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

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

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):

1. 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);
2. To describe the rehabilitation and corresponding activities for the treatment and improvement of complaints and quality of life (WP1);
3. To describe the pathophysiological processes that cause long COVID complaints, and the role of vulnerability/resilience factors (WP2);
4. To develop a prediction model for the persistence of complaints, with distinction between patients with and without pre-existing morbidity (WP3);
5. 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.

Study Overview

• Status: Completed
• Conditions: COVID-19; Long COVID; Post COVID-19 Condition
• Intervention / Treatment: Other: no intervention, the CORFU study conducts analyses based on data which has been prospectively collected (and aggregated when possible) in 7 existing cohorts

• Study Type: Observational
• Enrollment (Actual): 4291

Contacts and Locations

Study Locations

• Netherlands
  • Maastricht, Netherlands, 6229HX
    • Maastricht University Medical Center+

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

The study population consists of Dutch (former) COVID-19 patients and non-COVID-19 controls, who have been included in one of the cohorts and categorized in five 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).
• Controls who did not suffer from (confirmed or suspected) COVID-19.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Dutch COVID-19 patients; 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; (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.; Other Names: Integrated database
Dutch controls who did not experience COVID-19; 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; (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.; Other Names: Integrated database

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Collaborators: Radboud University Medical Center; UMC Utrecht; Leiden University Medical Center; Adelante, Centre of Expertise in Rehabilitation and Audiology; Zuyderland Medical Centre; Amsterdam University Medical Center
• Investigators: Principal Investigator: Sander MJ van Kuijk, PhD, Maastricht University Medical Center; Study Director: Chahinda Ghossein-Doha, MD, PhD, Maastricht University Medical Center

Publications and helpful links

General Publications

• Leijte WT, Wagemaker NMM, van Kraaij TDA, de Kruif MD, Mostard GJM, Leers MPG, Mostard RLM, Buijs J, van Twist DJL. [Mortality and re-admission after hospitalization with COVID-19]. Ned Tijdschr Geneeskd. 2020 Nov 19;164:D5423. Dutch.
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• Kozlov IA, Piliaeva IE, Matveev IuG, Kormer AIa. [Anesthesiological management in transplantation of the heart after temporary mechanical substitution of its function]. Anesteziol Reanimatol. 1994 Jan-Feb;(1):16-22. Russian.
• Keogh JP, Gordon J. Occupational lead poisoning: who should conduct surveillance and training? Am J Ind Med. 1994 Nov;26(5):713-5. doi: 10.1002/ajim.4700260513.
• Pittaluga A, Raiteri M. HIV-1 envelope protein gp120 potentiates NMDA-evoked noradrenaline release by a direct action at rat hippocampal and cortical noradrenergic nerve endings. Eur J Neurosci. 1994 Nov 1;6(11):1743-9. doi: 10.1111/j.1460-9568.1994.tb00566.x.
• Kaluzewski S, Jagielski M, Rastawicki W, Kochman M. [Evaluation of occurrence of infections caused by Mycoplasma pneumoniae during 1970-1973 based on serological investigations]. Przegl Epidemiol. 1994;48(3):165-72. Polish.
• Skelton-Stroud PN, Glaister JR. Oxalate nephrosis in Macaca fascicularis. Lab Anim. 1994 Jul;28(3):265-9. doi: 10.1258/002367794780681705.
• Schwarz T, Sindern S, Bartholmes P, Kaufmann M. The use of a hollow fiber membrane module in sample conditioning prior to electrophoresis. Electrophoresis. 1994 Aug-Sep;15(8-9):1118-9. doi: 10.1002/elps.11501501168.
• Klein DO, Waardenburg SF, Janssen EBNJ, Wintjens MSJN, Imkamp M, Heemskerk SCM, Birnie E, Bonsel GJ, Warle MC, Jacobs LMC, Hemmen B, Verbunt J, van Bussel BCT, van Santen S, Kietelaer BLJH, Jansen G, Klok FA, de Kruif MD, Vernooy K, Haagsma JA, Asselbergs FW, Linschoten M, Cals JWL, Ten Cate H, van der Horst ICC, Wilmes N; CAPACITY-COVID Collaborative Consortium; Ghossein-Doha C, van Kuijk SMJ. Two years and counting: a prospective cohort study on the scope and severity of post-COVID symptoms across diverse patient groups in the Netherlands-insights from the CORFU study. BMJ Open. 2025 Sep 11;15(9):e093639. doi: 10.1136/bmjopen-2024-093639.
• Jacobs LMC, Wintjens MSJN, Nagy M, Willems L, Ten Cate H, Spronk HMH, van Kuijk SMJ, Ghossein-Doha C, Netea MG, Groh LA, van Petersen AS, Warle MC. Biomarkers of sustained systemic inflammation and microvascular dysfunction associated with post-COVID-19 condition symptoms at 24 months after SARS-CoV-2-infection. Front Immunol. 2023 Oct 5;14:1182182. doi: 10.3389/fimmu.2023.1182182. eCollection 2023.
• Ghossein-Doha C, Wintjens MSJN, Janssen EBNJ, Klein D, Heemskerk SCM, Asselbergs FW, Birnie E, Bonsel GJ, van Bussel BCT, Cals JWL, Ten Cate H, Haagsma J, Hemmen B, van der Horst ICC, Kietselaer BLJH, Klok FA, de Kruif MD, Linschoten M, van Santen S, Vernooy K, Willems LH, Westerborg R, Warle M, van Kuijk SMJ. Prevalence, pathophysiology, prediction and health-related quality of life of long COVID: study protocol of the longitudinal multiple cohort CORona Follow Up (CORFU) study. BMJ Open. 2022 Nov 29;12(11):e065142. doi: 10.1136/bmjopen-2022-065142.

Helpful Links

• CAPACITY COVID-19: Registry of patients with COVID-19 including cardiovascular risk and complications

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2021
• Primary Completion (Actual): January 1, 2024
• Study Completion (Actual): November 1, 2024

Study Registration Dates

• First Submitted: November 26, 2021
• First Submitted That Met QC Criteria: February 11, 2022
• First Posted (Actual): February 15, 2022

Study Record Updates

• Last Update Posted (Estimated): October 1, 2025
• Last Update Submitted That Met QC Criteria: September 25, 2025
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Epidemiology; Pathophysiology; Prediction model; Patient platform
• Additional Relevant MeSH Terms: Post-Infectious Disorders; Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Pathological Conditions, Signs and Symptoms; COVID-19; Post-Acute COVID-19 Syndrome
• Other Study ID Numbers: METC2021-2990

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No