Application of Traditional Chinese Medicine in Prevention and Treatment of COVID-19

Corona virus disease 2019 (COVID-19) is a highly contagious acute respiratory disease. It has been considered as an international public health emergency by the World Health Organization due to its strong infectivity and extensive spread. As of May 27, 2021, a total of 168.04 million patients were diagnosed and 349.475 80 thousand patients died all around the world [1], which caused a major threat to the life safety of the people and seriously impacted the development of society. 

Currently, no specific drugs for the treatment of COVID-19 have been recorded except that isolation treatment and symptomatic supportive treatment are the main ones. Being a great treasure in China and a significant part in world medicine. TCM has great advantages and value in the sanitation and remedy of COVID-19, playing a pivotal role in preventing and blocking the spread of the virus in the early stage, enhancing patient symptoms during clinical treatment, reducing sequelae and accelerating patient recovery. With intent to provide a reference to the control of COVID-19 and subsequent researches, this paper clarifies the etiology and pathogenesis of COVID-19, and summarizes the application and the potential mechanism of TCM in the prophylaxis and treatment of COVID-19, laying a certain foundation for subsequent research.

COVID-19 is an emerging infectious disease with the characteristics of infectivity, epidemics, common clinical manifestations and phased pathological changes. COVID-19 belongs to the category of epidemic diseases in TCM, and its etiology and pathogenesis is to feel the Xie-qi (pathogenic factors) dominated by “dampness”, mainly including cold epidemic, cold and wet epidemic, damp poison epidemic and damp heat epidemic [2]. Clinical manifestations of COVID-19 involve fever, dry cough, fatigue, dyspnea, accompanied by nasal congestion, runny nose, sore throat, myalgia and diarrhea [3,4]. 

The “Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 8)” was issued by the National Health Commission of the People’s Republic of China [5], which divided COVID-19 into a medical observation period and a clinical treatment period (mild, moderate, severe and critical cases). According to the etiology and pathogenesis of each stage of COVID-19, the “Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 8)” recommends different treatment methods, and chooses the appropriate TCM prescriptions (Figure 1).  

 Figure 1: Chinese patent medicine or prescription for treatment by stages and types of COVID-19.

Early prevention of COVID-19 

TCM focuses on both internal and exterior factors in preventing diseases. On the one hand, TCM can enhance the body's resistance to diseases. On the other hand, it can prevent external evils from invading the body. Therefore, the early prevention of COVID-19 can be carried out in vivo and in vitro. 

Transmission of the virus happens mainly through respiratory droplets and close contact. There is the possibility of aerosol transmission in a relatively closed environment for a long-time exposure to high concentrations of aerosol [5]. During the outbreak of the epidemic, ancient doctors often used aromatic Chinese materia medica to make sachets or directly burn Chinese materia medica to isolate the virus and accomplish the purpose of prevention. Researchers have demonstrated that the sachet made of aromatic Chinese materia medica has the effects of inhibiting the proliferation of viruses and bacteria, strengthening immunity, fighting influenza viruses, and ameliorating lung function [6]. Zhao et al., found that the sachet made from the aromatic Chinese materia medica of Santalum album, Atractylodes lancea, Artemisia argyi, Angelica dahurica, Cinnamomum cassia Presl and Acorus tatarinowii has a certain inhibitory effect on Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Candida albicans in the air. It shows that the sachet can eliminate bacteria in the air to a certain extent [7]. Furthermore, Li et al., compared the incidence of influenza under the action of moxa fumigation with natural ventilation and air disinfection machines, and the results showed that the incidence of influenza in moxa fumigation environment was significantly lower than that of air disinfection [8]. It implies that fumigation of Chinese materia medica can better curb the spread of bacteria and viruses than other physical methods. 

Innate immunity is the first line of host defence against SRAS-CoV-2 infection, hence, it is crucial that the body's immunity and function be improved and enhanced to prevent COVID-19 occurrence and restore health. Studies have shown that taking preventive Chinese medicines can significantly reduce the probability of contracting COVID-19, because it can reinforce Zheng-qi (healthy energy) and dispel Xie-qi (pathogenic factors), strengthen the appearance of the body, spleen and tonify lung [9]. The study of Fuzheng Gubiao Fanggan Decoction bys Zhang et al., demonstrated that Fuzheng Gubiao Fanggan Decoction has a visible preventive function on COVID-19, and also showed a protective effect on upper respiratory tract infection, which was more obvious after two consecutive courses of treatment [10]. Ren et al., investigated the protective function of Qijing Fanggan mixture on medical staff during the epidemic of COVID-19, and learned that the symptoms of medical staff such as body temperature, cough, fatigue, nasal congestion, runny nose, sore limbs, and throat discomfort were conspicuously improved, indicating that Qijing Fanggan mixture has a better defensive effect on medical workers [11]. Besides, Yan et al., illustrated that Huoxiang Zhengqi Oral Liquid combined with Jinhao Jiere Granules can effectively reduce the incidence of respiratory diseases in residents with lower incidence and slight symptoms of adverse reactions, suggesting better safety and efficacy of TCM [12]. Furthermore, Hunan No. 2 Prescription proposed for the elderly and children can comprehensively enhance the human immune function by strengthening healthy energy, removing dirt and dampness, and clearing away heat and toxins [13]. 

Clinical treatment of COVID-19 

TCM has the characteristics of multi-target, multi-function and multi-pathway in the process of prevention and treatment of COVID-19 [14]. Regarding the different types and stages of COVID-19, personal physical condition of the patient, the doctor use Chinese medicine compounds as appropriate. TCM is more effective than Western medicine alone for the management of COVID-19 due to its enabling patients to receive maximum treatment efficacy with minimum side effects. For example, Wei et al., used Qingfei Paidu Decoction combined with Auricular-Point-Pressing Therapy and acupoint application treatment COVID-19 mild patient, showed that Qingfei Paidu Decoction reduced both the duration of diarrhea and the hospital stay duration [15]. In addition, Sun et al. reported that Qingfei Paidu Decoction can alleviate clinical symptoms, decrease the duration of fever and shorten the length of hospital stay, the effect is better than western medicine treatment [16]. Wang et al. discussed the clinical efficacy of Gegen Qinlian Pills in the treatment of COVID-19 and found that Gegen Qinlian Pills can improve patients' symptoms such as fever, cough, fatigue, cough, chest tightness, and nausea [17]. The survey on Qingfeiyin’s treatment of COVID-19 combined with hypertension showed that Qingfeiyin is effective in lowering blood pressure while healing COVID-19, implicating TCM produce their efficacy through the synergistic effects of multi-ingredients, multi-targets, and multi-pathways [18]. 

Integrated traditional Chinese and Western medicine therapy have been the most effective method in the treatment of COVID-19 in China. Chinese doctors and scientists have conducted many clinical studies on the treatment of COVID-19 with the integration of TCM and western medicine. They studied that quantity TCM prescriptions have excellent efficacy in the treatment of COVID-19 because TCM prescriptions can not only effectively relieve the complications of COVID-19 patients, alleviate oxidative stress, but also can regulate the number of immune cell and lower the levels of inflammatory cytokines (Table 1). 

Table 1: Clinical application of TCM prescriptions intervention on COVID-19.

Abbreviations: WBC = White Blood Cell Count; LYM = Lymphocyte count; LYMPH = percentage of Lymphocytes; GRAN = neutrophil count; PLT = Platelet Count; hs-CRP = High-sensitivity C-reactive protein; ESR = Erythrocyte Sedimentation Rate; IL-6 = Interleukin-6; SpO₂ = peripheral oxygen saturation; PTC = Procalcitonin; AST = Aspartate Aminotransferase; ALT = Alanine Aminotransferase; BUN= urea nitrogen; CR = Creatinine; FBG = Fasting Blood Glucose; UA = Uric Acid; TBIL = Total Bilirubin; LDH = Lactate Dehydrogenase. 

The analysis and evaluation of therapeutic efficacy on TCM for COVID-19 have been conducted by Chinese scholars, expressing that TCM has excellent advantages in curing COVID-19. For instance, Zhang et al. analyzed and inquired about the influence of early intervention of TCM on the disease outcome of severe patients with COVID-19. He found that TCM can effectively alleviate the inflammatory reaction, restore the internal homeostasis and reduce mortality [31]. Zhou et al., stated that comprehensive therapy of TCM can significantly improve the clinical symptoms of patients, concurrently, it also has a positive effect on facilitating patients' nucleic acid to turn negative [32]. Meanwhile, Qin et al., retrospectively analyzed the clinical data of severe and critical cases with COVID-19, and found that integrated traditional Chinese and Western medicine therapy can availably increase the cure rate, reduce the mortality rate, shorten the antipyretic time, and play a certain role in ameliorating lymphopenia and elevated transaminase [33]. Observations on the clinical efficacy of TCM used in the treatment of confirmed or alleged cases of COVID-19 have shown that the individual treatment protocol is based on the concept of "Syndrome Differentiation." can effectively improve patients' discomfort symptoms [34]. The retrospective analysis by Hu et al. claimed that the therapy of COVID-19 with integrated traditional Chinese and Western medicine can significantly change the abnormalities of laboratory or imaging and the clinical symptoms of patients. At the same time, it also can better increase the clinical cure rate than the western medicine treatment group [35].

Recovery treatment for COVID-19 

Apart from the respiratory system, COVID-19 has an impact on all systems of the body, including the immune, digestive, cardiovascular, neurological, genitourinary and other extra pulmonary systems [36]. In clinical cure cases, there are a considerable number of patients with varying degrees of sequelae and significantly decreased quality of life. The primary convalescence pathogenesis of COVID-19 is remained toxicity and lingering pathogen due to deficient vital qi, and it would lead to Qi and Yin deficiency and spleen and lung qi deficiency [37]. Therefore, it is essential to pay attention to dispel the evil qi caused by exogenous incubating pathogens, at the same time to strengthen spleen and tonify lung, nourish Qi and Yin, and restoring the balance of Yin and Yang. TCM has exclusive advantages in reducing the convalescent sequelae of COVID-19 and promoting patient rehabilitation. For example, Wang et al found that Qingfei Paidu Decoction combined with Western medicine treatment can significantly improve the clinical symptoms and signs of COVID-19 patients, and have a better effect on the recovery of patients after illness [38]. He et al., said that Shengmai San can ameliorate clinical symptoms such as dry throat, thirst and night sweats in convalescent patients, reduce inflammatory indicators, improve oxygenation, promote absorption of lung lesions and turn negative nucleic acid [25]. Besides, the investigation of the clinical efficacy of Yiqi Yangyin Granules combined with recovery-promoting exercises shows that this method can significantly improve adverse symptoms, and better strengthen the lung function and immune function [39].

Potential mechanisms of TCM to combat COVID-19

The potential mechanisms of COVID-19 pathogenesis include direct virus invasion of lung tissue, systemic inflammation and cytokine storm, apoptotic response, immune crosstalk disorders and abnormal blood coagulation, the decline of immune function and abnormal cellular metabolism [40-46]. Focusing on the potential mechanisms of COVID-19, TCM treatment can help to cure the COVID-19 by reducing the expression level of inflammatory factors and apoptosis, inhibiting the cytokine storm, minimizing the damage of free radicals, and enhancing the immune function of the body [47].

Antiviral 

COVID-19 is a new emerging pulmonary infection caused by SARS-COV-2, so anti-viral infection is crucial for combating the COVID-19 pandemic. Lianhua Qingwen Capsules significantly protects against virus attacks by inhibiting SARS-COV-2 replication, affects virus morphology and exerts anti-inflammatory activity in vitro [48]. Meanwhile, Tan et al., stated that Lianhua Qingwen Capsules exhibited an inhibitory effect on cytopathic changes caused by virus infection, appreciably reduced the number of vesicle virus particles, and had a strong inhibitory effect on SARS-CoV-2 [49]. Wang et al., confirmed that Qingfei Paidu Decoction can up-regulate intracellular γ-interferon (INF-γ) mRNA expression, and simultaneously induce the expression of Interferon-stimulated genes (ISGs), Oligoadenylate Synthase-1 (OAS1), PKR and IFITM3, which affects the combination of the S protein on the surface of the coronavirus and the cell surface receptor to restrain the invasion of SARS-COV-2 [50].

Anti-inflammatory and suppressive cytokine storm 

Secretion of pro-inflammatory cytokines in the lungs following SARS-CoV-2 infection represents a crucial step in promoting the inflammatory response in various lung diseases [51]. Therefore, inhibiting inflammatory cytokine storm is the key to curing COVID-19. Studies suggest that Xuebijing Injection can decrease pro-inflammatory factors such as TNF-α, IL-1, IL-6, IL-8, IL-17, and inhibit the expression of High Mobility Group Protein B1 (HMGB1). And it showed excellent anti-inflammatory effect via inhibiting the Toll-like receptor 4 (TLR4) and nuclear factor κB (NF-κB) signalling pathways [52]. At the same time, it can regulate the Th17/Treg balance in rat model of sepsis, trim down serum the level of TNF-α and IL-6, alleviate cytokine storm, and improve survival rate [53]. Besides, Jinhua Qinggan Granules can significantly reduce IFN-γ and C - reactive protein (CRP) levels in the serum of influenza patients, and enhance the immune function of the body [54]. Lianhua Qingwen Capsule can decrease the levels of IL-10, IL-17, TNF-α and other inflammatory factors of patients with pneumonia, and slow down the impairment of lung function [55]. Preparations containing Glycyrrhiza glabra have great anti-inflammatory activity because it can reduce intracellular oxidative stress, decrease HMGB1 expression and inhibit NF-κB expression and activity, and it is a potential drug for the treatment of COVID-19 [56].

Reduce oxidative stress and free radical damage 

Multiple organ damage and failure caused by COVID-19 are associated with oxidative stress free radicals. When human body is infected with the virus, the immune system is activated, and the excessive immune response causes T lymphocytes to attack various organs, and also produces a large number of free radicals, which can affect the body's organs. Many TCM exhibit an effect of reducing oxidative stress and have been applied to the different stages of COVID-19 treatment. For instance, the total flavonoids of licorice can down-regulate the phosphorylation of Extracellular regulated protein kinases (ERK) in the MAPK signaling pathway, decrease the accretion of free radicals via regulating the ERK/MAPK pathway, and reduce the damage to the organs [57]. Astragaloside IV can activate the PI3K/Akt/mTOR signaling pathway, increase the activity of SOD, and reduce the accretion of free radicals [58]. Shengmai injection has an anti-oxidant effect by inhibiting the accretion of high levels of free radicals that are accompanied by excessive activation of the Ras/MAPK pathway [59].

Inhibit apoptosis 

Some COVID-19 patients rapidly develop severe pneumonia symptoms and complications including Acute Respiratory Distress Syndrome (ARDS) or multiple organ failure due to damage to the pulmonary capillary endothelial cells and alveolar epithelial cells [60,61]. The study revealed that Xuebijing Injection can increase the proportion of Th1 cells in septic rats, promote the apoptosis of CD4+ CD25+ T cells, promote the apoptosis of CD4+ CD25+ T cells, inhibit the expression of Fas, Bax, PD-1 and other apoptosis-related proteins, and reduce the apoptosis of T cells and neutrophils [53]. Tongfu Qingying Decoction can down regulate the expression of Fas protein in lung tissue of model rats, inhibit the level of TNF-α inflammatory mediators, and have the effect of reducing inflammation and anti-apoptosis in rats with sepsis acute lung injury [62]. Jianpi Huatan Quyu Recipe can reduce the expression of Bax, Cyto C and Caspase3 in cardiomyocytes, increase the expression of Bcl-2, and then reduce the apoptosis of cardiomyocytes in atherosclerotic Bama mini-pigs [63].

As is known to all, TCM possesses a long history of preventing and treating diseases, and it emphasizes the overall concept, syndrome differentiation and treatment, which can treat even, prevent diseases, especially in the treatment of plague, which has unique advantages [64]. TCM can intervene in the prevention and treatment of COVID-19 in the whole process. In the early stage, some active measures such as TCM sachets, TCM fumigation, and preventive TCM compounds have produced positive effects in terms of blocking the transmission of the virus. During the clinical treatment, the doctors obtained excellent results by using the corresponding TCM compound and Chinese patent medicine according to the stage and type. When the patient is in the recovery stage, the use of appropriate TCM compound adjuvant treatment can speed up the patient's recovery and reduce the occurrence of sequelae. Moreover, the whole regulation, multi-target multi-ingredients andmulti-links makes TCM have a better therapeutic advantage in treatment of COVID-19. TCM achieves the treatment of COVID-19 by anti-virus, reducing the expression level of inflammatory factors and apoptosis, inhibiting the cytokine storm, minimizing the damage of free radicals, and enhancing the immune function of the body. 

In China, the epidemic situation of COVID-19 has been currently controlled in stages, and most of the confirmed cases have obtained favourable results due to the interventional diagnosis and therapy of TCM. As the COVID-19 has been developed into pandemics, there exist great challenges for global prevention and control of the pandemics. Therefore, we should give full play to the advantages of traditional Chinese medicine in the prevention and treatment of COVID-19, which can greatly alleviate the pressure of the epidemic on world development and contribute to the health and hygiene of mankind. 

TCM has achieved great success in the prevention and treatment of COVID-19. Clinical practice has proved that many traditional Chinese medicines and compounds can significantly alleviate and improve the clinical symptoms of COVID-19 patients, but there are still some shortcomings. On the one hand, TCM combat COVID-19 are short of experimental studies on pharmacological actions and pharmacodynamic material basis, which makes it difficult for TCM preparations to form a unified standard. On the other hand, the primary cellular target(s) for TCM preparations and its mechanisms for treating COVID-19 remain to be elucidated, and therefore TCM may not be globally generalizable. Perhaps, we can predict the material basis and molecular mechanism of TCM againstCOVID-19 through network pharmacology and molecular docking, and then verify it by a complex set of proteomic, transcriptomic and metabolomic profiling of the chemostat phase. Meanwhile, we can further combine the clinical efficacy to conduct systematic research on the prevention and treatment of COVID-19 with Traditional Chinese medicine.

This work was supported by Department of Science and Technology of Hunan Province (No. 2020SK3035) and First-class Discipline Project on Chinese Pharmacology of Hunan University of Chinese Medicine (No. 201803).

1. Diao Y, Liu XJ, Wang T, Zeng X, Dong C, et al. (2020) Estimating the cure rate and case fatality rate of the ongoing epidemic COVID-19. Chinese Sci Bull 65: 2342-2347.
2. Zhang MF (2020) A review of prevention and treatment of COVID-19 by Chinese medicine. Clin J Chinese Med 12: 27-31.
3. Lu YR, Wang YG, Jiao YQ (2020) Research Progress of Traditional Chinese Medicine Syndrome Differentiation and Treatment of Coronavirus Disease 2019. J Tradit Chinese Med 61: 1846-1851.
4. Huang CL, Wang YN, Li XW, Ren L, Zhao J, et al. (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395: 497-506.
5. National Health Commission of the People's Republic of China (2020) Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 8). National Health Commission of the People's Republic of China, China.
6. Chen Y, Su TS, Wu JJ (2021) Discussion on Application of Herbal Sachet in COVID-19. J Shaanxi Univ Chinese Med 44: 15-51.
7. Zhao H, Wang YH, Feng YQ (2013) Observation on the effect of air disinfection with the aromatic smell of Chinese herbal sachet. Chinese Med Mod Dist Edu Chin 11: 157-158.
8. Li RH, Jiang XS (2011) Clinical observation of moxibustion air disinfection in preventing influenza. Chinese J Nosocomiol 21: 1606-1607.
9. Li JC, Li SY, Gu J (2021) Retrospect and thinking on the prevention of novel coronavirus pneumonia by traditional Chinese medicine based on the theory of "preventing diseases". J Chinese Med Mater 2021: 1021-1030.
10. Zhang D (2021) A randomized controlled study of Fuzheng Gubiao Fanggan Decoction intervention in high risk group of Corona Virus Disease 2019. Pharm Clin Chinese Mater Med 12: 26-29.
11. Ren QL, Zhang M, Luo HY (2021) Prevention and protection effect of Qijing Fanggan Mixture for medical personnel during the COVID-19 epidemic period. J Sichuan Tradit Chinese Med 39: 19-22.
12. Yan BH, Jiang ZW, Zeng JP, Tang JY, Ding H, et al. (2020) Large-scale prospective clinical study on prophylactic intervention of COVID-19 in community population using Huoxiang Zhengqi Oral Liquid and Jinhao Jiere Granules. China J Chinese Mater Med 45: 2993-3000.
13. Zhao TJ, Shi YN, Jiang YL, et al. (2020) The Network Pharmacology Study of Hunan No.2 Prescription for Prevention and Treatment of COVID-19 Infection Based on Enhancing Immunity. Guid J Tradit Chinese Med Pharm 26: 1-9.
14. Li CH, Li B, Lei SS, Long L, Ke Q, et al. (2020) Advances in the Prevention and Treatment of Corona Virus Disease 2019. China Pharm 23: 1168-1174.
15. Wei YB (2021) Lung-Clearing Detoxification Decoction Combined with Auricular Point Sticking and Acupoint Application for Mild COVID-19. Henan Tradit Chinese Med 41: 491-494.
16. Sun YN, Lv WL, Li H, et al. (2021) Qingfei Paidu Decoction for Treatment of Mild/Moderate COVID-19 in 295 Cases:A Multi-Centered. J Tradit Chinese Med 62: 599-603.
17. Wang LQ, Li WN, Huang W, et al. (2020) Clinical study of Gegen Qinlian pill in treating COVID-19. Moder Tradit Chinese Med Mater Medica-World Sci Technol 22: 3509-3514.
18. Li JZ, Yao YJ, Yi N, et al. (2020) The Clinical Effect of Qingfei Decoction in Treating 152 Patients with COVID-19 Combined with Hypertension. J Zhejiang Chinese Med Univ 44: 729-733.
19. Ou JZ (2021) Clinical observation of Fuzheng Xuanfei Huashi Recipe on novel coronavirus pneumonia. J China Prescript Drug 19: 127-130.
20. He Q, Zhang QJ, Gan XW, et al. (2021) Analysis of clinical efficacy of Buzhong Yiqi Decoction in treating mild novel coronavirus pneumonia. J Emerg Tradi Chinese Med 30: 385-387.
21. Zhang P, Pan GT (2021) Clinical Study on the Improvement of Inflammatory Cytokines in Critically Ill Patients with COVID-19 Treated by Qingfei Paidu Decoction. Moder Tradit Chinese Med Mater Medica-World Sci Technol 23: 391-395.
22. Chen CW, Li XL, Liu YF, et al. (2021) Clinical Study of Lianhua Qingwen Capsule in the Treatment of Corona Virus Disease 2019. Res Integr Tradit Chinese West Med 13: 1-4.
23. Song QH, Liu Y, Zhu HJ, Yong Y, Chunyan L, et al. (2021) Clinical Study on Huashijiedu Decoction in Treating Patientswith Damp-heat Stagnation Lung Syndrome of New Coronavirus Pneumonia. Yunnan J Tradit Chinese Med Mater Medica 42: 23-27.
24. Wang Y, Chen L, Zheng L, et al. (2021) Clinical effects of Qingfei Paidu Decoction combined with conventional treatment on patients with coronavirus disease 2019. Chinese Tradit Patent Med 43: 656-659.
25. He Q, Zhang QJ (2021) Analysis of clinical efficacy of Shengmai San in the treatment of new type coronavirus pneumonia with Qi and Yin deficiency syndrome in the recovery period. Acta Chinese Med Pharmacol 49: 84-86.
26. Ping XH, Xu HL, Fu DF, et al. (2021) Clinical observation of Jiawei Yupingfeng powder combined with western medicine in the treatment of the novel coronavirus pneumonia. Med Forum 25: 149-151.
27. Dai QZ, Jiang SH, Liu T, et al. (2020) Novel Coronavirus Pneumonia Treated by Qingfei Paidu Decoction:A Clinical Analysis of 36 Cases. J Guizhou Univ Tradit Chinese Med 42: 34-38.
28. Liu YJ (2021) Analysis of the clinical efficacy of combined western medicine with Huashibaidu Decoction in the treatment of severe new coronavirus pneumonia. Laborat Med Clin 18: 1152-1153.
29. Hu F, Guo AH, Huang L, et al. (2021) Jinyinhua Liquid at different dosage combined with western medicine conventional treatment for common type COVID-19: a multicenter trial of 187 cases. J Tradit Chinese Med 62: 510-515.
30. Shi TF, Zhou GC, Zhang LY, et al. (2020) Clinical Efficacy of Xuanfei Huazhuo Prescription on 40 Cases of COVID-19. Chinese J Exp Tradit Med Formu 26: 26-31.
31. Zhang J, Shu TT, Luo WD, et al. (2021) Association between early treatment with chinese herbal medicine and clinical qutcomes in patients with severe coronavirus disease 2019: a petrospective study. J Tradit Chinese Med 62: 1046-1051.
32. Zhou HW, Chen XS, Du SS, et al. (2021) Treatment of 51 cases of COVID-19 nucleic acid Fuyang with traditional Chinese medicine[J]. Contemporary Medicine 27: 1-4.
33. Qin LX, Lv WL, Yang M, et al. (2021) Clinical characteristics, drug treatments and prognoses in 605 patients with severe and critical corona virus disease 2019 in Hubei,China: a multi-center, retrospective, cohort study. Chinese Arch of Tradit Chinese Med 39: 89-95.
34. Wang T, Shi L, Chen YY, Fang Y, Yang W, et al. (2020) Clinical Efficacy Analysis of 50 Cases of Corona Virus Disease 2019 in Traditional Chinese Medicine. Jilin J Chinese Med 40: 281-285.
35. Hu YQ, Lu JQ, Huang J, Launder, Jinhai H, et al. (2020) Clinical observation of 31 cases with COVID-2019 Treated with Guizhi erchen decoction based on triple-Jiao sequential therapy. Chinese Arch of Tradit Chinese Med 38: 1-5.
36. Shi SF, Zhang XN, Wang BH (2021) Progress on TCM Interventions of COVID-19 in Recovery Period. J Nanjing Univ Tradit Chinese Med 37: 473-476.
37. Chen L, Li GX, Li XY, et al. (2020) Initial differentiation and treatment in the recovery stage of COVID-19 based on academician Tong xiaolin’s theory of“Rheumatism in Zang-fu Organs”. J Yunnan Univ Tradit Chinese Med 43: 25-27.
38. Wang QL, Sun LF, Zhao MF, et al. (2021) The Application Effect of Qingfei Paidu Decoction in the Treatment of Patients with COVID-19 with the Syndrome of Deficiency of Both Qi and Yin. Acta Chinese Med 36: 910-914.
39. Shi SF, Fang ZY, Xiong K, et al. (2021) Clinical studies of comprehensive TCM treatment to 30 cases of Qi Yin deficiency type of COVID-19 in its recovery period. Jiangsu J Tradit Chinese Med 53: 25-28.
40. Xu X, Li P, Wei X (2021) The SARS-CoV-2 antibody and drug research based on the structure of the spike protein and the mechanism of cell entry. Chinese J Biochem Mol Biol 37: 1-10.
41. Zou X, Chen K, Zou JW, Han P, Hao J, et al. (2020) Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med-PRC 14: 185-192.
42. Dong CQ, Yang H (2020) Cytokine sorm by COVID-19 and treatment strategy of traditional Chinese medicine. Chinese Arch Tradit Chinese Med 38: 15-18.
43. Aaron JW, Arjun R, Nancy QZ, Roque J, Martínez-Colón GJ, et al. (2020) A single-cell atlas of the peripheral immune response in patients with severe COVID-19. Nat Med 26: 1070-1076.
44. Wang S, Wang GZ, Tang T, et al. (2021) Research progress on the pathogenesis and drug treatment of novel coronavirus pneumonia. Shaanxi Med J 50: 638-641.
45. Zhu N, Zhang DY, Wang WL, Li X, Yang B, et al. (2020) A Novel Coronavirus from Patients with Pneumonia in China, 2019. New Engl J Med 382: 727-733.
46. Shen B, Yi X, Sun Y, Bi X, Du J, et al. (2020) Proteomic and Metabolomic Characterization of COVID-19 Patient Sera. Cell 182: 59-72.
47. Zhang Y, Tang DZ, Shu B, et al. (2020) Study on the action mechanisms of traditional Chinese medicine for the intervention of coronavirus disease 2019 (COVID-19): based on the literature. J Tradit Chinese Med 61: 1110-1117.
48. Li RF, Hou YL, Huang JC, Weiqi P, Qinhai M, et al. (2020) Lianhuaqingwen exerts anti-viral and anti-inflammatory activity against novel coronavirus (SARS-CoV-2). Pharmacol Res 156: 104763.
49. Tan DX, Shi WL, Liu N, et al. (2021) Observation on the efficacy of Lianhua Qingwen Capsules in the early anti-virus and anti-inflammation of new coronary pneumonia. J China Prescript Drug 19: 92-93.
50. Wang K, Yan HY, Wu S, et al. (2021) Inhibitory effect of Qing-Fei-Pai-Du decoction on coronavirus in vitro. Acta Pharm Sinica 56: 1400-1408.
51. Batah SS, Fabro AT (2021) Pulmonary pathology of ARDS in COVID-19: A pathological review for clinicians. Respir Med 176: 106239.
52. Li CY, Zhang XY, Liu S, et al. (2020) Current Evidence and Research Prospects of Xuebijing Injection in Treating Novel Coronavirus-infected Pneumonia(COVID-19). Moder Tradit Chinese Med Mater Medica-World Sci Technol 22: 242-247.
53. Chen X, Feng YX, Shen XY, Pan G, Fan G, et al. (2018) Anti-sepsis protection of Xuebijing injection is mediated by differential regulation of pro- and anti-inflammatory Th17 and T regulatory cells in a murine model of polymicrobial sepsis. J Ethnopharmacol 211: 358-365.
54. Qi JP, Qi XY, Wang XJ (2016) Clinical efficacy of different doses of Jinhuaqinggan granule on influenza and serum levels of cytokines. Mod Med J 44: 1664-1669.
55. Chen TY, Zhu S, Bian HE, et al. (2018) Effect of Lianhua Qingwen Capsules on pulmonary function index, serum inflammatory factor level and curative effect in children with mycoplasma pneumoniae pneumonia. Chinese Arch Tradit Chinese Med 36: 2713-2715.
56. Ge FJ, Zeng CM, Yan FJ, et al. (2021) Glycyrrhizic acid:a potential drug against COVID-19. Acta Pharm Sinica 56: 1211-1216.
57. Yang XL, Liu D, Bian K, Zhang DD (2013) Study onin vitro anti-inflammatory activity of total flavonoids from Glycyrrhizae Radix et Rhizoma and its ingredients. China J Chinese Mater Med 38: 99-104.
58. Zhang J, Ma CL, Wang ZG (2014) Improvement effects of astragaloside ? on myocardial focal ischemia-reperfusion injury and its influence in PI3K/Akt/mTOR signaling pathway. J Jilin Univ 40: 991-1130.
59. Liu Y (2017) Study on the mechanism of Shengmai San inhibiting the overactivation of Ras/MAPK pathway. Lanzhou: Lanzhou Univ, China.
60. Zhang Y, Tang DZ, Shu B, Wenxiong L, Jiali Z, et al. (2020) Evaluation and analysis on the SARS-CoV-2-induced injuries in multiple organs and the intervention of traditional Chinese medicine based on renin-angiotensin system. Moder Tradit Chinese Med Mater Medica-World Sci Technol 22: 264-269.
61. Tom L, Neil K, Robert F (2014) Cell Death and Cell Death Responses in Liver Disease: Mechanisms and Clinical Relevance. Gastroenterology 147: 765-783.
62. Chen Q, Ren XX, Han D, Shi R, Hong SX, et al. (2019) Effects of Tongfu Qingying Decoction on Fas and TNF-α in Rats with Acute Lung Injury Induced by Sepsis. Chinese J Inform Tradit Chinese Med 26: 40-44.
63. Cheng YY, Liu L, Jia LQ, Song, Nangu L, et al. (2019) Invigorating spleen, removing phlegm and eliminating blood stasis method by oxidative stress improved spleen deficiency and phlegm turbidity atherosclerosis bama mini-pigs with myocardial apoptosis. Chinese Arch Tradit Chinese Med 37: 19-23.
64. Wei PY, Wei CH, Guo C, et al. (2021) Advantages of traditional Chinese medicine in the treatment of new coronavirus pneumonia. Chinese J Clin Rat Drug Use 14: 179-181.