Journal Article

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

Grundmann, Alexander, Irani, Sarosh R., Breen, Gerome, Semple, Malcolm G., Wood, Greta K., Ebrahimi, Soraya, Williams, Robyn, Clark, Jordan J., Bradley, John R., Held, Marie, Griffiths, Michael, Sunderland, Geraint, Dunai, Cordelia, Michael, Benedict D., Sharma, Parul, Tharmaratnam, Kukatharmini, Boardman, Sarah A., Stirrups, Kathy, Digby, Richard, Needham, Edward J., Norton, Emma, Fower, Andrew, Palmos, Alish, Baillie, J. Kenneth, Coles, Alasdair J., Stewart, James P., Chiollaz, Anne-Cecile, Ren, Alexander, Vincent, Angela, Subramaniam, Krishanthi, Hetherington, Claire, Kingston, Nathalie, Cavanagh, Jonathan, Fox, Hannah, Chinnery, Patrick F., Ellul, Mark A., Tato, Esteban, Egbe, Franklyn N., Openshaw, Peter J., Taams, Leonie S., Menon, David K., Collie, Ceryce, Leibowitz, Maya, Huang, Yun, Sanchez, Jean-Charles, Solomon, Tom

2023

Overview

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. COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/250/256 / 631/326/596/4130 / 692/1807/1693 / 692/617/375 / 82/1 / 82/47 / 82/51 / 82/79 / Autoantibodies / Biomarkers / Brain / Brain Injuries / Brain injury / Cerebrospinal fluid / Consciousness / COVID-19 / COVID-19 - complications / COVID-19 Serotherapy / Cytokines / Follow-Up Studies / Glial Fibrillary Acidic Protein / Head injuries / Humanities and Social Sciences / Humans / Immune response / Inflammation / Inflammation Mediators / Interleukin 1 receptor antagonist / Interleukin 1 receptors / Interleukins / Life Sciences / Macrophage colony-stimulating factor / Monocyte chemoattractant protein 1 / multidisciplinary / Neurological complications / Protein gene product 9.5 / Science / Science (multidisciplinary) / Severe acute respiratory syndrome coronavirus 2 / Traumatic brain injury / Viral diseases