CORona (COVID-19) Follow Up Study: Epidemiology, Pathophysiology, Prediction, and Communication

Study Overview
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Brief Summary
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The CORFU study, funded by ZonMW, is a prospective, multiple, cohort study with a maximum follow-up of 24 months after COVID-19. Dutch COVID-19 patients from 7 existing prospective cohorts, aiming and designed to conduct COVID-19 research, will be included in this study. The CORFU study has 5 aims, divided into 4 work packages (WPs): To describe the nature, severity, pattern and duration of long COVID complaints up to a maximum of two years after infection and its relationship with quality of life (WP1); To describe the rehabilitation and corresponding activities for the treatment and improvement of complaints and quality of life (WP1); To describe the pathophysiological processes that cause long COVID complaints, and the role of vulnerability/resilience factors (WP2); To develop a prediction model for the persistence of complaints, with distinction between patients with and without pre-existing morbidity (WP3); To develop a patient platform prototype in which patients can digitally consult their answers and compare their answers with reference populations (WP4, in collaboration with the EuroQol foundation). The 7 cohorts participating in the CORFU study are: POPCOrn, COVAS, ELVIS, MaastrICCht, DC&TC, CAPACITY-COVID, and Adelante cohort. (Clinical) baseline and follow-up data has been collected in these cohorts and will be used/aggregated to investigate CORFU study aims. In addition, questionnaires will be send to the (former) patients of the existing cohorts and patients will be asked about several domains such as persisting complaints and quality of life, at several moments, depending on when the patients have experienced COVID-19. Within this study a patient platform prototype will be developed, together with the EuroQol foundation, to be able to inform patients about the individual situation and course of disease.

Official Title
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Persistent Complaints After COVID-19: Epidemiology, Pathophysiology, Prediction, and Communication, the CORona Follow Up (CORFU) Study

Conditions
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COVID-19, Long COVID, Post COVID-19 Condition

Intervention / Treatment
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* Other: no intervention, the CORFU study conducts analyses based on data which has been prospectively collected (and aggregated when possible) in 7 existing cohorts


Participation Criteria
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Eligibility Criteria
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All 7 existing cohorts have specific inclusion and exclusion criteria. For the CORFU study, in general, the criteria are: Patients with proven or suspected COVID-19: Confirmed (or suspected) COVID-19 - both home-isolated patients and patients who were admitted to the hospital ward and/or ICU; Included in one of the seven cohorts from March 2020 onwards; Aged 18 years or older; Mastering the Dutch language sufficiently to answer the questionnaires; Informed consent. Controls who did not experience COVID-19: Aged 18 years or older; Mastering the Dutch language sufficiently to answer the questionnaires; Informed consent. There were no exclusion criteria.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Dutch COVID-19 patients<br>The study population consists of Dutch (former) COVID-19 patients who have been included in one of the cohorts and categorized in various subgroups: Patients who suffered from (confirmed) COVID-19 and were admitted to the hospital ward. Patient who suffered from (confirmed) COVID-19 and were admitted to the ICU. Patients who suffered from (confirmed or suspected) COVID-19 at home. Patients who suffered from (confirmed) COVID-19 and were in need of inpatient or outpatient rehabilitation after infection at home or in the hospital (ward and/or ICU). | Other: no intervention, the CORFU study conducts analyses based on data which has been prospectively collected (and aggregated when possible) in 7 existing cohorts<br>* (Clinical) baseline and follow-up data will be collected in the 7 existing cohorts. These data will be aggregated (when possible). The CORFU analyses will be conducted based on the aggregated data.<br>* Other names: Integrated database;|
| Dutch controls who did not experience COVID-19<br>One of the cohorts, the POPCOrn cohort, is a community-based cohort which partly consists of controls who did not experience COVID-19 | Other: no intervention, the CORFU study conducts analyses based on data which has been prospectively collected (and aggregated when possible) in 7 existing cohorts<br>* (Clinical) baseline and follow-up data will be collected in the 7 existing cohorts. These data will be aggregated (when possible). The CORFU analyses will be conducted based on the aggregated data.<br>* Other names: Integrated database;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of long COVID complaints (based on data from all 7 cohorts) | Long COVID complaints include: exhaustion, respiratory complaints, and mental health complaints. | 24 months follow-up after COVID-19 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| (Health-related) Quality of life (measured in all 7 cohorts) | Measured using the EuroQol - 5 Dimensions - 5 Levels (EQ-5D-5L) questionnaire. Based on the Dutch tariff, scores range between -0.446 (worst) and 1.000 (best). | 3, 6, 12, 18 and 24 months follow-up after COVID-19 | 
| Anxiety and depression (measured in all 7 cohorts) | Measured using the Hospital Anxiety and Depression Scale (HADS) questionnaire. Scores for both the Anxiety and Depression subscales range from 0 (best) to 21 (worst). A total subscale score of >8 points indicates considerable symptoms of anxiety or depression. | 3, 6, 12, 18 and 24 months follow-up after COVID-19 | 
| Prevalence of thrombo-embolic complications (not measured in all 7 cohorts) | Thrombo-embolic complications of interest are: acute pulmonary embolism, deep-vein thrombosis, ischemic stroke, myocardial infarction and systemic arterial embolism The diagnosis, and therefore, the prevalence of various thrombo-embolic complications will be measured based on a combination of cardiovascular and thrombosis and haemostasis biomarkers (such as troponin I, CK-MB, APTT, and D-dimer), radiologic imaging techniques (computed tomography pulmonary angiography (CTPA), compression ultrasonography (CUS), echocardiography, CT scan of the brain, and CT angiography of the carotid and intracerebral arteries), and electrocardiogram. | Measured during COVID-19 hospitalization (baseline), 3, 12, 24 months follow-up after COVID-19 | 
| Physical functioning (not measured in all 7 cohorts) | Measured using the 6 minute walk test (6MWT). The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity. An increase in the distance walked indicates improvement in basic mobility. The 6MWT result will be reported as a percentage of the predicted Dutch reference value which is based on the patient's age, sex, length and weight. A score <82% of the predicted value is considered deviant. | Measured during admission in the rehabilitation clinic (baseline), 3, 6, 12 months follow-up | 
| Prevalence of cardiovascular diseases (not measured in all 7 cohorts) | Cardiovascular diseases of interest are: coronary artery disease, heart failure, myocardial fibrosis, myocarditis, pericarditis. The diagnosis, and therefore, the prevalence of various cardiovascular diseases will be measured based on a combination of radiologic imaging techniques (such as cardiac magnetic resonance, CT and echocardiography), cardial biomarkers (such as troponin and CK-MB), and electrocardiogram. | Measured during COVID-19 hospitalization (baseline), 1 week, 1 month, and through study completion, an average of 2 years | 
| Prevalence of endothelium dysfunction (not measured in all 7 cohorts) | Measured using several biomarkers (such as endothelin-1, coagulation and inflammatory cytokines). | Measured during COVID-19 hospitalization (baseline), 3, 12 months after COVID-19 | 
| Disease severity during intensive care unit stay (not measured in all 7 cohorts) | Measured using the Sequential Organ Failure Assessment (SOFA) score which is based on the degree of dysfunction of six organ systems. For each organ system, scores range between 0 (best) to 4 (worst). A sum score per day at the intensive care unit can be calculated, which ranges between 0 (best) and 24 (worst). | Measured on the day of admission with COVID-19 to the intensive care unit (baseline), followed by daily measurement until discharge, an average of 18 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epidemiology, Pathophysiology, Prediction model, Patient platform