Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study
Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study
Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; p
adjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; p
adjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; p
adjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification. Funding: UK Research and Innovation and National Institute for Health Research.
1003-1019
Raman, Betty
cc45bc93-13ab-4093-8b3e-ace72b65bfab
McCracken, Celeste
6a6a4db0-547e-4e31-a496-5ae79d2b13ea
Cassar, Mark
486229fd-94a5-4d73-a530-01421ba43c7f
Jones, Mark
a6fd492e-058e-4e84-a486-34c6035429c1
Brightling, Christopher
45965616-2e05-4e55-a891-3e7f85dfc0e9
Neubauer, Stefan
35f8e56e-de57-4026-9de1-4f1bfbacbb54
C-More/PHOSP-COVID Collaborative Group,
ca40a3b2-2d52-4506-9b60-b736ab3dcd00
November 2023
Raman, Betty
cc45bc93-13ab-4093-8b3e-ace72b65bfab
McCracken, Celeste
6a6a4db0-547e-4e31-a496-5ae79d2b13ea
Cassar, Mark
486229fd-94a5-4d73-a530-01421ba43c7f
Jones, Mark
a6fd492e-058e-4e84-a486-34c6035429c1
Brightling, Christopher
45965616-2e05-4e55-a891-3e7f85dfc0e9
Neubauer, Stefan
35f8e56e-de57-4026-9de1-4f1bfbacbb54
C-More/PHOSP-COVID Collaborative Group,
ca40a3b2-2d52-4506-9b60-b736ab3dcd00
Raman, Betty, McCracken, Celeste, Cassar, Mark, Jones, Mark, Brightling, Christopher, Neubauer, Stefan and C-More/PHOSP-COVID Collaborative Group,
(2023)
Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study.
The Lancet Respiratory Medicine, 11 (11), .
(doi:10.1016/S2213-2600(23)00262-X).
Abstract
Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; p
adjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; p
adjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; p
adjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification. Funding: UK Research and Innovation and National Institute for Health Research.
Text
C-MORE manuscript 11062023 FINAL_tracked 3
- Accepted Manuscript
More information
Accepted/In Press date: 4 June 2023
Published date: November 2023
Additional Information:
Funding Information:
The PHOSP-COVID and C-MORE study are jointly supported by a grant from MRC Research and Innovation and the Department of Health and Social Care through the NIHR rapid response panel to tackle COVID-19 (MR/V027859/1 and COV0319). Funding of control participants was provided by NIHR Oxford Biomedical Research Centre. BR is funded by the BHF Oxford CRE. ABD is funded by a Wellcome Trust grant (216606/Z/19/Z). AMS acknowledges funding from the BHF. GPM is funded by an NIHR professorship. VMF acknowledges support from the BHF (CH/16/1/32013). RAE holds an NIHR clinician scientist fellowship (CS-2016-16-020). NJG holds an NIHR post-doctoral fellowship (PDF-2017-10-052). CMa was partly funded by the UCL NIHR Biomedical Research Centre. JRW-M is supported by the NIHR Cambridge Biomedical Research Centre (1215-20014). JJ was supported by a Wellcome Trust Clinical Research Career Development Fellowship (209553/Z/17/Z) and by the UCL NIHR Biomedical Research Centre. MB and KM were supported by UKRI project number 104688; D2ED&PM Challenge as the National Consortium for Intelligent Medical Imaging. MGS is supported by The Pandemic Institute Liverpool and the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool. CAM was supported by an advanced fellowship, (NIHR301338) funded by the NIHR, the University of Manchester BHF Accelerator Award (AA/18/4/34221), and the NIHR Manchester Biomedical Research Centre (NIHR203308). LVW was supported by a GSK and British Lung Foundation chair in respiratory research (C17-1). DGW is supported by an NIHR advanced fellowship (NIHR300669). ASi acknowledges joint funding support from UKRI and NIHR (grant references MR/V027859/1 and COV0319). AC acknowledges support from the NIHR MedTech Co-operative for Cardiovascular Disease at Guy's and St Thomas' NHS Foundation Trust. AHAS holds a doctoral scholarship funded by the Ministry of Higher Education Malaysia and Universiti Kebangsaan Malaysia. SP is supported by BHF grant number CH/16/2/32089. TAT is supported by a BHF fellowship (FS/19/35/34374) with further direct and indirect funding by the University College London Hospitals NIHR Biomedical Research Centre and Biomedical Research Unit at Barts Hospital. The views expressed in this publication are those of the authors and not necessarily those of the MRC, NIHR, or the UK Department of Health and Social Care. No form of payment was given to anyone to produce the manuscript. This study would not be possible without all the participants who have given their time and support. We thank all the participants and their families. We thank the many radiographers, research nurses, research administrators, and health-care and social-care professionals who contributed to setting up and delivering the study at all of the National Health Service trusts and research institutions across the UK, as well as all the supporting staff at the NIHR Clinical Research Network, Health Research Authority, Research Ethics Committee, Department of Health and Social Care Public Health Scotland, Public Health England, and support from the ISARIC Coronavirus Clinical Characterisation Consortium. We are very grateful to all the charities that have provided insight to the study: Action Pulmonary Fibrosis, Alzheimer's Research UK, Asthma UK, British Lung Foundation UK, BHF, BHF Oxford CRE (RE/18/3/34214), Diabetes UK, Cystic Fibrosis Trust, Kidney Research UK, MQ Mental Health, Muscular Dystrophy UK, Stroke Association Blood Cancer UK, McPin Foundations, and Versus Arthritis. We thank the NIHR Oxford and Leicester Biomedical Research Centre patient and public involvement group and the Long Covid Support Group.
Funding Information:
The PHOSP-COVID and C-MORE study are jointly supported by a grant from MRC Research and Innovation and the Department of Health and Social Care through the NIHR rapid response panel to tackle COVID-19 (MR/V027859/1 and COV0319). Funding of control participants was provided by NIHR Oxford Biomedical Research Centre. BR is funded by the BHF Oxford CRE. ABD is funded by a Wellcome Trust grant (216606/Z/19/Z). AMS acknowledges funding from the BHF. GPM is funded by an NIHR professorship. VMF acknowledges support from the BHF (CH/16/1/32013). RAE holds an NIHR clinician scientist fellowship (CS-2016-16-020). NJG holds an NIHR post-doctoral fellowship (PDF-2017-10-052). CMa was partly funded by the UCL NIHR Biomedical Research Centre. JRW-M is supported by the NIHR Cambridge Biomedical Research Centre (1215-20014). JJ was supported by a Wellcome Trust Clinical Research Career Development Fellowship (209553/Z/17/Z) and by the UCL NIHR Biomedical Research Centre. MB and KM were supported by UKRI project number 104688; D2ED&PM Challenge as the National Consortium for Intelligent Medical Imaging. MGS is supported by The Pandemic Institute Liverpool and the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool. CAM was supported by an advanced fellowship, (NIHR301338) funded by the NIHR, the University of Manchester BHF Accelerator Award (AA/18/4/34221), and the NIHR Manchester Biomedical Research Centre (NIHR203308). LVW was supported by a GSK and British Lung Foundation chair in respiratory research (C17-1). DGW is supported by an NIHR advanced fellowship (NIHR300669). ASi acknowledges joint funding support from UKRI and NIHR (grant references MR/V027859/1 and COV0319). AC acknowledges support from the NIHR MedTech Co-operative for Cardiovascular Disease at Guy's and St Thomas' NHS Foundation Trust. AHAS holds a doctoral scholarship funded by the Ministry of Higher Education Malaysia and Universiti Kebangsaan Malaysia. SP is supported by BHF grant number CH/16/2/32089. TAT is supported by a BHF fellowship (FS/19/35/34374) with further direct and indirect funding by the University College London Hospitals NIHR Biomedical Research Centre and Biomedical Research Unit at Barts Hospital. The views expressed in this publication are those of the authors and not necessarily those of the MRC, NIHR, or the UK Department of Health and Social Care. No form of payment was given to anyone to produce the manuscript. This study would not be possible without all the participants who have given their time and support. We thank all the participants and their families. We thank the many radiographers, research nurses, research administrators, and health-care and social-care professionals who contributed to setting up and delivering the study at all of the National Health Service trusts and research institutions across the UK, as well as all the supporting staff at the NIHR Clinical Research Network, Health Research Authority, Research Ethics Committee, Department of Health and Social Care Public Health Scotland, Public Health England, and support from the ISARIC Coronavirus Clinical Characterisation Consortium. We are very grateful to all the charities that have provided insight to the study: Action Pulmonary Fibrosis, Alzheimer's Research UK, Asthma UK, British Lung Foundation UK, BHF, BHF Oxford CRE (RE/18/3/34214), Diabetes UK, Cystic Fibrosis Trust, Kidney Research UK, MQ Mental Health, Muscular Dystrophy UK, Stroke Association Blood Cancer UK, McPin Foundations, and Versus Arthritis. We thank the NIHR Oxford and Leicester Biomedical Research Centre patient and public involvement group and the Long Covid Support Group.
Publisher Copyright:
© 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
Identifiers
Local EPrints ID: 479469
URI: http://eprints.soton.ac.uk/id/eprint/479469
ISSN: 2213-2600
PURE UUID: d2642ca2-37b5-41df-a26f-56223b7ab8f4
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Date deposited: 25 Jul 2023 16:31
Last modified: 18 Mar 2024 03:07
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Contributors
Author:
Betty Raman
Author:
Celeste McCracken
Author:
Mark Cassar
Author:
Christopher Brightling
Author:
Stefan Neubauer
Author:
C-More/PHOSP-COVID Collaborative Group
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