Integrated care pathway in individuals with Long COVID: STIMULATE-ICP, a cluster-randomized, phase 3 trial

Abstract Combining multidisciplinary care plans into integrated care pathways (ICPs) is scalable, generalizable and effective for several long-term conditions, but not evaluated in Long COVID (LC). Our phase 3, cluster-randomized, multicenter clinical trial investigated the effectiveness of ICP interventions for LC. Recruitment of adults ≥18 years with LC was conducted in 6 National Health Service LC clinics in England with specialist ICPs. The intervention arms were (i) multi-organ magnetic resonance imaging (MRI; Coverscan), (ii) digital rehabilitation (Living with COVID Recovery), (iii) both multi-organ MRI and digital rehabilitation, and (iv) neither multi-organ MRI nor digital rehabilitation (usual care); cluster randomizing at primary care network (PCN) level to deliver interventions as ‘standard of care’ in that area. The primary endpoint was mean Fatigue Assessment Scale (FAS) at 12 weeks. Secondary endpoints included FAS at 24 weeks and EQ-5D-5L visual assessment scale at 12 and 24 weeks. A total of 1,152 participants from allocated PCNs consented to data collection, and 122 PCN clusters were allocated to the multi-organ MRI (33 PCNs), digital rehabilitation (32 PCNs), ‘both’ (27 PCNs) and ‘neither’ (30 PCNs) arms. Baseline FAS was equivalent across groups (mean 35.8, s.d. 8.21, 66.4% female). Overall, the primary outcome was achieved in all arms, with scores improving by 4.5 points to 31.3 (s.d. 9.31) at 12 weeks. Compared with usual care, effects on 12-week FAS were −0.18 (95% confidence interval −0.72, 1.09; P = 0.69) with multi-organ MRI; −0.53 (−1.42, 0.36; P = 0.25) with digital rehabilitation; and −0.17 (−1.06, 0.72; P = 0.71) with their interaction. Absolute differences for other interventions from usual care were modest. There were no serious adverse events related to ICP interventions. Multidisciplinary holistic clinical care is associated with fatigue reduction in LC, irrespective of multi-organ MRI. Digital rehabilitation could be useful in longer-term LC management. Large, multi-site trials of optimal ICP interventions are feasible, but further trials are required. ISRCTN identifier: ISRCTN10665760 .

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Nature Medicine
Published
2026-07-28
DOI
https://doi.org/10.1038/s41591-026-04552-x
Primary Topic
Long-Term Effects of COVID-19
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article
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article

Integrated care pathway in individuals with Long COVID: STIMULATE-ICP, a cluster-randomized, phase 3 trial

Anu Chandra, Paula Lorgelly, Emma Mi, Manuel Gomes et al.
Nature Medicine
Long-Term Effects of COVID-19
article

Integrated care pathway in individuals with Long COVID: STIMULATE-ICP, a cluster-randomized, phase 3 trial

Anu Chandra, Paula Lorgelly, Emma Mi, Manuel Gomes, A. Sarna, Samantha Eccles, Joanna Peel, Mel Ramasawmy, Laura Pasea, Jonathan Waywell, David Sunkersing, Éamonn Foley, Ashkan Dashtban, Sophie Equi, Emily Attree, Charles Latchford, A. Clegg, Rob Suriano, W. David Strain, Jennifer Sweetman, Emily Fraser, Rebecca Livingston, Henry Goodfellow, Antony Loveless, Lyth Hishmeh, Jai Prashar, Kumaran Balasundaram, Rachel Botell, Rajarshi Banerjee, Anand Viswanathan, Al-Tahoor Butt, Ileana L. Selejan, Rachael A Evans, Denise Forshaw, Amitava Banerjee, Jasmine Hayer, Phil Cumberlidge, Jagdeep Sahota, Hakim‐Moulay Dehbi, Angela Green, Donna Clutterbuck, Chris Robson, Lere Fisher, Ondine Sherwood, Kim Horstmanshof, Kamlesh Khunti, Fauzia Begum, Alison Gibbon, Nisreen A. Alwan, Rachel Nyam, Melissa Heightman, Elena Bax, Gordon Prescott, Andrew Williams, Caroline L. Watkins, Christina M. Van der Feltz-Cornelis, Nefyn Williams, Mohamed Mohamed, Janet Scott, Michael Zandi, Andrea Dennis, Dan Wootton, Florence Mutesva, Mag Leahy, Helen Grice, Sarah Clegg, Rita Mallinson, Josie Newton, Maya Leach, Kiran Khan, Charlotte Adams-Heath, Francesco Gambino, Dan Cuthbertson, Amir Manzelat, Mark Gabbay, Stephen Cone, Elizabeth Murray, Natalie Smith, Lauren O'Mahoney, Sophie Burchell-Kirk, Keri Hildick, Nataliia Kryvutenko, Annalisa Parabita, Joanna Wright, Deepak Ravindran, Rachel Hext, Gail Allsopp, Michael Crooks, Claire Hooper, Dr Emma Wall, Marija Pantelic, Robert Bell, Christopher Brown, Writing Group, Rachel Williams, Hugh Montgomery, Gregory Y. H. Lip, Matthew Robert Burns, Han-I Wang, Pablo Fernandez Medina
article en

Abstract

Abstract Combining multidisciplinary care plans into integrated care pathways (ICPs) is scalable, generalizable and effective for several long-term conditions, but not evaluated in Long COVID (LC). Our phase 3, cluster-randomized, multicenter clinical trial investigated the effectiveness of ICP interventions for LC. Recruitment of adults ≥18 years with LC was conducted in 6 National Health Service LC clinics in England with specialist ICPs. The intervention arms were (i) multi-organ magnetic resonance imaging (MRI; Coverscan), (ii) digital rehabilitation (Living with COVID Recovery), (iii) both multi-organ MRI and digital rehabilitation, and (iv) neither multi-organ MRI nor digital rehabilitation (usual care); cluster randomizing at primary care network (PCN) level to deliver interventions as ‘standard of care’ in that area. The primary endpoint was mean Fatigue Assessment Scale (FAS) at 12 weeks. Secondary endpoints included FAS at 24 weeks and EQ-5D-5L visual assessment scale at 12 and 24 weeks. A total of 1,152 participants from allocated PCNs consented to data collection, and 122 PCN clusters were allocated to the multi-organ MRI (33 PCNs), digital rehabilitation (32 PCNs), ‘both’ (27 PCNs) and ‘neither’ (30 PCNs) arms. Baseline FAS was equivalent across groups (mean 35.8, s.d. 8.21, 66.4% female). Overall, the primary outcome was achieved in all arms, with scores improving by 4.5 points to 31.3 (s.d. 9.31) at 12 weeks. Compared with usual care, effects on 12-week FAS were −0.18 (95% confidence interval −0.72, 1.09; P = 0.69) with multi-organ MRI; −0.53 (−1.42, 0.36; P = 0.25) with digital rehabilitation; and −0.17 (−1.06, 0.72; P = 0.71) with their interaction. Absolute differences for other interventions from usual care were modest. There were no serious adverse events related to ICP interventions. Multidisciplinary holistic clinical care is associated with fatigue reduction in LC, irrespective of multi-organ MRI. Digital rehabilitation could be useful in longer-term LC management. Large, multi-site trials of optimal ICP interventions are feasible, but further trials are required. ISRCTN identifier: ISRCTN10665760 .

Nature Medicine
University College London Hospitals NHS Foundation Trust (GB), University of Liverpool (GB), University of Leicester (GB), University of Sussex (GB), Royal Free London NHS Foundation Trust (GB), University of Lancashire (GB), Barts Health NHS Trust (GB), University of Exeter (GB), Leicester Royal Infirmary (GB), Worthing Hospital (GB), Princess Alexandra Hospital NHS Trust (GB), Hull Royal Infirmary (GB), The Francis Crick Institute (GB), Royal London Hospital (GB), Northern General Hospital (GB), University Hospitals of Leicester NHS Trust (GB), John Radcliffe Hospital (GB), Department for Work and Pensions (GB), University of Oxford (GB), Reading Museum (GB), NHS Highland (GB), Sheffield Teaching Hospitals NHS Foundation Trust (GB), Tameside and Glossop Integrated Care NHS Foundation Trust (GB), Derbyshire Community Health Services NHS Foundation Trust (GB), Farr Institute (GB), University Hospitals Sussex NHS Foundation Trust (GB), University of Southampton (GB), NHS England, University College London (GB), University of York (GB), University of Brighton (GB)
Openalex Percentile: Top 9%
Long-Term Effects of COVID-19
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