Here we report a case of Covid-19-related acute necrotizing encephalopathy (ANE) where SARS-CoV-2 RNA was found in cerebrospinal spinal fluid (CSF) first 19 days after symptom onset after negative findings earlier. Even though monocytes and protein levels in CSF were only marginally increased, and our patient never experienced a hyperinflammatory state, she deteriorated in neurological function and became comatose. Magnetic resonance imaging of the brain showed pathological signal symmetrically in central thalami, subinsular regions, medial temporal lobes and brain stem. Extremely high concentrations of the neuronal injury markers neurofilament light (NfL) and tau, as well as an astrocytic activation marker glial fibrillary acidic protein (GFAp), were measured in CSF in parallel to in-depth proteomics analysis. The patient received intravenous immunoglobulins (IVIG) and plasma exchange (PLEX). Her neurological status improved and she was extubated four weeks after symptom onset. This case report highlights the neurotropism of SARS-CoV-2 in selected patients and emphasizes the importance of repeated lumbar punctures and CSF analyses in patients with suspected Covid-19 and neurological symptoms.