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Review Article| Volume 70, ISSUE 2, P243-257, April 2023

Coronavirus Disease-2019 Vaccine Hesitancy

  • E. Adrianne Hammershaimb
    Affiliations
    Division of Infectious Diseases and Tropical Pediatrics, Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD, USA

    Center for Vaccine Development and Global Health, University of Maryland, School of Medicine, Health Sciences Research Facility 1, Research Facility 1, Room 480, 685 West Baltimore Street, Baltimore, MD 21201, USA
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  • James D. Campbell
    Affiliations
    Division of Infectious Diseases and Tropical Pediatrics, Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD, USA

    Center for Vaccine Development and Global Health, University of Maryland, School of Medicine, Health Sciences Research Facility 1, Research Facility 1, Room 480, 685 West Baltimore Street, Baltimore, MD 21201, USA
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  • Sean T. O’Leary
    Correspondence
    Corresponding author. Adult and Child Center for Health Outcomes Research and Delivery Science, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, F443, 1890 North Revere Court, Aurora, CO 80045.
    Affiliations
    Department of Pediatrics, University of Colorado Anschutz Medical Campus, F443, 1890 North Revere Court, Aurora, CO 80045, USA
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Published:December 07, 2022DOI:https://doi.org/10.1016/j.pcl.2022.12.001

      Keywords

      Key points

      • Reluctance around coronavirus disease-2019 (COVID-19) vaccines is associated with unique concerns about their novelty and safety.
      • Parents weighing the risks of COVID-19 disease against the risks of COVID-19 vaccination may make different decisions for themselves versus their children.
      • Although COVID-19 vaccines have been highly politicized and subject to public scrutiny, pediatricians remain a trusted source of information and guidance.

      Introduction

      On December 30, 2019, the World Health Organization (WHO) announced the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a novel human pathogen and the causative agent of coronavirus disease 2019 (COVID-19).

      World Health Organization. Novel Coronavirus (2019-nCoV) Situation Report - 1. 2020.

      The pathogen quickly spread across the globe, resulting in a pandemic that caused more than half a billion cases and 6 million deaths by June 2022.
      • Dong E.
      • Du H.
      • Gardner L.
      An interactive web-based dashboard to track COVID-19 in real time.
      Efforts to develop a vaccine were promptly launched with the United States, UK, China, Russia, and India leading the race. COVID-19 vaccines were developed and authorized for use in Russia by August 11, 2020, the UK by December 2, 2020, the United States by December 11, 2020, and China by December 30, 2020.
      • Burki T.K.
      The Russian vaccine for COVID-19.
      • Ledford H.
      • Cyranoski D.
      • Van Noorden R.
      The UK has approved a COVID vaccine - here's what scientists now want to know.

      FDA Takes Key Action in Fight Against COVID-19 By Issuing Emergency Use Authorization for First COVID-19 Vaccine [press release]. December 11, 2020 2020.

      China gives its first COVID-19 vaccine approval to Sinopharm. 2020.

      It was estimated early on that 70% of the population would need to be vaccinated to end the pandemic; however, hesitancy around COVID-19 vaccines has proven a formidable obstacle to achieving target vaccination levels.
      • Randolph H.E.
      • Barreiro L.B.
      Herd Immunity: Understanding COVID-19.
      Understanding the factors related to COVID-19 vaccine acceptance vs. reluctance/refusal would be an integral component of eventual vaccination campaigns, theoretically providing opportunities to bolster acceptance and mitigate hesitancy.
      Early in the pandemic, before COVID-19 vaccines were authorized and disseminated, public opinion polls began tracking public acceptance of and concerns about a hypothetical COVID-19 vaccine. Over time, as vaccines and information about them have become more widely available, the focus has shifted from evaluating premeditative thoughts about COVID-19 vaccines to observing behaviors, measuring vaccine uptake, and characterizing factors associated with COVID-19 vaccine acceptance. Much of what was initially understood about public opinions of COVID-19 vaccines was both garnered by and shared through the lay media. Throughout the pandemic, a wealth of peer-reviewed literature examining the complexities of COVID-19 vaccine acceptance has also emerged, but our understanding of COVID-19 vaccine acceptance is constantly evolving along with the pandemic itself.

      Coronavirus disease-2019 vaccine intentions before authorization

      During the initial wave of the pandemic in North America and Western Europe, public opinion was largely supportive of vaccines against COVID-19. A large survey across 19 countries in June 2020 found that willingness to take a COVID-19 once available was 72% worldwide and as high as 76% and 75% in Mexico and the United States, respectively, and 69% in Canada.
      • Lazarus J.V.
      • Ratzan S.C.
      • Palayew A.
      • et al.
      A global survey of potential acceptance of a COVID-19 vaccine.
      By September 2020, at the height of a US presidential election campaign season, President Trump was promising an FDA-approved vaccine ahead of election day. At that time acceptance had dropped to as low as 63% in the general US population with only 34% saying they would “definitely get” a COVID-19 vaccine “if it were free and deemed safe by scientists.”
      • Hamel L.K.A.
      • Muñana C.
      • Brodie M.
      KFF COVID-19 vaccine monitor.

      Coronavirus disease-2019 vaccine intentions and uptake during rollouts

      Adult Rollout

      After the US Food and Drug Administration (FDA) authorized the first COVID-19 vaccines for use in the United States, initial guidance from the Centers for Diseases Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) prioritized residents of long-term care facilities (LTCFs), due to the high rates of morbidity and mortality in this population, and health care workers (HCWs), due to concerns about the strain on the health care system.
      • Dooling K.
      • McClung N.
      • Chamberland M.
      • et al.
      The Advisory Committee on Immunization Practices' Interim Recommendation for Allocating Initial Supplies of COVID-19 Vaccine - United States, 2020.
      In the first month of the US COVID-19 vaccine rollout, HCW uptake was generally high. Although receipt was also high (78%) LTCF residents only 38% of LTCF staff members had received one or more doses of a COVID-19 vaccine through the CDC Pharmacy Partnership for Long-Term Care Program.
      • Gharpure R.
      • Guo A.
      • Bishnoi C.K.
      • et al.
      Early COVID-19 First-Dose Vaccination Coverage Among Residents and Staff Members of Skilled Nursing Facilities Participating in the Pharmacy Partnership for Long-Term Care Program - United States, December 2020-January 2021.
      By April 2021, vaccination among health care providers working in LTCFs had increased to 57% with the highest rates among physicians and advanced practice providers (75%) and lower rates among nurses and ancillary services employees (57% and 59%, respectively).
      • Lee J.T.
      • Althomsons S.P.
      • Wu H.
      • et al.
      Disparities in COVID-19 Vaccination Coverage Among Health Care Personnel Working in Long-Term Care Facilities, by Job Category, National Health care Safety Network - United States, March 2021.
      Lower rates of vaccine acceptance among nurses relative to physicians have been noted in health care systems across the United States, Canada, and internationally.
      • Dzieciolowska S.
      • Hamel D.
      • Gadio S.
      • et al.
      Covid-19 vaccine acceptance, hesitancy, and refusal among Canadian health care workers: A multicenter survey.
      • Khubchandani J.
      • Bustos E.
      • Chowdhury S.
      • et al.
      COVID-19 vaccine refusal among nurses worldwide: review of trends and predictors.
      • Biswas N.
      • Mustapha T.
      • Khubchandani J.
      • et al.
      The nature and extent of covid-19 vaccination hesitancy in health care workers.
      • Ciardi F.
      • Menon V.
      • Jensen J.L.
      • et al.
      Knowledge, attitudes and perceptions of covid-19 vaccination among health care workers of an inner-city hospital in new york.
      • Farah W.
      • Breeher L.
      • Shah V.
      • et al.
      Disparities in COVID-19 vaccine uptake among health care workers.

      Ashley Kirzinger AK, Liz Hamel, Mollyann Brodie. KFF/The Washington post frontline health care workers survey. 2021.

      Other characteristics of HCWs associated with decreased acceptance include younger age, female sex, Black race, and Hispanic/Latino ethnicity. These were similar to characteristics associated with decreased acceptance found in the general US population at that time.
      • Farah W.
      • Breeher L.
      • Shah V.
      • et al.
      Disparities in COVID-19 vaccine uptake among health care workers.

      Ashley Kirzinger AK, Liz Hamel, Mollyann Brodie. KFF/The Washington post frontline health care workers survey. 2021.

      • Caiazzo V.
      • Witkoski Stimpfel A.
      Vaccine hesitancy in American health care workers during the COVID-19 vaccine roll out: an integrative review.
      Other frontline workers, older adults, and people with chronic medical conditions were also prioritized for early vaccination. Compared with healthy adults, those with chronic medical conditions, including immunocompromising conditions, were more accepting of COVID-19 vaccination, and the perception of being at increased risk of severe COVID-19 disease was associated with increased acceptance.
      • Warren A.M.
      • Perrin P.B.
      • Elliott T.R.
      • et al.
      Reasons for COVID-19 vaccine hesitancy in individuals with chronic health conditions.
      • Aberumand B.
      • Ayoub Goulstone W.
      • Betschel S.
      Understanding attitudes and obstacles to vaccination against COVID-19 in patients with primary immunodeficiency.
      • Nguyen K.H.
      • Srivastav A.
      • Razzaghi H.
      • et al.
      COVID-19 Vaccination Intent, Perceptions, and Reasons for Not Vaccinating Among Groups Prioritized for Early Vaccination - United States, September and December 2020.
      In contrast, a December 2020 survey found that 35% of US essential workers were not likely to get a COVID-19 vaccine.
      • Nguyen K.H.
      • Srivastav A.
      • Razzaghi H.
      • et al.
      COVID-19 Vaccination Intent, Perceptions, and Reasons for Not Vaccinating Among Groups Prioritized for Early Vaccination - United States, September and December 2020.
      By mid-March 2021%, 48% of non-health care essential workers in the United States had received a COVID-19 vaccine with 21% still reporting they would not get one, even if required.
      • Hamel L.S.A.
      • Stokes M.
      • Brodie M.
      KFF COVID-19 Vaccine Monitor: Vaccine Attitudes Among Essential Workers.
      Following the authorization of COVID-19 vaccines, surveys conducted in January 2021 showed that 47% of US adults were either vaccinated or intended to get a COVID-19 vaccine as soon as one became available to them, whereas 72% of Canadian adults intended to get a COVID-19 vaccine.,

      Canada Go. Vaccine uptake in Canadian adults: Highlights from the 2020-2021 Seasonal Influenza Vaccination Coverage Survey. 2021.

      Over the subsequent months with increasing access to vaccines, uptake among US adults increased with 62% reporting that they had received a COVID-19 vaccine by May 2021. Uptake among adults 65 years and older has been quite high in the United States and Canada (Mexico does not breakdown vaccination data by age). For example, in the US, as of July 29%, 2022%, 92% of adults 65 and older are fully vaccinated, although there is a great deal of geographic variability at the state and county levels.

      Pediatric Rollout

      In the United States, the Pfizer/BioNTech COVID-19 vaccine had been authorized for adolescents 16 years and older since December 2020, and in May 2021, the vaccine was authorized for adolescents 12 to 15 years of age. By the end of July 2021%, 43% of US adolescents 12 to 17 years old had received a COVID-19 vaccine with subsequent slow increases to a plateau of approximately 68% by February 2022. This trajectory is consistent with surveys showing that one-third of US parents wanted to “wait and see” before vaccinating their children.,
      Centers of Disease Control and Prevention
      Trends in Demographic Characteristics of People Receiving COVID-19 Vaccinations in the United States.
      Centers of Disease Control and Prevention
      Pediatric Data. COVID Data Tracker Web site.
      • Liz Hamel L.L.
      • Kirzinger Ashley
      • Kearney Audrey
      • et al.
      KFF COVID-19 vaccine monitor: winter 2021 update on parents' views of vaccines for kids.
      In October-November 2021, similar proportions of US parents of 5- to 11-year-old children reported wanting to wait before vaccinating their children, with 22% to 27% wanting to vaccinate them as soon as possible.,
      • Hammershaimb E.A.
      • Cole L.D.
      • Liang Y.
      • et al.
      COVID-19 Vaccine Acceptance Among US Parents: A Nationally Representative Survey.
      A vaccine was authorized for children 5 to 11 years old in the United States on October 29, 2021, and by the end of January 2022%, 31% of US children 5 to 11 years old had received at least a first dose of COVID-19 vaccine. However, as of July 2022%, 63% of US children in this age group remain completely unvaccinated.
      Centers of Disease Control and Prevention
      Trends in Demographic Characteristics of People Receiving COVID-19 Vaccinations in the United States.
      ,
      Centers of Disease Control and Prevention
      Pediatric Data. COVID Data Tracker Web site.
      As with the adult COVID-19 vaccine rollout, there is wide geographic variation in uptake.
      In December 2020%, 63% of Canadian parents intended to vaccinate their children 0 to 17 years of age, and by May 8%, 2022%, 57% and 88% of Canadians 5 to 11 and 12 to 17 years, respectively, had received a COVID-19 vaccine.
      • Humble R.M.
      • Sell H.
      • Dube E.
      • et al.
      Canadian parents' perceptions of COVID-19 vaccination and intention to vaccinate their children: Results from a cross-sectional national survey.
      , On June 17, 2022, the US FDA authorized COVID-19 vaccines for use in children 6 months-4 years of age, and as of this writing, the rollout of vaccines for children under 5 years was newly underway.

      Coronavirus (COVID-19) Update: FDA Authorizes Moderna and Pfizer-BioNTech COVID-19 Vaccines for Children Down to 6 Months of Age [press release]. June 17, 2022.

      There are limited data on vaccine attitudes among parents of Mexican children.
      • Delgado-Gallegos J.L.
      • Padilla-Rivas G.R.
      • Gastelum-Arias L.J.
      • et al.
      Parent's Perspective towards Child COVID-19 Vaccination: An Online Cross-Sectional Study in Mexico.
      Mexico delayed its vaccination campaign for children, only beginning to vaccinate children 12 years and older with comorbidities after a court order to do so in November 2021, starting with adolescents 15 to 17 years of age.
      • Lopez O.
      As other nations push to vaccinate children, Mexico is an outlier.
      On April 28, 2022, vaccination began for all children 12 and older and Mexico didn’t authorize vaccination of 5- to 11-year-olds until May 27, 2022.

      Coronavirus disease-2019 vaccine incentives and mandates

      Efforts to increase vaccine uptake among the general population included both monetary incentives and mandates tied to education, work, entertainment, and travel. Such mandates have been politically contentious and variably effective. A large survey found that cash incentives such as gift cards and entry into lotteries would have no effect on the intentions of roughly half of unvaccinated US adults and would make 40% of those who were disinclined to get a COVID-19 vaccine even less likely to get one.
      • Sargent R.H.
      • Laurie S.
      • Moncada L.
      • et al.
      Masks, money, and mandates: A national survey on efforts to increase COVID-19 vaccination intentions in the United States.
      The same survey found that 64% of those unvaccinated Americans who were not inclined to get a COVID-19 vaccine would not get one despite workplace requirements.
      • Sargent R.H.
      • Laurie S.
      • Moncada L.
      • et al.
      Masks, money, and mandates: A national survey on efforts to increase COVID-19 vaccination intentions in the United States.
      Despite opinion surveys suggesting that mandates may not be effective and vocal protests and legal actions against vaccine mandates, many entities, including corporations, colleges and universities, health care systems, and government agencies including the military saw significant increases in the numbers of vaccinated employees and students after the introduction of COVID-19 vaccine mandates.

      Pereira I. COVID-19 vaccine mandates moving the needle, experts say. In: ABC News.

      For example, Tyson Foods saw an increase in employee vaccinations from 50% to 96% within 3 months of instituting a vaccine mandate, with “very few” employees leaving the company.
      • Press JFaA.
      How Tyson Foods’ CEO convinced 96% of his 120,000 employees to get vaccinated for COVID in just 3 months.

      Special populations

      Black and Hispanic Communities

      Black and Latino/Hispanic communities in the United States have experienced disproportionately high rates of morbidity and mortality due to COVID-19 but in general were late adopters of COVID-19 vaccines.
      Centers of Disease Control and Prevention
      Trends in Demographic Characteristics of People Receiving COVID-19 Vaccinations in the United States.
      ,
      Centers of Disease Control and Prevention. Risk for COVID-19 Infection, Hospitalization, and Death By Race/Ethnicity.
      ,
      Prevention" CfDCa. Demographic Trends of COVID-19 cases and deaths in the US reported to CDC.
      Early reluctance to receive a COVID-19 vaccine was attributed to a mistrust of government and American medicine given personal experiences and a history of abuses by the medical community.
      • Bogart L.M.
      • Ojikutu B.O.
      • Tyagi K.
      • et al.
      COVID-19 Related Medical Mistrust, Health Impacts, and Potential Vaccine Hesitancy Among Black Americans Living With HIV.
      • Palamenghi L.
      • Barello S.
      • Boccia S.
      • et al.
      Mistrust in biomedical research and vaccine hesitancy: the forefront challenge in the battle against COVID-19 in Italy.
      • Brandt A.M.
      Racism and research: the case of the Tuskegee Syphilis Study.
      Data from the CDC’s National Immunization Survey – Adult COVID Module (NIS-ACM), which is based on self-report, suggest that the rates of Black, non-Hispanic and Hispanic Americans who have received a COVID-19 vaccine caught up to the rates of vaccinated White, non-Hispanic Americans by October 2021.
      Centers of Disease Control and Prevention
      Trends in Demographic Characteristics of People Receiving COVID-19 Vaccinations in the United States.
      However, using other data sources on vaccine administration, as of July 29, 2022, vaccination rates among Black, non-Hispanic Americans seem to continue to lag behind those of all other racial and ethnic categories. Similarly, other than Black, and Non-Hispanic Americans, all other racial and ethnic categories have outpaced White, and Non-Hispanic Americans in COVID-19 vaccine uptake.
      Centers of Disease Control and Prevention
      Trends in Demographic Characteristics of People Receiving COVID-19 Vaccinations in the United States.
      These vaccine administration data, however, are limited in that race and ethnicity are missing for a large portion of the population. This inconsistency between self-reported vaccination status and vaccine administration data highlights the challenge of collecting and reporting accurate data on vaccine-related attitudes and behaviors among different racial and ethnic groups.

      Detained Populations

      Congregate living settings were the foci of early outbreaks; however, residents of detention centers in the United States were not consistently prioritized in the way that residents of LTCFs were despite recommendations from CDC’s ACIP. However, limited access is not the only determinant of COVID-19 vaccine uptake in this population.
      • Strodel R.
      • Dayton L.
      • Garrison-Desany H.M.
      • et al.
      COVID-19 vaccine prioritization of incarcerated people relative to other vulnerable groups: An analysis of state plans.
      Studies in the United States and Canada found that incarcerated individuals reported their significant reasons for refusing COVID-19 vaccination to include (1) distrust of prison employees, including HCWs, and the government, and (2) perceiving themselves to be at low risk of COVID-19 disease.
      • Testa A.
      • Fahmy C.
      COVID-19 Mitigation Compliance and Vaccination Status Among Formerly Incarcerated Individuals in the United States.
      • Stern M.F.
      • Piasecki A.M.
      • Strick L.B.
      • et al.
      Willingness to Receive a COVID-19 Vaccination Among Incarcerated or Detained Persons in Correctional and Detention Facilities - Four States, September-December 2020.
      • Ortiz-Paredes D.
      • Varsaneux O.
      • Worthington J.
      • et al.
      Reasons for COVID-19 vaccine refusal among people incarcerated in Canadian federal prisons.
      Similar data on Mexico and other Central American countries are not available as of this writing.
      COVID-19 vaccinations for prison populations and staff: Report on global scan. Penal Reform International and Harm Reduction International.

      Pregnant Persons

      Pregnant persons were largely excluded from the early vaccine trials. Consequently, early prioritization schemes offered little guidance around COVID-19 vaccination during pregnancy, and concerns about safety were associated with hesitancy.
      • Cui Y.
      • Binger K.
      • Palatnik A.
      Attitudes and Beliefs Associated With COVID-19 Vaccination During Pregnancy.
      • Kharbanda E.O.
      • Vazquez-Benitez G.
      COVID-19 mRNA Vaccines During Pregnancy: New Evidence to Help Address Vaccine Hesitancy.
      • Reifferscheid L.
      • Marfo E.
      • Assi A.
      • et al.
      COVID-19 vaccine uptake and intention during pregnancy in Canada.
      • Gutierrez S.
      • Logan R.
      • Marshall C.
      • et al.
      Predictors of COVID-19 Vaccination Likelihood Among Reproductive-Aged Women in the United States.
      Based on the evidence of higher morbidity and mortality among pregnant persons with COVID-19, the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine issued guidance recommending both an initial vaccine series and booster vaccination for all eligible individuals regardless of pregnancy or lactation status.

      ACOG and SMFM recommend COVID-19 vaccination for pregnant individuals [press release]. July 30, 2021.

      , Despite accumulating evidence of the safety and effectiveness of COVID-19 vaccination for pregnant persons and their offspring and the dangers of COVID-19 disease in pregnancy, as of June 18, 2022, the CDC estimated that 71% of pregnant people in the United States had received a COVID-19 vaccine, with 54.9% having received a booster dose and 3.1% having received at least one COVID-19 dose while pregnant.
      • Goldshtein I.
      • Steinberg D.M.
      • Kuint J.
      • et al.
      Association of BNT162b2 COVID-19 Vaccination During Pregnancy With Neonatal and Early Infant Outcomes.
      Centers of Disease Control and Prevention. COVID-19 vaccination among pregnant people aged 18-49 years overall, by race/ethnicity, and date reported to CDC - Vaccine Safety Datalink, United States.
      • Fu W.
      • Sivajohan B.
      • McClymont E.
      • et al.
      Systematic review of the safety, immunogenicity, and effectiveness of COVID-19 vaccines in pregnant and lactating individuals and their infants.

      Children

      In surveys done to date, parents are less accepting of COVID-19 vaccines for their children than for themselves. In general, surveys performed later in the pandemic in late 2021 showed greater levels of parental acceptance of COVID-19 vaccines compared with surveys performed in 2020 and early 2021.
      • Liz Hamel L.L.
      • Kirzinger Ashley
      • Kearney Audrey
      • et al.
      KFF COVID-19 vaccine monitor: winter 2021 update on parents' views of vaccines for kids.
      ,
      • Goldman R.D.
      • Krupik D.
      • Ali S.
      • et al.
      Caregiver Willingness to Vaccinate Their Children against COVID-19 after Adult Vaccine Approval.
      • Rane M.S.
      • Robertson M.M.
      • Westmoreland D.A.
      • et al.
      Intention to Vaccinate Children Against COVID-19 Among Vaccinated and Unvaccinated US Parents.
      • Chen F.
      • He Y.
      • Shi Y.
      Parents' and Guardians' Willingness to Vaccinate Their Children against COVID-19: A Systematic Review and Meta-Analysis.
      • Szilagyi P.G.
      • Shah M.D.
      • Delgado J.R.
      • et al.
      Parents' Intentions and Perceptions About COVID-19 Vaccination for Their Children: Results From a National Survey.
      • Ruggiero K.M.
      • Wong J.
      • Sweeney C.F.
      • et al.
      Parents' Intentions to Vaccinate Their Children Against COVID-19.
      • Teasdale C.A.
      • Borrell L.N.
      • Kimball S.
      • et al.
      Plans to Vaccinate Children for Coronavirus Disease 2019: A Survey of United States Parents.
      • Teherani M.
      • Banskota S.
      • Camacho-Gonzalez A.
      • et al.
      Intent to Vaccinate SARS-CoV-2 Infected Children in US Households.

      Hamel L. LL, Sparks G., Stokes M., et al KFF COVID-19 Vaccine Monitor - April 2021. May 6, 2021 2021.

      • Sparks G.M.A.
      • Lopes L.
      • Hamel L.
      • et al.
      KFF COVID-19 Vaccine Monitor - April 2022.
      • Liz Hamel L.L.
      • Grace Sparks
      • Kirzinger Ashley
      • et al.
      KFF COVID-19 Vaccine Monitor: 2021.
      A nationally representative survey of US parents in October-November 2021 found that for children ages 0 to 4 years, 52% of parents were likely to have their children vaccinated, and for ages 5% to 11% and 12% to 17%, 54% and 70% of parents, respectively, reported they were likely to vaccinate or had already vaccinated their children.
      • Hammershaimb E.A.
      • Cole L.D.
      • Liang Y.
      • et al.
      COVID-19 Vaccine Acceptance Among US Parents: A Nationally Representative Survey.
      However, roughly 40% of parents with children 0 to 11 year old wanted to “wait and see” before vaccination, and another 36% would not let their children get a COVID-19 vaccine. Parents in that study who had received a COVID-19 vaccine themselves were 1.9, 3.7, and 6.2 times more likely to accept COVID-19 vaccination for their 0 to 4, 5 to 11, and 12- to 17-year-old children, respectively; however, this effect was not statistically significant for parents of children 0 to 4 years old, the age group for which a vaccine had not yet been authorized at the time of the study.
      • Hammershaimb E.A.
      • Cole L.D.
      • Liang Y.
      • et al.
      COVID-19 Vaccine Acceptance Among US Parents: A Nationally Representative Survey.
      Acceptance of COVID-19 vaccination for children is also associated with acceptance of routine childhood immunizations and prior receipt of a seasonal influenza vaccine.
      • Hammershaimb E.A.
      • Cole L.D.
      • Liang Y.
      • et al.
      COVID-19 Vaccine Acceptance Among US Parents: A Nationally Representative Survey.
      Male parents, older parents, and parents of older children have higher rates of COVID-19 vaccine acceptance compared with female parents, younger parents, and parents of younger children.
      • Rane M.S.
      • Robertson M.M.
      • Westmoreland D.A.
      • et al.
      Intention to Vaccinate Children Against COVID-19 Among Vaccinated and Unvaccinated US Parents.
      ,
      • Kreuter M.W.
      • Garg R.
      • Marsh A.
      • et al.
      Intention to vaccinate children for COVID-19: A segmentation analysis among Medicaid parents in Florida.
      • Gray A.
      • Fisher C.B.
      Determinants of COVID-19 Vaccine Uptake in Adolescents 12-17 Years Old: Examining Pediatric Vaccine Hesitancy Among Racially Diverse Parents in the United States.
      • Goldman R.D.
      • Ceballo R.
      • International C.-P.A.S.G.
      Parental gender differences in attitudes and willingness to vaccinate against COVID-19.
      Parents in the United States of Hispanic ethnicity are more likely to accept COVID-19 vaccination for children compared with non-Hispanic parents.
      • Kreuter M.W.
      • Garg R.
      • Marsh A.
      • et al.
      Intention to vaccinate children for COVID-19: A segmentation analysis among Medicaid parents in Florida.
      ,
      • Gray A.
      • Fisher C.B.
      Determinants of COVID-19 Vaccine Uptake in Adolescents 12-17 Years Old: Examining Pediatric Vaccine Hesitancy Among Racially Diverse Parents in the United States.
      ,
      • McKinnon B.
      • Quach C.
      • Dube E.
      • et al.
      Social inequalities in COVID-19 vaccine acceptance and uptake for children and adolescents in Montreal, Canada.
      ,
      • Fisher C.B.
      • Gray A.
      • Sheck I.
      COVID-19 Pediatric Vaccine Hesitancy among Racially Diverse Parents in the United States.
      Compared with the United States, Canadian parents’ acceptance of pediatric COVID-19 vaccines was initially higher, but that gap has narrowed with time.
      • Humble R.M.
      • Sell H.
      • Dube E.
      • et al.
      Canadian parents' perceptions of COVID-19 vaccination and intention to vaccinate their children: Results from a cross-sectional national survey.
      ,
      • Goldman R.D.
      • Bone J.N.
      • Gelernter R.
      • et al.
      National COVID-19 vaccine program progress and parents' willingness to vaccinate their children.
      Parents must balance the perceived risks of COVID-19 disease against perceived risks and benefits of COVID-19 vaccination. The media often report that pediatric COVID-19 disease is mild, but parental perception that pediatric COVID-19 disease is severe is a predictor of positive vaccination intention for children 0 to 4 and 5 to 11.
      • Hammershaimb E.A.
      • Cole L.D.
      • Liang Y.
      • et al.
      COVID-19 Vaccine Acceptance Among US Parents: A Nationally Representative Survey.
      At the same time, parents report concerns about the side effects of COVID-19 vaccines, and parents with attitudinal barriers to COVID-19 vaccination are less likely to accept the vaccine for their children.
      • Liz Hamel L.L.
      • Kirzinger Ashley
      • Kearney Audrey
      • et al.
      KFF COVID-19 vaccine monitor: winter 2021 update on parents' views of vaccines for kids.
      ,
      • Hammershaimb E.A.
      • Cole L.D.
      • Liang Y.
      • et al.
      COVID-19 Vaccine Acceptance Among US Parents: A Nationally Representative Survey.
      ,
      • Ruggiero K.M.
      • Wong J.
      • Sweeney C.F.
      • et al.
      Parents' Intentions to Vaccinate Their Children Against COVID-19.
      ,
      • Liz Hamel L.L.
      • Grace Sparks
      • Kirzinger Ashley
      • et al.
      KFF COVID-19 Vaccine Monitor: 2021.

      Reasons for coronavirus disease-2019 vaccine hesitancy

      Novelty of Vaccines

      Several aspects of COVID-19 vaccination are distinct from other vaccines. First, SARS-CoV-2 is a novel human pathogen, and no vaccines for human coronaviruses had ever reached late-stage development in the past. Second, the mRNA and viral-vectored technologies applied to COVID-19 vaccines had been in development for decades preceding the emergence of SARS-CoV-2 but had not been used in vaccines previously authorized for the general population. Third, the process through which the biomedical research community moved from pathogen identification to successful vaccine development and production was not only unprecedented in terms of speed but also in terms of public visibility. Perceptions that the vaccines were “rushed,” that the technologies were “too new,” and that SARS-CoV-2 might “burn out” on its own or provide sustained natural immunity fed reluctance toward COVID-19 vaccines and have prompted a “wait and see” approach for many people who are otherwise not reluctant toward other vaccines.
      • Tang L.
      • Douglas S.
      • Laila A.
      Among sheeples and antivaxxers: Social media responses to COVID-19 vaccine news posted by Canadian news organizations, and recommendations to counter vaccine hesitancy.
      ,
      • CfDCa Prevention
      Myths and Facts about COVID-19 Vaccines.

      Safety Concerns

      The high visibility of COVID-19 vaccination campaigns in the media amplified awareness of rare side effects following vaccination, beginning with anaphylaxis following mRNA vaccination.
      • Shimabukuro T.T.
      • Cole M.
      • Su J.R.
      Reports of Anaphylaxis After Receipt of mRNA COVID-19 Vaccines in the US-December 14, 2020-January 18, 2021.
      The identification of serious blood clots, caused by the entity now known as vaccine-induced immune thrombotic thrombocytopenia, and Guillain-Barré syndrome in recipients of viral-vectored vaccines and of myopericarditis in adolescent and young adult males following mRNA vaccination created further concerns about vaccine safety.

      T S. Thrombosis with thrombocytopenia syndrome (TTS) following Janssen COVID-19 vaccine. In. Advisory committee on immunization Practices. 2021.

      • American Society of Hematology
      Vaccine-induced Immune Thrombotic Thrombocytopenia.
      • Keh R.Y.S.
      • Scanlon S.
      • Datta-Nemdharry P.
      • et al.
      COVID-19 vaccination and Guillain-Barre syndrome: analyses using the National Immunoglobulin Database.
      • Hanson K.E.
      • Goddard K.
      • Lewis N.
      • et al.
      Incidence of Guillain-Barre Syndrome After COVID-19 Vaccination in the Vaccine Safety Datalink.
      • Oster M.E.
      • Shay D.K.
      • Su J.R.
      • et al.
      Myocarditis Cases Reported After mRNA-Based COVID-19 Vaccination in the US From December 2020 to August 2021.

      Ontario PH. Myocarditis and Pericarditis after COVID-19 mRNA Vaccines. In:2022:1-17

      In addition to concerns about rare but immediate or proximate side effects, some reluctance stemmed from concern about unknown long-term side effects. Among these are concerns about effects on fertility spurred by rumors associating COVID-19 vaccines with both female and male infertility that became widespread on social media. Some were rooted in the rhetoric of past anti-vaccine campaigns about human papillomavirus (HPV) vaccines, whereas others capitalized upon fears of forced sterilizations among the Black American community.
      • Abbasi J.
      Widespread Misinformation About Infertility Continues to Create COVID-19 Vaccine Hesitancy.
      Still others seized upon the rapidly expanding body of knowledge about SARS-CoV-2, drawing parallels between the spike protein and placental proteins and positing that vaccine-induced antibodies targeting the spike protein might also attack the placenta. Studies have shown no adverse effects on either female or male fertility after COVID-19 vaccination, but public concerns persist.
      • Kharbanda E.O.
      • Vazquez-Benitez G.
      COVID-19 mRNA Vaccines During Pregnancy: New Evidence to Help Address Vaccine Hesitancy.
      ,
      • Abbasi J.
      Widespread Misinformation About Infertility Continues to Create COVID-19 Vaccine Hesitancy.
      ,
      • Lu-Culligan A.
      • Tabachnikova A.
      • Perez-Then E.
      • et al.
      No evidence of fetal defects or anti-syncytin-1 antibody induction following COVID-19 mRNA vaccination.
      ,
      • Safrai M.
      • Herzberg S.
      • Imbar T.
      • et al.
      The BNT162b2 mRNA Covid-19 vaccine does not impair sperm parameters.

      Beliefs about Susceptibility, Severity, and Effectiveness

      From the first days of the COVID-19 pandemic, it was well known that the disease tended to be more severe in older populations, particularly when compared with children, and for a time, there was some evidence that children were less likely to become infected.
      • Davies N.G.
      • Klepac P.
      • Liu Y.
      • et al.
      Age-dependent effects in the transmission and control of COVID-19 epidemics.
      Thus, public perception that COVID-19 was a relatively benign illness in children was common and has contributed to parental resistance to vaccination.
      • Hammershaimb E.A.
      • Cole L.D.
      • Liang Y.
      • et al.
      COVID-19 Vaccine Acceptance Among US Parents: A Nationally Representative Survey.
      ,
      • Humble R.M.
      • Sell H.
      • Dube E.
      • et al.
      Canadian parents' perceptions of COVID-19 vaccination and intention to vaccinate their children: Results from a cross-sectional national survey.
      ,
      • Szilagyi P.G.
      • Shah M.D.
      • Delgado J.R.
      • et al.
      Parents' Intentions and Perceptions About COVID-19 Vaccination for Their Children: Results From a National Survey.
      In addition, as the COVID-19 vaccination campaign progressed and discussion of booster doses became public, some construed the need for boosters to mean that the vaccines were not effective. Contributing to this misperception in children specifically were the effectiveness results from the clinical trials in children, particularly those less than 5 years of age (or 6 for the Moderna vaccine).
      Coronavirus (COVID-19) Update
      FDA Authorizes Moderna and Pfizer-BioNTech COVID-19 Vaccines for Children Down to 6 Months of Age [press release].
      When mRNA vaccines were eventually authorized for children less than age 5, the studies in this age group were done during the omicron wave, when vaccine effectiveness against infection was known to be relatively low compared with the initial studies in adults undertaken during circulation of the ancestral variant, which showed very high effectiveness against all outcomes, including infection.
      FDA Takes Key Action in Fight Against COVID-19 By Issuing Emergency Use Authorization for First COVID-19 Vaccine [press release].

      Religious and Philosophic Concerns

      Although some groups argue against COVID-19 vaccine mandates on the grounds of personal liberty, others with reluctance around available COVID-19 vaccines have cited religious concerns about the vaccines.
      Religious Identities and the Race Against the Virus: American Attitudes on Vaccination Mandates and Religious Exemptions.
      Although essentially all major organized religions encourage vaccination with the available COVID-19 vaccines, groups with staunch objections to the use of embryonic stem cells in vaccine development and/or manufacturing have voiced preferences for vaccines other than the mRNA and viral-vectored vaccines currently available in the United States.

      J J. New Novavax Shot Could Appeal to Pro-Life Christian Skeptics. In. Christianity Today.

      Misinformation and Disinformation Campaigns

      Some false beliefs about COVID-19 disease and vaccines that contribute to hesitancy may result from the purposeful dissemination of disinformation; others stem from an abundance of readily available misinformation and may be informed by individual or group tendencies toward conspiratorial beliefs.
      • Liz Hamel A.K.
      • Kirzinger Ashley
      • Lopes Lunna
      • et al.
      KFF Health Tracking Poll - September 2020: Top Issues in 2020 Election, The Role of Misinformation, and Views on A Potential Coronavirus Vaccine.
      Some countries have denied the presence of COVID-19 within their borders altogether for the majority of the pandemic, but even in countries with high rates of COVID-19 transmission such as the United States, there are portions of the public that do not perceive COVID-19 to be a threat.
      • Hashim H.T.
      • El Rassoul A.E.A.
      • Bchara J.
      • et al.
      COVID-19 denial in Turkmenistan veiling the real situation.
      ,
      • Smith A.
      Kim Jong Un says pandemic has caused 'great crisis' in North Korea.
      This may be due to local transmission dynamics, personal experiences of mild COVID-19 disease, or skepticism about the severity of COVID-19 disease among other possible reasons.,
      • Tang L.
      • Douglas S.
      • Laila A.
      Among sheeples and antivaxxers: Social media responses to COVID-19 vaccine news posted by Canadian news organizations, and recommendations to counter vaccine hesitancy.
      ,
      • CfDCa Prevention
      Myths and Facts about COVID-19 Vaccines.
      Conspiratorial beliefs about the contents and functions of the vaccines also weigh into the considerations of the risks of COVID-19 disease versus the risks of COVID-19 vaccines. Some of these include the idea that the vaccines might alter the recipient’s DNA or allow a government or corporate entity to manipulate, control, or track the vaccine through the use of microchips.,
      • Tang L.
      • Douglas S.
      • Laila A.
      Among sheeples and antivaxxers: Social media responses to COVID-19 vaccine news posted by Canadian news organizations, and recommendations to counter vaccine hesitancy.
      ,
      • CfDCa Prevention
      Myths and Facts about COVID-19 Vaccines.

      Politics and Trust

      Breakdown of trust in authorities. Although social cohesion was initially galvanized by the perception of a common threat in the form of COVID-19, policy decisions in response to the pandemic became highly politicized and polarizing. In the United States and elsewhere, affiliation with right-leaning political parties has been associated with resistance to masking and COVID-19 vaccination, whereas left-leaning political parties largely promoted both interventions.
      • Stoler J.
      • Klofstad C.A.
      • Enders A.M.
      • et al.
      Sociopolitical and psychological correlates of COVID-19 vaccine hesitancy in the United States during summer 2021.
      ,
      • Albrecht D.
      Vaccination, politics and COVID-19 impacts.
      Political party affiliation may be used as a surrogate category to represent sociopolitical beliefs, but characterizing attitudes along party lines fails to account for large segments of the population that do not align with political parties, leaving gaps in our understanding of the ideological drivers of acceptance vs. reluctance toward COVID-19 vaccination.
      A general breakdown in trust of authorities worldwide has not spared government officials and public health authorities responding to the pandemic. Roughly 40% of Americans in an April 2020 poll felt that both the CDC and the FDA paid too much attention to politics. Although in April 2020 83% of respondents to the same poll reported that they considered CDC to be a trustworthy source of reliable information about the coronavirus, 2 years later only 64% of those polled reported the CDC is a trustworthy source of reliable information on COVID-19 vaccines.,
      • Liz Hamel A.K.
      • Kirzinger Ashley
      • Lopes Lunna
      • et al.
      KFF Health Tracking Poll - September 2020: Top Issues in 2020 Election, The Role of Misinformation, and Views on A Potential Coronavirus Vaccine.
      Continued trust in personal health care providers. Despite a breakdown of trust in government and public health authorities, individual health care providers still garner high levels of confidence. A November 2021 poll found that 77% of US parents trusted their children’s health care provider or pediatrician “a great deal” or “fair amount” to provide reliable information about COVID-19 vaccines for children, including 59% of unvaccinated parents.
      • Liz Hamel L.L.
      • Kirzinger Ashley
      • Kearney Audrey
      • et al.
      KFF COVID-19 vaccine monitor: winter 2021 update on parents' views of vaccines for kids.
      The percentage of parents reporting trust in their children’s pediatricians increased to 83% in April 2022%, and 85% of all US adults in the same poll reported trust in their own health care provider.
      • Sparks G.M.A.
      • Lopes L.
      • Hamel L.
      • et al.
      KFF COVID-19 Vaccine Monitor - April 2022.

      Interventions to Improve Coronavirus Disease-2019 Vaccine Acceptance

      Given the novelty of both the pathogen and the vaccines used to combat it, one challenge in addressing COVID-19 vaccine hesitancy is that the research and public health communities have had limited time to understand what works to improve confidence and uptake. We can apply best practices from other vaccines, such as strengthening patient-provider communication and community engagement campaigns, but more time and investigation are needed to determine whether some strategies work better than others. Framing communications around efficacy, side effects, and relative risks have been shown to influence COVID-19 vaccination preferences and acceptance among adults in general and may help encourage acceptance among parents deciding when and whether to vaccinate their children.
      • Kreps S.
      • Kriner D.L.
      Communication about vaccine efficacy and COVID-19 vaccine choice: Evidence from a survey experiment in the United States.
      ,
      • Thorpe A.
      • Fagerlin A.
      • Drews F.A.
      • et al.
      Communications to Promote Interest and Confidence in COVID-19 Vaccines.
      Behavioral nudges in the form of text message reminders improved adult COVID-19 vaccine uptake in two randomized controlled trials, although these interventions were targeting populations prioritized for vaccination, and the outcome was short-term uptake.
      • Dai H.
      • Saccardo S.
      • Han M.A.
      • et al.
      Behavioural nudges increase COVID-19 vaccinations.
      Similar recall-reminder strategies and the use of presumptive announcements have been shown to improve adherence to other recommended vaccines, including among pediatric populations.
      • Szilagyi P.G.
      • Thomas K.
      • Shah M.D.
      • et al.
      National Trends in the US Public's Likelihood of Getting a COVID-19 Vaccine-April 1 to December 8, 2020.
      ,
      • Brewer N.T.
      • Hall M.E.
      • Malo T.L.
      • et al.
      Announcements Versus Conversations to Improve HPV Vaccination Coverage: A Randomized Trial.
      Surveys of parental acceptance show that parents who receive a recommendation from their children’s health care provider are more likely to accept COVID-19 vaccination and that parents prefer for their younger children to receive a COVID-19 vaccine at their pediatric provider’s office as opposed to a pharmacy, where the bulk of COVID-19 vaccines are currently delivered.
      • Liz Hamel L.L.
      • Kirzinger Ashley
      • Kearney Audrey
      • et al.
      KFF COVID-19 vaccine monitor: winter 2021 update on parents' views of vaccines for kids.
      ,
      • Hammershaimb E.A.
      • Cole L.D.
      • Liang Y.
      • et al.
      COVID-19 Vaccine Acceptance Among US Parents: A Nationally Representative Survey.
      ,

      Oliver S. Updates to the Evidence to Recommendation Framework: Pfizer-BioNTech COVID-19 booster in children aged 5-11 years. In. Advisory committee on immunization practices: Centers for Disease Control and Prevention.

      Although 85% of pediatricians are enrolled in the Vaccines for Children (VFC) program and two-third of VFC providers are enrolled to give COVID-19 vaccines, only 1/3 are actually delivering the vaccines.

      Oliver S. Updates to the Evidence to Recommendation Framework: Pfizer-BioNTech COVID-19 booster in children aged 5-11 years. In. Advisory committee on immunization practices: Centers for Disease Control and Prevention.

      ,

      O’Leary S.T., Allison M.A., Vogt T., et al., Pediatricians’ experiences with and perceptions of the vaccines for children program, Pediatrics, 145 (3), 2020, e20191207.

      Ensuring that young children have access to COVID-19 vaccines requires that pediatric providers not only have the capacity to stock the vaccines but also that they are actively recommending vaccination to their patients’ families. Even among pediatric providers who do not stock the vaccine, their communication, advocacy, and assistance in getting children vaccinated is critical.
      There are issues unique to COVID-19 vaccination of children relative to other childhood vaccines that may require novel interventions to improve uptake. There is a need to develop interventions to address concerns about novelty in a rapidly developed pandemic vaccine that would be relevant to both this and other pandemics. There are also specific issues unique to COVID-19 vaccination. For example, it is now well-known that myocarditis is associated with mRNA vaccines,
      • Mevorach D.
      • Anis E.
      • Cedar N.
      • et al.
      Myocarditis after BNT162b2 mRNA Vaccine against Covid-19 in Israel.
      ,
      • Mevorach D.
      • Anis E.
      • Cedar N.
      • et al.
      Myocarditis after BNT162b2 Vaccination in Israeli Adolescents.
      particularly for adolescent and young adult males. Although it is clear that the benefits of vaccination clearly outweigh this rare risk (ie, the risk of myocarditis from infection is much higher than from vaccination),
      • Patone M.
      • Mei X.W.
      • Handunnetthi L.
      • et al.
      Risks of myocarditis, pericarditis, and cardiac arrhythmias associated with COVID-19 vaccination or SARS-CoV-2 infection.
      the risk is real, and many adolescents and young adults have been hospitalized as a result, a fact that has not been missed in both traditional and online media. Although other childhood vaccines can be associated with rare adverse events requiring hospitalization, these are very rare and not typically front-page news. Developing and testing interventions that can address these types of rare adverse events both during and outside of a pandemic is an important area for future research.

      Summary

      Acceptance of every vaccine that is authorized, licensed, and recommended may be influenced by factors common to all vaccines and by factors unique to, or amplified by, the individual vaccine and the time during which it was developed and rolled out. COVID-19 vaccines were developed, manufactured, tested, authorized, distributed, and first administered amidst recurring waves of the pandemic. Some of the factors related to COVID-19 vaccine acceptance or reluctance that has been exaggerated relative to general vaccine acceptance or reluctance include the use of newer manufacturing technologies, politicization of many aspects of pandemic control, and the intense public and media scrutiny of every aspect of COVID-19 vaccine research and implementation. Future work on vaccine hesitancy should focus not only on the factors common to all vaccines, but also on factors that are unique or intensified in relation to vaccines directed against pathogens causing epidemics and pandemics.

      Clinics care points

      • Pediatricians should strongly recommend and offer coronavirus disease-2019 (COVID-19) vaccination.
      • Do not assume that parents who accept routine childhood vaccines and/or COVID-19 vaccination for themselves will also accept COVID-19 vaccination for their children.
      • When counseling parents on COVID-19 vaccination, it is important to understand (1) their perceptions about the risk of COVID-19 disease in themselves and their children and (2) their concerns about the risks of vaccination.

      Disclosure

      Each individual listed as an author has contributed to the article to a significant extent in line with ICMJE guidelines. Dr. Hammershaimb drafted the outline with input from Drs. Campbell and O’Leary; Dr. Hammershaimb wrote the draft manuscript with input from Drs. Campbell and O’Leary. Dr. O’Leary revised the article based on the editor feedback. The submitted article was reviewed, edited, and agreed upon by all three authors.

      Funding and commercial and financial interests

      All authors will provide this information via a formal disclosure form, as noted in the instructions.

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