Pediatric Neurology and the COVID-19 Pandemic

Introduction: The Reduced Burden of COVID-19 on Childhood

Because children with COVID-19 are often asymptomatic or exhibit respiratory illness of only mild-to-moderate degree, the extent of disease in childhood is difficult to define with accuracy.

In reports skewed toward hospitalized and severely ill individuals from China, Italy, Spain, and the United States, children are found to comprise only 1%–2% of COVID-19 cases. On the other hand, children constitute up to 5%–13.7% of cases in Korea, Iceland, and Canada where broad population-based screening has been carried out.

Although it is uncertain why COVID-19 runs a mild course in most children, it is hypothesized that children may have higher antibody leveIs because of their frequent exposure to respiratory illnesses and that the pediatric immune system may respond differently to the virus. In children, reduced expression and binding ability of the ACE2 receptor, which negotiates entry of SARS-CoV-2 into human cells, may play a role in the attenuated vulnerability of children to severe infection.

In a series of 2143 Chinese pediatric cases, symptoms were mild in 50.9%, moderate in 38.8%, and 4.2% were asymptomatic. Severe disease was noted in only 2% of children and only 0.6% developed acute respiratory distress syndrome and multiorgan failure. This rate of critical illness was significantly lower than the 18.5% rate reported in adults.

In a descriptive study of 130 children from 28 hospitals in Italy, 75.4% had asymptomatic or mild disease. In all, 11.5% needed respiratory support and 6.9% were treated in an intensive care unit. There were no deaths. Of 57 children identified in a large community-based hospital system in the first 5 weeks of the Houston pandemic, the majority had the mild illness. Hospital admission was necessary for 14%.

A 25 country European multicenter cohort study of 582 children with COVID-19 reiterated that COVID-19 is generally a mild disease in children and infants. Only a small proportion of children required admission to ICU (8%) or mechanical ventilation (4%). Only 3% required inotropic support and only one child (< 1%) necessitated extracorporeal membrane oxygenation (ECMO). Four children died (case fatality rate of 0.69%). The remaining 578 were alive and only 4% of them were still symptomatic or requiring some kind of respiratory support.

In a cross-sectional report of the clinical course of critically ill infants and children with COVID-19 at 46 pediatric hospitals in North America between March 14 and April 3, 2020, it was remarkable that only 35% of the hospitals participating in the study reported admissions of children with COVID-19 infection to the PICU. Of the 48 children in this series, 38% required invasive ventilation, and all but two survived, reflecting the markedly decreased burden of disease from COVID-19 on children.

COVID-19 in the Fetus and Newborn

COVID-19 may also affect the fetus and the newborn. A review of nine case series and two case reports from Wuhan described outcomes of maternal COVID-19 infection during pregnancy in 65 women and 67 neonates. Two mothers (3%) were admitted to the ICU. Fetal distress was reported in 30% of pregnancies. Preterm birth occurred in 37% of the women. Neonatal complications included respiratory distress or pneumonia (18%), disseminated intravascular coagulation (3%), asphyxia (2%), and two perinatal deaths. Stringent measures to prevent transmission during delivery and separation of mother and child did not prevent infection in four neonates (three with pneumonia), suggesting the possibility of vertical transmission.

Risk Factors for Severe Disease

Presenting symptoms of COVID-19 in childhood include cough (48%), fever (47%), and sore throat or pharyngitis (28.6%). Other respiratory symptoms such as rhinorrhea, sneezing, and nasal congestion are less common. Vomiting or nausea occurs in 7.8% of cases and diarrhea in 10.1%.

Infants and preschool children are more likely to exhibit severe disease. In a systematic review of the literature, 27% of children hospitalized because of COVID-19 were under 1 year of age. As in adults, comorbidities such as chronic lung disease (asthma), cardiovascular disease, and immunosuppression may predispose to severe illness. In a CDC report, 28 of 37 (77%) hospitalized children had one or more underlying conditions. In a multicenter cohort study from Europe, neurological comorbidities were noted in 26 among 582 children, nine of whom had epilepsy and eight had cerebral palsy. Ten other children had chromosomal abnormalities, eight of whom with trisomy 21.