SARS CoV 2 InfectionORCHESTRA-4NCT05222139
Monitoring COVID-19 Vaccination Response in Fragile Populations
An observational study of SARS CoV 2 Infection and Vaccination; Infection, run by University of Bologna at 20 sites in 7 countries.
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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- SARS CoV 2 Infection, Vaccination; Infection, Breakthrough Infection
- What is being tested?
- COVID-19 vaccination
- Type of treatment
- Vaccines
- How many people
- 8,894 participants
- Where
- 20 sitesin 7 countries
- Study dates
- 24 May 2021to 30 Nov 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients of all age and any comorbidity included in an ORCHESTRA fragile population cohort
Who may be able to join
- 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.
Who cannot join
- Patients did not agree to participate
Trial locations and contacts
20 sites in 7 countries.
20 sites in 7 countries
Italy13 sites
University of Bologna
Bologna
ICONA Foundation
Milan
Aziena Ospedaliera Universitaria di Padova - Centro Trapianti di fegato
Padova
Azienda Ospedaliera Universitaria di Padova - Centro trapianti di polmone
Padova
Azienda Ospedaliera Universitaria di Padova - UOC Chirurgia dei trapianti di rene
Padova
Azienda Ospedaliera Universitaria di Padova - UOC Nefrologia Pediatrica
Padova
Azienda Ospedaliero Universitaria di Padova - Clinica Medica 5
Padova
Azienda Ospedaliero Universitaria di Padova - Trapianto Multiviscerale
Padova
Azienda Ospedaliero Universitaria di Padova - UOC Cardiochirurgia
Padova
Azienda Ospedaliero Universitaria di Padova - UOC Clinica Pediatrica
Padova
PENTA Foundation
Padova
Azienda ULSS2 Marca Trevigiana
Treviso
University of Verona
Verona
India2 sites
Catholics Bishops Conference of India, Society for Medical Education (CBCI)
Bangalore
Translational Health Science and Technology Institute (THSTI)
Faridabad
About this study
Official title: "Multicenter Observational Study to Assess the Incidence and Features of COVID-19 and the Response to COVID-19 Vaccination in Fragile Patients"
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.
Read the 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.
- Being tested
- COVID-19 vaccination
- Keywords
- Frail patients
- Medical subject headings
- COVID-19, Infections, Breakthrough Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
COVID-19 vaccinationBiological
Monitoring COVID-19 vaccination
| Study group | Role | What they receive |
|---|---|---|
| Solid organ transplant recipients | Solid organ transplant recipients Receives: Biological: COVID-19 vaccination | |
| People living with HIV | People living with HIV Receives: Biological: COVID-19 vaccination | |
| Patients with oncological diseases | Patients with oncological diseases Receives: Biological: COVID-19 vaccination | |
| Patients with hematological diseases | Patients with hematological diseases Receives: Biological: COVID-19 vaccination | |
| Patients with cystic fibrosis | Patients with cystic fibrosis Receives: Biological: COVID-19 vaccination | |
| Patients with Parkinson Disease | Patients with Parkinson Disease Receives: Biological: COVID-19 vaccination | |
| Patients with rheumatological diseases | Patients with rheumatological diseases Receives: Biological: COVID-19 vaccination | |
| Pregnant women/ New-borns | Pregnant women/ New-borns Receives: Biological: COVID-19 vaccination | |
| Children | Children Receives: Biological: COVID-19 vaccination |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 3 ± 1 month after vaccination onset
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
Measured: 12 ± 3 months after vaccination onset
Rate of COVID-19 breakthrough infections
To investigate the rate of COVID-19 breakthrough infections in fragile patients within 1 year after vaccination onset
Measured: within 1 year after vaccination onset
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
Measured: within 1 year after vaccination onset
Rate of death for COVID-19 breakthrough infections patients
To investigate the rate of death for COVID-19 breakthrough infections in fragile patients
Measured: within 1 year after vaccination onset
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2022
- Study start24 May 2021
- Primary completion16 Jul 2023
- Study completion30 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SARS CoV 2 InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 8,894 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Bologna
- Sponsor type
- University, hospital or other
- Collaborators
- Universita di Verona, Hospital Universitario Virgen Macarena, Azienda Ospedaliera di Padova, Azienda Ospedaliero-Universitaria di Parma, Azienda Ulss 2 Marca Trevigiana, University College Dublin, Luxembourg Institute of Health, Fondazione ICONA, University Medical Center Groningen, University of Buenos Aires, PENTA Foundation, Universiteit Antwerpen, Institut National de la Santé Et de la Recherche Médicale, France, Helmholtz Zentrum München, CINECA consorzio universitario italiano, Charite University, Berlin, Germany, Centre de Recherche Médicale de Lambaréné
- Responsible party
- Principal investigator, Maddalena Giannella, University of Bologna
- Investigators
- Maddalena Giannella, MD PhD, Principal investigator, University of Bologna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05222139
- Sponsor's protocol ID
- ORCHESTRA-4
- Acronym
- ORCHESTRA-4
- Status last verified
- Mar 2025
- First submitted
- 8 Nov 2021
- Last updated
- 25 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- "Multicenter Observational Study to Assess the Incidence and Features of COVID-19 and the Response to COVID-19 Vaccination in Fragile Patients"
- ClinicalTrials.gov ID
- NCT05222139
- Acronym / sponsor ID
- ORCHESTRA-4 / ORCHESTRA-4
- Keywords
- Frail patients
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 8,894 participants (actual)
- Lead sponsor
- University of BolognaUniversity, hospital or other
- Collaborators
- Universita di Verona, Hospital Universitario Virgen Macarena, Azienda Ospedaliera di Padova, Azienda Ospedaliero-Universitaria di Parma, Azienda Ulss 2 Marca Trevigiana, University College Dublin, Luxembourg Institute of Health, Fondazione ICONA, University Medical Center Groningen, University of Buenos Aires, PENTA Foundation, Universiteit Antwerpen, Institut National de la Santé Et de la Recherche Médicale, France, Helmholtz Zentrum München, CINECA consorzio universitario italiano, Charite University, Berlin, Germany, Centre de Recherche Médicale de Lambaréné
- Study start
- 24 May 2021 (actual)
- Primary completion
- 16 Jul 2023 (actual)
- Study completion
- 30 Nov 2024 (actual)
- First posted
- 3 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| Solid organ transplant recipients | – | Biological: COVID-19 vaccinationSolid organ transplant recipients |
| People living with HIV | – | Biological: COVID-19 vaccinationPeople living with HIV |
| Patients with oncological diseases | – | Biological: COVID-19 vaccinationPatients with oncological diseases |
| Patients with hematological diseases | – | Biological: COVID-19 vaccinationPatients with hematological diseases |
| Patients with cystic fibrosis | – | Biological: COVID-19 vaccinationPatients with cystic fibrosis |
| Patients with Parkinson Disease | – | Biological: COVID-19 vaccinationPatients with Parkinson Disease |
| Patients with rheumatological diseases | – | Biological: COVID-19 vaccinationPatients with rheumatological diseases |
| Pregnant women/ New-borns | – | Biological: COVID-19 vaccinationPregnant women/ New-borns |
| Children | – | Biological: COVID-19 vaccinationChildren |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients of all age and any comorbidity included in an ORCHESTRA fragile population cohort
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (1 listed)
- Patients did not agree to participate
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| COVID-19 vaccinationMonitoring COVID-19 vaccination | Biological | Children, Patients with Parkinson Disease, Patients with cystic fibrosis, Patients with hematological diseases, Patients with oncological diseases, Patients with rheumatological diseases, People living with HIV, Pregnant women/ New-borns, Solid organ transplant recipients |
Primary outcome
Early immune response to COVID-19 vaccine patients
Time frame: 3 ± 1 month after vaccination onset
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
Late immune response to COVID-19 vaccine
Time frame: 12 ± 3 months after vaccination onset
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
Rate of COVID-19 breakthrough infections
Time frame: within 1 year after vaccination onset
To investigate the rate of COVID-19 breakthrough infections in fragile patients within 1 year after vaccination onset
Rate of hospital admission for COVID-19 breakthrough infections condition and its impact on the outcome in fragile patients
Time frame: within 1 year after vaccination onset
To investigate the rate of hospital admission for COVID-19 breakthrough infections in fragile patients
Rate of death for COVID-19 breakthrough infections patients
Time frame: within 1 year after vaccination onset
To investigate the rate of death for COVID-19 breakthrough infections in fragile patients
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2025.
- SARS-CoV-2 vaccination in solid-organ transplant recipients: What the clinician needs to know.Link provided by the sponsor.
- Evaluation of the kinetics of antibody response to COVID-19 vaccine in solid organ transplant recipients: the prospective, multicenter ORCHESTRA cohort.Link provided by the sponsor.
- Relationship Between Immune Response to Severe Acute Respiratory Syndrome Coronavirus 2 Vaccines and Development of Breakthrough Infection in Solid Organ Transplant Recipients: The CONTRAST CohortLink provided by the sponsor.
- Effect of a Fourth Dose of mRNA Vaccine and of Immunosuppression in Preventing SARS-CoV-2 Breakthrough Infections in Heart Transplant Patients.Link provided by the sponsor.
- Using machine learning to predict antibody response to SARS-CoV-2 vaccination in Solid Organ Transplant Recipients. The multicentre ORCHESTRA cohort.Link provided by the sponsor.
- SARS-CoV-2 mRNA Vaccine Response in People Living with HIV According to CD4 Count and CD4/CD8 Ratio.Link provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Maddalena Giannella, MD PhD principal investigator
University of Bologna
20 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of SARS CoV 2 Infection and Vaccination; Infection, run by University of Bologna at 20 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in Italy, India, Argentina, Gabon, Luxembourg and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Early immune response to COVID-19 vaccine patients (time frame: 3 ± 1 month after vaccination onset). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2025.