Infectivity of severe acute respiratory syndrome coronavirus 2 in children compared with adults

Jared Bullard; Duane Funk; Kerry Dust; Lauren Garnett; Kaylie Tran; Alex Bello; James E. Strong; Santina J. Lee; Jillian Waruk; Adam Hedley; David Alexander; Paul Van Caeseele; Carla Loeppky; Guillaume Poliquin

doi:10.1503/cmaj.210263

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Figure 1:
Reverse transcription polymerase chain reaction cycle threshold values of the severe acute respiratory syndrome coronavirus 2 envelope gene by age group. Adult samples had a significantly lower cycle threshold value (18.7, interquartile range [IQR] 17.9–30.4) than children aged ≤ 10 years (25.1, IQR 17.7–31.3, p < 0.001) and those aged 11–17 years (22.2, IQR 18.3–29.0, p = 0.02).
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Figure 2:
Tissue culture infective dose 50% (TCID₅₀/mL) by age group. Adult samples had significantly higher TCID₅₀/mL (5620, IQR 1171–17 800) than children aged 11–17 years (316, interquartile range [IQR] 178–2125, p < 0.001), but were not significantly higher than children aged ≤ 10 years (1171, IQR 316 to 5620, p = 0.1).
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Figure 3:
Symptom onset to test time (days), the mean revere transcription polymerase chain reaction cycle threshold value of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) envelope gene and the probability of successful viral culture in pediatric samples. The probability of SARS-CoV-2 culture is shown by the pink bars. Black lines represent 95% confidence intervals. Cycle threshold values are represented by the blue line, with circles representing medians and blue bars representing the 95% confidence intervals. Numbers above the pink bar indicate the number of samples per day.

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Table 1:

Measures of SARS-CoV-2 infectivity in children and adults

Variable	Children aged ≤ 10 yr n = 97	Children aged 11–17 yr n = 78	Adults n = 130	p value
Asymptomatic, no. (%)	47 (48)	19 (24)	9 (7)	< 0.001^§
Positive culture, no. (%, 95% CI)	18 (19, 11–28)	18 (23, 14–34)	57 (44, 35–53)	< 0.001^¶
Symptom to test time, median (IQR), d	1 (1–4)	2 (1–3.5)	2 (1–4)	0.6
Cycle threshold^*, median (IQR)	25.1 (17.7–31.3)	22.2 (18.3–29.0)	18.7 (17.9–30.4)	< 0.001^**
RNAseP^†, mean ± SD	25.7 ± 2.8	26.1 ± 2.6	26.1 ± 2.0	0.6
TCID₅₀/mL^‡, median (IQR)	1171 (316–5620)	316 (178–2125)	5620 (1171–17 800)	< 0.001^††
Log RNA copies/mL, median (IQR)	5.4 (3.5–7.8)	6.4 (4.2–7.6)	7.5 (5.2–8.3)	< 0.001^‡‡

Note: CI = confidence interval, IQR = interquartile range, RT-PCR = reverse transcription polymerase chain reaction, SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2, SD = standard deviation.
↵* Cycle threshold is a semiquantitative measure of how much genetic material is present in the initial sample. If more RT-PCR cycles are required to detect SARS-CoV-2, then less viral RNA was present in the sample.
↵† Cycle threshold values for human RNAse P gene, an endogenous internal amplification control, were used as a marker of quality of the nasopharyngeal sample.
↵‡ Fifty percent tissue culture infective dose (TCID₅₀) is a measure of infectious virus titre and represents the amount of virus required to kill 50% of cells in inoculated tissue culture.
↵§ p value is < 0.001 for all comparisons: children ≤ 10 years old compared with children aged 11–17 years, children aged 11–17 compared with adults and children ≤ 10 years old compared with adults.
↵¶ p = 0.5 children ≤ 10 years v. children aged 11–17 years; p = 0.003 children aged 11–17 years v. adults; p < 0.001 children ≤ 10 years v. adults.
↵** p = 0.99 children ≤ 10 years v. children aged 11–17 years; p = 0.02 children aged 11–17 years v. adults; p < 0.001 children ≤ 10 years v. adults.
↵†† p = 0.6 children ≤ 10 years v. children aged 11–17 years; p < 0.001 children aged 11–17 years v. adults; p = 0.1 children ≤ 10 years v. adults.
↵‡‡ p = 0.99 children ≤ 10 years v. children aged 11–17 years; p = 0.2 children aged 11–17 years v. adults; p < 0.001 children ≤ 10 years v. adults.

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Table 2:

Measures of SARS-CoV-2 infectivity in pediatric culture-positive versus culture-negative samples

Variable	No. (%) of culture-positive samples^* n = 36	No. (%) of culture-negative samples^* n = 139	p value
Age, yr, median (IQR)	10 (5–15)	9 (5–14)	0.6
Asymptomatic	15 (42)	51 (37)	0.9
Male sex	22 (61)	80 (57)	0.7
Symptom to test time, median (IQR), d	1 (0–2)	2 (1–4)	0.3
Cycle threshold^†, median (IQR)	16.8 (16.3–18.8)	25.8 (20.7–31.9)	< 0.001
Log RNA copies/mL, median (IQR)	8.1 (7.4–8.2)	5.2 (3.2–6.8)	< 0.001

Note: IQR = interquartile range, RT-PCR = reverse transcription polymerase chain reaction, SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.
↵* Unless indicated otherwise.
↵† Cycle threshold is a semiquantitative measure of how much genetic material is present in the initial sample. If more RT-PCR cycles are required to detect SARS-CoV-2, then less viral RNA was present in the sample.

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Table 3:
Multivariable logistic regression model of measures associated with a positive viral culture from pediatric samples
Variable Adjusted odds ratio (95% CI)
Cycle threshold^* 0.81 (0.69–0.94)
Symptoms to test time 0.90 (0.64–1.27)
Age 1.13 (0.97–1.31)
Sex 2.18 (0.48–9.87)
RNAseP^† 0.69 (0.48–1.00)
Note: CI = confidence interval, RT-PCR = reverse transcription polymerase chain reaction, SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.
↵* Cycle threshold is a semiquantitative measure of how much genetic material is present in the initial sample. If more RT-PCR cycles are required to detect SARS-CoV-2, then less viral RNA was present in the sample.
↵† Cycle threshold values for human RNAse P gene, an endogenous internal amplification control, were used as a marker of quality of the nasopharyngeal sample.