Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

作者：Benedict Daniel Michael, Cordelia Dunai, Edward Needham, Kukatharmini Tharmaratnam, Robyn Williams, Yun Huang, Sarah Boardman, Jordan J. Clark, Parul Sharma, Krishanthi S. Subramaniam, Greta Karen Wood, Ceryce Collie, Richard John Digby, Alexander Liang Ren, Emma Jane Norton, Maya M. Leibowitz, Soraya Ebrahimi, Andrew Fower, Hannah Fox, Esteban Tato, Mark Alexander Ellul, Geraint J. Sunderland, Marie Held, Claire Hetherington, Franklyn Nkongho Egbe, Alish Palmos, Kathy Stirrups, Alexander Grundmann, Anne-Cécile Chiollaz, Jean‐Charles Sanchez, James P. Stewart, Michael John Griffiths, Tom Solomon, Gerome D. Breen, Alasdair J. Coles, Nathalie Kingston, John R. Bradley, Patrick Francis Chinnery, Jonathan Cavanagh, Sarosh R. Irani, Angela Carmen Vincent, John Kenneth Baillie, Peter Openshaw, Malcolm G. Semple, ISARIC4C Investigators, John Kenneth Baillie, Peter Openshaw, Malcolm G. Semple, Beatrice Alex, Petros Andrikopoulos, Benjamin Bach, William Barclay, Debby Bogaert, Meera A Chand, Kanta Chechi, Graham S. Cooke, Ana Sergio Da Silva, Thushan I. de Silva, Annemarie Beth Docherty, Gonçalo dos Santos, Marc‐Emmanuel Dumas, Jake W Dunning, Tom E. Fletcher, Chris A Green, William Greenhalf, Julian Leether Griffin, Rishi K Gupta, Ewen Munro Harrison, Antonia Y. Wai, Karl A. Holden, Peter Horby, Samreen Ijaz, Saye Khoo, Paul Klenerman, Andrew Law, Matthew R. Lewis, Sonia Liggi, Wei Shen Lim, Lynn Maslen, Alexander J. Mentzer, Laura Merson, Alison M. Meynert, Shona C. Moore, Mahdad Noursadeghi, Michael T. Olanipekun, Anthonia Osagie, Massimo Palmarini, Carlo Palmieri, William A. 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 Ian Stuart, Charlotte Summers, Olivia V. Swann, Zoltán Takáts, Panteleimon G. Takis, Richard S. Tedder, A. A. Roger Thompson, Emma C. Thomson, Ryan S. Thwaites, Lance C. W. Turtle, Maria Cristina Fleischmann Alves Zambon, Thomas M Drake, Cameron J Fairfield, Stephen Richard Knight, Kenneth A McLean, Derek M. Murphy, Lisa Norman, Riinu Pius, Catherine A. Shaw, Marie Connor, Jo Ann Dalton, Carrol L. Gamble, Michelle Girvan, Sophie Halpin, Janet Harrison, Clare Jackson, James Christopher Lee, Laura Clare Marsh, Daniel Plotkin, Stephanie Roberts, Egle Saviciute, Sara Clohisey, Ross Hendry, Susan Knight, Eva Lahnsteiner, Gary Leeming, Lucy Norris, James Scott-Brown, Sarah D. Tait, Murray Wham, Richard E. Clark, Audrey AC Coutts, Lorna Donnelly, Angie Fawkes, Tammy Gilchrist, Katarzyna Hafezi, Louise MacGillivray, Alan W Maclean, Sarah McCafferty, Kirstie Morrice, Lee D. Murphy, Nicola Wrobel, Gail Carson, Kayode Adebamiji Adeniji, Daniel D. Agranoff, Ken Agwuh, Dhiraj Ail, Erin L. Aldera, Ana Alegria, Sam Allen, Brian Angus, Abdul Ashish, Dougal Atkinson, Shahedal Bari, Gavin D Barlow, Stella Barnass, Nicholas A. Barrett, Christopher Bassford, Sneha Basude, David G. Baxter, Michael B. J. Beadsworth, Jolanta Bernatoniene, John C. Berridge, Colin Berry, Nicola G. Best, Pieter A. Bothma, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Andrew J. Burtenshaw, Vikki Caruth, David R. Chadwick, Duncan Chambler, Nigel Chee, Jenny Child, Srikanth Chukkambotla, Tom Clark, Paul Collini, Catherine Cosgrove, Jason Cupitt, Maria-Teresa Cutino-Moguel, Paul M Dark, Chris Dawson, Samir Dervisevic, Phil Donnison, Sam T Douthwaite, Andrew Drummond, Ingrid DuRand, Ahilanadan Dushianthan, Tristan Dyer, Cariad M. Evans, Chi Eziefula, Chrisopher Fegan, Adam H.R. Finn, Duncan Fullerton, Sanjeev Garg, Atul Garg, Effrossyni Gkrania‐Klotsas, Jo Godden, Arthur R. Goldsmith, Clive Graham, Tassos Grammatikopoulos, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Daniel B. Hawcutt, Maria Hobrok, Luke Eliot Hodgson, Anil P. Hormis, Joanne Howard, Michael Jacobs, Susan Jain, Paul Jennings, Agilan Kaliappan, Vidya Kasipandian, Stephen Kegg, Michael C. Kelsey, Jason Kendall, Caroline Kerrison, Ian Kerslake, Oliver Owen Koch, Gouri Koduri, George Koshy, Shondipon Laha, Steven Laird, Susan Larkin, Tamás Leiner, Patrick J. Lillie, James Limb, Vanessa Linnett, Jeff Little, Mark David Lyttle, Michael MacMahon, Emily MacNaughton, Ravish Mankregod, Huw Masson, Elijah Matovu, Katherine McCullough, Ruth McEwen, Manjula Meda, GARY H. MILLS, Jane Minton, Kavya Mohandas, Quen Mok, James Moon, Elinoor Moore, Patrick W. Morgan, Craig F. Morris, Katherine Mortimore, Samuel E Moses, Mbiye Mpenge, Rohinton Mulla, Michael V. Murphy, Thapas Nagarajan, Megan Nagel, Mark Raymond Nelson, Lillian Norris, Matthew K. O’Shea, Marlies Ostermann, Igor Otahal, Mark Pais, Selva Panchatsharam, Danai Papakonstantinou, Padmasayee Papineni, Hassan Paraiso, Brij Patel, Natalie Pattison, Justin Pepperell, Mark John Peters, Mandeep Phull, Stefania Pintus, Tim Planche, Frank A. Post, David Price, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Tim Reynolds, Neil E. Richardson, Mark Roberts, Devender Roberts, Alistair Rose, Guy Rousseau, Bobby Ruge, Brendan Ryan, Taranprit Saluja, Matthias Ludwig Schmid, Aarti Shah, Manu Shankar‐Hari, Prad Shanmuga, Anil Kumar Sharma, Anna Shawcross, Jagtur Singh Pooni, Jeremy Sizer, Richard M. Smith, Catherine M. Snelson, Nick Spittle, Nikki Staines, Tom Stambach, Richard A. Stewart, Pradeep Subudhi, Tamás Szakmány, Kate Colette Tatham, J. Regan 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 M. Wake, Andrew Walden, Ingeborg Dorothea Welters, Tony Whitehouse, Paul G. Whittaker, Ashley Whittington, Meme Wijesinghe, Martin Williams, Lawrence Wilson, Stephen Winchester, Martin J Wiselka, Adam Wolverson, Dan Wootton, Andrew Workman, Bryan Yates, P. A. Young, Sarah E. McDonald, Victoria E. Shaw, Katie A. Ahmed, Jane A. Armstrong, Milton Ashworth, Innocent Gerald Asiimwe, Siddharth Bakshi, 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 M. Cooper, Helen Suzanne Cox, Christopher Davis, Oslem Dincarslan, Alejandra Doce Carracedo, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna S Finch, Lewis WS Fisher, Lisa Flaherty, Terry Foster, Isabel García-Dorival, Philip Gunning, Catherine S. Hartley, Anthony M Holmes, Rebecca L. Jensen, Christopher B. Jones, Trevor R. Jones, Shadia Khandaker, Katharine King, Robyn T. Kiy, Chrysa Koukorava, Annette Lake, Suzannah B. Lant, Diane Latawiec, Lara Lavelle-Langham, Daniella A. Lefteri, Lauren Lett, Lucia A Livoti, Maria Vittoria Mancini, Hannah Massey, Nicole Maziere, Sarah E. McDonald, Laurence McEvoy, John McLauchlan, Soeren Metelmann, Nahida S Miah, Joanna Middleton, Joyce M. Mitchell, E. Gordon Murphy, Rebekah Penrice-Randal, Jack Pilgrim, Tessa Prince, Will Reynolds, Paul 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 v. Tonder, Eve Wilcock, J. E. Zhang, Seán Keating, Cara Donegan, Rebecca G. Spencer, Chloe Donohue, Fiona Griffiths, Hayley Hardwick, Wilna Oosthuyzen, Adam Hampshire, Adam Sieradzki, Adam W. Seed, Afagh Garjani, Akshay Gopinathan Nair, Alaisdair Coles, Alan J Carson, Alastair Darby, Alex Berry, Alex Dregan, Alexander Grundmann, Alish Palmos, Ammar Al‐Chalabi, Andrew Mark McIntosh, Angela E. Holland, Angela Charlotte Roberts, Angela Vincent, Annalena Venneri, Anthony S. David, Arina Tamborska, Arvind H. Patel, Ava Easton, Benedict Daniel Michael, Bethan Blackledge, Bethany Facer, Bhagteshwar Singh, Brendan Sargent, Ceryce Collie, E. Charles Leek, Chérie Armour, Christopher M. Morris, Christopher Martin Allen, Ciaran C. Mulholland, Claire MacIver, Cordelia Dunai, Craig J. Smith, Daniel J. van, Daniel Madarshahian, David M. Christmas, David Cousins, David Krishna Menon, David M. Christmas, David P. Breen, Dina Monssen, Edward Thomas Bullmore, Edward Needham, Emily McGlinchey, Emma C. Thomson, Eugene Paul Duff, Eva Maria Hodel, Ewan M. Harrison, Fernando O. Zelaya, Gabriella Lewis, Gavin V McDonnell, Gerome D. Breen, Greta K. Wood, Guy B. Williams, Claire E. Hannah, Henry C. Rogers, Ian Galea, Jacqueline Smith, Jade D. Harris, James B Lilleker, Jay K Amin, John P. Aggleton, John R. Bradley, John‐Paul Taylor, Jonathan Cavanagh, Jonathan R. I. Coleman, Jonathan W.R. Underwood, Judith Breuer, Julian A. Hiscox, Karla Miller, Katherine Claire Dodd, Kiran Glen, Laura A. Benjamin, Leonie S. Taams, Lily George, Marc Hardwick, Mark R. Baker, Masud Husain, Matthew P. Butler, Matthew H. Hotopf, Matthew R. Broome, Merna Samuel, Michael Griffiths, Michael Peter Lunn, Michael S. Zandi, Monika Hartmann, Nadine Cossette, Naomi H. Martin, Nathalie Nicholas, Neil Andrew Harrison, Neil Basu, Neil Andrew Harrison, Nicholas W. S. Davies, Nicholas Wood, Nikos Evangelou, Obioma Orazulume, Pamela J. Shaw, Parisa Mansoori, Paul J. Harrison, Peter Jezzard, Peter M. Fernandes, Rachel Upthegrove, Rahul Batra, Rebecca Gregory, Rhys Huw Thomas, Richard A. I. Bethlehem, Richard P. Francis, Ronan O’Malley, Rustam Al‐Shahi Salman, Ryan McIlwaine, Sandar Kyaw, Sarosh R. Irani, Savini Gunatilake, Scott Semple, Shahd H. M. Hamid, Sharon J. Peacock, Silvia Rota, Simon Sean Keller, Sophie L. Pendered, Suzanne Barrett, Stella Hughes, Stella‐Maria Paddick, Stephen J. Sawcer, Stephen M. Smith, Steven Williams, Sui Hsien Wong, Sylviane Defres, Thomas Jackson, Thomas Michael Jenkins, Thomas Arthur Pollak, Timothy R. Nicholson, Tonny Veenith, Victoria Grimbly, Virginia Newcombe, Leonie S. Taams, David Krishna Menon · 发表于：Nature Communications · 年份：2023 · DOI：10.1038/s41467-023-42320-4 · 被引用次数：43 · 研究领域：Long-Term Effects of COVID-19、Vagus Nerve Stimulation Research、SARS-CoV-2 and COVID-19 Research

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1-11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely.