Experts explain in detail the advantages of antigen detection + nucleic acid detection: one is fast, one is accurate, and they complement each other

Antigen testing has officially joined the epidemic prevention front, and community residents can also purchase self-tests.

According to the website of the National Health and Health Commission on March 11, the State Council issued a notice in response to the comprehensive group of the joint prevention and control mechanism of the new coronavirus pneumonia epidemic, decided to add antigen detection as a supplement on the basis of nucleic acid testing, and organized the formulation of the "New Coronavirus Antigen Detection Application Plan (Trial)" (hereinafter referred to as the "Plan").

The "Plan" stipulates three types of people with antigen testing, including those who have certain symptoms to go to primary medical and health institutions, isolation observers, and community residents with antigen self-testing needs. The "Plan" proposes that residents can purchase antigen detection reagents for self-testing through retail pharmacies, online sales platforms and other channels.

Why add antigen testing as a supplement? What are the advantages of antigen testing? How to cooperate with antigen detection and nucleic acid testing? In this regard, The Paper (www.thepaper.cn) interviewed Professor Lu Hongzhou, a well-known infectious researcher, president of the Third People's Hospital of Shenzhen and academician of the American Institute of Microbiology.

The Paper: Nucleic acid testing plays a pivotal role in the normalization of epidemic prevention and control in the mainland, why should antigen testing be added this time?

Lu Hongzhou: According to the latest version of the "Diagnosis and Treatment Plan for Novel Coronavirus Pneumonia (Trial Eighth Revised Edition)", real-time PCR testing positive for nucleic acid of novel coronavirus is one of the most important indicators for confirmed patients. "Early detection, early diagnosis, early isolation, and early treatment" are important strategies for the prevention and control of the new crown epidemic. After the emergence of the epidemic, large-scale nucleic acid screening of closely connected groups and high-risk groups is an important means for early detection of infected patients.

But with the advent of the more immune-escaping and more contagious Omiljung strain, we can see continued outbreaks around the world. Sporadic and cluster outbreaks have occurred in many provinces and cities in the mainland, and the demand for nucleic acid testing has shown an exponential growth trend. You can find that our nucleic acid testing from the initial single test, to "5 mixed 1", "10 mixed 1", and now "20 mixed 1", are to adapt to the increasing demand for nucleic acid testing.

Compared with nucleic acid detection, antigen detection has the advantages of convenience, speed and low cost, and ordinary people can easily achieve home detection. In November 2020, the State Food and Drug Administration approved two novel coronavirus antigen detection kits in an emergency manner, which is the first time that the mainland has approved the new coronavirus antigen detection reagent, and the product testing time is within 20 minutes. Based on the advantages of antigen detection, the use of antigen detection kits for self-testing can help us quickly find some infected people, and can also reduce the risk of possible exposure in the nucleic acid sampling process to a certain extent, providing a good supplement for the nucleic acid detection required in epidemic prevention and control. At present, Europe, the United States, Australia, Singapore, Japan, etc. have begun to take antigen detection as the core of the prevention and control strategy.

The Paper: The above-mentioned "Plan" mentions that the monitoring mode of "antigen screening and nucleic acid diagnosis" will be promoted. So, what are the characteristics of nucleic acid detection and antigen detection, and how to cooperate well?

Lu Hongzhou: The current nucleic acid detection methods are real-time PCR, which has the characteristics of high sensitivity, studies have shown that most fluorescence quantitative PCR detection sensitivity is more than 10 copies per milliliter, so in the case of low gene copy number, nucleic acids in the sample can also be detected.

Compared to nucleic acid detection, the sensitivity of antigen detection is much lower, and the results of the study show that it is about 10 copies per milliliter. For example, some studies have evaluated the consistency of antigen detection and nucleic acid detection, and found that when the Ct value (an indicator of laboratory testing, the lower the value means that the higher the viral load of the patient) is less than 25, the consistent performance of antigen detection and nucleic acid detection reaches 95.8%; when it is higher than 25, the consistency is only about 50.7%, and when the Ct value is higher than 30, it is only about 20.9%.

Nonetheless, the presence of viral nucleic acids does not imply the presence of live infectious viruses, and studies have found that many RNA-positive samples are not infectious, especially in samples with a duration greater than 14 days. In contrast, based on the characteristics of antigen detection, some studies have found that the use of antigen detection to detect infectious viruses in patients has a high sensitivity.

Therefore, based on the dynamics of the virus in the human body, the researchers summarized the efficacy of antigen detection and nucleic acid detection in patients with infectious diseases, as shown in the figure below (the picture shows respondents revised from the internationally renowned medical journal British Medical Journal article; Alex Crozier et al. BMJ 2021; 372:n208）。

Efficacy of antigen testing and nucleic acid testing in patients with infectious disease. Courtesy of respondents

We can see that nucleic acid testing can detect infected patients very early, and then have a very accurate monitoring of the patient's entire detoxification cycle. Although antigen detection is low in sensitivity and cannot detect patients during the incubation and post-infectious periods, its sensitivity can cover the entire infectious period. As a result, multiple antigen tests (e.g., 3 or more times a week) can detect the vast majority of contagious cases. In this way, for grass-roots medical personnel, isolation observers or other personnel with self-examination needs, antigen testing can provide a good supplement for nucleic acid testing.

The Paper: The above-mentioned "Plan" proposes that residents can purchase antigen detection reagents for self-testing through retail pharmacies, online sales platforms and other channels. So do ordinary residents still need to go for nucleic acid testing?

Lu Hongzhou: At present, the mainland still implements the prevention and control policy of "dynamic zero clearance". We can see that although the country has just issued the "application plan (trial)" for the new crown antigen test, the antigen test is still only used as a supplement to nucleic acid detection. Antigen testing is mainly aimed at patients with fever symptoms at the grass-roots level, isolated observers, and residents with self-testing needs. At present, based on our "dynamic zeroing" epidemic prevention policy, if residents feel that there is a risk of exposure and infection, if conditions permit, they should still go to the relevant institutions for nucleic acid testing in time.

It should be noted that due to the problem of the sensitivity of the antigen test, under the current epidemic prevention policy of the mainland, it is not suitable to use the antigen self-test results as the basis for medical treatment, travel and access to public places.

The Paper: In the future, how can antigen detection play a better role?

Lu Hongzhou: In the future, with the promotion of antigen detection and the update of corresponding supporting facilities, provinces and cities can also set up antigen self-test upload systems similar to nucleic acid testing, which complement nucleic acid testing and divert the nucleic acid testing needs of some low-risk populations, which can greatly alleviate the pressure of nucleic acid testing.