Correlates of critical illness-related encephalopathy predominate postmortem COVID-19 neuropathology

Neurological manifestations associated with SARS-CoV-2 and other coronaviruses: A narrative review for clinicians

“…The cytokine storm is also suspected of being involved in cytotoxic lesions of the corpus callosum, described in COVID-19 adult patients [9] , [22] and pediatric patients [45] , [46] , [47] . Some histopathological findings also supported the hypothesis of a critical illness-related encephalopathy [39] . Finally, endothelitis [29] , [48] and microvascular injury [37] , [38] may play a role in the pathogenesis of the encephalopathy,…”

“…Other studies have reported several hypoxic and hemorrhagic neuropathological changes in severe COVID-19 patients, such as acute hypoxic injury in the cerebrum and cerebellum [35] , widespread hemorrhagic white matter lesions and neocortical infarcts [36] , [37] , [38] , with no thrombi, encephalitis or vasculitis. One study found microglia activation in the brainstem of seven COVID-19 patients with strong systemic inflammation, but not more pronounced than in septic controls [39] . These studies did not support evidence for virus infiltration, and only a single autopsy case so far documented the presence of SARS-CoV-2 in endothelial and neural cells of frontal lobe sections [40] .…”

Neurological infections in 2020: COVID-19 takes centre stage

“…The most common brain autopsy findings in patients with SARS-CoV-2 infections are also commonly seen in patients who die of other severe illnesses. 9 Therefore, neuropathological changes such as reactive gliosis, mild chronic perivascular inflammatory infiltrates, and acute hypoxic–ischaemic injury in patients with SARS-CoV-2 infections probably reflect critical illness-related, non-specific changes rather than specific abnormalities induced by the virus.…”

Investigations of Pathologists as a Key to Understanding Coronavirus Disease 2019

“…Autopsy could also help to define high-risk patient cohorts and contribute to answering the question whether patients tested positive for SARS-CoV-2 and/or displaying symptoms of COVID-19 were dying with or of the disease [2, 5]. COVID-19 has led to an unprecedented flood of publications and theories related to the disease leading to controversies and uncertainties regarding many aspects, ranging from the occurrence of endothelialitis [6, 7] and the question of virally induced acute kidney injury [8] or encephalitis [9] to the visualisation of SARS-CoV-2 by electron microscopy [7]. To resolve these open issues, comprehensive and in-depth studies and larger meta-analyses will be needed, to which currently Pathobiology is contributing a dedicated fascicle.…”

“…However, they also raise the question whether coagulopathies seen in COVID-19 should rather be seen in the context of generalized inflammatory response and not as being a unique specific feature. Indeed, a report of an autopsy series focusing on liver pathology by Schmit et al [13] from Belgium showed that liver findings are primarily to be interpreted as secondary changes due to hypoxia or drug toxicity, in line with neuropathological data on COVID-19, which is likely a correlate of critical illness-related encephalopathy and thus not a result of virally induced damage [9].…”