COVID-19 studies:  C19 studies: C19:  IvermectinIVM Vitamin DV.D HC QHC Q Vitamin CV.C ZincZn PVP-IPVP-I FLVFLV REGNR2 LY-CoVLY RemdesivirRMD
Ivermectin is effective for COVID-19: real-time meta analysis of 42 studies
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100% of the 42 studies to date report positive effects. Random effects meta-analysis for early treatment and pooled effects shows a reduction of 83%, RR 0.17 [0.11-0.28]. Prophylactic use shows a reduction of 89%, RR 0.11 [0.05-0.23]. Mortality results show 75% lower mortality, RR 0.25 [0.14-0.44] for all treatment delays, and 86% lower, RR 0.14 [0.03-0.62] for early treatment.
100% of the 21 Randomized Controlled Trials (RCTs) report positive effects, with an estimated reduction of 70%, RR 0.30 [0.19-0.49].
The probability that an ineffective treatment generated results as positive as the 42 studies to date is estimated to be 1 in 4 trillion (p = 0.00000000000023).
Early treatment 83% improvement RR 0.17 [0.11-0.28]
Late treatment 51% improvement RR 0.49 [0.37-0.66]
Prophylaxis 89% improvement RR 0.11 [0.05-0.23]
Total42 studies331 authors14,906 patients
RCT21 studies180 authors2,869 patients
IndicationStudiesPatientsEffect sizeWHO status
Scabies [Kory]66130.65 [0.54‑0.78]
35% improvement
Approved
COVID-19 (RCT)212,869 0.30 [0.19‑0.49]
70% improvement
Not approved yet
COVID-19 (all)4214,906 0.25 [0.19‑0.34]
75% improvement
    
  
A
00.250.50.7511.251.51.752+Espitia-Hernandez0.03[0.01-0.11]12mgviral-35RRCIDoseNCarvallo0.12[0.01-1.06]36mgdeath45Cadegiani0.22[0.01-4.48]28mgdeath247Ahmed (DB RCT)0.15[0.01-2.70]24mgsymptoms36Chaccour (DB RCT)0.47[0.19-1.16]28mgsymptoms24Afsar0.08[0.00-1.32]24mgsymptoms90Babalola (DB RCT)0.36[0.10-1.27]12mgviral-60Kirti (DB RCT)0.11[0.01-2.05]24mgdeath112Asghar (RCT)0.18[0.06-0.53]14mgviral-100Raad (SB RCT)0.14[0.01-2.70]14mghospitalization100Mohan (DB RCT)0.38[0.08-1.75]28mgrecovery85Schwartz (DB RCT)0.19[0.01-3.92]24mghospitalization94Elalfy0.13[0.06-0.27]18mgviral-113Tau​2 = 0.12; I​2 = 17.2%Early treatment0.17[0.11-0.28]1,141 patients83% improvementShouman (RCT)0.09[0.03-0.23]18mgsymp. case304Carvallo0.04[0.00-0.63]2mgcase229Behera0.46[0.29-0.71]21mgcase372Elgazzar (RCT)0.20[0.04-0.89]28mgcase200Carvallo0.00[0.00-0.02]12mgcase1,195Hellwig0.22[0.05-0.89]14mgcaseBernigaud0.01[0.00-0.10]28mgdeath138Alam0.09[0.04-0.24]12mgcase118Vallejos0.26[0.14-0.50]12mgcase875Chala (RCT)0.05[0.00-0.89]12mgcase234Behera0.17[0.12-0.23]21mgcase3,346Tau​2 = 0.97; I​2 = 84.2%Prophylaxis0.11[0.05-0.23]7,011 patients89% improvementAll studies0.14[0.09-0.22]8,152 patients86% improvementIvermectin COVID-19 early treatment and prophylaxis studiesivmmeta.com 2/24/21Tau​2 = 0.68; I​2 = 71.6%; Z = 8.21 (p < 0.0001)Lower RiskIncreased Risk
    
  
B
00.250.50.7511.251.51.752+All studiesEarly treatmentmin, Q1, median, Q3, maxLower RiskIncreased Riskivmmeta.com 2/24/21
    
  
C
100+ 75 50 25 25 50 75 100 Espitia-Hernandezviral+, p<0.0001Carvallodeath, p=0.05Cadegianideath, p=0.50Ahmedsymptoms, p=0.09Chaccoursymptoms, p<0.05Afsarsymptoms, p=0.04Babalolaviral+, p=0.11Kirtideath, p=0.12Asgharviral+, p<0.001Raadhosp., p=0.24Mohanno recov., p=0.27Schwartzhosp., p=0.23Elalfyviral+, p<0.0001Early treatment% Lower Risk% Increased Riskivmmeta.com 2/24/21Probability results fromineffective treatmentJan 6 p<0.011 in 100Jan 16 p<0.0011 in 1 thousand
    
  
D
100+ 75 50 25 25 50 75 100 Gorialdeath, p=1.00Espitia-Hernandezviral+, p<0.0001Shoumansymp. case, p<0.001Podderrecov. time, p=0.34Carvallodeath, p=0.05Khandeath, p<0.05Chacharno recov., p=0.50Soto-Becerradeath, p=0.01Mahmuddeath, p=0.25Rajterdeath, p=0.04Carvallocases, p<0.0001Hashimdeath, p=0.27Beheracases, p<0.0001Cadegianideath, p=0.50CamprubíICU, p=1.00Elgazzardeath, p<0.0001Elgazzarcases, p=0.03Spoorthirecov. time, p=0.03Carvallocases, p<0.0001Budhirajadeath, p=0.04Niaeedeath, p=0.001Hellwigcases, p<0.02Bernigauddeath, p=0.08Ahmedsymptoms, p=0.09Chaccoursymptoms, p<0.05Afsarsymptoms, p=0.04Alamcases, p<0.0001Vallejoscases, p<0.0001Babalolaviral+, p=0.11Kirtideath, p=0.12Chalacases, p=0.003Okumuşdeath, p=0.55Asgharviral+, p<0.001Raadhosp., p=0.24Rezairecov. time, p=0.02Mohanno recov., p=0.27Bukhariviral+, p<0.0001Lima-Moralesdeath, p<0.001Schwartzhosp., p=0.23Beheracases, p<0.001Elalfyviral+, p<0.0001Beltran-Gonzalezdeath, p=1.00All studies% Lower Risk% Increased Riskivmmeta.com 2/24/21Probability results fromineffective treatmentSep 30 p<0.011 in 100Oct 13 p<0.0011 in 1 thousandNov 4 p<0.00011 in 10 thousandNov 13 p<0.000011 in 100 thousandNov 18 p<0.0000011 in 1 millionDec 2 p<0.00000011 in 10 millionJan 91 in 1 billionFeb 151 in 1 trillion
Figure 1. A. Random effects meta-analysis excluding late treatment. Simplified dosages are shown for comparison, these are the total dose in the first two days for treatment, and the monthly 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 all reported effects, with the probability that the observed frequency of positive results occurred due to random chance from an ineffective treatment.
Introduction
We analyze all significant 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 only, for COVID-19 case results only, and for Randomized Controlled Trials (RCTs) only.
We also perform a simple analysis of the distribution of study effects. If treatment was not effective, 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 >= k heads in n coin tosses, or the one-sided sign test / binomial test). Analysis of publication bias is important and adjustments may be needed if there is a bias toward publishing positive results.
Figure 2 shows stages of possible treatment for COVID-19. Prophylaxis refers to regularly taking medication before becoming sick, in order to prevent or minimize infection. Early Treatment refers to treatment immediately or soon after symptoms appear, while Late Treatment refers to more delayed treatment.
Figure 2. Treatment stages.
Results
Figure 3, 4, and 5 show results by treatment stage. Figure 6, 7, 8, and 9 show forest plots for a random effects meta-analysis of all studies with pooled effects, and for studies reporting mortality results, COVID-19 case results, and viral clearance results only. Table 1 summarizes the results.
Treatment timeNumber of studies reporting positive results Total number of studiesPercentage of studies reporting positive results Probability of an equal or greater percentage of positive results from an ineffective treatmentRandom effects meta-analysis results
Early treatment 13 13 100% 0.00012 0.00012
1 in 8 thousand
83% improvement
RR 0.17 [0.11‑0.28] p < 0.0001
Late treatment 18 18 100% 0.0000038 3.8e-06
1 in 262 thousand
51% improvement
RR 0.49 [0.37‑0.66] p < 0.0001
Prophylaxis 11 11 100% 0.00049 0.00049
1 in 2 thousand
89% improvement
RR 0.11 [0.05‑0.23] p < 0.0001
All studies 42 42 100% 0.00000000000023 2.3e-13
1 in 4 trillion
75% improvement
RR 0.25 [0.19‑0.34] p < 0.0001
Table 1. Results by treatment stage.
    
  
00.250.50.7511.251.51.752+All studiesLate treatmentEarly treatmentProphylaxismin, Q1, median, Q3, maxLower RiskIncreased Riskivmmeta.com 2/24/21
Figure 3. Results by treatment stage.
    
  
100+ 75 50 25 25 50 75 100 Espitia-Hernandezviral+, p<0.0001Carvallodeath, p=0.05Cadegianideath, p=0.50Ahmedsymptoms, p=0.09Chaccoursymptoms, p<0.05Afsarsymptoms, p=0.04Babalolaviral+, p=0.11Kirtideath, p=0.12Asgharviral+, p<0.001Raadhosp., p=0.24Mohanno recov., p=0.27Schwartzhosp., p=0.23Elalfyviral+, p<0.0001Early treatment% Lower Risk% Increased Riskivmmeta.com 2/24/21Probability results fromineffective treatmentJan 6 p<0.011 in 100Jan 16 p<0.0011 in 1 thousand
    
  
100+ 75 50 25 25 50 75 100 Gorialdeath, p=1.00Podderrecov. time, p=0.34Khandeath, p<0.05Chacharno recov., p=0.50Soto-Becerradeath, p=0.01Mahmuddeath, p=0.25Rajterdeath, p=0.04Hashimdeath, p=0.27CamprubíICU, p=1.00Elgazzardeath, p<0.0001Spoorthirecov. time, p=0.03Budhirajadeath, p=0.04Niaeedeath, p=0.001Okumuşdeath, p=0.55Rezairecov. time, p=0.02Bukhariviral+, p<0.0001Lima-Moralesdeath, p<0.001Beltran-Gonzalezdeath, p=1.00Late treatment% Lower Risk% Increased Riskivmmeta.com 2/24/21Probability results fromineffective treatmentOct 8 p<0.051 in 20Oct 13 p<0.011 in 100Nov 13 p<0.0011 in 1 thousandJan 12 p<0.00011 in 10 thousandFeb 10 p<0.000011 in 100 thousand
Figure 4. Chronological history of early and late treatment results, with the probability that the observed frequency of positive results occurred due to random chance from an ineffective treatment.
100+ 75 50 25 25 50 75 100 Shoumansymp. case, p<0.001Carvallocases, p<0.0001Beheracases, p<0.0001Elgazzarcases, p=0.03Carvallocases, p<0.0001Hellwigcases, p<0.02Bernigauddeath, p=0.08Alamcases, p<0.0001Vallejoscases, p<0.0001Prophylaxis% Lower Risk% Increased Riskivmmeta.com 1/10/21Probability results fromineffective treatmentNov 17 p<0.051 in 20Nov 28 p<0.011 in 100
Figure 5. Chronological history of prophylaxis results.
    
  
00.250.50.7511.251.51.752+Espitia-Hernandez0.03[0.01-0.11]12mgviral-35RRCIDoseNCarvallo0.12[0.01-1.06]36mgdeath45Cadegiani0.22[0.01-4.48]28mgdeath247Ahmed (DB RCT)0.15[0.01-2.70]24mgsymptoms36Chaccour (DB RCT)0.47[0.19-1.16]28mgsymptoms24Afsar0.08[0.00-1.32]24mgsymptoms90Babalola (DB RCT)0.36[0.10-1.27]12mgviral-60Kirti (DB RCT)0.11[0.01-2.05]24mgdeath112Asghar (RCT)0.18[0.06-0.53]14mgviral-100Raad (SB RCT)0.14[0.01-2.70]14mghospitalization100Mohan (DB RCT)0.38[0.08-1.75]28mgrecovery85Schwartz (DB RCT)0.19[0.01-3.92]24mghospitalization94Elalfy0.13[0.06-0.27]18mgviral-113Tau​2 = 0.12; I​2 = 17.2%Early treatment0.17[0.11-0.28]1,141 patients83% improvementGorial0.29[0.01-5.76]14mgdeath87Podder (RCT)0.84[0.55-1.12]14mgrecovery62Khan0.13[0.02-1.01]12mgdeath248Chachar (RCT)0.90[0.44-1.83]36mgrecovery50Soto-Becerra0.83[0.71-0.97]14mgdeath2,833Mahmud (DB RCT)0.14[0.01-2.75]12mgdeath366Rajter0.54[0.27-0.99]14mgdeath196Hashim (SB RCT)0.33[0.07-1.60]28mgdeath140Camprubí0.67[0.13-3.35]14mgICU admission26Elgazzar (RCT)0.08[0.02-0.35]56mgdeath400Spoorthi0.79[0.62-1.01]n/arecovery100Budhiraja0.01[0.00-0.15]n/adeath976Niaee (DB RCT)0.18[0.06-0.55]28mgdeath180Okumuş (DB RCT)0.67[0.27-1.64]28mgdeath60Rezai (RCT)0.79[0.63-0.98]14mgrecovery103Bukhari (RCT)0.18[0.07-0.46]12mgviral-86Lima-Morales0.22[0.12-0.41]12mgdeath768Beltran-G.. (DB RCT)0.86[0.29-2.56]12mgdeath73Tau​2 = 0.17; I​2 = 71.9%Late treatment0.49[0.37-0.66]6,754 patients51% improvementShouman (RCT)0.09[0.03-0.23]18mgsymp. case304Carvallo0.04[0.00-0.63]2mgcase229Behera0.46[0.29-0.71]21mgcase372Elgazzar (RCT)0.20[0.04-0.89]28mgcase200Carvallo0.00[0.00-0.02]12mgcase1,195Hellwig0.22[0.05-0.89]14mgcaseBernigaud0.01[0.00-0.10]28mgdeath138Alam0.09[0.04-0.24]12mgcase118Vallejos0.26[0.14-0.50]12mgcase875Chala (RCT)0.05[0.00-0.89]12mgcase234Behera0.17[0.12-0.23]21mgcase3,346Tau​2 = 0.97; I​2 = 84.2%Prophylaxis0.11[0.05-0.23]7,011 patients89% improvementAll studies0.25[0.19-0.34]14,906 patients75% improvementAll 42 ivermectin COVID-19 studiesivmmeta.com 2/24/21Tau​2 = 0.52; I​2 = 83.1%; Z = 8.95 (p < 0.0001)Lower RiskIncreased Risk
Figure 6. Random effects meta-analysis for all studies.
    
  
00.250.50.7511.251.51.752+Carvallo0.12[0.01-1.06]36mg45RRCIDoseNCadegiani0.22[0.01-4.48]28mg247Kirti (DB RCT)0.11[0.01-2.05]24mg112Tau​2 = 0.00; I​2 = 0.0%Early treatment0.14[0.03-0.62]404 patients86% improvementGorial0.29[0.01-5.76]14mg87Khan0.13[0.02-1.01]12mg248Soto-Becerra0.83[0.71-0.97]14mg2,833Mahmud (DB RCT)0.14[0.01-2.75]12mg366Rajter0.54[0.27-0.99]14mg196Hashim (SB RCT)0.33[0.07-1.60]28mg140Elgazzar (RCT)0.08[0.02-0.35]56mg400Budhiraja0.01[0.00-0.15]n/a976Niaee (DB RCT)0.18[0.06-0.55]28mg180Okumuş (DB RCT)0.67[0.27-1.64]28mg60Lima-Morales0.22[0.12-0.41]12mg768Beltran-G.. (DB RCT)0.86[0.29-2.56]12mg73Tau​2 = 0.56; I​2 = 78.1%Late treatment0.32[0.18-0.56]6,327 patients68% improvementBernigaud0.01[0.00-0.10]28mg138Tau​2 = 0.00; I​2 = 0.0%Prophylaxis0.01[0.00-0.10]138 patients99% improvementAll studies0.25[0.14-0.44]6,869 patients75% improvementAll 16 ivermectin COVID-19 mortality resultsivmmeta.com 2/24/21Tau​2 = 0.69; I​2 = 77.1%; Z = 4.75 (p < 0.0001)Lower RiskIncreased Risk
Figure 7. Random effects meta-analysis for mortality results only.
00.250.50.7511.251.51.752+Carvallo0.04[0.00-0.63]2mg229RRCIDoseNBehera0.46[0.29-0.71]21mg372Elgazzar (RCT)0.20[0.04-0.89]28mg200Carvallo0.00[0.00-0.02]12mg1,195Hellwig0.22[0.05-0.89]14mgBernigaud0.45[0.22-0.91]28mg138Alam0.09[0.04-0.24]12mg118Vallejos0.26[0.14-0.50]12mg875Chala (RCT)0.05[0.00-0.89]12mg234Behera0.17[0.12-0.23]21mg3,346Tau​2 = 0.55; I​2 = 73.9%Prophylaxis0.18[0.10-0.33]6,707 patients82% improvementAll studies0.18[0.10-0.33]6,707 patients82% improvementAll 10 ivermectin COVID-19 case resultsivmmeta.com 2/24/21Tau​2 = 0.55; I​2 = 73.9%; Z = 5.46 (p < 0.0001)Lower RiskIncreased Risk
Figure 8. Random effects meta-analysis for COVID-19 case results only.
00.250.50.7511.251.51.752+Espitia-Hernandez0.03[0.01-0.11]12mg35RRCIDoseNAhmed (DB RCT)0.57[0.37-0.90]24mg36Babalola (DB RCT)0.36[0.10-1.27]12mg60Kirti (DB RCT)1.12[0.89-1.40]24mg112Asghar (RCT)0.18[0.06-0.53]14mg100Mohan (DB RCT)0.90[0.62-1.31]28mg85Schwartz (DB RCT)0.49[0.30-0.79]24mg94Elalfy0.13[0.06-0.27]18mg113Tau​2 = 0.60; I​2 = 90.0%Early treatment0.36[0.20-0.66]635 patients64% improvementKhan0.27[0.12-0.62]12mg248Mahmud (DB RCT)0.58[0.44-0.81]12mg366Okumuş (DB RCT)0.20[0.05-0.81]28mg60Bukhari (RCT)0.18[0.07-0.46]12mg86Tau​2 = 0.19; I​2 = 48.8%Late treatment0.31[0.17-0.57]760 patients69% improvementAll studies0.34[0.21-0.55]1,395 patients66% improvementAll 12 ivermectin COVID-19 viral clearance resultsivmmeta.com 2/24/21Tau​2 = 0.56; I​2 = 87.2%; Z = 4.35 (p < 0.0001)Lower RiskIncreased Risk
Figure 9. Random effects meta-analysis for viral clearance results only.
Randomized Controlled Trials (RCTs)
Results restricted to Randomized Controlled Trials (RCTs) are shown in Figure 10, 11, 12, and 13, and Table 2. RCT results are similar to non-RCT results. Evidence shows that non-RCT trials can also provide reliable results. [Concato] find 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 significant differences in effect estimates. [Lee] shows that only 14% of the guidelines of the Infectious Diseases Society of America were based on RCTs. Evaluation of studies relies on an understanding of the study and potential biases. Limitations in an RCT can outweigh the benefits, 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].
    
  
00.250.50.7511.251.51.752+non-RCTsRandomized Controlled Trialsmin, Q1, median, Q3, maxLower RiskIncreased Riskivmmeta.com 2/24/21