On April 14, the Joint Prevention and Control Mechanism of the State Council held a press conference to update the progress of the research and development on COVID-19 drugs and vaccines. Wu Yuanbin, Director General of Science and Technology for Social Development Department, Ministry of Science and Technology, Li Yu, Director General of Science and Technology Department, National Administration of Traditional Chinese Medicine, Yang Sheng, Deputy Director General of Drug Registration Department, National Medical Products Administration, Sun Yanrong, Deputy Director General of China National Center for Biotechnology Development, Ministry of Science and Technology, Wang Zhijun, an academician with Chinese Academy of Engineering attended and answered the questions. The experts present also answered the questions about the TCM drugs projects, their approval in emergency response and their advantage to the rehabilitation of the convalescent.
Lung Cleansing and Detoxification Decoction Preventing or Mitigating the Cytokine Storm
People’s Daily: In the fight against COVID-19, we all see that TCM has played an important role and became a highlight in the prevention and control. Therefore, a TCM program was set up in the research team, and could explain how the TCM program has been conducted? And what about the progress now?
Li Yu: Thanks for your concern about TCM. TCM has played a very important role in the fight against COVID-19 and received a lot of attention. The Joint Prevention and Control Mechanism of the State Council set up a TCM program under the research team to coordinate the key TCM projects on the epidemic containment and the establishment of a middle- and long-term infectious disease containment mechanism by integrating TCM and western medicine. The program, led by Li Xiaohong, President of Chinese Academy of Engineering, and with the all-out collaboration from National Administration of Traditional Chinese Medicine, was composed of Ministry of Science and Technology, Ministry of Education, National Development and Reform Commission, National Health Commission, Ministry of Industry and Information Technology, Chinese Academy of Sciences and National Medical Products Administration, to facilitate the job. An expert group was set up in the frame of the TCM program, including two academicians, national TCM masters, TCM experts in clinical treatment and pharmaceutics. Within the program, there are four tasks, i.e. clinical treatment, mechanism study, formula and drug screening, system establishing. On the basis of the previous clinical observations, the subgroup of the clinical treatment selected “the three TCM drugs and three formulas”, which have proved effective and played a significant role in the clinical treatment, including Lung Cleansing and Detoxification Decoction. The subgroup of mechanism study have conducted a few theoretical studies and found that Lung Cleansing and Detoxification Decoction could be helpful to holistic adjustment through multiple compounds and targets. Intervening in the biological process of immunity, anti-inflammation, endocrine response and signal transduction, Lung Cleansing and Detoxification Decoction could inhibit the generation of bacterial endotoxin and help to balance the immunity and resolve inflammation, in this way, to avoid or mitigate the cytokine storm. In the TCM program, a research project has focused on TCM intervention in the convalescent rehabilitation, which was led by Tong Xiaolin, an academician with Chinese Academy of Sciences. The preliminary research results are included in the Advice on TCM Rehabilitation of the COVID-19 Convalescent issued jointly by National Health Commission and National Administration of Traditional Chinese Medicine and the revising is under way. The TCM program also deals with TCM intervention in the cluster and asymptomatic infections since the reopening of business and schools, which are in the charge of the teams of the two academicians, Wang Qi and Huang Luqi.
Review on the Applications of the three formulas Products for Clinical Trials
China Media Group: In the fight against the epidemic, TCM has played a great role. We would like to know what have been done for review and approval of TCM drugs registration in the emergency response.
Yang Sheng: Thank you for the question. With the important role of TCM in the epidemic containment, National Medical Products Administration has actively given a full play of TCM characteristics by supporting the use of TCM drugs and hospital-made products under the guidance of TCM theories for COVID-19 treatment. In regard to the review in the emergency response, first, NMPA activated the review mechanism immediately to guarantee the science-based, standard and efficient work with both legal principles and special measures. Second, NMPA connected directly with the key projects. We accepted as many application materials and consultations as we can, made fast decisions and feedbacks, and joined in the efforts to promote the projects. With early and in-depth participation, we strengthened the communication with the research institutions to for technical support and early preparation for registration. Third, NMPA raced against time to carry out emergency review. If the research results proved generally safe and effective, we put them in fast tract for emergency review. With the principle of taking safety as the bottom line, evidence-based efficacy, ensured quality and extraordinary review and approval, we do the joint review and evaluation to improve both speed and efficiency. Taking “the three TCM drugs and three formulas” as an example, we set up a special expert group, including academicians and front-line experts in the field of TCM, to give guidance. We appointed focal points to connect with the relevant manufactures and research institutions for technical support and registration service. With their good effect in the previous clinical practice, NMPA has already approved including COVID-19 in the indications of “the three drugs”, and is promoting to put relevant products of “the three formulas” into clinical trials.
In addition, NMPA also actively guided the policy making on hospital-made products in emergency response in local areas, carried out recording work on products made in TCM and ethno-medicine institutions in compliance with the relevant regulations to give a full play of TCM in the epidemic containment.
Next, with the principle of unified direction, early intervention, immediate review and science-based investigation, NMPA will make our best to do the emergency review jobs to guarantee the drug supplies in the epidemic containment.
Sharing TCM Products and Research Results Internationally
China Media Group: Now that COVID 19 has become a pandemic and a few drugs have proved significantly effective in the previous clinical treatments in China, did we share the drugs globally? What did China do to contribute to the pandemic containment? What experience we got can be learnt by other countries?
Sun Yanrong: Thank you for the question. Indeed, we all notice that the pandemic is spreading in the globe and the drugs which have studied in the previous clinical trials and been used got a great attention from the world. The experience of China has been learnt in the following aspects:
First, the Chinese researchers have conducted domestic clinical studies on drugs for COVID-19, and published their essays quickly in the international journals to share China’s clinical experience and results with the whole world within the shortest time.
Second, the Chinese researchers have had frequent exchanges and academic discussions with their international partners, roughly, of over 140 countries and regions. The topics are about a series of products and research results, such as TCM, chloroquine phosphate, Favipiravir, Tocilizumab, the convalescent plasma and cell stem therapy. The focus is given to the COVID-19 research progress and clinical practice experience. Through this way, we are sharing the China’s experience and solution for the global containment of the pandemic.
Third, some research results in China have been adopted in the clinical protocols of some countries. Meanwhile, WHO and some countries are also conducting clinical researches on chloroquine and hydroxychloroquine. Some therapies and drugs used in Chinese Protocols, such as the convalescent plasma and Tocilizumab, have been adopted in the treatment or clinical researches by some countries.
As we all know, the research and development of COVID-19 therapeutics is a research model formed in a short time, which crystalizes the wisdom of the whole world and the whole mankind. Chloroquine phosphate was invented by German scientists 80 years ago and Favipiravir was invented by Japanese scientists 20 years ago. Now we are promoting the research on kelimycin, which was invented by exclusively Chinese scientists 30 years ago. So we can see that, only by using the collective wisdom of the whole world and the whole mankind, can we contain the pandemic in such gravity.
At present, the key project group is actively expanding the international technological cooperation channels to promote, launch or participate in the international multi-centered clinical research. We hope to fight the pandemic by accumulating the global wisdom and improving China’s solution. In the future, we will continue our concerns on the update of the pandemic and the research progress in China and abroad and focus our attention on the key research projects to provide strong technological support and Chinese solution.
Including COVID-19 in Indications of the “Three TCM Drugs”
Southern Metropolitan Daily: Good drugs emerge with big epidemics. A few effective TCM drugs and classic formulas emerged in the fight against COVID-19, such as the so-called “three TCM drugs and three formulas”. What is the latest progress in this aspect?
Li Yu: Thank you for the question. Good drugs and good doctors emerge with big epidemics, which has been summarized in the fight of thousands of years against the diseases. In the fight against COVID-19, “the three TCM drugs and three formulas” have been screened in the clinical treatment and played a significant role. The three TCM drugs are Jinhua Qinggan Granule, Lianhua Qingwen Granule/Capsule and Xuebijing Injection. They have been approved by the authorities and used in the clinical treatment before the epidemic and repurposed in the COVID-19 treatment with good clinical effect. Jinhua Qinggan Granule, an effective TCM drug, was developed in the fight against influenza H1N1. Jinhua Qinggan Granule, with confirmatory effect for mild and moderate cases of COVID-19, cannot only shorten the fever time, help to bring lymphocyte and leukocyte levels back to normal, but also improve immunity markers. Recently, Jinhua Qinggan Granule has been categorized in the OTC A drugs to better meet the demand in the clinical treatment.
Lianhua Qingwen Capsule, also with good effect in mild and moderate cases, has significant effect in mitigate the symptoms of fever, cough and fatigue. It also works to prevent the mild and moderate disease from progressing to severe disease. Xuebijing Injection could resolve the cytokine and is suitable for the early and middle phase treatment of severe and critical cases. It can also increase the rate of recovery, discharge and decrease the rate of progression from severe disease to critical disease. Considering that “the three TCM drugs and three formulas”, especially the drugs, have played a significant role in the fight against COVID-19 with good clinical evidence, National Medical Products Administration has approved the adoption of COVID-19 to the indications of Jinhua Qinggan Granule, Lianhua Qingwen Granule/Capsule and Xuebijing Injection.
“The three formulas” refer to Lung Cleansing and Detoxification Decoction, Dampness Resolving and Detoxification Decoction, Lung Diffusing and Detoxification Decoction. Lung Cleansing and Detoxification Decoction originated from the integration of the five classic formulas in Treatise on Febrile and Miscellaneous Diseases. On Feb. 6, on the basis of good effect in the previous clinical treatment, Lung Cleansing and Detoxification Decoction was jointly recommended by National Health Commission and National Administration of Traditional Chinese Medicine for all types of COVID-19 cases. Through long time clinical observations, Lung Cleansing and Detoxification Decoction shows its role in preventing mild and moderate disease from progressing to severe and critical disease. In addition, it also helps in the life saving process of severe and critical cases. Lung Cleansing and Detoxification Decoction is recommended also in National Diagnosis and Treatment Protocol for COVID-19 as a general formula. Dampness Resolving and Detoxification Decoction and Lung Diffusing and Detoxification Decoction, summarized by the teams of Huang Luqi and Zhang Boli in the clinical treatment in Wuhan, could prevent the disease from developing, improve the symptoms, and especially, shorten the disease duration. Days ago, Lung Cleansing and Detoxification Granule and Dampness Resolving and Detoxification Granule have been approved by National Medical Products Administration for clinical trials.
Good Use of “the Three TCM Drugs and the Three Formulas”
Science and Technology Daily: At present, China’s epidemic prevention and control has been further strengthened, and the pressure to prevent the epidemic from coming abroad has been increasing. What new progress has been made in scientific research? Faced with the new situation of epidemic prevention and control, what are the key considerations for the next step?
Wu Yuanbin: As you just said, the phased achievements of epidemic prevention and control in China have been further strengthened. In scientific research work, the focus has been continuously adjusted according to the needs. Some colleagues just mentioned in the introduction that the early stage focused on drug screening, medical treatment, detection technique, vaccine development, including virus source tracing, animal model construction, to promote science and technology in supporting epidemic prevention and control. In general, the effectiveness and progress of these aspects have played a very active role in ensuring the prevention and control of the epidemic. For example, in terms of drugs and treatment protocols, more than 10 drugs and treatment protocols have been selected and included in the official diagnosis and treatment protocol, including "the three drugs and three formulas" of TCM introduced by Li Yu just now, which are also well used in practice. The construction of animal models provides the basis for the evaluation of vaccine and drug. In terms of testing, there are currently 26 testing reagent products on the market, which provide scientific and technological support for the overall epidemic prevention and control.
As mentioned earlier, after entering a new stage, we are now dealing with preventing the virus from spreading in the country from both inside and outside, which should be further strengthened, especially in preventing the imported cases. The coordination between scientific and technological research team and entry ports should be further strengthened, focusing on the promotion of the development of on-site rapid detection technology, and the use of the existing detection technologies and products, moving the detection threshold forward, timely detecting infected cases coming from abroad, so to provide scientific and technological support for the targeted prevention and control of the epidemic. At the same time, in terms of avoiding a new wave of epidemic, the focus is to promote the development of high-sensitivity detection reagents to further improve the detection rate of people with low viral load infection. At the same time, we will accelerate the development of high-throughput detection reagents to improve the detection speed and capabilities. Those are the work to be further strengthened.
In general, scientific and technological research will also focus on technological support required during the outbreak, timely adjust our focus, and strengthen the combination of science and technology, especially of the talents and backbones in this field, to bring into full play the multi-departmental collaborative working mechanism.
Initially Forming a Comprehensive Intervention of Integrated TCM and Western Medicine
China Education Television: As most patients have been cured and discharged, the rehabilitation of patients in convalescent period has attracted people's attention. What are the advantages of TCM in the rehabilitation of patients in this period? What are the specific jobs that will be done?
Li Yu: Thank you for the question. Today, you can see from the figures released by National Health Commission that nearly 78,000 patients have been cured and discharged. Among them, a considerable part of them have not been fully recovered although the nucleic acid test has turned negative. Continuous medical intervention and psychological rehabilitation treatment are still needed. In this regard, there is rich experience and intervention techniques in TCM. A TCM team led by Tong Xiaolin, an academician with Chinese Academy of Sciences, is carrying out related research, and some research results have been promoted and used in clinical practice. In addition, TCM authorities in various regions are also organizing teams of TCM experts to guide the rehabilitation treatment by using TCM and integrated TCM and western medicine on convalescent patients, and have achieved good results. On February 22, National Health Commission and National Administration of Traditional Chinese Medicine jointly issued the Advice on TCM Rehabilitation of the COVID-19 Convalescent, in which TCM measures and methods are proposed, including five categories of TCM prescriptions, suitable techniques, dietary guidance, emotional release therapy and other methods. Expert groups mobilized by National Administration of Traditional Chinese Medicine also helped to set up rehabilitation clinics and stations in Wuhan, to conduct intervention by combining with the multiple disciplines of TCM and western medicine, and using comprehensive technical means, especially TCM prescriptions, acupuncture, moxibustion, acupoint massage, ear acupressure, foot bath, diet, fitness exercises and emotion adjustment, which have also achieved good results. Clinical studies have shown that, there is a significant difference in the clinical efficacy of comprehensive intervention, compared with that without comprehensive intervention using TCM. At the same time, we are actively exploring to set up a national rehabilitation collaboration network, using the method of integrated TCM and western medicine, bringing into full play to the unique advantages of TCM, to carry out TCM rehabilitation interventions of convalescent patients in various regions. This was not only well participated by medical institutions in many places in Hubei Province, but also highly welcomed by many medical institutions across the country. With the guidance of National Health Commission and National Administration of Traditional Chinese Medicine, a comprehensive intervention of integrated TCM and western medicine has been initially formed.