Neuropathological findings in two patients with fatal COVID‐19

Neuropathological findings in two patients with fatal COVID‐19

Case 1 demonstrated multi‐territorial cerebral vascular injury with associated cerebral thrombotic microangiopathy; case 2 demonstrated a brainstem encephalitis centred on the dorsal medulla and a subacute regional infarct involving the cerebellar cortex. Viral RNA was not detected in post‐mortem br...

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Bibliographic Details
Published in:Neuropathology and applied neurobiology Vol. 47; no. 1; pp. 17 - 25
Main Authors: Jensen, M. P., Le Quesne, J., Officer‐Jones, L., Teodòsio, A., Thaventhiran, J., Ficken, C., Goddard, M., Smith, C., Menon, D., Allinson, K. S. J.
Format: Journal Article
Language:English
Published: England Wiley Subscription Services, Inc 01-02-2021
Subjects:
Aged
Autopsy
Brain - pathology
Brain Diseases - pathology
Brain Diseases - virology
Brain stem
Calcification
case series
Cerebellum
Cerebral infarction
Coronaviruses
COVID-19
COVID-19 - pathology
Encephalitis
Fatal Outcome
Humans
Hybridization
Invasiveness
Male
Medulla oblongata
Megakaryocytes
Neuropathology
Paraffin
Polymerase chain reaction
Reverse transcription
Ribonucleic acid
RNA
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
Thrombotic microangiopathy
COVID-19
SARS-CoV-2
case series
neuropathology
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Description
Summary:Case 1 demonstrated multi‐territorial cerebral vascular injury with associated cerebral thrombotic microangiopathy; case 2 demonstrated a brainstem encephalitis centred on the dorsal medulla and a subacute regional infarct involving the cerebellar cortex. Viral RNA was not detected in post‐mortem brain tissue, suggesting that these pathologies may not be a direct consequence of viral neuroinvasion and may represent para‐infectious phenomena, relating to the systemic hyperinflammatory and hypercoagulable syndromes that both patients suffered. Aims To describe the neuropathological findings in two cases of fatal Coronavirus Disease 2019 (COVID‐19) with neurological decline. Methods Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection was confirmed in both patients by reverse transcription polymerase chain reaction (RT‐PCR) from nasopharyngeal swabs antemortem. Coronial autopsies were performed on both patients and histological sampling of the brain was undertaken with a variety of histochemical and immunohistochemical stains. RNAscope® in situ hybridization (ISH) using the V‐nCoV2019‐S probe and RT‐PCR SARS‐CoV‐2 ribonucleic acid (RNA) was performed in paraffin‐embedded brain tissue sampled from areas of pathology. Results Case 1 demonstrated severe multifocal cortical infarction with extensive perivascular calcification and numerous megakaryocytes, consistent with a severe multi‐territorial cerebral vascular injury. There was associated cerebral thrombotic microangiopathy. Case 2 demonstrated a brainstem encephalitis centred on the dorsal medulla and a subacute regional infarct involving the cerebellar cortex. In both cases, ISH and RT‐PCR for SARS‐CoV‐2 RNA were negative in tissue sampled from the area of pathology. Conclusions Our case series adds calcifying cerebral cortical infarction with associated megakaryocytes and brainstem encephalitis to the spectrum of neuropathological findings that may contribute to the neurological decompensation seen in some COVID‐19 patients. Viral RNA was not detected in post‐mortem brain tissue, suggesting that these pathologies may not be a direct consequence of viral neuroinvasion and may represent para‐infectious phenomena, relating to the systemic hyperinflammatory and hypercoagulable syndromes that both patients suffered.
ISSN:0305-1846
1365-2990
DOI:10.1111/nan.12662