Ivermectin for COVID-19: real-time meta analysis of 56 studies
Covid Analysis, Nov 26, 2020 (Version 83, May 18, 2021 — Merck analysis)
https://ivmmeta.com/• 97% of 37 early treatment and prophylaxis studies report positive effects (95% of all 56 studies).
26 studies show statistically signi cant improvements in isolation.
• Random effects meta-analysis with pooled effects using the most serious outcome reportedshows 78% and 85% improvement for early treatment and prophylaxis (RR 0.22 [0.12-0.39] and0.15 [0.09-0.25]). Results are similar after exclusion based sensitivity analysis: 80% and 87% (RR
0.20 [0.14-0.28] and 0.13 [0.07-0.25]), and after restriction to 30 peer-reviewed studies: 80% and
88% (RR 0.20 [0.12-0.35] and 0.12 [0.05-0.30]).
• 81% and 96% lower mortality is observed for early treatment and prophylaxis (RR 0.19 [0.07-0.54]
and 0.04 [0.00-0.58]). Statistically signi cant improvements are seen for mortality, ventilation,
hospitalization, cases, and viral clearance.
• 100% of the 17 Randomized Controlled Trials (RCTs) for early treatment and prophylaxis report
positive effects, with an estimated improvement of 73% and 83% respectively (RR 0.27 [0.18-0.41]
and 0.17 [0.05-0.61]), and 93% of all 28 RCTs.
• The probability that an ineffective treatment generated results as positive as the 56 studies todate is estimated to be 1 in 2 trillion (p = 0.00000000000041).
• Heterogeneity arises from many factors including treatment delay, patient population, the effectmeasured, variants, and treatment regimens. The consistency of positive results across a wide
variety of cases is remarkable. Heterogeneity is low in speci c cases, for example early treatment
mortality.
• While many treatments have some level of e cacy, they do not replace vaccines and othermeasures to avoid infection. Only 29% of ivermectin studies show zero events in the treatment
arm. Multiple approaches are required to protect everyone from all existing and future variants.
• Many studies do not specify administration, or specify fasting. Administration with food may
signi cantly increase plasma and tissue concentration.
• 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

78% [61‑88%]

23

212

3,227

Late treatment

46% [28‑60%]

19

149

6,431

Prophylaxis

85% [75‑91%]

14

108

8,789

Mortality

74% [56‑85%]

20

179

7,361

RCTs only

66% [50‑76%]

28

270

4,997

All studies

72% [64‑79%]

56

469

18,447

Evidence base used for other COVID-19 approvals
Medication

StudiesPatients

Improvement

Budesonide (UK)

1

1,779

17%

Remdesivir (USA)

1

1,063

31%

Casiri/imdevimab (USA)

1

799

66%

Ivermectin evidence

56

18,44772% [64‑79%]

Ivermectin COVID-19 early treatment and prophylaxis studies
Chowdhury (RCT)
Espitia-Hernandez
Carvallo
Mahmud (DB RCT)
Szente Fonseca
Cadegiani
Ahmed (DB RCT)
Chaccour (DB RCT)
Afsar
Babalola (DB RCT)
Kirti (DB RCT)
Bukhari (RCT)
Raad (SB RCT)
Mohan (DB RCT)
Schwartz (DB RCT)
ElalfyLópez-Me.. (DB RCT)Roy
Chahla (CLUS. RCT)
MouryaLoue (QR)
Merino (QR)
Faisal (RCT)Treatment Control
hosp.
0/60
2/56
viral+
0/28
7/7
death
1/33
3/12
death
0/183
3/183
hosp.
340
377
death
0/110
2/137
symptoms 0/17
3/19
symp. prob. 12
12
symptoms 0/37
7/53
viral+
40
20
death
0/55
4/57
viral+
4/41
25/45
hosp.
0/50
3/50
no recov.
2/40
6/45
hosp.
1/47
3/42
viral+
7/62
44/51
death
0/200
1/198
recov. time 14
15
no disch.
2/110
20/144
viral+
5/50
47/50
death
1/10
5/15
hosp.
population-based cohort
no recov.
6/50
19/50

Dose (4d)
14mg
12mg
36mg
12mg
24mg
42mg
48mg
28mg
48mg
24mg
24mg
12mg
14mg
28mg
36mg
36mg
84mg
n/a
24mg
48mg
14mg
24mg
48mg

Early treatment

29/1,589

204/1,638

Treatment
15/2030/131
41/1172/100
0/788
ecological
0/69
4/58
13/3890/117
45/2,199
ecological32/617
0/271

Control
59/101
11/98
145/255
10/100237/407

RR
0.19
0.03
0.12
0.14
1.14
0.22
0.15
0.47
0.08
0.36
0.11
0.18
0.14
0.38
0.30
0.13
0.33
0.94
0.13
0.11
0.30
0.26
0.32

ivmmeta.com 5/18/21

CI[0.01-3.96][0.01-0.11][0.01-1.06][0.01-2.75][0.75-1.66][0.01-4.48][0.01-2.70][0.19-1.16][0.00-1.32][0.10-1.27][0.01-2.05][0.07-0.46][0.01-2.70][0.08-1.75][0.03-2.76][0.06-0.27][0.01-8.11][0.52-1.93][0.03-0.54][0.05-0.25][0.04-2.20][0.11-0.61][0.14-0.72]

OT1 CT2
CT2
CT2
CT2

OT1

MD3

CT2
CT2

0.22 [0.12-0.39]

78% improvement

Tau2 = 1.18; I2 = 82.6%

Shouman (RCT)
Carvallo
BeheraElgazzar (RCT)
Carvallo
Hellwig (ECO.)
Bernigaud
Alam
Vallejos
Chahla (RCT)
BeheraTanioka (ECO.)
Seet (CLUS. RCT)
Morgenstern (PSM)

Prophylaxis

symp. case
cases
cases
cases
cases
cases
death
cases
cases
cases
cases
death
severe casehosp.

150/3,062
44/60
61/486
10/117133/1,147
64/6192/271

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
12mg
0.50
56mg
0.20

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][0.33-0.76][0.01-4.15]

CT2

CT2
CL4
MD3
CT2

OT1

152/5,059 926/3,730

0.15 [0.09-0.25]

85% improvement

181/6,648

0.18 [0.12-0.27]

82% improvement

Tau2 = 0.58; I2 = 83.8%

All studies
1

OT: ivermectin vs. other treatment2
CT: study uses combined treatment
3
MD: minimal detail available currently4
CL: control group size limited in totals
Tau2 = 0.97; I2 = 89.5%; Z = 8.12 (p < 0.0001)

1,130/5,368

00.25 0.5 0.75

11.25 1.5 1.75 2+

Lower Risk Increased RiskA

ivmmeta.com 5/18/21
min, Q1, median, Q3, max

Early treatment

All studies
0

0.25

0.5

0.75

1

1.25

1.5

Lower Risk
Early treatment

Probability results fromineffective treatment

Feb 23
1 in 1 billion

Faisalno recov., p=0.005

Merinohosp., p<0.001

Faisal, no recov., p=0.005

Loue, death, p=0.34

Merino, hosp., p<0.001

Seet, severe case, p=0.01

Morgenstern, hosp., p=0.50

Tanioka, death, p=0.002

Mourya, viral+, p<0.0001

Chahla, no disch., p=0.004

Roy, recov. time, p=0.87

Huvemek, no improv., p=0.28

López-Medina, death, p=0.50

Pott-Junior, ventilation, p=0.25

Elalfy, viral+, p<0.0001

Behera, cases, p<0.001

Gonzalez, death, p=1.00

Schwartz, hosp., p=0.34

Lima-Morales, death, p<0.001

Shahbaznejad, death, p=1.00
Mohan, no recov., p=0.27

Raad, hosp., p=0.24

Okumuş, death, p=0.55

Bukhari, viral+, p<0.0001

Kirti, death, p=0.12

Nov 17 p<0.0001 Dec 15 p<0.000001
1 in 10 thousand
1 in 1 million
Nov 28 p<0.00001
Jan 9 p<0.0000001
1 in 100 thousand
1 in 10 million

Chahla, cases, p=0.002

Babalola, viral+, p=0.11

Vallejos, cases, p<0.0001

Alam, cases, p<0.0001

Afsar, symptoms, p=0.04

Chaccour, symp. prob., p<0.05

Bernigaud, death, p=0.08

Ahmed, symptoms, p=0.09

Niaee, death, p=0.001

Hellwig, cases, p<0.02

Budhiraja, death, p=0.04

Carvallo, cases, p<0.0001

Spoorthi, recov. time, p=0.03

Elgazzar, cases, p=0.03

Elgazzar, death, p<0.0001

Behera, cases, p<0.0001

Cadegiani, death, p=0.50

Camprubí, ventilation, p=0.67

Hashim, death, p=0.27

Rajter, death, p=0.04

C

ivmmeta.com 5/18/21

Szente Fonseca, hosp., p=0.45

Oct 9 p<0.01
1 in 100

Carvallo, cases, p<0.0001

Mahmud, death, p=0.25

Chachar, no recov., p=0.50

Soto-Becerra, death, p=0.01

Khan, death, p<0.05

Carvallo, death, p=0.05

Kishoria, no disch., p=1.00
Shouman, symp. case, p<0.001

Espitia-Hernandez, viral+, p<0.0001

Gorial, death, p=1.00

Chowdhury, hosp., p=0.23

25

Podder, recov. time, p=0.34

50

Loue
death, p=0.34

May 3 p<0.00001
1 in 100 thousand

All studies

75

Mouryaviral+, p<0.0001

Chahlano disch., p=0.004

Roy
recov. time, p=0.87

López-Medina
death, p=0.50

Elalfyviral+, p<0.0001

Schwartz
hosp., p=0.34

Mohan
no recov., p=0.27

Feb 2 p<0.001
1 in 1 thousand100% Increased Risk % Lower Risk

Raadhosp., p=0.24

Mar 12 p<0.0001
1 in 10 thousand

Probability results fromineffective treatment

75

B

ivmmeta.com 5/18/21

Jan 9 p<0.01
1 in 100

100+

100+

Bukhariviral+, p<0.0001

Kirti
death, p=0.12

Babalolaviral+, p=0.11

Afsar
symptoms, p=0.04

Cadegiani
death, p=0.50

Chaccoursymp. prob., p<0.05

75

Mahmuddeath, p=0.25

50

Carvallo
death, p=0.05

25

Espitia-Hernandezviral+, p<0.0001

25

Ahmed
symptoms, p=0.09

50

50

2+

Szente Fonseca
hosp., p=0.45

75

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

100

25

1.75

Increased Risk

May 3
1 in 1 trillion

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 heterogeneity 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, 9, 10, 11, and 12 show forest plots
for a random effects meta-analysis of all studies with pooled effects, and for studies reporting
mortality results, ICU admission, mechanical ventilation, hospitalization, COVID-19 cases, and viralclearance results only. Figure 13 shows results for peer reviewed trials only. Table 1 summarizes theresults.

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

22

23

95.7%

0.0000029
1 in 350 thousand

78% improvement
RR 0.22 [0.12‑0.39]
p < 0.0001

Late
treatment

17

19

89.5%

0.00036
1 in 3 thousand

46% improvement
RR 0.54 [0.40‑0.72]
p < 0.0001

Prophylaxis

14

14

100%

0.000061
1 in 16 thousand

85% improvement
RR 0.15 [0.09‑0.25]
p < 0.0001

All studies

53

56

94.6%

0.00000000000041
1 in 2 trillion

72% improvement
RR 0.28 [0.21‑0.36]
p < 0.0001

Table 1. Results by treatment stage.

ivmmeta.com 5/18/21
Prophylaxis

min, Q1, median, Q3, max

Early treatment

Late treatment

All studies
0

0.25

0.5

0.75

1

1.25

Lower Risk

1.5

Increased Risk

Figure 3. Results by treatment stage.

1.75

2+

% 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

Prophylaxis

Jan 11 p<0.001
1 in 1 thousand

Figure 5. Chronological history of prophylaxis results.
Morgenstern
hosp., p=0.50

Nov 14 p<0.01
1 in 100Seetsevere case, p=0.01

Apr 16 p<0.0001
1 in 10 thousand

Huvemekno improv., p=0.28

Pott-Juniorventilation, p=0.25

Late treatment

Gonzalezdeath, p=1.00

Feb 2 p<0.001
1 in 1 thousand

Lima-Morales
death, p<0.001

Shahbaznejad
death, p=1.00

Faisalno recov., p=0.005

Merinohosp., p<0.001

Louedeath, p=0.34

Mouryaviral+, p<0.0001

Chahlano disch., p=0.004

Roy
recov. time, p=0.87

López-Medina
death, p=0.50

Elalfyviral+, p<0.0001

Schwartz
hosp., p=0.34

Mohan
no recov., p=0.27

Raadhosp., p=0.24

Bukhariviral+, p<0.0001

Kirti
death, p=0.12

Babalolaviral+, p=0.11

Afsar
symptoms, p=0.04

Chaccoursymp. prob., p<0.05

Ahmed
symptoms, p=0.09

Cadegiani
death, p=0.50

Szente Fonseca
hosp., p=0.45

Early treatment

Taniokadeath, p=0.002

Beheracases, p<0.001

Okumuş
death, p=0.55

Niaeedeath, p=0.001

Budhiraja
death, p=0.04

Spoorthirecov. time, p=0.03

Jan 9 p<0.01
1 in 100

Chahlacases, p=0.002

100

Vallejoscases, p<0.0001

Oct 26 p<0.05
1 in 20
Elgazzar
death, p<0.0001

100

Camprubíventilation, p=0.67

Probability results fromineffective treatment

Alamcases, p<0.0001

Probability results fromineffective treatment
Hashimdeath, p=0.27

100+

Bernigauddeath, p=0.08

100+

Rajterdeath, p=0.04

Soto-Becerra
death, p=0.01

Chacharno recov., p=0.50

Mahmuddeath, p=0.25

25Hellwig
cases, p<0.0275

Carvallo
death, p=0.05

Espitia-Hernandezviral+, p<0.0001

50

Carvallo
cases, p<0.0001

50

Chowdhury
hosp., p=0.23

75

Elgazzarcases, p=0.03

25

Khan
death, p<0.05

25

Beheracases, p<0.0001

50

Podderrecov. time, p=0.34

75

Kishoria
no disch., p=1.00% Increased Risk % Lower Risk
75

Gorialdeath, p=1.00% Lower Risk
50

Carvallo
cases, p<0.0001% Increased Risk
25

Shoumansymp. case, p<0.001% Lower Risk

100

ivmmeta.com 5/18/21

Mar 12 p<0.0001
1 in 10 thousand
May 3 p<0.00001
1 in 100 thousand

ivmmeta.com 5/18/21

Mar 9 p<0.001
1 in 1 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.

ivmmeta.com 5/18/21

75

50

25

ivmmeta.com 5/18/21

All 56 ivermectin COVID-19 studies
Chowdhury (RCT)
Espitia-Hernandez
Carvallo
Mahmud (DB RCT)
Szente Fonseca
Cadegiani
Ahmed (DB RCT)
Chaccour (DB RCT)
Afsar
Babalola (DB RCT)
Kirti (DB RCT)
Bukhari (RCT)
Raad (SB RCT)
Mohan (DB RCT)
Schwartz (DB RCT)
ElalfyLópez-Me.. (DB RCT)Roy
Chahla (CLUS. RCT)
MouryaLoue (QR)
Merino (QR)
Faisal (RCT)Treatment Control
hosp.
0/60
2/56
viral+
0/28
7/7
death
1/33
3/12
death
0/183
3/183
hosp.
340
377
death
0/110
2/137
symptoms 0/17
3/19
symp. prob. 12
12
symptoms 0/37
7/53
viral+
40
20
death
0/55
4/57
viral+
4/41
25/45
hosp.
0/50
3/50
no recov.
2/40
6/45
hosp.
1/47
3/42
viral+
7/62
44/51
death
0/200
1/198
recov. time 14
15
no disch.
2/110
20/144
viral+
5/50
47/50
death
1/10
5/15
hosp.
population-based cohort
no recov.
6/50
19/50

Dose (4d)
14mg
12mg
36mg
12mg
24mg
42mg
48mg
28mg
48mg
24mg
24mg
12mg
14mg
28mg
36mg
36mg
84mg
n/a
24mg
48mg
14mg
24mg
48mg

Early treatment

29/1,589

204/1,638

Treatment
0/16
11/19
32
1/115
9/25
92/203
13/98
2/70
3/13
2/200
50
0/34
4/120
6/30
1/35
15/481
5/36
1/27
13/50

Control
2/71
7/13
30
9/133
10/25
1,438/2,630
24/98
6/70
5/13
24/20050
103/942
11/60
9/30
0/34
52/287
6/37
1/4
19/50

178/1,654

1,726/4,777

Treatment
15/2030/131
41/1172/100
0/788
ecological
0/69
4/58
13/3890/117
45/2,199
ecological32/617
0/271

Control
59/101
11/98
145/255
10/100237/407

RR
0.19
0.03
0.12
0.14
1.14
0.22
0.15
0.47
0.08
0.36
0.11
0.18
0.14
0.38
0.30
0.13
0.33
0.94
0.13
0.11
0.30
0.26
0.32

CI
[0.01-3.96][0.01-0.11][0.01-1.06][0.01-2.75][0.75-1.66][0.01-4.48][0.01-2.70][0.19-1.16][0.00-1.32][0.10-1.27][0.01-2.05][0.07-0.46][0.01-2.70][0.08-1.75][0.03-2.76][0.06-0.27][0.01-8.11][0.52-1.93][0.03-0.54][0.05-0.25][0.04-2.20][0.11-0.61][0.14-0.72]

0.22 [0.12-0.39]

OT1 CT2
CT2
CT2
CT2

OT1

MD3

CT2
CT2

78% improvement

Tau2 = 1.18; I2 = 82.6%

GorialKishoria (RCT)
Podder (RCT)
Khan
Chachar (RCT)
Soto-Becerra
Rajter (PSM)
Hashim (SB RCT)CamprubíElgazzar (RCT)
Spoorthi
Budhiraja
Niaee (DB RCT)
Okumuş (DB RCT)
Shahbazn.. (DB RCT)
Lima-Morales
Gonzalez (DB RCT)
Pott-Junior (RCT)
Huvemek (DB RCT)

death
no disch.
recov. timedeath
no recov.
death
death
death
ventilation
death
recov. time
death
death
death
death
death
death
ventilation
no improv.

Late treatment

Dose (4d)
14mg
12mg
14mg
12mg
36mg
14mg
14mg
28mg
14mg
112mg
n/a
n/a
28mg
56mg
14mg
12mg
12mg
14mg
84mg

RR
0.29
1.08
0.84
0.13
0.90
0.83
0.54
0.33
0.60
0.08
0.79
0.01
0.18
0.67
2.97
0.22
0.86
0.15
0.68

CI
[0.01-5.76][0.57-2.02][0.55-1.12][0.02-1.01][0.44-1.83][0.71-0.97][0.27-0.99][0.07-1.60][0.18-2.01][0.02-0.35][0.62-1.01][0.00-0.15][0.06-0.55][0.27-1.64][0.13-70.51][0.12-0.41][0.29-2.56][0.01-1.93][0.38-1.23]

0.54 [0.40-0.72]

CT2
OT1
CT2

CT2

46% improvement

Tau2 = 0.18; I2 = 66.9%

Shouman (RCT)
Carvallo
BeheraElgazzar (RCT)
Carvallo
Hellwig (ECO.)
Bernigaud
Alam
Vallejos
Chahla (RCT)
BeheraTanioka (ECO.)
Seet (CLUS. RCT)
Morgenstern (PSM)

symp. case
cases
cases
cases
cases
cases
death
cases
cases
cases
cases
death
severe casehosp.

Prophylaxis

150/3,062
44/60
61/486
10/117133/1,147
64/6192/271

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
12mg
0.50
56mg
0.20

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][0.33-0.76][0.01-4.15]

CT2

CT2
CL4
MD3
CT2

OT1

152/5,059 926/3,730

0.15 [0.09-0.25]

85% improvement359/8,302

0.28 [0.21-0.36]

72% improvement

Tau2 = 0.58; I2 = 83.8%

All studies
1
2

OT: ivermectin vs. other treatment

2,856/10,145

2

CT: study uses combined treatment
MD: minimal detail available currently
CL: control group size limited in totals
Tau2 = 0.52; I2 = 86.4%; Z = 9.63 (p < 0.0001)

03
40.25 0.5 0.75

11.25 1.5 1.75 2+

Lower Risk Increased Risk

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

ivmmeta.com 5/18/21

All 20 ivermectin COVID-19 mortality results
Treatment
Carvallo
1/33
Mahmud (DB RCT)
0/183
Cadegiani
0/110
Kirti (DB RCT)
0/55
López-Me.. (DB RCT) 0/200
Loue (QR)
1/10

Control
3/12
3/183
2/137
4/57
1/198
5/15

Dose (4d)
36mg
12mg
42mg
24mg
84mg
14mg

RR
0.12
0.14
0.22
0.11
0.33
0.30

CI
[0.01-1.06][0.01-2.75][0.01-4.48][0.01-2.05][0.01-8.11][0.04-2.20]

Early treatment 2/591

18/6020.19 [0.07-0.54]

CT2
CT2

81% improvement

Tau2 = 0.00; I2 = 0.0%

GorialKhan
Soto-Becerra
Rajter (PSM)
Hashim (SB RCT)
Elgazzar (RCT)
Budhiraja
Niaee (DB RCT)
Okumuş (DB RCT)
Shahbazn.. (DB RCT)
Lima-Morales
Gonzalez (DB RCT)

Treatment
0/16
1/115
92/203
13/98
2/70
2/200
0/34
4/120
6/30
1/35
15/481
5/36

Control
Dose (4d)
2/71
14mg
9/133
12mg
1,438/2,630 14mg
24/98
14mg
6/70
28mg
24/200112mg
103/942
n/a
11/60
28mg
9/30
56mg
0/34
14mg
52/287
12mg
6/37
12mg

RR
0.29
0.13
0.83
0.54
0.33
0.08
0.01
0.18
0.67
2.97
0.22
0.86

CI
[0.01-5.76][0.02-1.01][0.71-0.97][0.27-0.99][0.07-1.60][0.02-0.35][0.00-0.15][0.06-0.55][0.27-1.64][0.13-70.51][0.12-0.41][0.29-2.56]

Late treatment

141/1,438

1,684/4,592

0.34 [0.19-0.61]

Bernigaud
Tanioka (ECO.)

Treatment
0/69
ecologicalControl
150/3,062

Prophylaxis

0/69

150/690.04 [0.00-0.58]

96% improvement

143/2,098

1,852/5,263

0.26 [0.15-0.44]

74% improvement

CT2
OT1

CT2

66% improvement

Tau2 = 0.56; I2 = 78.0%

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

CI
[0.00-0.10][0.03-0.51]

CL3

Tau2 = 2.93; I2 = 69.8%

All studies
1

OT: ivermectin vs. other treatment
CT: study uses combined treatment
CL: control group size limited in totals
Tau2 = 0.68; I2 = 73.8%; Z = 5.06 (p < 0.0001)
2
3

0

0.25

0.5

0.75

1

Lower Risk

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

1.25

1.5

1.75

2+

Increased Risk

All 6 ivermectin COVID-19 mechanical ventilation results
Cadegiani
Kirti (DB RCT)

Treatment
0/110
1/55

Early treatment 1/165

Control
9/137
5/57

Dose (4d) RR
42mg
0.06
24mg
0.21

14/194

ivmmeta.com 5/18/21

CI[0.00-0.99][0.03-1.72]

0.13 [0.02-0.72]

87% improvement

Tau2 = 0.00; I2 = 0.0%

Rajter (PSM)
CamprubíShahbazn.. (DB RCT)
Pott-Junior (RCT)Treatment
4/98
3/13
2/35
1/27

Late treatment 10/173

Control
11/98
5/13
1/34
1/4

Dose (4d)
14mg
14mg
14mg
14mg

RR
0.36
0.60
1.94
0.15

CI
[0.12-1.10][0.18-2.01][0.18-20.45][0.01-1.93]

18/1490.48 [0.23-1.01]

52% improvement

32/3430.39 [0.20-0.77]

61% improvement

Tau2 = 0.00; I2 = 0.0%

All studies

11/338

0
2

0.25

0.5

0.75

1

Lower Risk2

Tau = 0.00; I = 0.0%; Z = 2.72 (p = 0.0033)

1.25

1.5

1.75

2+

Increased Risk

Figure 8. Random effects meta-analysis for mechanical ventilation results only.

All 4 ivermectin COVID-19 ICU results
Kirti (DB RCT)

Treatment
5/55

Early treatment 5/55

Control
6/57

Dose (4d) RR
24mg
0.86

6/57

ivmmeta.com 5/18/21
CI[0.28-2.67]

0.86 [0.28-2.67]

14% improvement

Tau2 = 0.00; I2 = 0.0%

Khan
CamprubíPott-Junior (RCT)Treatment
1/115
2/13
1/27

Late treatment 4/155

Control
11/133
3/13
1/4

Dose (4d)
12mg
14mg
14mg

RR
0.11
0.67
0.15

CI
[0.01-0.80][0.13-3.35][0.01-1.93]

15/1500.27 [0.08-0.91]

73% improvement

21/2070.43 [0.16-1.17]

57% improvement

Tau2 = 0.13; I2 = 10.6%

All studies

9/210

0
2

2

Tau = 0.29; I = 27.7%; Z = 1.65 (p = 0.049)

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 ICU admission results only.

All 11 ivermectin COVID-19 hospitalization results
Chowdhury (RCT)
Szente Fonseca
Cadegiani
Raad (SB RCT)
Schwartz (DB RCT)
Merino (QR)

Treatment
Control
0/60
2/56
340
377
0/110
27/137
0/50
3/50
1/47
3/42
population-based cohort

Early treatment 1/607

Dose (4d)
14mg
24mg
42mg
14mg
36mg
24mg

35/662

RR
0.19
1.14
0.02
0.14
0.30
0.26

ivmmeta.com 5/18/21

CI[0.01-3.96][0.75-1.66][0.00-0.33][0.01-2.70][0.03-2.76][0.11-0.61]

OT1 CT2

MD3

0.26 [0.11-0.59]

74% improvement

Tau2 = 0.18; I2 = 15.4%

GorialSpoorthiShahbazn.. (DB RCT)
Lima-Morales

Treatment
16
50
35
44/481

Late treatment 44/582

Control
71
50
34
89/28789/442

Dose (4d)
14mg
n/a
14mg
12mg

RR
0.58
0.84
0.85
0.33

CI
[0.41-0.82][0.73-0.97][0.72-0.99][0.22-0.47]

CT2
CT2

0.62 [0.44-0.88]

38% improvement

Tau2 = 0.11; I2 = 90.5%

Morgenstern (PSM)

Treatment
0/271

Control
2/271

Dose (1m) RR
56mg
0.20

CI
[0.01-4.15]

Prophylaxis

0/271

2/271

0.20 [0.01-4.15]

80% improvement

45/1,460

126/1,375

0.52 [0.37-0.73]

48% improvement

Tau2 = 0.00; I2 = 0.0%

All studies
1

OT: ivermectin vs. other treatment2
CT: study uses combined treatment
3
MD: minimal detail available currently
Tau2 = 0.14; I2 = 79.0%; Z = 3.72 (p < 0.0001)

0

0.25

0.5

0.75

1

Lower Risk

1.25

1.5

1.75

2+

Increased Risk

Figure 10. Random effects meta-analysis for hospitalization results only.

All 12 ivermectin COVID-19 case results
Carvallo
BeheraElgazzar (RCT)
Carvallo
Hellwig (ECO.)
Bernigaud
Alam
Vallejos
Chahla (RCT)
BeheraSeet (CLUS. RCT)
Morgenstern (PSM)

Control
11/98
145/255
10/100237/407

Prophylaxis

515/4,856

1,794/3,629

0.21 [0.11-0.39]

79% improvement515/4,856

1,794/3,629

0.21 [0.11-0.39]

79% improvement692/3,062
44/60
61/486
10/117133/1,147
433/619
18/271

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
12mg
0.94
56mg
0.26

ivmmeta.com 5/18/21

Treatment
0/131
41/1172/100
0/788
ecological
7/69
4/58
13/3890/117
45/2,199
398/617
5/271

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][0.61-1.19][0.10-0.71]

CT2

CT2
CL4
MD3
CT2
OT1

Tau2 = 0.84; I2 = 94.3%

All studies
1

OT: ivermectin vs. other treatment
CT: study uses combined treatment
3
MD: minimal detail available currently4
CL: control group size limited in totals
Tau2 = 0.84; I2 = 94.3%; Z = 4.90 (p < 0.0001)
2

0

0.25

0.5

0.75

Lower Risk

1

1.25

1.5

1.75

2+

Increased Risk

Figure 11. Random effects meta-analysis for COVID-19 case results only.

All 15 ivermectin COVID-19 viral clearance results
Chowdhury (RCT)
Espitia-Hernandez
Mahmud (DB RCT)
Ahmed (DB RCT)
Babalola (DB RCT)
Kirti (DB RCT)
Bukhari (RCT)Mohan (DB RCT)
Schwartz (DB RCT)
ElalfyMouryaTreatment
0/60
0/28
14/183
11/22
40
42/55
4/41
20/36
16/49
7/62
5/50

Early treatment 119/626

Control
2/56
7/7
36/180
20/23
20
39/57
25/45
26/42
25/45
44/51
47/50

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

271/576

RR
0.19
0.03
0.61
0.57
0.36
1.12
0.18
0.90
0.58
0.13
0.11

ivmmeta.com 5/18/21

CI[0.01-3.96][0.01-0.11][0.44-0.83][0.37-0.90][0.10-1.27][0.89-1.40][0.07-0.46][0.62-1.31][0.36-0.93][0.06-0.27][0.05-0.25]

OT1 CT2
CT2
CT2
OT1

CT2

0.34 [0.19-0.58]

66% improvement

Tau2 = 0.63; I2 = 89.0%

Kishoria (RCT)Khan
Okumuş (DB RCT)
Pott-Junior (RCT)Treatment
11/19
115
2/16
27

Late treatment 13/177

Control
7/13
133
5/8
3

Dose (4d)
12mg
12mg
56mg
14mg

RR
1.08
0.27
0.20
0.99

CI
[0.57-2.02][0.12-0.62][0.05-0.81][0.04-26.30]

12/1570.60 [0.30-1.18]

40% improvement283/733

0.42 [0.30-0.60]

58% improvement

Tau2 = 0.34; I2 = 79.3%

All studies
1

132/803

OT: ivermectin vs. other treatment
CT: study uses combined treatment
Tau2 = 0.31; I2 = 89.2%; Z = 4.83 (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 viral clearance results only.

ivmmeta.com 5/18/21

All 30 ivermectin COVID-19 peer reviewed trials
Chowdhury (RCT)
Espitia-Hernandez
Mahmud (DB RCT)
Szente Fonseca
Ahmed (DB RCT)
Chaccour (DB RCT)
Babalola (DB RCT)
ElalfyLópez-Me.. (DB RCT)
MouryaLoue (QR)
Faisal (RCT)Treatment
hosp.
0/60
viral+
0/28
death
0/183
hosp.
340
symptoms 0/17
symp. prob. 12
viral+
40
viral+
7/62
death
0/200
viral+
5/50
death
1/10
no recov.
6/50

Control
2/56
7/7
3/183
377
3/19
12
20
44/51
1/198
47/50
5/15
19/50

Dose (4d)
14mg
12mg
12mg
24mg
48mg
28mg
24mg
36mg
84mg
48mg
14mg
48mg

RR
0.19
0.03
0.14
1.14
0.15
0.47
0.36
0.13
0.33
0.11
0.30
0.32

CI
[0.01-3.96][0.01-0.11][0.01-2.75][0.75-1.66][0.01-2.70][0.19-1.16][0.10-1.27][0.06-0.27][0.01-8.11][0.05-0.25][0.04-2.20][0.14-0.72]

Early treatment

19/1,052

131/1,038

Treatment
11/19
32
9/25
13/98
3/13
50
6/30
1/35
15/481
5/36
1/27

Control
7/13
30
10/25
24/98
5/13
50
9/30
0/34
52/2876/37
1/4

64/846

114/621

Treatment
15/203
41/1170/788
ecological
0/69
4/58
32/617

Control
59/101
145/255
237/407

92/1,852

699/1,511

0.12 [0.05-0.30]

88% improvement

175/3,750 944/3,170

0.31 [0.21-0.44]

69% improvement

OT1 CT2
CT2
CT2

OT1
CT2

0.20 [0.12-0.35]

80% improvement

Tau2 = 0.36; I2 = 46.1%

Kishoria (RCT)
Podder (RCT)
Chachar (RCT)
Rajter (PSM)
CamprubíSpoorthiOkumuş (DB RCT)
Shahbazn.. (DB RCT)
Lima-Morales
Gonzalez (DB RCT)
Pott-Junior (RCT)no disch.
recov. time
no recov.
deathventilation
recov. time
death
death
death
death
ventilation

Late treatment

Dose (4d)
12mg
14mg
36mg
14mg
14mg
n/a
56mg
14mg
12mg
12mg
14mg

RR
1.08
0.84
0.90
0.54
0.60
0.79
0.67
2.97
0.22
0.86
0.15

CI
[0.57-2.02][0.55-1.12][0.44-1.83][0.27-0.99][0.18-2.01][0.62-1.01][0.27-1.64][0.13-70.51][0.12-0.41][0.29-2.56][0.01-1.93]

CT2

CT2

35% improvement

0.65 [0.46-0.92]

Tau2 = 0.15; I2 = 56.0%

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

Prophylaxis

symp. case
cases
cases
cases
death
cases
severe case150/3,062
44/60
64/619Dose (1m) RR
36mg
0.09
42mg
0.46
48mg
0.00
14mg
0.22
84mg
0.01
12mg
0.09
12mg
0.50

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][0.33-0.76]

CT2
CL3
OT1

Tau2 = 0.97; I2 = 90.8%

All studies
1

OT: ivermectin vs. other treatment2
CT: study uses combined treatment3
CL: control group size limited in totals
Tau2 = 0.62; I2 = 82.1%; Z = 6.38 (p < 0.0001)

00.25 0.5 0.75

11.25 1.5 1.75 2+

Lower Risk Increased Risk

Figure 13. Random effects meta-analysis for peer reviewed trials only.

Randomized Controlled Trials (RCTs)
Results restricted to Randomized Controlled Trials (RCTs) are shown in Figure 14, 15, 16, and 17,
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 thebene 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].

ivmmeta.com 5/18/21
min, Q1, median, Q3, max

Randomized Controlled Trials

non-RCTs
0

0.25

0.5

0.75

1

1.25

Lower Risk
Randomized Controlled Trials

100

1.75

2+

ivmmeta.com 5/18/21

25
50
75

Nov 13 p<0.05
1 in 20100+

Probability results fromineffective treatment

Dec 2 p<0.01
1 in 100
Jan 9 p<0.001
1 in 1 thousand

Mohan
no recov., p=0.27
Schwartz
hosp., p=0.34
Gonzalezdeath, p=1.00
López-Medina
death, p=0.50
Pott-Juniorventilation, p=0.25
Huvemekno improv., p=0.28
Chahlano disch., p=0.004
Seetsevere case, p=0.01
Faisalno recov., p=0.005

25

Podderrecov. time, p=0.34
Chacharno recov., p=0.50
Mahmuddeath, p=0.25
Hashimdeath, p=0.27
Elgazzar
death, p<0.0001
Elgazzarcases, p=0.03
Niaeedeath, p=0.001
Ahmed
symptoms, p=0.09
Chaccoursymp. prob., p<0.05
Babalolaviral+, p=0.11
Kirti
death, p=0.12
Chahlacases, p=0.002
Okumuş
death, p=0.55
Bukhariviral+, p<0.0001
Raad
hosp., p=0.24

50

Shahbaznejad
death, p=1.00

Kishoria
no disch., p=1.00

75

Chowdhury
hosp., p=0.23
Shoumansymp. case, p<0.001% Increased Risk % Lower Risk

1.5

Increased Risk

Feb 23 p<0.0001
1 in 10 thousand
Mar 25 p<0.00001
1 in 100 thousand

Figure 14. Randomized Controlled Trials. The distribution of results for RCTs is similar to the distribution for allother studies.

All 28 ivermectin COVID-19 Randomized Controlled Trials
Chowdhury (RCT)
Mahmud (DB RCT)
Ahmed (DB RCT)
Chaccour (DB RCT)
Babalola (DB RCT)
Kirti (DB RCT)
Bukhari (RCT)
Raad (SB RCT)
Mohan (DB RCT)
Schwartz (DB RCT)
López-Me.. (DB RCT)
Chahla (CLUS. RCT)Faisal (RCT)Treatment
hosp.
0/60
death
0/183
symptoms 0/17
symp. prob. 12
viral+
40
death
0/55
viral+
4/41
hosp.
0/50
no recov.
2/40
hosp.
1/47
death
0/200
no disch.
2/110
no recov.
6/50

Early treatment

Control
2/56
3/183
3/19
12
20
4/57
25/45
3/50
6/45
3/42
1/198
20/14419/50

15/90589/921Treatment
11/19
32
9/25
2/70
2/200
4/120
6/30
1/35
5/36
1/27
13/50

Control
7/13
30
10/25
6/70
24/200
11/60
9/30
0/34
6/37
1/4
19/50

54/64493/553Treatment
15/2032/100
0/117
32/617

Control
59/101
10/10010/11764/61949/1,037

143/937

Dose (4d)
14mg
12mg
48mg
28mg
24mg
24mg
12mg
14mg
28mg
36mg
84mg
24mg
48mg

RR
0.19
0.14
0.15
0.47
0.36
0.11
0.18
0.14
0.38
0.30
0.33
0.13
0.32

ivmmeta.com 5/18/21

CI[0.01-3.96][0.01-2.75][0.01-2.70][0.19-1.16][0.10-1.27][0.01-2.05][0.07-0.46][0.01-2.70][0.08-1.75][0.03-2.76][0.01-8.11][0.03-0.54][0.14-0.72]

OT1 CT2
CT2

OT1

MD3

73% improvement

0.27 [0.18-0.41]

Tau2 = 0.00; I2 = 0.0%

Kishoria (RCT)
Podder (RCT)
Chachar (RCT)
Hashim (SB RCT)
Elgazzar (RCT)
Niaee (DB RCT)
Okumuş (DB RCT)
Shahbazn.. (DB RCT)
Gonzalez (DB RCT)
Pott-Junior (RCT)
Huvemek (DB RCT)no disch.
recov. time
no recov.
death
death
death
death
death
death
ventilation
no improv.

Late treatment

Dose (4d)
12mg
14mg
36mg
28mg
112mg
28mg
56mg
14mg
12mg
14mg
84mg

RR
1.08
0.84
0.90
0.33
0.08
0.18
0.67
2.97
0.86
0.15
0.68

CI
[0.57-2.02][0.55-1.12][0.44-1.83][0.07-1.60][0.02-0.35][0.06-0.55][0.27-1.64][0.13-70.51][0.29-2.56][0.01-1.93][0.38-1.23]

CT2
OT1

42% improvement

0.58 [0.38-0.90]

Tau2 = 0.23; I2 = 49.5%

Shouman (RCT)Elgazzar (RCT)
Chahla (RCT)
Seet (CLUS. RCT)

Prophylaxis

symp. case
cases
cases
severe case

Dose (1m) RR
36mg
0.09
112mg
0.20
48mg
0.05
12mg
0.50

CI
[0.03-0.23][0.04-0.89][0.00-0.80][0.33-0.76]

CT2
OT1

0.17 [0.05-0.61]

83% improvement

0.34 [0.24-0.50]

66% improvement

Tau2 = 1.22; I2 = 89.5%

All studies

118/2,586 325/2,411

1

OT: ivermectin vs. other treatment
CT: study uses combined treatment
MD: minimal detail available currently
Tau2 = 0.51; I2 = 65.5%; Z = 5.57 (p < 0.0001)
2300.25 0.5 0.75

11.25 1.5 1.75 2+

Lower Risk Increased Risk

Figure 15. Random effects meta-analysis for Randomized Controlled Trials only.

ivmmeta.com 5/18/21
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

1.75

Randomized Controlled Trials (excluding late treatment)

100

2+

ivmmeta.com 5/18/21

75
50

100+

Jan 16 p<0.001
1 in 1 thousand

Faisalno recov., p=0.005

Chahlano disch., p=0.004

López-Medina
death, p=0.50

Schwartz
hosp., p=0.34

Mohan
no recov., p=0.27

Raadhosp., p=0.24

Bukhariviral+, p<0.0001

Chahlacases, p=0.002

Kirti
death, p=0.12

Babalolaviral+, p=0.11

Jan 6 p<0.01
1 in 100Seetsevere case, p=0.01

Dec 2 p<0.05
1 in 20

Chaccoursymp. prob., p<0.05

Ahmed
symptoms, p=0.09

75

Elgazzarcases, p=0.03

50

Mahmuddeath, p=0.25

25

Shoumansymp. case, p<0.001

25

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

1.5

Increased Risk

Mar 4 p<0.0001
1 in 10 thousand
May 10 p<0.00001
1 in 100 thousand

Probability results fromineffective treatment

Figure 17. RCTs excluding late treatment.

All 9 ivermectin COVID-19 RCT mortality results
Treatment
Mahmud (DB RCT)
0/183
Kirti (DB RCT)
0/55
López-Me.. (DB RCT) 0/200

Control
3/183
4/57
1/198

Early treatment 0/438

8/438

Dose (4d)
12mg
24mg
84mg

RR
0.14
0.11
0.33

ivmmeta.com 5/18/21

CI[0.01-2.75][0.01-2.05][0.01-8.11]

CT2

0.17 [0.03-0.96]

83% improvement

Tau2 = 0.00; I2 = 0.0%

Hashim (SB RCT)
Elgazzar (RCT)
Niaee (DB RCT)
Okumuş (DB RCT)
Shahbazn.. (DB RCT)
Gonzalez (DB RCT)

Treatment
2/70
2/200
4/120
6/30
1/35
5/36

Late treatment 20/491

Control
6/70
24/200
11/60
9/30
0/34
6/37

Dose (4d)
28mg
112mg
28mg
56mg
14mg
12mg

RR
0.33
0.08
0.18
0.67
2.97
0.86

CI
[0.07-1.60][0.02-0.35][0.06-0.55][0.27-1.64][0.13-70.51][0.29-2.56]

CT2
OT1

56/4310.38 [0.17-0.85]

62% improvement

64/8690.34 [0.17-0.67]

66% improvement

Tau2 = 0.54; I2 = 55.7%

All studies
1

20/929

OT: ivermectin vs. other treatment
CT: study uses combined treatment
Tau2 = 0.33; I2 = 35.5%; Z = 3.15 (p = 0.00082)
2

0

0.25

0.5

0.75

Lower Risk

1

1.25

1.5

1.75

2+

Increased Risk

Figure 16. 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

28

92.9%

0.0000015
1 in 660 thousand

66% improvement
RR 0.34 [0.24‑0.50]
p < 0.0001

Randomized
Controlled Trials(excluding latetreatment)

17

17

100%

0.0000076
1 in 131 thousand

77% improvement
RR 0.23 [0.14‑0.37]
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. Our bias evaluation is based on fullanalysis of each study and identifying when there is a signi cant chance that limitations will
substantially change the outcome of the study. We believe this is more valuable than checklistbased approaches such as Cochrane GRADE, which may underemphasize serious issues not
captured in the checklists, and overemphasize issues unlikely to alter outcomes (for example, lackof blinding for an objective mortality outcome, or certain speci cs of randomization with a verylarge effect size). However, these approaches are also valuable when done well and other groups
have used them [Bryant, Hill, Lawrie], with similar results con rming e cacy.
[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). Several
protocol violations have also been reported in this study [Yim]. Note that 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.
[López-Medina] has many issues. The primary outcome was changed mid-trial from clinicaldeterioration to complete resolution of symptoms including "not hospitalized and no limitation ofactivities" 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 of serious outcomes. With the low risk patient population in this study, there isalso little room for improvement - 58% recovered within the rst 2 days to "not hospitalized and nolimitation of activities" or better. There was only one death (in the control arm). This study also gave
ivermectin to the control arm for 38 patients and it 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 moreplacebo patients may have received treatment. Ivermectin was widely used in the population andavailable OTC at the time of the study. The study protocol allows other treatments but does notreport on usage. The name of the study drug was concealed by refering to it as "D11AX22". The
presentation of this study also appears to be signi cantly biased. While all outcomes show a bene t
for ivermectin, the abstract fails to mention that much larger bene ts are seen for serious
outcomes, including the original primary outcome, and that the reason for not reaching statisticalsign cance is the low number of events in a low risk population where most recover quickly without
treatment.
[Vallejos] reports prophylaxis results, however only very minimal details are currently available in anews 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 casesin October 2020 as a function of whether widespread prophylactic use of ivermectin is used forparasitic infections. [Tanioka] perform a similar 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 notprovide the results for the entire treatment group vs. control. [Galan] perform an RCT comparing
ivermectin and other treatments with very late stage severe condition hospitalized patients, notshowing 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 the northern 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 severe cases, hence the expected mortality, and therefore the bene t oftreatment, may be higher. [Kishoria] restrict inclusion to patients that did not respond to standard
treatment, provide no details on the time of the discharge status, and there are very large
unadjusted differences in the groups, with over twice as many patients in the ivermectin group withage >40, and all patients over 60 in the ivermectin group. Results for [Raad] 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
18.
[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.
[Kishoria], excessive unadjusted differences between groups.
[López-Medina], strong evidence of patients in the control group self-medicating, ivermectin widelyused in the population at that time, and the study drug identity was concealed by using the name
D11AX22.
[Raad], 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 5/18/21

All 47 ivermectin COVID-19 studies with exclusions
Chowdhury (RCT)
Espitia-Hernandez
Mahmud (DB RCT)
Szente Fonseca
Cadegiani
Ahmed (DB RCT)
Chaccour (DB RCT)
Afsar
Babalola (DB RCT)
Kirti (DB RCT)
Bukhari (RCT)Mohan (DB RCT)
Schwartz (DB RCT)
ElalfyChahla (CLUS. RCT)
MouryaLoue (QR)
Merino (QR)
Faisal (RCT)Treatment Control
hosp.
0/60
2/56
viral+
0/28
7/7
death
0/183
3/183
hosp.
340
377
death
0/110
2/137
symptoms 0/17
3/19
symp. prob. 12
12
symptoms 0/37
7/53
viral+
40
20
death
0/55
4/57
viral+
4/41
25/45
no recov.
2/40
6/45
hosp.
1/47
3/42
viral+
7/62
44/51
no disch.
2/110
20/144
viral+
5/50
47/50
death
1/10
5/15
hosp.
population-based cohort
no recov.
6/50
19/50

Dose (4d)
14mg
12mg
12mg
24mg
42mg
48mg
28mg
48mg
24mg
24mg
12mg
28mg
36mg
36mg
24mg
48mg
14mg
24mg
48mg

Early treatment

28/1,292

197/1,363

Treatment
0/16
32
1/115
9/25
13/98
2/70
3/13
2/200
50
0/34
4/120
6/30
1/35
15/481
5/36
1/27
13/50

Control
2/71
30
9/133
10/25
24/98
6/70
5/13
24/20050
103/942
11/60
9/30
0/34
52/287
6/37
1/4
19/50

75/1,432

281/2,134

Treatment
15/2030/131
41/117
2/100
0/788
0/69
4/58
0/117
45/2,199
32/617
0/271

Control
59/101
11/98
145/255
10/100237/407150/3,062
44/60
10/117133/1,147
64/619
2/271

RR
0.19
0.03
0.14
1.14
0.22
0.15
0.47
0.08
0.36
0.11
0.18
0.38
0.30
0.13
0.13
0.11
0.30
0.26
0.32

CI
[0.01-3.96][0.01-0.11][0.01-2.75][0.75-1.66][0.01-4.48][0.01-2.70][0.19-1.16][0.00-1.32][0.10-1.27][0.01-2.05][0.07-0.46][0.08-1.75][0.03-2.76][0.06-0.27][0.03-0.54][0.05-0.25][0.04-2.20][0.11-0.61][0.14-0.72]

OT1 CT2
CT2
CT2

OT1

CT2

80% improvement

0.20 [0.14-0.28]

Tau2 = 0.11; I2 = 19.7%

GorialPodder (RCT)
Khan
Chachar (RCT)
Rajter (PSM)
Hashim (SB RCT)CamprubíElgazzar (RCT)
Spoorthi
Budhiraja
Niaee (DB RCT)
Okumuş (DB RCT)
Shahbazn.. (DB RCT)
Lima-Morales
Gonzalez (DB RCT)
Pott-Junior (RCT)
Huvemek (DB RCT)

death
recov. timedeath
no recov.
death
death
ventilation
death
recov. time
death
death
death
death
death
death
ventilation
no improv.

Late treatment

Dose (4d)
14mg
14mg
12mg
36mg
14mg
28mg
14mg
112mg
n/a
n/a
28mg
56mg
14mg
12mg
12mg
14mg
84mg

RR
0.29
0.84
0.13
0.90
0.54
0.33
0.60
0.08
0.79
0.01
0.18
0.67
2.97
0.22
0.86
0.15
0.68

CI
[0.01-5.76][0.55-1.12][0.02-1.01][0.44-1.83][0.27-0.99][0.07-1.60][0.18-2.01][0.02-0.35][0.62-1.01][0.00-0.15][0.06-0.55][0.27-1.64][0.13-70.51][0.12-0.41][0.29-2.56][0.01-1.93][0.38-1.23]

CT2
OT1
CT2

CT2

55% improvement

0.45 [0.31-0.66]

Tau2 = 0.31; I2 = 64.6%

Shouman (RCT)
Carvallo
BeheraElgazzar (RCT)
Carvallo
Bernigaud
Alam
Chahla (RCT)
BeheraSeet (CLUS. RCT)
Morgenstern (PSM)

Prophylaxis

symp. case
cases
cases
cases
cases
death
cases
cases
cases
severe case
hosp.

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
12mg
0.50
56mg
0.20

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][0.33-0.76][0.01-4.15]

CT2

CT2
CL3
CT2
OT1

139/4,670 865/3,244

0.13 [0.07-0.25]

87% improvement242/7,394

0.25 [0.18-0.33]

75% improvement

Tau2 = 0.70; I2 = 87.4%

All studies

1,343/6,741

1

OT: ivermectin vs. other treatment2
CT: study uses combined treatment3
CL: control group size limited in totals
Tau2 = 0.58; I2 = 77.9%; Z = 9.15 (p < 0.0001)

00.25 0.5 0.75

11.25 1.5 1.75 2+

Lower Risk Increased Risk

Figure 18. Random effects meta-analysis excluding studies with signi cant issues.

Heterogeneity
Heterogeneity in COVID-19 studies arises from many factors including:Treatment delay. The time between infection or the onset of symptoms and treatment may criticallyaffect how well a treatment works. For example an antiviral may be very effective when used earlybut may not be effective in late stage disease, and may even be harmful. Figure 19 shows anexample where e cacy declines as a function of treatment delay. Other medications might bebene cial for late stage complications, while early use may not be effective or may even be harmful.
Oseltamivir, for example, is generally only considered effective for in uenza when used within 0-36
or 0-48 hours [McLean, Treanor].

Figure 19. Effectiveness may depend critically on treatment delay.
Patient demographics. Details of the patient population including age and comorbidities may criticallyaffect how well a treatment works. For example, many COVID-19 studies with relatively young lowcomorbidity patients show all patients recovering quickly with or without treatment. In such cases,
there is little room for an effective treatment to improve results (as in [López-Medina]).
Effect measured. E cacy may differ signi cantly depending on the effect measured, for example atreatment may be very effective at reducing mortality, but less effective at minimizing cases or
hospitalization. Or a treatment may have no effect on viral clearance while still being effective at
reducing mortality.
Variants. There are thousands of different variants of SARS-CoV-2 and e cacy may depend criticallyon the distribution of variants encountered by the patients in a study.
Regimen. Effectiveness may depend strongly on the dosage and treatment regimen. Higher dosages
have been found to be more successful for ivermectin [Hill]. Method of administration may also be
critical. [Guzzo] show that the plasma concentration of ivermectin is much higher whenadministered with food (Figure 20: geometric mean AUC 2.6 times higher). Many ivermectin studies
specify fasting, or they do not specify administration. Fasting administration is expected to reduce
effectiveness for COVID-19 due to lower plasma and tissue concentrations. Note that this isdifferent to anthelmintic use in the gastrointestinal tract where fasting is recommended.
Treatments. The use of other treatments may signi cantly affect outcomes, including anything fromsupplements, other medications, or other kinds of treatment such as prone positioning.

Figure 20. Mean plasma concentration (ng/ml) pro les of ivermectin following single oral doses of 30mg (fed andfasted administration), from [Guzzo].
The distribution of studies will alter the outcome of a meta analysis. Consider a simpli ed example
where everything is equal except for the treatment delay, and effectiveness decreases to zero or
below with increasing delay. If there are many studies using very late treatment, the outcome may
be negative, even though the treatment may be very effective when used earlier.
In general, by combining heterogeneous studies, as all meta analyses do, we run the risk ofobscuring an effect by including studies where the treatment is less effective, not effective, or
harmful.
When including studies where a treatment is less effective we expect the estimated effect size to belower than that for the optimal case. We do not a priori expect that pooling all studies will create apositive result for an effective treatment. Looking at all studies is valuable for providing an overview
of all research, and important to avoid cherry-picking, but the resulting estimate does not apply to
speci c cases such as early treatment in high-risk populations.
Ivermectin studies vary widely in all the factors above, which makes the consistently positive results
even more remarkable. A failure to detect an association after combining heterogeneous studies
does not mean the treatment is not effective (it may only work in certain cases), however thereverse is not true — an identi ed association is valid, although the magnitude of the effect may belarger for more optimal cases, and lower for less optimal cases. As above, the probability that an
ineffective treatment generated results as positive as the 56 studies to date is estimated to be 1 in 2
trillion (p = 0.00000000000041). This result bene ts from the fact that ivermectin shows somedegree of e cacy for COVID-19 in a wide variety of cases. It also likely bene ts from the fact that
relatively few ivermectin trials to date have been designed in a way that favors poor results.
However, more trials designed in this way are expected, for example the TOGETHER trial is testingivermectin in locations known to have a high degree of self-medication and using low doses
compared to current clinical recommendations as updated for current variants. As with acompanion trial, this trial may also include very low-risk patients, include relatively late treatment
while identifying as an early treatment trial, and use an active placebo (vitamin C). While we present
results for all studies in this paper, the individual outcome and treatment time analyses are more
relevant for speci c use cases.

Discussion
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 21 shows a scatter plot of results for prospective andretrospective studies. The median effect size for prospective studies is 79% improvement,
compared to 76% for retrospective studies, showing no signi cant difference. [Bryant] also performa funnel plot analysis, which they found did not suggest evidence of publication bias.

ivmmeta.com 5/18/21
min, Q1, median, Q3, max

Prospective

Retrospective
0

0.25

0.5

0.75

Lower Risk

1

1.25

1.5

1.75

2+

Increased Risk

Figure 21. Prospective vs. retrospective studies.
News coverage of ivermectin studies is extremely biased. Only one study to date has received
signi cant press coverage in western media [López-Medina], which is neither the largest or the least
biased study, and is one of the two studies with the most critical issues as discussed earlier.
4 of the 56 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 56 studies combine treatments, for example
ivermectin + doxycycline. The results of ivermectin alone may differ. 4 of 28 RCTs use combined
treatment, three with doxycycline, and one with iota-carrageenan. 2 of 56 studies currently haveminimal published details available.
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 22 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.
WHO (OR)
ivmmeta

RR
0.31
0.25
0.32
0.17
0.21
0.19
0.26

ivmmeta.com 5/18/21

CI[0.20-0.47][0.12-0.52][0.14-0.72][0.08-0.35][0.11-0.36][0.09-0.36][0.15-0.44]

0

0.25

0.5

0.75

1

Lower Risk

1.25

1.5

1.75

2+

Increased Risk

Figure 22. Comparison of mortality results from different meta analyses. OR converted to RR for [Kory, Nardelli].
OR displayed for [WHO] (they do not provide the details required to calculate the RR).
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 and Table 4 compare the amount ofevidence for ivermectin compared to that used for other COVID-19 approvals, and that used by
WHO for the approval of ivermectin for scabies and strongyloidiasis. Table 5 compares US CDC
recommendations for ibuprofen and ivermectin.

Medication

StudiesPatients

Improvement

Status

Budesonide (UK)

1

1,779

17%

Approved

Remdesivir (USA)

1

1,063

31%

Approved

Casiri/imdevimab (USA)

1

799

66%

Approved

Ivermectin evidence

56

18,44772% [64‑79%]

Pending

Table 3. Evidence base used for other COVID-19 approvals compared with the ivermectin evidence base.

Indication

StudiesPatients

StatusScabies [Kory (B)]

10

852

Approved

Strongyloidiasis [Kory (B)]5591

Approved

COVID‑1956

18,447COVID‑19 RCTs

28

4,997

Pending

Table 4. WHO ivermectin approval status.

Ibuprofen

Ivermectin for scabies

Ivermectin for COVID-19

Deaths per year

~450

<1

<1

Lives saved00>500,000

CDC recommended for COVID-19

Yes

Yes

No

Based on0 RCTs10 RCTs, 852 patients

28 RCTs, 4,997 patients

Table 5. Comparison of CDC recommendations [Kory (B)].

WHO Analysis
WHO updated their treatment recommendations on 3/30/2021 [WHO]. For ivermectin they reported
a mortality odds ratio of 0.19 [0.09-0.36] based on 7 studies with 1,419 patients. They do not specify
which trials they included. The report is inconsistent, with a forest plot that only shows 4 studies
with mortality results.
Despite this extremely positive result, they recommended only using ivermectin in clinical trials. The
analysis contains many aws [Kory (C)]:• Of the 56 studies (28 RCTs), they only included 16.
• They excluded all 14 prophylaxis studies (4 RCTs).
• There was no protocol for data exclusion.
• Trials included in the original UNITAID search protocol [Hill] were excluded.
• They excluded all epidemiological evidence, although WHO has considered such evidence in thepast.
• They combine early treatment and late treatment studies and do not provide heterogeneity
information. As above, early treatment is more successful, so pooling late treatment studies will
obscure the effectiveness of early treatment. They chose not to do subgroup analysis by disease
severity across trials, although treatment delay is clearly a critical factor in COVID-19 treatment,
the analysis is easily done (as above), and it is well known that the studies for ivermectin andmany other treatments clearly show greater effectiveness for early treatment.
• WHO downgraded the quality of trials compared to the UNITAID systematic review team [Hill] anda separate international expert guideline group that has long worked with the WHO [Bryant].
• They disregarded their own guidelines that stipulate quality assessments should be upgradedwhen there is evidence of a large magnitude effect (which there is), and when there is evidence ofa dose-response relationship (which there is). They claim there is no dose-response relationship,
while the UNITAID systematic review team found a clear relationship [Hill].
• Their risk of bias assessments do not match the actual risk of bias in studies. For example theyclassify [López-Medina] as low risk of bias, however this study has many issues making theresults unreliable [Covid Analysis], even prompting an open letter from over 170 physicians

concluding that the study is fatally awed [Open Letter]. [Gonzalez] is also classi ed as low risk ofbias, but is a study with very late stage severe condition high-comorbidity patients. There is aclear treatment delay-response relationship and very late stage treatment is not expected to be aseffective as early treatment. Conversely, much higher quality studies were classi ed as high riskof bias.
• Although WHO's analysis is called a "living guideline", it is rarely updated and very out of date. Asof May 14, 2021, four of the missing RCTs are known to WHO and labeled "RCTs pending data
extraction" [COVID-NMA]. We added these 4, 4, 2, and one month earlier.
• A single person served as Methods Chair, member of the Guidance Support Collaboraton
Committee, and member of the Living Systematic Review/NMA team.
• Public statements from people involved in the analysis suggest substantial bias. For example, aco-chair reportedly said that "the data available was sparse and likely based on chance" [Reuters].
As above, the data is comprehensive, and we estimate the probability that an ineffective
treatment generated results as positive as observed to be 1 in 2 trillion (p = 0.00000000000041).
The clinical team lead refers to their analysis of ivermectin as " ghting this overuse of unproventherapies ... without evidence of e cacy" [Reuters], despite the extensive evidence of e cacy
from the 56 studies by 469 scientists with 18,447 patients. People involved may be morefavorable to late stage treatment of COVID-19, for example the co-chair recommended treating
severe COVID-19 with remdesivir [Rochwerg].
In summary, although WHO's analysis predicts that over 2 million fewer people would be dead if
ivermectin was used from early in the pandemic, they recommend against use outside trials. Thisappears to be based primarily on excluding the majority of the evidence, and by assigning bias
estimates that do not match the actual risk of bias in studies.
Use early in the pandemic was proposed by Kitasato University including the co-discoverer ofivermectin, Dr. Satoshi Ōmura. They requested Merck conduct clinical trials of ivermectin for COVID19 in Japan, because Merck has priority to submit an application for an expansion of ivermectinʼs
indications. Merck declined [Yagisawa].

Merck Analysis
Merck has stated that there is "no scienti c basis for a potential therapeutic effect against COVID-19
from pre-clinical studies". This is contradicted by many papers and studies, including [Arévalo, Bello,
Choudhury, de Melo, DiNicolantonio, DiNicolantonio (B), Errecalde, Eweas, Francés-Monerris,
Heidary, Jans, Jeffreys, Kalfas, Kory, Lehrer, Li, Mody, Qureshi, Saha, Surnar, Udo a, Wehbe,
Yesilbag, Zatloukal].
They state that there is "no meaningful evidence for clinical activity or clinical e cacy in patients with
COVID-19 disease". This is contradicted by numerous studies including [Afsar, Alam, Babalola,
Behera, Behera (B), Bernigaud, Budhiraja, Bukhari, Cadegiani, Carvallo (B), Carvallo (C), Chaccour,
Chahla, Chahla (B), Chowdhury, Elalfy, Elgazzar, Elgazzar (B), Espitia-Hernandez, Faisal, Hashim,
Huvemek, Khan, Kirti, Lima-Morales, Loue, Mahmud, Merino, Mohan, Morgenstern, Mourya, Niaee,
Okumuş, Seet].

They also claim that there is "a concerning lack of safety data in the majority of studies". Safety
analysis is found in [Descotes, Errecalde, Guzzo, Kory, Madrid], and safety data can be found in
most studies, including [Afsar, Ahmed, Babalola, Behera (B), Bhattacharya, Bukhari, Camprubí,
Carvallo, Chaccour, Chahla (B), Chowdhury, Elalfy, Elgazzar, Espitia-Hernandez, Gorial, Huvemek,
Khan, Kishoria, Lima-Morales, Loue, López-Medina, Mahmud, Mohan, Morgenstern, Mourya, Niaee,
Okumuş, Pott-Junior, Schwartz, Seet, Shahbaznejad, Shouman, Spoorthi, Szente Fonseca].
Merck has a number of con icts of interest:• Merck has committed to give ivermectin away for free "as much as needed, for as long as needed"in the Mectizan® Donation Program [Merck], to help eliminate river blindness.
• Merck has their own new COVID-19 treatments MK-7110 (formerly CD24Fc) [Adams] andMolnupiravir (MK-4482) [WIkipedia].
• Ivermectin is off-patent, there are many manufactureres, and Merck is unlikely to be able tocompete with low cost manufacturers.
• Promoting the use of low cost off-patent medications compared to new products may beundesirable to some shareholders.
• Japan requested Merck conduct clinical trials early in the pandemic and they declined. Merck
may be reluctant to admit this mistake [Yagisawa].

Conclusion
Ivermectin is an effective treatment for COVID-19. The probability that an ineffective treatment
generated results as positive as the 56 studies to date is estimated to be 1 in 2 trillion (p =0.00000000000041). As expected for an effective treatment, early treatment is more successful,with an estimated reduction of 78% in the effect measured using random effects meta-analysis (RR
0.22 [0.12-0.39]). 81% and 96% lower mortality is observed for early treatment and prophylaxis (RR
0.19 [0.07-0.54] and 0.04 [0.00-0.58]). Statistically signi cant improvements are seen for mortality,
ventilation, hospitalization, cases, and viral clearance. The consistency of positive results across awide variety of heterogeneous studies is remarkable, with 95% of the 56 studies reporting positiveeffects (26 statistically signi cant in isolation).

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 (B), 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 total numberof patients.
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 [Bukhari].
1/19: We added [Raad, Shahbaznejad]. [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 updated [Bukhari] to the preprint.
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 (B)].
2/16: We updated [Behera] 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 [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.
4/5: We added [Mourya].
4/7: We identi ed studies where minimal detail is currently available in the forest plots.
4/9: We corrected a duplicate entry for [Bukhari].
4/10: We added [Kishoria].

4/14: We added [Seet].
4/16: We added [Morgenstern].
4/18: We updated [Morgenstern] to the preprint.
4/25: We updated [Schwartz] to the latest results reported at the International Ivermectin for Covid
Conference.
4/26: We added notes on heterogeneity.
4/27: We added analysis restricted to hospitalization results and a comparison with the evidencebase used in the approval of other COVID-19 treatments.
4/28: We added the WHO meta analysis results for comparison.
4/30: We added analysis of the WHO meta analysis and updated [Kory] to the journal version.
5/4: We added [Loue].
5/5: We previously limited the size of the control group in [Bernigaud] to be the same as thetreatment group for calculation of the total number of patients. This is now also re ected and notedin the forest plots.
5/5: We updated [Okumuş] to the journal paper.
5/6: We updated discussion based on peer review including discussion of heterogeneity, exclusion
based sensitivity analysis, and search criteria.
5/6: We added mechanical ventilation and ICU admission analysis.
5/6: We added a comparison of CDC recommendations.
5/6: We updated [Chahla] to the Research Square preprint.
5/7: We updated [Shahbaznejad] to the journal version, which includes additional outcomes notreported earlier.
5/8: We added [Merino].
5/10: We added additional information in the abstract.
5/10: We added [Faisal].
5/13: We updated [Mahmud] to the journal version.
5/15: We updated the discussion of the WHO analysis.
5/17: We added [Szente Fonseca].
5/18: We added analysis of Merck's recommendation.

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. The broad search terms result in a large volume of new studies on adaily basis which are reviewed for inclusion. All studies regarding the use of ivermectin for COVID19 that report an effect compared to a control group are included in the main analysis. Sensitivity
analysis is performed, excluding studies with critical issues, epidemiological studies, and studies
with minimal available information. This is a living analysis and is 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 (this does not result in the exclusion of any studies — the next mostserious outcome is 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 (1.6.3), pythonmeta (1.23), numpy (1.20.2), statsmodels (0.12.2), and plotly (4.14.3).
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.
[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.

[Bukhari], 1/16/2021, Randomized
Controlled Trial, Pakistan, Middle East,
preprint, 10 authors, dosage 12mg single
dose.

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

[Cadegiani], 11/4/2020, prospective,
Brazil, South America, preprint, 4 authors,
dosage 200μg/kg days 1-3.

risk of death, 78.3% lower, RR 0.22, p = 0.50,
treatment 0 of 110 (0.0%), control 2 of 137 (1.5%),
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 Blindsymptom probability, 52.9% lower, RR 0.47, p <Randomized Controlled Trial, Spain,
Europe, peer-reviewed, 23 authors,
dosage 400μg/kg single dose.

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 discharge, 86.9% lower, RR 0.13, p =0.004, treatment 2 of 110 (1.8%), control 20 of 144(13.9%), adjusted per study, odds ratio converted
to relative risk, logistic regression.

[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).

[Faisal], 5/10/2021, Randomized
Controlled Trial, Pakistan, South Asia,
peer-reviewed, 3 authors, dosage 12mg
days 1-5.

risk of no recovery, 68.4% lower, RR 0.32, p =0.005, treatment 6 of 50 (12.0%), control 19 of 50(38.0%), 6-8 days, mid-recovery.

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 no recovery, 27.3% lower, RR 0.73, p = 0.11,
treatment 24 of 50 (48.0%), control 33 of 50

(66.0%), 3-5 days.
risk of no recovery, 75.0% lower, RR 0.25, p = 0.09,
treatment 2 of 50 (4.0%), control 8 of 50 (16.0%),
9-10 days.
[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 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%).

[Loue], 4/17/2021, retrospective quasirandomized (patient choice), France,
Europe, peer-reviewed, 2 authors, dosage
200μg/kg single dose.

risk of death, 70.0% lower, RR 0.30, p = 0.34,
treatment 1 of 10 (10.0%), control 5 of 15 (33.3%).

[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 COVID-19 severe case, 55.0% lower, RR
0.45, p = 0.11, treatment 3 of 10 (30.0%), control
10 of 15 (66.7%).

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.
[Mahmud], 10/9/2020, Double Blind
Randomized Controlled Trial,
Bangladesh, South Asia, peer-reviewed,
15 authors, dosage 12mg single dose,
this trial 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 disease progression, 57.0% lower, RR 0.43,
p < 0.001, treatment 16 of 183 (8.7%), control 32 of
180 (17.8%), adjusted per study, Cox regression.
risk of no recovery, 94.0% lower, RR 0.06, p <0.001, treatment 72 of 183 (39.3%), control 100 of
180 (55.6%), adjusted per study, day 7, Cox
regression.
risk of no recovery, 38.5% lower, RR 0.61, p =0.005, treatment 40 of 183 (21.9%), control 64 of
180 (35.6%), day 11.
risk of no recovery, 96.0% lower, RR 0.04, p <0.001, treatment 42 of 183 (23.0%), control 67 of
180 (37.2%), adjusted per study, day 12, Cox
regression.
time to recovery, 27.0% lower, RR 0.73, p = 0.003,
treatment 183, control 180, Cox regression.
risk of no virological cure, 39.0% lower, RR 0.61, p= 0.002, treatment 14 of 183 (7.7%), control 36 of
180 (20.0%), adjusted per study, Cox regression.

[Merino], 5/3/2021, retrospective quasirandomized (patients receiving kit),
population-based cohort, Mexico, North
America, preprint, 7 authors, dosage
6mg bid days 1-2.

risk of hospitalization, 74.4% lower, RR 0.26, p <0.001, model 7, same time period, patients
receiving kit.

[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 hospitalization, 68.4% lower, RR 0.32, p <0.001, model 1, different time periods,
administrative rule.

risk of no discharge at day 14, 43.8% lower, RR
0.56, p = 0.49, treatment 3 of 40 (7.5%), control 6

of 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.
[Mourya], 4/1/2021, retrospective, India,
South Asia, peer-reviewed, 5 authors,
dosage 12mg days 1-7.

risk of no virological cure, 89.4% lower, RR 0.11, p< 0.001, treatment 5 of 50 (10.0%), control 47 of
50 (94.0%).

[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 thetreatment arm (combined withdoxycycline) - results of individual
treatments may vary.

relative time to clinical response of wellbeing,
5.6% lower, relative time 0.94, p = 0.87, treatment
14, control 15.

[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, 70.2% lower, RR 0.30, p =0.34, treatment 1 of 47 (2.1%), control 3 of 42(7.1%).
risk of no virological cure, 42.2% lower, RR 0.58, 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, 70.2% lower, RR 0.30, p= 0.02, treatment 4 of 47 (8.5%), control 12 of 42(28.6%), day 6, non-infectious samples (Ct>30 or
non-viable culture).
risk of no virological cure, 51.9% lower, RR 0.48, p= 0.08, treatment 7 of 47 (14.9%), control 13 of 42(31.0%), day 10, Ct>30.

risk of no virological cure, 57.9% lower, RR 0.42, p= 0.02, treatment 8 of 47 (17.0%), control 17 of 42(40.5%), day 8, Ct>30.
risk of no virological cure, 44.7% lower, RR 0.55, p= 0.05, treatment 13 of 47 (27.7%), control 21 of
42 (50.0%), day 6, Ct>30.
risk of no virological cure, 31.9% lower, RR 0.68, p= 0.16, treatment 13 of 28 (46.4%), control 15 of
22 (68.2%), day 4, Ct>30.
[Szente Fonseca], 10/31/2020,
retrospective, Brazil, South America,
peer-reviewed, mean age 50.6, 10
authors, dosage 12mg days 1-2.

risk of hospitalization, 13.9% higher, RR 1.14, p =0.45, treatment 340, control 377, adjusted per
study, odds ratio converted to relative risk, control
prevalence approximated with overall prevalence.

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.

[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).

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

risk of mechanical ventilation, 40.0% lower, RR
0.60, p = 0.67, treatment 3 of 13 (23.1%), control 5of 13 (38.5%).
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 (withreciprocal 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.
[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%).

[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%).
risk of ICU admission, 89.5% lower, RR 0.11, p =0.007, treatment 1 of 115 (0.9%), control 11 of 133(8.3%).
time to viral-, 73.3% lower, relative time 0.27, p <0.001, treatment 115, control 133.

[Kishoria], 8/31/2020, Randomized
Controlled Trial, India, South Asia, peerreviewed, 7 authors, dosage 12mg single
dose.

risk of no hospital discharge, 7.5% higher, RR
1.08, p = 1.00, treatment 11 of 19 (57.9%), control
7 of 13 (53.8%).
risk of no virological cure, 7.5% higher, RR 1.08, p =1.00, treatment 11 of 19 (57.9%), control 7 of 13(53.8%), day 3.
risk of no virological cure, 220.0% higher, RR 3.20,
p = 0.45, treatment 1 of 5 (20.0%), control 0 of 6
(0.0%), continuity correction due to zero event(with reciprocal of the contrasting arm), day 5.

[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.
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.

[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, peer-reviewed, 15 authors,risk of death, 33.3% lower, RR 0.67, p = 0.55,
treatment 6 of 30 (20.0%), control 9 of 30 (30.0%).

dosage 200μg/kg days 1-5, 36-50kg 9mg, 51-65kg - 12mg, 66-79kg - 15mg,>80kg 200μg/kg.

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 mechanical ventilation, 85.2% lower, RR
0.15, p = 0.25, treatment 1 of 27 (3.7%), control 1of 4 (25.0%).
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,
propensity score matching, 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.
risk of mechanical ventilation, 63.6% lower, RR
0.36, p = 0.10, treatment 4 of 98 (4.1%), control 11of 98 (11.2%), matched cohort excluding intubatedat baseline.

[Shahbaznejad], 1/19/2021, Double Blind
Randomized Controlled Trial, Iran, Middle
East, peer-reviewed, 8 authors, dosage
200μg/kg single dose.

risk of death, 197.1% higher, RR 2.97, p = 1.00,
treatment 1 of 35 (2.9%), control 0 of 34 (0.0%),
continuity correction due to zero event (withreciprocal of the contrasting arm), patient diedwithin 24 hours of admission.

risk of mechanical ventilation, 94.3% higher, RR
1.94, p = 1.00, treatment 2 of 35 (5.7%), control 1of 34 (2.9%).
recovery time, 31.6% lower, relative time 0.68, p =0.05, treatment 35, control 34, duration ofdsypnea.
recovery time, 19.2% lower, relative time 0.81, p =0.02, treatment 35, control 34, duration of all
symptoms.
hospitalization time, 15.5% lower, relative time
0.85, p = 0.02, treatment 35, control 34.
[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.
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 (B)], 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 45 of 2199 (2.0%), control 133 of
1147 (11.6%), two doses.
risk of COVID-19 case, 4.0% higher, RR 1.04, p =0.85, treatment 23 of 186 (12.4%), control 133 of
1147 (11.6%), patients only receiving the rst dose.

[Behera], 11/3/2020, retrospective, India,
South Asia, peer-reviewed, 13 authors,risk of COVID-19 case, 53.8% lower, RR 0.46, p <0.001, treatment 41 of 117 (35.0%), control 145 ofdosage 300μg/kg days 1, 4.

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 (C)], 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 (B)], 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

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

200μg/kg, dose varied, typically 150200μg/kg.

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

[Morgenstern], 4/16/2021, retrospective,
propensity score matching, Dominican
Republic, Caribbean, preprint, 16 authors,
dosage 200μg/kg weekly.

risk of hospitalization, 80.0% lower, RR 0.20, p =0.50, treatment 0 of 271 (0.0%), control 2 of 271(0.7%), continuity correction due to zero event(with reciprocal of the contrasting arm), PSM.
risk of COVID-19 case, 74.0% lower, RR 0.26, p =0.008, treatment 5 of 271 (1.8%), control 18 of 271(6.6%), adjusted per study, PSM, multivariate Cox
regression.

[Seet], 4/14/2021, Cluster Randomized
Controlled Trial, Singapore, Asia, peerreviewed, 15 authors, dosage 12mg
single dose, 200µg/kg, maximum 12mg,
this trial compares with anothertreatment - results may be better whencompared to placebo.

risk of COVID-19 severe case, 49.8% lower, RR
0.50, p = 0.01, treatment 32 of 617 (5.2%), control
64 of 619 (10.3%).

[Shouman], 8/28/2020, Randomized
Controlled Trial, Egypt, Africa, peerreviewed, 8 authors, dosage 18mg days
1, 3, dose varies depending on weight 40-60kg: 15mg, 60-80kg: 18mg, >80kg:
24mg.

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.

[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%).

risk of COVID-19 case, 5.8% lower, RR 0.94, p =0.61, treatment 398 of 617 (64.5%), control 433 of
619 (70.0%), adjusted per study, odds ratio
converted to relative risk, model 6.

risk of COVID-19 severe case, 92.9% lower, RR
0.07, p = 0.002, treatment 1 of 203 (0.5%), control
7 of 101 (6.9%), unadjusted.

References
1.

Adams, B., Fierce Biotech, Merck must do a new trial for faltering $425M COVID-19 drug the U.S. government
asked it to buy, https://www. ercebiotech.com/biot..rug-u-s-government-asked-it-to-buy.

2.

Afsar et al., SSRN, Ivermectin Use Associated with Reduced Duration of COVID-19 Febrile Illness in a Community
Setting, https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3734478.

3.

Ahmed et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.11.191, A ve day course ofivermectin for the treatment of COVID-19 may reduce the duration of illness,
https://www.sciencedirect.com/science/article/pii/S1201971220325066.

4.

Alam et al., European Journal ofMedical and Health Sciences, doi:10.24018/ejmed.2020.2.6.599, Ivermectin as
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