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Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread to almost every country in the world, causing death and economic havoc in its wake. Although children have been relatively spared the severe effects of this disease, they can still acquire and pass SARS-CoV-2 to others.
Detection of SARS-CoV-2 in children is therefore a priority, with more than two million pediatric cases of COVID-19 having been identified in the United States alone. A recent study published on the preprint server medRxiv * finds that antigen-based tests can reliably identify children who are infectious for SARS-CoV-2, despite the fact that this diagnostic approach is considered less sensitive than the benchmark reverse transcriptase-polymerase test chain (RT-PCR).
Study: Pediatric characteristics and antigen test performance at a community SARS-CoV-2 test site. Image Credit: Nenad Cavoski / Shutterstock.com
Background
Antigen-based tests are preferred for community-based screening and screening programs because they are cost-effective, can provide rapid test results, and are suitable for low-resource settings. These tests are based on the detection of a specific antigen and can be used on nasal swabs or nasopharyngeal swabs, regardless of the person’s age.
These antigen-based tests are most sensitive when the viral load is high and, in most cases, when cultivable virus can be extracted from the sample. In symptomatic adults, positive antigen tests correlate strongly with positive RT-PCR tests. However, this is not the case in asymptomatic adults or if the test is delayed for more than seven days from the onset of symptoms.
There remains a lack of information on the accuracy of antigen-based tests when used in children, especially when comparing their effectiveness in symptomatic versus asymptomatic patients. As a result, the current study focused on children who were tested at a community-based testing site to compare antigen test results with RT-PCR results and measurements of viral isolates. This triple comparison was useful in revealing the infectivity of children with a positive antigen test, as well as the reliability of the test in detecting infection compared to the RT-PCR approach for this population.
The researchers analyzed the results of more than 200 samples taken from children. About 20% of the samples were from children aged 5 to 8, while more than half were from children aged 9 to 15. The remaining samples were from children aged 16 to 17. Together, more than half of the samples were from children who had previously been exposed to SARS-CoV-2 within 2 weeks of testing.
What were the conclusions of the study?
The study found that of the 2,110 samples included in the study, nearly 50% of them were from children who had previously been exposed to COVID-19 in the past 14 days. Indeed, the exposure rate in children aged 16 to 17 was 60%, which was significantly higher compared to the adults included in this study.
Compared to adults, a greater number of children included in this study reported symptoms, although most of them reported only one symptom. For those who were symptomatic, samples were obtained at a median of two and three days from onset of symptoms in children and adults, respectively.
Taken together, positive RT-PCR results represented 15.8% and 16.4% of adult and pediatric patients, respectively. In the pediatric group, the highest RT-PCR positivity was observed at 27.3% in people aged 16 to 17 years. Additionally, this higher RT-PCR positivity rate in participants aged 16 to 17 was significantly higher compared to all other participants under 16.
(A) Percentage of presentations for testing, presentation, real-time reverse polymerase chain reaction (RT-PCR) or antigen test positive, and (B) positive and symptomatic by age group, collected at a site of community test – Oshkosh, Wisconsin, November-December 2020
a Sx: Symptomatic defined as signaling ≥ 1 symptom at the time of sampling
b Sx: Symptomatic defined as signaling symptoms meeting the clinical criteria of the State Council and Territorial Epidemiologists (CSTE) for COVID-19
Cycle cutoff (Ct) values were comparable between children and adults, and no difference was found between different age groups in children. Ct values in RT-PCR positive pediatric specimens were comparable in symptomatic and asymptomatic children. Additionally, these Ct values showed no change with duration of symptoms, which may be due to the fact that asymptomatic children were in fact presymptomatic for COVID-19.
Accuracy of antigen testing
Antigen tests were positive in 12.8% and 12% of adults and children, respectively, in the screening program, with an 82% agreement between antigen and RT-PCR test results. However, the sensitivity of the antigen-based test was slightly lower in children, with 73% agreement in this patient population.
A positive antigen test was quite accurate as a marker of infection in children, whether they were symptomatic or asymptomatic when they had a history of exposure. Conversely, a negative test was correlated with the absence of infection in 95% of cases.
Overall, the antigen-based test was 76% sensitive in symptomatic children; however, it has been shown to be less than 60% accurate in asymptomatic children. When symptomatic children had a history of exposure, the sensitivity was much higher at 88%, which is comparable to 67% of symptomatic children without prior exposure to the virus.
Virus isolation vs antigen / PCR testing
Among symptomatic child samples that were positive on subsequent RT-PCR tests but initially found negative by antigen-based tests, 86% of RT-PCR tests were performed within one week of symptom onset. This group of samples showed higher Ct values than when antigen tests were positive, and none of them produced culturable viruses.
More than half of the pediatric samples that tested positive by RT-PCR gave infectious virus particles, which was comparable to about 60% of the samples in the adult group. Exposure to a known case of COVID-19, or the presence of symptoms, could not predict the proportion of samples containing infectious virus.
This is again different from the scenario in adults, in which symptomatic adults were much more likely to produce infectious virus, as well as samples taken within 7 days of symptom onset.
Isolation of the virus was successful in 70% of pediatric samples when both tests were positive; however, this was not true for those samples which tested negative by the antigen-based test. Notably, approximately 75% of viral particle recoveries were obtained from symptomatic children, with only a fifth from asymptomatic children.
What were the implications?
Overall, any sample that has been used successfully for virus isolation has tested positive by both RT-PCR and antigen-based testing. These results corroborate previous studies showing that a history of exposure is associated with higher test sensitivity. The likelihood of this correlation increases in older adolescents with higher exposure rates, with almost all positive RT-PCR results in this age group reporting symptoms.
“It is important to test pediatric populations, especially adolescents, with symptoms or possible exposures due to their high levels of exposure and risk of community transmission. Confirmatory nucleic acid amplification testing is recommended for a negative antigen result in people with symptoms or known exposures. “
*Important Notice
medRxiv publishes preliminary scientific reports which are not peer reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behavior, or treated as established information.
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