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.
- Antigen and Molecular Tests for COVID-19. COVID-19 Testing Toolkit website. Accessed July 9, 2021. https://www.centerforhealthsecurity.org/covid-19TestingToolkit/molecular-based-tests/current-molecular-and-antigen-tests.html#Current-Molecular-Tests
- 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.
- 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.
- 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.