Review 1: "Investigating Sensitivity of Nasal or Throat (ISNOT): A Combination of Both Swabs Increases Sensitivity of SARS-CoV-2 Rapid Antigen Tests"

Gannon C.K. Mak

doi:doi:10.1162/2e3983f5.c2a955b7

RR:C19 Evidence Scale rating by reviewer:

Reliable. The main study claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision.

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Review:

The authors evaluated three swabs namely, (1) nasal swab, (2) throat swab and (3) combined nasal/throat swab with antigen-based rapid testing devices (Ag-RDTs) for detecting SARS-CoV-2. Participants invited were asymptomatic, they were required to self-collect the samples and self-perform the Ag-RDTs. COVID-19 cases were defined by RT-PCRs. All of the COVID-19 positive cases showed negative S gene PCR results (i.e. suspected Omicron variant). The strength of the study was large sample size. It was well-planned and the message conveyed was clear. The sensitivity of using combined nasal/throat swab to detect SARS-CoV-2 was higher than nasal swab or throat swab. The limitations of the study were defined and discussed.

Comments:

In the method section, the participants invited can be elaborated further. If I understood correctly, participants (N=1345) were divided into two groups.

For the group 1 participants (N=825; COVID-19 positive cases=62; COVID-19 negative cases=763): two swabs were used, one swab was used to collect nasal swab (bilateral nares), while another swab was used to collect throat swab (posterior oropharyngeal). The group 1 participants were used to compare the performance of nasal swab and throat swab to detect SARS-CoV-2. For the group 2 participants (N=520; COVID-19 positive cases=38; COVID-19 negative cases=482), three swabs were used, the first swab was used to collect nasal swab, the second swab was used to collect another nasal swab, the third swab was used to collect throat swab. The second swab and the third swab were combined together and were called as ‘combined nasal/throat swab’. The group 2 participants were used to compare the performance of nasal swab and combined nasal/throat swab to detect SARS-CoV-2.

2. COVID-19 cases were defined by RT-PCRs. The authors can define clearly that three targets were used: (1) N gene, (2) Orf1a gene, (3) S gene. Positive cases were defined as having positive PCR results for at least one target gene.

3. The authors discussed the reasons of high sensitivity of using combined nasal/throat swab to detect SARS-CoV-2. They suspected the different tissue tropism for different SARS-CoV-2 variants. Indeed, different studies showed that the nasal/throat swab demonstrated comparable performance with nasopharyngeal swab for detecting SARSCOV-2 before the emergence of Omicron variant.