Neurologic Aspects of Coronavirus Disease of 2019 Infection

Catherine E. Hassett; Jennifer A. Frontera


Curr Opin Infect Dis. 2021;34(3):217-227. 

In This Article

Hypoxic-ischemic Brain Injury

Severe hypoxemia and acute respiratory distress syndrome (ARDS) are hallmarks of severe SARS-CoV-2 infection. Consequences of prolonged hypoxemia include oligodendrocyte cell injury, blood–brain barrier disruption, and microhemorrhage formation.[38] Microscopic evidence of acute hypoxic injury was found in 18 COVID-19 patients whose clinical course was complicated by persistent confusional state or decreased arousal.[17] Histopathologic findings of neuronal loss noted in the typical CNS locations most affected by hypoxia including the cerebral cortex, hippocampus, and cerebellar Purkinje cell layers.[17,19]

Up to 1.4% of COVID-19 admissions have been found to have a hypoxic-ischemic brain injury, but this may be an underestimation.[34] This type of brain injury is not always apparent on CT imaging and may require additional neuroimaging. Typical posthypoxic MRI brain findings of leukoencephalopathy, white matter cytotoxic edema, and cerebral microbleeds have been described in COVID-19 patients with hypoxic-ischemic encephalopathy.[38–42] In addition, delayed posthypoxic leukoencephalopathy (DPHL) has been observed in COVID-19 patients with a profound neurologic deterioration occurring 1–4 weeks after the initial hypoxic insult.[42] Unlike the glutamate excitotoxicity driving acute hypoxic-ischemic brain injury, DPHL pathophysiology stems from necrosis of oligodendrocytes in arterial border zones leading to widespread, axonal-sparing demyelination.[42,43] It is important to recognize the consequence of prolonged hypoxia as COVID-related hypoxic brain injury has been associated with a 43% increased risk of in-hospital mortality.[34]