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

Type Journal Article 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 P. Matthew Ridley 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 URL https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30559-2/abstract Series Articles Volume 9 Issue 4 Pages 349-359 Publication The Lancet Respiratory Medicine ISSN 2213-2600, 2213-2619 Date 11/01/2021 Extra Publisher: Elsevier PMID: 33444539 Journal Abbr The Lancet Respiratory Medicine DOI 10.1016/S2213-2600(20)30559-2 Library Catalog www.thelancet.com Language English 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. Short Title Development and validation of the ISARIC 4C Deterioration model for adults hospitalised with COVID-19