The study investigates the neuropathological features of COVID-19 in 43 patients who died between March 13 and April 24, 2020, in Hamburg, Germany. The neuropathological workup included histological and immunohistochemical staining for activated astrocytes, microglia, and cytotoxic T lymphocytes in various brain regions. SARS-CoV-2 was detected in the brains of 21 (53%) patients, primarily in the brainstem and cerebellum. The presence of SARS-CoV-2 was not associated with the severity of neuropathological changes, which were generally mild, with pronounced neuroinflammatory changes in the brainstem being the most common finding. The study highlights the potential role of immune-mediated mechanisms in the neuropathology of COVID-19 and suggests that direct CNS damage caused by SARS-CoV-2 may be less significant. However, further studies are needed to better understand the mechanisms of viral entry and the distribution of SARS-CoV-2 in the brain.The study investigates the neuropathological features of COVID-19 in 43 patients who died between March 13 and April 24, 2020, in Hamburg, Germany. The neuropathological workup included histological and immunohistochemical staining for activated astrocytes, microglia, and cytotoxic T lymphocytes in various brain regions. SARS-CoV-2 was detected in the brains of 21 (53%) patients, primarily in the brainstem and cerebellum. The presence of SARS-CoV-2 was not associated with the severity of neuropathological changes, which were generally mild, with pronounced neuroinflammatory changes in the brainstem being the most common finding. The study highlights the potential role of immune-mediated mechanisms in the neuropathology of COVID-19 and suggests that direct CNS damage caused by SARS-CoV-2 may be less significant. However, further studies are needed to better understand the mechanisms of viral entry and the distribution of SARS-CoV-2 in the brain.