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

Benedict D. Michael*, Cordelia Dunai, Edward J. Needham, Kukatharmini Tharmaratnam, Robyn Williams, Yun Huang, Sarah A. Boardman, Jordan J. Clark, Parul Sharma, Krishanthi Subramaniam, Greta K. Wood, Ceryce Collie, Richard Digby, Alexander Ren, Emma Norton, Maya Leibowitz, Soraya Ebrahimi, Andrew Fower, Hannah Fox, Esteban TatoMark A. Ellul, Geraint Sunderland, Marie Held, Claire Hetherington, Franklyn N. Egbe, Alish Palmos, Kathy Stirrups, Alexander Grundmann, Anne Cecile Chiollaz, Jean Charles Sanchez, James P. Stewart, Michael Griffiths, Tom Solomon, Gerome Breen, Alasdair J. Coles, Nathalie Kingston, John R. Bradley, Patrick F. Chinnery, Jonathan Cavanagh, Sarosh R. Irani, Angela Vincent, J. Kenneth Baillie, Peter J. Openshaw, Malcolm G. Semple, J. Kenneth Baillie, Peter J. Openshaw, Malcolm G. Semple, Beatrice Alex, Petros Andrikopoulos, Benjamin Bach, Wendy S. Barclay, Debby Bogaert, Meera Chand, Kanta Chechi, Graham S. Cooke, Ana da Silva, Thushan de Silva, Annemarie B. Docherty, Gonçalo dos Santos, Marc Emmanuel Dumas, Jake Dunning, Tom Fletcher, Christoper A. Green, William Greenhalf, Julian L. Griffin, Rishi K. Gupta, Ewen M. Harrison, Antonia Y. Wai, Karl Holden, Peter W. Horby, Samreen Ijaz, Saye Khoo, Paul Klenerman, Andrew Law, Matthew R. Lewis, Sonia Liggi, Wei S. Lim, Lynn Maslen, Alexander J. Mentzer, Laura Merson, Alison M. Meynert, Shona C. Moore, Mahdad Noursadeghi, Michael 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, Shiranee Sriskandan, David Stuart, Charlotte Summers, Olivia V. Swann, Zoltan Takats, Panteleimon Takis, Richard S. Tedder, A. A.R. Thompson, Emma C. Thomson, Ryan S. Thwaites, Lance C. 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, Gary Leeming, Lucy Norris, James Scott-Brown, Sarah Tait, Murray Wham, Richard Clark, Audrey Coutts, Lorna Donnelly, Angie Fawkes, Tammy Gilchrist, Katarzyna Hafezi, Louise MacGillivray, Alan Maclean, Sarah McCafferty, Kirstie Morrice, Lee Murphy, Nicola Wrobel, Gail Carson, 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, 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, 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, Matthias L. Schmid, Aarti Shah, Manu Shankar-Hari, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jagtur S. 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. Catterall, Jordan J. Clark, Emily A. Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Alejandra D. Carracedo, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis W. 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, Ellen G. Murphy, Rebekah Penrice-Randal, Jack Pilgrim, Tessa Prince, Will Reynolds, P. M. 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 Nair, Alaisdair Coles, Alan Carson, Alastair Darby, Alex Dregan, Alexander Grundmann, Alish Palmos, Ammar Al-Chalabi, Andrew M. McIntosh, Angela E. Holland, Angela Roberts, Angela Vincent, Annalena Venneri, Anthony S. David, Arina Tamborska, Arvind Patel, Ava Easton, Benedict D. Michael*, Bethan Blackledge, Bethany Facer, Bhagteshwar Singh, Brendan Sargent, Ceryce Collie, Charles Leek, Cherie Armour, Christopher M. Morris, Christopher M. Allen, Ciaran Mulholland, Claire L. MacIver, Cordelia Dunai, Craig J. Smith, Daniel J. van, Daniel Madarshahian, David Christmas, David Cousins, David K. Menon, David M. Christmas, David P. Breen, Dina Monssen, Edward Bullmore, Edward Needham, Emily McGlinchey, Emma Thomson, Eugene Duff, Eva M. Hodel, Ewan Harrison, Fernando Zelaya, Gabriella Lewis, Gavin McDonnell, Greta K. Wood, Guy B. Williams, C. Hannah, Henry C. Rogers, Jacqueline Smith, Jade D. Harris, James B. Lilleker, Jay Amin, John P. Aggleton, John R. Bradley, John Paul Taylor, Jonathan Cavanagh, Jonathan R. Coleman, Jonathan Underwood, Judith Breuer, Julian Hiscox, Karla Miller, Katherine C. Dodd, Kiran Glen, Laura Benjamin, Leonie Taams, Lily George, Marc Hardwick, Mark R. Baker, Masud Husain, Matthew Butler, Matthew Hotopf, Matthew R. Broome, Merna Samuel, Michael Griffiths, Michael P. Lunn, Michael S. Zandi, Monika Hartmann, Nadine Cossette, Naomi Martin, Nathalie Nicholas, Neil A. Harrison, Neil Basu, Neil Harrison, Nicholas Davies, Nicholas Wood, Nikos Evangelou, Pamela J. Shaw, Parisa Mansoori, Paul J. Harrison, Peter Jezzard, Peter M. Fernandes, Rachel Upthegrove, Rahul Batra, Rebecca Gregory, Rhys H. Thomas, Richard Bethlehem, Richard Francis, Ronan O’Malley, Rustam A. Salman, Ryan McIlwaine, Sandar Kyaw, Sarosh Irani, Savini Gunatilake, Scott Semple, Shahd H. Hamid, Sharon Peacock, Silvia Rota, Simon Keller, Sophie Pendered, Suzanne Barrett, Stella Hughes, Stella Maria Paddick, Stephen J. Sawcer, Stephen Smith, Steven Williams, Sui H. Wong, Sylviane Defres, Thomas Jackson, Thomas M. Jenkins, Thomas Pollak, Timothy Nicholson, Tonny Veenith, Victoria Grimbly, Virginia Newcombe, Leonie S. Taams, David K. Menon

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number8487
JournalNature Communications
Volume14
Issue number1
DOIs
Publication statusPublished - Dec 2023

Bibliographical note

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© 2023, The Author(s).

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