013-23 – Biomarkers of neurological complications of COVID-19

Although SARS-CoV-2 causes a respiratory viral infection, there is a significant incidence of neurological complications, including headache, seizure, and stroke, occurring in COVID-19 patients. Little is known about the likely diverse mechanisms causing these pathologies and there is a dire need to understand them and learn how to prevent and treat them. We measured brain injury markers and cytokines in the serum of study participants who had COVID-19. Brain injury markers (Nfl-L, UCH-L1, Tau, and GFAP) were measured by Quanterix Simoa and 48 cytokines were measured by Bio-rad Bioplex-200. We found that two brain injury markers and several cytokines/receptors were significantly associated with an abnormal Glasgow Coma Scale Score in acute COVID-19 patients. Interestingly, when the COVID-CNS participants with neurological complications were studied (weeks to months post initial positive COVID test), the brain injury marker, Nfl-L remained elevated. For the mouse model of parainfectious effects on brain, 2-4 mo heterozygous K18-hACE2 transgenic C57BL/6 male and female mice were infected with 1×103 PFU SARS-CoV-2. On day 5 post-infection, mice were euthanized and serum, brain, and lungs collected for RNA and protein analysis. We observed microglia reactivation in the brain of low dose-infected mice —interestingly, this was in the absence of active viral replication. Overall, we highlight two findings: (1) SARS-CoV-2 does not directly invade the brain in the majority of cases and so the associated neurological complications might arise from indirect effects, such as immune activation (2) although the immune system plays a critical role in controlling the virus, its dysregulation can cause pathology.