Neuropathology of COVID-19: a spectrum of vascular and acute disseminated encephalomyelitis (ADEM)-like pathology

Abstract

We report the neuropathological findings of a patient who died from complications of COVID-19. The decedent was initially hospitalized for surgical management of underlying coronary artery disease. He developed post-operative complications and was evaluated with chest imaging studies. The chest computed tomography (CT) imaging results were indicative of COVID-19 and he was subsequently tested for SARS-CoV-2, which was positive. His condition worsened and he died after more than 2 weeks of hospitalization and aggressive treatment. The autopsy revealed a range of neuropathological lesions, with features resembling both vascular and demyelinating etiologies. Hemorrhagic white matter lesions were present throughout the cerebral hemispheres with surrounding axonal injury and macrophages. The subcortical white matter had scattered clusters of macrophages, a range of associated axonal injury, and a perivascular acute disseminated encephalomyelitis (ADEM)-like appearance. Additional white matter lesions included focal microscopic areas of necrosis with central loss of white matter and marked axonal injury. Rare neocortical organizing microscopic infarcts were also identified. Imaging and clinical reports have demonstrated central nervous system complications in patients' with COVID-19, but there is a gap in our understanding of the neuropathology. The lesions described in this case provide insight into the potential parainfectious processes affecting COVID-19 patients, which may direct clinical management and ongoing research into the disease. The clinical course of the patient also illustrates that during prolonged hospitalizations neurological complications of COVID may develop, which are particularly difficult to evaluate and appreciate in the critically ill.

COVID‐19: A Global Threat to the Nervous System

“…The lesions had features of both acute hemorrhagic leukoencephalitis and of acute disseminated encephalomyelitis. 53 The rarity of postinfectious potentially immunemediated cases following COVID-19 other than GBS and its variants, and the general paucity of details, makes their status unclear. The cases of ADEM-like illness are hard to distinguish from some of the patients with acute encephalopathy and associated MRI white matter lesions, but can be differentiated from cases of encephalitis by the absence of CSF pleocytosis.…”

Neurological manifestations of coronavirus infections – a systematic review

“…Signs of perivenular inflammation/demyelination suggestive of ADEM have also been described. 53,78 A neuropathological assessment of 18 SARS-CoV-2 patients showed changes consistent with hypoxic injury. However, RT-PCR and immunohistochemistry disclosed only minimal evidence of SARS-CoV-2 infection.…”

The SARS-CoV-2 main protease Mpro causes microvascular brain pathology by cleaving NEMO in brain endothelial cells

“…In COVID-19 patients, magnetic resonance imaging detected lesions that are compatible with a microvascular pathology [17][18][19][20][21] . Autopsy studies have con rmed this interpretation 17,[22][23][24] . However, the mechanisms that lead to small vessel disease in COVID-19 are still unclear.…”