Expert opinion (Violet)
As the COVID-19 pandemic developed and neurological manifestations were reported, concern grew that SARS-CoV-2 might directly invade neuronal cells. However, research throughout the year to address this concern has revealed a different story with inflammatory processes at its centre. Anosmia, encephalopathy and stroke are the most common neurological syndromes associated with SARS-CoV-2 infection, though many others have been reported. Analysis of human biopsy samples suggests that anosmia results predominantly from SARS-CoV-2 infection of non-neuronal cells in the olfactory epithelium and olfactory bulb, leading to local inflammation and neuronal malfunction. Moreover, a high proportion of patients admitted to intensive care units with COVID-19 develop delirium, and evidence suggests that this is caused by microvascular and inflammatory mechanisms. Furthermore, autopsy data show activation of astrocytes and microglia in COVID-19, particularly in the brainstem, where there is also infiltration of cytotoxic T cells. Finally, SARS-CoV-2 can be detected in the brain with PCR and immunohistochemistry, but the evidence to date suggests it is mostly in vascular and immune cells rather than directly infecting neurons.