key: cord-0946008-qhp8txs2 authors: Mierzewska-Schmidt, Magdalena; Baranowski, Artur; Szymanska, Krystyna; Ciaston, Michal; Kuchar, Ernest; Ploski, Rafal; Kosinska, Joanna; Pagowska-Klimek, Izabela title: The case of fatal acute hemorrhagic necrotizing encephalitis in a two-month-old boy with Covid-19. date: 2021-12-18 journal: Int J Infect Dis DOI: 10.1016/j.ijid.2021.12.334 sha: de629eadffd2f6ee398a5cf7097f385f6dc4fb8b doc_id: 946008 cord_uid: qhp8txs2 SARS-CoV-2 infection in healthy children is usually benign. However severe, life-threatening cases have previously been reported, noticeably in infants. We must be aware that data on natural history of COVID-19 are still full of gaps, especially as far as pediatric population is concerned. Therefore, it is important to describe rare manifestations of SARS-CoV-2 acute infection in children. Here we present the case of acute hemorrhagic necrotizing encephalitis (AHNE) in a previously healthy, 2-month-old infant with SARS-CoV-2 infection. After 2 days of fever with signs of respiratory tract infection, neurological manifestations appeared: irritability, nystagmus, agitation then apathy. As a consequence of apnea, he required emergent intubation and was transferred to our PICU. Brain MRI revealed diffuse areas of oedema associated with numerous symmetrical changes with punctate hemorrhages in basal ganglia, thalami, brainstem, and cerebral gray matter. CSF was clear with pleocytosis 484 cells/µl, elevated lactic acid and protein. Despite broad microbiological testing only SARS-CoV2 was detected in PCR nasal swab. Therefore, acute hemorrhagic necrotizing encephalitis (AHNE) as a result of COVID- 19 was the most probable diagnosis. The outcome was unfavorable - brain death was confirmed, life support was withdrawn. concerned. Therefore, it is important to describe rare manifestations of SARS-CoV-2 acute infection in children. Here we present the case of acute hemorrhagic necrotizing encephalitis (AHNE) in a previously healthy, 2-month-old infant with SARS-CoV-2 infection. After 2 days of fever with signs of respiratory tract infection, neurological manifestations appeared: irritability, nystagmus, agitation then apathy. As a consequence of apnea, he required emergent intubation and was transferred to our PICU. Brain MRI revealed diffuse areas of oedema associated with numerous symmetrical changes with punctate hemorrhages in basal ganglia, thalami, brainstem, and cerebral gray matter. CSF was clear with pleocytosis 484 cells/µl, elevated lactic acid and protein. Despite broad microbiological testing only SARS-CoV2 was detected in PCR nasal swab. Therefore, acute hemorrhagic necrotizing encephalitis (AHNE) as a result of COVID-19 was the most probable diagnosis. The outcome was unfavorable -brain death was confirmed, life support was withdrawn. An area of lower density in the left insula was found, so edema or encephalitis was suggested. On cranial ultrasound, meningitis was suspected. Analgosedation with morphine and midazolam was started, and 3% hypertonic saline was administered. On the second day, he was unconscious, his pupils were fixed and dilated, corneal, and gag reflexes were absent, with absent respiratory drive and motor response to painful stimuli. Global hypotonia and lack of deep reflexes were observed. His anterior fontanelle was remarkably elevated. The MRI (Fig. 1 ) revealed diffuse areas of edema associated with numerous symmetrical changes with punctate hemorrhages in basal ganglia, thalami, brainstem, and cerebral gray matter. It was suggested that Acute Hemorrhagic Necrotizing Encephalitis (AHNE) or Acute Necrotizing Encephalopathy (ANE) triggered by a viral infection should be considered. As ANE may result from genetic mutations, e.g., the RANBP2I gene and mitochondrial disease, genetic (including WES -Whole Exome Sequencing) and metabolic testing were performed. All the obtained laboratory results were negative, including bacterial cultures, except for repeated positive PCR swabs for SARS-CoV-2. Immunoglobulin treatment was considered, but due to neurologic sequelae, it was not administered. The later course of the disease was unfavorable. The baby showed signs of brain death. After confirming the diagnosis ventilatory support was switched off. Severe neurologic complications of pediatric COVID-19 are rare. They were more commonly parenchymal changes on neuroimaging. Its pathophysiology is unclear, but the immune mechanism is probably involved. Importantly, it is not considered inflammatory encephalitis as there are no signs of inflammation in the CSF (pleocytosis extremely rare) or the brain [Mizuguchi M. 1997 ]. The vast majority of SARS-CoV-2-related neurologic problems concern the adult population. Pediatric COVID-19 is commonly perceived as benign, with most severe cases concerning children with MIS-C/PIMS-TS. Severe neurologic manifestations in children are sporadic and data are sparse. The presented case with the fatal outcome is the first to our knowledge report of AHNE in, a previously healthy, SARS-CoV-2 acutely infected infant. The authors declare no conflict of interest. There was no funding for this case report. This case report complies ethical standards as we received the parental consent for publication. Hacohen Y. 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