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 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 adjusted by centering each value around the institutional median Ct value from symptomatic children tested with that assay, and converted to estimated VL (copies/mL) using internal or manufacturer data. Adjusted Ct values and estimated VL for asymptomatic versus symptomatic children (118 vs. 197 ages 0-4; 79 vs 97 ages 5-9; 69 vs 75 ages 10-13; 73 vs 109 ages 14-17) were compared. The median adjusted Ct value in asymptomatic children was 10.3 cycles higher than for symptomatic children (p< 0.0001), and VL 3-4 logs lower (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 (OR 6.5, p = 0.01), recent contact (OR 2.3, p = 0.02), and testing for surveillance (OR 2.7, p = 0.005) had higher estimated risk of having a Ct value in the lowest quartile than children without, while immunocompromise had no effect. Children with asymptomatic SARS-CoV-2 infection had lower levels of virus in the nasopharynx/oropharynx than symptomatic children, but timing of infection relative to diagnosis likely impacted levels in asymptomatic children. Caution is recommended when choosing diagnostic tests for screening of asymptomatic children.

Upper respiratory tract SARS-CoV-2 RNA loads in symptomatic and asymptomatic children and adults

“…Regarding children, we found similar SARS-CoV-2 loads in symptomatic and asymptomatic individuals, although a subtle trend towards higher viral loads was seen in the former. Our data concur with those of Hurst and et al 25 , but are in contradiction to those of Kociolek et al 12 which clearly pointed to lower SARS-CoV-2 RNA loads in asymptomatic children than in those with mild to moderate COVID-19.…”

“…Supporting this assumption, transmission risk was recently shown to be strongly associated with initial SARS-CoV-2 RNA levels of index cases [6]. There is scarce information on how SARS-CoV-2 RNA load in UTR compares between children and adults [7][8][9][10][11], whether viral load in pediatric subjects differ across ages [9,10], and whether dissimilarities in the dynamics of SARS-CoV-2 shedding in URT exist between symptomatic and asymptomatic children [12][13][14]. Elucidation of these questions is critically important for designing effective public health policies to fight the pandemic.…”

Correlation of SARS-CoV-2 Nucleocapsid Antigen and RNA Concentrations in Nasopharyngeal Samples from Children and Adults Using an Ultrasensitive and Quantitative Antigen Assay

“…For some of the patients who provided samples, the time between onset of symptoms and testing was long, but this reflects real life clinical test use. The majority of the patients whose samples were included in our study were symptomatic, so the results will need confirmation in asymptomatic individuals (31). Finally, the performance of the test in an independent clinical laboratory setting remains to be demonstrated.…”

Risk factors for severe and critically ill COVID‐19 patients: A review

“…Viral genome can be detected in asymptomatic individuals. Viral load has been shown to be higher in symptomatic children (1.3 × 10 7 copies/mL [IQR 5.6 × 10 4 to 3.8 × 10 8 ]) than in asymptomatic children (2.0 × 10 3 copies/mL [IQR 162 to 1.7 × 10 5 ]) 132 . These results stress the need for early detection of infection to minimize potential transmission 133–136 …”