Abstract
BACKGROUND: The role of children in the transmission and community spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. We aimed to quantify the infectivity of SARS-CoV-2 in nasopharyngeal samples from children compared with adults.
METHODS: We obtained nasopharyngeal swabs from adult and pediatric cases of coronavirus disease 2019 (COVID-19) and from their contacts who tested positive for SARS-CoV-2 in Manitoba between March and December 2020. We compared viral growth in cell culture, cycle threshold values from the reverse transcription polymerase chain reaction (RT-PCR) of the SARS-CoV-2 envelope (E) gene and the 50% tissue culture infective dose (TCID50/mL) between adults and children.
RESULTS: Among 305 samples positive for SARS-CoV-2 by RT-PCR, 97 samples were from children aged 10 years or younger, 78 were from children aged 11–17 years and 130 were from adults (≥ 18 yr). Viral growth in culture was present in 31% of samples, including 18 (19%) samples from children 10 years or younger, 18 (23%) from children aged 11–17 years and 57 (44%) from adults (children v. adults, odds ratio 0.45, 95% confidence interval [CI] 0.28–0.72). The cycle threshold was 25.1 (95% CI 17.7–31.3) in children 10 years or younger, 22.2 (95% CI 18.3–29.0) in children aged 11–17 years and 18.7 (95% CI 17.9–30.4) in adults (p < 0.001). The median TCID50/mL was significantly lower in children aged 11–17 years (316, interquartile range [IQR] 178–2125) than adults (5620, IQR 1171 to 17 800, p < 0.001). Cycle threshold was an accurate predictor of positive culture in both children and adults (area under the receiver-operator curve, 0.87, 95% CI 0.81–0.93 v. 0.89, 95% CI 0.83–0.96, p = 0.6).
INTERPRETATION: Compared with adults, children with nasopharyngeal swabs that tested positive for SARS-CoV-2 were less likely to grow virus in culture, and had higher cycle thresholds and lower viral concentrations, suggesting that children are not the main drivers of SARS-CoV-2 transmission.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the nonpharmaceutical public health interventions (NPIs) to control it have had a considerable impact on society. Public health efforts directed to reduce the spread of coronavirus disease 2019 (COVID-19) have employed a number of NPIs, including suspension of in-person school attendance for school-aged children. These decisions were largely based on historical observations that children played a substantial role as drivers of transmission for epidemic respiratory viruses, such as influenza.1 In the case of SARS-CoV-2, the role of children in transmission remains unclear, given few studies with conflicting data.2–9 Most studies have been limited to epidemiological investigations from which the direction of transmission is challenging to discern.3–7,9 As an alternative line of evidence, some studies have investigated the role of SARS-CoV-2 viral dynamics, also with heterogeneous results. Of these studies, some have shown higher viral loads in the nasopharynx of pediatric cohorts based on polymerase chain reaction testing, with others showing comparable levels of SARS-CoV-2 in children and adults.2,8,10,11 Furthermore, evidence relating to other viruses has shown that detectable viral RNA can persist beyond infectivity.3,4 An important proxy of in vivo infectiousness is recovery of live virus on cell culture. Assessment of this critical dimension has been lacking in virtually all pediatric studies, limiting the ability to perform a more complete risk–benefit analysis when considering the role of children in SARS-CoV-2 transmission. Evidence shows that the infectivity of SARS-CoV-2 may be predicted using available data, such as the cycle threshold from the reverse transcription polymerase chain reaction (RT-PCR).12,13 Cycle threshold is a relative measure of the quantity of genetic material, with lower values indicating the presence of more viral genetic material in the sample.
As an increasing number of jurisdictions consider whether in-school learning, daycares and extracurricular activities should continue or resume, a better understanding of the relative contributions of children and adolescents to SARS-CoV-2 transmission, when compared with adults, is essential. This is particularly important given the increased likelihood of asymptomatic infection in this group.14,15 Our goal was to quantify rates of SARS-CoV-2 culture positivity from nasopharyngeal swabs positive for the virus after RT-PCR testing in children. We then characterized the viral load and titres in culture-positive specimens and compared this with an adult group.