COVID-19 Point-of-Care Diagnostics That Satisfy Global Target Product Profiles
Abstract
:1. Introduction
- ▪
- Rapid Test: a qualitative or semi-quantitative in vitro diagnostic medical device, intended to be used singly or in a small series, which involves non-automated procedures and has been designed to give a fast result.
- ▪
- Point of Care Testing: testing that is performed near or at the site of the patient, outside a general laboratory environment, with the result leading to possible change in the care of the patient.
- ▪
- Improved turnaround time
- ▪
- Improved monitoring during pandemics where frequent testing is desirable
- ▪
- Smaller sample (may be less invasive) and reagent volumes
- ▪
- Advantages in remote regions where access to laboratory is limited
- ▪
- Economic—POCTs may offer wider economic benefit with a reduced number of clinical visit and fewer hospital admissions
- ▪
- Greater patient involvement in their own care, improved patient experience
- ▪
- Availability outside core laboratory normal hours
- ▪
- Reduced quality of analysis (e.g., sensitivity/specificity)
- ▪
- Poor record keeping
- ▪
- Lack of result interpretation
- ▪
- Unnecessary duplication of equipment
- ▪
- Data recording may be complex and less robust
- ▪
- Incompatibility with laboratory results
- ▪
- POCT can be expensive in absence of economies of scale that come from centralized laboratory testing
2. Target Product Profiles of COVID-19 Rapid Diagnostic Tests
- Point-of-care test for suspected COVID-19 cases and their close contacts to diagnose acute SARS-CoV-2 infection;
- Test for diagnosis or confirmation of acute or subacute SARS-CoV-2 infection, suitable for high-volume needs;
- Point-of-care test for prior infection with SARS-CoV-2;
- Test for prior infection with SARS-CoV-2 for high volume needs.
- ▪
- Differences in test population
- ▪
- Time of testing; proportion of early versus late COVID-19 disease stage
- ▪
- Specimen type (nasal swab, saliva, sputum, whole blood, serum/plasma, etc.)
- ▪
- Differences in RT-PCR protocols used as reference assay
3. Direct POCTs to Detect Acute SARS-CoV-2 Infection
4. POCTs to Detect Prior SARS-CoV-2 Infection
5. Concluding Remarks
- ▪
- DetectaChem MobileDetect Bio BCC19 Test (RT-LAMP)
- ▪
- Mammoth Biosciences SARS-CoV-2 Detectr Test (RT-LAMP/CRISPR)
- ▪
- Quidel Sofia-2 Flu+SARS Antigen Test
- ▪
- Seasun Biomaterials AQ-TOP Plus COVID-19 Rapid Test (RT-LAMP)
- ▪
- Shenzhen Bioeasy Biotechnology Bioeasy Diagnostic Kit COVID-19 Antigen Test
- ▪
- Guangzhou Wondfo Biotech Wondfo SARS-CoV-2 Ab Test (These POCTs show relatively low 95% confidence internals in sensitivity/specificity assessment)
- ▪
- Hangzhou Biotest Biotech RightSign COVID-19 IgG/IgM Rapid Test
- ▪
- Hangzhou Alltest Biotech AllTest COVID-19 IgG/IgM Rapid Test (These POCTs show relatively low 95% confidence internals in sensitivity/specificity assessment)
- ▪
- NG Biotech NG IgG/IgM Rapid Test
- ▪
- Sugentech SGTi-flex COVID-19 IgG
- ▪
- VivaCheck Biotech COVID-19 IgM/IgG Rapid Test
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Rasmussen, A.L. Vaccination Is the Only Acceptable Path to Herd Immunity. Med 2020, 1, 21–23. [Google Scholar] [CrossRef]
- Wang, W.; Xu, Y.; Gao, R.; Lu, R.; Han, K.; Wu, G.; Tan, W. Detection of SARS-CoV-2 in Different Types of Clinical Specimens. JAMA 2020, 323, 1843–1844. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Vandenberg, O.; Martiny, D.; Rochas, O.; Van Belkum, A.; Kozlakidis, Z. Considerations for diagnostic COVID-19 tests. Nat. Rev. Genet. 2020, 1–13. [Google Scholar] [CrossRef]
- Brendish, N.J.; Poole, S.; Naidu, V.V.; Mansbridge, C.T.; Norton, N.J.; Wheeler, H.; Presland, L.; Kidd, S.; Cortes, N.J.; Borca, F.; et al. Clinical impact of molecular point-of-care testing for suspected COVID-19 in hospital (COV-19POC): A prospective, interventional, non-randomised, controlled study. Lancet Respir. Med. 2020, 8, 1192–1200. [Google Scholar] [CrossRef]
- Sethuraman, N.; Jeremiah, S.S.; Ryo, A. Interpreting Diagnostic Tests for SARS-CoV-2. JAMA 2020, 323, 2249. [Google Scholar] [CrossRef] [PubMed]
- Guglielmi, G. The explosion of new coronavirus tests that could help to end the pandemic. Nature 2020, 583, 506–509. [Google Scholar] [CrossRef] [PubMed]
- Woloshin, S.; Patel, N.; Kesselheim, A.S. False Negative Tests for SARS-CoV-2 Infection—Challenges and Implications. N. Engl. J. Med. 2020, 383, e38. [Google Scholar] [CrossRef] [PubMed]
- Ghaffari, A.; Meurant, R.; Ardakani, A. COVID-19 Serological Tests: How Well Do They Actually Perform? Diagnostics 2020, 10, 453. [Google Scholar] [CrossRef] [PubMed]
- Lee, K.-Y.; Rhim, J.-W.; Kang, J.-H. Immunopathogenesis of COVID-19 and early immunomodulators. Clin. Exp. Pediatr. 2020, 63, 239–250. [Google Scholar] [CrossRef] [PubMed]
- Afzal, A. Molecular diagnostic technologies for COVID-19: Limitations and challenges. J. Adv. Res. 2020, 26, 149–159. [Google Scholar] [CrossRef] [PubMed]
- Arevalo-Rodriguez, I.; Buitrago-Garcia, D.; Simancas-Racines, D.; Zambrano-Achig, P.; Del Campo, R.; Ciapponi, A.; Sued, O.; Martinez-García, L.; Rutjes, A.W.; Low, N.; et al. False-negative results of initial RT-PCR assays for COVID-19: A systematic review. PLoS ONE 2020, 15, e0242958. [Google Scholar] [CrossRef] [PubMed]
- Peeling, R.W.; Wedderburn, C.J.; Garcia, P.J.; Boeras, D.; Fongwen, N.; Nkengasong, J.; Sall, A.; Tanuri, A.; Heymann, D.L. Serology testing in the COVID-19 pandemic response. Lancet Infect. Dis. 2020, 20, e245–e249. [Google Scholar] [CrossRef]
- World Health Organization. COVID-19 Target Product Profiles for Priority Diagnostics to Support Response to the COVID-19 Pandemic v.1.0. Available online: https://www.who.int/publications/m/item/covid-19-target-product-profiles-for-priority-diagnostics-to-support-response-to-the-covid-19-pandemic-v.0.1 (accessed on 18 November 2020).
- FDA. COVID-19 Diagnostic Tests Emergency Use Authorization Database. Available online: https://www.fda.gov/medical-devices/emergency-situations-medical-devices/emergency-use-authorizations#covid19ivd (accessed on 18 November 2020).
- FINDDx. SARS-COV-2 DIAGNOSTICS: PERFORMANCE DATA. Available online: https://www.finddx.org/covid-19/dx-data/ (accessed on 18 November 2020).
- UK Gov. MHRA. Target Product Profile: Point of Care SARS-CoV-2 Detection Tests. Available online: https://www.gov.uk/government/publications/how-tests-and-testing-kits-for-coronavirus-covid-19-work/target-product-profile-point-of-care-sars-cov-2-detection-tests (accessed on 18 November 2020).
- UK Gov. MHRA. Target Product Profile: Antibody Tests to Help Determine if People Have Recent Infection to SARS-CoV-2: Version 2. Available online: https://www.gov.uk/government/publications/how-tests-and-testing-kits-for-coronavirus-covid-19-work/target-product-profile-antibody-tests-to-help-determine-if-people-have-recent-infection-to-sars-cov-2-version-2 (accessed on 18 November 2020).
- Ghaffari, A.; McGill, I.; Ardakani, A. Trends in COVID-19 Diagnostic Test Development. BioProcess Int. 2020, 18, 34. [Google Scholar]
- Wolfel, R.; Corman, V.M.; Guggemos, W.; Seilmaier, M.; Zange, S.; Muller, M.A.; Niemeyer, D.; Jones, T.C.; Vollmar, P.; Rothe, C.; et al. Virological assessment of hospitalized patients with COVID-2019. Nature 2020, 581, 465–469. [Google Scholar] [CrossRef][Green Version]
- Bullard, J.; Dust, K.; Funk, D.; Strong, J.E.; Alexander, D.; Garnett, L.; Boodman, C.; Bello, A.; Hedley, A.; Schiffman, Z.; et al. Predicting infectious SARS-CoV-2 from diagnostic samples. Clin. Infect. Dis. 2020, ciaa638. [Google Scholar] [CrossRef]
- Jiang, S.; Hillyer, C.; Du, L. Neutralizing Antibodies against SARS-CoV-2 and Other Human Coronaviruses. Trends Immunol. 2020, 41, 355–359. [Google Scholar] [CrossRef]
- U.S. Centers for Disease Control and Prevention. Interim Guidelines for COVID-19 Antibody Testing. Available online: https://www.cdc.gov/coronavirus/2019-ncov/lab/resources/antibody-tests-guidelines.html (accessed on 1 August 2020).
WHO TPP | UK MHRA TPP | |||
---|---|---|---|---|
Features | Acceptable | Desirable | Acceptable | Desirable |
Intended Use | Regions with confirmed cases, confirmed outbreaks, and in high-risk groups: early detection of SARS-CoV-2 cases where reference assays are not available or overloaded | Aid in triage of current SARS-CoV-2 infection during the acute phase of infection | Aid in triage of current SARS-CoV-2 infection at any point during active infection | |
Target Population | Patients with respiratory symptoms; contact with confirmed/probable COVID-19 cases; living in area of cluster | People with COVID-19 clinical signs and symptoms | People with or without COVID-19 clinical signs and symptoms | |
Target User/Setting | Outside laboratory in screening point of healthcare facilities by trained healthcare workers | Same but can be performed by trained lay workers | Trained healthcare worker at the point of care healthcare and non-healthcare (school, airport, prison) settings | |
Target Analyte | SARS-CoV biomarker (assuming SARS-CoV-1 is not circulating) | SARS-CoV-2 only biomarker | Single SARS-CoV-2 RNA or antigen | Dual (or more) SARS-CoV-2 RNA or antigen |
Sample Type | NP, OP, Nasal swab, nasal wash, sputum | Anterior nares, saliva/oral fluid, sputum | NP, OP swabs, BAL, NP, nasal wash | Sputum, saliva (not using invasive swab) |
Clinical Sensitivity | ≥80% | ≥90% | ≥80% [70–100%] | ≥97% [93–100%] |
Clinical Specificity | ≥97% | ≥99% | ≥95% | ≥99% |
Analytical Sensitivity (LOD) | 1 × 106 copies/mL Ct ~ 25–30 | 1 × 104 copies/mL Ct ~ >30 | <1 × 104 copies/ml | <1 × 102 copies/ml |
Time to Results | ≤40 min | ≤20 min | ≤2 h | ≤30 min |
Result Stability | Fixed reading time | Stored image or 6 weeks | <30 min | <1 h |
Storage | 12 mo at 4–30 °C | 18–24 mo at 4–40 °C | 12 mo at 2–8 °C | 12 mo at 4–30 °C |
WHO TPP | UK MHRA TPP | ||||
---|---|---|---|---|---|
Features | Acceptable | Desirable | Acceptable | Desirable | |
Intended use | Easy to use test to detect prior SARS-CoV-2 infection | Detect prior exposure to SARS-CoV-2 | Detect immunity to SARS-CoV-2 | ||
Target population | General population in survey/surveillance studies, group at high risk of exposure to SARS-CoV-2 | Recovered from suspected or confirmed SARS-CoV-2 infection | Group that need to know immunity to SARS-CoV-2 | ||
Target user/setting | Outside laboratory in screening point of healthcare facilities by trained healthcare workers | Same but can be performed by trained lay workers | Health care professionals (clinics, pharmacies, workplace, non-lab settings) | Person trained in operating the test kit (clinics, pharmacies, workplace, non-lab settings) | |
Target analyte | At least one isotype or other biomarker specific to prior SARS-CoV-2 infection | Total antibodies to SARS-CoV-2 | IgG antibodies to SARS-CoV-2 | ||
Sample type | Plasma/serum, fingerstick, saliva/oral fluids | Fingerstick blood | Fingerstick blood, venous blood, serum/plasma | ||
Clinical sensitivity | ≥90% | ≥95% | ≥98% (96–100%) (test min 200 positive samples) | ||
Clinical specificity | ≥97% | ≥99% | ≥98% (96–100%) (test min 200 negative samples) | ||
Time to results | ≤40 min | ≤20 min | ≤20 min | ≤15 min | |
Result stability | Fixed reading time | Stored image or 6 weeks | <30 min | <1 h | |
Storage | 12 mo at 2–30 °C, 70% RH | 18–24 mo at 2–40 °C, 90% RH | 12 mo at 5–30 °C, 80% RH |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Ghaffari, A.; Meurant, R.; Ardakani, A. COVID-19 Point-of-Care Diagnostics That Satisfy Global Target Product Profiles. Diagnostics 2021, 11, 115. https://doi.org/10.3390/diagnostics11010115
Ghaffari A, Meurant R, Ardakani A. COVID-19 Point-of-Care Diagnostics That Satisfy Global Target Product Profiles. Diagnostics. 2021; 11(1):115. https://doi.org/10.3390/diagnostics11010115
Chicago/Turabian StyleGhaffari, Abdi, Robyn Meurant, and Ali Ardakani. 2021. "COVID-19 Point-of-Care Diagnostics That Satisfy Global Target Product Profiles" Diagnostics 11, no. 1: 115. https://doi.org/10.3390/diagnostics11010115