Choice of SARS-CoV-2 diagnostic test: challenges and key considerations for the future

Figures & data

Table 1. A summary of the diagnostic testing methodologies for COVID-19.

	Measure	Platforms/technologies	Turnaround time (range)	Number of samples per run/test	Performance range LOD sensitivity/specificity (%)
NAATs for viral RNA antigen detection (NP swab, oropharyngeal swab, nasal swab, sputum, bronchoalveolar lavage fluid, others)	Direct detection of SARS-CoV-2 viral RNA	High-throughput RT-PCR [6]	1.5–8 hours	Up to 384	>1.23 cp/μL [7] 450–540,000 NDU/mL [8] >90%/up to 100%
		Point-of-care RT-PCR	20 min	1	>12 cp/mL [7]
		High-throughput TMA	3 hours	Unconfirmed	600 NDU/mL [9]
		Point-of-care LAMP	20–60 min	1	>10 cp/μL [7] >75% sensitivity [10]
		High-throughput LAMP (fluorescence)	45 min	96	>1 cp/μL
		CRISPR/LAMP lateral flow	15 min	1	>6.75 cp/μL [7]
Antigen detection (saliva, NP swab)	Immunoassays for the detection of SARS-CoV-2 viral antigens	High-throughput centralized	From 18 min	Up to 300	Sensitivity (95% CI) <5 days post symptom onset and Ct <30: 97.5% (92.8–99.5%), Ct >30: 26.7% (12.3–45.9%) [11]
		Point-of-care (lateral flow)	15–30 min	1	Sensitivity (95% CI): 28.9% (16.4–44.3) to 98.3% (91.1–99.7) Specificity (95% CI): 92.4% (87.4–95.9) to 100% (99.7–100) [12]
Antibody detection (serum, plasma)	Detection of immune response, i.e. past exposure to SARS-CoV-2	High-throughput centralized	First results from 18 min to 24 hours	Up to 500	Typically, >90% sensitive and >95% specific [13]
		Point-of-care (lateral flow)	15 min	1	Typically, >90% sensitive and >95% specific [13]

CI: confidence interval; cp: copies; CRISPR: clustered regularly interspaced short palindromic repeats; Ct: cycle threshold; LAMP: isothermal loop-mediated amplification; NAAT: nucleic acid amplification test; NDU: NAAT detectable units; NP: nasalpharyngeal; RNA: ribonucleic acid; RT-PCR: reverse transcription polymerase chain reaction; TMA: transcription-mediated amplification.

Figure 1. Testing strategies and considerations for the different diagnostic settings considered in this publication. Ag: antigen; CT: computed tomography; NAAT: nucleic acid amplification test; PCR: polymerase chain reaction.

Mostafa HH, Hardick J, Morehead E, et al. Comparison of the analytical sensitivity of seven commonly used commercial SARS-CoV-2 automated molecular assays. J Clin Virol. 2020;130:104578.

 PubMed Web of Science ®Google Scholar

Yu CY, Chan KG, Yean CY, et al. Nucleic acid-based diagnostic tests for the detection SARS-CoV-2: an update. Diagnostics. 2021;11(1):53.

 Web of Science ®Google Scholar

FDA. SARS-CoV-2 reference panel comparative data; 2020 [cited 2021 Nov 30]. Available from: https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/sars-cov-2-reference-panel-comparative-data

 Google Scholar

Hologic. Hologic SARS-CoV-2 assays; 2021 [cited 2021 Mar]. Available from: https://www.hologic.com/hologic-products/diagnostic-solutions/hologic-sars-cov-2-assays

 Google Scholar

Rodel J, Egerer R, Suleyman A, et al. Use of the variplex™ SARS-CoV-2 RT-LAMP as a rapid molecular assay to complement RT-PCR for COVID-19 diagnosis. J Clin Virol. 2020;132:104616.

 PubMed Web of Science ®Google Scholar

Roche Diagnostics. Elecsys SARS-CoV-2 antigen; 2021 [cited 2021 Mar]. Available from: https://diagnostics.roche.com/global/en/products/params/elecsys-sars-cov-2-antigen-test.html

 Google Scholar

Hayer J, Kasapic D, Zemmrich C. Real-world clinical performance of commercial SARS-CoV-2 rapid antigen tests in suspected COVID-19: a systematic meta-analysis of available data as of November 20, 2020. Int J Infect Dis. 2021;108:592–602.

 PubMed Web of Science ®Google Scholar

FDA. EUA authorized serology test performance; 2021 [cited 2021 Mar]. Available from: https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/eua-authorized-serology-test-performance

 Google Scholar