On the evening of April 9, Cao Xuetao, academician of the Chinese Academy of Engineering and president of Nankai University, published a review article entitled "Immunopathology of New Coronavirus Pneumonia and Its Implications for Treatment" in the "Nature-Immunology Review" online.
"Nature-Immunology Review" belongs to the Nature Publishing Group, and will be directed to the famous scientists with academic influence to make manuscripts.
Prior to this, Cao Xuetao had been invited to publish two long summaries of reviews in the magazine in 2015 and 2019 respectively. Among them, the review published in 2015 is the first review article published by Chinese scholars in this journal.
What is the moral of this review? From what perspective of immunology should we study the mechanism and treatment of new coronavirus pneumonia?
In an interview with "China Science Daily", Cao Xuetao answered.
"China Science Daily": When did "Nature-Immunology Review" propose this draft to you? What is the background and requirements of the draft?
Cao Xuetao: On March 16, the magazine made an appointment with me. At that time, the new coronavirus pneumonia epidemic in the UK began to attract attention from all parties. In the process of discussing how to deal with it, everyone is increasingly aware of the importance of learning from China's epidemic prevention and control measures and experience.
In particular, they have successively seen reports on the clinical treatment of patients with severe new coronavirus pneumonia in China. The academic community is very interested in how this part of severe patients is cured and what methods are used.
Therefore, they hope that I will introduce the immunopathological characteristics of the new coronavirus pneumonia to international colleagues from the perspective of immunology and the implications for clinical treatment and related drug development.
"China Science Daily": Unlike the previous long article, why is this comment only 2 pages? What do you want to state through this review?
Cao Xuetao: This is a brief review, not a review. This magazine rarely publishes review styles. The magazine hopes to introduce the relevant situation of a new topic of coronavirus pneumonia in a timely manner as soon as possible for the reference of colleagues in the biomedical field.
In fact, many magazines have set up a special column for new coronavirus pneumonia, and even a green channel for submission.
The new coronavirus pneumonia is a common challenge faced by all mankind, so the magazine asked for it, hoping to be concise and clear and write it quickly. The specific requirements are within 1500 words and 10 references.
In the process of writing, new articles related to the new coronavirus pneumonia were published one after another. I wrote more than 3,000 words one after another, which could only be deleted in the end.
So in my final thanks to the comment, I stated that, due to the word limit, I apologize for the research results that could not be cited.
In this review, I focused on a theme, namely, the role of immunity in the pathogenesis and treatment of new coronavirus pneumonia. Immune pathology is discussed to discuss how immune regulation affects the outcome and treatment of new coronavirus pneumonia, so as to further explore new types New targets for Coronavirus pneumonia treatment and new ways of intervention.
"China Science Daily": In the review, regarding the content of traditional Chinese medicine for the treatment of new coronavirus pneumonia, you quoted the views exchanged between personal and academician Zhong Nanshan and marked them. Is there a special reason?
Cao Xuetao: Although this part of the content is just a sentence, it actually expresses an attitude in refined language.
Chinese medicine has indeed played a role in combating the epidemic of the new coronavirus pneumonia. Academician Zhang Boli and I often communicate with each other. He has been applying clinical achievements in traditional Chinese medicine to treat patients with new-type coronavirus pneumonia at various stages, and has achieved remarkable clinical results.
I communicated with Academician Zhong Nanshan, and learned from him that his team proved that Chinese medicine can inhibit the replication of new coronavirus and the production of inflammatory factors induced by in vitro experiments (published articles). Through double-blind controlled trials, clinically Also see the efficacy (coming soon article).
Therefore, the magazine agreed to indicate in the text that Chinese medicine has a clinical effect on the treatment of new coronavirus pneumonia, but there was no officially published clinical efficacy paper for reference. After communicating with the editorial department of the magazine, it was decided to adopt the "personal communication" method with academician Zhong Nanshan.
The article is quoted in the form of the full name of Academician Zhong Nanshan. I think this reflects the enormous international influence of Academician Zhong Nanshan as a Chinese clinical expert, and also reflects the increasing attention of Chinese medicine in the international academic community.
"China Science Daily": Since the outbreak of the new coronavirus pneumonia, what relevant research work have you been involved in?
Cao Xuetao: I have always been concerned about the research progress of new coronavirus pneumonia, including virology, immunology, pathology, and drug development including antibodies and vaccines, because infection immunity is also my research field.
In the early stage of the epidemic, my laboratory did not carry out research on new coronaviruses due to limited conditions, but I have been maintaining communication with many laboratories and personnel conducting relevant research and providing consulting guidance to give them some ideas and suggestions.
At present, my team members are working with the hospital to study the pathogenesis of immune inflammatory factors and new coronavirus pneumonia, and also maintain academic exchanges with international counterparts.
In addition, I submitted two policy recommendations for the prevention and control of the new coronavirus pneumonia epidemic to the Chinese Academy of Engineering in mid to late February. One is the proposal to establish a national scientific and technological institution for the prevention, control, early warning and prediction of epidemic situations.
In this new coronavirus pneumonia epidemic, the society has widely paid attention to the "development situation of the epidemic" and how to answer "what prevention and control strategies and interventions are effective and feasible and efficient" at the decision-making level, "proactively predict the demand for disease control resource protection And dynamically optimize the deployment "and so on.
Practice has proved that the timely collection of epidemic parameters, the analysis of corresponding epidemiological mathematical models and the rational application of medical big data technology systems can provide forward-looking early warning and pre-judgment for the answers to these questions and the prevention and control of the epidemic.
We should have such a special scientific and technological institution. Considering the trend of the global pandemic of the new coronavirus pneumonia epidemic, it is also necessary to establish an international joint research center.
This can not only highlight China's strength, but also benefit the win-win cooperation and benefit all mankind.
The second is the thinking and suggestions on the issues related to overseas epidemic response, scientific and technological breakthroughs, and health emergency management systems for the prevention and control of new coronavirus pneumonia at the current stage, and at the same time, it is recommended that the national level long-term adherence to the research on new coronavirus.
I suggest setting up a special laboratory or entrusting an existing national key laboratory to study a series of issues such as coronavirus etiology, immunology, vaccine development, antibody development, etc. for a long time.
This is not only needed by China, but also needed by the world. Scientific research in China must stand on the international background and talk about innovation and practice.
"China Science Daily": Is the immune response of patients with new coronavirus pneumonia protective or pathogenic? There are studies suggesting the antibody-dependent enhancement effect (ADE) of new coronaviruses. What kind of problems do you think this will bring to vaccine development and antibody therapy?
Cao Xuetao: After being infected with the new coronavirus, the natural immune response initiated by the body at the early stage plays a role in clearing the virus, which means that the early immune response is definitely protective, so there is a situation where the mild patient recovers quickly.
However, when the immune system is over-activated, especially if the virus is not controlled (a breakthrough of the immune defense line), it will lead to the destruction of the immune system, which will lead to excessive inflammation.
Excessive inflammation and immune disorders can damage the lungs and other tissues, leading to immune pathology.
Compared with other viruses that can produce a large amount of antibodies within 7 to 10 days of infection, it takes longer to produce antibodies to the new coronavirus. How long the new coronavirus antibody exists in the body and whether it can play a protective role remains to be further studied.
At present, some studies suggest that the middle-aged and elderly people with new coronavirus infection have a higher level of antibody production, but they tend to develop more severe cases among the middle-aged and elderly people.
In addition, there are two clinical analyses that indicate that the higher the level of new coronavirus antibody production, the higher the degree of disease progression and the greater the proportion, which suggests that there may be a new coronavirus ADE effect.
Therefore, the protection and pathogenicity of new coronavirus antibodies are worthy of in-depth study. This is a very important issue that needs to be paid attention to in vaccine development and antibody-based therapy. For example, dengue virus and respiratory syncytial virus have the ADE effect, and their vaccine development has always had problems.
In fact, virus vaccine development and antibody treatment have always been challenged by virus mutations, weak virus immunogenicity, which leads to poor antibody efficacy, and antibody binding does not kill the virus, but strengthens the virus infection ADE effect.
In this regard, more independent large-scale clinical studies are needed to confirm or exclude the possibility of new coronavirus ADE.
"China Science Daily": What are the current treatments for the cytokine storm in patients with severe new coronavirus pneumonia?
Cao Xuetao: Cytokine storm is an important pathogenic factor for severe new coronavirus pneumonia.
Elevated IL-6 levels are an indicator of poor prognosis in patients with severe new coronavirus pneumonia and ARDS. Clinical trials organized by the Chinese University of Science and Technology have shown that monoclonal antibody therapy targeting IL-6 receptors is effective, and many European countries are imitating applications.
This suggests that neutralizing monoclonal antibodies may also be useful against other pro-inflammatory cytokines, and potential targets include IL-1, IL-17 and their respective receptors.
In addition, small molecule inhibitors of signaling elements downstream of cytokines may hopefully prevent immune responses related to cytokine storms. The treatment of cytokine storm can draw on CART cell therapy.
We have also observed activation of the complement system in patients with severe new coronavirus pneumonia, suggesting that if complement inhibitors are used, inflammatory damage may be attenuated. It is hoped that these methods can be approved for clinical trials and benefit patients.
"China Science Daily": In your review, you mentioned that the new coronavirus involves neuroendocrine-immune interactions. What is this concept?
Cao Xuetao: It is well known that cytokines released by the natural immune response after viral infection can induce the neuroendocrine system to release glucocorticoids and other neuropeptides, thereby regulating the immune response. This involves stress disturbances in the interaction between the neuroendocrine system and the immune system.
The new coronavirus has been isolated from the human respiratory tract, feces, tears and other samples, which means that the virus has infected multiple tissues and organs.
Recently, the United States reported that the brain of a person infected with a new coronavirus has been damaged. So whether the new coronavirus can infect the central nervous system and whether it can promote the release of inflammation-induced pathological neuroendocrine mediators, affecting respiratory function and the pathogenesis of ARDS, whether it is to promote the recovery of the patient or cause the condition to deteriorate is worth studying.
"China Science Daily": The global fight against the new coronavirus pneumonia epidemic will be a protracted battle. Do you have any suggestions for this?
Cao Xuetao: In the context of the current global pandemic of new coronavirus pneumonia, we have not yet found a special drug against new coronavirus.
We are facing many problems in fighting the epidemic. In addition to the aforementioned uncertainties, we also need to find the risk factors for the deterioration of the new coronavirus pneumonia and predictive biomarkers.
In this way, once the infected person is diagnosed, we can infer the degree of deterioration of the disease to a certain extent through the detection of markers, which helps early intervention and early treatment.
To solve these problems, independent innovation and international scientific and technological cooperation are particularly important.
Use the network to carry out multi-center cooperation in the world and carry out joint research around key and difficult scientific issues. This not only requires us to unite when fighting the epidemic. After the epidemic, we should continue this cooperation and work together to solve more biomedical fields.
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