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

Gupta, Rishi K, Harrison, Ewen M, Ho, Antonia, Docherty, Annemarie B, Knight, Stephen R, van Smeden, Maarten, Abubakar, Ibrahim, Lipman, Marc, Quartagno, Matteo, Pius, Riinu, Buchan, Iain, Carson, Gail, Drake, Thomas M, Dunning, Jake, Fairfield, Cameron J, Gamble, Carrol, Green, Christopher A, Halpin, Sophie, Hardwick, Hayley E, Holden, Karl A, Horby, Peter W, Jackson, Clare, Mclean, Kenneth A, Merson, Laura, Nguyen-Van-Tam, Jonathan S, Norman, Lisa, Olliaro, Piero L, Pritchard, Mark G, Russell, Clark D, Scott-Brown, James, Shaw, Catherine A, Sheikh, Aziz, Solomon, Tom, Sudlow, Cathie, Swann, Olivia V, Turtle, Lance, Openshaw, Peter J M, Baillie, J Kenneth, Semple, Malcolm G, Noursadeghi, Mahdad, Baillie, J Kenneth, Semple, Malcolm G, Openshaw, Peter JM, Carson, Gail, Alex, Beatrice, Bach, Benjamin, Barclay, Wendy S, Bogaert, Debby, Chand, Meera, Cooke, Graham S, Docherty, Annemarie B, Dunning, Jake, Filipe, Ana da Silva, Fletcher, Tom, Green, Christopher A, Harrison, Ewen M, Hiscox, Julian A, Ho, Antonia Ying Wai, Horby, Peter W, Ijaz, Samreen, Khoo, Saye, Klenerman, Paul, Law, Andrew, Lim, Wei Shen, Mentzer, Alexander J, Merson, Laura, Meynert, Alison M, Noursadeghi, Mahdad, Moore, Shona C, Palmarini, Massimo, Paxton, William A, Pollakis, Georgios, Price, Nicholas, Rambaut, Andrew, Robertson, David L, Russell, Clark D, Sancho-Shimizu, Vanessa, Scott, Janet T, de Silva, Thushan, Sigfrid, Louise, Solomon, Tom, Sriskandan, Shiranee, Stuart, David, Summers, Charlotte, Tedder, Richard S, Thomson, Emma C, Thompson, AA Roger, Thwaites, Ryan S, Turtle, Lance CW, Zambon, Maria, Hardwick, Hayley, Donohue, Chloe, Lyons, Ruth, Griffiths, Fiona, Oosthuyzen, Wilna, Norman, Lisa, Pius, Riinu, Drake, Tom M, Fairfield, Cameron J, Knight, Stephen, Mclean, Kenneth A, Murphy, Derek, Shaw, Catherine A, Dalton, Jo, Lee, James, Plotkin, Daniel, Girvan, Michelle, Mullaney, Scott, Petersen, Claire, Saviciute, Egle, Roberts, Stephanie, Harrison, Janet, Marsh, Laura, Connor, Marie, Halpin, Sophie, Jackson, Clare, Gamble, Carrol, Leeming, Gary, Law, Andrew, Wham, Murray, Clohisey, Sara, Hendry, Ross, Scott-Brown, James, Greenhalf, William, Shaw, Victoria, McDonald, Sarah, Keating, Seán, Ahmed, Katie A., Armstrong, Jane A, Ashworth, Milton, Asiimwe, Innocent G, Bakshi, Siddharth, Barlow, Samantha L, Booth, Laura, Brennan, Benjamin, Bullock, Katie, Catterall, Benjamin WA, Clark, Jordan J, Clarke, Emily A, Cole, Sarah, Cooper, Louise, Cox, Helen, Davis, Christopher, Dincarslan, Oslem, Dunn, Chris, Dyer, Philip, Elliott, Angela, Evans, Anthony, Finch, Lorna, Fisher, Lewis WS, Foster, Terry, Garcia-Dorival, Isabel, Greenhalf, Willliam, Gunning, Philip, Hartley, Catherine, Ho, Antonia, Jensen, Rebecca L, Jones, Christopher B, Jones, Trevor R, Khandaker, Shadia, King, Katharine, Kiy, Robyn T., Koukorava, Chrysa, Lake, Annette, Lant, Suzannah, Latawiec, Diane, Lavelle-Langham, L, Lefteri, Daniella, Lett, Lauren, Livoti, Lucia A, Mancini, Maria, McDonald, Sarah, McEvoy, Laurence, McLauchlan, John, Metelmann, Soeren, Miah, Nahida S, Middleton, Joanna, Mitchell, Joyce, Moore, Shona C, Murphy, Ellen G, Penrice-Randal, Rebekah, Pilgrim, Jack, Prince, Tessa, Reynolds, Will, Ridley, P. Matthew, Sales, Debby, Shaw, Victoria E, Shears, Rebecca K, Small, Benjamin, Subramaniam, Krishanthi S, Szemiel, Agnieska, Taggart, Aislynn, Tanianis-Hughes, Jolanta, Thomas, Jordan, Trochu, Erwan, van Tonder, Libby, Wilcock, Eve, Zhang, J. Eunice, Adeniji, Kayode, Agranoff, Daniel, Agwuh, Ken, Ail, Dhiraj, Alegria, Ana, Angus, Brian, Ashish, Abdul, Atkinson, Dougal, Bari, Shahedal, Barlow, Gavin, Barnass, Stella, Barrett, Nicholas, Bassford, Christopher, Baxter, David, Beadsworth, Michael, Bernatoniene, Jolanta, Berridge, John, Best, Nicola, Bothma, Pieter, Brealey, David, Brittain-Long, Robin, Bulteel, Naomi, Burden, Tom, Burtenshaw, Andrew, Caruth, Vikki, Chadwick, David, Chambler, Duncan, Chee, Nigel, Child, Jenny, Chukkambotla, Srikanth, Clark, Tom, Collini, Paul, Cosgrove, Catherine, Cupitt, Jason, Cutino-Moguel, Maria-Teresa, Dark, Paul, Dawson, Chris, Dervisevic, Samir, Donnison, Phil, Douthwaite, Sam, DuRand, Ingrid, Dushianthan, Ahilanadan, Dyer, Tristan, Evans, Cariad, Eziefula, Chi, Fegan, Chrisopher, Finn, Adam, Fullerton, Duncan, Garg, Sanjeev, Garg, Sanjeev, Garg, Atul, Gkrania-Klotsas, Effrossyni, Godden, Jo, Goldsmith, Arthur, Graham, Clive, Hardy, Elaine, Hartshorn, Stuart, Harvey, Daniel, Havalda, Peter, Hawcutt, Daniel B, Hobrok, Maria, Hodgson, Luke, Hormis, Anil, Jacobs, Michael, Jain, Susan, Jennings, Paul, Kaliappan, Agilan, Kasipandian, Vidya, Kegg, Stephen, Kelsey, Michael, Kendall, Jason, Kerrison, Caroline, Kerslake, Ian, Koch, Oliver, Koduri, Gouri, Koshy, George, Laha, Shondipon, Laird, Steven, Larkin, Susan, Leiner, Tamas, Lillie, Patrick, Limb, James, Linnett, Vanessa, Little, Jeff, MacMahon, Michael, MacNaughton, Emily, Mankregod, Ravish, Masson, Huw, Matovu, Elijah, McCullough, Katherine, McEwen, Ruth, Meda, Manjula, Mills, Gary, Minton, Jane, Mirfenderesky, Mariyam, Mohandas, Kavya, Mok, Quen, Moon, James, Moore, Elinoor, Morgan, Patrick, Morris, Craig, Mortimore, Katherine, Moses, Samuel, Mpenge, Mbiye, Mulla, Rohinton, Murphy, Michael, Nagel, Megan, Nagarajan, Thapas, Nelson, Mark, Otahal, Igor, Pais, Mark, Panchatsharam, Selva, Paraiso, Hassan, Patel, Brij, Pattison, Natalie, Pepperell, Justin, Peters, Mark, Phull, Mandeep, Pintus, Stefania, Pooni, Jagtur Singh, Post, Frank, Price, David, Prout, Rachel, Rae, Nikolas, Reschreiter, Henrik, Reynolds, Tim, Richardson, Neil, Roberts, Mark, Roberts, Devender, Rose, Alistair, Rousseau, Guy, Ryan, Brendan, Saluja, Taranprit, Shah, Aarti, Shanmuga, Prad, Sharma, Anil, Shawcross, Anna, Sizer, Jeremy, Shankar-Hari, Manu, Smith, Richard, Snelson, Catherine, Spittle, Nick, Staines, Nikki, Stambach, Tom, Stewart, Richard, Subudhi, Pradeep, Szakmany, Tamas, Tatham, Kate, Thomas, Jo, Thompson, Chris, Thompson, Robert, Tridente, Ascanio, Tupper-Carey, Darell, Twagira, Mary, Ustianowski, Andrew, Vallotton, Nick, Vincent-Smith, Lisa, Visuvanathan, Shico, Vuylsteke, Alan, Waddy, Sam, Wake, Rachel, Walden, Andrew, Welters, Ingeborg, Whitehouse, Tony, Whittaker, Paul, Whittington, Ashley, Wijesinghe, Meme, Williams, Martin, Wilson, Lawrence, Wilson, Sarah, Winchester, Stephen, Wiselka, Martin, Wolverson, Adam, Wooton, Daniel G, Workman, Andrew, Yates, Bryan and Young, Peter (2021) Development and validation of the ISARIC 4C Deterioration model for adults hospitalised with COVID-19: a prospective cohort study. The Lancet Respiratory Medicine, 9 (4). pp. 349-359. ISSN 22132600

Item Type: 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.

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More Information

Depositing User: Matthew Ridley

Identifiers

Item ID: 19018
Identification Number: https://doi.org/10.1016/S2213-2600(20)30559-2
ISSN: 22132600
URI: http://sure.sunderland.ac.uk/id/eprint/19018
Official URL: http://dx.doi.org/10.1016/S2213-2600(20)30559-2

Users with ORCIDS

ORCID for P. Matthew Ridley: ORCID iD orcid.org/0000-0001-9642-2483

Catalogue record

Date Deposited: 12 May 2025 10:44
Last Modified: 04 Jun 2025 16:16

Contributors

Author: P. Matthew Ridley ORCID iD
Author: Rishi K Gupta
Author: Ewen M Harrison
Author: Antonia Ho
Author: Annemarie B Docherty
Author: Stephen R Knight
Author: Maarten van Smeden
Author: Ibrahim Abubakar
Author: Marc Lipman
Author: Matteo Quartagno
Author: Riinu Pius
Author: Iain Buchan
Author: Gail Carson
Author: Thomas M Drake
Author: Jake Dunning
Author: Cameron J Fairfield
Author: Carrol Gamble
Author: Christopher A Green
Author: Sophie Halpin
Author: Hayley E Hardwick
Author: Karl A Holden
Author: Peter W Horby
Author: Clare Jackson
Author: Kenneth A Mclean
Author: Laura Merson
Author: Jonathan S Nguyen-Van-Tam
Author: Lisa Norman
Author: Piero L Olliaro
Author: Mark G Pritchard
Author: Clark D Russell
Author: James Scott-Brown
Author: Catherine A Shaw
Author: Aziz Sheikh
Author: Tom Solomon
Author: Cathie Sudlow
Author: Olivia V Swann
Author: Lance Turtle
Author: Peter J M Openshaw
Author: J Kenneth Baillie
Author: Malcolm G Semple
Author: Mahdad Noursadeghi
Author: J Kenneth Baillie
Author: Malcolm G Semple
Author: Peter JM Openshaw
Author: Gail Carson
Author: Beatrice Alex
Author: Benjamin Bach
Author: Wendy S Barclay
Author: Debby Bogaert
Author: Meera Chand
Author: Graham S Cooke
Author: Annemarie B Docherty
Author: Jake Dunning
Author: Ana da Silva Filipe
Author: Tom Fletcher
Author: Christopher A Green
Author: Ewen M Harrison
Author: Julian A Hiscox
Author: Antonia Ying Wai Ho
Author: Peter W Horby
Author: Samreen Ijaz
Author: Saye Khoo
Author: Paul Klenerman
Author: Andrew Law
Author: Wei Shen Lim
Author: Alexander J Mentzer
Author: Laura Merson
Author: Alison M Meynert
Author: Mahdad Noursadeghi
Author: Shona C Moore
Author: Massimo Palmarini
Author: William A Paxton
Author: Georgios Pollakis
Author: Nicholas Price
Author: Andrew Rambaut
Author: David L Robertson
Author: Clark D Russell
Author: Vanessa Sancho-Shimizu
Author: Janet T Scott
Author: Thushan de Silva
Author: Louise Sigfrid
Author: Tom Solomon
Author: Shiranee Sriskandan
Author: David Stuart
Author: Charlotte Summers
Author: Richard S Tedder
Author: Emma C Thomson
Author: AA Roger Thompson
Author: Ryan S Thwaites
Author: Lance CW Turtle
Author: Maria Zambon
Author: Hayley Hardwick
Author: Chloe Donohue
Author: Ruth Lyons
Author: Fiona Griffiths
Author: Wilna Oosthuyzen
Author: Lisa Norman
Author: Riinu Pius
Author: Tom M Drake
Author: Cameron J Fairfield
Author: Stephen Knight
Author: Kenneth A Mclean
Author: Derek Murphy
Author: Catherine A Shaw
Author: Jo Dalton
Author: James Lee
Author: Daniel Plotkin
Author: Michelle Girvan
Author: Scott Mullaney
Author: Claire Petersen
Author: Egle Saviciute
Author: Stephanie Roberts
Author: Janet Harrison
Author: Laura Marsh
Author: Marie Connor
Author: Sophie Halpin
Author: Clare Jackson
Author: Carrol Gamble
Author: Gary Leeming
Author: Andrew Law
Author: Murray Wham
Author: Sara Clohisey
Author: Ross Hendry
Author: James Scott-Brown
Author: William Greenhalf
Author: Victoria Shaw
Author: Sarah McDonald
Author: Seán Keating
Author: Katie A. Ahmed
Author: Jane A Armstrong
Author: Milton Ashworth
Author: Innocent G Asiimwe
Author: Siddharth Bakshi
Author: Samantha L Barlow
Author: Laura Booth
Author: Benjamin Brennan
Author: Katie Bullock
Author: Benjamin WA Catterall
Author: Jordan J Clark
Author: Emily A Clarke
Author: Sarah Cole
Author: Louise Cooper
Author: Helen Cox
Author: Christopher Davis
Author: Oslem Dincarslan
Author: Chris Dunn
Author: Philip Dyer
Author: Angela Elliott
Author: Anthony Evans
Author: Lorna Finch
Author: Lewis WS Fisher
Author: Terry Foster
Author: Isabel Garcia-Dorival
Author: Willliam Greenhalf
Author: Philip Gunning
Author: Catherine Hartley
Author: Antonia Ho
Author: Rebecca L Jensen
Author: Christopher B Jones
Author: Trevor R Jones
Author: Shadia Khandaker
Author: Katharine King
Author: Robyn T. Kiy
Author: Chrysa Koukorava
Author: Annette Lake
Author: Suzannah Lant
Author: Diane Latawiec
Author: L Lavelle-Langham
Author: Daniella Lefteri
Author: Lauren Lett
Author: Lucia A Livoti
Author: Maria Mancini
Author: Sarah McDonald
Author: Laurence McEvoy
Author: John McLauchlan
Author: Soeren Metelmann
Author: Nahida S Miah
Author: Joanna Middleton
Author: Joyce Mitchell
Author: Shona C Moore
Author: Ellen G Murphy
Author: Rebekah Penrice-Randal
Author: Jack Pilgrim
Author: Tessa Prince
Author: Will Reynolds
Author: Debby Sales
Author: Victoria E Shaw
Author: Rebecca K Shears
Author: Benjamin Small
Author: Krishanthi S Subramaniam
Author: Agnieska Szemiel
Author: Aislynn Taggart
Author: Jolanta Tanianis-Hughes
Author: Jordan Thomas
Author: Erwan Trochu
Author: Libby van Tonder
Author: Eve Wilcock
Author: J. Eunice Zhang
Author: Kayode Adeniji
Author: Daniel Agranoff
Author: Ken Agwuh
Author: Dhiraj Ail
Author: Ana Alegria
Author: Brian Angus
Author: Abdul Ashish
Author: Dougal Atkinson
Author: Shahedal Bari
Author: Gavin Barlow
Author: Stella Barnass
Author: Nicholas Barrett
Author: Christopher Bassford
Author: David Baxter
Author: Michael Beadsworth
Author: Jolanta Bernatoniene
Author: John Berridge
Author: Nicola Best
Author: Pieter Bothma
Author: David Brealey
Author: Robin Brittain-Long
Author: Naomi Bulteel
Author: Tom Burden
Author: Andrew Burtenshaw
Author: Vikki Caruth
Author: David Chadwick
Author: Duncan Chambler
Author: Nigel Chee
Author: Jenny Child
Author: Srikanth Chukkambotla
Author: Tom Clark
Author: Paul Collini
Author: Catherine Cosgrove
Author: Jason Cupitt
Author: Maria-Teresa Cutino-Moguel
Author: Paul Dark
Author: Chris Dawson
Author: Samir Dervisevic
Author: Phil Donnison
Author: Sam Douthwaite
Author: Ingrid DuRand
Author: Ahilanadan Dushianthan
Author: Tristan Dyer
Author: Cariad Evans
Author: Chi Eziefula
Author: Chrisopher Fegan
Author: Adam Finn
Author: Duncan Fullerton
Author: Sanjeev Garg
Author: Sanjeev Garg
Author: Atul Garg
Author: Effrossyni Gkrania-Klotsas
Author: Jo Godden
Author: Arthur Goldsmith
Author: Clive Graham
Author: Elaine Hardy
Author: Stuart Hartshorn
Author: Daniel Harvey
Author: Peter Havalda
Author: Daniel B Hawcutt
Author: Maria Hobrok
Author: Luke Hodgson
Author: Anil Hormis
Author: Michael Jacobs
Author: Susan Jain
Author: Paul Jennings
Author: Agilan Kaliappan
Author: Vidya Kasipandian
Author: Stephen Kegg
Author: Michael Kelsey
Author: Jason Kendall
Author: Caroline Kerrison
Author: Ian Kerslake
Author: Oliver Koch
Author: Gouri Koduri
Author: George Koshy
Author: Shondipon Laha
Author: Steven Laird
Author: Susan Larkin
Author: Tamas Leiner
Author: Patrick Lillie
Author: James Limb
Author: Vanessa Linnett
Author: Jeff Little
Author: Michael MacMahon
Author: Emily MacNaughton
Author: Ravish Mankregod
Author: Huw Masson
Author: Elijah Matovu
Author: Katherine McCullough
Author: Ruth McEwen
Author: Manjula Meda
Author: Gary Mills
Author: Jane Minton
Author: Mariyam Mirfenderesky
Author: Kavya Mohandas
Author: Quen Mok
Author: James Moon
Author: Elinoor Moore
Author: Patrick Morgan
Author: Craig Morris
Author: Katherine Mortimore
Author: Samuel Moses
Author: Mbiye Mpenge
Author: Rohinton Mulla
Author: Michael Murphy
Author: Megan Nagel
Author: Thapas Nagarajan
Author: Mark Nelson
Author: Igor Otahal
Author: Mark Pais
Author: Selva Panchatsharam
Author: Hassan Paraiso
Author: Brij Patel
Author: Natalie Pattison
Author: Justin Pepperell
Author: Mark Peters
Author: Mandeep Phull
Author: Stefania Pintus
Author: Jagtur Singh Pooni
Author: Frank Post
Author: David Price
Author: Rachel Prout
Author: Nikolas Rae
Author: Henrik Reschreiter
Author: Tim Reynolds
Author: Neil Richardson
Author: Mark Roberts
Author: Devender Roberts
Author: Alistair Rose
Author: Guy Rousseau
Author: Brendan Ryan
Author: Taranprit Saluja
Author: Aarti Shah
Author: Prad Shanmuga
Author: Anil Sharma
Author: Anna Shawcross
Author: Jeremy Sizer
Author: Manu Shankar-Hari
Author: Richard Smith
Author: Catherine Snelson
Author: Nick Spittle
Author: Nikki Staines
Author: Tom Stambach
Author: Richard Stewart
Author: Pradeep Subudhi
Author: Tamas Szakmany
Author: Kate Tatham
Author: Jo Thomas
Author: Chris Thompson
Author: Robert Thompson
Author: Ascanio Tridente
Author: Darell Tupper-Carey
Author: Mary Twagira
Author: Andrew Ustianowski
Author: Nick Vallotton
Author: Lisa Vincent-Smith
Author: Shico Visuvanathan
Author: Alan Vuylsteke
Author: Sam Waddy
Author: Rachel Wake
Author: Andrew Walden
Author: Ingeborg Welters
Author: Tony Whitehouse
Author: Paul Whittaker
Author: Ashley Whittington
Author: Meme Wijesinghe
Author: Martin Williams
Author: Lawrence Wilson
Author: Sarah Wilson
Author: Stephen Winchester
Author: Martin Wiselka
Author: Adam Wolverson
Author: Daniel G Wooton
Author: Andrew Workman
Author: Bryan Yates
Author: Peter Young

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