Monitoring COVID-19 Vaccination Response in Fragile Populations

SARS CoV 2 Infection Clinical Trial

— ORCHESTRA-4  

Official title:

"Multicenter Observational Study to Assess the Incidence and Features of COVID-19 and the Response to COVID-19 Vaccination in Fragile Patients"

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05222139
• Other study ID #: ORCHESTRA-4
• Status: Recruiting
• Start date: May 24, 2021
• Est. completion date: July 16, 2023

Study information

• Verified date: February 2022
• Source: University of Bologna
• Contact: Maddalena Giannella, MD
• Phone: +39 0512143199
• Email: maddalena.giannella[@]unibo.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The present study is part of ORCHESTRA project, a three-year international research project aimed at tackling the coronavirus pandemic. ORCHESTRA provides an innovative approach to learn from the pandemic SARS-CoV-2 crisis, derive recommendations to further management of COVID-19 and be prepared for the possible future pandemic waves. The ORCHESTRA project aims to deliver sound scientific evidence for the prevention and treatment of the infections caused by SARS-CoV-2 assessing epidemiological, clinical, microbiological, and genotypic aspects of population, environment and socio-economic features. The project builds upon existing, and new largescale population cohorts in Europe (France, Germany, Spain, Italy, Belgium, Romania, Netherlands, Luxemburg, and Slovakia) and non-European countries (India, Perú, Ecuador, Colombia, Venezuela, Argentina, Brazil and Gabon) including SARS-CoV-2 infected and non-infected individuals of all ages and conditions. The primary aim of ORCHESTRA is the creation of a new pan European cohort applying homogenous protocols for data collection, data sharing, sampling, and follow-up, which can rapidly advance the knowledge on the control and management of the COVID-19. ORCHESTRA will include SARS-CoV-2-negative individuals and thereby enable a prospective follow-up and an analysis of vaccination response. The cohort will involve four different populations: general population, COVID-19 patients, fragile individuals (children, elderly, transplanted, oncological, HIV infected, and those with Parkinson disease), and health-care workers. Each of these "perpetual" cohorts can answer different research questions and vaccine strategies.

Within the ORCHESTRA project, the Work Package 4 (WP4) will focus on the cohort of fragile patients including pregnant women/new-born, children, patients with HIV infection, patients with autoimmune disease, solid organ transplant recipients, patients with oncological and hematological diseases, patients with cystic fibrosis, patients with Parkinson Disease and rheumatological diseases from from 14 countries (5 European and 9 non-European countries), with approximately 20000 subjects.

Description:

Since the beginning of COVID-19 pandemic, several special settings have been identified regarding the susceptibility to SARS-CoV-2 infection, the associated clinical spectrum and outcome. The participants include pregnant women, pediatric patients, elderly in particular those whole live in long-term care facilities (LTCFs), and immunocompromised hosts including solid organ transplant recipients (SOT), hematopoietic stem cell transplant (HSCT) recipients and patients with cancer. Among pregnant women and children, asymptomatic or mild diseases have been frequently reported, prompting controversial concerns about their role in the infection transmission in community and hospital settings.

On the other hand, a high impact of COVID-19 on morbidity and mortality has been described in elderly and immuno-compromised hosts. Thus, optimization of prevention strategies, screening practices and therapeutic management is strongly advocated in fragile patients. Indeed, these settings have been established as priority groups for vaccines. However, safety and efficacy of vaccination in these populations should be carefully assessed. Thus, preliminary epidemiological data are strongly needed to design further intervention trials and health policies.

Besides, an increasing body of evidence suggests that the gut microbiota plays a role in determining the severity of COVID-19, possibly through the modulation of immune responses. Furthermore, dysbiosis of the gut microbiota could contribute to the persistence of symptoms, even after the resolution of the disease.

For the same reasons, the microbiota could be involved in the onset of adverse reactions induced by vaccination, especially in fragile populations, as recently discussed. Defining the impact of the microbiota on immunity to vaccination and therefore on its effectiveness is currently considered a priority in various clinical settings.

Moreover, early observations show that vaccines do not induce an immune response conferring protection to many fragile patients, resulting in severe Covid-19 cases. It is important to understand what cellular networks and molecular pathways are switched on/off by the administration of vaccines, and to identify the biological patterns that characterize responders and non-responders. DNA methylation and gene expression analyses may inform on the genomic patterns involved in response to vaccines and in the differences between responders and non-responders. Indeed, DNA sequencing may reveal that the perturbation detected at the regulatory levels may be influenced by alterations in the genome of the divergent subjects.

With this premise, the Investigators deem that a WP dedicated to fragile patients in the ORCHESTRA project is necessary to inform about the peculiarities of the fragile cohort as a whole, and of each subgroup as well, providing clinical and biological information useful to design targeted prevention and therapeutic strategies.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20000
• Est. completion date: July 16, 2023
• Est. primary completion date: July 16, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Any age

• Any comorbidity

• Person (or attorney or deputy who has been authorized to make the decision for patients who lack capacity) consent to participate or appropriate local waiver of consent.

Exclusion Criteria:

• Patients did not agree to participate

Related Conditions & MeSH terms

• Communicable Diseases
• COVID-19
• Infections
• Vaccination; Infection

Intervention

Biological:
• COVID-19 vaccination
Monitoring COVID-19 vaccination

Locations

Country	Name	City	State
Argentina	Universidad de Buenos Aires (UBA)	Buenos Aires
Gabon	Centre de Recherches Medicales de Lambaréné (CERMEL)	Lambaréné
India	Catholics Bishops Conference of India, Society for Medical Education (CBCI)	Bangalore
India	Translational Health Science and Technology Institute (THSTI)	Faridabad
Ireland	University College Dublin	Dublin
Italy	University of Bologna	Bologna
Italy	ICONA Foundation	Milano
Italy	Aziena Ospedaliera Universitaria di Padova - Centro Trapianti di fegato	Padova
Italy	Azienda Ospedaliera Universitaria di Padova - Centro trapianti di polmone	Padova
Italy	Azienda Ospedaliera Universitaria di Padova - UOC Chirurgia dei trapianti di rene	Padova
Italy	Azienda Ospedaliera Universitaria di Padova - UOC Nefrologia Pediatrica	Padova
Italy	Azienda Ospedaliero Universitaria di Padova - Clinica Medica 5	Padova
Italy	Azienda Ospedaliero Universitaria di Padova - Trapianto Multiviscerale	Padova
Italy	Azienda Ospedaliero Universitaria di Padova - UOC Cardiochirurgia	Padova
Italy	Azienda Ospedaliero Universitaria di Padova - UOC Clinica Pediatrica	Padova
Italy	PENTA Foundation	Padova
Italy	Azienda Ospedaliera Universitaria di Parma	Parma
Italy	Azienda ULSS2 Marca Trevigiana	Treviso
Italy	University of Verona	Verona
Luxembourg	Luxembourg Institute of Health (LIH)	Luxembourg
Netherlands	University Medical Center Groningen (UMCG)	Groningen
Spain	Hosp. Univ. Virgen Macarena / Universidad de Sevilla	Sevilla

Sponsors (18)

Lead Sponsor

Collaborator

University of Bologna

Azienda Ospedaliera di Padova, Azienda Ospedaliero-Universitaria di Parma, Azienda Ulss 2 Marca Trevigiana, Centre de Recherche Médicale de Lambaréné, Charite University, Berlin, Germany, CINECA consorzio universitario italiano, Helmholtz Zentrum München, Hospital Universitario Virgen Macarena, ICONA Foundation, Institut National de la Santé Et de la Recherche Médicale, France, Luxembourg Institute of Health, PENTA Foundation, Universita di Verona, Universiteit Antwerpen, University College Dublin, University Medical Center Groningen, University of Buenos Aires

Countries where clinical trial is conducted

Argentina,  Gabon,  India,  Ireland,  Italy,  Luxembourg,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Early immune response to COVID-19 vaccine patients	To investigate the early immune response to COVID-19 vaccine in fragile patients assessing the levels of antibodies against Spike antigens and the patterns of cellular immune response	3 ± 1 month after vaccination onset
Primary	Late immune response to COVID-19 vaccine	To investigate the late immune response to COVID-19 vaccine in fragile patients assessing the levels of antibodies against Spike antigens and the patterns of cellular immune response	12 ± 3 months after vaccination onset
Primary	Rate of COVID-19 breakthrough infections	To investigate the rate of COVID-19 breakthrough infections in fragile patients within 1 year after vaccination onset	within 1 year after vaccination onset
Primary	Rate of hospital admission for COVID-19 breakthrough infections condition and its impact on the outcome in fragile patients	To investigate the rate of hospital admission for COVID-19 breakthrough infections in fragile patients	within 1 year after vaccination onset
Primary	Rate of death for COVID-19 breakthrough infections patients	To investigate the rate of death for COVID-19 breakthrough infections in fragile patients	within 1 year after vaccination onset