Variation in SARS-CoV-2 molecular test sensitivity by specimen types in a large sample of emergency department patients

Abstract

Background: Provider-collected nasopharyngeal specimens for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) molecular testing are the standard of care in many clinical settings, but patient-collected saliva and anterior nares specimens are less invasive and more flexible alternatives. Prior studies comparing specimen types for SARS-CoV-2 molecular testing have been limited by small sample sizes and low pretest probability. We conducted a large observational study among symptomatic adults at 7 emergency departments of Kaiser Permanente Southern California to examine sensitivity of SARS-CoV-2 molecular tests by specimen type and patient characteristics.

Methods: Provider-collected nasopharyngeal/oropharyngeal (NP/OP) specimens and patient-collected saliva and anterior nares specimens were collected at the same visit and analyzed with the Roche cobas® SARS-CoV-2 assay. Patients were considered truly positive for SARS-CoV-2 if any of the three specimens was positive and negative if all three specimens were negative. Factors associated with discordant and missed positive results were examined with multivariable logistic regression.

Results: Of 2112 patients, 350 (16.6%) were positive for SARS-CoV-2. Sensitivity of NP/OP was 93.7% (95% confidence interval [CI] 90.6%-96.0%), sensitivity of saliva was 87.7% (83.8%-91.0%), and sensitivity of anterior nares was 85.4% (81.3%-89.0%). Patients ages 18-39 years versus ≥40 years were more likely to have discordant results [adjusted odds ratio (aOR) 1.97 (1.12-3.45)], as were patients with <4 symptoms versus ≥4 [aOR 2.43 (1.39-4.25)]. Cycle threshold values were higher for saliva and anterior nares than NP/OP specimens, as well as for specimens in discordant versus concordant sets and patients with fewer symptoms.

Conclusion: This study provides robust evidence that patient-collected saliva and anterior nares are sensitive for SARS-CoV-2 molecular testing in emergency department settings, particularly among adults ages ≥40 years and those with multiple symptoms. Higher sensitivity of provider-collected NP/OP specimens must be weighed against the benefits of patient-collected specimens in tailored strategies for SARS-CoV-2 testing.

Keywords: Anterior nares; COVID-19; Molecular diagnostic test; SARS-CoV-2; Saliva; Self-collection.