Diagnostic accuracy of covid-19 rapid antigen tests with unsupervised self-sampling in people with symptoms in the omicron period: cross sectional study

Abstract

Objective

To assess the performance of rapid antigen tests with unsupervised nasal and combined oropharyngeal and nasal self-sampling during the omicron period.

Design

Prospective cross sectional diagnostic test accuracy study.

Setting

Three public health service covid-19 test sites in the Netherlands, 21 December 2021 to 10 February 2022.

Participants

6497 people with covid-19 symptoms aged ≥16 years presenting for testing.

Interventions

Participants had a swab sample taken for reverse transcription polymerase chain reaction (RT-PCR, reference test) and received one rapid antigen test to perform unsupervised using either nasal self-sampling (during the emergence of omicron, and when omicron accounted for >90% of infections, phase 1) or with combined oropharyngeal and nasal self-sampling in a subsequent (phase 2; when omicron accounted for >99% of infections). The evaluated tests were Flowflex (Acon Laboratories; phase 1 only), MPBio (MP Biomedicals), and Clinitest (Siemens-Healthineers).

Main outcome measures

The main outcomes were sensitivity, specificity, and positive and negative predictive values of each self-test, with RT-PCR testing as the reference standard.

Results

During phase 1, 45.0% (n=279) of participants in the Flowflex group, 29.1% (n=239) in the MPBio group, and 35.4% ((n=257) in the Clinitest group were confirmatory testers (previously tested positive by a self-test at own initiative). Overall sensitivities with nasal self-sampling were 79.0% (95% confidence interval 74.7% to 82.8%) for Flowflex, 69.9% (65.1% to 74.4%) for MPBio, and 70.2% (65.6% to 74.5%) for Clinitest. Sensitivities were substantially higher in confirmatory testers (93.6%, 83.6%, and 85.7%, respectively) than in those who tested for other reasons (52.4%, 51.5%, and 49.5%, respectively). Sensitivities decreased from 87.0% to 80.9% (P=0.16 by χ ² test), 80.0% to 73.0% (P=0.60), and 83.1% to 70.3% (P=0.03), respectively, when transitioning from omicron accounting for 29% of infections to >95% of infections. During phase 2, 53.0% (n=288) of participants in the MPBio group and 44.4% (n=290) in the Clinitest group were confirmatory testers. Overall sensitivities with combined oropharyngeal and nasal self-sampling were 83.0% (78.8% to 86.7%) for MPBio and 77.3% (72.9% to 81.2%) for Clinitest. When combined oropharyngeal and nasal self-sampling was compared with nasal self-sampling, sensitivities were found to be slightly higher in confirmatory testers (87.4% and 86.1%, respectively) and substantially higher in those testing for other reasons (69.3% and 59.9%, respectively).

Conclusions

Sensitivities of three rapid antigen tests with nasal self-sampling decreased during the emergence of omicron but was only statistically significant for Clinitest. Sensitivities appeared to be substantially influenced by the proportion of confirmatory testers. Sensitivities of MPBio and Clinitest improved after the addition of oropharyngeal to nasal self-sampling. A positive self-test result justifies prompt self-isolation without the need for confirmatory testing. Individuals with a negative self-test result should adhere to general preventive measures because a false negative result cannot be ruled out. Manufacturers of MPBio and Clinitest may consider extending their instructions for use to include combined oropharyngeal and nasal self-sampling, and other manufacturers of rapid antigen tests should consider evaluating this as well.

SciScore for 10.1101/2022.03.24.22272891: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Ethics	Consent: Individuals were eligible if 16 years or older and were willing and able to sign a digital informed consent form in Dutch. IRB: MPBio and Clinitest were not CE-marked for OP-N sampling, but after safety checks by the quality team of the PHS West-Brabant, and consultation with in-house in-vitro diagnostic regulation experts and the Medical Ethical Committee Utrecht, both Ag-RDTs were considered safe for use with OP-N sampling.
Sex as a biological variable	not detected.
Randomization	not detected.
Blinding	not detected.
Power Analysis	7 For the present study, we conservatively assumed sensitivities of 70% for all three Ag-RDTs irrespective of self-sampling method, with an error margin of 5%, type I error of 5% and power of 80%.

Table 2: Resources

Software and Algorithms
Sentences	Resources
The study is reported according to the STARD 2015 guidelines.	STARD suggested: None

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:

Our study also has some limitations. First, the sample size calculation was based on the primary analysis and diagnostic accuracy parameters are by definition less precise for stratified and weekly analyses. Second, we did not determine the virus lineage in individual samples but relied on the national pathogen surveillance data to estimate the weekly Omicron variant prevalence.16 This surveillance system includes approximately 2,000 random samples from positive samples across the country on a weekly basis. Since regional variations in the Netherlands are very small (data not shown), we are confident that Omicron’s share was over 90% in all test-sites from 12 January 2022 onwards. Third, the viral load cut-off that we used was the cut-off above which 95% of people with a positive RT-PCR test result had a positive virus culture in our similar previous study.2 Those experiments were done when the Alpha variant dominated and participants were mostly unvaccinated. However, we believe that this estimate is still more meaningful than using arbitrary Ct value cut-offs of 25 or 30, as is often done.21,22 We found that Ag-RDT performance with nasal self-sampling declined during the period that Omicron emerged. We also showed that Ag-RDT performance can be improved by adding oropharyngeal to nasal self-sampling. Therefore, after proper evaluation, Ag-RDT manufacturers may consider extending their instructions for use to include combined oropharyngeal and nasal self-sampling. Positive p...

Results from TrialIdentifier: No clinical trial numbers were referenced.

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

Results from rtransparent:

Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
No protocol registration statement was detected.

Results from scite Reference Check: We found no unreliable references.

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