The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to threaten human health worldwide. Although young and old adults have been affected, children are much less likely to suffer serious illness; however, little is known about its role in SARS-CoV-2 transmission.
A new study published on the preprint server medRxiv* examines the infectivity of pediatric samples to determine whether children are less susceptible to SARS-CoV-2 and, as a result, are at lower risk of viral spread than adults.
Study: Viral infectivity in pediatric SARS-CoV-2 clinical samples does not vary by age. Image credit: Rido / Shutterstock.com
Introduction
Most children infected with SARS-CoV-2 experience mild symptoms, with a small proportion affected by severe disease. This continued to be the pattern, even after Delta and Omicron variants emerged, and was often seen among very young children who were not initially included in the vaccine-eligible groups.
One hypothesis is that the behavior of SARS-CoV-2 in children differs from its biology in adult victims. For example, viral replication has been shown to be less efficient in children compared to adult nasal epithelium.
This theory was further examined with viral load in adult and pediatric samples using the standard reverse transcriptase polymerase chain reaction (RT-PCR) assay in its quantitative format. Cycle threshold (Ct) was used as an indicator of viral load in clinical samples.
However, these studies showed no difference between children and adults when patient samples with comparable severities of infection were measured.
Another approach involved using the semiquantitative mean tissue culture infectious dose (TCID50) assay. This method measures SARS-CoV-2 titers, both in terms of viral load and infectious viral particles, in the sample.
With the currently circulating Omicron strain, children and adults appear to allow viral replication at equivalent levels, unlike earlier SARS-CoV-2 variants. Therefore, more work is needed to explain why children still seem to experience less severe symptoms and lower transmissibility compared to adults.
Recently, the authors of the current preprint reported that Ct is indirectly related to infectious titers of SARS-CoV-2 in samples and is affected by both viral and host factors, allowing differences to emerge important in the final estimate. However, this work did not include children.
The current study extended previous work to assess children up to 18 years of age. The aim was to identify an increase in viral ribonucleic acid (RNA) loads with age.
What did the study show?
The study used samples stored at Children’s Wisconsin Hospital in Milwaukee, Wis., from September 14, 2020, to May 17, 2021. Determinations of the 144 samples showed that, in general, an RNA load of more high was correlated with a higher infectious viral load. , although not in a strictly linear way. However, no significant association was found between infectious viral titer and age.
“These data indicate that there is no difference in the infectivity of SARS-CoV-2 produced by children, regardless of age.”
SARS-CoV-2 viral infectivity does not vary by age in a pediatric population. A set of 144 clinical samples from children infected with SARS-CoV-2 was used to examine the relationship between infectious virus titer and RNA viral load as a function of patient age. Individual specimen measurements of E gene RNA levels (CT) on the x-axis are plotted against viral titer, as measured in focus-forming units (FFU/mL) on the y-axis . The dashed line indicates the limit of detection of the infectious titer (20 FFU/mL). Samples for which we could not measure a viral titer were assigned fixed values of one-tenth the limit of detection (2 FFU/mL). Lines of best fit were generated by linear regression on log-transformed titer data as a function of CT and age group.
These results indicate that children are as infectious as adults with equivalent viral RNA loads. Notably, this does not account for changes in the SARS-CoV-2 variant responsible for infection, which could lead to significant variation in infectivity. This is supported by the fact that many samples came from older adolescents who might be expected to closely resemble adults in their physiology.
The researchers also did not examine the timing of samples in terms of days since symptom onset, host immune status, and vaccination status. Additional studies involving these factors would better elucidate the role of these factors in facilitating or inhibiting viral replication and/or infectivity in adults versus children.
*Important news
medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guide clinical practice/health-related behavior, or be treated as established information.