COVID-19 Testing and Diagnostics: A Review of Commercialized Technologies for Cost, Convenience and Quality of Tests

Abstract

Population-scale and rapid testing for SARS-CoV-2 continues to be a priority for several parts of the world. We revisit the in vitro technology platforms for COVID-19 testing and diagnostics-molecular tests and rapid antigen tests, serology or antibody tests, and tests for the management of COVID-19 patients. Within each category of tests, we review the commercialized testing platforms, their analyzing systems, specimen collection protocols, testing methodologies, supply chain logistics, and related attributes. Our discussion is essentially focused on test products that have been granted emergency use authorization by the FDA to detect and diagnose COVID-19 infections. Different strategies for scaled-up and faster screening are covered here, such as pooled testing, screening programs, and surveillance testing. The near-term challenges lie in detecting subtle infectivity profiles, mapping the transmission dynamics of new variants, lowering the cost for testing, training a large healthcare workforce, and providing test kits for the masses. Through this review, we try to understand the feasibility of universal access to COVID-19 testing and diagnostics in the near future while being cognizant of the implicit tradeoffs during the development and distribution cycles of new testing platforms.

Keywords: COVID-19 diagnostic test; FDA authorized test kit; SARS-CoV-2 detection; at home test; mass testing; rapid antigen test; serology test; universal access.

Figure 1

Suitability of different types of in vitro diagnostic tests during the progression of COVID-19 infection. Approximate time intervals of SARS-CoV-2 exposure, incubation, symptoms, and recovery are illustrated. The detectability of the viral genetic material, viral proteins, and antibodies (IgM and IgG) to the virus are shown for the RT-PCR test, rapid antigen test, and antibody tests, respectively.

Figure 2

Steps for the reverse transcriptase PCR (RT-PCR) COVID-19 testing. (a) The sample is collected and put in a transport medium. (b) The virus is inactivated by detergents or by heating. (c) Viral RNA is extracted. (d,e) The contents are transferred to a 96 well plate for cDNA synthesis and detection by RT-qPCR or sample barcoding and high-throughput DNA sequencing. (f,g) In alternate method, the RNA extraction step can be omitted through direct inactivation of the virus by heating or direct lysis by detergents. The figure is reproduced and adapted under the Creative Commons license from Ioanna Smyrlaki et al., Nature Communications, Springer Nature (2020) [19].

Figure 3

Everywell’s COVID-19 Test Home Collection Kit DTC (direct-to-consumer). (a) The procedure involves ordering the test kit, completing a health intake survey, registering the unique kit ID, self-collecting a nasal swab, shipping overnight to a CLIA-certified laboratory, and obtaining RT-PCR results within 24 to 48 h of the lab receiving the sample. A telehealth consult is available to follow up on the test results. (b) The Everywell test kit consists of a gentle lower nasal swab, nasal swab tube, biohazard bag, and prepaid shipping label. Images are reproduced and adapted with permission from Everywell [20].

Figure 4

Instructions for using the Lucira COVID-19 All-in-One Test Kit. This involves at-home nasal swab collection followed by RT-LAMP reaction to detect the SARS-CoV-2 genetic material. The steps for use are as follows: (a) Wash and dry hands. (b) Remove seal from Sample Vial. (c) Set the sample vial in the test unit. (d) Swab both nostrils. (e) Insert swab into the sample vial. (f) Snap the cap closed and press the vial into the test unit. (g) Wait 30 min and obtain the result. Images are reproduced and adapted with permission from Lucira Health [25].

Figure 5

Lucira’s COVID-19 All-In-One Test Kit product and community testing data. (a) The single-use, over-the-counter test kit intended for the molecular detection of SARS-CoV-2 RNA from nasal swab samples. (b) In a Community Testing Study, the Lucira test was compared with high sensitivity Hologic Panther Fusion SARS-CoV-2 test, and achieved a 94% positive percent agreement (PPA) and a 98% negative percent agreement (NPA). Images are reproduced and adapted with permission from Lucira Health [25].

Figure 6

Benefits of using saliva specimens for SARS-CoV-2 detection compared to respiratory specimens. Images are reproduced and adapted with permission from IBX Infinity Biologix [26].

Figure 7

Spectrum Solution’s SDNA collection kit for molecular diagnostics of saliva. The self-collection device is capable of live viral neutralization at room temperature to mitigate risk exposure and sample preservation to identify viral RNA with only 200 copies/mL. Images are reproduced and adapted with permission from Spectrum Solution [27].

Figure 8

Demonstration of the manufacturing and testing facilities for laboratory processing, data storage, sample preservation, and analytical processes at IBX Infinity Biologix. (a) IBX Saliva Collection Kit. (b) A repository for cryo-preserving and storing a vast number of biological samples and consumables. (c) Automated instrumentation for sample purification, precision liquid handling, viral nucleic acid extraction and testing, Next Generation Sequencing, and analytical quality control. Images are reproduced and adapted with permission from IBX Infinity Biologix [26].

Figure 9

The Foundation for Innovative New Diagnostics (FIND) has partnered with several leading global organizations for the rapid development, scale-up, and universal access to COVID-19 diagnostics, vaccines, and therapeutics. The figure is reproduced under the Creative Commons license from the World Health Organization (WHO) publication [64].