15

Can false negative lead to missed diagnosis? False negative of new crown pneumonia

category:Hot
 Can false negative lead to missed diagnosis? False negative of new crown pneumonia


On February 9, the news conference of the joint prevention and control mechanism of the State Council showed that the nucleic acid test results of any virus could not be 100% positive, and it was inevitable that the nucleic acid test of patients with new crown pneumonia would be false negative.

In addition, for the diagnosis of new crown pneumonia, nucleic acid detection is an indispensable means. If the test is positive, it can be diagnosed as new crown pneumonia. If the suspected patients with negative initial test are required to be isolated and observed in designated hospitals according to the current diagnosis and treatment plan of the national health and Health Commission.

What is the probability of false negative? Why can appear false negative? Will it lead to missed diagnosis? Today, reporters from Beijing News interviewed authoritative experts for answers.

Question 1:

What is the probability of false negative?

u2014u2014The positive rate of nucleic acid test in real cases is 30% to 50%

False negative, i.e. no viral nucleic acid was detected in patients with new coronavirus infection, resulting in the negative detection of pathogenic nucleic acid. At present, false negative cases have been found in many places.

A febrile pneumonia patient from Wuhan came to Beijing on February 5. He was diagnosed as a new type of coronavirus infected pneumonia in four Chinese and Japanese hospitals. In this case, three times of throat swab new coronavirus nucleic acid tests were negative before admission, and alpha flow nucleic acid tests were positive, so on January 30, the patient was admitted to the hospital as severe alpha flow. After admission, intubation on the ventilator, through the alveolar lavage test, we found that the new coronavirus nucleic acid was positive.

According to a respiratory doctor in a top three hospital in Beijing, the suspected patients were routinely tested twice for pharyngeal swab nucleic acid. If there was one positive test, the diagnosis was confirmed. If there were two negative tests, the infection could be basically ruled out. Three times of throat swab new crown virus nucleic acid detection were negative, indicating that the virus concealment is very strong.

According to the public data, in addition to the false negative patient in the Chinese and Japanese hospitals, Zhejiang, Ningxia, Fujian and Tianjin have seen a number of cases of false negative nucleic acid test. The first four times of nucleic acid test of the patient were all negative, and they did not turn positive until the fifth time.

According to the announcement issued on February 8 in Qingtian County, Zhejiang Province, the patient Zhang had fever symptoms and went to the hospital for treatment on January 24. Four consecutive nucleic acid tests were negative since February 1, and the fifth nucleic acid test was positive on February 7. He was confirmed as a new crown pneumonia case.

According to the Beijing News, a patient in Zhangzhou, Fujian Province, was negative in four previous nucleic acid tests, but positive in the fifth test.

On February 9, the joint defense and control mechanism of the State Council held a press conference. According to the situation of false negative in nucleic acid test of patients with new crown pneumonia, Gao Zhancheng, director of respiratory and Critical Medicine Department of Peking University Peoples Hospital, responded that the nucleic acid test results of any virus can not be 100% positive, and the nucleic acid test of new crown virus is no exception, false negative is inevitable.

On February 5, Wang Chen, an expert in respiratory and critical care medicine and vice president of the Chinese Academy of engineering, pointed out in an interview with CCTV that the current detection method is mainly the detection of viral nucleic acids. He pointed out that not all people with the disease can be detected positive for nucleic acid, and the detection rate of nucleic acid for real cases is only 30% to 50%.

Tong Zhaohui, an expert of the central steering group and vice president of Chaoyang Hospital in Beijing, introduced to the Beijing news that PCR (polymerase chain reaction) test has a high specificity, but sampling methods and reagents may affect the results, with a low positive rate of only 20% - 30% on average, which is not stable. Good hospitals can reach about 50%, and some hospitals only have more than 10%, which brings about the question of false negative A lot of suspected cases can not be confirmed.

Question 2:

What causes false negative?

u2014u2014Lower positive rate of upper respiratory tract sampling

According to Ding Xinmin, chief physician of respiratory department of Beijing Shijitan Hospital, there may be several reasons for the appearance of false negative.

From a technical point of view, the sensitivity of the kit will have an impact on the positive rate, and any detection method has a limit, especially for new diseases, there is still room for further improvement of the kit. At the stage of specimen collection, there are corresponding quality control requirements for sampling, preservation and transportation. Under the current situation of outbreak and manpower shortage, these links cannot be ruled out.

However, he believes that the main reason for false negative lies in the characteristics of new crown disease itself.

Ding Xinmin told the Beijing news that the concentration of virus load in the respiratory tract of patients is closely related to the disease process. Sampling at different times may lead to different results. In addition, the new crown lesions are mainly in the deep part of the lung, far away from the large trachea, more dry coughing and less sputum in the infected patients, and the virus is difficult to remain in the upper respiratory tract. In the upper respiratory tract sampling, the positive rate will be relatively low, but at present, it is difficult to sample each patients lower respiratory tract.

Gao Zhancheng responded at the conference on the 9th, and the test results were affected by the severity of the patients condition, different stages of the disease, sampling methods and laboratory test conditions.

According to the new crown pneumonia laboratory test technical guidelines issued by the national health and Health Commission, there are strict requirements for the types, methods, packaging and preservation of specimen collection. Similarly, each link will affect the test results.

According to the guidelines, each case must be collected from the acute respiratory tract and blood samples, and the lower respiratory tract samples (such as bronchoalveolar lavage fluid, etc.) should be collected preferentially from the severe cases. The samples of upper respiratory tract include throat swab, nose swab, nasopharynx extract, and the samples of lower respiratory tract include deep expectoration liquid, respiratory tract extract, bronchial lavage liquid, etc.

There are also strict requirements for specimen preservation. Specimens that can be detected within 24 hours can be stored at 4 u2103; specimens that cannot be detected within 24 hours should be stored at - 70 u2103 or below (if there is no - 70 u2103 preservation condition, they should be temporarily stored in - 20 u2103 refrigerator).

In particular, the guide points out that negative results cannot exclude the infection of new coronavirus, and factors that may cause false negative results need to be excluded, including: poor quality of samples, such as respiratory samples from the oropharynx and other parts; too early or too late collection of samples; incorrect preservation, transportation and processing of samples; reasons for the existence of technology itself, such as virus variation, PCR inhibition, etc.

Li Xingwang, a member of the national medical expert group and chief expert of the infectious diseases diagnosis and research center of Beijing Ditan Hospital, previously said that in terms of respiratory specimens, the sensitivity of alveolar lavage fluid is higher than that of sputum, and the result of sputum is higher than that of pharynx. Therefore, the more critical the patient is, the higher the diagnosis rate is, because the alveolar lavage fluid can be collected.

In practical operation, more simple and faster throat swab sampling is used, while in early stage, many patients have dry cough and no sputum, which brings difficulty to sample collection and detection.

Question 3:

Is there a better way to diagnose?

u2014u2014Nucleic acid detection is currently irreplaceable

False negative frequency, do you want to give up nucleic acid test? Gao Zhancheng said at the press conference of the joint prevention and control mechanism of the State Council on September 9 that nucleic acid detection is an indispensable means for the diagnosis of new crown pneumonia.

According to the State Food and drug administration, as of January 31, seven new coronavirus nucleic acid detection reagents had been approved in an emergency. In addition, a number of enterprises are stepping up R & D.

It is reported that the kit is used to determine whether there is a new coronavirus in the samples of suspected patients, fast and accurate. The scientific principle of this kind of testing kit is called fluorescence PCR (polymerase chain reaction) method. It is a molecular biological technology for amplifying and amplifying specific DNA (deoxyribonucleic acid) fragments. It can use polymerase chain reaction to amplify a small amount of DNA, so as to detect viruses with specific gene fragments.

Up to now, nucleic acid detection is still the gold standard for the diagnosis of new crown pneumonia.

Experts have previously suggested that CT images should also be included in the diagnostic criteria due to the possible omission of nucleic acid detection.

Cheng Zhenshun, director of respiratory and Critical Medicine Department of Central South Hospital of Wuhan University, said at a conference in Hubei province that CT detection only takes a few minutes and is relatively fast.

In Wuhan, where the epidemic is more serious, early diagnosis, diagnosis and treatment can be achieved through CT, and the source of infection can be controlled in advance, which also enables the epidemic to be controlled in time.

Some experts say that CT is an imaging method for the diagnosis of pneumonia, but there are many kinds of viruses that cause pneumonia, not necessarily the new coronavirus. However, nucleic acid detection is a new diagnosis method of coronavirus, which can not replace each other. Nucleic acid detection is not only a basis for pathogen diagnosis, but also the most important basis for current diagnosis.

Question 4:

Will false negative result in missed diagnosis?

u2014u2014It will be analyzed in combination with clinical conditions

The false negative results of nucleic acid detection frequently aggravate the trust crisis in epidemic prevention and control. Experts said that it is not necessary to worry too much about the diagnosis and exclusion of cases. In addition to nucleic acid testing, it will also be combined with epidemic history and clinical symptoms.

As of September 9, the national health and Health Commission has issued six new crown pneumonia diagnosis and treatment programs, among which the third and fifth editions (Revised Edition) are open to the public. In each edition of the scheme, the diagnostic criteria of the cases were specified in detail.

Taking the latest version as an example, case diagnosis can be divided into suspected cases, confirmed cases and clinical diagnosis cases (only in Hubei Province). Specific analysis factors include epidemiological history (Wuhan travel history within 14 days before the onset), clinical manifestations (fever, pneumonia imaging characteristics, etc.) and virus nucleic acid detection.

In other words, nucleic acid detection is not the only criterion, but also combined with clinical diagnosis and patient specific conditions.

In Hubei, CT images were included in the diagnostic criteria. On February 5, the national health and Health Commission issued the fifth version of the new crown pneumonia diagnosis and treatment plan, which stipulates that Hubei Province will take the image characteristics of pneumonia as a clinical diagnosis case. On the morning of September 9, the national health and Health Commission issued the latest version of the diagnosis and treatment plan, the fifth edition of the revised version. The case diagnosis is consistent with the fifth edition, and Hubei Province and other provinces outside Hubei Province are treated differently.

Among them, Hubei Province increased the classification of clinical diagnosis. Moreover, the standard of suspected case is modified to be: no matter whether there is an epidemiological history or not, as long as it meets the two clinical manifestations of fever and / or respiratory symptoms and normal or reduced total white blood cells or lymphocyte count in the early stage of the disease, it can be considered as a suspected case. The standard of suspected cases has been relaxed. If the suspected cases have the imaging characteristics of pneumonia, they will be regarded as clinical diagnosis cases.

For suspected cases, the national health and Health Commissions diagnosis and treatment plan has strict regulations. Taking Hubei Province as an example, medical staff of all kinds of medical institutions at all levels are required to conduct isolation treatment immediately after finding suspected cases and clinically diagnosed cases. Suspected cases and clinically diagnosed cases should be isolated separately, and samples should be collected as soon as possible for etiological testing. Suspected cases can only be excluded if the nucleic acid test is negative for two consecutive times (at least one day apart).

That is to say, the first nucleic acid test is negative, and the second nucleic acid test should be carried out at least 24 hours later.

Ding Xinmin, chief physician of respiratory department of Beijing Shijitan Hospital, said that the result of nucleic acid test could not be the only basis for judgment, which is relatively clear clinically at present. For patients with highly suspected symptoms and imaging features, even if negative, further observation is needed.

Question 5:

How to avoid false negative discharge from isolation?

u2014u2014Improve discharge standard by wide access and strict exit

After the patients were cured, in order to avoid false negative discharge, more measures of wide in and strict out were taken.

According to the diagnosis and treatment plan of the national health and Health Commission, there are four requirements for the release of isolation and discharge standards, including: the temperature returns to normal for more than three days, the respiratory symptoms improve significantly, the pulmonary imaging shows that the inflammation is obviously absorbed, and the detection of respiratory pathogenic nucleic acid is negative for two consecutive times (the sampling interval is at least one day). To meet these four requirements, we can release the isolation and discharge or transfer to the corresponding department for treatment of other diseases according to the condition.

In order to prevent and control the epidemic to the greatest extent, compared with the discharge standard issued by the national health and Health Commission, the discharge requirements have been improved in many places, including additional fecal nucleic acid test, extended observation time, etc.

For example, in Hubei Province, after reaching the national standard, it needs to be observed for another 10-12 days. Fecal nucleic acid detection was increased in Shanghai and Zhejiang. Based on the national plan, Guangdongs standard for lifting isolation also requires that the course of disease of patients should be more than or equal to 14 days before patients are allowed to leave the hospital.

Tong Zhaohui, an expert of the central guidance group and vice president of Chaoyang Hospital in Beijing, believes that when judging whether a patient can be discharged from hospital, the time of onset should be taken into account. The presence of a false negative may result in the discharge of the actual positive patient. So clinical diagnosis is very important.

He said, new crown infection may peak in the second week, some people will have suffocation, respiratory failure, and imaging progress. At present, the discharge standard does not emphasize the discharge of 21 days after the onset of SARS, so at least two weeks after the onset of the disease, reexamination of images, two times of negative discharge should be considered, and after discharge, self isolation and follow-up should also be carried out.

Ding Xinmin also believes that for discharged patients, it is suggested that they should be isolated at home for a period of time, and doctors should continue to follow up and master the dynamic situation of patients.

[case

Negative patients suspected of infecting their families

On February 8, Wang Jian, a citizen of Wuhan, left the isolation ward and returned home.

Wang Jian, who is suspected of being infected by the new crown, was admitted to a requisitioned hospital in Wuhan on January 31. Doctors told the Beijing news that although Wang Jian had no positive nucleic acid test results, he showed typical symptoms when he was admitted to the hospital: fever, cough, diarrhea, pulmonary signs of multiple spots in both lungs and ground glass changes. After a period of treatment, Wang Jians body temperature returned to normal, the two nucleic acid tests were negative, and there were no other obvious symptoms, so he was discharged smoothly.

Although there is no positive diagnosis, Wang Jian believes that he is indeed infected with the new coronavirus.

On January 12, Wang Jian had a cold, fever and headache. The next day, he asked for leave to go to the fever clinic of Wuhan Union Medical College Hospital and was diagnosed as a cold. At that time, the new crown epidemic situation in Wuhan didnt attract attention. Wang Jian didnt wear a mask when he was admitted to the hospital. He wore it at the doctors request and took it off after he was discharged from the hospital. On January 16, Wang Jian went to the otolaryngology department of Wuhan Union Medical College Hospital for diagnosis because of the obstruction of the nasopharynx and suspected the recurrence of his rhinitis and pharyngitis. He was judged as pharyngitis caused by sinusitis and prescribed medicine. He didnt wear a mask during the whole process, Patients in contact were also not wearing them.

At that time, no one wore masks in Wuhan, nor did I. in the subway and hospital, there was a possibility of infection. Wang Jian analysis.

On the evening of the 21st, Wang Jian had a low fever and took cold medicine at home to reduce the fever; on the 24th, he had a high fever and failed to line up in three hospitals. On the 26th, he carried out nucleic acid test in a hospital in Wuhan. On the 31st, he was transferred to the above-mentioned requisitioned hospital as a suspected case. During the period of admission, Wang Jian carried out the second and third nucleic acid tests, all of which were negative. On February 8th, Wang Jian had a CT examination. According to the nucleic acid test and CT results, the doctor comprehensively judged that Wang Jians condition was under control, so he was discharged.

There has never been a positive test, why do you believe that you are infected? Wang Jian said that although he was not diagnosed, his mother was infected by himself and became a confirmed patient.

(function() {(window. Slotbydup = window. Slotbydup| []). Push ({ID: u5811557, container: ssp_, async: true});}) ()); after fever on the 21st, Wang Jian returned home and began to self isolate until he was admitted to the hospital on the 31st. Wang Jian told his family to wear masks. In addition to going to the toilet and not going out of the bedroom door, he also disinfected the door handle and hand washing table with 84. But during the isolation period, Wang Jians mother once went into the room to take care of Wang Jian, sending him rice and water. On January 30 or so, Wang Jians mother developed symptoms of high temperature and frequent sweating. On February 2, she was admitted to hospital. After that, the community informed the group that there was a confirmed case in Wang Jians family. Since Wang Jian has not been diagnosed and other family members have not been infected, Wang Jian has determined that the diagnosed person is the mother. I have been isolated at home for 11 days, and the incubation period of the virus is about 14 days. If my mother was infected before I was isolated, it is unlikely that she would get sick on January 30. During my isolation, she has not been to the hospital. At present, only our family has infection in our community, and she wears masks when she goes out, so the probability of infection is not high. According to the comprehensive analysis, the mother should be infected by herself. Source: responsible editor of Beijing News: Wang ning_nb12468

After a fever on the 21st, Wang Jian returned home and began to isolate himself until he was admitted to the hospital on the 31st. Wang Jian told his family to wear masks. In addition to going to the toilet and not going out of the bedroom door, he also disinfected the door handle and hand washing table with 84. But during the isolation period, Wang Jians mother once went into the room to take care of Wang Jian, sending him rice and water. On January 30 or so, Wang Jians mother developed symptoms of high temperature and frequent sweating. On February 2, she was admitted to hospital. After that, the community informed the group that there was a confirmed case in Wang Jians family. Since Wang Jian has not been diagnosed and other family members have not been infected, Wang Jian has determined that the diagnosed person is the mother.

I have been isolated at home for 11 days, and the incubation period of the virus is about 14 days. If my mother was infected before I was isolated, it is unlikely that she would get sick on January 30. During my isolation, she has not been to the hospital. At present, only our family has infection in our community, and she wears masks when she goes out, so the probability of infection is not high. According to the comprehensive analysis, the mother should be infected by herself.