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Altamirano J, Govindarajan P, Blomkalns AL, et al. Assessment of Sensitivity and Specificity of Patient-Collected Lower Nasal Specimens for Severe Acute Respiratory Syndrome Coronavirus 2 Testing. JAMA Netw Open. 2020;3(6):e2012005. doi:10.1001/jamanetworkopen.2020.12005
Since the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in Wuhan, China, in December 2019, the virus has spread to 173 countries, resulting in 3 855 788 confirmed cases and 265 862 deaths as of May 9, 2020.1 Stanford Health Care was one of the first nonfederal facilities to obtain US Food and Drug Administration approval for a proprietary test using reverse transcriptase–polymerase chain reaction for SARS-CoV-2 using nasopharyngeal and oropharyngeal specimens on March 2, 2020. However, specimen collection must be done by health care workers and requires extensive use of personal protective equipment. To minimize the risk of exposure during testing, reduce personal protective equipment use, and increase access to testing, we compared the diagnostic equivalence of a modified specimen collection method, patient-collected lower nasal swabs, with that of the current clinical standard, health care worker–collected oropharyngeal swabs. If the 2 methods proved to be diagnostically equivalent, patients would be able to collect specimens themselves without exposing health care workers to respiratory secretions.
This prognostic study was approved by the Stanford University institutional review board. Participants provided oral informed consent to clinical research coordinators and then signed a consent form with the physician who collected the oropharyngeal swab. This study complies with the Standards for Reporting of Diagnostic Accuracy (STARD) reporting guideline.
The target population was Stanford Health Care outpatients with a reverse transcriptase–polymerase chain reaction test that was positive for SARS-CoV-2 in March 2020. We included a convenience sample of patients who consented to be contacted by our study staff. Our study staff obtained informed consent remotely, to minimize exposure of research staff to infected patients and to reduce the duration of study visits, and sent instructional materials electronically. Health care workers were excluded because of their familiarity with specimen collection, as were patients enrolled in drug trials for SARS-CoV-2.
After informed consent was obtained, participants were scheduled to return to Stanford Health Care for drive-through collection of 3 specimens using a patient-collected lower nasal swab (Puritan Sterile Foam Tipped Applicator; Puritan Medical Products), a physician-collected lower nasal swab (Puritan Sterile Foam Tipped Applicator; Puritan Medical Products), and a physician-collected oropharyngeal swab (FLOQ Swabs; Copan Diagnostics). During the visit, participants received a $20 incentive. The 3 specimens were placed in separate 3-mL tubes of viral transport medium (M4RT Transport; Remel MicroTest), stored in a cooler, and delivered to the Stanford Clinical Virology Laboratory. Specimens were tested for SARS-CoV-2 using reverse transcriptase–polymerase chain reaction targeting the envelope or open reading frame 1 ab genes.2,3
We report participant demographic characteristics, sensitivity and specificity, and discordant probabilities with 95% binomial CIs of patient-collected lower nasal compared with physician-collected oropharyngeal specimens. All analyses were performed with SAS statistical software version 9.4 (SAS Institute). Data analysis was performed in May 2020.
Of 129 eligible SARS-CoV-2–infected patients, 30 participated in the study (mean [SD] age, 48.2 [16.0] years; 16 men [53%]). We do not have reasons for refusal for nonparticipants. Participants were predominantly white (20 participants [66%]), with no sex or age group predominance. Twelve participants (40%) self-reported possible exposure to SARS-CoV-2. Cough (20 participants [67%]), fever (13 participants [43%]), and sore throat (8 participants [27%]) were commonly reported symptoms during the first visit. Approximately one-half of the participants had documentation of chronic medical conditions (16 participants [53%]), and 5 participants (17%) tested positive for coinfections with other respiratory viruses (Table 1).
We observed diagnostic equivalence across the 3 methods of specimen collection (Table 2). Eleven participants (37%) had test results that were positive for SARS-CoV-2 across patient- and physician-collected specimens, and 18 participants (60%) had results that were negative for SARS-CoV-2 across patient- and physician-collected specimens. The only discordant result was a participant whose self-collected nasal specimen tested positive, whereas both of their physician-collected specimens tested negative (3.30%; 95% CI, 0.08%-17.00%). The sensitivity of the patient-collected specimens was 100% (95% CI, 72%-100%), and the specificity was 95% (95% CI, 74%-100%).
These findings contribute to the recently released US Food and Drug Administration guidance4 that lists patient-collected lower nasal swab as an acceptable specimen collection method for SARS-CoV-2 testing. Self-collected lower nasal swabs could also be used for home- or office-based testing of asymptomatic patients. However, these preliminary findings are limited by small sample size, have limited generalizability, and need to be validated further in diverse clinical settings. These validation efforts are currently under way at our institution.
Accepted for Publication: May 18, 2020.
Published: June 12, 2020. doi:10.1001/jamanetworkopen.2020.12005
Correction: This article was corrected on July 13, 2020, to change the term sudden acute respiratory syndrome coronavirus 2 to severe acute respiratory syndrome coronavirus 2 in the title, text, and tables and to correct the corresponding author’s address.
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2020 Altamirano J et al. JAMA Network Open.
Corresponding Author: Jonathan Altamirano, MS, Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Dr, Stanford, CA 94305 (email@example.com).
Author Contributions: Mr Altamirano and Mr Govindarajan had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Altamirano, Govindarajan, Blomkalns, Maldonado.
Acquisition, analysis, or interpretation of data: Altamirano, Govindarajan, Kushner, Stevens, Pinsky, Maldonado.
Drafting of the manuscript: Altamirano, Pinsky, Maldonado.
Critical revision of the manuscript for important intellectual content: Govindarajan, Blomkalns, Kushner, Stevens, Pinsky, Maldonado.
Statistical analysis: Altamirano, Govindarajan, Maldonado.
Administrative, technical, or material support: Govindarajan, Blomkalns, Kushner, Stevens, Pinsky.
Supervision: Altamirano, Govindarajan, Blomkalns, Pinsky, Maldonado.
Conflict of Interest Disclosures: None reported.
Additional Contributions: We thank the study participants for their invaluable contributions and time. Karen Heichman, PhD, Andrew Trister, MD, PhD, Dan Wattendorf, MD, and Emily Turner, PhD (all from The Bill & Melinda Gates Foundation) provided technical advice. Shawna Cooper, BA (Audere), and John Tamerius, PhD (Quidel), provided instructional materials and information on lower nasal swab use. Jonasel Roque, BS, Steven Levitte, MD, PhD, Monique B. de Araujo, MD, MPH, and Simran Gambhir, MD (all from Stanford University School of Medicine), performed screening, recruitment, and sample collection. None of these individuals was compensated for these contributions.