Healthcare workers' Attitude and Knowledge Towards the Safety of Nucleotide-Based Vaccines.

doi:10.21203/rs.3.rs-744975/v1

Background and objectives: With the implementation of nucleotide-based vaccines (NBVs) in the COVID-19 vaccination campaigns, a wide controversy surrounding NBVs has become a heated subject of debate, and it did not spare healthcare workers and staff. The latter group has a powerful influence on the acceptance of NBVs by the general public. Hence, the aim of this study to assess the knowledge and attitude of healthcare workers regarding this new vaccine technology.

Methods: This is a cross-sectional study using an online survey involving health workers in Jordan. The survey assessed the participants' socio-demographic characteristics, knowledge, and attitude about the safety and efficacy if NBVs. The study population was divided into two groups, educated and uneducated groups, whereby the former received a small educational pamphlet on NBVs. The Mann-Whitney test was used to compare between the response of the two groups.

Results: A total of 330 health workers participated in this study. Respondents believed that RNA-based NBVs would be a safer option compared to DNA-based ones, with the educated group showing significant difference. The notion of NBVs being a form of gene therapy was more common among the educated group. The majority of the participants, particularly amongst the uneducated group, were concerned about undiscovered effects of NBVs. Respondents also agreed that NBVs must be reevaluated in phase 1 trials. As for efficacy, our study population agreed that these vaccines would prevent severe illness.

Conclusions: Although healthcare workers have positive knowledge and attitude towards NBVs, misconceptions and skepticism exist and must be addressed with more education efforts.

Health Economics & Outcomes Research

Health Policy

Vaccine Development

COVID-19

Education

Gene therapy

Healthcare Workers

Nucleotide-based vaccine

Vaccine Safety.

This project could lead to developing better educational material for healthcare workers regarding NBVs. Healthcare workers are the most important players in combating stigma and controversies surrounding the COVID-19 vaccination campaign. Thus, correcting any knowledge gaps they have will help them better infom the public and raising vaccination turnout rates, which is the single most important factor in ending the pandemic.

The Coronavirus Disease 2019 (COVID-19) is caused by the novel SARS-CoV-2 coronavirus and is characterized by pneumonia and respiratory failure (Poor et al. 2020) (Li et al. 2020). The first cases of COVID-19 were traced back to a popular seafood market in Wuhan city of the Hubei province in China (Rothan and Byrareddy 2020) (Hou et al. 2020). Despite strict measures mandated in the affected province to contain SARS-CoV-2, the virus spread dramatically outside of China and COVID-19 was designated as a pandemic in March of 2020 (Chen et al. 2020) (Yang et al. 2021). By February of 2021, SARS-CoV-2 had infected more than 110 million people worldwide and was linked with the death of more than two and a half million individuals (World Health Organization 2021). Non-pharmacological preventive measures such as social distancing, lockdowns, and frequent handwashing are effective in lowering viral transmission (Qian and Jiang 2020) (Mesa Vieira et al. 2020) (Chowdhury et al. 2020). However, these measures remain impractical and may have devastating ramifications on mental health and the world economy if maintained for an extended time (Kshirsagar et al. 2021) (Bandyopadhyay and Meltzer 2020) (Dalal et al. 2020) (Khan et al. 2021).

Since the beginning of the pandemic, several medications have been proposed to manage COVID-19 (Ostuzzi et al. 2020) (Mehta et al. 2020). However, the use of these medications often stirs controversies amid conflicting reports regarding their efficacy and/or safety. For example, in a small-scale clinical trial led by Gautret et al., hydroxychloroquine reduced the viral load of SARS-CoV-2 in 20 patients (NCT04371523 2020) (Kang et al. 2020) (Cui et al. 2020). Other groups, however, failed to validate the findings of Gautret et al. using other endpoints. Furthermore, in a meta-analysis of three studies that assessed the effect of hydroxychloroquine on viral clearance, not only this drug did not significantly reduce the viral load (Wu et al. 2020), the use of hydroxychloroquine was associated with an increase in patient mortality (Funck-Brentano et al. 2020) (Lane et al. 2020). Current treatment of COVID-19 involves the use of Remdesivir, an experimental antiviral drug previously tested for its clinical utility in controlling the Ebola virus, and dexamethasone (Pardo et al. 2020). However, the former has been approved for use in a small number of countries and both have yer to undergo further clinical trials to conclude their efficacy (Lamb 2020).

The scientific community worldwide quickly sensed the impact developing a vaccine against SARS-CoV-2 would have on ending the pandemic (Rosales-Mendoza et al. 2020). In addition, it appears that a safe, well-tolerated, and effective vaccine against SARS-CoV-2 may be the most cost-effective method to mitigate its spread(Perry et al. 2020). Over 40 vaccines are currently under evaluation and three of them have already passed phase III clinical trials (Calina et al. 2020) (Forni et al. 2021). The bases of these vaccines are diverse and some of the approved ones are based on new technology platforms (Yoo 2021), specifically, they are nucleotide-based. Nucleotide-based vaccines (NBVs) offer a relatively quick production cycle (Jaciubek and Prasek 2021) Their main strategy is to exploit the molecular machinery responsible for protein synthesis in the cells to produce a viral protein, which is presented on the cell surface and, in turn, stimulates an effective immune response (Kowalczyk et al. 2016) (Ho et al. 2021). NBVs have a surprisingly high efficacy rate and are successful in preventing symptomatic COVID-19 disease as measured by negative PCR results in immunized individuals by nearly 95% as compared to non-vaccinated groups (Walsh et al. 2020) (Baden et al. 2021) (Yuan et al. 2020). Importantly, NBVs are pathogen-free eliminating the possibility of infection among staff that administers the vaccine or among the patients receiving it.(Vogel et al. 2018)

This is the first time in history that NBVs are used at this wide scale and there are disproportionate controversy and misinformation regarding this important subject (Knezevic et al. 2021). Mounting controversy regarding their safety has been increasing in societies including among healthcare workers. For a vaccination program to succeed, public compliance and acceptance must prevail starting with healthcare workers (Agyekum et al. 2021) (Sallam 2021). Therefore, it is important to elucidate the attitude and knowledge of healthcare workers in regards to vaccines.(Shekhar et al. 2021) This study aims to assess the attitude and knowledge among these workers in regards to the new NBVs, which would provide a successful base to improve the overall public attitude towards this new vaccine technology.

Study design and population:

This is a cross-sectional study conducted in Jordan through an online survey. The survey was prepared in Google Forms with a consent form appended as the first page. It was delivered to medical health professionals from different healthcare sectors including physicians, nurses, pharmacists, biomedical researchers, and medical, dental, and nursing students. The invitations were delivered to participants via closed groups on Facebook and WhatsApp, the most popular social media applications used in Jordan. All participants confirmed working or studying in Jordan. Study objectives were clearly explained at the beginning of the survey, and the participants were encouraged to distribute the survey to their colleagues. The study population was divided into two groups of similar numbers. One group was given a short description describing NBVs before the data collection sheet and after consenting to the form and, hence, named “the educated” group. The other group, labeled “the uneducated group” was not provided with the same educational material (see appendix 1).

Study instrument:

The tool was developed in the English language after a thorough search in the recent literature and based on the most recently available information from the World Health Organization (WHO) on emerging respiratory viruses, including COVID-19, and vaccines. A draft survey instrument was sent to a group of experts chosen according to their experience and expertise in the related fields to assess its readability, simplicity, and relevance. A pilot study was initially carried out by randomly selecting 20 participants at Jordan University Hospital (JUH) to assess clarity, readability, and acceptability and highlight issues that they deemed important on the subject of NBVs. Refinements were made accordingly before the final survey was distributed to the study population. The data of the pilot analysis were not used for the final sample of the study.

Contents of the survey instrument and scoring system:

The survey instrument consisted of 19 closed-ended questions with responses based on a three-point Likert scale composed of the options of agree, neutral, or disagree. This survey was divided into four main sections to assess the participants' socio-demographic characteristics, the safety of RNA- versus DNA-based NBVs, the safety of NBVs in general, and attitude of and knowledge towards NBVs efficacy. The first section covered the participants' demographic and professional attributes namely age, gender, educational degree, profession, and healthcare sector. The second section consisted of 6 questions assessing the attitude and knowledge towards the safety of DNA versus RNA-based NBVs. The third section consisted of 6 questions that assessed the knowledge and attitude of respondents towards the new technology of NBVs in general and relative to non-NBVs. The fourth section inquired about the basic knowledge NBVs.

Ethical considerations:

The survey was anonymous to maintain the privacy and confidentiality of all information collected in the study. Participation in this survey was voluntary and was not monetarily compensated. Informed consent was obtained from each participant before participation. Ethical approval was obtained from the Institutional Review Board at JUH (reference number: 221000013). The study was performed following the Helsinki Declaration as revised in 2013.

Data analysis:

Descriptive and none parametric statistics were conducted by using the statistical package for social
sciences (IBM, 25). Mann-Whitney test was used to compare between the two groups of thestudy on the preference and safety of DNA vs RNA NBVs. We used the Mann-Whitney test because the dependent variables were measured in ordinal level (disagree, neutral, agree). Furthermore, the responses of the participants to the questions: Would DNA or RNA NBVs be more effective?

Were depicted in themes in the result section. (IBMCorp Ibm, S. P. S. S. (2017). Statistics for Windows, version 25.0. Armonk, NY: IBM Corp.)

Table 1 presents the descriptive statistics for the study sample. The study sample included 330 participants who were divided into two groups. The first group was composed of 157 (49.1%) participants who received educational materials of NBVs and the other group consisted of 163 (50.9%) participants who did not receive the educational materials. The ratio of males to females was almost equal in the study. The highest age group was the youngest (18–24 years), which constituted almost half of the study population. The medical students composed the highest percentage (41.3%) according to the profession of the participants. Most participants (64.7%) were associated with university hospitals.

Table 1

Descriptive statistics of the study sample (N = 320)
Variables	Uneducated N = 163	Educated N = 157	Total sample
Variables	Number (%)	Number (%)	Number (%)
Age in year
18–24	79 (48.5)	84 (53.5)	163 (50.9)
25–34	34 (20.9)	36 (22.9)	70 (21.9)
35–44	28 (17.2)	18 (11.5)	46 (14.4)
≥45	22 (13.5)	19 (12.1)	41 (12.8)
Gender
Male	92 (56.4)	65 (41.4)	157 (49.1)
Female	71 (43.6)	92 (58.6)	163 (509.)
Profession
Medical students	69 (42.3)	63 (40.1)	132 (41.3)
Physicians	55 (33.7)	34 (21.7)	89 (27.8)
Healthcare fields other than physicians	39 (23.9)	60 (38.2)	99 (30.9)
Place of work
Private sector	30 (18.4)	45 (28.7)	75 (23.4)
Public sector	21 (12.9)	17 (10.8)	38 (11.9)
University	112 (68.7)	95 (60.5)	207 (64.7)

Participants were then asked about their preference of the type of NBVs, that is DNA-based or RNA-based NBV, based on the molecular characteristics of RNA and DNA molecules, in association with the safety of the NBVs. The respondents within each group were given several statements and they would have to answer whether they agreed or disagreed with these statements, or if they had a neutral stance. Interestingly, there was good agreement among respondents that RNA-based NBVs could be safer than DNA-based NBVs since RNA cannot integrate into the human genome(Lundstrom 2018), whereas the latter can,(Ledwith et al. 2000) and that RNA molecules are degraded more easily (Table 2). In addition, whereas one-third of respondents thought that both types of vaccines are safe to be used, one-fourth of them thought that both could pose harm to humans and should not be used. The only difference between the educated and uneducated groups was their preference towards RNA-based NBVs since RNA molecules cannot be integrated into the human genome whereby more respondent within the educated group thought that RNA-based NBVs were safer than DNA-based NBVs since RNA molecules cannot integrate into the human genome (66.9% vs. 55.2%).

Table 2

Comparisons between groups on the preference and safety of DNA vs RNA Nucleotide-Based Vaccines.
	Uneducated group	Educated group	Mann-Whitney test
Items	Disagree N (%) Neutral N (%) Agree N (%)	Disagree N (%) Neutral N (%) Agree N (%)	Mann-Whitney test
Would RNA NBVs be preferred over DNA-based (or vice versa) for safety concerns? [RNA would be safer as it is degraded more easily]	13 (8.0) 62 (38.0) 88 (54.0)	14 (8.9) 60 (38.2) 83 (52.9)	12728.5
Would RNA NBVs be preferred over DNA-based (or vice versa) for safety concerns? [RNA would be safer as it is not incorporated in the genome]	14 (8.6) 59 (36.2) 90 (55.2)	10 (6.4) 42 (26.8) 105 (66.9)	11064.0*
Would RNA NBVs be preferred over DNA-based (or vice versa) for safety concerns? [DNA is safer as it only produces foreign particles]	37 (22.7) 87 (53.4) 38 (23.9)	42 (26.8) 78 (49.7) 37 (23.6)	12451.0
Would RNA NBVs be preferred over DNA-based (or vice versa) for safety concerns? [DNA is less safe as it may integrate with vital regions]	20 (12.3) 73 (44.8) 70 (42.9)	17 (10.8) 62 (39.5) 78 (49.7)	11690.0
Would RNA NBVs be preferred over DNA-based (or vice versa) for safety concerns? [Both DNA and RNA have concerning qualities and should be avoided]	43 (26.4) 80 (49.1) 40 (24.5)	50 (31.8) 67 (42.7) 40 (25.5)	12573.5
Would RNA NBVs be preferred over DNA-based (or vice versa) for safety concerns? [Both are safe to use]	22 (13.5) 88 (54.0) 53 (32.5)	22 (14.0) 77 (49.1) 58 (36.9)	12516.0
*p ≤ .05

    </tfoot>
</table>

Although in the comparison between the study groups on their knowledge and attitude toward the safety of NBVs, no significant differences were found. However, the highest percentage in the two groups agreed (71.8 & 67.5%) that NBVs full effect cannot be yet determined. Furthermore, the highest percentage of the participants in both groups agree that NBVs should be reevaluated in phase 1 trials (Table 3)

Table 3

Comparisons between groups on the safety of Nucleotide-Based vaccines.
	Uneducated group	Educated group	Mann-Whitney test
Items	Disagree N (%) Neutral N (%) Agree N (%)	Disagree N (%) Neutral N (%) Agree N (%)	Mann-Whitney test
How do you view the safety of NBVs? [NBVs full effect cannot be yet determined]	10 (6.1) 36 (22.1) 117 (71.8)	7 (4.5) 44 (28.0) 106 (67.5)	12479.5
How do you view the safety of NBVs? [NBVs should be reevaluated in phase 1 trials]	23 (14.1) 55 (33.7) 85 (52.1)	19 (12.1) 52 (33.1) 86 (54.8)	12752.0
How do you view the safety of NBVs? [NBVs are as safe as non NBV counterparts]	31 (19.0) 77 (47.2) 55 (33.7)	26 (16.6) 79 (50.3) 52 (33.1)	12711.0
How do you view the safety of NBVs? [NBVs are safer than non-NBVs]	32 (19.6) 89 (54.6) 42 (25.8)	24 (15.3) 83 (52.9) 50 (31.8)	11842.5
How do you view the safety of NBVs? [NBVs are harmful and should be reconsidered altogether]	65 (39.9) 74 (45.4) 24 (14.7)	67 (42.7) 62 (39.5) 28 (17.8)	12323.5
How do you view the safety of NBVs? [NBVs may cause new/more dangerous bacterial or viral strains]	41 (25.2) 78 (47.9) 44 (27.0)	47 (29.9) 57 (36.3) 53 (33.8)	12438.0

The participants in the education group showed significantly more agreement that ‘NBVs is a form of gene therapy’ (Kallen and Theß 2014) (Zarai et al. 2020) than the group with no education (p < .01), as well as an agreement that ‘RNA based one is more effective (p < .05). Furthermore, the majority of the participants in both groups (52.1% & 56.1%) agree that ‘NBVs would prevent severe illness of COVID’(Baden et al. 2021) (Moore 2021)(Table 4).

Table 4

Comparisons between groups on their knowledge about DNA or RNA Nucleotide-Based vaccines and their effectiveness.
	Uneducated group	Educated group	Mann-Whitney test
Items	Disagree N (%) Neutral N (%) Agree N (%)	Disagree N (%) Neutral N (%) Agree N (%)	Mann-Whitney test
How well do you agree with the following statements? [NBVs should become the industry standard for vaccine development]	19 (11.7) 82 (50.3) 62 (38.0)	15 (9.6) 69 (43.9) 73 (46.5)	11847.0
How well do you agree with the following statements? [NBVs are a form of gene therapy]	31 (19.0) 72 (44.2) 60 (36.8)	22 (14.0) 49 (31.2) 86 (54.8)	10482.0**
How well do you agree with the following statements? [Nucleotide-based vaccines (NBV) are more effective than traditional non-nucleotide-based vaccines]	14 (8.6) 92 (56.4) 57 (35.0)	16 (10.2) 69 (43.9) 72 (45.9)	11563.0
How well do you agree with the following statements? [NBVs would prevent severe illness of COVID]	10 (6.1) 68 (41.7) 85 (52.1)	7 (4.5) 62 (39.5) 88 (56.1)	12516.0
How well do you agree with the following statements? [NBVs address concerns over transmission of the virus]	18 (11.0) 76 (46.6) 69 (42.3)	19 (12.2) 69 (43.9) 69 (43.9)	12402.5
Would DNA or RNA NBVs be more effective? [DNA-based ones are more effective.]	26 (16.0) 96 (58.9) 41 (25.2)	38 (24.2) 79 (50.3) 40 (25.5)	12030.5
Would DNA or RNA NBVs be more effective? [RNA-based ones are more effective.]	13 (8.0) 96 (58.9) 54 (33.1)	9 (5.9) 79 (50.3) 69 (43.9)	11322.0*
p ≤ .05 *p ≤ .01

While few other studies examined the attitude and behavior of healthcare workers and medical students towards the COVID-19 vaccines based on their personal experiences and past vaccination history (Galanis et al. 2020) (Fu et al. 2020) (Papagiannis et al. 2021) Medical Students and SARS-CoV-2 Vaccination: Attitude and Behaviors). To our knowledge, this is the first paper to provide a deeper view of the attitudes and beliefs of healthcare workers and students on the molecular mechanism of NBVs, predominantly the newly approved mRNA COVID-19 vaccines. Additionally, the study showcased the difference in attitudes between DNA-based and RNA-based vaccines, also a poorly covered area in literature.

The participants’ demographics and their professional characteristics discussed in (Table 1) showed similar patterns in both the educated and uneducated groups. A higher percentage of female participants (59%) chose to fill the questionnaire with educational material attached than male participants (41%), suggesting that female healthcare workers show greater willingness to read educational materials than males. Noting that the study participants of both sexes had almost identical attributes concerning their level of education and other demographic factors. Surprisingly, physicians showed the least interest in being part of the “educated” group’s sample than any other healthcare field which could be referred to them having confidence in their previous knowledge on the topic or due to their heavier workload.

In assessing the knowledge and attitude of healthcare workers, students, and researchers on their preferred type of NBVs, the analysis revealed the population to view RNA-based NBVs as a safer option as compared to DNA based ones as a whole (Table 2), which perhaps reveals an issue of skepticism towards the safety of DNA therapy as a whole.(Park et al. 2021) (Soleimanpour and Yaghoubi 2021)

Giving a brief educational material about NBVs yielded no difference when challenged by questions not solidly based on scientific theory (RNA being more readily degraded than DNA, or DNA producing foreign proteins only), which indicates a healthy scientific base among Jordans’ healthcare workers regarding this topic (Table 2). On the other hand, the educational material proved significant in altering the participants' views on NBVs safety in favor of the RNA-based NBVs as opposed to DNA-based NBVs due to the reduced risk of genome incorporation (gene editing)(Pacheco et al. 2021), a very common theme in the controversy surrounding NBVs. Yet, about one third were still surprisingly skeptical of the possibility of this emerging type of vaccines being a form of gene therapy(Schlick et al. 2021), despite that the educational material provided them with improved knowledge and agreement of the population as shown in (Table 2), and that RNA does not get incorporated into the genome(Pacheco et al. 2021), which shows a heightened concern against NBVs (perhaps more so of DNA based ones). It may be that healthcare workers view NBVs as a form of gene therapy merely due to the possible misconception that NBVs is a “therapeutic” module against a disease utilizing a “gene” albeit a viral gene. Other parameters of (Table 2) yielded no difference in views regarding their safety when a comparison is made between the educated versus the uneducated groups.

When asked about the safety of NBVs in general (Table 3), only a mere third of the population across both groups (33%) considered NBVs as safe as their non-NBVs counterparts while as much as half of the total study population stayed neutral, pointing towards a clear alarm against NBVs in the population. Educational material did not play any significant role in changing the knowledge base or attitude towards NBVs in healthcare workers. The majority of the population were concerned about possible undiscovered long-term effects of NBVs and agreed that phase 1 trials were not successful in adequately revealing any potential adverse effects of these vaccines. This could indicate a significant gap in knowledge regarding the components of NBVs or knowledge of their previous safety profile assessment in these components in vaccines and therapeutics years before SARS-CoV-2 vaccines such as flu, Zika, and CMV. Interestingly enough, the controversy on the safety of NBVs was not as pronounced as it is now with COVID-19, which could be due to the pandemic, aggressive and unprecedented nature of COVID-19 which was not experienced by most people alive today.

Table 3 also showed that more than two-thirds of the population agreed that the full safety effect of NBVs cannot yet be determined, which can be viewed in a very positive light as phase 4 trials only just begun, and healthcare workers are only adopting a healthy approach towards the safety of these vaccines. Moreover, the study’s population agreed that these vaccines would be effective in preventing severe illness with COVID-19,(Moore 2021) a very important result coming out of the phase 3 trials, which would effectively reshape the health emergency of COVID-19.

Table 4 dives deeper into the participants' knowledge about NBVs and their effectiveness(Mahase 2020). The educated group showed noticeable agreement that NBVs should be the industry standard, although not significant. The most significant difference between the two study groups was, without surprises, the sharp increase amongst the educated group in declaring that “NBVs is a form of gene therapy” is a true statement when they faced it, confirming all of the previous points made about the skepticism surrounding “gene therapy”. The belief that RNA-based NBVs are more effective than their DNA-based counterpart was also significantly elevated in the educational group. The remaining statements did not illustrate any significant difference between the two groups.

Assessing the impact of the provided educational material on changing the attitudes of the healthcare population in Jordan towards NBVs leaves us with interesting findings. To our surprise, barring eliminating the fear of participants regarding RNA-based NBVs being incorporated into the human genome, the educational material failed to drastically improve the attitudes of the study’s population towards the safety of NBVs in general. This indicates the evident need for a clear, rich, and routinely updated educational material well integrated with the curriculum of various healthcare programs regarding NBVs and other modern techniques used in vaccinology. That shall aim to diminish fear arising from various misconceptions circulating around the topic, especially ‘gene therapy’, ultimately ensuring an elevated quality of knowledge and formulated opinions of healthcare workers towards NBVs.

The healthcare workers’ knowledge and attitudes are of extreme importance for healthcare sectors to improve the success of vaccination programs (Finney Rutten et al. 2021). The majority of controversy in the population relies in part on the opinion of healthcare workers or physicians (in or out of context). Thus, a well-educated front of vaccine providers (which are ultimately the healthcare workers themselves) would serve to paint an accurate picture to the patients to make a well-informed decision and consequently reduce the heated controversy surrounding the topic. Efforts from different well reputable organizations (CDC, WHO…etc) have attempted to adopt this role with varying degrees of success however, with the unprecedented anti-vaccine sentiment that is mounting in the general masses and stemming from many political, social, and educational factors, healthcare workers are still touched by these sentiments. This may serve as fuel for further controversy with the current vaccine rollout and any possible future NBVs vaccination campaigns. In our view, a unified front that has a less governmental characteristic and more of a popular front would be essential in improving vaccine efforts and outcomes, both inpatients and the healthcare field staff.

This is the first paper to examine the attitudes of healthcare workers and medical students towards the safety of the recent technology of NBVs that has been utilized in several COVID-19 vaccines while offering a deeper insight at their reasoning in terms of their knowledge on the molecular mechanism of NBVs. The study population is representative to an extent as both genders were almost equally involved and healthcare workers of various professions, specialties, and workplaces took part.

As for limitations, firstly: data collection was performed through an online survey which limited access to the survey and made it impossible to confirm the inclusion criteria for each respondent, thus putting a dent in the accuracy. Secondly: students and healthcare workers with previous knowledge about NBVs may have been more inclined to fill the survey and thus are overrepresented. Finally, the educational material being in the written form and containing in-depth molecular mechanisms may have caused several participants to skip or skim through the material without fully comprehending it. We advise future studies on the topic to rather use an animated approach to describe the topic.

The healthcare population in Jordan seems to be hesitant to declare NBVs as safe in general, lingering worries about the short duration of phase 1 trials and the uncertainty surrounding the full spectrum of possible long-term side effects.(Sharma et al. 2020) (Hodgson et al. 2021) Fears and misconceptions regarding the concept of “gene therapy” and the ability of NBVs to incorporate within the human genome are not uncommon among the study’s participants (Al-Kassmy et al. 2020). While the provided educational material was deemed unsuccessful in reshaping the opinions of participants toward NBVs, it significantly lowered the notion of RNA-based NBVS being a form of “gene therapy” among the study participants.

The research team obtained IRB approval and ethics committee approval. An adequate consent statement was added at the begging of each survey. All authors gave their consent to publish. This research did not receive any funding or grants from any party and there is no conflict of interest to declare.

We would like to acknowledge the International Federation for Medical Students Association in Jordan (IFMSA-JO) for their much-thanked help in data collection.

Authors’ contributions:

Dr. Mohammad Madadha - Study design, data analysis, manuscript writing.

Khalid Ahmed, Rama Rayyan , Nancy Al-Sanouri - Data collection, manuscript writing.

Dr. Mamoun Ahram - Manuscript writing.

Dr. Saddam Al Demour - Data collection.

Dr. Muayyad Ahmad - Data analysis.

Agyekum, M. W., Frempong Afrifa-Anane, G., Kyei-Arthur, F., Addo, B., & Author, C. (2021). Acceptability of COVID-19 vaccination among health care workers in Ghana. medRxiv.

Al-Kassmy, J., Pedersen, J., & Kobinger, G. (2020). Vaccine candidates against coronavirus infections. Where does COVID-19 stand? Viruses. https://doi.org/10.3390/v12080861

Baden, L. R., El Sahly, H. M., Essink, B., Kotloff, K., Frey, S., Novak, R., et al. (2021). Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. New England Journal of Medicine. https://doi.org/10.1056/nejmoa2035389

Bandyopadhyay, G., & Meltzer, A. (2020). Let us unite against COVID-19 - A New Zealand perspective. Irish Journal of Psychological Medicine. https://doi.org/10.1017/ipm.2020.44

Calina, D., Sarkar, C., Arsene, A. L., Salehi, B., Docea, A. O., Mondal, M., et al. (2020). Recent advances, approaches and challenges in targeting pathways for potential COVID-19 vaccines development. Immunologic Research. https://doi.org/10.1007/s12026-020-09154-4

Chen, J., Guo, Y. C., Ye, L., Zhou, M. Y., Cheng, Y. R., Wang, M. W., & Feng, Z. H. (2020). Internet+ and COVID-19 - A short report. European Review for Medical and Pharmacological Sciences. https://doi.org/10.26355/eurrev_202005_21213

Chowdhury, R., Heng, K., Shawon, M. S. R., Goh, G., Okonofua, D., Ochoa-Rosales, C., et al. (2020). Dynamic interventions to control COVID-19 pandemic: a multivariate prediction modelling study comparing 16 worldwide countries. European Journal of Epidemiology. https://doi.org/10.1007/s10654-020-00649-w

Cui, C., Tu, S., En, V. S. J., Li, X., Yao, X., Li, H., & Liu, D. (2020). Review on the Clinical Pharmacology of Hydroxychloroquine Sulfate for the Treatment of COVID-19. Current Drug Metabolism. https://doi.org/10.2174/1389200221666200610172929

Dalal, P. K., Roy, D., Choudhary, P., Kar, S. K., & Tripathi, A. (2020). Emerging mental health issues during the COVID-19 pandemic: An Indian perspective. Indian Journal of Psychiatry. https://doi.org/10.4103/psychiatry.IndianJPsychiatry_372_20

Finney Rutten, L. J., Zhu, X., Leppin, A. L., Ridgeway, J. L., Swift, M. D., Griffin, J. M., et al. (2021). Evidence-Based Strategies for Clinical Organizations to Address COVID-19 Vaccine Hesitancy. Mayo Clinic Proceedings. https://doi.org/10.1016/j.mayocp.2020.12.024

Forni, G., Mantovani, A., Forni, G., Mantovani, A., Moretta, L., Rappuoli, R., et al. (2021). COVID-19 vaccines: where we stand and challenges ahead. Cell Death and Differentiation. https://doi.org/10.1038/s41418-020-00720-9

Fu, C., Wei, Z., Pei, S., Li, S., Sun, X., & Liu, P. (2020). Acceptance and preference for COVID-19 vaccination in health-care workers (HCWs). medRxiv. https://doi.org/10.1101/2020.04.09.20060103

Funck-Brentano, C., Nguyen, L. S., & Salem, J.-E. (2020). Retraction and republication: cardiac toxicity of hydroxychloroquine in COVID-19. The Lancet. https://doi.org/10.1016/s0140-6736(20)31528-2

Galanis, P. A., Vraka, I., Fragkou, D., Bilali, A., & Kaitelidou, D. (2020). Intention of health care workers to accept COVID-19 vaccination and related factors: a systematic review and meta-analysis. medRxiv. https://doi.org/10.1101/2020.12.08.20246041

Ho, W., Gao, M., Li, F., Li, Z., Zhang, X. Q., & Xu, X. (2021). Next-Generation Vaccines: Nanoparticle-Mediated DNA and mRNA Delivery. Advanced Healthcare Materials. https://doi.org/10.1002/adhm.202001812

Hodgson, S. H., Mansatta, K., Mallett, G., Harris, V., Emary, K. R. W., & Pollard, A. J. (2021). What defines an efficacious COVID-19 vaccine? A review of the challenges assessing the clinical efficacy of vaccines against SARS-CoV-2. The Lancet Infectious Diseases. https://doi.org/10.1016/S1473-3099(20)30773-8

Hou, C., Chen, J., Zhou, Y., Hua, L., Yuan, J., He, S., et al. (2020). The effectiveness of quarantine of Wuhan city against the Corona Virus Disease 2019 (COVID-19): A well-mixed SEIR model analysis. Journal of Medical Virology. https://doi.org/10.1002/jmv.25827

Jaciubek, M., & Prasek, K. (2021). COVID-19 vaccine - Technical aspects of vaccination. Pielegniarstwo XXI Wieku. https://doi.org/10.2478/pielxxiw-2021-0009

Kallen, K. J., & Theß, A. (2014). A development that may evolve into a revolution in medicine: MRNA as the basis for novel, nucleotide-based vaccines and drugs. Therapeutic Advances in Vaccines. https://doi.org/10.1177/2051013613508729

Kang, C. K., Seong, M. W., Choi, S. J., Kim, T. S., Choe, P. G., Song, S. H., et al. (2020). In vitro activity of lopinavir/ritonavir and hydroxychloroquine against severe acute respiratory syndrome coronavirus 2 at concentrations achievable by usual doses. Korean Journal of Internal Medicine. https://doi.org/10.3904/KJIM.2020.157

Khan, K. I., Niazi, A., Nasir, A., Hussain, M., & Khan, M. I. (2021). The effect of COVID-19 on the hospitality industry: The implication for open innovation. Journal of Open Innovation: Technology, Market, and Complexity. https://doi.org/10.3390/joitmc7010030

Knezevic, I., Liu, M. A., Peden, K., Zhou, T., & Kang, H. N. (2021). Development of mRNA vaccines: Scientific and regulatory issues. Vaccines. https://doi.org/10.3390/vaccines9020081

Kowalczyk, A., Doener, F., Zanzinger, K., Noth, J., Baumhof, P., Fotin-Mleczek, M., & Heidenreich, R. (2016). Self-adjuvanted mRNA vaccines induce local innate immune responses that lead to a potent and boostable adaptive immunity. Vaccine. https://doi.org/10.1016/j.vaccine.2016.05.046

Kshirsagar, M. M., Dodamani, A. S., Dodamani, G. A., Khobragade, V. R., & Deokar, R. N. (2021). Impact of Covid-19 on Mental Health: An Overview. Reviews on Recent Clinical Trials. https://doi.org/10.2174/1574887115666210105122324

Lamb, Y. N. (2020). Remdesivir: First Approval. Drugs. https://doi.org/10.1007/s40265-020-01378-w

Lane, J. C. E., Weaver, J., Kostka, K., Duarte-Salles, T., Abrahao, M. T. F., Alghoul, H., et al. (2020). Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis: a multinational, retrospective study. The Lancet Rheumatology. https://doi.org/10.1016/S2665-9913(20)30276-9

Ledwith, B. J., Manam, S., Troilo, P. J., Barnum, A. B., Pauley, C. J., Griffiths, T. G., et al. (2000). Plasmid DNA vaccines: Investigation of integration into host cellular DNA following intramuscular injection in mice. Intervirology. https://doi.org/10.1159/000053993

Li, Y. C., Bai, W. Z., & Hashikawa, T. (2020). The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. Journal of Medical Virology. https://doi.org/10.1002/jmv.25728

Lundstrom, K. (2018). Latest development on RNA-based drugs and vaccines. Future Science OA. https://doi.org/10.4155/fsoa-2017-0151

Mahase, E. (2020). Covid-19: Moderna vaccine is nearly 95% effective, trial involving high risk and elderly people shows. BMJ. https://doi.org/10.1136/bmj.m4471

Mehta, B., Moezinia, C. J., Jannat-Khah, D., Gibofsky, A., Tornberg, H., Pearce-Fisher, D., et al. (2020). Hydroxychloroquine and Chloroquine in COVID-19: A Survey of Prescription Patterns among Rheumatologists. Journal of Clinical Rheumatology. https://doi.org/10.1097/RHU.0000000000001539

Mesa Vieira, C., Franco, O. H., Gómez Restrepo, C., & Abel, T. (2020). COVID-19: The forgotten priorities of the pandemic. Maturitas. https://doi.org/10.1016/j.maturitas.2020.04.004

Moore, J. P. (2021). Approaches for Optimal Use of Different COVID-19 Vaccines. JAMA. https://doi.org/10.1001/jama.2021.3465

NCT04371523. (2020). Hydroxychloroquine to Prevent COVID-19 Disease Amongst Healthcare Workers. https://clinicaltrials.gov/show/NCT04371523.

Ostuzzi, G., Papola, D., Gastaldon, C., Schoretsanitis, G., Bertolini, F., Amaddeo, F., et al. (2020). Safety of psychotropic medications in people with COVID-19: Evidence review and practical recommendations. BMC Medicine. https://doi.org/10.1186/s12916-020-01685-9

Pacheco, T. J. A., Silva, V. C. M. da, Souza, D. G. de, Borges, M. B. S., & Silva, S. A. e. (2021). COVID-19: Do DNA / RNA vaccines integrate into the genome? Research, Society and Development. https://doi.org/10.33448/rsd-v10i1.12103

Papagiannis, D., Rachiotis, G., Malli, F., Papathanasiou, I. V., Kotsiou, O., Fradelos, E. C., et al. (2021). Acceptability of covid-19 vaccination among greek health professionals. Vaccines. https://doi.org/10.3390/vaccines9030200

Pardo, J., Shukla, A. M., Chamarthi, G., & Gupte, A. (2020). The journey of remdesivir: From Ebola to COVID-19. Drugs in Context. https://doi.org/10.7573/DIC.2020-4-14

Park, K. S., Sun, X., Aikins, M. E., & Moon, J. J. (2021). Non-viral COVID-19 vaccine delivery systems. Advanced Drug Delivery Reviews. https://doi.org/10.1016/j.addr.2020.12.008

Perry, C., Mizer, A., Wynn, A., & Kruczek, C. (2020). Countering COVID-19 vaccine hesitancy. The Southwest Respiratory and Critical Care Chronicles. https://doi.org/10.12746/swrccc.v8i36.749

Poor, H. D., Ventetuolo, C. E., Tolbert, T., Chun, G., Serrao, G., Zeidman, A., et al. (2020). COVID‐19 critical illness pathophysiology driven by diffuse pulmonary thrombi and pulmonary endothelial dysfunction responsive to thrombolysis. Clinical and Translational Medicine. https://doi.org/10.1002/ctm2.44

Qian, M., & Jiang, J. (2020). COVID-19 and social distancing. Journal of Public Health (Germany). https://doi.org/10.1007/s10389-020-01321-z

Rosales-Mendoza, S., Márquez-Escobar, V. A., González-Ortega, O., Nieto-Gómez, R., & Arévalo-Villalobos, J. I. (2020). What does plant-based vaccine technology offer to the fight against COVID-19? Vaccines. https://doi.org/10.3390/vaccines8020183

Rothan, H. A., & Byrareddy, S. N. (2020). The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. Journal of Autoimmunity. https://doi.org/10.1016/j.jaut.2020.102433

Sallam, M. (2021). Covid-19 vaccine hesitancy worldwide: A concise systematic review of vaccine acceptance rates. Vaccines. https://doi.org/10.3390/vaccines9020160

Schlick, T., Zhu, Q., Jain, S., & Yan, S. (2021). Structure-altering mutations of the SARS-CoV-2 frameshifting RNA element. Biophysical Journal. https://doi.org/10.1016/j.bpj.2020.10.012

Sharma, O., Sultan, A. A., Ding, H., & Triggle, C. R. (2020). A Review of the Progress and Challenges of Developing a Vaccine for COVID-19. Frontiers in Immunology. https://doi.org/10.3389/fimmu.2020.585354

Shekhar, R., Sheikh, A. B., Upadhyay, S., Singh, M., Kottewar, S., Mir, H., et al. (2021). COVID-19 vaccine acceptance among health care workers in the united states. Vaccines. https://doi.org/10.3390/vaccines9020119

Soleimanpour, S., & Yaghoubi, A. (2021). COVID-19 vaccine: where are we now and where should we go? Expert Review of Vaccines. https://doi.org/10.1080/14760584.2021.1875824

Vogel, A. B., Lambert, L., Kinnear, E., Busse, D., Erbar, S., Reuter, K. C., et al. (2018). Self-Amplifying RNA Vaccines Give Equivalent Protection against Influenza to mRNA Vaccines but at Much Lower Doses. Molecular Therapy. https://doi.org/10.1016/j.ymthe.2017.11.017

Walsh, E. E., Frenck, R. W., Falsey, A. R., Kitchin, N., Absalon, J., Gurtman, A., et al. (2020). Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates. New England Journal of Medicine, 383(25), 2439–2450. https://doi.org/10.1056/nejmoa2027906

World Health Organization. (2021). COVID-19 Weekly Epidemiological Update. 7 february 2021. World Health Organization.

Wu, R., Wang, L., Kuo, H. C. D., Shannar, A., Peter, R., Chou, P. J., et al. (2020). An Update on Current Therapeutic Drugs Treating COVID-19. Current Pharmacology Reports. https://doi.org/10.1007/s40495-020-00216-7

Yang, Q., Xiao, X., Gu, X., Liang, D., Cao, T., Mou, J., et al. (2021). Surveillance of common respiratory infections during the COVID-19 pandemic demonstrates the preventive efficacy of non-pharmaceutical interventions. International Journal of Infectious Diseases. https://doi.org/10.1016/j.ijid.2021.02.027

Yoo, J. H. (2021). What We Do Know and Do Not Yet Know about COVID-19 Vaccines as of the Beginning of the Year 2021. Journal of Korean Medical Science. https://doi.org/10.3346/jkms.2021.36.e54

Yuan, P., Ai, P., Liu, Y., Ai, Z., Wang, Y., Cao, W., et al. (2020). Safety, Tolerability, and Immunogenicity of COVID-19 Vaccines: A Systematic Review and Meta-Analysis. medRxiv. https://doi.org/10.1101/2020.11.03.20224998

Zarai, Y., Zafrir, Z., Siridechadilok, B., Suphatrakul, A., Roopin, M., Julander, J., & Tuller, T. (2020). Evolutionary selection against short nucleotide sequences in viruses and their related hosts. DNA Research. https://doi.org/10.1093/dnares/dsaa008

Healthcare workers' Attitude and Knowledge Towards the Safety of Nucleotide-Based Vaccines.

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Version 1

Abstract

Statement of Impact

Introduction

Materials And Methods

Results

Discussion

Strengths And Limitations

Conclusion

Declarations

References

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Version 1