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Biomarker identification using dynamic time warping analysis: a longitudinal cohort study of patients with COVID-19 in a UK tertiary hospital

Biomarker identification using dynamic time warping analysis: a longitudinal cohort study of patients with COVID-19 in a UK tertiary hospital
Biomarker identification using dynamic time warping analysis: a longitudinal cohort study of patients with COVID-19 in a UK tertiary hospital

Objectives COVID-19 is a heterogeneous disease, and many reports have described variations in demographic, biochemical and clinical features at presentation influencing overall hospital mortality. However, there is little information regarding longitudinal changes in laboratory prognostic variables in relation to disease progression in hospitalised patients with COVID-19. Design and setting This retrospective observational report describes disease progression from symptom onset, to admission to hospital, clinical response and discharge/death among patients with COVID-19 at a tertiary centre in South East England. Participants Six hundred and fifty-one patients treated for SARS-CoV-2 between March and September 2020 were included in this analysis. Ethical approval was obtained from the HRA Specific Review Board (REC 20/HRA/2986) for waiver of informed consent. Results The majority of patients presented within 1 week of symptom onset. The lowest risk patients had low mortality (1/45, 2%), and most were discharged within 1 week after admission (30/45, 67%). The highest risk patients, as determined by the 4C mortality score predictor, had high mortality (27/29, 93%), with most dying within 1 week after admission (22/29, 76%). Consistent with previous reports, most patients presented with high levels of C reactive protein (CRP) (67% of patients >50 mg/L), D-dimer (98%>upper limit of normal (ULN)), ferritin (65%>ULN), lactate dehydrogenase (90%>ULN) and low lymphocyte counts (81%<lower limit of normal (LLN)). Increases in platelet counts and decreases in CRP, neutrophil:lymphocyte ratio (p<0.001), lactate dehydrogenase, neutrophil counts, urea and white cell counts (all p<0.01) were each associated with discharge. Conclusions Serial measurement of routine blood tests may be a useful prognostic tool for monitoring treatment response in hospitalised patients with COVID-19. Changes in other biochemical parameters often included in a â € COVID-19 bundle' did not show significant association with outcome, suggesting there may be limited clinical benefit of serial sampling. This may have direct clinical utility in the context of escalating healthcare costs of the pandemic.

COVID-19, respiratory infections, respiratory medicine (see thoracic medicine)
2044-6055
Burke, Hannah
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Freeman, Anna
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O'Regan, Paul
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Wysocki, Oskar
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Freitas, Andre
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Dushianthan, Ahilanandan
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Celinski, Michael
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Batchelor, James
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Phan, Hang
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Borca, Florina
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Sheard, Natasha
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Williams, Sarah
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Watson, Alastair
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Fitzpatrick, Paul
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Landers, Dónal
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Wilkinson, Tom
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REACT COVID group
Burke, Hannah
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Freeman, Anna
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O'Regan, Paul
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Wysocki, Oskar
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Freitas, Andre
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Dushianthan, Ahilanandan
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Celinski, Michael
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Batchelor, James
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Phan, Hang
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Borca, Florina
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Sheard, Natasha
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Williams, Sarah
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Watson, Alastair
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Fitzpatrick, Paul
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Landers, Dónal
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Wilkinson, Tom
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Burke, Hannah, Freeman, Anna, O'Regan, Paul, Wysocki, Oskar, Freitas, Andre, Dushianthan, Ahilanandan, Celinski, Michael, Batchelor, James, Phan, Hang, Borca, Florina, Sheard, Natasha, Williams, Sarah, Watson, Alastair, Fitzpatrick, Paul, Landers, Dónal and Wilkinson, Tom , REACT COVID group (2022) Biomarker identification using dynamic time warping analysis: a longitudinal cohort study of patients with COVID-19 in a UK tertiary hospital. BMJ Open, 12 (2), [e050331]. (doi:10.1136/bmjopen-2021-050331).

Record type: Article

Abstract

Objectives COVID-19 is a heterogeneous disease, and many reports have described variations in demographic, biochemical and clinical features at presentation influencing overall hospital mortality. However, there is little information regarding longitudinal changes in laboratory prognostic variables in relation to disease progression in hospitalised patients with COVID-19. Design and setting This retrospective observational report describes disease progression from symptom onset, to admission to hospital, clinical response and discharge/death among patients with COVID-19 at a tertiary centre in South East England. Participants Six hundred and fifty-one patients treated for SARS-CoV-2 between March and September 2020 were included in this analysis. Ethical approval was obtained from the HRA Specific Review Board (REC 20/HRA/2986) for waiver of informed consent. Results The majority of patients presented within 1 week of symptom onset. The lowest risk patients had low mortality (1/45, 2%), and most were discharged within 1 week after admission (30/45, 67%). The highest risk patients, as determined by the 4C mortality score predictor, had high mortality (27/29, 93%), with most dying within 1 week after admission (22/29, 76%). Consistent with previous reports, most patients presented with high levels of C reactive protein (CRP) (67% of patients >50 mg/L), D-dimer (98%>upper limit of normal (ULN)), ferritin (65%>ULN), lactate dehydrogenase (90%>ULN) and low lymphocyte counts (81%<lower limit of normal (LLN)). Increases in platelet counts and decreases in CRP, neutrophil:lymphocyte ratio (p<0.001), lactate dehydrogenase, neutrophil counts, urea and white cell counts (all p<0.01) were each associated with discharge. Conclusions Serial measurement of routine blood tests may be a useful prognostic tool for monitoring treatment response in hospitalised patients with COVID-19. Changes in other biochemical parameters often included in a â € COVID-19 bundle' did not show significant association with outcome, suggesting there may be limited clinical benefit of serial sampling. This may have direct clinical utility in the context of escalating healthcare costs of the pandemic.

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e050331.full - Version of Record
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Accepted/In Press date: 27 January 2022
Published date: 15 February 2022
Additional Information: Funding The REACT platform has been supported by the digital Experimental Cancer Medicine Team free of charge (grant number not applicable). The biobanking sub-cohort is supported the NIHR Southampton CRF and NIHR Southampton Biomedical Research Centre at University Hospital Southampton NHS Foundation Trust and as part of a broader effort (Enabling New Treatment Approaches for COVID-19 Treatment) by the University of Southampton (UoS) charity (Office of Development and Alumni Relations) (grant number not applicable). In addition, the Clinical Informatics Research Unit, UoS has supported infrastructure costs (Grant number not applicable). The support described previously was not provided from a specific award or grant. The digital Experimental Cancer Medicine Team are supported by the AstraZeneca iDECIDE Programme (grant number: 119106), awarded to Manchester Cancer Research Centre and by Cancer Research UK via an Accelerator Award (award number: A29374) through the CRUK Manchester Institute (award number: C147/A25254).
Keywords: COVID-19, respiratory infections, respiratory medicine (see thoracic medicine)

Identifiers

Local EPrints ID: 455280
URI: http://eprints.soton.ac.uk/id/eprint/455280
ISSN: 2044-6055
PURE UUID: 2539c878-3256-4c35-a27d-495c91574517
ORCID for Ahilanandan Dushianthan: ORCID iD orcid.org/0000-0002-0165-3359
ORCID for James Batchelor: ORCID iD orcid.org/0000-0002-5307-552X

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Date deposited: 16 Mar 2022 17:49
Last modified: 17 Nov 2022 02:50

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Contributors

Author: Hannah Burke
Author: Anna Freeman
Author: Paul O'Regan
Author: Oskar Wysocki
Author: Andre Freitas
Author: Ahilanandan Dushianthan ORCID iD
Author: Michael Celinski
Author: James Batchelor ORCID iD
Author: Hang Phan
Author: Florina Borca
Author: Natasha Sheard
Author: Sarah Williams
Author: Alastair Watson
Author: Paul Fitzpatrick
Author: Dónal Landers
Author: Tom Wilkinson
Corporate Author: REACT COVID group

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