European Vaccine Research Articles

Chapter 14: TBE-Prevention: Vaccines and Immunoglobulins

Worldwide there are 6 different TBE vaccines – two from Western Europe, three from Russia and one from China. The two western European vaccines and one of the Russian vaccines have an adult and a pediatric formulation. The products names are FSME IMMUN and FSME-IMMUN Junior; Encepur adults and Encepur children, Klesch-E-Vac, EnceVir and EnceVir Neo, Dry lyophilized TBE Moscow and Sen Tai Bao All TBE vaccines except the one from China have similar but not identical immunization schedules with primary immunization (>3 doses) and regular booster vaccinations. For FSME-IMMUN, Encepur and EnceVir rapid immunization schedules are also licensed. The Chinese vaccine is given with 2 primary doses 2 weeks apart followed by annual boosters. All vaccines induce significant immune responses. In the absence of a formal correlate of protection, the presence of neutralizing antibodies is used as a surrogate marker for protection. Recent clinical studies show long-term seropersistence of TBE antibodies after the first booster vaccination (dose 4) with the two European vaccines. An effectiveness of approximately 99% (years 2000–2006) and 98.7% (years 2000-2011) was calculated for regularly vaccinated persons in Austria, a country with established high vaccination uptake. Whereas in Western Europe post-exposure prophylaxis with immunoglobulins was discontinued in the late 1990s, in the highly endemic regions of Russia it continues to be common practice. Both – FSME-IMMUN and Encepur are well tolerated with a well-established safety profile. TBE-Moscow and EnceVir appear to be somewhat more reactogenic.

In the Name of Transparency: Organizing European pharmaceutical markets through struggles over transparency devices

The controversies surrounding the heavily redacted contracts between the European Commission and Covid-19 vaccine producers have highlighted ‘transparency’ as a hotly debated concept in the pharmaceutical market. We combine research on transparency with literature on the organization of markets to investigate how such struggles over competing visions of transparency end up shaping markets and their politics. Focusing on the case of the European pharmaceutical market, we demonstrate how market transparency was implemented through devices that enacted specific visions of transparency and produced distinct market organizations over time: transparency for states (until about 1990), transparency for corporations (ca. 1990 to 2010) and transparency for state coalitions (since 2010). We discuss how the specific instrumentations and materializations of such visions of transparency play a crucial role in market politics. This debate also highlights why engaging in controversies over transparency has become increasingly important for those contesting the market status quo – in pharmaceutical markets and beyond.

Oral side effects of COVID-19 vaccines in 32 European countries: Analysis of EudraVigilance reports.

The recent reports of oral side effects (SEs) following COVID-19 vaccination warrant further investigation into their prevalence, severity, and aetiology. This study was conducted to synthesize the first-ever population-level evidence about oral SEs of COVID-19 vaccines in Europe. The European Union Drug Regulating Authorities Pharmacovigilance (EudraVigilance) database was accessed in August 2022 to extract summary data of all potential oral SEs reported after COVID-19 vaccination. The data were reported descriptively and cross-tabulated to facilitate sub-group analysis per vaccine type, sex, and age group. Dysgeusia was the most commonly reported oral SE (0.381 case per each 100 received reports), followed by oral paraesthesia (0.315%), ageusia (0.296%), lip swelling (0.243%), dry mouth (0.215%), oral hypoaesthesia (0.210%), swollen tongue (0.207%), and taste disorder (0.173%). Females had significantly (Sig. < 0.001) a higher prevalence of all most common (top 20) oral SEs, except for salivary hypersecretion, which was equally prevalent among females and males. The present study revealed a low prevalence of oral SEs, with taste-related, other sensory and anaphylactic SEs being the most common SEs in Europe, similar to what was found earlier among the US population. Future studies should explore the potential risk factors of oral sensory and anaphylactic SEs to verify whether they are causally linked to COVID-19 vaccines.

Safety of COVID-19 Vaccines Among the Paediatric Population: Analysis of the European Surveillance Systems and Pivotal Clinical Trials.

The European Medicine Agency extended the use of Comirnaty, Spikevax, and Nuvaxovid in paediatrics; thus, these vaccines require additional real-world safety evidence. Herein, we aimed to monitor the safety of COVID-19 vaccines through Covid-19 Vaccine Monitor (CVM) and EudraVigilance surveillance systems and the published pivotal clinical trials. In a prospective cohort of vaccinees aged between 5 and 17 years, we measured the frequency of commonly reported (local/systemic solicited) and serious adverse drug events (ADRs) following the first and second doses of COVID-19 vaccines in Europe using data from the CVM cohort until April 2022. The results of previous pivotal clinical trials and data in the EudraVigilance were also analysed. The CVM study enrolled 658 first-dose vaccinees (children aged 5-11 years; n = 250 and adolescents aged 12-17 years; n = 408). Local/systemic solicited ADRs were common, whereas serious ADRs were uncommon. Among Comirnaty first and second dose recipients, 28.8% and 17.1% of children and 54.2% and 52.2% of adolescents experienced at least one ADR, respectively; injection-site pain (29.2% and 20.7%), fatigue (16.1% and 12.8%), and headache (22.1% and 19.3%) were the most frequent local and systemic ADRs. Results were consistent but slightly lower than in pivotal clinical trials. Reporting rates in Eudravigilance were lower by a factor of 1000. The CVM study showed high frequencies of local solicited reactions after vaccination but lower rates than in pivotal clinical trials. Injection-site pain, fatigue, and headache were the most commonly reported ADRs for clinical trials, but higher than spontaneously reported data.

Oral Adverse Events of COVID-19 Vaccines in Europe: Analysis of EudraVigilance Database

Oral Adverse Events of COVID-19 Vaccines in Europe: Analysis of EudraVigilance Database

A Pharmacoepidemiological Study of Myocarditis and Pericarditis Following the First Dose of mRNA COVID-19 Vaccine in Europe.

This study assessed the myocarditis and pericarditis reporting rate of the first dose of mRNA COVID-19 vaccines in Europe. Myocarditis and pericarditis data pertinent to mRNA COVID-19 vaccines (1 January 2021-11 February 2022) from EudraVigilance database were combined with European Centre for Disease Prevention and Control (ECDC)'s vaccination tracker data. The reporting rate was expressed as events (occurring within 28 days of the first dose) per 1 million individuals vaccinated. An observed-to-expected (OE) analysis quantified excess risk for myocarditis or pericarditis following the first mRNA COVID-19 vaccination. The reporting rate of myocarditis per 1 million individuals vaccinated was 17.27 (95% CI, 16.34-18.26) for CX-024414 and 8.44 (95% CI, 8.18-8.70) for TOZINAMERAN; and of pericarditis, 9.76 (95% CI, 9.06-10.51) for CX-024414 and 5.79 (95% CI, 5.56-6.01) for TOZINAMERAN. Both vaccines produced a myocarditis standardized morbidity ratio (SMR) > 1, with the CX-024414 vaccine having a greater SMR than TOZINAMERAN. Regarding TOZINAMERAN, SMR for pericarditis was >1 when considering the lowest background incidence, but <1 when considering the highest background incidence. Our results suggest an excess risk of myocarditis following the first dose of the mRNA COVID-19 vaccine, but the relationship between pericarditis and the mRNA COVID-19 vaccine remains unclear.

Examination of Preferences for COVID-19 Vaccines in Hungary Based on Their Properties-Examining the Impact of Pandemic Awareness with a Hybrid Choice Approach.

The COVID-19 pandemic has posed a huge challenge to the world in recent years. The development of vaccines that are as effective as possible and accessible to society offers a promising alternative for addressing the problems caused by this situation as soon as possible and to restore the pre-epidemic system. The present study investigated the preferences of residents in Hungary's second-largest city (Debrecen) for the COVID-19 vaccine. To achieve this aim, a discrete choice experiment was conducted with 1011 participants, and the vaccine characteristics included in the design of the experiment were determined by qualitative methods and a pilot survey: (1) country of origin; (2) efficiency; (3) side effect; and (4) duration of protection. During the data collection at three vaccination sites, respondents were asked to choose between three vaccine alternatives and one "no choice" option in eight decision situations. Discrete choice model estimations were performed using a random parameter logit (RPL) specification with the final model extended to include a latent variable measuring pandemic awareness. The results showed that the vaccine with a Chinese country of origin is the least preferred among the respondents, while the Hungarian and the European vaccines are the most preferred. Furthermore, the increase in the vaccine efficiency level increased the respondents' sense of utility for the vaccine; the short-term side effect was preferred to the long-term one; and the increase in the duration of protection provided by the vaccine increased the respondents' sense of utility for the vaccine. Based on the parameter estimated for the latent variable, it can be concluded that as the level of pandemic awareness (which is more positive among people with chronic diseases and less important among health workers) increases, the choice of a vaccine option becomes more preferred among respondents compared to the "no choice". The results of our investigation could contribute towards increasing compliance in the case of the vaccination-rejecting population, not only for COVID-19, but for any kind of vaccination procedure.

The Value of Rotavirus Vaccination in Europe: A Call for Action.

The severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) pandemic has pushed many healthcare systems into crisis. High vaccine coverage amongst children reduces emergency room presentations, hospital admissions and deaths due to vaccine-preventable diseases, freeing up healthcare resources including polymerase chain reaction testing for patients with SARS-CoV-2. In Europe, rotavirus gastroenteritis leads to 75,000-150,000 hospitalisations and up to 600,000 medical encounters annually. Nevertheless, in 2022, only 18 countries in Europe (out of 38) have a publicly funded routine universal mass immunisation programme against rotavirus gastroenteritis. Evidence available in the last few years re-emphasises that rotavirus vaccines currently available in Europe are highly effective, preventing up to 96% of rotavirus-related hospitalisations in children less than 1year of age (potentially 72,000-144,000 hospitalisations Europe-wide). Long-term surveillance indicates that rotavirus vaccination does not result in an overall increase in intussusception. On the contrary, increasing evidence suggests an overall reduction in intussusception in the first 12months of life when early, high rotavirus vaccine coverage is achieved. Prevention of rotavirus gastroenteritis has marked positive impacts on parental wages and government tax revenue, with benefits extending across the whole economy. In the SARS-CoV-2 pandemic setting there is a new imperative to achieve high levels of paediatric vaccination against vaccine-preventable diseases, including rotavirus gastroenteritis. The introduction of rotavirus universal mass vaccination can be expected to reduce the number of preventable illnesses, hospitalisations and deaths caused by rotavirus gastroenteritis. Reducing vaccine-preventable diseases is particularly urgent at this time when healthcare systems are preoccupied and overwhelmed with SARS-CoV-2. Graphical abstract available for this article.

H1N1 G4 swine influenza T cell epitope analysis in swine and human vaccines and circulating strains uncovers potential risk to swine and humans.

Pandemic influenza viruses may emerge from animal reservoirs and spread among humans in the absence of cross-reactive antibodies in the human population. Immune response to highly conserved T cell epitopes in vaccines may still reduce morbidity and limit the spread of the new virus even when cross-protective antibody responses are lacking. We used an established epitope content prediction and comparison tool, Epitope Content Comparison (EpiCC), to assess the potential for emergent H1N1 G4 swine influenza A virus (G4) to impact swine and human populations. We identified and computed the total cross-conserved T cell epitope content in HA sequences of human seasonal and experimental influenza vaccines, swine influenza vaccines from Europe and the United States (US) against G4. The overall T cell epitope content of US commercial swine vaccines was poorly conserved with G4, with an average T cell epitope coverage of 35.7%. EpiCC scores for the comparison between current human influenza vaccines and circulating human influenza strains were also very low. In contrast, the T cell epitope coverage of a recent European swine influenza vaccine (HL03) was 65.8% against G4. Poor T cell epitope cross-conservation between emergent G4 and swine and human influenza vaccines in the US may enable G4 to spread in swine and spillover to human populations in the absence of protective antibody response. One European influenza vaccine, HL03, may protect against emergent G4. This study illustrates the use of the EpiCC tool for prospective assessment of existing vaccine strains against emergent viruses in swine and human populations.

The implications of globalization on COVID-19 vaccination in Europe

Although globalization has left its mark on economic dynamism, causing conditionalities among various aspects (market openness, production networks, technological and information developments, migratory flows, international cooperation, humanitarian support, etc.), the less pleasant side of it should not be omitted, i.e. the emergence of the framework for the faster diffusion of epidemiological diseases. Thus, with the onset of the SARS-CoV-2 virus, its widespread circulation is a serious challenge for the provision of efficient solutions to combat it, especially in countries with fragile health systems, poor institutional quality and lack of resources. In this paper we aim to investigate the implications of globalization on the COVID-19 vaccination of the population. The period under analysis is January 1, 2021–January 1, 2022, using montly data, and the object of our study are 48 European states. To capture the relationship between globalization and the vaccination rate, we applied regression models, including a number of factors that may influence the progress of vaccination. In order to test the robustness of the results, the two-stage least squares (2SLS) regressions was used. The regression models developed underlined that globalization impacts the degree of vaccination. More globalized economies are more competitive in COVID-19 management, and the significance of this effect comes from better interconnection in global markets and easier access to medical discoveries. At the same time, countries with a higher vaccination rate are associated with higher levels of development. Based on the results obtained, we proposed some policy recommendations to increase the propensity to vaccinate, ensure equity in the distribution of vaccines and provide financial support to developing countries.

COVID-19 Infection in Chronic Kidney Disease Patients in Bulgaria: Risk Factors for Death and Acute Kidney Injury.

Regarding COVID-19 infection, Bulgaria has one of the lowest rates of vaccination in Europe, and its COVID-19-related mortality rate has been one of the highest in the European Union. Chronic kidney disease (CKD)-COVID-19 patients are at higher risk of developing acute kidney injury (AKI) and death after hospital admission. This single-center prospective cohort study from Bulgaria included 120 in-patient COVID-19 subjects of whom 70 had CKD and 50 normal renal function. Diabetes mellitus, hypertension, obesity, and cardiovascular disease were statistically more prevalent in the CKD group as compared to the non-CKD group. At admission, D-dimer, creatinine, and urea levels were significantly higher in the CKD group, whereas estimated glomerular-filtration rate was significantly lower as compared to the non-CKD patients. During hospitalization, 23 patients (19.1%) died, of which 19 were in the CKD group (p-value = 0.0096); in addition, 38 developed AKI (31.6%), of which 31 were in the CKD group (p-value = 0.0006). Using binary logistic regression, being male, having experienced AKI, and not having been treated with remdesivir were independent risk factors for COVID-19-induced mortality. Regarding risk of AKI, having had COVID-19-related symptoms for more than 6 days before admission, having CKD at baseline, and having not received remdesivir therapy were independent predictive factors for developing AKI after admission.

Comparative assessment of myocarditis and pericarditis reporting rates related to mRNA COVID-19 vaccines in Europe and the United States

ABSTRACT Objectives The novel mRNA vaccines proved to be safe and effective in averting severe COVID-19. Vaccine-related complications recorded by pharmacovigilance systems, such as ‘EudraVigilance’ in Europe and ‘VAERS’ in the United States (US), rarely include myocarditis and pericarditis. Given the novelty of the platform and the increasing global-scale vaccine production needs, we assessed their reporting rates comparatively across continents. Methods Data of myocarditis and pericarditis cases post COVID-19 vaccination reported from week 52/2020 (December 21 to 27, 2020) to week 40/2021 (October 4 to 10, 2021) were collected for mRNA vaccines from EudraVigilance and VAERS. The corresponding administered vaccine doses were used as denominators to estimate reporting rates for comparison purposes. Cross-tabulation analysis was employed to compare the reporting rates of mRNA vaccines-associated myocarditis and pericarditis between EudraVigilanceand VAERS. Results Low reporting rates of myocarditis (7.64/million vaccine doses) and pericarditis (5.32/million) were found, with higher rates of both disorders in EudraVigilance compared to VAERS; these differences were more pronounced post-mRNA-1273 (5-6-fold, p=0.000 for myocarditis and p<0.001 for pericarditis) than post-BNT162b2 vaccination (1.5-2-fold, p<0.001 for both conditions). Most myocarditis cases occurred in males <30 years. Pericarditis affected predominantly males <40 and both sexes >40 years. The extremely rare fatalities related to myocarditis (0.102/million) or pericarditis (0.017/million) were also higher in EudraVigilance versus VAERS. Conclusions Understanding the underlying causes of the observed differences could provide guidance for the enhanced quality of mRNA vaccines that would also foster vaccine acceptance.

Chapter 14: Prevention: vaccines and immunoglobulins

Worldwide there are 6 different TBE vaccines – two from Western Europe, three from Russia and one from China. The two western European vaccines and one of the Russian vaccines have an adult and a pediatric formulation. The products names are FSME IMMUN and FSME-IMMUN Junior; Encepur adults and Encepur children, Klesch-E-Vac, EnceVir and EnceVir Neo, Dry lyophilized TBE Moscow and Sen Tai Bao All TBE vaccines except the one from China have similar but not identical immunization schedules with primary immunization (&gt;3 doses) and regular booster vaccinations. For FSME-IMMUN, Encepur and EnceVir rapid immunization schedules are also licensed. The Chinese vaccine is given with 2 primary doses 2 weeks apart followed by annual boosters. All vaccines induce significant immune responses. In the absence of a formal correlate of protection, the presence of neutralizing antibodies is used as a surrogate marker for protection. Recent clinical studies show long-term seropersistence of TBE antibodies after the first booster vaccination (dose 4) with the two European vaccines. An effectiveness of approximately 99% (years 2000–2006) and 98,7% (years 2000-2011) was calculated for regularly vaccinated persons in Austria, a country with established high vaccination uptake. Whereas in Western Europe post-exposure prophylaxis with immunoglobulins was discontinued in the late 1990s, in the highly endemic regions of Russia it continues to be common practice. Both - FSME-IMMUN and Encepur are well tolerated with a well-established safety profile. TBE-Moscow and EnceVir appear to be somewhat more reactogenic.

A 5-year look-back at the notification and management of vaccine supply shortages in Germany.

BackgroundUnavailability of vaccines endangers the overall goal to protect individuals and whole populations against infections.MethodsThe German notification system includes the publication of vaccine supply shortages reported by marketing authorisation holders (MAH), information on the availability of alternative vaccine products, guidance for physicians providing vaccinations and an unavailability reporting tool to monitor regional distribution issues.AimThis study provides a retrospective analysis of supply issues and measures in the context of European and global vaccine supply constraints.Resultsbetween October 2015 and December 2020, the 250 notifications concerned all types of vaccines (54 products). Most shortages were caused by increased demand associated with immigration in Germany in 2015 and 2016, new or extended vaccine recommendations, increased awareness, or changes in global immunisation programmes. Shortages of a duration up to 30 days were mitigated using existing storage capacities. Longer shortages, triggered by high demand on a national level, were mitigated using alternative products and re-allocation; in a few cases, vaccines were imported. However, for long lasting supply shortages associated with increased global demand, often occurring in combination with manufacturing issues, few compensatory mechanisms were available. Nevertheless, only few critical incidents were identified: (i) shortage of hexavalent vaccines endangering neonatal immunisation programmes in 2015;(ii) distribution issues with influenza vaccines in 2018; and (iii) unmet demand for pneumococcal and influenza vaccines during the coronavirus disease (COVID)-19 pandemic.ConclusionVaccine product shortages in Germany resemble those present in neighbouring EU states and often reflect increased global demand not matched by manufacturing capacities.

Effectiveness of an mRNA vaccine booster dose against SARS-CoV-2 infection and severe COVID-19 in persons aged ≥60 years and other high-risk groups during predominant circulation of the delta variant in Italy, 19 July to 12 December 2021

ABSTRACT Background Consolidated information on the effectiveness of COVID-19 booster vaccination in Europe are scarce. Research design and methods We assessed the effectiveness of a booster dose of an mRNA vaccine against any SARS-CoV-2 infection (symptomatic or asymptomatic) and severe COVID-19 (hospitalization or death) after over two months from administration among priority target groups (n = 18,524,568) during predominant circulation of the Delta variant in Italy (July–December 2021). Results Vaccine effectiveness (VE) against SARS-CoV-2 infection and, to a lesser extent, against severe COVID-19, among people ≥60 years and other high-risk groups (i.e. healthcare workers, residents in long-term-care facilities, and persons with comorbidities or immunocompromised), peaked in the time-interval 3–13 weeks (VE against infection = 67.2%, 95% confidence interval (CI): 62.5–71.3; VE against severe disease = 89.5%, 95% CI: 86.1–92.0) and then declined, waning 26 weeks after full primary vaccination (VE against infection = 12.2%, 95% CI: −4.7–26.4; VE against severe disease = 65.3%, 95% CI: 50.3–75.8). After 3–10 weeks from the administration of a booster dose, VE against infection and severe disease increased to 76.1% (95% CI: 70.4–80.7) and 93.0% (95% CI: 90.2–95.0), respectively. Conclusions These results support the ongoing vaccination campaign in Italy, where the administration of a booster dose four months after completion of primary vaccination is recommended.

A gaps-and-needs analysis of vaccine R&D in Europe: Recommendations to improve the research infrastructure

The COVID-19 pandemic has brought into sharp focus the importance of strategies supporting vaccine development. During the pandemic, TRANSVAC, the European vaccine–research-infrastructure initiative, undertook an in-depth consultation of stakeholders to identify how best to position and sustain a European vaccine R&D infrastructure. The consultation included an online survey incorporating a gaps-and-needs analysis, follow-up interviews and focus-group meetings.Between October 2020 and June 2021, 53 organisations completed the online survey, including 24 research institutes and universities, and 9 pharmaceutical companies; 24 organisations participated in interviews, and 14 in focus-group meetings. The arising recommendations covered all aspects of the vaccine-development value chain: from preclinical development to financing and business development; and covered prophylactic and therapeutic vaccines, for both human and veterinary indications.Overall, the recommendations supported the expansion and elaboration of services including training programmes, and improved or more extensive access to expertise, technologies, partnerships, curated databases, and-data analysis tools. Funding and financing featured as critical elements requiring support throughout the vaccine-development programmes, notably for academics and small companies, and for vaccine programmes that address medical and veterinary needs without a great potential for commercial gain. Centralizing the access to these research infrastructures via a single on-line portal was considered advantageous.

Conditionality of COVID-19 vaccine acceptance in European countries

The COVID-19 vaccine rollout has offered a powerful preventive measure to help control SARS-CoV-2 transmission. Nevertheless, long-standing public hesitation around vaccines heightened concerns that vaccine coverage would not achieve desired public health impacts, particularly in light of more contagious variants. This cross-sectional survey was conducted online just before the European vaccine rollout in December 2020 among 7000 respondents (aged 18–65) in Belgium, France, Germany, Italy, Spain, Sweden, and Ukraine. The survey included open text boxes for fuller explanation of responses. Overall, 56.9% of respondents would accept a COVID-19 vaccine, 19.0% would not, and 24.1% did not know or preferred not to say. By country, between 44% (France) and 66% (Italy) of respondents would accept a COVID-19 vaccine. Respondents expressed conditionality in open responses, voicing concerns about vaccine safety and mistrust of authorities. We highlight lessons learned about the dynamism of vaccine conditionality and persistence of safety concerns.

“We don’t have the same bodies; we don’t react the same way”: mothers and adolescent girls’ perceptions of the risks and benefits of HPV vaccination in France

ABSTRACT Human Papillomavirus (HPV) vaccination is one of the most publicly mistrusted vaccines in Europe, with countries such as France struggling with low vaccine uptake due to parental questioning of vaccine risks and benefits. However, limited evidence exists on adolescent girls’ perceptions of the risks and benefits of HPV vaccination. The aim of this qualitative study was to provide an in-depth exploration and comparison of French mothers (n = 21) and adolescent girls’ (n = 36) perceptions of the risks and benefits of HPV vaccination. A thematic analysis showed that adolescent girls and mothers perceived the risks and benefits of HPV vaccination differently, with girls reporting positive and beneficial views and emotions toward vaccination and mothers expressing concerns about possible risks. Adolescent girls also reported that both perceptions and actual risks and benefits may vary from one individual to another. Vaccine safety was also understood differently, with mothers reporting a widespread view that vaccines are unsafe and focusing on controversial side effects and girls discussing short-term consequences of vaccination (e.g. pain, fever) and administration and storage issues. Strategies to improve uptake of HPV vaccination should consider and address both the mothers’ and daughters’ perceptions and understandings of HPV vaccination.

Explaining EU integration dynamics in the wake of COVID-19: a domain of application approach

ABSTRACT This article explores the heterogeneous and uneven EU response to the COVID-19 pandemic across policy fields and examines how integration theories can contribute to explaining the presence (or absence) of new integration steps and their varying nature. To analyse European activities in three policy fields, namely fiscal policy, centralised European vaccine procurement, and border politics, we develop a ‘Domain of Application’ approach (DOA). Instead of testing integration theories against each other, DOA allows bridging different theoretical traditions by making use of their complementary explanatory power to derive better explanations of complex empirical issues. We find that Liberal Intergovernmentalism and Neofunctionalism offer complementary explanations for several empirical puzzles, which together provide a more compelling picture of the effects of the pandemic on European integration. In addition, DOA advances our understanding of the scopes of both theories.

Assessment of COVID-19 Fear in Five European Countries before Mass Vaccination and Key Predictors among Nurses and Nursing Students.

Background: Levels of fear have increased since the COVID-19 pandemic outbreak. The absence of a safe and effective vaccine for mass-vaccination deteriorates this situation, which has a significant impact on mental health. This study aimed to assess the feelings of fear among nurses and nursing students in five European countries. Methods: A multicenter cross-sectional study was conducted in five European countries (Greece, Albania, Cyprus, Spain, and Kosovo) before the start of mass vaccination in Europe. Data collection was conducted in December 2020–January 2021 using an online questionnaire for nursing students and professional nurses. Fear of COVID-19 Scale (FCV-19S) was used for measuring levels of fear. IBM SPSS version 21.0 was used for statistical analysis. Results: The study population included 1135 nurses and 1920 nursing students from Kosovo (n = 1085), Spain (n = 663), Greece (n = 534), Albania (n = 529), and Cyprus (n = 244). According to multivariable analysis, females (OR = 2.53, 95% CI = 1.89–3.15), married (OR = 0.86, 95% CI = 0.24–1.48), nurses (OR = 0.87, 95% CI = 0.28–1.45) and those with a chronic disease (OR = 0.86, 95% CI = 0.11–1.62) were more fearful of COVID-19. Conclusions: It is important to decrease fear in the population of nurses who are at the frontlines of the pandemic. The provision of appropriate education and training activities for nurses and students to manage their stress levels is of high importance. Future studies should focus on levels of fear after the administration of several safe and effective vaccines worldwide.