Coronavirus disease 2019 (COVID-19) which is caused by the virus Severe Acute RespiratorySyndrome Coronavirus-2 (SARS-CoV-2) has resulted in an ongoing global pandemic. It isunclear 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 protectivegenetic/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 antibodiesover a two-year period. This study will also examine whether pwCF who have antibodies forSARS-CoV-2 have a different clinical presentation and what impact this has on their CFdisease. The proposed study will recruit pwCF from paediatric and adult CF centresthroughout the United Kingdom. Serological testing to detect antibodies will be performedon blood samples taken at month 0, 6, 12, 18 and 24 with additional time-points ifbloodwork is available via normal clinical care. Clinical data on, lung function,CF-related medical history, pulmonary exacerbations, antibiotic use, and microbiology andvaccination receipt, will be collected during routine clinical assessments.Associations will be examined between socio-demographic and clinical variables andserologic testing. The investigators will also examine the effects of SARS-CoV-2infection on clinical outcomes and analyse end-points to explore any age-related orgender-based differences, as well as subgroup analysis of outcomes in lung-transplantrecipients and pwCF receiving cystic fibrosis transmembrane conductance regulator (CFTR)modulator therapies. As pwCF receive COVID-19 vaccination the investigators will performa comparison of the development and progression of anti-SARS-CoV-2 antibodies in pwCFfollowing natural infection and vaccination SARS-CoV-2 over time.
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.
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.
Hannover Medical School, Clinic for Pediatric Pneumology, Allergology and Neonatology & Clinic for Pneumology, Hannover
Hannover, Lower Saxony, Germany
University Children's Hospital Bochum, Paediatric Pneumology and CF Center
Bochum, Germany
CF Center, University Hospital Cologne
Cologne, Germany
Pediatric Pulmonology and Sleep Medicine, Cystic Fibrosis Center, Children's Hospital, University of Duisburg-Essen
Essen, Germany
Ruhrlandklinik, Westdeutsches Lungenzentrum gGmbH
Essen, Germany
Universitätsklinikum Frankfurt a.M., Allergologie, Pneumologie & Mukoviszidose
Frankfurt am Main, Germany
University of Jena, Cystic Fibrosis Centre for children and adults
Jena, Germany
Cystic Fibrosis Center for Adults, Department of Pneumology
München, Germany
Silke van Koningsbruggen-Rietschel, MD, PhD, Principal Investigator
CF Center, University Hospital, University of Cologne, Faculty of Medicine