[Preprint] The central nervous systems proteogenomic and spatial imprint upon systemic viral infections with SARS-CoV-2, 2023, Radke et al

The central nervous systems proteogenomic and spatial imprint upon systemic viral infections with SARS-CoV-2

Spoiler: Radke et al

Josefine Radke, Jenny Meinhardt, Tom Aschman, Robert Lorenz Chua, Vadim Farztdinov, Soren Lukkassen, Foo Wei Ten, Friebel Ekaterina, Naveed Ishaque, Jonas Franz, Valerie Helena Huhle, Ronja Mothes, Kristin Peters, Carolina Thomas, Simon Streit, Regina von Manitius, Peter Kortvelyessy, Stefan Vielhaber, Dirk Reinhold, Anja Hauser, Anja Osterloh, Philipp Enghard, Jana Ihlow, Sefer Elezkurtaj, David Horst, Florian Kurth, Marcel A Muller, Nils C Gassen, Julia Schneider, Katharina Jechow, Bernd Timmermann, Camila Fernandez-Zapata, Chotima Bottcher, Werner Stenzel, Emanuel Wyler, Victor Corman, Christine Stadelmann-Nessler, Markus Ralser, Roland Eils, Frank L Heppner, Michael Mulleder, Christian Conrad, Helena Radbruch

In COVID-19 neurological alterations are noticed during the systemic viral infection. Various pathophysiological mechanisms on the central nervous system (CNS) have been suggested in the past two years, including the viral neurotropism hypothesis. Nevertheless, neurological complications can also occur independent of neurotropism and at different stages of the disease and may be persistent. Previous autopsy studies of the CNS from patients with severe COVID-19 show infiltration of macrophages and T lymphocytes, especially in the perivascular regions as well as pronounced microglial activation, but without signs of viral encephalitis. However, there is an ongoing debate about long-term changes and cytotoxic effects in the CNS due to the systemic inflammation.

Here, we show the brain-specific host response during and after COVID-19. We profile single-nucleus transcriptomes and proteomes of brainstem tissue from deceased COVID-19 patients who underwent rapid autopsy. We detect a disease phase-dependent inflammatory type-I interferon response in acute COVID-19 cases. Integrating single-nucleus RNA sequencing and spatial transcriptomics, we could localize two patterns of reaction to severe systemic inflammation. One neuronal with direct focus on cranial nerve nuclei and one diffusely affecting the whole brainstem, the latter reflecting a bystander effect that spreads throughout the vascular unit and alters the transcriptional state of oligodendrocytes, microglia and astrocytes.

Our results indicate that even without persistence of SARS-CoV-2 in the CNS, the tissue activates highly protective mechanisms, which also cause functional disturbances that may explain the neurological symptoms of COVID-19, triggered by strong systemic type-I IFN signatures in the periphery.

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Thanks for sharing. I find this area of research hard to follow in the details as a non-expert but my intuitive sense/lived experience of ME/CFS always brings me back to this sort of mechanism as a likely candidate. If anyone has the knowledge and experience to provide informed comment on this paper I'd really welcome that.

 

Post-mortem arm —

CSF evaluation arm —

Some selected quotes —