https://orcid.org/0000-0003-1787-6896
Abstract
Since the beginning of the COVID-19 pandemic, catastrophic mortality and morbidity rates and unknown long-term ramifications were caused, leading to focused efforts on implementing effective vaccination. Nucleic acid-based vaccines (NBVs), an emergent advance in vaccine development, presented high efficacy rates but controversy regarding this approach soon spread. This study assesses healthcare workers (HCWs) knowledge and attitude towards NBVs’ effectiveness. This cross-sectional study was conducted in Jordan from November 2020 to January 2021 through a web-based questionnaire. 320 participants were split into educated and uneducated groups, with the former being exposed to educational material on NBVs before survey completion. The educated group expressed increased concern towards NBVs’ side effects. Specifically, the risk of developing cancer due to genetic modification(40.8%), fever(69.4%), skin rash(58.0%), and amyloid deposition(40.8%) showed a significant difference. The educated group preferred RNA-based NBVs over DNA-based ones(43.9%), had double the response rate, provided more scientifically accurate answers, and showed a more positive attitude towards the ability of NBVs to induce cellular immunity (57.3%) and prevent chronic forms of COVID-19(57.3%) (p < 0.05). Because HCWs are the most integral players in shaping public opinion about NBVs, thorough educational material on NBVs needs to be integrated within the curricula of health-related programs to bridge the gap present. This could prove vital in ensuring the success of the current and future vaccination campaigns.
1. Introduction
Coronavirus Disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2; Sharma et al., Citation2020; Singh & Sharma, Citation2020), characterized by high transmissibility and mortality rate close to 3–4% worldwide (Cheng et al., Citation2020; Noor et al., Citation2020). Several medications have been proposed to manage COVID-19 but their usage often stirred controversies amid conflicting reports regarding their effectiveness and/or safety (Mehta et al., Citation2020). With the treatment regimen and public health measures failing to attain an effective solution that would eliminate the risk of mortality, and morbidity, or prevent illness altogether, most efforts have been focused on developing a safe and effective vaccine against SARS-CoV-2 (Sallam, Citation2021). The scientific community worldwide immediately recognized the impact of a developed vaccine in ending the pandemic (Rosales-Mendoza et al., Citation2020). As of June 2021, many vaccines with various efficacies are being added to vaccination programs that are well underway across most of the world (Xing et al., Citation2021). Technology platforms used in developing the COVID-19 vaccines are diverse (Kotarya et al., Citation2020), some of which have been adopted for this purpose for the first time in history (Shin et al., Citation2020). The novelty of these technologies and the relatively short development time did in fact stir controversies and increase vaccine hesitancy whilst acting as a barrier to effective vaccine distribution (Gupta & Morain, Citation2021).
Nucleic acid-based vaccines (NBVs) are an emergent advance in vaccine production that was employed early in the spread of SARS-CoV-2 as a viable effective measure to prevent disease (Ho et al., Citation2021). NBVs phase III trials presented strong proof in preventing COVID by almost 95% and severe disease by virtually 100% (Mahase, Citation2020). Another vital characteristic of NBVs is their faster production cycle when compared to other vaccine development methods (Jaciubek & Prasek, Citation2021). This provided the two NBVs, Moderna and Pfizer, earlier rollout to the public than other candidates (Cross, Citation2020). NBVs also offer safe production, distribution, and inoculation due to the lack of use of live viruses or any other microorganisms (Vogel et al., Citation2018). Despite the above, controversy regarding the effectiveness and safety of NBVs is an ongoing concern to many worldwide, including healthcare and medical science workers (Alley et al., Citation2021). A portion of the controversy especially among healthcare workers (HCWs) can be attributed to the novelty of the mechanism of action of NBVs (Bloom et al., Citation2020). NBVs employ DNA and/or RNA delivery to inoculated patient’s cells, which in turn produce and present the viral protein (such as the spike protein of SARS-CoV-2) that would ultimately induce immunity (Ho et al., Citation2021; Kowalczyk et al., Citation2016; Thompson et al., Citation2021). The use of our cell mechanisms, or perhaps the inoculation of genetic material into our cells could be the basis behind the current controversy. Furthermore, lipid nanoparticle carriers and optimized codons have been utilized to provide nucleotide sequences with a safe passage inside our cells and to prevent these sequences from being tagged for destruction before they enter the cells (Aldosari et al., Citation2021; Polack et al., Citation2020), respectively. Although demonstrating safety in trials, both additions were not part of previous conventional vaccines, further justifying the hesitancy (Soares et al., Citation2021).
To alleviate concerns about NBVs in the population and to improve immunization efforts by healthcare organizations worldwide, a positive attitude and rich knowledge among the healthcare providers would greatly aid in dissipating the fog around this new vaccination technology among concerned patients (Papagiannis et al., Citation2021). This study aims to assess the attitude and knowledge regarding the effectiveness of NBVs among HCWs and medical students and measure the impact of assigned educational material in alleviating concerns regarding NBVs. Novelty of this study stems from the fact that the perception of healthcare workers towards such advance in vaccination that have been also utilized recently in COVID-19 vaccines is extremely vital yet quite neglected. Healthcare workers form one of the major factors in determining the acceptance of society of certain medications and vaccines, as individuals tend to strongly trust their opinions. Therefore, measuring their attitude is essential in addressing gaps in knowledge.
2. Materials and methods
2.1. Study design and population
This is a cross-sectional study carried out in Jordan from November 2020 to January 2021 through a structured web-based survey. A convenience sample of 320 HCWs from various professions and sectors such as physicians, nurses, pharmacists, medical, dental, and nursing students, biomedical researchers, all of whom confirmed to work or study in Jordan, were involved. Data were collected using “Google Forms” and participation invites were delivered via healthcare-associated “Facebook” and “WhatsApp” closed groups to possible study participants. Moreover, participants were encouraged to share the survey with colleagues, thus, expanding the reach from the first point of contact onwards. The study population was divided into two almost equal groups. One of the groups was given a short education material on NBVs before data collection and hence, labelled the “educated group” while the other group, the “uneducated group”, was not provided with any educational material. Blinded links to both questionnaires were included in each of the invites and each participant chose one without prior knowledge to the group assigned to it.
The educational material was provided at the beginning of an identical questionnaire, while the uneducated group had the questionnaire without the preceding educational material. The material was provided and reviewed by Dr. M Al Madadha and Dr. M Ahram, as field experts, and was modelled with the information provided by public health international agencies (WHO, CDC). To ensure only the relevant population had access to the questionnaire only closed moderated groups were used, as well as seminars or public forums with the target population, and the material was distributed face to face with links sent to personal devices of participants. The two groups were controlled for demographic, social, and educational factors shown in Table .
Table 1. Descriptive statistics of the study sample (N = 320)
2.2. Study instrument
A structured questionnaire was developed in English to assess HCWs’ knowledge and attitude regarding NBVs. Questionnaire items were chosen by expert researchers and medical consultants after carrying out a face validity test. Preceding distribution of the survey, it was pilot tested on 20 randomly selected resident doctors at Jordan University Hospital, and refinements were made accordingly. Data collected through the pilot analysis were excluded from the final sample.
2.3. Contents of the survey instrument and scoring system
The questionnaire consisted of 23 closed-ended questions with responses in the Likert scale format composed of the options: agree, neutral, or disagree and one open question for participants to elaborate on their answers in the third section focused on NBV effectiveness. The survey was divided into three main sections to assess the participants’ socio-demographics and their attitude and knowledge on NBVs and towards different types of vaccines’ effectiveness and side effects. The first section covered the participants’ socio-demographics and professional traits including age, gender, educational degree, healthcare profession, and place of work. The second section consisted of 10 items assessing knowledge and agreeability regarding possible side effects of NBVs. Agreeability was measured by providing the statements illustrated in Table and asking the participants whether they agreed, disagreed, or were neutral regarding these statements. The possible side-effects proposed ranged from fever and skin rashes to more serious and life-threatening conditions such as cancer and heart and kidney diseases. The scoring was 1 for every correct answer and 0 for incorrect ones, giving a score for each question that falls between 0 and 10. The third section consisted of 10 items assessing participants’ attitude and knowledge towards the effectiveness of different types of vaccines including NBVs. The open-ended question that asked participants to elaborate on why they believed DNA or RNA NBVs were more effective was analysed by grouping participants’ answers into categories and subcategories that were derived based on their submitted answers. Considering that some individuals gave more than one reason, thus, the total of presented reasons is more than the sample size in each group. The five main categories are: No response, Lack of knowledge/Neutral, Published research/previous knowledge, Genetic alteration/formation/interaction, and Mechanism of action.
Table 2. Comparisons between groups on the side effects of NBVs, with “agree” referring to the number of participants who believed that NBVs could cause that certain side effect
2.4. Ethical considerations
Study objectives were thoroughly clarified before data collection and informed consent was submitted by each participant. All data were collected anonymously, ensuring its privacy and confidentiality is protected and participation was voluntary. Ethical approval was obtained from the Institutional Review Board at the Jordan University Hospital (reference number 221,000,013). The study was performed following the Helsinki Declaration as revised in 2013.
2.5. Data analysis
Frequency distribution was used to describe participants in the educated and uneducated study groups. The non-parametric Mann-Whitney test statistics, Chi-square test, and t-test were used to compare the two groups. Data analysis was performed using Statistical Package for Social Sciences (IBM Corp. Released 2017. IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp.)
3. Results
The main descriptive characteristics of the study population are presented in Table . The “18–25 year old” age group is the most common in our study population, forming about half the sample. The study population has an almost equal female to male ratio, and the most common profession to participate in our study was medical students (41.3%), followed by healthcare fields other than physicians (30.9%). The total study population (n = 320) was divided into two groups, one group (n = 157, 49.1%) received educational material, while the other (n = 163, 50.9%) did not receive educational material. The distribution of the participants according to the age groups was almost parallel in both groups. The educated group included more females (almost 59%), while the uneducated group included more males (56%). The largest age group was the (Aldosari et al., Citation2021; Bloom et al., Citation2020; Kowalczyk et al., Citation2016; Papagiannis et al., Citation2021; Polack et al., Citation2020; Soares et al., Citation2021; Thompson et al., Citation2021) years group and medical students formed the biggest share (41.3%) of the participant’s profession. The Chi-square test showed that more males were included in the educated group, and physicians were the least healthcare workers to be included in the educated group.
Table Compares the knowledge and agreeability level between the “educated” (E) and “uneducated” (UE) study groups among HCWs and students regarding the possible side effects of NBVs. The difference in agreeability was statistically significant in the following items: “Cancer due to gene modification” (E: 40.8% vs. UE: 27.6%, p = 0.03); “Skin rash” (E: 58.0% vs. UE: 46.0%, p = 0.02) and “fever” (E: 69.4% vs. UE: 57.7%, p = 0.03) could all be possible side effects of NBVs. Whilst “Amyloid/NBV product protein deposits” in particular showed a very significant difference in agreeability levels between the two groups (E: 40.8% vs. UE: 25.8%, p = 0.008). On the other hand, participants did not show statistically significant contrast in agreeability regarding “Hypersensitivity reactions”, “renal/hepatic dysfunction”, “heart disease”, “Central Nervous System dysfunction” and “joint destruction” being possible side effects. Overall, the educated group was more likely to agree about potential side effects than the uneducated group.
After calculating the total correct scores for each group, we did an independent sample t-test to compare the two groups based on their knowledge regarding the side effects of NBVs. The results showed no significant differences between the two groups (t = 0.09, p = 0.93).
Table demonstrates the knowledge and attitude of participants on the effectiveness and preferences of different types of vaccines including NBVs. Although there were no statistically significant differences between their attitude towards a certain type of vaccine to prescribe to patients between the two groups, the highest ratio in both groups preferred traditional vaccines to be prescribed to patients (E: 47.8% vs. UE: 54.6%), followed by RNA-based NBVs (E: 51.6% vs. UE: 49.7%), while DNA-based NBVs had the least level of preference (E: 33.1% vs. UE: 29.4%). The educational material group however did show significantly higher agreement (p ≤ 0.05) that NBVs would provide patients with cellular immunity, prevent chronic forms of COVID-19 and that RNA NBVs would be more effective than DNA NBVs. Meanwhile, no significant difference between the two groups’ agreeability was noted when asked about the ability of NBVs to provide patients with humoral immunity, those traditional vaccines could prevent chronic forms of COVID-19, and whether they thought that DNA-based NBVs are more effective.
Table 3. Comparisons between groups on the effectiveness and preferences of different types of vaccine
Table highlights the reasoning given by the participants for the answer to the questions: Would DNA or RNA NBVs be more effective? Participants in the group who received educational materials have fewer individuals with “no response”, establishing a response rate of 54 out of 157 (34%); while the response rate in the group who did not receive an education was 30 out of 163 (18%). Furthermore, the lack of knowledge was more among the group which did not receive education (56.4% vs. 743.6%). However, no significant difference was found when comparing the two groups using the Chi-square test (χ2 = 6.36, p = .17).
Table 4. What is your reasoning for your answer to the questions: Would DNA or RNA Nucleic acid-based vaccines be more effective?
4. Discussion
Although a handful of studies revealed the attitude of HCWs and medical students towards the COVID-19 vaccines on basis of their personal experiences and past vaccination history (Szmyd et al., Citation2021). To our knowledge, this is the first paper in the MENA region -and possibly worldwide- to examine the attitudes and knowledge of HCWs and students on the effectiveness of different types of NBVs. Similar studies were conducted worldwide showing diverse views and attitudes towards NBVs and their possible side effects. A study in Turkey used an online survey to assess the willingness of 273 primary healthcare physicians to take the COVID-19 vaccine and found that nearly half of all participants were either hesitant or straight up refused to take the vaccine, reflecting a very high level of untrust in the safety and effectiveness of the new technology (İkiışık et al., Citation2022). Another cross-sectional study compared the attitudes of HCWs and medical students towards COVID-19 vaccines and found that respondents were more worried about developing adverse effects from the vaccine than getting infected with COVID-19 itself, again demonstrating a similar level of skepticism to that illustrated in our study (Jankowska-Polańska et al., Citation2022). The study also assesses HCW’s knowledge regarding the molecular mechanism of NBVs, which is a hot area in research gaining rapid traction as some variants of NBV technologies are being used to tackle HIV and possibly some types of cancers and showing promising early results (Mu et al., Citation2021).
The study population’s demographic characteristics (Table ) were not parallel between the educated and uneducated groups. More females (59%) chose the educational material sample than males (41%), perhaps indicating that females in a healthcare setting are more willing to obtain educational material than males, especially since the level of education and other demographic characteristics were equal between the two sexes. Interestingly, fewer physicians chose to take the educational material sample over other HCWs, which could be perhaps explained by the more intense workload or confidence factors.
When asked about possible side effects that NBVs could pose (Table ), to our surprise, the educational material group was concerned about NBVs causing all the proposed side effects as compared to the non-educational material group. The possibility of new cancer formation due to gene modification displayed a statistically significant worry in the educational group, which highlights a major concern for HCWs that is reflected in the controversy seen in the population and over news and media outlets, particularly the concern of possible genetic and epigenetic modification that may aid in new cancer formation.
Other significant concerns amongst the educational group were the fear of causing immediate inflammatory reactions such as fever or rash, some of which are documented reactions to NBVs and other types of vaccines (Munavalli et al., Citation2021). The concern could stem from the strong immune reaction shown in NBV vaccines over other types of vaccines produced against SARS-CoV-2, coupled with the added knowledge of the supplementary T-cell response seen in these vaccines, which could explain the educational group being more skeptical towards acute inflammatory reactions (Okay et al., Citation2020). The most striking difference between the two groups however was the very significant alarm among the “educated” group that the protein product formed overtime from NBVs could result in misshapen/amyloid type deposits, indicating concern about the possibility of the inability of cellular mechanisms to control the rate and duration of translation of gene products from NBVs.
To assess the participants’ attitudes and knowledge of the effectiveness between different forms of NBVs (especially DNA vs RNA based vaccines, Table ). It was noted that participants had a higher ratio of a preference for RNA NBVs over DNA ones. Surprisingly, however, most of our healthcare participants preferred prescribing traditional or recombinant vaccines over NBVs. Besides, in a pilot sample that included 10 highly specialized physicians in Infectious disease/microbiology and related field, 9/10 of this pilot sample preferred mRNA vaccines if they were allowed to choose any vaccine they want (data not shown). This was not reflected among our sample of 320 HCWs, which had a more positive attitude towards non-NBVs, albeit, preferring RNA-based ones, possibly due to more concern over gene modification with DNA-based ones as shown previously (Sandbrink & Koblentz, Citation2021). Interestingly, a few knowledge gaps were detected among our HCWs’ sample, which showed a significant change in knowledge once exposed to the educational material. Namely, educated participants were significantly more agreeable about the ability of NBVs to elicit cellular immunity as well as prevent chronic forms of COVID-19 (Kallen et al., Citation2013). Combining the above points, HCWs remained cautious towards NBVs, although less so towards RNA-based ones. Despite being educated regarding the improved immunity of these vaccines, providing cellular immunity, and preventing chronic forms, our participants still preferred traditional vaccine, perhaps viewing it as a tried and tested technology with a skepticism towards the newly used technology with not enough time to assess long-term efficacy, even when provided with educational support.
When asked to provide reasoning for their previous answers (Table ) the rate of response among the education material group was almost double that of the uneducated group, as well as more answers with “I don’t know” among the uneducated group, depicting a certain level of lack of knowledge towards NBV technology. More knowledge-based answers were provided by the educated group, providing answers on the mechanism of action of RNA being utilized faster than DNA, as well as displaying concern over DNA causing alterations in the genetic material of human cells (Schlick et al., Citation2021). The last commonly displayed answer among the educated group showed concern over the lack of studies on NBV efficacy, which could be explained due to less penetration of these studies to the general knowledge of HCWs despite their rising number, as well as having fewer studies due to the novelty of this technology and having only relatively recent studies regarding this topic as compared to the decades of studies of traditional vaccines. This point becomes more interesting especially when providing the high efficacy numbers to the educated group, which still did not change the attitude towards NBVs.
The failure of our brief educational material in altering the attitudes of HCW towards accepting NBVs as the new norm in the field of vaccinology exposes a dire need for a clear, concise, and frequently updated educational material that is well integrated with the curriculum of various healthcare programs regarding NBVs on both a clinical and molecular levels. Societies hold HCW, especially physicians, to a very high standard of knowledge and credibility when seeking verification of any news (true or not) regarding new medical advancements, even more so in the current state of the world and the massive attention centered around the COVID-19 vaccination controversy and the anti-vax movement that has risen against it. Thus, it is of extreme importance for all health care communities across the globe to have their members knowledgeable and up to date with the literature regarding NBVs to direct the public towards the acceptance of NBVs vaccination campaigns and ensure their success, not only in the current pandemic but also in any possible future NBVs derived intervention this technology promises.
4.1. Limitations
Our study had a few limitations; First, the timeframe of data collection was from November 2020 to January 2021, which means it might not reflect the views of HCWs today. Also, although the educational material has provided a significant change to the knowledge gap, participants’ attitude towards prescribing NBVs did not change. This could be due to the failure of providing adequate education on the topic or the resistance to new technology. Additionally, bias may arise when participants with richer knowledge of NBVs are more interested in completing the survey than others. Like any other web-based questionnaire, it is difficult to limit access to a specific group. However, measures such as only sharing the link on HCWs and medical students’ groups and asking demographic questions were taken.
5. Conclusion
Healthcare workers’ and medical students’ knowledge gaps regarding NBVs pose a threat to any potential future vaccination campaign using this emerging technology. The study population had negative attitudes towards the possible side effects of NBVs and got even more negative when provided with the educational material. The educational material did alter the attitude of participants towards RNA-based vaccines, and they were able to provide more scientifically sound answers to back up their preference.
Authors’ contributions
Conceptualization: MM.
Study Design: MM.
Data collection: RR KS SD.
Writing: MM RR KS NS.
Data analysis: MM MA.
Acknowledgements
We would like to express our deepest appreciation to IFMSA-Jo for their help in data collection.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Additional information
Funding
References
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