Author: Jeff Campbell, Fellow, Boston Children’s, Harvard

Background

Following the emergence of SARS-CoV-2 in Wuhan, China in December 2019, early epidemiological reports using data reported to the Chinese government suggested that increasing age was associated with severe symptoms and poor clinical outcomes. Although these reports identified SARS-CoV-2 infection in children, they did not provide thorough clinical descriptions or details of outcomes.

Methods

To fill the early hole in reported disease characteristics in children, Liu and colleagues1 and Lu and colleagues2 conducted retrospective case series of children with SARS-CoV-2 infection in Wuhan. Early in the epidemic, Liu and colleagues reviewed records of children (≤16 years old) with respiratory infections hospitalized from January 7–January 15 in central Wuhan’s Tongji hospital system. After the epidemic had grown, Lu and colleagues reviewed records of children (<16 years old) treated for SARS-CoV-2 infection at the Wuhan Children’s Hospital between January 28 – February 26. Both teams diagnosed SARS-CoV-2 infection using RT-PCR from nasopharyngeal or throat swabs, and assessed clinical features, treatment, and outcomes for PCR-positive patients. Both groups used frequencies and proportions to summarize data; neither performed comparison-group analysis.

Results

Of 366 hospitalized children reviewed, Liu and colleagues identified 6 (1.6%) (median age 3 [range 1-7]) with SARS-CoV-2 infection, all of whom had been previously healthy. Clinical features included fever (6/6), cough (6/6), and vomiting (4/6). Four patients had lung abnormalities on chest CT. One patient developed hypoxia and required PICU admission but like the other five patients, she recovered. Patients in this case series received a variety of therapies, including ribavirin (2/6), oseltamivir (6/6), IVIg (1/6), and glucocorticoids (4/6). Lu and colleagues identified 171 children (median age 6.7 [range 1 day – 15 years]) infected with SARS-CoV-2, out of 1391 patients tested. Common clinical features were fever (41.5%), cough (48.5%) and pharyngeal erythema (46.2%); less frequent symptoms included diarrhea, fatigue, rhinorrhea/congestion, and vomiting. By chest CT, 64.9% of children had pneumonia. Three patients developed severe illness requiring mechanical ventilation. All three had pre-existing illness (hydronephrosis, intussusception, leukemia on maintenance chemotherapy). One of these patients (with intussusception) died of multi-organ failure after 4 weeks of hospitalization. In contrast, at time of publication, the remaining children were either in stable condition on the wards or had been discharged home. Notably, 15.8% of children were found to be asymptomatic with no radiographic features of infection.

Limitations

Both studies are small, geographically restricted, retrospective case series, and may not fully capture the range of pediatric clinical manifestations of SARS-CoV-2 infection—particularly asymptomatic or minimally symptomatic children who did not present for care or were not hospitalized. Patients in both case series were relatively young: patients over age 16 were excluded in both series, although newer data suggest that older adolescents may have different clinical features and trajectories than young children. At the other extreme of age, although Lu and colleagues report that they include children as young as 1 day old, unique clinical features or details on virus acquisition in neonates or infants are not provided (notably, another publication reports on neonates infected with SARS-CoV-2 at Wuhan Children’s Hospital born in January and February;3 it is unclear if the same patients are included in both publications). Finally, these case series include few patients with pre-existing conditions, and shine only faint light on how SARS-CoV-2 may affect children with baseline comorbidities.

Conclusions

These case series report the earliest detailed descriptions of SARS-CoV-2 infection in children under 16 years old. Hospitalized children in these studies generally experienced mild illness, with symptoms of fever and cough predominating. Radiographic features of pneumonia were common. Despite generally benign clinical courses in most patients, some children did develop critical illness, and one patient died.

In Context

Liu and colleagues conducted their review when the epidemic was nascent in Wuhan, while Lu and colleagues reported on children hospitalized during the epidemic’s peak in the region. Their reports are the first in what has become a growing bibliography of pediatric SARS-CoV-2 case series. Subsequent series have largely reaffirmed these teams’ observations that SARS-CoV-2 infection typically produces mild clinical illness in infected children. To date, there have been scant data published on infection in children with underlying comorbidities. Reported mortality has remained thankfully rare.

References:

  1. Liu W, Zhang Q, Chen J, Xiang R, Song H, Shu S, et al. Detection of Covid-19 in Children in Early January 2020 in Wuhan, China. The New England journal of medicine. 2020.
  2. Lu X, Zhang L, Du H, Zhang J, Li YY, Qu J, et al. SARS-CoV-2 Infection in Children. The New England journal of medicine. 2020.
  3. Zeng L, Xia S, Yuan W, Yan K, Xiao F, Shao J, et al. Neonatal Early-Onset Infection With SARS-CoV-2 in 33 Neonates Born to Mothers With COVID-19 in Wuhan, China. JAMA Pediatr. 2020.