Antigen testing detects SARS-CoV-2 better than PCR

A team of scientists from the United States demonstrates that rapid antigen tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more effective in determining the actual infection status in patients with coronavirus disease 2019 (COVID-19) than real-time polymerase chain reaction (RT PCR)-based tests. The study is currently available in the medRxiv* preprint server.

SARS-CoV-2, the causative pathogen of the COVID-19 pandemic, is a single-stranded RNA virus that rapidly spread from human to human primarily via respiratory droplets. The average incubation time for the virus is 5.8 days, which can be extended up to 14 days. Studies have shown that although viral RNA can be detected by polymerase chain reaction (PCR), no infectious virus (live virus) remains in patients’ specimens after around 8 days of symptom onset.

Regarding the detection of SARS-CoV-2, the US Food and Drug Administration (FDA) has recently approved antigen-based tests for the rapid diagnosis of COVID-19. These tests are a type of immunoassay that directly detects the presence of a target viral protein (antigen) in biological samples. There is evidence showing that compared to PCR-based test results, antigen-based test results correlate better with culture-based test results.

Current study objective

Given the significance of antigen-based testing in defining infectiousness, the current study aimed at evaluating the efficacy of antigen-based SARS-CoV-2 testing in differentiating contagious people from non-contagious people compared to that of PCR-based testing.

Current study design

The scientists performed both PCR-based and antigen-based tests using respiratory swab samples obtained from various regions across the United States. The results were compared with the SARS-CoV-2 TMPRSS2 culture, a sensitive virus culture test used as the reference method for determining infectiousness.

Important observations

Of 38 PCR-derived positive samples, 28 were positive, and 10 were negative in virus culture testing. By comparing antigen-based test results, the scientists observed that all samples except one were positive in both PCR-based and culture-based tests were also positive in the antigen-based test. Of 10 samples that were positive in PCR but negative in viral culture, two were positive in the antigen-based testing. These findings indicate that antigen-based test results correlate better with virus culture results.

In addition, the scientists found that of 38 PCR-positive samples, nine were negative in the antigen-based test. The viral RNA load was significantly lower in these 9 samples compared to that in other samples. By comparing viral RNA load with test type, the scientists observed no difference between the antigen test and viral culture in providing positive results; however, the PCR test showed minimal similarity with viral culture by generating positive results at much lower RNA loads.

Regarding test efficacy, the antigen test showed 96% sensitivity and 98% specificity, whereas the PCR test showed 100% sensitivity and 95% specificity. With a study prevalence of 11%, which was determined by virus culture-positive results (a total of 251 samples), the antigen test and PCR test showed positive predictive values of 90% and 73%, respectively.

Current study significance

The current study findings indicate that both antigen tests and PCR tests have almost equal sensitivity in detecting SARS-CoV-2 over a time period of less than 8 days post symptom onset. However, alike virus culture tests, antigen tests perform better in detecting the presence of the infectious virus in patients’ samples compared to PCR-based tests. It is possible to detect viral RNA in respiratory swab samples by PCR tests even after the complete attenuation of the infectious virus.

Studies have shown that in COVID-19 patients, the infectious virus cannot be detected in samples collected from the upper respiratory tract after 10 days of symptom onset. Therefore, the chance of viral transmission from these people is very less.

With a comparatively higher positive predictive value than PCR tests, antigen tests may be more effective in rapidly and timely differentiating contagious people from non-contagious people.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.     

Journal reference:
Dr. Sanchari Sinha Dutta

Written by

Dr. Sanchari Sinha Dutta

Dr. Sanchari Sinha Dutta is a science communicator who believes in spreading the power of science in every corner of the world. She has a Bachelor of Science (B.Sc.) degree and a Master's of Science (M.Sc.) in biology and human physiology. Following her Master's degree, Sanchari went on to study a Ph.D. in human physiology. She has authored more than 10 original research articles, all of which have been published in world renowned international journals.

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