Impact of corticosteroids use on midterm sequelae in survivors of COVID-19 admitted to hospital: A prospective cohort study.

An understanding of the midterm sequelae in COVID-19 and their association with corticosteroids use are needed. Between March and July 2020, we evaluated 1227 survivors of COVID-19, 3 months posthospitalization, of whom 213 had received corticosteroids within 7 days of admission. Main outcome was any midterm sequelae (oxygen therapy, shortness of breath, one major clinical sign, two minor clinical signs or three minor symptoms). Association between corticosteroids use and midterm sequelae was assessed using inverse propensity-score weighting models. Our sample included 753 (61%) male patients, and 512 (42%) were older than 65 years. We found a higher rate of sequelae among users than nonusers of corticosteroids (42% vs. 35%, odds ratio [OR] 1.40 [1.16-1.69]). Midterm sequelae were more frequent in users of low-dose corticosteroids than nonusers (64% vs. 51%, OR 1.60 [1.10-2.32]), whereas no association between higher doses (≥20 mg/day equivalent of dexamethasone) and sequelae was evidenced (OR 0.95 [0.56-1.61]). Higher risk of sequelae with corticosteroids use was observed among subjects with propensity score below the 90th percentile. Our study suggest that corticosteroids use during hospitalization for COVID-19 is associated with higher risk of midterm sequelae.

VACCELERATE Site Network: Real-time definition of clinical study capacity in Europe.

BACKGROUND: The inconsistent European vaccine trial landscape rendered the continent of limited interest for vaccine developers. The VACCELERATE consortium created a network of capable clinical trial sites throughout Europe. VACCELERATE identifies and provides access to state-of-the-art vaccine trial sites to accelerate clinical development of vaccines. METHODS: Login details for the VACCELERATE Site Network (vaccelerate.eu/site-network/) questionnaire can be obtained after sending an email to. Interested sites provide basic information, such as contact details, affiliation with infectious disease networks, main area of expertise, previous vaccine trial experience, site infrastructure and preferred vaccine trial settings. In addition, sites can recommend other clinical researchers for registration in the network. If directly requested by a sponsor or sponsor representative, the VACCELERATE Site Network pre-selects vaccine trial sites and shares basic study characteristics provided by the sponsor. Interested sites provide feedback with short surveys and feasibility questionnaires developed by VACCELERATE and are connected with the sponsor to initiate the site selection process. RESULTS: As of April 2023, 481 sites from 39 European countries have registered in the VACCELERATE Site Network. Of these, 137 (28.5 %) sites have previous experience conducting phase I trials, 259 (53.8 %) with phase II, 340 (70.7 %) with phase III, and 205 (42.6 %) with phase IV trials, respectively. Infectious diseases were reported as main area of expertise by 274 sites (57.0 %), followed by any kind of immunosuppression by 141 (29.3 %) sites. Numbers are super additive as sites may report clinical trial experience in several indications. Two hundred and thirty-one (47.0 %) sites have the expertise and capacity to enrol paediatric populations and 391 (79.6 %) adult populations. Since its launch in October 2020, the VACCELERATE Site Network has been used 21 times for academic and industry trials, mostly interventional studies, focusing on different pathogens such as fungi, monkeypox virus, Orthomyxoviridae/influenza viruses, SARS-CoV-2, or Streptococcus pneumoniae/pneumococcus. CONCLUSIONS: The VACCELERATE Site Network enables a constantly updated Europe-wide mapping of experienced clinical sites interested in executing vaccine trials. The network is already in use as a rapid-turnaround single contact point for the identification of vaccine trials sites in Europe.

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.

One-month humoral response following two or three doses of messenger RNA coronavirus disease 2019 vaccines as primary vaccination in specific populations in France: first results from the Agence Nationale Recherche contre le Sida (ANRS)0001S COV-POPART cohort.

OBJECTIVES: We aimed to investigate the 1-month humoral response to two or three doses of a messenger RNA coronavirus disease 2019 (COVID-19) vaccine as a primary vaccination regimen in specific populations compared with that in healthy adults. METHODS: Agence Nationale Recherche contre le Sida (ANRS)0001S-COV-POPART (NCT04824651) is a French nation-wide, multi-centre, prospective, observational cohort study assessing the immune response to COVID-19 vaccines routinely administered to 11 sub-groups of patients with chronic conditions and two control groups. Patients and controls who received at least two vaccine doses and whose results 1 month after the second dose were available were included. The humoral response was assessed 1 month after the first, second and third doses (if applicable) based on the percentage of responders (positive for anti-Spike severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] IgG antibodies), geometric means of anti-Spike SARS-CoV-2 IgG antibodies (enzyme-linked immunosorbent assay) and proportion of participants with anti-SARS-CoV-2-specific neutralizing antibodies (in vitro neutralization assay for the original SARS-CoV-2 strain). All analyses were centralized. RESULTS: We included 4091 participants in this analysis: 2979 participants from specific sub-populations and 1112 controls. Only 522 (17.5%) participants from the specific populations received three doses as a primary vaccination regimen. Patients living with human immunodeficiency virus, cancer and diabetes had high percentages of responders after two doses, whereas patients with solid organ transplants, allogeneic hematopoietic stem cell transplants and hypogammaglobulinaemia had the lowest percentage of responders (35.9% [95% CI, 29.2-43.0], 57.4% [95% CI, 48.1-66.3] and 77.1% [95% CI, 65.6-86.3], respectively). In those who received the third dose, the percentage of responders reached 54.2% (95% CI, 42.9-65.2) (vs. 32.3% [95% CI, 16.7-51.4] after 2 doses) among those with solid organ transplants and 73.9% (95% CI, 58.9-85.7) (vs. 56.1% [95% CI, 46.2-65.7] after 2 doses) among those with hematopoietic stem cell transplants. Similar results were found with anti-SARS-CoV-2-specific neutralizing antibodies. CONCLUSIONS: A lower humoral response to COVID-19 vaccines was observed in the specific populations compared with that in the controls. The third dose of this vaccine in the primary regimen had a positive effect on the percentages of patients who developed anti-Spike IgG antibodies and specific neutralizing antibodies.

Prevalence of post-acute coronavirus disease 2019 symptoms twelve months after hospitalization in participants retained in follow-up: analyses stratified by gender from a large prospective cohort.

OBJECTIVES: Persistent post-acute coronavirus disease 2019 (COVID-19) symptoms (PACSs) have been reported up to 6 months after hospital discharge. Herein we assessed the symptoms that persisted 12 months (M12) after admission for COVID-19 in the longitudinal prospective national French coronavirus disease cohort. METHODS: Hospitalized patients with a confirmed virological diagnosis of COVID-19 were enrolled. Follow-up was planned until M12 after admission. Associations between persistence of ≥3 PACSs at M12 and clinical characteristics at admission were assessed through logistic regression according to gender. RESULTS: We focused on participants enrolled between 24 January 2020 and 15 July 2020, to allow M12 follow-up. The M12 data were available for 737 participants. Median age was 61 years, 475 (64%) were men and 242/647 (37%) were admitted to intensive care units during the acute phase. At M12, 27% (194/710) of the participants had ≥3 persistent PACS, mostly fatigue, dyspnoea and joint pain. Among those who had a professional occupation before the acute phase, 91 out of 339 (27%) were still on sick leave at M12. Presence of ≥3 persistent PACS was associated with female gender, both anxiety and depression, impaired health-related quality of life and Medical Muscle Research Council Scale <57. Compared with men, women more often reported presence of ≥3 persistent PACSs (98/253, 39% vs. 96/457, 21%), depression and anxiety (18/152, 12% vs. 17/268, 6% and 33/156, 21% vs. 26/264, 10%, respectively), impaired physical health-related quality of life (76/141, 54% vs. 120/261, 46%). Women had less often returned to work than men (77/116, 66% vs. 171/223, 77%). CONCLUSIONS: One fourth of the individuals admitted to hospital for COVID-19 still had ≥3 persistent PACSs at M12 post-discharge. Women reported more often ≥3 persistent PACSs, suffered more from anxiety and depression and had less often returned to work than men.

Early humoral response to COVID-19 vaccination in patients living with obesity and diabetes in France. The COVPOP OBEDIAB study with results from the ANRS0001S COV-POPART cohort.

BACKGROUND: Patients with diabetes and obesity are populations at high-risk for severe COVID-19 outcomes and have shown blunted immune responses when administered different vaccines. Here we used the 'ANRS0001S COV-POPART' French nationwide multicenter prospective cohort to investigate early humoral response to COVID-19 vaccination in the sub-cohort ('COVPOP OBEDIAB') of patients with obesity and diabetes. METHODS: Patients with diabetes (n = 390, type 1 or 2) or obesity (n = 357) who had received two vaccine doses and had no history of previous COVID-19 infection and negative anti-nucleocapsid (NCP) antibodies were included and compared against healthy subjects (n = 573). Humoral response was assessed at baseline, at one month post-first dose (M0) and one-month post-second dose (M1), through percentage of responders (positive anti-spike SARS-CoV-2 IgG antibodies (Sabs), geometric means of Sabs; BAU/mL), proportion of individuals with anti-RBD antibodies, and proportion of individuals with anti-SARS-CoV-2-specific neutralizing antibodies (Nabs). Potential clinical and biological factors associated with weak response (defined as Sabs < 264 BAU/mL) and presence of non-reactive anti-RBD antibodies at M1 were evaluated. Univariate and multivariate regressions were performed to estimate crude and adjusted coefficients with 95 % confidence intervals. Poor glycemic control was defined as HbA1c ≥ 7.5 % at inclusion. RESULTS: Patients with diabetes, particularly type 2 diabetes, and patients with obesity were less likely to have positive Sabs and anti-RBD antibodies after the first and second dose compared to controls (p < 0.001). At M1, we found Sabs seroconversion in 94.1 % of patients with diabetes versus 99.7 % in controls, anti-RBD seroconversion in 93.8 % of patients with diabetes versus 99.1 % in controls, and Nabs seroconversion in 95.7 % of patients with diabetes versus 99.6 % in controls (all p < 0.0001). Sabs and anti-RBD seroconversion at M0 and M1 were also significantly lower in obese patients than controls, at respectively 82.1 % versus 89.9 % (p = 0.001; M0 Sabs), 94.4 % versus 99.7 % (p 0.001; M1 Sabs), 79.0 % vs 86.2 % (p = 0.004 M0 anti-RBD), and 96.99 % vs 99.1 % (p = 0.012 M1 anti-RBD). The factors associated with low vaccine response (BAU < 264/mL) in patients with diabetes were chronic kidney disease (adjusted OR = 6.88 [1.77;26.77], p = 0.005) and poor glycemic control (adjusted OR = 3.92 [1.26;12.14], p = 0.018). In addition, BMI ≥ 40 kg/m2 was found to be associated with a higher vaccine response (adjusted OR = 0.10 [0.01;0.91], p = 0.040) than patients with BMI < 40 kg/m2. CONCLUSION: COVID-19 vaccine humoral response was lower in patients with obesity and diabetes one month after second dose compared to controls, especially in diabetic patients with CKD or inadequate glycemic control. These findings point to the need for post-vaccination serological checks in these high-risk populations.

Neutralizing antibodies against SARS-CoV-2 variants following mRNA booster vaccination in adults older than 65 years.

Immune response induced by COVID-19 vaccine booster against delta and omicron variants was assessed in 65 adults (65-84 years old) early aftesr a first booster dose. An increase in SARS-CoV-2 neutralizing antibodies was shown in individuals not previously infected without evidence of an age-related effect, with lower increase in those infected before a single dose of primary vaccination. Of note, humoral response was observed only starting from the 5th day after the boost.

Coadministration of seasonal influenza and COVID-19 vaccines: A systematic review of clinical studies.

The lifting of non-pharmaceutical measures preventing transmission of SARS-CoV-2 (and other viruses, including influenza viruses) raises concerns about healthcare resources and fears of an increased number of cases of influenza and COVID-19. For the 2021-2022 influenza season, the WHO and >20 European countries promoted coadministration of influenza and COVID-19 vaccines. Recently, the French Health Authority recommended coupling the COVID-19 vaccination with the 2022-2023 influenza vaccination campaign for healthcare professionals and people at risk of severe COVID-19. The present systematic review examines published data on the safety, immunogenicity, efficacy/effectiveness, and acceptability/acceptance of coadministration of influenza and COVID-19 vaccines. No safety concerns or immune interferences were found whatever the vaccines or the age of vaccinated subjects (65- or 65+). No efficacy/effectiveness data were available. The results should reassure vaccinees and vaccinators in case of coadministration and increase vaccine coverage. Healthcare systems promoting coupled campaigns must provide the necessary means for successful coadministration.

The lifting of non-pharmaceutical measures recommended to prevent transmission of SARS-CoV-2 (and other viruses, including influenza viruses) raises concerns about healthcare resources, already under pressure. It also raises fears of an increase in the number of cases of influenza or COVID-19 infection during the winter season. For the 2021­2022 influenza season, the World Health Organization and several European countries promoted concomitant administration in distinct anatomic sites (i.e., coadministration) of influenza and COVID-19 vaccines to avoid additional stress on healthcare systems. In May 2022, the French Health Authority recommended coupling the COVID-19 vaccination with the 2022­2023 influenza vaccination campaign (i.e., starting COVID-19 vaccination at the date of influenza vaccination) for healthcare professionals and people at risk of severe COVID-19, in case of epidemic wave. Coadministration of influenza and COVID-19 vaccines is one of the factors of success for a coupled campaign. The present systematic review examines all published data (articles or reports, clinical trials, or surveys) on the safety, immunogenicity, efficacy/effectiveness, and acceptability/acceptance of coadministration of influenza and COVID-19 vaccines. The PRISMA method was used to collect information. No safety concerns or immune interferences were found whatever the vaccines or the age of vaccinated subjects (65- or 65+). No efficacy/effectiveness data were available. Acceptability and acceptance were good but could be improved. By reassuring vaccinees and vaccinators, these results are expected to favor coadministration and ultimately increase vaccine coverage, thus offering better protection. Healthcare systems promoting coupled campaigns with coadministration must provide the necessary means for their successful implementation.

The value of public-private collaborative real-world evidence platforms to monitor vaccine performance post authorization: DRIVE - a European initiative.

INTRODUCTION: Fighting pandemics requires an established infrastructure for pandemic preparedness, with existing, sustainable platforms ready to be activated. This includes platforms for disease surveillance, virus circulation, and vaccine performance monitoring based on Real-World data, to complement clinical trial evidence. AREAS COVERED: Because of its complexity, this can best be done by combining efforts between public and private sectors, developing a multi-stakeholder approach. Public-Private-Partnerships increasingly play a critical role in combating infectious diseases but are still looked at with hesitancy. The Development of Robust and Innovative Vaccine Effectiveness (DRIVE) project, which established a platform for measuring brand-specific influenza vaccine effectiveness in Europe, exemplifies how to build a collaborative platform with transparent governance, state-of-the-art methodology, and a large network of participating sites. Lessons learned from DRIVE have been cardinal to set up COVIDRIVE, a platform for brand-specific COVID-19 vaccine effectiveness monitoring. EXPERT OPINION: The DRIVE partners propose that a debate on the benefits of Public-Private-Partnership-generated real-world evidence for vaccine effectiveness monitoring should be pursued to clarify roles and responsibilities, set up expectations, and decide the future environment for vaccine monitoring in Europe. In parallel, the driving factors behind PPP hesitancy should be studied.

Prevalence of post-acute COVID-19 symptoms twelve months after hospitalisation in participants retained in follow-up: analyses stratified by gender from a large prospective cohort

Objectives Persistent post-acute COVID-19 symptom (PACS) have been reported up to 6-months (M6) after hospital discharge. Here we assessed, in the longitudinal prospective national French COVID cohort, symptoms that persisted 12-months (M12) after admission for COVID-19. Methods Hospitalized patients with a virologically-confirmed COVID-19 were enrolled. Follow-up was planned until M12 post-admission. Associations between persistence of ≥3 PACS at M12 and clinical characteristics at admission were assessed through logistic regression according to gender. Results We focused on participants enrolled between January 24th and July 15th 2020, in order to allow M12 follow-up. M12 data were available for 737 participants. Median age was 61 years, 475 (64%) were men and 242/647 (37%) were admitted to ICU during the acute phase. At M12, 194/710 (27%) of participants had ≥3 persistent PACS, mostly fatigue, dyspnea and joint pain. Among those who had a professional occupation before the acute phase 91/339 (27%) were still on sick leave at M12. Presence of ≥3 persistent PACS was associated with female gender, both anxiety and depression, impaired health-related quality of life (HRQL) and mMRC scale <57. Compared to men, women more often reported presence of >3 persistent PACS (98/253, 39% vs 96/457, 21%), depression and anxiety (18/152, 12% vs 17/268, 6% and 33/156, 21% vs 26/264, 10%, respectively), impaired physical HRQL (76/141, 54% vs 120/261, 46%). Women had less often returned to work than men (77/116, 66% vs 171/223, 77%). Conclusions A fourth of individuals admitted to hospital for COVID-19 still had ≥3 persistent PACS at M12 post-discharge. Women reported more often ≥3 persistent PACS, suffered more from anxiety and depression, and had less often returned to work than men.

COVID-19 Vaccines against Omicron Variant: Real-World Data on Effectiveness.

The efficacy of vaccines against coronavirus disease 2019 (COVID-19) has now been well established in phase III clinical trials. However, clinical studies based on real-world data remain critical to assess vaccines effectiveness (VE), especially in specific populations and against variants of concern (VOC). This review presents the principles and methods of VE studies and the main available results on VE of COVID-19 vaccines at the time of Omicron circulation. References for this narrative review were identified through searches of PubMed database up to 13 September 2022. The results of phase III clinical trials have been globally confirmed by VE in real-life studies, including in the elderly. Emergence of VOC Omicron emphasized the importance of booster doses to maintain a high level of protection against severe forms. There are still numerous challenges regarding booster(s) and duration of immunity, particularly in specific subpopulations, and regarding the need for adapted vaccines.

A national platform for Covid-19 vaccine studies recruitment in France: Covireivac volunteer's characteristics.

During the Covid-19 pandemic, the urgent need for safe and effective vaccines has led to many vaccine trials, implying fast and extensive recruitment of volunteers. In France, until 2020, vaccine clinical research participants were usually recruited locally, through center-based pools of volunteers, and local communication plans. Covireivac is a French public online platform launched on 10/01/2020 that enables national, large-scale recruitment of volunteers for Covid-19 vaccine studies. On the Covireivac website, all adult participants registered online, gave their informed consent, and filled out two online forms with information on their identity, health status (comorbidities, treatments), and known exposure to SARS-CoV-2. Since July 2021, volunteers could mention if their children are interested in participating in a Covid-19 vaccine trial. The objective of this work is to describe Covireivac's volunteer characteristics registered from 10/01/2020 to 11/02/2022. To identify independent volunteer characteristics associated with a period of registration we performed a multivariate logistic regression. Among 54,424 registrations, 52,391 (96%) were analysed; 61% were male (n = 31,893), median age was 50 y; 13% (n = 6586) were healthcare workers. At registration, 15,879 volunteers (33%) reported at least one comorbidity, among whom 16% (n = 7349) were obese and 17% (n = 8346) had hypertension. Most volunteers registered during the first month (n = 35,876, 66%). The Covireivac platform allowed quick and large recruitment of potential volunteers for Covid-19 vaccine trials and could be used on a larger scale for vaccine trials in France. It could facilitate recruitment in vaccine trials and provide sponsors with better visibility of the recruitment capacities of clinical research centers.

Association between mental disorders and COVID-19 outcomes among inpatients in France: A retrospective nationwide population-based study.

BACKGROUND: Mental disorders are at-risk of severe COVID-19 outcomes. There is limited and heterogeneous national data in hospital settings evaluating the risks associated with any pre-existing mental disorder, and susceptible subgroups. Our study aimed to investigate the association between pre-existing psychiatric disorders and outcomes of adults hospitalised for COVID-19. METHOD: We used data obtained from the French national hospital database linked to the state-level psychiatric registry. The primary outcome was 30-days in-hospital mortality. Secondary outcomes were to compare the length of hospital stay, Intensive Care Unit (ICU) admission and ICU length. Propensity score matching analysis was used to control for COVID-19 confounding factors between patients with or without mental disorder and stratified by psychiatric subgroups. RESULTS: Among 97 302 adults hospitalised for COVID-19 from March to September 2020, 10 083 (10.3%) had a pre-existing mental disorder, mainly dementia (3581 [35.5%]), mood disorders (1298 [12.9%]), anxiety disorders (995 [9.9%]), psychoactive substance use disorders (960 [9.5%]), and psychotic disorders (866 [8.6%]). In propensity-matched analysis, 30-days in-hospital mortality was increased among those with at least one pre-existing mental disorder (hazard ratio (HR) 1.15, 95% CI 1.08-1.23), psychotic disorder (1.90, 1.24-2.90), and psychoactive substance disorders (1.53, 1.10-2.14). The odds of ICU admission were consistently decreased for patients with any pre-existing mental disorder (OR 0.83, 95% CI 0.76-0.92) and for those with dementia (0.64, 0.53-0.76). CONCLUSION: Pre-existing mental disorders were independently associated with in-hospital mortality. These findings underscore the important need for adequate care and targeted interventions for at-risk individuals with severe mental illness.

Factors associated with COVID-19 vaccine uptake among French population aged 65 years and older: results from a national online survey.

BACKGROUND: In France, the increase in COVID-19 vaccine uptake among older adults slowed down between May and June 2021. Using the data from a national survey, we aimed to assess COVID-19 vaccine uptake among French residents aged 65 years and older, particularly at risk of severe form of the infection, and identify factors associated with non-vaccination. METHODS: A cross-sectional online survey collected the immunization status/intention to get the COVID-19 vaccine, reasons for vaccination/non-vaccination and factors potentially associated with vaccine uptake between May 10 and 23, 2021 among a large sample of French residents. Characteristics of participants were compared according to immunization status. Factors potentially associated with non-vaccination were computed into a multivariate logistic regression. RESULTS: Among the 1941 survey participants, 1612 (83%) reported having received at least one dose of COVID-19 vaccine. Among the 329 unvaccinated, 197 (60%) declared having the intention to get vaccinated. Younger age (adjusted odds ratio (aOR) = 1.50; 95% confidence interval (CI), 1.05-2.14), thinking previously having COVID-19 (aOR = 4.01; 95% CI, 2.17-7.40), having suffered economic impact due to the pandemic (aOR = 2.63; 95% CI, 1.71-4.04), reporting an "unsafe" opinion about COVID-19 vaccine safety (aOR = 6.79; 95% CI, 4.50-10.26), reporting an "unsupportive" opinion about vaccination in general (aOR = 4.24; 95% CI, 2.77-6.49) were independent risk factors for non-vaccination. On the other hand, trust in COVID-19 vaccine information delivered by the doctor (aOR = 0.28; 95% CI, 0.16-0.48) and trust in the government's actions (aOR = 0.50; 95% CI, 0.34-0.74) were independent protective factors for non-vaccination. Political affiliation also remained significantly associated with vaccine uptake. CONCLUSIONS: Despite high overall COVID-19 vaccine uptake among the study participants, differences in vaccine uptake according to the level of concerns regarding COVID-19 vaccine safety, socioeconomic profile and trust in the government were observed. Our results reinforce the importance of "reaching out" vaccination strategy that specifically targets the most vulnerable fringe of older adult population.

Immunogenicity and reactogenicity of heterologous and homologous mRNA-1273 and BNT162b2 vaccination: A multicenter non-inferiority randomized trial.

Background: Although effective mRNA vaccines for SARS-CoV-2 infection have been deployed worldwide, their interchangeability could facilitate the scale-up of vaccination programs. The objective of the trial was to assess whether the immune response induced by a heterologous SARS-CoV-2 mRNA primo vaccination is non-inferior to that of a homologous mRNA vaccination. Methods: We conducted a multicenter, randomized, open-label trial in adults 18 years of age and older who received a first dose of SARS-CoV-2 mRNA vaccine. Participants were randomly assigned in a 1:1 ratio to receive a second dose of BNT162b2 or mRNA-1273, 28 to 49 days after the first dose. Randomization was stratified on the vaccine received at the first vaccination. The primary endpoint was the anti-spike IgG antibodies titer measured 28 days after the second vaccine dose. This study is registered with ClinicalTrials.gov, Trial, NCT04900467. Findings: Of the 414 randomized participants recruited from May 28 to July 2, 2021, 390 were included in the per protocol analysis: 94 participants in group 1 (BNT162b2/BNT162b2), 96 in group 2 (BNT162b2/mRNA-1273), 97 in group 3 (mRNA-1273/mRNA-1273), and 103 in group 4 (mRNA-1273/BNT162b2). The geometric mean titers ratios of anti-spike IgG antibodies for each heterologous regimen relative to the corresponding homologous regimen were 1·37 (two-sided 95% CI, 1·10 to 1·72) in the groups 1 and 2 and 0·67 (two-sided 95% CI, 0·55 to 0·82) in the groups 3 and 4. Levels of neutralizing antibodies to the main circulating SARS-Cov-2 viral strains were higher with the vaccine regimen containing mRNA-1273. Participants who received mRNA-1273 as a second dose experienced a higher rate of local adverse reactions and general symptoms than those who received BNT162b2 (p < 0·0001). Interpretation: The two SARS-CoV-2 mRNA vaccines could be used with flexibility for the second dose of COVID-19 primo vaccination. Tolerance remains good regardless of vaccine sequence although mRNA-1273 was more reactogenic. Funding: French Ministries of Solidarity and Health and Research. BNT162b2 was provided by Pfizer/BioNTech. mRNA-1273 was provided by Moderna.

Vaccination COVID-19 : technologies vaccinales, efficacité en vie réelle et spécificités

résumé Le développement et l’évaluation accélérés de vaccins efficaces contre le SARS-CoV-2 ont permis de contrôler en partie la pandémie de COVID-19, responsable d'une crise sanitaire sans précédent. En juin 2022, six vaccins ont été autorisés en Europe, onze ont été reconnus par l'Organisation mondiale de la santé (OMS), et plus de 160 candidats vaccins sont en développement clinique. La remarquable efficacité de ces vaccins, démontrée lors des études pivots, a été confirmée dans les essais en vie réelle. Les données d'efficacité contre le variant Omicron montrent une protection limitée de la primovaccination vis-à-vis des formes symptomatiques, mais qui reste élevée contre les formes graves. L'efficacité n'est qu'en partie restaurée par l'administration d'une ou deux doses de rappel. Les données d'immunogénicité et de sécurité des schémas hétérologues et la possible interchangeabilité entre les vaccins à ARNm sont autant d'outils précieux pour faciliter l'intensification des campagnes de vaccination et envisager de nouvelles stratégies vaccinales. The rapid development and accelerated evaluation of effective vaccines against SARS-CoV-2 have made it possible to partially control the COVID-19 pandemic, responsible for an unprecedented health crisis. In June 2022, six vaccines are authorized in Europe, eleven are recognized by the World Health Organization and more than 160 candidate vaccines are in clinical development. The remarkable efficacy of these vaccines assessed in pivotal trials has been confirmed effectiveness trials. Current efficacy data against the Omicron variant show limited protection conferred by primary vaccination against symptomatic forms, but which remains significant against severe forms. Vaccine efficacy is partially restored by administration of a booster dose. The reassuring data on immunogenicity and safety of heterologous regimens, the possible interchangeability between mRNA vaccines are all valuable tools to facilitate the intensification of vaccination campaigns and consider new vaccine strategies.

VACCELERATE Volunteer Registry: A European study participant database to facilitate clinical trial enrolment.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has evidenced the key role of vaccine design, obtention, production and administration to successfully fight against infectious diseases and to provide efficient remedies for the citizens. Although clinical trials were rapidly established during this pandemic, identifying suitable study subjects can be challenging. For this reason, the University Hospital Cologne established a volunteer registry for participation in clinical trials first in Germany, which has now been incorporated into the European VACCELERATE clinical trials network and grew to a European Volunteer Registry. As such, VACCELERATE's Volunteer Registry aims to become a common entry point for potential volunteers in future clinical trials in Europe. METHODS: Interested volunteers who would like to register for clinical trials in the VACCELERATE Volunteer Registry can access the registration questionnaire via http://www.vaccelerate.eu/volunteer-registry. Potential volunteers are requested to provide their current country and area of residence, contact information, including first and last name and e-mail address, age, gender, comorbidities, previous SARS-CoV-2 infection and vaccination status, and maximum distance willing to travel to a clinical trial site. The registry is open to both adults and children, complying with national legal consent requirements. RESULTS: As of May 2022, the questionnaire is available in 12 countries and 14 languages. Up to date, more than 36,000 volunteers have registered, mainly from Germany. Within the first year since its establishment, the VACCELERATE Volunteer Registry has matched more than 15,000 volunteers to clinical trials. The VACCELERATE Volunteer Registry will be launched in further European countries in the coming months. CONCLUSIONS: The VACCELERATE Volunteer Registry is an active single-entry point for European residents interested in COVID-19 clinical trials participation in 12 countries (i.e., Austria, Cyprus, Germany, Greece, Ireland, Lithuania, Norway, Portugal, Spain, Sweden and Turkey). To date, more than 15,000 registered individuals have been connected to clinical trials in Germany alone. The registry is currently in the implementation phase in 5 additional countries (i.e., Belgium, Czech Republic, Hungary, Israel and the Netherlands).