key: cord-0991428-2u4d235j authors: Ho, Leonard T.F.; Chan, Karina K.H.; Chung, Vincent C.H.; Leung, Ting Hung title: Highlights of traditional Chinese medicine frontline expert advice in the China national guideline for COVID-19 date: 2020-04-03 journal: Eur J Integr Med DOI: 10.1016/j.eujim.2020.101116 sha: 9fc9f7167f8950a389c6b8eeab1117cbb6ff87d8 doc_id: 991428 cord_uid: 2u4d235j INTRODUCTION: The World Health Organization has declared the coronavirus disease (COVID-19) as a pandemic on 11 March 2020, after the number of confirmed cases outside China increased 13-fold. As the epicentre of the initial outbreak, China has been updating the National COVID-19 Diagnostic and Treatment Guideline with up-to-date information about the disease. To facilitate the implementation of integrative Chinese–Western Medicine in COVID-19 management, Traditional Chinese medicine (TCM) has been recommended in recent editions of the national guideline. METHODS: The national guideline summarised the opinions and frontline experience of medical experts across the country to provide by far the best management for COVID-19. We extracted the case definition and clinical classifications of COVID-19 in China along with relevant TCM treatments cited in the seventh edition of the guideline, with an intend to disseminate practical information to TCM practitioners and researchers around the world. RESULTS: We presented the most recent case definition, clinical classifications, and relevant TCM treatments of COVID-19 in accordance to recommendations of the Chinese guideline. TCM treatments are stratified into two groups based on patients’ disease status. Four types of Chinese patent medicines are recommended for suspected COVID-19 cases. Several herbal formulae are recommended for confirmed COVID-19 cases according to their clinical classification and TCM pattern diagnoses. Two herbal formulae are also recommended for rehabilitation of recovering cases. CONCLUSION: To control the waves of COVID-19 outbreak, countries must ensure the adherence of their citizens to local public health measures. Medical professionals should diagnose and treat patients according to up-to-date guidelines. Future evaluation of the outcomes of implementing TCM recommendations will strengthen the evidence base for COVID-19 management for the sake of public health and the internationalisation of TCM. The coronavirus disease (COVID-19) unfolded in Wuhan, China, in December 2019 (1) . Without effective control measures, the disease has spread across the globe with more than one hundred countries reported confirmed cases (2) . Having realised that the number of new confirmed cases outside China has increased 13-folds, the World Health Organization finally decided to characterise COVID-19 as a pandemic on 11 March 2020 and requested member states to scale up their emergency response mechanisms (2) . Being the epicentre of the initial outbreak, China developed and has been constantly updating its National COVID-19 Diagnostic and Treatment Guideline with up-to-date information about the aetiology, epidemiology, pathology, clinical features, diagnosis, and treatments of the disease. With strong support from the Chinese government (3) , Traditional Chinese Medicine (TCM), as a core component of the national healthcare system, has also been recommended in recent editions of the national guideline for the treatment of COVID-19. A month after the implementation of the guideline, Chinese officials reported that the preliminary outcome of the integrative Chinese-Western Medicine treatment approach appeared to be promising (4) . To disseminate practical information to TCM practitioners and researchers around the world, we extracted and present the case definition and clinical classifications of COVID-19 in China along with relevant TCM treatments citied in the seventh edition of the National COVID-19 Diagnostic and Treatment Guideline released on 3 March 2020 (5) . J o u r n a l P r e -p r o o f TCM treatments recommended in the Chinese national guideline are stratified into two groups based on patients' disease status (suspected COVID-19 case or confirmed COVID-19 case). Four types of Chinese patent medicines are recommended for suspected COVID-19 cases according to their clinical features, while different herbal formulae are recommended for confirmed COVID-19 cases according to their clinical classification (mild, moderate, severe, or critical) and TCM pattern diagnosis. Two herbal formulae are also recommended for rehabilitation of recovering cases. In the Chinese guideline, healthcare professionals are encouraged to offer integrative Chinese-Western Medicine treatments for COVID-19 patients, regardless of their disease status and clinical classification, as soon as possible to achieve the best clinical outcome (5) . Those who would like to implement an integrative treatment approach may consult the conventional medicine section of the Chinese national guideline, which describe how the two types of the interventions maybe used in a coordinated manner (6). We extracted the case definition and clinical classifications of COVID-19 in China along with relevant TCM treatments cited in the seventh edition of the guideline. The current translation is for educational and non-profit purposes. We have satisfied the conditions of fair use of opensource materials (7) . Since the guideline is an administrative document issued by The National Health Commission of the People's Republic of China, it is not necessary to obtain approval from Chinese officials according to the country's Copyright Law (8) . Suspected COVID-19 case To be classified as a suspected case in China, the patient should fulfil one of the following epidemiological risks criteria and two of the following clinical features:  Epidemiological risks criteria -(1) travelled to or lived in Wuhan or other Chinese cities with confirmed cases in the last 14 days before symptom onset; (2) contacted with a confirmed case (tested positive for viral nucleic acid) in the last 14 days before symptom onset; (3) contacted with a person with fever or respiratory symptoms who travelled to or lived in Wuhan or other Chinese cities with confirmed cases in the last 14 days before symptom onset; or (4) cluster onset.  Clinical features -(1) fever and/or respiratory symptoms; (2) radiological characteristics of COVID-19; or (3) normal or reduced total white blood cell count, or normal or reduced lymphocyte count in early-onset. To be classified as a confirmed case in China, the suspected case should fulfil one of the following pathological or serological criteria: (1) Test positive for SARS-CoV-2 nucleic acid in real-time rRT-PCR; (2) Viral genome sequencing reveals a high similarity to SARS-CoV-2; or (3) Test positive for serum SARS-CoV-2-specific IgM and IgG, serum SARS-CoV-2-specific IgG seroconversion, or a fourfold or greater rise in SARS-CoV-2-specific IgG titre between acute-and convalescent-phase sera. Mild case  Mild clinical features without radiological characteristics of pneumonia. Moderate case  Fever and respiratory symptoms with radiological characteristics of pneumonia. Severe case  Fulfils one of the following: (1) tachypnoea with respiratory rate ≥ 30 breaths per minute; (2) resting peripheral capillary oxygen saturation ≤ 93%; or (3) arterial oxygen partial pressure (PaO2) / fractional inspired oxygen (FiO2) ≤ 300mmHg. Critical case  Fulfil one of the following: (1) respiratory failure and requires invasive mechanical ventilation; (2) shock; or (3) multiple organ failure and requires admission into intensive care unit. (9) . + No endangered animal species is included. # These are animal products and may not be available outside China. The integrative Chinese-Western Medicine treatment approach has been widely implemented in China. For instance, up to 67% of confirmed cases in Zhejiang province received TCM interventions, in conjunction to conventional treatment (10) . The Chinese official reported that this has yielded promising outcomes, with 23 confirmed cases in Wuhan discharged from hospital after receiving integrative medicine treatment (11) . Considering the urgency of treating an increasing number of patients in some countries and jurisdictions, TCM clinicians suggested that the practical application of Chinese herbal medicine should be given priority (12) . It seems to be impossible to conduct a rigorous evaluation of its efficacy and effectiveness in the midst of an epidemic. Individuals sceptical of TCM posed a serious doubt to this suggestion, criticising that the Chinese government is battling against the COVID-19 with "politicalised pseudoscience" (13) . However, the Ebola experience demonstrated the feasibility of rigorously evaluating therapeutic measures during an epidemic (14) , and the evaluation of Chinese herbal medicine for COVID-19 is by no means an exception. Indeed, in the case of COVID-19 where experimental infection could not be used to facilitate the conduct of randomised trials, the current outbreak provides the only opportunity for evaluating the efficacy of Chinese herbal medicine. It is now the prime time to start randomised trials as the peak of the epidemic has pasted in China (15) , and the healthcare system has more capacity to plan for evaluation. In fact, on 3 February 2020, the Ministry of Science and Technology has launched a clinical research programme on integrative medicine treatment for COVID-19, in which COVID-19 treatment centres in Hubei, Beijing, Tianjin, Hebei and Guangdong will participate (16) . The launching of this programme represents an important step towards researching integrative treatment. However, divergent views on what constitute the most promising investigational TCM intervention seem to challenge the coordinated effort. Despite the prompt development of a national guideline, only four provinces, namely Shanxi, Anhui, Fujian and Qinghai, have adopted it, and Beijing, Tianjin and Xinjiang implemented its revised version (17) . Shanghai, Henan and Chongqing decided to develop their own Chinese herbal medicine treatment scheme J o u r n a l P r e -p r o o f (17) . The National Administration of Traditional Chinese Medicine initiated another clinical research programme in Shanxi, Shaanxi, Hebei and Heilongjiang, investigating a single Chinese herbal formula intended for different stages of the disease (18) . To seize the opportunity of conducting quality research, establishing a national coalition of stakeholders across these initiatives is urgently needed. A multi-disciplinary team would be the key to success; it should consist of members who have expertise in COVID-19, TCM, clinical research methodology, as well as ethics and regulations, and those who are patient representatives. Additional research investment in terms of resources and personnel will enable the immediate systematic collection of data on outcomes which could later be shared across centres in a coordinated manner. Such data are expected to provide an insight as to how TCM interventions impact prognosis. Besides, they will help identify which promising Chinese herbal medications should be prioritised for further assessment in randomised trials. Since Chinese herbal medicine has already been widely prescribed across the nation, an efficacydriven approach could be adopted, focusing on phase II or III randomised trials. In the midst of the epidemic, a trial design should be practical yet reliable, aiming to quickly generate interpretable efficacy and short-term safety results. A rigorous randomised trial conducted in a transparent manner would help in clearly determining the worthiness of the current national policy on the use of Chinese herbal medicine. The World Health Organization has characterised COVID-19 as a pandemic. Whenever possible, healthcare professionals may diagnose and treat patients with reference to the most recent guidelines on COVID-19. More importantly, the global community must endeavour to ensure the adherence of public health measures, such as the recommendations from Public Health England who have strongly encouraged their citizens to stay at home unless they have legitimate reasons, to stay two metres away from each other, and to wash hands frequently for 20 seconds using soap and water (19) . We hope that future evaluation of the outcomes of implementing TCM recommendations will strengthen the evidence base for COVID-19 management not only for the sake of public health but also for the promotion of TCM status in the world. A conflicting interest exists when professional judgement concerning a primary interest (such as patient's welfare or the validity of research) may be influenced by a secondary interest (such as financial gain or personal rivalry). It may arise for the authors when they have financial interest that may influence their interpretation of their results or those of others. Examples of potential conflicts of interest include employment, consultancies, stock ownership, honoraria, paid expert testimony, patent applications/registrations, and grants or other funding. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. World Health Organization. Coronavirus disease (COVID-19) outbreak Geneva: World Health Organization Geneva: World Health Organization; 2020. 3. National Administration of Traditional Chinese Medicine. The Party Group of the National Administration of Traditional Chinese Medicine conveyed the spirit of the key instructions of general secretary Xi Jinping and the request of Premier Li Keqiang to study the prevention and control of novel coronavirus pneumonia (Chinese). China: National Administration of Traditional Chinese Medicine National Administration of Traditional Chinese Medicine. 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London: The Government of the United Kingdom Dr Vincent CH Chung is a Visiting Associate Professor of the Bachelor of Science in Biomedical Sciences & Bachelor of Medicine (Chinese Medicine) Programme, School of Biological Science, Nanyang Technological University, Singapore at the time of writing this manuscript.