Cerebrovascular Disease in COVID-19

DISCUSSION

A recent case series of 214 patients with COVID-19 from Wuhan, China, reported that 36% of patients demonstrated neurologic manifestations, and acute cerebrovascular disease was reported in 6% of severely affected patients.⁵ The precise mechanism for the cerebral ischemia in the clinical setting of COVID-19 is not known, but there is strong evidence for the development of a transient hypercoagulable state, especially in severe disease.⁷

In a study of 191 patients with COVID-19 in Wuhan, China, researchers found that D-dimer levels of >1 µg/L were associated with an 18-fold increase in odds of death before discharge.² D-dimer is a product of fibrin clot degradation and is indicative of recent or current clot formation.

In Zhou et al,² patients with COVID-19 with an elevated serum ferritin level of >300 µg/L had a 9-fold increase in the odds of death before discharge. Hyperferritinemia, although nonspecific, can be a marker of an inflammatory response.⁸ Hyperferritinemia can also be seen in the antiphospholipid syndrome and its variant, catastrophic antiphospholipid syndrome, both of which are associated with arterial and venous thromboses.⁹ This patient with hyperferritinemia also had elevated anticardiolipin immunoglobulin M antibodies, and antiphospholipid syndrome has been recently implicated in the coagulopathy associated with cerebral ischemia in patients with COVID-19.¹⁰

Endothelial damage may also play a role in the pathogenesis of cerebral ischemia in severe COVID-19. Specifically, SARS-CoV-2 infects cells via binding of the spike protein of the virus to the angiotensin converting enzyme 2 (ACE2) receptors.¹¹ ACE2 receptors are found not only in the alveolar epithelial cells of the lungs but also in the vascular endothelium.¹² Therefore, patients with severe COVID-19 may be at risk of thrombogenesis and cerebral ischemia due to both biochemical hypercoagulable states and direct vascular endothelial injury. In our patient, this risk is a distinct possibility because there were large territorial infarcts despite the absence of an intracranial large-vessel occlusion.

In addition, myocardial injury has been reported in 22% of patients with COVID-19 requiring an intensive care unit, and cardiac embolization may also have a contributory role in COVID-19-related cerebral ischemia.¹³

Finally, this patient had evidence of atherosclerotic disease. Systemic infection, such as that demonstrated in this patient, is associated with activation of immune and inflammatory pathways leading to plaque disruption, serving as a source of thrombosis.¹⁴

This patient died on hospital day 3 due to COVID-19, and clinical and laboratory evaluations were incomplete; therefore, a more precise pathogenic mechanism of the cerebral infarcts in this patient is indeterminate. It is also not known why only a small percentage of severely affected patients with COVID-19 have cerebral ischemia, whereas most do not.

In conclusion, we report a case of COVID-19 with acute cerebrovascular disease. We believe this is the first published case to include angiographic imaging. Manifestations of COVID-19 are not limited to the respiratory system, and neuroradiologists should be aware of the associated cerebrovascular disease and its potential underlying etiologies.