Neuropathological findings in COVID-19: an autopsy cohort

Abstract

The literature regarding the neuropathological findings in cases of SARS-CoV-2 infection, which causes coronavirus disease 2019 (COVID-19), is expanding. We identified 72 patients who died of COVID-19 (n = 48) or had recovered shortly before death (n = 24) and had autopsies performed at our institution (49 males, 23 females; median age at death 76.4 years, range: 0.0–95.0 years). Droplet digital polymerase chain reaction (ddPCR) for the detection of SARS-CoV-2 was performed (n = 58) in multiple brain regions. In cases the assay was successfully completed (n = 50), 98.0% were negative (n = 49) and 2% were indeterminate (n = 1). Most histologic findings were typical of the patient age demographic, such as neurodegenerative disease and arteriolosclerosis. A subset of cases demonstrated findings which may be associated with sequelae of critical illness. We identified 3 cases with destructive perivascular lesions with axonal injury, one of which also harbored perivascular demyelinating lesions. These rare cases may represent a parainfectious process versus sequelae of vascular injury. The lack of detectable SARS-CoV-2 by ddPCR or significant histologic evidence of direct infection suggests that active encephalitis is not a feature of COVID-19.

Severe CTE and TDP-43 pathology in a former professional soccer player with dementia: a clinicopathological case report and review of the literature

“…Although APP leakage has been described in brains of subjects that died after hypoxic or ischemic events, the typical pattern of hypoxic APP leakage is not observed in this case [ 40 ]. Post-mortem indications for axonal injury (including positive APP staining) have also been described in three cases with a recent COVID-19 infection, but we did not observe other acute pathologies related to COVID-19, such as hemorrhagic lesions or microvascular injury [ 41 , 42 ]. APP positivity has also been reported after traumatic diffuse axonal injury, or exposure to multiple blast injuries, even years after the injury [ 40 , 43 – 45 ].…”

On the merits and potential of advanced neuroimaging techniques in COVID-19: A scoping review

“…However, the COVID-19 decedents did not have more severe axonal damage than the non-COVID-19 pneumonia control patients alone. Multiple other studies also did not observe damage specific to COVID-19, as the histological findings were typically age-related ( Eschbacher et al, 2022 , Serrano et al, 2021 ), were similar to abnormalities observed in non-COVID-19 severely ill patients ( Gelpi et al, 2023 ), and corresponded with sequelae of critical illness or treatment ( Gelpi et al, 2023 , Normandin et al, 2023 , Eschbacher et al, 2022 ). These studies did not find clear evidence of viral infection of the brain, which is in line with many studies failing to detect viral protein in most COVID-19 decedents ( Agrawal et al, 2022 , Fabbri et al, 2022 , Gelpi et al, 2023 , Normandin et al, 2023 , Ruz-Caracuel et al, 2022 , Khan et al, 2022 , Khan et al, 2021 , Eschbacher et al, 2022 , Serrano et al, 2021 ).…”

“…Multiple other studies also did not observe damage specific to COVID-19, as the histological findings were typically age-related ( Eschbacher et al, 2022 , Serrano et al, 2021 ), were similar to abnormalities observed in non-COVID-19 severely ill patients ( Gelpi et al, 2023 ), and corresponded with sequelae of critical illness or treatment ( Gelpi et al, 2023 , Normandin et al, 2023 , Eschbacher et al, 2022 ). These studies did not find clear evidence of viral infection of the brain, which is in line with many studies failing to detect viral protein in most COVID-19 decedents ( Agrawal et al, 2022 , Fabbri et al, 2022 , Gelpi et al, 2023 , Normandin et al, 2023 , Ruz-Caracuel et al, 2022 , Khan et al, 2022 , Khan et al, 2021 , Eschbacher et al, 2022 , Serrano et al, 2021 ). However, viral protein has been found in the brainstem ( Matschke et al, 2020 ) and viral antigen has been detected in cells expressing the ACE2-receptor – a receptor known for the SARS-CoV-2 virus to bind ( Beyerstedt et al, 2021 ) – in the vascular compartment ( Schwabenland et al, 2021 ).…”

Neuroimaging of COVID-19

“…This manifested as punctate and linear hypointensities on susceptibility-weighted imaging (SWI), which may correspond to the perivascular “ball-and-ring” hemorrhages reported in the pathology literature. 51 52 Microhemorrhages have mainly been reported in the corpus callosum and subcortical and deep hemispheric white matter ( Fig. 6 ).…”