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34 colchicine COVID-19 controlled studies, 17 RCTs
https://c19colchicine.com/meta.html
0
0.5
1
1.5+
All studies 40% 34
22,738
Improvement, Studies, Patients Relative Risk Mortality 42% 29
21,010
Ventilation 43% 6
12,814
ICU admission 29% 5
815
Hospitalization 23% 10
6,815
Progression 81% 3
289
Recovery 30% 9
12,419
Cases -73% 1
1,278
RCTs 22% 17
19,059
RCT mortality 7% 14
18,677
Peer-reviewed 42% 31
22,217
Prophylaxis 26% 3
1,278
Early 68% 1
0
Late 39% 30
21,460
Colchicine for COVID-19 c19colchicine.com Aug 2022
Favors colchicine Favors control after exclusions
• Statistically significant improvements are seen for
mortality ,
ICU admission ,
hospitalization , and
recovery . 21 studies from 21 independent teams in 13 different countries show statistically significant
improvements in isolation (12 for the most serious outcome).
• Results are robust — in exclusion sensitivity analysis 24 of 34
studies must be excluded to avoid finding statistically significant efficacy
in pooled analysis.
0
0.5
1
1.5+
All studies 40% 34
22,738
Improvement, Studies, Patients Relative Risk Mortality 42% 29
21,010
Ventilation 43% 6
12,814
ICU admission 29% 5
815
Hospitalization 23% 10
6,815
Progression 81% 3
289
Recovery 30% 9
12,419
Cases -73% 1
1,278
RCTs 22% 17
19,059
RCT mortality 7% 14
18,677
Peer-reviewed 42% 31
22,217
Prophylaxis 26% 3
1,278
Early 68% 1
0
Late 39% 30
21,460
Colchicine for COVID-19 c19colchicine.com Aug 2022
Favors colchicine Favors control after exclusions
• RCT results are less favorable, however they are dominated by the very late stage RECOVERY RCT,
for which the results are not generalizable to earlier usage.
• While
many treatments have some level
of efficacy, they do not replace vaccines and other measures to avoid
infection.
Only 15% of colchicine
studies show zero events in the treatment arm.
Multiple treatments are typically used
in combination, and
other treatments
may be more effective.
• No treatment, vaccine, or intervention is 100%
available and effective for all variants. All practical, effective, and safe
means should be used.
Denying the efficacy of treatments increases mortality, morbidity, collateral
damage, and endemic risk.
• All data to reproduce this paper and
sources are in the
appendix .
Other meta analyses for colchicine can be found in
[Rai , Yasmin , Zein ] , showing significant improvements for mortality and severity.
Highlights
We show traditional outcome specific analyses and combined
evidence from all studies, incorporating treatment delay, a primary
confounding factor in COVID-19 studies.
A
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Hunt 68%
0.32 [0.15-0.67]
death
Improvement, RR [CI] Treatment Control Tau2 = 0.00, I2 = 0.0%, p = 0.0006
Early treatment 68%
0.32 [0.15-0.67]
68% improvement Deftereos (RCT) 77%
0.23 [0.03-1.97]
death
1/55
4/50
Improvement, RR [CI] Treatment Control Lopes (DB RCT) 80%
0.20 [0.01-4.03]
death
0/36
2/36
Brunetti (PSM) 73%
0.27 [0.08-0.89]
death
3/33
11/33
Scarsi 85%
0.15 [0.06-0.37]
death
122 (n)
140 (n)
Salehzadeh (RCT) 23%
0.77 [0.66-0.90]
hosp. time
50 (n)
50 (n)
Pinzón 35%
0.65 [0.34-1.21]
death
14/145
23/156
Sandhu 42%
0.58 [0.40-0.85]
death
16/34
63/78
Rodriguez-Nava 6%
0.94 [0.61-1.47]
death
16/52
85/261
Mahale -7%
1.07 [0.59-1.96]
death
11/39
25/95
Valerio Pas.. (ICU) 23%
0.77 [0.31-1.94]
death
5/35
12/30
ICU patients CT1
Tardif (DB RCT) 44%
0.56 [0.19-1.67]
death
5/2,235
9/2,253
Mareev 80%
0.20 [0.01-4.01]
death
0/21
2/22
García-Posada 57%
0.43 [0.16-0.84]
death
48/99
59/110
CT1
Manenti (PSW) 76%
0.24 [0.09-0.67]
death
71 (n)
70 (n)
Mostafaie (RCT) 83%
0.17 [0.02-1.34]
death
1/60
6/60
CT1
Recovery C.. (RCT) -1%
1.01 [0.93-1.10]
death
1,173/5,610
1,190/5,730
Hueda-Zavaleta 54%
0.46 [0.23-0.91]
death
10/50
109/301
Kevorkian 96%
0.04 [0.01-0.21]
progression
28 (n)
40 (n)
CT1
Gaitán-Dua.. (RCT) 22%
0.78 [0.44-1.36]
death
22/153
28/161
CT1
Pascual-Fi.. (RCT) 80%
0.20 [0.01-4.03]
death
0/52
2/51
Dorward (RCT) 70%
0.30 [0.01-7.37]
death
0/156
1/120
Absalón-.. (DB RCT) 29%
0.71 [0.21-2.40]
death
4/56
6/60
Diaz (RCT) 12%
0.88 [0.70-1.12]
death
131/640
142/639
Alsultan (RCT) 36%
0.64 [0.20-2.07]
death
3/14
7/21
Karakaş 13%
0.87 [0.46-1.64]
death
16/165
19/171
Pourdowlat (RCT) 73%
0.27 [0.11-0.71]
hosp.
5/102
18/100
Gorial (RCT) 67%
0.33 [0.04-3.14]
death
1/80
3/80
Pimenta B.. (RCT) 79%
0.21 [0.01-4.05]
death
0/14
2/16
Jalal (RCT) 24%
0.76 [0.62-0.93]
hosp. time
36 (n)
44 (n)
Cecconi (DB RCT) 29%
0.71 [0.28-1.79]
death
7/119
10/120
Tau2 = 0.10, I2 = 73.5%, p < 0.0001
Late treatment 39%
0.61 [0.51-0.73]
1,492/10,362
1,838/11,098
39% improvement Monserrat V.. (PSM) 80%
0.20 [0.02-0.93]
death
n/a
n/a
Improvement, RR [CI] Treatment Control Topless 23%
0.77 [0.56-1.07]
death
Oztas -406%
5.06 [0.59-43.2]
hosp.
5/635
1/643
Tau2 = 0.86, I2 = 69.7%, p = 0.66
Prophylaxis 26%
0.74 [0.21-2.66]
5/635
1/643
26% improvement All studies 40%
0.60 [0.50-0.71]
1,497/10,997
1,839/11,741
40% improvement 34 colchicine COVID-19 studies c19colchicine.com Aug 2022
Tau2 = 0.11, I2 = 73.7%, p < 0.0001
Effect extraction pre-specified (most serious outcome, see appendix) 1 CT: study uses combined treatment Favors colchicine
Favors control
B
C
Figure 1. A. Random effects
meta-analysis. This plot shows pooled effects, discussion can be found in the heterogeneity section,
and results for specific outcomes can be found in the individual outcome analyses.
Effect extraction is pre-specified, using the most serious outcome reported.
For details of effect extraction see the
appendix .
B. Scatter plot showing the
distribution of effects reported in studies.
C. History of all reported
effects (chronological within treatment stages).
Introduction
We analyze all significant studies
concerning the use of
colchicine
for COVID-19.
Search methods, inclusion criteria, effect
extraction criteria (more serious outcomes have priority), all individual
study data, PRISMA answers, and statistical methods are detailed in
Appendix 1 . We present random effects meta-analysis results for all
studies, for studies within each treatment stage, for individual outcomes, for
peer-reviewed studies, for Randomized Controlled Trials (RCTs), and after
exclusions.
Figure 2 shows stages of possible treatment for
COVID-19.
Prophylaxis refers to regularly taking medication before
becoming sick, in order to prevent or minimize infection.
Early
Treatment refers to treatment immediately or soon after symptoms appear,
while
Late Treatment refers to more delayed treatment.
Results
Figure 3 shows a visual overview of the results, with details in
Table 1 and
Table 2 .
Figure
4 ,
5 ,
6 ,
7 ,
8 ,
9 ,
10 ,
11 , and
12
show forest plots for a random effects meta-analysis of
all studies with pooled effects, mortality results, ventilation, ICU admission, hospitalization, progression, recovery, cases, and peer reviewed studies.
0
0.5
1
1.5+
ALL STUDIES
MORTALITY
VENTILATION
ICU ADMISSION
HOSPITALIZATION
PROGRESSION
RECOVERY
CASES
RANDOMIZED CONTROLLED TRIALS
RCT MORTALITY
PEER-REVIEWED
After Exclusions
ALL STUDIES
All
Prophylaxis
Early
Late
Colchicine for COVID-19
C19COLCHICINE.COM AUG 2022
Treatment time Number of studies reporting positive effects
Total number of studies Percentage of studies reporting positive effects
Random effects meta-analysis results
Early treatment
1
1
100%
68% improvement
Late treatment
28
30
93.3%
39% improvement
Prophylaxis
2
3
66.7%
26% improvement
All studies
31
34
91.2%
40% improvement
Table 1. Results by treatment stage.
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Hunt 68%
0.32 [0.15-0.67]
death
Improvement, RR [CI] Treatment Control Tau2 = 0.00, I2 = 0.0%, p = 0.0006
Early treatment 68%
0.32 [0.15-0.67]
68% improvement Deftereos (RCT) 77%
0.23 [0.03-1.97]
death
1/55
4/50
Improvement, RR [CI] Treatment Control Lopes (DB RCT) 80%
0.20 [0.01-4.03]
death
0/36
2/36
Brunetti (PSM) 73%
0.27 [0.08-0.89]
death
3/33
11/33
Scarsi 85%
0.15 [0.06-0.37]
death
122 (n)
140 (n)
Salehzadeh (RCT) 23%
0.77 [0.66-0.90]
hosp. time
50 (n)
50 (n)
Pinzón 35%
0.65 [0.34-1.21]
death
14/145
23/156
Sandhu 42%
0.58 [0.40-0.85]
death
16/34
63/78
Rodriguez-Nava 6%
0.94 [0.61-1.47]
death
16/52
85/261
Mahale -7%
1.07 [0.59-1.96]
death
11/39
25/95
Valerio Pas.. (ICU) 23%
0.77 [0.31-1.94]
death
5/35
12/30
ICU patients CT1
Tardif (DB RCT) 44%
0.56 [0.19-1.67]
death
5/2,235
9/2,253
Mareev 80%
0.20 [0.01-4.01]
death
0/21
2/22
García-Posada 57%
0.43 [0.16-0.84]
death
48/99
59/110
CT1
Manenti (PSW) 76%
0.24 [0.09-0.67]
death
71 (n)
70 (n)
Mostafaie (RCT) 83%
0.17 [0.02-1.34]
death
1/60
6/60
CT1
Recovery C.. (RCT) -1%
1.01 [0.93-1.10]
death
1,173/5,610
1,190/5,730
Hueda-Zavaleta 54%
0.46 [0.23-0.91]
death
10/50
109/301
Kevorkian 96%
0.04 [0.01-0.21]
progression
28 (n)
40 (n)
CT1
Gaitán-Dua.. (RCT) 22%
0.78 [0.44-1.36]
death
22/153
28/161
CT1
Pascual-Fi.. (RCT) 80%
0.20 [0.01-4.03]
death
0/52
2/51
Dorward (RCT) 70%
0.30 [0.01-7.37]
death
0/156
1/120
Absalón-.. (DB RCT) 29%
0.71 [0.21-2.40]
death
4/56
6/60
Diaz (RCT) 12%
0.88 [0.70-1.12]
death
131/640
142/639
Alsultan (RCT) 36%
0.64 [0.20-2.07]
death
3/14
7/21
Karakaş 13%
0.87 [0.46-1.64]
death
16/165
19/171
Pourdowlat (RCT) 73%
0.27 [0.11-0.71]
hosp.
5/102
18/100
Gorial (RCT) 67%
0.33 [0.04-3.14]
death
1/80
3/80
Pimenta B.. (RCT) 79%
0.21 [0.01-4.05]
death
0/14
2/16
Jalal (RCT) 24%
0.76 [0.62-0.93]
hosp. time
36 (n)
44 (n)
Cecconi (DB RCT) 29%
0.71 [0.28-1.79]
death
7/119
10/120
Tau2 = 0.10, I2 = 73.5%, p < 0.0001
Late treatment 39%
0.61 [0.51-0.73]
1,492/10,362
1,838/11,098
39% improvement Monserrat V.. (PSM) 80%
0.20 [0.02-0.93]
death
n/a
n/a
Improvement, RR [CI] Treatment Control Topless 23%
0.77 [0.56-1.07]
death
Oztas -406%
5.06 [0.59-43.2]
hosp.
5/635
1/643
Tau2 = 0.86, I2 = 69.7%, p = 0.66
Prophylaxis 26%
0.74 [0.21-2.66]
5/635
1/643
26% improvement All studies 40%
0.60 [0.50-0.71]
1,497/10,997
1,839/11,741
40% improvement 34 colchicine COVID-19 studies c19colchicine.com Aug 2022
Tau2 = 0.11, I2 = 73.7%, p < 0.0001
Effect extraction pre-specified (most serious outcome, see appendix) 1 CT: study uses combined treatment Favors colchicine
Favors control
Figure 4. Random effects meta-analysis for all studies with pooled effects.
This plot shows pooled effects, discussion can be found in the heterogeneity section,
and results for specific outcomes can be found in the individual outcome analyses.
Effect extraction is pre-specified, using the most serious outcome reported.
For details of effect extraction see the
appendix .
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Hunt 68%
0.32 [0.15-0.67]
Improvement, RR [CI] Treatment Control Tau2 = 0.00, I2 = 0.0%, p = 0.0006
Early treatment 68%
0.32 [0.15-0.67]
68% improvement Deftereos (RCT) 77%
0.23 [0.03-1.97]
1/55
4/50
Improvement, RR [CI] Treatment Control Lopes (DB RCT) 80%
0.20 [0.01-4.03]
0/36
2/36
Brunetti (PSM) 73%
0.27 [0.08-0.89]
3/33
11/33
Scarsi 85%
0.15 [0.06-0.37]
122 (n)
140 (n)
Pinzón 35%
0.65 [0.34-1.21]
14/145
23/156
Sandhu 42%
0.58 [0.40-0.85]
16/34
63/78
Rodriguez-Nava 6%
0.94 [0.61-1.47]
16/52
85/261
Mahale -7%
1.07 [0.59-1.96]
11/39
25/95
Valerio Pas.. (ICU) 23%
0.77 [0.31-1.94]
5/35
12/30
ICU patients CT1
Tardif (DB RCT) 44%
0.56 [0.19-1.67]
5/2,235
9/2,253
Mareev 80%
0.20 [0.01-4.01]
0/21
2/22
García-Posada 57%
0.43 [0.16-0.84]
48/99
59/110
CT1
Manenti (PSW) 76%
0.24 [0.09-0.67]
71 (n)
70 (n)
Mostafaie (RCT) 83%
0.17 [0.02-1.34]
1/60
6/60
CT1
Recovery C.. (RCT) -1%
1.01 [0.93-1.10]
1,173/5,610
1,190/5,730
Hueda-Zavaleta 54%
0.46 [0.23-0.91]
10/50
109/301
Gaitán-Dua.. (RCT) 22%
0.78 [0.44-1.36]
22/153
28/161
CT1
Pascual-Fi.. (RCT) 80%
0.20 [0.01-4.03]
0/52
2/51
Dorward (RCT) 70%
0.30 [0.01-7.37]
0/156
1/120
Absalón-.. (DB RCT) 29%
0.71 [0.21-2.40]
4/56
6/60
Diaz (RCT) 12%
0.88 [0.70-1.12]
131/640
142/639
Alsultan (RCT) 36%
0.64 [0.20-2.07]
3/14
7/21
Karakaş 13%
0.87 [0.46-1.64]
16/165
19/171
Gorial (RCT) 67%
0.33 [0.04-3.14]
1/80
3/80
Pimenta B.. (RCT) 79%
0.21 [0.01-4.05]
0/14
2/16
Cecconi (DB RCT) 29%
0.71 [0.28-1.79]
7/119
10/120
Tau2 = 0.13, I2 = 71.6%, p < 0.0001
Late treatment 40%
0.60 [0.48-0.75]
1,487/10,146
1,820/10,864
40% improvement Monserrat V.. (PSM) 80%
0.20 [0.02-0.93]
n/a
n/a
Improvement, RR [CI] Treatment Control Topless 23%
0.77 [0.56-1.07]
Tau2 = 0.64, I2 = 71.1%, p = 0.24
Prophylaxis 53%
0.47 [0.13-1.67]
53% improvement All studies 42%
0.58 [0.47-0.72]
1,487/10,146
1,820/10,864
42% improvement 29 colchicine COVID-19 mortality results c19colchicine.com Aug 2022
Tau2 = 0.14, I2 = 72.7%, p < 0.0001
1 CT: study uses combined treatment Favors colchicine
Favors control
Figure 5. Random effects meta-analysis for mortality results.
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Deftereos (RCT) 82%
0.18 [0.02-1.50]
1/55
5/50
Improvement, RR [CI] Treatment Control Sandhu 53%
0.47 [0.33-0.67]
16/34
68/68
Tardif (DB RCT) 47%
0.53 [0.25-1.09]
11/2,235
21/2,253
Recovery C.. (RCT) -18%
1.18 [0.99-1.40]
259/3,815
228/3,962
Pascual-Fi.. (RCT) 80%
0.20 [0.01-4.03]
0/52
2/51
Cecconi (DB RCT) 50%
0.50 [0.18-1.43]
5/119
10/120
Tau2 = 0.34, I2 = 82.5%, p = 0.075
Late treatment 43%
0.57 [0.31-1.06]
292/6,310
334/6,504
43% improvement All studies 43%
0.57 [0.31-1.06]
292/6,310
334/6,504
43% improvement 6 colchicine COVID-19 mechanical ventilation results c19colchicine.com Aug 2022
Tau2 = 0.34, I2 = 82.5%, p = 0.075
Favors colchicine
Favors control
Figure 6. Random effects meta-analysis for ventilation.
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Lopes (DB RCT) 50%
0.50 [0.10-2.56]
2/36
4/36
Improvement, RR [CI] Treatment Control Valerio Pas.. (ICU) 40%
0.60 [0.38-0.95]
35 (n)
30 (n)
ICU patients CT1
Pascual-Fi.. (RCT) 51%
0.49 [0.09-2.56]
2/52
4/51
Karakaş 16%
0.84 [0.55-1.29]
30/165
37/171
Cecconi (DB RCT) 21%
0.79 [0.38-1.67]
11/119
14/120
Tau2 = 0.00, I2 = 0.0%, p = 0.018
Late treatment 29%
0.71 [0.54-0.94]
45/407
59/408
29% improvement All studies 29%
0.71 [0.54-0.94]
45/407
59/408
29% improvement 5 colchicine COVID-19 ICU results c19colchicine.com Aug 2022
Tau2 = 0.00, I2 = 0.0%, p = 0.018
1 CT: study uses combined treatment Favors colchicine
Favors control
Figure 7. Random effects meta-analysis for ICU admission.
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Lopes (DB RCT) 22%
0.78 [0.64-0.94]
hosp. time
36 (n)
36 (n)
Improvement, RR [CI] Treatment Control Salehzadeh (RCT) 23%
0.77 [0.66-0.90]
hosp. time
50 (n)
50 (n)
Tardif (DB RCT) 20%
0.80 [0.61-1.03]
hosp.
101/2,235
128/2,253
Mareev 26%
0.74 [0.53-1.04]
hosp. time
21 (n)
22 (n)
Mostafaie (RCT) 35%
0.65 [0.53-0.81]
hosp. time
59 (n)
54 (n)
CT1
Pascual-Fi.. (RCT) -15%
1.15 [0.87-1.51]
hosp. time
52 (n)
51 (n)
Karakaş 25%
0.75 [0.65-0.87]
hosp. time
165 (n)
171 (n)
Pourdowlat (RCT) 73%
0.27 [0.11-0.71]
hosp.
5/102
18/100
Jalal (RCT) 24%
0.76 [0.62-0.93]
hosp. time
36 (n)
44 (n)
Tau2 = 0.01, I2 = 47.1%, p < 0.0001
Late treatment 23%
0.77 [0.69-0.85]
106/2,756
146/2,781
23% improvement Oztas -406%
5.06 [0.59-43.2]
hosp.
5/635
1/643
Improvement, RR [CI] Treatment Control Tau2 = 0.00, I2 = 0.0%, p = 0.14
Prophylaxis -406%
5.06 [0.59-43.2]
5/635
1/643
-406% improvement All studies 23%
0.77 [0.69-0.86]
111/3,391
147/3,424
23% improvement 10 colchicine COVID-19 hospitalization results c19colchicine.com Aug 2022
Tau2 = 0.01, I2 = 50.2%, p < 0.0001
1 CT: study uses combined treatment Favors colchicine
Favors control
Figure 8. Random effects meta-analysis for hospitalization.
