Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19
Ryan S. Thwaites(Lung Institute), Ashley Sanchez Sevilla Uruchurtu(Lung Institute), Matthew K. Siggins(Lung Institute), Felicity Liew(Edinburgh Cancer Research), Clark D Russell(University of Liverpool), Shona C Moore(University of Liverpool), Cameron J. Fairfield(Imperial College London), Edwin Carter(Edinburgh Cancer Research), Simon T. Abrams(University of Liverpool), Charlotte‐Eve Short(Imperial College London), Thilipan Thaventhiran(Imperial College London), Emma Bergstrom(MRC Centre for Regenerative Medicine), Zoe Gardener(Edinburgh Cancer Research), Stephanie Ascough(Imperial College London), Christopher Chiu(Roslin Institute), Annemarie B Docherty(University of Liverpool), David Hunt(Lung Institute), Yanick J. Crow(Edinburgh Cancer Research), Tom Solomon(University of Liverpool), Graham P. Taylor(Imperial College London), Lance Turtle(University of Liverpool), Ewen M Harrison(University of Edinburgh), Jake Dunning(Public Health England), Malcolm G. Semple(University of Liverpool), J Kenneth Baillie(Roslin Institute), Peter JM Openshaw(Lung Institute), on behalf of the ISARIC4C investigators(University of Liverpool), J. Kenneth Baillie(Roslin Institute), Malcolm G. Semple(University of Liverpool), Peter JM Openshaw(Lung Institute), Beatrice Alex(Imperial College London), Benjamin Bach, William Barclay, Debby Bogaert, Meera Chand, G Cooke, Annemarie B Docherty(Edinburgh Royal Infirmary), Jake Dunning(Public Health England), Ana da Silva Filipe, Tom Fletcher, Christopher Green, Rishi K Gupta, Ewen M Harrison(University of Edinburgh), Julian A. Hiscox, Antonia Ho, Peter Horby, Samreen Ijaz, Saye Khoo, Paul Klenerman(Centre for Inflammation Research), Andrew Law, Wei Shen Lim, Alexander J. Mentzer, Laura Merson, Alison Meynert(University of Liverpool), Mahdad Noursadeghi, Shona C Moore(University of Liverpool), Massimo Palmarini(Imperial College London), Carlo Palmieri, William A. Paxton, Georgios Pollakis, Nicholas Price(Lung Institute), Andrew Rambaut(University of Liverpool), David Robertson, Clark D Russell(Centre for Inflammation Research), Vanessa Sancho‐Shimizu, J T Scott, Thushan I. de Silva, Louise Sigfrid, Tom Solomon(University of Liverpool), Shiranee Sriskandan, David I. Stuart, Charlotte Summers(University of Edinburgh), Richard S. Tedder, Emma C. Thomson(Roslin Institute), Roger Thompson AA, Ryan S. Thwaites(Lung Institute), Lance Turtle(University of Liverpool), Maria Zambon, Hayley Hardwick, Chloe Donohue(Imperial College London), Ruth Lyons(University of Edinburgh), Fiona Griffiths, Wilna Oosthuyzen(Edinburgh Royal Infirmary), Lisa Norman, Riinu Pius, Tom Drake, Cameron J. Fairfield(University of Edinburgh), Stephen R Knight, Kenneth A McLean, Derek Murphy, Catherine A. Shaw, Jo Dalton, Michelle Girvan, Egle Saviciute, Stephanie Roberts, Janet Harrison, Laura Marsh, Marie Connor, Sophie Halpin, Clare Jackson, Carrol Gamble, Gary Leeming, Andrew Law, Murray Wham, Sara Clohisey, Ross Hendry, James Scott-Brown, William Greenhalf(Centre for Inflammation Research), Victoria Shaw, Sarah McDonald, Seán Keating, Katie A. Ahmed, J. A. Armstrong(Imperial College London), Milton Ashworth, Innocent G. Asiimwe, Siddharth Bakshi(Public Health England), Samantha L Barlow, Laura Booth, Benjamin Brennan, Katie Bullock, Nicola Carlucci, Emily Cass, Benjamin WA Catterall, Jordan J Clark, Emily A Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Alejandra Doce Carracedo, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis WS Fisher, Lisa Flaherty, Terry Foster(Roslin Institute), Isabel García-Dorival, Willliam Greenhalf, Philip Gunning, Catherine Hartley, Anthony Holmes, Rebecca L. Jensen, Christopher B. Jones, Trevor R. Jones, Shadia Khandaker, Katharine King, Robyn T. Kiy, Chrysa Koukorava, Annette Lake, Suzannah Lant, Diane Latawiec, Lara Lavelle-Langham, Daniella Lefteri, Lauren Lett, Lucia A Livoti, Alan Maclean, Hannah Massey, Nicole Maziere, Maria Vittoria Mancini, Sarah McCafferty, Sarah McDonald(Lung Institute), Laurence McEvoy, John McLauchlan, Soeren Metelmann, Nahida S Miah, Joanna Middleton, Joyce Mitchell, Shona C Moore(University of Liverpool), Kirstie Morrice, E. Gordon Murphy, Lee Murphy(Imperial College London), Rebekah Penrice-Randal, Jack Pilgrim, Tessa Prince, Will Reynolds, Paul Ridley(Roslin Institute), Debby Sales(Roslin Institute), Victoria Shaw, Rebecca K. Shears, Benjamin Small, Krishanthi Subramaniam, Agnieska Szemiel, Aislynn Taggart, Jolanta Tanianis-Hughes, Jordan Thomas, Erwan Trochu, Libby van Tonder(Imperial College London), Eve Wilcock, Nicola Wrobel(MRC Centre for Regenerative Medicine), Jihui Zhang, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Erin L. Aldera(MRC Centre for Regenerative Medicine), Ana Alegria, Brian Angus, Abdul Ashish(University of Liverpool), Dougal Atkinson, Shahedal Bari, Gavin Barlow(MRC Centre for Regenerative Medicine), Stella Barnass, Nicholas Barrett, Christopher Bassford, Sneha Basude, David Baxter(Centre for Inflammation Research), Michael Beadsworth, Jolanta Bernatoniene, John C. Berridge, Nicola Best, Pieter Bothma, David Brealey, Robin Brittain-Long(Imperial College London), Naomi Bulteel, Tom Burden, Andrew Burtenshaw, Vikki Caruth, David Chadwick, Duncan Chambler, Nigel Chee, Jenny Child(Imperial College London), Srikanth Chukkambotla, Tom Clark, Sarah Cole, Paul Collini, Catherine Cosgrove, Jason Cupitt, Maria-Teresa Cutino-Moguel, Paul Dark, Chris Dawson, Samir Dervisevic(Imperial College London), Phil Donnison, Sam Douthwaite, Ingrid DuRand, Ahilanadan Dushianthan(Lung Institute), Tristan Dyer, Cariad Evans, Chi Eziefula, Chrisopher Fegan, Adam Finn, Duncan Fullerton, Sanjeev Garg, Sanjeev Garg, Atul Garg, Effrossyni Gkrania‐Klotsas, Jo Godden, Arthur Goldsmith, Clive Graham, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Daniel B. Hawcutt, Maria Hobrok, Luke Hodgson, Anita Holme, Anil Hormis, Michael E. Jacobs, Susan Jain, Paul B. Jennings, Agilan Kaliappan, Vidya Kasipandian, Stephen Kegg, Michael Kelsey, Jason Kendall, Caroline Kerrison, Ian Kerslake, Oliver Koch, Gouri Koduri, George Koshy, Shondipon Laha, Steven Laird, Susan Larkin, Tamás Leiner, Patrick Lillie, James Limb, Vanessa Linnett(University of Liverpool), Jeff Little, Mark D Lyttle, Michael MacMahon, Emily MacNaughton, Ravish Mankregod, Huw Masson, Elijah Matovu, Katherine McCullough, Ruth McEwen, Manjula Meda, Gary Mills(Lung Institute), Jane Minton, Mariyam Mirfenderesky, Kavya Mohandas, Quen Mok, James Moon, Elinoor Moore, Patrick Morgan, Craig F. Morris, Katherine Mortimore, Samuel Moses, Mbiye Mpenge, Rohinton Mulla, Michael Murphy, Megan Nagel, Thapas Nagarajan, Mark E. Nelson(MRC Centre for Regenerative Medicine), Matthew K. O’Shea, Igor Otahal, Marlies Ostermann, Mark Pais, Padmasayee Papineni, Selva Panchatsharam, Danai Papakonstantinou, Hassan Paraiso, Brij Patel, Natalie Pattinson(Lung Institute), Justin Pepperell, Mark Peters, Mandeep Phull, Stefania Pintus, Jagtur Singh Pooni, Frank A. Post, David Price, Rachel Prout, Nikolas Rae, Henrik Reschreiter(Edinburgh Cancer Research), Tim Reynolds, Neil Richardson(University of Liverpool), Mark Roberts, Devender Roberts, Alistair Rose, Guy Rousseau, Brendan Ryan, Taranprit Saluja(Imperial College London), Aarti Shah, Prad Shanmuga, Anil Kumar Sharma, Anna Shawcross, Jeremy Sizer, Manu Shankar‐Hari(Edinburgh Cancer Research), Richard Smith, Catherine Snelson, Nick Spittle, Nikki Staines, Tom Stambach, Richard Stewart, Pradeep Subudhi, Tamás Szakmány, Kate Tatham, J. Regan Thomas(Lung Institute), Chris Thompson, Robert Thompson, Ascanio Tridente, Darell Tupper-Carey, Mary Twagira, Andrew Ustianowski, Nick Vallotton, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Sam Waddy(Lung Institute), Rachel Wake, Andrew Walden, Ingeborg Welters, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Meme Wijesinghe, Martin A. K. Williams, Lawrence Wilson, Sarah Wilson, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G Wooton, Andrew Workman, Bryan Yates, P. A. Young
Cited by 257Open Access
Abstract
While it is now widely accepted that host inflammatory responses contribute to lung injury, the pathways that drive severity and distinguish coronavirus disease 2019 (COVID-19) from other viral lung diseases remain poorly characterized. We analyzed plasma samples from 471 hospitalized patients recruited through the prospective multicenter ISARIC4C study and 39 outpatients with mild disease, enabling extensive characterization of responses across a full spectrum of COVID-19 severity. Progressive elevation of levels of numerous inflammatory cytokines and chemokines (including IL-6, CXCL10, and GM-CSF) were associated with severity and accompanied by elevated markers of endothelial injury and thrombosis. Principal component and network analyses demonstrated central roles for IL-6 and GM-CSF in COVID-19 pathogenesis. Comparing these profiles to archived samples from patients with fatal influenza, IL-6 was equally elevated in both conditions whereas GM-CSF was prominent only in COVID-19. These findings further identify the key inflammatory, thrombotic, and vascular factors that characterize and distinguish severe and fatal COVID-19.
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