• Summary Report on Lianhua Qingwen Capsule/Granule for the Treatment of Influenza, Cold and Coronavirus Disease 2019 (COVID-19)

    Lianhua Qingwen Capsule/Granule (hereinafter referred to as LHQW) is a new Chinese patent medicine (SFDA Approval No.: Z20040063) developed under the guidance of collateral disease theory in traditional Chinese medicine (TCM) for the treatment of cold and influenza. LHQW is the first new medicine approved through fast-track approval process by the National Medical Products Administration during the SARS epidemic, has been awarded with the second prize of “National Science and Technology Progress Award”, and also become the first Chinese patent medicine that enters Phase II clinical trial approved by FDA, the US for the treatment of influenza.

    Since the outbreak of coronavirus disease 2019 (COVID-19), LHQW has been widely used for the epidemic prevention and control of accumulated 70 million people in national epidemic areas including designated hospitals and mobile cabin hospitals in Hubei Province. From January to March 2020, prospective clinical study, retrospective clinical study and basic experimental research of LHQW in the treatment of COVID-19 have been carried out successively in China, of which (1) prospective clinical study: prospective, controlled and multi-center clinical study (284 cases) of LHQW in the treatment of COVID-19 participated jointly by more than 20 hospitals from 9 provinces in China; prospective, controlled and multi-center clinical study (240 cases) of LHQW in the treatment of suspected COVID-19 participated jointly by more than 10 hospitals of China, the results showed that: the application of LHQW on the basis of conventional treatment can improve the clinical symptoms such as fever, fatigue, and cough etc of confirmed and suspected COVID-19 patients, and can also significantly improve the CT characteristics of lungs, shorten the duration of symptoms and treatment time and improve the clinical recovery rate. (2) Regressive clinical study in epidemic of Wuhan: LHQW can effectively alleviate fever, cough, sputum, shortness of breath and other symptoms in patients confirmed and suspected, and shorten the fever time. (3) Basic experimental research: The latest study made by the State Key Laboratory of Respiratory Diseases of the First Affiliated Hospital of Guangzhou Medical University confirmed that LHQW has inhibitory effect on the cytopathic effect of VeroE6 cells infected by novel crown virus (SARS-CoV-2) in vitro. The expression of virus particles in the cells was significantly reduced after the treatment of LHQW, which significantly inhibited the over-expression of TNF-a, IL-6, MCP-1 and IP-10 mRNA in a dose-dependent manner. A study by the Institute of Laboratory Animal Sciences, CAM&PUMC confirmed that LHQW can effectively inhibit the weight loss of mouse model with Covid-19, and it can improve the lung inflammatory injury and clinical symptoms of the model mouse. LHQW was successively included in the Guideline for the Diagnosis and Treatment of Novel Coronavirus (2019-nCoV) Pneumonia (On Trials, the Fourth/Fifth/Sixth/Seventh Edition) issued by National Health Commission of the People’s Republic of China and also recommended by 20 provincial health commissions including Hubei, Beijing, and Shanghai as well as National Administration of Traditional Chinese Medicine for the treatment of COVID-19. As the most recommended Chinese patent medicine, LHQW plays a pivotal role in the prevention and control of COVID-19 in China.

    1. Features of LHQW in the treatment of COVID-19

    The main lesion of COVID-19 is in the lung, inducing such classical symptoms as fever, fatigue and dry cough. The pathological manifestations are bilateral diffuse alveolar damage, mucus exudate from cells and fibers, and lymphocytic infiltration in pulmonary interstitium [1], suggesting that this disease falls into the categories of pestilence and collateral disease in TCM [2]. Its pathogenesis, transmission are identified based on the collateral disease theory in TCM, and then the corresponding therapeutic principles for active intervention are put forward as follows: exploration of the etiological factor for eliminating the toxic factors; drug formulation based on syndrome differentiation for active intervention; development of multi-target regimen for the regulation of the whole body [3]. On this basis, the therapeutic methods of “eliminating pestilence, removing toxin, dispersing lung and clearing away heat” are therefore established.

    LHQW is composed of 13 Chinese herbs, namely, Fructus Forsythiae, Flos Lonicerae, processed Herba Ephedrae, Cyrtomium Rhizome, Radix Isatidis, Gypsum Fibrosum, menthol, Herba Pogostemonis, Herba Rhodiolae, Herba Houttuyniae, Radix et Rhizoma Rhei, fried Semen Armeniacae Amarae, and Radix Glycyrrhizae. It is modified from Maxing Shigan Decoction in Treatise on Cold Damage and Miscellaneous Diseases by Zhang Zhongjing from the Han Dynasty,, Yinqiao Powder in Systematic Differentiation of Warm Diseases by Wu Jutong from the Qing Dynasty, as well as Radix et Rhizoma Rhei adopted for the treatment of pestilence by Wu Youke from Ming Dynasty in his book Treatise on Warm-Heat Pestilence. After further addition of Herba Rhodiolae and Herba Pogostemonis, it comes into being. Maxing Shigan Decoction is efficient in dispersing lung and clearing away heat, thereby relieving the accumulated heat-toxin in collaterals. Yinqiao Powder is effective for expelling pathogen through exterior and removing toxin. Radix et

    Rhizoma Rhei has the effect of relaxing bowels to clear, purge and quiet lung. Herba Pogostemonis is capable of resolving dampness, dispelling filth and eliminating pathogen due to its aroma. Herba Rhodiolae is good at clearing lung, resolving stasis, benefiting qi and nourishing yin. This formula is a collection of valuable experience for the treatment of pestilence with TCM over the past 2,000 years [4].

    2. Experimental evidence for LHQW against respiratory infections

    2.1 Study on Anti-COVID-19 virus and its related Mechanism In vitro research: A recent study led by researchers from the State Key Laboratory of Respiratory Diseases, the First Affiliated Hospital of Guangzhou Medical University has confirmed that traditional Chinese medicine Lianhua Qingwen (LHQW) could inhibit the cytopathic effect of VeroE6 cells infected by novel coronavirus in vitro, leading to significantly reduced expression of the virus particles in VeroE6 cells. The State Key Laboratory of Respiratory Diseases had used RT-qPCR to analyze the mRNAs expression of cell factors, they found that LHQW significantly inhibited the novel coronavirus (SARS-CoV-2)-induced mRNAs overexpression of inflammatory factors TNF-a, IL-6, MCP-1 and IP-10 in a dose-dependent manner. The above research has been published in Pharmacological Research (impact Factor: 5.572) Through the search of CNKI, SCI and MEDLINE databases, this article is the first basic research article on the effective anti-SARS-Cov-2 virus of proprietary Chinese medicine.

    In vivo research: Studies by researchers from the Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences have confirmed that the mice in the model group experienced weight loss after infection, with an average reduction of 5.75%. Compared with the model group, the weight loss of mice at 3 and 5 days after infection was significantly inhibited in LHQW group (P<0.01). In addition, as compared with the model group, the lung tissue inflammation of LHQW group was partially alleviated, suggesting that LHQW could reduce lung inflammation and ameliorate clinical symptoms in model mice.

    2.2 Pharmacodynamic study

    2.2.1 Anti-virus

    The latest research by State Key Laboratory of Respiratory Diseases revealed that LHQW inhibited the influenza viruses including H3N2 via resisting their adhesion and proliferation and directly killing them [6]. According to Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, the pre-treatment, co-treatment, and post-treatment with LHQW would prolong the survival time of mice infected with H3N2 virus, reducing their lung index, and alleviated their lung inflammation [6]. Moreover, accumulating evidence has shown that LHQW significantly regulated the immune response after virus infection [7] and exerted broad-spectrum antiviral effects against common respiratory viruses, such as FM1 virus, parainfluenza virus [8], respiratory syncytial virus (RSV) [9], enteric virus (EV) 71, and coxsackie virus [10], [11]. Besides, LHQW exhibited definite antibacterial effects on Staphylococcus aureus, Hemophilus influenza, and Pneumococcus, and inhibited the biofilm formation of methicillin-resistant strains including Staphylococcus aureus and Staphylococcus epidermidis [12], [15], [14].

    2.2.2 Anti-inflammation

    LHQW exerted the effects in FM1- infected mice by inhibiting virus replication and reducing the expression levels of cytokines and chemokines including TNF-α, IL-4, IL-6, IL-1β, IL-12, and L-13 from several tissue cells [15]. Besides, LHQW also attenuated the acute lung damage in mice induced by LPS through reducing the infiltration of inflammatory cells and increasing the expression levels of connexins in alveolar epithelial cells and pulmonary vascular endothelial cells [16].

    2.2.3 Symptom improvement and immunoregulation

    LHQW has been prescribed for treating bronchitis, pneumonia and early stage of measles due to its pharmacological activities like abatement of fever, anti-inflammation, anti-tussive effect, and immunoregulation. (1) Antipyretic effect: LHQW has been proved to be able to relieve the fever in rabbit induced by subcutaneous injection of triple vaccine. (2) Anti-inflammation: LHQW is capable of attenuating the ear edema in mice induced by xylene and paw edema induced by carrageenan, and decreasing the capillary permeability in the abdominal cavity of mice induced by acetic acid. (3) Anti-tussive effect: LHQW is able to increase the phenol red excretion in trachea of mice, prolong the incubation period of cough in mice induced by ammonium hydroxide and reduce its occurrence, and also decrease the cough frequency in guinea pigs induced by citric acid. (4) Immunoregulatory effect: LHQW is capable of enhancing the delayed hypersensitivity in mice with immune deficiency induced by hydrocortisone, improving the phagocytosis of peritoneal macrophages in mice with immune deficiency induced by cyclophosphamide and up-regulating the serum hemolysin antibody level.

    3 Clinical studies on the treatment of respiratory infections with LHQW

    During the influenza A H1N1 pandemic in 2009, Lianhua Qingwen played an important role in the epidemic prevention and control. According to CCTV news, a total of 60 million boxes of Lianhua Qingwen were used in China during three months. It is because of its major role in this pandemic; Lianhua Qingwen was awarded the 2011 Annual National Second Prize of Scientific and Technological Progress, which is the significant scientific and technological innovation achievement no other drugs achieved.

    3.1 Treatment of novel coronavirus pneumonia - effectively relieving the symptoms like fever, cough, expectoration, shortness of breath and shortening fever duration

    3.1.1 A prospective, randomized, controlled, multi-center clinical study of traditional Chinese medicine Lianhua Qingwen in the treatment of Corona Virus Disease 2019 (COVID-19)

    A total of 284 patients with COVID-19 who met the inclusion criteria were enrolled and randomly divided into a control group (conventional treatment) and a treatment group (conventional treatment supplemented with LHQW Capsule, 4 capsules each time, 3 times daily). The course of treatment was 14 d. The results of the study showed that (1) the disappearance rate (the percentage of patients recovering from fever, fatigue, and cough) of major clinical symptoms (fever, fatigue, and cough) was higher in the LHQW group than in the conventional treatment group (P <0.05). (2) The duration of clinical symptoms (fever, fatigue, and cough) was shorter in LHQW group than in the control group. The duration of symptom disappearance, including fever and fatigue, and cough, was shortened in the LHQW group, respectively, as compared with the conventional treatment group (P<0.05). (3) The improvement rate on CT was higher in the LHQW group than in the conventional treatment group (P <0.001). (4) The clinical cure rate was significantly higher in the LHQW group than in the conventional treatment group (P <0.05). The duration of the disease in the treatment group was significantly better t that of the control group. (P <0.05). In addition, the nucleic acid negative conversion rate and duration of negative-to-positive conversion of the treatment group showed a favorable trend, as compared with the control group. In terms of reducing the possibility of mild infections becoming severe, the treatment group was lower than the control group, showing a good trend. During the course of the trial, no severe adverse events were reported in either group. With respect to the experimental drug, no abnormalities were detected on laboratory examinations as well as on electrocardiogram in both groups, including routine blood test, markers of liver and kidney function, and myocardial enzymes. The results of his study confirmed that LHQW Capsule/Granule on the basis of conventional treatment could ameliorate clinical symptoms such as fever, fatigue, and cough in patients diagnosed with COVID-19. In addition, it could significantly improve CT characteristics of the lungs, shorten the duration of symptoms and treatment duration, and improve the clinical cure rate, which is, therefore, safe and effective for patients with COVID-19.

    3.1.2 A prospective, randomized, controlled, multi-center clinical study of traditional Chinese medicine Lianhua Qingwen in the treatment of suspected patients with novel coronavirus pneumonia

    In a prospective, randomized, controlled, and multi-center clinical study on traditional Chinese medicine Lianhua Qingwen (LHQW) in the treatment of suspected patients with novel coronavirus pneumonia COVID-19, leading researchers from Renmin Hospital of Wuhan University working in collaboration with other researchers from more than 10 hospitals across China have made great progress.

    A total of 240 patients with suspected COVID-19 were enrolled in this study and randomly divided into the control group (conventional treatment) and the LHQW group (conventional treatment supplemented with LHQW capsules, 4 capsules 3 times daily). The course of treatment was 14 days. The results of the study were as follows: (1) the disappearance rate (the percentage of patients recovering from fever, fatigue and cough) of major clinical symptoms (fever, fatigue, and cough) was higher in the LHQW group than in the control group. (2) The duration of clinical symptoms was significantly shorter in the LHQW group than in the control group (P<0.01). (3) The median disappearance time of fever, fatigue and cough in the treatment group was shorter than that in the control group (P < 0.05). Compared with the disappearance rate of single symptom, the disappearance rate of cough in the treatment group was significantly higher than that in the routine treatment group. (4) The improvement rate on lung CT was higher in the LHQW group than in the control group. (5) The clinical cure rate was significantly higher in LHQW group than in the control group, and the duration of disease was shorter than that of the control group (P<0.05). With respect to the possibility of mild infections becoming severe, the two treatment groups were lower than the control group, showing a favorable trend. During the study period, no serious adverse events occurred in either group. The blood routine, liver and kidney function, myocardial enzyme, inflammation index, electrocardiogram and chest CT examination of the two groups were judged by

    the researchers, no abnormalities related to the experimental drugs were found, which confirmed that LHQW was safe in clinical application. The results of this study confirmed that LHQW on the basis of conventional treatment could safely and effectively ameliorate clinical symptoms of patients with suspected COVID-19, such as fever, fatigue, and cough. Furthermore, it could improve the imaging characteristics of the lungs, shorten the duration of symptoms and treatment duration, and improve clinical cure rate.

    3.1.3 Retrospective clinical study of Lianhua Qingwen in the treatment of Corona Virus Disease 2019 (COVID-19)

    One hundred and two patients diagnosed with general COVID-19 were included in a controlled study carried out by the Puren Hospital affiliated to Wuhan University of Science and Technology, China Resources & WISCO General Hospital affiliated to Wuhan University of Science and Technology and the Ninth Hospital of Wuhan. 51 cases in the treatment group were administered with routine treatment combined with Lianhua Qingwen Granules (1 pack per time, 3 times a day), and 51 cases in the control group were treated with only routine treatment. Compared with the control group, the disappearance rate of cardinal symptom in the treatment group was 83.7%, 61.3%, and 62.2%, respectively, in contrast to 61.0%, 34.3%, and 35.9% in the control group (P<0.05). The average duration of cardinal symptom in the treatment group was (2.9±1.7) d, (3.5±1.5) d, and (3.9±2.0) d, respectively, in contrast to (3.9±1.3) d, (4.8±1.5) d, and (5.2±1.8) d, in the control group (P<0.05). The cardinal symptoms relief occurred in forty-four patients of the treatment group (86.3%) and thirty-five patients of the control group (68.6%), indicating a significant difference between the two groups (P<0.05). The disappearance rate of expectoration, shortness of breath, chest distress, and appetite loss was 55.0%, 61.5%, 54.6%, 34.8% , respectively, in the treatment group in contrast to 15.8%, 14.3%, 15.8%, 7.7% in the control group (P<0.05). Four patients in the treatment group (7.8%) and eleven patients in the control group (21.6%) progressed to the severeCOVID-19 during treatment (P<0.05). Twenty-eight patients in the treatment group (54.9%) and twenty-three patients in the control group (45.1%) had pulmonary CT imagining improvement (P>0.05). Conclusion: LH-C combined with a conventional therapy could significantly improve clinical symptoms of COVID-19 patients including fever, weakness, cough, expectoration, shortness of breath, chest distress, and appetite loss, alleviate pulmonary moist rale, enhance the effective rate of cardinal symptom, and reduce progression. These findings suggested LH-C could be effective in the common COVID-19 patients.

    Forty-two patients with COVID-19 confirmed by Wuhan Ninth Hospital and CR&WISCO General Hospital were included in this trial and then randomly divided into a treatment group (21 cases, conventional treatment combined with LHQW, one bag per time, three times per day) and a control group (21 cases, conventional treatment). Compared with the control group, the disappearance rates of fever, cough, expectoration, and shortness of breath in the treatment group were 85.7% (control group: 57.1%), 46.7% (control group: 5.6%), respectively, with statistically significant differences (P < 0.05). In addition, the duration of fever in the treatment group was (4.6 ± 3.2) d, which was 1.5 days shorter than (6.1 ± 3.1) d in the control group. Conclusion: Chinese patent medicine LHQW significantly alleviated fever, cough, expectoration and shortness of breath in patients with novel coronavirus pneumonia [17]. A total of 101 suspected COVID-19 patients in CR&WISCO General Hospital affiliated to Wuhan University of Science and Technology were included for anther clinical trial. They were randomized into a treatment group (63 patients provided with LHQW in combination with conventional treatment) and a control group (38 patients treated with only conventional treatment). The disappearance rates of fever, cough and fatigue in the treatment group were 86.7%, 55.6%, and 82.5%, respectively, which were significantly better than 67.7%, 30.6%, and 58.6% in the control group (P < 0.05). The median duration of fever in the treatment group was six days, while that in the control group was seven days. The disappearance rates of shortness of breath and moist rale in the treatment group were 68.2% and 56.0%, respectively, which were significantly higher than 20.0% and 20.0% of the control group (P < 0.05). During the study, four patients (6.4%) in the treatment group reported aggravation, while six patients (15.8%) in the control group suffered from aggravation, suggesting that the alleviation in the treatment group was significant as compared with that in the control group [18].

    After seven days of treatment, fifty-four general patients with COVID-19 at Wuhan Puren Hospital exhibited the disappearance rates of 80.0%, 75.7%, and 76.7% for fever, fatigue, and cough, respectively. The remission of fever, fatigue, and cough after the treatment lasted for (3.6 ± 2.14), (4.1 ± 2.58), and (5.3 ± 2.63) days, respectively. Besides, the disappearance rates of other symptoms and signs such as chest tightness, dyspnea, and moist rale were 84.6%, 100%, and 89.5%, respectively. The effective rate was 81.6%, and it was safe for clinical application [19]. The above-mentioned clinical research data from the epidemic area have confirmed that Lianhua Qingbing was effective for alleviating the symptoms of patients with novel coronavirus pneumonia and shortening the duration of fever.

    3.2 Treatment of H1N1 influenza (swine flu) – negative conversion rate of viral nucleic acid test comparable to that of oseltamivir, while the effect of alleviating clinical symptoms better than that of oseltamivir

    Since its marketing in 2003, Lianhua Qingwen has always played an important role in every epidemic prevention and control. It has been highly praised by clinicians and patients from many hospitals and pharmacies across China, awarded the title of Medicine for Treating Cold Commonly Prepared by Families by the Beijing Evening News for successive 8 years, and become one of the representative medicines in response to public health events associated with viral infection.

    Since its marketing in 2003, Lianhua Qingwen has always played an important role in every epidemic prevention and control. It has been highly praised by clinicians and patients from many hospitals and pharmacies across China, awarded the title of Medicine for Treating Cold Commonly Prepared by Families by the Beijing Evening News for successive 8 years, and become one of the representative medicines in response to public health events associated with viral infection.

    During the outbreak of the 2009 pandemic influenza A (H1N1) virus infection in China, a randomized, double-blind, multi-center clinical trial on Lianhua Qingwen (LHQW) Capsule for the treatment of pandemic influenza H1N1 was conducted by researchers from You’an Hospital Affiliated to Capital Medical University working in collaboration with other researchers from eight hospitals across China. Patients had to meet the following criteria for inclusion: with confirmed influenza A virus infection by virological testing, age between 16 and 65 years, axillary temperature ≥ 37.4℃, and illness onset within 36 hours. Therefore, a total of 244 patients were enrolled and randomly divided into LHQW Capsule group (n=122) and Oseltamivir group (n=122). LHQW Capsule or Oseltamivir was administered for 5 days, followed by observation for 7 days. The results of this study were as follows: (1) The median time to relief of all flu-like symptoms and the 95% CI between LHQW Capsule group and Oseltamivir group were (69 hours vs. 85 hours) and (63.00-84.00 vs. 72.00-90.00), respectively. The absolute value of the median difference between the two groups was less than the non-inferiority margin (24h), and there was no difference between LHQW Capsule and Oseltamivir. (2) The average duration of virus nucleic acid negative conversion in LHQW Capsule group and Oseltamivir group was (108±36) hours and (101±34) hours, respectively, with no significant difference observed (P>0.05). (3) The average time to defervescence was (17±14) h for LHQW Capsule group and (23±17) h for Oseltamivir group, a significantly improved defervescence effect for LHQW Capsule (P<0.05). In conclusion, LHQW Capsule did not differ significantly from Oseltamivir in terms of duration of viral nucleic acid negative conversion and alleviation of flu-like symptoms. However, LHQW Capsule had a significant effect on amelioration of disease severity, and reduction of symptom duration, including fever, cough, sore throat, and fatigue (P <0.05). In addition, the drug was well tolerated. No serious drug-related adverse events occurred during the study [20].

    A randomized, positive drug-controlled clinical trial concerning the treatment of 124 cases with H1N1 influenza by LHQW has shown that LHQW was similar to oseltamivir in inducing the negative conversion of viral nucleic acid test, but superior to oseltamivir in relieving cough, sore throat, fatigue, and muscular soreness [21]. In addition, a retrospective analysis of the use of LHQW in the designated hospital (Beijing Ditan Hospita) has also confirmed that LHQW was equivalent to oseltamivir in alleviating fever and inducing the negative conversion of viral nucleic acid test. According to a completed clinical study [21] on the prevention of influenza A with LHQW, after the treatment of close contacts and surrounding populations (20,553 people) in Langfang City, Hebei Province, the symptom occurrence rate of the LHQW group was 1.2%, while the symptom occurrence rates of the other medication group and the non-medication group were 6.8% and 8.8%, respectively, verifying the good therapeutic effect of LHQW against H1N1 viral infection. The above clinical trial results have demonstrated that LHQW is effective for the treatment, control and prevention of influenza. In terms of clinical safety, a meta-analysis based on 4,906 patients revealed the good safety of LHQW [22], [23].

    4 Wide application of LHQW for the prevention and control of novel coronavirus pneumonia in China

    The research project of "LHQW for the treatment of influenza" was awarded with the second prize of “National Science and Technology Progress Award” by the State Council of the People’s Republic of China in 2011, which reflects the scientific and technological innovation in formulation as well as basic and clinical research based on TCM theory. Since its marketing in 2003, LHQW has been listed in various public health event diagnosis and treatment plans or guidelines for the diagnosis and treatment for infectious diseases such as influenza A, influenza B, avian influenza, Ebola hemorrhagic fever, and Middle East respiratory syndrome for more than 20 times [Annex 4], making it become a representative Chinese patent medicine in response to public health events and included in 2019 National Basic Medical Insurance, Work Injury Insurance and Maternity Insurance Drug List and 2018 National Essential Medicines List [24-26].

    LHQW has been included in the Guideline for the Diagnosis and Treatment of Novel Coronavirus (2019-nCoV) Pneumonia (On Trials, the Fourth/Fifth/Sixth /Seventh Edition) jointly issued by National Health Commission of the People’s Republic of China and National Administration of Traditional Chinese Medicine for the treatment of novel coronavirus pneumonia throughout the country. At the same time, it has also been recommended in the Expert Consensus on the Diagnosis, Treatment and Prevention of New Coronavirus Infection in Children and Recommendations form TCM Experts on Treatment of Novel Coronavirus Pneumonia in Pregnancy (On Trials). Consequently, it has also been listed in the treatment plans for novel coronavirus infection in 20 provincial health commissions including Hubei, Beijing, and Shanghai and the corresponding provincial administration of TCM, making it become the most frequently recommended Chinese patent medicine [26]. Moreover, it has been classified as the standby medicine and listed in the inventory of emergency medical supplies by 13 provinces. In more than 200 cities and counties across the country, the corresponding health commissions requested the medical institutions under their management to stock LHQW for epidemic prevention and control. The designated hospitals and mobile cabin hospitals in Wuhan were ordered to stock LHQW, since it has been listed in Handbook for Mobile Cabin Hospitals (Third Edition) issued by the National Health Commission of the People’s Republic of China as a recommended Chinese patent medicine [Annex 4]. Academician Zhang Boli recommended the use of Lianhua Qingwen Capsule/Granule in the treatment of COVID-19 in the press conference of the Joint Prevention and Control Mechanism of the State Council of China, and Academician Zhong Nanshan introduced the clinical study results of Lianhua Qingwen Capsule/Granule against COVID-19 and confirmed its efficacy at the Sino-European Anti-Epidemic Exchange Meeting. According to sales data from January to the end of February, 2020, about 70 million people have taken LHQW during the outbreak of novel coronavirus pneumonia, indicating that it has played an active role in epidemic prevention and control. During the epidemic, Shijiazhuang Yiling Pharmaceutical in response to the national call, undertake the responsibilities and obligations of national enterprises to ensure the health and safety of the people. We had donated LHQW worth 10.27 million RMB, 1.776 million RMB and 1.48 million RMB to the Chinese Red Cross to support the prevention and treatment of COVID-19 in China, Iraq and Italy. The China Administration of traditional Chinese Medicine donated LHQW to Iran, Hong Kong and Macao for novel coronavirus epidemic prevention and control. It has been registered in China's Hong Kong and Macao regions, as well as Canada, Mozambique, Indonesia, Brazil, Romania, Thailand, and obtained temporary permission in Hungary for the prevention and control of COVID-19. The National Administration of Traditional Chinese Medicine is ready to carry out international cooperation on TCM participation in epidemic prevention and control with countries in need.

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