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Paxton,Georgios Pollakis,Nicholas Price,Andrew Rambaut,David L. Robertson,Clark D. Russell,Vanessa Sancho-Shimizu,Caroline J. Sands,Janet T. Scott,Louise Sigfrid,Tom Solomon,Shiranee Sriskandan,David Stuart,Charlotte Summers,Olivia Swann,Zoltan Takats,Panteleimon Takis,Richard S. Tedder,A. A. Roger Thompson,Emma C. Thomson,Ryan S. Thwaites,Lance C. W. Turtle,Maria Zambon,Thomas M. Drake,Cameron J. Fairfield,Stephen R. Knight,Kenneth A. Mclean,Derek Murphy,Lisa Norman,Riinu Pius,Catherine A. Shaw,Marie Connor,Jo Dalton,Carrol Gamble,Michelle Girvan,Sophie Halpin,Janet Harrison,Clare Jackson,James Lee,Laura Marsh,Daniel Plotkin,Stephanie Roberts,Egle Saviciute,Sara Clohisey,Ross Hendry,Susan Knight,Eva Lahnsteiner,Andrew Law,Gary Leeming,Lucy Norris,James Scott-Brown,Sarah Tait,Murray Wham,Gail Carson,Richard Clark,Audrey Coutts,Lorna Donnelly,Angie Fawkes,Tammy Gilchrist,Katarzyna Hafezi,Louise Macgillivray,Alan Maclean,Sarah Mccafferty,Kirstie Morrice,Lee Murphy,Nicola Wrobel,Kayode Adeniji,Daniel Agranoff,Ken Agwuh,Dhiraj Ail,Erin L. Aldera,Ana Alegria,Sam Allen,Brian Angus,Abdul Ashish,Dougal Atkinson,Shahedal Bari,Gavin Barlow,Stella Barnass,Nicholas Barrett,Christopher Bassford,Sneha Basude,David Baxter,Michael Beadsworth,Jolanta Bernatoniene,John Berridge,Colin Berry,Nicola Best,Pieter Bothma,Robin Brittain-Long,Naomi Bulteel,Tom Burden,Andrew Burtenshaw,Vikki Caruth,David Chadwick,David Chadwick,Duncan Chambler,Nigel Chee,Jenny Child,Srikanth Chukkambotla,Tom Clark,Paul Collini,Catherine Cosgrove,Jason Cupitt,Maria-Teresa Cutino-Moguel,Paul Dark,Chris Dawson,Samir Dervisevic,Phil Donnison,Sam Douthwaite,Andrew Drummond,Ingrid Durand,Ahilanadan Dushianthan,Tristan Dyer,Cariad Evans,Chi Eziefula,Chrisopher Fegan,Adam Finn,Duncan Fullerton,Sanjeev Garg,Atul Garg,Effrossyni Gkrania-Klotsas,Jo Godden,Arthur Goldsmith,Clive Graham,Tassos Grammatikopoulos,Elaine Hardy,Stuart Hartshorn,Daniel Harvey,Peter Havalda,Daniel B. Hawcutt,Maria Hobrok,Luke Hodgson,Anil Hormis,Joanne Howard,Michael Jacobs,Susan Jain,Paul 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,Tamas Leiner,Patrick Lillie,James Limb,Vanessa Linnett,Jeff Little,Mark Lyttle,Michael Macmahon,Emily Macnaughton,Ravish Mankregod,Huw Masson,Elijah Matovu,Katherine Mccullough,Ruth Mcewen,Manjula Meda,Gary Mills,Jane Minton,Kavya Mohandas,Quen Mok,James Moon,Elinoor Moore,Patrick Morgan,Craig Morris,Katherine Mortimore,Samuel Moses,Mbiye Mpenge,Rohinton Mulla,Michael Murphy,Thapas Nagarajan,Megan Nagel,Mark Nelson,Lillian Norris,Matthew K. O'Shea,Marlies Ostermann,Igor Otahal,Mark Pais,Carlo Palmieri,Selva Panchatsharam,Danai Papakonstantinou,Padmasayee Papineni,Hassan Paraiso,Brij Patel,Natalie Pattison,Justin Pepperell,Mark Peters,Mandeep Phull,Stefania Pintus,Tim Planche,Frank Post,David Price,Rachel Prout,Nikolas Rae,Henrik Reschreiter,Tim Reynolds,Neil Richardson,Mark Roberts,Devender Roberts,Alistair Rose,Guy Rousseau,Bobby Ruge,Brendan Ryan,Taranprit Saluja,Sarah Cole,Matthias L. Schmid,Aarti Shah,Manu Shankar-Hari,Prad Shanmuga,Anil Sharma,Anna Shawcross,Jagtur Singh Pooni,Jeremy Sizer,Richard Smith,Catherine Snelson,Nick Spittle,Nikki Staines,Tom Stambach,Richard Stewart,Pradeep Subudhi,Tamas Szakmany,Kate Tatham,Jo Thomas,Chris Thompson,Robert Thompson,Ascanio Tridente,Darell Tupper-Carey,Mary Twagira,Nick Vallotton,Rama Vancheeswaran,Rachel Vincent,Lisa Vincent-Smith,Shico Visuvanathan,Alan Vuylsteke,Sam Waddy,Rachel Wake,Andrew Walden,Ingeborg Welters,Tony Whitehouse,Paul Whittaker,Ashley Whittington,Meme Wijesinghe,Martin Williams,Lawrence Wilson,Stephen Winchester,Martin Wiselka,Adam Wolverson,Daniel G. Wootton,Andrew Workman,Bryan Yates,Peter Young,Sarah E. Mcdonald,Victoria Shaw,Katie A. Ahmed,Jane A. Armstrong,Milton Ashworth,Innocent G. Asiimwe,Siddharth Bakshi,Samantha L. Barlow,Laura Booth,Benjamin Brennan,Katie Bullock,Nicola Carlucci,Emily Cass,Benjamin W. A. 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 W. S. Fisher,Lisa Flaherty,Terry Foster,Isabel Garcia-Dorival,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,Maria Mancini,Hannah Massey,Nicole Maziere,Sarah Mcdonald,Laurence Mcevoy,John Mclauchlan,Soeren Metelmann,Nahida S. Miah,Joanna Middleton,Joyce Mitchell,Shona C. Moore,Ellen G. Murphy,Rebekah Penrice-Randal,Jack Pilgrim,Tessa Prince,Will Reynolds,P. Matthew Ridley,Debby Sales,Victoria E. Shaw,Rebecca K. Shears,Benjamin Small,Krishanthi S. Subramaniam,Agnieska Szemiel,Aislynn Taggart,Jolanta Tanianis-Hughes,Jordan Thomas,Erwan Trochu,Libby van Tonder,Eve Wilcock,J. Eunice Zhang,Sean Keating,Cara Donegan,Rebecca G. Spencer,Primrose Chikowore,Chloe Donohue,Fiona Griffiths,Hayley Hardwick,Wilna Oosthuyzen
The Journal of infectious diseases（2023）
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摘要
Fatal COVID-19 is associated with robust peripheral inflammation; however, early interferon-led responses in the respiratory mucosa are delayed relative to responses in those who will survive severe SARS-CoV-2 infection. Background While inflammatory and immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in peripheral blood are extensively described, responses at the upper respiratory mucosal site of initial infection are relatively poorly defined. We sought to identify mucosal cytokine/chemokine signatures that distinguished coronavirus disease 2019 (COVID-19) severity categories, and relate these to disease progression and peripheral inflammation.Methods We measured 35 cytokines and chemokines in nasal samples from 274 patients hospitalized with COVID-19. Analysis considered the timing of sampling during disease, as either the early (0-5 days after symptom onset) or late (6-20 days after symptom onset) phase.Results Patients that survived severe COVID-19 showed interferon (IFN)-dominated mucosal immune responses (IFN-gamma, CXCL10, and CXCL13) early in infection. These early mucosal responses were absent in patients who would progress to fatal disease despite equivalent SARS-CoV-2 viral load. Mucosal inflammation in later disease was dominated by interleukin 2 (IL-2), IL-10, IFN-gamma, and IL-12p70, which scaled with severity but did not differentiate patients who would survive or succumb to disease. Cytokines and chemokines in the mucosa showed distinctions from responses evident in the peripheral blood, particularly during fatal disease.Conclusions Defective early mucosal antiviral responses anticipate fatal COVID-19 but are not associated with viral load. Early mucosal immune responses may define the trajectory of severe COVID-19.
