With the normalization of the COVID-19 epidemic, COVID-19 nucleic acid testing and COVID-19 antibody testing have become necessary passes in many situations, because COVID-19 nucleic acid testing is an absolutely important indicator of the diagnosis and prognosis of new coronary pneumonia.

Therefore, the country has issued a lot of guidelines and technical specifications on COVID-19 nucleic acid testing, which regulates COVID-19 nucleic acid testing from sample collection before inspection, site, reagents, equipment, waste treatment requirements, and inspection quality control during the inspection process to after inspection. The entire inspection process, including the issuance of reports, also clarified the different biological safety protection levels of nucleic acid testing sample collection and inspection processes in different scenarios.

COVID-19 Antibody Testing

However, compared with COVID-19 nucleic acid detection, there is a lack of standardized documents on COVID-19 antibody testing at the national level and within the inspection industry. Even if the COVID-19 antibody testing is mentioned in some documents, it is only mentioned in a brief, rarely detailed introduction.

Combining actual work, we found that there are still some problems in the current new crown antibody detection, these problems are as follows:

(1) Biosafety issues of the staff involved in COVID-19 antibody testing

Check the relevant documents related to the biosafety of new coronavirus antibody detection, including the “New Coronavirus Laboratory Biosafety Guidelines (Second Edition)” issued by the National Health Commission, and the “New Coronavirus Laboratory Testing Technical Guidelines for Pneumonia (Second Edition)” Version)” and the “Specifications for Collection, Packaging, Transportation and Testing of New Coronavirus Pneumonia Samples (T/BPMA 0004-2020)” issued by the Beijing Preventive Medicine Association.

The first two require that the virus antigen detection, serological detection, nucleic acid detection, biochemical analysis, and other operations of uncultured infectious materials before inactivation by reliable methods should be performed in the second-level biological safety laboratory, but personal protection. The equipment refers to the protection requirements of the third-level biosafety laboratory.

The latter explicitly mentions antibody testing, requiring that the operation of the inactivated samples be carried out in the second-level biosafety laboratory, and the personal protective equipment is N95 and above protective masks/goggles / protective clothing / double latex gloves / waterproof boot covers. However, the sample collection objects targeted by the latter two documents are all suspected cases, clustered cases, and others who need to diagnose or differentially diagnose new coronavirus infections.

With the current overall stability of the national epidemic situation, faced with the needs of routine inpatients or resumption of labor for antibody testing, especially in low-risk areas, are inspectors still required to perform three-level protection for antibody testing?

After all, the latest “New Coronavirus Nucleic Acid 10-in-1 Mixed Collection Testing Technical Specifications” released on August 19 clearly stated that when collecting nucleic acid testing samples from people in low-risk areas, collectors should adopt secondary biosafety protection.

The specimen transport personnel shall adopt first-level biological safety protection, and the specimen receivers shall be designated personnel from the nucleic acid testing laboratory who have undergone biological safety protection training and shall adopt the second-level or higher biological safety protection. Secondly, there is no clear authoritative statement on whether the new coronavirus is transmitted through blood. The “New Coronavirus Pneumonia Diagnosis and Treatment Plan (Trial Eighth Edition)” does not mention the blood transmission route of the new coronavirus.

Therefore, in such an epidemic environment, inspectors are still required to perform three-level protection, whether there is a problem of excessive biological safety protection. Perhaps the article “Discussion on the Biosafety Implementation Plan of the Hospital Laboratory under the 2019 Novel Coronavirus Epidemic” published by the Chinese Journal of Laboratory Medicine proposed that the hospital’s laboratory department takes the protective measures of the secondary biosafety laboratory as a benchmark and conducts inspections based on the risk of the post. It is more practical to implement hierarchical biosafety protection for professional posts.

(2) Site requirements for COVID-19 antibody testing

There are currently no clear requirements for the site for COVID-19 antibody testing. The most basic requirement is that it should be carried out in a secondary biosafety laboratory, but there is no clear requirement on whether an independent testing space is required.

At present, most of them are above the county level. The clinical laboratory of the hospital has basically realized the construction of an integrated hall-like laboratory structure, lacking spare independent inspection space; whether the inspection space separated in an emergency or temporarily opened from other parts of the hospital meets the second level. The requirements of biosafety laboratories are worth discussing.

Nowadays, more and more laboratory methods for detecting COVID-19 antibodies have transitioned from the simple colloidal gold method to the chemiluminescence method that requires large-scale instruments and equipment. Higher requirements are placed on the experimental site. The basic conditions such as water and electricity in these emergency spaces can be used.

There are also many questions about whether the requirements are met. Under the current stable conditions of the epidemic, whether it can be carried out in the inspection hall like ordinary chemiluminescence testing or imitate the management of the HIV preliminary screening laboratory requires clear requirements at the national or industry level.

(3) Problems in the process of COVID-19 antibody testing

As a new test item, the detection of COVID-19 antibodies must be standardized before, during, and after the test. First, before the test, it is mainly the collection and transportation of specimens. For the collection of specimens, the operations should be compared. It’s easy, but there is one point that needs to be clearly explained, that is, whether antibody testing requires a single blood sampling first, or it can be collected at the same time as other routine tests in the laboratory.

The second is the test, which mainly involves test methodological issues. At present, the State Food and Drug Administration has approved a total of 21 new coronavirus antibody test kits, including 11 chemiluminescence methods and 7 colloidal gold methods.

The first point is that there are many false positives or false negatives in the detection of new crown antibodies. False positives are mainly affected by various interfering substances in the receptor. False negatives are mainly susceptible to detection sensitivity and cut-off threshold. There are many reports of influencing factors, and the existence of these influencing factors is also clarified in the “New Coronavirus Pneumonia Diagnosis and Treatment Plan (Trial Eighth Edition)”.

Although the chemiluminescence method is less affected than the colloidal gold method, it is still difficult to set a suitable cutoff threshold, and there is still a problem that the gray zone specimens are difficult to define, especially the lower antibody concentration in patients with asymptomatic infection, it is more difficult to judge.

The second point is that there is no clear comparison between the various kits, and there is no suitable quality control material for quality control in the testing process, and the inter-laboratory quality assessment plan is not mentioned; therefore, the process of antibody testing and testing needs to be standardized. It takes a long process.

The third point is that the value of total antibody detection is high, or the value of separate combined detection of IgM and IgG antibodies is high. It is also a problem worthy of continuing to explore. Although all versions of the new coronavirus pneumonia diagnosis and treatment plan did not mention total antibody detection, the World Health Organization and other magazines have reported the important role of total antibodies in the auxiliary diagnosis of new coronary pneumonia.

The last point is whether the re-examination of a positive report needs to learn from the relevant procedures of HIV antibody testing. After all, a positive report must be issued with extreme caution.

Finally, after the inspection, it mainly includes the release time of the report and a series of processing problems caused by the positive report; the release time of the report for outpatient and emergency patients, inpatients, and people who are willing to undergo a thorough examination also requires clear regulations at the national or industry level.

It can not only reflect the timeliness of antibody test reports than nucleic acid tests but also take care of the differences in the time consumed by different levels of hospitals and different test methods, so as to avoid medical disputes caused by inconsistent setting time in different hospitals. If a positive report is issued, how to deal with patients in a timely manner and standardize the treatment process. If there is an authoritative treatment process, many social problems can be reduced.

In short, as a necessary inspection item under the current epidemic conditions, COVID-19 antibody testing, industry, and even country-level standardized guidelines should be introduced as soon as possible to change the current situation of COVID-19 antibody testing.

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