The landscape of human brain immune response in patients with severe COVID-19

Fullard, J. F.; Lee, H.-c.; Voloudakis, G.; Suo, S.; Shao, Z.; Peter, C.; Javidfar, B.; Zhang, W.; Jiang, S.; Corvelo, A.; Woodoff-Leith, E.; Purohit, D. P.; Hoffman, G. E.; Akbarian, S.; Fowkes, M.; Crary, J.; Yuan, G.-C.; Roussos, P.

doi:10.1101/2021.01.08.425999

bioRxiv · 10.1101/2021.01.08.425999

The landscape of human brain immune response in patients with severe COVID-19

Fullard, J. F.·Lee, H.-c.·Voloudakis, G.·Suo, S.·Shao, Z.·Peter, C.·Javidfar, B.·Zhang, W.·Jiang, S.·Corvelo, A.·Woodoff-Leith, E.·Purohit, D. P.·Hoffman, G. E.·Akbarian, S.·Fowkes, M.·Crary, J.·Yuan, G.-C.·Roussos, P.

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Abstract

In coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the relationship between brain tropism, neuroinflammation and host immune response has not been well characterized. We analyzed 68,557 single-nucleus transcriptomes from three brain regions (dorsolateral prefrontal cortex, medulla oblongata and choroid plexus) and identified an increased proportion of stromal cells and monocytes in the choroid plexus of COVID-19 patients. Differential gene expression, pseudo-temporal trajectory and gene regulatory network analyses revealed microglial transcriptome perturbations, mediating a range of biological processes, including cellular activation, mobility and phagocytosis. Quantification of viral spike S1 protein and SARS-CoV-2 transcripts did not support the notion of brain tropism. Overall, our findings suggest extensive neuroinflammation in patients with acute COVID-19. One Sentence SummarySingle-nucleus transcriptome analysis suggests extensive neuroinflammation in human brain tissue of patients with acute coronavirus disease 2019.

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Fullard, J. F., Lee, H.-c., Voloudakis, G., Suo, S., Shao, Z., Peter, C., Javidfar, B., Zhang, W., Jiang, S., Corvelo, A., Woodoff-Leith, E., Purohit, D. P., Hoffman, G. E., Akbarian, S., Fowkes, M., Crary, J., Yuan, G.-C., Roussos, P.. 2021-01-11. The landscape of human brain immune response in patients with severe COVID-19. https://doi.org/10.1101/2021.01.08.425999

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