Neuropathology in COVID-19 autopsies is defined by microglial activation and lesions of the white matter with emphasis in cerebellar and brain stem areas

Julian A Stein; Manuel Kaes; Sigrun Smola; Walter J Schulz-Schaeffer

doi:10.3389/fneur.2023.1229641

Neuropathology in COVID-19 autopsies is defined by microglial activation and lesions of the white matter with emphasis in cerebellar and brain stem areas

Front Neurol. 2023 Jul 13:14:1229641. doi: 10.3389/fneur.2023.1229641. eCollection 2023.

Authors

Julian A Stein¹, Manuel Kaes¹, Sigrun Smola^{2

3}, Walter J Schulz-Schaeffer¹

Affiliations

¹ Institute of Neuropathology, Medical Faculty of the Saarland University, Homburg, Germany.
² Institute of Virology, Saarland University Medical Center, Homburg, Germany.
³ Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research, Saarbrücken, Germany.

Abstract

Introduction: This study aimed to investigate microglial and macrophage activation in 17 patients who died in the context of a COVID-19 infection in 2020 and 2021.

Methods: Through immunohistochemical analysis, the lysosomal marker CD68 was used to detect diffuse parenchymal microglial activity, pronounced perivascular macrophage activation and macrophage clusters. COVID-19 patients were compared to control patients and grouped regarding clinical aspects. Detection of viral proteins was attempted in different regions through multiple commercially available antibodies.

Results: Microglial and macrophage activation was most pronounced in the white matter with emphasis in brain stem and cerebellar areas. Analysis of lesion patterns yielded no correlation between disease severity and neuropathological changes. Occurrence of macrophage clusters could not be associated with a severe course of disease or preconditions but represent a more advanced stage of microglial and macrophage activation. Severe neuropathological changes in COVID-19 were comparable to severe Influenza. Hypoxic damage was not a confounder to the described neuropathology. The macrophage/microglia reaction was less pronounced in post COVID-19 patients, but detectable i.e. in the brain stem. Commercially available antibodies for detection of SARS-CoV-2 virus material in immunohistochemistry yielded no specific signal over controls.

Conclusion: The presented microglial and macrophage activation might be an explanation for the long COVID syndrome.

Keywords: CD68; CNS infection; COVID-19; immunohistochemistry; macrophage; neuropathology.