IRUS Total

Development and validation of the ISARIC 4C Deterioration model for adults hospitalised with COVID-19: a prospective cohort study

File Description SizeFormat 
ISARIC 4C Deterioration model.pdfPublished version754.34 kBAdobe PDFView/Open
Title: Development and validation of the ISARIC 4C Deterioration model for adults hospitalised with COVID-19: a prospective cohort study
Authors: Gupta, RK
Harrison, EM
Ho, A
Docherty, AB
Knight, SR
Van Smeden, M
Abubakar, I
Lipman, M
Quartagno, M
Pius, R
Buchan, I
Harvey, D
Havalda, P
Hawcutt, DB
Hobrok, M
Hodgson, L
Olliaro, PL
Hormis, A
Jacobs, M
Jain, S
Petersen, C
Pilgrim, J
Jennings, P
Kaliappan, A
Kasipandian, V
Kegg, S
Kelsey, M
Kendall, J
Kerrison, C
Pritchard, MG
Kerslake, I
Koch, O
Prince, T
Saviciute, E
Koduri, G
Koshy, G
Laha, S
Laird, S
Larkin, S
Leiner, T
Lillie, P
Limb, J
Russell, CD
Reynolds, W
Linnett, V
Carson, G
Little, J
MacMahon, M
MacNaughton, E
Mankregod, R
Masson, H
Matovu, E
McCullough, K
McEwen, R
Ridley, PM
Meda, M
Scott-Brown, J
Roberts, S
Mills, G
Minton, J
Mirfenderesky, M
Mohandas, K
Mok, Q
Moon, J
Moore, E
Sales, D
Morgan, P
Morris, C
Mortimore, K
Harrison, J
Shaw, CA
Moses, S
Mpenge, M
Mulla, R
Murphy, M
Nagel, M
Shaw, VE
Nagarajan, T
Nelson, M
Otahal, I
Pais, M
Marsh, L
Panchatsharam, S
Sheikh, A
Paraiso, H
Patel, B
Pattison, N
Shears, RK
Pepperell, J
Peters, M
Phull, M
Pintus, S
Pooni, JS
Connor, M
Post, F
Price, D
Solomon, T
Prout, R
Small, B
Rae, N
Reschreiter, H
Reynolds, T
Richardson, N
Roberts, M
Roberts, D
Halpin, S
Rose, A
Rousseau, G
Ryan, B
Subramaniam, KS
Sudlow, C
Saluja, T
Shah, A
Shanmuga, P
Sharma, A
Shawcross, A
Sizer, J
Jackson, C
Shankar-Hari, M
Smith, R
Holden, KA
Snelson, C
Spittle, N
Swann, OV
Staines, N
Stambach, T
Stewart, R
Subudhi, P
Szakmany, T
Gamble, C
Tatham, K
Mclean, KA
Thomas, J
Thompson, C
Thompson, R
Tridente, A
Turtle, L
Tupper-Carey, D
Twagira, M
Ustianowski, A
Vallotton, N
Leeming, G
Szemiel, A
Vincent-Smith, L
Visuvanathan, S
Vuylsteke, A
Waddy, S
Wake, R
Walden, A
Openshaw, PJM
Welters, I
Whitehouse, T
Whittaker, P
Taggart, A
Law, A
Whittington, A
Wijesinghe, M
Williams, M
Wilson, L
Wilson, S
Winchester, S
Wiselka, M
Baillie, JK
Wolverson, A
Tanianis-Hughes, J
Wooton, DG
Wham, M
Workman, A
Yates, B
Young, P
Semple, MG
Noursadeghi, M
Baillie, JK
Semple, MG
Openshaw, PJM
Thomas, J
Carson, G
Alex, B
Drake, TM
Bach, B
Barclay, WS
Bogaert, D
Chand, M
Cooke, GS
Docherty, AB
Dunning, J
Trochu, E
Filipe, ADS
Fletcher, T
Green, CA
Clohisey, S
Harrison, EM
Hiscox, JA
Horby, PW
Ijaz, S
Khoo, S
Van Tonder, L
Klenerman, P
Law, A
Lim, WS
Mentzer, AJ
Hendry, R
Merson, L
Meynert, AM
Noursadeghi, M
Moore, SC
Palmarini, M
Wilcock, E
Paxton, WA
Pollakis, G
Price, N
Rambaut, A
Robertson, DL
Scott-Brown, J
Russell, CD
Sancho-Shimizu, V
Scott, JT
De Silva, T
Zhang, JE
Sigfrid, L
Solomon, T
Sriskandan, S
Stuart, D
Summers, C
Tedder, RS
Greenhalf, W
Thomson, EC
Thompson, AAR
Thwaites, RS
Adeniji, K
Turtle, LCW
Zambon, M
Hardwick, H
Donohue, C
Lyons, R
Griffiths, F
Oosthuyzen, W
Shaw, V
Norman, L
Pius, R
Agranoff, D
Drake, TM
Fairfield, CJ
Knight, S
McDonald, S
Keating, S
Ahmed, KA
Armstrong, JA
Ashworth, M
Dunning, J
Asiimwe, IG
Murphy, D
Bakshi, S
Barlow, SL
Booth, L
Brennan, B
Bullock, K
Catterall, BWA
Clark, JJ
Clarke, EA
Cole, S
Fairfield, CJ
Horby, PW
Cooper, L
Cox, H
Davis, C
Dincarslan, O
Dunn, C
Dyer, P
Elliott, A
Evans, A
Finch, L
Fisher, LWS
Agwuh, K
Gamble, C
Foster, T
Garcia-Dorival, I
Greenhalf, W
Gunning, P
Hartley, C
Ho, A
Jensen, RL
Jones, CB
Jones, TR
Ail, D
Khandaker, S
Green, CA
King, K
Kiy, RT
Koukorava, C
Lake, A
Lant, S
Latawiec, D
Lavelle-Langham, L
Lefteri, D
Alegria, A
Lett, L
Livoti, LA
Halpin, S
Mancini, M
McDonald, S
McEvoy, L
McLauchlan, J
Metelmann, S
Miah, NS
Middleton, J
Angus, B
Mitchell, J
Moore, SC
Murphy, EG
Hardwick, HE
Penrice-Randal, R
Ashish, A
Atkinson, D
Bari, S
Barlow, G
Barnass, S
Shaw, CA
Barrett, N
Jackson, C
Bassford, C
Baxter, D
Beadsworth, M
Bernatoniene, J
Berridge, J
Best, N
Bothma, P
Brealey, D
Dalton, J
Brittain-Long, R
Bulteel, N
Mclean, KA
Burden, T
Burtenshaw, A
Caruth, V
Chadwick, D
Chambler, D
Chee, N
Child, J
Lee, J
Chukkambotla, S
Clark, T
Collini, P
Merson, L
Cosgrove, C
Cupitt, J
Cutino-Moguel, M
Dark, P
Dawson, C
Dervisevic, S
Plotkin, D
Donnison, P
Douthwaite, S
DuRand, I
Dushianthan, A
Nguyen-Van-Tam, JS
Dyer, T
Evans, C
Eziefula, C
Fegan, C
Finn, A
Girvan, M
Fullerton, D
Garg, S
Garg, S
Garg, A
Gkrania-Klotsas, E
Norman, L
Godden, J
Goldsmith, A
Graham, C
Hardy, E
Mullaney, S
Hartshorn, S
Item Type: Journal Article
Abstract: Background Prognostic models to predict the risk of clinical deterioration in acute COVID-19 cases are urgently required to inform clinical management decisions. Methods We developed and validated a multivariable logistic regression model for in-hospital clinical deterioration (defined as any requirement of ventilatory support or critical care, or death) among consecutively hospitalised adults with highly suspected or confirmed COVID-19 who were prospectively recruited to the International Severe Acute Respiratory and Emerging Infections Consortium Coronavirus Clinical Characterisation Consortium (ISARIC4C) study across 260 hospitals in England, Scotland, and Wales. Candidate predictors that were specified a priori were considered for inclusion in the model on the basis of previous prognostic scores and emerging literature describing routinely measured biomarkers associated with COVID-19 prognosis. We used internal–external cross-validation to evaluate discrimination, calibration, and clinical utility across eight National Health Service (NHS) regions in the development cohort. We further validated the final model in held-out data from an additional NHS region (London). Findings 74 944 participants (recruited between Feb 6 and Aug 26, 2020) were included, of whom 31 924 (43·2%) of 73 948 with available outcomes met the composite clinical deterioration outcome. In internal–external cross-validation in the development cohort of 66 705 participants, the selected model (comprising 11 predictors routinely measured at the point of hospital admission) showed consistent discrimination, calibration, and clinical utility across all eight NHS regions. In held-out data from London (n=8239), the model showed a similarly consistent performance (C-statistic 0·77 [95% CI 0·76 to 0·78]; calibration-in-the-large 0·00 [–0·05 to 0·05]); calibration slope 0·96 [0·91 to 1·01]), and greater net benefit than any other reproducible prognostic model. Interpretation The 4C Deterioration model has strong potential for clinical utility and generalisability to predict clinical deterioration and inform decision making among adults hospitalised with COVID-19. Funding National Institute for Health Research (NIHR), UK Medical Research Council, Wellcome Trust, Department for International Development, Bill & Melinda Gates Foundation, EU Platform for European Preparedness Against (Re-)emerging Epidemics, NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool, NIHR HPRU in Respiratory Infections at Imperial College London.
Issue Date: 1-Apr-2021
Date of Acceptance: 1-Jan-2021
URI: http://hdl.handle.net/10044/1/85694
DOI: 10.1016/S2213-2600(20)30559-2
ISSN: 2213-2600
Publisher: Elsevier
Start Page: 349
End Page: 359
Journal / Book Title: The Lancet Respiratory Medicine
Volume: 9
Issue: 4
Copyright Statement: © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
Sponsor/Funder: National Institute for Health Research
Commission of the European Communities
Medical Research Council (MRC)
National Institute for Health Research
UKRI MRC COVID-19 Rapid Response Call
UK Research and Innovation
UK Research and Innovation
Funder's Grant Number: RDA06 79560
PO 4050681719
9815274 MC_PC_19025
Keywords: ISARIC4C Investigators
1103 Clinical Sciences
1117 Public Health and Health Services
1199 Other Medical and Health Sciences
Publication Status: Published
Online Publication Date: 2021-01-11
Appears in Collections:Department of Metabolism, Digestion and Reproduction
Department of Surgery and Cancer
Department of Infectious Diseases
National Heart and Lung Institute
Faculty of Medicine
Imperial College London COVID-19

This item is licensed under a Creative Commons License Creative Commons