The gold standard dispute between CT screening and kit testing: experts say non substitution relationship

And various means of screening patients are also in full swing On the evening of February 5, Wuhan "eye of fire" laboratory, jointly built by Wuhan municipal government, Donghu high tech Zone, CCCC Second Harbor Engineering Bureau, Shanghai norui laboratory and BGI, was put into trial operation The daily flux of nucleic acid detection reached million people In addition to the quantitative pressure, the accuracy of nucleic acid detection is still questioned by the outside world In February 5th, the novel coronavirus infection pneumonia diagnosis and treatment plan (trial version fifth) was released by the national health and Health Committee, and the image results were used as the basis for clinical diagnosis This has nothing to do with the previous article entitled "first line doctors cry: replace nucleic acid detection with CT as soon as possible as a new diagnostic standard for pneumonia" For a time, the doubts about the lagging speed and low accuracy of nucleic acid detection were pushed to the forefront At present, which is more reliable for CT and nucleic acid detection? How to define their relationship? In February 2nd, novel coronavirus Zhang Xiaochun, from the Zhongnan Hospital of Wuhan, called on WeChat's friends circle: do not superstitious nucleic acid detection, and strongly recommend the CT image as the main basis for 2019-nCoV pneumonia Zhang Xiaochun said that at present, there are more and more cases of family clustering in Wuhan, and most of them have occult onset, or even multiple times of nucleic acid negative, without any clinical symptoms If we take the way of staying at home, the epidemic will spread further We should immediately start the screening of CT as long as we have contact with suspected cases, as long as the CT positive is concentrated and isolated in the hotel or school nearby, and mobilize social forces to participate in the work Zhang Xiaochun stressed that, as a family of doctors, parents are still infected after taking protective measures "Our common people are unable to achieve real medical isolation due to limited cognition!" She said in a loud voice: the control of epidemic situation is related to human life, so we can't let the asymptomatic or nucleic acid negative CT positive people stay at home! Governments at all levels should act to prevent families from staying and staying, which will lead to the spread of secondary epidemic! In novel coronavirus pneumonia, the First Affiliated Hospital of Xi'an Jiao Tong University, Guo Youmin, Professor of medicine, said that the imaging features and identification of imported new crown pneumonia were mentioned in January 31st A novel coronavirus general headquarters at Huazhong University of Science and Technology also submitted a recommendation on the recommendation of CT imaging as the main diagnostic basis for 2019nCoV pneumonia at the same time Three days later, novel coronavirus infection pneumonia diagnosis and treatment plan (trial version fifth) was released in February 5th by the health and Health Committee In addition to "suspected cases" and "confirmed cases", Hubei province increased the classification of clinical diagnosis cases It is worth noting that in the updated guidelines, the suspected cases with pneumonia imaging characteristics were clinically diagnosed Example In addition, the fifth edition of the guide revised the standard of "suspected cases" to: no matter whether there is an epidemiological history or not, as long as the two clinical manifestations of "fever and / or respiratory symptoms" and "normal or reduced leukocyte count in the early stage of the disease, or decreased lymphocyte count" are met, the standard of suspected cases can be considered, which is equivalent to the relaxation of the standard of suspected cases The number of people who advocate that CT imaging replace nucleic acid detection as the "gold standard" is increasing Then, experts in the field of detection have voiced, pointing out that in a short period of time, nucleic acid detection reagents are rapidly developed and launched, and there are still some problems in the quality of detection, and pointing out that inspection enterprises can continuously improve, any product can not be 100% perfect when it is completed and at the beginning of application, usually has a process of continuous improvement, improvement and improvement It has also been pointed out that CT imaging and nucleic acid detection have different opinions, one is to diagnose patients, the other is to screen suspected patients and healthy carriers (infection sources) At present, the efficiency of single CT scan is far less than that of nucleic acid detection Before January 26, the nucleic acid detection kit entered a state of gallop Novel coronavirus products from 4 enterprises were tested and approved by the State Administration of drug control (FDA) on the same day The process of approval before and after the approval process took four days Generally, the approval time for the listing of these three types of medical devices is about two years, according to industry sources Novel coronavirus, the Deputy Secretary of the Hubei provincial Party committee, and Wang Xiaodong, the head of the epidemic prevention and control command of the new type of coronavirus, stressed in February 2nd that when trying to supervise the case detection and medical treatment, we should do our best to speed up the detection of cases, enhance the detection ability of medical institutions, ensure the supply of medical supplies for inspection machines, ensure that the stock is detected in two days, and we must pursue the responsibility for not completing the tasks Accountability Li Xingwang, a member of the national medical team, explained that the main reason for the sharp rise of severe patients was that the number of severe cases was increasing, while the number of confirmed cases was also increasing, and the overall data growth trend was obvious Han Dongsheng, a technician in charge of the laboratory department of Subei people's Hospital in Jiangsu Province, pointed out that the low positive rate does not necessarily occur in the quality of the kit The quality problems of the specimen (such as sampling timing, sampling location, sampling volume, storage and transport media), and the personnel operation (such as nucleic acid extraction, sample addition volume, system preparation, etc.) are also important reasons affecting the quality of the test Therefore, to do a good job in testing, we must strictly abide by the operating procedures, and each step is the key But the nucleic acid test needs professional training from sample extraction to test results At the same time, the industry insiders pointed out that because it is all operated by the hospital itself, every step of the test may result in low positive rate results County level hospitals have not been able to test, but they are all allocated by the CDC With the supply of kits and technology keeping up, the suspected patient stock can be released Since January 26th, novel coronavirus nucleic acid detection kit has been approved by the State Administration of drug administration and approved by 7 countries These products are respectively from Zhijiang biological, Shengxiang biological, huirui biological, Jienuo biological, Berger medical, Da'an gene and Huada group On February 3, Academician Li Lanjuan, a member of the high level expert group of the national health and Health Commission, said in an interview with CCTV that the number of detection kits in Wuhan is not enough We hope to send more accurate reagents (boxes) to Wuhan so that more people can be tested Up to now, 103 IVD enterprises have produced "2019-ncov" nucleic acid detection kits This means that more testing products can enter hospitals in compliance, greatly expanding the scope of use of testing reagents Previously, even if these testing products are produced, if they are not approved for marketing, they can only be used for Disease Control System for "scientific research purpose" According to a Suzhou reagent company, in the early morning of December 31, 2019, the company received a call from the disease control department, and needed diagnostic reagents to prove whether the pneumonia of unknown cause was SARS In the morning of that day, the company did the production and quality inspection of diagnostic reagents, and sent the reagents to Wuhan in the afternoon Until the new coronavirus sequence was released on January 12, 2020, the research on the new coronavirus kit was completed within 24 hours We are increasing our production capacity In fact, fast track approval has greatly saved the time for these new medical devices to go on the market According to industry sources, the approval time for the three types of medical devices is usually about two years, including one year of clinical trial data collection period; at least 1000 samples of in vitro diagnostic reagents must be provided The person in charge of the above-mentioned reagent enterprise also said that after the successful development of medical devices, clinical data collection must be done first, and after the reliability and effectiveness of the data are verified, they will be approved for listing However, in order to control the current epidemic situation, this fast channel shortens the time for the disease control system to collect clinical data Some enterprises, like getting a driver's license, have not passed the "internship period" Industry insiders pointed out that some enterprises did not get the first-line clinical samples, but completed the development of the kit with standard reference materials, which must be different from the actual samples If the kit is not calibrated, there may be false negative and false positive, which needs to be jointly diagnosed with CT imaging Previously, the novel coronavirus pneumonia confirmed the need for disease control departments to detect or review, so the use of these non approved listing test kit is not illegal The operation of the CDC is considered part of the clinical trial After the production capacity is solved, the next contradiction directly refers to the mixed quality problem of a large number of kits For this reason, some people in the industry doubt whether the current over publicity of the epidemic is appropriate? The nucleic acid test kit mainly focuses on the fluorescent quantitative PCR method, and the standard test time is 2 hours The industry insiders pointed out that if an enterprise claims to diagnose within 30 minutes, or uses the colloidal gold method for diagnosis, the probability of false positive and false negative will be higher However, after the data of the mngs method is obtained, it needs to be analyzed by software, and the efficiency cannot meet the needs of the current epidemic situation It should be noted that, at present, the epidemic situation is serious, the body concentration of asymptomatic or light disease patients is low, if you blindly pursue quick response, the rate of missed detection increases, and the consequences are serious Li Jin, an inspector in the laboratory of Central South Hospital of Wuhan University, pointed out that the two diagnostic methods have their own value and complement each other, not who replaces whom The value of nucleic acid detection cannot be "killed by one stick" With the improvement of the sensitivity of detection reagents, the rate of missed diagnosis will decrease, but the rate of misdiagnosis will increase Relevant industry insiders pointed out that, in other words, the detection method with high sensitivity can identify patients with detected diseases more accurately, but it is also more likely to be misdiagnosed False positives (misdiagnosed cases) can be eliminated by multiple tests, but false negatives (missed medical records) have a great impact Gu Bing, a professor at Xuzhou Medical University, pointed out that CT could not distinguish which virus a patient was infected with, while nucleic acid detection could be batch screened out, and etiological evidence played an important role in the diagnosis of infectious diseases Only when imaging and laboratory examination are equally important, can it be more conducive to diagnosis and prevention and control of epidemic situation Li Xingwang, in the interpretation of the fifth edition of the guidelines of the epidemic news conference on February 5, stressed that "asymptomatic infected people may also be the source of infection", pointing out that if the nucleic acid is positive by throat swab, it will be positioned as asymptomatic infected people At present, asymptomatic patients are mainly those who have close contact with patients Family members spread more and patients themselves have no obvious clinical manifestations, such as fever, fatigue and other symptoms At the same time, he pointed out that such patients may not have pneumonia symptoms Li Xingwang explained the problem of sudden and substantial increase of severe patients before According to previous experience, the new crown patients had sustained high fever at the onset of the disease However, some patients had moderate and low fever at the onset of the disease The symptoms were not very serious Many doctors called it "separation of symptoms and imaging" That is to say, pneumonia was very serious, but the symptoms were not serious In summing up the case experience, the patients In the previous week, the relative condition is relatively light, and the disease may be aggravated after one week.