Ivermectin is effective for COVID-19: real-time meta analysis of 49
studies
Covid Analysis, Nov 26, 2020 (Version 53, Apr 4, 2021)
https://ivmmeta.com/• 100% of the 49 studies to date report positive effects (24 statistically signi cant in isolation).
Random effects meta-analysis for early treatment and pooled effects shows an 80% reduction, RR
0.20 [0.09-0.41], and prophylactic use shows 89% improvement, RR 0.11 [0.06-0.22]. Mortality
results show 76% lower mortality, RR 0.24 [0.14-0.42] for all treatment delays, and 84% lower, RR
0.16 [0.04-0.63] for early treatment.
• 100% of the 26 Randomized Controlled Trials (RCTs) report positive effects, with an estimated
70% improvement, RR 0.30 [0.20-0.46].
• The probability that an ineffective treatment generated results as positive as the 49 studies todate is estimated to be 1 in 563 trillion (p = 0.000000000000002).
• All data to reproduce this paper and the sources are in the appendix. See [Bryant, Hill, Kory, Lawrie,Nardelli] for other meta analyses, all with similar results con rming effectiveness.
Improvement

Studies

Authors

Patients

Early treatment

80% [59‑91%]

17

161

1,856

Late treatment

50% [34‑62%]

20

146

6,885

Prophylaxis

89% [78‑94%]

12

77

7,011

Mortality

76% [58‑86%]

18

155

7,267

RCTs only

70% [54‑80%]

26

225

3,686

All studies

73% [64‑79%]

49

384

15,752WHO ivermectin approval status
Indication

StudiesPatients

Effect size

StatusScabies

6613

35% [22‑46%]

Approved

COVID‑1949

15,75273% [64‑79%]

Pending

ivmmeta.com 4/4/21

Ivermectin COVID-19 early treatment and prophylaxis studies
Treatment Control
Chowdhury (RCT) hosp.
0/60
2/56
Espitia-Hernandez viral+
0/28
7/7
Carvallo
death
1/33
3/12
Cadegiani
death
0/110
2/137
Ahmed (DB RCT)
symptoms 0/17
3/19
Chaccour (DB RCT) symp. prob. 12
12
Afsar
symptoms 0/37
7/53
Babalola (DB RCT) viral+
40
20
Kirti (DB RCT)
death
0/55
4/57
Asghar (RCT)
viral+
5/50
28/50
Raad (SB RCT)
hosp.
0/50
3/50
Mohan (DB RCT)no recov.
2/40
6/45
Schwartz (DB RCT) hosp.
0/49
2/45
Elalfyviral+
7/62
44/51
López-Me.. (DB RCT) death
0/200
1/198
Roy
recov. time 14
15
Chahla (CLUS. RCT) no disch.
2/110
8/62

Early treatment

17/967

Dose (4d) RR
14mg
0.19
12mg
0.03
36mg
0.12
42mg
0.22
48mg
0.15
28mg
0.47
48mg
0.08
24mg
0.36
24mg
0.11
14mg
0.18
14mg
0.14
28mg
0.38
36mg
0.19
36mg
0.13
84mg
0.33
n/a
0.94
24mg
0.11

120/889CI[0.01-3.96][0.01-0.11][0.01-1.06][0.01-4.48][0.01-2.70][0.19-1.16][0.00-1.32][0.10-1.27][0.01-2.05][0.08-0.43][0.01-2.70][0.08-1.75][0.01-3.92][0.06-0.27][0.01-8.11][0.52-1.93][0.02-0.52]

OT1 CT2
CT2
CT2

OT1
OT1

CT2
CT2

80% improvement

0.20 [0.09-0.41]

Tau2 = 1.38; I2 = 82.6%

Treatment Control
symp. case 15/203
59/101
cases
0/131
11/98
cases
41/117145/255
cases
2/100
10/100cases
0/788
237/407cases
ecological
death
0/69
150/3,062
cases
4/58
44/60
cases
13/38961/486cases
0/117
10/117
cases
2,199
1,147
death
ecological

Shouman (RCT)
Carvallo
BeheraElgazzar (RCT)
Carvallo
Hellwig (ECO.)
Bernigaud
Alam
Vallejos
Chahla (RCT)
BeheraTanioka (ECO.)

Prophylaxis

Dose (1m)RR
36mg
0.09
14mg
0.04
42mg
0.46
112mg 0.20
48mg
0.00
14mg
0.22
84mg
0.01
12mg
0.09
48mg
0.27
48mg
0.05
42mg
0.17
14mg
0.12

CI
[0.03-0.23][0.00-0.63][0.29-0.71][0.04-0.89][0.00-0.02][0.05-0.89][0.00-0.10][0.04-0.24][0.15-0.48][0.00-0.80][0.12-0.23][0.03-0.51]

CT2

CT2

CT2

75/4,171 727/5,833

0.11 [0.06-0.22]

89% improvement

92/5,138 847/6,722

0.15 [0.09-0.25]

85% improvement

Tau2 = 0.90; I2 = 83.0%

All studies

01

OT: ivermectin vs. other treatment
CT: study uses combined treatment
Tau2 = 1.11; I2 = 89.3%; Z = 7.43 (p < 0.0001)
2

0.25

0.5

0.75

1

Lower Risk

1.25

1.5

1.75

2+

Increased Risk A
ivmmeta.com 4/4/21
min, Q1, median, Q3, max

Early treatment

All studies
0

0.25

0.5

0.75

1

1.25

Lower Risk

1.75

Early treatment

100

2+

B
ivmmeta.com 4/4/21

75
50

Dec 15 p<0.01
1 in 100100+Probability results fromineffective treatment

Jan 16 p<0.001
1 in 1 thousand

Chahlano disch., p=0.005

Roy
recov. time, p=0.87

López-Medina
death, p=0.50

Elalfyviral+, p<0.0001

Schwartz
hosp., p=0.23

Mohan
no recov., p=0.27

Raadhosp., p=0.24

Asgharviral+, p<0.001

Kirti
death, p=0.12

Babalolaviral+, p=0.11

Afsar
symptoms, p=0.04

Chaccoursymp. prob., p<0.05

Ahmed
symptoms, p=0.09

75

Cadegiani
death, p=0.50

50

Carvallo
death, p=0.05

25

Espitia-Hernandezviral+, p<0.0001

25

Chowdhury
hosp., p=0.23% Increased Risk % Lower Risk

1.5

Increased Risk

Feb 16 p<0.0001
1 in 10 thousand
Mar 30 p<0.00001
1 in 100 thousand

CAll studies

ivmmeta.com 4/4/21

75
50
25

25
50

Gorialdeath, p=1.00
Chowdhury
hosp., p=0.23
Espitia-Hernandezviral+, p<0.0001
Shoumansymp. case, p<0.001
Podderrecov. time, p=0.34
Carvallo
death, p=0.05
Khandeath, p<0.05
Chacharno recov., p=0.50
Soto-Becerra
death, p=0.01
Mahmuddeath, p=0.25
Rajterdeath, p=0.04
Carvallo
cases, p<0.0001
Hashimdeath, p=0.27
Beheracases, p<0.0001
Cadegiani
death, p=0.50
Camprubí
ICU, p=1.00
Elgazzar
death, p<0.0001
Elgazzarcases, p=0.03
Spoorthirecov. time, p=0.03
Carvallo
cases, p<0.0001
Budhiraja
death, p=0.04
Niaee
death, p=0.001
Hellwig
cases, p<0.02
Bernigauddeath, p=0.08
Ahmed
symptoms, p=0.09
Chaccoursymp. prob., p<0.05
Afsar
symptoms, p=0.04
Alamcases, p<0.0001
Vallejoscases, p<0.0001
Babalolaviral+, p=0.11
Kirti
death, p=0.12
Chahlacases, p=0.002
Okumuş
death, p=0.55
Asgharviral+, p<0.001
Raad
hosp., p=0.24
Rezai
recov. time, p=0.02
Mohan
no recov., p=0.27
Bukhariviral+, p<0.0001
Lima-Morales
death, p<0.001
Schwartz
hosp., p=0.23
Beheracases, p<0.001
Elalfyviral+, p<0.0001
Beltran-Gonzalez
death, p=1.00
López-Medina
death, p=0.50
Pott-Junior
ICU, p=0.25
Roy
recov. time, p=0.87
Huvemekno improv., p=0.28
Taniokadeath, p=0.002
Chahlano disch., p=0.005% Increased Risk % Lower Risk

100

75

100+

Sep 24 p<0.01
1 in 100
Probability results fromineffective treatment

Nov 13 p<0.00001
Nov 28 p<0.0000001
1 in 100 thousand
1 in 10 million
Nov 3 p<0.0001
Nov 17 p<0.000001
1 in 10 thousand
1 in 1 million

Feb 12
1 in 1 trillion
Jan 6
1 in 1 billion

D

Figure 1. A. Random effects meta-analysis excluding late treatment. This plot shows pooled effects, analysis forindividual outcomes is below, and more details on pooled effects can be found in the discussion section.
Simpli ed dosages are shown for comparison, these are the total dose in the rst four days for treatment, and themonthly dose for prophylaxis, for a 70kg person. For full details see the appendix. B. Scatter plot showing the
distribution of effects reported in early treatment studies and in all studies. C and D. Chronological history of allreported effects, with the probability that the observed frequency of positive results occurred due to random
chance from an ineffective treatment.

Introduction
We analyze all signi cant studies concerning the use of ivermectin 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 mortality
results, for COVID-19 case results, for viral clearance results, for peer-reviewed studies, forRandomized Controlled Trials (RCTs), and after exclusions.
We also perform a simple analysis of the distribution of study effects. If treatment was noteffective, the observed effects would be randomly distributed (or more likely to be negative if
treatment is harmful). We can compute the probability that the observed percentage of positive
results (or higher) could occur due to chance with an ineffective treatment (the probability of >= kheads in n coin tosses, or the one-sided sign test / binomial test). Analysis of publication bias isimportant and adjustments may be needed if there is a bias toward publishing positive results.
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.

Figure 2. Treatment stages.

Results
Figure 3, 4, and 5 show results by treatment stage. Figure 6, 7, 8, and 9 show forest plots for arandom effects meta-analysis of all studies with pooled effects, and for studies reporting mortality
results, COVID-19 case results, and viral clearance results only. Figure 10 shows results for peer
reviewed trials only. Table 1 summarizes the results.

Treatment
time

Number ofstudiesreportingpositive
effects

Total
numberofstudies

Percentage ofstudiesreportingpositive effects

Probability of an equal or
greater percentage of positive
results from an ineffective
treatment

Random effects
meta-analysis
results

Early
treatment

17

17

100%

0.0000076
1 in 131 thousand

80% improvement
RR 0.20 [0.09‑0.41]
p < 0.0001

Late
treatment

20

20

100%

0.00000095
1 in 1 million

50% improvement
RR 0.50 [0.38‑0.66]
p < 0.0001

Prophylaxis

12

12

100%

0.00024
1 in 4 thousand

89% improvement
RR 0.11 [0.06‑0.22]
p < 0.0001

All studies

49

49

100%

0.000000000000002
1 in 563 trillion

73% improvement
RR 0.27 [0.21‑0.36]
p < 0.0001

Table 1. Results by treatment stage.

% Increased Risk % Lower Risk
25

50

75

100+

Probability results fromineffective treatment
Oct 8 p<0.05
Oct 13 p<0.01
1 in 20
1 in 100
Nov 13 p<0.001
1 in 1 thousand

Late treatment

Jan 12 p<0.0001
1 in 10 thousand
Huvemekno improv., p=0.28

Probability results fromineffective treatment
Chahlano disch., p=0.005

Roy
recov. time, p=0.87

1.5

Pott-Junior
ICU, p=0.25

Early treatment

López-Medina
death, p=0.50

Elalfyviral+, p<0.0001

Prophylaxis

Beltran-Gonzalez
death, p=1.00

Lima-Morales
death, p<0.001

Jan 16 p<0.001
1 in 1 thousand

Bukhariviral+, p<0.0001

1.25

Schwartz
hosp., p=0.23

Mohan
no recov., p=0.27

Lower Risk

Rezai
recov. time, p=0.02

Okumuş
death, p=0.55

Raadhosp., p=0.24

Asgharviral+, p<0.001

Kirti
death, p=0.12

1

Niaee
death, p=0.001

Budhiraja
death, p=0.04

100

Babalolaviral+, p=0.11

0.75

Spoorthirecov. time, p=0.03

Dec 15 p<0.01
1 in 100

Elgazzar
death, p<0.0001

100

Camprubí
ICU, p=1.00

Afsar
symptoms, p=0.04

Chaccoursymp. prob., p<0.05

Ahmed
symptoms, p=0.09

0.5

Hashimdeath, p=0.27

Rajterdeath, p=0.04

100+

Mahmuddeath, p=0.25

Cadegiani
death, p=0.50

Carvallo
death, p=0.05

0.25

Soto-Becerra
death, p=0.01

Chacharno recov., p=0.50

Espitia-Hernandezviral+, p<0.0001

75

Khan
death, p<0.05

0Podderrecov. time, p=0.34

50

Chowdhury
hosp., p=0.23

25

Gorialdeath, p=1.00% Increased Risk % Lower Risk

ivmmeta.com 4/4/21
min, Q1, median, Q3, max

Early treatment

Late treatment

All studies

Increased Risk

1.75
2+

Figure 3. Results by treatment stage.

ivmmeta.com 4/4/21

75

50

25

Feb 16 p<0.0001
1 in 10 thousand
Mar 30 p<0.00001
1 in 100 thousand

ivmmeta.com 4/4/21

75

50

25

Mar 25 p<0.000001
1 in 1 million

Feb 10 p<0.00001
1 in 100 thousand

Figure 4. Chronological history of early and late treatment results, with the probability that the observed frequencyof positive results occurred due to random chance from an ineffective treatment.

% Increased Risk
25

50

75

100+

Probability results fromineffective treatment
Nov 17 p<0.05
1 in 20
Nov 28 p<0.01
1 in 100

Figure 5. Chronological history of prophylaxis results.

Prophylaxis

Vallejoscases, p<0.0001

Alamcases, p<0.0001

Bernigauddeath, p=0.08

Hellwig
cases, p<0.02

Carvallo
cases, p<0.0001

Elgazzarcases, p=0.03

Beheracases, p<0.0001

Carvallo
cases, p<0.0001

Shoumansymp. case, p<0.001% Lower Risk
100

ivmmeta.com 1/10/21

75

50

25

ivmmeta.com 4/4/21

All 49 ivermectin COVID-19 studies
Treatment Control
Chowdhury (RCT) hosp.
0/60
2/56
Espitia-Hernandez viral+
0/28
7/7
Carvallo
death
1/33
3/12
Cadegiani
death
0/110
2/137
Ahmed (DB RCT)
symptoms 0/17
3/19
Chaccour (DB RCT) symp. prob. 12
12
Afsar
symptoms 0/37
7/53
Babalola (DB RCT) viral+
40
20
Kirti (DB RCT)
death
0/55
4/57
Asghar (RCT)
viral+
5/50
28/50
Raad (SB RCT)
hosp.
0/50
3/50
Mohan (DB RCT)no recov.
2/40
6/45
Schwartz (DB RCT) hosp.
0/49
2/45
Elalfyviral+
7/62
44/51
López-Me.. (DB RCT) death
0/200
1/198
Roy
recov. time 14
15
Chahla (CLUS. RCT) no disch.
2/110
8/62

Early treatment

17/967

Dose (4d) RR
14mg
0.19
12mg
0.03
36mg
0.12
42mg
0.22
48mg
0.15
28mg
0.47
48mg
0.08
24mg
0.36
24mg
0.11
14mg
0.18
14mg
0.14
28mg
0.38
36mg
0.19
36mg
0.13
84mg
0.33
n/a
0.94
24mg
0.11

120/889CI[0.01-3.96][0.01-0.11][0.01-1.06][0.01-4.48][0.01-2.70][0.19-1.16][0.00-1.32][0.10-1.27][0.01-2.05][0.08-0.43][0.01-2.70][0.08-1.75][0.01-3.92][0.06-0.27][0.01-8.11][0.52-1.93][0.02-0.52]

OT1 CT2
CT2
CT2

OT1
OT1

CT2
CT2

80% improvement

0.20 [0.09-0.41]

Tau2 = 1.38; I2 = 82.6%

GorialPodder (RCT)
Khan
Chachar (RCT)
Soto-Becerra
Mahmud (DB RCT)
RajterHashim (SB RCT)CamprubíElgazzar (RCT)
Spoorthi
Budhiraja
Niaee (DB RCT)
Okumuş (DB RCT)
Rezai (DB RCT)
Bukhari (RCT)Lima-Morales
Beltran-.. (DB RCT)
Pott-Junior (RCT)
Huvemek (DB RCT)

Late treatment

death
recov. timedeath
no recov.
death
death
death
death
ICU
death
recov. time
death
death
death
recov. time
viral+
death
death
ICU
no improv.

Treatment Control
Dose (4d) RR
0/16
2/71
14mg
0.29
32
30
14mg
0.84
1/115
9/133
12mg
0.13
9/25
10/25
36mg
0.90
92/203
1,438/2,630 14mg
0.83
0/183
3/183
12mg
0.14
13/98
24/98
14mg
0.54
2/70
6/70
28mg
0.33
2/13
3/13
14mg
0.67
2/200
24/200112mg 0.08
50
50
n/a
0.79
0/34
103/942
n/a
0.01
4/120
11/60
28mg
0.18
6/30
9/30
56mg
0.67
51
52
14mg
0.79
4/41
25/45
12mg
0.18
15/48152/287
12mg
0.22
5/36
6/37
12mg
0.86
1/27
1/4
14mg
0.15
13/50
19/50
84mg
0.68

169/1,875 1,745/5,010

CI[0.01-5.76][0.55-1.12][0.02-1.01][0.44-1.83][0.71-0.97][0.01-2.75][0.27-0.99][0.07-1.60][0.13-3.35][0.02-0.35][0.62-1.01][0.00-0.15][0.06-0.55][0.27-1.64][0.63-0.98][0.07-0.46][0.12-0.41][0.29-2.56][0.01-1.93][0.38-1.23]

CT2
CT2
OT1
CT2

CT2

50% improvement

0.50 [0.38-0.66]

Tau2 = 0.16; I2 = 69.4%

Shouman (RCT)
Carvallo
BeheraElgazzar (RCT)
Carvallo
Hellwig (ECO.)
Bernigaud
Alam
Vallejos
Chahla (RCT)
BeheraTanioka (ECO.)

Prophylaxis

Treatment Control
symp. case 15/203
59/101
cases
0/131
11/98
cases
41/117145/255
cases
2/100
10/100cases
0/788
237/407cases
ecological
death
0/69
150/3,062
cases
4/58
44/60
cases
13/38961/486cases
0/117
10/117
cases
2,199
1,147
death
ecological

Dose (1m)RR
36mg
0.09
14mg
0.04
42mg
0.46
112mg 0.20
48mg
0.00
14mg
0.22
84mg
0.01
12mg
0.09
48mg
0.27
48mg
0.05
42mg
0.17
14mg
0.12

CI
[0.03-0.23][0.00-0.63][0.29-0.71][0.04-0.89][0.00-0.02][0.05-0.89][0.00-0.10][0.04-0.24][0.15-0.48][0.00-0.80][0.12-0.23][0.03-0.51]

CT2

CT2

CT2

75/4,171 727/5,833

0.11 [0.06-0.22]

89% improvement261/7,013 2,592/11,732

0.27 [0.21-0.36]

73% improvement

Tau2 = 0.90; I2 = 83.0%

All studies
1

OT: ivermectin vs. other treatment
CT: study uses combined treatment
Tau2 = 0.41; I2 = 85.1%; Z = 9.74 (p < 0.0001)
2

0

0.25

0.5

0.75

Lower Risk

Figure 6. Random effects meta-analysis for all studies.

1

1.25

1.5

1.75

2+

Increased Risk

ivmmeta.com 4/4/21

All 18 ivermectin COVID-19 mortality results
Treatment
Carvallo
1/33
Cadegiani
0/110
Kirti (DB RCT)
0/55
López-Me.. (DB RCT) 0/200

Control
3/12
2/137
4/57
1/198

Early treatment 1/398

Dose (4d)
36mg
42mg
24mg
84mg

RR
0.12
0.22
0.11
0.33

CI
[0.01-1.06][0.01-4.48][0.01-2.05][0.01-8.11]

10/4040.16[0.04-0.63]

Control
Dose (4d)
2/71
14mg
9/133
12mg
1,438/2,630 14mg
3/183
12mg
24/98
14mg
6/70
28mg
24/200112mg
103/942
n/a
11/60
28mg
9/30
56mg
52/287
12mg
6/37
12mg

RR
0.29
0.13
0.83
0.14
0.54
0.33
0.08
0.01
0.18
0.67
0.22
0.86

CI
[0.01-5.76][0.02-1.01][0.71-0.97][0.01-2.75][0.27-0.99][0.07-1.60][0.02-0.35][0.00-0.15][0.06-0.55][0.27-1.64][0.12-0.41][0.29-2.56]

0.32[0.18-0.56]

CT2

84% improvement

Tau2 = 0.00; I2 = 0.0%

GorialKhan
Soto-Becerra
Mahmud (DB RCT)
RajterHashim (SB RCT)
Elgazzar (RCT)
Budhiraja
Niaee (DB RCT)
Okumuş (DB RCT)
Lima-Morales
Beltran-.. (DB RCT)

Treatment
0/16
1/115
92/203
0/183
13/98
2/70
2/200
0/34
4/120
6/30
15/481
5/36

Late treatment 140/1,586 1,687/4,741

CT2
CT2
OT1

CT2

68% improvement

Tau2 = 0.56; I2 = 78.1%

Bernigaud
Tanioka (ECO.)

Treatment
0/69
ecologicalControl
150/3,062

Prophylaxis

0/69

150/3,062

Dose (1m) RR
84mg
0.01
14mg
0.12

CI
[0.00-0.10][0.03-0.51]

0.04[0.00-0.58]

96% improvement

0.24[0.14-0.42]

76% improvement

Tau2 = 2.93; I2 = 69.8%

All studies

141/2,053 1,847/8,207

01

OT: ivermectin vs. other treatment
CT: study uses combined treatment
Tau2 = 0.71; I2 = 76.1%; Z = 5.09 (p < 0.0001)
2

0.25

0.5

0.75

1

Lower Risk

1.25

1.5

1.75

2+

Increased Risk

Figure 7. Random effects meta-analysis for mortality results only.

All 10 ivermectin COVID-19 case results
Carvallo
BeheraElgazzar (RCT)
Carvallo
Hellwig (ECO.)
Bernigaud
Alam
Vallejos
Chahla (RCT)
BeheraControl
11/98
145/255
10/100237/407

Prophylaxis

67/3,968

1,210/5,732

0.18[0.10-0.33]

82% improvement

67/3,968

1,210/5,732

0.18[0.10-0.33]

82% improvement692/3,062
44/60
61/486
10/117
1,147

Dose (1m) RR
14mg
0.04
42mg
0.46
112mg
0.20
48mg
0.00
14mg
0.22
84mg
0.45
12mg
0.09
48mg
0.27
48mg
0.05
42mg
0.17

ivmmeta.com 4/4/21

Treatment
0/131
41/1172/100
0/788
ecological
7/69
4/58
13/389
0/117
2,199

CI
[0.00-0.63][0.29-0.71][0.04-0.89][0.00-0.02][0.05-0.89][0.22-0.91][0.04-0.24][0.15-0.48][0.00-0.80][0.12-0.23]

CT1

CT1

CT1

Tau2 = 0.53; I2 = 74.1%

All studies01

CT: study uses combined treatment
Tau2 = 0.53; I2 = 74.1%; Z = 5.52 (p < 0.0001)

0.25

0.5

0.75

Lower Risk

1

1.25

1.5

1.75

2+

Increased Risk

Figure 8. Random effects meta-analysis for COVID-19 case results only.

All 14 ivermectin COVID-19 viral clearance results
Chowdhury (RCT)
Espitia-Hernandez
Ahmed (DB RCT)
Babalola (DB RCT)
Kirti (DB RCT)
Asghar (RCT)Mohan (DB RCT)
Schwartz (DB RCT)
ElalfyTreatment
0/60
0/28
11/22
40
42/55
5/50
20/36
16/49
7/62

Early treatment 101/402

Control
2/56
7/7
20/23
20
39/57
28/50
26/42
25/45
44/51

Dose (4d)
14mg
12mg
48mg
24mg
24mg
14mg
28mg
36mg
36mg

ivmmeta.com 4/4/21

RR
0.19
0.03
0.57
0.36
1.12
0.18
0.90
0.49
0.13

CI
[0.01-3.96][0.01-0.11][0.37-0.90][0.10-1.27][0.89-1.40][0.08-0.43][0.62-1.31][0.30-0.79][0.06-0.27]

0.35[0.19-0.63]

RR
0.27
0.58
0.20
0.18
0.99

CI
[0.12-0.62][0.44-0.81][0.05-0.81][0.07-0.46][0.04-26.30]

66/3690.40[0.19-0.85]

60% improvement257/7200.40[0.28-0.57]

60% improvement

191/351

OT1 CT2
CT2
OT1
OT1

CT2

65% improvement

Tau2 = 0.61; I2 = 89.2%

Khan
Mahmud (DB RCT)
Okumuş (DB RCT)
Bukhari (RCT)Pott-Junior (RCT)Treatment
115
14/183
2/16
4/41
27

Late treatment 20/382

Control
133
36/1805/8
25/45
3Dose (4d)
12mg
12mg
56mg
12mg
14mg

CT2

Tau2 = 0.57; I2 = 86.7%

All studies
1

121/784

OT: ivermectin vs. other treatment
CT: study uses combined treatment
Tau2 = 0.31; I2 = 89.2%; Z = 4.97 (p < 0.0001)
2

0

0.25

0.5

0.75

Lower Risk

1

1.25

1.5

1.75

2+

Increased Risk

Figure 9. Random effects meta-analysis for viral clearance results only.

ivmmeta.com 4/4/21

All 21 ivermectin COVID-19 peer reviewed trials
Treatment Control
Chowdhury (RCT) hosp.
0/60
2/56
Espitia-Hernandez viral+
0/28
7/7
Ahmed (DB RCT)
symptoms 0/17
3/19
Chaccour (DB RCT) symp. prob. 12
12Babalola (DB RCT) viral+
40
20
Elalfyviral+
7/62
44/51
López-Me.. (DB RCT) death
0/200
1/198

Early treatment

7/419

Dose (4d) RR
14mg
0.19
12mg
0.03
48mg
0.15
28mg
0.47
24mg
0.36
36mg
0.13
84mg
0.33

57/363

CI[0.01-3.96][0.01-0.11][0.01-2.70][0.19-1.16][0.10-1.27][0.06-0.27][0.01-8.11]

OT1 CT2
CT2

OT1
CT2

83% improvement

0.17 [0.07-0.40]

Tau2 = 0.60; I2 = 54.4%

Podder (RCT)
Chachar (RCT)
RajterCamprubíSpoorthi
Lima-Morales
Beltran-.. (DB RCT)
Pott-Junior (RCT)

Late treatment

recov. time
no recov.
death
ICU
recov. time
death
death
ICU

Treatment Control
32
30
9/25
10/25
13/98
24/98
2/13
3/13
50
50
15/48152/287
5/36
6/37
1/27
1/4

45/762

Dose (4d) RR
14mg
0.84
36mg
0.90
14mg
0.54
14mg
0.67
n/a
0.79
12mg
0.22
12mg
0.86
14mg
0.15

96/544CI[0.55-1.12][0.44-1.83][0.27-0.99][0.13-3.35][0.62-1.01][0.12-0.41][0.29-2.56][0.01-1.93]

CT2
CT2

41% improvement

0.59 [0.38-0.90]

Tau2 = 0.20; I2 = 64.4%

Shouman (RCT)
BeheraCarvallo
Hellwig (ECO.)
Bernigaud
Alam

Prophylaxis

Treatment Control
symp. case 15/203
59/101cases
41/117145/255
cases
0/788
237/407cases
ecological
death
0/69
150/3,062
cases
4/58
44/60

Dose (1m)RR
36mg
0.09
42mg
0.46
48mg
0.00
14mg
0.22
84mg
0.01
12mg
0.09

CI
[0.03-0.23][0.29-0.71][0.00-0.02][0.05-0.89][0.00-0.10][0.04-0.24]

CT260/1,235 635/3,885

0.08 [0.02-0.25]

92% improvement

112/2,416 788/4,792

0.25 [0.16-0.40]

75% improvement

Tau2 = 1.60; I2 = 91.6%

All studies
1

OT: ivermectin vs. other treatment
CT: study uses combined treatment
Tau2 = 0.75; I2 = 85.5%; Z = 5.80 (p < 0.0001)
2

0

0.25

0.5

0.75

Lower Risk

1

1.25

1.5

1.75

2+

Increased Risk

Figure 10. Random effects meta-analysis for peer reviewed trials only.

Randomized Controlled Trials (RCTs)
Results restricted to Randomized Controlled Trials (RCTs) are shown in Figure 11, 12, 13, and 14,
and Table 2. RCT results are similar to non-RCT results. Evidence shows that non-RCT trials canalso provide reliable results. [Concato] nd that well-designed observational studies do not
systematically overestimate the magnitude of the effects of treatment compared to RCTs.
[Anglemyer] summarized reviews comparing RCTs to observational studies and found little
evidence for signi cant differences in effect estimates. [Lee] shows that only 14% of the guidelinesof the Infectious Diseases Society of America were based on RCTs. Evaluation of studies relies onan understanding of the study and potential biases. Limitations in an RCT can outweigh thebene ts, for example excessive dosages, excessive treatment delays, or Internet survey bias could
have a greater effect on results. Ethical issues may also prevent running RCTs for known effective
treatments. For more on issues with RCTs see [Deaton, Nichol].

% Increased Risk % Lower Risk
25

50

100+

Probability results fromineffective treatment
Oct 9 p<0.05
1 in 20

Nov 13 p<0.01
1 in 100
Dec 2 p<0.001
1 in 1 thousand
Jan 11 p<0.0001
1 in 10 thousand

Jan 16 p<0.00001
1 in 100 thousand

1.75

Chahlano disch., p=0.005

Huvemekno improv., p=0.28

1.5

Pott-Junior
ICU, p=0.25

Randomized Controlled Trials

López-Medina
death, p=0.50

Randomized Controlled Trials

Beltran-Gonzalez
death, p=1.00

Schwartz
hosp., p=0.23

1.25

Bukhariviral+, p<0.0001

Mohan
no recov., p=0.27

Lower Risk

Rezai
recov. time, p=0.02

Raad
hosp., p=0.24

1

Asgharviral+, p<0.001

Okumuş
death, p=0.55

Chahlacases, p=0.002

0.75

Kirti
death, p=0.12

Babalolaviral+, p=0.11

100

Chaccoursymp. prob., p<0.05

Ahmed
symptoms, p=0.09

0.5

Niaee
death, p=0.001

Elgazzarcases, p=0.03

Elgazzar
death, p<0.0001

0.25

Hashimdeath, p=0.27

Mahmuddeath, p=0.25

Chacharno recov., p=0.50

Podderrecov. time, p=0.34

0Shoumansymp. case, p<0.001

75

Chowdhury
hosp., p=0.23

ivmmeta.com 4/4/21
min, Q1, median, Q3, max

non-RCTs

Increased Risk

2+

ivmmeta.com 4/4/21

75

50

25

Mar 9 p<0.0000001
1 in 10 million

Feb 5 p<0.000001
1 in 1 million

Figure 11. Randomized Controlled Trials. The distribution of results for RCTs is similar to the distribution for allother studies.

ivmmeta.com 4/4/21

All 26 ivermectin COVID-19 Randomized Controlled Trials
Treatment Control
Chowdhury (RCT) hosp.
0/60
2/56
Ahmed (DB RCT)
symptoms 0/17
3/19
Chaccour (DB RCT) symp. prob. 12
12Babalola (DB RCT) viral+
40
20
Kirti (DB RCT)
death
0/55
4/57
Asghar (RCT)
viral+
5/50
28/50
Raad (SB RCT)
hosp.
0/50
3/50
Mohan (DB RCT)no recov.
2/40
6/45
Schwartz (DB RCT) hosp.
0/49
2/45
López-Me.. (DB RCT) death
0/200
1/198
Chahla (CLUS. RCT) no disch.
2/110
8/62

Early treatment

9/683

Dose (4d) RR
14mg
0.19
48mg
0.15
28mg
0.47
24mg
0.36
24mg
0.11
14mg
0.18
14mg
0.14
28mg
0.38
36mg
0.19
84mg
0.33
24mg
0.11

57/614CI[0.01-3.96][0.01-2.70][0.19-1.16][0.10-1.27][0.01-2.05][0.08-0.43][0.01-2.70][0.08-1.75][0.01-3.92][0.01-8.11][0.02-0.52]

OT1 CT2

OT1
OT1

75% improvement

0.25 [0.16-0.40]

Tau2 = 0.00; I2 = 0.0%

Podder (RCT)
Chachar (RCT)
Mahmud (DB RCT)Hashim (SB RCT)
Elgazzar (RCT)
Niaee (DB RCT)
Okumuş (DB RCT)
Rezai (DB RCT)
Bukhari (RCT)
Beltran-.. (DB RCT)
Pott-Junior (RCT)
Huvemek (DB RCT)

Late treatment

recov. time
no recov.
death
death
death
death
death
recov. time
viral+death
ICU
no improv.

Treatment Control
32
30
9/25
10/25
0/183
3/183
2/70
6/70
2/200
24/200
4/120
11/60
6/30
9/30
51
52
4/41
25/45
5/36
6/37
1/27
1/4
13/50
19/50

46/865

Dose (4d) RR
14mg
0.84
36mg
0.90
12mg
0.14
28mg
0.33
112mg 0.08
28mg
0.18
56mg
0.67
14mg
0.79
12mg
0.18
12mg
0.86
14mg
0.15
84mg
0.68

114/786

CI[0.55-1.12][0.44-1.83][0.01-2.75][0.07-1.60][0.02-0.35][0.06-0.55][0.27-1.64][0.63-0.98][0.07-0.46][0.29-2.56][0.01-1.93][0.38-1.23]

CT2
CT2
OT1

51% improvement

0.49 [0.33-0.73]

Tau2 = 0.23; I2 = 59.7%

Shouman (RCT)Elgazzar (RCT)
Chahla (RCT)Treatment Control
symp. case 15/203
59/101cases
2/100
10/100cases
0/117
10/117Prophylaxis

17/420

Dose (1m)RR
36mg
0.09
112mg 0.20
48mg
0.05

79/318CI[0.03-0.23][0.04-0.89][0.00-0.80]

CT2

0.09 [0.06-0.15]

91% improvement

0.30 [0.20-0.46]

70% improvement

Tau2 = 0.00; I2 = 0.0%

All studies
1

72/1,968 250/1,718

OT: ivermectin vs. other treatment
CT: study uses combined treatment
Tau2 = 0.66; I2 = 74.8%; Z = 5.52 (p < 0.0001)
2

0

0.25

0.5

0.75

Lower Risk

1

1.25

1.5

1.75

2+

Increased Risk

Figure 12. Random effects meta-analysis for Randomized Controlled Trials only.

ivmmeta.com 4/4/21
min, Q1, median, Q3, max

RCTs excluding late treatment

non-RCTs excluding late treatment
0

0.25

0.5

0.75

1

1.25

Lower Risk

2+

ivmmeta.com 4/4/21

75

50

Probability results fromineffective treatment

Dec 7 p<0.05
1 in 20

Jan 9 p<0.01
1 in 100

Jan 16 p<0.001
1 in 1 thousand

Chahlano disch., p=0.005

López-Medina
death, p=0.50

Schwartz
hosp., p=0.23

Mohan
no recov., p=0.27

Raadhosp., p=0.24

Asgharviral+, p<0.001

Chahlacases, p=0.002

Kirti
death, p=0.12

Babalolaviral+, p=0.11

Chaccoursymp. prob., p<0.05

75

100+

Ahmed
symptoms, p=0.09

50

Elgazzarcases, p=0.03

25

Shoumansymp. case, p<0.001

25

Chowdhury
hosp., p=0.23% Lower Risk

1.75

Randomized Controlled Trials (excluding late treatment)

100% Increased Risk

1.5

Increased Risk

Mar 30 p<0.0001
1 in 10 thousand

Figure 14. RCTs excluding late treatment.

All 8 ivermectin COVID-19 RCT mortality results

ivmmeta.com 4/4/21

Treatment
Kirti (DB RCT)
0/55
López-Me.. (DB RCT) 0/200

Control
4/57
1/198

Dose (4d) RR
24mg
0.11
84mg
0.33

CI
[0.01-2.05][0.01-8.11]

Early treatment 0/255

5/255

0.18

[0.02-1.57]

RR
0.14
0.33
0.08
0.18
0.67
0.86

CI
[0.01-2.75][0.07-1.60][0.02-0.35][0.06-0.55][0.27-1.64][0.29-2.56]

59/5800.32[0.15-0.69]

68% improvement

64/8350.31[0.16-0.61]

69% improvement

82% improvement

Tau2 = 0.00; I2 = 0.0%

Mahmud (DB RCT)Hashim (SB RCT)
Elgazzar (RCT)
Niaee (DB RCT)
Okumuş (DB RCT)
Beltran-.. (DB RCT)

Treatment
0/183
2/70
2/200
4/120
6/30
5/36

Late treatment 19/639

Control
3/183
6/70
24/200
11/60
9/30
6/37

Dose (4d)
12mg
28mg
112mg
28mg
56mg
12mg

CT2
CT2
OT1

Tau2 = 0.43; I2 = 50.5%

All studies
1

19/894

OT: ivermectin vs. other treatment
CT: study uses combined treatment
Tau2 = 0.29; I2 = 34.6%; Z = 3.41 (p = 0.00032)
2

0

0.25

0.5

0.75

Lower Risk

1

1.25

1.5

1.75

2+

Increased Risk

Figure 13. Random effects meta-analysis for Randomized Controlled Trial mortality results only.

Treatment time

Number ofstudiesreportingpositive
effects

Total
numberofstudies

Percentage ofstudiesreportingpositive
effects

Probability of an equal or
greater percentage of
positive results from an
ineffective treatment

Random effects
meta-analysis
results

Randomized
Controlled Trials

26

26

100%

0.000000015
1 in 67 million

70% improvement
RR 0.30 [0.20‑0.46]
p < 0.0001

Randomized
Controlled Trials(excluding latetreatment)

14

14

100%

0.000061
1 in 16 thousand

83% improvement
RR 0.17 [0.11‑0.25]
p < 0.0001

Table 2. Summary of RCT results.

Exclusions
To avoid bias in the selection of studies, we include all studies in the main analysis. Here we show
the results after excluding studies with critical issues likely to alter results, non-standard studies,and studies where very minimal detail is currently available.
[Soto-Becerra] is a database analysis covering anyone with ICD-10 COVID-19 codes, which includes
asymptomatic PCR+ patients. Therefore many patients in the control group are likely asymptomaticwith regards to SARS-CoV-2, but in the hospital for another reason. For those that had symptomatic
COVID-19, there is also likely signi cant confounding by indication. KM curves show that thetreatment groups were in more serious condition, with more than the total excess mortality at 30
days occurring on day 1. All treatments are worse than the control group at 30 days, while at thelatest followup all treatments show lower mortality than control. The machine learning system usedalso appears over-parameterized and likely to result in signi cant over tting and inaccurate results.
There is also no real control group in this study - patients receiving the treatments after 48 hours
were put in the control group. Authors also state that outcomes within 24 hours were excluded,
however the KM curves show signi cant mortality at day 1 (only for the treatment groups). Notethat this study provides both 30 day mortality and weighted KM curves up to day 43 for ivermectin,
we use the day 43 results as per our protocol. Several protocol violations have also been reported inthis study [Yim].
There is no paper currently available for [Asghar]. [Vallejos] reports prophylaxis results, however
only very minimal details are currently available in a news report. We include these results for
additional con rmation of the e cacy observed in other trials, however this study is excluded here.
[Hellwig] analyze African countries and COVID-19 cases in October 2020 as a function of whether
widespread prophylactic use of ivermectin is used for parasitic infections. [Tanioka] perform asimilar analysis for COVID-19 mortality in January 2021. These studies are excluded because they
are not clinical trials. [Krolewiecki] show a concentration dependent antiviral activity of ivermectin
whereby the viral decay rate for patients with ivermectin >160ng/mL was 0.64 log10
copies/reaction/day versus 0.13 for control. However, they do not provide the results for the entire
treatment group vs. control. [Galan] perform an RCT comparing ivermectin and other treatmentswith very late stage severe condition hospitalized patients, not showing signi cant differences
between the treatments. Authors were unable to add a control arm due to ethical issues. The
closest control comparison we could nd is [Baqui], which shows 43% hospital mortality in thenorthern region of Brazil where the study was performed, from which we can estimate the mortality

with ivermectin in this study as 47% lower, RR 0.53. Further, the study is restricted to more severecases, hence the expected mortality, and therefore the bene t of treatment, may be higher. Resultsfor [Raad, Rezai] are available in [Hill], however no paper is currently available.
Summarizing, the studies excluded are as follows, and the resulting forest plot is shown in Figure
15.
[Asghar], detail too minimal.
[Carvallo], control group formed from cases in the same hospital not in the study.
[Hellwig], not a typical trial, analysis of African countries that used or did not use ivermectin
prophylaxis for parasitic infections.
[Raad], detail too minimal.
[Rezai], detail too minimal.
[Roy], no serious outcomes reported and fast recovery in treatment and control groups, there is little
room for a treatment to improve results.
[Soto-Becerra], substantial unadjusted confounding by indication likely, includes PCR+ patients that
may be asymptomatic for COVID-19 but in hospital for other reasons.
[Tanioka], not a typical trial, analysis of African countries that used or did not use ivermectin
prophylaxis for parasitic infections.
[Vallejos], detail too minimal.

ivmmeta.com 4/4/21

All 40 ivermectin COVID-19 studies with exclusions
Treatment Control
Chowdhury (RCT) hosp.
0/60
2/56
Espitia-Hernandez viral+
0/28
7/7
Cadegiani
death
0/110
2/137
Ahmed (DB RCT)
symptoms 0/17
3/19
Chaccour (DB RCT) symp. prob. 12
12
Afsar
symptoms 0/37
7/53
Babalola (DB RCT) viral+
40
20
Kirti (DB RCT)
death
0/55
4/57
Mohan (DB RCT)no recov.
2/40
6/45
Schwartz (DB RCT) hosp.
0/49
2/45
Elalfyviral+
7/62
44/51
López-Me.. (DB RCT) death
0/200
1/198
Chahla (CLUS. RCT) no disch.
2/110
8/62

Early treatment

11/820

Dose (4d) RR
14mg
0.19
12mg
0.03
42mg
0.22
48mg
0.15
28mg
0.47
48mg
0.08
24mg
0.36
24mg
0.11
28mg
0.38
36mg
0.19
36mg
0.13
84mg
0.33
24mg
0.11

86/762

CI[0.01-3.96][0.01-0.11][0.01-4.48][0.01-2.70][0.19-1.16][0.00-1.32][0.10-1.27][0.01-2.05][0.08-1.75][0.01-3.92][0.06-0.27][0.01-8.11][0.02-0.52]

OT1 CT2
CT2

OT1

CT2

83% improvement

0.17 [0.10-0.29]

Tau2 = 0.16; I2 = 19.4%

GorialPodder (RCT)
Khan
Chachar (RCT)
Mahmud (DB RCT)
RajterHashim (SB RCT)CamprubíElgazzar (RCT)
Spoorthi
Budhiraja
Niaee (DB RCT)
Okumuş (DB RCT)
Bukhari (RCT)Lima-Morales
Beltran-.. (DB RCT)
Pott-Junior (RCT)
Huvemek (DB RCT)

Late treatment

death
recov. timedeath
no recov.
death
death
death
ICU
death
recov. time
death
death
death
viral+
death
death
ICU
no improv.

Treatment Control
0/16
2/71
32
30
1/115
9/133
9/25
10/25
0/183
3/183
13/98
24/98
2/70
6/70
2/13
3/13
2/200
24/2005050
0/34
103/942
4/120
11/60
6/30
9/30
4/41
25/45
15/48152/287
5/36
6/37
1/27
1/4
13/50
19/50

Dose (4d) RR
14mg
0.29
14mg
0.84
12mg
0.13
36mg
0.90
12mg
0.14
14mg
0.54
28mg
0.33
14mg
0.67
112mg 0.08
n/a
0.79
n/a
0.01
28mg
0.18
56mg
0.67
12mg
0.18
12mg
0.22
12mg
0.86
14mg
0.15
84mg
0.68

77/1,621 307/2,328

CI[0.01-5.76][0.55-1.12][0.02-1.01][0.44-1.83][0.01-2.75][0.27-0.99][0.07-1.60][0.13-3.35][0.02-0.35][0.62-1.01][0.00-0.15][0.06-0.55][0.27-1.64][0.07-0.46][0.12-0.41][0.29-2.56][0.01-1.93][0.38-1.23]

CT2
CT2
OT1
CT2

CT2

60% improvement

0.40 [0.27-0.59]

Tau2 = 0.34; I2 = 66.7%

Shouman (RCT)
Carvallo
BeheraElgazzar (RCT)
Carvallo
Bernigaud
Alam
Chahla (RCT)
BeheraProphylaxis

Treatment Control
symp. case 15/203
59/101
cases
0/131
11/98
cases
41/117145/255
cases
2/100
10/100cases
0/788
237/407death
0/69
150/3,062
cases
4/58
44/60
cases
0/117
10/117
cases
2,199
1,147

Dose (1m)RR
36mg
0.09
14mg
0.04
42mg
0.46
112mg 0.20
48mg
0.00
84mg
0.01
12mg
0.09
48mg
0.05
42mg
0.17

CI
[0.03-0.23][0.00-0.63][0.29-0.71][0.04-0.89][0.00-0.02][0.00-0.10][0.04-0.24][0.00-0.80][0.12-0.23]

CT2

CT2

CT2

62/3,782 666/5,347

0.08 [0.03-0.21]

92% improvement

150/6,223 1,059/8,437

0.23 [0.16-0.32]

77% improvement

Tau2 = 1.40; I2 = 87.4%

All studies
1

OT: ivermectin vs. other treatment
CT: study uses combined treatment
Tau2 = 0.67; I2 = 77.6%; Z = 8.36 (p < 0.0001)
2

0

0.25

0.5

0.75

Lower Risk

1

1.25

1.5

1.75

2+

Increased Risk

Figure 15. Random effects meta-analysis excluding studies with signi cant issues.

Discussion
We show results with both pooled effects and for individual outcomes. The true effect size may
differ for different outcomes, for example the bene t for mortality and hospitalization could be
different, or a treatment could be effective at minimizing serious cases while not being very
effective for viral clearance. Ivermectin studies show strong bene ts for all outcomes, supporting
pooled effects which has the advantage of visualizing all studies and providing the most evidence
for the question "is ivermectin effective for COVID-19?". For speci c estimates regarding mortality
etc., the individual outcome analyses are more appropriate.
The expected effect size between studies varies for many other reasons including the patient
population, the medication dosage and regimen, and the treatment time, all of which could
introduce greater heterogeneity compared to that from different outcomes, or from biases in welldone retrospective studies. Patient population could remove the potential bene t of treatment - forexample there is less room for improvement with low risk patients that heal quickly without
treatment (as in [López-Medina]). Treatment time may have the largest effect for many successful
COVID-19 treatments. For example an antiviral may be very effective when used early and noteffective at a later stage (for comparison, oseltamivir is generally only considered effective forin uenza when used within 0-36 or 0-48 hours [McLean, Treanor]). We address treatment time byseparating early and late treatment, showing a clear difference and advantage for early treatment.
Only one study to date has received signi cant press coverage in western media [López-Medina]
although it is neither the largest or the least biased study. This study has many problems. The
primary outcome was changed mid-trial from clinical deterioration to complete resolution ofsymptoms including "not hospitalized and no limitation of activities" as a negative outcome.
Critically, temporary side effects of a successful treatment may be considered as a negative
outcome, which could result in falsely concluding that the treatment is not effective. Such an
outcome is also not very meaningful in terms of assessing how treatment affects the incidence ofserious outcomes. With the low risk patient population in this study, there is also little room for
improvement - 58% recovered within the rst 2 days to "not hospitalized and no limitation ofactivities" or better. There was only one death (in the control arm), as compared to 17 studies withmany more mortality events. This study also gave ivermectin to the control arm for 38 patients andit is unknown if the full extent of the error was identi ed, or if there were additional undiscovered
errors. The side effect data reported in this trial raises major concerns, with more side effects
reported in the placebo arm, suggesting that more placebo patients may have received treatment.
The study protocol allows other treatments but does not report on usage. The presentation of thisstudy also appears to be signi cantly biased. While all outcomes show a bene t for ivermectin, theabstract fails to mention that much larger bene ts are seen for serious outcomes, including theoriginal primary outcome, and that the reason for not reaching statistical sign cance is the low
number of events in a low risk population where most recover quickly without treatment.
Publishing is often biased towards positive results, which we would need to adjust for whenanalyzing the percentage of positive results. For ivermectin, there is currently not enough data toevaluate publication bias with high con dence. One method to evaluate bias is to compare
prospective vs. retrospective studies. Prospective studies are likely to be published regardless of theresult, while retrospective studies are more likely to exhibit bias. For example, researchers may
perform preliminary analysis with minimal effort and the results may in uence their decision tocontinue. Retrospective studies also provide more opportunities for the speci cs of data extraction
and adjustments to in uence results. Figure 16 shows a scatter plot of results for prospective andretrospective studies. The median effect size for prospective studies is 81% improvement,

compared to 78% for retrospective studies, i.e., currently the prospective studies, which are lesslikely to exhibit a positive publication bias, show more positive results. [Bryant] also perform afunnel plot analysis, which they found did not suggest evidence of publication bias.

ivmmeta.com 4/4/21
min, Q1, median, Q3, max

Prospective

Retrospective
0

0.25

0.5

0.75

1

1.25

Lower Risk

1.5

1.75

2+

Increased Risk

Figure 16. Prospective vs. retrospective studies.
4 of the 49 studies compare against other treatments rather than placebo. Currently ivermectin
shows better results than these other treatments, however ivermectin may show greater
improvement when compared to placebo. 12 of 49 studies combine treatments, for example
ivermectin + doxycycline. The results of ivermectin alone may differ. 4 of 26 RCTs use combined
treatment, three with doxycycline, and one with iota-carrageenan.
Typical meta analyses involve subjective selection criteria, effect extraction rules, and study bias
evaluation, which can be used to bias results towards a speci c outcome. In order to avoid bias we
include all studies and use a pre-speci ed method to extract results from all studies (we alsopresent results after exclusions). The results to date are overwhelmingly positive, very consistent,
and very insensitive to potential selection criteria, effect extraction rules, and/or bias evaluation.
Additional meta analyses con rming the effectiveness of ivermectin can be found in [Bryant, Hill,
Kory, Lawrie]. Figure 17 shows a comparison of mortality results across meta analyses. [Kory] also
review epidemiological data and provide suggested treatment regimens.

Ivermectin meta analysis mortality results
Kory et al.
Hill et al.
Bryant et al.
Lawrie et al.
Nardelli et al.
ivmmeta

RR
0.31
0.25
0.32
0.17
0.21
0.24

ivmmeta.com 4/4/21

CI[0.20-0.47][0.12-0.52][0.14-0.72][0.08-0.35][0.11-0.36][0.14-0.42]

0

0.25

0.5

0.75

Lower Risk

1

1.25

1.5

1.75

2+

Increased Risk

Figure 17. Comparison of mortality results from different meta analyses. OR converted to RR for [Kory, Nardelli].
The evidence supporting ivermectin for COVID-19 far exceeds the typical amount of evidence used
for the approval of treatments. [Lee] shows that only 14% of the guidelines of the Infectious
Diseases Society of America were based on RCTs. Table 3 compares the amount of evidence usedby the WHO to approve ivermectin for scabies, compared with the current evidence for COVID-19.

WHO ivermectin approval status
Indication

StudiesPatients

Effect size

StatusScabies [Kory (B)]

6613

35% [22‑46%]

Approved

COVID‑1949

15,75273% [64‑79%]

Pending

Table 3. Ivermectin approval status.

Conclusion
Ivermectin is an effective treatment for COVID-19. The probability that an ineffective treatment
generated results as positive as the 49 studies to date is estimated to be 1 in 563 trillion (p =0.000000000000002). As expected for an effective treatment, early treatment is more successful,with an estimated reduction of 80% in the effect measured using a random effects meta-analysis,
RR 0.20 [0.09-0.41].

RevisionsThis paper is data driven, all graphs and numbers are dynamically generated. We will update thepaper as new studies are released or with any corrections. Please submit updates and corrections
at https://ivmmeta.com/.
12/2: We added [Ahmed].
12/7: We added [Chaccour].
12/11: We added [Soto-Becerra].
12/16: We added [Afsar].
12/17: We added [Alam].
12/26: We added [Carvallo (C), Vallejos].
12/27: We added the total number of authors and patients.
12/29: We added meta analysis excluding late treatment.
12/31: We added additional details about the studies in the appendix.
1/2: We added dosage information and we added the number of patients to the forest plots.
1/5: We added direct links to the study details in the forest plots.
1/6: We added [Babalola].
1/7: We added direct links to the study details in the chronological plots.

1/9: We added [Kirti]. Due to the much larger size of the control group in [Bernigaud], we limited thesize of the control group to be the same as the treatment group for calculation of the number ofpatients.
1/10: We put all prophylaxis studies in a single group.
1/11: We added [Chahla (B)].
1/12: We added [Okumuş].
1/15: We added the effect measured for each study in the forest plots.
1/16: We moved the analysis with exclusions to the main text, and added additional commentary.
1/17: We added [Asghar].
1/19: We added [Raad, Rezai]. [Chaccour] was updated to the journal version of the paper.
1/25: We updated [Vallejos] with the recently released results.
1/26: We updated [Shouman] with the journal version of the article.
2/2: We added [Mohan].
2/5: We added [Bukhari].
2/10: We added [Lima-Morales].
2/11: We added more details on the analysis of prospective vs. retrospective studies.
2/12: We added [Schwartz].
2/14: We added analysis restricted to COVID-19 case outcomes, and we added additional results inthe abstract.
2/15: We added [Behera].
2/16: We updated [Behera (B)] to the journal version of the paper.
2/17: We added [Elalfy], and we added analysis restricted to viral clearance outcomes, and mortality
results restricted to RCTs.
2/18: We updated [Babalola] to the journal version of the paper.
2/23: We added [Beltran-Gonzalez].
2/24: We added a comparison of the evidence base and WHO approval status for the use ofivermectin with scabies and COVID-19. We updated [Okumuş] with the Research Square preprint.
2/27: We added analysis restricted to peer reviewed studies.
3/2: We updated [Vallejos] with the latest results [Vallejos (B)].

3/3: We updated the graphs to indicate the time period for the dosage column, now showing thedosage over one month for prophylaxis and over four days for other studies.
3/4: We added [López-Medina], and we added more information in the abstract.
3/5: We added discussion of pooled effects (we show both pooled effects and individual outcome
results).
3/6: We added [Chowdhury] and we identify studies that compare with another treatment.
3/10: We added [Pott-Junior].
3/12: We added [Bryant, Roy].
3/17: We added [Nardelli].
3/25: We added [Huvemek].
3/26: We added [Tanioka].
3/28: We highlighted and added discussion for studies that use combined treatments.
3/30: We added [Chahla].
3/31: We updated [Chahla (B)] to the preprint.
4/4: We added event counts to the forest plots.

Appendix 1. Methods and Study Results
We performed ongoing searches of PubMed, medRxiv, ClinicalTrials.gov, The Cochrane Library,
Google Scholar, Collabovid, Research Square, ScienceDirect, Oxford University Press, the reference
lists of other studies and meta-analyses, and submissions to the site c19ivermectin.com, which
regularly receives submissions of studies upon publication. Search terms were ivermectin and
COVID-19 or SARS-CoV-2, or simply ivermectin. Automated searches are performed every hour withnoti cations of new matches. All studies regarding the use of ivermectin for COVID-19 that reportan effect compared to a control group are included in the main analysis. This is a living analysis andis updated regularly.
We extracted effect sizes and associated data from all studies. If studies report multiple kinds ofeffects then the most serious outcome is used in calculations for that study. For example, if effects
for mortality and cases are both reported, the effect for mortality is used, this may be different to
the effect that a study focused on. If symptomatic results are reported at multiple times, we used
the latest time, for example if mortality results are provided at 14 days and 28 days, the results at 28
days are used. Mortality alone is preferred over combined outcomes. Outcomes with zero events inboth arms were not used. Clinical outcome is considered more important than PCR testing status.
When basically all patients recover in both treatment and control groups, preference for viralclearance and recovery is given to results mid-recovery where available (after most or all patients
have recovered there is no room for an effective treatment to do better). When results provide anodds ratio, we computed the relative risk when possible, or converted to a relative risk according to[Zhang]. Reported con dence intervals and p-values were used when available, using adjusted
values when provided. If multiple types of adjustments are reported including propensity scorematching (PSM), the PSM results are used. When needed, conversion between reported p-values
and con dence intervals followed [Altman, Altman (B)], and Fisher's exact test was used to
calculate p-values for event data. If continuity correction for zero values is required, we use thereciprocal of the opposite arm with the sum of the correction factors equal to 1 [Sweeting]. Results
are all expressed with RR < 1.0 suggesting effectiveness. Most results are the relative risk ofsomething negative. If studies report relative times, results are expressed as the ratio of the time forthe ivermectin group versus the time for the control group. Calculations are done in Python (3.9.1)
with scipy (1.5.4), pythonmeta (1.11), numpy (1.19.4), statsmodels (0.12.1), and plotly (4.14.1).
The forest plots are computed using PythonMeta [Deng] with the DerSimonian and Laird random
effects model (the xed effect assumption is not plausible in this case). The forest plots show
simpli ed dosages for comparison, these are the total dose in the rst four days for treatment, andthe monthly dose for prophylaxis, for a 70kg person. For full dosage details see below.
We received no funding, this research is done in our spare time. We have no a liations with any
pharmaceutical companies or political parties.
We have classi ed studies as early treatment if most patients are not already at a severe stage at
the time of treatment, and treatment started within 5 days after the onset of symptoms, although ashorter time may be preferable. Antivirals are typically only considered effective when used within ashorter timeframe, for example 0-36 or 0-48 hours for oseltamivir, with longer delays not being
effective [McLean, Treanor].
Due to the much larger size of the control group in [Bernigaud], we limit the size of the control group
to be the same as the treatment group for calculation of the number of patients.
A summary of study results is below. Please submit updates and corrections at
https://ivmmeta.com/.
Early treatment
Effect extraction follows pre-speci ed rules as detailed above and gives priority to more serious
outcomes. Only the rst (most serious) outcome is used in calculations, which may differ from theeffect a paper focuses on.

[Afsar], 12/15/2020, retrospective,
Pakistan, South Asia, preprint, 6 authors,
dosage 12mg days 1-6.

risk of fever at day 14, 92.2% lower, RR 0.08, p =0.04, treatment 0 of 37 (0.0%), control 7 of 53(13.2%), continuity correction due to zero event(with reciprocal of the contrasting arm).

[Ahmed], 12/2/2020, Double Blind
Randomized Controlled Trial,
Bangladesh, South Asia, peer-reviewed,
mean age 42.0, 15 authors, dosage
12mg days 1-5, ivermectin + doxycyclinegroup took only a single dose ofivermectin.

risk of unresolved symptoms, 85.0% lower, RR
0.15, p = 0.09, treatment 0 of 17 (0.0%), control 3of 19 (15.8%), continuity correction due to zero
event (with reciprocal of the contrasting arm), day
7 fever ivermectin.
risk of unresolved symptoms, 62.7% lower, RR
0.37, p = 0.35, treatment 1 of 17 (5.9%), control 3of 19 (15.8%), day 7 fever ivermectin +doxycycline.

risk of no virological cure, 42.5% lower, RR 0.58, p= 0.01, treatment 11 of 22 (50.0%), control 20 of
23 (87.0%), day 7 ivermectin.
risk of no virological cure, 20.0% lower, RR 0.80, p= 0.28, treatment 16 of 23 (69.6%), control 20 of
23 (87.0%), day 7 ivermectin + doxycycline.
risk of no virological cure, 62.7% lower, RR 0.37, p= 0.02, treatment 5 of 22 (22.7%), control 14 of 23(60.9%), day 14 ivermectin.
risk of no virological cure, 35.7% lower, RR 0.64, p= 0.24, treatment 9 of 23 (39.1%), control 14 of 23(60.9%), day 14 ivermectin + doxycycline.
time to viral-, 23.6% lower, relative time 0.76, p =0.02, treatment 22, control 23, ivermectin.
time to viral-, 9.4% lower, relative time 0.91, p =0.27, treatment 23, control 23, ivermectin +doxycycline.
hospitalization time, 1.0% lower, relative time 0.99,
ivermectin.
hospitalization time, 4.1% higher, relative time
1.04, ivermectin + doxycycline.
[Asghar], 1/16/2021, Randomized
Controlled Trial, Pakistan, South Asia,
preprint, 1 author, dosage 200μg/kg days
1, 8, this trial compares with anothertreatment - results may be better whencompared to placebo.

risk of no virological cure, 82.1% lower, RR 0.18, p< 0.001, treatment 5 of 50 (10.0%), control 28 of
50 (56.0%), day 7.

[Babalola], 1/6/2021, Double Blind
Randomized Controlled Trial, Nigeria,
Africa, peer-reviewed, baseline oxygen
requirements 8.3%, 10 authors, dosage
12mg or 6mg q84h for two weeks, thistrial compares with another treatment results may be better when compared toplacebo.

adjusted risk of viral+ at day 5, 63.9% lower, RR
0.36, p = 0.11, treatment 40, control 20, adjusted
per study.
risk of no virological cure, 58.0% lower, RR 0.42, p= 0.01, treatment 20, control 20, 12mg - Cox
proportional hazard model.
risk of no virological cure, 40.5% lower, RR 0.60, p= 0.12, treatment 20, control 20, 6mg - Cox
proportional hazard model.
time to viral-, 49.2% lower, relative time 0.51,
treatment 20, control 20, 12mg.
time to viral-, 34.4% lower, relative time 0.66,
treatment 20, control 20, 6mg.

[Cadegiani], 11/4/2020, prospective,
Brazil, South America, preprint, 4 authors,risk of death, 78.3% lower, RR 0.22, p = 0.50,
treatment 0 of 110 (0.0%), control 2 of 137 (1.5%),

dosage 200μg/kg days 1-3.

continuity correction due to zero event (withreciprocal of the contrasting arm), control group 1.
risk of mechanical ventilation, 94.2% lower, RR
0.06, p = 0.005, treatment 0 of 110 (0.0%), control
9 of 137 (6.6%), continuity correction due to zero
event (with reciprocal of the contrasting arm),
control group 1.
risk of hospitalization, 98.0% lower, RR 0.02, p <0.001, treatment 0 of 110 (0.0%), control 27 of 137(19.7%), continuity correction due to zero event(with reciprocal of the contrasting arm), control
group 1.

[Carvallo], 9/15/2020, prospective,
Argentina, South America, preprint, mean
age 55.7, 3 authors, dosage 36mg days
1, 8, dose varied depending on patient
condition - mild 24mg, moderate 36mg,
severe 48mg, this trial uses multiple
treatments in the treatment arm(combined with dexamethasone,enoxaparin, and aspirin) - results ofindividual treatments may vary.

risk of death for hospitalized cases in study vs.
cases in the same hospital not in the study, 87.9%
lower, RR 0.12, p = 0.05, treatment 1 of 33 (3.0%),
control 3 of 12 (25.0%), the only treatment death
was a patient already in the ICU before treatment.

[Chaccour], 12/7/2020, Double Blind
Randomized Controlled Trial, Spain,
Europe, peer-reviewed, 23 authors,
dosage 400μg/kg single dose.

symptom probability, 52.9% lower, RR 0.47, p <0.05, treatment 12, control 12, relative probabilityof symptoms at day 28, mixed effects logistic
regression, data in supplementary appendix.
viral load, 94.6% lower, relative load 0.05,
treatment 12, control 12, day 7 mid-recovery, datain supplementary appendix.

[Chahla], 3/30/2021, Cluster Randomized
Controlled Trial, Argentina, SouthAmerica, preprint, 9 authors, dosage
24mg days 1, 8, 15, 22.

risk of no medical release, 89.1% lower, RR 0.11, p= 0.005, treatment 2 of 110 (1.8%), control 8 of 62(12.9%), adjusted per study, odds ratio converted
to relative risk.

[Chowdhury], 7/14/2020, Randomized
Controlled Trial, Bangladesh, South Asia,
peer-reviewed, 6 authors, dosage
200μg/kg single dose, this trial
compares with another treatment results may be better when compared toplacebo, this trial uses multiple
treatments in the treatment arm(combined with doxycycline) - results ofindividual treatments may vary.

risk of hospitalization, 80.6% lower, RR 0.19, p =0.23, treatment 0 of 60 (0.0%), control 2 of 56(3.6%), continuity correction due to zero event(with reciprocal of the contrasting arm).
risk of no recovery, 46.4% lower, RR 0.54, p <0.001, treatment 27 of 60 (45.0%), control 47 of 56(83.9%), mid-recovery day 5.
recovery time, 15.2% lower, relative time 0.85, p =0.07, treatment 60, control 56.
risk of no virological cure, 80.6% lower, RR 0.19, p= 0.23, treatment 0 of 60 (0.0%), control 2 of 56(3.6%), continuity correction due to zero event(with reciprocal of the contrasting arm).

time to viral-, 4.3% lower, relative time 0.96, p =0.23, treatment 60, control 56.
[Elalfy], 2/16/2021, retrospective, Egypt,
Middle East, peer-reviewed, 15 authors,
dosage 18mg days 1, 4, 7, 10, 13, <90kg
18mg, 90-120kg 24mg, >120kg 30mg,
this trial uses multiple treatments in thetreatment arm (combined withnitazoxanide, ribavirin, and zinc) - resultsof individual treatments may vary.

risk of no virological cure, 86.9% lower, RR 0.13, p< 0.001, treatment 7 of 62 (11.3%), control 44 of
51 (86.3%), day 15.

[Espitia-Hernandez], 8/15/2020,
retrospective, Mexico, North America,
peer-reviewed, mean age 45.1, 5 authors,
dosage 6mg days 1-2, 8-9, this trial uses
multiple treatments in the treatment arm(combined with azithromycin andcholecalciferol) - results of individual
treatments may vary.

risk of viral+ at day 10, 97.2% lower, RR 0.03, p <0.001, treatment 0 of 28 (0.0%), control 7 of 7(100.0%), continuity correction due to zero event(with reciprocal of the contrasting arm).

[Kirti], 1/9/2021, Double Blind
Randomized Controlled Trial, India, SouthAsia, preprint, 11 authors, dosage 12mg
days 1, 2.

risk of death, 88.7% lower, RR 0.11, p = 0.12,
treatment 0 of 55 (0.0%), control 4 of 57 (7.0%),
continuity correction due to zero event (withreciprocal of the contrasting arm).

risk of no virological cure, 58.1% lower, RR 0.42, p< 0.001, treatment 26 of 62 (41.9%), control 51 of
51 (100.0%), day 7.

risk of mechanical ventilation, 79.3% lower, RR
0.21, p = 0.09, treatment 1 of 55 (1.8%), control 5of 57 (8.8%).
risk of ICU admission, 13.6% lower, RR 0.86, p =0.80, treatment 5 of 55 (9.1%), control 6 of 57(10.5%).
risk of no virological cure, 11.6% higher, RR 1.12, p= 0.35, treatment 42 of 55 (76.4%), control 39 of
57 (68.4%).
[López-Medina], 3/4/2021, Double Blind
Randomized Controlled Trial, Columbia,
South America, peer-reviewed, medianage 37.0, 19 authors, dosage 300μg/kg
days 1-5.

risk of death, 66.8% lower, RR 0.33, p = 0.50,
treatment 0 of 200 (0.0%), control 1 of 198 (0.5%),
continuity correction due to zero event (withreciprocal of the contrasting arm).
risk of escalation of care, 60.8% lower, RR 0.39, p =0.10, treatment 4 of 200 (2.0%), control 10 of 198(5.1%), odds ratio converted to relative risk.
risk of escalation of care with post-hoc <12hexclusion, 34.3% lower, RR 0.66, p = 0.51,
treatment 4 of 200 (2.0%), control 6 of 198 (3.0%),
odds ratio converted to relative risk.
risk of deterioration by >= 2 points on an 8-point
scale, 43.1% lower, RR 0.57, p = 0.35, treatment 4of 200 (2.0%), control 7 of 198 (3.5%), odds ratio
converted to relative risk.

risk of fever post randomization, 24.8% lower, RR
0.75, p = 0.33, treatment 16 of 200 (8.0%), control
21 of 198 (10.6%), odds ratio converted to relativerisk.
risk of unresolved symptoms at day 21, 15.3%
lower, RR 0.85, p = 0.53, treatment 36 of 200(18.0%), control 42 of 198 (21.2%), odds ratio
converted to relative risk, Cox proportional-hazard
model.
hazard ratio for lack of resolution of symptoms,
6.5% lower, RR 0.93, p = 0.53, treatment 200,
control 198.
relative median time to resolution of symptoms,
16.7% lower, relative time 0.83, treatment 200,
control 198.
[Mohan], 2/2/2021, Double Blind
Randomized Controlled Trial, India, SouthAsia, preprint, 27 authors, dosage
400μg/kg single dose, 200μg/kg also
tested.

risk of no discharge at day 14, 62.5% lower, RR
0.38, p = 0.27, treatment 2 of 40 (5.0%), control 6of 45 (13.3%), ivermectin 24mg.
risk of no discharge at day 14, 43.8% lower, RR
0.56, p = 0.49, treatment 3 of 40 (7.5%), control 6of 45 (13.3%), ivermectin 12mg.
risk of no virological cure, 10.3% lower, RR 0.90, p= 0.65, treatment 20 of 36 (55.6%), control 26 of
42 (61.9%), ivermectin 24mg, day 7.
risk of no virological cure, 3.2% higher, RR 1.03, p =1.00, treatment 23 of 36 (63.9%), control 26 of 42(61.9%), ivermectin 12mg, day 7.
risk of no virological cure, 23.8% lower, RR 0.76, p= 0.18, treatment 21 of 40 (52.5%), control 31 of
45 (68.9%), ivermectin 24mg, day 5.
risk of no virological cure, 5.6% lower, RR 0.94, p =0.82, treatment 26 of 40 (65.0%), control 31 of 45(68.9%), ivermectin 12mg, day 5.

[Raad], 1/16/2021, Single Blind
Randomized Controlled Trial, Lebanon,
Middle East, preprint, 1 author, dosage
200μg/kg single dose.

risk of hospitalization, 85.7% lower, RR 0.14, p =0.24, treatment 0 of 50 (0.0%), control 3 of 50(6.0%), continuity correction due to zero event(with reciprocal of the contrasting arm).
risk of viral load, 59.0% lower, RR 0.41, p = 0.01,
treatment 50, control 50, percentage relative
improvement in Ct value with treatment at day 3.

[Roy], 3/12/2021, retrospective, database
analysis, India, South Asia, preprint, 5authors, dosage not speci ed, this trial
uses multiple treatments in therelative time to clinical response of wellbeing,
5.6% lower, relative time 0.94, p = 0.87, treatment
14, control 15.

treatment arm (combined withdoxycycline) - results of individual
treatments may vary.
[Schwartz], 2/12/2021, Double Blind
Randomized Controlled Trial, Israel,
Middle East, preprint, 1 author, dosage
12mg days 1-3, 15mg for patients >=70kg.

risk of hospitalization, 80.7% lower, RR 0.19, p =0.23, treatment 0 of 49 (0.0%), control 2 of 45(4.4%), continuity correction due to zero event(with reciprocal of the contrasting arm).
risk of no virological cure, 51.4% lower, RR 0.49, p= 0.01, treatment 16 of 49 (32.7%), control 25 of
45 (55.6%), adjusted per study, odds ratio
converted to relative risk, multivariable logistic
regression, day 6, Ct>30.
risk of no virological cure, 54.1% lower, RR 0.46, p= 0.02, treatment 9 of 49 (18.4%), control 18 of 45(40.0%), day 10, Ct>30.
risk of no virological cure, 54.1% lower, RR 0.46, p= 0.02, treatment 10 of 49 (20.4%), control 20 of
45 (44.4%), day 8, Ct>30.
risk of no virological cure, 41.2% lower, RR 0.59, p= 0.04, treatment 16 of 49 (32.7%), control 25 of
45 (55.6%), day 6, Ct>30.
risk of no virological cure, 37.9% lower, RR 0.62, p= 0.09, treatment 11 of 26 (42.3%), control 15 of
22 (68.2%), day 4, Ct>30.

Late treatment
Effect extraction follows pre-speci ed rules as detailed above and gives priority to more serious
outcomes. Only the rst (most serious) outcome is used in calculations, which may differ from theeffect a paper focuses on.

[Beltran-Gonzalez], 2/23/2021, Double
Blind Randomized Controlled Trial,
Mexico, North America, peer-reviewed,
mean age 53.8, 13 authors, dosage
12mg single dose, 18mg for patients>80kg.

risk of death, 14.4% lower, RR 0.86, p = 1.00,
treatment 5 of 36 (13.9%), control 6 of 37 (16.2%).
risk of respiratory deterioration or death, 8.6%
lower, RR 0.91, p = 1.00, treatment 8 of 36 (22.2%),
control 9 of 37 (24.3%).
risk of no hospital discharge, 37.0% higher, RR
1.37, p = 0.71, treatment 4 of 36 (11.1%), control 3of 37 (8.1%).

[Budhiraja], 11/18/2020, retrospective,
India, South Asia, preprint, 12 authors,
dosage not speci ed.

risk of death, 99.1% lower, RR 0.009, p = 0.04,
treatment 0 of 34 (0.0%), control 103 of 942(10.9%), continuity correction due to zero event(with reciprocal of the contrasting arm).

[Bukhari], 2/5/2021, Randomized

risk of no virological cure, 82.4% lower, RR 0.18, p

Controlled Trial, Pakistan, Middle East,
preprint, 10 authors, dosage 12mg single
dose.

< 0.001, treatment 4 of 41 (9.8%), control 25 of 45(55.6%), day 7.
risk of no virological cure, 38.7% lower, RR 0.61, p< 0.001, treatment 24 of 41 (58.5%), control 43 of
45 (95.6%), day 3.

[Camprubí], 11/11/2020, retrospective,
Spain, Europe, peer-reviewed, 9 authors,
dosage 200μg/kg single dose.

risk of ICU admission, 33.3% lower, RR 0.67, p =1.00, treatment 2 of 13 (15.4%), control 3 of 13(23.1%), ICU at day 8.
risk of no improvement at day 8, 33.3% higher, RR
1.33, p = 1.00, treatment 4 of 13 (30.8%), control 3of 13 (23.1%).

[Chachar], 9/30/2020, Randomized
Controlled Trial, India, South Asia, peerreviewed, 6 authors, dosage 36mg, 12mg
stat, 12mg after 12 hours, 12mg after 24hours.

risk of no recovery at day 7, 10.0% lower, RR 0.90,
p = 0.50, treatment 9 of 25 (36.0%), control 10 of
25 (40.0%).

[Elgazzar], 11/13/2020, Randomized
Controlled Trial, Egypt, Africa, preprint, 6
authors, dosage 400μg/kg days 1-4, thistrial compares with another treatment results may be better when compared toplacebo.

risk of death, 91.7% lower, RR 0.08, p < 0.001,
treatment 2 of 200 (1.0%), control 24 of 200(12.0%).
risk of death, 88.9% lower, RR 0.11, p = 0.12,
treatment 0 of 100 (0.0%), control 4 of 100 (4.0%),
continuity correction due to zero event (withreciprocal of the contrasting arm), mild/moderate
COVID-19.
risk of death, 90.0% lower, RR 0.10, p < 0.001,
treatment 2 of 100 (2.0%), control 20 of 100(20.0%), severe COVID-19.

[Gorial], 7/8/2020, retrospective, Iraq,
Middle East, preprint, 9 authors, dosage
200μg/kg single dose.

risk of death, 71.0% lower, RR 0.29, p = 1.00,
treatment 0 of 16 (0.0%), control 2 of 71 (2.8%),
continuity correction due to zero event (withreciprocal of the contrasting arm).
hospitalization time, 42.0% lower, relative time
0.58, p < 0.001, treatment 16, control 71.

[Hashim], 10/26/2020, Single Blind
Randomized Controlled Trial, Iraq, Middle
East, preprint, 6 authors, dosage
200μg/kg days 1-2, some patients
received a third dose on day 8, this trial
uses multiple treatments in thetreatment arm (combined withdoxycycline) - results of individual
treatments may vary.

risk of death, 66.7% lower, RR 0.33, p = 0.27,
treatment 2 of 70 (2.9%), control 6 of 70 (8.6%), allpatients.

[Huvemek], 3/25/2021, Double Blind
Randomized Controlled Trial, Bulgaria,
Europe, preprint, 1 author, dosage
400μg/kg days 1-3.

risk of no improvement, 31.6% lower, RR 0.68, p =0.28, treatment 13 of 50 (26.0%), control 19 of 50(38.0%), day 7, patients with improvement on WHO
scale.

risk of death, 91.7% lower, RR 0.08, p = 0.03,
treatment 0 of 59 (0.0%), control 6 of 70 (8.6%),
continuity correction due to zero event (withreciprocal of the contrasting arm), excluding
critical patients.

risk of no improvement, 34.5% lower, RR 0.66, p =0.07, treatment 19 of 50 (38.0%), control 29 of 50(58.0%), day 4, patients with improvement on WHO
scale.
[Khan], 9/24/2020, retrospective,
Bangladesh, South Asia, preprint, medianage 35.0, 8 authors, dosage 12mg single
dose.

risk of death, 87.0% lower, RR 0.13, p < 0.05,
treatment 1 of 115 (0.9%), control 9 of 133 (6.8%).

[Lima-Morales], 2/10/2021, prospective,
Mexico, North America, peer-reviewed, 9authors, dosage 12mg single dose, thistrial uses multiple treatments in thetreatment arm (combined withazithromycin, montelukast, and aspirin) results of individual treatments may vary.

risk of death, 77.7% lower, RR 0.22, p < 0.001,
treatment 15 of 481 (3.1%), control 52 of 287(18.1%), adjusted per study, odds ratio converted
to relative risk, multivariate.

time to viral-, 73.3% lower, relative time 0.27, p <0.001, treatment 115, control 133.

risk of hospitalization, 67.4% lower, RR 0.33, p <0.001, treatment 44 of 481 (9.1%), control 89 of
287 (31.0%), adjusted per study, odds ratio
converted to relative risk, multivariate.
risk of no recovery, 58.6% lower, RR 0.41, p <0.001, treatment 75 of 481 (15.6%), control 118 of
287 (41.1%), adjusted per study, odds ratio
converted to relative risk, recovery at day 14 after
symptoms, multivariate.

[Mahmud], 10/9/2020, Double Blind
Randomized Controlled Trial,
Bangladesh, South Asia, preprint, 1
author, dosage 12mg single dose, thistrial uses multiple treatments in thetreatment arm (combined withdoxycycline) - results of individual
treatments may vary.

risk of death, 85.7% lower, RR 0.14, p = 0.25,
treatment 0 of 183 (0.0%), control 3 of 183 (1.6%),
continuity correction due to zero event (withreciprocal of the contrasting arm).
risk of no recovery, 49.0% lower, RR 0.51, p <0.004, treatment 42 of 183 (23.0%), control 67 of
180 (37.2%), adjusted per study.
risk of disease progression, 55.0% lower, RR 0.45,
p < 0.01, treatment 16 of 183 (8.7%), control 32 of
180 (17.8%), adjusted per study.
risk of no virological cure, 42.0% lower, RR 0.58, p< 0.001, treatment 14 of 183 (7.7%), control 36 of
180 (20.0%), adjusted per study.

[Niaee], 11/24/2020, Double Blind
Randomized Controlled Trial, Iran, Middle
East, preprint, mean age 56.0, 14
authors, dosage 400μg/kg single dose,
dose varies in different groups.

risk of death, 81.8% lower, RR 0.18, p = 0.001,
treatment 4 of 120 (3.3%), control 11 of 60(18.3%), All IVM vs. all control.
risk of death, 94.3% lower, RR 0.06, p = 0.01,
treatment 0 of 30 (0.0%), control 11 of 60 (18.3%),
continuity correction due to zero event (withreciprocal of the contrasting arm), IVM single dose
200mcg/kg vs. all control.
risk of death, 45.5% lower, RR 0.55, p = 0.37,
treatment 3 of 30 (10.0%), control 11 of 60

(18.3%), IVM three dose 200mcg/kg vs. all control.
risk of death, 94.3% lower, RR 0.06, p = 0.01,
treatment 0 of 30 (0.0%), control 11 of 60 (18.3%),
continuity correction due to zero event (withreciprocal of the contrasting arm), IVM single dose
400mcg/kg vs. all control.
risk of death, 81.8% lower, RR 0.18, p = 0.06,
treatment 1 of 30 (3.3%), control 11 of 60 (18.3%),
IVM three dose 400/200/200mcg/kg vs. allcontrol.
[Okumuş], 1/12/2021, Double Blind
Randomized Controlled Trial, Turkey,
Middle East, preprint, 15 authors, dosage
200μg/kg days 1-5, 36-50kg - 9mg, 5165kg - 12mg, 66-79kg - 15mg, >80kg
200μg/kg.

risk of death, 33.3% lower, RR 0.67, p = 0.55,
treatment 6 of 30 (20.0%), control 9 of 30 (30.0%).
risk of no improvement at day 10, 42.9% lower, RR
0.57, p = 0.18, treatment 8 of 30 (26.7%), control
14 of 30 (46.7%).
risk of no improvement at day 5, 15.8% lower, RR
0.84, p = 0.60, treatment 16 of 30 (53.3%), control
19 of 30 (63.3%).
risk of no virological cure, 80.0% lower, RR 0.20, p= 0.02, treatment 2 of 16 (12.5%), control 5 of 8(62.5%), day 10.

[Podder], 9/3/2020, Randomized
Controlled Trial, Bangladesh, South Asia,
peer-reviewed, 4 authors, dosage
200μg/kg single dose.

recovery time from enrollment, 16.1% lower,
relative time 0.84, p = 0.34, treatment 32, control
30.

[Pott-Junior], 3/9/2021, Randomized
Controlled Trial, Brazil, South America,
peer-reviewed, 10 authors, dosage
200μg/kg single dose, dose varies inthree arms 100, 200, 400μg/kg.

risk of ICU admission, 85.2% lower, RR 0.15, p =0.25, treatment 1 of 27 (3.7%), control 1 of 4
(25.0%).
relative improvement in Ct value, 0.8% lower, RR
0.99, p = 1.00, treatment 27, control 3.
risk of no virological cure, 11.1% higher, RR 1.11, p= 1.00, treatment 10 of 27 (37.0%), control 1 of 3
(33.3%).
time to viral-, 16.7% lower, relative time 0.83,
treatment 27, control 3.

[Rajter], 10/13/2020, retrospective, USA,
North America, peer-reviewed, 6 authors,
dosage 200μg/kg single dose.

risk of death, 46.0% lower, RR 0.54, p = 0.04,
treatment 13 of 98 (13.3%), control 24 of 98(24.5%), adjusted per study, odds ratio converted
to relative risk, PSM.
risk of death, 66.9% lower, RR 0.33, p = 0.03,
treatment 26 of 173 (15.0%), control 27 of 107(25.2%), adjusted per study, odds ratio converted
to relative risk, multivariate.

[Rezai], 1/19/2021, Double Blind
Randomized Controlled Trial, Iran, Middle
East, preprint, 1 author, dosage 200μg/kg
single dose.

recovery time, 21.2% lower, relative time 0.79, p =0.02, treatment 51, control 52.

[Soto-Becerra], 10/8/2020, retrospective,
database analysis, Peru, South America,
preprint, median age 59.4, 4 authors,
dosage 200μg/kg single dose.

risk of death, 17.1% lower, RR 0.83, p = 0.01,
treatment 92 of 203 (45.3%), control 1438 of 2630
(54.7%), IVM vs. control day 43 (last day available)
weighted KM from gure 3, per the pre-speci edrules, the last available day mortality results havepriority.

hospitalization time, 17.9% lower, relative time
0.82, p = 0.01, treatment 51, control 52.

risk of death, 39.0% higher, RR 1.39, p = 0.16,
treatment 47 of 203 (23.2%), control 401 of 2630
(15.2%), adjusted per study, day 30, Table 2, IVM
wHR.
[Spoorthi], 11/14/2020, prospective,
India, South Asia, peer-reviewed, 2authors, dosage not speci ed, this trial
uses multiple treatments in thetreatment arm (combined withdoxycycline) - results of individual
treatments may vary.

recovery time, 21.1% lower, relative time 0.79, p =0.03, treatment 50, control 50.

hospitalization time, 15.5% lower, relative time
0.84, p = 0.01, treatment 50, control 50.

Prophylaxis
Effect extraction follows pre-speci ed rules as detailed above and gives priority to more serious
outcomes. Only the rst (most serious) outcome is used in calculations, which may differ from theeffect a paper focuses on.

[Alam], 12/15/2020, prospective,
Bangladesh, South Asia, peer-reviewed,
13 authors, dosage 12mg monthly.

risk of COVID-19 case, 90.6% lower, RR 0.09, p <0.001, treatment 4 of 58 (6.9%), control 44 of 60(73.3%).

[Behera], 2/15/2021, prospective, India,
South Asia, preprint, 13 authors, dosage
300μg/kg days 1, 4.

risk of COVID-19 case, 83.0% lower, RR 0.17, p <0.001, treatment 2199, control 1147, two doses.
risk of COVID-19 case, 4.0% higher, RR 1.04, p =0.85, treatment 186, control 1147, patients only
receiving the rst dose.

[Behera (B)], 11/3/2020, retrospective,
India, South Asia, peer-reviewed, 13
authors, dosage 300μg/kg days 1, 4.

risk of COVID-19 case, 53.8% lower, RR 0.46, p <0.001, treatment 41 of 117 (35.0%), control 145 of
255 (56.9%), adjusted per study, odds ratio
converted to relative risk, model 2 2+ doses
conditional logistic regression.
risk of COVID-19 case, 44.5% lower, RR 0.56, p <0.001, treatment 41 of 117 (35.0%), control 145 of
255 (56.9%), odds ratio converted to relative risk,
matched pair analysis.

[Bernigaud], 11/28/2020, retrospective,
France, Europe, peer-reviewed, 12
authors, dosage 200μg/kg days 1, 8, 15,
400μg/kg days 1, 8, 15, two different
dosages.

risk of death, 99.4% lower, RR 0.006, p = 0.08,
treatment 0 of 69 (0.0%), control 150 of 3062
(4.9%), continuity correction due to zero event(with reciprocal of the contrasting arm).
risk of COVID-19 case, 55.1% lower, RR 0.45, p =0.01, treatment 7 of 69 (10.1%), control 692 of
3062 (22.6%).

[Carvallo (B)], 11/17/2020, prospective,
Argentina, South America, peer-reviewed,
4 authors, dosage 12mg weekly, this trial
uses multiple treatments in thetreatment arm (combined with iotacarrageenan) - results of individual
treatments may vary.

risk of COVID-19 case, 99.9% lower, RR 0.001, p <0.001, treatment 0 of 788 (0.0%), control 237 of
407 (58.2%), continuity correction due to zero
event (with reciprocal of the contrasting arm).

[Carvallo (C)], 10/19/2020, prospective,
Argentina, South America, preprint, 1
author, dosage 1mg days 1-14, this trial
uses multiple treatments in thetreatment arm (combined with iotacarrageenan) - results of individual
treatments may vary.

risk of COVID-19 case, 96.3% lower, RR 0.04, p <0.001, treatment 0 of 131 (0.0%), control 11 of 98(11.2%), continuity correction due to zero event(with reciprocal of the contrasting arm).

[Chahla (B)], 1/11/2021, Randomized
Controlled Trial, Argentina, SouthAmerica, preprint, 1 author, dosage
12mg weekly, this trial uses multiple
treatments in the treatment arm(combined with iota-carrageenan) results of individual treatments may vary.

risk of COVID-19 case, 95.2% lower, RR 0.05, p =0.002, treatment 0 of 117 (0.0%), control 10 of 117(8.5%), continuity correction due to zero event(with reciprocal of the contrasting arm),
moderate/severe COVID-19.
risk of COVID-19 case, 84.0% lower, RR 0.16, p <0.001, treatment 4 of 117 (3.4%), control 25 of 117(21.4%), adjusted per study, odds ratio converted
to relative risk, all cases.
risk of COVID-19 case, 84.0% lower, RR 0.16, p <0.001, treatment 4 of 117 (3.4%), control 25 of 117(21.4%), all cases.

[Elgazzar (B)], 11/13/2020, Randomized
Controlled Trial, Egypt, Africa, preprint, 6
authors, dosage 400μg/kg weekly.

risk of COVID-19 case, 80.0% lower, RR 0.20, p =0.03, treatment 2 of 100 (2.0%), control 10 of 100(10.0%).

[Hellwig], 11/28/2020, retrospective,
Ecological Study, multiple countries,
Africa, peer-reviewed, 2 authors, dosage
200μg/kg, dose varied, typically 150200μg/kg.

risk of COVID-19 case, 78.0% lower, RR 0.22, p <0.02, African countries, PCTI vs. no PCT, relative
cases per capita.

[Shouman], 8/28/2020, Randomized
Controlled Trial, Egypt, Africa, peerreviewed, 8 authors, dosage 18mg days

risk of symptomatic case, 91.3% lower, RR 0.09, p< 0.001, treatment 15 of 203 (7.4%), control 59 of
101 (58.4%), adjusted per study, multivariate.

risk of COVID-19 case, 80.0% lower, RR 0.20, p <0.001, worldwide, PCTI vs. no PCT, relative cases
per capita.

risk of COVID-19 severe case, 92.9% lower, RR

1, 3, dose varies depending on weight 40-60kg: 15mg, 60-80kg: 18mg, >80kg:
24mg.

0.07, p = 0.002, treatment 1 of 203 (0.5%), control
7 of 101 (6.9%), unadjusted.

[Tanioka], 3/26/2021, retrospective,
Ecological Study, multiple countries,
Africa, preprint, 3 authors, dosage
200μg/kg, dose varied, typically 150200μg/kg.

risk of death, 88.2% lower, RR 0.12, p = 0.002,
relative mean mortality per million.

[Vallejos], 12/20/2020, retrospective,
Argentina, South America, preprint, 1
author, dosage 12mg weekly.

risk of COVID-19 case, 73.4% lower, RR 0.27, p <0.001, treatment 13 of 389 (3.3%), control 61 of
486 (12.6%).

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