3.1 literature search
As shown in Fig. 1, 608 articles were initially collected in total. The duplicates, reviews, comments, animal experiments were removed (n = 559). After reading the abstract and full-text of the remain articles, forty articles that did not meet the inclusion criteria were excluded. Finally, nine literatures were included [18–26].
3.2 Characteristics of the included studies
Six studies were RCTs, and three studies were case-control studies, and all the studies were published in 2020, seven written in Chinese and two written in English, The total sample size was 1163 (616 males), and sample size per study ranged from 42 to 295,The oldest age of the participants was 75 and the youngest was 21༌the disease stages of the patients with COVID-19 were mild or ordinary, and the shortest duration of the Lianhua Qingwen treatment was 7 days and the longest was 21 days, All the characteristics of the included studies were shown in Table 1.
3.3 Risk of bias assessment and quality assessment
The quality of the included RCTs were shown in the Table 2, all the six studies described the low risk of the random sequence generation, allocation concealment, incomplete outcome data, Selective reporting. but only one study reported the blinding of participants, personnel, and outcome assessment. The other bias is not clear in four RCTs, Overall, the quality of the included RCTs was high.
As was shown in the Table 3, three CCSs were assessed for quality by the NOS, all the studies did not decscribed representativeness of the cases, selection of controls, no study reported non-response rate.
Table 1
Summary of included studies.
Study (year,country)
|
Sample Size(I/C)
gender (M/F)
Age (Years)(I/C)
|
Study
type
|
Type
of
disease
|
Intervention
group
|
control
group
|
study
outcomes
|
Hu (2020, China)
|
284(142/142);
150/134;
37.1 ± 0.7/37.09 ± 0.668
|
RCT
|
Common
|
Plan I:Qingwen
capsule, 4 capsules for 3
times daily for two weeks,and with the plan II
|
paln II: antiviral and antimicrobial therapy
|
① the clinical symptom effective rate;② Improvement of abnormalities in chest CT;③ the progress into severe clinical disease.
|
Wang (2020, China)
|
60(30/30);
23/37;
28∼69/29∼68
|
RCT
|
Common
|
plan I: Lianhua Qingwen
capsule, 4 capsules for 3
times daily for 7–10 days,and with the plan II
|
paln II: antiviral and antimicrobial therapy
|
① The clinical effective rate.
|
Yu (2020, China)
|
295(147/148);
171/124;
48.3 ± 9.6/47.3 ± 8.3
|
RCT
|
Light
/Common
|
Plan I:Lianhua
Qingwen granules, 1
packet per time for 2 times
daily for 7 days,and with the plan II
|
PlanII:Arbidol
Hydrochloride Tablets, 200 mg
+ Ambroxol Hydrochloride
Tablets, 30 mg for 3 times daily
+ Moxifloxacin tablets, 400 mg
for 1 time daily, 30 mg for 3
times daily
|
①The clinical effective rate;② Improvement of abnormalities in chest CT; ③ Rate of conversion of severe cases.
|
Chen JJ(2020, China)
|
70(35/35);
38/32;
45.21 ± 4.68/44.75 ± 4.92
|
RCT
|
Light
|
plan I: Lianhua Qingwen
capsule, 4 capsules for 2
times daily for 15 days, and nutriton support antiviral and antimicrobial therapy
|
paln II: Arbidol Hydrochloride Tablets, 200 mg for 2 times daily for 15 days, and nutriton support antiviral and antimicrobial therapy
|
①clinical effective rate
② Improvement of abnormalities in chest CT
|
CW Chen(2020, China)
|
60(30/30);
35/25;
49.52 ± 5.06/50.16 ± 5.11
|
RCT
|
Light
/Common
|
plan I: Lianhua Qingwen
capsule, 4 capsules for 3
times daily for 7–10 days,and with the plan II
|
paln II:nutriton support antiviral and antimicrobial therapy
|
③ Rate of conversion of severe cases
|
Liu(2020, China)
|
108(68/40);
47/61; 54.8 ± 19.1/59.5 ± 15.6
|
RCT
|
Common
|
plan I:Lianhua Qingwen
1400mg for 3
times daily for 5–21 days,and with the plan II.
|
paln II: Arbidol Hydrochloride Tablets, 200 mg for 2 times daily for 5–21 days, and nutriton support antiviral and antimicrobial therapy
|
② Improvement of abnormalities in chest CT
|
Cheng (2020, China)
|
102(51/51);
53/49; 55.5 ± 12.3/55.8 ± 11.6
|
CCs
|
Common
|
plan I: Lianhua Qingwen
granules, 1 packet for 3
times daily for 7 days.and with the plan II
|
paln II:nutriton support antiviral and antimicrobial therapy
|
①The clinical effective rate;② Improvement of abnormalities in chest CT; ③ Rate of conversion of severe cases;④ duration of fever;⑤disappearance rate of fever;⑥disappearance rate of cough;⑦disappearance rate of fatigue
|
HY Yu (2020,China)
|
123(85/38); 62/61; 21∼69/
21∼68
|
CCs
|
Light
|
plan I: Lianhua Qingwen
capsule, 4 capsules for 3
times daily for 8 days, and nutriton support antiviral and antimicrobial therapy
|
paln II: Arbidol
Hydrochloride Tablets, 200 mg for 3 times daily for 5 days, and nutriton support antiviral and antimicrobial therapy
|
③ Rate of conversion of severe cases
|
Yao (2020, China)
|
42(21/21);28/14;57. 1 ± 14. 0/62. 4 ± 12. 3
|
CCs
|
Common
|
plan I:Lianhua Qingwen
granules, 1 packet for 3
times daily for 7 days.and with the plan II.
|
plan II:antiviral and antimicrobial therapy
|
①clinical effective rate ② duration of fever; ③cardinal symptom disappearance rate (fever, cough, fatigue).
|
Table 2
The risk of bias of included Randomized Controlled Trials
Study
|
Random sequence generation
(selection bias)
|
Allocation concealment
(selection bias)
|
Blinding of participants and personnel
(performance bias)
|
Blinding of outcome assessment
(detection bias)
|
Incomplete outcome data
(attrition bias)
|
Selective reporting
(reporting bias)
|
Other bias
|
Hu
|
L
|
L
|
U
|
H
|
L
|
L
|
L
|
Liu
|
L
|
L
|
H
|
H
|
L
|
L
|
U
|
Wang
|
L
|
L
|
U
|
U
|
L
|
L
|
U
|
Yu
|
L
|
L
|
H
|
H
|
L
|
L
|
U
|
CW Chen
|
L
|
L
|
L
|
L
|
L
|
L
|
U
|
JJ Chen
|
L
|
L
|
H
|
U
|
L
|
L
|
L
|
H: High risk, L: Low risk, U: Unclear risk
Table 3
The quality of included Case-Control Studies
Author(year)
|
case definition
|
Representativeness of the
Cases
|
Selection of
Controls
|
Definition of
Controls
|
Comparability of Cases and
Control
|
Ascertainment of
Exposure
|
Same method of ascertainment for cases and controls
|
Non-Response
Rate
|
NOS
|
Cheng(2020)
|
☆
|
-
|
-
|
☆
|
☆☆
|
☆
|
☆
|
-
|
6
|
Yao(2020)
|
☆
|
-
|
-
|
☆
|
☆☆
|
☆
|
☆
|
-
|
6
|
HY Hu(2020)
|
☆
|
-
|
-
|
☆
|
☆☆
|
☆
|
☆
|
-
|
6
|
Table 4
Comparison of the adverse drug reaction between two group
Outcome measure
|
Total
|
Events/Intervention
|
Events/Control
|
Statistical method
|
Effect estimate
|
P-value
|
Liver damage
|
341
|
36/170
|
35/171
|
RR (Random) 95%CI
|
1.03(0.68,1.56)
|
0.880
|
nausea vomiting
|
341
|
10/170
|
10/171
|
RR (Random) 95%CI
|
1.01(0.43, 2.36)
|
0.987
|
headache
|
341
|
2/170
|
3/171
|
RR (Random) 95%CI
|
0.68(0.117,3.972 )
|
0.699
|
3.4 Meta-analysis
(1) The clinical effective rate: six researches[18–21, 24, 25], reported the clinical effective rate in the two groups. The intervention group that combined Lianhua Qingwen with the western medicine showed a significantly better effective rate.(Fig. 3)[RR = 1.20, 95%CI 1.20(1.11, 1.31), P = 0.000].
(2) Cardinal symptom disappearance rate:two studies[24, 26] reported the symptom disappearance rate, including symptom of fever, cough and fatigue. Compared with the control group, the intervention group performed a higher disappearance rate.[disappearance rate of fever: OR:3.64, 95%CI(1.57, 8.47), P = 0.001;disappearance rate of cough: OR:3.96, 95%CI(1.72, 9.14), P = 0.001; disappearance rate of fatigue: OR:2.55, 95%CI(1.09, 5.99), P = 0.032](Fig. 4–6).
(3) Improvement of abnormalities in chest CT: the improvement of abnormalities in chest CT cases were investigated by five[18, 20, 21, 23, 24] studies, finding that the patients, CT manifestations had been improved in the group of Lianhua Qingwen [RR:1.25, 95%CI(1.13,1.38), P = 0.000].( Fig. 7)
(4) The progress into severe diseases: Five [18, 20, 25, 22, 24] studies compared the progress into severe diseases between the two groups. Compared with the western medicine alone, the combination of Lianhua Qingwen can significantly reduce the rate of the progress into severe diseases of COVID-19 patients.[RR:0.43, 95%CI(0.30, 0.62), P = 0.000](Fig. 8).
(5) Duration of fever: Two studies[24, 26] evaluated the duration of fever between the two groups. The results indicated that the patients with the therapy of combining Lianhua Qingwen with western medicine had a shorter duration of fever than those patients given western medicine alone, with a significant P value[WMD=-1.07,95%CI(-1.77, -0.37), P = 0.003].
(6) Adverse events: two studies[22, 25] reported the adverse events in two gourps, and the common adverse events were nausea and vomiting, liver damage, and headache. These studies described that there was no significant difference adverse drug reactions caused by the two different interventions(Table 4)
3.5 Publication bias
Since the number of studies in any comparative analysis did not exceed ten, we did not assess the publication bias.