Study design

COVID-PCD is an international observational cohort study using anonymous online questionnaires to collect information directly from people with PCD (clinicaltrials.gov registration number: NCT04602481). It is a participatory research project where people who have PCD have an active role in all stages of research. The study was requested by PCD support groups from Switzerland, Germany, the UK, the USA and Australia and set up in collaboration with a study team at the University of Bern, Switzerland, and the University of Southampton, UK. The study is designed for three age groups: children below 14 years, adolescents between 14 and 17 years, and adults aged 18 years or more. For children, the questionnaires are addressed to the parents, but the child is encouraged to help complete the questionnaires. Adolescents complete the questionnaires themselves. The study is currently available in English, German and Spanish with the possibility to expand to more languages.

Inclusion criteria

The study is addressed to people of any age from any country with a confirmed or suspected diagnosis of PCD. Eligibility of participants is assessed in the baseline questionnaire. We exclude people who answer “no” to both questions: “Have you been told by a doctor that you have PCD or are likely to have PCD?” and “Do you have a reason to believe that you have PCD, even though you have not received a diagnosis by a doctor?”.

Validating the diagnosis of PCD

Diagnosing PCD is complex and requires several tests to be performed by an experienced team. Historically, patients may not have been diagnosed according to current standards [25] and in some patients, even experts are unable to confirm the diagnosis. We validate the diagnosis through questions asking the patients about results of the diagnostic tests. Many patients have received copies of their test results and can therefore report the type of tests they have had and their results. For the analysis, we can stratify the study population into people with a definite diagnosis, people with probable PCD and people with suspected PCD. During the study, we will further attempt to validate the diagnoses with original documents. We considered it important to have an inclusive approach and also allow people whose diagnosis is not proven into the study, because whether or not participants have a formal confirmation of PCD, they suffer from chronic lung disease and thus should be allowed to contribute their experiences.

Recruitment of study participants

The study is primarily advertised through PCD support groups (table 1) who contact and inform potential participating people with PCD through social media and e-mail networks and encourage them to take part in the study. The adverts include a link to the project website (www.covid19pcd.ispm.ch) which leads directly to the study information and registration. Initially, support groups from the UK (www.pcdsupport.org.uk), Germany (www.kartagener-syndrom.org/index.php), Switzerland, the USA and Canada (www.pcdfoundation.org), and Australia (www.pcdaustralia.org.au/) were involved, but more countries are joining as the study progresses. In regions of the world where PCD-specific patient support groups are lacking, healthcare specialists seeing people with PCD are asked to help inform patients about the study.

Study procedures

All aspects of the COVID-PCD study are online, including registration and consent and completing the baseline questionnaire, weekly questionnaires, information on hospitalisation and occasional thematic questionnaires (figure 1). The website includes detailed information about the study results and allows participants to register via a link that leads them directly into the study database. At first, participants are asked to enter their year of birth which directs them to the age-specific study information and questionnaires. Participants give digital consent to participate and are then asked to enter an e-mail address where the online questionnaires can be sent to. Immediately after the registration, participants receive an e-mail with the link to the baseline questionnaire. Adolescents are asked to also enter the e-mail address of a parent. The parent must give consent before the adolescent receives the baseline questionnaire. Participants must complete the baseline questionnaire to be enrolled in the study.

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FIGURE 1

Timeline and follow-up procedures of the coronavirus disease 2019 (COVID-19) and primary ciliary dyskinesia (PCD) study.

One week after completing the baseline questionnaire, and in weekly intervals thereafter, participants receive short follow-up questionnaires (figure 1). The follow-up questionnaire is not dependent on participants completing it every week; if participants miss one or more of the follow-up questionnaires, they will receive the links for the next ones. If a participant is hospitalised due to COVID-19, a link to an additional short questionnaire is sent. The study also allows thematic questionnaires that focus on specific topics related to the COVID-19 pandemic to be conceived and sent out. Participants and interested people can follow the progress of the study on the study website where information on number of recruited participants, incident COVID-19 infections and selected results from the questionnaires are uploaded regularly.

Information collected

The baseline questionnaire aims to assess whether the participant has PCD, how the disease was diagnosed, what the person's usual symptoms are how severe the disease is, and how it is treated. It also aims to collect information on the social and environmental context such as people living in the same household, school and work environment, and physical activity. The baseline questionnaire is divided into four modules (table 2). Module 1 collects demographic data, contact information and information on SARS-CoV-2 infections that have occurred prior to study entry. Module 2 collects information on PCD diagnosis and baseline disease status. Module 3 asks about regular PCD-related symptoms, and module 4 collects information on work, education, lifestyle and health behaviours. Module 3 and 4 are based on the FOLLOW-PCD questionnaire [26].

The weekly follow-up questionnaire collects information on symptoms and incident SARS-CoV-2 infections, physical activity and time-varying lifestyle factors such as social contacts. If a participant has no symptoms, the weekly follow-up questionnaire is short. If a participant has symptoms, extra questions appear asking details about tests for SARS-CoV-2 and other infections, symptoms duration, healthcare contacts and medication taken.

A short questionnaire is sent in the event of a hospitalisation due to COVID-19. It asks about duration of the hospitalisation, unit where the patient was treated, treatments and recommendations received after discharge.

Additional thematic questionnaires developed throughout the study focus on special topics related to the pandemic such as mask use, anxiety, home schooling of children, physical activity or availability of medications. PCD support organisations and study participants are encouraged to suggest special topics and participate in developing those questionnaires.

Participant engagement

Participants shape the study in a participatory approach and can influence all aspects of the study (table 3). They had a decisive role in study design and content of baseline questionnaire. As the study goes on, participants are encouraged to propose research questions and topics for extra questionnaires, help to make sure questions are written in a language that is easily understandable, advise on logistics such as how to approach affected people, and choose results for publication on the website. A patient advisory group from the European Lung Foundation (ELF) (www.europeanlung.org/en/) includes interested people who have PCD. The group meets to discuss the COVID-19 outbreak, the PCD-COVID study and questions relevant to people with PCD.

Study database and data protection

The web-based database uses the Research Electronic Data Capture (REDCap) platform developed at Vanderbilt University (www.project-redcap.org) [27]. The database is hosted by the Swiss medical registries and data linkage centre (SwissRDL) at the University of Bern, Switzerland, and complies with all legal requirements for data security and data protection. Access to the database is regulated by a system with personal passwords. Only study team members who need to perform database management can access the database. Daily, weekly and monthly back-ups are performed and securely stored at the SwissRDL servers.

Ethics

The Bern Cantonal Ethics Committee (Kantonale Ethikkomission Bern) has approved this study (Study ID: 2020-00830). Informed consent to participate in the study is provided at registration into the study. Study participation is anonymous. Participants can withdraw their consent to participate at any time by contacting the study team.

Comparison with other studies

To our knowledge, very few studies investigate the effect of COVID-19 on people with a rare disease and very few focus on respiratory diseases. A questionnaire survey from the rare diseases clinical research network based in Ohio, USA, collects cross-sectional information on the effect of COVID-19 from people with all types of rare diseases [28]. A major strength of this study is that recruitment is not happening through healthcare facilities, but any person with a rare disease and access to the internet can participate via a link on the study website. This also ensures that people with mild disease or limited access to healthcare may participate. However, the study is limited to the USA; the questionnaire is short and collects information only once, and it remains general as it includes people with any kind of rare diseases. Another research project, the ImmunoCOVID19 study, at the University of Southampton, UK, monitors COVID-19 in children with primary or secondary immunosuppression (below 18 years) [29]. Recruitment happens through hospitals. Participants complete a short baseline questionnaire and are followed up weekly through a short online questionnaire. This study follows participants longitudinally, which makes it fit for studying incidence of COVID-19 and study symptoms and prognosis. Other studies on people with rare respiratory diseases use data from hospital records. The European Cystic Fibrosis Society set up the COVID-CF project in Europe where data from national cystic fibrosis (CF) registries are pooled to identify people with CF who have been infected with SARS-CoV-2 [30, 31]. By October 4, 144 cases of COVID-19 in patients with CF were documented in 18 countries. A study in Spain investigated incidence of SARS-CoV-2 from March to May 2020 in 2500 CF patients registered in the national registry using information from hospital records [32]. However, these studies only identify the most severe cases of SARS-CoV-2 infections that result in hospitalisations. Mild cases are missed, and this type of study biases the results towards more severe infections.

Strengths and limitations

A key feature and major strength of this study is the participatory approach where people with PCD together with the team of researchers shape the study, recruit participants, and interpret and decide which results should be presented on the study website. The close collaboration between people with PCD and researchers ensures the relevance for participants and makes sure that study material is meaningful for people with PCD. It may also positively influence response rate in the weekly follow-up questionnaires. Another strength is the web-based study design, which allows participants to contribute their data to the database in real-time. This limits the risk of recall bias as participants only report symptoms from the last 7 days, and there is no delay caused by data entry as participants enter data themselves into the database. The PCD support groups provided essential inputs to the study questionnaires and study design. The broad inclusion criteria allowing people of any age from anywhere in the world to participate is another strength of the study. The COVID-PCD study is one of the largest international studies including data reported directly from people with a rare disease. COVID-PCD not only covers infection rates, severity of symptoms and prognosis of COVID-19 but also studies factors related to the COVID-19 pandemic such as social isolation and physical activity habits. Additionally, special topics can be studied at short notice using extra questionnaires that are sent out once and can be proposed by participants themselves.

One limitation of the study is the convenience sampling method. It is difficult to estimate the response rate without information on how many people with PCD have seen the study information, and it is difficult to know if the study participants are representative of the average population of people with PCD.

We thank all participants and their families, and we thank the primary ciliary dyskinesia support groups and physicians who have advertised the study. We would like to thank Helena Koppe, Maria Christina Mallet and Dominique Rubi, University of Bern, for helping to set up the COVID-PCD database.