Comparison of Upper Respiratory Viral Load Distributions in Asymptomatic and Symptomatic Children Diagnosed with SARS-CoV-2 Infection in Pediatric Hospital Testing Programs

Abstract

The distribution of upper respiratory viral loads (VL) in asymptomatic children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. We assessed PCR cycle threshold (Ct) values and estimated VL in infected asymptomatic children diagnosed in nine pediatric hospital testing programs. Records for asymptomatic and symptomatic patients with positive clinical SARS-CoV-2 tests were reviewed. Ct values were (i) adjusted by centering each value around the institutional median Ct value from symptomatic children tested with that assay and (ii) converted to estimated VL (numbers of copies per milliliter) using internal or manufacturer data. Adjusted Ct values and estimated VL for asymptomatic versus symptomatic children (118 asymptomatic versus 197 symptomatic children aged 0 to 4 years, 79 asymptomatic versus 97 symptomatic children aged 5 to 9 years, 69 asymptomatic versus 75 symptomatic children aged 10 to 13 years, 73 asymptomatic versus 109 symptomatic children aged 14 to 17 years) were compared. The median adjusted Ct value for asymptomatic children was 10.3 cycles higher than for symptomatic children (P < 0.0001), and VL were 3 to 4 logs lower than for symptomatic children (P < 0.0001); differences were consistent (P < 0.0001) across all four age brackets. These differences were consistent across all institutions and by sex, ethnicity, and race. Asymptomatic children with diabetes (odds ratio [OR], 6.5; P = 0.01), a recent contact (OR, 2.3; P = 0.02), and testing for surveillance (OR, 2.7; P = 0.005) had higher estimated risks of having a Ct value in the lowest quartile than children without, while an immunocompromised status had no effect. Children with asymptomatic SARS-CoV-2 infection had lower levels of virus in their nasopharynx/oropharynx than symptomatic children, but the timing of infection relative to diagnosis likely impacted levels in asymptomatic children. Caution is recommended when choosing diagnostic tests for screening of asymptomatic children.

Keywords: COVID-19; SARS-CoV-2; diagnostics; pediatric infectious disease.

FIG 1

Comparison of adjusted Ct values (A) and estimated viral loads (B) for asymptomatic (n = 339) versus symptomatic (n = 478) children. The bottom and top edges of the boxes for each cohort indicate the interquartile range (IQR), the horizontal line bisecting the box indicates the median value, and the whiskers represent values 1.5 times the IQR. P values for comparison of the respective medians are shown.

FIG 2

Comparison of adjusted Ct values (A) and estimated viral loads (B) for asymptomatic versus symptomatic children, separated by age brackets (118 asymptomatic versus 197 symptomatic children aged 0 to 4 years, 79 asymptomatic versus 97 symptomatic children aged 5 to 9 years, 69 asymptomatic versus 75 symptomatic children aged 10 to 13 years, 73 asymptomatic versus 109 symptomatic children aged 14 to 17 years). The bottom and top edges of the boxes for each cohort indicate the interquartile range (IQR), the horizontal line bisecting the box indicates the median value, and the whiskers represent values 1.5 times the IQR.

FIG 3

Comparison of adjusted Ct values (A) and estimated viral loads (B) for asymptomatic children tested for three different indications (surveillance, preop/aerosol-generating procedure, and preadmission) versus symptomatic children. The bottom and top edges of the boxes for each cohort indicate the interquartile range (IQR), the horizontal line bisecting the box indicates the median value, and the whiskers represent values 1.5 times the IQR. The P values for the comparison of the medians of the surveillance and preprocedure groups are shown.