The accuracy of saliva versus nasopharyngeal and/or oropharyngeal samples for the detection of SARS-CoV-2 in children – A rapid systematic review and meta-analysis

Abstract

Background The comparative performance of saliva and nasopharyngeal samples for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by reverse transcriptase polymerase chain reaction (RT-PCR) in children remains unclear. As schools reopen around the world, there is an interest in the use of saliva samples for detection of SARS-CoV-2 in children to circumvent barriers with nasopharyngeal sampling. We systematically reviewed the literature to understand the performance of saliva sampling using RT-PCR on naso- and/or oropharyngeal swabs as the reference standard. Methods Articles from PubMed/MEDLINE and Living Evidence were accessed until 28th April 2021. A search method without restriction to children population was applied and during the review phase, if a study included patients <18 years old, authors were contacted to provide additional information on the subset of children. Studies were eligible if they reported on matched saliva and naso- and/or oropharyngeal samples, taken from the same patient on the same day. Studies using other respiratory samples such as sputum samples were excluded. Each paired patient sample had to be tested on the same RT-PCR platform. Results Ten studies were included, comprising 1486 matched saliva and on naso- and/or oropharyngeal pairs from children aged 0 to 18 years old. The pooled absolute sensitivity and specificity of saliva sampling using RT-PCR on nasopharyngeal samples as the reference standard was 84.5% (95% CI; 78.0%-90.3%) and 99.5% (95% CI; 98.2%-100.0%). Comparable performance of saliva to nasopharyngeal samples was shown in both symptomatic and asymptomatic children. Stratified analyses of various covariates showed no significant differences. Discussion Our pooled accuracy estimates of RT-PCR SARS-CoV-2 testing on saliva in children did not seem to be different from meta-analyses of studies that enrolled mainly adults. Saliva could potentially be considered an alternative sampling method for screening in children and to pick up those with high viral load.

Equivalence of saliva RT-qPCR testing to nasal-throat/nasopharyngeal swab testing in the general practitioner’s setting to detect SARS-CoV-2

“…While our patient cohort size is modest, our results are perfectly in line with recent metaanalyses on the use of saliva as an alternative to nasopharyngeal swabs 3,4 . We observed a 100% concordance, across all demographic groups, irrespective of age, presence of symptoms, or high-risk status.…”

“…Furthermore, maximizing diagnostic sensitivity may not be the best strategy to prevent spreading; instead, frequency of testing should be prioritized over sensitivity in controlling the spread of this virus 5 . Saliva may provide an excellent alternative for a swab as it allows non-invasive and repeated self-collection and has been demonstrated to result in equivalent sensitivity 3,4 . Nonetheless, noticeable performance differences among individual studies are published, likely resulting from varying collection devices, with or without stabilizing medium (likely important because of large amounts of RNases in saliva), sample storage conditions, time delays between collection and testing, phase of the pandemic 6 during which sampled are collected, donor inclusion criteria (hospitalized vs. asymptomatic persons), and unstandardized laboratory saliva testing.…”

“…Given the ease of sample collection and increased patient comfort, the authors suggest that laboratories should consider adopting saliva as their first sample choice, especially in screening programs. In a more recent systematic review and meta-analysis, saliva PCR testing was specifically evaluated in children 4 . Comparable performance of saliva to nasopharyngeal samples was shown in both symptomatic and asymptomatic pediatric patients.…”

Performance of saline and water gargling for SARS-CoV-2 reverse transcriptase PCR testing: a systematic review and meta-analysis

“…Although a stratified comparison of performance in adults versus children is not permissible by the data, the lack of notable difference in sensitivity (91% versus 89%) between the pooled overall estimate from all 18 studies and eight of the studies including children aged 3–18 years in their study population potentially suggested a comparable performance of gargling in adults and children, and that gargle would be an appropriate sampling option for children. The higher pooled sensitivity (89%) by gargle in studies including children as compared to that reported previously for saliva (83.6%) [ 64 ] further suggests gargling to be a viable option for a child population. Although some caution has been advocated for its use in infants due to the technical difficulty for this age group [ 65 ], gargling has also been used in some settings for the molecular testing of common respiratory infections in children [ 66 , 67 ].…”