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

Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study
Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study
Background
There are currently no effective pharmacological or non-pharmacological interventions for Long-COVID. We aimed to describe recovery one year after hospital discharge for COVID-19 and identify factors associated with patient-perceived recovery. To identify potential therapeutic targets, we focussed on previously described four recovery clusters five months after hospital discharge, their underlying inflammatory profiles and relationship with clinical outcomes at one year.

Methods
PHOSP-COVID is a prospective longitudinal cohort study, recruiting adults hospitalised with COVID-19 across the UK. Recovery was assessed using patient reported outcomes measures (PROMs), physical performance, and organ function at five months and one year post-discharge. Inflammatory protein profiling from plasma at the 6-m visit was performed. Hierarchical logistic regression modelling was performed for patient-perceived recovery at one-year. Cluster analysis was performed using clustering large applications (CLARA) k-medoids approach using clinical outcomes at five months.

Findings
2,320 participants have been assessed at 6m post-discharge and 807 participants have completed both five-month and one-year visits. Of these, 35.6% were female, mean age 58.7 (SD 12.5) years, and 27.8% received invasive mechanical ventilation (IMV). The proportion of patients reporting full recovery was unchanged between five-months (25.6%) and one-year (28.5%). Risk factors for not reporting full recovery at one year were: female sex OR=0.55 (95% CI 0.33-0.90); obesity OR=0.69 (95% CI 0.49-0.97); and IMV OR=0.43 (95% CI 0.21-0.86). Cluster analysis (n=1,636) corroborated the previously reported four groups relating to the severity of physical, mental health and cognitive impairments at six months. Interleukin-6 (IL-6) and other inflammatory mediators of tissue damage and repair, including Trefoil Factor 2 and Transforming Growth Factor Alpha, were elevated at five-months in the ‘very severe’ versus ‘mild’ clusters. Overall, there was a substantial deficit in EQ5D-5L utility index from pre-COVID (0.88 (95% CI 0.74-1.00)), five months (0.74 (95% CI 0.60-0.88)) to one year (0.74 (95% CI 0.59-0.88)), with minimal improvements across all measurements at one year post-discharge in the whole cohort and in each of the four clusters.

Interpretation
The sequelae of a hospital admission with COVID-19 remain substantial one 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 remains reduced at one year compared to pre-hospital admission. Systematic inflammation and obesity are potential treatable traits that warrant further investigation in clinical trials.
2213-2600
Evans, Rachel
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Leavy, Olivia C
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Richardson, Matthew
0549bcf9-39ad-4e28-9ecb-45b177e1f914
Elneima, Omer
727194c9-1800-41ae-b17a-b0831c3e2eaa
McAuley, Hamish J C
35d122ef-8fb4-4e0e-af6d-ed6033520da8
Shikotra, Aarti
f14d8109-212a-4f9e-bd74-85145248f7cd
Singapuri, Amisha
be297922-5f8d-4c49-aea5-c113b5d2bd27
Sereno, Marco
9116563f-1b96-4cbe-beb4-cc51b1a9fe4b
Saunders, Ruth
008510ca-5706-47ee-99f4-17b7f0cd25b5
Hart, Nick
08a3bfeb-b59e-4ad5-b5da-96f0629798e2
Hurst, John R
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Jones, Mark
a6fd492e-058e-4e84-a486-34c6035429c1
Raman, Betty
cf22d7e8-3038-4b6b-90f4-e01339b26010
Harrison, Ewen
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Wain, Louise V
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Brightling, Christopher
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Calder, Philip
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PHOSP-COVID Collaborative Group
Evans, Rachel
a01fc97c-1d36-4c38-959a-29477e4f28aa
Leavy, Olivia C
31fedd8a-9d66-42a3-bf92-0ea370a8aaee
Richardson, Matthew
0549bcf9-39ad-4e28-9ecb-45b177e1f914
Elneima, Omer
727194c9-1800-41ae-b17a-b0831c3e2eaa
McAuley, Hamish J C
35d122ef-8fb4-4e0e-af6d-ed6033520da8
Shikotra, Aarti
f14d8109-212a-4f9e-bd74-85145248f7cd
Singapuri, Amisha
be297922-5f8d-4c49-aea5-c113b5d2bd27
Sereno, Marco
9116563f-1b96-4cbe-beb4-cc51b1a9fe4b
Saunders, Ruth
008510ca-5706-47ee-99f4-17b7f0cd25b5
Hart, Nick
08a3bfeb-b59e-4ad5-b5da-96f0629798e2
Hurst, John R
20d9dac3-7eaa-4764-8aa1-8572534f53ee
Jones, Mark
a6fd492e-058e-4e84-a486-34c6035429c1
Raman, Betty
cf22d7e8-3038-4b6b-90f4-e01339b26010
Harrison, Ewen
b1d53078-fdec-445f-a0c3-a27ffdc17c63
Wain, Louise V
53f269b3-a454-4305-b664-fe8102c48452
Brightling, Christopher
b89d0d96-7947-49ab-9b6c-02112c8d4db0
Calder, Philip
1797e54f-378e-4dcb-80a4-3e30018f07a6

Evans, Rachel, Leavy, Olivia C, Richardson, Matthew, Elneima, Omer, McAuley, Hamish J C, Shikotra, Aarti, Singapuri, Amisha, Sereno, Marco, Saunders, Ruth, Hart, Nick, Hurst, John R, Raman, Betty, Harrison, Ewen, Wain, Louise V, Brightling, Christopher and Calder, Philip , PHOSP-COVID Collaborative Group (2022) Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study. The Lancet Respiratory Medicine. (doi:10.1016/S2213-2600(22)00127-8).

Record type: Article

Abstract

Background
There are currently no effective pharmacological or non-pharmacological interventions for Long-COVID. We aimed to describe recovery one year after hospital discharge for COVID-19 and identify factors associated with patient-perceived recovery. To identify potential therapeutic targets, we focussed on previously described four recovery clusters five months after hospital discharge, their underlying inflammatory profiles and relationship with clinical outcomes at one year.

Methods
PHOSP-COVID is a prospective longitudinal cohort study, recruiting adults hospitalised with COVID-19 across the UK. Recovery was assessed using patient reported outcomes measures (PROMs), physical performance, and organ function at five months and one year post-discharge. Inflammatory protein profiling from plasma at the 6-m visit was performed. Hierarchical logistic regression modelling was performed for patient-perceived recovery at one-year. Cluster analysis was performed using clustering large applications (CLARA) k-medoids approach using clinical outcomes at five months.

Findings
2,320 participants have been assessed at 6m post-discharge and 807 participants have completed both five-month and one-year visits. Of these, 35.6% were female, mean age 58.7 (SD 12.5) years, and 27.8% received invasive mechanical ventilation (IMV). The proportion of patients reporting full recovery was unchanged between five-months (25.6%) and one-year (28.5%). Risk factors for not reporting full recovery at one year were: female sex OR=0.55 (95% CI 0.33-0.90); obesity OR=0.69 (95% CI 0.49-0.97); and IMV OR=0.43 (95% CI 0.21-0.86). Cluster analysis (n=1,636) corroborated the previously reported four groups relating to the severity of physical, mental health and cognitive impairments at six months. Interleukin-6 (IL-6) and other inflammatory mediators of tissue damage and repair, including Trefoil Factor 2 and Transforming Growth Factor Alpha, were elevated at five-months in the ‘very severe’ versus ‘mild’ clusters. Overall, there was a substantial deficit in EQ5D-5L utility index from pre-COVID (0.88 (95% CI 0.74-1.00)), five months (0.74 (95% CI 0.60-0.88)) to one year (0.74 (95% CI 0.59-0.88)), with minimal improvements across all measurements at one year post-discharge in the whole cohort and in each of the four clusters.

Interpretation
The sequelae of a hospital admission with COVID-19 remain substantial one 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 remains reduced at one year compared to pre-hospital admission. Systematic inflammation and obesity are potential treatable traits that warrant further investigation in clinical trials.

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More information

Accepted/In Press date: 1 April 2022
e-pub ahead of print date: 23 April 2022
Published date: 23 April 2022
Additional Information: Professor Calder is an author on this paper. Just to let you know he does not have the accepted version and does not know the exact acceptance date. Paper is fully open access. PHOSP-COVID Collaborative Group.Lancet Respir Med. 2022 Apr 22:S2213-2600(22)00127-8. doi: 10.1016/S2213-2600(22)00127-8. Online ahead of print. PMID: 35472304

Identifiers

Local EPrints ID: 456711
URI: http://eprints.soton.ac.uk/id/eprint/456711
ISSN: 2213-2600
PURE UUID: cc148938-1d76-4434-9115-d3c178be1ce4
ORCID for Mark Jones: ORCID iD orcid.org/0000-0001-6308-6014
ORCID for Philip Calder: ORCID iD orcid.org/0000-0002-6038-710X

Catalogue record

Date deposited: 09 May 2022 17:21
Last modified: 24 Jul 2022 01:41

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Contributors

Author: Rachel Evans
Author: Olivia C Leavy
Author: Matthew Richardson
Author: Omer Elneima
Author: Hamish J C McAuley
Author: Aarti Shikotra
Author: Amisha Singapuri
Author: Marco Sereno
Author: Ruth Saunders
Author: Nick Hart
Author: John R Hurst
Author: Mark Jones ORCID iD
Author: Betty Raman
Author: Ewen Harrison
Author: Louise V Wain
Author: Christopher Brightling
Author: Philip Calder ORCID iD
Corporate Author: PHOSP-COVID Collaborative Group

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