key: cord-0733178-8m1mhrw8
authors: Patriquin, Glenn; LeBlanc, Jason J.
title: SARS-CoV-2 sensitivity limbo – how low can we go?
date: 2020-11-17
journal: Int J Infect Dis
DOI: 10.1016/j.ijid.2020.11.138
sha: 100494a59a77590fbba09a493cb419d702a83f7b
doc_id: 733178
cord_uid: 8m1mhrw8

• SARS-CoV-2 rapid diagnostic tests are less sensitive than traditional RT-PCR assays. • SARS-CoV-2 rapid diagnostic tests may play a role in specific circumstances. • The context in which SARS-CoV-2 rapid diagnostic tests are utilized effectively requires critical thinking and further data.

To the Editor, Since the beginning of the pandemic, molecular methods such as real-time RT-PCR have been used as references for SARS-CoV-2 detection. With unprecedented demands for SARS-CoV-2 testing, and difficulties acquiring NAAT supplies, clinical laboratories are challenged with providing timely results.

Rapid diagnostic tests (RDTs) are simple, rapid, and portable technologies that offer a potential solution to increase diagnostic testing capacity. Recently, some RDTs have become licensed under emergency use authorization for SARS-CoV-2 detection in the laboratory or point-of-care settings [1] , but despite their high specificity, the applicability of RDTs has been hampered by poor clinical sensitivity, which often falls below the ideal target product profiles recommended by the World Health Organization (WHO). [2] [3] [4] In a recent systematic review and meta-analysis [2] , the average pooled sensitivity of antigen-based RDTs was 56%, and values as low as 11.7% have been reported. [5] In contrast, a recent study in this journal by Porte et al. [6] described high clinical sensitivity of an antigen-based RDT at 93.9%. Given the wide variability in RDT sensitivity, careful consideration is needed on the generalizability and applicability of these findings.

Traditionally, SARS-CoV-2 detection methods strived to achieve the highest sensitivity possible. [7] From an individual diagnostic perspective, the decreased analytical sensitivity of RDTs (~10 5 copies/ml vs. ~10 3 copies/ml for NAATs) would likely only be relevant during a short period in the acute stage of illness, or late in disease. [7] [8] [9] [10] As individuals with resolving viral loads are less likely to be infective [i.e. high cycle thresholds (Ct values) in real-time RT-PCR], this situation may adequately be served by an RDT. [8] [9] [10] However, on a population level, identification of individuals with early or late disease would allow for more complete contact tracing and potentially lead to more case finding and interventions.

In recent publications, an alternative strategy has been proposed that might overcome the poor sensitivity of RDTs by repeat testing of target populations over time, thereby increasing the probability of capturing individuals who fall into a period of high viral shedding. [9, 10] To date, the feasibility of repeat testing using RDTs has been hampered by limitations such as scalability (with low throughput devices), human and material resources requirements, and acceptability of repeat collections with the authorized specimen types (e.g. nasopharyngeal swabs). Regardless of the challenges of RDT implementation, thorough validation is required with consideration for factors that are method-, virus-, host-, and contextdependent.

With the considerations above in mind, key parameters that remain to be defined for repeat testing using RDTs is the minimal acceptable value for sensitivity, the optimal testing frequency in target populations, and for which population or setting RDTs would best be of benefit. If the goal is case-finding and

Food and Drug Administration (FDA)

Diagnostic Test Accuracy Group. Rapid, point-of-care antigen and molecular-based tests for diagnosis of SARS-CoV-2 infection. Cochrane Database Syst Rev

Antigen-detection in the diagnosis of SARS-CoV-2 infection using rapid immunoassays. Interim guidance

COVID-19 Target product profiles for priority diagnostics to support response to the COVID-19 pandemic v.1.0

Clinical Evaluation of Self-Collected Saliva by Quantitative Reverse Transcription-PCR (RT-qPCR), Direct RT-qPCR, Reverse Transcription-Loop-Mediated Isothermal Amplification, and a Rapid Antigen Test To Diagnose COVID-19

Evaluation of a novel antigen-based rapid detection test for the diagnosis of J o u r n a l P r e -p r o o f SARS-CoV-2 in respiratory samples

COVID-19 Pandemic Diagnostics Investigation Team of the Canadian Public Health Laboratory Network (CPHLN) Respiratory Virus Working Group. Real-time PCR-based SARS-CoV-2 detection in Canadian laboratories

Virological assessment of hospitalized patients with COVID-2019

Rethinking Covid-19 Test Sensitivity -A Strategy for Containment

Epub ahead of print

Test sensitivity is secondary to frequency and turnaround time for COVID-19 surveillance. medRxiv