key: cord-0813175-ui11jr2h
authors: Patel, Monita R; Carroll, Darin; Ussery, Emily; Whitham, Hilary; Elkins, Christopher A; Noble-Wang, Judith; Rasheed, James Kamile; Lu, Xioayan; Lindstrom, Stephen; Bowen, Virginia; Waller, Jessica; Armstrong, Gregory; Gerber, Susan; Brooks, John T
title: Performance of oropharyngeal swab testing compared to nasopharyngeal swab testing for diagnosis of COVID-19 —United States, January-February 2020
date: 2020-06-16
journal: Clin Infect Dis
DOI: 10.1093/cid/ciaa759
sha: 5299a1745541074c656e5a49d5fdeb409250a01f
doc_id: 813175
cord_uid: ui11jr2h

Among 146 nasopharyngeal (NP) and oropharyngeal (OP) swab pairs collected ≤7 days since illness onset, CDC real-time RT-PCR SARS-CoV-2 assay diagnostic results were 95.2% concordant. However, NP swab Ct values were lower (indicating more virus) in 66.7% of concordant-positive pairs, suggesting NP swabs may more accurately detect amount of SARS-CoV-2.

M a n u s c r i p t

Testing for SARS-CoV-2, the virus that causes coronavirus disease 2019 , remains critical to identify persons with COVID-19 and implement clinical and public health interventions to reduce morbidity and mortality and prevent virus transmission. Current US Centers for Disease Control and Prevention (CDC) guidelines identify nasopharyngeal (NP) and oropharyngeal (OP) swabs as acceptable upper respiratory specimens to test for presence of SARS-CoV-2 ribonucleic acid (RNA) (1) . Relative to NP swabs, OP swabs may be less challenging to collect, require less healthcare provider training or may logistically be the only option based on available supplies. Some indirect evidence from testing for other respiratory illnesses and coronaviruses suggests OP swabs may be less sensitive than NP swabs (2, 3) . However, to date, limited published data exist about testing performance of OP swab compared to NP swab for SARS-CoV-2 RNA (4).

We analyzed data on OP and NP swabs tested for SARS-CoV-2 RNA by CDC through March 3, 2020 A c c e p t e d M a n u s c r i p t

We matched NP and OP swabs collected on the same date in the same person to create NP-OP swab pairs. In our main analysis, we analyzed pairs collected ≤7 days since of the reported illness onset date; if more than one pair was collected from a person in this timeframe, we included the earliest (first) pair in our primary analysis. As sensitivity analyses, we also examined first pairs collected >7 days since illness onset date and second follow-up pairs collected >7 days since illness onset (regardless of timing of first pair).

We examined concordance/discordance in diagnostic results and Ct value distributions between NP and OP swabs within pairs. We also calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with 95% confidence intervals (CI) for OP swab, compared with NP swab. NP swab was selected as the comparator because during the testing timeframe, NP swab was the preferred upper respiratory specimen per CDC Guidelines; however, OP swab was an acceptable alternative specimen for diagnostic testing (independent of NP swab testing/result) (1). Accordingly, we also calculated absolute sensitivities for OP and NP A c c e p t e d M a n u s c r i p t

Overall, among persons with specimens collected early in the illness course, SARS-CoV-2 RNA diagnostic results were highly concordant between OP and NP swabs. Despite this, among concordant-positive specimens, Ct values were significantly lower among NP swabs. These findings are partially aligned with a study from Germany among persons tested ≤5 days since illness, which similarly did not find meaningful differences in SARS-CoV-2 RNA detection between NP and OP swabs, but contrastingly did not find differences in viral loads between NP and OP swabs (6) .

In our analysis, using NP swab as the comparator, specificity and NPV of OP swab were high and sensitivity and PPV of OP swab were moderate, but had wide CIs that included low values. Absolute sensitivity was only slightly lower for OP swab compared to NP swab. Differences in Ct values between NP and OP swab among concordantpositive pairs, did not ultimately impact most diagnostic results in our main analysis where Ct values were relatively low and well under the cutoff value of 40 cycles.

In contrast, in sensitivity analyses of NP-OP swab pairs collected >7 days since illness onset, sensitivity of OP swab was comparatively low. Current Infectious Diseases Society of America Guidelines specifically recommend collection of NP, mid-turbinate or nasal swabs rather than OP swabs alone for all symptomatic persons; our findings suggest this recommendation may be particularly relevant for persons later in the illness course and who may have lower amount of SARS-CoV-2 viral RNA (7).

The findings in this report are subject to at least four limitations. First, specimen collection procedures, including type and material of swab used, and specimen handling may also impact test performance. These data were not available to us, so sub-analyses, for instance by type of swab used, were not possible. Second, missing and erroneous personal identification numbers or specimen collection dates limited our ability to match all potential NP and OP swab pairs and account for all specimen pairs within a unique person. If missing data or errors were A c c e p t e d M a n u s c r i p t not at random, this may have biased our results. Third, the number of specimen pairs and the number of positive results were small and precluded our ability to estimate sensitivity and PPV with better precision.

Fourth, specimens were tested using the CDC 2019-nCoV Real-Time RT PCR Diagnostic Panel currently approved under an Emergency Use Authorization, and our findings, particularly those around Ct values, may not be generalizable to other nucleic acid tests. Consequently, our findings may not be fully generalizable to current specimen collection and testing circumstances and should thus be interpreted accordingly.

Together, our findings support CDC guidelines that identify NP and OP swabs as acceptable specimens for SARS-CoV-2 RNA testing; but suggest that NP swab may comparatively be a more sensitive specimen type for testing persons later in the illness course. Regardless of type of specimen collected, in persons with a single negative SARS-CoV-2 RNA test, signs and symptoms of COVID-19, epidemiological links, and other risk factors may need to be considered to inform subsequent clinical management and public health interventions to prevent further transmission (5). M a n u s c r i p t 

Interim guidelines for collecting, handling, and testing clinical specimens from persons for coronavirus disease 2019 (COVID-19)

Identification of respiratory viruses in adults: nasopharyngeal versus oropharyngeal sampling

Comparison of nasopharyngeal and oropharyngeal swabs for the diagnosis of eight respiratory viruses by real-time reverse transcription-PCR assays

SARS-CoV-2 viral load in upper respiratory specimens of infected patients

CDC. CDC 2019-nCoV Real-Time RT-PCR Diagnostic Panel Instructions for Use

GA: US Department of Health and Human Services, CDC

Virological assessment of hospitalized patients with COVID-2019

Guidelines on the Diagnosis of COVID-19

A c c e p t e d M a n u s c r i p t