Acute Meningoencephalitis as Initial Presentation of SARS-CoV-2 Infection in Pediatrics.

Abstract

To the Editors: We read with great interest the recently published article by Lorenz et al describing a newborn with acute encephalitis caused by SARS-CoV-2. Acute meningoencephalitis in children is mostly of viral origin, without long-term damage. We describe an infant with acute meningoencephalitis a initial presentation of COVID-19, with a very suggestive picture of Enterovirus infection, manifested with respiratory, gastrointestinal, and neurologic symptoms. This case description adds to the broad clinical spectrum of COVID-19 in pediatrics, a disease with newly described findings every day. A 5-month-old infant presented to the emergency department with 4 days of fever, vomiting, loose stools, cough, without respiratory distress. Clinical evaluation revealed a bulging anterior fontanel, neck stiffness, and excessive irritability. After performance of a lumbar puncture, empirical vancomycin, ceftriaxone, and dexamethasone were initiated. Cerebrospinal fluid (CSF) analysis was abnormal with high proteins (164.4 mg/dL), normal glucose (59 mg/dL), and elevated white cells (22 cells/μL), with 12 cells/μL neutrophils, 10 cells/μL monocytes, 0 erythrocytes. CSF FilmArray (BioFire Diagnostics), Gram and Ziehl Neelsen stain, India ink, molecular analysis for M. tuberculosis complex (Xpert MTB/RIF) and stool Rotavirus, and Adenovirus antigens were negative. An initial nasopharyngeal real-time polymerase chain reaction (RT-PCR) for SARS-CoV-2 was negative. Two days after admission, the child presented with obnubilation and 3 episodes of generalized seizures. Phenobarbital was initiated. A cerebral CT scan was normal. Bleeding times were prolonged. A repeat nasopharyngeal RT-PCR for SARS-CoV-2 was positive, consistent with acute COVID-19. No IgG serology for SARS-CoV-2 was performed, since acute COVID-19 was suspected and had already been confirmed with a positive specific molecular test. Cerebral magnetic resonance image was abnormal, with hypointensities in cerebellum, compatible with bleeding. A second lumbar puncture on the fifth day after admission reported elevated proteins (262 mg/dL), normal glucose (36 mg/dL), pleocytosis with neutrophil predominance (leukocytes: 108 cells/μL, neutrophils: 91 cells/μL, monocytes: 17 cells/μL, erythrocytes: 720 cells/μL), with negative CSF RT-PCR for SARS-CoV-2. Again, BioFire Film Array Meningitis/Encephalitis (ME) panel was negative. Dengue specific IgG, IgM, and NS1 antigen were nonreactive. Electroencephalographic changes described abnormal diffuse cerebral dysfunction. Considering possible multisystem inflammatory syndrome in children (MIS-C) following SARS-CoV-2 infection, a single dose of intravenous immunoglobulin of 2 g/kg was administered. Complete resolution of neurologic compromise was accomplished. Neurologic compromise by SARS-CoV-2 in pediatrics is not unusual. According to Toubiana et al,1 headache is reported in 29%, irritability in 57%, meningismus in 30% of cases. Acute meningoencephalitis, however, has not been considered a common presentation of COVID-19 in pediatrics, and first reports were described in adult patients. In the last 2 months, we found 3 reports of pediatric patients with SARS-CoV-2 associated meningoencephalitis.2–4 After reviewing these pediatric and adult reports, we noticed that CSF cytochemical characteristics, as in our patient, are consistent with high-protein levels, associated with abnormal cellularity, with low-cellular counts (<500 cells/μL), with acute clinical presentation. Also important is that PCR for SARS-CoV-2 in meningoencephalitis is infrequently positive on CSF, a case described only in 1 Japanese patient, and respiratory specimens remain as the sites of diagnosis for SARS-CoV-2 with specific RT-PCR.5 Concomitant respiratory and gastrointestinal symptoms were suggestive of Enterovirus-meningoencephalitis but not the finding of hyperproteinorrachy. CSF BioFire Film Array Meningitis/Encephalitis (ME) panel that includes Enterovirus detection was negative. Gastrointestinal symptoms in COVID-19 are reported in 80%–100% of children.1 With the present pandemic, acute meningoencephalitis suggestive of Enterovirus infection can be the initial presentation of COVID-19 in pediatrics, and physicians should be aware and familiar with this clinical presentation. Catalina Arango Ferreira, MDDepartment of Pediatrics, Universidad de Antioquia, Hospital Universitario San Vicente Fundación, Medellín, Colombia Manuela Correa-Rodas, MDDepartment of Pediatrics, Universidad de Antioquia, Medellín, Colombia