Background We report the first case of COVID-19 associated acute necrotizing encephalopathy (ANE) without pulmonary disease in a patient with an extremely high interleukin-6 (IL-6) level and Ran Binding Protein 2 (RANBP2) mutation. Case presentation A 29-year-old woman recently immunized with inactivated viral vaccine—BBIBP32-CorV (Sinopharm) presented with alteration of consciousness. Her body temperature was 37° Celsius, blood pressure 42/31 mmHg, heart rate 130 bpm, respiratory rate 20 per minute, and oxygen saturation 98%. Respiratory examination was unremarkable. Neurological examination revealed stupor but preserved brainstem reflexes. Non-contrast computerized tomography of the brain showed symmetrical hypodense lesions involving bilateral thalami and cerebellar hemispheres characteristic of ANE. No pulmonary infiltration was found on chest radiograph. SARS-CoV-2 was detected by PCR; whole genome sequencing later confirmed the Delta variant. RANBP2 gene analysis revealed heterozygous Thr585Met mutation. Serum IL-6 was 7390 pg/mL. Urine examination showed pyelonephritis. Her clinical course was complicated by seizure, septic shock, acute kidney injury, and acute hepatic failure. She later developed coma and passed away in 6 days. Conclusions ANE is caused by cytokine storm leading to necrosis and hemorrhage of the brain. IL-6 was deemed as a prognostic factor and a potential treatment target of ANE in previous studies. RANBP2 missense mutation strongly predisposes this condition by affecting mitochondrial function, viral entry, cytokine signaling, immune response, and blood–brain barrier maintenance. Also, inactivated vaccine has been reported to precipitate massive production of cytokines by antibody dependent enhancement (ADE). The true incidence of COVID-19 associated ANE is not known as were the predictors of its development. We proposed these potential two factors (RANBP2 mutation and ADE) that could participate in the pathogenesis of ANE in COVID-19 apart from SARS-CoV2 infection by itself. Further study is needed to confirm this hypothesis, specifically in the post-vaccination period. Role of RANBP2 mutation and its application in COVID-19 and ANE should be further elaborated.

Introduction Phosphorylated tau (p‐tau)181 has become a promising blood‐based Alzheimer's disease (AD) biomarker. We studied the agreement of plasma p‐tau181 and cerebrospinal fluid (CSF) markers in patients with alteration of consciousness (AOC). Methods Plasma and CSF were simultaneously collected in participants presenting with AOC. Plasma p‐tau181 was measured using the single‐molecule array. CSF biomarkers were classified according to the amyloid/tau/neurodegeneration (AT[N]) framework. Results Among participants enrolled, the median (interquartile range) age was 57 (28.5–75) years and 5.8% had AD. Plasma p‐tau181 yielded area under the curve of 0.85 and showed moderate correlation with CSF p‐tau181 (Rho = 0.42, P < .001). Using the historical cut‐point, many non‐AD participants had elevated plasma p‐tau181 resulting in a specificity of 0.57. Plasma p‐tau181 correlated with the glomerular filtration rate (Rho = –0.52, P < .001). Among A− participants with elevated plasma p‐tau181, 42% had kidney dysfunction. Discussion Plasma p‐tau181 showed inadequate specificity in patients with AOC partially attributable to concomitant kidney dysfunction.