New crown patients “fuyang” mystery: someone does not produce antibodies, viruses or chronic carrying

February 17, is Xu Jia (pseudonym) discharged from the hospital, but also the day of her admission. That afternoon, she was discharged from Wuhan Living Room Square Cabin Hospital after two consecutive negative tests for the new coronavirus nucleic acid. After returning home, after eating her mother’s cooking lamb hot pot, took a bath, before the time to have a good night’s sleep, the phone rang – she was discharged the day before the third nucleic acid test results, positive.

So, more than two hours after being discharged from the hospital, she returned to the fang cabin hospital.

As of 10 March, a total of 80,924 people had been diagnosed with new coronary pneumonia, of whom 59,982 had been cured and discharged from hospital. Since February, many patients in China have been discharged from the hospital after the nucleic acid test positive phenomenon (hereinafter referred to as “Fuyang”).

In Xuzhou, Jiangsu Province, two patients were discharged from the hospital, the community residents to meet with flowers, not expected two days later, two people nucleic acid review as positive, re-admitted to the hospital, the community was also sealed. In Tianjin, a patient was tested positive 16 days after being discharged from the hospital, admitted to hospital again, and both nucleic acids were negative and discharged three days later. In Guangdong, 14% of discharged patients appear “Fuyang” – The Guangdong Provincial Center for Disease Control and Prevention deputy director Song Tie announced the data at a press conference on February 25.

Mr. Wang, a patient with New Corona pneumonia in Xuzhou, was welcomed by residents of the community when he returned home from isolation on February 24. Two days later he re-tested positive for nucleic acid. Video screenshot

Doctors at several fixed-point hospitals in Wuhan told the news that a considerable number of “fuyang” patients are actually nucleic acid detection errors caused by the “false negative”, in addition, the patient’s body virus is not completely removed, after discharge immunity decline, may lead to “fuyang.”

Several experts interviewed said that some patients have been unable to produce antibodies, resulting in many “sun”. And the “new crown” also does not rule out the development of chronic carrying possibility, so that its pathogenicity will also become weak.

The seventh edition of the new coronary pneumonia treatment program, released in early March, adds antibody testing for diagnosis and detection of confirmed and suspected cases. Several front-line doctors have recommended that it be included in the discharge criteria to reduce the “fuyang”. Some of the doctors interviewed also proposed to quantify the lung imaging indicators in the discharge criteria to further reduce miscalculations.

“Monitoring found that there was no recurrence of infection in Fuyang patients. Guo Yanhong, Inspector General of the Medical, Political and Hospital Authority of the National Health and Health Commission, said on February 28th that the pathogenic mechanism, the full picture of the disease and the characteristics of the disease course of the new coronavirus still need edathemed.

“Fuyang” Enigma Bureau

Xu Jia still do not understand, the virus is how to find her.

I felt unwell on 22 January. She was weak, coughing, and then began to have a fever, went to Wuhan Tianyou Hospital to do A CT, showing a small infection in the lower right lung, the doctor prescribed medicine to let her go home quarantine. After 4 days of review, the disease worsened and became a double lung infection, partly a glass-like change. She started queuing up at the hospital for infusions and making an appointment for nucleic acid tests.

On February 7, she was admitted to Wuhan Living Room Square Cabin Hospital because of a positive nucleic acid test.

In fangcabin hospital, Xu Jia saw the sick friends from the disease to become optimistic, mental state is getting better and better. Some people chased the popular drama, some people followed the nurse dance square dance, we encourage each other, gas, let her feel warm.

After being hospitalized, Xu Jia had two nucleic acid tests, both of which were negative. It was made for the third time on 16 February. On the same day, the attending physician and her video face, said that she twice nucleic acid negative, significant absorption of inflammation of the lungs, coupled with consecutive days without fever, in line with the fifth version of the treatment program discharge standards. She was shocked and delighted.

On February 17, Xu Jia said goodbye to her sick friend and nurse, and she smiled brightly in a photo of her with the nurse in her circle.

Unexpectedly, more than 2 hours after being discharged from the hospital, she was told that the third nucleic acid was positive and that she would return to the hospital immediately. The nurse saw her back and said, “I really don’t know if I’m welcome or not…”

She had no sleep all night. The next day, she had a fourth nucleic acid test and prayed that the last positive was an accident, but she was quickly disappointed. And the family originally home isolation, only 2 days to observe the expiration of the end, because she was briefly discharged from the hospital, were sent to school to re-segregate 14 days.

Xu Jia himself also began to feel unwell, dizziness, high fever, a few days later transferred to Jinyintan Hospital. Fortunately, after the infusion, the condition is under control.

On March 5, Xu Jia was discharged from the hospital for the second time. This time, instead of returning home, she was sent to a school’s isolation point for observation, an additional requirement in the New Coronary Pneumonia Treatment Program (Trial Seventh Edition), released by the National Health and Reform Commission on March 4.

The sixth version of the consultation plan released on February 19th was first proposed, and patients were recommended for 14 days of “self-health monitoring” after discharge, followed by the hospital in the second and fourth weeks of discharge, and the seventh edition was strengthened to 14 days of “isolation management and health monitoring”.

This change stems from the phenomenon of fuyang in many places in China.

Interviewed experts believe that the so-called “Fuyang” population is a considerable part of the “false negative”, the patient’s body virus has not been removed, but the pre-hospital nucleic acid test has not been detected.

Tong Zhaoxuan, a member of the expert group of the Central Steering Group to Hubei, also said in an interview with CCTV that Fuyang is related to the detection of nucleic acids that are not stable, there are problems with kits, there are sampling problems, the national fuyang ratio is about 0.1%, within the control of the range.

In addition, “Fuyang” may also be the body detected virus fragments or dead virus, “this does not mean that the patient has not been cured or repeated.” Guo Wei, deputy director of the infection department of Tongji Hospital in Wuhan, told The News that there are very few symptoms known to Fuyang patients, and that “recurrence” is very rare.

Peng Zhiyong, director of the Department of Critical Medicine at Zhongnan Hospital, Wuhan University, found that one of the commonities of Fuyang patients was that the lungs improved and were basically normal when discharged from the hospital, but the immune system was not fully recovered after being attacked by the virus, and the number of lymphocytes, absolute value and so on were 20%-30% lower than the normal level, resulting in the virus “up again”.

Xu Haibo, director of the hospital’s imaging department, also believes that Fuyang is related to the patient’s immunity. Zhang Xiaochun, deputy director of the imaging department, added to The News that the decline of immunity is prone to repeated disease, the amount of virus in the body increased again, but the pathological mechanism of the phenomenon of Fuyang has yet to be demonstrated.

Trace “false negative”

Nucleic acid testing has long been regarded as the main criterion for the diagnosis and discharge of new coronary pneumonia. Samples include pharynx swabs, swabs, sputum and bronchial alveoli lotions. The most commonly used are pharynx swabs, including nasopharyngeal swabs and mouth swabs.

Swallow swabs are cotton swabs extended to the depths of the patient’s throat to extract secretions, the process of collection, the patient prone to cough, vomiting reaction, collection is more difficult.

Zhong Nanshan team worked with the Shenyang Automation Research Institute to conduct robot tests in the disease area. On March 8, the team conducted the first sample of robotic pharynx swabs for confirmed positive patients.

Nasopharyngeal swabs need to go deep into the nasal cavity, the man-made interference is relatively small, can get a larger number of specimens, but the patient will not be very comfortable, or even nosebleed.

Li Yan, director of the inspection department at Wuhan University People’s Hospital, said the new coronavirus is mainly located in the lower respiratory tract of the lungs, trachea, bronchial tubes, and other lower respiratory tracts, while the nasopharynx and the mouth and the mouth of the upper respiratory tract. Early onset of the upper respiratory tract there are some viruses, late relatively small, nasopharyngeal may have virus residue, but not necessarily to extract.

Guo Wei, deputy director of the infection department of Tongji Hospital in Wuhan, told The News that according to clinical observation, the positive rate of nasopharyngeal swabs is slightly higher than the pharynx swabs, so his hospital tends to take nasopharyngeal swabs, but also considers the needs of patients.

A number of clinicians introduced, the patient’s viral load, virus distribution location, kit quality, sampling operation method, sample quality, testing, technical level, etc., will affect the nucleic acid test results.

Wang Chen, president of the Chinese Academy of Medical Sciences, said in an interview with CCTV on February 5 that nucleic acid testing has a positive rate of only 30%-50%, there are many false negative new coronapatient patients, clinical symptoms are serious, nucleic acid testing has not been detected.

Of the 44 patients with two consecutive nucleic acid-negative care infections, 26 tested positive for the third time — a study by Zhang Wei, a respiratory and critically ill physician at Wuhan University People’s Hospital. Zhang Wei believes that this may be the kit problem led to false negative, or the patient in the process of improvement, the virus load decreased, intermittent detoxification, may cause intermittent negative, detox positive results. To this end, she recommends that nucleic acid sat negative three times in a row before being discharged from the hospital.

Wang Wei (pseudonym), a neurologist at a fixed-point hospital in Wuhan, found that taking only one part of the pharynx swab, it is easy to appear false negative. He met a patient who checked his pharynx 12 times, all negative, and the 13th time he checked his urine, which became positive.

In order to improve the diagnostic accuracy, the sixth version of the diagnosis and treatment plan, nucleic acid testing increased the “sputum, nasopharyngeal swabs, etc. ” respiratory samples, it is recommended to leave sputum as far as possible. In the seventh version of the diagnosis and treatment, emphasis is placed on nucleic acid testing, lower respiratory tract specimens (sputum or airway extract) more accurate.

Wang Wei told the news that he was in the hospital “in the early mouth to do more, now the mouth, urine, sputum have to do.”

It is understood that some hospitals also through continuous multiple sampling, swab (feces), the use of different batches of kits and other ways to improve the accuracy of nucleic acid detection.

Zhang Xiaochun explained that nucleic acid testing needs the virus to reach the basic amount to be detected, compared to the upper respiratory tract, the lower respiratory tract virus content is higher, so no matter how many times, sampling from the upper respiratory tract may appear false negative. In addition, some patients have a high amount of virus in the upper respiratory tract, some patients have a high amount of virus in the digestive tract, different sampling sites, nucleic acid test results may be different.

Guo Wei suggested that, on the basis of the national diagnosis and treatment program, all localities should respond flexibly according to their own medical resources and patient situation. In some areas with high rates of re-sun, two pharynx swabs can be added to the swab test, three times negative to be discharged from the hospital.

Controversy over discharge criteria

In addition to nucleic acid testing, lung imaging is another important indicator of discharge. The previous standard of treatment required that the “obvious absorption” of inflammation in the lungs before the patient was discharged from the hospital – the sixth and seventh editions were adjusted to be “significantly improved acute oozing lesions”.

“Obvious absorption, refers to the extent of absorption?” A radiologist at Wuhan University People’s Hospital told The News that different people have different abilities to absorb inflammation in their lungs, and some people take a long time. Without objective criteria and quantitative indicators, diagnosis depends mainly on the experience of doctors.

Wang Wei revealed that his hospital in February bed tight, in order to speed up turnover, improve the capacity of admission, patients as long as the standard of discharge, have been discharged.

“You don’t let him out of the hospital, who’s going to help the other patients?” There are many trade-offs that need to be made. “One of the doctors interviewed told the news that there were more early patients, and that “significant lygility” in the standard of treatment and “significant improvement” gave doctors some flexibility.

But Wang Wei found that when his patients in the hospital were discharged from the hospital, some were still suffering from oxygen absorption and walking, some of the symptoms were obvious and needed treatment, and some patients had no significant improvement in his lungs. “The discharge criteria are too broad. He felt.

This leads to more severe clinical symptoms in some discharged patients than in newly admitted patients with mild illness. If they are tested as “false negative” for nucleic acid before they are discharged from the hospital, the risk of “fuyang” is high.

Wang Wei received patients discharged from other fixed-point hospitals, because “not completely good was released”, after discharge symptoms worsened, re-admission.

By late February, however, the number of patients had decreased and their hospitals began to extend the length of stay some patients.

Another doctor interviewed said that now, in the hospital, he will be some of the use of hormones, older, slow recovery patients to be discharged late, more observation for a period of time, to avoid after discharge “sun”.

Zhang Told reporters that the standards implemented by the hospital are more detailed than in the national consultation plan. Taking her Hospital central and southern, for example, patients are now required to be fully absorbed with acute inflammation and to be discharged from the hospital five times in a row.

Guangdong Province has quantified the “obvious absorption” of lung inflammation set out in the discharge criteria to at least 50 percent of the lung’s condition, in order to allow front-line doctors to measure and judge the lung condition, Southern Weekend reported.

But Zhang Xiaochun believes that the image is not good quantitative, everyone’s physique is different, some lung lesions recover 50%, will not be a problem, some recovery 90% may also be repeated, need to combine with other indicators of comprehensive judgment.

Zhang Xiaochun People’s Daily Client Figure

Add “antibody detection”

Antibody testing was added for the first time in the seventh edition of the standard, released on March 4.

New additions to the diagnostic criteria: serum neo-coronavirus-specific IgM antibodies and IgG antibodies are positive, IgG antibodies from negative to positive or 4 times higher than the acute period. Suspected case exclusion needs to be satisfied: two consecutive neo-coronavirus nucleic acid tests are negative (at least 24 hours apart) and IgM and IgG antibodies remain negative 7 days after the onset of the disease.

When a patient becomes infected with the virus, IgM and IgG antibodies are generally produced in the body. IgM antibody is the earliest antibody after infection with the virus in the human body, generally 3-5 days after infection, indicating a new infection, can be used for early diagnosis of infection, the disease soon disappeared after recovery.

IgG antibodies are protective antibodies that begin to develop 2 weeks after infection and last longer and are likely to be carried for life, indicating that they have been infected with the virus. The higher the IgG value, the more antibodies the more, the stronger the resistance to the virus.

Antibody testing can determine whether a new coronavirus antibody appears in the body. Li Yan, director of the inspection department of Wuhan University People’s Hospital, told Yu News that IgM and IgG antibodies were negative, indicating that they were not infected, or infected with no antibodies;

Li Yan said that their hospital was initially infected doctors to do antibody testing volunteers, every three days to take blood, to observe the antibody testing rules, doctors are willing to participate. The results of the assessment are also good, and are now being used in the screening of admitted patients.

Compared with nucleic acid testing, antibody detection sampling is convenient, only need to draw blood, ten minutes out of the results, and, as long as there is a virus in the blood, can be detected, by other factors interference is relatively small, can make up for the lack of nucleic acid detection, the evaluation and diagnosis of patientimmunity are helpful.

Some hospitals have also begun to use antibody testing on discharged patients to avoid nucleic acid false negatives.

On March 3, Wuhan Riverside Square Cabin Hospital received a notice from the Municipal Epidemic Prevention Command, in order to reduce the recurrence of the disease, to achieve the “zero back” goal, will be all patients to be discharged from the hospital blood and do virus antibody testing, to ensure that patients fully recovered from the hospital.

Li Yan explained that IgG is more than 4 times the IgM value, indicating that the patient produced a strong antibody, recovery is very good, coupled with two nucleic acid negative, “out of the hospital” no problem. “

After doing antibody testing for some fuyang patients, Li Yan found that they basically have antibodies, but the value is not high, immunity is relatively weak.

“Now to the late stageof of the outbreak, recessively infected patients should have produced antibodies, can be newly admitted patients to do antibody testing, troubleshooting. Li Yan suggested.

Zhang Also suggested that the sensitivity of antibody testing to reach the sensitive nature of nucleic acid testing, can be included in the discharge standard, but can not be required to meet the antibody test positive standards, because a small number of patients may not be able to produce antibodies.

She believes that, with antibody testing, patients in the five discharge criteria meet four, can be discharged.

However, the current antibody detection technology is not yet mature, the kit has just been developed soon, still need to improve. In addition, each person produces antibodies at different times and quantities, it is difficult to give an absolute answer in the treatment plan.

The possibility of chronic carrying

Is it possible that Fuyang is a second infection after a patient is discharged from the hospital?

In an interview with Caijing, Professor of Biomedical Sciences at the Li Ka-shing School of Medicine at the University of Hong Kong, Jin Dongxuan said that reinfection immediately by the recovering person is contrary to the basic principles of virology and immunology. The human body’s anti-virus response depends on the immune response, the immune response after the outbreak of the virus will be stimulated, will not quickly fade in a short period of time. At least 6 months, not infected for another year.

“From SARS experience, the vast majority of people can produce antibodies, can last for a period of time, but do not rule out that some people have not produced antibodies when discharged from the hospital, after discharge of the disease repeatedly.” Guo Wei told the news.

The age, eating habits, sleep, physical condition, etc. affect immunity, which in turn affects the production of antibodies. Doctors often advise patients to eat eggs, drink milk, vitaminsupplements, high-quality protein, improve immunity.

But Li Yan found that some patients clinical recovery is very good, 5 nucleic acids are positive, that is, do not produce antibodies.

One of her colleagues, in her 50s, and his wife have been infected for a month, nucleic acid tested positive, have no clinical symptoms, have very little shadow in the lungs, and have not been tested for antibodies. Two people a day to eat 10 vitamins, supplements with high protein nutrition, the younger wife finally appeared antibodies, but colleagues themselves have not.

“The virus is a bit weird, some people don’t produce antibodies, but they develop disease, and some people don’t produce antibodies, but they don’t have any clinical symptoms. Li Yan said that if the patient and other indicators meet the discharge criteria, but do not produce antibodies, will not be discharged from the hospital.

Zhang Xiaochun’s colleague’s experience is even more ups and downs. The colleague, who is in his 30s, contracted the new coronavirus before February, was hospitalized for about a week, had lung inflammation absorbed cleanly, two nucleic acid tests were negative, no clinical symptoms, and was discharged from the hospital.

After 20 days of discharge, nucleic acid was tested positive and sent to isolation point, during which there were no clinical symptoms, a few days later the review turned negative. By the end of the 14-day quarantine period, the review became positive again, “making everyone very depressed, do not know what to do.” Only let him stay at the isolation point until the nucleic acid is continuously negative, or antibodies are detected. “

Zhang said, do not produce antibodies or produce antibodies relatively late patients, once discharged from the hospital, once the immunity is reduced, unable to resist the virus, it is easy to appear repeated lying, the amount of virus in the body increased, this time, do nucleic acid review, it is likely to return to yang.

Zhang stressed that the disease repeated lying can not be counted as “recurrence”, but “the same virus repeated, may also be contagious.”

In order to avoid the repeated transmission of patients, the sixth and seventh version of the diagnosis and treatment plan, both proposed discharge patient isolation, and health monitoring.

On March 3rd two researchers from Peking University and the Chinese Academy of Sciences published a paper in the National Scientific Review, saying that the new coronavirus had produced 149 mutation points and had evolved two subtypes, two of which showed great differences. At the same time, the Hindu newspaper reported that the Australian Federal Organisation for Scientific and Industrial Research said the new coronavirus was mutated. Brazilian researchers have also found two confirmed cases in the country, one similar to the virus found in Germany and one in the UK.

At present, there is no final decision on whether the new coronavirus has mutated. “Clinically, it is not clear that the virus has mutated, ” Liu Hening, head of the army’s front-line expert group and a respiratory specialist at the PLA General Hospital, said on CCTV. “

Guo Wei is concerned that there are now studies that show that there are two different types of new coronavirus, patients discharged from the hospital, if the body antibodies can not resist the invasion of another variant of the virus, may be re-infected.

In addition, whether the new coronavirus will develop into a chronic carrying virus is also a matter of concern.

On February 19th, In an interview with News 1, Academician Wang Chen mentioned that the SARS virus is very propagative and pathogenic, not easy to survive and continue to spread, because if it kills the host, it is gone. The new coronavirus is likely to become chronic, as long-term as flu, “this possibility is entirely present, and we need to be prepared for this.” “

Zhang laughs the same view: the new coronavirus may develop into a chronic carry, like influenza, and humans coexist for a long time. In this way, the virus will become more and more contagious, less and less pathogenic, patientsymptoms of mild or no symptoms.

However, Guo Wei believes that the possibility of the new coronavirus being carried by chronic disease is not high, but there may be a small number of viruses attached to the patient’s nasopharynx, mouth and throat mucosa, generally do not become ill, nor invade the respiratory mucosa.

Another expert, who did not want to be named, said that there should be no need to panic over the possibility of chronic carrying of the new coronavirus, take hepatitis B as an example, the country’s 120 million carriers of hepatitis B virus, about 90% of carriers do not become ill.

Peng Zhiyong felt that the lower the virus toxicity, the higher the chance of developing a chronic disease, “the new coronavirus will not become chronic carry, it is too early to say.” “

Focus on “Fuyang” infectious

Whether the patient of Fuyang is contagious is also a matter of public opinion.

On February 25, at a press conference of the Guangzhou Municipal Government, Li Yueping, director of the ICU of the Infection Center of the Eighth People’s Hospital in Guangzhou, said that technically, it is difficult to distinguish between live or dead viruses in Fuyang patients. But their close contacts were all negative. This shows that the patients of Fuyang have not yet experienced the phenomenon of infection.

Li Yueping, director of the ICU of the Infection Center at the Eighth People’s Hospital in Guangzhou. Nandu reporter Liang Weipei Tu

In response to the patient’s situation, Xu Haibo, director of the imaging department of Wuhan University Zhongnan Hospital, and his team studied four medically infected people and found that they tested positive for nucleic acid after 5 to 13 days after discharge, and in the next 4 to 5 days, they were tested positive for three nucleic acids, all of which were positive, and the kit of another manufacturer tested again, or all positive. During the isolation period, four people had no symptoms and had no contact with people with respiratory symptoms, as they did when they were discharged from the hospital. Three of them were discharged from the hospital and quarantined at home, leaving their families uninfected. As a result, he argues, “a certain proportion of the recovered patients may still be carriers of the virus.” The findings were published February 27 in the Journal of the American Medical Association, a leading medical journal.

Xu Haibo told the news, the pathological mechanism of Fuyang phenomenon is not clear, whether Fuyang patients are infectious still need to study and demonstrate, first of all, need to rule out the test is not in place, or different quality testing, resulting in “false negative” situation.

Peng Zhiyong encountered the fuyang patients, most of them do not have any clinical symptoms, “its infectious need to be observed again, may be a period of time before a more adequate conclusion.” It also takes time to verify what happens after the patient recovers. “

Guo Wei suggested that patients should do a good job of protection after discharge from the hospital, wear ingresss, pay attention to hygiene habits, family members also do a good job of protection to reduce the possibility of infection. He believes that Fuyang patients may have residual virus, but the amount is small, the infectious power is also lower, after discharge to the designated location of medical isolation for 14 days, will further reduce infectiousness.

At present, the seventh version of the consultation plan, it is recommended that patients after discharge from the second week, the fourth week of re-diagnosis. Guo Wei suggested that the patient after discharge from the hospital review layered, well recovered young people, according to national standards, used hormones, critical, elderly patients, etc. can be discharged from the first week after the re-diagnosis, in order to identify the patients with re-yang or repeated diseases earlier.