The Risk-Benefit Balance in the COVID-19 “Vaccine Hesitancy” Literature: An Umbrella Review Protocol


  • Chaufan Claudia School of Health Policy and Management, Faculty of Health, York University, Canada
  • Natalie Hemsing School of Health Policy and Management, Faculty of Health, York University, Canada
  • Jennifer McDonald School of Health Policy and Management, Faculty of Health, York University, Canada
  • Camila Heredia School of Health Policy and Management, Faculty of Health, York University, Canada



adverse effects, COVID-19 vaccine, critical policy analysis, risk-benefit analysis, risk-benefit ratio, informed consent, side effects of COVID vaccines, COVID vaccine hesitancy, COVID vaccine safety


Background: “Vaccine hesitancy” has been described as a major public health problem, especially in the COVID-19 era. Identified factors driving “hesitancy” include the concerns of recipients with the safety, side effects, and risk-benefit ratio of COVID-19 vaccines[1] — a proper assessment and disclosure of which are critical to the requisite process of informed consent. However, the expert literature has given little attention to the evidence informing these concerns, focusing instead on features of the recipients themselves to explain the phenomenon of so-called “hesitancy”.

Goal: This umbrella review will expand the scope of research on “vaccine hesitancy” by examining how the safety, side effects, and risk-benefit ratio concerns of recipients of COVID-19 vaccines are addressed in the expert literature. 

Inclusion criteria: We will include systematic reviews on COVID-19 “vaccine hesitancy” that examine hesitancy in any population involved with COVID-19 vaccination decisions for themselves or as caretakers (e.g., decisions about “vaccinating” their children) to capture the broadest possible range of perspectives on the phenomenon of interest. Only completed, published, and refereed systematic reviews in English will be included.

Methods: We will search PubMed, the Epistemonokos COVID-19 platform (COVID-19 L·OVE), and the WHO Global Research on COVID-19 Database to locate quantitative, qualitative, and mixed methods studies reviews. Reviews that meet the inclusion criteria will undergo quality assessment (AMSTAR) and data extraction. Two reviewers will independently conduct title and abstract screening and extract and synthesize the data. Disagreements will be resolved through full team discussion. Subgroup analyses will be performed to compare findings according to social indicators of target populations, country location of the first author, and other contextual factors. Thematic analysis and synthesis will be used to “transform the data” into themes by applying a deductive-inductive approach. Frequency distributions will be calculated to assess the strength of support for each theme. Findings will be presented in tabular and narrative forms to facilitate their interpretation.

Significance: Informed consent is a fundamental bioethical principle in medical research and practice. Insufficient attention to the concerns of vaccine recipients about these matters, compounded by a neglect to discuss the evidence-base informing these concerns, may contribute to the very problem that the COVID-19 “vaccine hesitancy” expert literature purports to address. This is especially true of an intervention based on novel technologies and intended to be delivered on a global scale. Identifying if and how the expert literature engages with these concerns is critical.

Systematic review registration: PROSPERO CRD42022351489.


[1] Although we use the phrase “COVID-19 vaccines” throughout, we believe they should more appropriately be referred to as “COVID-19 genetic vaccines”, “COVID-19 injections”, or "mRNA biologicals”. However, we have chosen “vaccine” with no quotation marks for better readability. For an in-depth discussion of this issue, see Rose (2021).

Author Biography

  • Chaufan Claudia, School of Health Policy and Management, Faculty of Health, York University, Canada

    Claudia Chaufan, MD, PhD, is an Associate Professor of Health Policy and Global Health at York University (Canada). She is also a past US Fulbright Scholar in Public/Global Health, and former Graduate Program Director in Health, has published widely in academic and lay venues, has held grants from the US National Institutes of Health (NIH), the Canadian Institute for Health Information (CIHI), the Social Sciences and Humanities Research Council in Canada (SSHRC), and is an editorial board member and reviewer for various professional journals including IJVTPR. Professor CChaufan has taught at universities in Argentina, the USA, Taiwan, and Canada. She specializes in the determinants  and geopolitics of global health, focusing on how narratives drive perceptions of risk, practices of stigmatization, and policies of exclusion. The current contribution to the COVID Aftermath addresses medicalization and social control in the COVID-19 era.


Abba-Aji, M., Stuckler, D., Galea, S., & McKee, M. (2022). Ethnic/racial minorities’ and migrants’ access to COVID-19 vaccines: A systematic review of barriers and facilitators. J Migr Health, 5, 100086—100086. MEDLINE.

Acharya, C. B., Schrom, J., Mitchell, A. M., Coil, D. A., Marquez, C., Rojas, S., Wang, C. Y., Liu, J., Pilarowski, G., Solis, L., Georgian, E., Belafsky, S., Petersen, M., DeRisi, J., Michelmore, R., & Havlir, D. (2022). Viral load among vaccinated and unvaccinated, asymptomatic and symptomatic persons infected with the SARS-CoV-2 Delta variant. Open Forum Infectious Diseases, 9(5), ofac135.

AMSTAR. (n.d.). Assessing the Methodological Quality of Systematic Reviews. Retrieved October 12, 2022, from

Anakpo, G., & Mishi, S. (2022). Hesitancy of COVID-19 vaccines: rapid systematic review of the measurement, predictors, and preventive strategies. Human Vaccines & Immunotherapeutics, 2074716.

Bacchi, C. (2012). Why study problematizations? making politics visible. Open Journal of Political Science, 02(01), 1—8.

Batteux, E., Mills, F., Jones, L. F., Symons, C., & Weston, D. (2022). The effectiveness of interventions for increasing COVID-19 vaccine uptake: a systematic review. Vaccines, 10(3).

Blumenthal, K. G., Robinson, L. B., Camargo, C. A., Jr, Shenoy, E. S., Banerji, A., Landman, A. B., & Wickner, P. (2021). Acute allergic reactions to mRNA COVID-19 vaccines. JAMA, 325(15), 1562—1565.

Braun, V., & Clarke, V. (2006). Using thematic analysis in psychology. Qualitative Research in Psychology, 3(2), 77—101.

Broudy, D. (2021). Vaccine development and social control: A psychopathology of impaired reasoning in the global push for mass compliance. International Journal of Vaccine Theory, Practice, and Research, 2(1), 93–124.

Bruder, M., Haffke, P., Neave, N., Nouripanah, N., & Imhoff, R. (2013). Measuring individual differences in generic beliefs in conspiracy theories across cultures: Conspiracy Mentality Questionnaire. Frontiers in Psychology, 4.

Català, A., Muñoz-Santos, C., Galván-Casas, C., Roncero Riesco, M., Revilla Nebreda, D., Solá-Truyols, A., Giavedoni, P., Llamas-Velasco, M., González-Cruz, C., Cubiró, X., Ruíz-Villaverde, R., Gómez-Armayones, S., Gil Mateo, M. p., Pesqué, D., Marcantonio, O., Fernández-Nieto, D., Romaní, J., Iglesias Pena, N., Carnero Gonzalez, L., … Guilabert, A. (2022). Cutaneous reactions after SARS-CoV-2 vaccination: a cross-sectional Spanish nationwide study of 405 cases*. British Journal of Dermatology, 186(1), 142—152.

Chow, K. W., Pham, N. V., Ibrahim, B. M., Hong, K., & Saab, S. (2022). Autoimmune Hepatitis-Like Syndrome Following COVID-19 Vaccination: A Systematic Review of the Literature. Digestive Diseases and Sciences.

Classen, J. B. (2021). US COVID-19 Vaccines Proven to Cause More Harm than Good Based on Pivotal Clinical Trial Data Analyzed Using the Proper Scientific Endpoint, “All Cause Severe Morbidity.” 6.

Doshi, P., Godlee, F., & Abbasi, K. (2022). COVID-19 vaccines and treatments: we must have raw data, now. BMJ, o102.

Fisman, D. N., Amoako, A., & Tuite, A. R. (2022). Impact of population mixing between vaccinated and unvaccinated subpopulations on infectious disease dynamics: implications for SARS-CoV-2 transmission. CMAJ, 194(16), E573—E580.

Fraiman, J., Erviti, J., Jones, M., Greenland, S., Whelan, P., Kaplan, R. M., & Doshi, P. (2022). Serious adverse events of special interest following mRNA COVID-19 vaccination in randomized trials in adults. Vaccine.

Goffman, E. (2009). Stigma: Notes on the Management of Spoiled Identity. Simon and Schuster.

Guyatt, G. H., Sackett, D. L., Sinclair, J. C., Hayward, R., Cook, D. J., Cook, R. J., Bass, E., Gerstein, H., Haynes, B., Holbrook, A., Jaeschke, R., Laupacls, A., Moyer, V., & Wilson, M. (1995). Users’ Guides to the Medical Literature: IX. a method for grading health care recommendations. JAMA, 274(22), 1800—1804.

Hammond, J., Leister-Tebbe, H., Gardner, A., Abreu, P., Bao, W., Wisemandle, W., Baniecki, M., Hendrick, V. M., Damle, B., Simón-Campos, A., Pypstra, R., & Rusnak, J. M. (2022). Oral nirmatrelvir for high-risk, nonhospitalized adults with COVID-19. New England Journal of Medicine, 386(15), 1397—1408.

Hoffmann, M., Krüger, N., Schulz, S., Cossmann, A., Rocha, C., Kempf, A., Nehlmeier, I., Graichen, L., Moldenhauer, A.-S., Winkler, M. S., Lier, M., Dopfer-Jablonka, A., Jäck, H.-M., Behrens, G. M. N., & Pöhlmann, S. (2022). The Omicron variant is highly resistant against antibody-mediated neutralization: Implications for control of the COVID-19 pandemic. Cell, 185(3), 447-456.e11.

Hudson, A., & Montelpare, W. J. (2021). Predictors of vaccine hesitancy: implications for COVID-19 public health messaging. International Journal of Environmental Research and Public Health, 18(15), 8054.

Ioannidis, J. P. A. (2022). The end of the COVID-19 pandemic. European Journal of Clinical Investigation, 52(6), e13782.

Khairat, S., Zou, B., & Adler-Milstein, J. (2022). Factors and reasons associated with low COVID-19 vaccine uptake among highly hesitant communities in the US. American Journal of Infection Control, 50(3), 262-267.

Ledford, C. J. W., Cafferty, L. A., Moore, J. X., Roberts, C., Whisenant, E. B., Garcia Rychtarikova, A., & Seehusen, D. A. (2022). The dynamics of trust and communication in COVID-19 vaccine decision making: a qualitative inquiry. Journal of Health Communication, 27(1), 17—26.

Light, D. W., Lexchin, J., & Darrow, J. J. (2013). Institutional corruption of pharmaceuticals and the myth of safe and effective drugs. Journal of Law, Medicine & Ethics, 41(3), 590—600.

Malhotra, A. (2022a). Curing the pandemic of misinformation on COVID-19 mRNA vaccines through real evidence-based medicine—Part 1. Journal of Insulin Resistance, 5(1), Article 1.

Malhotra, A. (2022b). Curing the pandemic of misinformation on COVID-19 mRNA vaccines through real evidence-based medicine—Part 2. Journal of Insulin Resistance, 5(1), Article 1.

Mansanguan, S., Charunwatthana, P., Piyaphanee, W., Dechkhajorn, W., Poolcharoen, A., & Mansanguan, C. (2022). Cardiovascular manifestation of the BNT162b2 mRNA COVID-19 vaccine in adolescents. Tropical Medicine and Infectious Disease, 19 Aug 2022, 7(8):196

Matić, Z., & Šantak, M. (2022). Current view on novel vaccine technologies to combat human infectious diseases. Applied Microbiology and Biotechnology, 106(1), 25—56.

Mena, G. E., Martinez, P. P., Mahmud, A. S., Marquet, P. A., Buckee, C. O., & Santillana, M. (2021). Socioeconomic status determines COVID-19 incidence and related mortality in Santiago, Chile. Science, 372(6545), eabg5298.

Mevorach, D., Anis, E., Cedar, N., Bromberg, M., Haas, E. J., Nadir, E., Olsha-Castell, S., Arad, D., Hasin, T., Levi, N., Asleh, R., Amir, O., Meir, K., Cohen, D., Dichtiar, R., Novick, D., Hershkovitz, Y., Dagan, R., Leitersdorf, I., Alroy-Preis, S. (2021). Myocarditis after BNT162b2 mRNA vaccine against COVID-19 in Israel. New England Journal of Medicine, 385(23), 2140—2149.

Mills, E., Jadad, A. R., Ross, C., & Wilson, K. (2005). Systematic review of qualitative studies exploring parental beliefs and attitudes toward childhood vaccination identifies common barriers to vaccination. Journal of Clinical Epidemiology, 58(11), 1081—1088.

Momplaisir, F., Haynes, N., Nkwihoreze, H., Nelson, M., Werner, R. M., & Jemmott, J. (2021). Understanding drivers of coronavirus disease 2019 vaccine hesitancy among blacks. Clinical Infectious Diseases, 73(10), 1784—1789.

New York State Department of Health. (n.d.). The Science Behind Vaccine Research and Testing. 2014. Retrieved October 12, 2022, from

Page, M. J., McKenzie, J. E., Bossuyt, P. M., Boutron, I., Hoffmann, T. C., Mulrow, C. D., Shamseer, L., Tetzlaff, J. M., Akl, E. A., Brennan, S. E., Chou, R., Glanville, J., Grimshaw, J. M., Hróbjartsson, A., Lalu, M. M., Li, T., Loder, E. W., Mayo-Wilson, E., McDonald, S., … Moher, D. (2021). The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ, n71.

Park, H. K., Ham, J. H., Jang, D. H., Lee, J. Y., & Jang, W. M. (2021). Political Ideologies, Government Trust, and COVID-19 vaccine hesitancy in South Korea: a cross-sectional survey. International Journal of Environmental Research and Public Health, 18(20), Article 20.

Pluye, P., & Hong, Q. N. (2014). Combining the power of stories and the power of numbers: mixed methods research and mixed studies reviews. Annual Review of Public Health, 35(1), 29—45.

Polack, F. P., Thomas, S. J., Kitchin, N., Absalon, J., Gurtman, A., Lockhart, S., Perez, J. L., Pérez Marc, G., Moreira, E. D., Zerbini, C., Bailey, R., Swanson, K. A., Roychoudhury, S., Koury, K., Li, P., Kalina, W. V., Cooper, D., Frenck, R. W., Hammitt, L. L., … Gruber, W. C. (2020). Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. New England Journal of Medicine, 383(27), 2603—2615.

Popay, J., Roberts, H., Sowden, A., Petticrew, M., Arai, L., Rodgers, M., & Britten, N. (2006). Guidance on the conduct of narrative synthesis in systematic reviews: A product from the ESRC methods programme.

Ridgway, J. P., Tideman, S., Wright, B., & Robicsek, A. (2022). Rates of COVID-19 Among unvaccinated adults with prior COVID-19. JAMA Network Open, 5(4), e227650.

Rose, J. “A Report on the U.S. Vaccine Adverse Events Reporting System (VAERS) of the COVID-1 9 messenger ribonucleic acid (mRNA) biologicals.” Science, Public Health Policy, and the Law, 2 (2021): 59–80.

SAGE. (2014). Report of the SAGE Working Group on Vaccine Hesitancy. WHO.

Sallam, M. (2021). COVID-19 Vaccine Hesitancy Worldwide: A Concise Systematic Review of Vaccine Acceptance Rates. Vaccines, 9(2), 160.

Santiago, D. (2022). Playing Russian Roulette with every COVID-19 injection: The deadly global game. International Journal of Vaccine Theory, Practice, and Research, 2(2), 619–650.

Say, D., Crawford, N., McNab, S., Wurzel, D., Steer, A., & Tosif, S. (2021). Post-acute COVID-19 outcomes in children with mild and asymptomatic disease. The Lancet Child & Adolescent Health, 5(6), e22-e23.

Seneff, S., & Nigh, G. (2021). Worse than the disease? Reviewing some possible unintended consequences of the mRNA vaccines against COVID-19. International Journal of Vaccine Theory, Practice, and Research, 2(1), 38–79.

Shea, B. J., Hamel, C., Wells, G. A., Bouter, L. M., Kristjansson, E., Grimshaw, J., Henry, D. A., & Boers, M. (2009). AMSTAR is a reliable and valid measurement tool to assess the methodological quality of systematic reviews. Journal of Clinical Epidemiology, 62(10), 1013—1020.

Shuster, E. (1997). Fifty Years Later: The Significance of the Nuremberg Code. New England Journal of Medicine, 337(20), 1436—1440.

Singanayagam, A., Hakki, S., Dunning, J., Madon, K. J., Crone, M. A., Koycheva, A., Derqui-Fernandez, N., Barnett, J. L., Whitfield, M. G., Varro, R., Charlett, A., Kundu, R., Fenn, J., Cutajar, J., Quinn, V., Conibear, E., Barclay, W., Freemont, P. S., Taylor, G. P., … Lackenby, A. (2022). Community transmission and viral load kinetics of the SARS-CoV-2 Delta (B.1.617.2) variant in vaccinated and unvaccinated individuals in the UK: A prospective, longitudinal, cohort study. The Lancet Infectious Diseases, 22(2), 183—195.

Smith, V., Devane, D., Begley, C. M., & Clarke, M. (2011). Methodology in conducting a systematic review of systematic reviews of healthcare interventions. BMC Medical Research Methodology, 11(1), 15.

Subramanian, S. V., & Kumar, A. (2021). Increases in COVID-19 are unrelated to levels of vaccination across 68 countries and 2947 counties in the United States. European Journal of Epidemiology.

Thomas, J., & Harden, A. (2008). Methods for the thematic synthesis of qualitative research in systematic reviews. BMC Medical Research Methodology, 8(1), 45.

Thornley, S., Morris, A. J., Sundborn, G., & Bailey, S. (2022). How fatal is COVID-19 compared with seasonal influenza? The devil is in the detail.

Tiede, A., Sachs, U. J., Czwalinna, A., Werwitzke, S., Bikker, R., Krauss, J. K., Donnerstag, F., Weißenborn, K., Höglinger, G., Maasoumy, B., Wedemeyer, H., & Ganser, A. (2021). Prothrombotic immune thrombocytopenia after COVID-19 vaccination. Blood, 138(4), 350353.

Tram, K. H., Saeed, S., Bradley, C., Fox, B., Eshun-Wilson, I., Mody, A., & Geng, E. (2021). Deliberation, dissent, and distrust: understanding distinct drivers of coronavirus disease 2019 vaccine hesitancy in the United States. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, ciab633.

van Mulukom, V., Pummerer, L. J., Alper, S., Bai, H., Čavojová, V., Farias, J., Kay, C. S., Lazarevic, L. B., Lobato, E. J. C., Marinthe, G., Pavela Banai, I., Šrol, J., & Žeželj, I. (2022). Antecedents and consequences of COVID-19 conspiracy beliefs: A systematic review. Social Science & Medicine (1982), 301, 114912.

Wise, J. (2021). COVID-19: Highest death rates seen in countries with most overweight populations. BMJ, n623.

Wise, J. (2022). COVID-19: Symptomatic infection with Omicron variant is milder and shorter than with Delta, study reports. BMJ, 377, o922.

World Health Organization. (2019). Ten health issues WHO will tackle this year.

World Health Organization. (2022). Global COVID-19 Vaccination Strategy in a Changing World: July 2022 update.

World Medical Association. (1964). Declaration of Helsinki. New England Journal of Medicine, 271(9), 473-474.

Yamamoto, K. (2022). Adverse effects of COVID-19 vaccines and measures to prevent them. Virology Journal, 19(1), 100.



How to Cite

The Risk-Benefit Balance in the COVID-19 “Vaccine Hesitancy” Literature: An Umbrella Review Protocol. (2022). International Journal of Vaccine Theory, Practice, and Research , 2(2), 652-669.

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