ORAL SALIVA SWAB RT-PCR AS A FIT-FOR-PURPOSE DIAGNOSTIC TEST for COVID-19 in CHILDREN

ABSTRACT

Background: Testing using nasopharyngeal swabs (NPS) samples is the cornerstone for the control of the COVID-19 pandemic, but the procedure is uncomfortable and generates anxiety, especially in children. We aimed to evaluate the adequacy of oral saliva swab analysis using RT-PCR comparing to NPS by RT-PCR and Antigen Rapid Test (AgRT) on NPS in children. Methods: Cross-sectional multicenter diagnostic study nested in a prospective, observational cohort (EPICO-AEP) carried out between February and March 2021 at 10 hospitals in Spain. Participants were children 0 to 18 years old with symptoms compatible with SARS-CoV-2 infection of ≤5 days of duration attending at emergency departments. Three samples were collected, two NPS (for AgRT and for RT-PCR) and one oral saliva swab for RT-PCR. In patients with discordant results, new NPS was collected for viral culture and original samples were tested for viral RNA subgenomic (sgRNA) study. Results: 1174 children were included in the analysis, aged 3.8 years (IQR, 1.7-9.0), 647/1174 (55.1%) were male and 760/1174 (64.7%) presented fever 1 day before emergency department admission (IQR 1.0-2.0). Overall, 73/1174 (6.2%) patients tested positive in at least one of the techniques. Sensitivity for RT-PCR in oral saliva swab was 72.1% (95%CI, 59.7-81.9) and specificity 99.6% (95%CI, 99.0-99.9);AgRT in NPS was 61.8% (95%CI, 49.1-73.0) and 99.9% (95%CI, 99.4-100). Kappa index for RT-PCR oral saliva swab was 0.80 (95%CI, 0.72-0.88), and for AgRT was 0.74 (95%CI, 0.65-0.84) vs RT-PCR in NPS. A Bayesian model was used to estimate the accuracy assuming that RT-PCR in NPS is not a perfect gold standard. In this model, sensitivity for RT-PCR oral saliva swab was 84.8% (95%Cr 71.5-93.6), and for AgRT, it was 72.5% (95%Cr, 58.8-83.6). Specificity for RT-PCR oral saliva swab was 99.7% (95%Cr, 99.2-99.9), and for AgRT it was 99.9% (95% Cr, 99.6-100). The Cts were higher in oral saliva swabs compared with NPS;being Ct (NPS)=0.5 x (Ct saliva) + 4.5 (p=0.027). Overall, 4 (10.8%) patients with discordant results had a positive culture. In 3 of the 4 patients, the discordance consisted of positive result on oral saliva swab and nasopharyngeal swabs RT-PCR but negative by antigen rapid diagnostic test. No patient had (+) culture, (+)NP, (-)oral swab. Conclusion: RT-PCR on oral saliva swab is an accurate option for SARS-CoV-2 testing in children. A friendlier technique for younger patients, who must be tested very frequently, may help to increase the number of patients tested.