Cao Xuetao On the evening of April 9, Cao Xuetao, an academician of the Chinese Academy of Engineering and president of Nankai University, published a review article titled "The Immunopathology of New Coronavirus Pneumonia and its Implications for Treatment" online in "Natural Immunologic Review".
It is reported that "Nature-Immunology Review" belongs to the Nature Publishing Group and will target famous scientists with academic influence.
Previously, Cao Xuetao had been invited to publish two review commentary articles in the magazine in 2015 and 2019 respectively. Among them, the review published in 2015 is the first review review article published by Chinese scholars in this journal.
What is the meaning of this comment? What are the aspects of immunology to study the mechanism and treatment of new coronary pneumonia? What suggestions do you have for the global fight against the new coronavirus epidemic? " China Science Daily " interviewed Cao Xuetao and asked him to answer related questions.
"China Science Daily": When did "Natural Immunology Review" propose this application to you? What are the background and requirements for the commissioning?
Cao Xuetao: The magazine asked me for an article on March 16th, when the COVID-19 epidemic in the UK began to attract attention from all parties. In the process of discussing how to respond, everyone is increasingly aware of the importance of learning from China's epidemic prevention and control measures and experience.
In particular, they have seen reports on the clinical treatment of severe COVID-19 patients one after another. The academic community is very interested in how these severe patients are cured and what methods are used.
Therefore, they hope that I will introduce to international colleagues the immunopathological characteristics of COVID-19 and its implications for clinical treatment and related drug development from an immunologic perspective.
"China Science Daily": Unlike the previous review article, why is this review only 2 pages? What point do you want to state through this review?
Cao Xuetao: This is a brief review, not a review. This magazine rarely publishes commentary styles. The magazine hopes to introduce relevant situations on a certain topic of COVID-19 as soon as possible for reference by colleagues in the biomedical community.
In fact, many magazines currently have special columns for COVID-19, and even green channels for submission.
The new coronavirus is a common challenge facing all mankind. Therefore, the magazine has put forward requirements, hoping to be concise and clear, and write it as soon as possible. The specific requirements are less than 1500 words and 10 references. While I was writing the article, new articles related to COVID-19 were published one after another. I wrote more than 3,000 words one after another, but in the end I could only delete them.
So in my final acknowledgment, I apologize for the research results that cannot be cited due to word count limitations.
focuses on a topic in this review, namely what role immunity plays in the onset and treatment of COVID-19. Focusing on immune pathology, we discuss how immune regulation affects the outcome and treatment of COVID-19, so as to further explore new targets and new ways of intervention in COVID-19 treatment.
"China Science Daily": In the commentary, you quoted the views you personally exchanged with Academician Zhong Nanshan on the efficacy of traditional Chinese medicine in the treatment of new coronary pneumonia and marked them. Is there any special reason for this?
Cao Xuetao: Although this part of the content is just one sentence in the article, it actually expresses an attitude in refined language.
Traditional medicine has indeed played a role in fighting the new coronary pneumonia epidemic. I often communicate with Academician Zhang Boli and . He has been using traditional Chinese medicine achievements on the front line of clinical practice to treat patients with new coronary pneumonia at all stages, and has achieved remarkable clinical results.
I communicated with Academician Zhong Nanshan and learned from him that his team has also seen clinical efficacy through double-blind controlled trials (an article will be published) based on the in vitro experiments that Chinese medicine can inhibit the replication of the new coronavirus and the production of inflammatory factors it induced (an article will be published soon).
Therefore, the magazine agreed to indicate in the article that traditional Chinese medicine has clinical efficacy in the treatment of new coronary pneumonia, but there was no formally published clinical efficacy paper for citation at that time. After communicating with the editorial department of the magazine, it was decided to adopt the "personal communication" method with Academician Zhong Nanshan.
is quoted and marked in the form of the full name of Academician Zhong Nanshan. I think this reflects Academician Zhong Nanshan's huge international influence as a Chinese clinical expert, and also reflects that traditional Chinese medicine has received more and more attention in the international academic community.
"China Science Daily": Since the outbreak of the new crown pneumonia epidemic, what related research have you participated in?
Cao Xuetao: I have been paying attention to the progress of research related to COVID-19, including virology, immunology, pathology, and drug development including antibodies and vaccines, because infection and immunity is also my research field.
In the early stage of the epidemic, due to the limitations of conditions, my laboratory did not conduct related research on the new coronavirus, but I have been communicating with many laboratories and personnel who carried out related research and providing consulting guidance to give them some ideas and suggestions.
At present, my team members are working with the hospital to study immune inflammatory factors and the pathological mechanism of COVID-19, and are also maintaining academic exchanges with international peers.
In addition, I submitted two policy suggestions on the prevention and control of the new coronavirus pneumonia epidemic to in mid-to-late February. One is the suggestion on establishing a national scientific and technological organization for epidemic prevention and control warning and prediction.
During this COVID-19 epidemic, the society has paid extensive attention to the "epidemic development trend" and how to answer "what prevention and control strategies and intervention measures are effective and feasible and efficient", "foresightly predict the needs of disease control resource guarantee and dynamically optimize the deployment", etc.
Practice has proved that the timely collection of epidemic parameters, the analysis of corresponding epidemiological mathematical model and the rational application of medical big data technology systems can provide forward-looking warnings and predictions for the answers to these questions and the prevention and control of the epidemic.
We should have such a specialized scientific and technological organization. Considering the global pandemic trend of the new crown pneumonia epidemic, it is also necessary to establish an international joint research center. This not only demonstrates China's strength, but also helps win-win cooperation and benefit all mankind.
The second is thinking and suggestions on issues related to overseas epidemic response, scientific and technological research, and health emergency management systems in the prevention and control of the new coronavirus pneumonia at this stage. It is also recommended that the national level adhere to relevant research on the new coronavirus for a long time.
I suggest setting up a special laboratory or entrust an existing national key laboratory to study a series of problems such as etiology, immunology, vaccine development, and antibody development of coronaviruses in a long and stable manner.
This is not only what China needs, but the world needs it. China's scientific research must talk about innovation and practice from an international context.
"China Science Daily": Is the immune response in patients with new coronary pneumonia protective or pathogenic? There are studies that suggest the antibody-dependent enhancement effect (ADE) of the new coronavirus. What problems do you think this will bring to vaccine development and antibody treatment?
Cao Xuetao: After being infected with the new coronavirus, the body's early natural immune response plays a role in clearing the virus, which means that the early immune response is definitely protective, so patients with mild symptoms recover quickly.
However, when the immune system is overactivated, especially if the virus is not controlled (breaking through the immune defense line), it will cause the immune system to be damaged, which will trigger an excessive inflammatory response.
Excessive inflammatory response and immune disorders can damage the lungs and other self-organizations, leading to immune pathology. Compared with other viruses that can produce a large number of antibodies after being infected for 7 to 10 days, it takes longer to produce antibodies to the new coronavirus. It remains to be further studied how long the new coronavirus antibodies exist in the body and whether they can play a protective role.
Currently, some studies suggest that the level of antibody production in middle-aged and elderly people infected with the new coronavirus is relatively high, but more people often develop severe diseases in middle-aged and elderly people.
In addition, two clinical analyses say that the higher the level of new coronavirus antibody, the higher the degree of disease progression and the greater the proportion, which suggests that there may be ADE effect of the new coronavirus.
Therefore, the protective and pathogenicity of new coronavirus antibodies are worthy of in-depth research, which is a very important issue that needs to be paid attention to when developing vaccines and antibody-based treatments. For example, dengue virus and respiratory syncytial virus have ADE effects, and there are always difficulties in their vaccine development.
In fact, virus vaccine development and antibody treatment have always faced the challenges of viral mutation, weak virus immunogenicity, and poor antibody efficacy, and the non-killing of the virus after the antibody binds to strengthen the ADE effect of viral infection.
Considering this aspect, more independent large-sample clinical studies are needed to confirm or rule out the possibility of ADE in the new coronavirus.
"China Science Daily": What are the current treatments for the cytokine storm problem in patients with severe COVID-19?
Cao Xuetao: cytokine storm is an important pathogenic factor for severe COVID-19. Elevated IL-6 levels are an indicator of poor prognosis in patients with severe COVID-19 and ARDS. Clinical trials organized by the University of Science and Technology of China show that targeted monoclonal antibody therapy for IL-6 receptors is effective, and many European countries are imitating and applying it.
This suggests that neutralizing monoclonal antibodies may also be useful against other proinflammatory cytokines, with potential targets including IL-1, IL-17 and their respective receptors.
In addition, small molecule inhibitors of signaling elements downstream of cytokine may hopefully prevent cytokine storm-related immune responses. The treatment of cytokine storms can be used to refer to CART cell therapy.
We also observed complement system activation in patients with severe COVID-19, suggesting that if complement inhibitors are used, it may attenuate inflammatory damage. It is hoped that these methods will be approved for clinical trials to benefit patients.
"China Science Daily": In your commentary, you mentioned that the new coronavirus involves neuroendocrine-immune interactions. What is this concept?
Cao Xuetao: As we all know, cytokines released by natural immune responses after viral infection can induce the neuroendocrine system to release glucocorticoids and other neural peptides, thereby regulating the immune response, which involves stress disorders in the interaction between the neuroendocrine system and the immune system.
The new coronavirus has been isolated from the human body's respiratory tract, feces, tears and other samples, which means that the virus has infected multiple tissues and organs.
Recently, the United States reported that a person infected with the new coronavirus was damaged. So whether the new coronavirus can infect the central nervous system, whether it can promote the release of pathological neuroendocrine mediators induced by inflammation, affect respiratory function and the pathogenesis of ARDS, and whether it promotes patients' recovery or leads to worsening of the disease, is worth studying.
"China Science Daily": The global fight against the new coronavirus epidemic will be a protracted war. What suggestions do you have for this?
Cao Xuetao: Against the background of the current global pandemic of COVID-19, we have not found a special medicine to fight the COVID-19 virus.
The most prominent reason why our country has controlled the epidemic is our social organizational strength. At the order of the Party Central Committee and the State Council, various social organizations actively responded to the call and participated pragmatically nationwide. At the same time, scientific and technological research and development have been timely kept up and controlled the spread of the epidemic. This institutional advantage is incomparable to foreign countries.
We face many difficulties in fighting the epidemic. In addition to the uncertainties mentioned above, we also need to look for risk factors and predictive biomarkers for the worsening of the new coronavirus pneumonia.
In this way, once the infected person is diagnosed, we can infer to the degree of the worsening of the disease to a certain extent through the detection of markers, which will help early intervention and early treatment.
To solve these problems, independent innovation and international scientific and technological cooperation are particularly important.
uses the Internet to carry out multi-center cooperation in the world and conduct joint research on key and difficult scientific issues. This not only requires us to unite in the fight against the epidemic, but after the epidemic is over, we should also continue this cooperation and solve more scientific problems in the field of biomedical.
(Original title: What role does immunity play in the onset and treatment of new coronary pneumonia - an exclusive interview with Cao Xuetao, an academician of the Chinese Academy of Engineering and president of Nankai University)
Source: China Science Daily
