Why is nucleic acid testing the gold standard?


 

      There are two methods to detect virus: one is the direct method, including virus-specific antigen detection and virus nucleic acid detection, such as qPCR and next generation sequence. And the other is the indirect method, which measures serum IgM and IgG antibodies, such as chemiluminescent immunoassay, enzyme-linked immunosorbent assay and colloidal gold-based immunochromatographic assay. Each test has its advantages and disadvantages, and the real-world application scenario and order should be determined according to the clinical characteristics of different virus infections and clinical circumstances. When facing 2019-nCoV, the cause of an outbreak of respiratory illness, it is essential to choose a reliable test for preventing its spreading worldwide.
 

      Many factors are affecting the accuracy of virus detection:
      1、Pathways and latency cycles of pathogens entering the human body.
      In the virus infection cycles, the distribution of high-titer viruses varies dynamically,as a result, even using the same detection method, it will also lead to diagnosis bias recording to the different sampling methods and sampling time. For example, SARS-CoV-2019 massively proliferates in the lower respiratory tract in the early stage of infection, so the sputum sample has the highest tier, and subsequently, it is mainly detected in nasopharyngeal swab sample in the upper respiratory tract, indicating strong infection ability. While during the rehabilitation process, anal swabs have a higher detection rate than nasopharyngeal swabs.
 

      2、Kinds of viral markers:
      Viral markers, including antigens, nucleic acids, antibodies and so on, whose positive value and peak distribution time vary with different viral infection phases. Therefore, it should optimize the combination of the sampling period and the detection method to avoid the diagnostic error. For example, the nucleic acid test is generally higher sensitive in the initial phase of viral infection, and the IgM antibody test should be taken in the early and middle phases with median sensitivity. IgG antibodies only appear in the middle and late stages of infection, so the IgG antibody test could be used as an assist diagnosis to help to decide whether to discharge, which has higher sensitivity, but lower specificity.
 

      Can blood virus antibody test replace virus nucleus acid test?
      From the experience of SARS-CoV-2019 detection in China, several problems are existing in the detection of viral antibodies in serum:
      1) IgM antibody detection has low sensitivity for patients at the initial stage of infection, so it needs to take samples repeatedly every other day. 
      2) IgG antibody is not suitable for screening for potential infections, but for identifying self-healing and a few asymptomatic people.
      3) IgM and IgG antibody testing require high-quality virus antigens, however, the first and second generation of blood virus antibody tests in the market did not use the SARS-CoV-2019 antigen instead of SARS antigens as lack of special antigen at that time. It is recommended to perform the double-blind evaluation for IgM and IgG antibody testing
 

      At present, nucleic acid testing is the gold standard for the diagnosis of SARS CoV-2019, recommended by SARS-CoV-2019 diagnosis and treatment guideline in China, FDA, and WHO, and virus antibody test can be an important supplement to nucleic acid testing.


FDA indicates that the virus antibody test cannot be used to confirm
the infection of SARS-CoV-2019


WHO instructs suspected SARS-CoV-2019 cases should be
screened with RT-PCR

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