Covid-19 Antibody Responses in Cystic Fibrosis (CAR-CF)

February 23, 2024 updated by: Universitätsklinikum Köln

Corona-Virus-Disease 2019 (Covid-19) Antibody Responses in Cystic Fibrosis

Coronavirus disease 2019 (COVID-19) which is caused by the virus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has resulted in an ongoing global pandemic. It is unclear whether the relatively low number of reported cases of COVID-19 in people with CF (pwCF) is due to enhanced infection prevention practices or whether pwCF have protective genetic/immune factors. This study aims to prospectively assess the proportion of pwCF, including both adults and children with CF who have evidence of SARS-CoV-2 antibodies over a two-year period. This study will also examine whether pwCF who have antibodies for SARS-CoV-2 have a different clinical presentation and what impact this has on their CF disease. The proposed study will recruit pwCF from paediatric and adult CF centres throughout the United Kingdom. Serological testing to detect antibodies will be performed on blood samples taken at month 0, 6, 12, 18 and 24 with additional time-points if bloodwork is available via normal clinical care. Clinical data on, lung function, CF-related medical history, pulmonary exacerbations, antibiotic use, and microbiology and vaccination receipt, will be collected during routine clinical assessments.

Associations will be examined between socio-demographic and clinical variables and serologic testing. The investigators will also examine the effects of SARS-CoV-2 infection on clinical outcomes and analyse end-points to explore any age-related or gender-based differences, as well as subgroup analysis of outcomes in lung-transplant recipients and pwCF receiving cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies. As pwCF receive COVID-19 vaccination the investigators will perform a comparison of the development and progression of anti-SARS-CoV-2 antibodies in pwCF following natural infection and vaccination SARS-CoV-2 over time.

Study Overview

Status

Active, not recruiting

Conditions

Cystic Fibrosis

Detailed Description

This is a prospective, longitudinal cohort study in people with Cystic Fibrosis (pwCF) that involves repeated serial sampling of participants. This study design was chosen to provide comprehensive information on SARS-CoV-2 seroprevalence changes over time and the subsequent clinical impact on pwCF. The study will be conducted at participating CF centres over a 3-year period. Study participants will include paediatric and adult pwCF. For the United Kingdom (UK) section of the study, UK investigators in the European Cystic Fibrosis Society-Clinical Trials Network (ECFS-CTN) will be invited to participate. Participating investigators can enrol all eligible pwCF over a 12-month period. Participants are then followed up for 24 months. Participants will donate blood samples at their routine clinic visits. Blood samples will be collected at Day 0 (baseline), at Months 6, 12, 18 and 24 (to coincide with routine clinical reviews). Additional blood samples will be taken opportunistically every time the participant visits the clinic for blood draws. These blood samples could be related to, routine care, annual review visits, pulmonary exacerbations (PEx), CF complications or when initiating new treatments (e.g. CFTR modulators).

Serum from blood samples will be shipped to a central laboratory (Queen's University Belfast) for standardized measurement of SARS-CoV-2 antibodies.

Alongside the blood samples the investigator will also collect clinical data from the patient's health records and will input this data into the case report form (CRF). Clinical data will be collected in conjunction with routine care visits, according to local clinical practice. Investigators will collect data elements from information routinely recorded in the patients' medical records. Data will be collected at baseline, month 6, 12, 18 and 24 as per the study schedule, and at additional blood sampling timepoints as previously explained above. Data collection will include routine data available from CF clinic follow-ups including background demographic information, CF medical history, medications, exacerbation information, sputum microbiology and clinical and lung function parameters. Information on SARS-CoV-2 infection history and vaccine receipt will also be collected.

The maximum follow-up duration of participation in the study for each patient will be 24 months. This study duration (24-month follow-up) is justified as it provides sufficient time to observe changes in antibody prevalence over the course of the COVID-19 pandemic as well as sufficient time to determine long term clinical outcomes for pwCF who are SARS-CoV-2 seropositive. Furthermore, the investigators anticipate the 2-year study follow-up period will provide sufficient time to observe the impact of vaccination on antibody levels given that a number of vaccines are now commercially available.

The investigators will compare the level of antibody responses between natural COVID-19 infection and vaccination in pwCF and how this varies over time. This will be achieved by analyzing seroprevalence and antibody levels according to natural infection and vaccination status and according to time of sample post infection or post vaccination, if known.

Optional Study sample collection:

For participants who consent, a second blood sample will also be drawn into Ethylenediamine tetraacetic acid (EDTA) tubes (plasma). Consent to this optional study sample would allow this sample and any remaining serum (following antibody testing) to be stored for future analysis and allow further research to be carried out on related studies to COVID-19 and CF.

Study Type

Observational

Enrollment (Estimated)

500

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Germany
- - Bochum, Germany, 44791
    - University Children's Hospital Bochum, Paediatric Pneumology and CF Center
  - Cologne, Germany, 50924
    - CF Center, University Hospital Cologne
  - Essen, Germany, 45147
    - Pediatric Pulmonology and Sleep Medicine, Cystic Fibrosis Center, Children's Hospital, University of Duisburg-Essen
  - Essen, Germany, 45239
    - Ruhrlandklinik, Westdeutsches Lungenzentrum gGmbH
  - Frankfurt am Main, Germany, 60596
    - Universitätsklinikum Frankfurt a.M., Allergologie, Pneumologie & Mukoviszidose
  - Jena, Germany, 07747
    - University of Jena, Cystic Fibrosis Centre for children and adults
  - München, Germany, 80336
    - Cystic Fibrosis Center for Adults, Department of Pneumology
- Lower Saxony
  - Hannover, Lower Saxony, Germany, 30625
    - Hannover Medical School, Clinic for Pediatric Pneumology, Allergology and Neonatology & Clinic for Pneumology, Hannover

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

Child
Adult
Older Adult

Accepts Healthy Volunteers

Sampling Method

Non-Probability Sample

Study Population

Participants already enrolled in a clinical trial are eligible for enrolment in this study. Inclusion in CAR-CF should not preclude enrolment in other observational clinical trial studies or clinical trials of an investigational medicinal product (CTIMP).

Description

Inclusion Criteria:

Consenting people with cystic fibrosis of any age, genotype, transplant status and disease severity will be eligible to participate in the study. The study population is expected to be representative of the general CF population.

Exclusion Criteria:

There are no specific exclusion criteria other than refusal to give informed consent, or contraindication to venepuncture.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Observational Models: Cohort
Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate SARS-CoV-2 seroprevalence Time Frame: 3-year period (comprising a 1-year enrollment period and a 2-year follow-up)	To evaluate SARS-CoV-2 seroprevalence in a cohort of people with cystic fibrosis, followed longitudinally over a 3-year period (comprising a 1-year enrollment period and a 2-year follow-up). [ Time Frame: 3-year period (comprising a 1-year enrollment period and a 2-year follow-up) ] To examine the associations between SARS-CoV-2 seropositivity, clinical symptoms and clinical outcomes in a cohort of people with cystic fibrosis	3-year period (comprising a 1-year enrollment period and a 2-year follow-up)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Storage of samples for future analysis Time Frame: anticipated 5-10 years	Storage of samples for future analysis on the impact of COVID-19 immune response in people with cystic fibrosis	anticipated 5-10 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universitätsklinikum Köln

Investigators

Principal Investigator: Silke van Koningsbruggen-Rietschel, MD, PhD, CF Center, University Hospital, University of Cologne, Faculty of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 28, 2021

Primary Completion (Estimated)

May 1, 2024

Study Completion (Estimated)

May 1, 2024

Study Registration Dates

First Submitted

August 18, 2021

First Submitted That Met QC Criteria