Causes of re positive: false negative? Secondary infection?
Since January this year, at least seven places in China have reported cases of new crown patients returning to positive, and the number of cases is close to 40. In fact, since covid-19 outbreak has occurred, the phenomenon of relapse has occurred. As early as the end of February last year, Wuhan, Guangzhou and other places reported that a small number of patients recovered and discharged after nucleic acid re examination was positive. To this end, the New Coronavirus pneumonia diagnosis and treatment plan (trial version 7) released by China’s national health and Health Committee in March 2020 will be discharged from patients who had been asked for 14 days “ self health monitoring ” changed to 14 days “ isolation management and health monitoring ” further strengthen the follow-up investigation of discharged patients.
Why do patients who have been cured and discharged appear the phenomenon of re positive? At present, the mainstream view of experts is that nucleic acid testing & quot; false negative & quot; and secondary infection are the main causes of re positive.
Liu Youning, a famous respiratory specialist in the General Hospital of the Chinese people’s Liberation Army, said in an interview with China news agency that Fuyang can be divided into two categories:
The first is the early stage of cure, which has turned negative when discharged from hospital and turned positive again in a short time. This situation is mostly due to the last nucleic acid detection, sample collection is not ideal or the reagent sensitivity is not enough;.
The second is that nucleic acid is positive after several months. There are two possibilities for this situation. One is secondary infection. Although there are not many confirmed cases, it does exist. Second, some patients, especially those with low immune function, are in a state of “stalemate” between the body’s immunity and the virus, resulting in patients carrying the virus for a long time. It is worth noting that nucleic acid detection itself can not reflect the amount of viral load, or even distinguish whether the virus is complete, dead or alive. In order to determine whether the patient has infected animals, at least live virus should be isolated.
In response to the problem of “false negative”, Wang Daming, a researcher at Suzhou Institute of biomedical engineering technology, Chinese Academy of Sciences, said that any test has a minimum detection limit. If the new coronavirus in the patient’s body is lower than the minimum detection limit of the detection reagent, it can not be detected in theory, resulting in negative nucleic acid. In addition, the nucleic acid results of throat swab, nasal swab and anal swab were also different.
Wang Daming, for example, said that some patients could not detect the new coronavirus in the respiratory tract and nasopharynx, but the virus may still continue to replicate in the gastrointestinal tract, but it did not cause clinical symptoms. The nucleic acid positive may be detected by anal swab. The research of Guangzhou Eighth People’s Hospital and other teams in 2020 also corroborates Wang Daming’s view. The study of 21 patients with re positive results showed that as many as 15 patients had re positive results from anal swabs, and the viral load was significantly less than that at the beginning of infection.
The re positive phenomenon caused by secondary infection is also worthy of attention. On August 24, 2020, the world’s first new coronal patient with secondary infection appeared in Hong Kong. There was a 142 day interval between the two infections. The whole genome sequencing showed that the viral gene spectrum of the two infections was different. The appearance of this case provides a new explanation for the re positive of patients with new crown.
Is the patient infected?
Previously, Zhong Nanshan, academician of the Chinese Academy of engineering, pointed out that most of the so-called “Fuyang” should be nucleic acid fragments rather than the virus itself; at present, it seems that patients with Fuyang are not infectious. Zhang Wenhong, director of infection department of Huashan Hospital Affiliated to Shanghai Fudan University, said that Fuyang had no significant clinical significance and would not cause a large-scale outbreak in the epidemiological history.
Since last year, the follow-up study results of many hospitals may provide some reference. The joint team of Wuhan Jinyintan hospital and Peking Union Medical College Hospital carried out a follow-up study on 37 patients with a course of disease of more than 4 weeks, who reached the clinical cure standard but showed positive nucleic acid test. Among them, 9 patients had been living closely with their families for 258 person days before their recovery, but nucleic acid and antibody tests confirmed that there was no infection in any close contacts. Based on the above results, the joint team of the two hospitals believes that continuous or repeated positive nucleic acid does not necessarily mean high-risk infectivity.
In foreign countries, the local CDC of South Korea carried out virus isolation and culture on nasopharyngeal swab samples of 108 re positive patients, and the results were all negative. The Korean Center for Disease Control and prevention believes that there is no evidence to show that patients with new coronavirus positive are infectious. So far, no cases of infection due to contact with Fuyang patients have been reported in South Korea.
In Liu Youning’s view, positive nucleic acid does not mean that there is a live virus in the patient’s body. If it is a dead virus or only a virus sequence fragment, the patient is not infectious; but it is difficult to judge whether the virus in the patient’s body is dead or alive clinically, so we can not take it lightly in the face of the patient’s recovery. Wang Daming also stressed that as long as the new coronavirus is detected in patients, there is still the possibility of infection in theory.
How to deal with the patients with new crown restoration?
One after another, people pay more attention to the re positive probability of new crown patients. At the press conference of the joint prevention and control mechanism of the State Council held on May 7, 2020, Wang GuiQiang, director of the Department of infectious diseases of the first hospital of Peking University, released the relevant data. At that time, the overall incidence of re positive cases in China was 5% – 15%, and the incidence of re positive cases varied greatly in different places.
Now more than half a year has passed since the data was released, and the latest data on the incidence of new crown Fuyang has not yet been released. With the gradual deepening of scientists’ research on the new coronavirus and the improvement of treatment methods, has the probability of recovery of new coronavirus patients decreased? Wang Daming said that the medical resources in the early stage of the epidemic are relatively tight. In order to treat as many patients as possible, patients can be discharged when their symptoms are relieved and they meet the discharge standards, so the early recovery rate is slightly higher. At this stage, whether the standard of cure and discharge or follow-up after discharge, it is more in place than before, and the recovery rate of positive will decrease in theory.
Liu Youning holds a similar view. He pointed out that the high recovery rate of patients in some areas in the early stage was mainly due to the lack of sensitivity of the kit, and that some patients only need one negative nucleic acid test when they leave hospital. Now, with the further improvement of nucleic acid reagents and stricter discharge standards, the overall probability of re positive should be lower.
Novel coronavirus pneumonia treatment expert Tong Zhaohui gives advice on how to cope with the challenges posed by the rehabilitation of the patients in the current situation of normalization of epidemic prevention and control. He pointed out that the vast majority of re positive patients have no respiratory tract and fever and other clinical symptoms. In the face of re positive patients, we should first re isolate them, and then review the blood routine, nucleic acid, CT images and other indicators, until the end of 14 days of isolation, nucleic acid turned negative and then discharged. Interviewees also stressed that the re positive rate of patients with new crown is a small probability event, and there is no need for the public to panic excessively about the re positive rate of new crown.