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COVID-19 Molecular Testing

Meeting the changing needs of the rapidly evolving COVID-19 pandemic.

A Dynamic Situation

 

The emergence of SARS-CoV-2 in late 2019 led to tremendous upheaval as COVID-19 transitioned from a localized epidemic to a global pandemic. Since that time, the global biomedical and public health communities have accomplished groundbreaking work, with the rapid development of molecular diagnostic tests and, approximately a year later, a number of highly effective vaccines.1

Despite vaccine availability in much of the developed world, localized COVID-19 surges continue to appear due to the development of new SARS-CoV-2 variants, such as the more transmissible Delta variant2, and more recently the Omicron variant. With ongoing challenges to global vaccine distribution3, it’s become increasingly clear that new variants will be a constant threat4, and that even regions with high vaccination rates will need to be prepared for new disease surges.

January 10, 2020
The first SARS-CoV-2 genome sequence was released to the public at virological.org5
January 20, 2020
The first SARS-CoV-2 molecular diagnostic assay was published5
March 11, 2020
The World Health Organization (WHO) declares COVID-19 a pandemic1

A Continued Need for COVID-19 Molecular Testing

 

Given the continued threat of new variants, testing remains a critical and much needed component of ongoing pandemic response measures, although demand may vary over time as caseloads change.6–8 While there are many different types of tests that have emergency use approval (EUA) in the United States, including molecular diagnostics/nucleic acid amplification tests (NAAT), antigen tests, and serological tests, molecular testing remains the gold standard for identifying SARS-CoV-2 infection.9

Current diagnostic tests for the SARS-CoV-2 pandemic use nucleic acid, antibody and protein-based detections, but viral nucleic acid detection by RT–PCR remains the gold standard.

–Kevadiya, et al.10

Table 1. Molecular diagnostic testing vs. antigen testing at a glance (excerpted and adapted from CDC’s Overview of Testing for SARS-CoV-2 (COVID-19) page11)

COVID-19 Molecular Tests (NAATs)

COVID-19 Antigen Tests

Analyte

Viral Ribonucleic Acid (RNA)

Viral Antigens

Sensitivity

Varies by test, but generally high for laboratory-based tests and moderate-high for point-of-care (POC) tests

Varies depending on the course of infection, but generally moderate-to-high at times of peak viral load*

Specificity

High

High

Turnaround time

Most 1-3 days. Some could be rapid in 15 minutes**

Ranges from 15 minutes to 30 minutes

Advantages

Most sensitive test method available

Short turnaround time for NAAT POC tests (~30 minutes), but few available**

Usually does not need to be repeated to confirm results

Short turnaround time (~30 minutes)***

When performed at or near POC, allows for rapid identification of infected people, thus preventing further virus transmission in the community, workplace, etc.

Comparable performance to NAATs in symptomatic persons and/or if culturable virus present, when the person is presumed to be infectious

Disadvantages

Longer turnaround time for lab-based tests (1–3 days)**

Higher cost per test

A positive NAAT diagnostic test should not be repeated within 90 days, because people may continue to have detectable RNA after risk of transmission has passed

May need confirmatory testing

Less sensitive (more false negative results) compared to NAATs, especially among asymptomatic people

*The decreased sensitivity of antigen tests might be offset if the POC antigen tests are repeated more frequently (i.e., serial testing at least weekly).
**The Talis One COVID-19 Test System delivers central lab quality test results in less than 30 minutes in a variety of health care settings.
***Refers to POC antigen tests only

Different Scenarios for COVID-19 Testing

As we move into cycles of COVID-19 containment and spread, there are a number of different ways COVID-19 testing can be implemented11:

  • Diagnosis—Testing people with COVID-19 symptoms for presence of the virus
  • Containment—Testing asymptomatic people who have been in close contact with individuals who have tested positive for SARS-CoV-2
  • Screening—Testing asymptomatic individuals to limit disease spread in specific settings, such as places of work, schools, universities, and other large gatherings

Different types of tests are better suited for each of these scenarios. Antigen testing is most accurate with symptomatic people and early in infection when viral load is high10,11, making it best suited for diagnostic applications or potentially for screening when the frequency of testing is high.11 NAAT is suitable for all three applications, although assays that are performed in a central lab are not scalable or fast enough for screening applications.

Note that the current CDC guidelines recommend using a symptom-based approach to ending isolation and precautions for individuals diagnosed with COVID-19 instead of using a test-based approach.11

TALIS BIOMEDICAL

The GenBody COVID-19 Ag Test is for use under Emergency Use Authorization (EUA) only. For In Vitro Diagnostic (IVD) use. For prescription use only. Talis is an authorized distributor of the GenBody COVID-19 Ag test.

†The Talis One Test System is not authorized, cleared, or approved by the FDA and is not available for sale.

© Talis and Talis One are trademarks of Talis Biomedical Corporation. All Rights Reserved.

* Testing solutions are currently in development and not available for sale.

References

  1. CDC. CDC Museum COVID-19 Timeline. Centers for Disease Control and Prevention. Published August 4, 2021. Accessed August 23, 2021.
  2. Tracking SARS-CoV-2 variants. Accessed August 23, 2021.
  3. Wouters OJ, Shadlen KC, Salcher-Konrad M, et al. Challenges in ensuring global access to COVID-19 vaccines: production, affordability, allocation, and deployment. The Lancet. 2021;397(10278):1023-1034. doi:10.1016/S0140-6736(21)00306-8
  4. Fontanet A, Autran B, Lina B, Kieny MP, Karim SSA, Sridhar D. SARS-CoV-2 variants and ending the COVID-19 pandemic. The Lancet. 2021;397(10278):952-954. doi:10.1016/S0140-6736(21)00370-6
  5. Corman VM, Landt O, Kaiser M, et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Eurosurveillance. 2020;25(3):2000045. doi:10.2807/1560-7917.ES.2020.25.3.2000045
  6. Quidel says COVID-19 test demand is plunging. Wall Street is underwhelmed. MedTech Dive. Accessed August 23, 2021.
  7. Janin ST Brianna Abbott and Alex. Delta Variant Increases Demand and Wait Times for Covid-19 Tests. Wall Street Journal. Published August 5, 2021. Accessed August 23, 2021.
  8. Fink S. Maker of Popular Covid Test Told Factory to Destroy Inventory. The New York Times. Published August 20, 2021. Accessed August 23, 2021.
  9. Hanson KE, Caliendo AM, Arias CA, et al. The Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Molecular Diagnostic Testing. Clin Infect Dis. 2021;(ciab048). doi:10.1093/cid/ciab048
  10. Kevadiya BD, Machhi J, Herskovitz J, et al. Diagnostics for SARS-CoV-2 infections. Nat Mater. 2021;20(5):593-605. doi:10.1038/s41563-020-00906-z
  11. CDC. Overview of Testing for SARS-CoV-2 (COVID-19). Centers for Disease Control and Prevention. Published February 11, 2020. Accessed August 24, 2021.
  12. Tu Y-P, Iqbal J, O’Leary T. Sensitivity of ID NOW and RT–PCR for detection of SARS-CoV-2 in an ambulatory population. eLife. 10:e65726. doi:10.7554/eLife.65726