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Sensitivity and Diagnostic Yield of the First SARS-CoV-2 Nucleic Acid Amplification Test Performed for Patients Presenting to the Hospital

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To identify the key insights or developments described in this article
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Key Points

Question  What is the diagnostic sensitivity of the SARS-CoV-2 nucleic acid amplification test (NAAT) by date of symptom onset among patients presenting to the hospital?

Findings  In this diagnostic study, the sensitivity of the first SARS-CoV-2 NAAT performed in the hospital was high within 14 days of symptom onset. Diagnostic yield was highest among patients presenting on day 10 of illness.

Meaning  The high diagnostic sensitivity of the NAAT in this study suggests that 1 negative test result can rule out SARS-CoV-2 infection among patients in the emergency department; only patients with high clinical pretest probability of disease should undergo repeated testing.

Abstract

Importance  Early and accurate diagnostic testing for SARS-CoV-2 is essential to initiate appropriate treatment and infection control and prevention measures among patients presenting to the hospital.

Objective  To evaluate the diagnostic sensitivity of the SARS-CoV-2 nucleic acid amplification test (NAAT) performed within 24 hours of arrival to the emergency department among a nationally representative sample of patients.

Design, Setting, and Participants  This diagnostic study was conducted at 47 hospitals across 7 provinces in Canada participating in the Canadian COVID-19 Rapid Response Emergency Department Network among consecutive eligible patients presenting to a participating emergency department who were tested for SARS-CoV-2 from March 1, 2020, to December 31, 2021. Patients not tested within 24 hours of arrival and those presenting with a positive result from a test performed in the community were excluded.

Main Outcomes and Measures  The primary outcome was a positive result from the SARS-CoV-2 NAAT. Outcome measures were the diagnostic sensitivity and yield of the SARS-CoV-2 NAAT.

Results  Of 132 760 eligible patients (66 433 women [50.0%]; median age, 57 years [IQR, 37-74 years]), 17 174 (12.9%) tested positive for SARS-CoV-2 within 14 days of their first NAAT. The diagnostic sensitivity of the SARS-CoV-2 NAAT was 96.2% (17 070 of 17 740 [95% CI, 95.9%-96.4%]) among all of the tests performed. Estimates ranged from a high of 97.7% (1710 of 1751 [95% CI, 96.8%-98.3%]) on day 2 of symptoms to a low of 90.4% (170 of 188 [95% CI, 85.3%-94.2%]) on day 11 of symptoms among patients presenting with COVID-19 symptoms. Among patients reporting COVID-19 symptoms, the sensitivity of the SARS-CoV-2 NAAT was 97.1% (11 870 of 12 225 [95% CI, 96.7%-97.3%]) compared with 87.6% (812 of 927 [95% CI, 85.2%-89.6%]) among patients without COVID-19 symptoms. The diagnostic yield of the SARS-CoV-2 NAAT was 12.0% (18 985 of 158 004 [95% CI, 11.8%-12.2%]) and varied from a high of 20.0% (445 of 2229 [95% CI, 18.3%-21.6%]) among patients tested on day 10 after symptom onset to a low of 8.1% (1686 of 20 719 [95% CI, 7.7%-8.5%]) among patients presenting within the first 24 hours of symptom onset.

Conclusions and Relevance  This study suggests that the diagnostic sensitivity was high for the first SARS-CoV-2 NAAT performed in the hospital and did not vary significantly by symptom duration. Repeated testing of patients with negative test results should be avoided unless their pretest probability of disease is high.

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Article Information

Accepted for Publication: August 26, 2022.

Published: October 12, 2022. doi:10.1001/jamanetworkopen.2022.36288

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Hohl CM et al. JAMA Network Open.

Corresponding Author: Corinne M. Hohl, MD, MHSc, Department of Emergency Medicine, Faculty of Medicine, University of British Columbia, 2775 Laurel St, Vancouver, BC V5Z 1M9, Canada (corinne.hohl@ubc.ca).

Author Contributions: Drs Hohl and Rosychuk 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: Hohl, Vaillancourt, Grant, Morrison, Rosychuk.

Acquisition, analysis, or interpretation of data: Hau, Vaillancourt, Brooks, Morrison, Perry, Rosychuk.

Drafting of the manuscript: Hohl, Hau, Rosychuk.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Hau, Vaillancourt, Rosychuk.

Obtained funding: Hohl, Brooks, Morrison, Rosychuk.

Administrative, technical, or material support: Hohl, Grant, Morrison, Perry, Rosychuk.

Supervision: Hohl.

Conflict of Interest Disclosures: Dr Hohl reported receiving grants from the Canadian Institutes of Health Research, Genome BC, Health Research BC, the Canadian Immunity Task Force/Public Health Agency of Canada, Ontario Ministry of Colleges and Universities, the Saskatchewan Health Research Foundation, and Fondation du CHU de Québec during the conduct of the study. Dr Brooks reported receiving grants from the Canadian Institutes of Health Research, Ontario Ministry of Colleges and Universities, the Saskatchewan Health Research Foundation, Genome BC, Fondation du CHU de Québec, COVID-19 Immunity Task Force, BC Academic Health Science Network, and BioTalent Canada during the conduct of the study. Dr Perry reported receiving the Heart and Stroke Foundation Canada Mid-Career Salary Award outside the submitted work. No other disclosures were reported.

Funding/Support: The network is funded by the Canadian Institutes of Health Research (447679, 464947, and 466880), Ontario Ministry of Colleges and Universities (C-655-2129), Saskatchewan Health Research Foundation (5357), Genome BC (COV024 and VAC007), Fondation du CHU de Québec (Octroi No. 4007), and Sero-Surveillance and Research (COVID-19 Immunity Task Force Initiative), which provided peer-reviewed funding; the BC Academic Health Science Network and BioTalent Canada provided non–peer-reviewed funding.

Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: The Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN) investigators for the Network of Canadian Emergency Researchers and the Canadian Critical Care Trials Group are listed in Supplement 2.

Additional Contributions: We gratefully acknowledge the University of British Columbia clinical coordinating centre staff; the University of British Columbia legal, ethics, privacy, and contracts staff; and the research staff at each of the participating institutions in the network. Coordinating centre and site staff were paid from research grants from not-for-profit organizations. The network would not exist today without the dedication of these professionals. Thank you to all of our patient partners who shared their lived experiences and perspectives to ensure that the knowledge we co-create addresses the concerns of patients and the public. Creating the largest network of collaboration across Canadian emergency departments would not have been feasible without the tireless efforts of emergency department chiefs as well as research coordinators and research assistants at participating sites. Finally, our most humble and sincere gratitude to all of our colleagues in medicine, nursing, and the allied health professions who have been on the front lines of this pandemic from day 1 by staffing our ambulances, emergency departments, intensive care units, and hospitals and bravely facing the risks of COVID-19 to look after our fellow citizens and after one another. We dedicate this network to you.

Additional Information: The CCEDRRN governance structure includes patient partners on the Executive, Steering, Protocol Review and Publications, Data Access and Monitoring, Knowledge Translation, and Patient Engagement Committees. The Patient Engagement Committee with patient partners from across Canada with lived experience with COVID-19 provided input into study design and manuscript writing and provided advice on knowledge translation strategies.

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