Table 3.

Neurologic manifestations of the human coronaviruses, and their potential etiologies

CNS manifestation	Potential pathogenesis
Febrile seizures in children	Fever as trigger, possible cytokine response to infection; no evidence of direct CNS viral effect
General seizures in adults and children	Uncertain trigger, may be generalized CNS response to systemic illness, inclusive of hypoxia, cytokine storm, and microvascular abnormalities; CNS virus (patients with CSF detection are documented) with possible neuronal infection (unproven); CNS inflammation (patients with CSF pleocytosis have been documented)
Meningitis and meningoencephalitis	Inflammatory cell invasion of CNS (documented through CSF analysis and rare post mortem cases), possible mononuclear cell trafficking with our without viral infection of monocytes; or immune response to primary brain infection of uncertain cell type (infection not well documented for many species)
Stroke (both large vessel ischemic infarction and intracranial hemorrhage)	Coronavirus-associated coagulopathy; antiphospholipid antibodies; direct endothelial infection
Anosmia and hypogeusia	Infection of nasopharyngeal mucosa (well documented); possible infection of neuroepithelium (not established); concern for olfactory bulb, tract, and primary cortical infection (not documented in humans)
Non-focal phenomena: changes in sensorium including lethargy and confusion; agitation; dizziness; headache	Possibly a generalized CNS response to hypoxemia, cytokine storms, and microangiopathy of critical disease; or undisclosed inflammatory/infectious pathology in the absence of a diagnostic neurologic workup
Acute disseminated encephalomyelitis and hemorrhagic necrotizing encephalopathy	Para-infectious immune response