Molecular Detection of SARS-CoV-2 From Throat Swabs Performed With or Without Specimen Collection From the Tonsils: Protocol for a Multicenter Randomized Controlled Trial.

BACKGROUND: Testing for SARS-CoV-2 is essential to provide early COVID-19 treatment for people at high risk of severe illness and to limit the spread of infection in society. Proper upper respiratory specimen collection is the most critical step in the diagnosis of the SARS-CoV-2 virus in public settings, and throat swabs were the preferred specimens used for mass testing in many countries during the COVID-19 pandemic. However, there is still a discussion about whether throat swabs have a high enough sensitivity for SARS-CoV-2 diagnostic testing, as previous studies have reported a large variability in the sensitivity from 52% to 100%. Many previous studies exploring the diagnostic accuracy of throat swabs lack a detailed description of the sampling technique, which makes it difficult to compare the different diagnostic accuracy results. Some studies perform a throat swab by only collecting specimens from the posterior oropharyngeal wall, while others also include a swab of the palatine tonsils for SARS-CoV-2 testing. However, studies suggest that the palatine tonsils could have a tissue tropism for SARS-CoV-2 that may improve the SARS-CoV-2 detection during sampling. This may explain the variation of sensitivity reported, but no clinical studies have yet explored the differences in sensitivity and patient discomfort whether the palatine tonsils are included during the throat swab or not. OBJECTIVE: The objective of this study is to examine the sensitivity and patient discomfort of a throat swab including the palatine tonsils compared to only swabbing the posterior oropharyngeal wall in molecular testing for SARS-CoV-2. METHODS: We will conduct a randomized controlled study to compare the molecular detection rate of SARS-CoV-2 by a throat swab performed from the posterior oropharyngeal wall and the palatine tonsils (intervention group) or the posterior oropharyngeal wall only (control group). Participants will be randomized in a 1:1 ratio. All participants fill out a baseline questionnaire upon enrollment in the trial, examining their reason for being tested, symptoms, and previous tonsillectomy. A follow-up questionnaire will be sent to participants to explore the development of symptoms after testing. RESULTS: A total of 2315 participants were enrolled in this study between November 10, 2022, and December 22, 2022. The results from the follow-up questionnaire are expected to be completed at the beginning of 2024. CONCLUSIONS: This randomized clinical trial will provide us with information about whether throat swabs including specimens from the palatine tonsils will improve the diagnostic sensitivity for SARS-CoV-2 molecular detection. These results can, therefore, be used to improve future testing recommendations and provide additional information about tissue tropism for SARS-CoV-2. TRIAL REGISTRATION: ClinicalTrials.gov NCT05611203; https://clinicaltrials.gov/study/NCT05611203. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47446.

Higher SARS-CoV-2 detection of oropharyngeal compared with nasopharyngeal or saliva specimen for molecular testing: a multicentre randomised comparative accuracy study.

BACKGROUND: Testing is critical for detecting SARS-CoV-2 infection, but the best sampling method remains unclear. OBJECTIVES: To determine whether nasopharyngeal swab (NPS), oropharyngeal swab (OPS) or saliva specimen collection has the highest detection rate for SARS-CoV-2 molecular testing. METHODS: We conducted a randomised clinical trial at two COVID-19 outpatient test centres where NPS, OPS and saliva specimens were collected by healthcare workers in different orders for reverse transcriptase PCR testing. The SARS-CoV-2 detection rate was calculated as the number positive by a specific sampling method divided by the number in which any of the three sampling methods was positive. As secondary outcomes, test-related discomfort was measured with an 11-point numeric scale and cost-effectiveness was calculated. RESULTS: Among 23 102 adults completing the trial, 381 (1.65%) were SARS-CoV-2 positive. The SARS-CoV-2 detection rate was higher for OPSs, 78.7% (95% CI 74.3 to 82.7), compared with NPSs, 72.7% (95% CI 67.9 to 77.1) (p=0.049) and compared with saliva sampling, 61.9% (95% CI 56.9 to 66.8) (p<0.001). The discomfort score was highest for NPSs, at 5.76 (SD, 2.52), followed by OPSs, at 3.16 (SD 3.16) and saliva samples, at 1.03 (SD 18.8), p<0.001 between all measurements. Saliva specimens were associated with the lowest cost, and the incremental costs per detected SARS-CoV-2 infection for NPSs and OPSs were US$3258 and US$1832, respectively. CONCLUSIONS: OPSs were associated with higher SARS-CoV-2 detection and lower test-related discomfort than NPSs for SARS-CoV-2 testing. Saliva sampling had the lowest SARS-CoV-2 detection but was the least costly strategy for mass testing. TRIAL REGISTRATION NUMBER: NCT04715607.

Combined nasal- and oropharyngeal self-swab provides equivalent performance compared to professionally collected oropharyngeal swabs in detecting SARS-CoV-2 in a real-life setting.

PURPOSE: To investigate the performance of a combined nasal midturbinate- and oropharyngeal (NAOP) self-swab compared to a deep oropharyngeal (OP) swab by health care workers (HCW) in detecting SARS-CoV-2 in a real-life setting. METHODS: Paired swabs from 1119 participants were included. RT-PCR were used to detect SARS-CoV-2 in both swab samples. RESULTS: 330 participants tested positive. The sensitivity of the combined self-swab and OP swab was 96.9 % and 95.4 % respectively, whereas the Ct-values for self-swabs were significantly lower compared to OP swabs. CONCLUSION: The combined NAOP self-swab outperformed the OP swab and thus, the NAOP self-swab may be an alternative sampling method under the given circumstances.