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Ben Ting

Importance of Sensitivity and Turnaround Time for COVID-19 Testing

This summer during the 2021 College World Series, the North Carolina State University baseball team had to withdraw from the pinnacle event in college baseball due to an outbreak of COVID-19 inside the team and travel party. This was extremely disappointing to NC State and college baseball fans around the world. With the safety of the players and staff being the number one priority, the question still exists whether the testing protocols deployed by the NCAA could have been further optimized to prevent the outbreak from spreading as large as it did, causing the team’s removal from the College World Series.1

NCAA Testing Protocol Utilized at College World Series: Each player, coach, or travel party member took a SARS-CoV-2 antigen test upon arrival and at pre-determined intervals during the entirety of the College World Series. If a person tested positive on the antigen test, the NCAA would send the person to take a more sensitive molecular test. If the molecular test was positive as well, the individual became subject to what the NCAA dubs “blue protocol,” meaning the individual was not cleared to participate and would immediately go into isolation and contract tracing was initiated.

Timeline of Events for NC State Baseball Team:

  • June 20: There were no positive SARS-CoV-2 antigen tests for any members of the NC State baseball team and traveling party.
  • June 21: One member of the team was reported to have a “bug” and multiple members requested the need for extra rest. The roommate of the member of the team with the “bug” was removed overnight June 20 from the shared hotel room.
  • June 22: The member of the team with the bug tested positive by antigen and then positive again by molecular test and was deemed not clear to participate and was isolated. The roommate of this individual was directed to quarantine. The roommate and the members of the team that requested extra rest on June 21 were all tested by antigen and tested negative.
  • June 23 – 25: The roommate of the member of the team that tested positive eventually tested positive by antigen and molecular by June 25. Two additional team members that requested extra rest earlier in the week, too, tested positive for COVID-19, bringing the team’s total to four COVID-19 positive members, deemed “outbreak” status by the NCAA. With this status, the entire team, including all vaccinated and unvaccinated players, were tested with a molecular test.
  • June 26: Four additional members of the team tested positive by COVID-19, bringing the team total to eight members with COVID-19 infections. The NC State baseball team was removed from the College World Series, and members with COVID-19 infections followed state and local regulations before traveling home days later.

Could a Different Testing Strategy have made a Difference?2

SARS-CoV-2 antigen testing has been widely used because of the low cost, portability, and ease-of-use. These tests, however, are plagued by poor sensitivity.2 With the high level of infectiousness and transmissibility of SARS-CoV-2, especially with the Delta variant, it may be important to shift to using the more sensitive molecular point-of-care (mPOC) SARS-CoV- 2 tests as front-line tests instead of antigen tests.3 Use of more sensitive mPOC SARS-CoV-2 tests with rapid <30-minute turnaround times in settings like the College World Series, workplaces, and schools can detect infections earlier than antigen tests, allowing individuals positive for COVID-19 and close contacts to be isolated hours to days faster to prevent further spread of disease. Because of the higher sensitivity of mPOC tests, they can also be used with high confidence to understand if close contacts are infected in what is called “test to stay” testing.

With the significant risks posed by COVID-19 to unvaccinated individuals and even some vaccinated individuals, antigen testing is being swapped out in many traditional and non-traditional settings for more sensitive mPOC tests.3 It is unknown whether this change would have made a difference for the NC State baseball team, but given the data available showing the capability of molecular tests to detect the virus earlier, the NCAA may have benefitted from choosing to use mPOC testing as a frontline test versus antigen testing.

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Antigen vs Molecular Test: Which type of COVID-19 test is more reliable?

In the antigen vs molecular test debate, understanding which test is best is a matter of timing and application—the answer could change depending on how you’re using the test and how quickly you need the test results. In addition, the emergence of newer testing technologies may change the parameters of the debate, tipping the balance towards molecular testing for a number of situations.

To understand which test technology will work best for your application, let’s take a closer look at the pros and cons of each technology (note that for the sake of brevity, we are leaving the discussion of sample type for another article).

Molecular tests performed in a central lab are sensitive and specific, but take time to deliver results

What a molecular test detects

In general, molecular tests detect nucleic acid—either RNA or DNA.

Why this matters for diagnosing COVID-19

Molecular tests can detect the presence of SARS-CoV-2 even during the early stages of infection because they detect viral RNA, which can accumulate to high levels within a cell before virus particles are formed.

Benefits of molecular tests

Molecular tests are ideal for detecting emerging infectious diseases such as the SARS-CoV-2 virus because they are quick to develop and deploy.

Most molecular tests that are conducted in a central lab setting are very sensitive and specific, with commercially available SARS-CoV-2 molecular tests exhibiting >95% sensitivity and >99% specificity, with the potential to detect as little as a few dozen to a few hundred copies/mL of a nucleic acid sequence from the pathogen (i.e., they have low limits of detection (LOD)).1

Thus, molecular tests can detect disease in the very early stages of infection, when the viral load is fairly low.

Challenges of molecular tests

While the sensitivity and specificity of lab-conducted molecular tests is high and the LOD is low, the complexity of these tests typically restricts their use to the central lab setting. This adds time between when the sample is taken and when results are delivered. At best, the turnaround time can be as little as 24-48 hours, but at the height of the pandemic, some labs were experiencing turnaround times of as much as two weeks due to reagent shortages and insufficient testing throughput.

For highly infectious diseases like SARS-CoV-2, the delay in receiving test results can negatively impact both the patient—by potentially forcing them to quarantine while waiting for results—and public health, if an infectious patient does not quarantine while waiting for results.

Best applications for SARS-CoV-2 molecular tests

With their high sensitivity and specificity, SARS-CoV-2 molecular tests are often considered the gold standard for diagnosis. The Infectious Disease Society of America (ISDA) recommends molecular tests for symptomatic patients even if the suspicion of COVID-19 is low, and prefers that results be available within 48 hours.2

For asymptomatic patients, the ISDA recommends testing only in certain situations2, such as:

  • Upon known or suspected exposure to COVID-19
  • Upon admission to a hospital in an area with a high prevalence of COVID-19
  • Before certain medical procedures

Antigen tests can be performed at the point-of-care, but are not as sensitive as molecular tests leading to higher false negative rates

What an antigen test detects

In general, an antigen test detects a protein that’s unique to the pathogen. For SARS-CoV-2 detection, the antigen tests detect a protein of the virus particle.

Why this matters for diagnosing COVID-19

Because antigen tests rely on production of virus particles, they can miss newly-infected patients that have virus replicating within their cells but have not yet produced measurable amounts of virus particles.

Benefits of antigen tests

Antigen tests are easy to conduct, inexpensive, and deliver results in minutes. They are also highly specific and can be done at the point-of-care.3

Challenges of antigen tests

The benefits of antigen testing are balanced by a lower sensitivity than molecular tests, with sensitivity dependent on whether or not symptoms are present and how long after symptom onset the test is given. For tests given within seven days of symptom onset, pooled antigen test sensitivity is 84%, dropping to 49% in asymptomatic individuals.3

The lower sensitivity can lead to a higher false negative rate, i.e., more missed infections, which restricts their usefulness to certain situations when molecular tests are widely available.

Best applications for SARS-CoV-2 antigen tests

While the ISDA recommends molecular tests over antigen tests for symptomatic individuals unless test results will not be delivered within three days, their recommendations for asymptomatic individuals are neither for nor against antigen testing due to a lack of sufficient evidence either way.3

That said, a more recent simulation study based on real-world data suggests that although RT-PCR tests perform better than antigen tests in detecting infected individuals and preventing transmission, more frequent antigen testing, e.g., every day or every 3 days, is comparable to less frequent RT-PCR tests, at the expense of many more false-negative tests. This indicates that frequent antigen tests, potentially self-administered at home could be an important tool in combating spread of infection.4

The Talis One delivers all the benefits of molecular tests with similar speed and convenience of antigen tests

As can be seen from the above discussion, the antigen vs. molecular test debate has primarily been one of test quality versus speed, with the molecular test being used as the gold standard, although it can take days to get results, and the antigen test being used when speed is more important than sensitivity.

However, the Talis One is set to change the cost/benefit balance in this debate. It’s a molecular test that can be done quickly and easily at the point-of-care, delivering results in under 30 minutes. And unlike other point-of-care tests, the Talis One’s unique cartridge technology includes solid-phase nucleic acid extraction, which gives it a sensitivity and LOD that’s comparable to molecular tests performed in a lab, enabling excellence at the point of care.


In the antigen vs. molecular test debate, the best test is the one that gives you the highest sensitivity and specificity in the shortest amount of time. Molecular testing is the gold standard, although antigen testing can be effective when speed is necessary. Now, with the Talis One, you can get similar speed and point-of-care convenience as an antigen test with the quality you could previously only get from a central lab molecular test.


  1. Antigen and Molecular Tests for COVID-19. COVID-19 Testing Toolkit website. Accessed July 9, 2021.
  2. Hanson KE, et al. IDSA Guidelines on the Diagnosis of COVID-19: Molecular Diagnostic Testing. Clin Infect Dis. 2020 Jun 16;ciaa760. doi: 10.1093/cid/ciaa760.
  3. Hanson KE, et al. IDSA Guidelines on the Diagnosis of COVID-19: Antigen Testing. Clin Infect Dis. 2021 Jun 23;ciab557. doi: 10.1093/cid/ciab557.
  4. Ke R, et al. In vivo kinetics of SARS-CoV-2 infection and its relationship with a person’s infectiousness. medRxiv. Preprint. 2021 Jun 30. doi: 10.1101/2021.06.26.21259581. Accessed July 10, 2021.

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