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Observational Study
. 2025 Sep 11;15(9):e093639.
doi: 10.1136/bmjopen-2024-093639.

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

Dorthe O Klein  1   2 , Sophie F Waardenburg  3   2   4 , Emma B N J Janssen  3   2   5   6 , Marieke S J N Wintjens  3   2   7 , Maike Imkamp  3 , Stella C M Heemskerk  8 , Erwin Birnie  9 , Gouke J Bonsel  9 , Michiel C Warlé  10 , Lotte M C Jacobs  10 , Bea Hemmen  2   11   12 , Jeanine Verbunt  2   11   12 , Bas C T van Bussel  2   6   7 , Susanne van Santen  7 , Bas L J H Kietelaer  13   14 , Gwyneth Jansen  5   14 , Frederikus A Klok  15 , Martijn D de Kruif  16 , Kevin Vernooy  6   17 , Juanita A Haagsma  8 , Folkert W Asselbergs  18   19   20 , Marijke Linschoten  18   21 , Jochen W L Cals  22 , Hugo Ten Cate  6   23   24   25 , Iwan C C van der Horst  6   7 , Nick Wilmes  6   17 ; CAPACITY-COVID Collaborative Consortium; Chahinda Ghossein-Doha #  6   17   26 , Sander M J van Kuijk #  3   2
Collaborators, Affiliations
Observational Study

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

Dorthe O Klein et al. BMJ Open. .

Abstract

Importance: Little research has been done on post-COVID symptoms at 24 months postinfection and on the association these may have on health-related quality of life (HRQOL).

Objective: We assessed the prevalence and severity of post-COVID symptoms and quantified EuroQol 5 Dimension 5 Level (EQ-5D-5L), self-perceived health question (EuroQol Visual Analogue Scale (EQ-VAS)) and health utility scores (HUS) up to 24 months follow-up.

Design: The longitudinal multiple cohort CORona Follow-Up (CORFU) study combines seven COVID-19 patient cohorts and a survey among the general public. The participants received questionnaires on several time points. Participants were stratified by: without a known SARS-CoV-2 infection (control group), proven SARS-CoV-2 infection but non-hospitalised, proven SARS-CoV-2 infection hospitalised to the ward, and proven SARS-CoV-2 infection hospitalised to the intensive care unit (ICU).

Setting: In this study, data of seven COVID-19 patient cohorts and a survey among the general public are included.

Participants: Former COVID-19 patients and controls participated in this cohort study.

Main outcomes and measures: Former COVID-19 patients and non-COVID-19 controls were sent questionnaires on symptoms associated with post-COVID condition. The CORFU questionnaire included 14 symptom questions on post-COVID condition using a five-level Likert-scale format. Furthermore, HRQOL was quantified using the EuroQol EQ-5D-5L questionnaire: EQ-VAS and the EQ-5D-5L utility score. The EQ-5D-5L questionnaire includes five domains that are scored on a five-point Likert scale: mobility, self-care, usual activities, pain/discomfort and anxiety/depression.

Results: A total of 901 participants (and 434 controls) responded at 24 months follow-up. In all former COVID-19 patients, the presence of post-COVID condition at 24 months was observed in 62 (42.5%, 95% CI 34.3% to 50.9%) of the non-hospitalised patients, 333 (65.0%, 95% CI 60.7% to 69.2%) of the hospitalised ward patients and 156 (63.2%, 95% CI 56.8% to 69.2%) of the ICU patients, respectively (p<0.001). The most common symptoms included fatigue, sleep problems, muscle weakness/pain and breathing issues, with hospitalised participants reporting most often having symptoms. Multiple post-COVID symptoms were significantly associated with EQ-5D-5L measures. The mean and SD of the EQ-VAS were 71.6 (17.9), 70.0 (17.3) and 71.4 (17.5) for non-hospitalised, ward and ICU participants, respectively, and 75.6 (17.7) for the controls (p<0.001). The HUS resulted in 0.81 (0.20), 0.77 (0.19) and 0.79 (0.22) for non-hospitalised, hospitalised ward and ICU participants, respectively, and 0.84 (0.19) for the control group (CG) (p<0.001).

Conclusions: Many former COVID-19 patients experience post-COVID symptoms at 24 months follow-up, with the highest prevalence in hospitalised participants. Also, former patients reported a lower HRQOL.

Trial registration number: The CORFU study was registered at clinicaltrials.gov (registration number NCT05240742).

Keywords: COVID-19; Patients; Post-Acute COVID-19 Syndrome; Prevalence.

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Conflict of interest statement

Competing interests: BCTvB, BH, BLJHK, CG-D, DOK, EB, EBNJJ, GJ, GJB, ICCvdH, JAH, JWLC, MSJNW, MCW, MI, NW, SCMH, SMJvK, SvS and SFW declare no competing interests. FAK received research support from Bayer, BMS, Boehringer-Ingelheim, MSD, Daiichi-Sankyo, Actelion, Boston Scientific, The Netherlands Organisation for Health Research and Development (ZonMw), The Dutch Thrombosis Association and The Dutch Heart Foundation. FWA is supported by the National Institute of Health Research University College London Hospitals Biomedical Research Centre. For the CAPACITY-COVID cohort participating in CORFU, FWA and ML received support from the Dutch Heart Foundation (2020B006 CAPACITY) and The Netherlands Organisation for Health Research and Development (ZonMw grant number 10430102110006 DEFENCE). HTC received support from Bayer, received consulting fees from Pfizer, Leo, Alveron, Viatris, Astra Zeneca and Galapagos and has stock (options) in Coagulation Profile. KV is a consultant for Philips, Medtronic, Boston Scientific, Abbott and Biosense Webster, and has a role in the European Heart Rhythm Association congress organisation and educational committee and is a member of the digital committee of the European Society of Cardiology. MDdK received a presentation fee from Glaxo Smith Kline. JV received research support from The Netherlands Organisation for Health Research and Development (ZonMw) for other COVID-related research.

Figures

Figure 1
Figure 1. Overview of cohorts in the CORFU study. CORFU, CORona Follow-Up; ICU, intensive care unit; POPCOrn, POPulation health impact of the COVID-19 pandemic.
Figure 2
Figure 2. Questionnaires. CORFU, CORona Follow-Up; POPCORN, POPulation health impact of the COVID-19 pandemic.
Figure 3
Figure 3. Distribution of five-point Likert scores at 24 months stratified by subgroup. Note that the symptoms are ordered from most to least prevalent, and this may differ between subgroups. Data of participants who completed the third survey and had not contracted COVID-19 by then were used, as those questionnaires were completed closest in time to the calendar period of the 24 months questionnaires, that is, between April and May 2022. ICU, intensive care unit.
Figure 4
Figure 4. HRQOL expressed as the EQ-5D-5L VAS score and the EQ-HUS, for former COVID-19 patients stratified by follow-up time. A vertical line for patients admitted to the ward at 18 months is due to the fact that too few questionnaires were available to estimate the distribution. Note that no data of controls are presented as all presented data are relative to the index date of infection with SARS-CoV-2. EQ-5D-5L, EuroQol 5 Dimension 5 Level; HRQOL, health-related quality of life; HUS, health utility score; ICU, intensive care unit; VAS, Visual Analogue Scale.
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