Encephalitis Associated with COVID-19 Infection in an 11-Year-Old Child

Abstract

Neurological complications associated with COVID-19 infection are not well understood in children or adults. An adult with acute necrotizing encephalitis associated with COVID-191Yeh E.A. Collins A. Cohen M.E. et al.Detection of coronavirus in the central nervous system of a child with acute disseminated encephalomyelitis.Pediatrics. 2004; 113: e73-e76Crossref PubMed Scopus (219) Google Scholar and a child with acute disseminated encephalomyelitis and non-COVID coronavirus2Poyiadji N. Shahin G. Noujaim D. et al.COVID-19-associated acute necrotizing encephalopathy: CT and MRI features.Radiology. 2020; : 201187Crossref PubMed Scopus (927) Google Scholar have been reported. The infection is typically mild in children, and no neurological complications were reported in the 171 children from Wuhan Children’s Hospital.3Lu X. Zhang L. Du H. et al.SARS-CoV-2 infection in children.N Engl J Med. 2020; 382: 1663-1665Crossref PubMed Scopus (1578) Google Scholar In preliminary data from US cases, headache was the only neurological symptom.4CDC COVID-19 Response TeamCoronavirus disease 2019 in children – United States, February 12-April 2, 2020.MMWR Morb Mortal Wkly Rep. 2020; 69: 422-426Crossref PubMed Scopus (0) Google Scholar We describe an 11-year-old previously well child who presented with status epilepticus requiring four anticonvulsant medications and cerebrospinal fluid evidence for encephalitis (921 red cells, 16 white cells, 8% neutrophils [normal 0% to 6%] with protein of 97 [normal: 40 to 170 mg/dL], and glucose of 92 [normal: 20 to 100 mg/dL]). He had a two-day history of generalized weakness without respiratory symptoms or fever at home; emergency room temperature was 102.7°F. Head computed tomography was negative. Electroencephalography revealed frontal intermittent delta activity. Nasopharyngeal swab was positive for COVID-19 as well as rhinovirus/enterovirus but the latter was absent in cerebrospinal fluid polymerase chain reaction. Recovery without treatment was complete in six days. We believe this is the first child reported with COVID-19 viral encephalitis, and the condition was reversible. How coronavirus affects the brain is not known. This child’s findings suggest that direct brain infection may be possible. An autoimmune process may also be possible. The acuteness of our patient’s neurological manifestations coupled with the occurrence of fever and generalized systemic weakness mitigates against a postinfectious process. Because the virus binds the surface spike protein to the human angiotensin-converting enzyme 2 receptor (ACE-2) and ACE-2 is present in the brain vascular endothelium, a vascular process with clotting and infarction may also be possible, although this was not the mechanism in our patient.5Clerkin K.J. Fried J.A. Raikhelkar J. et al.Coronavirus disease 19 (Covid-19) and cardiovascular disease.Circulation. 2020; 141: 1648-1655Crossref PubMed Scopus (964) Google Scholar, 6Zhang Y. Xiao M. Zhang S. et al.Coagulopathy and antiphospholipid antibodies in patients with Covid-19.N Engl J Med. 2020; 382: e38Crossref PubMed Scopus (1408) Google Scholar, 7Jiang T. Gao L. Lu J. et al.ACE2-Ang-(1-7)-Mas axis in brain: a potential target for prevention and treatment of ischemic stroke.Curr Neuropharm. 2013; 11: 209-217Crossref PubMed Scopus (91) Google Scholar Although preliminary, we recommend screening children presenting with encephalitis for COVID-19 as infected patients require special precautions to prevent further spread.