A randomized clinical trial on LHQW of 284 COVID-19 patients is useful to confirm the beneficial effect of TCM. In the trial, 142 patients were given LHQW for 14 consecutive days (4 capsules, three times a day), the results manifested that the recovery rate (91.5% vs 82.4%), the improvement rate (83.8% vs 64.1%) and the clinical cure rate (78.9% vs 66.2%) of the treatment group were higher than the control group, with no serious adverse reactions . This trial showed that LHQW could be considered to ameliorate clinical symptoms of COVID-19. Furthermore, 22 065 subjects were given HXZQ and Jinhao Jiere Granules (JHJR) for preventive administration for 5 consecutive days with the protection rate of the intervention group was 91.8%, which indicated that they provided effective protection for the community . Then, 123 COVID-19 patients were additionally given JHQG for 5 consecutive days , and the disappearance rate of fever symptoms in the treatment group was about 85.0%, which was 27.0% higher than that in the control group, and the Hamilton anxiety score decreased significantly in the treatment group (6.37) than in the control group (4.88), indicating that JHQG could effectively relieve the symptoms and anxiety of patients. A retrospective analysis of 68 patients found that the effective rate (91.2%) of the treatment group combined with the SFJD for 7 days was dramatically higher than that of the control group (70.6%, P < 0.05), and no adverse events occurred . The analysis revealed that the combined use of SFJD was effective and safe.
On the other hand, 214 confirmed cases in four pilot provinces were treated with QFPD (3 days as a course of treatment), which showed a total effective rate of more than 90% . Among these, 98 patients were treated for 9 days and the total effective rate was 92.09%, of which the recovery rate was 41.13%, the significant efficiency was 26.92%, and the effective rate was 24.04% . These trials provided strong evidence for the clinical application of QFPD. Furthermore, 80 patients were given MXSG for 5−7 days, the effective rate was 95% ; Forty patients were given MXSG combined with conventional treatment for 7 days, and the disappearance rates of the main clinical symptoms (fever, fatigue, cough) were 96.8% (30/31), 100.0% (28/28) and 81.8% (18/22) respectively . It showed that the combined use of MXSG could effectively improve the symptoms of patients. And 44 patients were given XBJ treatment for 7 consecutive days, which indicated that the overall effectiveness of the intervention group (68.2%) was slightly higher than that of the control group (50.0%), and no serious adverse reactions occurred . The clinical trials showed that XBJ also had a certain therapeutic effect. Nevertheless, there are dozens of TCM are conducting clinical trials at present, certain specific Chinese medicines are also incorporated (Table 3).
No. Registration number Scientific title Date of Registration 1 ChiCTR2000029434 A randomized, open-label, blank controlled trial for Lian-Hua Qing-Wen Capsule/Granule in the treatment of 2019-nCoV pneumonia (novel coronavirus pneumonia, NCP) 2020-02-01 2 ChiCTR2000033133 A randomized, open-label, blank-controlled, multicenter trial for Shuang-Huang-Lian oral solution in the treatment of novel coronavirus pneumonia (COVID-19) 2020-05-21 3 ChiCTR2000035633 Clinical study of safety, tolerance, and pharmacokinetics of nebulizer (INF-K + anti-inflammatory factor TFF2) in healthy volunteers and exploration of PK/PD fitting modeling in clinical trials of Novel Coronavirus Pneumonia (COVID-19) patients 2020-08-15 4 ChiCTR2000032767 A Medical Records Based Study for Clinical Efficacy and Safety of “clear lung detoxification soup” in the treatment of Novel Coronavirus Pneumonia (COVID-19) 2020-05-09 5 ChiCTR2000032205 A multicenter randomized, double-blind, placebo-controlled trial for Sheng-Mai-Yin for improvement of the pulmonary heart function related symptoms of convalescence patients of new coronavirus pneumonia 2020-04-23 6 ChiCTR2000030545 Efficacy and safety of honeysuckle oral liquid in the treatment of novel coronavirus pneumonia (COVID-19): a multicenter, randomized, controlled, open clinical trial 2020-03-16 7 ChiCTR2000030388 Efficacy and safety of Xue-Bi-Jing injection in the treatment of severe cases of novel coronavirus pneumonia (COVID-19) 2020-03-01
Table 3. The representative clinical trials of TCM for anti-COVID-19
TCM has accumulated thousands of years’ experience in the treatment of pandemic and endemic diseases. Literature analysis has indicated the potential feasibility of QFJD, HSBD, XBJ and other Chinese herbal preparations to treat COVID-19. Although its safety and effectiveness need to be clarified, it can provide a theoretical basis for subsequent experiments and clinical research. At present, most of the TCM preparations have been explored their potential mechanisms and targets by network pharmacology and molecular docking. The results showed that some TCM preparations could inhibit virus entry and replication in vivo by binding to Mpro and ACE2 targets, such as HXZQ, JHQG, LHQW, XBJ, TRQ and XYP. Also, they could play an anti-inflammatory role by acting on TNF, MAPK, Toll, NF-κB, IL-17, HIF-1 and other signaling pathways, which embodied the unique characteristics and advantages in the improvement of multiple organ damage. HSBD might act on the RIG-1/IRF/IFN-β, NF-κB/TNF-1L signaling pathways to reduce the release of inflammatory factors to alleviate lung injury. LHQW possibly modulated AGE/RAG1/ROS, PI3K/AKT and other signaling pathways to reduce kidney damage caused by inflammation. QFPD, MXSG potentially reduced the heart and brain damage linked with Caspase-3/Bcl-2, TNF-R1/MAPK and other signaling pathways. Compared with Western medicine treatment, TCM has its unique treatment concepts and principles. For example, QFPD is a common and core prescription in the prevention and treatment of COVID-19, and patients can be treated based on syndrome differentiation individually following the TCM theory . Also, HXZQ could not only act on the main pathogenesis of “ wet poison ”, but also restore the qi mechanism to improve patients’ symptoms . LHQW is a representative Chinese drug for treating viral infection-related diseases and has a broad clinical application basis . XBJ showed no immunosuppressive effects in the treatment of clinical severe and critical COVID-19 patients. What’s more, the incidence of adverse reactions was low and the clinical effect was remarkable . These findings have shown that compounds and preparations of TCM have their unique characteristics and potential advantages in treating COVID-19 (Fig. 1) and also provided a clinical basis for the follow-up TCM treatment plan and new drug development. Among them, the TCM composition and the action pathways for the prevention and treatment of the COVID-19 are shown in Table 1.
Figure 1. Schematic diagram of possible action pathways of traditional Chinese medicine for prevention and treatment of COVID-19. 1 HXZQ; 2 JHQG; 3 LHQW; 4 XBJ; 5 TRQ; 6 QFPD; 7 SJS; 8 HSBD; 9 MXSG; 10 XCHT; 11 RDN; 12 XYP; 13 SFJD; 14 SMI; 15 YQFM
Name Composition Treatment approach References Huoxiang Zhengqi Oral Liquid (HXZQ) Patchouli oil, Perilla leaf oil, Angelica dahurica, Atractylodes lancea, Magnolia officinalis (processing with Zingiber officinale), Born Pinellia ternate, Indian Bread, Tangerine peel, Arecae Pericarpium, Licorice extract Inhibit virus entry and replication; inhibit inflammation, and cytokine storm [26, 37] Jinhua Qinggan Granules (JHQG) Flos Lonicerae, Gypsum Fibrosum, honey-prepared Herba Ephedrae, Armeniacae Semen Amarum, Scutellaria baicalensis Geor, Fructus Forsythiae, Fritillaria thunbergii, Anemarrhena asphodeloides, Arctium lappa, Artemisia annua, Herba Menthae, Radix Glycyrrhizae Inhibit virus, regulate immunity, inflammation and apoptosis [27, 38, 39] Lianhua Qingwen Prescription (LHQW) Fructus Forsythiae, Flos Lonicerae, Ephedra sinica, Armeniacae Semen Amarum, Gypsum Fibrosum, Isatis indigotica, Dryopteris crassirhizoma, Houttuynia cordata, Pogostemon cablin, Rheum palmatum, Rhodiola rosea, Mentha haplocalyx, Radix Glycyrrhizae Inhibit viral replication and reduce cytokine release from host cells; regulate immunity  Shengjiang powder (SJS) Bombyx batryticat, Cryptotympana pustulata ecdysis, Curcuma longa, Rheum palmatum Intervene in virus invasion and suppress stress response  Huashibaidu prescription(HSBD) Raw ephedra, Armeniacae Semen Amarum, Gypsum Fibrosum, Radix Glycyrrhizae, Agastache rugosa, Magnoliae Officinalis Cortex, Atractylodes lancea, Amomum tsao-ko, Rhizoma Pinellinae Praeparata, Poria cocos, Rhubarb, Astragali radix, Draba nemorosa, Paeonia lactiflora Inhibit inflammation, improve cytokine storm [41, 57] Qingfei Paidu Decoction(QFPD) Ephedrae Herba, Fried Glycyrrhiza uralensis, Armeniacae Semen Amarum, Gypsum Fibrosum, Cinnamomun cassia, Alismaorientalein, Polyporus umbellatus, Atractylodes macrocephala, Poria cocos, Bupleuri Radix, Scutellaria baicalensis Geor, ginger-processed Pinelliaternata, Ginger, Aster tararicus, Farfarae Flos, Belamcandae Rhizoma, Asari Radix et Rhizoma, Dioscorea opposite Rhizoma, Aurantii Fructus Immaturus, Tangerine peel, Agastache rugosa Inhibit virus invasion and replication; inhibit inflammation, improve cytokine stormy [33, 42] Maxing Shigan Decoction(MXSG) Ephedra, Armeniacae Semen Amarum, Gypsum Fibrosum, Radix Glycyrrhizae Inhibit inflammation; improve cytokine stormy and pulmonary interstitial edema  Xiaochaihu Tang(XCHT) Bupleuri Radix, Scutellaria baicalensis Geor, Pinellia ternate, Ginger, Ginseng Radix et Rhizoma, Radix Glycyrrhizae, Jujube Inhibit inflammation;Reduce the temperature  Xuebijing injection(XBJ) Carthamus tinctorius, Radix Paeoniae Rubra, Ligusticum chuanxiong Hort, Salvia miltiorrhiza, Angelica sinensis Inhibit viral invasion and replication; inhibit inflammation [29, 46, 47] Reduning Injection(RDN) Artemisia annua, Flos Lonicerae, Gardeniae Fructus Inhibit inflammation  Shengmai injection(SMI) Ginseng Radix et Rhizoma, Ophiopogonis Radix, Schisandra chinensis Inhibit inflammation and oxidative stress; improve pulmonary fibrosis and microcirculation; regulate immune function  Yiqi Fumai Lyophilized Injection(YQFM) Red ginseng, Ophiopogonis Radix, Schisandra chinensis Inhibit inflammation and oxidative stress; improve pulmonary fibrosis and microcirculation; regulate immune function  Tanreqing Injection(TRQ) Scutellaria baicalensis Geor, Bear Bile Powder, Caprae hircus cornu, Flos Lonicerae, Fructus Forsythiae Inhibit inflammation;regulate immunity  Xiyanping Injection(XYP) Andrographis Herba Inhibit inflammation;regulate immunity  Shufeng Jiedu Capsules(SFJD) Polygonum cuspidatum, Fructus Forsythiae, Isatis indigotica, Bupleuri Radix, Herba Patriniae, Verbenae Herba, Rhizoma Phragmitis, Radix Glycyrrhizae Inhibit inflammation and virus infection; [55, 56] Chinese medicine composition Agastache rugosa, Chrysanthemi Indici Flos, Moslae Herba, Artemisia annua Inhibit inflammation and virus infection;  Chinese medicine aromatherapy air disinfectant Artemisia argyi, Isatidis Radix, Folium Isatidis, Dryopteris crassirhizoma Nakai, Flos Lonicerae, Fructus Forsythiae, Scutellaria baicalensis Geor, Herba Menthae, Atractylodis Rhizoma, Aquilariae Lignum Resinatum, Viola yedoensis, Chrysanthemi Indici Flos, Houttuynia cordata Sterilization, inbit virus  Chinese medicine composition sachet Syzygium aromaticum, Platycladus orientalis, Angelica dahurica, Flos Lonicerae, Agastache rugosa, Eupatorium fortune, Cinnamomum cassia, Camphor, Saposhnikovia divaricata, Isatidis Radix, Artemisia argyi, borneol Inhibit bacterial and viral infection  Chinese medicine atomizing agent Qingai Oil, Artemisia annua oil, Ginseng oil, Astragalus oil, Rhodiola rosea, Grape seed oil Inhibit virus; improve immunity;improve fatigue  Chinese medicine fumigating bath preparation Semiliquidambar Cathayesis, Cinnamomum camphora roots, Cymbopogon citratus, Scutellaria barbata, Polygonum Cuspidatum, Caulis Lonicerae, Fructus Forsythiae, Dandelion, Bupleuri Radix, Cynanchi Stauntonii, Armeniacae Semen Amarum, Aster tararicus, Rhizoma Phragmitis, Gaultheria yunnanensis Promote metabolism and circulation;improve human immunity; inhibit virus  Fuzheng lung-saving medicine composition Aconitum carmichaelii, Dried ginger, Honey-fried Licorice, Flos Lonicerae, Spina Gleditsiae, Ipomoea cairica, Pogostemon cablin, Tangerine peel Inhibit inflammation and virus infection;Improve body immunity  Chinese medicine composition Tripterygium wilfordii, Gypsum Fibrosum, Dioscorea opposite Rhizoma, Scrophulariae Radix, Fructus Forsythiae, Cryptotympana pustulata ecdysis, Codonopsis pilosula, Herba Menthae, Arctium lappa, Haematitum Inhibit virus; regulate immunity; reduce temperature 
Table 1. Chinese herbal compound for anti-COVID-19
Moreover, literature mining and big data analysis showed that some natural products including quercetin, puerarin, porphyrin, quercetin-7-O-β-D-glucoside and patchouli alcohol in Patchouli have a better combination with Mpro, which could reduce virus replication. Seven effective compounds such as β-sitosterol and aloe-emodin in Rhubarb purportedly had the anti-viral, anti-inflammatory, anti-oxidative stress, anti-apoptosis and regulation of body immunity effects through multiple pathways and multiple targets. Meanwhile, the active ingredients of TCM such as glycyrrhizin and baicalin could inhibit the virus activity. For the experimental study of single Chinese herbs or extracts, Rhubarb, Scutellaria baicalensis Geor, Coptidis Rhizoma, Flos Lonicerae, Folium isatidis and other antipyretics or antidotes have a certain therapeutic effect, which could provide a reference for the new combination of TCM. For example, there are some TCM sachets and sprays which have applied for patents to help reduce the prevalence and mortality. The effective components and action pathways of single TCM and natural active components for anti- SARS-CoV-2 are shown in Table 2.
Name Composition Treatment approach References Pogostemonis Herb Quercetin, Genkwanin, Quercetin-7-O-β-D-glucoside ect. Act on Toll, NOD, RIG-I-like receptor signaling pathway, MAPK signaling pathway, T cell receptor signaling pathway  Rhubarb β-sitosterol, Aloe-emodin, Rhein, Catechins Inhibit virus; Inhibit inflammation, oxidative stress, and apoptosis; regulate body immunity  Natural active ingredients Baicalin, Hesperidin, Glycyrrhizin, Nicotinamide Bind with ACE2 enzyme, act on ACE2 receptor to prevent and treat pneumonia  Quercetin, (-)-Epigallocatechin gallate Act on IL-6 target protein, inhibit cytokine storm  Natural active compound combinations Vitamin C, Curcumin, Glycyrrhizin Regulate immune response; inhibit CoV infection; suppresses excessive inflammation and prevents cytokine storms 
Table 2. Single traditional Chinese medicine and natural active ingredients for anti-COVID-19
The above summary suggests that TCM and its preparations showed the unique superiority of a full course of treatment and a full range of treatments. Early prevention and early treatment could reduce the mortality rate, improve symptoms, decrease the occurrence of complications and recurrence, which showed broad application prospects. The network pharmacological analysis indicates that the possible mechanisms of TCM were anti-virus, anti-inflammation, immune regulation, and organ protection through multiple components acting on multiple targets or pathways for the treatment of COVID-19. Different TCM may act on the same or similar targets or pathways. Nevertheless, the current understanding of the mechanisms of TCM is mainly produced from virtual simulation through molecular docking and network pharmacology analysis. To confirm these predicted mechanisms, well designed in vitro cell experiments and in vivo animal studies based on these predictions are needed. Furthermore, many clinical studies and statistical methods still have deficiencies such as limited sample size and nonstandard trial methods etc. Therefore, the safety and effectiveness of TCM used in the treatment of emerging coronavirus infections should be carefully evaluated. The mechanism of action to improve COVID-19 remained not clear. It is worth to further evaluate its clinical efficacy for COVID-19, explore its potential molecular mechanism to improve multiple organ damage and identify their substance basis of the possible drug by multiple modern science and technology. Hopefully, the present study will provide reference and lay the foundation for the further development of new drugs for the prevention and treatment of COVID-19 and other viral infectious diseases.
Recent advances of traditional Chinese medicine on the prevention and treatment of COVID-19
- Received Date: 2020-06-23
- Available Online: 2020-12-20
Abstract: Coronavirus disease-2019 (COVID-19) is a new highly infectious disease caused by a novel coronavirus. Recently, the number of new cases infected pneumonia in the world continues to increase, which has aroused great concern from the international community. At present, there are no small-molecule specific anti-viral drugs for the treatment. The high mortality rate seriously threatens human health. Traditional Chinese medicine (TCM) is a unique health resource in China. The combination of TCM and Western medicine has played a positive and important role in combating COVID-19 in China. In this review, through literature mining and analysis, it was found that TCM has the potential to prevent and treat the COVID-19. Then, the network pharmacological studies demonstrated that TCM played roles of anti-virus, anti-inflammation and immunoregulation in the management of COVID-19 via multiple components acting on multiple targets and multiple pathways. Finally, clinical researches also confirmed the beneficial effects of TCM on the treatment of patients. This review may provide meaningful and useful information on further drug development of COVID-19 and other viral infectious diseases.