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Frontiers of Medicine

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Front. Med.    2020, Vol. 14 Issue (6) : 752-759    https://doi.org/10.1007/s11684-020-0813-6
RESEARCH ARTICLE
Chinese herbal medicine reduces mortality in patients with severe and critical coronavirus disease 2019: a retrospective cohort study
Guohua Chen1, Wen Su1, Jiayao Yang1, Dan Luo1, Ping Xia1, Wen Jia1, Xiuyang Li2, Chuan Wang1, Suping Lang3, Qingbin Meng1, Ying Zhang4, Yuhe Ke1, An Fan3, Shuo Yang1, Yujiao Zheng2, Xuepeng Fan1, Jie Qiao5, Fengmei Lian2(), Li Wei1(), Xiaolin Tong2()
1. Wuhan No.1 Hospital (Wuhan Integrated TCM & Western Medicine Hospital), Wuhan 430022, China
2. Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
3. GCP ClinPlus Co., Ltd., Beijing 100160, China
4. Beijing University of Chinese Medicine, Beijing 100029, China
5. Hubei University of Traditional Chinese Medicine, Wuhan 430060, China
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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     
Corresponding Author(s): Fengmei Lian,Li Wei,Xiaolin Tong   
Just Accepted Date: 12 August 2020   Online First Date: 14 September 2020    Issue Date: 24 December 2020
 Cite this article:   
Guohua Chen,Wen Su,Jiayao Yang, et al. Chinese herbal medicine reduces mortality in patients with severe and critical coronavirus disease 2019: a retrospective cohort study[J]. Front. Med., 2020, 14(6): 752-759.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-020-0813-6
https://academic.hep.com.cn/fmd/EN/Y2020/V14/I6/752
Fig.1  Study profile.
Total
(n = 662)		 CHM users
(n = 484)		 CHM non-users
(n = 178)		 P value
Age (year) 60 (47, 70) 57 (45, 68) 66 (54, 76) <0.001
Sex 0.011
Men 296 (44.7%) 202 (41.7%) 94 (52.8%)
Women 366 (55.3%) 282 (58.3%) 84 (47.2%)
Smoking history 0.348
Never 575 (86.9%) 417 (86.2%) 158 (88.8%)
Ever 15 (2.3%) 12 (2.5%) 3 (1.7%)
Current 20 (3.0%) 18 (3.7%) 2 (1.1%)
Other 52 (7.9%) 37 (7.6%) 15 (8.4%)
Comorbidity 354 (53.5%) 246 (50.8%) 108 (60.7%) 0.024
Chronic obstructive lung disease 19 (2.9%) 10 (2.1%) 9 (5.1%) 0.041
Hypertension 208 (31.4%) 147 (30.4%) 61 (34.3%) 0.338
Cardiovascular disease 53 (8.0%) 40 (8.3%) 13 (7.3%) 0.686
Diabetes 94 (14.2%) 69 (14.3%) 25 (14.0%) 0.945
Malignancy 12 (1.8%) 7 (1.4%) 5 (2.8%) 0.321
Cerebrovascular disease 38 (5.7%) 26 (5.4%) 12 (6.7%) 0.502
Chronic kidney disease 3 (0.6%) 0 (0.0%) 3 (0.5%) 0.568
Chronic liver disease 8 (1.2%) 5 (1.0%) 3 (1.7%) 0.449
Signs and symptoms 658 (99.4%) 481 (99.4%) 177 (99.4%) 1.000
Fever 450 (68.0%) 345 (71.3%) 105 (59.0%) 0.003
Dry cough 408 (61.6%) 298 (61.6%) 110 (61.8%) 0.957
Expectoration 184 (27.8%) 129 (26.7%) 55 (30.9%) 0.280
Fatigue 298 (45.0%) 209 (43.2%) 89 (50.0%) 0.118
Shortness of breath 221 (33.4%) 153 (31.6%) 68 (38.2%) 0.111
Nasal obstruction 21 (3.2%) 18 (3.7%) 3 (1.7%) 0.186
Pharyngalgia 39 (5.9%) 33 (6.8%) 6 (3.4%) 0.095
Hemoptysis 4 (0.6%) 1 (0.2%) 3 (1.7%) 0.062
Chills 46 (6.9%) 33 (6.8%) 13 (7.3%) 0.828
Headache 45 (6.8%) 30 (6.2%) 15 (8.4%) 0.312
Myalgia 74 (11.2%) 55 (11.4%) 19 (10.7%) 0.803
Vomiting 35 (5.3%) 22 (4.5%) 13 (7.3%) 0.160
Diarrhea 71 (10.7%) 55 (11.4%) 16 (9.0%) 0.381
Constipation 12 (1.8%) 5 (1.0%) 7 (3.9%) 0.020
Laboratory tests
White blood cell count, ×109 /L 5.39 (4.30, 6.87) 5.46 (4.42, 7.00) 5.02 (3.83, 6.60) 0.020
Red blood cell count,×109 /L 4.200 (3.860, 4.590) 4.205 (3.870, 4.610) 4.150 (3.810, 4.560) 0.314
Neutrophil count, ×109 /L 3.200 (2.380, 4.460) 3.260 (2.430, 4.530) 3.010 (2.210, 4.000) 0.089
Lymphocyte count, ×109 /L 1.38 (0.96, 1.81) 1.44 (1.01, 1.88) 1.19 (0.84, 1.58) <0.001
Monocyte count, ×109 /L 0.51 (0.37, 0.66) 0.52 (0.39, 0.68) 0.46 (0.34, 0.61) 0.002
Platelet count, ×109 /L 208.00 (161.00, 274.00) 211.00 (166.00, 277.00) 202.00 (149.00, 260.00) 0.093
Hemoglobin, g/L 128.00 (118.00, 140.00) 128.00 (118.00, 141.20) 128.00 (118.00, 138.00) 0.515
C-reactive protein, mg/L 7.00 (3.11, 30.04) 4.60 (3.11, 26.50) 14.00 (3.11, 41.50) <0.001
Albumin, g/L 35.70 (32.35, 39.00) 35.70 (32.50, 39.00) 35.50 (32.20, 38.60) 0.102
Alanine aminotransferase, U/L 22 (14, 36) 23 (14, 37) 20 (14, 32) 0.207
Aspartate aminotransferase, U/L 25 (19, 37) 25 (19, 37) 25 (19, 37) 0.879
Blood urea nitrogen, mmol/L 4.10 (3.30, 5.30) 4.10 (3.30, 5.30) 4.00 (3.20, 5.40) 0.703
Creatinine, mmol/L 63.0 (54.0, 77.4) 63.0 (54.0, 77.0) 62.0 (54.0, 79.4) 0.937
Creatine kinase, U/L 61.00 (41.00, 94.00) 58.00 (39.00, 85.00) 70.00 (46.00, 143.00) 0.002
Lactate dehydrogenase, U/L 211.0 (163.0, 285.0) 207.0 (161.0, 285.0) 223.5 (170.0, 309.0) 0.195
High-sensitivity cardiac troponin I, pg/mL 0.007 (0.002, 0.034) 0.006 (0.002, 0.020) 0.012 (0.004, 2.900) 0.004
IgG, g/L 10.40 (8.15, 12.90) 10.40 (8.17, 13.90) 10.60 (7.94, 11.90) 0.555
IgA, g/L 2.19 (1.56, 2.94) 2.27 (1.83, 3.12) 2.05 (1.36, 2.51) 0.071
IgM, g/L 0.95 (0.73, 1.33) 0.94 (0.63, 1.38) 0.96 (0.83, 1.33) 0.516
C3, g/L 1.07 (0.92, 1.24) 1.05 (0.91, 1.25) 1.14 (0.93, 1.24) 0.355
C4, g/L 0.270 (0.206, 0.340) 0.245 (0.192, 0.326) 0.303 (0.253, 0.349) 0.066
Imaging features
Consolidation 522 (78.9%) 386 (79.8%) 136 (76.4%) 0.322
Pleural effusion 28 (4.2%) 16 (3.3%) 12 (6.7%) 0.050
Treatment
Antibiotics 516 (77.9%) 362 (74.8%) 154 (86.5%) 0.001
Antiviral treatment 553 (83.5%) 407 (84.1%) 146 (82.0%) 0.525
Chinese patent medicine 437 (66.0%) 331 (68.4%) 106 (59.6%) 0.033
Hormone 149 (22.5%) 95 (19.6%) 54 (30.3%) 0.003
Oxygen therapy <0.001
Mask oxygen inhalation 454 (68.6%) 361 (74.6%) 93 (52.2%)
Nasal tube of oxygen inhalation 161 (24.3%) 107 (22.1%) 54 (30.3%)
Noninvasive mechanical ventilation 45 (6.8%) 16 (3.3%) 29 (16.3%)
Invasive mechanical ventilation 2 (0.3%) 0 (0.0%) 2 (1.1%)
Tab.1  Baseline characteristics of study patients
Total (n = 312) CHM users(n = 156) CHM non-users (n = 156) P value
Age (year) 63 (51, 72) 63 (54, 72) 63 (49, 73) 0.973
Sex 0.495
Men 142 (45.5%) 68 (43.6%) 74 (47.4%)
Women 170 (54.5%) 88 (56.4%) 82 (52.6%)
The stage of disease 1.000
Severe cases 236 (75.6%) 118 (75.6%) 118 (75.6%)
Critical cases 76 (24.4%) 38 (24.4%) 38 (24.4%)
Comorbidity 174 (55.8%) 77 (49.4%) 97 (62.2%) 0.023
Imaging features 287 (92.0%) 147 (94.2%) 140 (89.7%) 0.144
Treatment
Antibiotics 251 (80.4%) 116 (74.4%) 135 (86.5%) 0.007
Antiviral treatment 266 (85.3%) 136 (87.2%) 130 (83.3%) 0.338
Chinese patent medicine 200 (64.1%) 107 (68.6%) 93 (59.6%) 0.098
Hormone 84 (26.9%) 33 (21.2%) 51 (32.7%) 0.022
Oxygen therapy 0.657
Mask oxygen inhalation 184 (59.0%) 95 (60.9%) 89 (57.1%)
Nasal tube of oxygen inhalation 95 (30.4%) 46 (29.5%) 49 (31.4%)
Noninvasive mechanical ventilation 31 (9.9%) 15 (9.6%) 16 (10.3%)
Invasive mechanical ventilation 2 (0.6%) 0 (0.0%) 2 (1.3%)
Tab.2  Baseline characteristics of study patients after PSM
Univariable Multivariable
OR (95% CI) P value OR (95% CI) P value
CHM (vs. non-CHM) 0.303 (0.154, 0.598) <0.001 0.178 (0.076, 0.418) <0.001
Female (vs. male) 0.698 (0.379, 1.287) 0.249
Age (year)* 1.068 (1.040, 1.096) <0.001 1.053 (1.023, 1.084) <0.001
Severe cases (vs. critical cases) 0.065 (0.032, 0.133) <0.001 0.063 (0.028, 0.143) <0.001
Comorbidity present (vs. not present) 1.305 (0.699, 2.435) 0.403
Imaging features present (vs. not present) 0.724 (0.258, 2.031) 0.539
Treatment (vs. non-treatment)
?Antibiotics 1.095 (0.500, 2.399) 0.820
?Antiviral treatment 0.619 (0.284, 1.347) 0.227
?Chinese patent medicine 0.780 (0.418, 1.455) 0.435
Tab.3  Risk factors associated with in-hospital death after PSM
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