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Changes in in-hospital mortality in the first wave of COVID-19: a multicentre prospective observational cohort study using the WHO Clinical Characterisation Protocol UK

Docherty, Annemarie B; Mulholland, Rachel H; Lone, Nazir I; Cheyne, Christopher P; De Angelis, Daniela; Diaz-Ordaz, Karla; Donegan, Cara; Drake, Thomas M; Dunning, Jake; Funk, Sebastian; García-Fiñana, Marta; Girvan, Michelle; Hardwick, Hayley E; Harrison, Janet; Ho, Antonia; Hughes, David M; Keogh, Ruth H; Kirwan, Peter D; Leeming, Gary; Nguyen Van-Tam, Jonathan S; Pius, Riinu; Russell, Clark D; Spencer, Rebecca G; DM Tom, Brian; Turtle, Lance; JM Openshaw, Peter; Kenneth Baillie, J; Harrison, Ewen M; Semple, Malcolm G; Investigators, ISARIC4C

Changes in in-hospital mortality in the first wave of COVID-19: a multicentre prospective observational cohort study using the WHO Clinical Characterisation Protocol UK Thumbnail


Authors

Annemarie B Docherty

Rachel H Mulholland

Nazir I Lone

Christopher P Cheyne

Daniela De Angelis

Karla Diaz-Ordaz

Cara Donegan

Thomas M Drake

Jake Dunning

Sebastian Funk

Marta García-Fiñana

Michelle Girvan

Hayley E Hardwick

Janet Harrison

Antonia Ho

David M Hughes

Ruth H Keogh

Peter D Kirwan

Gary Leeming

Jonathan S Nguyen Van-Tam

Riinu Pius

Clark D Russell

Rebecca G Spencer

Brian DM Tom

Lance Turtle

Peter JM Openshaw

J Kenneth Baillie

Ewen M Harrison

Malcolm G Semple

ISARIC4C Investigators



Contributors

J Kenneth Baillie
Research Group

Malcolm G Semple
Research Group

Peter JM Openshaw
Research Group

Gail Carson
Research Group

Beatrice Alex
Research Group

Benjamin Bach
Research Group

Wendy S Barclay
Research Group

Debby Bogaert
Research Group

Meera Chand
Research Group

Graham S Cooke
Research Group

Annemarie B Docherty
Research Group

Jake Dunning
Research Group

Ana da Silva Filipe
Research Group

Tom Fletcher
Research Group

Christopher A Green
Research Group

Ewen M Harrison
Research Group

Julian A Hiscox
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Antonia YW Ho
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Peter W Horby
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Samreen Ijaz
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Say Khoo
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Paul Klenerman
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Andrew Law
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Wei Shen Lim
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Alexander J Mentzer
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Laura Merson
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Alison M Meynert
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Mahdad Noursadeghi
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Shona C Moore
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Massimo Palmarini
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William A Paxton
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Georgios Pollakis
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Nicholas Price
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Andrew Rambaut
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David L Robertson
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Clark D Russell
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Vanessa Sancho-Shimizu
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Janet T Scott
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Thushan de Silva
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Louise Sigfrid
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Tom Solomon
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Shiranee Sriskandan
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David Stuart
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Charlotte Summers
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Richard S Tedder
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Emma C Thomson
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AA Roger Thompson
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Ryan S Thwaites
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Lance CW Turtle
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Rishi K Gupta
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Carlo Palmieri
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Maria Zambon
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Hayley Hardwick
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Chloe Donohue
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Ruth Lyons
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Fiona Griffiths
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Wilna Oosthuyzen
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Lisa Norman
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Riinu Pius
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Thomas M Drake
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Cameron J Fairfield
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Stephen R Knight
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Kenneth A Mclean
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Derek Murphy
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Catherine A Shaw
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Jo Dalton
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Michelle Girvan
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Egle Saviciute
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Stephanie Roberts
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Janet Harrison
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Laura Marsh
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Marie Connor
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Sophie Halpin
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Clare Jackson
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Carrol Gamble
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Gary Leeming
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Andrew Law
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Murray Wham
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Sara Clohisey
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Ross Hendry
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James Scott-Brown
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William Greenhalf
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Victoria Shaw
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Sarah E McDonald
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Katie A Ahmed
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Jane A Armstrong
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Milton Ashworth
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Innocent G Asiimwe
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Siddharth Bakshi
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Samantha L Barlow
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Laura Booth
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Benjamin Brennan
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Katie Bullock
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Benjamin WA Catterall
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Jordan J Clark
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Emily A Clarke
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Sarah Cole
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Louise Cooper
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Helen Cox
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Christopher Davis
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Oslem Dincarslan
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Chris Dunn
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Philip Dyer
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Angela Elliott
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Anthony Evans
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Lorna Finch
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Lewis WS Fisher
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Terry Foster
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Isabel Garcia-Dorival
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William Greenhalf
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Philip Gunning
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Catherine Hartley
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Rebecca L Jensen
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Christopher B Jones
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Trevor R Jones
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Shadia Khandaker
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Katharine King
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Robyn T Kiy
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Chrysa Koukorava
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Lucia A Livoti
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Maria Mancini
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Sarah McDonald
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Laurence McEvoy
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Soeren Metelmann
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Nahida S Miah
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Joanna Middleton
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Joyce Mitchell
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Shona C Moore
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Ellen G Murphy
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Rebekah Penrice-Randal
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Tessa Prince
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Will Reynolds
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Victoria E Shaw
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Benjamin Small
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Krishanthi S Subramaniam
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Agnieska Szemiel
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Aislynn Taggart
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Jolanta Tanianis-Hughes
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Jordan Thomas
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Erwan Trochu
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Eve Wilcock
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J. Eunice Zhang
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Lisa Flaherty
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Emily Cass
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Anthony Holmes
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Hannah Massey
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Lee Murphy
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Nicola Wrobel
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Sarah McCafferty
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Alan MacLean
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Kayode Adeniji
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Daniel Agranoff
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Dhiraj Ail
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Brian Angus
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Abdul Ashish
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Dougal Atkinson
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Nicholas Barrett
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Christopher Bassford
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Sneha Basude
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David Baxter
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Michael Beadsworth
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John Berridge
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Nicola Best
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Pieter Bothma
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Robin Brittain-Long
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Naomi Bulteel
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Chi Eziefula
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Chrisopher Fegan
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Adam Finn
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Jo Godden
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Arthur Goldsmith
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Stuart Hartshorn
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Daniel Harvey
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Daniel B Hawcutt
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Luke Hodgson
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Anil Hormis
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Michael Jacobs
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Paul Jennings
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Stephen Kegg
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Michael Kelsey
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Susan Larkin
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Tamas Leiner
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James Limb
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Jeff Little
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Michael MacMahon
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Emily MacNaughton
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Ravish Mankregod
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Huw Masson
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Elijah Matovu
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Katherine McCullough
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Ruth McEwen
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Manjula Meda
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Gary Mills
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Jane Minton
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Mariyam Mirfenderesky
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Kavya Mohandas
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Quen Mok
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James Moon
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Patrick Morgan
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Craig Morris
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Katherine Mortimore
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Samuel Moses
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Mbiye Mpenge
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Michael Murphy
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Megan Nagel
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Thapas Nagarajan
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Mark Nelson
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Matthew K O'Shea
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Igor Otahal
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Marlies Ostermann
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Mark Pais
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Selva Panchatsharam
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Justin Pepperell
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Mark Peters
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Devender Roberts
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Jeremy Sizer
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Manu Shankar-Hari
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Andrew Ustianowski
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Nick Vallotton
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Lisa Vincent-Smith
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Shico Visuvanathan
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Alan Vuylsteke
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Sam Waddy
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Rachel Wake
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Andrew Walden
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Ingeborg Welters
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Tony Whitehouse
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Paul Whittaker
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Ashley Whittington
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Padmasayee Papineni
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Meme Wijesinghe
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Martin Williams
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Lawrence Wilson
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Sarah Sarah
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Stephen Winchester
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Martin Wiselka
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Adam Wolverson
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Daniel G Wooton
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Andrew Workman
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Bryan Yates
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Peter Young
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Abstract

Background Mortality rates in hospitalised patients with COVID-19 in the UK appeared to decline during the first wave of the pandemic. We aimed to quantify potential drivers of this change and identify groups of patients who remain at high risk of dying in hospital. Methods In this multicentre prospective observational cohort study, the International Severe Acute Respiratory and Emerging Infections Consortium WHO Clinical Characterisation Protocol UK recruited a prospective cohort of patients with COVID-19 admitted to 247 acute hospitals in England, Scotland, and Wales during the first wave of the pandemic (between March 9 and Aug 2, 2020). We included all patients aged 18 years and older with clinical signs and symptoms of COVID-19 or confirmed COVID-19 (by RT-PCR test) from assumed community-acquired infection. We did a three-way decomposition mediation analysis using natural effects models to explore associations between week of admission and in-hospital mortality, adjusting for confounders (demographics, comorbidities, and severity of illness) and quantifying potential mediators (level of respiratory support and steroid treatment). The primary outcome was weekly in-hospital mortality at 28 days, defined as the proportion of patients who had died within 28 days of admission of all patients admitted in the observed week, and it was assessed in all patients with an outcome. This study is registered with the ISRCTN Registry, ISRCTN66726260. Findings Between March 9, and Aug 2, 2020, we recruited 80?713 patients, of whom 63?972 were eligible and included in the study. Unadjusted weekly in-hospital mortality declined from 32·3% (95% CI 31·8–32·7) in March 9 to April 26, 2020, to 16·4% (15·0–17·8) in June 15 to Aug 2, 2020. Reductions in mortality were observed in all age groups, in all ethnic groups, for both sexes, and in patients with and without comorbidities. After adjustment, there was a 32% reduction in the risk of mortality per 7-week period (odds ratio [OR] 0·68 [95% CI 0·65–0·71]). The higher proportions of patients with severe disease and comorbidities earlier in the first wave (March and April) than in June and July accounted for 10·2% of this reduction. The use of respiratory support changed during the first wave, with gradually increased use of non-invasive ventilation over the first wave. Changes in respiratory support and use of steroids accounted for 22·2%, OR 0·95 (0·94–0·95) of the reduction in in-hospital mortality. Interpretation The reduction in in-hospital mortality in patients with COVID-19 during the first wave in the UK was partly accounted for by changes in the case-mix and illness severity. A significant reduction in in-hospital mortality was associated with differences in respiratory support and critical care use, which could partly reflect accrual of clinical knowledge. The remaining improvement in in-hospital mortality is not explained by these factors, and could be associated with changes in community behaviour, inoculum dose, and hospital capacity strain.

Citation

Docherty, A. B., Mulholland, R. H., Lone, N. I., Cheyne, C. P., De Angelis, D., Diaz-Ordaz, K., …Investigators, I. (2021). Changes in in-hospital mortality in the first wave of COVID-19: a multicentre prospective observational cohort study using the WHO Clinical Characterisation Protocol UK. Lancet Respiratory Medicine, 9(7), 773 - 785. https://doi.org/10.1016/s2213-2600%2821%2900175-2

Journal Article Type Article
Acceptance Date May 14, 2021
Publication Date Jul 1, 2021
Journal The Lancet Respiratory Medicine
Print ISSN 2213-2600
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 9
Issue 7
Pages 773 - 785
DOI https://doi.org/10.1016/s2213-2600%2821%2900175-2
Publisher URL https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00175-2/fulltext