Virologic Features of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Children

Abstract

Background: Data on pediatric coronavirus disease 2019 (COVID-19) has lagged behind adults throughout the pandemic. An understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral dynamics in children would enable data-driven public health guidance.

Methods: Respiratory swabs were collected from children with COVID-19. Viral load was quantified by reverse-transcription polymerase chain reaction (RT-PCR); viral culture was assessed by direct observation of cytopathic effects and semiquantitative viral titers. Correlations with age, symptom duration, and disease severity were analyzed. SARS-CoV-2 whole genome sequences were compared with contemporaneous sequences.

Results: One hundred ten children with COVID-19 (median age, 10 years [range, 2 weeks-21 years]) were included in this study. Age did not impact SARS-CoV-2 viral load. Children were most infectious within the first 5 days of illness, and severe disease did not correlate with increased viral loads. Pediatric SARS-CoV-2 sequences were representative of those in the community and novel variants were identified.

Conclusions: Symptomatic and asymptomatic children can carry high quantities of live, replicating SARS-CoV-2, creating a potential reservoir for transmission and evolution of genetic variants. As guidance around social distancing and masking evolves following vaccine uptake in older populations, a clear understanding of SARS-CoV-2 infection dynamics in children is critical for rational development of public health policies and vaccination strategies to mitigate the impact of COVID-19.

Keywords: SARS-CoV-2; pediatric COVID-19; viral dynamics.

Figure 1.

Coronavirus disease 2019 (COVID-19) disease severity and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load across age groups. A, Age of pediatric patients with SARS-CoV-2 infection, stratified by disease severity: asymptomatic (n = 27), mild disease, outpatient (n = 48), or moderate/severe COVID-19, hospitalized (n = 18). Analyzed by ordinary 1-way analysis of variance (ANOVA). B, SARS-CoV-2 viral load was quantified across a range of disease severities. Patients presenting with <10 days of symptoms were compared, including asymptomatic pediatric outpatients (n = 27), mildly symptomatic pediatric outpatients (n = 44), moderate/severe pediatric hospitalized patients with oxygen requirement (n = 18), and moderate/severe adult hospitalized patients (n = 29). Analyzed by ordinary 1-way ANOVA. C, Correlation of viral load and age, stratified by asymptomatic (n = 30), mild outpatient (n = 48), and moderate/severe hospitalized (n = 18) cohorts. Analyzed by Pearson correlation. D, Viral load of hospitalized adults (n = 29), hospitalized pediatric participants requiring respiratory support (n = 18), and pediatric outpatients with mild disease (n = 48), plotted against duration of symptoms. Dotted lines depict limit of detection. Analyzed by simple linear regression, comparison of slopes. ∗P < .05, ∗∗P < .01; ∗∗∗P < .001, ∗∗∗∗P < .0001; ns = not significant.

Figure 2.

Severe acute respiratory syndrome coronavirus 2 culture results across age groups and viral load. A and B, Samples with observable cytopathic effect (CPE) (culture positive [+], n = 31) or without observable CPE (culture negative [-], n = 95) plotted against viral load (A) and participant age (B) and compared using t test. C and D, Semiquantitative viral titer expressed as median tissue culture infectious dose (TCID₅₀)/mL for culture-positive samples plotted against corresponding viral load (C) or participant age (D). Analyzed using Pearson correlation. Dotted line depicts limit of detection. ∗∗∗∗P < .0001.

Figure 3.

Culture positivity and duration of symptoms. A, Viral load for each specimen was determined by quantitative polymerase chain reaction and plotted against the duration of symptoms (in days). Analysis by Pearson correlation. B, Viral load reported by binned duration of symptoms. Ordinary 1-way analysis of variance (ANOVA) used for analysis. C, Duration of symptoms for samples with observable cytopathic effect (CPE) (culture positive [+], n = 29) and without observable CPE (culture negative [-], n = 85). Analysis by t test. D, Semiquantitative viral titer reported by binned duration of symptoms, analyzed by ordinary 1-way ANOVA. Dotted lines depict limit of detection. ∗∗P < .01, ∗∗∗∗P < .0001.

Figure 4.

Phylogenetic analysis of pediatric and community severe acute respiratory syndrome coronavirus 2 sequences. Maximum likelihood tree generated from pediatric sequences (red) and 183 contemporaneous Massachusetts sequences from GISAID.