动物实验,新冠病毒 z-bo 2020-09-14 337

　　Recently, some media reported that people infected with the new coronavirus tested positive again after being discharged from the hospital and had to return to the hospital for observation. This has aroused public concern about whether there is a risk of "recurrence" or "re-infection" in patients during the recovery period. On March 14, the Qin Chuan research group of the Institute of Medical Laboratory Animals of the Chinese Academy of Medical Sciences published a paper on the preprinted website bioRxiv, stating that the study found that rhesus monkeys infected with the new crown virus will not be reinfected. This has important implications for disease prognosis and vaccine design.

　　In this new study, the research team used a non-human primate model infected with the new coronavirus to conduct the same virus attack to determine the possibility of re-infection.

　　Analysis of initial infection in rhesus monkeys

　　The research team used a certain amount of new coronavirus strains to infect 4 adult Chinese rhesus monkeys through the trachea. After the initial infection, the weight of the three monkeys lost 200-400 grams, but no changes in rectal temperature were observed. Other clinical symptoms such as decreased appetite, increased respiratory rate, and hunched posture were short-lived. The viral load in nasopharyngeal swabs and anal swabs reached their highest level on the 3rd day after infection and then naturally decreased.

　　In order to determine the virus distribution and histopathological changes of the monkeys infected by the new coronavirus, the research team euthanized the monkey No. 1 on the 7th day after infection and performed an autopsy. The results were in the nose, pharynx, lung, intestine, spinal cord, heart, skeletal muscle and bladder. Virus replication was found in both. It was confirmed by HE staining and SARS-CoV-2 anti-spike protein staining that the lesions mainly occurred in the lungs, with mild to moderate interstitial pneumonia, and the main features were thickened alveolar septum, alveolar macrophages in the alveoli, and Alveolar degeneration, alveolar epithelial cells and inflammatory cell infiltration.

　　In addition, the chest X-ray on the 7th day of infection showed that the upper lobe of the right lung had different degrees of local infiltration and interstitial markers, showing mild to bilateral ground-glass opacity.

　　Compared with the 3rd and 7th days of infection, the neocoronavirus-specific antibodies of monkeys 2, 3, and 4 increased significantly on the 14th, 21st and 28th days after infection. On the 28th day of infection, the 3 alive monkeys had relatively stable body weight and rectal temperature. No new coronavirus was detected in nasopharyngeal and anal swabs, and no obvious abnormalities were found in chest X-rays.

　　The above data shows that the three monkeys have recovered from the new coronavirus infection and similarly meet the clinical discharge evaluation criteria (no clinical symptoms and radiological abnormalities and two negative RT-PCR results).

　　Rhesus monkey re-exposure analysis

　　Subsequently, the research group used the same dose of the new coronavirus strain on monkeys 3 and 4 to infect the trachea again, and the unexposed monkey 2 served as a control.

　　After the re-exposure, the weight of the two monkeys did not lose weight, and their body temperature rose briefly, but the virus test in the nasopharyngeal and anal swabs was negative. On the 5th day after re-infection, monkey 3 was euthanized and autopsy was performed. Compared with monkey 1 on day 7 of the initial infection, no virus replication was found in all tissues of monkey 3, and no pathological damage was found in lung tissue. And viral antigens. The chest X-ray showed that monkey No. 4 was normal on day 5 after reinfection.

　　The results of the study show that monkeys who have recovered from the new coronavirus infection will not be re-infected and will not relapse.

　　Significance

　　According to reports, high levels of neutralizing antibodies have a protective effect on SARS-CoV infection, while low levels of neutralizing antibodies are more likely to enhance SARS-CoV infection and trigger antibody-dependent infection enhancement (ADE).

　　In this study, no ADE was found in recovered monkeys who were exposed to the new coronavirus twice. Since the neutralizing antibodies obtained in the animal experiments of this study are comparable to those obtained in convalescent patients, this finding is of great significance for evaluating vaccine development.

　　The study also found that if monkeys produce neutralizing antibodies early after the initial infection, reinfection will not occur. Correspondingly, as long as patients who are recovering have established enough specific antibodies to enhance their immunity to the new coronavirus, they will not be infectious.

　　On the other hand, no virus replication was detected in all the main tissues of the monkeys that were re-exposed, which indicates that the new coronavirus may not be latent for a long time. For discharged patients to be tested for reyang, this may be due to the “false negative” result of RT-PCR test before discharge, or the patient meets the discharge criteria but has not fully recovered, not caused by re-infection. Therefore, the further improvement of lower respiratory tract diagnostic technology, antibody monitoring and sample testing is essential for the treatment of new coronavirus infections.