COVID-19 Vaccine Refusal among Nurses Worldwide: Review of Trends and Predictors

COVID-19 vaccination hesitancy has become a major concern around the world. Recent reports have also highlighted COVID-19 vaccination hesitancy in healthcare workers. Despite media reports and scientific publications, little is known about the extent and predictors of COVID-19 vaccination refusal among nurses. Thus, the purpose of this study was to assess COVID-19 vaccine refusal rates among nurses globally and to explore the reasons for refusal and factors associated with the uptake of the vaccines. A scoping review of the published literature was conducted, and a final pool of 51 studies (n = 41,098 nurses) from 36 countries was included in this review. The overall pooled prevalence rate of COVID-19 vaccine refusal among 41,098 nurses worldwide was 20.7% (95% CI = 16.5–27%). The rates of vaccination refusal were higher from March 2020–December 2020 compared to the rates from January 2021–May 2021. The major reasons for COVID-19 vaccine refusal were concerns about vaccine safety, side effects, and efficacy; misinformation and lack of knowledge; and mistrust in experts, authorities, or pharmaceutical companies. The major factors associated with acceptance of the vaccines were: male sex, older age, and flu vaccination history. Evidence-based strategies should be implemented in healthcare systems worldwide to increase the uptake of COVID-19 vaccines among nurses to ensure their safety and the safety of their patients and community members.


Background
Nurses are the backbone of modern-day healthcare systems. During the COVID-19 pandemic, nurses played a major role in caring for and treating COVID-19 patients. As a result, many nurses worldwide were infected with COVID-19 and lost their lives [1][2][3][4]. A very conservative estimate by the WHO from summer 2021 suggested that more than 100,000 healthcare workers (HCWs) worldwide (including nurses) died due to COVID-19 infection [4]. Another conservative estimate from the International Council of Nurses suggests that by October 2020, more than 1500 nurses died of COVID-19 across 44 countries, and by January 2021, this number may have exceeded 2200 [5,6]. A recent report from the United States indicated that from March 2020 to April 2021, more than 3600 healthcare workers died due to COVID-19, and almost a third of those who died were nurses [7]. These numbers are estimates and the true representation of COVID-19 related deaths among healthcare workers and nurses is still unknown. While the world is now in the second year of the pandemic, and general life situations may look different for the public in various parts of the world, nurses continue to fight the COVID-19 pandemic at the frontlines, risking their lives and health.
In late 2020 and early 2021, COVID-19 vaccines were rolled out, and in most countries, healthcare workers were designated as priority groups for vaccination [8,9]. There was enormous anticipation for these vaccines, and for healthcare workers, these vaccines were a reason for optimism, a tool to fight the pandemic and continue to serve others while protecting themselves. By late 2021, it was estimated that the majority (>50%) of HCWs (including nurses) in many western countries were either fully vaccinated or planned to get vaccinated [9][10][11] Despite these optimistic reports from some countries, by summer 2021 vaccine hesitancy and refusal among healthcare workers became a major global concern [8, [12][13][14]. For example, the earliest global review conducted in December 2020 included eight studies, and in almost half of the studies, COVID-19 vaccine acceptance rates among healthcare workers (HCWs) were less than 75% [13]. Another review of 76,471 HCWs published in April 2021 estimated that more than a fifth (22.5%) of the HCWs worldwide were hesitant about getting COVID-19 vaccination. Similarly, a review published in May 2021 estimated that COVID-19 vaccine acceptance in HCWs ranged from 27.7% to 77.3% worldwide [14]. These reviews did not specifically provide the proportion of nurses included in their data or the COVID-19 vaccine hesitancy rates exclusively for nurses. Still, and surprisingly, many of these reviews and reports suggest that worldwide, among all HCWs, nurses could have one of the highest hesitancy rates for COVID-19 vaccination [13][14][15][16]. By the last quarter of 2021, some countries around the world started mandating COVID-19 vaccinations for HCWs, including nurses [16,17]. As a result, protests by nurses along with other HCWs garnered substantial media coverage and public discourse. Despite these reports, controversies, and scattered evidence in comprehensive reviews of literature, we could not find a global assessment of COVID-19 vaccination refusal rates among nurses, the reasons for refusal, or the factors associated with COVID-19 vaccination uptake among nurses. Thus, the purpose of this review was to conduct a global assessment of COVID-19 vaccine refusal rates among nurses, reasons for refusal, and factors associated with acceptance (enablers) of vaccination.

Methods
A scoping review methodology was adopted to synthesize evidence on COVID-19 vaccination refusal rates among nurses by using databases such as PubMed, EBSCO Host, CINAHL, pre-print servers (e.g., medRxiv), and Google Scholar. First, three independent investigators (EB, SC, NB) searched for studies using the following keywords: "nurses", "nursing", "coronavirus", "COVID-19", "SARS-CoV2", "vaccine", "vaccination", "hesitancy", "refusal", "healthcare", "hospital", "professional", "worker", "employee". Next, different order of keywords was used by the investigators across repeated searches in scholarly databases to extract the final pool of relevant studies. Then, articles that were to be included in the final review were screened carefully for suitability and to identify other articles that pertained to this review. Additional hand searches were conducted by the senior investigator (JK) to include articles that cited the initially selected pool of articles. Finally, discrepancies on the suitability and relevance of the studies to be included were sorted by discussion (among EV, SAC, NB) with the senior investigators (JK, TK).
The studies that were finally included in this review were those that were published in the English language, between 1 March 2020-30 November 2021, and included nurses as study participants (Figure 1). COVID-19 vaccination refusal rates data were extracted from individual studies if the participating nurses in these studies responded as "no", "refused", "declined", "disagreed", "did not want to get", or "do not intend to get" for questions on obtaining the COVID-19 vaccines. Nurses who responded as "unsure", "uncertain", and "undecided" about getting COVID-19 vaccines were not grouped with those who refused COVID-19 vaccination. Data were also divided into two categories (March 2020 to December 2020 and January 2021 to October 2021) to explore the difference in global vaccine refusal rates among nurses before (Table 1) and after ( Table 2) the COVID-19 vaccines were available for use. Pooled prevalence for COVID-19 vaccination refusal rates was computed from the studies included in this review (with 95% confidence intervals) using randomeffects modeling. Subsequently, for each study, the major reasons for COVID-19 vaccine refusal and the enablers of vaccine acceptance were summarized .   COVID-19 vaccine refusal and the enablers of vaccine acceptance were summarized .

Results
The final pool of articles included 51 studies from 36 countries (Tables 1 and 2). Multiple studies were conducted in the USA (n = 10), China (n = 4), France (n = 4), Saudi Arabia (n = 4), Greece (n = 3), and Spain (n = 3). Two studies each were found for Cyprus, Germany, Vietnam, Egypt, India, Kuwait, Ghana, Canada, Hong Kong, Palestine, and Turkey; and the rest of the countries had one study each. Females comprised the majority (>50%) of study participants in 48 out of 51 studies. The vast majority of studies (44 of 51) did not exclusively include nurses as participants (i.e., study participants included nurses along with other healthcare professionals). The sample size of participants ranged from 51 to 9701 participating nurses across the studies where data collection occurred between March 2020 and May 2021 .
Before the vaccine rollout (March 2020-December 2020), among the 27 studies with 20,037 nurses from 29 countries, we found that more than a fifth (23.4%) did not want to obtain the COVID-19 vaccines (Table 1)  . In contrast, after the COVID-19 vaccines were available (January 2021-May 2021), among the 24 studies from 18 countries with 21,061 nurses, we found that less than a fifth (18.3%) of the nurses did not want to obtain the vaccine . Overall, from March 2020 to May 2021, among the 51 studies from 36 countries, for a total sample size of 41,098 nurses, the pooled prevalence rate of COVID-19 vaccine refusal was 20.7% (95% CI = 16.5-27%) .
The major reasons for vaccine refusal were: concerns about COVID-19 vaccine efficacy, safety/speedy approvals, effectiveness, and side effects; mistrust in government/authorities, pharmaceutical companies, and science or experts; misinformation or lack of knowledge about vaccines; and a belief that COVID-19 is a mild disease or does not exist. In contrast, the major factors associated with COVID-19 vaccine acceptance in nurses were: male gender; older age; and history of flu or other vaccinations. Additional factors were higher education/knowledge or work experience; higher perceived risk of getting infected or becoming seriously ill with COVID-19, having chronic diseases; and caring for COVID-19 patients or having greater contact with such patients (Tables 1 and 2) .

Discussion
In this global review of COVID-19 vaccination refusal among nurses, we found that more than a fifth (23.4%) refused vaccines in 2020, but slightly less than a fifth (18.3%) refused in 2021. This modest decline may be due to more knowledge and information, popularity, or mass uptake in 2021 (compared to 2020 when the vaccine development and approvals were surrounded by a lot of questions and curiosity). Additionally, it should be noted that most of the studies included in this review were conducted when the vaccines were approved under emergency use authorization. With full approvals and more safety data, vaccine options, and greater availability, the rates of refusal worldwide could decline further. Overall, from March 2020 to May 2021, based on our review, nearly a fifth (20.7%) of the nurses worldwide did not want to obtain COVID-19 vaccination. Additional evidence for a modest decline in COVID-19 vaccine refusal rates among nurses may be seen from previous studies that have found slightly higher rates of vaccine refusal among HCWs or trainees in healthcare professions compared to what we found in our current review [8,[12][13][14][15]69]. Despite these optimistic but weak assumptions, the COVID-19 vaccination refusal rates among nurses remain highly disconcerting given the high mortality numbers in nurses, the major frontline role of nurses in caring for COVID-19 patients, and their potential to infect themselves, patients, family, and community members.
Despite the unique working situation and risks faced by nurses, the vaccine refusal rates among nurses remain almost similar to other groups of HCWs and somewhat lower than the general population [11][12][13][14][15][16][34][35][36][37][69][70][71][72][73]. Two recent global reviews found that the rates of COVID-19 vaccine refusal were 22% for college students and 18.9% for trainees/students in healthcare professions [12,71]. A recent global review of 82 studies from 45 countries found the vaccination refusal rates worldwide to be in the range of 0-24% [72]. Similarly, one of the earliest meta-analyses with data until November 2020 found that among 81,173 individuals worldwide, the COVID-19 vaccine refusal/hesitancy rates could be 26.7% [73]. Based on the training, expertise, and work setting of nurses, the refusal rates for COVID-19 vaccines should have been much lower than other groups of individuals who are not HCWs. Continued surveillance and research of predictors, enablers, and barriers to COVID-19 vaccination are warranted to help increase vaccination among nurses.
As a significant proportion of nurses in our review refused to obtain COVID-19 vaccines, we assessed major reasons for refusal and acceptance of vaccination. Surprisingly, the major reasons for COVID-19 vaccination refusal among nurses in this review are very similar to the reasons for refusal observed among other HCWs and the general population (e.g., concerns about vaccine safety, side effects, efficacy; misinformation and lack of knowledge; mistrust in government or pharmaceutical companies and experts) [69][70][71][72][73][74][75][76][77]. Similar to our findings among nurses, studies on other HCWs and the general population have also found that males, older adults, those with flu vaccination history or higher trust in vaccines, and those who perceive themselves as being at higher risk of COVID-19 infections, or believed in protecting others, are more likely to accept the COVID-19 vaccines [12][13][14][15][70][71][72][73][74][75][76][77]. Additionally, the vast majority of study participants in our review were females, and their perspectives are very similar to those of females among the general public (e.g., fear of infertility, getting COVID from the vaccine, serious adverse effects, the influence of social media rumors, misinformation, and conspiracy theories, etc.). While nurses and other HCWs are assumed to have more knowledge about medicine and science, they are not a monolithic group of individuals and are a part of the larger society with multiple external influences on their preferences and perspectives (e.g., family, friends, media, political and social climate, etc.).
Several recommendations and best practices have been suggested to increase uptake of COVID-19 vaccines among nurses, other HCWs, and the general population [66][67][68][69][70][71][72][73][74][75][76][77]. Much of the earlier focus during vaccine roll-out emphasized better communication and education. Recently, mandates, incentives, and workplace policy changes have gained traction in the push to obtain higher vaccination rates. Scholars and experts are also recommending the use of models, such as the five Cs and their extensions. Essentially, to increase COVID-19 vaccine uptake in nurses, healthcare systems should focus on removing Constraints and increasing vaccination Convenience, building Confidence for vaccines and reducing Complacency, as well as using best practices in Communication for unique Context and Cultures [12][13][14][70][71][72][73][74][75][76][77]. Combining this model with additional incentives and mandates might also improve vaccination rates. Nurses play a key role as frontline care providers and are expected to advocate for patient and population health. Increasing the vaccination rate among nurses is an opportunity to improve vaccination rates among other HCWs and the general population (i.e., by role modeling and advocacy).
The findings of this review are subject to several potential limitations [70][71][72][73][74][75][76][77]. First, our data could be limited by the inclusion/exclusion criteria and the search processes we used could have led to the inadvertent omission of certain studies (e.g., only the studies published in English language were included). If so, inherent biases could limit the validity of our findings (e.g., selection bias). Second, vaccine refusal and hesitancy are measured in several different ways across studies (e.g., refused, declined, disagreed, will not take, no, etc.). The lack of uniformity in the measurement of the primary outcome (i.e., vaccine refusal) across studies may have introduced bias in our review. Additionally, if a significant proportion of those who were unsure and undecided about vaccination never get vaccinated, the rates of hesitancy would be much higher than estimates presented in this review. Third, for the studies we included in this review, there were substantial differences in sample sizes, geographic region, and characteristics of study participants, such as age, gender, income, education, health risk profiles, etc. Due to these variations, our estimates of nurses' vaccine refusal may not appropriately represent COVID-19 vaccination preference for any specific group of nurses. Many studies also had professionals, such as nurse aides, orderlies, midwives, nursing assistants-we did not include these samples in this review, which could limit the generalizability of our findings on COVID-19 vaccination refusal in nursing professions. Finally, we did not adopt a systematic review or meta-analysis methodology because most nurses included in this review were part of a larger sample of HCWs, with few exclusive details on nurse participants reported in the studies included for this review. Given these circumstances, our methods preclude extensive analyses of nurses' characteristics (e.g., occupational settings or working environments) related to COVID-19 vaccination and robust analysis of quality of studies included for review (e.g., risk of bias analysis). Despite all these limitations, this is one of the largest global assessments of COVID-19 vaccination refusal rates among nurses using rigorous search methods by a team of multiple investigators. Additionally, all the included studies were screened multiple times to assess major reasons for COVID-19 vaccination refusal, and the results were summarized after a consensus among the study team. Finally, our pooled prevalence rates accounted for variations in sample sizes and vaccination refusal rates across studies, providing robust global estimates for COVID-19 vaccination refusal among nurses.

Conclusions
In this review of COVID-19 vaccine refusal rates among nurses, we found that a little more than a fifth (20.7%) of the nurses worldwide refused to obtain COVID-19 vaccination. The reasons for the refusal of COVID-19 vaccines among nurses are similar to the reasons found in HCWs and, to some extent, in the general public (e.g., concerns about side effects and safety of COVID-19 vaccines). Older individuals, males, and those with past flu vaccination history or compliance with other vaccines were more likely to accept COVID-19 vaccination. Given these findings, healthcare facility leaders and professional nursing organizations should help implement and advocate for measures to increase COVID-19 vaccination uptake among nurses (e.g., educational interventions, incentives, mandates). Researchers and healthcare facility administrators should continue to assess the reasons for COVID-19 vaccination refusal among nurses and help design tailored strategies for reducing vaccine hesitancy among nurses. Nurses have been involved at the frontlines in the battle against COVID-19 and also serve as advocates for population health. To ensure that nurses play a major role in helping vaccinate the general public against COVID-19, COVID-19 vaccination refusal and hesitancy must be reduced among nurses by evidencebased interventions.
Author Contributions: J.K., E.B., and S.C. conceptualized and designed the study; E.B., S.C. and N.B. collected data for the study; J.K. analyzed the data; J.K. and T.K. wrote the initial drafts of the paper; N.B. and T.K. provided critical inputs on the drafts. All authors have read and agreed to the published version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: Not applicable (this is a review paper).

Informed Consent Statement: Not applicable (no human subjects involved).
Data Availability Statement: All data is available within the studies included for this review.

Conflicts of Interest:
The authors declare no conflict of interest.