Monitoring COVID-19 Vaccination Response in Fragile Populations

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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SARS CoV 2 Infection, Vaccination; Infection, Breakthrough Infection

Intervention / Treatment
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* Biological: COVID-19 vaccination


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Solid organ transplant recipients<br>Solid organ transplant recipients | Biological: COVID-19 vaccination<br>* Monitoring COVID-19 vaccination<br>|
| Patients with HIV infection<br>Patients with HIV infection | Biological: COVID-19 vaccination<br>* Monitoring COVID-19 vaccination<br>|
| Patients with oncological diseases<br>Patients with oncological diseases | Biological: COVID-19 vaccination<br>* Monitoring COVID-19 vaccination<br>|
| Patients with hematological diseases<br>Patients with hematological diseases | Biological: COVID-19 vaccination<br>* Monitoring COVID-19 vaccination<br>|
| Patients with autoimmune diseases<br>Patients with autoimmune diseases | Biological: COVID-19 vaccination<br>* Monitoring COVID-19 vaccination<br>|
| Patients with cystic fibrosis<br>Patients with cystic fibrosis | Biological: COVID-19 vaccination<br>* Monitoring COVID-19 vaccination<br>|
| Patients with Parkinson Disease<br>Patients with Parkinson Disease | Biological: COVID-19 vaccination<br>* Monitoring COVID-19 vaccination<br>|
| Patients with rheumatological diseases<br>Patients with rheumatological diseases | Biological: COVID-19 vaccination<br>* Monitoring COVID-19 vaccination<br>|
| Pregnant women/ New-borns<br>Pregnant women/ New-borns | Biological: COVID-19 vaccination<br>* Monitoring COVID-19 vaccination<br>|
| Children<br>Children | Biological: COVID-19 vaccination<br>* Monitoring COVID-19 vaccination<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Frail patients