Abstract
This study aimed to evaluate the efficacy of Chinese herbal medicine (CHM) in patients with severe/critical coronavirus disease 2019 (COVID-19). In this retrospective study, data were collected from 662 patients with severe/critical COVID-19 who were admitted to a designated hospital to treat patients with severe COVID-19 in Wuhan before March 20, 2020. All patients were divided into an exposed group (CHM users) and a control group (non-users). After propensity score matching in a 1:1 ratio, 156 CHM users were matched by propensity score to 156 non-users. No significant differences in seven baseline clinical variables were found between the two groups of patients. All-cause mortality was reported in 13 CHM users who died and 36 non-users who died. After multivariate adjustment, the mortality risk of CHM users was reduced by 82.2% (odds ratio 0.178, 95% CI 0.076–0.418; P < 0.001) compared with the non-users. Secondly, age (odds ratio 1.053, 95% CI 1.023–1.084; P < 0.001) and the proportion of severe/critical patients (odds ratio 0.063, 95% CI 0.028–0.143; P < 0.001) were the risk factors of mortality. These results show that the use of CHM may reduce the mortality of patients with severe/critical COVID-19.
Keywords: COVID-19, CHM, mortality, a retrospective cohort study
Acknowledgements
This research was supported by the Special Project for Emergency of the Ministry of Science and Technology of China (No. 2020YFC0845000) and Special Project for Emergency of the National Administration of Tradition Chinese Medicine of China (No. 2020ZYLCYJ03-11). The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Compliance with ethics guidelines
Guohua Chen, Wen Su, Jiayao Yang, Dan Luo, Ping Xia, Wen Jia, Xiuyang Li, Chuan Wang, Suping Lang, Qingbin Meng, Ying Zhang, Yuhe Ke, An Fan, Shuo Yang, Yujiao Zheng, Xuepeng Fan, Jie Qiao, Fengmei Lian, Li Wei, and Xiaolin Tong declare that they have no conflict of interest. This study was approved by the institutional ethics board of Wuhan Integrated TCM and Western Medicine Hospital (No. [2020]8) and was registered with chictr.org. cn (ChiCTR2000030719), and all procedures followed were in accordance with the ethical standards.
Footnotes
These authors contributed equally to this work.
Contributor Information
Fengmei Lian, Email: lfm565@sohu.com.
Li Wei, Email: y077088@sina.com.
Xiaolin Tong, Email: tongxiaolin@vip.163.com.
References
- 1.Sohrabi C, Alsafi Z, O’Neill N, Khan M, Kerwan A, Al-Jabir A, Iosifidis C, Agha R. World Health Organization declares global emergency: a review of the 2019 novel coronavirus (COVID-19) INT J SURG. 2020;76:71–76. doi: 10.1016/j.ijsu.2020.02.034. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Rajgor DD, Lee MH, Archuleta S, Bagdasarian N, Quek SC. The many estimates of the COVID-19 case fatality rate. Lancet Infect Dis. 2020;20(7):776–777. doi: 10.1016/S1473-3099(20)30244-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.World Health Organization. Coronavirus disease 2019 (COVID-19) situation report-69. 2020. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200329-itrep-69-covid-19.pdf? sfvrsn = 8d6620fa_8 (accessed March 20, 2020)
- 4.Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020;8(5):475–481. doi: 10.1016/S2213-2600(20)30079-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, Song B, Cai Y, Wei M, Li X, Xia J, Chen N, Xiang J, Yu T, Bai T, Xie X, Zhang L, Li C, Yuan Y, Chen H, Li H, Huang H, Tu S, Gong F, Liu Y, Wei Y, Dong C, Zhou F, Gu X, Xu J, Liu Z, Zhang Y, Li H, Shang L, Wang K, Li K, Zhou X, Dong X, Qu Z, Lu S, Hu X, Ruan S, Luo S, Wu J, Peng L, Cheng F, Pan L, Zou J, Jia C, Wang J, Liu X, Wang S, Wu X, Ge Q, He J, Zhan H, Qiu F, Guo L, Huang C, Jaki T, Hayden FG, Horby PW, Zhang D, Wang C. A trial of lopinavir-ritonavir in adults hospitalized with severe COVID-19. N Engl J Med. 2020;382(19):1787–1799. doi: 10.1056/NEJMoa2001282. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Zhang K. Is traditional Chinese medicine useful in the treatment of COVID-19? Am J Emerg Med 2020; [Epub ahead of print] doi: 10.1016/j.ajem.2020.03.046 [DOI] [PMC free article] [PubMed]
- 7.National Health Commission of the People’s Republic of China. Notice on the issuance of the fifth edition of the Diagnosis and Treatment Guideline for COVID-19 (Trial Version). 2020. http://www.nhc.gov.cn/yzygj/s7653p/202002/3b09b894ac9b4204a79db-5b8912d4440.shtml (in Chinese) (accessed February 5, 2020)
- 8.Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054–1062. doi: 10.1016/S0140-6736(20)30566-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, Huang H, Zhang L, Zhou X, Du C, Zhang Y, Song J, Wang S, Chao Y, Yang Z, Xu J, Zhou X, Chen D, Xiong W, Xu L, Zhou F, Jiang J, Bai C, Zheng J, Song Y. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020;180(7):934. doi: 10.1001/jamainternmed.2020.0994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061. doi: 10.1001/jama.2020.1585. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Runfeng L, Yunlong H, Jicheng H, Weiqi P, Qinhai M, Yongxia S, Chufang L, Jin Z, Zhenhua J, Haiming J, Kui Z, Shuxiang H, Jun D, Xiaobo L, Xiaotao H, Lin W, Nanshan Z, Zifeng Y. Lianhuaqingwen exerts anti-viral and anti-inflammatory activity against novel coronavirus (SARS-CoV-2) Pharmacol Res. 2020;156:104761. doi: 10.1016/j.phrs.2020.104761. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Zhang W, Zhao Y, Zhang F, Wang Q, Li T, Liu Z, Wang J, Qin Y, Zhang X, Yan X, Zeng X, Zhang S. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): the perspectives of clinical immunologists from China. Clin Immunol. 2020;214:108393. doi: 10.1016/j.clim.2020.108393. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Li G, De Clercq E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV) Nat Rev Drug Discov. 2020;19(3):149–150. doi: 10.1038/d41573-020-00016-0. [DOI] [PubMed] [Google Scholar]
- 14.Deng L, Li C, Zeng Q, Liu X, Li X, Zhang H, Hong Z, Xia J. Arbidol combined with LPV/r versus LPV/r alone against coronavirus disease 2019: a retrospective cohort study. J Infect. 2020;81(1):e1–e5. doi: 10.1016/j.jinf.2020.03.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Al-Tawfiq JA, Al-Homoud AH, Memish ZA. Remdesivir as a possible therapeutic option for the COVID-19. Travel Med Infect Dis. 2020;34:101615. doi: 10.1016/j.tmaid.2020.101615. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269–271. doi: 10.1038/s41422-020-0282-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Ren JL, Zhang AH, Wang XJ. Traditional Chinese medicine for COVID-19 treatment. Pharmacol Res. 2020;155:104743. doi: 10.1016/j.phrs.2020.104743. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Ni L, Zhou L, Zhou M, Zhao J, Wang DW. Combination of western medicine and Chinese traditional patent medicine in treating a family case of COVID-19. Front Med. 2020;14(2):210–214. doi: 10.1007/s11684-020-0757-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Wang Z, Chen X, Lu Y, Chen F, Zhang W. Clinical characteristics and therapeutic procedure for four cases with 2019 novel coronavirus pneumonia receiving combined Chinese and Western medicine treatment. Biosci Trends. 2020;14(1):64–68. doi: 10.5582/bst.2020.01030. [DOI] [PubMed] [Google Scholar]
- 20.Waldeck B, Widmark E. The interaction of ephedrine with β-adrenoceptors in tracheal, cardiac and skeletal muscles. Clin Exp Pharmacol Physiol. 1985;12(4):439–442. doi: 10.1111/j.1440-1681.1985.tb00891.x. [DOI] [PubMed] [Google Scholar]
- 21.Chang HK, Yang HY, Lee TH, Shin MC, Lee MH, Shin MS, Kim CJ, Kim OJ, Hong SP, Cho S. Armeniacae semen extract suppresses lipopolysaccharide-induced expressions of cyclooxygenase [correction of cycloosygenase]-2 and inducible nitric oxide synthase in mouse BV2 microglial cells. Biol Pharm Bull. 2005;28(3):449–454. doi: 10.1248/bpb.28.449. [DOI] [PubMed] [Google Scholar]
- 22.Sun SM, Song YM, Liu J, Yu SR. Pharmacological effects of volatile compounds from Eupatorium fortunei Turcz. Nothwest Pharm J (Xi Bei Yao Xue Za Zhi) 1995;10:24–26. [Google Scholar]
- 23.Shen HH, Wang K, Li W, Ying YH, Gao GX, Li XB, Huang HQ. Astragalus membranaceus prevents airway hyperreactivity in mice related to Th2 response inhibition. J Ethnopharmacol. 2008;116(2):363–369. doi: 10.1016/j.jep.2007.12.002. [DOI] [PubMed] [Google Scholar]
- 24.Li YC, Xian YF, Su ZR, Ip SP, Xie JH, Liao JB, Wu DW, Li CW, Chen JN, Lin ZX, Lai XP. Pogostone suppresses proinflammatory mediator production and protects against endotoxic shock in mice. J Ethnopharmacol. 2014;157:212–221. doi: 10.1016/j.jep.2014.09.023. [DOI] [PubMed] [Google Scholar]
- 25.Hyuga S, Hyuga M, Oshima N, Maruyama T, Kamakura H, Yamashita T, Yoshimura M, Amakura Y, Hakamatsuka T, Odaguchi H, Goda Y, Hanawa T. Ephedrine alkaloids-free Ephedra Herb extract: a safer alternative to ephedra with comparable analgesic, anticancer, and anti-influenza activities. J Nat Med. 2016;70(3):571–583. doi: 10.1007/s11418-016-0979-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Fu J, Wang Z, Huang L, Zheng S, Wang D, Chen S, Zhang H, Yang S. Review of the botanical characteristics, phytochemistry, and pharmacology of Astragalus membranaceus (Huangqi) Phytother Res. 2014;28(9):1275–1283. doi: 10.1002/ptr.5188. [DOI] [PubMed] [Google Scholar]
- 27.Liu D, Chen L, Zhao J, Cui K. Cardioprotection activity and mechanism of Astragalus polysaccharide in vivo and in vitro. Int J Biol Macromol. 2018;111:947–952. doi: 10.1016/j.ijbiomac.2018.01.048. [DOI] [PubMed] [Google Scholar]
- 28.Li Z, Zhu L, Zhang H, Yang J, Zhao J, Du D, Meng J, Yang F, Zhao Y, Sun J. Protective effect of a polysaccharide from stem of Codonopsis pilosula against renal ischemia/reperfusion injury in rats. Carbohydr Polym. 2012;90(4):1739–1743. doi: 10.1016/j.carbpol.2012.07.062. [DOI] [PubMed] [Google Scholar]
- 29.Liu C, Chen J, Li E, Fan Q, Wang D, Li P, Li X, Chen X, Qiu S, Gao Z, Li H, Hu Y. The comparison of antioxidative and hepatoprotective activities of Codonopsis pilosula polysaccharide (CP) and sulfated CP. Int Immunopharmacol. 2015;24(2):299–305. doi: 10.1016/j.intimp.2014.12.023. [DOI] [PubMed] [Google Scholar]
- 30.Lee JC, Lee KY, Son YO, Choi KC, Kim J, Kim SH, Chung GH, Jang YS. Stimulating effects on mouse splenocytes of glycoproteins from the herbal medicine Atractylodes macrocephala Koidz. Phytomedicine. 2007;14(6):390–395. doi: 10.1016/j.phymed.2006.09.012. [DOI] [PubMed] [Google Scholar]
- 31.Sun Y. Biological activities and potential health benefits of polysaccharides from Poria cocos and their derivatives. Int J Biol Macromol. 2014;68:131–134. doi: 10.1016/j.ijbiomac.2014.04.010. [DOI] [PubMed] [Google Scholar]
- 32.Ríos JL. Chemical constituents and pharmacological properties of Poria cocos. Planta Med. 2011;77(7):681–691. doi: 10.1055/s-0030-1270823. [DOI] [PubMed] [Google Scholar]
- 33.Wang C, Ming H, Jia W, Su W, Zhang LR, Luo D, Yang JY. Analysis on medication regularity and pharmacodynamic characteristics of traditional Chinese medicine treatment of 444 severe cases of COVID-19. China J Chin Materia Medica (Zhongguo Zhong Yao Za Zhi) 2020; [Epub ahead of print] doi:10.19540/j.cnki.cjcmm.20200427.501 (in Chinese) [DOI] [PubMed]