Clinical trial NCT05222139: Monitoring COVID-19 Vaccination Response in Fragile Populations
Official title: "Multicenter Observational Study to Assess the Incidence and Features of COVID-19 and the Response to COVID-19 Vaccination in Fragile Patients"
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: SARS CoV 2 Infection
Vaccination; Infection
Breakthrough Infection
Keywords: Frail patients
Lead sponsor: University of Bologna
Sponsor class: OTHER
Collaborators: name: Universita di Verona
name: Hospital Universitario Virgen Macarena
name: Azienda Ospedaliera di Padova
name: Azienda Ospedaliero-Universitaria di Parma
name: Azienda Ulss 2 Marca Trevigiana
name: University College Dublin
name: Luxembourg Institute of Health
name: Fondazione ICONA
name: University Medical Center Groningen
name: University of Buenos Aires
name: PENTA Foundation
name: Universiteit Antwerpen
name: Institut National de la Santé Et de la Recherche Médicale, France
name: Helmholtz Zentrum München
name: CINECA consorzio universitario italiano
name: Charite University, Berlin, Germany
name: Centre de Recherche Médicale de Lambaréné
First posted: 2022-02-03
Enrollment: 8894
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients of all age and any comorbidity included in an ORCHESTRA fragile population cohort

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Early immune response to COVID-19 vaccine patients
timeFrame: 3 ± 1 month after vaccination onset
measure: Late immune response to COVID-19 vaccine
timeFrame: 12 ± 3 months after vaccination onset
measure: Rate of COVID-19 breakthrough infections
timeFrame: within 1 year after vaccination onset
measure: Rate of hospital admission for COVID-19 breakthrough infections condition and its impact on the outcome in fragile patients
timeFrame: within 1 year after vaccination onset
measure: Rate of death for COVID-19 breakthrough infections patients
timeFrame: within 1 year after vaccination onset
Secondary outcomes:
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Universidad de Buenos Aires (UBA)
city: Lambaréné
country: Gabon
facility: Centre de Recherches Medicales de Lambaréné (CERMEL)
city: Bangalore
country: India
facility: Catholics Bishops Conference of India, Society for Medical Education (CBCI)
city: Faridabad
country: India
facility: Translational Health Science and Technology Institute (THSTI)
city: Bologna
country: Italy
facility: University of Bologna
city: Milano
country: Italy
facility: ICONA Foundation
city: Padova
country: Italy
facility: Aziena Ospedaliera Universitaria di Padova - Centro Trapianti di fegato
city: Padova
country: Italy
facility: Azienda Ospedaliera Universitaria di Padova - Centro trapianti di polmone
city: Padova
country: Italy
facility: Azienda Ospedaliera Universitaria di Padova - UOC Chirurgia dei trapianti di rene
city: Padova
country: Italy
facility: Azienda Ospedaliera Universitaria di Padova - UOC Nefrologia Pediatrica
city: Padova
country: Italy
facility: Azienda Ospedaliero Universitaria di Padova - Clinica Medica 5
city: Padova
country: Italy
facility: Azienda Ospedaliero Universitaria di Padova - Trapianto Multiviscerale
city: Padova
country: Italy
facility: Azienda Ospedaliero Universitaria di Padova - UOC Cardiochirurgia
city: Padova
country: Italy
facility: Azienda Ospedaliero Universitaria di Padova - UOC Clinica Pediatrica
city: Padova
country: Italy
facility: PENTA Foundation
city: Treviso
country: Italy
facility: Azienda ULSS2 Marca Trevigiana
city: Verona
country: Italy
facility: University of Verona
city: Luxembourg
country: Luxembourg
facility: Luxembourg Institute of Health (LIH)
city: Groningen
country: Netherlands
facility: University Medical Center Groningen (UMCG)
city: Sevilla
country: Spain
facility: Hosp. Univ. Virgen Macarena / Universidad de Sevilla
Study officials:
affiliation: University of Bologna
name: Maddalena Giannella, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: