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

Michael, Benedict D., Dunai, Cordelia, Needham, Edward J., Tharmaratnam, Kukatharmini, Williams, Robyn, Huang, Yun, Boardman, Sarah A., Clark, Jordan J., Sharma, Parul, Subramaniam, Krishanthi, Wood, Greta K., Collie, Ceryce, Digby, Richard, Ren, Alexander, Norton, Emma, Leibowitz, Maya, Ebrahimi, Soraya, Fower, Andrew, Fox, Hannah, Tato, Esteban, Ellul, Mark A., Sunderland, Geraint, Held, Marie, Hetherington, Claire, Egbe, Franklyn N., Palmos, Alish, Stirrups, Kathy, Grundmann, Alexander, Chiollaz, Anne-Cecile, Sanchez, Jean-Charles, Stewart, James P., Griffiths, Michael, Solomon, Tom, Breen, Gerome, Coles, Alasdair J., Kingston, Nathalie, Bradley, John R., Chinnery, Patrick F., Cavanagh, Jonathan, Irani, Sarosh R., Vincent, Angela, Baillie, J. Kenneth, Openshaw, Peter J., Semple, Malcolm G., Baillie, J. 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Peter, McDonald, Sarah E., Shaw, Victoria, Ahmed, Katie A., Armstrong, Jane A., Ashworth, Milton, Asiimwe, Innocent G., Bakshi, Siddharth, Barlow, Samantha L., Booth, Laura, Brennan, Benjamin, Bullock, Katie, Carlucci, Nicola, Cass, Emily, Catterall, Benjamin W., Clark, Jordan J., Clarke, Emily A., Cole, Sarah, Cooper, Louise, Cox, Helen, Davis, Christopher, Dincarslan, Oslem, Carracedo, Alejandra D., Dunn, Chris, Dyer, Philip, Elliott, Angela, Evans, Anthony, Finch, Lorna, Fisher, Lewis W., Flaherty, Lisa, Foster, Terry, Garcia-Dorival, Isabel, Gunning, Philip, Hartley, Catherine, Holmes, Anthony, Jensen, Rebecca L., Jones, Christopher B., Jones, Trevor R., Khandaker, Shadia, King, Katharine, Kiy, Robyn T., Koukorava, Chrysa, Lake, Annette, Lant, Suzannah, Latawiec, Diane, Lavelle-Langham, Lara, Lefteri, Daniella, Lett, Lauren, Livoti, Lucia A., Mancini, Maria, Massey, Hannah, Maziere, Nicole, McDonald, Sarah, McEvoy, Laurence, McLauchlan, John, Metelmann, Soeren, Miah, Nahida S., 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Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses. Nature Communications 14 , 8487. 10.1038/s41467-023-42320-4

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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.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Publisher:	Nature Research
ISSN:	2041-1723
Date of First Compliant Deposit:	2 January 2024
Date of Acceptance:	6 October 2023
Last Modified:	03 Jan 2024 16:04
URI:	https://orca.cardiff.ac.uk/id/eprint/165123

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