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The microglial NLRP3 inflammasome is involved in human SARS-CoV-2 cerebral pathogenicity: A report of three post-mortem cases

Viviana Falcón Cama

We herein report, by using confocal immunofluorescence, the localization of the SARS-CoV-2 nucleocapsid within neurons, astrocytes, oligodendrocytes and microglia in three deceased COVID-19 cases, of between 78 and 85?years of age at death. The viral nucleocapsid was detected together with its ACE2 cell entry receptor, as well as the NLRP3 inflammasome in cerebral cortical tissues. It is noteworthy that NLRP3 was colocalized with CD68?+?macrophages in the brain and lung of the deceased, suggesting the critical role of this type of inflammasome in SARS-CoV-2 lesions of the nervous system/lungs and supporting its potential role as a therapeutic target. It is widely recognized that patients with coronavirus disease 2019 (COVID-19) present diverse neurological injuries leading to long-term sequels, but the pathogenic mechanisms involved are still largely unknown (Azizi and Azizi, 2020). Using confocal immunofluorescence analysis (Supplementary Materials and Methods), we report the potential role of NLRP3 inflammasome in brain pathogenicity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in three deceased patients with COVID-19. Importantly, the viral nucleocapsid (NC) protein was localized in a variety of typical cells of the central nervous system (CNS), that were identified using antibodies against NeuN (neurons), GFAP (astrocytes), CNPase (oligodendrocytes) and Iba-1 (microglia);In contrast, immunostaining was not detected with only secondary fluorescent probes-conjugated antibodies without primary antibodies in postmortem brain samples from COVID-19 deceased (Supp 1).Next, potential mediators of the pathogenicity of this virus were identified in the human CNS. Interestingly, NC colocalized with the cell entry receptor of SARS-CoV-2, Angiotensin-Converting Enzyme 2 (ACE2), in the brain tissue .Notably, co-immunostaining of NC with a key player of the neuroinflammatory axis: the inflammasome NLRP3 was also observed. Furthermore, NLRP3 was co-detected with CD68, a monocyte/macrophage and microglia marker