Saliva Is Not a Useful Diagnostic Specimen in Children With Coronavirus Disease 2019 (COVID-19)

Abstract

To the Editor—Saliva specimens have shown promise for diagnosing coronavirus disease 2019 (COVID-19) in adults, with a sensitivity of 50.5–96% [1–8]. However, in children, the utility of saliva specimens is uncertain; thus, we compared saliva with nasopharyngeal (NP) swabs for diagnosing COVID-19 in children. Children with COVID-19 admitted from 22 June to 22 July 2020 had paired NP and saliva specimens tested using a real-time reverse transcription–polymerase chain reaction (-PCR) assay for the E gene of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [9]. After abstaining from food and drink for 0.5 hours or more, saliva (minimum, 0.5 mL) was collected by patients spitting into a sterile container or by nurses who syringed saliva from inside the mouths of children who were unable to spit. Cycle threshold (Ct) values of specimens were recorded according to the day of illness (onset of symptoms) for symptomatic patients or day of diagnosis for asymptomatic patients. We grouped days into days 1–3, 4–7, 8–10, and 11–15 for analysis. The Ct cutoff for undetectable virus was 45. Saliva PCR sensitivity was calculated by the percentage of patients with positive saliva results among those with positive NP results for a given time period. Eighteen children were included: 12 (66.7%) who were asymptomatic and 8 (33.3%) who were symptomatic with mild upper respiratory tract infection. The mean age was 6.6 years (interquartile range [IQR], 1.8–11.1 years), and 10 (55.6%) patients were male. Patients provided a mean of 3.1 ± 1.4 paired samples (IQR, 2–4; range, 1–7 samples). Saliva and NP Ct trends are shown in Figure 1. In 5 (27.8%) patients, saliva PCR was persistently negative, including 1 asymptomatic child who only had samples tested on day 6 of admission (NP Ct, 37.9; saliva negative). In another 5 (27.8%) patients, saliva that was initially negative on day 1–3 turned positive on day 4–7. Nasopharyngeal and saliva SARS-CoV-2 temporal Ct values. Data points denote the mean; error bars indicate the SD. The annotations below the graph show the number of specimens, sensitivity, and Ct grouped by time period. Abbreviations: Ct, cycle threshold; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SD, standard deviation. Saliva PCR had higher Ct values compared with NP swabs. The Ct differences were statistically significant for all time periods, except for days 11–15. Saliva PCR sensitivity was highest at 52.9% on days 4–7 compared with the other time periods. Both paired samples were negative in 1 patient on days 8–10 and in 4 patients on days 11–15. Saliva PCR became negative at a mean of 9 ± 3.7 days (IQR, 6–11 days); the mean corresponding NP Ct was 31.0 ± 6.0 (IQR, 28.8–33.3).Young children less than 5 years old (n = 5) had lower mean NP Ct when saliva was negative compared with older children 5 years and older (n = 13; 27 ± 6.8 vs 33.3 ± 4.2; P = .037). Males were more likely to be asymptomatic (90% [9/10] vs 37.5% [3/8]; P = .043) and had higher saliva Ct on days 1–3 (29.2 ± 5.6 vs 22.2 ± 6.4; P = .045) compared with females. When saliva PCR was negative, males also had higher NP Ct values compared with females (33.5 ± 4.8 vs 28.0 ± 6.1; P = .048). There were no age or Ct differences between symptomatic and asymptomatic patients. Our study’s limitation was that 7 out of 55 (12.7%) paired samples had a delayed (3–28 hours) first saliva collection while awaiting NP confirmation of COVID-19. In conclusion, saliva is not a useful specimen for diagnosing COVID-19 in children. The peak saliva sensitivity was only 52.9% compared with NP swabs. Our previous buccal swab study had a peak sensitivity of 71.4% [10]. Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.

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