COVID-19 Antibody Responses In Cystic Fibrosis (CAR-CF)

COVID-19 Antibody Responses In Cystic Fibrosis: CAR-CF

Coronavirus disease 2019 (COVID-19) which is caused by the virus 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 effects of SARS-CoV-2 infection on clinical outcomes and analyse end-points will be examined to explore any age-related or gender-based differences, as well as subgroup analysis of outcomes in lung-transplant recipients and pwCF receiving CFTR modulator therapies. As pwCF receive COVID-19 vaccination 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 will be performed.

Study Overview

• Status: Recruiting
• Conditions: Covid19; 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 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 investigators 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, we 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 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 (Anticipated): 1000

Contacts and Locations

• Study Contact: Name: Damian Downey; Phone Number: 02895041135; Email: d.downey@qub.ac.uk
• Study Contact Backup: Name: Helen Groves; Phone Number: 02895041135; Email: h.groves@qub.ac.uk

Study Locations

• United Kingdom
  • Engladn
    • Southampton, Engladn, United Kingdom, SO16 6YD
      • Not yet recruiting
      • University Hospital Southampton NHS Foundation Trust
      • Contact: Shobonna Akhter
  • England
    • Birmingham, England, United Kingdom, B15 2GW
      • Not yet recruiting
      • University Hospitals Birmingham NHS Foundation Trust
      • Contact: Joanna Whitehouse
    • Birmingham, England, United Kingdom, B4 6NH
      • Not yet recruiting
      • Birmingham Women's and Children's NHS Foundation Trust
      • Contact: Maya Desai
    • Leeds, England, United Kingdom, LS9 7TF
      • Not yet recruiting
      • Leeds Teaching Hospitals NHS Trust
      • Contact: Daniel Peckham
    • London, England, United Kingdom, SE5 9RS
      • Not yet recruiting
      • King's College Hospital NHS Foundation Trust
      • Contact: Michael Waller
    • London, England, United Kingdom, SW3 6NP
      • Not yet recruiting
      • Royal Brompton & Harefield NHS Foundation Trust
      • Contact: Nicholas Simmonds
    • Nottingham, England, United Kingdom, NG7 2UH
      • Not yet recruiting
      • Nottingham University Hospitals NHS Trust
      • Contact: Helen Barr
  • Northern Ireland
    • Belfast, Northern Ireland, United Kingdom
      • Recruiting
      • Queens University Belfast
      • Contact: Damian Downey; Email: d.downey@qub.ac.uk
      • Principal Investigator: Damian Downey
  • Scotland
    • Glasgow, Scotland, United Kingdom, G12 0XH
      • Not yet recruiting
      • NHS Greater Glasgow and Clyde
      • Contact: Gordon MacGregor
  • Wales
    • Cardiff, Wales, United Kingdom, CF14 4HH
      • Not yet recruiting
      • Cardiff & Vale University LHB
      • Contact: Thia Lena
    • Cardiff, Wales, United Kingdom
      • Not yet recruiting
      • Cardiff & Vale University LHB
      • Contact: Jamie Duckers

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

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.

Description

Inclusion Criteria:

• Consenting people with cystic fibrosis of any age, genotype, transplant status and disease severity

Exclusion Criteria:

• Refusal to give informed consent
• Contraindication to venepuncture.

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SARS-COV-2 seroprevalence	proportion of pwCF with at least 1 seropositive result over the study period and the difference in this proportion by age, geographical area and over time.	3-year period (comprising a 1-year enrollment period and a 2-year follow-up)
Association of SARS-CoV-2 seropositivity, clinical symptoms and clinical outcomes in pwCF	incidence of symptomatic COVID-19 over the study period and severity; proportion of seropositive pwCF with subsequent CF exacerbation compared to pwCF who are seronegative; death rate in pwCF with at least one seropositive result compared to pwCF who are seronegative.	3-year period (comprising a 1-year enrollment period and a 2-year follow-up)
Longitudinal comparison of the detection of anti-SARS-CoV-2 antibodies in pwCF following natural infection and SARS-CoV-2 vaccination.	Measuring detectable antibody levels for each study participant at baseline and at each study time point including 6,12, 18 and 24 months post enrollment with additional samples if participant has blood drawn for other clinical care reason.	3-year period (comprising a 1-year enrollment period and a 2-year follow-up)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum proteomic and genomic responses of pwCF who are SARS-CoV-2 seropositive and seronegative.	Measuring detectable proteomic and genomic responses in pwCF according to serostatus (positive or negative for antibodies) as well as according to natural infection versus vaccination	anticipated 5-10 years

Collaborators and Investigators

• Sponsor: Queen's University, Belfast
• Collaborators: Cystic Fibrosis Foundation
• Investigators: Principal Investigator: Damian Downey, Queens University Belfast

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 19, 2021
• Primary Completion (ANTICIPATED): May 1, 2024
• Study Completion (ANTICIPATED): May 1, 2024

Study Registration Dates

• First Submitted: April 27, 2021
• First Submitted That Met QC Criteria: April 27, 2021
• First Posted (ACTUAL): April 28, 2021

Study Record Updates

• Last Update Posted (ACTUAL): February 1, 2022
• Last Update Submitted That Met QC Criteria: January 17, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; COVID-19; Cystic Fibrosis
• Other Study ID Numbers: B21/07

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No