease burden in the future.

The burden of severe illness due to COVID-19 is lowest among children ages 5 – 17 years. Despite lower burden relative to other age groups, hundreds of deaths due to COVID-19 occurred in this age group in 2021 and 2022; and half of pediatric COVID-19 deaths were in individuals with no underlying conditions. The number of COVID-19 hospitalizations and deaths in this age group are comparable to the burden seen in other vaccine preventable diseases for which there are universal recommendations. There are potential additional benefits of vaccination, such as prevention of post-COVID conditions and potential for reduced school absenteeism. The risk of myocarditis appears lower than the risk observed following primary series doses. Risk is potentially lower due to increased intervals between doses and certainty is limited by a relatively lower sample size of booster recipients in VSD. Future COVID-19 epidemiology remains uncertain and the low disease burden we are currently seeing may not last. After a robust discussion, the Work Group was supportive of a universal recommendation at this time.

__________________________

1 National Health Statistics Reports; https://stacks.cdc.gov/view/cdc/106273

Implementation and Considerations for Equity

Balance of consequences

The majority of the Work Group felt that the desirable consequences probably outweigh undesirable consequences in most settings, and a minority felt that the desirable consequences clearly outweigh undesirable consequences in most settings

Is there sufficient information to move forward with a recommendation? Yes

Policy options for ACIP consideration

ACIP recommends the intervention

Draft recommendation (text)

On September 12, 2023, ACIP voted (13-1) in favor of recommending:

Final ACIP recommendation

ACIP recommends the intervention.

ACIP recommends 2023-2024 (monovalent, XBB containing) COVID-19 vaccines as authorized under Emergency Use Authorization (EUA) or approved by Biologics License Application (BLA) in persons ≥6 months of age

Proposed 2023 – 2024 mRNA COVID-19 vaccine recommendations:

  • Everyone ages 5 years and older is recommended to receive 1 dose of a 2023 – 2024 mRNA COVID-19 vaccine
  • Children ages 6 months – 4 years should complete a multi-dose initial series (2 doses of Moderna or 3 doses of Pfizer-BioNTech mRNA COVID-19 vaccine) with at least one dose of the 2023 – 2024 COVID-19 vaccine
  • People who are moderately or severely immunocompromised should complete a 3-dose initial series with at least one dose of the 2023 – 2024 COVID-19 vaccine and may receive 1 or more additional 2023 – 2024 COVID-19 vaccine doses
  • Bivalent mRNA COVID-19 vaccines are no longer recommended in the United States

Key changes from bivalent mRNA recommendations:

There are a few key changes in the proposed 2023 – 2024 mRNA COVID-19 vaccine recommendations compared to the bivalent recommendations. Previously, everyone aged 6 years and older were recommended for a single bivalent dose, but this age has moved to 5 years for the 2023 – 2024 vaccine because Moderna’s age cut off for the youngest pediatric group shifted from 6 months – 5 years to 6 months – 4 years, which now aligns with the Pfizer age groups. This eliminates the complex recommendations that were previously in place for 5-year-olds.

There were previously two Moderna dosages authorized for 6 months – 5 years. Now, the dosages have been streamlined. All Moderna doses in ages 6 months – 11 years are now 25 micrograms, reducing the number of COVID-19 vaccine products in use.

Finally, there was an optional 2nd bivalent dose for those ages 65 years and older. Currently, there is no additional dose recommendation for the 2023 – 2024 vaccine. However, the epidemiology and vaccine effectiveness will be monitored to determine if additional doses are needed.

References

Problem:

  1. COVID-NET. Weekly population-based rates of COVID-19-associated hospitalizations. March 2020 – August 26, 2023
  2. COVID-19-associated hospitalization data reported to CDC's National Healthcare Safety Network (NHSN). https://covid.cdc.gov/covid-data-tracker/#trends_weeklyhospitaladmissions_select_00
  3. https://www.cdc.gov/mmwr/preview/mmwrhtml/ss5603a1.htm
  4. Davis MM, Patel MS, Gebremariam A. Decline in varicella-related hospitalizations and expenditures for children and adults after introduction of varicella vaccine in the United States. Pediatrics. 2004;114(3):786-792. doi:10.1542/peds.2004-0012
  5. Centers for Disease Control and Prevention (CDC). Direct and indirect effects of routine vaccination of children with 7-valent pneumococcal conjugate vaccine on incidence of invasive pneumococcal disease—United States, 1998-2003. MMWR Morb Mortal Wkly Rep. 2005 Sep 16;54(36):893-7. PMID: 16163262
  6. COVID-NET data October 2021 – September 2022 and October 2022 – July 2023. COVID-19 rates have not been adjusted for reason for admission. COVID vaccine first introduced in 12-17 years in May 2021; in 5-11 years in November 2021 and in 6 months – 4 years in June 2022
  7. https://covid19scenariomodelinghub.org/
  8. COVID-NET. Underlying medical conditions among patients admitted to ICU among children, adolescents, and adults ages 6 months – 49 years. July 2022 – June 2023
  9. Provisional Deaths from the CDC's National Center for Health Statistics (NCHS) National Vital Statistics System (NVSS). https://covid.cdc.gov/covid-data-tracker/#trends_weeklydeaths_weeklydeathrateaa_00
  10. Centers for Disease Control and Prevention, National Center for Health Statistics. National Vital Statistics System, Provisional Mortality on CDC WONDER Online Database. Data are from the final Multiple Cause of Death Files, 2018-2021, and from provisional data for years 2022-2023, as compiled from data provided by the 57 vital statistics jurisdictions through the Vital Statistics Cooperative Program. Number of deaths includes COVID-19 code (U07.1) as the underlying cause of death. Accessed at http://wonder.cdc.gov/mcd-icd10-provisional.html on Aug 25, 2023
  11. Centers for Disease Control and Prevention, National Center for Health Statistics. National Vital Statistics System, Provisional Mortality on CDC WONDER Online Database. Data are from the final Multiple Cause of Death Files, 2018-2021, and from provisional data for years 2022-2023, as compiled from data provided by the 57 vital statistics jurisdictions through the Vital Statistics Cooperative Program. Number of deaths includes influenza codes (J09-J11) or COVID-19 code (U07.1) as the underlying cause of death. Accessed at http://wonder.cdc.gov/mcd-icd10-provisional.html on Aug 25, 2023
  12. COVID-NET. Underlying medical conditions among patients with in-hospital death among children and adolescents ages ≤17 years. January 2022 – June 2023
  13. Vogt TM , Wise ME, Bell BP, Finelli L. Declining hepatitis A mortality in the United States during the era of hepatitis A vaccination. J Infect Dis2008; 197:1282–8.
  14. National Notifiable Diseases Surveillance System with additional serogroup and outcome data from Enhanced Meningococcal Disease Surveillance for 2015-2019.
  15. Meyer PA, Seward JF, Jumaan AO, Wharton M. Varicella mortality: trends before vaccine licensure in the United States, 1970-1994. J Infect Dis. 2000;182(2):383-390. doi:10.1086/315714
  16. Roush SW , Murphy TV; Historical comparisons of morbidity and mortality for vaccine-preventable diseases in the United States. JAMA 2007; 298:2155–63.
  17. Glass RI, Kilgore PE, Holman RC, et al. The epidemiology of rotavirus diarrhea in the United States: surveillance and estimates of disease burden. J Infect Dis. 1996 Sep;174 Suppl 1:S5-11
  18. http://wonder.cdc.gov/mcd-icd10-provisional.html on Aug 1, 2023. COVID vaccine first introduced in 12-17 years in May 2021; in 5-11 years in November 2021 and in 6 months – 4 years in June 2022
  19. COVID-NET: https://www.cdc.gov/coronavirus/2019-ncov/covid-data/covid-net/purpose-methods.html. Data March 1, 2020 through August 26, 2023
  20. Kompaniyets L, Pennington AF, Goodman AB, Rosenblum HG, Belay B, Ko JY, et al. Underlying Medical Conditions and Severe Illness Among 540,667 Adults Hospitalized With COVID-19, March 2020 – March 2021. Prev Chronic Dis 2021;18:210123. DOI: http://dx.doi.org/10.5888/pcd18.210123
  21. Based on Razzaghi H, Wang Y, Lu H, Marshall KE, Dowling NF, Paz-Bailey G, Twentyman ER, Peacock G, Greenlund KJ, Estimated County-Level Prevalence of Selected Underlying Medical Conditions Associated with Increased Risk for Severe COVID-19 Illness—United States, 2018 MMWR Morb Mortal Wkly Rep 2020;69[945-950]. The underlying medical conditions included in these prevalence estimates were selected using a subset of the list of conditions with the strongest and most consistent evidence of association with increased risk for severe COVID-19-associated illness on CDC's website as of June 25, 2020 and for which questions on the BRFSS are available. https://covid.cdc.gov/covid-data-tracker/#underlying-med-conditions
  22. Caraballo C, Herrin J, Mahajan S, et al. Temporal Trends in Racial and Ethnic Disparities in Multimorbidity Prevalence in the United States, 1999-2018. Am J Med. 2022;135(9):1083-1092.e14. doi:10.1016/j.amjmed.2022.04.010

Benefits and Harms:

  1. Tenforde, M.W., et al., Early Estimates of Bivalent mRNA Vaccine Effectiveness in Preventing COVID-19-Associated Emergency Department or Urgent Care Encounters and Hospitalizations Among Immunocompetent Adults—VISION Network, Nine States, September-November 2022. MMWR Morb Mortal Wkly Rep, 2023. 71(53): p. 1637-1646.
  2. Tseng, H.F., et al., Effectiveness of mRNA-1273 bivalent (Original and Omicron BA.4/BA.5) COVID-19 vaccine in preventing hospitalizations for COVID-19, medically attended SARS-CoV-2 infections, and hospital death in the United States. medRxiv, 2023: p. 2023.05.25.23290456.
  3. Lin, D.-Y., et al., Durability of Bivalent Boosters against Omicron Subvariants. New England Journal of Medicine, 2023. 388(19): p. 1818-1820.
  4. Link-Gelles, R., et al., Estimates of Bivalent mRNA Vaccine Durability in Preventing COVID-19-Associated Hospitalization and Critical Illness Among Adults with and Without Immunocompromising Conditions—VISION Network, September 2022-April 2023. MMWR Morb Mortal Wkly Rep, 2023. 72(21): p. 579-588.
  5. Surie, D., et al., Early Estimates of Bivalent mRNA Vaccine Effectiveness in Preventing COVID-19-Associated Hospitalization Among Immunocompetent Adults Aged ≥65 Years—IVY Network, 18 States, September 8-November 30, 2022. MMWR Morb Mortal Wkly Rep, 2022. 71(5152): p. 1625-1630.
  6. GRADE web tables
  7. https://www.cdc.gov/mmwr/volumes/72/wr/mm7231a4.htm
  8. https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/COVID-02-Shimabukuro-508.pdf
  9. https://www.cdc.gov/acip/media/pdfs/2024/09/11-COVID-Moulia-508.pdf
  10. https://www.cdc.gov/acip/media/pdfs/2024/09/04-COVID-Kracalic-508.pdf
  11. https://www.cdc.gov/mmwr/volumes/71/wr/mm7114e1.htm?s_cid=mm7114e1_w
  12. Based on preliminary Pfizer-BioNTech bivalent booster safety data from VSD (incident rate/million doses): 0 (95% CI: 0-54) in males and 0 (95% CI: 0-52) in females
  13. https://covid19scenariomodelinghub.org/
  14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9619452/
  15. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9763212/

Values:

  1. GALLUP. At Year Three, Americans Split on Whether Pandemic Is Over. https://news.gallup.com/poll/471734/year-three-americans-split-whether-pandemic.aspx Accessed August 29, 2023
  2. IPSOS KnowledgePanel and NORC AmeriSpeak Omnibus Surveys, results from August 2023 (N=4,299), unpublished data
  3. Monmouth University. Life Mostly Back to Pre-Covid Normal. Life Mostly Back to Pre-Covid Normal | Monmouth University Polling Institute | Monmouth University Accessed August 29, 2023

Acceptability:

  1. IPSOS KnowledgePanel and NORC AmeriSpeak Omnibus Surveys, results from August 2023 (N=4,299), unpublished data
  2. IPSOS KnowledgePanel and NORC AmeriSpeak Omnibus Surveys, results from June 2023 (N=4,214), unpublished data
  3. Fall 2022 DocStyles, unpublished data (data will be published in MMWR on September 28, 2023)
  4. VTrcks, IIS, Federal Pharmacy Program, Federal Entities Program, U.S. Census Bureau 10-year July 2019 National Population Estimates https://covid.cdc.gov/covid-data-tracker/#vaccination-demographics-trends. Accessed 9/5/2023
  5. National Immunization Survey Adult COVID Module. https://covid.cdc.gov/covid-data-tracker/#vaccination-demographics-trends. Accessed 9/5/2023
  6. COVID-19 vaccination among pregnant people aged 18-49 years overall, by race and ethnicity, and date reported to CDC—Vaccine Safety Datalink,* United States. https://covid.cdc.gov/covid-data-tracker/#vaccinations-pregnant-women Accessed August 9, 2023

Feasibility:

  1. CDC. HHS Commercialization Transition Guide: Sunsetting the US Government COVID-19 Vaccine Distribution Program. https://www.cdc.gov/vaccines/covid-19/downloads/HHS-Commercialization-Transition-Guide-508.pdf Accessed August 4, 2023
  2. Immunization Services Division, internal planning documents
  3. S. Census Bureau, 2021 American Community Survey 1-year estimates: https://data.census.gov/table?q=race&t=Health+Insurance&tid=ACSST1Y2021.S2701
  4. CDC. VFC Information for Parents. https://www.cdc.gov/vaccines-for-children/vfc-information-for-parents/index.htm. Accessed August 30, 2023
  5. CDC. Bridge Access Program for COVID-19 Vaccines. https://www.cdc.gov/vaccines/programs/bridge/index.html Accessed September 7, 2023
  6. ASPR Administration for Strategic Preparedness & Response. Commercialization of COVID-19 Medical Countermeasures. https://aspr.hhs.gov/COVID-19/Pages/FAQ-Commercialization.aspx Accessed August 25, 2023

Resource Use:

  1. https://www.cdc.gov/acip/downloads/slides-2023-09-12/06-COVID-Prosser-508.pdf

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