Spectrum of Hemorrhagic Encephalitis in COVID-19 Patients: A Case Series and Review

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is an ongoing pandemic that has affected over 400 million people worldwide and caused nearly 6 million deaths. Hemorrhagic encephalitis is an uncommon but serious complication of COVID-19. The etiology of this disease is multifactorial, including secondary to severe hypoxemia, systemic inflammation, direct viral invasion, hypercoagulability, etc. The clinical spectrum of COVID-19-related hemorrhagic encephalitis is also varied, ranging from leukoencephalopathy with microhemorrhage, acute necrotizing hemorrhagic encephalitis (ANHE) involving the cortex, basal ganglia, rarely brain stem and cervical spine, hemorrhagic posterior reversible encephalopathy syndrome (PRES) to superimposed co-infection with other organisms. We report a case series of three young patients with different presentations of hemorrhagic encephalitis after COVID-19 infection and a review of the literature. One patient had self-limiting ANHE in the setting of mild COVID-19 systemic illness. The second patient had self-limiting leukoencephalopathy with microhemorrhages in the setting of severe systemic diseases and ARDS, and clinically improved with the resolution of systemic illness. Both patients were healthy and did not have any premorbid conditions. The third patient with poorly controlled diabetes and hypertension had severe systemic illness with neurological involvement including multiple ischemic strokes, basal meningitis, hemorrhagic encephalitis with pathological evidence of cerebral mucormycosis, and Epstein-Barr virus coinfection, and improved after antifungal therapy.