Source: Laboratory, IVD information Angola Letters Author: Zhang Herui, Li Qi
Coronavirus disease 19 (COVID-19) is an infectious disease caused by 2019 novel coronavirus (2019-nCoV) infection. While causing tens of thousands of infections across the country, the epidemic has rapidly spread to many countries around the world. On March 4, 2020, the National Health Commission released the latest version of the "New Coronavirus Pneumonia Diagnosis and Treatment Plan (Trial Seventh Edition)", which adds serological testing to the original diagnosis and treatment plan, as a test for confirmed and suspected cases. One of the basis for diagnosis.
What substance is tested by serology? How to interpret the test results? This article introduces you one by one.
After the virus invades the human body, the human body will produce corresponding specific antibodies for defense. Among them, the specific antibody IgM is produced first and performs early defense, and then produces IgG antibodies. Serological testing is to detect the presence and content of specific antibodies IgM and IgG in blood samples to indirectly determine the presence or absence of viruses and viral infections in the body.
What is IgM and IgG and the difference between the two
Both IgM and IgG belong to the immunoglobulin family. Immunoglobulin is a type of serum active component produced by plasma cells under the stimulation of antigen substances that can specifically bind to antigen. According to their molecular structure and antigen specificity, immunoglobulins are divided into five categories: IgG, IgA, IgM, IgD, IgE (as shown in Figure 1):
Figure 1: Types of immunoglobulinsUnder normal circumstances, after being infected by a virus, the body will produce a series of changes to resist this invasion, among which the content of immunoglobulin will change as shown in Figure 2: After the antigen enters the body for the first time, it will produce plasma after a certain incubation period. The cells synthesize and secrete antibodies. IgM appeared first, but the antibody maintained for a short time and disappeared quickly, lasting for several days to several weeks in the blood. Next came IgG.Figure 2: Changes in the content of IgM and IgG during infectionIgG is the main component of immunoglobulin, and it is the only immunoglobulin that can pass through the placenta. When IgM is about to disappear, the content of IgG reaches a peak and lasts for a long time in the blood. When exposed to the same antigen again for several months or even years, the amount of the original antibody decreased slightly, which may be due to part of the original antibody being bound by the re-entered antigen, which temporarily reduces the antibody content, but the antibody content increases rapidly in the short term. It may be several to several tens of times higher than the original antibody content, mainly IgG, which lasts for a long time in the body, and IgM rarely increases.In this epidemic, we have conducted research on COVID-19 patients and found that after the virus invades the human body, it takes about 5 to 7 days for IgM antibodies to be produced, and IgG antibodies to be produced after 10 to 15 days. IgM and IgG are both immunoglobulins. What is the difference? We summarize the difference between the two in terms of content, production time, and clinical diagnostic function, as shown in Table 1:Interpretation of IgM and IgG test results
As mentioned above, it takes a certain incubation period for antigens to enter the body before IgM and IgG are produced. During this period, IgM and IgG could not be detected in the serum. At this time, the advantage of nucleic acid testing is reflected: it can detect whether patients in the window period are infected. However, nucleic acid testing is greatly affected by sample collection, what should I do?The two combined detection, comprehensive interpretation, to make up for the shortcomings. Therefore, when interpreting the results, we regard the nucleic acid test results as negative and positive, which are divided into two categories:When the nucleic acid test result is positive
(1) When the nucleic acid test result is positive, IgM(+)IgG(-) or IgM(-)IgG(-): It indicates that the patient is in the early stage of infection, especially if the nucleic acid test result is positive alone, IgM(-)IgG(-) ), suggesting that the patient may be in the "window period", and the relevant specific antibodies have not been produced in the body or the antibody content is low, resulting in no detection in the laboratory.(2) When the nucleic acid test result is positive, IgM(-)IgG(+), it indicates that the patient may be in the middle or late stage of infection or recurrent infection. During this period, the virus in the human body will be gradually neutralized by the IgM antibody, and the IgM antibody will gradually decrease as the disease recovers until it is below the detection limit.(3) When the nucleic acid test result is positive, IgM(+)IgG(+), it indicates that the patient is in the active phase of infection, but has produced IgG antibodies with lasting immunity.When the nucleic acid test result is negative
(1) When the nucleic acid test result is negative, IgM(-)IgG(+), it indicates that the virus has been cleared from the body of a previously infected person.(2) When the nucleic acid test result is negative, IgM(+)IgG(+), it indicates that it is a convalescent patient, and the IgM(+) content in the body has not yet reached the lower limit of detection.(3) When the nucleic acid test result is negative, IgM(+)IgG(-), the following factors must be considered:a. Whether the sample collection, transportation and testing process are affected during the nucleic acid testing process, and the patient specimens should be re-acquired for nucleic acid retest;b. Whether due to other diseases of the patient, or certain drugs taken, the false positive of IgM(+) antibody is caused, which is also an advantage of nucleic acid testing over serum antibody testing.Serological testing and nucleic acid testing
Compared with serological testing, nucleic acid testing can detect patients in the window period and detect infections early; compared with nucleic acid testing, blood samples for serological testing are easier to obtain and the quality of the specimens is guaranteed, the operation is simple and fast, and to a large extent This reduces the risk of medical staff being infected during specimen collection and testing, and makes it easier for primary laboratories to carry out screening work. If nucleic acid detection of virus ribonucleic acid (RNA) is the direct evidence and the gold standard for the existence of the virus; then the antibody detection is the stimulated antibody produced in the patient's blood, which is indirect evidence and has a clinical prompting effect. One is for the differential diagnosis of diseases to ensure "good", and the other is for initial screening of diseases to ensure "not leaking."However, it is worth noting that due to the window period of antibody detection, as well as the sensitivity and specificity of different antibody reagent methods and different manufacturers, clinical diagnosis cannot be based solely on antibody serological results. Therefore, combining nucleic acid detection methods and other indications for comprehensive interpretation and combined application can help increase the detection rate of the disease, find the confirmed patients as much as possible, and be more conducive to the control of the epidemic.(1.) The best doctor of mankind is himself——Talking about immunoglobulin and human health. Chinese Journal of Immunology. 2016;32(12):1889-90.(2.) Li Quan, Liu Dingbin, Qiao Zhengrong, Zhu Xiaolan, Peng Xiaobin, Wu Xiaolan, et al. The value of SARS-CoV-2 IgM/IgG antibody detection in the diagnosis of new coronavirus pneumonia. International Journal of Laboratory Medicine. 1-10 . http://nvsm.cnki.net/KCMS/detail/50.1176.r.20200304.1041.006.html [Internet pre-release](3.) Ning Yating, Hou Xin, Lu Minya, Wu Xian, Li Yongzhe, Xu Yingchun. Discussion on the application of new coronavirus serum-specific antibody detection technology. Union Medical Journal. 1-9.http://nvsm.cnki.net/KCMS/detail/11.5882.R.20200305.1652.002.html[Internet pre-release]