During severe systemic infections with and without sepsis neurological changes are common and range from sickness behavior to septic associated encephalopathy. Encephalopathy is due to a system-wide inflammatory response leading to an often fatal increase in the permeability of the blood-brain barrier. To elucidate the cytotoxic impact and brain-specific host response during coronavirus disease 2019 (COVID-19), we profiled the olfactory mucosa, olfactory bulb, brainstem and cerebellum from deceased COVID-19 patients who underwent rapid autopsy.