Acute necrotizing encephalopathy associated with COVID-19 in a pediatric patient and a systematic review

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, can lead to neurological complications such as acute necrotizing encephalopathy (ANE). However, the pathogenesis of ANE associated with COVID-19 remains unclear. We report a case of ANE associated with COVID-19 and then conducted a literature review using PubMed for cases reported up to June 30, 2024. Clinical data from 74 patients were analyzed. Among those with severe sequelae (n = 28), 39.2% (n = 11) had hemorrhagic findings on CT or MRI, significantly more than in the mild sequelae group (10.8% [n = 5], P = 0.04). 16 patients underwent genetic testing for RANBP2 mutations, of whom four (25%, n = 16) tested positive. These findings suggest that imaging evidence of hemorrhage may be a poor prognostic factor and that RANBP2 mutations could contribute to disease susceptibility. Further genetic studies involving larger cohorts are needed to better understand the mechanisms of ANE associated with COVID-19 and improve outcomes for affected patients.