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Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series

BMJ 2020; 368 doi: https://doi.org/10.1136/bmj.m606 (Published 19 February 2020) Cite this as: BMJ 2020;368:m606

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Covid-19: a puzzle with many missing pieces

Rapid Response:

Traditional Chinese medicine for COVID-19

Dear Editor,

Xu and colleagues reported clinical features of patients infected with coronavirus disease 2019 (COVID-19) in Zhejiang province, with treatments including antivirals, antibiotics, or steroids.[1] However, it’s noteworthy that traditional Chinese medicine (TCM) has also been applied widely, and has played substantial roles in management of COVID-19 in China.

Since the ongoing pandemic of COVID-19 that first outbroke in Wuhan, more than 3,100 TCM practitioners across China have been sent to Wuhan, and contributed their joint efforts with doctors of modern Western medicine to control the disease. According to the press conference of the State Council,[2] up to 60107 confirmed cases of COVID-19 in the country have received TCM treatment by February 17, 2020.

The latest version of the Diagnosis and Treatment Protocol of COVID-19 by the National Health Commission has advised to apply TCM in the treatment of COVID-19 patients.[3] TCM prescriptions and patent drugs were recommended based on patients’ symptoms and signs, vary with severity from mild ones to critical conditions. According to the press conference,[2] the therapeutic strategies of combining the merits of both TCM and modern Western medicine for the treatment of COVID-19 patients can effectively relieve symptoms such as fever, cough, sore throat, myalgia and fatigue, shorten the course of disease, reduce the probability of mild infections turning into severe or critical conditions.

The application of TCM in management of infectious diseases dates back thousands of years. Pestilent diseases have been described in details in TCM literatures. The Yellow Emperor’s Internal Classic (about 425-221 BC) described the ancient medical scholars’ understanding of pestilences: During the epidemic, people are generally susceptible, regardless of adults and children, and the symptoms are similar. During the Han dynasty (202 BC-220 AD), Treatise on Febrile Diseases written by an eminent physician Zhongjing Zhang (150-219 AD) is the earliest monograph on the treatment of acute infectious diseases with TCM. Zhang prescribed many formulas for the febrile diseases, such as Mahuang decoction for chill, myalgia, and cough, and Maxingshigan decoction for high fever and dyspnea, which are still popular in clinical use.

Although the TCM theory is obscure and complicated for Western medicine doctors and researchers, several clinical trials have confirmed some herbal formulas may be safe and effective. Chen Wang, member of the Chinese Academy of Sciences, together with his colleagues[4] investigated the efficacy of maxingshigan-yinqiaosan, a traditional herbal formula, in a clinical trial including 410 patients with laboratory-confirmed H1N1 influenza. The multicenter, prospective, randomized, controlled trial was conducted at 11 medical sites in 4 provinces in China during the H1N1 influenza epidemic. The results showed that maxingshigan-yinqiaosan, alone and in combination with Oseltamivir, significantly shorten the course of fever in patients with H1N1 influenza virus infection. Only 2 of 103 patients who have taken maxingshigan-yinqiaosan experienced nausea and vomiting. They suggested that maxingshigan-yinqiaosan may have beneficial immunomodulatory effects for rapid recovery of viral infections, and it could be used as an alternative treatment of H1N1 influenza virus infection.

The underlying mechanisms of TCM in management of infectious diseases have also been investigated. Lianhuaqingwen Capsule (LH-C), another TCM prescription, inhibited the proliferation of a series of influenza viruses in vitro, suppressed virus-induced NF-kB activation, and alleviated virus-induced gene expression of IL-6, IL-8, TNF-α, IP-10, and MCP-1 in a dose-dependent manner, indicating that LH-C regulates the immune response of virus infection.[5] A latest study identified five active natural compounds from Chinese herbal medicine, including Baicalin, Scutellarin, Hesperetin, Nicotianamine, and Glycyrrhizin, which are potential compounds that target the Angiotensin-converting enzyme 2 (ACE2) receptor, and may exert antiviral effects for preventing novel coronavirus infection.[6]

These studies showed TCM remedies may have both antiviral and anti-inflammatory effects. Such properties are particularly important in the treatment of severe cases of COVID-19, because the host inflammatory response is a major cause of lung damage and subsequent mortality.[7] Although TCM has been applied widely to the treatment of COVID-19, by far, to our knowledge, there is still no scientific articles regarding this experience.[1,8,9] The main reason is that herbal formulas contain many compounds, they are tailored to patient's symptoms and environmental factors, and often work in a holistic approach. Given the complexity of TCM, it is very important to conduct high-quality clinical trials and basic researches to determine the exact efficacy and safety profiles, so that we can put the effective agents into large-scale clinical applications to benefit more patients.

Traditional medicines are potential sources of new drug candidates. The antimalarial drug artemisinin that has saved millions of lives, was extracted from traditional Chinese herb sweet wormwood. Irrespective of TCM or modern Western medicine doctors, we share the same goal to help, to care, to relieve, and to cure our patients. When we face the challenges of COVID-19 outbreak, drug-resistant infections, or future public health crises, it could be an option to give a warm embrace to this millennium-old practice. Several effective formulas and compounds originate from TCM, deserve further validation by rigorous clinical trials.

Yichang Yang, Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China. yangyichang.ll@163.com

Ting Zhang, Department of Immunology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.

Competing interests: We have read and understood BMJ policy on declaration of interests and declare that we have no competing interests.

References
1 Xu XW, Wu XX, Jiang XG, et al. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series. BMJ 2020; 368: m606. DOI: 10.1136/bmj.m606.
2 National Health Commission. Press conference of the joint prevention and control mechanism of the State Council on Feb 17, 2020. http://www.nhc.gov.cn/xcs/fkdt/202002/f12a62d10c2a48c6895cedf2faea6e1f.s... (in Chinese, accessed Feb 20, 2020).
3 National Health Commission. Diagnosis and Treatment Protocol of COVID-19 (Seventh Edition). published March 3, 2020. http://www.nhc.gov.cn/xcs/zhengcwj/202003/46c9294a7dfe4cef80dc7f5912eb19... (in Chinese).
4 Wang C, Cao B, Liu QQ, et al. Oseltamivir compared with the Chinese traditional therapy maxingshigan-yinqiaosan in the treatment of H1N1 influenza: a randomized trial. Ann Intern Med 2011; 155: 217-25.
5 Ding Y, Zeng L, Li R, et al. The Chinese prescription lianhuaqingwen capsule exerts anti-influenza activity through the inhibition of viral propagation and impacts immune function. BMC Complement Altern Med 2017; 17: 130.
6 Chen H, Du Q. Potential natural compounds for preventing 2019-nCoV infection. Preprints. 2020; 2020010358. https://www.preprints.org/manuscript/202001.0358/v1.
7 Stebbing J, Phelan A, Griffin I, et al. COVID-19: combining antiviral and anti-inflammatory treatments. Lancet Infect Dis 2020; published online Feb 27. DOI: 10.1016/S1473-3099(20)30132-8.
8 Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020; published online Feb 28. DOI: 10.1056/NEJMoa2002032.
9 Wang FS, Zhang C. What to do next to control the 2019-nCoV epidemic? Lancet 2020; 395: 391-93.

Competing interests: No competing interests

16 March 2020
Yichang Yang
physician
Ting Zhang
The Second Affiliated Hospital of Zhejiang University School of Medicine
88 Jiefang Road, Hangzhou, 310009, China