A review on the treatment of Herbal Medicine for asymptomatically infected COVID-19 patients

Article information

J Korean Med. 2021;42(1):99-109
Publication date (electronic) : 2021 March 01
doi : https://doi.org/10.13048/jkm.21007
1Department of Korean Medicine, College of Korean Medicine, Woosuk University
2Department of Pediatrics, College of Korean Medicine, Woosuk University
3Kyunghee Oriental Medical Clinic, Seoul
4Department of Internal Medicine, College of Korean Medicine, Woosuk University
Correspondence to: 장인수 54987 전라북도 전주시 완산구 어은로 46 우석대학교부속한방병원 Tel:+82-63-220-8617 Fax:+82-63-220-8616, E-mail: mackayj@naver.com
Received 2021 February 3; Revised 2021 February 16; Accepted 2021 February 18.

Abstract

Objectives

Objective: The purpose of this study is to investigate the treatment of herbal medicine for patients with COVID-19 asymptomatic infections.

Method

In English, search engines such as ‘PubMed’, ‘Science Direct’, and ‘Cumulative Index to Nursing and Allied Health Literature (CINAHL)’ were used. In Chinese, search engines such as ‘China National Knowledge Infrastructure (CNKI)’ and Wanfang were used. The keywords for the search engines were ‘COVID-19’, ‘asymptomatic infection’, ‘Korean Medicine’, ‘traditional Chinese medicine’, ‘herbal medicine’, and etc. Only clinical studies using herbal medicine for patients without fever or respiratory symptoms were selected. We excluded the cases that do not fit the research topic.

Results

A total of 5 studies were finally selected. Among them, four of them used integrated herbal medicine and Western medicine, and one of the studies treated exclusively for herbal medicine. There were a total of seven prescriptions for herbal medicine used in the study. Outcome variables were used as following: lab test, nucleic acid conversion time, hospitalization period, chest CT, and etc. In the RCT study, herbal medicine and Western medicine decreased nucleic acid conversion time, average hospitalization time compared to the control group, but it was not statistically significant. No other adverse reactions were reported in all studies.

Conclusion

According to the results, integrated herbal medicine and Western medicine might be an effective treatment for patients with COVID-19 asymptomatic infection reducing hospitalization period, time of nucleic acid turning negative. No severe adverse effects were reported. However, it is thought that better-designed research will be needed in the future.

Fig. 1

PRISMA flow chart.

Summary of Included Studies

Composition of herbal medicine formula

References

1. Lee S, Kim T, Lee E, Lee C, Kim H, Rhee H, Park S, Son H, Yu S, Park J, Choo E, Park S, Loeb M, Kim T. Clinical course and molecular viral shedding among asymptomatic and symptomatic patients with SARS-CoV-2 infection in a community treatment center in the Republic of Korea. JAMA Intern Med 2020;180(11):1–6. 10.1001/jamainternmed.2020.3862.
2. Oran DP, Topol EJ. Prevalence of Asymptomatic SARS-CoV-2 Infection - A Narrative Review. Ann Intern Med 2020;173(5):362–367. 10.7326/M20-3012.
3. Shi H, Han X, Jiang N, Cao Y, Alwalid O, Gu J, Fan Y, Zheng C. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect Dis 2020;20:425–434. 10.1016/S1473-3099(20)30086-4.
4. Lee D, Kim Y, Lee H, Hwang H, Nam S, Kim J. The influence of public fear, and psycho-social experiences during the coronavirus disease 2019 (COVID-19) pandemic on depression and anxiety in South Korea. Kor J Counsel Psychoth 2020;32(4):2119–2156.
5. Chen P, Lee N, Cia C, Ko W, Hsueh P. A review of treatment of coronavirus disease 2019 (COVID-19): therapeutic repurposing and unmet clinical needs. Front Pharmacol 2020;11:584956. 10.3389/fphar.2020.584956.
6. Gao Z, Xu Y, Sun C, Wang X, Guo Y, Qiu S, Ma K. A systematic review of asymptomatic infections with COVID-19. J Microbiol Immunol Infect 2020;10.1016/j.jmii.2020.05.001. Epub ahead of print.
7. Jang I, Baik Y, Sun S, Lee J, Han C. An overview of the herbal remedies for severe acute respiratory syndrome (SARS) in WHO official report (2004). Korean J Orient Int Med 2009;30(3):571–581. uci: G704-000999.2009. 30.3.014.
8. Wang Y, Xue J, Dai E. Department of Internal Medicine, The Fifth Hospital of Shijiazhuang City, Hebei. Clinical study on the treatment of patients with novel coronavirus pneumonia and asymptomatic infection with integrated traditional Chinese and western medicine. Hebei J TCM 2020;42(05):645–649. 10.3969/j.issn.1002-2619.2020.05.001.
9. Xie X, Song Y, Ran C, Chen S, Wei D, Wang C, Zhou Z, Ran J, Xiang Y, Yu Z, Zhao Y, Luo X, Tao W, Li Y, Tang J, Liu H. Clinical research of Chaihu Ganlu Decoction on COVID-19 asymptomatic infected patients. JETCM 2020;29(11):1888–1890. 10.3969/j.issn.1004-745X.2020.11.003.
10. Luo X, Liu H, Xie X, Song Y, Ran C, Wei D, Chen S, Xiang Y, Zhao Y, Tang J. Clinical Observation on 50 cases of asymptomatic infected with COVID-19 by treatment of integrated of Traditional Chinese and Western Medicine. J Chengdu Univ of TCM 2020;43(04):14–18. 10.13593/j.cnki.51-1501/r.2020.04.014.
11. Chen S, Wei Y, Jiao Y, Li M. A case report on the treatment of a COVID-19 asymptomatic infected child. China’s Naturopathy 2020;28(14):1–3. 10.19621/j.cnki.11-3555/r.2020.1401.
12. Liu Q, Zhang Y, Long Y. A child infected with severe acute respiratory syndrome coronavirus 2 presenting with diarrhea without fever and cough: A case report. Medicine (Baltimore) 2020;99(33):e21427. 10.1097/MD.0000000000021427.
13. Cella L, Gagliardi G, Hedman M, Palma G. Injuries from asymptomatic COVID-19 disease: New hidden toxicity risk factors in thoracic radiation therapy. Int J Radiat Oncol Biol Phys 2020;108(2):394–396. 10.1016/j.ijrobp.2020.06.055.
14. Qiu J. Covert coronavirus infections could be seeding new outbreaks. Nature 2020;10.1038/d41586-020-00822-x. Epub ahead of print.
15. Dalskov L, Møhlenberg M, Thyrsted J, Blay-Cadanet J, Poulsen ET, Folkersen BH, Skaarup SH, Olagnier D, Reinert L, Enghild JJ, Hoffmann HJ, Holm CK, Hartmann R. SARS-CoV-2 evades immune detection in alveolar macrophages. EMBO Rep 2020;21(12):e51252. 10.15252/embr.202051252.
16. Han H, Xu Z, Cheng X, Zhong Y, Yuan L, Wang F, Li Y, Liu F, Jiang Y, Zhu C, Xia Y. Descriptive, retrospective study of the clinical characteristics of asymptomatic COVID-19 patients. mSphere 2020;5(5):e00922–20. 10.1128/mSphere.00922-20.
17. Meyerowitz EA, Richterman A, Bogoch II, Low N, Cevik M. Towards an accurate and systematic characterisation of persistently asymptomatic infection with SARS-CoV-2. Lancet Infect Dis 2020;S1473-3099(20)30837-9. 10.1016/S1473-3099(20)30837-9.
18. Jang I, Hsing L, Han C. An overview on severe acute respiratory syndrome(SARS) in WHO clinical reports. Korean J Orient Int Med 2005;26(2):440–452. uci: G704-000999. 2005.26.2.001.
19. Korean Institute of Oriental Medicine. TCM treatment trend on COVID-19 in China. 2020;25:88.
20. Kim D, Chu H, Min B, Moon Y, Park S, Kim K, Park S, Kim Y, Song M, Choi G, Lee E. Telemedicine center of Korean Medicine for treating patients with COVID-19: a retrospective analysis. Integr Med Res 2020;9(3):100492. 10.1016/j.imr.2020.100492.
21. Ge H, Wang X, Yuan X, Xiao G, Wang C, Deng T, Yuan Q, Xiao X. The epidemiology and clinical information about COVID-19. Eur J Clin Microbiol Infect Dis 2020;39(6):1011–1019. 10.1007/s10096-020-03874-z.
22. Dong Z, Lu X, Tong X, Dong Y, Tang L, Liu M. Forsythiae Fructus: A Review on its phytochemistry, quality control, pharmacology and pharmacokinetics. Molecules 2017;22(9):1466. 10.3390/molecules22091466.
23. Chang H, Yeh C, Sheu F. A novel immunomodulatory protein from Poria cocos induces Toll-like receptor 4-dependent activation within mouse peritoneal macrophages. J Agric Food Chem 2009;57(14):6129–39. 10.1021/jf9011399.
24. Abe H, Sakaguchi M, Odashima S, Arichi S. Protective effect of saikosaponin-d isolated from Bupleurum falcatum L. on CCl4-induced liver injury in the rat. Naunyn Schmiedebergs Arch Pharmacol 1982;320(3):266–71. 10.1007/BF00510139.
25. Hattori T, Furuta K, Hayashi K, Nagamatsu T, Ito M, Suzuki Y. Studies on the antinephritic effects of plant components (6): antinephritic effects and mechanisms of phellodendrine (OB-5) on crescentic-type anti-GBM nephritis in rats (2). Jpn J Pharmacol 1992;60(3):187–95. 10.1254/jjp.60.187.
26. Jang M, Kim Y, Bae E, Oh T, Choi H, Lee J, Oh H, Lee S. Saikosaponin D isolated from Bupleurum falcatum inhibits selectin-mediated cell adhesion. Molecules 2014;19(12):20340–9. 10.3390/molecules191220340.
27. Ying Z, Li X, Dang H, Wang F, Xu X. Saikosaponin-d affects the differentiation, maturation and function of monocyte-derived dendritic cells. Exp Ther Med 2014;7(5):1354–1358. 10.3892/etm.2014.1568.
28. Ozaki Y, Rui J, Tang Y, Satake M. Antiinflammatory effect of Forsythia suspensa Vahl and its active fraction. Biol Pharm Bull 1997;20(8):861–4. 10.1248/bpb.20.861.
29. Ozaki Y, Rui J, Tang Y. Antiinflammatory effect of Forsythia suspensa V(AHL) and its active principle. Biol Pharm Bull 2000;23(3):365–7. 10.1248/bpb.23.365.
30. Abdel-Rahman MK. Can apricot kernels fatty acids delay the atrophied hepatocytes from progression to fibrosis in dimethylnitrosamine (DMN)-induced liver injury in rats? Lipids Health Dis 2011;10:114. 10.1186/1476-511X-10-114.
31. Yurt B, Celik I. Hepatoprotective effect and antioxidant role of sun, sulphited-dried apricot (Prunus armeniaca L.) and its kernel against ethanol-induced oxidative stress in rats. Food Chem Toxicol 2011;49(2):508–13. 10.1016/j.fct.2010.11.035.
32. Yuan B, Yang R, Ma Y, Zhou S, Zhang X, Liu Y. A systematic review of the active saikosaponins and extracts isolated from Radix Bupleuri and their applications. Pharm Biol 2017;55(1):620–635. 10.1080/13880209.2016.1262433.
33. Dai Y, Wan S, Gong S, Liu J, Li F, Kou J. Recent advances of traditional Chinese medicine on the prevention and treatment of COVID-19. Chin J Nat Med 2020;18(12):881–889. 10.1016/S1875-5364(20)60031-0.

Article information Continued

Fig. 1

PRISMA flow chart.

Table 1

Summary of Included Studies

First author Study design Participants N gender (number): age Interventions Control Outcome variables Results Treatment duration Adverse event
Herbal medicine Western medicine
Wang8 RCT N=16
Control group (n=8)
M (4), F (4): 36.3±12.4/Treatment group (n=8)
M (5), F (3): 30.1±17.9
Lanxiang Jiedu oral liquid (蘭香解毒口服液) Interferon α2b+Umifenovir Interferon α2b+Umi fenovir
  1. Nucleic acid conversion time

  2. Average hospitalization duration

  3. Ct values

  1. 15.3±8.2 days/11.9±5.4 days (p>0.05)

  2. 18.5±8.4 days/13.0±6.0 days (p>0.05)

  3. p>0.05

7 days Not mentioned
Xie9 Case series N=46
M (18): 38.3±14.0, F (28): 36.6±13.8
Chaihu Ganlu Decoction (柴胡甘露飮) Not mentioned (−)
  1. Nucleic acid conversion time

  2. Conversion rate of severe cases

  3. Lung imaging indexes

    • 3–1. Time of beginning inflammation absorption

    • 3–2. Time of inflammation absorption

  4. Lab test (lymphocytes)

  1. 10.7±4.2 days

  2. 0%

    • 3–1. 5.2±2.6 days (n=18)

    • 3–2. 10.2±4.2 days (n=12)

  3. 1.7± 0.57×10/L

Not mentioned (−)
Luo10 Case series N=50
M (21), F (29): 37.3±13.8
Huopu Touxie Decoction (藿朴透邪湯) (n=24), Chaihu Ganlu Decoction (柴胡甘露飮) (n=26) Interferon (n=50), Thymopentin (n=45), Umifenovir (n=31), Ribavirin (n=29), Thymalfasin (n=12), Antibiotics (n=9), Antidiabetic drug (n=12) (−)
  1. Lab test

  2. Chest CT

  3. Average hospitalization duration

  4. Nucleic acid conversion time

  1. WBC, LYM, BUN: p>0.05, CRP, ALT, AST, Cr: p<0.05

  2. Inflammation completely or apparently absorbed

  3. 14.0±4.9 days

  4. 6.8±3.1 days

14.0±4.9 days (−)
Chen11 Case report N=1
M: 7-year-old
Zhengyang Decoction (正陽湯), Qingfei Paidu Decoction (清肺排毒湯), Toujie Quwen Granules (透解祛瘟顆粒) Interferon, Lopinavir/Ritonavir, Ribavirin (−) Lab test (leukocyte, granulocyte, lymphocyte) WNL 22 days Not mentioned
Liu12 Case report N=1
M: 23-month-old
Not mentioned the prescription’s name (−) (−)
  1. Chest CT

  2. Lab test

  1. WNL

  2. WNL

21 days Not mentioned

Ct: Cycle threshold, WBC: white blood cell, LYM: lymphocyte, BUN: blood urea nitrogen, CRP: C-reactive protein, ALT: alanine transaminase, AST: aspartate transaminase, Cr: creatinine, WNL: within normal limits

Table 2

Composition of herbal medicine formula

Herbal medicine Composition (g)
Chaihu Ganlu Decoction (柴胡甘露飮)9,10) Bupleurum falcatum (柴胡) 10, Scutellaria baicalensis (黃芩) 10, Acorus gramineus (石菖蒲) 15, Agastache rugosa (藿香) 10, Amomum kravanh (白豆蔲) 6, Forsythia suspensa (蓮翹) 15, Adenophora triphylla (南沙蔘) 30, Coix lacryma-jobi var. mayuen (薏苡仁) 30, Magnolia officinalis (厚朴) 10 g, Poria cocos (茯苓) 15, Pinellia ternata (薑半夏) 12, Citrus unshiu (陳皮) 6, Cryptotympana dubia (蟬蛻) 10, Bombyx mori (白殭蠶) 15, Prunus ansu (杏仁) 10, Platycodon grandiflorum (桔梗) 10, Hordeum vulgare (麥芽) 15 g/day
Lanxiang Jiedu oral liquid (蘭香解毒口服液)8) Pogostemon cablin (廣藿香), Eupatorium fortunei (佩蘭), Atractylodes chinensis (蒼朮), Magnolia officinalis (厚朴), Citrus unshiu (陳皮), Zingiber officinale (生薑), Poria cocos (茯苓), Pinellia ternata (清半夏), Lonicera japonica (金銀花), Forsythia suspensa (蓮翹), Dryopteris crassirhizoma (貫衆), Prunus persica (桃仁), Angelica sinensis (當歸), Glycyrrhiza uralensis (甘草)*
Zhengyang Decoction (正陽湯)11) Astragalus membranaceus (黄芪) 10, Morus alba (桑白皮) 10, Atractylodes macrocephala (白术) 6, Zingiber officinale (炮薑) 4, Pseudosrellaria heterophylla (太子蔘) 10, Paeoniae lactiflora (白芍藥) 6, Belamcanda chinensis (射干) 3, Glycyrrhiza uralensis (甘草) 3, Scrophularia buergeriana (玄蔘) 6, Lonicera japonica (金銀花) 6 g/day
Qingfei Paidu Decoction (清肺排毒湯)11) Ephedra sinica (麻黃) 9, Glycyrrhiza uralensis (灸甘草) 6, Prunus ansu (杏仁) 9, CaSO4 (石膏) 15, Cinnamomum cassia (桂枝) 9, Alisma plantago-aquatica (澤瀉) 9, Polyporus umbellatus (豬苓) 9, Atractylodes macrocephala (白朮) 9, Poria cocos (茯苓) 15, Bupleurum falcatum (柴胡) 16, Scutellaria baicalensis (黃芩) 6, Pinellia ternata (半夏) 9, Zingiber officinale (生薑) 9, Aster tataricus (紫莞) 9, Belamcanda chinensis (射干) 9, Asarum sieboldii (細辛) 6, Discorea japonica (山藥) 12, Poncirus trifoliata (枳實) 6, Citrus unshiu (陳皮) 6, Agastache rugosa (藿香) 9 g/day
Toujie Quwen Granules (透解祛瘟顆粒)11) Forsythia suspensa (蓮翹) 30, Lonicera japonica (金銀花) 15, Cremastra appendiculata (山慈菇) 20, Scutellaria baicalensis (黄芩片) 10, Persicaria tintoria (大青葉) 10, Bupleurum falcatum (柴胡) 5, Artemisia annua (青蒿) 10, Cryptotympana dubia (蟬蛻) 10, Peucedanum decursivum (前胡) 5, Fritillaria cirrhosa (川貝母) 10, Fritillaria thunbergii (浙貝母) 10, Poria cocos (茯苓) 30, Prunnus mume (烏梅) 30, Scrophularia buergeriana (玄蔘) 10, Astragalus membranaceus (黄芪) 45, Pseudosrellaria heterophylla (太子蔘) 15 g/day
Huopu Touxie Decoction (藿朴透邪湯)10) Agastache rugosa (藿香) 10, Magnolia officinalis (厚朴) 10, Poria cocos (茯苓) 15, Citrus unshiu (陳皮) 6, Massa Medicata Fermentata (神麴) 10, Areca catechu (大腹皮) 10, Coix lacryma-jobi var. mayuen (薏苡仁) 15, Cryptotympana dubia (蟬蛻) 10, Bombyx mori (白殭蠶) 15, Prunus ansu (杏仁) 10, Cimicifuga heracleifolia (升麻) 10, Paeoniae lactiflora (赤芍藥) 10, Pinellia ternata (法半夏) 12 g/day
Herbal medicine prescription12 Prunus ansu (杏仁) 4, Lophatherum gracile (淡竹葉) 6, Poria cocos (茯苓) 6, Forsythia suspensa (蓮翹) 6, Amomum villosum (砂仁) 4, Crataegus pinnatifida (山査) 6, Massa Medicata Fermentata (神麴) 6, Hordeum vulgare (麥芽) 6, Pueraria lobata (葛根) 9 g/day
*

not mentioned the weight