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Non-steroidal anti-inflammatory drug use and outcomes of COVID-19 in the ISARIC Clinical Characterisation Protocol UK cohort: a matched, prospective cohort study

Drake, Thomas M; Fairfield, Cameron J; Pius, Riinu; Knight, Stephen R; Norman, Lisa; Girvan, Michelle; Hardwick, Hayley E; Docherty, Annemarie B; Thwaites, Ryan S; Openshaw, Peter J M; Baillie, J Kenneth; Harrison, Ewen M; Semple, Malcolm G; Investigators, ISARIC4C

Non-steroidal anti-inflammatory drug use and outcomes of COVID-19 in the ISARIC Clinical Characterisation Protocol UK cohort: a matched, prospective cohort study Thumbnail


Authors

Thomas M Drake

Cameron J Fairfield

Riinu Pius

Stephen R Knight

Lisa Norman

Michelle Girvan

Hayley E Hardwick

Annemarie B Docherty

Ryan S Thwaites

Peter J M 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

Ana da Silva Filipe
Research Group

Thushan de Silva
Research Group

Annemarie B Docherty
Research Group

Jake Dunning
Research Group

Tom Fletcher
Research Group

Christopher A Green
Research Group

Ewen M Harrison
Research Group

Julian A Hiscox
Research Group

Antonia YW Ho
Research Group

Peter W Horby
Research Group

Samreen Ijaz
Research Group

Say Khoo
Research Group

Paul Klenerman
Research Group

Andrew Law
Research Group

Wei Shen Lim
Research Group

Alexander J Mentzer
Research Group

Laura Merson
Research Group

Alison M Meynert
Research Group

Shona C Moore
Research Group

Mahdad Noursadeghi
Research Group

Massimo Palmarini
Research Group

William A Paxton
Research Group

Georgios Pollakis
Research Group

Nicholas Price
Research Group

Andrew Rambaut
Research Group

David L Robertson
Research Group

Clark D Russell
Research Group

Vanessa Sancho-Shimizu
Research Group

Janet T Scott
Research Group

Louise Sigfrid
Research Group

Tom Solomon
Research Group

Shiranee Sriskandan
Research Group

David Stuart
Research Group

Charlotte Summers
Research Group

Richard S Tedder
Research Group

AA Roger Thompson
Research Group

Emma C Thomson
Research Group

Ryan S Thwaites
Research Group

Lance CW Turtle
Research Group

Maria Zambon
Research Group

Chloe Donohue
Research Group

Fiona Griffiths
Research Group

Hayley Hardwick
Research Group

Ruth Lyons
Research Group

Wilna Oosthuyzen
Research Group

Thomas M Drake
Research Group

Cameron J Fairfield
Research Group

Stephen R Knight
Research Group

Kenneth A Mclean
Research Group

Derek Murphy
Research Group

Lisa Norman
Research Group

Riinu Pius
Research Group

Catherine A Shaw
Research Group

Marie Connor
Research Group

Jo Dalton
Research Group

Carrol Gamble
Research Group

Michelle Girvan
Research Group

Sophie Halpin
Research Group

Janet Harrison
Research Group

Clare Jackson
Research Group

Laura Marsh
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Stephanie Roberts
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Egle Saviciute
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Sara Clohisey
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Ross Hendry
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Andrew Law
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Gary Leeming
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James Scott-Brown
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Murray Wham
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William Greenhalf
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Sara McDonald
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Victoria Shaw
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Seán Keating
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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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Nicola Carlucci
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Emily Cass
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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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Alejandra Doce Carracedo
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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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Lisa Flaherty
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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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Anthony Holmes
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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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Annette Lake
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Suzannah Lant
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Diane Latawiec
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Lara Lavelle-Langham
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Daniella Lefteri
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Lauren Lett
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Lucia A Livoti
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Maria Mancini
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Hannah Massey
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Nicole Maziere
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Sarah McDonald
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Laurence McEvoy
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John McLauchlan
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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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Jack Pilgrim
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Tessa Prince
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Will Reynolds
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P. Matthew Ridley
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Debby Sales
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Victoria E Shaw
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Rebecca K Shears
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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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Libby van Tonder
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Eve Wilcock
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J. Eunice Zhang
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Alan MacLean
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Sarah McCafferty
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Kirstie Morrice
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Lee Murphy
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Nicola Wrobel
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Kayode Adeniji
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Daniel Agranoff
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Ken Agwuh
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Dhiraj Ail
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Erin L. Aldera
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Ana Alegria
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Brian Angus
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Abdul Ashish
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Dougal Atkinson
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Shahedal Bari
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Gavin Barlow
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Stella Barnass
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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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Jolanta Bernatoniene
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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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Tom Burden
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Andrew Burtenshaw
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Vikki Caruth
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David Chadwick
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David Chadwick
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Duncan Chambler
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Nigel Chee
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Jenny Child
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Srikanth Chukkambotla
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Tom Clark
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Paul Collini
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Catherine Cosgrove
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Jason Cupitt
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Maria-Teresa Cutino-Moguel
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Paul Dark
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Chris Dawson
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Samir Dervisevic
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Phil Donnison
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Sam Douthwaite
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Ingrid DuRand
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Ahilanadan Dushianthan
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Tristan Dyer
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Cariad Evans
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Chi Eziefula
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Chrisopher Fegan
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Adam Finn
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Duncan Fullerton
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Sanjeev Garg
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Sanjeev Garg
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Atul Garg
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Effrossyni Gkrania-Klotsas
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Jo Godden
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Arthur Goldsmith
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Clive Graham
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Elaine Hardy
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Stuart Hartshorn
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Daniel Harvey
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Peter Havalda
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Daniel B Hawcutt
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Maria Hobrok
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Luke Hodgson
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Anil Hormis
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Michael Jacobs
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Susan Jain
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Paul Jennings
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Agilan Kaliappan
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Vidya Kasipandian
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Stephen Kegg
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Michael Kelsey
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Jason Kendall
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Caroline Kerrison
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Ian Kerslake
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Oliver Koch
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Gouri Koduri
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George Koshy
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Shondipon Laha
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Steven Laird
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Susan Larkin
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Tamas Leiner
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Patrick Lillie
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James Limb
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Vanessa Linnett
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Jeff Little
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Mark Lyttle
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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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Elinoor Moore
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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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Rohinton Mulla
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Michael Murphy
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Thapas Nagarajan
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Megan Nagel
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Mark Nelson
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Matthew K. O'Shea
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Marlies Ostermann
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Igor Otahal
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Mark Pais
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Selva Panchatsharam
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Padmasayee Papineni
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Hassan Paraiso
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Brij Patel
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Natalie Pattison
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Justin Pepperell
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Mark Peters
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Mandeep Phull
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Stefania Pintus
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Frank Post
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David Price
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Rachel Prout
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Nikolas Rae
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Henrik Reschreiter
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Tim Reynolds
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Neil Richardson
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Mark Roberts
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Devender Roberts
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Alistair Rose
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Guy Rousseau
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Brendan Ryan
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Taranprit Saluja
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Sarah Sarah
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Aarti Shah
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Manu Shankar-Hari
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Prad Shanmuga
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Anil Sharma
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Anna Shawcross
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Jagtur Singh Pooni
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Jeremy Sizer
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Richard Smith
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Catherine Snelson
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Nick Spittle
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Nikki Staines
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Tom Stambach
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Richard Stewart
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Pradeep Subudhi
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Tamas Szakmany
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Kate Tatham
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Jo Thomas
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Chris Thompson
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Robert Thompson
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Ascanio Tridente
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Darell Tupper-Carey
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Mary Twagira
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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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Meme Wijesinghe
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Martin Williams
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Lawrence Wilson
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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 Early in the pandemic it was suggested that pre-existing use of non-steroidal anti-inflammatory drugs (NSAIDs) could lead to increased disease severity in patients with COVID-19. NSAIDs are an important analgesic, particularly in those with rheumatological disease, and are widely available to the general public without prescription. Evidence from community studies, administrative data, and small studies of hospitalised patients suggest NSAIDs are not associated with poorer COVID-19 outcomes. We aimed to characterise the safety of NSAIDs and identify whether pre-existing NSAID use was associated with increased severity of COVID-19 disease. Methods This prospective, multicentre cohort study included patients of any age admitted to hospital with a confirmed or highly suspected SARS-CoV-2 infection leading to COVID-19 between Jan 17 and Aug 10, 2020. The primary outcome was in-hospital mortality, and secondary outcomes were disease severity at presentation, admission to critical care, receipt of invasive ventilation, receipt of non-invasive ventilation, use of supplementary oxygen, and acute kidney injury. NSAID use was required to be within the 2 weeks before hospital admission. We used logistic regression to estimate the effects of NSAIDs and adjust for confounding variables. We used propensity score matching to further estimate effects of NSAIDS while accounting for covariate differences in populations. Results Between Jan 17 and Aug 10, 2020, we enrolled 78?674 patients across 255 health-care facilities in England, Scotland, and Wales. 72?179 patients had death outcomes available for matching; 40?406 (56·2%) of 71?915 were men, 31?509 (43·8%) were women. In this cohort, 4211 (5·8%) patients were recorded as taking systemic NSAIDs before admission to hospital. Following propensity score matching, balanced groups of NSAIDs users and NSAIDs non-users were obtained (4205 patients in each group). At hospital admission, we observed no significant differences in severity between exposure groups. After adjusting for explanatory variables, NSAID use was not associated with worse in-hospital mortality (matched OR 0·95, 95% CI 0·84–1·07; p=0·35), critical care admission (1·01, 0·87–1·17; p=0·89), requirement for invasive ventilation (0·96, 0·80–1·17; p=0·69), requirement for non-invasive ventilation (1·12, 0·96–1·32; p=0·14), requirement for oxygen (1·00, 0·89–1·12; p=0·97), or occurrence of acute kidney injury (1·08, 0·92–1·26; p=0·33).

Citation

Drake, T. M., Fairfield, C. J., Pius, R., Knight, S. R., Norman, L., Girvan, M., …Investigators, I. (2021). Non-steroidal anti-inflammatory drug use and outcomes of COVID-19 in the ISARIC Clinical Characterisation Protocol UK cohort: a matched, prospective cohort study. The Lancet Rheumatology, 3(7), e498 - e506. https://doi.org/10.1016/s2665-9913%2821%2900104-1

Journal Article Type Article
Acceptance Date May 7, 2021
Publication Date Jul 1, 2021
Journal The Lancet Rheumatology
Print ISSN 2665-9913
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 3
Issue 7
Pages e498 - e506
DOI https://doi.org/10.1016/s2665-9913%2821%2900104-1
Publisher URL https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(21)00104-1/fulltext