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Curcumin for COVID-19: real-time meta analysis of 26 studies

@CovidAnalysis, September 2023
https://c19early.org/tmeta.html
 
0 0.5 1 1.5+ All studies 42% 26 14,736 Improvement, Studies, Patients Relative Risk Mortality 63% 8 714 Ventilation 80% 4 435 ICU admission 78% 2 169 Hospitalization 27% 12 13,478 Progression 79% 3 143 Recovery 40% 16 1,097 Viral clearance 37% 6 389 RCTs 45% 20 1,562 RCT mortality 63% 8 714 Peer-reviewed 42% 25 14,490 Prophylaxis 36% 3 12,149 Early 30% 10 1,534 Late 51% 13 1,053 Curcumin for COVID-19 c19early.org Sep 2023 after exclusions Favorscurcumin Favorscontrol
Statistically significant lower risk is seen for mortality, ventilation, hospitalization, progression, recovery, and viral clearance. 18 studies from 16 independent teams in 8 countries show statistically significant improvements.
Meta analysis using the most serious outcome reported shows 42% [30‑52%] lower risk. Results are similar for Randomized Controlled Trials, higher quality studies, and peer-reviewed studies.
Results are robust — in exclusion sensitivity analysis 24 of 26 studies must be excluded to avoid finding statistically significant efficacy in pooled analysis.
Studies typically use advanced formulations for greatly improved bioavailability.
No treatment or intervention is 100% effective. All practical, effective, and safe means should be used based on risk/benefit analysis. Multiple treatments are typically used in combination, and other treatments may be more effective. The quality of non-prescription supplements can vary widely Crawford, Crighton.
All data to reproduce this paper and sources are in the appendix. Other meta analyses show significant improvements with curcumin for mortality Kow, Shafiee, Shojaei, Vahedian-Azimi, hospitalization Shojaei, Vahedian-Azimi, recovery Shafiee, and symptoms Vahedian-Azimi.
Evolution of COVID-19 clinical evidence Curcumin p=0.000000046 Acetaminophen p=0.0000018 2020 2021 2022 2023 Effective Harmful c19early.org September 2023 meta analysis results (pooled effects) 100% 50% 0% -50%
Highlights
Curcumin reduces risk for COVID-19 with very high confidence for mortality, hospitalization, recovery, and in pooled analysis, high confidence for ventilation, progression, and viral clearance, and low confidence for ICU admission. 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 56 treatments.
A
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 Aldwihi 31% 0.69 [0.43-1.04] hosp. 30/144 207/594 Pawar (DB RCT) 82% 0.18 [0.04-0.79] death 2/70 11/70 OT​1 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​2 Majeed (DB RCT) 66% 0.34 [0.01-8.09] ventilation 0/45 1/47 CT​2 Khan (RCT) 33% 0.67 [0.37-1.19] no recov. 10/25 15/25 CT​2 Askari (DB RCT) -125% 2.25 [0.30-16.6] no recov. 3/8 1/6 Chitre (DB RCT) 11% 0.89 [0.79-0.99] recov. time 89 (n) 86 (n) CT​2 Din Ujjan (RCT) 29% 0.71 [0.50-1.03] no recov. 15/25 21/25 CT​2 Tau​2 = 0.05, I​2 = 43.3%, p = 0.0083 Early treatment 30% 0.70 [0.54-0.91] 60/544 271/990 30% lower risk 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​2 Phyto-V Thomas (DB RCT) 44% 0.56 [0.34-0.91] improv. 74 (n) 73 (n) LONG COVID CT​2 Sankhe (SB RCT) 86% 0.14 [0.01-2.71] death 0/60 3/60 CT​2 Hellou (DB RCT) 77% 0.23 [0.06-0.95] NEWS2 33 (n) 17 (n) CT​2 Abbaspour-A.. (RCT) 71% 0.29 [0.06-1.26] death 2/30 7/30 Sadeghiz.. (DB RCT) 92% 0.08 [0.01-0.68] progression 0/21 6/21 Gérain (RCT) 67% 0.33 [0.01-7.70] death 0/25 1/24 CT​2 Ahmadi (DB RCT) 58% 0.42 [0.17-1.01] oxygen 5/29 16/39 Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Late treatment 51% 0.49 [0.39-0.61] 31/548 83/505 51% lower risk Bejan 59% 0.41 [0.17-1.00] hosp. 148 (n) 9,600 (n) Improvement, RR [CI] Treatment Control Shehab 42% 0.58 [0.14-2.32] severe case 2/32 24/221 Nimer 31% 0.69 [0.45-1.04] hosp. 29/329 179/1,819 Tau​2 = 0.00, I​2 = 0.0%, p = 0.008 Prophylaxis 36% 0.64 [0.45-0.89] 31/509 203/11,640 36% lower risk All studies 42% 0.58 [0.48-0.70] 122/1,601 557/13,135 42% lower risk 26 curcumin COVID-19 studies c19early.org Sep 2023 Tau​2 = 0.06, I​2 = 42.3%, p < 0.0001 Effect extraction pre-specified(most serious outcome, see appendix) 1 OT: comparison with other treatment2 CT: study uses combined treatment Favors curcumin Favors control
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Saber-Moghaddam 94% progression Improvement Relative Risk [CI] Aldwihi 31% hospitalization Pawar (DB RCT) 82% death OT​1 Ahmadi (DB RCT) 86% hospitalization Sankhe (RCT) 89% death CT​2 Majeed (DB RCT) 66% ventilation CT​2 Khan (RCT) 33% recovery CT​2 Askari (DB RCT) -125% recovery Chitre (DB RCT) 11% recovery CT​2 Din Ujjan (RCT) 29% recovery CT​2 Tau​2 = 0.05, I​2 = 43.3%, p = 0.0083 Early treatment 30% 30% lower risk Valizadeh (DB RCT) 50% death Tahmas.. (DB RCT) 83% death Hassani.. (DB RCT) -46% SpO2 imp. Asadirad (RCT) 26% death Kartika 41% hospitalization Hartono (RCT) 53% viral- CT​2 Phyto-V Thomas (DB RCT) 44% improv. LONG COVID CT​2 Sankhe (SB RCT) 86% death CT​2 Hellou (DB RCT) 77% NEWS2 CT​2 Abbaspour-.. (RCT) 71% death Sadeghi.. (DB RCT) 92% progression Gérain (RCT) 67% death CT​2 Ahmadi (DB RCT) 58% oxygen therapy Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Late treatment 51% 51% lower risk Bejan 59% hospitalization Shehab 42% severe case Nimer 31% hospitalization Tau​2 = 0.00, I​2 = 0.0%, p = 0.008 Prophylaxis 36% 36% lower risk All studies 42% 42% lower risk 26 curcumin C19 studies c19early.org Sep 2023 Tau​2 = 0.06, I​2 = 42.3%, p < 0.0001 Effect extraction pre-specifiedRotate device for footnotes/details Favors curcumin Favors control
B
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D
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Figure 1. A. Random effects meta-analysis. This plot shows pooled effects, see the specific outcome analyses for individual outcomes, and the heterogeneity section for discussion. Effect extraction is pre-specified, using the most serious outcome reported. For details of effect extraction see the appendix. B. Scatter plot showing the most serious outcome in all studies, and for studies within each stage. Diamonds shows the results of random effects meta-analysis. C. Results within the context of multiple COVID-19 treatments. 0.7% of 5,019 proposed treatments show efficacy c19early.org. D. Timeline of results in curcumin studies. The marked dates indicate the time when efficacy was known with a statistically significant improvement of ≥10% from ≥3 studies for pooled outcomes, one or more specific outcome, pooled outcomes in RCTs, and one or more specific outcome in RCTs. Efficacy based on RCTs only was delayed by 2.9 months, compared to using all studies. Efficacy based on specific outcomes was delayed by 2.4 months, compared to using pooled outcomes.
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, studies within each treatment stage, individual outcomes, peer-reviewed studies, 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.
Table 1 shows potential mechanisms of action for the treatment of COVID-19 using curcumin.
Table 1. Curcumin mechanisms of action. Submit updates.
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.
9 In Silico studies support the efficacy of curcumin Kandeil, Nag, Rampogu, Sekiou, Singh, Srivastava, Suravajhala, Thapa, Winih Kinasih.
9 In Vitro studies support the efficacy of curcumin Bahun, Bormann, Goc, Goc (B), Guijarro-Real, Kandeil, Leka, Teshima, Wu.
Panda investigate 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.
Table 2 summarizes the results for all stages combined, with different exclusions, and for specific outcomes. Table 3 shows results by treatment stage. Figure 3, 4, 5, 6, 7, 8, 9, 10, and 11 show forest plots for random effects meta-analysis of all studies with pooled effects, mortality results, ventilation, ICU admission, hospitalization, progression, recovery, viral clearance, and peer reviewed studies.
Table 2. Random effects meta-analysis for all stages combined, with different exclusions, and for specific outcomes. Results show the percentage improvement with treatment and the 95% confidence interval. * p<0.05  ** p<0.01  *** p<0.001  **** p<0.0001.
Improvement Studies Patients Authors
All studies42% [30‑52%]
****
26 14,736 225
After exclusions40% [27‑50%]
****
24 14,423 205
Peer-reviewed studiesPeer-reviewed42% [29‑53%]
****
25 14,490 219
Randomized Controlled TrialsRCTs45% [29‑58%]
****
20 1,562 185
Mortality63% [36‑78%]
***
8 714 83
VentilationVent.80% [25‑95%]
*
4 435 30
ICU admissionICU78% [-27‑96%]2 169 18
HospitalizationHosp.27% [18‑35%]
****
12 13,478 92
Recovery40% [27‑51%]
****
16 1,097 140
Viral37% [10‑56%]
*
6 389 46
RCT mortality63% [36‑78%]
***
8 714 83
RCT hospitalizationRCT hosp.20% [9‑29%]
***
7 557 59
Table 3. Random effects meta-analysis results by treatment stage. Results show the percentage improvement with treatment, the 95% confidence interval, and the number of studies for the stage.treatment and the 95% confidence interval. * p<0.05  ** p<0.01  *** p<0.001  **** p<0.0001.
Early treatment Late treatment Prophylaxis
All studies30% [9‑46%]
**
51% [39‑61%]
****
36% [11‑55%]
**
After exclusions30% [9‑46%]
**
50% [34‑63%]
****
37% [6‑58%]
*
Peer-reviewed studiesPeer-reviewed30% [9‑46%]
**
54% [40‑64%]
****
36% [11‑55%]
**
Randomized Controlled TrialsRCTs27% [2‑46%]
*
54% [40‑64%]
****
Mortality84% [39‑96%]
**
56% [19‑76%]
**
VentilationVent.72% [-65‑95%]88% [3‑98%]
*
ICU admissionICU78% [-27‑96%]
HospitalizationHosp.30% [7‑48%]
*
24% [12‑34%]
***
37% [6‑58%]
*
Recovery30% [15‑43%]
***
58% [37‑72%]
****
Viral36% [-26‑67%]43% [22‑58%]
***
RCT mortality84% [39‑96%]
**
56% [19‑76%]
**
RCT hospitalizationRCT hosp.32% [-69‑73%]22% [10‑33%]
***
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Figure 3. Random effects meta-analysis for all studies with pooled effects. This plot shows pooled effects, see the specific outcome analyses for individual outcomes, and the heterogeneity section for discussion. Effect extraction is pre-specified, using the most serious outcome reported. For details of effect extraction see the appendix.
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Figure 4. Random effects meta-analysis for mortality results.
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Figure 5. Random effects meta-analysis for ventilation.
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Figure 6. Random effects meta-analysis for ICU admission.
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Figure 7. Random effects meta-analysis for hospitalization.
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Figure 8. Random effects meta-analysis for progression.
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Figure 9. Random effects meta-analysis for recovery.
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Figure 10. Random effects meta-analysis for viral clearance.
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Figure 11. Random effects meta-analysis for peer reviewed studies. Zeraatkar analyze 356 COVID-19 trials, finding no significant evidence that preprint results are inconsistent with peer-reviewed studies. They also show extremely long peer-review delays, with a median of 6 months to journal publication. A six month delay was equivalent to around 1.5 million deaths during the first two years of the 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.
Figure 12 shows a comparison of results for RCTs and non-RCT studies. The median effect size for RCTs is 62% improvement, compared to 42% for other studies. Figure 13, 14, and 15 show forest plots for random effects meta-analysis of all Randomized Controlled Trials, RCT mortality results, and RCT hospitalization results. RCT results are included in Table 2 and Table 3.
Bias in clinical research may be defined as something that tends to make conclusions differ systematically from the truth. RCTs help to make study groups more similar and can provide a higher level of evidence, however they are subject to many biases Jadad, and analysis of double-blind RCTs has identified extreme levels of bias Gøtzsche. For COVID-19, the overhead may delay treatment, dramatically compromising efficacy; they may encourage monotherapy for simplicity at the cost of efficacy which may rely on combined or synergistic effects; the participants that sign up may not reflect real world usage or the population that benefits most in terms of age, comorbidities, severity of illness, or other factors; standard of care may be compromised and unable to evolve quickly based on emerging research for new diseases; errors may be made in randomization and medication delivery; and investigators may have hidden agendas or vested interests influencing design, operation, analysis, and the potential for fraud. All of these biases have been observed with COVID-19 RCTs. There is no guarantee that a specific RCT provides a higher level of evidence.
High quality RCTs for novel acute diseases are more challenging, with increased ethical issues due to the urgency of treatment, increased risk due to enrollment delays, and more difficult design with a rapidly evolving evidence base. For COVID-19, the most common site of initial infection is the upper respiratory tract. Immediate treatment is likely to be most successful and may prevent or slow progression to other parts of the body. For a non-prophylaxis RCT, it makes sense to provide treatment in advance and instruct patients to use it immediately on symptoms, just as some governments have done by providing medication kits in advance. Unfortunately, no RCTs have been done in this way. Every treatment RCT to date involves delayed treatment. Among the 56 treatments we have analyzed, 64% of RCTs involve very late treatment 5+ days after onset. No non-prophylaxis COVID-19 RCTs match the potential real-world use of early treatments (they may more accurately represent results for treatments that require visiting a medical facility, e.g., those requiring intravenous administration).
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.
Currently, 38 of the treatments we analyze show statistically significant efficacy or harm, defined as ≥10% decreased risk or >0% increased risk from ≥3 studies. Of the 38 treatments with statistically significant efficacy/harm, 24 have been confirmed in RCTs, with a mean delay of 5.7 months. For the 14 unconfirmed treatments, 4 have zero RCTs to date. The point estimates for the remaining 10 are all consistent with the overall results (benefit or harm), with 8 showing >20%. The only treatments showing >10% efficacy for all studies, but <10% for RCTs are sotrovimab and aspirin.
We need to evaluate each trial on its own merits. RCTs for a given medication and disease may be more reliable, however they may also be less reliable. For off-patent medications, very high conflict of interest trials may be more likely to be RCTs, and more likely to be large trials that dominate meta analyses.
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Figure 12. Results for RCTs and non-RCT studies.
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Figure 13. Random effects meta-analysis for all Randomized Controlled Trials. This plot shows pooled effects, see the specific outcome analyses for individual outcomes, and the heterogeneity section for discussion. Effect extraction is pre-specified, using the most serious outcome reported. For details of effect extraction see the appendix.
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Figure 14. Random effects meta-analysis for RCT mortality results.
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Figure 15. Random effects meta-analysis for RCT hospitalization results.
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 16 shows a forest plot for random effects meta-analysis of all studies after exclusions.
Hartono, randomization resulted in significant baseline differences that were not adjusted for.
Shehab, unadjusted results with no group details.
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Figure 16. Random effects meta-analysis for all studies after exclusions. This plot shows pooled effects, see the specific outcome analyses for individual outcomes, and the heterogeneity section for discussion. Effect extraction is pre-specified, using the most serious outcome reported. For details of effect extraction see the appendix.
Heterogeneity in COVID-19 studies arises from many factors including:
The time between infection or the onset of symptoms and treatment may critically affect how well a treatment works. For example an antiviral may be very effective when used early but may not be effective in late stage disease, and may even be harmful. Oseltamivir, for example, is generally only considered effective for influenza when used within 0-36 or 0-48 hours McLean, Treanor. Baloxavir studies for influenza also show that treatment delay is critical — Ikematsu report an 86% reduction in cases for post-exposure prophylaxis, Hayden show a 33 hour reduction in the time to alleviation of symptoms for treatment within 24 hours and a reduction of 13 hours for treatment within 24-48 hours, and Kumar report only 2.5 hours improvement for inpatient treatment.
Table 4. Studies of baloxavir for influenza show that early treatment is more effective.
Treatment delayResult
Post exposure prophylaxis86% fewer cases Ikematsu
<24 hours-33 hours symptoms Hayden
24-48 hours-13 hours symptoms Hayden
Inpatients-2.5 hours to improvement Kumar
Figure 17 shows a mixed-effects meta-regression for efficacy as a function of treatment delay in COVID-19 studies from 56 treatments, showing that efficacy declines rapidly with treatment delay. Early treatment is critical for COVID-19.
Figure 17. Early treatment is more effective. Meta-regression showing efficacy as a function of treatment delay in COVID-19 studies from 56 treatments.
Details of the patient population including age and comorbidities may critically affect how well a treatment works. For example, many COVID-19 studies with relatively young low-comorbidity 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).
Efficacy may differ significantly depending on the effect measured, for example a treatment 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.
There are many different variants of SARS-CoV-2 and efficacy may depend critically on the distribution of variants encountered by the patients in a study. For example, the Gamma variant shows significantly different characteristics Faria, Karita, Nonaka, Zavascki. Different mechanisms of action may be more or less effective depending on variants, for example the viral entry process for the omicron variant has moved towards TMPRSS2-independent fusion, suggesting that TMPRSS2 inhibitors may be less effective Peacock, Willett.
Effectiveness may depend strongly on the dosage and treatment regimen.
The use of other treatments may significantly affect outcomes, including anything from supplements, other medications, or other kinds of treatment such as prone positioning.
The quality of medications may vary significantly between manufacturers and production batches, which may significantly affect efficacy and safety. Williams analyze ivermectin from 11 different sources, showing highly variable antiparasitic efficacy across different manufacturers. Xu analyze a treatment from two different manufacturers, showing 9 different impurities, with significantly different concentrations for each manufacturer. Non-prescription supplements may show very wide variations in quality Crawford, Crighton.
We present both pooled analyses and specific outcome analyses. Notably, pooled analysis often results in earlier detection of efficacy as shown in Figure 18. For many COVID-19 treatments, a reduction in mortality logically follows from a reduction in hospitalization, which follows from a reduction in symptomatic cases, etc. An antiviral tested with a low-risk population may report zero mortality in both arms, however a reduction in severity and improved viral clearance may translate into lower mortality among a high-risk population, and including these results in pooled analysis allows faster detection of efficacy. Trials with high-risk patients may also be restricted due to ethical concerns for treatments that are known or expected to be effective.
Pooled analysis enables using more of the available information. While there is much more information available, for example dose-response relationships, the advantage of the method used here is simplicity and transparency. Note that pooled analysis could hide efficacy, for example a treatment that is beneficial for late stage patients but has no effect on viral replication or early stage disease could show no efficacy in pooled analysis if most studies only examine viral clearance. While we present pooled results, we also present individual outcome analyses, which may be more informative for specific use cases.
Currently, 38 of the treatments we analyze show statistically significant efficacy or harm, defined as ≥10% decreased risk or >0% increased risk from ≥3 studies. 91% of treatments showing statistically significant efficacy/harm with pooled effects have been confirmed with one or more specific outcomes, with a mean delay of 3.3 months. When restricting to RCTs only, 57% of treatments showing statistically significant efficacy/harm with pooled effects have been confirmed with one or more specific outcomes, with a mean delay of 3.9 months.
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Figure 18. The time when studies showed that treatments were effective, defined as statistically significant improvement of ≥10% from ≥3 studies. Pooled results typically show efficacy earlier than specific outcome results. Results from all studies often shows efficacy much earlier than when restricting to RCTs. Results reflect conditions as used in trials to date, these depend on the population treated, treatment delay, and treatment regimen.
The distribution of studies will alter the outcome of a meta analysis. Consider a simplified 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 early treatment is very effective. This may have a greater effect than pooling different outcomes such as mortality and hospitalization. For example a treatment may have 50% efficacy for mortality but only 40% for hospitalization when used within 48 hours. However efficacy could be 0% when used late.
All meta analyses combine heterogeneous studies, varying in population, variants, and potentially all factors above, and therefore may obscure efficacy by including studies where treatment is less effective. Generally, we expect the estimated effect size from meta analysis to be less than that for the optimal case. Looking at all studies is valuable for providing an overview of all research, important to avoid cherry-picking, and informative when a positive result is found despite combining less-optimal situations. However, the resulting estimate does not apply to specific cases such as early treatment in high-risk populations. While we present results for all studies, we also present treatment time and individual outcome analyses, which may be more informative for specific use cases.
Publishing is often biased towards positive results, however evidence suggests that there may be a negative bias for inexpensive treatments for COVID-19. Both negative and positive results are very important for COVID-19, media in many countries prioritizes negative results for inexpensive treatments (inverting the typical incentive for scientists that value media recognition), and there are many reports of difficulty publishing positive results Boulware, Meeus, Meneguesso. For curcumin, there is currently not enough data to evaluate publication bias with high confidence.
One method to evaluate bias is to compare prospective vs. retrospective studies. Prospective studies are more likely to be published regardless of the result, while retrospective studies are more likely to exhibit bias. For example, researchers may perform preliminary analysis with minimal effort and the results may influence their decision to continue. Retrospective studies also provide more opportunities for the specifics of data extraction and adjustments to influence results.
Figure 19 shows a scatter plot of results for prospective and retrospective studies. 40% of retrospective studies report a statistically significant positive effect for one or more outcomes, compared to 76% of prospective studies, consistent with a bias toward publishing negative results. The median effect size for retrospective studies is 41% improvement, compared to 66% for prospective studies, suggesting a potential bias towards publishing results showing lower efficacy.
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Figure 19. Prospective vs. retrospective studies. The diamonds show the results of random effects meta-analysis.
Funnel plots have traditionally been used for analyzing publication bias. This is invalid for COVID-19 acute treatment trials — the underlying assumptions are invalid, which we can demonstrate with a simple example. Consider a set of hypothetical perfect trials with no bias. Figure 20 plot A shows a funnel plot for a simulation of 80 perfect trials, with random group sizes, and each patient's outcome randomly sampled (10% control event probability, and a 30% effect size for treatment). Analysis shows no asymmetry (p > 0.05). In plot B, we add a single typical variation in COVID-19 treatment trials — treatment delay. Consider that efficacy varies from 90% for treatment within 24 hours, reducing to 10% when treatment is delayed 3 days. In plot B, each trial's treatment delay is randomly selected. Analysis now shows highly significant asymmetry, p < 0.0001, with six variants of Egger's test all showing p < 0.05 Egger, Harbord, Macaskill, Moreno, Peters, Rothstein, Rücker, Stanley. Note that these tests fail even though treatment delay is uniformly distributed. In reality treatment delay is more complex — each trial has a different distribution of delays across patients, and the distribution across trials may be biased (e.g., late treatment trials may be more common). Similarly, many other variations in trials may produce asymmetry, including dose, administration, duration of treatment, differences in SOC, comorbidities, age, variants, and bias in design, implementation, analysis, and reporting.
Figure 20. Example funnel plot analysis for simulated perfect trials.
Pharmaceutical drug trials often have conflicts of interest whereby sponsors or trial staff have a financial interest in the outcome being positive. Curcumin for COVID-19 lacks this because it is an inexpensive and widely available supplement. In contrast, most COVID-19 curcumin trials have been run by physicians on the front lines with the primary goal of finding the best methods to save human lives and minimize the collateral damage caused by COVID-19. While pharmaceutical companies are careful to run trials under optimal conditions (for example, restricting patients to those most likely to benefit, only including patients that can be treated soon after onset when necessary, and ensuring accurate dosing), not all curcumin trials represent the optimal conditions for efficacy.
Summary statistics from meta analysis necessarily lose information. As with all meta analyses, studies are heterogeneous, with differences in treatment delay, treatment regimen, patient demographics, variants, conflicts of interest, standard of care, and other factors. We provide analyses by specific outcomes and by treatment delay, and we aim to identify key characteristics in the forest plots and summaries. Results should be viewed in the context of study characteristics.
Some analyses classify treatment based on early or late administration, as done here, while others distinguish between mild, moderate, and severe cases. Viral load does not indicate degree of symptoms — for example patients may have a high viral load while being asymptomatic. With regard to treatments that have antiviral properties, timing of treatment is critical — late administration may be less helpful regardless of severity.
Details of treatment delay per patient is often not available. For example, a study may treat 90% of patients relatively early, but the events driving the outcome may come from 10% of patients treated very late. Our 5 day cutoff for early treatment may be too conservative, 5 days may be too late in many cases.
Comparison across treatments is confounded by differences in the studies performed, for example dose, variants, and conflicts of interest. Trials affiliated with special interests may use designs better suited to the preferred outcome.
In some cases, the most serious outcome has very few events, resulting in lower confidence results being used in pooled analysis, however the method is simpler and more transparent. This is less critical as the number of studies increases. Restriction to outcomes with sufficient power may be beneficial in pooled analysis and improve accuracy when there are few studies, however we maintain our pre-specified method to avoid any retrospective changes.
Studies show that combinations of treatments can be highly synergistic and may result in many times greater efficacy than individual treatments alone Alsaidi, Andreani, Biancatelli, De Forni, Gasmi, Jeffreys, Jitobaom, Jitobaom (B), Ostrov, Thairu. Therefore standard of care may be critical and benefits may diminish or disappear if standard of care does not include certain treatments.
This real-time analysis is constantly updated based on submissions. Accuracy benefits from widespread review and submission of updates and corrections from reviewers. Less popular treatments may receive fewer reviews.
No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. Efficacy may vary significantly with different variants and within different populations. All treatments have potential side effects. Propensity to experience side effects may be predicted in advance by qualified physicians. We do not provide medical advice. Before taking any medication, consult a qualified physician who can compare all options, provide personalized advice, and provide details of risks and benefits based on individual medical history and situations.
1 of the 26 studies compare against other treatments, which may reduce the effect seen. 10 of 26 studies combine treatments. The results of curcumin alone may differ. 10 of 20 RCTs use combined treatment. Other meta analyses show significant improvements with curcumin for mortality Kow, Shafiee, Shojaei, Vahedian-Azimi, hospitalization Shojaei, Vahedian-Azimi, recovery Shafiee, and symptoms Vahedian-Azimi.
Curcumin is an effective treatment for COVID-19. Statistically significant lower risk is seen for mortality, ventilation, hospitalization, progression, recovery, and viral clearance. 18 studies from 16 independent teams in 8 countries show statistically significant improvements. Meta analysis using the most serious outcome reported shows 42% [30‑52%] lower risk. Results are similar for Randomized Controlled Trials, higher quality studies, and peer-reviewed studies. Results are robust — in exclusion sensitivity analysis 24 of 26 studies must be excluded to avoid finding statistically significant efficacy in pooled analysis.
Studies typically use advanced formulations for greatly improved bioavailability.
Other meta analyses show significant improvements with curcumin for mortality Kow, Shafiee, Shojaei, Vahedian-Azimi, hospitalization Shojaei, Vahedian-Azimi, recovery Shafiee, and symptoms Vahedian-Azimi.
0 0.5 1 1.5 2+ Mortality 71% Improvement Relative Risk Recovery, dyspnea 86% Recovery, fever >39.0 90% Recovery, bilateral chest.. 38% Recovery, cough 59% Recovery, headache 82% Curcumin  Abbaspour-Aghdam et al.  LATE TREATMENT  RCT Is late treatment with curcumin beneficial for COVID-19? RCT 60 patients in Iran Improved recovery with curcumin (p=0.037) c19early.org Abbaspour-Aghdam et al., European J. P.., Sep 2022 Favors curcumin Favors control
Abbaspour-Aghdam: RCT with 30 nanocurcumin and 30 control patients in Iran, showing lower mortality and improved recovery, without statistical significance, and improved NK cell function. 160mg nanocurcumin for 21 days.
0 0.5 1 1.5 2+ Hospitalization 86% Improvement Relative Risk Recovery time 21% Curcumin  Ahmadi et al.  EARLY TREATMENT  DB RCT Is early treatment with curcumin beneficial for COVID-19? Double-blind RCT 60 patients in Iran (April - July 2020) Lower hospitalization (p=0.24) and faster recovery (p=0.37), not sig. c19early.org Ahmadi et al., Food Science and Nutrit.., Jun 2021 Favors curcumin Favors control
Ahmadi: RCT 60 outpatients in Iran, 30 treated with nano-curcumin showing lower hospitalization and faster recovery with treatment.
0 0.5 1 1.5 2+ Oxygen therapy 58% Improvement Relative Risk Improvement in SpO2 67% Recovery, chest pain 50% Recovery, chills -34% Recovery, cough 58% Recovery, sore throat 78% Recovery, fatigue 64% Recovery, myalgia 91% Recovery, anosmia -9% Recovery, ageusia 10% Recovery, anorexia 10% Recovery, diarrhea 64% Recovery, nausea -234% Curcumin  Ahmadi et al.  LATE TREATMENT  DB RCT Is late treatment with curcumin beneficial for COVID-19? Double-blind RCT 76 patients in Iran (December 2021 - March 2022) Improved recovery with curcumin (p=0.041) c19early.org Ahmadi et al., Int. J. Clinical Practice, Jul 2023 Favors curcumin Favors control
Ahmadi (B): RCT 76 hospitalized patients, showing improved recovery with nanocurcumin. Authors note that pure curcumin is limited due to rapid metabolism, low bio-availability, weak aqueous solubility, and systemic deletion, and that the nanocurcumin formulation used improves curcumin’s solubility, stability, half-life, and bioavailability. The dropout rate was higher in the curcumin group, in part due to discontinuation for side effects. Authors do not provide detailed discharge criteria.
0 0.5 1 1.5 2+ Hospitalization 31% Improvement Relative Risk Curcumin for COVID-19  Aldwihi et al.  EARLY TREATMENT Is early treatment with curcumin beneficial for COVID-19? Retrospective 738 patients in Saudi Arabia (August - October 2020) Lower hospitalization with curcumin (not stat. sig., p=0.096) c19early.org Aldwihi et al., Int. J. Environmental .., May 2021 Favors curcumin Favors control
Aldwihi: Retrospective survey-based analysis of 738 COVID-19 patients in Saudi Arabia, showing lower hospitalization with vitamin C, turmeric, zinc, and nigella sativa, and higher hospitalization with vitamin D. For vitamin D, most patients continued prophylactic use. For vitamin C, the majority of patients continued prophylactic use. For nigella sativa, the majority of patients started use during infection. Authors do not specify the fraction of prophylactic use for turmeric and zinc.
0 0.5 1 1.5 2+ Mortality 26% Improvement Relative Risk Progression 50% Unresolved fever 45% Unresolved dyspnea 29% Unresolved cough 41% O2 <92% 37% O2 <97% 20% Curcumin  Asadirad et al.  LATE TREATMENT  RCT Is late treatment with curcumin beneficial for COVID-19? RCT 60 patients in Iran (June - July 2020) Lower progression (p=0.47) and improved recovery (p=0.094), not sig. c19early.org Asadirad et al., Phytotherapy Research, Jan 2022 Favors curcumin Favors control
Asadirad: RCT 60 hospitalized patients in Iran, 30 treated with nano-curcumin, showing significant improvements in inflammatory cytokines, and improvements in clinical outcomes without statistical significance. 240 mg/day nano-curcumin for 7 days.
0 0.5 1 1.5 2+ Recovery, dyspnea -125% Improvement Relative Risk Recovery, ague -433% Recovery, weakness 73% Recovery, muscular pain 40% Recovery, headache 38% Recovery, sore throat -71% Recovery, sputum cough 12% Recovery, dry cough 0% Curcumin  Askari et al.  EARLY TREATMENT  DB RCT Is early treatment with curcumin beneficial for COVID-19? Double-blind RCT 26 patients in Iran (November 2020 - April 2021) Worse recovery with curcumin (not stat. sig., p=0.58) c19early.org Askari et al., Trials, June 2022 Favors curcumin Favors control
Askari: Small RCT 46 outpatients in Iran, 23 treated with curcimin-piperine, showing no significant differences in recovery. 1000mg curcumin and 10mg piperine/day for 14 days.
0 0.5 1 1.5 2+ Hospitalization 59% Improvement Relative Risk Curcumin for COVID-19  Bejan et al.  Prophylaxis Is prophylaxis with curcumin beneficial for COVID-19? Retrospective 9,748 patients in the USA No significant difference in hospitalization c19early.org Bejan et al., Clinical Pharmacology &a.., Feb 2021 Favors curcumin Favors control
Bejan: Retrospective 9,748 COVID-19 patients in the USA showing lower hospitalization with turmeric extract.
0 0.5 1 1.5 2+ Recovery time 11% Improvement Relative Risk Fever 11% Congestion 20% Sore throat 20% Cough 14% Dyspnea 15% Pain 8% Fatigue 17% Headache 17% Chills 18% Diarrhea 25% Vomiting 18% Smell 17% Taste 17% Curcumin  Chitre et al.  EARLY TREATMENT  DB RCT Is early treatment with curcumin + combined treatments beneficial for COVID-19? Double-blind RCT 175 patients in India (September 2020 - April 2021) Faster recovery with curcumin + combined treatments (p=0.036) c19early.org Chitre et al., Phytotherapy Research, Nov 2022 Favors curcumin Favors control
Chitre: RCT 208 moderate COVID-19 patients in India, 103 treated with a combination of turmeric, ashwagandha, boswellia, and ginger, showing improved recovery with treatment. The dose of curcumin is unknown and bioavailability may be poor.
0 0.5 1 1.5 2+ Recovery 29% Improvement Relative Risk Recovery (b) 71% Recovery (c) 77% Recovery (d) 86% Viral clearance, day 14 91% Viral clearance, day 7 74% Curcumin  Din Ujjan et al.  EARLY TREATMENT  RCT Is early treatment with curcumin + quercetin and vitamin D beneficial for COVID-19? RCT 50 patients in Pakistan (September 2021 - January 2022) Improved recovery with curcumin + quercetin and vitamin D (not stat. sig., p=0.11) c19early.org Din Ujjan et al., Frontiers in Nutrition, Jan 2023 Favors curcumin Favors control
Din Ujjan: Small RCT with 50 outpatients, 25 treated with curcumin, quercetin, and vitamin D, showing improved recovery and viral clearance with treatment. 168mg curcumin, 260mg, 360IU vitamin D3 daily for 14 days.
0 0.5 1 1.5 2+ Mortality 67% Improvement Relative Risk Death/ICU 91% Ventilation 89% ICU admission 89% Discharge, day 14 73% Discharge, day 7 59% Hospitalization time 38% WHO score 50% Curcumin  Gérain et al.  LATE TREATMENT  RCT Is late treatment with curcumin + quercetin beneficial for COVID-19? RCT 49 patients in Belgium (April - October 2021) Lower death/ICU (p=0.022) and improved recovery (p=0.04) c19early.org Gérain et al., Frontiers in Nutrition, Jun 2023 Favors curcumin Favors control
Gérain: RCT 49 hospitalized COVID-19 patients, 25 treated with curcumin and quercetin, shower lower mortality/ICU admission and improved recovery with treatment. All patients received vitamin D.

336mg curcumin, 520mg quercetin, and 18μg vitamin D3 daily for 14 days. The control arm received 20μg vitamin D3 daily. Baseline fever favored treatment while vaccination favored control.
0 0.5 1 1.5 2+ Viral clearance, day 10 53% Improvement Relative Risk Viral clearance, day 14 75% Viral clearance, day 21 67% Curcumin  Hartono et al.  LATE TREATMENT  RCT Is late treatment with curcumin + virgin coconut oil beneficial for COVID-19? RCT 60 patients in Indonesia (May - September 2020) Improved viral clearance with curcumin + virgin coconut oil (p=0.0000019) c19early.org Hartono et al., Pharmacognosy J., February 2022 Favors curcumin Favors control
Hartono: RCT with 30 patients treated with curcumin and virgin coconut oil (VCO), and 30 SOC patients in Indonesia, showing faster viral clearance with treatment. Treatment also reduced IL-1β, IL-2, IL-6, IL-18, and IFN-β levels. VCO improves the bioavailability of curcumin. There were large unadjusted differences in baseline severity and age, for example 20% vs. 47% of patients >50. VCO 30ml and curcumin 1g tid for 21 days. 066/UN27.06.6.1/KEPK/EC/2020.
0 0.5 1 1.5 2+ Improvement in SpO2 -46% Improvement Relative Risk Curcumin  Hassaniazad et al.  LATE TREATMENT  DB RCT Is late treatment with curcumin beneficial for COVID-19? Double-blind RCT 40 patients in Iran No significant difference in recovery c19early.org Hassaniazad et al., Phytotherapy Resea.., Sep 2021 Favors curcumin Favors control
Hassaniazad: Small RCT with 40 low risk patients in Iran, 20 treated with nano-curcumin, showing no significant difference in outcomes with treatment. Authors note that treatment can improve peripheral blood inflammatory indices and modulate immune response by decreasing Th1 and Th17 responses, increasing T regulatory responses, further reducing IL-17 and IFN-γ, and increasing suppressive cytokines TGF-β and IL-4.
0 0.5 1 1.5 2+ NEWS2 score 77% Improvement Relative Risk Oxygen therapy 92% Oxygen time 70% Hospitalization time 13% Viral clearance 10% Curcumin  Hellou et al.  LATE TREATMENT  DB RCT Is late treatment with curcumin + combined treatments beneficial for COVID-19? Double-blind RCT 50 patients in Israel (May - December 2020) Improved recovery (p=0.042) and lower oxygen therapy (p=0.01) c19early.org Hellou et al., J. Cellular and Molecul.., May 2022 Favors curcumin Favors control
Hellou: RCT 50 hospitalized patients in Israel, 33 treated with curcumin, vitamin C, artemisinin, and frankincense oral spray, showing improved recovery with treatment.
0 0.5 1 1.5 2+ Hospitalization time 41% Improvement Relative Risk Curcumin for COVID-19  Kartika et al.  LATE TREATMENT Is late treatment with curcumin beneficial for COVID-19? Retrospective 246 patients in Indonesia (January - June 2021) Shorter hospitalization with curcumin (p=0.048) c19early.org Kartika et al., ICE on IMERI, 2021, Jan 2022 Favors curcumin Favors control
Kartika: Retrospective 246 hospitalized patients in Indonesia, 136 treated with curcumin, showing shorter hospitalization time with treatment. All patients received vitamin C, D, and zinc.
0 0.5 1 1.5 2+ Recovery 33% Improvement Relative Risk CRP reduction 39% Viral clearance 50% Curcumin  Khan et al.  EARLY TREATMENT  RCT Is early treatment with curcumin + quercetin and vitamin D beneficial for COVID-19? RCT 50 patients in Pakistan (September - November 2021) Improved viral clearance with curcumin + quercetin and vitamin D (p=0.0086) c19early.org Khan et al., Frontiers in Pharmacology, May 2022 Favors curcumin Favors control
Khan: RCT 50 COVID+ outpatients in Pakistan, 25 treated with curcumin, quercetin, and vitamin D, showing significantly faster viral clearance, significantly improved CRP, and faster resolution of acute symptoms (p=0.154). 168mg curcumin, 260mg quercetin and 360IU cholecalciferol.
0 0.5 1 1.5 2+ Ventilation 66% Improvement Relative Risk Hospitalization 80% Ordinal scale 43% Time to improve one unit.. 30% no CI Recovery 25% Time to viral- 6% Curcumin  Majeed et al.  EARLY TREATMENT  DB RCT Is early treatment with curcumin + combined treatments beneficial for COVID-19? Double-blind RCT 92 patients in India (September - November 2020) Improved recovery with curcumin + combined treatments (p=0.0043) c19early.org Majeed et al., Evidence-Based Compleme.., Oct 2021 Favors curcumin Favors control
Majeed: RCT 100 patients in India, 50 treated with ImmuActive (curcumin, andrographolides, resveratrol, zinc, selenium, and piperine), showing improved recovery with treatment.
0 0.5 1 1.5 2+ Hospitalization 31% Improvement Relative Risk Severe case 13% Curcumin for COVID-19  Nimer et al.  Prophylaxis Is prophylaxis with curcumin beneficial for COVID-19? Retrospective 2,148 patients in Jordan (March - July 2021) Lower hospitalization (p=0.08) and severe cases (p=0.47), not sig. c19early.org Nimer et al., F1000Research, June 2022 Favors curcumin Favors control
Nimer: Survey 2,148 COVID-19 recovered patients in Jordan, showing lower hospitalization with turmeric prophylaxis, not reaching statistical significance.
0 0.5 1 1.5 2+ Mortality 82% Improvement Relative Risk Mortality (b) 60% Mortality (c) 91% Mortality (d) 67% Curcumin  Pawar et al.  EARLY TREATMENT  DB RCT Is early treatment with curcumin beneficial for COVID-19? Double-blind RCT 140 patients in India (July - September 2020) Trial compares with probiotics, results vs. placebo may differ Lower mortality with curcumin (p=0.017) c19early.org Pawar et al., Frontiers in Pharmacology, May 2021 Favors curcumin Favors probiotics
Pawar: RCT 140 patients, 70 treated with curcumin and piperine (for absorption), and 70 treated with probiotics, showing faster recovery, lower progression, and lower mortality with curcumin.
0 0.5 1 1.5 2+ Progression 94% Improvement Relative Risk Recovery 38% Hospitalization time 45% Curcumin  Saber-Moghaddam et al.  EARLY TREATMENT Is early treatment with curcumin beneficial for COVID-19? Prospective study of 41 patients in Iran Lower progression (p=0.0013) and improved recovery (p=0.043) c19early.org Saber-Moghaddam et al., Phytotherapy R.., Jan 2021 Favors curcumin Favors control
Saber-Moghaddam: Small prospective nonrandomized trial with 41 patients, 21 treated with curcumin, showing lower disease progression and faster recovery with treatment. IRCT20200408046990N1.
0 0.5 1 1.5 2+ Progression 92% Improvement Relative Risk Hospitalization time 25% Chest CT score 68% Recovery, dyspnea/oxy.. 67% Recovery, fever 80% Recovery, cough 86% Recovery, headache 80% Recovery, fatigue 75% Recovery, myalgia 75% Recovery, diarrhea 67% Recovery, inappetence 50% Recovery, nausea 67% Curcumin  Sadeghizadeh et al.  LATE TREATMENT  DB RCT Is late treatment with curcumin beneficial for COVID-19? Double-blind RCT 42 patients in Iran Lower progression (p=0.021) and shorter hospitalization (p=0.0069) c19early.org Sadeghizadeh et al., Phytotherapy Rese.., Apr 2023 Favors curcumin Favors control
Sadeghizadeh: RCT 42 hospitalized moderate/severe COVID-19 patients in Iran, showing lower progression and improved recovery with nano-curcumin. Nano-curcumin 70mg bid for 14 days.
0 0.5 1 1.5 2+ Mortality 89% Improvement Relative Risk Ventilation 75% 2-point improvement 46% Hospitalization time 10% Curcumin  Sankhe et al.  EARLY TREATMENT  RCT Is early treatment with curcumin + combined treatments beneficial for COVID-19? RCT 174 patients in India (October 2020 - March 2021) Improved recovery with curcumin + combined treatments (p=0.002) c19early.org Sankhe et al., J. Ayurveda and Integra.., Aug 2021 Favors curcumin Favors control
Sankhe: RCT 174 patients in India, 87 treated with AyurCoro-3 (turmeric, gomutra, potassium alum, khadisakhar, bos indicus milk, ghee), showing faster recovery with treatment. EC/NEW/INST/2019/245.
0 0.5 1 1.5 2+ Mortality 86% Improvement Relative Risk Ventilation 86% ICU admission 67% Hospitalization time 10% Hospitalization time (b) 17% Recovery time, fever 32% Recovery time, dyspnea 36% Recovery time, fever (b) 4% Recovery time, dyspnea (b) -5% Ct increase 44% Curcumin  Sankhe et al.  LATE TREATMENT  RCT Is late treatment with curcumin + combined treatments beneficial for COVID-19? RCT 120 patients in India (June - November 2020) Faster recovery (p=0.001) and improved viral clearance (p=0.0026) c19early.org Sankhe et al., Complementary Therapies.., Mar 2022 Favors curcumin Favors control
Sankhe (B): RCT with 60 hospitalized patients treated with Ayurcov and 60 control patients in India, showing improved viral clearance and faster symptom resolution in the mild/moderate group, but no significant differences in the severe group. Ayurcov contains curcuma longa, go ark, sphatika (alum), sita (rock candy), godugdham (bos indicus) milk, and goghritam (bos indicus ghee).
0 0.5 1 1.5 2+ Severe case 42% unadjusted Improvement Relative Risk Curcumin for COVID-19  Shehab et al.  Prophylaxis Is prophylaxis with curcumin beneficial for COVID-19? Retrospective 253 patients in multiple countries (Sep 2020 - Mar 2021) Lower severe cases with curcumin (not stat. sig., p=0.55) c19early.org Shehab et al., Tropical J. Pharmaceuti.., Feb 2022 Favors curcumin Favors control
Shehab: Retrospective survey-based analysis of 349 COVID-19 patients, showing a lower risk of severe cases with vitamin D, zinc, turmeric, and honey prophylaxis in unadjusted analysis, without statistical significance. REC/UG/2020/03.
0 0.5 1 1.5 2+ Mortality 83% Improvement Relative Risk Mortality (b) 67% Mortality (c) 80% Curcumin  Tahmasebi et al.  LATE TREATMENT  DB RCT Is late treatment with curcumin beneficial for COVID-19? Double-blind RCT 80 patients in Iran Lower mortality with curcumin (not stat. sig., p=0.11) c19early.org Tahmasebi et al., Life Sciences, March 2021 Favors curcumin Favors control
Tahmasebi: RCT 40 hospitalized, 40 ICU, and 40 control patients in Iran, showing lower mortality and improved regulatory T cell responses with nanocurcumin treatment (SinaCurcumin).
0 0.5 1 1.5 2+ Improvement, CFS 44% Improvement Relative Risk Improvement, SWS 82% Improvement, CSS 64% Curcumin  Phyto-V  LATE TREATMENT  DB RCT  LONG COVID Does curcumin + combined treatments reduce the risk of Long COVID (PASC)? Double-blind RCT 147 patients in the United Kingdom (May 2020 - May 2021) Greater improvement with curcumin + combined treatments (p=0.018) c19early.org Thomas et al., COVID, March 2022 Favors curcumin Favors control
Thomas: RCT 147 long COVID patients in the UK, 56 treated with a phytochemical-rich concentrated food capsule, showing improved recovery with treatment. Treatment included curcumin, bioflavonoids, chamomile, ellagic acid, and resveratrol.
0 0.5 1 1.5 2+ Mortality 50% Improvement Relative Risk Curcumin  Valizadeh et al.  LATE TREATMENT  DB RCT Is late treatment with curcumin beneficial for COVID-19? Double-blind RCT 40 patients in Iran Lower mortality with curcumin (not stat. sig., p=0.3) c19early.org Valizadeh et al., Int. Immunopharmacol., Oct 2020 Favors curcumin Favors control
Valizadeh: Small RCT with 40 nano-curcumin patients and 40 control patients showing lower mortality with treatment. Authors conclude that nano-curcumin may be able to modulate the increased rate of inflammatory cytokines especially IL-1β and IL-6 mRNA expression and cytokine secretion in COVID-19 patients, which may improve clinical outcomes.
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 c19early.org. Search terms were curcumin, filtered for papers containing the terms COVID-19 or SARS-CoV-2. Automated searches are performed every few hours with notification of new matches. All studies regarding the use of curcumin for COVID-19 that report a comparison with a control group are included in the main analysis. Sensitivity analysis is performed, excluding studies with major 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 of effects then the most serious outcome is used in pooled analysis, while other outcomes are included in the outcome specific analyses. 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 in both arms were not used (the next most serious outcome is used — no studies were excluded). For example, in low-risk populations with no mortality, a reduction in mortality with treatment is not possible, however a reduction in hospitalization, for example, is still valuable. Clinical outcome is considered more important than PCR testing status. When basically all patients recover in both treatment and control groups, preference for viral clearance 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). If only individual symptom data is available, the most serious symptom has priority, for example difficulty breathing or low SpO2 is more important than cough. When results provide an odds ratio, we computed the relative risk when possible, or converted to a relative risk according to Zhang. Reported confidence intervals and p-values were used when available, using adjusted values when provided. If multiple types of adjustments are reported including propensity score matching (PSM), the PSM results are used. Adjusted primary outcome results have preference over unadjusted results for a more serious outcome when the adjustments significantly alter results. When needed, conversion between reported p-values and confidence 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 the reciprocal of the opposite arm with the sum of the correction factors equal to 1 Sweeting. Results are expressed with RR < 1.0 favoring treatment, and using the risk of a negative outcome when applicable (for example, the risk of death rather than the risk of survival). If studies only report relative continuous values such as relative times, the ratio of the time for the treatment group versus the time for the control group is used. Calculations are done in Python (3.11.4) with scipy (1.11.1), pythonmeta (1.26), numpy (1.25.0), statsmodels (0.14.0), and plotly (5.15.0).
Forest plots are computed using PythonMeta Deng with the DerSimonian and Laird random effects model (the fixed effect assumption is not plausible in this case) and inverse variance weighting. Mixed-effects meta-regression results are computed with R (4.1.2) using the metafor (3.0-2) and rms (6.2-0) packages, and using the most serious sufficiently powered outcome.
We received no funding, this research is done in our spare time. We have no affiliations with any pharmaceutical companies or political parties.
We have classified studies as early treatment if most patients are not already at a severe stage at the time of treatment (for example based on oxygen status or lung involvement), and treatment started within 5 days of the onset of symptoms. If studies contain a mix of early treatment and late treatment patients, we consider the treatment time of patients contributing most to the events (for example, consider a study where most patients are treated early but late treatment patients are included, and all mortality events were observed with late treatment patients). We note that a shorter time may be preferable. Antivirals are typically only considered effective when used within a shorter timeframe, for example 0-36 or 0-48 hours for oseltamivir, with longer delays not being effective McLean, Treanor.
A summary of study results is below. Please submit updates and corrections at the bottom of this page.
A summary of study results is below. Please submit updates and corrections at https://c19early.org/tmeta.html.
Effect extraction follows pre-specified rules as detailed above and gives priority to more serious outcomes. For pooled analyses, the first (most serious) outcome is used, which may differ from the effect a paper focuses on. Other outcomes are used in outcome specific analyses.
Ahmadi, 6/19/2021, Double Blind Randomized Controlled Trial, Iran, peer-reviewed, 11 authors, study period April 2020 - July 2020. risk of hospitalization, 85.7% lower, RR 0.14, p = 0.24, treatment 0 of 30 (0.0%), control 3 of 30 (10.0%), NNT 10.0, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
recovery time, 20.6% lower, relative time 0.79, p = 0.37, treatment 30, control 30.
Aldwihi, 5/11/2021, retrospective, Saudi Arabia, peer-reviewed, survey, mean age 36.5, 8 authors, study period August 2020 - October 2020. risk of hospitalization, 31.2% lower, RR 0.69, p = 0.10, treatment 30 of 144 (20.8%), control 207 of 594 (34.8%), NNT 7.1, adjusted per study, odds ratio converted to relative risk, multivariable.
Askari, 6/6/2022, Double Blind Randomized Controlled Trial, placebo-controlled, Iran, peer-reviewed, 11 authors, study period November 2020 - April 2021, trial IRCT20121216011763N46. risk of no recovery, 125.0% higher, RR 2.25, p = 0.58, treatment 3 of 8 (37.5%), control 1 of 6 (16.7%), dyspnea.
risk of no recovery, 433.3% higher, RR 5.33, p = 0.19, treatment 2 of 6 (33.3%), control 0 of 7 (0.0%), continuity correction due to zero event (with reciprocal of the contrasting arm), ague.
risk of no recovery, 72.9% lower, RR 0.27, p = 0.04, treatment 2 of 12 (16.7%), control 8 of 13 (61.5%), NNT 2.2, weakness.
risk of no recovery, 40.0% lower, RR 0.60, p = 0.42, treatment 3 of 10 (30.0%), control 7 of 14 (50.0%), NNT 5.0, muscular pain.
risk of no recovery, 38.5% lower, RR 0.62, p = 0.65, treatment 4 of 13 (30.8%), control 4 of 8 (50.0%), NNT 5.2, headache.
risk of no recovery, 71.4% higher, RR 1.71, p = 1.00, treatment 2 of 7 (28.6%), control 1 of 6 (16.7%), sore throat.
risk of no recovery, 12.5% lower, RR 0.88, p = 1.00, treatment 1 of 8 (12.5%), control 1 of 7 (14.3%), NNT 56, sputum cough.
risk of no recovery, no change, RR 1.00, p = 1.00, treatment 3 of 13 (23.1%), control 3 of 13 (23.1%), dry cough.
Chitre, 11/23/2022, Double Blind Randomized Controlled Trial, placebo-controlled, India, peer-reviewed, 8 authors, study period September 2020 - April 2021, this trial uses multiple treatments in the treatment arm (combined with ashwagandha, boswellia, ginger) - results of individual treatments may vary, trial CTRI/2020/09/027817. recovery time, 11.3% lower, relative time 0.89, p = 0.04, treatment 89, control 86.
fever, 11.0% lower, RR 0.89, p = 0.03, treatment 70 of 89 (78.7%), control 76 of 86 (88.4%), NNT 10, day 4.
congestion, 20.0% lower, RR 0.80, p = 0.05, treatment 89, control 86, mid-recovery, day 7.
sore throat, 20.0% lower, RR 0.80, p = 0.09, treatment 89, control 86, mid-recovery, day 7.
cough, 14.3% lower, RR 0.86, p = 0.14, treatment 89, control 86, mid-recovery, day 7.
dyspnea, 15.4% lower, RR 0.85, p = 0.15, treatment 89, control 86, mid-recovery, day 7.
pain, 8.3% lower, RR 0.92, p = 0.41, treatment 89, control 86, mid-recovery, day 7.
fatigue, 16.7% lower, RR 0.83, p = 0.13, treatment 89, control 86, mid-recovery, day 7.
headache, 16.7% lower, RR 0.83, p = 0.12, treatment 89, control 86, mid-recovery, day 7.
chills, 18.2% lower, RR 0.82, p = 0.09, treatment 89, control 86, mid-recovery, day 7.
diarrhea, 25.0% lower, RR 0.75, p = 0.08, treatment 89, control 86, mid-recovery, day 7.
vomiting, 18.2% lower, RR 0.82, p = 0.07, treatment 89, control 86, mid-recovery, day 7.
smell, 16.7% lower, RR 0.83, p = 0.06, treatment 89, control 86, mid-recovery, day 7.
taste, 16.7% lower, RR 0.83, p = 0.14, treatment 89, control 86, mid-recovery, day 7.
Din Ujjan, 1/18/2023, Randomized Controlled Trial, Pakistan, peer-reviewed, 6 authors, study period 21 September, 2021 - 21 January, 2022, this trial uses multiple treatments in the treatment arm (combined with quercetin and vitamin D) - results of individual treatments may vary, trial NCT04603690 (history). risk of no recovery, 28.6% lower, RR 0.71, p = 0.11, treatment 15 of 25 (60.0%), control 21 of 25 (84.0%), NNT 4.2, no symptoms, day 7.
risk of no recovery, 71.4% lower, RR 0.29, p < 0.001, treatment 6 of 25 (24.0%), control 21 of 25 (84.0%), NNT 1.7, <= 1 symptom, day 7.
risk of no recovery, 76.9% lower, RR 0.23, p = 0.005, treatment 3 of 25 (12.0%), control 13 of 25 (52.0%), NNT 2.5, <= 2 symptoms, day 7.
risk of no recovery, 85.7% lower, RR 0.14, p = 0.23, treatment 0 of 25 (0.0%), control 3 of 25 (12.0%), NNT 8.3, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), <= 3 symptoms, day 7.
risk of no viral clearance, 90.9% lower, RR 0.09, p = 0.05, treatment 0 of 25 (0.0%), control 5 of 25 (20.0%), NNT 5.0, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), day 14.
risk of no viral clearance, 73.7% lower, RR 0.26, p < 0.001, treatment 5 of 25 (20.0%), control 19 of 25 (76.0%), NNT 1.8, day 7.
Khan, 5/1/2022, Randomized Controlled Trial, Pakistan, peer-reviewed, 7 authors, study period 2 September, 2021 - 28 November, 2021, this trial uses multiple treatments in the treatment arm (combined with quercetin and vitamin D) - results of individual treatments may vary, trial NCT05130671 (history). risk of no recovery, 33.3% lower, RR 0.67, p = 0.15, treatment 10 of 25 (40.0%), control 15 of 25 (60.0%), NNT 5.0.
relative CRP reduction, 39.1% better, RR 0.61, p = 0.006, treatment 25, control 25.
risk of no viral clearance, 50.0% lower, RR 0.50, p = 0.009, treatment 10 of 25 (40.0%), control 20 of 25 (80.0%), NNT 2.5.
Majeed, 10/11/2021, Double Blind Randomized Controlled Trial, India, peer-reviewed, 4 authors, study period September 2020 - November 2020, this trial uses multiple treatments in the treatment arm (combined with andrographolides, resveratrol, zinc, selenium, and piperine) - results of individual treatments may vary, trial CTRI/2020/09/027841. risk of mechanical ventilation, 66.2% lower, RR 0.34, p = 1.00, treatment 0 of 45 (0.0%), control 1 of 47 (2.1%), NNT 47, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
risk of hospitalization, 79.7% lower, RR 0.20, p = 0.49, treatment 0 of 45 (0.0%), control 2 of 47 (4.3%), NNT 24, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
relative ordinal scale, 43.0% better, RR 0.57, p = 0.004, treatment 45, control 47, day 28.
risk of no recovery, 24.6% lower, RR 0.75, p = 0.08, treatment 26 of 45 (57.8%), control 36 of 47 (76.6%), NNT 5.3, day 28.
time to viral-, 5.8% lower, relative time 0.94, p = 0.47, treatment 45, control 47.
Pawar, 5/28/2021, Double Blind Randomized Controlled Trial, India, peer-reviewed, 8 authors, study period July 2020 - September 2020, this trial compares with another treatment - results may be better when compared to placebo, trial CTRI/2020/05/025482. risk of death, 81.8% lower, RR 0.18, p = 0.02, treatment 2 of 70 (2.9%), control 11 of 70 (15.7%), NNT 7.8.
risk of death, 60.0% lower, RR 0.40, p = 0.39, treatment 2 of 15 (13.3%), control 5 of 15 (33.3%), NNT 5.0, severe group.
risk of death, 90.9% lower, RR 0.09, p = 0.05, treatment 0 of 25 (0.0%), control 5 of 25 (20.0%), NNT 5.0, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), moderate group.
risk of death, 66.7% lower, RR 0.33, p = 1.00, treatment 0 of 30 (0.0%), control 1 of 30 (3.3%), NNT 30, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), mild group.
Saber-Moghaddam, 1/3/2021, prospective, Iran, peer-reviewed, 9 authors. risk of progression, 94.3% lower, RR 0.06, p = 0.001, treatment 0 of 21 (0.0%), control 8 of 20 (40.0%), NNT 2.5, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
risk of no recovery, 38.4% lower, RR 0.62, p = 0.04, treatment 11 of 21 (52.4%), control 17 of 20 (85.0%), NNT 3.1.
hospitalization time, 44.8% lower, relative time 0.55, p < 0.001, treatment 21, control 20.
Sankhe, 8/10/2021, Randomized Controlled Trial, India, peer-reviewed, 8 authors, study period October 2020 - March 2021, this trial uses multiple treatments in the treatment arm (combined with gomutra, potassium alum, khadisakhar, bos indicus milk, ghee) - results of individual treatments may vary. risk of death, 88.9% lower, RR 0.11, p = 0.12, treatment 0 of 87 (0.0%), control 4 of 87 (4.6%), NNT 22, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
risk of mechanical ventilation, 75.0% lower, RR 0.25, p = 0.37, treatment 1 of 87 (1.1%), control 4 of 87 (4.6%), NNT 29.
risk of no 2-point improvement, 46.5% lower, RR 0.54, p = 0.002, treatment 29 of 87 (33.3%), control 60 of 87 (69.0%), NNT 2.8, inverted to make RR<1 favor treatment, odds ratio converted to relative risk, day 7 mid-recovery.
hospitalization time, 10.0% lower, relative time 0.90, p = 0.40, treatment 87, control 87.
Effect extraction follows pre-specified rules as detailed above and gives priority to more serious outcomes. For pooled analyses, the first (most serious) outcome is used, which may differ from the effect a paper focuses on. Other outcomes are used in outcome specific analyses.
Abbaspour-Aghdam, 9/17/2022, Randomized Controlled Trial, placebo-controlled, Iran, peer-reviewed, 16 authors, trial IRCT20200324046851N1. risk of death, 71.4% lower, RR 0.29, p = 0.15, treatment 2 of 30 (6.7%), control 7 of 30 (23.3%), NNT 6.0.
risk of no recovery, 86.3% lower, RR 0.14, p = 0.04, treatment 1 of 28 (3.6%), control 6 of 23 (26.1%), NNT 4.4, dyspnea.
risk of no recovery, 89.9% lower, RR 0.10, p = 0.04, treatment 0 of 28 (0.0%), control 4 of 23 (17.4%), NNT 5.8, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), fever >39.0.
risk of no recovery, 38.4% lower, RR 0.62, p = 0.17, treatment 9 of 28 (32.1%), control 12 of 23 (52.2%), NNT 5.0, bilateral chest radiograph involvement.
risk of no recovery, 58.9% lower, RR 0.41, p = 0.27, treatment 3 of 28 (10.7%), control 6 of 23 (26.1%), NNT 6.5, cough.
risk of no recovery, 81.6% lower, RR 0.18, p = 0.20, treatment 0 of 28 (0.0%), control 2 of 23 (8.7%), NNT 12, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), headache.
Ahmadi (B), 7/28/2023, Double Blind Randomized Controlled Trial, placebo-controlled, Iran, peer-reviewed, 5 authors, study period December 2021 - March 2022, trial IRCT20211126053183N1. risk of oxygen therapy, 58.0% lower, RR 0.42, p = 0.06, treatment 5 of 29 (17.2%), control 16 of 39 (41.0%), NNT 4.2.
relative improvement in SpO2, 67.2% better, RR 0.33, p = 0.04, treatment mean 3.32 (±3.84) n=29, control mean 1.09 (±4.71) n=39.
risk of no recovery, 49.6% lower, RR 0.50, p = 0.33, treatment 3 of 29 (10.3%), control 8 of 39 (20.5%), NNT 9.8, chest pain.
risk of no recovery, 34.5% higher, RR 1.34, p = 1.00, treatment 1 of 29 (3.4%), control 1 of 39 (2.6%), chills.
risk of no recovery, 58.0% lower, RR 0.42, p = 0.06, treatment 5 of 29 (17.2%), control 16 of 39 (41.0%), NNT 4.2, cough.
risk of no recovery, 77.7% lower, RR 0.22, p = 0.50, treatment 0 of 29 (0.0%), control 2 of 39 (5.1%), NNT 20, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), sore throat.
risk of no recovery, 63.8% lower, RR 0.36, p < 0.001, treatment 7 of 29 (24.1%), control 26 of 39 (66.7%), NNT 2.4, fatigue.
risk of no recovery, 91.3% lower, RR 0.09, p = 0.03, treatment 0 of 29 (0.0%), control 6 of 39 (15.4%), NNT 6.5, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), myalgia.
risk of no recovery, 8.9% higher, RR 1.09, p = 0.81, treatment 17 of 29 (58.6%), control 21 of 39 (53.8%), anosmia.
risk of no recovery, 10.3% lower, RR 0.90, p = 1.00, treatment 8 of 29 (27.6%), control 12 of 39 (30.8%), NNT 31, ageusia.
risk of no recovery, 10.3% lower, RR 0.90, p = 1.00, treatment 2 of 29 (6.9%), control 3 of 39 (7.7%), NNT 126, anorexia.
risk of no recovery, 63.6% lower, RR 0.36, p = 1.00, treatment 0 of 29 (0.0%), control 1 of 39 (2.6%), NNT 39, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), diarrhea.
risk of no recovery, 234.5% higher, RR 3.34, p = 0.43, treatment 1 of 29 (3.4%), control 0 of 39 (0.0%), continuity correction due to zero event (with reciprocal of the contrasting arm), nausea.
Asadirad, 1/17/2022, Randomized Controlled Trial, placebo-controlled, Iran, peer-reviewed, 7 authors, study period June 2020 - July 2020. risk of death, 25.9% lower, RR 0.74, p = 0.74, treatment 5 of 27 (18.5%), control 6 of 24 (25.0%), NNT 15, excluding patients that stopped treatment due to progression - 3 for curcumin and 6 for control.
risk of progression, 50.0% lower, RR 0.50, p = 0.47, treatment 3 of 30 (10.0%), control 6 of 30 (20.0%), NNT 10.0.
risk of unresolved fever, 45.3% lower, RR 0.55, p = 0.09, treatment 8 of 27 (29.6%), control 13 of 24 (54.2%), NNT 4.1.
risk of unresolved dyspnea, 28.9% lower, RR 0.71, p = 0.72, treatment 4 of 27 (14.8%), control 5 of 24 (20.8%), NNT 17.
risk of unresolved cough, 40.7% lower, RR 0.59, p = 0.36, treatment 6 of 27 (22.2%), control 9 of 24 (37.5%), NNT 6.5.
risk of O2 <92%, 36.5% lower, RR 0.63, p = 0.51, treatment 5 of 27 (18.5%), control 7 of 24 (29.2%), NNT 9.4.
risk of O2 <97%, 20.0% lower, RR 0.80, p = 0.21, treatment 18 of 27 (66.7%), control 20 of 24 (83.3%), NNT 6.0.
Gérain, 6/22/2023, Randomized Controlled Trial, Belgium, peer-reviewed, 8 authors, study period 1 April, 2021 - 29 October, 2021, this trial uses multiple treatments in the treatment arm (combined with quercetin) - results of individual treatments may vary, trial NCT04844658 (history). risk of death, 67.1% lower, RR 0.33, p = 0.49, treatment 0 of 25 (0.0%), control 1 of 24 (4.2%), NNT 24, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), day 7.
risk of death/ICU, 91.1% lower, RR 0.09, p = 0.02, treatment 0 of 25 (0.0%), control 5 of 24 (20.8%), NNT 4.8, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), day 7.
risk of mechanical ventilation, 89.1% lower, RR 0.11, p = 0.05, treatment 0 of 25 (0.0%), control 4 of 24 (16.7%), NNT 6.0, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), day 7.
risk of ICU admission, 89.1% lower, RR 0.11, p = 0.05, treatment 0 of 25 (0.0%), control 4 of 24 (16.7%), NNT 6.0, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), day 7.
risk of no hospital discharge, 72.6% lower, RR 0.27, p = 0.07, treatment 2 of 25 (8.0%), control 7 of 24 (29.2%), NNT 4.7, day 14.
risk of no hospital discharge, 58.9% lower, RR 0.41, p = 0.02, treatment 6 of 25 (24.0%), control 14 of 24 (58.3%), NNT 2.9, day 7.
hospitalization time, 37.5% lower, relative time 0.62, p = 0.008, treatment median 5.0 IQR 4.0 n=25, control median 8.0 IQR 6.0 n=24.
relative WHO score, 50.0% better, RR 0.50, p = 0.04, treatment 22, control 24, day 7.
Hartono, 2/22/2022, Randomized Controlled Trial, Indonesia, peer-reviewed, 13 authors, study period May 2020 - September 2020, this trial uses multiple treatments in the treatment arm (combined with virgin coconut oil) - results of individual treatments may vary, excluded in exclusion analyses: randomization resulted in significant baseline differences that were not adjusted for. risk of no viral clearance, 53.3% lower, RR 0.47, p < 0.001, treatment 14 of 30 (46.7%), control 30 of 30 (100.0%), NNT 1.9, day 10.
risk of no viral clearance, 75.0% lower, RR 0.25, p = 0.002, treatment 4 of 30 (13.3%), control 16 of 30 (53.3%), NNT 2.5, day 14.
risk of no viral clearance, 66.7% lower, RR 0.33, p = 1.00, treatment 0 of 30 (0.0%), control 1 of 30 (3.3%), NNT 30, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), day 21.
Hassaniazad, 9/19/2021, Double Blind Randomized Controlled Trial, placebo-controlled, Iran, peer-reviewed, 12 authors. relative improvement in SpO2, 45.7% worse, RR 1.46, p = 0.90, treatment 20, control 20.
Hellou, 5/19/2022, Double Blind Randomized Controlled Trial, placebo-controlled, Israel, peer-reviewed, 6 authors, study period 8 May, 2020 - 21 December, 2020, this trial uses multiple treatments in the treatment arm (combined with vitamin C, artemisinin, and frankincense) - results of individual treatments may vary, trial NCT04382040 (history). relative NEWS2 score, 76.7% better, RR 0.23, p = 0.04, treatment mean 0.52 (±0.67) n=33, control mean 2.23 (±3.2) n=17, day 15.
risk of oxygen therapy, 92.2% lower, RR 0.08, p = 0.01, treatment 0 of 33 (0.0%), control 4 of 17 (23.5%), NNT 4.2, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), day 15.
oxygen time, 69.7% lower, relative time 0.30, p = 0.17, treatment mean 2.3 (±1.4) n=33, control mean 7.6 (±4.6) n=17.
hospitalization time, 13.3% lower, relative time 0.87, p = 0.92, treatment mean 7.8 (±7.3) n=33, control mean 9.0 (±8.0) n=17.
risk of no viral clearance, 9.8% lower, RR 0.90, p = 0.77, treatment 14 of 33 (42.4%), control 8 of 17 (47.1%), NNT 22, day 15.
Kartika, 1/28/2022, retrospective, Indonesia, preprint, 6 authors, study period January 2021 - June 2021. hospitalization time, 41.0% lower, relative time 0.59, p = 0.048, treatment 139, control 107.
Sadeghizadeh, 4/29/2023, Double Blind Randomized Controlled Trial, placebo-controlled, Iran, peer-reviewed, 12 authors, trial IRCT20170128032241N3. risk of progression, 92.3% lower, RR 0.08, p = 0.02, treatment 0 of 21 (0.0%), control 6 of 21 (28.6%), NNT 3.5, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
hospitalization time, 24.5% lower, relative time 0.75, p = 0.007, treatment mean 7.7 (±2.3) n=21, control mean 10.2 (±3.3) n=21.
relative chest CT score, 67.5% better, RR 0.33, p < 0.001, treatment mean 1.3 (±0.82) n=21, control mean 4.0 (±1.8) n=21, day 14.
risk of no recovery, 66.7% lower, RR 0.33, p = 0.61, treatment 1 of 21 (4.8%), control 3 of 21 (14.3%), NNT 10, day 14, dyspnea/oxygen need.
risk of no recovery, 80.0% lower, RR 0.20, p = 0.18, treatment 1 of 21 (4.8%), control 5 of 21 (23.8%), NNT 5.2, day 14, fever.
risk of no recovery, 85.7% lower, RR 0.14, p = 0.04, treatment 1 of 21 (4.8%), control 7 of 21 (33.3%), NNT 3.5, day 14, cough.
risk of no recovery, 80.0% lower, RR 0.20, p = 0.49, treatment 0 of 21 (0.0%), control 2 of 21 (9.5%), NNT 10, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), day 14, headache.
risk of no recovery, 75.0% lower, RR 0.25, p = 0.34, treatment 1 of 21 (4.8%), control 4 of 21 (19.0%), NNT 7.0, day 14, fatigue.
risk of no recovery, 75.0% lower, RR 0.25, p = 0.34, treatment 1 of 21 (4.8%), control 4 of 21 (19.0%), NNT 7.0, day 14, myalgia.
risk of no recovery, 66.7% lower, RR 0.33, p = 1.00, treatment 0 of 21 (0.0%), control 1 of 21 (4.8%), NNT 21, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), day 14, diarrhea.
risk of no recovery, 50.0% lower, RR 0.50, p = 1.00, treatment 1 of 21 (4.8%), control 2 of 21 (9.5%), NNT 21, day 14, inappetence.
risk of no recovery, 66.7% lower, RR 0.33, p = 1.00, treatment 0 of 21 (0.0%), control 1 of 21 (4.8%), NNT 21, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), day 14, nausea.
Sankhe (B), 3/25/2022, Single Blind Randomized Controlled Trial, India, peer-reviewed, 10 authors, study period June 2020 - November 2020, this trial uses multiple treatments in the treatment arm (combined with gomutra, potassium alum, khadisakhar, bos indicus milk, ghee) - results of individual treatments may vary. risk of death, 85.7% lower, RR 0.14, p = 0.24, treatment 0 of 60 (0.0%), control 3 of 60 (5.0%), NNT 20, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
risk of mechanical ventilation, 85.7% lower, RR 0.14, p = 0.24, treatment 0 of 60 (0.0%), control 3 of 60 (5.0%), NNT 20, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
risk of ICU admission, 66.7% lower, RR 0.33, p = 0.62, treatment 1 of 60 (1.7%), control 3 of 60 (5.0%), NNT 30.
hospitalization time, 10.0% lower, relative time 0.90, p = 0.40, treatment 45, control 45, moderate group.
hospitalization time, 16.7% lower, relative time 0.83, p = 0.20, treatment 15, control 15, severe group.
recovery time, 31.9% lower, relative time 0.68, p < 0.001, treatment 45, control 45, moderate group, fever.
recovery time, 36.1% lower, relative time 0.64, p < 0.001, treatment 45, control 45, moderate group, dyspnea.
recovery time, 4.3% lower, relative time 0.96, p = 0.74, treatment 15, control 15, severe group, fever.
recovery time, 4.8% higher, relative time 1.05, p = 0.10, treatment 15, control 15, severe group, dyspnea.
relative Ct increase, 44.4% better, RR 0.56, p = 0.003, treatment mean 9.98 (±6.39) n=44, control mean 5.55 (±6.91) n=43, moderate group.
Tahmasebi, 3/28/2021, Double Blind Randomized Controlled Trial, Iran, peer-reviewed, 14 authors. risk of death, 83.3% lower, RR 0.17, p = 0.11, treatment 1 of 40 (2.5%), control 6 of 40 (15.0%), NNT 8.0.
risk of death, 66.7% lower, RR 0.33, p = 1.00, treatment 0 of 20 (0.0%), control 1 of 20 (5.0%), NNT 20, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), non-ICU patients.
risk of death, 80.0% lower, RR 0.20, p = 0.18, treatment 1 of 20 (5.0%), control 5 of 20 (25.0%), NNT 5.0, ICU patients.
Thomas, 3/22/2022, Double Blind Randomized Controlled Trial, placebo-controlled, United Kingdom, peer-reviewed, 7 authors, study period May 2020 - May 2021, this trial uses multiple treatments in the treatment arm (combined with bioflavonoids, chamomile, ellagic acid, resveratrol) - results of individual treatments may vary, Phyto-V trial. relative improvement, 44.3% better, RR 0.56, p = 0.02, treatment mean 6.1 (±7.5) n=74, control mean 3.4 (±6.1) n=73, CFS.
relative improvement, 81.8% better, RR 0.18, p < 0.001, treatment mean 6.6 (±10.5) n=74, control mean 1.2 (±7.4) n=73, SWS.
relative improvement, 63.6% better, RR 0.36, p = 0.02, treatment mean 1.1 (±2.0) n=74, control mean 0.4 (±1.5) n=73, CSS.
Valizadeh, 10/20/2020, Double Blind Randomized Controlled Trial, Iran, peer-reviewed, 12 authors. risk of death, 50.0% lower, RR 0.50, p = 0.30, treatment 4 of 20 (20.0%), control 8 of 20 (40.0%), NNT 5.0.
Effect extraction follows pre-specified rules as detailed above and gives priority to more serious outcomes. For pooled analyses, the first (most serious) outcome is used, which may differ from the effect a paper focuses on. Other outcomes are used in outcome specific analyses.
Bejan, 2/28/2021, retrospective, USA, peer-reviewed, mean age 42.0, 6 authors. risk of hospitalization, 59.0% lower, OR 0.41, p = 0.048, treatment 148, control 9,600, adjusted per study, RR approximated with OR.
Nimer, 6/10/2022, retrospective, Jordan, peer-reviewed, survey, mean age 40.2, 4 authors, study period March 2021 - July 2021. risk of hospitalization, 30.8% lower, RR 0.69, p = 0.08, treatment 29 of 329 (8.8%), control 179 of 1,819 (9.8%), adjusted per study, odds ratio converted to relative risk, multivariable.
risk of severe case, 12.6% lower, RR 0.87, p = 0.47, treatment 40 of 329 (12.2%), control 211 of 1,819 (11.6%), adjusted per study, odds ratio converted to relative risk, multivariable.
Shehab, 2/28/2022, retrospective, multiple countries, peer-reviewed, survey, 7 authors, study period September 2020 - March 2021, excluded in exclusion analyses: unadjusted results with no group details. risk of severe case, 42.4% lower, RR 0.58, p = 0.55, treatment 2 of 32 (6.2%), control 24 of 221 (10.9%), NNT 22, unadjusted, severe vs. mild cases.
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