Five possibilities behind the false-negative nucleic acid test
It was reported that a patient with febrile pneumonia was diagnosed with New Coronavirus pneumonia on February 5 at China-Japan Hospital. The patient was admitted to the hospital on January 30 with "severe influenza A" after three negative pharyngeal swabs for nucleic acid testing for the new coronavirus and a positive nucleic acid test for influenza A. After admission, he was intubated and put on a ventilator, and was only found to be positive for nucleic acid for the new coronavirus through alveolar lavage testing.
Zhang Xiaochun told People's Daily that similar false-negative problems do exist, mainly due to the following reasons.
"First, there are limitations in nucleic acid sampling, which usually takes secretions from the oropharynx or nasopharynx. Whereas it is possible for there to be a difference between the viral load in the patient's alveoli and the viral load rising to the upper respiratory tract.
Second, the accuracy of sampling is related to the individual operator, and the different operation of each person when sampling may also lead to sampling errors.
Third, the current nucleic acid kits are developed in a particularly short period of time, and the stability of the products is not high; fourth, also because the time is too hasty, the manufacturers are different, and the quality of the nucleic acid test kits produced is uneven, which can also affect the test results;.
Fifth, and also the latest discovery, there are differences in the specificity of the novel coronavirus for human organ attack.
"The latest clinical finding is that there is fecal-oral transmission of novel coronavirus. negative, but detected positive for the virus in their stool, a finding echoed by Li Jinqing (Chongqing), director of the Department of Diagnostic Radiology at the Army's Ninety-Five Eight Hospital.
"This finding suggests to us that, first, there is fecal-oral transmission of novel coronavirus, and second, novel coronavirus can cause damage to the patient's GI tract, so some NCP patients may have symptoms of abdominal pain and diarrhea. Only, the symptoms of the digestive tract may not be as obvious as the pulmonary symptoms, so they have not attracted our sufficient attention before."
Recently, the virus has also been found in the feces of confirmed patients in Shenzhen and Wuhan. In response, Feng Luzhao, a researcher at the CDC's infectious disease division, gave a response at a press conference held by the National Health Commission on Feb. 2 that further confirmation was needed on whether there was fecal-oral transmission. The latest clinical findings by Zhang Xiaochun's team further validate the existence of fecal-oral transmission of the novel coronavirus on top of droplet transmission and contact transmission. It is strongly recommended to sample suspected patients at multiple points "Even if the nucleic acid test is negative in suspected patients, we cannot exclude the possibility of NCP (New Coronavirus Pneumonia).
"Zhang Xiaochun stressed that "as long as we find the imaging signs of acute pneumonia on their CT images, and the patient is from key infected areas such as Wuhan, or has a history of close contact with infected or highly suspected patients, even in other provinces outside Hubei Province, should be in line with the 'suspected disease from there ' principle of early isolation and admission, and then further exclusion pathogenetic examination."
In the case of the above-mentioned NCP patient at the Sino-Japanese Hospital, Zhang Xiaochun strongly recommends that multiple points be sampled for suspected patients or repeated nucleic acid testing of the same site. "As long as there are lesions in the lungs, we rank influenza, fungus, bacteria, mycoplasma, chlamydia, and even fungus, and continuously go for nucleic acid testing for 2019nCOV, and if the throat swab shows negative, then look at the anal swab, and finally also test their stool, or take samples at multiple points at the same time. No method is 100%.
In the current epidemic, we have to strictly check, never let one go." Zhang Xiaochun suggested that "if the lung images support acute inflammation and other pathogens are ruled out or not ruled in, all should continue to test for 2019nCOV nucleic acid, and further testing should not be abandoned just because one or two nucleic acid presentations are negative."
"Nucleic acid testing may also have the problem of false positives," Zhang Xiaochun also mentioned in the interview that the problem of false positives in individual patients should also receive a high degree of attention, "especially before sending them to a square cabin hospital, it is still recommended that they be sampled at multiple points at the same time, such as taking stool, anal swabs, pharyngeal swabs and blood, or repeated sampling of the same site for nucleic acid testing.
"Nucleic acid testing is still the gold standard for final pathogenic diagnosis previously, Zhang Xiaochun has called for: in the key infected areas Hubei Province or Wuhan, CT imaging of the lungs should be performed on suspected patients or with a history of close contact with confirmed patients as the main basis for screening for 2019nCoV pneumonia at present; at the same time, it is called for giving asymptomatic or nucleic acid test negative but CT imaging positive people to be treated in isolation to prevent family clusters of infection that could allow the outbreak to spread further.
"Nucleic acid testing remains the gold standard for final pathogenic diagnosis, and its etiological evidence is irreplaceable and unquestionable. However, it is recommended that suspected patients undergo CT imaging of the lungs in conjunction with nucleic acid testing. CT imaging of the lungs is both an adjunct to nucleic acid negativity and an effective means of staging the severity of lung lesions and monitoring drug efficacy.
"In the current situation, the hospital imaging department will encounter two problems after the CT images are included as one of the bases for NCP screening.
First, a large number of suspected patients and close contacts have CT examination needs, while the number of hospital fixed CT equipment and technical personnel are insufficient, so the CT carrying capacity is greatly challenged.
"Zhang Xiaochun said, "For this reason, I call for mobile CT or square cabin CT to enter Wuhan as soon as possible, in order to meet the demand for CT examinations of people staying in square cabin hospitals and community isolation sites. This has been echoed by a wide range of major companies. They have opened mobile CT or square cabin CT to Wuhan one after another, but now they are facing new problems."
In the interview, Zhang Xiaochun suggested that the Wuhan NCP Prevention and Control Command should set up a "mobile CT service team for new coronary pneumonia screening" as soon as possible to unify the centralized management, deployment and revitalization of mobile CT or square CT resources.
Zhang Xiaochun said, mobile CT detection volume is very large, a day can detect about 300 people. Moreover, it can also serve the next cabin hospital, or even be extended to the community. This is very effective for Hubei Province to contain the source of infection and cut off the transmission route. "I call on Wuhan to unify and centralize the management and deployment of mobile CT or square-cabin CT resources as soon as possible, and to establish a mobile CT new crown pneumonia screening service team with dedicated personnel to implement an emergency detection mechanism." Zhang Xiaochun said, "Let the idle mobile CT or square cabin CT inventory up, more conducive to the control of the epidemic, to help win the war epidemic."
Is there a risk of cross-infection when a large number of people go for mobile CT or cube CT? In this regard, Zhang Xiaochun pointed out that "to avoid cross-infection between patients, it is necessary to do a good job of disinfecting one person and one machine, while protecting the person being examined and the doctor." Calling on the majority of netizens to give tolerance at the end of the interview, Zhang Xiaochun said, "In the process of fighting with the disease, we medical personnel to understand the disease is also a gradual process, at first may be relatively superficial, perhaps we mention the view may be a little abrupt, with the accumulation of experience in medical practice, will gradually correct the previous understanding.
In the current extraordinary period, I hope that the majority of netizens give our medical staff the greatest tolerance."
"Only in a relaxed public opinion environment can medical professionals dare to express their true thoughts and share their experiences based on medical practice summaries" Zhang Xiaochun said, "In front of the catastrophe and pandemic, please be more tolerant and listen to more voices. For these voices, the expert professors 'remove the falsehoods and keep the truth' after that is the 'good prescription'."
Original title "Zhang Xiaochun, deputy director of imaging department of Central South Hospital: there are differences in the specificity of the new coronavirus to human organ attack
People's Daily Online reporter Chen Yuanding
