Three-stage classification of the impact of COVID-19 on the central nervous system

A new review (Journal of Alzheimer's Disease) outlines a three-stage classification of the impact of COVID-19 on the central nervous system and recommends hospitalized patients with the virus all undergo MRI to flag potential neurologic damage and inform postdischarge monitoring.

In stage 1, viral damage is limited to epithelial cells of the nose and mouth, and in stage 2 blood clots that form in the lungs may travel to the brain, leading to stroke. In stage 3, the virus crosses the blood-brain barrier and invades the brain.

According to the authors hospitalized patients with COVID-19 should have a neurological evaluation and ideally a brain MRI before leaving the hospital; and, if there are abnormalities, they should follow up with a neurologist in 3 to 4 months.

It has become "increasingly evident" that SARS-CoV-2 can cause neurologic manifestations, including anosmia, seizures, stroke, confusion, encephalopathy, and total paralysis.

SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2) that facilitates the conversion of angiotensin II to angiotensin. After ACE2 has bound to respiratory epithelial cells, and then to epithelial cells in blood vessels, SARS-CoV-2 triggers the formation of a "cytokine storm."

These cytokines, in turn, increase vascular permeability, edema, and widespread inflammation, as well as triggering "hypercoagulation cascades," which cause small and large blood clots that affect multiple organs.

If SARS-CoV-2 crosses the blood-brain barrier, directly entering the brain, it can contribute to demyelination or neurodegeneration.

Three-Stage Classification

Stage 1

The extent of SARS-CoV-2 binding to the ACE2 receptors is limited to the nasal and gustatory epithelial cells, with the cytokine storm remaining "low and controlled." During this stage, patients may experience smell or taste impairments, but often recover without any interventions.

Stage 2

A "robust immune response" is activated by the virus, leading to inflammation in the blood vessels, increased hypercoagulability factors, and the formation of blood clots in cerebral arteries and veins. The patient may therefore experience either large or small strokes.

Additional stage 2 symptoms include fatigue, hemiplegia, sensory loss, double vision, tetraplegia, aphasia, or ataxia.

Stage 3

The cytokine storm in the blood vessels is so severe that it causes an "explosive inflammatory response" and penetrates the blood-brain barrier, leading to the entry of cytokines, blood components, and viral particles into the brain parenchyma and causing neuronal cell death and encephalitis.

This stage can be characterized by seizures, confusion, delirium, coma, loss of consciousness, or death.

As a result, patients should be monitored over time after discharge, as they may develop cognitive dysfunction down the road.