A multinational, phase 2, randomised, adaptive protocol to evaluate immunogenicity and reactogenicity of different COVID-19 vaccines in adults >= 75 already vaccinated against SARS-CoV-2 (EU-COVAT-1-AGED): a trial conducted within the VACCELERATE network

Background: In the ongoing COVID-19 pandemic, advanced age is a risk factor for a severe clinical course of SARSCoV-2 infection. Thus, older people may benefit in particular from booster doses with potent vaccines and research should focus on optimal vaccination schedules. In addition to each individual's medical history, immunosenescence warrants further research in this population. This study investigates vaccine-induced immune response over 1 year. Methods/design: EU-COVAT-1-AGED is a randomised controlled, adaptive, multicentre phase II protocol evaluating different booster strategies in individuals aged >= 75 years (n=600) already vaccinated against SARS-CoV-2. The initial protocol foresaw a 3rd vaccination (1st booster) as study intervention. The present modified Part B of this trial foresees testing of mRNA-1273 (Spikevax (R)) vs. BNT162b2 (Comirnaty (R)) as 4th vaccination dose (2nd booster) for comparative assessment of their immunogenicity and safety against SARS-CoV-2 wild-type and variants. The primary endpoint of the trial is to assess the rate of 2-fold antibody titre increase 14 days after vaccination measured by quantitative enzyme-linked immunosorbent assay (Anti-RBD-ELISA) against wild-type virus. Secondary endpoints include the changes in neutralising antibody titres (Virus Neutralisation Assay) against wild-type as well as against Variants of Concern (VOC) at 14 days and up to 12 months. T cell response measured by qPCR will be performed in subgroups at 14 days as exploratory endpoint. Biobanking samples are being collected for neutralising antibody titres against potential future VOC. Furthermore, potential correlates between humoral immune response, T cell response and neutralising capacity will be assessed. The primary endpoint analysis will be triggered as soon as for all patients the primary endpoint (14 days after the 4th vaccination dose) has been observed. Discussion: The EU-COVAT-1-AGED trial Part B compares immunogenicity and safety of mRNA-1273 (Spikevax (R)) and BNT162b2 (Comirnaty (R)) as 4th SARS-CoV-2 vaccine dose in adults >= 75 years of age. The findings of this trial have the potential to optimise the COVID-19 vaccination strategy for this at-risk population

A Cohort of Patients with COVID-19 in a Major Teaching Hospital in Europe

BACKGROUND: Since the confirmation of the first patient infected with SARS-CoV-2 in Spain in January 2020, the epidemic has grown rapidly, with the greatest impact on the region of Madrid. This article describes the first 2226 adult patients with COVID-19, consecutively admitted to La Paz University Hospital in Madrid. METHODS: Our cohort included all patients consecutively hospitalized who had a final outcome (death or discharge) in a 1286-bed hospital of Madrid (Spain) from 25 February (first case admitted) to 19 April 2020. The data were manually entered into an electronic case report form, which was monitored prior to the analysis. RESULTS: We consecutively included 2226 adult patients admitted to the hospital who either died (460) or were discharged (1766). The patients’ median age was 61 years, and 51.8% were women. The most common comorbidity was arterial hypertension (41.3%), and the most common symptom on admission was fever (71.2%). The median time from disease onset to hospital admission was 6 days. The overall mortality was 20.7% and was higher in men (26.6% vs. 15.1%). Seventy-five patients with a final outcome were transferred to the intensive care unit (ICU) (3.4%). Most patients admitted to the ICU were men, and the median age was 64 years. Baseline laboratory values on admission were consistent with an impaired immune-inflammatory profile. CONCLUSIONS: We provide a description of the first large cohort of hospitalized patients with COVID-19 in Europe. Advanced age, male sex, the presence of comorbidities and abnormal laboratory values were more common among the patients with fatal outcomes

The challenges of vaccine trial participation among underserved and hard-to-reach communities : an internal expert consultation of the VACCELERATE Consortium

Abstract: Underserved and hard-to-reach population groups are under-represented in vaccine trials. Thus, we aimed to identify the challenges of vaccine trial participation of these groups in member countries of the VACCELERATE network. Seventeen National Coordinators (NC), each representing their respective country (15 European countries, Israel, and Turkey), completed an online survey. From 15 eligible groups, those that were more frequently declared underserved/hard-to-reach in vaccine research were ethnic minorities (76.5%), persons experiencing homelessness (70.6%), illegal workers and refugees (64.7%, each). When prioritization for education on vaccine trials was considered, ethnic groups, migrants, and immigrants (5/17, 29.4%) were the groups most frequently identified by the NC as top targets. The most prominent barriers in vaccine trial participation affecting all groups were low levels of health literacy, reluctance to participate in trials due to engagement level, and low levels of trust in vaccines/vaccinations. This study highlighted population groups considered underserved/hard-to-reach in countries contained within the European region, and the respective barriers these groups face when participating in clinical studies. Our findings aid with the design of tailored interventions (within-and across-countries of the European region) and with the development of strategies to overcome major barriers in phase 2 and phase 3 vaccine trial participation

The Challenges of Vaccine Trial Participation among Underserved and Hard-to-Reach Communities: An Internal Expert Consultation of the VACCELERATE Consortium

: Underserved and hard-to-reach population groups are under-represented in vaccine trials. Thus, we aimed to identify the challenges of vaccine trial participation of these groups in member countries of the VACCELERATE network. Seventeen National Coordinators (NC), each representing their respective country (15 European countries, Israel, and Turkey), completed an online survey. From 15 eligible groups, those that were more frequently declared underserved/hard-to-reach in vaccine research were ethnic minorities (76.5%), persons experiencing homelessness (70.6%), illegal workers and refugees (64.7%, each). When prioritization for education on vaccine trials was considered, ethnic groups, migrants, and immigrants (5/17, 29.4%) were the groups most frequently identified by the NC as top targets. The most prominent barriers in vaccine trial participation affecting all groups were low levels of health literacy, reluctance to participate in trials due to engagement level, and low levels of trust in vaccines/vaccinations. This study highlighted population groups considered underserved/hard-to-reach in countries contained within the European region, and the respective barriers these groups face when participating in clinical studies. Our findings aid with the design of tailored interventions (within-and across-countries of the European region) and with the development of strategies to overcome major barriers in phase 2 and phase 3 vaccine trial participation

Enhancing public health communication of vaccine trials: The pan-European VACCELERATE Toolkit

Background: The pan-European VACCELERATE network aims to implement the first transnational harmonised and sustainable vaccine trial Volunteer Registry, serving as single entry-point for volunteers willing to participate in large scale vaccine clinical studies across the European region. The present work exhibits a set of harmonised vaccine trial educational and promotional tools for the general public, designed and disseminated by the pan-European VACCELERATE network. Objective: The main objectives of the present study are the design and creation of a standard toolkit to increase positive attitudes, and access to trustful information for better access and increased recruitment to vaccine trials for the public community. More specifically, the produced tools are focused on inclusiveness, equity, and they are targeting different population groups, including underserved ones, as potential volunteers for the VACCELERATE Volunteer Registry (elderly, migrants, children and adolescents). The promotion/education material is aligned with the main objectives of the Volunteer Registry, to increase public literacy and awareness regarding vaccine clinical research/trials and trial participation, such as informed consent and legal issues, side effects and frequently asked questions on vaccine trial design. Methods: The tools' development has followed the aims and principles of the VACCELERATE project, focusing on trial inclusiveness and equity and they are adjusted to the local country requirements to improve public health communication. The selection of the produced tools has been based on the cognitive theory, inclusiveness and equity of different aged and under-represented groups, and standardised material from several official trustful sources (e.g. COVAX, ECDC, EUPATI, GAVI and WHO). In addition, team of specialists from different fields (infectious diseases, vaccine research, medicine, education) edited and reviewed the subtitles and scripts for the educational videos, extended brochures, interactive cards and puzzles. Graph designers also selected the colour palette, audio settings and dubbing for the video story-tales and implementation of QR codes. Results: This study presents the first set of harmonised promotional and educational materials/tools (i.e. educational cards, educational and promotional videos, extended brochures, flyers, posters, and puzzles) for vaccine clinical research (e.g. COVID-19). The developed tools inform the public about possible benefits and disadvantages of trial participation, but also build the confidence of participants about the safety and efficacy for COVID-19 vaccines and healthcare system. The present material has been translated into several languages and meant to be freely and easily accessible to facilitate dissemination among the participating countries of the VACCELERATE network, as well as among the European and global scientific, industrial, and public community, in general. Conclusions: The produced material could also be useful for filling knowledge gaps of healthcare personnel and providing the appropriate future patient education for vaccine trials, as well as to tackle vaccine hesitancy and parents' concerns for potential participation of children in vaccine trials

Enhancing Public Health Communication Regarding Vaccine Trials: Design and Development of the Pan-European VACCELERATE Toolkit

BACKGROUND: The pan-European VACCELERATE network aims to implement the first transnational harmonized and sustainable vaccine trial Volunteer Registry, being a single entry point for potential volunteers of large-scale vaccine trials across Europe. This work exhibits a set of harmonized vaccine trial-related educational and promotional tools for the general public, designed and disseminated by the pan-European VACCELERATE network. OBJECTIVE: This study primarily aimed to design and develop a standard toolkit to increase positive attitudes and access to trustworthy information for better access and increased recruitment to vaccine trials for the public. More specifically, the produced tools are focused on inclusiveness and equity, and are targeting different population groups, including underserved ones, as potential volunteers for the VACCELERATE Volunteer Registry (older individuals, migrants, children, and adolescents). The promotional and educational material is aligned with the main objectives of the Volunteer Registry to increase public literacy and awareness regarding vaccine-related clinical research or trials and trial participation, including informed consent and legal issues, side effects, and frequently asked questions regarding vaccine trial design. METHODS: Tools were developed per the aims and principles of the VACCELERATE project, focusing on trial inclusiveness and equity, and are adjusted to local country-wise requirements to improve public health communication. The produced tools are selected based on the cognitive theory, inclusiveness, and equity of differently aged and underrepresented groups, and standardized material from several official trustworthy sources (eg, COVID-19 Vaccines Global Access; the European Centre for Disease Prevention and Control; the European Patients' Academy on Therapeutic Innovation; Gavi, the Vaccine Alliance; and the World Health Organization). A team of multidisciplinary specialists (infectious diseases, vaccine research, medicine, and education) edited and reviewed the subtitles and scripts of the educational videos, extended brochures, interactive cards, and puzzles. Graphic designers selected the color palette, audio settings, and dubbing for the video story-tales and implemented QR codes. RESULTS: This study presents the first set of harmonized promotional and educational materials and tools (ie, educational cards, educational and promotional videos, extended brochures, flyers, posters, and puzzles) for vaccine clinical research (eg, COVID-19 vaccines). These tools inform the public about possible benefits and disadvantages of trial participation and build confidence among participants about the safety and efficacy of COVID-19 vaccines and the health care system. This material has been translated into several languages and is intended to be freely and easily accessible to facilitate dissemination among VACCELERATE network participant countries and the European and global scientific, industrial, and public community. CONCLUSIONS: The produced material could help fill knowledge gaps of health care personnel, providing the appropriate future patient education for vaccine trials, and tackling vaccine hesitancy and parents' concerns for potential participation of children in vaccine trials