The diagnostic accuracy of isothermal nucleic acid point-of-care tests for human coronaviruses: A systematic review and meta-analysis

Abstract

Many recent studies reported coronavirus point-of-care tests (POCTs) based on isothermal amplification. However, the performances of these tests have not been systematically evaluated. Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy was used as a guideline for conducting this systematic review. We searched peer-reviewed and preprint articles in PubMed, BioRxiv and MedRxiv up to 28 September 2020 to identify studies that provide data to calculate sensitivity, specificity and diagnostic odds ratio (DOR). Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) was applied for assessing quality of included studies and Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA) was followed for reporting. We included 81 studies from 65 research articles on POCTs of SARS, MERS and COVID-19. Most studies had high risk of patient selection and index test bias but low risk in other domains. Diagnostic specificities were high (> 0.95) for included studies while sensitivities varied depending on type of assays and sample used. Most studies (n = 51) used reverse transcription loop-mediated isothermal amplification (RT-LAMP) to diagnose coronaviruses. RT-LAMP of RNA purified from COVID-19 patient samples had pooled sensitivity at 0.94 (95% CI: 0.90–0.96). RT-LAMP of crude samples had substantially lower sensitivity at 0.78 (95% CI: 0.65–0.87). Abbott ID Now performance was similar to RT-LAMP of crude samples. Diagnostic performances by CRISPR and RT-LAMP on purified RNA were similar. Other diagnostic platforms including RT- recombinase assisted amplification (RT-RAA) and SAMBA-II also offered high sensitivity (> 0.95). Future studies should focus on the use of un-bias patient cohorts, double-blinded index test and detection assays that do not require RNA extraction.

One swab, two tests: Validation of dual SARS-CoV-2 testing on the Abbott ID NOW™

“…Rapid identification of individuals with COVID-19 is critical to prevent transmission and ensure patients receive optimal care. In agreement with others, we report that the ID NOW™ COVID-19 assay has high specificity but low sensitivity for detecting SARS-CoV-2 in dry swabs [ 9 , 10 , 16 , 17 ]. We noted a percent positivity of 13.4% (46/343) which reflected COVID-19 infection dynamics occurring at the time the study was conducted, which was during the peak of the second pandemic wave in Ontario, Canada.…”

“…The ID NOW™ COVID-19 assay (Abbott Diagnostics Inc, USA), is a rapid (<15 minutes) molecular in vitro diagnostic test that uses isothermal nucleic acid amplification technology to qualitatively detect SARS-CoV-2 viral RNA directly from nasal, throat or nasopharyngeal (NP) swabs [4] . To date, the assay has demonstrated variable performance, with reported sensitivities ranging from 45% to 94% [5] , [6] , [7] , [8] , [9] , [10] . A recent systematic review noted an average sensitivity of 76.8% (95% CI: 72.9-80.3%) and a specificity of 99.6% (95% CI: 98.4-99.9%) across 5 independent evaluations [9] .…”

Evaluation of RT-qPCR and Loop-Mediated Isothermal Amplification (LAMP) Assays for the Detection of SARS-CoV-2 in Argentina

“…Some, such as the ELA CHEMSTRIP, demonstrated high clinical sensitivity, whereas others, such as the ATILA and NEOKIT tests, showed high clinical specificity. These data are in accordance with previous studies reporting lower diagnostic ability with respect to that of RT-qPCR methods for the detection of SARS-CoV-2 [ 26 , 27 , 28 ], although some previous reports have described analytical sensitivities similar to those of RT-PCR assays [ 29 , 30 ]. In this regard, most LAMP studies have shown that the diagnostic specificity is of less concern than the sensitivity [ 27 ].…”

A Smartphone Camera Colorimetric Assay of Acetylcholinesterase and Butyrylcholinesterase Activity

“…The smartphone camera-based colorimetric assay also meets the common requirements and expectations of point-of-care tests: simplicity, portability, no elaborative manipulations with samples, low cost, no use of harmful reagents, etc. [ 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. Additionally, it meets the requirements of thin layer detectors like paper biosensors [ 36 ].…”