Tackling Misconceptions That Result in COVID-19 Vaccine Hesitancy


After reviewing the mechanisms of the first three COVID-19 vaccines granted emergency use authorization, we can now address some of the most common concerns that have been expressed regarding vaccine hesitancy.

In 2020, an estimated 83.1 million people (data current as of March 31, 2021) in the United States have been infected with SARS-CoV-2, the virus that causes COVID-19, and case counts continue to rise.1 Individuals can be reinfected after an undetermined period of immunity, but research has shown the risk of reinfection is reduced for at least 8 months.2,3

COVID-19 can cause cold- and flu-like symptoms as well as more serious consequences such as difficulty breathing, chest pain and pressure, inadequate oxygen perfusion, and death.1,4 Although many people recover from COVID-19, some patients may experience long-term effects on different organ systems, primarily affecting the heart, lungs, and brain.5

The true extent of morbidity and mortality associated with COVID-19 is not fully known,6 but the United States has an approximately 1.7% case-fatality ratio.7 Certain patient groups are at higher risk for the negative consequences of COVID-19 than others, including older adults, patients who are immunocompromised or obese, and those with lung or chronic diseases (eg, heart disease, type 2 diabetes, and chronic kidney disease).4,8

Because of the consequences of COVID-19 infection, several vaccines were developed and recently granted emergency use authorization (EUA) by the FDA for the prevention of symptomatic infection.9 However, as public health efforts to conduct mass vaccination begin, vaccine hesitancy and concerns regarding the vaccine continue to limit vaccination efforts. The percentage of Americans willing to get vaccinated increased from 51% in September 2020 to 60% in November 2020, which Pew Research Center attributes to increased confidence in the research and vaccine development process.10

Among those who were still hesitant, as many as 46% reported they would probably get the COVID-19 vaccine once more information becomes available and others start getting vaccinated.10 The proportion of individuals who prefer this “wait and see” approach continues to steadily trend down, reportedly to 17% in March 2021.11 Furthermore, a study conducted by the University of California, Davis in June 2020 found that 14.8% of participants were extremely or somewhat unlikely to get vaccinated and 23.0% were unsure, with a greater likelihood of vaccination associated with increased vaccine knowledge.12

Therefore, the dissemination of accurate information and dispelling of common misconceptions will be important roles for pharmacists in order to increase vaccination rates.

Pharmacists have been on the frontlines of answering many questions about these novel vaccines, such as: “Is the COVID-19 vaccine safe?” “Will it really work, or will I still get COVID-19?” “Will this vaccine change my DNA?” “Is the vaccine being tested on me to see if it works?”13,14 Providers also may have concerns about the safety and efficacy of the vaccine, particularly because of how quickly it was developed.15

This article focuses on answering questions regarding the 3 vaccines that have received EUA in the United States, the Moderna COVID-19 vaccine (mRNA-1273; ModernaTX, Inc), the Pfizer-BioNTech COVID-19 vaccine (BNT162b2; Pfizer, Inc, and BioNTech), and the Johnson & Johnson COVID-19 vaccine (Ad.26.COV2.S or JNJ-78436725, Janssen Biotech, Inc).9,16-18 Notably, AstraZeneca and Novavax, Inc, vaccines are still in large scale, phase 3 clinical trials.19

How Do the COVID-19 Vaccines Work?

The first 2 COVID-19 vaccines granted EUAs are messenger RNA (mRNA) vaccines, a vaccine approach that leverages mRNA’s cellular function to trigger an immune response. The vaccines work by injecting mRNA that encodes for a portion of the spike protein carried on SARS-CoV-2 into the deltoid. After the mRNA is integrated into our cells, the spike protein is produced by ribosomes and displayed on the cell surface. The spike protein flags the immune system, which identifies the virus as a threat and mounts an immune response. Once the instructions are delivered by the mRNA, the cell gets rid of the mRNA delivered through the vaccine.14,20

The Johnson & Johnson vaccine is a viral vector vaccine that uses a modified adenovirus (Ad26) vector to deliver a strand of DNA that codes for a portion of the spike protein carried on SARS-CoV-2,21 much like the mRNA vaccines. Although efficacy in preventing symptomatic illness associated with COVID-19 is reportedly lower than the mRNA vaccine, there are some advantages of this vaccine, including single-dose administration and a less stringent storage requirements. After reviewing the mechanisms of these vaccines, we can now address some of the most common concerns that have been expressed about the first COVID-19 vaccines.

Misconception 1: The COVID-19 vaccine is unsafe because of expedited development

Common concerns regarding the safety of the COVID-19 vaccines center around the speed of vaccine development, particularly whether all criteria were met and the lack of long-term safety data. First, it should be noted that mRNA-based vaccines are not new. The mRNA technology was developed over the past few decades to address other infectious diseases, such as Zika and rabies, and was created to address some of the weaknesses of other vaccine approaches (eg, live virus, inactivated virus, subunit protein, and DNA-based vaccines), by increasing stability and manufacturing speed.20

Further, the manufacturing of mRNA vaccines is associated with improved safety because it does not require toxic chemicals or cell cultures, and the rapid pace limits exposure to contaminating microorganisms.20 Viral vector vaccines also have been studied for decades in order to address similar challenging infectious disease as well as provide potential treatment options for cancer and other diseases.21 The manufacturing of the viral vector vaccine currently available (Johnson & Johnson) was developed in response to the Ebola outbreak and applied to SARS-CoV-2, allowing for rapid production of vaccines.22

Second, the type of virus that causes COVID-19 is not completely new. Coronaviruses were responsible for previous global illness in recent years, including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS).23 Research on these diseases has been ongoing, and scientists were able to use that research when creating the COVID-19 vaccines.23 Additionally, the quick pace of vaccine development can be attributed in part to the substantial public and private financial support for creating the vaccine.

Under normal circumstances, the process for vaccine development occurs over several years because the company developing the vaccine is responsible for the cost of clinical trials.23 However, governments and private entities across the world funded vaccine development, removing financial barriers and incentivizing the development of more than 50 potential vaccines.23

Finally, although the vaccines were quickly studied and manufactured, all steps in the evaluation process were completed, including development of vaccine candidates, preclinical trials in animals and primates, 3 phases of clinical trials in human volunteers including comparisons against a control group, and review by the FDA.16,17,23-26

This process is what led the FDA to grant EUAs for 3 vaccine candidates.23 Some of the steps were conducted at the same time, allowing for greater efficiency.16,23 The vaccines underwent full testing for both safety and efficacy as required by the FDA.9,27 In short, a rapid pace of development does not mean that shortcuts were taken in the development of these first 3 COVID-19 vaccines.

Misconception 2: There are a lack of data on the safety and efficacy of the COVID-19 vaccine

The Pfizer-BioNTech COVID-19 vaccine had positive results during phase 1 clinical trials,24 which led to a combined phase 2/3 trial, in which the vaccine was 95% effective overall in patients 16 years of age and older at preventing symptomatic COVID-19 infection.16 In subgroup analyses, an efficacy rate of at least 87% was reported in all demographic groups.16 Similarly, the Moderna COVID-19 vaccine demonstrated efficacy in both animal and phase 1 human trials.25,26

Because the vaccine met efficacy criteria at the interim analysis of the phase 3 trial, the preliminary data were published, wherein the vaccine was found to be 94.1% effective at preventing symptomatic COVID-19 infection overall in patients 18 years of age and older.17 In subgroup analyses, the vaccine was at least 90% effective in all subgroups, with the exception of patients 65 years of age or older, in whom the vaccine was 86.4% effective.17 These efficacy rates are robust for vaccine clinical trials.

The Johnson & Johnson COVID-19 vaccine phase 3 clinical trial (ENSEMBLE) found 72% efficacy in preventing moderate and severe COVID-19 cases among US patients and 85% efficacy in preventing severe/critical COVID-19 cases among all patients in 8 countries.28 While the ability of these vaccines to prevent transmission of SARS-CoV-2 is not yet fully known, investigations are ongoing to determine the impact.16,17

In terms of long-term safety data, current data point toward immunity lasting longer than 2 months beyond the second vaccine dose, as the cumulative incidence of symptomatic COVID-19 infection remains stable even 4 months from the first dose in the initial clinical trials.16,17

Although the investigators do not yet have long-term safety data for the vaccines, efforts to examine the safety is consistent with other vaccine development. Moderna tested its vaccine in 30,420 people,17 Pfizer–BioNTech tested its vaccine in 43,458 people,16 and Johnson & Johnson tested its vaccine in 44,325 patients.28 In comparison, the safety study for the Shingrix vaccine (recombinant zoster vaccine; GSK) was approved based on a 2017 study of 30,000 people.29

Additionally, as part of normal phase 4 drug development, any safety issues or adverse events (AEs) associated with COVID-19 vaccine administration should be reported.23,30 To monitor these AEs and evaluate for risk, the CDC has created V-safe, a smartphone-based tool that leverages text messaging and online surveys to rapidly gather data on the tolerability of the vaccine.30 This is in addition to the National Healthcare Safety Network and the Vaccine Adverse Event Reporting System, which are also monitored to quickly detect safety signals with the COVID-19 vaccines.30

In the safety studies, the most common AEs reported with both vaccines were pain at the injection site, tiredness, headache, muscle pain, chills, joint pain, and fever, as well as swollen lymph nodes, nausea, and vomiting with the Moderna vaccine.31,32 These symptoms could last several days in the trials and may be more pronounced after the second injection.31,32 There also have been a number of phase 4 documented cases of anaphylaxis in patients receiving the Pfizer-BioNTech vaccine, with 17 of these cases occurring in individuals with a history of allergies or anaphylactic reactions.33

All patients had recovered as of January 6, 2021.33 Preliminary reports estimate that the incidence rate of anaphylaxis is 11.1 cases per million doses, with the reaction typically occurring within 15 minutes of vaccination.33 It is unknown at this time what causes this anaphylaxis, so patients with a history of anaphylactic reactions should talk with their provider before receiving the vaccine.

These patients should be monitored for 15 to 30 minutes after administration of the COVID-19 vaccine.33 The Johnson & Johnson vaccine is associated with similar adverse effects to the Moderna and Pfizer-BioNTech vaccines, including injection site pain, tiredness, headache, muscle pain, and nausea.34

The misconceptions discussed previously are 2 of the bigger and most common questions posed by both providers and patients. A few other misconceptions are important to mention in case questions arise, and those will be covered briefly.

Misconception 3: The COVID-19 vaccine will alter DNA or cause gene editing

Some concerns have been expressed related to the use of mRNA and its impact on our DNA. DNA is housed in the cell nucleus, and the mRNA delivered through the COVID-19 vaccines does not enter the nucleus.14 Thus, COVID-19 vaccines that use mRNA technology do not change the DNA of your own cells.14

This is also true of the DNA-based vaccine from Johnson & Johnson.35 This genetic information can only provide a “code” for a portion of the spike protein, so the body can form a response to the protein on the outside of the coronavirus.14 Once that task is completed, the cell destroys the genetic material through normal cellular processes that ensure that too much of a given protein is not made by our cells.14

Misconception 4: Patients recovered from COVID-19 do not need to be vaccinated

Early data suggest that natural immunity from infection with COVID-19 may last at least 6-8 months.2 However, although uncommon, it is possible to be diagnosed with a second case of COVID-19 after recovery of a previous infection even within a few months of having COVID-19.3

Due to this risk and the potential for severe illness if reinfected, the vaccine could still be helpful even if the patient already had COVID-19.3,13 Based on this information, the CDC currently recommends that those who have recovered from COVID-19 should still receive the COVID-19 vaccine 3 months after a positive diagnosis.13

Misconception 5: The first vaccine dose provides full immunity and negates the need to practice physical distancing measures

It is important to note that 2 doses are necessary to be fully protected against COVID-19 for those receiving the Pfizer and Moderna vaccines.16,17 The phase 3 trials of both vaccines noted partial immunity after the first dose, with greater than 90% protection after the second dose.16,17 For patients receiving the Johnson & Johnson vaccine, only a single dose is needed to provide 85% efficacy.36

The CDC currently recommends that 2 weeks after completing a 2-dose COVID-19 vaccine series or single dose of the Johnson & Johnson vaccine, fully vaccinated individuals may interact with other vaccinated individuals or unvaccinated people from a single household if not at high risk for severe COVID-19 illness.

Even though the CDC has loosened recommendations for fully vaccinated persons, it is still recommended to follow precautions such as wearing a well-fitted mask and practicing physical distancing when in public, when interacting with unvaccinated individuals at higher risk for severe COVID-19 illness, or when interacting with unvaccinated individuals from multiple households.37

Given that the Pfizer-BioNTech and Moderna vaccines are between 94% and 95% effective overall, there are people who could still get COVID-19 after vaccination.16,17 Unless and until herd immunity is achieved, it is important to keep preventive measures in place to ensure that high-risk patients are protected.13

Misconception 6: The COVID-19 vaccines will not protect against variant strains of SARS-CoV-2

Emerging in the United States in the fall of 2020, the 3 most notable variant strains of SARS-CoV-2 are the United Kingdom (UK) variant, B.1.1.7; the South African variant, B.1.351; and the Brazilian variant, P.1.38 The UK variant is one of the CDC’s variants of concern due to its association with increased transmissibility and increased risk of death, according to early evidence from UK scientists.38

However, a pre-print in vitro neutralization study conducted by Pfizer and the University of Texas Medical Branch, the Pfizer-BioNTech COVID-19 vaccine was effective against key mutations in the UK and South African variants. It was slightly less effective against the South African variant than the UK variant, but investigators noted that the difference in efficacy was insignificant.39

Additionally, a pre-print in vitro neutralization study of the Moderna COVID-19 vaccine showed no significant impact on neutralizing titers against the UK variant, but showed a 6-fold reduction in neutralizing titers in the South African variant.40 Even with this reduction, the levels of neutralizing titers remained above the level expected to be protective.40 Additional trials to explore the efficacy of the available COVID-19 vaccines against these variants are ongoing.

Recommendations to Improve Vaccination Rates

Although not every patient will be willing to receive a COVID-19 vaccine, health care providers can aid in dispelling concerns and provide accurate information for decision-making. We also can help the roughly large percentage of patients who are “on the fence” about receiving the COVID-19 vaccine by helping to steer vaccine hesitancy toward vaccine confidence.10

It is important to note that patients make decisions not based purely on information, but on the health beliefs they hold, through which they filter this information. This requires a different way of dialoguing with patients beyond a simple provision of information. How can we do that? Here are our tips gleaned from the literature related to vaccine hesitancy:

  1. Make a strong, positive, presumptive recommendation regarding the vaccine at each encounter. Often, providers approach patients about vaccines by asking whether they would like to receive the dose. Instead, use more presumptive, positive messaging such as, “This appointment is a great opportunity to get the coronavirus vaccine.” These statements can increase vaccine uptake when used consistently.41
  2. Explore the patient’s reasons for hesitancy using open-ended questions or statements. Do not just start with providing information. Instead, explore the patient’s concerns using a statement like, “Tell me more about your concerns about getting the COVID-19 vaccine.”42
  3. Express empathy and care when patients share their concerns. Actively listen and avoid any negative responses to concerns that patients express. Instead, acknowledge the challenges faced and show care and concern. It helps build the patient–provider relationship.42
  4. Share facts with the patient that address the expressed concerns. With the patient’s permission, use the information provided by the CDC and other agencies to address the specific concerns raised. Although they may not change their mind, provision of facts within the context of a collaborative conversation will help many patients dispel concerns.42
  5. Affirm the patient’s self-efficacy and ownership of the decision. Ensure that the patient knows that they have the autonomy to decide whether to be vaccinated.43

With pharmacists on the front line of vaccination efforts, it is imperative that we provide accurate information and dispel common misconceptions using patient-centered communication. This may play a key role in turning the tide of the COVID-19 pandemic.

Aleda M. H. Chen, PharmD, PhD, FAPhA, is the assistant dean and an associate professor at the Cedarville University School of Pharmacy in Cedarville, Ohio.

Justin W. Cole, PharmD, BCPS, is the chair of pharmacy practice and an associate professor at the Cedarville University School of Pharmacy in Cedarville, Ohio.


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