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Curcumin for COVID-19: real-time meta analysis of 16 studies
Covid Analysis, May 27, 2022, DRAFT
https://c19curcumin.com/meta.html
0 0.5 1 1.5+ All studies 42% 16 1,697 Improvement, Studies, Patients Relative Risk Mortality 61% 6 605 Ventilation 77% 3 386 ICU admission 67% 1 120 Hospitalization 25% 7 753 Progression 76% 2 101 Recovery 38% 9 648 Viral clearance 35% 5 339 RCTs 42% 13 1,157 RCT mortality 61% 6 605 Peer-reviewed 45% 15 1,451 Prophylaxis 42% 1 253 Early 48% 7 757 Late 51% 8 687 Curcumin for COVID-19 c19curcumin.com May 2022 Favorscurcumin Favorscontrol after exclusions
Statistically significant improvements are seen for mortality, hospitalization, recovery, and viral clearance. 10 studies from 9 independent teams in 5 different countries show statistically significant improvements in isolation (6 for the most serious outcome).
Meta analysis using the most serious outcome reported shows 42% [32‑50%] improvement. Results are similar for Randomized Controlled Trials, similar after exclusions, and similar for peer-reviewed studies.
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 42% 16 1,697 Improvement, Studies, Patients Relative Risk Mortality 61% 6 605 Ventilation 77% 3 386 ICU admission 67% 1 120 Hospitalization 25% 7 753 Progression 76% 2 101 Recovery 38% 9 648 Viral clearance 35% 5 339 RCTs 42% 13 1,157 RCT mortality 61% 6 605 Peer-reviewed 45% 15 1,451 Prophylaxis 42% 1 253 Early 48% 7 757 Late 51% 8 687 Curcumin for COVID-19 c19curcumin.com May 2022 Favorscurcumin Favorscontrol after exclusions
Studies typically use advanced formulations for greatly improved bioavailability.
While many treatments have some level of efficacy, they do not replace vaccines and other measures to avoid infection. Only 31% of curcumin 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. Other meta analyses for curcumin can be found in [Kow, Vahedian-Azimi], showing significant improvements for mortality, hospitalization, and symptoms.
Highlights
Curcumin reduces risk for COVID-19 with very high confidence for mortality, recovery, and in pooled analysis, high confidence for hospitalization and viral clearance, low confidence for ventilation, and very low confidence for progression. Studies typically use advanced formulations for greatly improved bioavailability.
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 42 treatments.
A
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Dound (RCT) 33% 0.67 [0.54-0.82] 6 pt. scale 100 (n) 100 (n) CT​1 Improvement, RR [CI] Treatment Control Saber-Moghaddam 94% 0.06 [0.00-0.93] progression 0/21 8/20 Pawar (DB RCT) 82% 0.18 [0.04-0.79] death 2/70 11/70 Ahmadi (DB RCT) 86% 0.14 [0.01-2.65] hosp. 0/30 3/30 Sankhe (RCT) 89% 0.11 [0.01-2.03] death 0/87 4/87 CT​1 Majeed (DB RCT) 66% 0.34 [0.01-8.09] ventilation 0/45 1/47 CT​1 Khan (RCT) 33% 0.67 [0.37-1.19] no recov. 10/25 15/25 CT​1 Tau​2 = 0.09, I​2 = 28.7%, p = 0.0041 Early treatment 48% 0.52 [0.33-0.81] 12/378 42/379 48% improvement Valizadeh (DB RCT) 50% 0.50 [0.18-1.40] death 4/20 8/20 Improvement, RR [CI] Treatment Control Tahmasebi (DB RCT) 83% 0.17 [0.02-1.32] death 1/40 6/40 Hassania.. (DB RCT) -46% 1.46 [0.01-329] SpO2 imp. 20 (n) 20 (n) Asadirad (RCT) 26% 0.74 [0.26-2.12] death 5/27 6/24 Kartika 41% 0.59 [0.35-1.00] hosp. time 139 (n) 107 (n) Hartono (RCT) 53% 0.47 [0.32-0.68] viral+ 14/30 30/30 CT​1 Sankhe (SB RCT) 86% 0.14 [0.01-2.71] death 0/60 3/60 CT​1 Hellou (DB RCT) 77% 0.23 [0.06-0.95] NEWS2 33 (n) 17 (n) CT​1 Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Late treatment 51% 0.49 [0.37-0.64] 24/369 53/318 51% improvement Shehab 42% 0.58 [0.14-2.32] severe case 2/32 24/221 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.45 Prophylaxis 42% 0.58 [0.14-2.32] 2/32 24/221 42% improvement All studies 42% 0.58 [0.50-0.68] 38/779 119/918 42% improvement 16 curcumin COVID-19 studies c19curcumin.com May 2022 Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Effect extraction pre-specified(most serious outcome, see appendix) 1 CT: study uses combined treatment Favors curcumin 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 curcumin 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.
Mechanisms of Action
3CLpro inhibitorCurcumin inhibits SARS-CoV-2 3CLpro [Bahun, Guijarro-Real, Rehman].
RdRp inhibitorSARS-CoV-2 RNA‐dependent RNA polymerase (RdRp) inhibition [Singh].
ACE2 inhibitorCurcumin inhibits ACE2 activity. SARS-CoV-2 viral entry requires host cell surface proteins ACE2 and TMPRSS2 [Jena, Patel].
TMPRSS2 downregulationCurcumin downregulates transmembrane serine protease 2 (TMPRSS2). SARS-CoV-2 viral entry requires host cell surface proteins ACE2 and TMPRSS2 [Goc].
Cathepsin L inhibitorCurcumin inhibits cathepsin L activity. Cathepsin L plays a key role in viral entry [Goc].
Anti‑inflammatoryCurcumin shows anti-inflammatory effects [Daily, Derosa, Gupta, Marín-Palma, Rattis, Sahebkar].
Inhibition in Vero E6 cells demonstratedIn Vitro research shows curcumin inhibits SARS-CoV-2 in Vero E6 cells [Bormann, Marín-Palma].
Inhibition in Calu-3 cells demonstratedIn Vitro research shows curcumin inhibits SARS-CoV-2 in Calu-3 cells [Bormann].
Table 1. Curcumin mechanisms of action. Submit updates.
Preclinical and Phase I Research
5 In Silico studies support the efficacy of curcumin [Kandeil, Nag, Rampogu, Sekiou, Singh].
7 In Vitro studies support the efficacy of curcumin [Bahun, Bormann, Goc, Goc (B), Guijarro-Real, Kandeil, Leka].
[Panda] present a phase I clinical study investigating a novel formulation of curcumin that may be more effective for COVID-19.
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 2 and Table 3. Figure 4, 5, 6, 7, 8, 9, 10, 11, and 12 show forest plots for a random effects meta-analysis of all studies with pooled effects, mortality results, ventilation, ICU admission, hospitalization, progression, recovery, viral clearance, and peer reviewed studies.
0 0.5 1 1.5+ ALL STUDIES MORTALITY VENTILATION ICU ADMISSION HOSPITALIZATION PROGRESSION RECOVERY VIRAL CLEARANCE RANDOMIZED CONTROLLED TRIALS RCT MORTALITY PEER-REVIEWED After Exclusions ALL STUDIES All Prophylaxis Early Late Curcumin for COVID-19 C19CURCUMIN.COM MAY 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 7 7 100% 48% improvement
RR 0.52 [0.33‑0.81]
p = 0.0041
Late treatment 7 8 87.5% 51% improvement
RR 0.49 [0.37‑0.64]
p < 0.0001
Prophylaxis 1 1 100% 42% improvement
RR 0.58 [0.14‑2.32]
p = 0.45
All studies 15 16 93.8% 42% improvement
RR 0.58 [0.50‑0.68]
p < 0.0001
Table 2. Results by treatment stage.
Studies Early treatment Late treatment Prophylaxis PatientsAuthors
All studies 1648% [19‑67%]51% [36‑63%]42% [-132‑86%] 1,697 139
With exclusions 1369% [28‑87%]48% [23‑65%] 1,184 114
Peer-reviewed 1548% [19‑67%]54% [37‑67%]42% [-132‑86%] 1,451 133
Randomized Controlled TrialsRCTs 1339% [18‑55%]54% [37‑67%] 1,157 117
Table 3. 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+ Dound (RCT) 33% 0.67 [0.54-0.82] 6 pt. scale 100 (n) 100 (n) CT​1 Improvement, RR [CI] Treatment Control Saber-Moghaddam 94% 0.06 [0.00-0.93] progression 0/21 8/20 Pawar (DB RCT) 82% 0.18 [0.04-0.79] death 2/70 11/70 Ahmadi (DB RCT) 86% 0.14 [0.01-2.65] hosp. 0/30 3/30 Sankhe (RCT) 89% 0.11 [0.01-2.03] death 0/87 4/87 CT​1 Majeed (DB RCT) 66% 0.34 [0.01-8.09] ventilation 0/45 1/47 CT​1 Khan (RCT) 33% 0.67 [0.37-1.19] no recov. 10/25 15/25 CT​1 Tau​2 = 0.09, I​2 = 28.7%, p = 0.0041 Early treatment 48% 0.52 [0.33-0.81] 12/378 42/379 48% improvement Valizadeh (DB RCT) 50% 0.50 [0.18-1.40] death 4/20 8/20 Improvement, RR [CI] Treatment Control Tahmasebi (DB RCT) 83% 0.17 [0.02-1.32] death 1/40 6/40 Hassania.. (DB RCT) -46% 1.46 [0.01-329] SpO2 imp. 20 (n) 20 (n) Asadirad (RCT) 26% 0.74 [0.26-2.12] death 5/27 6/24 Kartika 41% 0.59 [0.35-1.00] hosp. time 139 (n) 107 (n) Hartono (RCT) 53% 0.47 [0.32-0.68] viral+ 14/30 30/30 CT​1 Sankhe (SB RCT) 86% 0.14 [0.01-2.71] death 0/60 3/60 CT​1 Hellou (DB RCT) 77% 0.23 [0.06-0.95] NEWS2 33 (n) 17 (n) CT​1 Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Late treatment 51% 0.49 [0.37-0.64] 24/369 53/318 51% improvement Shehab 42% 0.58 [0.14-2.32] severe case 2/32 24/221 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.45 Prophylaxis 42% 0.58 [0.14-2.32] 2/32 24/221 42% improvement All studies 42% 0.58 [0.50-0.68] 38/779 119/918 42% improvement 16 curcumin COVID-19 studies c19curcumin.com May 2022 Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Effect extraction pre-specified(most serious outcome, see appendix) 1 CT: study uses combined treatment Favors curcumin 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+ Pawar (DB RCT) 82% 0.18 [0.04-0.79] 2/70 11/70 Improvement, RR [CI] Treatment Control Sankhe (RCT) 89% 0.11 [0.01-2.03] 0/87 4/87 CT​1 Tau​2 = 0.00, I​2 = 0.0%, p = 0.007 Early treatment 84% 0.16 [0.04-0.61] 2/157 15/157 84% improvement Valizadeh (DB RCT) 50% 0.50 [0.18-1.40] 4/20 8/20 Improvement, RR [CI] Treatment Control Tahmasebi (DB RCT) 83% 0.17 [0.02-1.32] 1/40 6/40 Asadirad (RCT) 26% 0.74 [0.26-2.12] 5/27 6/24 Sankhe (SB RCT) 86% 0.14 [0.01-2.71] 0/60 3/60 CT​1 Tau​2 = 0.00, I​2 = 0.0%, p = 0.038 Late treatment 51% 0.49 [0.25-0.96] 10/147 23/144 51% improvement All studies 61% 0.39 [0.21-0.71] 12/304 38/301 61% improvement 6 curcumin COVID-19 mortality results c19curcumin.com May 2022 Tau​2 = 0.00, I​2 = 0.0%, p = 0.0021 1 CT: study uses combined treatment Favors curcumin 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+ Sankhe (RCT) 75% 0.25 [0.03-2.19] 1/87 4/87 CT​1 Improvement, RR [CI] Treatment Control Majeed (DB RCT) 66% 0.34 [0.01-8.09] 0/45 1/47 CT​1 Tau​2 = 0.00, I​2 = 0.0%, p = 0.16 Early treatment 72% 0.28 [0.05-1.65] 1/132 5/134 72% improvement Sankhe (SB RCT) 86% 0.14 [0.01-2.71] 0/60 3/60 CT​1 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.2 Late treatment 86% 0.14 [0.01-2.71] 0/60 3/60 86% improvement All studies 77% 0.23 [0.05-1.06] 1/192 8/194 77% improvement 3 curcumin COVID-19 mechanical ventilation results c19curcumin.com May 2022 Tau​2 = 0.00, I​2 = 0.0%, p = 0.06 1 CT: study uses combined treatment Favors curcumin Favors control
Figure 6. Random effects meta-analysis for ventilation.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Sankhe (SB RCT) 67% 0.33 [0.04-3.11] 1/60 3/60 CT​1 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.34 Late treatment 67% 0.33 [0.04-3.11] 1/60 3/60 67% improvement All studies 67% 0.33 [0.04-3.11] 1/60 3/60 67% improvement 1 curcumin COVID-19 ICU result c19curcumin.com May 2022 Tau​2 = 0.00, I​2 = 0.0%, p = 0.34 1 CT: study uses combined treatment Favors curcumin Favors control
Figure 7. Random effects meta-analysis for ICU admission.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Saber-Moghaddam 45% 0.55 [0.39-0.79] hosp. time 21 (n) 20 (n) Improvement, RR [CI] Treatment Control Ahmadi (DB RCT) 86% 0.14 [0.01-2.65] hosp. 0/30 3/30 Sankhe (RCT) 10% 0.90 [0.71-1.15] hosp. time 87 (n) 87 (n) CT​1 Majeed (DB RCT) 80% 0.20 [0.01-4.13] hosp. 0/45 2/47 CT​1 Tau​2 = 0.09, I​2 = 57.4%, p = 0.09 Early treatment 33% 0.67 [0.42-1.06] 0/183 5/184 33% improvement Kartika 41% 0.59 [0.35-1.00] hosp. time 139 (n) 107 (n) Improvement, RR [CI] Treatment Control Sankhe (SB RCT) 10% 0.90 [0.71-1.15] hosp. time 45 (n) 45 (n) CT​1 Hellou (DB RCT) 13% 0.87 [0.07-10.6] hosp. time 33 (n) 17 (n) CT​1 Tau​2 = 0.00, I​2 = 2.8%, p = 0.12 Late treatment 17% 0.83 [0.66-1.05] 0/217 0/169 17% improvement All studies 25% 0.75 [0.59-0.94] 0/400 5/353 25% improvement 7 curcumin COVID-19 hospitalization results c19curcumin.com May 2022 Tau​2 = 0.03, I​2 = 36.8%, p = 0.012 1 CT: study uses combined treatment Favors curcumin Favors control
Figure 8. Random effects meta-analysis for hospitalization.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Saber-Moghaddam 94% 0.06 [0.00-0.93] 0/21 8/20 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.044 Early treatment 94% 0.06 [0.00-0.93] 0/21 8/20 94% improvement Asadirad (RCT) 50% 0.50 [0.14-1.82] 3/30 6/30 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.3 Late treatment 50% 0.50 [0.14-1.82] 3/30 6/30 50% improvement All studies 76% 0.24 [0.03-1.80] 3/51 14/50 76% improvement 2 curcumin COVID-19 progression results c19curcumin.com May 2022 Tau​2 = 1.11, I​2 = 47.5%, p = 0.17 Favors curcumin Favors control
Figure 9. Random effects meta-analysis for progression.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Saber-Moghaddam 38% 0.62 [0.39-0.96] no recov. 11/21 17/20 Improvement, RR [CI] Treatment Control Ahmadi (DB RCT) 21% 0.79 [0.48-1.31] recov. time 30 (n) 30 (n) Sankhe (RCT) 46% 0.54 [0.35-0.76] no recov. 29/87 60/87 CT​1 Majeed (DB RCT) 43% 0.57 [0.39-0.84] no recov. 45 (n) 47 (n) CT​1 Khan (RCT) 33% 0.67 [0.37-1.19] no recov. 10/25 15/25 CT​1 Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Early treatment 40% 0.60 [0.50-0.73] 50/208 92/209 40% improvement Hassania.. (DB RCT) -46% 1.46 [0.01-329] SpO2 imp. 20 (n) 20 (n) Improvement, RR [CI] Treatment Control Asadirad (RCT) 45% 0.55 [0.27-1.09] no recov. 8/27 13/24 Sankhe (SB RCT) 32% 0.68 [0.54-0.86] recov. time 45 (n) 45 (n) CT​1 Hellou (DB RCT) 77% 0.23 [0.06-0.95] NEWS2 33 (n) 17 (n) CT​1 Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Late treatment 35% 0.65 [0.53-0.81] 8/125 13/106 35% improvement All studies 38% 0.62 [0.54-0.72] 58/333 105/315 38% improvement 9 curcumin COVID-19 recovery results c19curcumin.com May 2022 Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 1 CT: study uses combined treatment Favors curcumin Favors control
Figure 10. Random effects meta-analysis for recovery.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Majeed (DB RCT) 6% 0.94 [0.80-1.10] viral time 45 (n) 47 (n) CT​1 Improvement, RR [CI] Treatment Control Khan (RCT) 50% 0.50 [0.30-0.84] viral+ 10/25 20/25 CT​1 Tau​2 = 0.16, I​2 = 80.9%, p = 0.3 Early treatment 28% 0.72 [0.39-1.33] 10/70 20/72 28% improvement Hartono (RCT) 53% 0.47 [0.32-0.68] viral+ 14/30 30/30 CT​1 Improvement, RR [CI] Treatment Control Sankhe (SB RCT) 44% 0.56 [0.38-0.81] viral load 44 (n) 43 (n) CT​1 Hellou (DB RCT) 10% 0.90 [0.47-1.71] viral+ 14/33 8/17 CT​1 Tau​2 = 0.03, I​2 = 33.3%, p = 0.00045 Late treatment 43% 0.57 [0.42-0.78] 28/107 38/90 43% improvement All studies 35% 0.65 [0.45-0.93] 38/177 58/162 35% improvement 5 curcumin COVID-19 viral clearance results c19curcumin.com May 2022 Tau​2 = 0.12, I​2 = 78.4%, p = 0.017 1 CT: study uses combined treatment Favors curcumin Favors control
Figure 11. Random effects meta-analysis for viral clearance.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Dound (RCT) 33% 0.67 [0.54-0.82] 6 pt. scale 100 (n) 100 (n) CT​1 Improvement, RR [CI] Treatment Control Saber-Moghaddam 94% 0.06 [0.00-0.93] progression 0/21 8/20 Pawar (DB RCT) 82% 0.18 [0.04-0.79] death 2/70 11/70 Ahmadi (DB RCT) 86% 0.14 [0.01-2.65] hosp. 0/30 3/30 Sankhe (RCT) 89% 0.11 [0.01-2.03] death 0/87 4/87 CT​1 Majeed (DB RCT) 66% 0.34 [0.01-8.09] ventilation 0/45 1/47 CT​1 Khan (RCT) 33% 0.67 [0.37-1.19] no recov. 10/25 15/25 CT​1 Tau​2 = 0.09, I​2 = 28.7%, p = 0.0041 Early treatment 48% 0.52 [0.33-0.81] 12/378 42/379 48% improvement Valizadeh (DB RCT) 50% 0.50 [0.18-1.40] death 4/20 8/20 Improvement, RR [CI] Treatment Control Tahmasebi (DB RCT) 83% 0.17 [0.02-1.32] death 1/40 6/40 Hassania.. (DB RCT) -46% 1.46 [0.01-329] SpO2 imp. 20 (n) 20 (n) Asadirad (RCT) 26% 0.74 [0.26-2.12] death 5/27 6/24 Hartono (RCT) 53% 0.47 [0.32-0.68] viral+ 14/30 30/30 CT​1 Sankhe (SB RCT) 86% 0.14 [0.01-2.71] death 0/60 3/60 CT​1 Hellou (DB RCT) 77% 0.23 [0.06-0.95] NEWS2 33 (n) 17 (n) CT​1 Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Late treatment 54% 0.46 [0.33-0.63] 24/230 53/211 54% improvement Shehab 42% 0.58 [0.14-2.32] severe case 2/32 24/221 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.45 Prophylaxis 42% 0.58 [0.14-2.32] 2/32 24/221 42% improvement All studies 45% 0.55 [0.45-0.68] 38/640 119/811 45% improvement 15 curcumin COVID-19 peer reviewed trials c19curcumin.com May 2022 Tau​2 = 0.01, I​2 = 5.7%, p < 0.0001 Effect extraction pre-specified(most serious outcome, see appendix) 1 CT: study uses combined treatment Favors curcumin Favors control
Figure 12. 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 13 shows a forest plot for random effects meta-analysis of all studies after exclusions.
[Dound], potential randomization failure.
[Hartono], randomization resulted in significant baseline differences that were not adjusted for.
[Shehab], unadjusted results with no group details.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Saber-Moghaddam 94% 0.06 [0.00-0.93] progression 0/21 8/20 Improvement, RR [CI] Treatment Control Pawar (DB RCT) 82% 0.18 [0.04-0.79] death 2/70 11/70 Ahmadi (DB RCT) 86% 0.14 [0.01-2.65] hosp. 0/30 3/30 Sankhe (RCT) 89% 0.11 [0.01-2.03] death 0/87 4/87 CT​1 Majeed (DB RCT) 66% 0.34 [0.01-8.09] ventilation 0/45 1/47 CT​1 Khan (RCT) 33% 0.67 [0.37-1.19] no recov. 10/25 15/25 CT​1 Tau​2 = 0.30, I​2 = 26.7%, p = 0.0065 Early treatment 69% 0.31 [0.13-0.72] 12/278 42/279 69% improvement Valizadeh (DB RCT) 50% 0.50 [0.18-1.40] death 4/20 8/20 Improvement, RR [CI] Treatment Control Tahmasebi (DB RCT) 83% 0.17 [0.02-1.32] death 1/40 6/40 Hassania.. (DB RCT) -46% 1.46 [0.01-329] SpO2 imp. 20 (n) 20 (n) Asadirad (RCT) 26% 0.74 [0.26-2.12] death 5/27 6/24 Kartika 41% 0.59 [0.35-1.00] hosp. time 139 (n) 107 (n) Sankhe (SB RCT) 86% 0.14 [0.01-2.71] death 0/60 3/60 CT​1 Hellou (DB RCT) 77% 0.23 [0.06-0.95] NEWS2 33 (n) 17 (n) CT​1 Tau​2 = 0.00, I​2 = 0.0%, p = 0.0011 Late treatment 48% 0.52 [0.35-0.77] 10/339 23/288 48% improvement All studies 50% 0.50 [0.36-0.68] 22/617 65/567 50% improvement 13 curcumin COVID-19 studies after exclusions c19curcumin.com May 2022 Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Effect extraction pre-specified(most serious outcome, see appendix) 1 CT: study uses combined treatment Favors curcumin Favors control
Figure 13. 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 14 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 66% improvement, compared to 42% for other studies. Figure 15 and 16 show forest plots for a random effects meta-analysis of all Randomized Controlled Trials and RCT mortality results. Table 4 summarizes the results.
Figure 14. 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+ Dound (RCT) 33% 0.67 [0.54-0.82] 6 pt. scale 100 (n) 100 (n) CT​1 Improvement, RR [CI] Treatment Control Pawar (DB RCT) 82% 0.18 [0.04-0.79] death 2/70 11/70 Ahmadi (DB RCT) 86% 0.14 [0.01-2.65] hosp. 0/30 3/30 Sankhe (RCT) 89% 0.11 [0.01-2.03] death 0/87 4/87 CT​1 Majeed (DB RCT) 66% 0.34 [0.01-8.09] ventilation 0/45 1/47 CT​1 Khan (RCT) 33% 0.67 [0.37-1.19] no recov. 10/25 15/25 CT​1 Tau​2 = 0.02, I​2 = 9.9%, p = 0.0011 Early treatment 39% 0.61 [0.45-0.82] 12/357 34/359 39% improvement Valizadeh (DB RCT) 50% 0.50 [0.18-1.40] death 4/20 8/20 Improvement, RR [CI] Treatment Control Tahmasebi (DB RCT) 83% 0.17 [0.02-1.32] death 1/40 6/40 Hassania.. (DB RCT) -46% 1.46 [0.01-329] SpO2 imp. 20 (n) 20 (n) Asadirad (RCT) 26% 0.74 [0.26-2.12] death 5/27 6/24 Hartono (RCT) 53% 0.47 [0.32-0.68] viral+ 14/30 30/30 CT​1 Sankhe (SB RCT) 86% 0.14 [0.01-2.71] death 0/60 3/60 CT​1 Hellou (DB RCT) 77% 0.23 [0.06-0.95] NEWS2 33 (n) 17 (n) CT​1 Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Late treatment 54% 0.46 [0.33-0.63] 24/230 53/211 54% improvement All studies 42% 0.58 [0.49-0.69] 36/587 87/570 42% improvement 13 curcumin COVID-19 Randomized Controlled Trials c19curcumin.com May 2022 Tau​2 = 0.00, I​2 = 1.5%, p < 0.0001 Effect extraction pre-specified(most serious outcome, see appendix) 1 CT: study uses combined treatment Favors curcumin Favors control
Figure 15. Random effects meta-analysis for all Randomized Controlled Trials. 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+ Pawar (DB RCT) 82% 0.18 [0.04-0.79] 2/70