• Jakob Matschke, Marc Lütgehetmann, Christian Hagel, Jan P Sperhake, Ann Sophie Schröder, Carolin Edler, Herbert Mushumba, Antonia Fitzek, Lena Allweiss, Maura Dandri, Matthias Dottermusch, Axel Heinemann, Susanne Pfefferle, Marius Schwabenland, Daniel Sumner Magruder, Stefan Bonn, Marco Prinz, Christian Gerloff, Klaus Püschel, Susanne Krasemann, Martin Aepfelbacher, and Markus Glatzel.
• Institute of Neuropathology, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany.
• Lancet Neurol. 2020 Nov 1; 19 (11): 919929919-929.

BackgroundProminent clinical symptoms of COVID-19 include CNS manifestations. However, it is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, gains access to the CNS and whether it causes neuropathological changes. We investigated the brain tissue of patients who died from COVID-19 for glial responses, inflammatory changes, and the presence of SARS-CoV-2 in the CNS.MethodsIn this post-mortem case series, we investigated the neuropathological features in the brains of patients who died between March 13 and April 24, 2020, in Hamburg, Germany. Inclusion criteria comprised a positive test for SARS-CoV-2 by quantitative RT-PCR (qRT-PCR) and availability of adequate samples. We did a neuropathological workup including histological staining and immunohistochemical staining for activated astrocytes, activated microglia, and cytotoxic T lymphocytes in the olfactory bulb, basal ganglia, brainstem, and cerebellum. Additionally, we investigated the presence and localisation of SARS-CoV-2 by qRT-PCR and by immunohistochemistry in selected patients and brain regions.Findings43 patients were included in our study. Patients died in hospitals, nursing homes, or at home, and were aged between 51 years and 94 years (median 76 years [IQR 70-86]). We detected fresh territorial ischaemic lesions in six (14%) patients. 37 (86%) patients had astrogliosis in all assessed regions. Activation of microglia and infiltration by cytotoxic T lymphocytes was most pronounced in the brainstem and cerebellum, and meningeal cytotoxic T lymphocyte infiltration was seen in 34 (79%) patients. SARS-CoV-2 could be detected in the brains of 21 (53%) of 40 examined patients, with SARS-CoV-2 viral proteins found in cranial nerves originating from the lower brainstem and in isolated cells of the brainstem. The presence of SARS-CoV-2 in the CNS was not associated with the severity of neuropathological changes.InterpretationIn general, neuropathological changes in patients with COVID-19 seem to be mild, with pronounced neuroinflammatory changes in the brainstem being the most common finding. There was no evidence for CNS damage directly caused by SARS-CoV-2. The generalisability of these findings needs to be validated in future studies as the number of cases and availability of clinical data were low and no age-matched and sex-matched controls were included.FundingGerman Research Foundation, Federal State of Hamburg, EU (eRARE), German Center for Infection Research (DZIF).Copyright © 2020 Elsevier Ltd. All rights reserved.

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