On COVID-19-Associated Central Nervous System Complications

Abstract

The acute and long-term neurological impacts of COVID-19 have raised important concerns regarding the involvement of the central nervous system (CNS) in SARS-CoV-2 infection. This thesis examines the biochemical and neurochemical effects of COVID-19 on the CNS, focusing on acute injury and persistent manifestations. The primary aims were to assess markers of CNS injury in plasma and cerebrospinal fluid (CSF), investigate neuroinflammation and immune activation, and explore the associations between acute biomarker profiles and persistent neurological sequelae. Four studies employing cross-sectional, case series, and longitudinal design were conducted to evaluate CNS involvement across varying COVID-19 severities. Biomarker analyses focused on neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and CSF markers of immune activation. Our findings demonstrated elevated plasma NfL and GFAP levels during the acute phase in moderate to severe COVID-19, indicating astrocytic activation followed by neuronal injury. Longitudinal follow-up showed normalization of biomarker levels within six months, even in individuals reporting symptoms such as fatigue and cognitive impairment. CSF analyses in patients with post-COVID-19 condition (PCC) revealed no evidence of viral presence or sustained CNS inflammation. This thesis highlights the transient neurochemical impact of COVID-19, characterized by astrocytic and neuronal injury during the acute phase. The normalization of biomarkers despite PCC symptoms suggests that these sequelae may result from initial inflammatory or hypoxic insults rather than ongoing CNS damage. These findings underscore the complexity of neuro-COVID, emphasizing the role of systemic and neuroimmune pathways over direct viral effects in both acute and chronic CNS complications.