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1.
Vaccine ; 40(31): 4090-4097, 2022 Jul 29.
Article in English | MEDLINE | ID: covidwho-1867869

ABSTRACT

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).


Subject(s)
COVID-19 , Clinical Trials as Topic , Patient Participation , Adult , COVID-19/epidemiology , COVID-19/prevention & control , Child , Europe/epidemiology , Humans , Registries , Volunteers
2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-337653

ABSTRACT

ABSTRACT Background Variant-adaptated vaccines against coronavirus disease 2019 (COVID-19) as boosters are needed to increase a broader protection against SARS CoV-2 variants. New adjuvanted recombinant protein vaccines as heterologous boosters could maximize the response. Methods In this randomized, single-blinded, multicenter trial, adults who had received two doses of Pfizer-BioNTech mRNA vaccine (BNT162b2) 3 to7 months before were randomly assigned to receive a boost of BNT162b2, Sanofi/GSK SARS-CoV-2 adjuvanted recombinant protein MV D614 (monovalent parental formulation) or SARS-CoV-2 adjuvanted recombinant protein MV B.1.351 vaccine (monovalent Beta formulation). The primary endpoint was the percentage of subjects with a ≥10-fold increase in neutralizing antibody titers for the Wuhan (D614) and B.1.351 (Beta) SARS-CoV-2 viral strains between day 0 and day 15. Findings The percentages of participants whose neutralizing antibody titers against the Wuhan (D614) SARS-CoV-2 strain increased by a factor ≥10 between day 0 and day 15 was 55.3% (95% CI 43.4-66.7) in MV D614 group (n=76), 76.1% (64.5-85.4) in MV B.1.351 (Beta) group (n=71) and 63.2% (51.3-73.9) in BNT162b2 group (n=76). These percentages were 44.7% (33.3-56.6), 84.5% (74.0-92.0) and 51.3% (39.6-63.0) for the B.1.351 (Beta) viral strain, respectively. Higher neutralizing antibodies rates against Delta and Omicron BA.1 variants were also elicited after Sanofi/GSK MV Beta vaccine compared to the other vaccines. Comparable reactogenicity profile was observed with the three vaccines. Interpretation Heterologous boosting with the Sanofi/GSK Beta formulation vaccine resulted in a higher neutralizing antibody response against Beta variant but also the original strain and Delta and Omicron BA.1 variants, compared with mRNA BNT162b2 vaccine or the Sanofi/GSK MVD614 formulation. New vaccines containing Beta spike protein may represent an interesting strategy for broader protection against SARS CoV-2 variants. Funding French Ministries of Solidarity and Health and Research and Sanofi Trial registration number ClinicalTrials.gov identifier NCT05124171 ;EudraCT identifier 2021-004550-33.

3.
EClinicalMedicine ; 48:101444-101444, 2022.
Article in English | EuropePMC | ID: covidwho-1842851

ABSTRACT

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.

4.
The Lancet. Infectious diseases ; 2022.
Article in English | EuropePMC | ID: covidwho-1837516
6.
N Engl J Med ; 386(23): 2188-2200, 2022 06 09.
Article in English | MEDLINE | ID: covidwho-1805743

ABSTRACT

BACKGROUND: The monoclonal-antibody combination AZD7442 is composed of tixagevimab and cilgavimab, two neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that have an extended half-life and have been shown to have prophylactic and therapeutic effects in animal models. Pharmacokinetic data in humans indicate that AZD7442 has an extended half-life of approximately 90 days. METHODS: In an ongoing phase 3 trial, we enrolled adults (≥18 years of age) who had an increased risk of an inadequate response to vaccination against coronavirus disease 2019 (Covid-19), an increased risk of exposure to SARS-CoV-2, or both. Participants were randomly assigned in a 2:1 ratio to receive a single dose (two consecutive intramuscular injections, one containing tixagevimab and the other containing cilgavimab) of either 300 mg of AZD7442 or saline placebo, and they were followed for up to 183 days in the primary analysis. The primary safety end point was the incidence of adverse events after a single dose of AZD7442. The primary efficacy end point was symptomatic Covid-19 (SARS-CoV-2 infection confirmed by means of reverse-transcriptase-polymerase-chain-reaction assay) occurring after administration of AZD7442 or placebo and on or before day 183. RESULTS: A total of 5197 participants underwent randomization and received one dose of AZD7442 or placebo (3460 in the AZD7442 group and 1737 in the placebo group). The primary analysis was conducted after 30% of the participants had become aware of their randomized assignment. In total, 1221 of 3461 participants (35.3%) in the AZD7442 group and 593 of 1736 participants (34.2%) in the placebo group reported having at least one adverse event, most of which were mild or moderate in severity. Symptomatic Covid-19 occurred in 8 of 3441 participants (0.2%) in the AZD7442 group and in 17 of 1731 participants (1.0%) in the placebo group (relative risk reduction, 76.7%; 95% confidence interval [CI], 46.0 to 90.0; P<0.001); extended follow-up at a median of 6 months showed a relative risk reduction of 82.8% (95% CI, 65.8 to 91.4). Five cases of severe or critical Covid-19 and two Covid-19-related deaths occurred, all in the placebo group. CONCLUSIONS: A single dose of AZD7442 had efficacy for the prevention of Covid-19, without evident safety concerns. (Funded by AstraZeneca and the U.S. government; PROVENT ClinicalTrials.gov number, NCT04625725.).


Subject(s)
Antiviral Agents , COVID-19 , Adult , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing/administration & dosage , Antibodies, Neutralizing/therapeutic use , Antiviral Agents/administration & dosage , Antiviral Agents/therapeutic use , COVID-19/prevention & control , Double-Blind Method , Drug Combinations , Humans , Injections, Intramuscular , SARS-CoV-2
7.
SSRN; 2022.
Preprint in English | SSRN | ID: ppcovidwho-333367

ABSTRACT

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has demonstrated the key role that vaccines play against infectious diseases. 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 January 2022, the questionnaire is available in 9 countries and 11 languages. Up to date, more than 35,000 volunteers have registered, mainly from Germany. Within the first year since its establishment, the VACCELERATE Volunteer Registry has matched 13,719 volunteers to clinical trials. The VACCELERATE Volunteer Registry will be launched in further European countries in the coming months. Conclusion: The VACCELERATE Volunteer Registry is an active single-entry point for European residents interested in COVID-19 clinical trials participation in 9 countries. To date, more than 13,000 registered individuals have been connected to clinical trials in Germany alone. The registry is currently in the implementation phase in 6 additional countries.

8.
Travel Med Infect Dis ; 48: 102321, 2022.
Article in English | MEDLINE | ID: covidwho-1773809

ABSTRACT

BACKGROUND: We aimed to elucidate which vaccines were accepted by European countries as valid proof of vaccination against COVID-19 for international travelers. METHOD: On 27-September-2021 a cross-sectional study was conducted on VisaGuide.World, that reports on valid vaccines for international travelers. Other databases, lay press and regulatory agencies were also checked. The main outcome measure was which of the vaccines included on the WHO emergency use listing (EUL) [ChAdOx1 (Vaxzevria, Covishield),BNT162b2,mRNA-1273,Ad26.CoV2.S,BBIBP-CorV,CoronaVac] and Sputnik V, were accepted in each country. The influence of the vaccines approved for COVID-19 vaccination programs on the vaccines recognized as proof of vaccination was assessed. RESULTS: There was a remarkable heterogeneity on the vaccines accepted as proof of vaccination among 46 countries. Russia accepted only one. Cyprus, Greece and Slovenia accepted all vaccines considered. Eleven countries accepted the seven WHO EUL vaccines: eight EU countries, plus Iceland, Norway and Switzerland. Seven EU countries accepted only the four EMA-authorized vaccines. Considering Covishield as equivalent to Vaxzevria, 69% of countries recognized only vaccinated travelers who received any of the vaccines approved for vaccination programs in the country of arrival as valid. CONCLUSION: Vaccines accepted as proof of vaccination should be harmonized. Accepting any of the WHO EUL vaccines would be a scientifically sound objective.


Subject(s)
COVID-19 , Vaccines , COVID-19/prevention & control , COVID-19 Vaccines , Cross-Sectional Studies , Health Policy , Humans
10.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327725

ABSTRACT

Objectives: We evaluated the clinical, virological and safety outcomes of lopinavir/ritonavir, lopinavir/ritonavir-interferon (IFN)-beta-1a, hydroxychloroquine or remdesivir in comparison to standard of care (control) in COVID-19 inpatients requiring oxygen and/or ventilatory support. While preliminary results were previously published, we present here the final results, following completion of the data monitoring. Methods We conducted a phase 3 multi-centre open-label, randomized 1:1:1:1:1, adaptive, controlled trial (DisCoVeRy), add-on trial to Solidarity ( NCT04315948 , EudraCT2020-000936-23). The primary outcome was the clinical status at day 15, measured by the WHO 7-point ordinal scale. Secondary outcomes included SARS-CoV-2 quantification in respiratory specimens, pharmacokinetic and safety analyses. We report the results for the lopinavir/ritonavir-containing arms and for the hydroxychloroquine arm, which were stopped prematurely. Results The intention-to-treat population included 593 participants (lopinavir/ritonavir, n=147;lopinavir/ritonavir-IFN-beta-1a, n=147;hydroxychloroquine, n=150;control, n=149), among whom 421 (71.0%) were male, the median age was 64 years (IQR, 54-71) and 214 (36.1%) had a severe disease. The day 15 clinical status was not improved with investigational treatments: lopinavir/ritonavir versus control, adjusted odds ratio (aOR) 0.82, (95% confidence interval [CI] 0.54-1.25, P=0.36);lopinavir/ritonavir-IFN-beta-1a versus control, aOR 0.69 (95%CI 0.45-1.05, P=0.08);hydroxychloroquine versus control, aOR 0.94 (95%CI 0.62-1.41, P=0.76). No significant effect of investigational treatment was observed on SARS-CoV-2 clearance. Trough plasma concentrations of lopinavir and ritonavir were higher than those expected, while those of hydroxychloroquine were those expected with the dosing regimen. The occurrence of Serious Adverse Events was significantly higher in participants allocated to the lopinavir/ritonavir-containing arms. Conclusion In adults hospitalized for COVID-19, lopinavir/ritonavir, lopinavir/ritonavir-IFN-beta-1a and hydroxychloroquine did not improve the clinical status at day 15, nor SARS-CoV-2 clearance in respiratory tract specimens.

11.
Int J Infect Dis ; 112: 247-253, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1654532

ABSTRACT

OBJECTIVES: Few studies have reported clinical COVID-19 sequelae six months (M6) after hospital discharge, but none has studied symptom severity. METHODS: Prevalence and severity of 7 symptoms were estimated until M6 using the self-administered influenza severity scale in COVID-19 hospitalized patients enrolled in the French COVID cohort. Factors associated with severity were assessed by logistic regression. Anxiety, depression and health-related quality of life (HRQL) were also assessed. RESULTS: At M6, among the 324 patients (median age 61 years, 63% men, 19% admitted to intensive care during the acute phase), 187/324 (58%) reported at least one symptom, mostly fatigue (47%) and myalgia (23%). Symptom severity was scored, at most, mild in 125 (67%), moderate in 44 (23%) and severe in 18 (10%). Female gender was the sole factor associated with moderate/severe symptom reporting (OR = 1.98, 95%CI=1.13-3.47). Among the 225 patients with psychological assessment, 24 (11%) had anxiety, 18 (8%) depressive symptoms, and their physical HRQL was significantly poorer than the general population (p=0.0005). CONCLUSION: Even if 58% of patients reported ≥1 symptom at M6, less than 7% rated any symptom as severe. Assessing symptoms severity could be helpful to identify patients requiring appropriate medical care. Women may require special attention.


Subject(s)
COVID-19 , Cohort Studies , Female , Hospitals , Humans , Male , Middle Aged , Prospective Studies , Quality of Life , SARS-CoV-2 , Self Report
12.
EBioMedicine ; 75: 103810, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1634471

ABSTRACT

BACKGROUND: V591 (TMV-083) is a live recombinant measles vector-based vaccine candidate expressing a pre-fusion stabilized SARS-CoV-2 spike protein. METHODS: We performed a randomized, placebo-controlled Phase I trial with an unblinded dose escalation and a double-blind treatment phase at 2 sites in France and Belgium to evaluate the safety and immunogenicity of V591. Ninety healthy SARS-CoV-2 sero-negative adults (18-55 years of age) were randomized into 3 cohorts, each comprising 24 vaccinees and 6 placebo recipients. Participants received two intramuscular injections of a low dose vaccine (1 × 105 median Tissue Culture Infectious Dose [TCID50]), one or two injections of a high dose vaccine (1 × 106 TCID50), or placebo with a 28 day interval. Safety was assessed by solicited and unsolicited adverse events. Immunogenicity was measured by SARS-CoV-2 spike protein-binding antibodies, neutralizing antibodies, spike-specific T cell responses, and anti-measles antibodies. ClinicalTrials.gov, NCT04497298. FINDINGS: Between Aug 10 and Oct 13, 2020, 148 volunteers were screened of whom 90 were randomized. V591 showed a good safety profile at both dose levels. No serious adverse events were reported. At least one treatment-related adverse event was reported by 15 (20.8%) participants receiving V591 vs. 6 (33.3%) of participants receiving placebo. Eighty-one percent of participants receiving two injections of V591 developed spike-binding antibodies after the second injection. However, neutralizing antibodies were detectable on day 56 only in 17% of participants receiving the low dose and 61% receiving the high dose (2 injections). Spike-specific T cell responses were not detected. Pre-existing anti-measles immunity had a statistically significant impact on the immune response to V591, which was in contrast to previous results with the measles vector-based chikungunya vaccine. INTERPRETATION: While V591 was generally well tolerated, the immunogenicity was not sufficient to support further development. FUNDING: Themis Bioscience GmbH, a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA; Coalition for Epidemic Preparedness Innovations (CEPI).


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/immunology , Genetic Vectors , Immunogenicity, Vaccine , Measles virus , SARS-CoV-2/immunology , Adolescent , Adult , COVID-19/genetics , COVID-19/prevention & control , COVID-19 Vaccines/genetics , COVID-19 Vaccines/immunology , Double-Blind Method , Female , Humans , Male , Middle Aged , SARS-CoV-2/genetics
15.
Hum Vaccin Immunother ; 17(12): 5082-5088, 2021 12 02.
Article in English | MEDLINE | ID: covidwho-1569475

ABSTRACT

The French health authorities extended vaccination against COVID-19 to adolescents in June 2021, during the epidemic resurgence linked to the delta variant and because of insufficient vaccination coverage to ensure collective protection. In May 2021, we conducted a national online cross-sectional survey of 2533 adults in France to study their attitudes toward COVID-19 vaccines and their acceptance of child/adolescent vaccination according to targeted age groups (<6 years; 6-11; 12-17) and its determinants. We applied a multi-model averaged logistic regression for each of these age groups to study the determinants of favorability to vaccination. Among the respondents, 62.7% (1597) accepted COVID-19 vaccination for adolescents, 48.3% (1223) for children aged 6-11 years, and only 31% (783) for children under 6 years. Acceptance increased with fear of contracting COVID-19 and trust in institutions and decreased as the COVID-19 vaccine risk perception score increased. People favorable to vaccination in general and those sensitive to social pressure were also more often favorable to vaccinating children/adolescents than those who were not. Drivers of acceptance were ranked differently for the different age groups. Understanding these differences is essential to anticipating obstacles to vaccination of these age groups and designing appropriate information and motivational strategies to support it.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adolescent , Adult , COVID-19/epidemiology , COVID-19/prevention & control , Child , Child, Preschool , Cross-Sectional Studies , Humans , SARS-CoV-2 , Vaccination
16.
Therapie ; 77(1): 59-67, 2022.
Article in English | MEDLINE | ID: covidwho-1569090

ABSTRACT

The COVID-19 pandemic led to the deployment of an unprecedented academic and industrial research effort, the sometimes redundant nature of which is regrettable, as is the lack of both national and international management. However, it must be noted that during this crisis, regulatory procedures were adapted and certain obstacles in the organisation of clinical research were partly removed to contribute to the deployment of trials as close as possible to patients and to facilitate monitoring and control procedures. The digitisation of certain processes and the decentralisation of certain activities were implemented under the cover of a mobilisation of the authorities and all institutional, academic and industrial players. While in the UK, the optimisation of resources through a single platform trial has made it possible to demonstrate or invalidate the efficacy of many treatments, in France the health crisis has highlighted the fragility of the organisation of clinical research, in particular a lack of coordination and funding, difficulties in implementing studies and a certain reluctance to share data. However, the crisis has also revealed the adaptability of the various stakeholders and has led to the improvement of several processes useful for the deployment of therapeutic innovation. Let us hope that the lessons learned during this crisis will allow for greater efficiency in the event of a new pandemic and, above all, that the progress made will continue to apply to all future clinical research activities.


Subject(s)
COVID-19 , Pandemics , Biomedical Research , COVID-19/drug therapy , COVID-19/epidemiology , Clinical Trials as Topic , France/epidemiology , Humans , Pharmaceutical Preparations , United Kingdom/epidemiology
17.
Infect Dis Now ; 52(1): 40-43, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1568740

ABSTRACT

BACKGROUND: Measuring vaccine effectiveness (VE) using real-life data is critical to confirm the effectiveness of licensed vaccine, which could strengthen vaccination adherence. METHODS: We measured VE against adult COVID-19 hospitalization in five hospitals in France using a test negative design. We compared the odds of vaccinated patients hospitalized with COVID-19 with the odds of vaccinated patients hospitalized for the same symptoms with a negative test. RESULTS: A total of 853 patients (463 cases and 390 controls) were included, with a total of 170 patients vaccinated (104 with one dose, 65 with two doses, and one with three doses). There were four cases of breakthrough infections, all in immunocompromised patients. The VE was 84.0% (CI0.95=[72.6; 90.6]) for one dose and 96.2% (CI0.95=[86.8; 98.9]) for two doses. CONCLUSION: Our results confirm the high VE of COVID-19 vaccine in France to prevent hospitalizations due to the alpha variant.


Subject(s)
COVID-19 , Adult , COVID-19 Vaccines , Case-Control Studies , Hospitalization , Humans , SARS-CoV-2
18.
Open forum infectious diseases ; 8(Suppl 1):S810-S810, 2021.
Article in English | EuropePMC | ID: covidwho-1564407

ABSTRACT

Background Vaccines effectively prevent COVID-19, but some individuals have medical comorbidities or receive therapies that impair their immune response to vaccination, or are ineligible for vaccination. For such individuals who remain at risk of COVID-19, monoclonal antibodies may provide additional rapid protection. AZD7442 comprises 2 fully human extended half-life SARS-CoV-2–neutralizing antibodies that bind distinct epitopes of the viral spike protein receptor binding domain. AZD7442 is in development for the prevention and treatment of COVID-19. Here, we report primary Phase 3 study results of AZD7442 for pre-exposure prophylaxis of symptomatic COVID-19. Methods PROVENT (NCT04625725) is a Phase 3, 2:1 randomized, double-blind, placebo-controlled study of a single 300-mg AZD7442 dose (2 intramuscular injections;150 mg each of tixagevimab and cilgavimab) for symptomatic COVID-19 prevention. Participants were unvaccinated adults (≥ 18 years old) without prior SARS-CoV-2 infection, who may benefit from immunoprophylaxis with antibodies due to an increased risk of either inadequate response to vaccination or SARS-CoV-2 exposure. The primary study endpoints were first case of SARS-CoV-2 RT-PCR-positive symptomatic illness post dose and prior to Day 183 (efficacy), and safety of AZD7442. Results In total, 5197 participants (mean age 53.5 years, 46% female) were randomized and dosed (safety analysis set): AZD7442 n=3460;placebo n=1737. In the primary efficacy analysis (full pre-exposure analysis set, n=5172), AZD7442 reduced the risk of developing symptomatic COVID-19 by 77% (95% confidence interval 46.0, 90.0) vs placebo (P< 0.001) (Table). Adverse events occurred in 35% and 34% of participants administered AZD7442 and placebo, respectively, and injection site reactions occurred in 2.4% and 2.1% of participants, respectively (safety analysis set). There was 1 case of severe/critical COVID-19 and 2 COVID-19–related deaths in the placebo arm. Conclusion The primary study endpoints were met: a one-time dose of AZD7442 demonstrated statistically significant protection against symptomatic COVID-19 and was well tolerated. AZD7442 is the first long-acting monoclonal antibody combination that represents a potential new option to augment COVID-19 prevention. PROVENT funding statement image Disclosures Myron J. Levin, MD, GSK group of companies (Employee, Research Grant or Support) Andrew Ustianowski, MBBS, Vir/GlaxoSmithKline (Advisor or Review Panel member) Stéphane De Wit, MD, Gilead (Grant/Research Support)Janssen (Grant/Research Support)Merck Sharpe & Dohme (Grant/Research Support)ViiV Healthcare (Grant/Research Support) Odile Launay, MD, PhD, AstraZeneca (Grant/Research Support)GlaxoSmithKline (Consultant, Grant/Research Support, Other Financial or Material Support, Data safety monitoring board)Johnson & Johnson (Consultant, Grant/Research Support)Moderna (Consultant)Pfizer (Consultant, Grant/Research Support)Sanofi Pasteur (Consultant, Grant/Research Support) Miles Avila, MPH, GStat, AstraZeneca (Employee, Shareholder) Seth Seegobin, PhD, AstraZeneca (Employee, Shareholder) Alison Templeton, PhD, AstraZeneca (Employee, Shareholder) Yuan Yuan, PhD, AstraZeneca (Employee, Shareholder) Philip Ambery, FRCP, AstraZeneca (Employee, Shareholder) Rosalinda H. Arends, PhD, AstraZeneca (Employee, Shareholder) Rohini Beavon, PhD, AstraZeneca (Employee, Shareholder) Karen A. Near, MD, AstraZeneca (Employee, Shareholder) Kelly W. Padilla, PharmD, AstraZeneca (Employee, Shareholder) Konstantina Psachoulia, PhD, AstraZeneca (Employee, Shareholder) Audrey Sharbaugh, PhD, AstraZeneca (Employee, Shareholder) Katie Streicher, PhD, AstraZeneca (Employee, Shareholder) Menelas N. Pangalos, PhD, AstraZeneca (Employee, Shareholder) Mark T. Esser, PhD, AstraZeneca (Employee, Shareholder) Robert A. Gasser, Jr., MD, AstraZeneca (Employee, Shareholder)

19.
Therapie ; 2021.
Article in French | EuropePMC | ID: covidwho-1564057

ABSTRACT

La pandémie de coronavirus disease -19 (COVID-19) a conduit au déploiement d’un effort de recherche académique et industriel sans précédent dont on peut regretter le caractère parfois redondant ainsi que le manque de pilotage tant national qu’international. Pourtant, force est de constater qu’à l’occasion de cette crise, les procédures réglementaires ont été adaptées de même que certains freins dans l’organisation de la recherche clinique ont pu être en partie levés pour contribuer au déploiement d’essais au plus près des patients et faciliter les modalités de suivi et de contrôle. La digitalisation de certains processus et la décentralisation de certaines activités ont pu être mises en œuvre sous couvert d’une mobilisation des autorités et de l’ensemble des acteurs institutionnels, académiques ou industriels. Si outre-manche, l’optimisation des ressources, au travers d’un essai de plateforme unique, a permis de montrer ou d’infirmer l’efficacité de nombreux traitements, en France la crise sanitaire a mis en lumière la fragilité de l’organisation de la recherche clinique, notamment un déficit de coordination et de financement, des difficultés dans la mise en œuvre des études ou encore une certaine frilosité concernant le partage des données. Cependant, la crise a aussi révélé les capacités d’adaptation des différents acteurs et permis l’amélioration de plusieurs processus utiles au déploiement de l’innovation thérapeutique. Gageons que les leçons tirées à l’occasion de cette crise permettront une meilleure efficacité en cas de nouvelle pandémie et surtout que les progrès obtenus continueront de s’appliquer à l’ensemble des activités de recherche clinique futures.

20.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-294750

ABSTRACT

Objectives Reaching the last pockets of unvaccinated people is challenging, and has led to consider COVID-19 mandatory vaccination. Our aim was to assess attitudes toward COVID-19 mandatory vaccination in France before the announcement and factors associated with opposition to this type of policy. Methods Between the 10th and the 23rd of May 2021, we conducted a cross-sectional online survey among a representative sample of the French population aged 18 and over and a specific sample of the French Senior Population over 65. Results Among 3,056 respondents, 1,314 (43.0 %) were in favor of mandatory COVID-19 vaccination, 1,281 (41.9 %) were opposed to such a policy, and 461 (15.1 %) were undecided. Among opponents to COVID-19 mandatory vaccination for the general population, 385 (30.05 %) were in favor of a mandatory COVID-19 vaccination for healthcare workers (HCWs). In multivariate analysis, age groups 18-24 years, and 25-34 years were significantly more opposed than the reference group (>75 years old) with respective adjusted odds ratio (aOR) and 95 % confidence interval (95 % CI) 4.67 (1.73-12.61) and 3.74 (1.57-8.93). No intention of getting COVID-19 vaccine was strongly associated with opposition to mandatory vaccination with aOR 10.67 (95 % CI 6.41-17.76). In comparison with partisans of the center, partisans of the far left and green parties were more likely to be opposed to COVID-19 mandatory vaccine with respective aOR (95 % CI) 1;89 (1.06-3.38) and 2.08 (1.14-3.81). Conclusion Attitudes toward mandatory COVID-19 vaccination are split in the French general population, and the debate might become politicized.

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