In 6 databases, we identified 814 articles; 499 duplicates were removed. Out of the remaining 315 abstracts, we excluded 298 after screening. Thus, 17 full-text studies were assessed for eligibility and 9 were excluded. Finally, eight studies were included for further qualitative and quantitative analyses (Figure 1).
Characteristics of the included studies: Two studies were cohort (Brunetti et al. and Scarsi et al.) while the other studies were four randomized controlled clinical trials (Deftereos et al., RECOVERY Collaborative Group, Lopes et al., and Tardif et al.) and two non-randomized controlled clinical trials (Mareev et al., and Sandhu et al.).
Two studies were multicentre clinical trials (RECOVERY Collaborative Group, and Tardif et al.). The other six studies were conducted in Greece (Deftereos et al.), Brazil (Lopes et al.), the USA (Brunetti et al. and Sandhu et al.), Russia (Mareev et al.), and Italy (Scarsi et al.) [22-29].
The studies included both hospitalized and non-hospitalized COVID-19 patients, who were diagnosed either clinically or by laboratory diagnosis with PCR–RT testing and CT chest imaging (Table 1).
Table (1): Characteristics of included studies evaluating the efficacy of colchicine in COVID-19.
Authors
|
Year of publication
|
Type of study
|
Study population
|
Participants (Colchicine/ Control)
|
Colchicine drug dose
|
Control
|
Outcomes
|
Deftereos et al.
|
2020
|
RCT
|
Hospitalized COVID-19 adult patients
|
55/50
|
Loading dose: 1.5 mg followed by 0.5 mg 60 minutes later.
Maintenance dose: 0.5 mg twice daily until hospital discharge or for 21 days.
|
Standard treatment
|
Mortality, Mechanical Ventilation
|
Tardif et al.
|
2021
|
RCT
|
Non-hospitalized COVID-19 adult patients
|
2235/2253
|
0·5 mg twice per day for the first 3 days and then once per day for 27 days
|
Placebo
|
Mortality, Hospitalization, Mechanical Ventilation
|
Lopes et al.
|
2021
|
RCT
|
Hospitalized COVID-19 adult patients
|
36/36
|
0.5mg 3 times daily for 5days, then 0.5mg twice daily for 5days
|
Placebo
|
Mortality, ICU Admission, ICU length of stay
|
RECOVERY Collaborative Group
|
2021
|
RCT
|
Hospitalized COVID-19 adult patients
|
5610/5730
|
1 mg followed by 500 µg 12 hours later and then 500 µg twice a day for 10 days or until discharge
|
Standard care
|
Mortality
|
Sandhu et al.
|
2020
|
NRCT
|
Hospitalized COVID-19 adult patients
|
34/78
|
0.6 mg twice daily for 3 days and then 0.6 mg daily for 12 days
|
Standard care
|
Mortality, rate of intubation, rate of hospital discharge
|
Mareev et al.
|
2021
|
NRCT
|
Hospitalized COVID-19 adult patients
|
21/22
|
1 mg colchicine during the first 1–3 days followed by 0.5 mg/day
|
Placebo
|
Mortality, length of hospital stay.
|
Brunetti et al.
|
2020
|
Cohort
|
Hospitalized COVID-19 adult patients
|
33/33
|
loading dose: 1.2 mg. maintenance dose: 0.6 mg twice daily
|
Standard care
|
Mortality, hospital discharge, clinical improvement
|
Scarsi et al.
|
2020
|
Cohort
|
Hospitalized COVID-19 adult patients
|
122/140
|
colchicine 1mg/day (reduced to 0.5mg/day, if severe diarrhoea)
|
Standard care
|
survival
|
RCT, Randomized controlled clinical trial. NRCT, Nonrandomized controlled clinical trial.
Mortality
Table 2 and Figure 2 showed that the meta-analysis of all included studies showed a significant difference in mortality between the treatment group with colchicine and the control group (RR 0.35, 95% CI: 0.15- 0.79). There is significant heterogeneity among the studies (Homogeneity Test X2: 42.219, P-value <0.000).
Table (2): Meta-analysis for the efficacy of colchicine on mortality in patients with COVID-19.
Study
|
Type of study
|
Relative Risk
|
95% CI
|
P-value
|
Deftereos et al. 2020
|
RCT
|
0.23
|
0.03 - 2.14
|
0.163144
|
Tardif et al. 2021
|
RCT
|
0.56
|
0.19-1.67
|
0.081
|
Lopes et al. 2021
|
RCT
|
0.47
|
0.04 -5.45
|
0.555346
|
RECOVERY Collaborative Group 2021
|
RCT
|
1.01
|
0.93 - 1.10
|
0.77
|
Sandhu et al. 2020
|
NRCT
|
0.21
|
0.09 - 0.51
|
0.00032
|
Mareev et al. 2021
|
NRCT
|
0.48
|
0.04 - 5.67
|
0.57753
|
Brunetti et al. 2020
|
Cohort
|
0.21
|
0.06 - 0.71
|
0.012
|
Scarsi et al. 2020
|
Cohort
|
0.151
|
0.062 - 0.368
|
<0.0001
|
Fixed Effect Model
|
0.911
|
0.827 - 1.005
|
---
|
Random Effect Model
|
0.35
|
0.15 - 0.79
|
95% CI, 95% confidence interval. RCT, Randomized controlled clinical trial. NRCT, Nonrandomized controlled clinical trial.
The meta-analytical result of the six clinical trials was insignificant between the treatment and control groups (RR 0.48, 95% CI 0.22 -1.07). There is significant heterogeneity among the studies (Homogeneity Test X2: 11.562, P-value: 0.000). The meta-analytical result of the two cohort studies was significant between the treatment and control groups (RR 0.17, 95%CI 0.08-0.35)
Duration of COVID-19 illness till recovery
Table 3 shows the efficacy of colchicine on the duration of COVID-19 illness till recovery. Lopes et al. reported that the median duration of COVID-19 illness in the treatment group with colchicine was 7 days vs 9 days in the control group (P-value =0.003) [25]. While Sandhu et al., and Mareev et al., demonstrated that colchicine had no significant effect on the illness duration [26,27]. (table 3).
Table (3): Efficacy of colchicine on the duration of COVID-19 illness till recovery.
Study
|
Type of study
|
Median duration of illness
Colchicine vs control
|
P-value
|
Lopes et al. 2021
|
RCT
|
7.0 vs 9.0
|
0.003
|
Sandhu et al. 2020
|
NRCT
|
10.5 vs 11
|
0.947
|
Mareev et al. 2021
|
NRCT
|
13.0 vs 17.5
|
0.079
|
RCT, Randomized controlled clinical trial. NRCT, Nonrandomized controlled clinical trial
Need for Hospitalization
Tardif et al., reported that colchicine did not show a significant effect on the COVID-19 patients’ need for hospitalization RR 0.79, 95% CI 0.60-1.03, P-value =0.081) [23].
Need for O2 Therapy
Lopes et al., demonstrated that colchicine use resulted in a significant decrease in the need for O2 therapy in patients with COVID-19 (RR 0.07, 95% CI 0.02-0.27, P =0.000024) [25].
Need for ICU Admission
Table 4 and figure 3 show the efficacy of colchicine on need for ICU admission in patients with COVID-19. The meta-analytical result did not show a significant effect (RR 0.29, 95% CI: 0.07-1.17).
Table (4): Meta-analysis for the efficacy of colchicine on need for ICU admission in patients with COVID-19.
Study
|
Type of study
|
Relative Risk
|
95% CI
|
P-value
|
Deftereos et al. 2020
|
RCT
|
0.12
|
0.01- 1.05
|
0.025696
|
Lopes et al. 2021
|
RCT
|
0.47
|
0.08-2.75
|
0.393769
|
Fixed Effect Model
|
0.29
|
0.07-1.17
|
---
|
95% CI, 95% confidence interval. RCT, Randomized controlled clinical trial
Need for Artificial Ventilation
Table 5 and figure 4 show the efficacy of colchicine on need for artificial ventilation in patients with COVID-19. The meta-analysis of four studies demonstrated that colchicine has no significant effect on the need for artificial ventilation (RR 0.40, 95% CI 0.14 -1.13). There is significant heterogeneity among the studies (Homogeneity Test X2: 18.417, P-value: 0.000).
Table (5): Meta-analysis of the efficacy of colchicine on need for artificial ventilation in patients with COVID-19.
Study
|
Type of study
|
Relative Risk
|
95% CI
|
P-value
|
Deftereos et al. 2020
|
RCT
|
0.18
|
0.02-1.61
|
0.088555
|
Tardif et al. 2021
|
RCT
|
0.53
|
0·25-1.09
|
0·081
|
Recovery Collaborative Group 2021
|
RCT
|
1.04
|
0.93-1.16
|
0·48
|
Sandhu et al. 2020
|
NRCT
|
0.13
|
0.05-0.34
|
< 0.00001
|
Fixed Effect Model
|
0.992
|
0.874-1.126
|
---
|
Random Effect Model
|
0.40
|
0.14-1.13
|
Homogeneity Test X2: 18.417 P Value: 0.000
|
95% CI, 95% confidence interval. RCT, Randomized controlled clinical trial. NRCT, Nonrandomized controlled clinical trial
Hospital Discharge Rate
Table 6 and figure 5 show the efficacy of colchicine on hospital discharge rate in patients with COVID-19. The meta-analytical result of the three studies demonstrated that colchicine did not show a significant effect on the hospital discharge rate (RR 0.99, 95%CI 0.12-7.85).
Table (6): Meta-analysis for the efficacy of colchicine on hospital discharge rate in patients with COVID-19.
Study
|
Type of study
|
Relative Risk
|
95% CI
|
P-value
|
Recovery Collaborative Group 2021
|
RCT
|
0.98
|
0.94-1.03
|
0·44
|
Sandhu et al. 2020
|
NRCT
|
4.76
|
1.96-11.11
|
0.00032
|
Brunetti et al. 2020
|
Cohort
|
5.0
|
1.25-20.08
|
0.023
|
Fixed Effect Model
|
0.99
|
0.12-7.85
|
---
|
95% CI, 95% confidence interval. RCT, Randomized controlled trial. NRCT, Nonrandomized controlled trial
The effect of colchicine on the hospital discharge rate in the clinical trials was not significant (RR 0.98, 95%CI 0.12-8.02), while a cohort study reported that colchicine showed a significant effect on the hospital discharge rate (RR 5.0, 95%CI 1.25-20.08, P-value 0.023) [28].
Subgroup analysis among PCR confirmed COVID-19 Patients
Mortality among PCR confirmed COVID-19 patients
Table 7 and figure 6 show the efficacy of colchicine on mortality among PCR confirmed COVID-19 Patients. Colchicine did not show a significant effect on mortality among PCR confirmed COVID-19 patients (RR 1.02, 95% CI 0.74-1.41).
Table (7): Meta-analysis for the efficacy of colchicine on mortality among PCR confirmed COVID-19 Patients.
Study
|
Type of study
|
Relative Risk
|
95% CI
|
P-value
|
Tardif et al. 2021
|
RCT
|
0.56
|
0.19-1.66
|
0.042
|
Recovery Collaborative Group 2021
|
RCT
|
1.02
|
0.94-1.10
|
0.70
|
Fixed Effect Model
|
1.02
|
0.74-1.41
|
---
|
95% CI, 95% confidence interval. RCT, Randomized controlled trial.
Hospitalization among PCR confirmed COVID-19 patients
Tardif et al. assessed the efficacy of colchicine on hospitalization and reported that colchicine resulted in decreased hospitalization among the PCR confirmed COVID-19 patients (RR 0.75, 95%CI 0.57-0.99, P 0.042) [23].
Mechanical Ventilation among PCR confirmed COVID-19 patients
Tardif et al. found that colchicine has no significant effect on mechanical ventilation among PCR confirmed COVID-19 Patients (RR 0.50, 95%CI 0.23-1.07, P 0.042) [23].