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Povidone-Iodine for COVID-19: real-time meta analysis of 16 studies
Covid Analysis, August 8, 2022, DRAFT
https://c19pvpi.com/meta.html
0 0.5 1 1.5+ All studies 50% 16 2,833 Improvement, Studies, Patients Relative Risk Mortality 72% 2 872 Hospitalization 84% 3 885 Recovery 25% 3 286 Cases 45% 1 1,354 Viral clearance 68% 13 1,124 RCTs 52% 14 2,496 RCT mortality 88% 1 606 Peer-reviewed 50% 14 2,744 Prophylaxis 45% 1 1,354 Early 69% 10 1,143 Late 42% 5 336 Povidone-Iodine for COVID-19 c19pvpi.com Aug 2022 Favorspovidone-iodine Favorscontrol after exclusions
Statistically significant improvements are seen for mortality, hospitalization, cases, and viral clearance. 7 studies from 7 independent teams in 5 different countries show statistically significant improvements in isolation (5 for the most serious outcome).
Meta analysis using the most serious outcome reported shows 50% [37‑61%] improvement. Results are similar for Randomized Controlled Trials, similar after exclusions, and similar for peer-reviewed studies. Early treatment is more effective than late treatment.
Results are robust — in exclusion sensitivity analysis 13 of 16 studies must be excluded to avoid finding statistically significant efficacy in pooled analysis.
0 0.5 1 1.5+ All studies 50% 16 2,833 Improvement, Studies, Patients Relative Risk Mortality 72% 2 872 Hospitalization 84% 3 885 Recovery 25% 3 286 Cases 45% 1 1,354 Viral clearance 68% 13 1,124 RCTs 52% 14 2,496 RCT mortality 88% 1 606 Peer-reviewed 50% 14 2,744 Prophylaxis 45% 1 1,354 Early 69% 10 1,143 Late 42% 5 336 Povidone-Iodine for COVID-19 c19pvpi.com Aug 2022 Favorspovidone-iodine Favorscontrol after exclusions
Some studies only test short term viral load after a single application. Excessive use of PVP-I could affect thyroid function.
While many treatments have some level of efficacy, they do not replace vaccines and other measures to avoid infection. Only 19% of povidone-iodine studies show zero events in the treatment arm. Multiple treatments are typically used in combination, and other treatments may be more effective.
No treatment, vaccine, or intervention is 100% available and effective for all variants. All practical, effective, and safe means should be used. Denying the efficacy of treatments increases mortality, morbidity, collateral damage, and endemic risk.
All data to reproduce this paper and sources are in the appendix.
Highlights
PVP-I reduces risk for COVID-19 with very high confidence for hospitalization, cases, viral clearance, and in pooled analysis, high confidence for mortality, and very low confidence for recovery.
We show traditional outcome specific analyses and combined evidence from all studies, incorporating treatment delay, a primary confounding factor in COVID-19 studies.
Real-time updates and corrections, transparent analysis with all results in the same format, consistent protocol for 43 treatments.
A
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Mohamed (RCT) 86% 0.14 [0.01-2.21] viral+ 0/5 3/5 Improvement, RR [CI] Treatment Control Choudhury (RCT) 88% 0.12 [0.03-0.50] death 2/303 17/303 Guenezan (RCT) 63% 0.37 [0.06-1.63] viral load 12 (n) 12 (n) Elzein (DB RCT) 89% 0.11 [0.01-1.00] viral load 25 (n) 9 (n) Short term viral Arefin (RCT) 79% 0.21 [0.08-0.54] viral+ 4/27 19/27 Short term viral Baxter (RCT) 65% 0.35 [0.01-8.27] hosp. 0/37 1/42 OT​1 Pablo-Marcos 29% 0.71 [0.32-1.56] viral load 31 (n) 40 (n) Elsersy (DB RCT) 91% 0.09 [0.01-1.62] hosp. 0/100 5/100 CT​2 Sevinç Gül (RCT) 99% 0.01 [0.00-439] viral load 21 (n) 20 (n) Short term viral OT​1 Natto (RCT) 74% 0.26 [0.02-2.80] viral load 12 (n) 12 (n) Short term viral OT​1 Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Early treatment 69% 0.31 [0.19-0.50] 6/573 45/570 69% improvement Seneviratne (RCT) 33% 0.67 [0.50-0.91] viral load 4 (n) 2 (n) Short term viral Improvement, RR [CI] Treatment Control Zarabanda (RCT) -27% 1.27 [0.26-6.28] no recov. 3/13 2/11 OT​1 Jamir (ICU) 57% 0.43 [0.27-0.69] death 39/163 62/103 ICU patients Ferrer (RCT) 34% 0.66 [0.02-19.0] viral load 9 (n) 12 (n) Short term viral Fantozzi (RCT) 31% 0.69 [0.39-1.21] viral+ 5/8 10/11 Short term viral OT​1 Tau​2 = 0.03, I​2 = 28.0%, p = 0.00014 Late treatment 42% 0.58 [0.44-0.76] 47/197 74/139 42% improvement Seet (CLUS. RCT) 45% 0.55 [0.38-0.80] symp. case 42/735 64/619 OT​1 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.002 Prophylaxis 45% 0.55 [0.38-0.80] 42/735 64/619 45% improvement All studies 50% 0.50 [0.39-0.63] 95/1,505 183/1,328 50% improvement 16 povidone-iodine COVID-19 studies c19pvpi.com Aug 2022 Tau​2 = 0.04, I​2 = 24.3%, p < 0.0001 Effect extraction pre-specified(most serious outcome, see appendix) 1 OT: comparison with other treatment2 CT: study uses combined treatment Favors povidone-iodine Favors control
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Mohamed (RCT) 86% viral- Improvement Relative Risk [CI] Choudhury (RCT) 88% death Guenezan (RCT) 63% viral load Elzein (DB RCT) 89% viral- Short term viral Arefin (RCT) 79% viral- Short term viral Baxter (RCT) 65% hospitalization OT​1 Pablo-Marcos 29% viral- Elsersy (DB RCT) 91% hospitalization CT​2 Sevinç Gül (RCT) 99% viral load Short term viral OT​1 Natto (RCT) 74% viral load Short term viral OT​1 Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Early treatment 69% 69% improvement Seneviratne (RCT) 33% viral- Short term viral Zarabanda (RCT) -27% recovery OT​1 Jamir (ICU) 57% death ICU patients Ferrer (RCT) 34% viral load Short term viral Fantozzi (RCT) 31% viral- Short term viral OT​1 Tau​2 = 0.03, I​2 = 28.0%, p = 0.00014 Late treatment 42% 42% improvement Seet (CLUS. RCT) 45% symp. case OT​1 Tau​2 = 0.00, I​2 = 0.0%, p = 0.002 Prophylaxis 45% 45% improvement All studies 50% 50% improvement 16 povidone-iodine COVID-19 studies c19pvpi.com Aug 2022 Tau​2 = 0.04, I​2 = 24.3%, p < 0.0001 Effect extraction pre-specifiedRotate device for footnotes/details Favors povidone-iodine Favors control
Figure 1. A. Random effects meta-analysis. This plot shows pooled effects, discussion can be found in the heterogeneity section, and results for specific outcomes can be found in the individual outcome analyses. Effect extraction is pre-specified, using the most serious outcome reported. For details of effect extraction see the appendix. B. Scatter plot showing the distribution of effects reported in studies. C. History of all reported effects (chronological within treatment stages).
Introduction
We analyze all significant studies concerning the use of povidone-iodine for COVID-19. Search methods, inclusion criteria, effect extraction criteria (more serious outcomes have priority), all individual study data, PRISMA answers, and statistical methods are detailed in Appendix 1. We present random effects meta-analysis results for all studies, for studies within each treatment stage, for individual outcomes, for peer-reviewed studies, for Randomized Controlled Trials (RCTs), and after exclusions.
Figure 2 shows stages of possible treatment for COVID-19. Prophylaxis refers to regularly taking medication before becoming sick, in order to prevent or minimize infection. Early Treatment refers to treatment immediately or soon after symptoms appear, while Late Treatment refers to more delayed treatment.
Figure 2. Treatment stages.
Preclinical Research
Several in vitro studies show that PVP-I is effective for SARS-CoV-2 at clinically relevant concentrations [Anderson, Bidra, Frank, Hassandarvish, Pelletier, Tucker, Xu].
Preclinical research is an important part of the development of treatments, however results may be very different in clinical trials. Preclinical results are not used in this paper.
Results
Figure 3 shows a visual overview of the results, with details in Table 1 and Table 2. Figure 4, 5, 6, 7, 8, 9, and 10 show forest plots for a random effects meta-analysis of all studies with pooled effects, mortality results, hospitalization, recovery, cases, viral clearance, and peer reviewed studies.
0 0.5 1 1.5+ ALL STUDIES MORTALITY HOSPITALIZATION RECOVERY CASES VIRAL CLEARANCE RANDOMIZED CONTROLLED TRIALS RCT MORTALITY PEER-REVIEWED After Exclusions ALL STUDIES All Prophylaxis Early Late Povidone-Iodine for COVID-19 C19PVPI.COM AUG 2022
Figure 3. Overview of results.
Treatment timeNumber of studies reporting positive effects Total number of studiesPercentage of studies reporting positive effects Random effects meta-analysis results
Early treatment 10 10 100% 69% improvement
RR 0.31 [0.19‑0.50]
p < 0.0001
Late treatment 4 5 80.0% 42% improvement
RR 0.58 [0.44‑0.76]
p = 0.00014
Prophylaxis 1 1 100% 45% improvement
RR 0.55 [0.38‑0.80]
p = 0.002
All studies 15 16 93.8% 50% improvement
RR 0.50 [0.39‑0.63]
p < 0.0001
Table 1. Results by treatment stage.
Studies Early treatment Late treatment Prophylaxis PatientsAuthors
All studies 1669% [50‑81%]42% [24‑56%]45% [20‑62%] 2,833 158
With exclusions 1581% [65‑90%]42% [24‑56%]45% [20‑62%] 2,762 152
Peer-reviewed 1472% [48‑85%]42% [24‑56%]45% [20‑62%] 2,744 133
Randomized Controlled TrialsRCTs 1481% [65‑90%]31% [11‑47%]45% [20‑62%] 2,496 146
Table 2. Results by treatment stage for all studies and with different exclusions.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Mohamed (RCT) 86% 0.14 [0.01-2.21] viral+ 0/5 3/5 Improvement, RR [CI] Treatment Control Choudhury (RCT) 88% 0.12 [0.03-0.50] death 2/303 17/303 Guenezan (RCT) 63% 0.37 [0.06-1.63] viral load 12 (n) 12 (n) Elzein (DB RCT) 89% 0.11 [0.01-1.00] viral load 25 (n) 9 (n) Short term viral Arefin (RCT) 79% 0.21 [0.08-0.54] viral+ 4/27 19/27 Short term viral Baxter (RCT) 65% 0.35 [0.01-8.27] hosp. 0/37 1/42 OT​1 Pablo-Marcos 29% 0.71 [0.32-1.56] viral load 31 (n) 40 (n) Elsersy (DB RCT) 91% 0.09 [0.01-1.62] hosp. 0/100 5/100 CT​2 Sevinç Gül (RCT) 99% 0.01 [0.00-439] viral load 21 (n) 20 (n) Short term viral OT​1 Natto (RCT) 74% 0.26 [0.02-2.80] viral load 12 (n) 12 (n) Short term viral OT​1 Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Early treatment 69% 0.31 [0.19-0.50] 6/573 45/570 69% improvement Seneviratne (RCT) 33% 0.67 [0.50-0.91] viral load 4 (n) 2 (n) Short term viral Improvement, RR [CI] Treatment Control Zarabanda (RCT) -27% 1.27 [0.26-6.28] no recov. 3/13 2/11 OT​1 Jamir (ICU) 57% 0.43 [0.27-0.69] death 39/163 62/103 ICU patients Ferrer (RCT) 34% 0.66 [0.02-19.0] viral load 9 (n) 12 (n) Short term viral Fantozzi (RCT) 31% 0.69 [0.39-1.21] viral+ 5/8 10/11 Short term viral OT​1 Tau​2 = 0.03, I​2 = 28.0%, p = 0.00014 Late treatment 42% 0.58 [0.44-0.76] 47/197 74/139 42% improvement Seet (CLUS. RCT) 45% 0.55 [0.38-0.80] symp. case 42/735 64/619 OT​1 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.002 Prophylaxis 45% 0.55 [0.38-0.80] 42/735 64/619 45% improvement All studies 50% 0.50 [0.39-0.63] 95/1,505 183/1,328 50% improvement 16 povidone-iodine COVID-19 studies c19pvpi.com Aug 2022 Tau​2 = 0.04, I​2 = 24.3%, p < 0.0001 Effect extraction pre-specified(most serious outcome, see appendix) 1 OT: comparison with other treatment2 CT: study uses combined treatment Favors povidone-iodine Favors control
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Mohamed (RCT) 86% viral- Improvement Relative Risk [CI] Choudhury (RCT) 88% death Guenezan (RCT) 63% viral load Elzein (DB RCT) 89% viral- Short term viral Arefin (RCT) 79% viral- Short term viral Baxter (RCT) 65% hospitalization OT​1 Pablo-Marcos 29% viral- Elsersy (DB RCT) 91% hospitalization CT​2 Sevinç Gül (RCT) 99% viral load Short term viral OT​1 Natto (RCT) 74% viral load Short term viral OT​1 Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Early treatment 69% 69% improvement Seneviratne (RCT) 33% viral- Short term viral Zarabanda (RCT) -27% recovery OT​1 Jamir (ICU) 57% death ICU patients Ferrer (RCT) 34% viral load Short term viral Fantozzi (RCT) 31% viral- Short term viral OT​1 Tau​2 = 0.03, I​2 = 28.0%, p = 0.00014 Late treatment 42% 42% improvement Seet (CLUS. RCT) 45% symp. case OT​1 Tau​2 = 0.00, I​2 = 0.0%, p = 0.002 Prophylaxis 45% 45% improvement All studies 50% 50% improvement 16 povidone-iodine COVID-19 studies c19pvpi.com Aug 2022 Tau​2 = 0.04, I​2 = 24.3%, p < 0.0001 Effect extraction pre-specifiedRotate device for footnotes/details Favors povidone-iodine Favors control
Figure 4. Random effects meta-analysis for all studies with pooled effects. This plot shows pooled effects, discussion can be found in the heterogeneity section, and results for specific outcomes can be found in the individual outcome analyses. Effect extraction is pre-specified, using the most serious outcome reported. For details of effect extraction see the appendix.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Choudhury (RCT) 88% 0.12 [0.03-0.50] 2/303 17/303 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.004 Early treatment 88% 0.12 [0.03-0.50] 2/303 17/303 88% improvement Jamir (ICU) 57% 0.43 [0.27-0.69] 39/163 62/103 ICU patients Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Late treatment 57% 0.43 [0.27-0.69] 39/163 62/103 57% improvement All studies 72% 0.28 [0.08-0.92] 41/466 79/406 72% improvement 2 povidone-iodine COVID-19 mortality results c19pvpi.com Aug 2022 Tau​2 = 0.55, I​2 = 65.6%, p = 0.036 Favors povidone-iodine Favors control
Figure 5. Random effects meta-analysis for mortality results.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Choudhury (RCT) 84% 0.16 [0.09-0.28] hosp. 12/303 77/303 Improvement, RR [CI] Treatment Control Baxter (RCT) 65% 0.35 [0.01-8.27] hosp. 0/37 1/42 OT​1 Elsersy (DB RCT) 91% 0.09 [0.01-1.62] hosp. 0/100 5/100 CT​2 Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Early treatment 84% 0.16 [0.09-0.28] 12/440 83/445 84% improvement All studies 84% 0.16 [0.09-0.28] 12/440 83/445 84% improvement 3 povidone-iodine COVID-19 hospitalization results c19pvpi.com Aug 2022 Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 1 OT: comparison with other treatment2 CT: study uses combined treatment Favors povidone-iodine Favors control
Figure 6. Random effects meta-analysis for hospitalization.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Baxter (RCT) 57% 0.43 [0.20-0.94] no recov. 6/27 18/35 OT​1 Improvement, RR [CI] Treatment Control Elsersy (DB RCT) 15% 0.85 [0.76-0.96] recov. time 100 (n) 100 (n) CT​2 Tau​2 = 0.15, I​2 = 65.5%, p = 0.23 Early treatment 32% 0.68 [0.36-1.28] 6/127 18/135 32% improvement Zarabanda (RCT) -27% 1.27 [0.26-6.28] no recov. 3/13 2/11 OT​1 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.78 Late treatment -27% 1.27 [0.26-6.28] 3/13 2/11 -27% improvement All studies 25% 0.75 [0.47-1.18] 9/140 20/146 25% improvement 3 povidone-iodine COVID-19 recovery results c19pvpi.com Aug 2022 Tau​2 = 0.07, I​2 = 36.5%, p = 0.22 1 OT: comparison with other treatment2 CT: study uses combined treatment Favors povidone-iodine Favors control
Figure 7. Random effects meta-analysis for recovery.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Seet (CLUS. RCT) 45% 0.55 [0.38-0.80] symp. case 42/735 64/619 OT​1 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.002 Prophylaxis 45% 0.55 [0.38-0.80] 42/735 64/619 45% improvement All studies 45% 0.55 [0.38-0.80] 42/735 64/619 45% improvement 1 povidone-iodine COVID-19 case result c19pvpi.com Aug 2022 Tau​2 = 0.00, I​2 = 0.0%, p = 0.002 1 OT: comparison with other treatment Favors povidone-iodine Favors control
Figure 8. Random effects meta-analysis for cases.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Mohamed (RCT) 86% 0.14 [0.01-2.21] viral+ 0/5 3/5 Improvement, RR [CI] Treatment Control Choudhury (RCT) 96% 0.04 [0.02-0.07] viral+ 8/303 213/303 Guenezan (RCT) 63% 0.37 [0.06-1.63] viral load 12 (n) 12 (n) Elzein (DB RCT) 89% 0.11 [0.01-1.00] viral load 25 (n) 9 (n) Short term viral Arefin (RCT) 79% 0.21 [0.08-0.54] viral+ 4/27 19/27 Short term viral Pablo-Marcos 29% 0.71 [0.32-1.56] viral load 31 (n) 40 (n) Elsersy (DB RCT) 68% 0.32 [0.22-0.49] viral+ 21/100 65/100 CT​2 Sevinç Gül (RCT) 99% 0.01 [0.00-439] viral load 21 (n) 20 (n) Short term viral OT​1 Natto (RCT) 74% 0.26 [0.02-2.80] viral load 12 (n) 12 (n) Short term viral OT​1 Tau​2 = 1.00, I​2 = 79.2%, p = 0.00026 Early treatment 80% 0.20 [0.09-0.47] 33/536 300/528 80% improvement Seneviratne (RCT) 33% 0.67 [0.50-0.91] viral load 4 (n) 2 (n) Short term viral Improvement, RR [CI] Treatment Control Zarabanda (RCT) 0% 1.00 [0.19-5.24] viral+ 2/7 2/7 OT​1 Ferrer (RCT) 34% 0.66 [0.02-19.0] viral load 9 (n) 12 (n) Short term viral Fantozzi (RCT) 31% 0.69 [0.39-1.21] viral+ 5/8 10/11 Short term viral OT​1 Tau​2 = 0.00, I​2 = 0.0%, p = 0.0044 Late treatment 32% 0.68 [0.52-0.89] 7/28 12/32 32% improvement All studies 68% 0.32 [0.17-0.59] 40/564 312/560 68% improvement 13 povidone-iodine COVID-19 viral clearance results c19pvpi.com Aug 2022 Tau​2 = 0.75, I​2 = 82.5%, p = 0.00031 1 OT: comparison with other treatment2 CT: study uses combined treatment Favors povidone-iodine Favors control
Figure 9. Random effects meta-analysis for viral clearance.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Choudhury (RCT) 88% 0.12 [0.03-0.50] death 2/303 17/303 Improvement, RR [CI] Treatment Control Guenezan (RCT) 63% 0.37 [0.06-1.63] viral load 12 (n) 12 (n) Elzein (DB RCT) 89% 0.11 [0.01-1.00] viral load 25 (n) 9 (n) Short term viral Arefin (RCT) 79% 0.21 [0.08-0.54] viral+ 4/27 19/27 Short term viral Pablo-Marcos 29% 0.71 [0.32-1.56] viral load 31 (n) 40 (n) Elsersy (DB RCT) 91% 0.09 [0.01-1.62] hosp. 0/100 5/100 CT​2 Sevinç Gül (RCT) 99% 0.01 [0.00-439] viral load 21 (n) 20 (n) Short term viral OT​1 Natto (RCT) 74% 0.26 [0.02-2.80] viral load 12 (n) 12 (n) Short term viral OT​1 Tau​2 = 0.14, I​2 = 18.8%, p < 0.0001 Early treatment 72% 0.28 [0.15-0.52] 6/531 41/523 72% improvement Seneviratne (RCT) 33% 0.67 [0.50-0.91] viral load 4 (n) 2 (n) Short term viral Improvement, RR [CI] Treatment Control Zarabanda (RCT) -27% 1.27 [0.26-6.28] no recov. 3/13 2/11 OT​1 Jamir (ICU) 57% 0.43 [0.27-0.69] death 39/163 62/103 ICU patients Ferrer (RCT) 34% 0.66 [0.02-19.0] viral load 9 (n) 12 (n) Short term viral Fantozzi (RCT) 31% 0.69 [0.39-1.21] viral+ 5/8 10/11 Short term viral OT​1 Tau​2 = 0.03, I​2 = 28.0%, p = 0.00014 Late treatment 42% 0.58 [0.44-0.76] 47/197 74/139 42% improvement Seet (CLUS. RCT) 45% 0.55 [0.38-0.80] symp. case 42/735 64/619 OT​1 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.002 Prophylaxis 45% 0.55 [0.38-0.80] 42/735 64/619 45% improvement All studies 50% 0.50 [0.39-0.65] 95/1,463 179/1,281 50% improvement 14 povidone-iodine COVID-19 peer reviewed trials c19pvpi.com Aug 2022 Tau​2 = 0.06, I​2 = 31.2%, p < 0.0001 Effect extraction pre-specified(most serious outcome, see appendix) 1 OT: comparison with other treatment2 CT: study uses combined treatment Favors povidone-iodine Favors control
Figure 10. Random effects meta-analysis for peer reviewed studies. [Zeraatkar] analyze 356 COVID-19 trials, finding no significant evidence that peer-reviewed studies are more trustworthy. They also show extremely slow review times during a pandemic. Authors recommend using preprint evidence, with appropriate checks for potential falsified data, which provides higher certainty much earlier. Effect extraction is pre-specified, using the most serious outcome reported, see the appendix for details.
Exclusions
To avoid bias in the selection of studies, we analyze all non-retracted studies. Here we show the results after excluding studies with major issues likely to alter results, non-standard studies, and studies where very minimal detail is currently available. Our bias evaluation is based on analysis of each study and identifying when there is a significant chance that limitations will substantially change the outcome of the study. We believe this can be more valuable than checklist-based approaches such as Cochrane GRADE, which may underemphasize serious issues not captured in the checklists, overemphasize issues unlikely to alter outcomes in specific cases (for example, lack of blinding for an objective mortality outcome, or certain specifics of randomization with a very large effect size), or be easily influenced by potential bias. However, they can also be very high quality.
The studies excluded are as below. Figure 11 shows a forest plot for random effects meta-analysis of all studies after exclusions.
[Pablo-Marcos], unadjusted results with no group details.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Mohamed (RCT) 86% 0.14 [0.01-2.21] viral+ 0/5 3/5 Improvement, RR [CI] Treatment Control Choudhury (RCT) 88% 0.12 [0.03-0.50] death 2/303 17/303 Guenezan (RCT) 63% 0.37 [0.06-1.63] viral load 12 (n) 12 (n) Elzein (DB RCT) 89% 0.11 [0.01-1.00] viral load 25 (n) 9 (n) Short term viral Arefin (RCT) 79% 0.21 [0.08-0.54] viral+ 4/27 19/27 Short term viral Baxter (RCT) 65% 0.35 [0.01-8.27] hosp. 0/37 1/42 OT​1 Elsersy (DB RCT) 91% 0.09 [0.01-1.62] hosp. 0/100 5/100 CT​2 Sevinç Gül (RCT) 99% 0.01 [0.00-439] viral load 21 (n) 20 (n) Short term viral OT​1 Natto (RCT) 74% 0.26 [0.02-2.80] viral load 12 (n) 12 (n) Short term viral OT​1 Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Early treatment 81% 0.19 [0.10-0.35] 6/542 45/530 81% improvement Seneviratne (RCT) 33% 0.67 [0.50-0.91] viral load 4 (n) 2 (n) Short term viral Improvement, RR [CI] Treatment Control Zarabanda (RCT) -27% 1.27 [0.26-6.28] no recov. 3/13 2/11 OT​1 Jamir (ICU) 57% 0.43 [0.27-0.69] death 39/163 62/103 ICU patients Ferrer (RCT) 34% 0.66 [0.02-19.0] viral load 9 (n) 12 (n) Short term viral Fantozzi (RCT) 31% 0.69 [0.39-1.21] viral+ 5/8 10/11 Short term viral OT​1 Tau​2 = 0.03, I​2 = 28.0%, p = 0.00014 Late treatment 42% 0.58 [0.44-0.76] 47/197 74/139 42% improvement Seet (CLUS. RCT) 45% 0.55 [0.38-0.80] symp. case 42/735 64/619 OT​1 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.002 Prophylaxis 45% 0.55 [0.38-0.80] 42/735 64/619 45% improvement All studies 52% 0.48 [0.37-0.62] 95/1,474 183/1,288 52% improvement 15 povidone-iodine COVID-19 studies after exclusions c19pvpi.com Aug 2022 Tau​2 = 0.05, I​2 = 27.2%, p < 0.0001 Effect extraction pre-specified(most serious outcome, see appendix) 1 OT: comparison with other treatment2 CT: study uses combined treatment Favors povidone-iodine Favors control
Figure 11. Random effects meta-analysis for all studies after exclusions. This plot shows pooled effects, discussion can be found in the heterogeneity section, and results for specific outcomes can be found in the individual outcome analyses. Effect extraction is pre-specified, using the most serious outcome reported. For details of effect extraction see the appendix.
Randomized Controlled Trials (RCTs)
Figure 12 shows the distribution of results for Randomized Controlled Trials and other studies, and a chronological history of results. The median effect size for RCTs is 70% improvement, compared to 43% for other studies. Figure 13 and 14 show forest plots for a random effects meta-analysis of all Randomized Controlled Trials and RCT mortality results. Table 3 summarizes the results.
Figure 12. The distribution of results for Randomized Controlled Trials and other studies, and a chronological history of results.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Mohamed (RCT) 86% 0.14 [0.01-2.21] viral+ 0/5 3/5 Improvement, RR [CI] Treatment Control Choudhury (RCT) 88% 0.12 [0.03-0.50] death 2/303 17/303 Guenezan (RCT) 63% 0.37 [0.06-1.63] viral load 12 (n) 12 (n) Elzein (DB RCT) 89% 0.11 [0.01-1.00] viral load 25 (n) 9 (n) Short term viral Arefin (RCT) 79% 0.21 [0.08-0.54] viral+ 4/27 19/27 Short term viral Baxter (RCT) 65% 0.35 [0.01-8.27] hosp. 0/37 1/42 OT​1 Elsersy (DB RCT) 91% 0.09 [0.01-1.62] hosp. 0/100 5/100 CT​2 Sevinç Gül (RCT) 99% 0.01 [0.00-439] viral load 21 (n) 20 (n) Short term viral OT​1 Natto (RCT) 74% 0.26 [0.02-2.80] viral load 12 (n) 12 (n) Short term viral OT​1 Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Early treatment 81% 0.19 [0.10-0.35] 6/542 45/530 81% improvement Seneviratne (RCT) 33% 0.67 [0.50-0.91] viral load 4 (n) 2 (n) Short term viral Improvement, RR [CI] Treatment Control Zarabanda (RCT) -27% 1.27 [0.26-6.28]