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Diet for COVID-19: real-time meta analysis of 7 studies
Covid Analysis, May 22, 2022, DRAFT
https://c19early.com/dtmeta.html
0 0.5 1 1.5+ All studies 54% 7 585,031 Improvement, Studies, Patients Relative Risk Mortality 25% 2 281,639 Cases 35% 5 303,392 Prophylaxis 54% 7 585,031 Diet for COVID-19 c19early.com/dt May 2022 Favorshealthy diet Favorscontrol after exclusions
Statistically significant improvement is seen for cases. 5 studies from 5 independent teams in 3 different countries show statistically significant improvements in isolation.
Meta analysis using the most serious outcome reported shows 54% [27‑71%] improvement. Results are similar after exclusions.
0 0.5 1 1.5+ All studies 54% 7 585,031 Improvement, Studies, Patients Relative Risk Mortality 25% 2 281,639 Cases 35% 5 303,392 Prophylaxis 54% 7 585,031 Diet for COVID-19 c19early.com/dt May 2022 Favorshealthy diet Favorscontrol after exclusions
Studies analyze diet quality before infection, and use different definitions of diet quality.
No treatment, vaccine, or intervention is 100% available and effective for all variants. All practical, effective, and safe means should be used. Denying the efficacy of treatments increases mortality, morbidity, collateral damage, and endemic risk.
All data to reproduce this paper and sources are in the appendix.
Highlights
A healthier diet reduces risk for COVID-19 with very high confidence for cases and in pooled analysis.
We show traditional outcome specific analyses and combined evidence from all 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+ Kim 72% 0.28 [0.10-0.82] m/s case 41 (n) 527 (n) Improvement, RR [CI] Treatment Control Merino 41% 0.59 [0.47-0.74] severe case 148,142 (n) 148,143 (n) Moludi 92% 0.08 [0.05-0.19] cases n/a n/a Ahmadi -3% 1.03 [0.77-1.39] death 185/206,286 62/75,264 Nguyen 15% 0.85 [0.75-0.96] symp. case 345/1,054 433/1,082 Magaña 53% 0.47 [0.22-0.99] death 58 (n) 31 (n) Perez-Araluce 78% 0.22 [0.03-1.77] severe case 1/1,103 10/3,300 Tau​2 = 0.28, I​2 = 91.0%, p = 0.00099 Prophylaxis 54% 0.46 [0.29-0.73] 531/356,684 505/228,347 54% improvement All studies 54% 0.46 [0.29-0.73] 531/356,684 505/228,347 54% improvement 7 diet COVID-19 studies c19early.com/dt May 2022 Tau​2 = 0.28, I​2 = 91.0%, p = 0.00099 Effect extraction pre-specified(most serious outcome, see appendix) Favors healthy diet 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 reporting COVID-19 outcomes as a function of diet quality and providing adjusted results. 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.
Results
Figure 2 shows a visual overview of the results, with details in Table 1 and Table 2. Figure 3, 4, and 5 show forest plots for a random effects meta-analysis of all studies with pooled effects, mortality results, and cases.
0 0.5 1 1.5+ ALL STUDIES MORTALITY CASES After Exclusions ALL STUDIES All Prophylaxis Diet for COVID-19 C19EARLY.COM/DT MAY 2022
Figure 2. Overview of results.
Treatment timeNumber of studies reporting positive effects Total number of studiesPercentage of studies reporting positive effects Random effects meta-analysis results
Prophylaxis 6 7 85.7% 54% improvement
RR 0.46 [0.29‑0.73]
p = 0.00099
All studies 6 7 85.7% 54% improvement
RR 0.46 [0.29‑0.73]
p = 0.00099
Table 1. Results by treatment stage.
Studies Prophylaxis PatientsAuthors
All studies 754% [27‑71%] 585,031 77
With exclusions 655% [25‑73%] 584,942 71
Table 2. Results by treatment stage for all studies and with different exclusions.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Kim 72% 0.28 [0.10-0.82] m/s case 41 (n) 527 (n) Improvement, RR [CI] Treatment Control Merino 41% 0.59 [0.47-0.74] severe case 148,142 (n) 148,143 (n) Moludi 92% 0.08 [0.05-0.19] cases n/a n/a Ahmadi -3% 1.03 [0.77-1.39] death 185/206,286 62/75,264 Nguyen 15% 0.85 [0.75-0.96] symp. case 345/1,054 433/1,082 Magaña 53% 0.47 [0.22-0.99] death 58 (n) 31 (n) Perez-Araluce 78% 0.22 [0.03-1.77] severe case 1/1,103 10/3,300 Tau​2 = 0.28, I​2 = 91.0%, p = 0.00099 Prophylaxis 54% 0.46 [0.29-0.73] 531/356,684 505/228,347 54% improvement All studies 54% 0.46 [0.29-0.73] 531/356,684 505/228,347 54% improvement 7 diet COVID-19 studies c19early.com/dt May 2022 Tau​2 = 0.28, I​2 = 91.0%, p = 0.00099 Effect extraction pre-specified(most serious outcome, see appendix) Favors healthy diet Favors control
Figure 3. 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+ Ahmadi -3% 1.03 [0.77-1.39] 185/206,286 62/75,264 Improvement, RR [CI] Treatment Control Magaña 53% 0.47 [0.22-0.99] 58 (n) 31 (n) Tau​2 = 0.22, I​2 = 72.6%, p = 0.47 Prophylaxis 25% 0.75 [0.36-1.60] 185/206,344 62/75,295 25% improvement All studies 25% 0.75 [0.36-1.60] 185/206,344 62/75,295 25% improvement 2 diet COVID-19 mortality results c19early.com/dt May 2022 Tau​2 = 0.22, I​2 = 72.6%, p = 0.47 Favors healthy diet Favors control
Figure 4. Random effects meta-analysis for mortality results.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Kim 19% 0.81 [0.56-1.15] cases 41 (n) 527 (n) Improvement, RR [CI] Treatment Control Merino 18% 0.82 [0.78-0.86] cases 148,142 (n) 148,143 (n) Moludi 92% 0.08 [0.05-0.19] cases n/a n/a Nguyen 15% 0.85 [0.75-0.96] symp. case 345/1,054 433/1,082 Perez-Araluce 15% 0.85 [0.62-1.15] symp. case 52/1,103 214/3,300 Tau​2 = 0.07, I​2 = 92.2%, p = 0.0017 Prophylaxis 35% 0.65 [0.49-0.85] 397/150,340 647/153,052 35% improvement All studies 35% 0.65 [0.49-0.85] 397/150,340 647/153,052 35% improvement 5 diet COVID-19 case results c19early.com/dt May 2022 Tau​2 = 0.07, I​2 = 92.2%, p = 0.0017 Favors healthy diet Favors control
Figure 5. Random effects meta-analysis for cases.
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 6 shows a forest plot for random effects meta-analysis of all studies after exclusions.
[Magaña], unadjusted results with no group details.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Kim 72% 0.28 [0.10-0.82] m/s case 41 (n) 527 (n) Improvement, RR [CI] Treatment Control Merino 41% 0.59 [0.47-0.74] severe case 148,142 (n) 148,143 (n) Moludi 92% 0.08 [0.05-0.19] cases n/a n/a Ahmadi -3% 1.03 [0.77-1.39] death 185/206,286 62/75,264 Nguyen 15% 0.85 [0.75-0.96] symp. case 345/1,054 433/1,082 Perez-Araluce 78% 0.22 [0.03-1.77] severe case 1/1,103 10/3,300 Tau​2 = 0.29, I​2 = 92.3%, p = 0.0022 Prophylaxis 55% 0.45 [0.27-0.75] 531/356,626 505/228,316 55% improvement All studies 55% 0.45 [0.27-0.75] 531/356,626 505/228,316 55% improvement 6 diet COVID-19 studies after exclusions c19early.com/dt May 2022 Tau​2 = 0.29, I​2 = 92.3%, p = 0.0022 Effect extraction pre-specified(most serious outcome, see appendix) Favors healthy diet Favors control
Figure 6. 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.
Conclusion
People with healthier diets have reduced risk for COVID-19. Statistically significant improvement is seen for cases. 5 studies from 5 independent teams in 3 different countries show statistically significant improvements in isolation. Meta analysis using the most serious outcome reported shows 54% [27‑71%] improvement. Results are similar after exclusions.
Studies analyze diet quality before infection, and use different definitions of diet quality.
Study Notes
0 0.5 1 1.5 2+ Mortality -3% Improvement Relative Risk c19early.com/dt Ahmadi et al. Diet for COVID-19 Prophylaxis Favors healthy diet Favors control
[Ahmadi] Retrospective 468,569 adults in the UK, showing significantly lower COVID-19 mortality with physical activity.
0 0.5 1 1.5 2+ Moderate/severe case 72% Improvement Relative Risk Moderate/severe case (b) 59% Case 19% Case (b) 23% c19early.com/dt Kim et al. Diet for COVID-19 Prophylaxis Favors healthy diet Favors control
[Kim] Retrospective healthcare workers in six countries with exposure to COVID-19 patients, showing lower risk of moderate/severe COVID-19 with plant-based diets.
0 0.5 1 1.5 2+ Mortality 53% Improvement Relative Risk c19early.com/dt Magaña et al. Diet for COVID-19 Prophylaxis Favors healthy diet Favors control
[Magaña] Retrospective 89 COVID-19 patients in Spain, showing lower mortality with adherence to the Mediterranean diet.
0 0.5 1 1.5 2+ Severe case 41% Improvement Relative Risk Case 18% Case (b) 9% c19early.com/dt Merino et al. Diet for COVID-19 Prophylaxis Favors healthy diet Favors control
[Merino] Retrospective 592,571 participants in the UK and USA with 31,815 COVID-19 cases, showing lower risk or COVID-19 cases and severity for higher healthful plant-based diet scores. Notably, the assocation was less evident with higher levels of physical activity.
0 0.5 1 1.5 2+ Case 92% Improvement Relative Risk c19early.com/dt Moludi et al. Diet for COVID-19 Prophylaxis Favors healthy diet Favors control
[Moludi] Retrospective 60 COVID-19 hospitalized patients and 60 controls in Iran, showing pro-inflammatory diets associated with COVID-19 cases and severity. IR.KUMS.REC.1399·444, IR.TBZMED.REC.1399·225.
0 0.5 1 1.5 2+ Symptomatic case 15% Improvement Relative Risk Symptomatic case (b) 42% c19early.com/dt Nguyen et al. Diet for COVID-19 Prophylaxis Favors healthy diet Favors control
[Nguyen] Analysis of 3,947 participants in Vietnam, showing significantly lower risk of COVID-19-like symptoms with physical activity and with a healthy diet. The combination of being physically active and eating healthy reduced risk further compared to either alone. The analyzed period was Feb 14 to Mar 2, 2020, which may have been before testing was widely available.
0 0.5 1 1.5 2+ Severe case 78% Improvement Relative Risk Symptomatic case 15% Case 20% c19early.com/dt Perez-Araluce et al. Diet for COVID-19 Prophylaxis Favors healthy diet Favors control
[Perez-Araluce] Retrospective 5,194 participants in Spain with 382 COVID-19 cases, showing lower risk of COVID-19 with high adherence to a Mediterranean diet, with statistical significance only when excluding healthcare professionals.
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.com. Search terms were diet AND COVID-19. Automated searches are performed every few hours with notification of new matches. All studies regarding the use of diet 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 (3.9.12) with scipy (1.8.0), pythonmeta (1.26), numpy (1.22.2), statsmodels (0.14.0), and plotly (5.6.0).
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.com/dtmeta.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], 8/31/2021, retrospective, United Kingdom, Europe, peer-reviewed, 5 authors. risk of death, 3.0% higher, RR 1.03, p = 0.85, adjusted per study, good vs. poor, model 2, multivariable.
[Kim], 6/7/2021, retrospective, multiple countries, multiple regions, peer-reviewed, survey, 8 authors, study period 17 July, 2020 - 25 September, 2020. risk of moderate/severe case, 72.0% lower, OR 0.28, p = 0.02, higher quality diet 41, lower quality diet 527, adjusted per study, plant-based diets, multivariable, RR approximated with OR.
risk of moderate/severe case, 59.0% lower, OR 0.41, p = 0.05, higher quality diet 46, lower quality diet 522, adjusted per study, plant-based or pescatarian diets, multivariable, RR approximated with OR.
risk of case, 19.0% lower, OR 0.81, p = 0.24, higher quality diet 41, lower quality diet 527, adjusted per study, plant-based diets, multivariable, RR approximated with OR.
risk of case, 23.0% lower, OR 0.77, p = 0.14, higher quality diet 46, lower quality diet 522, adjusted per study, plant-based or pescatarian diets, multivariable, RR approximated with OR.
[Magaña], 12/31/2021, retrospective, Spain, Europe, peer-reviewed, 6 authors, excluded in exclusion analyses: unadjusted results with no group details. risk of death, 53.0% lower, HR 0.47, p = 0.049, higher quality diet 58, lower quality diet 31.
[Merino], 6/25/2021, retrospective, multiple countries, multiple regions, peer-reviewed, survey, 30 authors, study period 24 March, 2020 - 2 December, 2020. risk of severe case, 41.0% lower, HR 0.59, p < 0.001, higher quality diet 148,142, lower quality diet 148,143, adjusted per study, model 3, high vs. low hPDI, multivariable, Cox proportional hazards.
risk of case, 18.0% lower, HR 0.82, p < 0.001, higher quality diet 148,142, lower quality diet 148,143, adjusted per study, model 3, high vs. low hPDI, PCR+, multivariable, Cox proportional hazards.
risk of case, 9.0% lower, HR 0.91, p < 0.001, higher quality diet 148,142, lower quality diet 148,143, adjusted per study, model 3, high vs. low hPDI, multivariable, Cox proportional hazards.
[Moludi], 8/23/2021, retrospective, Iran, Middle East, peer-reviewed, 7 authors, study period June 2020 - July 2020. risk of case, 91.6% lower, OR 0.08, p < 0.001, case control OR, model 3, E-DII tertile 1 vs. tertile 3.
[Nguyen], 9/18/2021, retrospective, Vietnam, South Asia, peer-reviewed, survey, 17 authors, study period 14 February, 2020 - 2 March, 2020. risk of symptomatic case, 15.2% lower, RR 0.85, p = 0.006, higher quality diet 345 of 1,054 (32.7%), lower quality diet 433 of 1,082 (40.0%), NNT 14, adjusted per study, odds ratio converted to relative risk, high vs. low HES, COVID-19-like symptoms, multivariable.
[Perez-Araluce], 1/24/2022, retrospective, Spain, Europe, peer-reviewed, survey, 4 authors, study period March 2020 - December 2020. risk of severe case, 77.9% lower, RR 0.22, p = 0.15, higher quality diet 1 of 1,103 (0.1%), lower quality diet 10 of 3,300 (0.3%), NNT 471, odds ratio converted to relative risk, high vs. low adherence.
risk of symptomatic case, 15.1% lower, RR 0.85, p = 0.31, higher quality diet 52 of 1,103 (4.7%), lower quality diet 214 of 3,300 (6.5%), odds ratio converted to relative risk, high vs. low adherence.
risk of case, 19.7% lower, RR 0.80, p = 0.14, higher quality diet 58 of 1,103 (5.3%), lower quality diet 248 of 3,300 (7.5%), odds ratio converted to relative risk, high vs. low adherence.
Supplementary Data
References
Please send us corrections, updates, or comments. Vaccines and treatments are both valuable and complementary. All practical, effective, and safe means should be used. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. Denying the efficacy of any method increases mortality, morbidity, collateral damage, and the risk of endemic status. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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