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On February 5th, the National Health and Medical Commission launched the “Pneumonitis Diagnosis and Treatment Program for New Coronavirus Infection (trial version 5) ” < sup> [1] , updated the diagnostic criteria for patients with a new type of coronavirus infection, and distinguished patients outside Hubei and Hubei provinces. On the basis of “suspected cases” and “confirmed cases”, patients in Hubei Province have added the classification of “clinical diagnosis cases”. Those who have CT imaging findings of pneumonia in suspected cases can be included in this group.

Figure | Screenshot of “New Coronary Virus Infected Pneumonia Diagnosis and Treatment Plan (Trial Version 5)”

In addition to revising the criteria for “clinical diagnosis of cases”, the new scheme is also more active in the isolation of Hubei Province. The significance of this move is to strengthen isolation in Hubei Province, where the epidemic is severe, and to make up for the lack of nucleic acid testing lags and false negatives with “clinical diagnosis” of positive CT imaging.

Why can CT make up for the lack of nucleic acid detection?

Too long to watch:

• Nucleic acid test results are prone to false negative results and missed diagnosis.

  
  

• The shortcomings of nucleic acid testing include high testing qualification requirements and long testing time.

  
  

• CT has high popularity, convenient operation, and high sensitivity to pneumonia.

  
  

• It should be noted that the common CT has a high risk of cross-infection, the easy identification of new coronary pneumonia by CT, and the limitations of the CT test itself means that CT screening for new coronary virus pneumonia is not perfect.
  
  

  Diagnosis of new coronary pneumonia is inseparable from the detection of pathogenic nucleic acids

  The status of qualitative detection of new coronavirus pneumonia by nucleic acid is unquestionable. The current detection method uses fluorescent PCR technology to detect the content of novel coronavirus nucleic acids in patient biological samples. If the nucleic acid content exceeds a certain threshold, (ie, positive results ) , the patient is considered to be infected with the new coronavirus; however, when the nucleic acid content in the sample is below a certain threshold (ie negative results) , can not rule out new coronavirus infection!

  New Coronavirus Nucleic Acid Detection Kit (ie, fluorescence PCR method)
  < / p>

  Because the accuracy of nucleic acid test results is restricted by conditions such as sample quality, test timing, and mature technology, false negative results are prone to occur and missed diagnosis occurs. In addition to the possibility of false negatives, nucleic acid testing also has disadvantages such as higher testing qualification requirements and longer testing time.

  Why do nucleic acid tests have false negatives?

  1. Sample collection and quality impact test results

  At present, viral nucleic acids can be extracted from a variety of biological samples derived from patients. Including:

  Upper respiratory tract specimens: including throat swabs, nasal swabs, and nasopharyngeal extracts.

  Lower respiratory tract specimens: including deep cough sputum, respiratory tract extracts, bronchial lavage fluid, alveolar lavage fluid, and lung tissue biopsy specimens.

  In addition, there are blood samples, eye and conjunctival swabs, and stool samples.
  

  The samples used for nucleic acid detection of new coronary pneumonia are mostly respiratory specimens. After all, the cases transmitted through the eye conjunctiva or fecal-oral are not clear. The advantage of the upper respiratory tract sample is that it is easy to obtain materials, especially pharyngeal and nasal swabs. It can be quickly and easily deployed in epidemic areas where patients are concentrated and medical conditions are tight. However, due to the operation method and other factors, if the number of collected cells is too small, it may result in the number of virus copies. (viral volume) Not enough, it directly affects the detection results.

  Relatively speaking, the quality of the lower respiratory tract samples is better, but bronchial fiberscopes are generally used in clinical practice to obtain materials. The requirements for medical equipment and professionals in epidemic areas are high, and they cannot be popularized to primary hospitals. In addition, the specimens used for virus isolation and nucleic acid detection need to be tested as soon as possible. The 4 ° C refrigerator can store the specimens to be tested for 24 hours, which is also a challenge for grassroots hospitals without detection conditions.

  Figure 丨 Wikicommens
  

  2, it is difficult to guarantee the timing of detection
  

  Some early patients will be “false negative”, which means that some early patients will have a positive CT scan but a negative nucleic acid test. This is due to the fact that the number of copies of pharyngeal virus in some early patients is lower than the detection limit of the instrument.

  3. Quality of the kit

  As of February 5, at the current stage, the SFDA has approved 7 new coronavirus nucleic acid detection kits in an emergency, but there are still more than 30 kinds of kits on the market. The difference in sensitivity of the kit is also one of the reasons for the false negatives and yin and yang of clinical test results.

  Seven new crown virus nucleic acid detection kits, one related protein ELISA kit, and one related software approved by the State Food and Drug Administration | National Drug Administration Bureau screenshot
  

  New coronavirus nucleic acid detection efficiency is lower than CT

  1, relatively high requirements for testing qualifications

  The new coronavirus is a highly infectious virus. In order to prevent biosafety events such as virus leakage or human infection during the test, the laboratory must reach the level of biosafety laboratories of Level 2 or higher. The laboratory’s personal protection needs to adopt the third level of biosafety, and the operators must also be professionally trained inspectors. As of February 5, 18 disease control centers, 66 hospitals, and 13 third-party testing institutions in Hubei Province have obtained the New Crown Virus nucleic acid testing qualification.

  Different testing institutions have different numbers of equipment and different daily testing volumes. Assuming that one institution can test 500 cases per day, the 18 CDCs, 66 hospitals, and 13 third-party testing machines can detect about 1 day. There are only 50,000 cases.

  The good news is that the trial operation of the “Fire Eye” laboratory in Wuhan on February 5th will result in a daily throughput of tens of thousands of nucleic acid tests, which will greatly fill the gap in epidemic situation.

  Report on the “Fire Eye” Lab published by People’s Daily Online | Screenshots of People’s Daily Online
  

  2. Relatively long detection time

  Now the Internet is full of various advertisements about the rapid detection of new crown virus. Some claim that they can produce results within ten minutes. They use immature technology and cannot be used as clinical diagnostic standards. In fact, almost all nucleic acid kits approved by the SFDA are fluorescent PCs.R technology. Normal fluorescent PCR takes at least three or four hours. If you analyze the data and report, it may take five to six hours. Compared with CT, fluorescent PCR takes longer.

  In particular, the number of patients to be confirmed is relatively large, and the speed of diagnosis is particularly important. At present, the number of suspected cases in the epidemic area in Hubei is still increasing, and the medical resources in various places are uneven. The emphasis on the clinical proportion of CT is more in line with the needs of the epidemic area.

  Figure | Lilac Garden
  

  CT makes up for lack of nucleic acid detection

  1. CT is more popular

  Basic hospitals in China and above are basically equipped with CT, including some private medical hospitals and physical examination institutions, which have corresponding testing equipment and personnel.

  2. CT operation is more convenient

  Compared to nucleic acid detection, CT has exploded the former in a time-consuming manner. It only takes tens of seconds to complete a lung CT scan, and a CT can screen at least hundreds of people a day. A few days ago, the mobile CT inspection vehicle has been reinforced in Wuhan, which can directly enter the community for screening to avoid cross-infection caused by patients getting together.

  Figure 丨 Posted by Sohu Tieling
  

  In addition, high-resolution CT images can be transmitted through the network, and remote reading by national imaging experts can be implemented. Experienced clinical experts can help grass-roots hospitals with less experience in time to relieve the pressure of front-line imaging doctors. Such measures can not only ensure the clinical medical needs, but also reduce the movement and gathering of people, and further alleviate the pressure of the epidemic.

  3. CT has high sensitivity to pneumonia

  Compared with X-ray images, CT has a higher density resolution and can better show the lesions in the lungs. In clinical screening of pneumonia, CT is currently the most efficient test method.

  “Diagnosis and treatment plan for new coronavirus infections (trial version 5) points out that there is no epidemiological history in Hubei epidemic area For those who have fever and abnormal blood, if the imaging features are found by CT early, they can be confirmed as clinically diagnosed cases, achieving the purpose of “early isolation and early diagnosis”, and early intervention for cases that have not been diagnosed with positive nucleic acid.

  CT screening is not perfect

  1. High risk of cross-infection with shared CT

  In order to achieve the purpose of dust prevention and temperature control, the CT room is designed to have the characteristics of closed space, poor air circulation, and easy breeding of bacteria ^{[3] . The complexity of personnel in the epidemic area and the high concentration of virus in the air have increased the probability of cross-infection in the common CT population.}

  On February 2nd, the Imaging Technology Branch of the Chinese Medical Association released the “New Coronavirus (2019-nCoV) Radiological Examination Scheme and Infection of Pneumonia Expert consensus on prevention and control (First Edition) ” clearly states that in order to reduce the risk of nosocomial infections and prevent the spread of the epidemic, conditional hospitals are required to open dedicated CT for fever patients. Once a patient is examined, the equipment is disinfected once.

  Pictures ^{[4]
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  If the “one person, one disinfection” guideline is strictly implemented, under the current situation of disinfection and shortage of protective materials, the CT utilization efficiency of some hospitals with less disinfection conditions and poor hospital sense control will be restricted.

  2. CT recognizes new coronary pneumonia and it is easy to “wrong kill”

  Contrary to the high sensitivity of pneumonia recognition, the specificity of CT for this new coronary pneumonia is low. The winter and spring seasons are originally the season of high influenza. Neocoronal pneumonia overlaps with other viral pneumonia, organizing pneumonia, and eosinophilic pneumonia in imaging performance, which has certain difficulties in identification. .

  Hangzhou City Health Committee announced the results of 120 confirmed cases with detailed medical history from January 26. The analysis showed that only 76 patients had positive images with a sensitivity of 63%, and all patients were positive by nucleic acid testing. The final diagnosis was ^{[6] .}

  3.CT checks its limitations

  As a popular imaging CT, if there is a difference in the lung tissue density of the subject, there may be artifacts of different imaging performances, which will confuse the doctor’s judgment. Moreover, the time of infection in the lungs may be different depending on the immune status of the human body, and the CT manifestations may also vary with the timing of diagnosis.