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

Fullard, John F.; Lee, Hao-Chih; Voloudakis, Georgios; Suo, Shengbao; Shao, Zhiping; Peter, Cyril; Javidfar, Behnam; Zhang, Wen; Jiang, Shan; Corvelo, André; Woodoff-Leith, Emma; Purohit, Dushyant P.; Hoffman, Gabriel E.; Akbarian, Schahram; Fowkes, Mary; Crary, John; Yuan, Guo-Cheng; Roussos, Panos

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 Summary Single-nucleus transcriptome analysis suggests extensive neuroinflammation in human brain tissue of patients with acute coronavirus disease 2019.