The neuropathology spectrum in deceased patients with COVID-19

There is increasing evidence of neurological and psychiatric manifestations in patients with COVID-19 [1, 2]. Recent postmortem studies reported a large spectrum of neuropathological features that support the neuro-invasive potential of SARS-CoV-2 [3-5]. Given the complex pathophysiology of COVID-19 associated neurological manifestation, the pathological changes observed at postmortem examination often reflect the combination of both direct and indirect cytopathic effects mediated by the virus, as well as of nonspecific complications of severe disease in the deceased patients with COVID-19 (i.e. critical illness-related encephalopathy [6]; and/or pre-existing medical conditions). Thus, all these factors need to be considered when interpreting neuropathological findings [3, 7]. Hypoxia-ischemia, observed in the majority of critically ill cases of Covid-19, does not account for all relevant neuropathological observations provided by postmortem neuropathological studies in single cases or small patient cohorts [8-14]. However, among these studies the extent and significance of neuroinflammatory changes associated with SARS-CoV-2 infection are still matter of discussion, with often contradictory conclusions. In particular, it remains unclear to what extent the reported microglia activation and occasionally the presence of sparse lymphocytic infiltrates (T lymphocytes) represents COVID-19-specific findings [6, 7].