COVID-19 studies:  C19 studies: C19:  IvermectinIVM Vitamin DV.D PXPX FLVFLV PVP-IPI BUBU BHBH BLBL CICI HC QHC Q NZNZ COCO More..
Ivermectin for COVID-19: real-time meta analysis of 60 studies
Share  
Tweet  
https://ivmmeta.com/
Meta analysis using the most serious outcome reported shows 76% and 85% improvement for early treatment and prophylaxis (RR 0.24 [0.14-0.41] and 0.15 [0.09-0.25]), with similar results after exclusion based sensitivity analysis, restriction to peer-reviewed studies, and restriction to Randomized Controlled Trials.
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 significant improvements are seen for mortality, ventilation, hospitalization, cases, and viral clearance. 28 studies show statistically significant improvements in isolation.
Studies Prophylaxis Early treatment Late treatment PatientsAuthors
All studies 60 85% [75‑91%] 76% [59‑86%] 46% [29‑59%] 18,931 549
With exclusions 51 87% [75‑93%] 78% [69‑84%] 54% [33‑68%] 14,554 495
Peer-reviewed 34 88% [70‑95%] 77% [62‑86%] 38% [15‑55%] 7,431 343
Randomized Controlled Trials 31 83% [39‑95%] 69% [57‑77%] 40% [11‑60%] 5,316 340
Mortality results 22 96% [42‑100%] 81% [46‑93%] 61% [38‑76%] 7,690 205
Percentage improvement with ivermectin treatment
The probability that an ineffective treatment generated results as positive as the 60 studies to date is estimated to be 1 in 2 trillion (p = 0.00000000000045).
Heterogeneity arises from many factors including treatment delay, population, effect measured, variants, and regimens. The consistency of positive results is remarkable. Heterogeneity is low in specific cases, for example early treatment mortality.
While many treatments have some level of efficacy, they do not replace vaccines and other measures to avoid infection. Only 27% of ivermectin studies show zero events in the treatment arm.
Elimination of COVID-19 is a race against viral evolution. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. All practical, effective, and safe means should be used. Not doing so increases the risk of COVID-19 becoming endemic; and increases mortality, morbidity, and collateral damage.
Administration with food, often not specified, may significantly increase plasma and tissue concentration.
The evidence base is much larger and has much lower conflict of interest than typically used to approve drugs.
All data to reproduce this paper and sources are in the appendix. See [Bryant, Hariyanto, Hill, Kory, Lawrie, Nardelli] for other meta analyses, all with similar results confirming effectiveness.
00.250.50.7511.251.51.752+Kory et al.69%0.31 [0.20-0.47]Improvement, RR [CI]Hill et al.75%0.25 [0.12-0.52]Bryant et al.62%0.38 [0.19-0.73]Lawrie et al.83%0.17 [0.08-0.35]Nardelli et al.79%0.21 [0.11-0.36]Hariyanto et al.69%0.31 [0.15-0.62]WHO (OR)81%0.19 [0.09-0.36]ivmmeta70%0.30 [0.19-0.47]Ivermectin meta analysis mortality resultsivmmeta.com 6/21/21Lower RiskIncreased Risk
Evidence base used for other COVID-19 approvals
MedicationStudiesPatientsImprovement
Budesonide (UK)11,77917%
Remdesivir (USA)11,06331%
Casiri/imdevimab (USA)179966%
Ivermectin evidence6018,931 71% [62‑77%]
    
  
A
00.250.50.7511.251.51.752+Chowdhury (RCT)81%0.19 [0.01-3.96]14mghosp.0/602/56OT​1 CT​2Improvement, RR [CI]Dose (4d)TreatmentControlEspitia-Hernandez97%0.03 [0.01-0.11]12mgviral+0/287/7CT​2Carvallo88%0.12 [0.01-1.06]36mgdeath1/333/12CT​2Mahmud (DB RCT)86%0.14 [0.01-2.75]12mgdeath0/1833/183CT​2Szente Fonseca-14%1.14 [0.75-1.66]24mghosp.340377Cadegiani78%0.22 [0.01-4.48]42mgdeath0/1102/137Ahmed (DB RCT)85%0.15 [0.01-2.70]48mgsymptoms0/173/19Chaccour (DB RCT)53%0.47 [0.19-1.16]28mgsymp. prob.1212Afsar92%0.08 [0.00-1.32]48mgsymptoms0/377/53Babalola (DB RCT)64%0.36 [0.10-1.27]24mgviral+4020OT​1Kirti (DB RCT)89%0.11 [0.01-2.05]24mgdeath0/554/57Bukhari (RCT)82%0.18 [0.07-0.46]12mgviral+4/4125/45Samaha (RCT)86%0.14 [0.01-2.70]12mghosp.0/503/50Mohan (DB RCT)62%0.38 [0.08-1.75]28mgno recov.2/406/45Biber (DB RCT)70%0.30 [0.03-2.76]36mghosp.1/473/42Elalfy87%0.13 [0.06-0.27]36mgviral+7/6244/51CT​2López-Me.. (DB RCT)67%0.33 [0.01-8.11]84mgdeath0/2001/198Roy6%0.94 [0.52-1.93]n/arecov. time1415CT​2Chahla (CLUS. RCT)87%0.13 [0.03-0.54]24mgno disch.2/11020/144Mourya89%0.11 [0.05-0.25]48mgviral+5/5047/50Loue (QR)70%0.30 [0.04-2.20]14mgdeath1/105/15Merino (QR)74%0.26 [0.11-0.61]24mghosp.population-based cohortFaisal (RCT)68%0.32 [0.14-0.72]48mgno recov.6/5019/50Aref (RCT)63%0.37 [0.22-0.62]recov. time5757Krolewiecki (RCT)-152%2.52 [0.11-58.1]168mgventilation1/270/14Tau​2 = 0.98; I​2 = 82.3%Early treatment76%0.24 [0.14-0.41]30/1,673204/1,70976% improvementShouman (RCT)91%0.09 [0.03-0.23]36mgsymp. case15/20359/101Improvement, RR [CI]Dose (1m)TreatmentControlCarvallo96%0.04 [0.00-0.63]14mgcases0/13111/98CT​2Behera54%0.46 [0.29-0.71]42mgcases41/117145/255Elgazzar (RCT)80%0.20 [0.04-0.89]112mgcases2/10010/100Carvallo100%0.00 [0.00-0.02]48mgcases0/788237/407CT​2Hellwig (ECO.)78%0.22 [0.05-0.89]14mgcasesecologicalBernigaud99%0.01 [0.00-0.10]84mgdeath0/69150/3,062CL​4Alam91%0.09 [0.04-0.24]12mgcases4/5844/60Vallejos73%0.27 [0.15-0.48]48mgcases13/38961/486MD​3Chahla (RCT)95%0.05 [0.00-0.80]48mgcases0/11710/117CT​2Behera83%0.17 [0.12-0.23]42mgcases45/2,199133/1,147Tanioka (ECO.)88%0.12 [0.03-0.51]14mgdeathecologicalSeet (CLUS. RCT)50%0.50 [0.33-0.76]12mgsevere case32/61764/619OT​1Morgenstern (PSM)80%0.20 [0.01-4.15]56mghosp.0/2712/271Tau​2 = 0.58; I​2 = 83.8%Prophylaxis85%0.15 [0.09-0.25]152/5,059926/3,73085% improvementAll studies81%0.19 [0.13-0.29]182/6,7321,130/5,43981% improvementIvermectin COVID-19 early treatment and prophylaxis studiesivmmeta.com 6/21/211 OT: ivermectin vs. other treatment2 CT: study uses combined treatment3 MD: minimal detail available currently4 CL: control group size limited in totalsTau​2 = 0.91; I​2 = 89.1%; Z = 8.18 (p < 0.0001)Lower RiskIncreased Risk
    
  
B
00.250.50.7511.251.51.752+All studiesEarly treatmentmin, Q1, median, Q3, maxLower RiskIncreased Riskivmmeta.com 6/21/21
    
  
C
100+ 75 50 25 25 50 75 100 Chowdhuryhosp., p=0.23Espitia-Hernandezviral+, p<0.0001Carvallodeath, p=0.05Mahmuddeath, p=0.25Szente Fonsecahosp., p=0.45Cadegianideath, p=0.50Ahmedsymptoms, p=0.09Chaccoursymp. prob., p<0.05Afsarsymptoms, p=0.04Babalolaviral+, p=0.11Kirtideath, p=0.12Bukhariviral+, p<0.0001Samahahosp., p=0.24Mohanno recov., p=0.27Biberhosp., p=0.34Elalfyviral+, p<0.0001López-Medinadeath, p=0.50Royrecov. time, p=0.87Chahlano disch., p=0.004Mouryaviral+, p<0.0001Louedeath, p=0.34Merinohosp., p<0.001Faisalno recov., p=0.005Arefrecov. time, p=0.0001Krolewieckiventilation, p=1.00Early treatment% Lower Risk% Increased Riskivmmeta.com 6/21/21Probability results fromineffective treatmentJan 9 p<0.011 in 100Feb 2 p<0.0011 in 1 thousandMar 12 p<0.00011 in 10 thousandMay 3 p<0.000011 in 100 thousand
    
  
D
100+ 75 50 25 25 50 75 100 Gorial, death, p=1.00Chowdhury, hosp., p=0.23Espitia-Hernandez, viral+, p<0.0001Shouman, symp. case, p<0.001Kishoria, no disch., p=1.00Podder, recov. time, p=0.34Carvallo, death, p=0.05Khan, death, p<0.05Chachar, no recov., p=0.50Soto-Becerra, death, p=0.01Mahmud, death, p=0.25Rajter, death, p=0.04Carvallo, cases, p<0.0001Hashim, death, p=0.27Szente Fonseca, hosp., p=0.45Behera, cases, p<0.0001Cadegiani, death, p=0.50Camprubí, ventilation, p=0.67Elgazzar, death, p<0.0001Elgazzar, cases, p=0.03Spoorthi, recov. time, p=0.03Carvallo, cases, p<0.0001Budhiraja, death, p=0.04Niaee, death, p=0.001Hellwig, cases, p<0.02Bernigaud, death, p=0.08Ahmed, symptoms, p=0.09Chaccour, symp. prob., p<0.05Afsar, symptoms, p=0.04Alam, cases, p<0.0001Vallejos, cases, p<0.0001Babalola, viral+, p=0.11Kirti, death, p=0.12Chahla, cases, p=0.002Okumuş, death, p=0.55Bukhari, viral+, p<0.0001Samaha, hosp., p=0.24Shahbaznejad, death, p=1.00Mohan, no recov., p=0.27Lima-Morales, death, p<0.001Biber, hosp., p=0.34Behera, cases, p<0.001Elalfy, viral+, p<0.0001Gonzalez, death, p=1.00López-Medina, death, p=0.50Pott-Junior, ventilation, p=0.25Roy, recov. time, p=0.87Huvemek, no improv., p=0.28Tanioka, death, p=0.002Chahla, no disch., p=0.004Mourya, viral+, p<0.0001Seet, severe case, p=0.01Morgenstern, hosp., p=0.50Loue, death, p=0.34Ahsan, death, p=0.03Merino, hosp., p<0.001Faisal, no recov., p=0.005Abd-Elsalam, death, p=0.70Aref, recov. time, p=0.0001Krolewiecki, ventilation, p=1.00All studies% Lower Risk% Increased Riskivmmeta.com 6/21/21Probability results fromineffective treatmentOct 9 p<0.011 in 100Nov 17 p<0.00011 in 10 thousandNov 28 p<0.000011 in 100 thousandDec 15 p<0.0000011 in 1 millionJan 9 p<0.00000011 in 10 millionFeb 231 in 1 billionApr 291 in 1 trillion
Figure 1. A. Random effects meta-analysis excluding late treatment. This plot shows pooled effects, analysis for individual outcomes is below, and more details on pooled effects can be found in the heterogeneity section. Effect extraction is pre-specified, see the appendix for details. Simplified dosages are shown for comparison, these are the total dose in the first four 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, for COVID-19 case results, for viral clearance results, for peer-reviewed studies, for Randomized Controlled Trials (RCTs), and after exclusions.
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, 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 viral clearance results only. Figure 13 shows results for peer reviewed trials only. Table 1 summarizes the results.
Treatment timeNumber of studies reporting positive effects Total number of studiesPercentage of studies reporting positive effects Probability of an equal or greater percentage of positive results from an ineffective treatmentRandom effects meta-analysis results
Early treatment 23 25 92.0% 0.0000097 9.7e-06
1 in 103 thousand
76% improvement
RR 0.24 [0.14‑0.41] p < 0.0001
Late treatment 19 21 90.5% 0.00011 0.00011
1 in 9 thousand
46% improvement
RR 0.54 [0.41‑0.71] p < 0.0001
Prophylaxis 14 14 100% 0.000061 6.1e-05
1 in 16 thousand
85% improvement
RR 0.15 [0.09‑0.25] p < 0.0001
All studies 56 60 93.3% 0.00000000000045 4.5e-13
1 in 2 trillion
71% improvement
RR 0.29 [0.23‑0.38] 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 6/21/21
Figure 3. Results by treatment stage.
    
  
100+ 75 50 25 25 50 75 100 Chowdhuryhosp., p=0.23Espitia-Hernandezviral+, p<0.0001Carvallodeath, p=0.05Mahmuddeath, p=0.25Szente Fonsecahosp., p=0.45Cadegianideath, p=0.50Ahmedsymptoms, p=0.09Chaccoursymp. prob., p<0.05Afsarsymptoms, p=0.04Babalolaviral+, p=0.11Kirtideath, p=0.12Bukhariviral+, p<0.0001Samahahosp., p=0.24Mohanno recov., p=0.27Biberhosp., p=0.34Elalfyviral+, p<0.0001López-Medinadeath, p=0.50Royrecov. time, p=0.87Chahlano disch., p=0.004Mouryaviral+, p<0.0001Louedeath, p=0.34Merinohosp., p<0.001Faisalno recov., p=0.005Arefrecov. time, p=0.0001Krolewieckiventilation, p=1.00Early treatment% Lower Risk% Increased Riskivmmeta.com 6/21/21Probability results fromineffective treatmentJan 9 p<0.011 in 100Feb 2 p<0.0011 in 1 thousandMar 12 p<0.00011 in 10 thousandMay 3 p<0.000011 in 100 thousand
    
  
100+ 75 50 25 25 50 75 100 Gorialdeath, p=1.00Kishoriano disch., p=1.00Podderrecov. time, p=0.34Khandeath, p<0.05Chacharno recov., p=0.50Soto-Becerradeath, p=0.01Rajterdeath, p=0.04Hashimdeath, p=0.27Camprubíventilation, p=0.67Elgazzardeath, p<0.0001Spoorthirecov. time, p=0.03Budhirajadeath, p=0.04Niaeedeath, p=0.001Okumuşdeath, p=0.55Shahbaznejaddeath, p=1.00Lima-Moralesdeath, p<0.001Gonzalezdeath, p=1.00Pott-Juniorventilation, p=0.25Huvemekno improv., p=0.28Ahsandeath, p=0.03Abd-Elsalamdeath, p=0.70Late treatment% Lower Risk% Increased Riskivmmeta.com 6/21/21Probability results fromineffective treatmentOct 26 p<0.051 in 20Nov 14 p<0.011 in 100Mar 9 p<0.0011 in 1 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<0.0001Chahlacases, p=0.002Beheracases, p<0.001Taniokadeath, p=0.002Seetsevere case, p=0.01Morgensternhosp., p=0.50Prophylaxis% Lower Risk% Increased Riskivmmeta.com 6/21/21Probability results fromineffective treatmentNov 17 p<0.051 in 20Nov 28 p<0.011 in 100Jan 11 p<0.0011 in 1 thousandApr 16 p<0.00011 in 10 thousand
Figure 5. Chronological history of prophylaxis results.
    
  
00.250.50.7511.251.51.752+Chowdhury (RCT)81%0.19 [0.01-3.96]14mghosp.0/602/56OT​1 CT​2Improvement, RR [CI]Dose (4d)TreatmentControlEspitia-Hernandez97%0.03 [0.01-0.11]12mgviral+0/287/7CT​2Carvallo88%0.12 [0.01-1.06]36mgdeath1/333/12CT​2Mahmud (DB RCT)86%0.14 [0.01-2.75]12mgdeath0/1833/183CT​2Szente Fonseca-14%1.14 [0.75-1.66]24mghosp.340377Cadegiani78%0.22 [0.01-4.48]42mgdeath0/1102/137Ahmed (DB RCT)85%0.15 [0.01-2.70]48mgsymptoms0/173/19Chaccour (DB RCT)53%0.47 [0.19-1.16]28mgsymp. prob.1212Afsar92%0.08 [0.00-1.32]48mgsymptoms0/377/53Babalola (DB RCT)64%0.36 [0.10-1.27]24mgviral+4020OT​1Kirti (DB RCT)89%0.11 [0.01-2.05]24mgdeath0/554/57Bukhari (RCT)82%0.18 [0.07-0.46]12mgviral+4/4125/45Samaha (RCT)86%0.14 [0.01-2.70]12mghosp.0/503/50Mohan (DB RCT)62%0.38 [0.08-1.75]28mgno recov.2/406/45Biber (DB RCT)70%0.30 [0.03-2.76]36mghosp.1/473/42Elalfy87%0.13 [0.06-0.27]36mgviral+7/6244/51CT​2López-Me.. (DB RCT)67%0.33 [0.01-8.11]84mgdeath0/2001/198Roy6%0.94 [0.52-1.93]n/arecov. time1415CT​2Chahla (CLUS. RCT)87%0.13 [0.03-0.54]24mgno disch.2/11020/144Mourya89%0.11 [0.05-0.25]48mgviral+5/5047/50Loue (QR)70%0.30 [0.04-2.20]14mgdeath1/105/15Merino (QR)74%0.26 [0.11-0.61]24mghosp.population-based cohortFaisal (RCT)68%0.32 [0.14-0.72]48mgno recov.6/5019/50Aref (RCT)63%0.37 [0.22-0.62]recov. time5757Krolewiecki (RCT)-152%2.52 [0.11-58.1]168mgventilation1/270/14Tau​2 = 0.98; I​2 = 82.3%Early treatment76%0.24 [0.14-0.41]30/1,673204/1,70976% improvementGorial71%0.29 [0.01-5.76]14mgdeath0/162/71Improvement, RR [CI]Dose (4d)TreatmentControlKishoria (RCT)-8%1.08 [0.57-2.02]12mgno disch.11/197/13Podder (RCT)16%0.84 [0.55-1.12]14mgrecov. time3230Khan87%0.13 [0.02-1.01]12mgdeath1/1159/133Chachar (RCT)10%0.90 [0.44-1.83]36mgno recov.9/2510/25Soto-Becerra17%0.83 [0.71-0.97]14mgdeath92/2031,438/2,630Rajter (PSM)46%0.54 [0.27-0.99]14mgdeath13/9824/98Hashim (SB RCT)67%0.33 [0.07-1.60]28mgdeath2/706/70CT​2Camprubí40%0.60 [0.18-2.01]14mgventilation3/135/13Elgazzar (RCT)92%0.08 [0.02-0.35]112mgdeath2/20024/200OT​1Spoorthi21%0.79 [0.62-1.01]n/arecov. time5050CT​2Budhiraja99%0.01 [0.00-0.15]n/adeath0/34103/942Niaee (DB RCT)82%0.18 [0.06-0.55]28mgdeath4/12011/60Okumuş (DB RCT)33%0.67 [0.27-1.64]56mgdeath6/309/30Shahbazn.. (DB RCT)-197%2.97 [0.13-70.5]14mgdeath1/350/34Lima-Morales78%0.22 [0.12-0.41]12mgdeath15/48152/287CT​2Gonzalez (DB RCT)14%0.86 [0.29-2.56]12mgdeath5/366/37Pott-Junior (RCT)85%0.15 [0.01-1.93]14mgventilation1/271/4Huvemek (DB RCT)32%0.68 [0.38-1.23]84mgno improv.13/5019/50Ahsan50%0.50 [0.28-0.90]21mgdeath17/11017/55CT​2Abd-Elsalam (RCT)25%0.75 [0.17-3.06]36mgdeath3/824/82Tau​2 = 0.17; I​2 = 64.2%Late treatment46%0.54 [0.41-0.71]198/1,8461,747/4,91446% improvementShouman (RCT)91%0.09 [0.03-0.23]36mgsymp. case15/20359/101Improvement, RR [CI]Dose (1m)TreatmentControlCarvallo96%0.04 [0.00-0.63]14mgcases0/13111/98CT​2Behera54%0.46 [0.29-0.71]42mgcases41/117145/255Elgazzar (RCT)80%0.20 [0.04-0.89]112mgcases2/10010/100Carvallo100%0.00 [0.00-0.02]48mgcases0/788237/407CT​2Hellwig (ECO.)78%0.22 [0.05-0.89]14mgcasesecologicalBernigaud99%0.01 [0.00-0.10]84mg