February 17 was the day Xu Jia (a pseudonym) was discharged from the hospital and the day she was admitted. This afternoon, after two consecutive negative nucleic acid tests for the new coronavirus, she was discharged from the Wuhan Living Room Fangzhi Hospital. After returning home, she ate the lamb hot pot cooked by her mother, took a shower, and before she could get a good night’s sleep, the phone rang – the third nucleic acid test she had done the day before her discharge had come back positive. So, more than 2 hours after her discharge, she returned to Fangcai Hospital. As of March 10, 2010, a total of 80,924 people had been diagnosed with Newcastle pneumonia and 59,982 of them had been discharged from the hospital. In Xuzhou, Jiangsu Province, two patients were discharged from the hospital and welcomed with flowers by the residents of the community, but two days later, they were re-admitted to the hospital with positive nucleic acid tests, and the community was sealed. In Tianjin, a patient was discharged 16 days later with a positive re-test and was re-admitted, both times with negative nucleic acid, and was discharged 3 days later. In Guangdong, 14% of patients discharged from the hospital were “re-positive” – Song Tie, deputy director of the Guangdong CDC, informed this data at a conference on Feb. 25. Doctors at several designated hospitals in Wuhan told Punch News that a significant portion of the “re-positive” patients are actually “false negatives” caused by errors in nucleic acid testing, in addition to the fact that the virus is not completely cleared from the patient’s body and the immunity decreases after discharge from the hospital, which may lead to “In addition, patients’ bodies have not been completely cleared of the virus and their immune system has decreased after discharge from the hospital, which may lead to “re-positive. Several experts interviewed said that some patients have been unable to produce antibodies, resulting in multiple “re-positives”. The possibility of developing chronic carriage of NCC is not ruled out, and its pathogenicity will be weakened. The seventh edition of the Neoplasmosis protocol, released in early March, added antibody testing to confirm the diagnosis and to screen for suspected cases. Several frontline physicians suggested that it be included in the discharge criteria to reduce the number of “re-positives”. Some doctors interviewed also suggested quantifying the lung imaging indicators in the discharge criteria to further reduce misclassification. “Surveillance found that there was no recurrence of transmission to others in patients with re-surgery.” Guo Yanhong, an inspector from the National Health Care Commission’s Medical Administration, said on Feb. 28 that there is still a need to deepen the understanding of the pathogenic mechanism, disease profile and disease course of the new coronavirus. “Xu Jia still can’t understand how the virus got to her. She felt sick on Jan. 22. She started with weakness and coughing, then started to get fever, and went to Wuhan Tianyou Hospital for a CT scan, which showed a small infection in the lower right lung, and was prescribed medication and sent home for isolation. On Feb. 7, she was admitted to Wuhan Living Room Fangcao Hospital after a positive nucleic acid test. In the square cabin hospital, Xu Jia saw her patients go from sickly to optimistic and in better and better spirits. Some people chased popular dramas, others followed the nurses in square dancing, and they encouraged and cheered each other on, which made her feel warm. After being hospitalized, Xu Jia had two nucleic acid tests, both of which were negative, and a third one on February 16. On the same day, the attending physician met with her by video interview and said that she met the criteria for discharge in the 5th edition of the treatment plan with two negative nucleic acid tests, significant absorption of inflammation in her lungs, and no fever for several days. On February 17, Xu Jia said goodbye to her patients and nurses, and posted a photo of her and the nurses in her circle of friends, in which she was smiling brightly. Unexpectedly, more than 2 hours after she was discharged from the hospital, she was told that her third nucleic acid test was positive and she had to return to the hospital immediately. The nurse saw her back and said, “I really don’t know if you are welcome or not ……” She had a hard night’s sleep. The next day she had her fourth nucleic acid test, praying that the last positive was just an accident, but she was quickly disappointed. The family was originally in home isolation, just 2 days short of the end of the observation period, because of her brief discharge this time, were sent to school to re-isolate 14 days. Xu Jia herself began to feel sick, dizzy and weak, high fever, and was transferred to Jinyintan Hospital a few days later. On March 5, Xu Jia was discharged from the hospital for the second time. This time, instead of going home, she was sent to a school isolation site for observation – an addition to the “New Coronary Pneumonia Treatment Protocol (Trial Version 7)” released by the National Health Commission on March 4. The sixth edition of the treatment protocol, released on February 19, first suggested that patients should be discharged from the hospital for 14 days for “self-monitoring of their health status” and be re-examined at the hospital during the second and fourth weeks of discharge, while the seventh edition reinforced the 14-day “isolation management and health status monitoring”. This change comes from the phenomenon of re-surgery in many places in China. Experts interviewed believe that a significant portion of the so-called “re-positive” population is “false negative”, the virus in the patient’s body has not been cleared, but only before discharge nucleic acid test was not detected. In an interview with CCTV, Tong Zhaohui, a member of the central steering group in Hubei, said that the re-positive is related to the detection of nucleic acid is not very stable, there are problems with kits and sampling, the national re-positive ratio is about 0.1%, which is within the control range. In addition, “re-positive” may also be detected in the body of the virus fragments or dead virus, “which does not mean that the patient has not been cured or recurring disease.” Guo Wei, deputy director of the Department of Infection at Wuhan Tongji Hospital, told Punch News that few patients with known re-surgery have symptoms, and “relapse” is a very small number. The director of the Department of Critical Care Medicine at Wuhan University Central and South Hospital, Peng Zhiyong, found that one of the commonalities among patients with re-surgery is that the lungs were better and basically normal when they were discharged, but the immune system had not fully recovered from the virus, and the number and absolute value of lymphocytes were 20-30% lower than normal, causing the virus to “come back”. Xu Haibo, director of the hospital’s imaging department, also believes that the resurgence is related to the patient’s immunity. Zhang Xiaochun, deputy director of the imaging department, added to Punch News that the immune system is prone to recurrence of the disease and the amount of virus in the body increases again, but the pathological mechanism of the re-positive phenomenon remains to be proven. The “false negative” nucleic acid test has been regarded as the main criterion for confirming the diagnosis and discharge of new coronary pneumonia. Sampling methods include pharyngeal swabs, anal swabs, sputum, and bronchoalveolar lavage fluid. The most commonly used swabs are pharyngeal swabs, including nasopharyngeal swabs and oropharyngeal swabs. Oropharyngeal swab collection is to extend the swab deep into the patient’s throat to extract secretions, and during the collection process, the patient is prone to coughing and vomiting reactions, making the collection more difficult. On March 8, the team conducted the first robotic pharyngeal swab sampling trial for patients with a positive diagnosis. Zhong Nanshan’s team collaborated with a team from the Shenyang Institute of Automation to conduct a robotic trial in the hospital area. on March 8, the team conducted the first robotic pharyngeal swab sampling trial for patients with a positive diagnosis. Nasopharyngeal swab collection, on the other hand, requires deeper penetration into the nasal cavity, which is less subject to human interference and can yield a more adequate amount of specimens, but patients can be less comfortable and even bleed from the nasal cavity. Wuhan University People’s Hospital, director of the Department of Laboratory Li Yan, the new coronavirus is mainly located in the lungs, trachea, bronchi and other parts of the lower respiratory tract, while the nasopharynx and oropharynx in the upper respiratory tract. There are some viruses in the upper respiratory tract in the early stages of the disease, less in the late stages, and there may be viral residues in the nasopharynx, but they are not always picked up. Guo Wei, deputy director of the Department of Infection at Wuhan Tongji Hospital, told Punch News that according to clinical observation, the positive rate of nasopharyngeal swabs is slightly higher than that of oropharyngeal swabs, so his hospital tends to take nasopharyngeal swabs, but will also consider the needs of patients. A number of clinicians introduced, the amount of the patient’s viral load, the location of the virus distribution, the quality of the kit, sampling operation methods, sample quality, detection, the level of technicians, etc., will affect the nucleic acid test results. Academician Wang Chen, president of the Chinese Academy of Medical Sciences, mentioned in an interview with CCTV on February 5 that nucleic acid testing has only a 30-50 percent positive rate, and there are many false-negative patients with new crowns who have severe clinical symptoms that are not detected by nucleic acid testing. Of the 44 healthcare patients who had two consecutive negative nucleic acid tests, 26 turned positive for nucleic acid for the third time – this was the finding of a study by Zhang Qian, a doctor at the Department of Respiratory and Critical Care Medicine at Wuhan University People’s Hospital. According to Zhang Qian, this could be a result of a kit problem that leads to false negatives, or a situation in which the patient’s viral load drops during the course of improvement and intermittent detoxification occurs, possibly resulting in an intermittent period of negativity and a positive result during detoxification. For this reason, she recommends three consecutive negative nucleic acid tests before discharge. Wang Wei (a pseudonym), a neurologist at a sentinel hospital in Wuhan, found that it is easy to take a pharyngeal swab from only one site and have a false negative. He met a patient who checked the pharyngeal swab 12 times and was negative, and the 13th time he checked the urine, it turned out to be positive. In order to improve the diagnostic accuracy, the sixth edition of the treatment protocol added “sputum and nasopharyngeal swab” as respiratory specimens for nucleic acid testing, and recommended that sputum be collected whenever possible. In the seventh edition of the treatment plan, nucleic acid testing is emphasized, and lower respiratory specimens (sputum or airway extracts) are more accurate. Wang Wei told Surfing News that his hospital “did more oropharynx in the early stage, but now oropharynx, urine and sputum are all done”. It is understood that some hospitals also improve the accuracy of nucleic acid testing by sampling multiple times in a row, taking anal swabs (stool), and using different batches of kits. Zhang Xiaochun explained that nucleic acid testing requires a basic amount of virus to be detected, and the virus content in the lower respiratory tract is higher compared to the upper respiratory tract, so no matter how many times the test is taken, a false negative may occur when sampling from the upper respiratory tract. In addition, some patients have a high amount of virus in the upper respiratory tract and some have a high amount of virus in the digestive tract, and the results of the nucleic acid test may differ depending on the sampling site. Guo Wei suggested that, based on the national treatment plan, localities should respond flexibly according to their own medical resources and patient conditions. In some areas with a high rate of re-positive tests, in addition to two pharyngeal swabs, anal swabs can be added, and only after three negative tests can the patient be discharged from the hospital. Discharge Criteria Controversy In addition to nucleic acid testing, lung imaging is another important discharge indicator. The previous standard of care required “significant absorption” of lung inflammation before a patient could be discharged from the hospital – the sixth and seventh editions were adjusted to “significant improvement of acute exudative lesions. “Significantly absorbed, to what extent?” A radiologist at Wuhan University People’s Hospital told Punch News that different people have different abilities to absorb lung inflammation, and some take a long time. Without objective criteria and quantitative indicators, the diagnosis depends mainly on the experience of doctors. Wang Wei revealed that his hospital was tight on beds in February, and in order to speed up turnover and increase capacity, patients were discharged as long as they met the discharge criteria. “If you don’t discharge him, who will help the other patients? It needs to be weighed in many ways.” An interviewed doctor told Punch News that there are many patients in the early stage, and the “obvious absorption” and “obvious improvement” in the treatment criteria give doctors some flexibility. But Wang Wei found that when patients at his hospital were discharged, some were still on oxygen and struggling to walk, some had obvious symptoms and needed treatment, and some had lungs that did not seem to him to be significantly better. “The discharge criteria are too broad.” He felt. This has led to the fact that some discharged patients have worse clinical symptoms than newly admitted patients with mild disease. If their pre-discharge nucleic acid test is “false negative,” the risk of a “re-positive” is high. Wang Wei has seen patients who were discharged from other designated hospitals, and because they were “discharged before they were fully recovered,” their symptoms worsened after discharge and they were readmitted. However, by late February, the number of patients decreased and their hospital began to extend the length of stay for some patients. Another doctor interviewed said that now, his hospital would let some patients who had used hormones, were old and slow to recover to be discharged later and observed for a longer period of time to avoid “re-surgery” after discharge. Zhang Xiaochun told reporters that the standards implemented by the hospital are more detailed than those in the national treatment plan. Her hospital, Zhongnan Hospital, for example, now requires patients to have complete absorption of acute inflammation and five consecutive negative nucleic acid tests before they can be discharged. According to Southern Weekend, Guangdong Province has quantified “significant absorption” of lung inflammation as at least 50 percent recovery in the discharge criteria in order to facilitate front-line doctors to measure and judge lung conditions. However, Zhang Xiaochun believes that it is not easy to quantify the image, as each person’s physique is different, and some lung lesions recover 50% without problems, while others recover 90% and may recur, and need to be combined with other indicators. The seventh edition of the treatment criteria released on March 4 added antibody testing for the first time. The new criteria for confirmation of diagnosis include: positive serum IgM and IgG antibodies specific to the new coronavirus; IgG antibodies turn from negative to positive or increase 4-fold or more in the recovery period compared to the acute period. Suspected case exclusion requires that: two consecutive negative nucleic acid tests for neo-coronavirus (at least 24 hours between sampling times) and IgM and IgG antibodies remain negative 7 days after onset. IgM and IgG antibodies are generally produced in the body after a patient is infected with the virus. IgM antibodies are the earliest antibodies to appear in the body after infection with the virus, and are generally produced 3-5 days after infection, suggesting a recent infection, and can be used for early diagnosis of infection and disappear soon after recovery from the disease. IgG antibodies are protective antibodies that begin to be produced 2 weeks after infection with the virus and last for a longer period of time, and may be carried for life, indicating that the virus has been contracted. higher IgG values indicate more antibodies and greater resistance to the virus. The antibody test can determine whether antibodies to the new coronavirus are present in the body. Li Yan, director of the Department of Laboratory at the People’s Hospital of Wuhan University, told Punch News that IgM and IgG antibodies are both negative, indicating that there is no infection, or infection has not produced antibodies; both positive, indicating a recent infection, there is still virus in the body; IgM is negative, IgG is positive, indicating that the patient is in recovery, has produced antibodies, is the safest. Li Yan said that their hospital initially was infected doctors to be volunteers for antibody testing, and blood was drawn every three days to observe the regularity of antibody testing, and the doctors were willing to participate. The evaluation results were also quite good, and it has now begun to be used in the screening of patients admitted to the hospital. Compared to the nucleic acid test, the antibody test is easy to sample, requires only a blood draw, and produces results in ten minutes; moreover, as long as the virus is present in the blood, it can be detected with less interference from other factors, which can make up for the lack of the nucleic acid test and help in the assessment and diagnosis of a patient’s immunity. Some hospitals have also started to use antibody tests on discharged patients to avoid the phenomenon of false negative nucleic acid. On March 3, Wuhan Jiangan Fangzhi Hospital received notice from the city’s epidemic prevention command that in order to reduce relapse and achieve the goal of “zero return”, blood will be drawn from all patients to be discharged plus virus antibody testing to ensure that patients are fully recovered and discharged. Li Yan explained that IgG is greater than four times the value of IgM, indicating that the patient has produced strong antibodies and recovered very well, plus two negative nucleic acid, “(discharge) is not a problem.” After doing antibody tests on some of the patients who had regained positivity, Li Yan found that they basically had antibodies, but the values were not high and their immunity was relatively weak. “Now that we are in the middle and late stages of the epidemic, patients who have been recessively infected should have developed antibodies, and antibody tests can be done on all newly admitted patients to screen them.” Li Yan suggested. Zhang Xiaochun also suggested that antibody testing can be included in the discharge criteria if the sensitivity of the antibody test reaches the sensitivity of the nucleic acid test, but it cannot be required to meet the criteria of a positive antibody test because a few patients may not be able to produce antibodies. She believes that with the addition of antibody testing, patients can be discharged if they meet four of the five discharge criteria. However, antibody testing technology is not yet mature and the kits have just been developed, so there is still room for improvement. In addition, each person produces antibodies at different times and in different amounts, and it is difficult to give an absolute answer in the treatment plan. The possibility of chronic carriage: Is it possible that the “re-positive” test is a secondary infection after the patient is discharged from the hospital? Professor Jin Dongyan of the School of Biomedical Sciences, The University of Hong Kong Li Ka Shing Faculty of Medicine, said in an interview with Caijing that it is against the basic principles of virology and immunology for a recovered person to be reinfected immediately. The human body relies on the immune response against the virus, and the immune response will be stimulated when it encounters the virus again after it is generated, and will not fade away quickly in a short period of time. It will not be reinfected for at least 6 months or a year. “From the experience of SARS, the vast majority of people can produce antibodies that can last for a period of time, but do not rule out that some people have not yet produced antibodies when they are discharged from the hospital, and the disease recurs after discharge.” Guo Wei analyzed to the surging news. Personal age, diet, sleep, and physical condition can affect immunity, which in turn affects antibody production. Doctors often advise patients to eat eggs and drink milk to supplement vitamins and high-quality protein to improve immunity. However, Li Yan found that some patients recovered well clinically and were positive for nucleic acid five times, but just did not produce antibodies. One of her colleagues, in her 50s, and his wife, both infected for a month, tested positive for nucleic acid, had no clinical symptoms, only few shadows in their lungs, and never measured antibodies. The two took 10 vitamins and high-protein supplements daily, and the younger wife finally developed antibodies, but the colleague herself had not. ” The virus is a bit bizarre, some people do not produce antibodies, but will develop; others do not produce antibodies, but without any clinical symptoms.” Li Yan said the patient would not be discharged now if all other indicators met the criteria for discharge, but no antibodies were produced. The experience of Zhang Xiaochun’s colleague was even more tumultuous. The colleague, who is in his 30s, was infected with the new coronavirus 2 months ago and was discharged after about a week in the hospital with clean lung inflammation, two negative nucleic acid tests and no clinical symptoms. Twenty days after discharge, the nucleic acid re-test was positive and he was sent to an isolation site for quarantine, during which he also had no clinical symptoms and was re-tested a few days later and turned negative. When the 14-day quarantine period was almost over, the re-test became positive again, “making everyone very depressed, do not know what to do. We can only let him stay in the isolation site until the nucleic acid is continuously negative, or detect antibodies.” Zhang Xiaochun said that patients who do not produce antibodies or produce antibodies late, after discharge, once the immunity is reduced, can not resist the virus, it is easy to recurrence of the disease, the amount of virus in the body increased, at this time, and then do nucleic acid re-testing, it is likely to regain positive. Zhang Xiaochun stressed that the recurrence of the disease can not be considered a “relapse”, but “the same virus repeatedly, may also be contagious”. In order to prevent patients from repeatedly infecting others, both the sixth and seventh editions of the treatment plan propose isolation of patients discharged from the hospital and health monitoring. On March 3, two researchers from Peking University and the Chinese Academy of Sciences published a paper in the National Science Review stating that the new coronavirus has produced 149 mutation sites and evolved two subtypes, both of which exhibit significant differences. At the same time, The Hindu reported that Australia’s Commonwealth Scientific and Industrial Research Organization said that the new coronavirus was mutating. Brazilian researchers also found 2 confirmed cases in the country, one similar to the virus found in Germany and one similar to the virus found in the UK. There is no conclusive information about whether the new coronavirus is mutating in the country. Liu Youning, head of the army’s forward expert group and a respiratory specialist at the PLA General Hospital, said on the CCTV program, “Clinically, it is not evident that the virus has mutated.” Guo Wei is concerned that there are now studies showing that the new coronavirus has two types, and that patients may be re-infected after discharge if their body antibodies are unable to resist another mutated virus. In addition, there is concern whether the new coronavirus will develop into a chronic carrier virus. On February 19, academician Wang Chen mentioned in an interview with News 1+1 that the SARS virus is highly transmissible and pathogenic, and does not easily survive and continue to spread, because if it kills the host, it is not there itself. There is a possibility that the new coronavirus will turn chronic and persist for a long time like the flu, “a possibility that is completely present and for which we have to be prepared.” Zhang Xiaochun holds the same view: the new coronavirus may develop into a chronic carrier, like the flu, and coexist with humans for a long time. The virus would then become more and more contagious, less and less pathogenic, and patients would have mild or little symptoms. However, Guo Wei believes that the possibility of the new coronavirus being carried chronically is not high, although there may be a small amount of virus attached to the patient’s nasopharynx and oropharynx mucosa, which generally does not develop and does not invade the respiratory mucosa. Another expert, who did not want to be named, believes that there is no need to panic too much about the possibility of chronic carriage of the new coronavirus, taking hepatitis B as an example, about 90% of the 120 million carriers of hepatitis B virus in the country do not develop the disease. Peng Zhiyong feels that the lower the viral toxicity, the higher the chance of developing chronic disease, “whether the new crown virus will become chronic carriers, it is still too early (to judge), remains to be seen.” The focus on the “re-positive” infectious “re-positive” patients are infectious, is also a matter of public opinion focus. On Feb. 25, at a Guangzhou government press conference, Li Yueping, director of the ICU of the Infectious Disease Center of Guangzhou Eighth People’s Hospital, mentioned that technically, it is difficult to distinguish between live or dead viruses in the rebound patients. However, their close contacts were all negative. This means that the rebound patients are not infectious for the time being. In response to the patients’ re-positive situation, Xu Haibo, director of the imaging department at Wuhan University Central South Hospital, and his team, studied the four health care infected patients and found that they became positive for nucleic acid 5 to 13 days after discharge; three nucleic acid tests were done in the following 4 to 5 days, all of which were positive; and all of them were still positive when they were tested again by changing to another manufacturer’s kit. During the quarantine period, four people were asymptomatic, had the same lung images as when they were discharged, and had no contact with people with respiratory symptoms. Three of them were discharged from the hospital in home isolation and their families were not infected. From this, he concluded that “a certain percentage of healed patients may still be carriers of the virus.” The findings were published Feb. 27 in the top medical journal, the Journal of the American Medical Association. Xu Haibo told the Surfing News that the pathological mechanism of the phenomenon of re-positive is still unclear, whether the re-positive patients are infectious need to be studied and proven, first of all, need to exclude the detection is not in place, or different quality of testing, resulting in a “false negative” situation. Peng Zhiyong has encountered the re-positive patients, most of them have no clinical symptoms, “its infectiousness needs to be observed again, may be a period of time to have a more adequate conclusion. It will take time to verify what will happen to the patient after the resurgence.” Guo Wei suggests that patients should be well protected after discharge from the hospital, wear masks and pay attention to hygiene habits, and family members should also be well protected to reduce the possibility of infection. He believes that the residual virus may remain in the body of the re-positive patient, but the amount is not much and the infectivity is lower. 14 days of medical isolation at the designated place after discharge will further reduce the infectivity. Currently, the seventh edition of the treatment protocol recommends that patients be re-examined in the second and fourth weeks after discharge. Guo Wei suggested that patients be discharged from the hospital for a stratified review, young people who recover well, according to national standards; patients who have used hormones, critical, elderly patients, etc. can be discharged for a follow-up in the first week after discharge to identify earlier patients with re-surgery or recurrent disease. Content source: Surge News