Differential Infectivity of Original and Delta Variants of SARS-CoV-2 in Children Compared to Adults

Abstract

Although children of all ages are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, they have not been implicated as major drivers of transmission thus far. However, it is still unknown if this finding holds true with new variants of concern (VOC), such as Delta (B.1.617.2). This study aimed to examine differences in both viral RNA (as measured by cycle threshold [C_T]) and viable-virus levels from children infected with Delta and those infected with original variants (OV). Furthermore, we aimed to compare the pediatric population infection trends to those in adults. We obtained 690 SARS-CoV-2 RT-PCR positive nasopharyngeal swabs from across Manitoba, Canada, which were further screened for mutations characteristic of VOC. Aliquots of sample were then provided for TCID₅₀ (50% tissue culture infective dose) assays to determine infectious titers. Using a variety of statistical analyses we compared C_T and infectivity of VOC in different age demographics. Comparing 122 Delta- to 175 OV-positive nasopharyngeal swab samples from children, we found that those infected with Delta are 2.7 times more likely to produce viable SARS-CoV-2 with higher titers (in TCID₅₀ per milliliter), regardless of viral RNA levels. Moreover, comparing the pediatric samples to 130 OV- and 263 Delta-positive samples from adults, we found only that the Delta pediatric culture-positive samples had titers (TCID₅₀ per milliliter) similar to those of culture-positive adult samples. IMPORTANCE These important findings show that children may play a larger role in viral transmission of Delta than for previously circulating SARS-CoV-2 variants. Additionally, they may suggest a mechanism for why Delta has evolved to be the predominant circulating variant.

Keywords: COVID-19; Delta variant; RT-PCR; SARS-CoV-2; TCID50.

FIG 1

Comparison of SARS-CoV-2 E gene RT-PCR C_T value by VOC versus age group. Median C_T values were higher for the Delta variant in pediatric age groups than in adults (P < 0.001; Kruskal-Wallis ANOVA), implying lower viral RNA levels. Median [IQR] C_T was similar for children 0 to 17 years old between OV and Delta variant (24 [18 to 30] versus 23 [20 to 28]; P = 0.97).

FIG 2

Comparison of TCID₅₀ per milliliter by VOC versus age group. There was no difference in numbers of TCID₅₀ per milliliter between the different age categories with respect to the Delta variant specifically (P = 0.68; Kruskal-Wallis ANOVA). In the pediatric age groups, the TCID₅₀/mL value was significantly higher for the Delta variant in the 11- to 17-year age category than for OV (5,620 [1,780 to 17,800] versus 316 [178 to 2,125]; P < 0.001), but there was no difference in the 0- to 10-year age category.

FIG 3

Linear regression analysis of swab beta globin (BGB) gene C_T versus age shows no statistical difference between BGB C_T level and age at which the sample was obtained.