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Introduction Neuroinflammatory conditions accounted for 9.3% of neurological complications in hospitalised COVID-19 patients. The underlying pathophysiology remains unknown. Currently knowledge is based on case studies.Methods We carried out a prospective COVID-19 Clinical Neuroscience Study, across 17 UK sites between March 2021 and October 2022. Adults hospitalised with COVID-19, who fulfilled a neurological or neuropsychiatric diagnostic criteria were recruited as cases, while controls were patients hospitalised with COVID-19 without neurological complications. Participant’s acute admission data, clinical follow-up assessments, blood sampling and neuroimaging were collected for analyses.Results 1. 730 participants were recruited, including 401 cases and 329 controls. 59/401 (14.7%) of cases developed an inflammatory or autoimmune neurological condition. Inflammatory complications predominantly affected the central nervous system (CNS) 43/59 (73%), while 16/59 (27%) affected the peripheral nervous system.2. Multivariable analysis revealed inflammatory complications were associated with reduced Glasgow Coma Scale and worsening functional outcome despite milder COVID-193. Makers of axonal and dendritic injury (NfL and T-Tau) were significantly higher in cases compared to time-matched controls (adjusted p=0.0013, p=0.0043 respectively), and specifically in those who have developed CNS complications.Conclusion This is the first case-control study to characterise neuroinflammatory complications following COVID-19, including clinical syndrome, risk factors and biomarkers.yun.huang@nhs.net