A study conducted by researchers in Canada suggests that children may be less likely than adults to spread the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19).
As recently reported in The Canadian Medical Association Journal (CMAJ), the study found that samples taken from 175 children aged 17 years or younger were about half as likely to contain culturable viruses than samples taken from adults.
Furthermore, when SARS-CoV-2 was successfully cultured, a significantly less viable virus was present in samples from children than from adults.
The team from Cadham Provincial Laboratory in Winnipeg, Manitoba, says the findings suggest that children do not appear to be the main drivers of SARS-CoV-2 transmission, which has important public health and clinical implications.
Jared Bullard and colleagues say the study also suggests that the cycle threshold value – the number of cycles required for the virus to be detected by polymerase chain reaction (PCR) testing – may be highly valuable in determining the potential infectiousness of a child.
Improved understanding of childhood transmission is essential
Public health measures taken to reduce the transmission of SARS-CoV-2 have included the suspension of in-person school attendance. This decision was primarily based on observations that children have previously played a role in driving the transmission of respiratory viruses such as influenza.
However, Bullard and the team say the role children play in SARS-CoV-2 transmission remains unclear, given the lack of studies and conflicting results so far.
“As an increasing number of jurisdictions consider whether in-school learning, daycare 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,” they write. “This is particularly important given the increased likelihood of asymptomatic infection in this group.”
Studies have been lacking a “critical dimension”
An important proxy of in vivo infectivity is the recovery of the live virus on cell culture. The researchers say assessment of this critical dimension has been lacking in almost all pediatric studies of SARS-CoV-2 transmission, thereby limiting the ability to perform a more complete risk-to-benefit analysis of the role children play in spreading the virus.
Furthermore, evidence suggests that SARS-CoV-2 infectivity can be predicted using data such as the cycle threshold value generated during reverse transcription PCR (RT-PCR).
The cycle threshold value is a relative measure of the quantity of genetic material in a sample, with a lower value indicating the presence of more viral genetic material.
What did the researchers do?
The researchers obtained nasopharyngeal swabs from adult and pediatric cases of COVID-19 and their contacts who tested positive for SARS-CoV-2 between March and December 2020.
The rates of SARS-CoV-2 culture positivity were quantified and compared between adults and children. Cycle threshold values from RT-PCR and the 50% tissue culture infective dose (TCID50/mL) were also compared between adults and children. The TCID50/mL is a commonly used assay for quantifying infectious viral titers.
What did the study find?
Of 305 samples cultured, 97 were from children aged 10 years or younger, 78 were from children aged 11 to 17 years and 130 were from adults (aged 18 years or older).
The team successfully grew SARS-CoV-2 in 93 (31%) of the 305 samples, including 57 (44%) of the samples from adults.
By contrast, the virus could only be cultured in 18 (19%) of the samples from children aged 10 years or younger and 18 (23%) of the samples from children aged 11 to 17 years.
The likelihood of growing live virus from the children’s samples was 55% lower than for the adults’ samples.
For the children aged 10 years or younger and those aged 11 to 17 years, the median cycle threshold was 25.1 and 22.2, respectively, compared with 18.7 for adults.
For both children and adults, the cycle threshold value was highly predictive of SARS-CoV-2 culture positivity.
In addition, the median TCID50/mL was significantly lower among the samples from children aged 11–17 years than among samples from adults, at 316 versus 5620. The median TCID50/mL did not significantly differ between adults and children aged 10 years or younger.
What are the implications of the study?
The researchers say the results demonstrate that RT-PCR positivity does not necessarily equate to culture positivity.
“In children who have tested positive for SARS-CoV-2 by RT-PCR, knowing the cycle threshold value may be more informative for determining the potential infectiousness of a child, and may have implications for duration of isolation,” writes Bullard and colleagues.
“Given the difficulties in keeping children isolated within the home environment and the significant impact of prolonged isolation on both child development and parental function (such as loss of work or income), a robust tool to decrease the length of, or need for, quarantine would be an important public health development,” concludes the team.