Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study

PHOSP-COVID Collaborative Group; V Kamwa; Kay Por Yip; Neil Hanley

doi:10.1016/s2213-2600(22)00127-8

Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study

PHOSP-COVID Collaborative Group, V Kamwa, Kay Por Yip, Neil Hanley

Research output: Contribution to journal › Article › peer-review

9 Downloads (Pure)

Abstract

Background
No effective pharmacological or non-pharmacological interventions exist for patients with long COVID. We aimed to describe recovery 1 year after hospital discharge for COVID-19, identify factors associated with patient-perceived recovery, and identify potential therapeutic targets by describing the underlying inflammatory profiles of the previously described recovery clusters at 5 months after hospital discharge.

Methods
The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study recruiting adults (aged ≥18 years) discharged from hospital with COVID-19 across the UK. Recovery was assessed using patient-reported outcome measures, physical performance, and organ function at 5 months and 1 year after hospital discharge, and stratified by both patient-perceived recovery and recovery cluster. Hierarchical logistic regression modelling was performed for patient-perceived recovery at 1 year. Cluster analysis was done using the clustering large applications k-medoids approach using clinical outcomes at 5 months. Inflammatory protein profiling was analysed from plasma at the 5-month visit. This study is registered on the ISRCTN Registry, ISRCTN10980107, and recruitment is ongoing.

Findings
2320 participants discharged from hospital between March 7, 2020, and April 18, 2021, were assessed at 5 months after discharge and 807 (32·7%) participants completed both the 5-month and 1-year visits. 279 (35·6%) of these 807 patients were women and 505 (64·4%) were men, with a mean age of 58·7 (SD 12·5) years, and 224 (27·8%) had received invasive mechanical ventilation (WHO class 7–9). The proportion of patients reporting full recovery was unchanged between 5 months (501 [25·5%] of 1965) and 1 year (232 [28·9%] of 804). Factors associated with being less likely to report full recovery at 1 year were female sex (odds ratio 0·68 [95% CI 0·46–0·99]), obesity (0·50 [0·34–0·74]) and invasive mechanical ventilation (0·42 [0·23–0·76]). Cluster analysis (n=1636) corroborated the previously reported four clusters: very severe, severe, moderate with cognitive impairment, and mild, relating to the severity of physical health, mental health, and cognitive impairment at 5 months. We found increased inflammatory mediators of tissue damage and repair in both the very severe and the moderate with cognitive impairment clusters compared with the mild cluster, including IL-6 concentration, which was increased in both comparisons (n=626 participants). We found a substantial deficit in median EQ-5D-5L utility index from before COVID-19 (retrospective assessment; 0·88 [IQR 0·74–1·00]), at 5 months (0·74 [0·64–0·88]) to 1 year (0·75 [0·62–0·88]), with minimal improvements across all outcome measures at 1 year after discharge in the whole cohort and within each of the four clusters.

Interpretation
The sequelae of a hospital admission with COVID-19 were substantial 1 year after discharge across a range of health domains, with the minority in our cohort feeling fully recovered. Patient-perceived health-related quality of life was reduced at 1 year compared with before hospital admission. Systematic inflammation and obesity are potential treatable traits that warrant further investigation in clinical trials.

Funding
UK Research and Innovation and National Institute for Health Research.

Original language	English
Pages (from-to)	761-775
Number of pages	15
Journal	The Lancet Respiratory Medicine
Volume	10
Issue number	8
Early online date	23 Apr 2022
DOIs	https://doi.org/10.1016/s2213-2600(22)00127-8
Publication status	Published - 8 Aug 2022

Bibliographical note

Funding Information:
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 research administrators and health-care and social-care professionals who contributed to setting up and delivering the study at all of the 69 NHS trusts and 25 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. At the NIHR Office for Clinical Research Infrastructure, we thank Kate Holmes for her support in coordinating the charities group. 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, British Heart Foundation, 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 Leicester Biomedical Research Centre patient and public involvement group and the Long Covid Support Group. This research used the SPECTRE High Performance Computing Facility at the University of Leicester, Leicester, UK. PHOSP-COVID is 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). Core funding was provided by NIHR Leicester Biomedical Research Centre to support the PHOSP-COVID coordination team and NIHR biomedical research centres, clinical research facilities, NIHR health protection research unit, and translational research collaborations network across the country. The institutional funding that supports the outbreak labs that process the PHOSP samples are from the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK, in partnership with Public Health England and Liverpool Experimental Cancer Medicine Centre (C18616/A25153). ABD is funded by a Wellcome Trust grant (216606/Z/19/Z); RAE holds an NIHR clinician scientist fellowship (CS-2016-16-020); NJG holds an NIHR post-doctoral fellowship (PDF-2017-10-052); JJ was supported by a Wellcome Trust Clinical Research Career Development Fellowship (209553/Z/17/Z) and by the NIHR University College London Hospital Biomedical Research Centre, UK; LVW was supported by a GlaxoSmithKline and British Lung Foundation chair in respiratory research (C17-1); and DGW is supported by an NIHR advanced fellowship (NIHR300669). The views expressed in this publication are those of the author(s) 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.

Publisher Copyright:
© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Access to Document

10.1016/s2213-2600(22)00127-8Licence: Creative Commons: Attribution (CC BY)

PHOSPCOVID2022clinicalFinal published version, 1.74 MBLicence: Creative Commons: Attribution (CC BY)

1 Preprint

Clinical characteristics with inflammation profiling of Long-COVID and association with one-year recovery following hospitalisation in the UK: a prospective observational study
PHOSP-COVID Collaborative Group, 20 Dec 2021, medRxiv.
Research output: Working paper/Preprint › Preprint

Open Access

Cite this

@article{45ecf0dc38104ecabe24cfb173be4239,

title = "Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study",

abstract = "BackgroundNo effective pharmacological or non-pharmacological interventions exist for patients with long COVID. We aimed to describe recovery 1 year after hospital discharge for COVID-19, identify factors associated with patient-perceived recovery, and identify potential therapeutic targets by describing the underlying inflammatory profiles of the previously described recovery clusters at 5 months after hospital discharge.MethodsThe Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study recruiting adults (aged ≥18 years) discharged from hospital with COVID-19 across the UK. Recovery was assessed using patient-reported outcome measures, physical performance, and organ function at 5 months and 1 year after hospital discharge, and stratified by both patient-perceived recovery and recovery cluster. Hierarchical logistic regression modelling was performed for patient-perceived recovery at 1 year. Cluster analysis was done using the clustering large applications k-medoids approach using clinical outcomes at 5 months. Inflammatory protein profiling was analysed from plasma at the 5-month visit. This study is registered on the ISRCTN Registry, ISRCTN10980107, and recruitment is ongoing.Findings2320 participants discharged from hospital between March 7, 2020, and April 18, 2021, were assessed at 5 months after discharge and 807 (32·7%) participants completed both the 5-month and 1-year visits. 279 (35·6%) of these 807 patients were women and 505 (64·4%) were men, with a mean age of 58·7 (SD 12·5) years, and 224 (27·8%) had received invasive mechanical ventilation (WHO class 7–9). The proportion of patients reporting full recovery was unchanged between 5 months (501 [25·5%] of 1965) and 1 year (232 [28·9%] of 804). Factors associated with being less likely to report full recovery at 1 year were female sex (odds ratio 0·68 [95% CI 0·46–0·99]), obesity (0·50 [0·34–0·74]) and invasive mechanical ventilation (0·42 [0·23–0·76]). Cluster analysis (n=1636) corroborated the previously reported four clusters: very severe, severe, moderate with cognitive impairment, and mild, relating to the severity of physical health, mental health, and cognitive impairment at 5 months. We found increased inflammatory mediators of tissue damage and repair in both the very severe and the moderate with cognitive impairment clusters compared with the mild cluster, including IL-6 concentration, which was increased in both comparisons (n=626 participants). We found a substantial deficit in median EQ-5D-5L utility index from before COVID-19 (retrospective assessment; 0·88 [IQR 0·74–1·00]), at 5 months (0·74 [0·64–0·88]) to 1 year (0·75 [0·62–0·88]), with minimal improvements across all outcome measures at 1 year after discharge in the whole cohort and within each of the four clusters.InterpretationThe sequelae of a hospital admission with COVID-19 were substantial 1 year after discharge across a range of health domains, with the minority in our cohort feeling fully recovered. Patient-perceived health-related quality of life was reduced at 1 year compared with before hospital admission. Systematic inflammation and obesity are potential treatable traits that warrant further investigation in clinical trials.FundingUK Research and Innovation and National Institute for Health Research.",

author = "{PHOSP-COVID Collaborative Group} and V Kamwa and Yip, {Kay Por} and Neil Hanley",

note = " Funding Information: 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 research administrators and health-care and social-care professionals who contributed to setting up and delivering the study at all of the 69 NHS trusts and 25 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. At the NIHR Office for Clinical Research Infrastructure, we thank Kate Holmes for her support in coordinating the charities group. 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, British Heart Foundation, 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 Leicester Biomedical Research Centre patient and public involvement group and the Long Covid Support Group. This research used the SPECTRE High Performance Computing Facility at the University of Leicester, Leicester, UK. PHOSP-COVID is 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). Core funding was provided by NIHR Leicester Biomedical Research Centre to support the PHOSP-COVID coordination team and NIHR biomedical research centres, clinical research facilities, NIHR health protection research unit, and translational research collaborations network across the country. The institutional funding that supports the outbreak labs that process the PHOSP samples are from the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK, in partnership with Public Health England and Liverpool Experimental Cancer Medicine Centre (C18616/A25153). ABD is funded by a Wellcome Trust grant (216606/Z/19/Z); RAE holds an NIHR clinician scientist fellowship (CS-2016-16-020); NJG holds an NIHR post-doctoral fellowship (PDF-2017-10-052); JJ was supported by a Wellcome Trust Clinical Research Career Development Fellowship (209553/Z/17/Z) and by the NIHR University College London Hospital Biomedical Research Centre, UK; LVW was supported by a GlaxoSmithKline and British Lung Foundation chair in respiratory research (C17-1); and DGW is supported by an NIHR advanced fellowship (NIHR300669). The views expressed in this publication are those of the author(s) 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. Publisher Copyright: {\textcopyright} 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license ",

year = "2022",

month = aug,

day = "8",

doi = "10.1016/s2213-2600(22)00127-8",

language = "English",

volume = "10",

pages = "761--775",

journal = "The Lancet Respiratory Medicine",

issn = "2213-2600",

publisher = "Elsevier",

number = "8",

}

Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study. / PHOSP-COVID Collaborative Group ; Kamwa, V ; Yip, Kay Por et al.
In: The Lancet Respiratory Medicine, Vol. 10, No. 8, 08.08.2022, p. 761-775.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK

T2 - a prospective observational study

AU - PHOSP-COVID Collaborative Group

AU - Kamwa, V

AU - Yip, Kay Por

AU - Hanley, Neil

N1 - Funding Information: 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 research administrators and health-care and social-care professionals who contributed to setting up and delivering the study at all of the 69 NHS trusts and 25 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. At the NIHR Office for Clinical Research Infrastructure, we thank Kate Holmes for her support in coordinating the charities group. 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, British Heart Foundation, 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 Leicester Biomedical Research Centre patient and public involvement group and the Long Covid Support Group. This research used the SPECTRE High Performance Computing Facility at the University of Leicester, Leicester, UK. PHOSP-COVID is 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). Core funding was provided by NIHR Leicester Biomedical Research Centre to support the PHOSP-COVID coordination team and NIHR biomedical research centres, clinical research facilities, NIHR health protection research unit, and translational research collaborations network across the country. The institutional funding that supports the outbreak labs that process the PHOSP samples are from the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK, in partnership with Public Health England and Liverpool Experimental Cancer Medicine Centre (C18616/A25153). ABD is funded by a Wellcome Trust grant (216606/Z/19/Z); RAE holds an NIHR clinician scientist fellowship (CS-2016-16-020); NJG holds an NIHR post-doctoral fellowship (PDF-2017-10-052); JJ was supported by a Wellcome Trust Clinical Research Career Development Fellowship (209553/Z/17/Z) and by the NIHR University College London Hospital Biomedical Research Centre, UK; LVW was supported by a GlaxoSmithKline and British Lung Foundation chair in respiratory research (C17-1); and DGW is supported by an NIHR advanced fellowship (NIHR300669). The views expressed in this publication are those of the author(s) 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. Publisher Copyright: © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

PY - 2022/8/8

Y1 - 2022/8/8

N2 - BackgroundNo effective pharmacological or non-pharmacological interventions exist for patients with long COVID. We aimed to describe recovery 1 year after hospital discharge for COVID-19, identify factors associated with patient-perceived recovery, and identify potential therapeutic targets by describing the underlying inflammatory profiles of the previously described recovery clusters at 5 months after hospital discharge.MethodsThe Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study recruiting adults (aged ≥18 years) discharged from hospital with COVID-19 across the UK. Recovery was assessed using patient-reported outcome measures, physical performance, and organ function at 5 months and 1 year after hospital discharge, and stratified by both patient-perceived recovery and recovery cluster. Hierarchical logistic regression modelling was performed for patient-perceived recovery at 1 year. Cluster analysis was done using the clustering large applications k-medoids approach using clinical outcomes at 5 months. Inflammatory protein profiling was analysed from plasma at the 5-month visit. This study is registered on the ISRCTN Registry, ISRCTN10980107, and recruitment is ongoing.Findings2320 participants discharged from hospital between March 7, 2020, and April 18, 2021, were assessed at 5 months after discharge and 807 (32·7%) participants completed both the 5-month and 1-year visits. 279 (35·6%) of these 807 patients were women and 505 (64·4%) were men, with a mean age of 58·7 (SD 12·5) years, and 224 (27·8%) had received invasive mechanical ventilation (WHO class 7–9). The proportion of patients reporting full recovery was unchanged between 5 months (501 [25·5%] of 1965) and 1 year (232 [28·9%] of 804). Factors associated with being less likely to report full recovery at 1 year were female sex (odds ratio 0·68 [95% CI 0·46–0·99]), obesity (0·50 [0·34–0·74]) and invasive mechanical ventilation (0·42 [0·23–0·76]). Cluster analysis (n=1636) corroborated the previously reported four clusters: very severe, severe, moderate with cognitive impairment, and mild, relating to the severity of physical health, mental health, and cognitive impairment at 5 months. We found increased inflammatory mediators of tissue damage and repair in both the very severe and the moderate with cognitive impairment clusters compared with the mild cluster, including IL-6 concentration, which was increased in both comparisons (n=626 participants). We found a substantial deficit in median EQ-5D-5L utility index from before COVID-19 (retrospective assessment; 0·88 [IQR 0·74–1·00]), at 5 months (0·74 [0·64–0·88]) to 1 year (0·75 [0·62–0·88]), with minimal improvements across all outcome measures at 1 year after discharge in the whole cohort and within each of the four clusters.InterpretationThe sequelae of a hospital admission with COVID-19 were substantial 1 year after discharge across a range of health domains, with the minority in our cohort feeling fully recovered. Patient-perceived health-related quality of life was reduced at 1 year compared with before hospital admission. Systematic inflammation and obesity are potential treatable traits that warrant further investigation in clinical trials.FundingUK Research and Innovation and National Institute for Health Research.

AB - BackgroundNo effective pharmacological or non-pharmacological interventions exist for patients with long COVID. We aimed to describe recovery 1 year after hospital discharge for COVID-19, identify factors associated with patient-perceived recovery, and identify potential therapeutic targets by describing the underlying inflammatory profiles of the previously described recovery clusters at 5 months after hospital discharge.MethodsThe Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study recruiting adults (aged ≥18 years) discharged from hospital with COVID-19 across the UK. Recovery was assessed using patient-reported outcome measures, physical performance, and organ function at 5 months and 1 year after hospital discharge, and stratified by both patient-perceived recovery and recovery cluster. Hierarchical logistic regression modelling was performed for patient-perceived recovery at 1 year. Cluster analysis was done using the clustering large applications k-medoids approach using clinical outcomes at 5 months. Inflammatory protein profiling was analysed from plasma at the 5-month visit. This study is registered on the ISRCTN Registry, ISRCTN10980107, and recruitment is ongoing.Findings2320 participants discharged from hospital between March 7, 2020, and April 18, 2021, were assessed at 5 months after discharge and 807 (32·7%) participants completed both the 5-month and 1-year visits. 279 (35·6%) of these 807 patients were women and 505 (64·4%) were men, with a mean age of 58·7 (SD 12·5) years, and 224 (27·8%) had received invasive mechanical ventilation (WHO class 7–9). The proportion of patients reporting full recovery was unchanged between 5 months (501 [25·5%] of 1965) and 1 year (232 [28·9%] of 804). Factors associated with being less likely to report full recovery at 1 year were female sex (odds ratio 0·68 [95% CI 0·46–0·99]), obesity (0·50 [0·34–0·74]) and invasive mechanical ventilation (0·42 [0·23–0·76]). Cluster analysis (n=1636) corroborated the previously reported four clusters: very severe, severe, moderate with cognitive impairment, and mild, relating to the severity of physical health, mental health, and cognitive impairment at 5 months. We found increased inflammatory mediators of tissue damage and repair in both the very severe and the moderate with cognitive impairment clusters compared with the mild cluster, including IL-6 concentration, which was increased in both comparisons (n=626 participants). We found a substantial deficit in median EQ-5D-5L utility index from before COVID-19 (retrospective assessment; 0·88 [IQR 0·74–1·00]), at 5 months (0·74 [0·64–0·88]) to 1 year (0·75 [0·62–0·88]), with minimal improvements across all outcome measures at 1 year after discharge in the whole cohort and within each of the four clusters.InterpretationThe sequelae of a hospital admission with COVID-19 were substantial 1 year after discharge across a range of health domains, with the minority in our cohort feeling fully recovered. Patient-perceived health-related quality of life was reduced at 1 year compared with before hospital admission. Systematic inflammation and obesity are potential treatable traits that warrant further investigation in clinical trials.FundingUK Research and Innovation and National Institute for Health Research.

UR - http://www.scopus.com/inward/record.url?scp=85135217228&partnerID=8YFLogxK

U2 - 10.1016/s2213-2600(22)00127-8

DO - 10.1016/s2213-2600(22)00127-8

M3 - Article

C2 - 35472304

SN - 2213-2600

VL - 10

SP - 761

EP - 775

JO - The Lancet Respiratory Medicine

JF - The Lancet Respiratory Medicine

IS - 8

ER -

Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study

Abstract

Bibliographical note

Access to Document

Fingerprint

Research output

Clinical characteristics with inflammation profiling of Long-COVID and association with one-year recovery following hospitalisation in the UK: a prospective observational study

Cite this