Analysis of the Feasibility of a Vaccination Campaign against Influenza Epidemic and COVID-19 Pandemic in French Emergency Departments: A National Survey

Background: Vaccination is one of the most effective ways to fight the influenza epidemic and the coronavirus disease 2019 (COVID-19) pandemic, which represent a major public issue. The objective was to investigate the adherence of heads of French emergency departments (ED) and nursing departments on a potential vaccination campaign of healthcare workers (HCW) and patients in ED. Method: In February 2021, ED and nursing department heads were asked to answer a national survey. It included 24 questions designed to cover some dimensions, including characteristics of the hospital and emergency departments (ED) and questions on vaccination. Results: 414 responses out of 800 questionnaires (51.8%) were collected. Scores out of 10 were, respectively, 7 (6–8) and 8 (6–9) for vaccination against influenza and COVID-19 for HCW and 2 (2–3) and 2 (2–4) for ED patients (H = 989.3; p < 0.0001). Multivariate logistic regression found that the existence of a vaccine program in the hospital and the use of point of care influenza PCR in ED were positively associated with the acceptance of influenza vaccination campaign for HCW (p = 0.003) and patients (p = 0.015). Factors limiting adherence to a vaccination program of HCW and patients were lack of medical staff (p = 0.041 for HCW and p < 0.0001 for patients), overcrowded ED (p < 0.001), and the inability to follow up with patients after the ED visit (p < 0.0001). Conclusions: There have been many missed opportunities for influenza vaccination, and there is pressure to vaccinate against COVID-19 as soon as possible. Vaccination campaigns in ED could help to improve vaccination coverage. ED staff are more likely to vaccinate HCW than patients. There are factors that support the implementation of such programs, which can be grouped into a culture of diagnosis, control, and prevention of viral infectious diseases within the hospital and ED. On the other hand, there are limiting factors, such as overcrowding and lack of personnel.


Introduction
The seasonal influenza epidemic remains a major public health issue with 3-5 million severe cases resulting in up to 650,000 deaths annually [1]. Every winter, the seasonal flu affects 2 to 8 million people in France, causing several thousand deaths, mainly elderly people or patients with chronic diseases [2]. On the other hand, 2020-2021 are exceptional years in terms of global health crisis due to the coronavirus disease 2019 (COVID- 19) pandemic. SARS-CoV-2, the virus, is responsible for COVID-19, which was first reported in China and then became a worldwide pandemic [3]. The COVID-19 pandemic is an emergency of international concern [4]. France has been confronted with two pandemic waves, one in spring 2020 and the other since autumn 2020 ( Figure A1). France has experienced significant regional disparities, from 3.6% to more than 20% seroprevalence of anti-COVID-19 antibodies. The Grand Est region and the Ile de France region were the most affected in France by the COVID-19 pandemic [5]. Considering its high mortality and rapid spread, effective action was urgently needed [6]. The control, not only of influenza epidemics, but also of COVID-19, depends on preventive barrier and hygiene measures. Nevertheless, vaccination is certainly the most effective way to fight against these viruses [7]. Influenza vaccination coverage rates in populations at risk for severe disease vary widely around the world, ranging from 10% to 80% [8,9]; low rates are partially due to missed opportunities to vaccinate [10]. With regard to vaccination against COVID-19, the race is on to vaccinate the population. Vaccination began the last week of December 2020 and, as of March 5, has been given to about 4,000,000 people [11]. The French government is expanding vaccination training to various trained health workers to accelerate the pace of vaccination. On the other hand, according to the Ministry of Health, in 2019 there were 19,714,060 emergency department (ED) visits [12]. In this context, the aim of this study was to investigate the perception of EDs regarding the possibility of vaccinating patients with the seasonal influenza and COVID-19 vaccinations. The study hypothesis is that there may be a difference in acceptability because influenza vaccination is an annual public health mission, whereas the world is currently experiencing an unprecedented health crisis due to the COVID-19 pandemic.

Study Design
In this cross-sectional study that was undertaken in all EDs in France, ED and nursing department heads were requested to answer an electronic survey. In France, 636 hospitals have Eds, including 473 public hospitals, 36 private non-profit hospitals, and 127 private for-profit hospitals. Of these hospitals, 59% EDs receive less than 30,000 patients per year. Adult EDs number 547, while there are 73 mixed adult and pediatric EDs and 16 pediatric EDs [13]. On 12 February 2021, an electronic survey was distributed via email. Emails were compiled by using the following lists: study group for efficiency and quality of EDs and non-scheduled activities departments, as well as academic and hospital associations [13]. They were contacted on 12 February 2021. They received reminders for filling out the survey the next day and then every two days until 26 February 2021. There was an informatics check for duplication to prevent participants from responding more than once. ED department heads were asked to share the survey with nurse supervisors and physicians with responsibility for disaster response. The survey (Appendix B) included 24 questions designed to cover characteristics of the hospital and ED, management, resources, ED visits, and questions on a potential adherence to the influenza and COVID-19 vaccination campaign of healthcare workers (HCW) and patients with indication to be vaccinated. The questionnaire asked about the activity of the department, which could influence the perception of whether or not a vaccination campaign would be carried out in the ED. The questions also aimed to assess whether there was a culture of vaccination in the ED and in the hospital. Similarly, the participants were asked about the current practice of PCR testing in their ED (tetanus, influenza, and COVID-19), based on the assumption that such a practice could modify adherence to the implementation of a vaccination campaign in the ED. These questions were validated by a committee of experts using the Delphi method, wherein questions were added, removed, or modified until a consensus of at least 65% agreement was reached [13]. The experts were ED department heads with a university degree in management teaching at the University of Paris. After validation, the survey was sent to the participants.

Data Analysis
The Shapiro-Wilk test was used to assess data distribution. Continuous variables are presented as mean ± SD and, if necessary, as median and interquartile range (Q1-Q3); and categorical variables, such as number and percentage. Comparative analysis between several questions used ANOVA or Kruskal-Wallis non-parametric test to test the equality of multiple scores. In case of statistically significant results, Scheffe post hoc test was pre-specified to explore differences between multiple mean scores while controlling the experiment-wise error rate. Chi-square test, or McNemar Chi-square test, was used to compare categorical data. Univariate and multivariate logistic regression were used to determine factors associated with the willingness of ED medical and paramedical staff to vaccinate HCW and patients against influenza and COVID-19. Then, multiple logistic regression was conducted to determine the factors that might predispose respondents to agree to vaccinate HCW and patients. Factors, for which a median score of 0 to 10 was greater than the median score, related to the agreement to vaccinate HCW and patients were retained to perform the multivariate regression. Variables with p < 0.2 in univariate analysis were included in the multivariate stepwise logistic regression model to determine those related to influenza and COVID-19 vaccination.
All in all, factors that were hypothesized to impact ED caregivers to vaccinate hospital health workers and/or patients against influenza and/or COVID-19 were: geographic location of the hospital, professional status of the caregiver (medical or nursing), type of ED (adult, pediatric, or mixed), number of ED visits, characteristics of ED, existence of a vaccination center, whether or not the health workers were vaccinated against influenza in the hospital, whether or not patients were vaccinated against influenza in the hospital, existence or not of an infectious disease department in the hospital, whether or not the ED vaccinated HCW and/or patients against influenza, use of influenza PCR, use of pointof-care influenza PCR in the ED, use of influenza and/or tetanus antigen tests in the ED, and performance of tetanus vaccination in the ED. The other factors analyzed were the lack of follow-up of ED patients, the ED's lack of medical staff, the team's adherence to a possible vaccination campaign, the refusal of certain patients to be vaccinated, and lack of vaccines available on the site. p value of <0.05 was considered significant. All statistical analysis was conducted using Statistica v12 software.

Ethics Statement
Data collection and storage were approved by the French National Commission for Data Protection and Liberties. All data were completely anonymous, and the study was conducted in accordance with the 1964 Helsinki Declaration. The Emergency Ethics Committee for Biomedical Research of Assistance Publique-Hôpitaux de Paris approved this study (study number: DAG-3-BCH-21). No ethical number was required. Participants were informed about the objectives and the method. Answering the questionnaire was considered as agreeing to the terms of the study.

Results
In all, 414 responses out of 800 questionnaires (51.8%) were collected. All the responses were included in the analysis. Since all questions were mandatory, there were no missed responses. A little more than half of the participants worked in Paris (21.50%) or the Paris region (36.23%). The other participants came from 40 other French departments, including the overseas departments. Among the respondents, there were 356 (85.58%) physicians, including 82 (23.03%) ED heads and 58 (14.42%) nursing department heads. The characteristics of EDs and hospitals where they were working are given in Table 1. Participants were asked to respond with a score of 0 to 10 whether they thought that influenza and COVID-19 vaccination of HCW and patients could be part of the ED's mission. Scores are given in Figure 1. Scores out of 10 were respectively 7 (6-8) and 8 (6-9) against influenza and COVID-19 for HCW and 2 (2-3) and 2 (2-4) against influenza and COVID-19 for patients with indication to be vaccinated. These four propositions of vaccination were significantly different (H = 989.3; p < 0.0001). Significant differences were found between HCW and patients for the two vaccines (p < 0.0001) and between the two vaccines (against influenza and COVID-19) in the HCW group (p = 0.0003).
As presented in Table 2, several factors are associated with potential adherence or non-adherence to a vaccination campaign. The factors that seem to positively influence any form of vaccination are implementation of a previous vaccination campaign (p < 0.05) and use of point of care PCR in the ED (p < 0.05). Factors that seem to negatively influence any form of vaccination (especially for patient vaccination) were overload of clinical activity (p < 0.0001) and lack of staff (p < 0.0001). Lastly, lack of vaccine available in the hospital was negatively associated with the development of a vaccination strategy (p < 0.0001). As presented in Table 2, several factors are associated with potential adherence or non-adherence to a vaccination campaign. The factors that seem to positively influence any form of vaccination are implementation of a previous vaccination campaign (p < 0.05) and use of point of care PCR in the ED (p < 0.05). Factors that seem to negatively influence any form of vaccination (especially for patient vaccination) were overload of clinical activity (p < 0.0001) and lack of staff (p < 0.0001). Lastly, lack of vaccine available in the hospital was negatively associated with the development of a vaccination strategy (p < 0.0001).

Discussion
The present study aimed to explore the feasibility of vaccinating HCW, and patients in EDs with indication to be vaccinated against influenza and COVID-19. We were interested in the influenza virus, which is recurrent every year and responsible for annual deaths. This mission could be considered a public health mission, especially since there have been many missed opportunities to vaccinate patients [2]. For HCW, some studies even suggest that vaccination be mandatory so as to increase coverage [14]. Moreover, simplifying access to vaccination through decentralizing vaccination centers and providing incentives for HCW can improve the vaccination rate [15]. The vision may be different for the COVID-19 virus, which is responsible for an exceptional pandemic that is causing an unprecedented global health crisis. Seasonal influenza epidemics are responsible for a high number of severe forms of flu and deaths in unvaccinated patients with indication to be vaccinated, especially in cases where the indications for the vaccine are recognized [16], impacting the health care system with additional costs [17]. In a previous study in a Parisian academic hospital, it was found that 24% of the patients admitted in the ED during the early-and epidemic seasonal influenza period were at high risk for severe influenza, while only one third of them were vaccinated against influenza. Furthermore, missed opportunities for vaccination concerned nearly 70% of emergency patients [2]. On the other hand, 2020 and 2021 are exceptional years with an international COVID-19 pandemic that globally, by 12 March 2021, affected 118,058,503 patients, including 2,621,046 deaths reported to WHO [18]. As of 10 March 2021, a total of 300,002,228 vaccine doses have been administered. France is currently facing its second wave of the COVID-19 pandemic, which is responsible for 3,894,447 cases including 89,077 deaths according to the WHO [18]. As of 9 March 2021, 4,164,418 people have received at least one dose of COVID-19 vaccine, representing 6% of the overall population [19]. However, many patients who need to be vaccinated come to the ED and could, therefore, be vaccinated during their visit, unless they are suffering from an acute pathology contraindicating the vaccination. The present study therefore aimed to assess, by means of a survey of ED managers in France, the possibility of vaccinating HCW and patients who present to the ED and who have an indication to be vaccinated against influenza and/or COVID-19. Respondents were found to be significantly more supportive of vaccinating HCW than vaccinating patients. Among HCW, they were significantly more likely to vaccinate caregivers against COVID-19 than against influenza.
Univariate and multivariate analysis explain these differences. Factors that inhibit the ability to vaccinate patients appeared to be overcrowding, lack of medical staff, and lack of patient follow-up. Lack of follow-up of vaccinated persons was not found for HCW. The lack of difficulty in following up with colleagues may explain the more favorable opinion about vaccinating HCW compared with vaccinating patients. Logically, the factors of lack of medical staff and overload of activity were found to limit the realization of any vaccination campaign. However, a recent study showed that a vaccination campaign could be carried out in the ED without impacting the clinical activity of the department. This campaign in a French ED led to an increase of influenza vaccination coverage from 32.2 to 65.9% [20], while many multi-strategy campaigns increased vaccination coverage from 4 to 10% [21][22][23][24][25]. The strategy, developed to improve vaccination coverage, was for doctors and nurses to propose, several times if necessary, immediate vaccination during the ED consultation. In addition, the vaccine was immediately available and could be quickly administered by the nurses [20]. This strategy of vaccination by nurses could be a solution for developing vaccination programs in EDs. Indeed, our study seems to find that the lack of medical staff was a hindrance, whereas this did not seem to be the case in nursing departments. In addition, nurses seemed to be more willing to participate in a vaccination campaign than physicians. It is possible that they consider there is less of a staffing problem, and that, contrary to physicians, nurses routinely inject medication. Moreover, in univariate analysis, this study demonstrated the value of having a vaccine available to promote adherence to the vaccination program. This is consistent with the findings of Casalino et al., who hypothesized a significant increase in vaccination coverage because the vaccine was immediately available [20].
The factors that seem to favor adherence to a vaccination campaign addressed to HCW and patients seemed to be linked to an institutional and ED culture of combatting infectious viral diseases. For example, when point of care influenza PCR was carried out in the ED, and when vaccination campaigns are carried out in the hospital and in the ED, the acceptability of a vaccination campaign was promoted. Surprisingly, we found that respondents from Paris and the Paris region were more likely to support a vaccination campaign. One hypothesis could be that the Paris region was one of the most affected by the COVID-19 pandemic during the first wave. However, this hypothesis is limited by the fact that more than half of the respondents were from Paris and the Paris region (Ile de France) and by the fact that there was not much response from the Grand Est region, which is the other region that was severely affected by the COVID-19 pandemic [5]. Furthermore, this study was conducted during the second wave, during which other regions were markedly affected by COVID-19. The present study should be completed by analyzing other parameters that could influence a team's adherence to a possible vaccination campaign. Recent HCW education and experience are factors that could influence the acceptability of a vaccine for themselves [26] and, therefore, potentially influence adherence to a vaccination program of other caregivers and emergency patients. Increasing caregivers' awareness of the need to vaccinate would increase adherence to the implementation of vaccination campaigns [27]. In the study by Pichon et al., the authors also discussed the importance of training in influencing the adoption of the vaccine. They also highlighted other factors that should be analyzed, such as vaccination status and care for at-risk patients. These factors are indeed two parameters strongly influenced by a social desirability bias that can impact beliefs and adherence to the vaccination campaign [28]. In addition, HCW already vaccinated against influenza were more in favor of vaccination and even of it becoming mandatory [28].
Finally, the choice of participants was based on the fact that, in March, doctors and nurses could possibly vaccinate in France. The questionnaire therefore targeted managers and leaders in EDs. Nevertheless, as the health crisis evolves into a third wave, vaccination skills could be extended to other categories of health personnel. It might be interesting to address the survey to these categories to assess adherence to mass vaccination campaigns.

Limitations
The present study is not without limitations. First, this survey was voluntary and not all EDs responded. Respondents may be those most motivated to answer. The rate of unanswered questionnaires was high but hardly surprising in such surveys [28]. Slightly more than half of the responses came from the Paris region, which is, therefore, overrepresented compared to the other regions. This may create a bias in the weight of the responses. However, this bias is mitigated by the fact that this is the most populated region in France; the general population of this region (12.3 million inhabitants) represents 18% of the general population. Finally, there is a lack of data on non-responding EDs, which might have had a different point of view from those who answered.

Conclusions
The seasonal influenza epidemic and COVID-19 pandemic are responsible for heavy morbidity and mortality and represent a major public health issue. Vaccination is one of the most effective ways to fight these epidemics. However, there have been many missed opportunities for influenza vaccination and there is pressure to vaccinate against COVID-19 as soon as possible. Vaccination campaigns in EDs could help improve vaccination coverage. This French national survey demonstrates that ED staff are more likely to vaccinate HCW than to vaccinate patients. There are factors that support the implementation of such programs, which can be grouped into a culture of diagnosis, control, and prevention of viral infectious diseases within the hospital and ED. On the other hand, there are limiting factors, such as overcrowding and lack of personnel. This survey highlights elements for developing future vaccination campaigns against influenza and COVID-19.    Type of ED * Adult ED Pediatric ED Adult/Pediatric ED 5.
Specify the type of facility * University hospital General Hospital Private non-profit Private for profit 6.
Specify the number of annual visits * <30,000 between 30,000 and 60,000 more than 60,000 7.
Would you say that your ED (multiple responses possible) * Is very often overcrowded Waiting times are long There is not enough downstream care in the hospital The premises are inadequate Patients are often in the emergency room waiting for a hospital bed None of the above 8.
Your facility has an immunization center *. Select (Yes/No) 9.
Your facility conducts annual flu vaccination campaigns among health care staff Select (Yes/No) 10. Your facility conducts annual influenza vaccination campaigns for the general population * Select (Yes/No) 11. Your facility has an infectious disease service * Select (Yes/No) 12. The ED conducts an annual flu vaccination campaign for its staff * Select (Yes/No) 13 19. It is the ED' mission to vaccinate its staff against the flu * Select (Yes/No) Strongly disagree (0)-Strongly agree (10) 20. It is the ED's mission to vaccinate its staff against Covid * Strongly disagree (0) Strongly disagree (0)-Strongly agree (10) 21. It is the ED's mission to vaccinate ED patients with an indication for vaccination against influenza * Strongly disagree (0) Strongly disagree (0)-Strongly agree (10) 22. It is the role of the ED to vaccinate ED patients with an indication for vaccination against the flu * Strongly disagree (0) Strongly disagree (0)-Strongly agree (10)