1. Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses
- Author
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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 Tato, Mark 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, ISARIC4C Investigators, COVID-CNS Consortium, Leonie S. Taams, and David K. Menon
- Subjects
Science - Abstract
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.
- Published
- 2023
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