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Dexamethasone for COVID-19: real-time meta analysis of 11 studies

@CovidAnalysis, June 2025, Version 8V8
Serious Outcome Risk
Hospital Icon Control
Hospital Icon Dexamethasone
0 0.5 1 1.5+ All studies -12% 11 11K Improvement, Studies, Patients Relative Risk Mortality -10% 9 11K Ventilation 2% 2 5K ICU admission -351% 2 156 Hospitalization -51% 3 162 Recovery -67% 2 6K RCTs 10% 4 6K RCT mortality 12% 2 6K Early -132% 2 678 Late 1% 9 11K Dexamethasone for COVID-19 c19early.org June 2025 after exclusions Favorsdexamethasone Favorscontrol
Abstract
Meta analysis using the most serious outcome reported shows 12% [-7‑34%] higher risk, without reaching statistical significance.
Serious Outcome Risk
Hospital Icon Control
Hospital Icon Dexamethasone
0 0.5 1 1.5+ All studies -12% 11 11K Improvement, Studies, Patients Relative Risk Mortality -10% 9 11K Ventilation 2% 2 5K ICU admission -351% 2 156 Hospitalization -51% 3 162 Recovery -67% 2 6K RCTs 10% 4 6K RCT mortality 12% 2 6K Early -132% 2 678 Late 1% 9 11K Dexamethasone for COVID-19 c19early.org June 2025 after exclusions Favorsdexamethasone Favorscontrol
While overall meta-analysis shows poor results, dexamethasone may reduce risk for a subgroup of later stage patients1,2.
All data and sources to reproduce this analysis are in the appendix.
Evolution of COVID-19 clinical evidence Meta analysis results over time Dexamethasone p=0.25 Vitamin D p<0.0000000001 2020 2021 2022 2023 2024 2025 Lowerrisk Higherrisk c19early.org June 2025 100% 50% 0% -50%
Dexamethasone for COVID-19 — Highlights
Meta analysis of studies to date shows no significant improvements with dexamethasone.
Real-time updates and corrections with a consistent protocol for 172 treatments. Outcome specific analysis and combined evidence from all studies including treatment delay, a primary confounding factor.
A
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ COPPER Kocks (DB RCT) -300% 4.00 [0.27-58.2] hosp. 2/4 0/2 Improvement, RR [CI] Treatment Control Madamombe -130% 2.30 [1.60-3.40] death 245 (n) 427 (n) Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Early treatment -132% 2.32 [1.60-3.38] 2/249 0/429 132% higher risk CoDEX Tomazini (RCT) 3% 0.97 [0.72-1.31] death 85/151 91/148 Improvement, RR [CI] Treatment Control RECOVERY Horby (RCT) 17% 0.83 [0.75-0.93] death 482/2,104 1,110/4,321 Mourad 10% 0.90 [0.86-0.95] death EARLY-DEX Franco-Mor.. (RCT) -134% 2.34 [0.45-12.3] ventilation 4/58 2/68 Yen -103% 2.03 [1.40-2.94] death 572 (n) 1,624 (n) Bhat (PSM) -35% 1.35 [0.88-2.07] death 46/529 34/529 Zhao (PSM) 34% 0.66 [0.47-0.92] death 288 (n) 288 (n) Garneau -31% 1.31 [0.09-19.0] death 1/13 1/17 Bepouka -104% 2.04 [0.20-25.0] death 70 (n) 340 (n) Tau​2 = 0.02, I​2 = 73.9%, p = 0.87 Late treatment 1% 0.99 [0.85-1.15] 618/3,785 1,238/7,335 1% lower risk All studies -12% 1.12 [0.93-1.34] 620/4,034 1,238/7,764 12% higher risk 11 dexamethasone COVID-19 studies c19early.org June 2025 Tau​2 = 0.05, I​2 = 81.9%, p = 0.25 Effect extraction pre-specified(most serious outcome, see appendix) Favors dexamethasone Favors control
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ COPPER Kocks (DB RCT) -300% hospitalization Improvement Relative Risk [CI] Madamombe -130% death Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Early treatment -132% 132% higher risk CoDEX Tomazini (RCT) 3% death RECOVERY Horby (RCT) 17% death Mourad 10% death EARLY-DEX Franco-Mo.. (RCT) -134% ventilation Yen -103% death Bhat (PSM) -35% death Zhao (PSM) 34% death Garneau -31% death Bepouka -104% death Tau​2 = 0.02, I​2 = 73.9%, p = 0.87 Late treatment 1% 1% lower risk All studies -12% 12% higher risk 11 dexamethasone C19 studies c19early.org June 2025 Tau​2 = 0.05, I​2 = 81.9%, p = 0.25 Effect extraction pre-specifiedRotate device for details Favors dexamethasone Favors control
B
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Figure 1. A. Random effects meta-analysis. This plot shows pooled effects, see the specific outcome analyses for individual outcomes. Analysis validating pooled outcomes for COVID-19 can be found below. Effect extraction is pre-specified, using the most serious outcome reported. For details see the appendix. B. Timeline of results in dexamethasone studies.
Figure 2. SARS-CoV-2 spike protein fibrin binding leads to thromboinflammation and neuropathology, from3.
SARS-CoV-2 infection primarily begins in the upper respiratory tract and may progress to the lower respiratory tract, other tissues, and the nervous and cardiovascular systems, which may lead to cytokine storm, pneumonia, ARDS, neurological injury4-16 and cognitive deficits7,12, cardiovascular complications17-21, organ failure, and death. Even mild untreated infections may result in persistent cognitive deficits22—the spike protein binds to fibrin leading to fibrinolysis-resistant blood clots, thromboinflammation, and neuropathology. Minimizing replication as early as possible is recommended.
SARS-CoV-2 infection and replication involves the complex interplay of 100+ host and viral proteins and other factorsA,23-30, providing many therapeutic targets for which many existing compounds have known activity. Scientists have predicted that over 9,000 compounds may reduce COVID-19 risk31, either by directly minimizing infection or replication, by supporting immune system function, or by minimizing secondary complications.
We analyze all significant controlled studies of dexamethasone 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, Randomized Controlled Trials (RCTs), and higher quality studies.
Figure 3 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.
regular treatment to prevent or minimize infectionstreat immediately on symptoms or shortly thereafterlate stage after disease progressionexposed to virusEarly TreatmentProphylaxisTreatment delayLate Treatment
Figure 3. Treatment stages.
Table 1 summarizes the results for all stages combined, for Randomized Controlled Trials, after exclusions, and for specific outcomes. Table 2 shows results by treatment stage. Figure 4 plots individual results by treatment stage. Figure 5, 6, 7, 8, 9, and 10 show forest plots for random effects meta-analysis of all studies with pooled effects, mortality results, ventilation, ICU admission, hospitalization, and recovery.
Table 1. Random effects meta-analysis for all stages combined, for Randomized Controlled Trials, after exclusions, and for specific outcomes. Results show the percentage improvement with treatment and the 95% confidence interval. ** p<0.01  **** p<0.0001.
Improvement Studies Patients Authors
All studies-12% [-34‑7%]11 11,798 139
After exclusions1% [-16‑15%]10 11,126 130
Randomized Controlled TrialsRCTs10% [-6‑24%]4 6,856 83
Mortality-10% [-32‑9%]9 11,666 116
VentilationVent.2% [-131‑58%]2 5,544 40
ICU admissionICU-351% [-2454‑20%]2 156 20
HospitalizationHosp.-51% [-244‑34%]3 162 29
Recovery-67% [-939‑73%]2 6,431 35
RCT mortality12% [-1‑24%]2 6,724 60
Table 2. 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<0.01  **** p<0.0001.
Early treatment Late treatment
All studies-132% [-238‑-60%]
****
1% [-15‑15%]
After exclusions-300% [-5722‑73%]1% [-15‑15%]
Randomized Controlled TrialsRCTs-300% [-5722‑73%]11% [-4‑24%]
Mortality-130% [-240‑-60%]
****
2% [-14‑16%]
VentilationVent.2% [-131‑58%]
ICU admissionICU-351% [-2454‑20%]
HospitalizationHosp.-300% [-5722‑73%]-40% [-252‑44%]
Recovery-600% [-8840‑45%]9% [3‑15%]
**
RCT mortality12% [-1‑24%]
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Figure 4. 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.
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Figure 5. Random effects meta-analysis for all studies. This plot shows pooled effects, see the specific outcome analyses for individual outcomes. Analysis validating pooled outcomes for COVID-19 can be found below. Effect extraction is pre-specified, using the most serious outcome reported. For details see the appendix.
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Figure 6. Random effects meta-analysis for mortality results.
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Figure 7. Random effects meta-analysis for ventilation.
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Figure 8. Random effects meta-analysis for ICU admission.
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Figure 9. Random effects meta-analysis for hospitalization.
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Figure 10. Random effects meta-analysis for recovery.
Figure 11 shows a comparison of results for RCTs and non-RCT studies. Figure 12 and 13 show forest plots for random effects meta-analysis of all Randomized Controlled Trials and RCT mortality results. RCT results are included in Table 1 and Table 2.
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Figure 11. Results for RCTs and non-RCT studies.
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Figure 12. Random effects meta-analysis for all Randomized Controlled Trials. This plot shows pooled effects, see the specific outcome analyses for individual outcomes. Analysis validating pooled outcomes for COVID-19 can be found below. Effect extraction is pre-specified, using the most serious outcome reported. For details see the appendix.
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Figure 13. Random effects meta-analysis for RCT mortality results.
RCTs help to make study groups more similar and can provide a higher level of evidence, however they are subject to many biases32, and analysis of double-blind RCTs has identified extreme levels of bias33. 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, reporting, 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.
RCTs are expensive and many RCTs are funded by pharmaceutical companies or interests closely aligned with pharmaceutical companies. For COVID-19, this creates an incentive to show efficacy for patented commercial products, and an incentive to show a lack of efficacy for inexpensive treatments. The bias is expected to be significant, for example Als-Nielsen et al. analyzed 370 RCTs from Cochrane reviews, showing that trials funded by for-profit organizations were 5 times more likely to recommend the experimental drug compared with those funded by nonprofit organizations. For COVID-19, some major philanthropic organizations are largely funded by investments with extreme conflicts of interest for and against specific COVID-19 interventions.
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 172 treatments we have analyzed, 67% 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.
Currently, 54 of the treatments we analyze show statistically significant efficacy or harm, defined as ≥10% decreased risk or >0% increased risk from ≥3 studies. Of these, 59% have been confirmed in RCTs, with a mean delay of 7.7 months (66% with 8.9 months delay for low-cost treatments). The remaining treatments either have no RCTs, or the point estimate is consistent.
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.
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 can be easily influenced by potential bias, may ignore or underemphasize serious issues not captured in the checklists, and may overemphasize issues unlikely to alter outcomes in specific cases (for example certain specifics of randomization with a very large effect size and well-matched baseline characteristics).
The studies excluded are as below. Figure 14 shows a forest plot for random effects meta-analysis of all studies after exclusions.
Madamombe, substantial unadjusted confounding by indication possible.
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Figure 14. Random effects meta-analysis for all studies after exclusions. This plot shows pooled effects, see the specific outcome analyses for individual outcomes. Analysis validating pooled outcomes for COVID-19 can be found below. Effect extraction is pre-specified, using the most serious outcome reported. For details 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 hours36,37. Baloxavir marboxil studies for influenza also show that treatment delay is critical — Ikematsu et al. report an 86% reduction in cases for post-exposure prophylaxis, Hayden et al. 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 et al. report only 2.5 hours improvement for inpatient treatment.
Table 3. Studies of baloxavir marboxil for influenza show that early treatment is more effective.
Treatment delayResult
Post-exposure prophylaxis86% fewer cases38
<24 hours-33 hours symptoms39
24-48 hours-13 hours symptoms39
Inpatients-2.5 hours to improvement40
Figure 15 shows a mixed-effects meta-regression for efficacy as a function of treatment delay in COVID-19 studies from 172 treatments, showing that efficacy declines rapidly with treatment delay. Early treatment is critical for COVID-19.
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Figure 15. Early treatment is more effective. Meta-regression showing efficacy as a function of treatment delay in COVID-19 studies from 172 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, for example as in López-Medina et al.
Efficacy may depend critically on the distribution of SARS-CoV-2 variants encountered by patients. Risk varies significantly across variants42, for example the Gamma variant shows significantly different characteristics43-46. Different mechanisms of action may be more or less effective depending on variants, for example the degree to which TMPRSS2 contributes to viral entry can differ across variants47,48.
Effectiveness may depend strongly on the dosage and treatment regimen.
The quality of medications may vary significantly between manufacturers and production batches, which may significantly affect efficacy and safety. Williams et al. analyze ivermectin from 11 different sources, showing highly variable antiparasitic efficacy across different manufacturers. Xu et al. analyze a treatment from two different manufacturers, showing 9 different impurities, with significantly different concentrations for each manufacturer.
The use of other treatments may significantly affect outcomes, including supplements, other medications, or other interventions such as prone positioning. Treatments may be synergistic51-67, therefore efficacy may depend strongly on combined treatments.
Across all studies there is a strong association between different outcomes, for example improved recovery is strongly associated with lower mortality. However, efficacy may differ depending on the effect measured, for example a treatment may be more effective against secondary complications and have minimal effect on viral clearance.
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. 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.
For COVID-19, delay in clinical results translates into additional death and morbidity, as well as additional economic and societal damage. Combining the results of studies reporting different outcomes is required. There may be no mortality in a trial with low-risk patients, however a reduction in severity or improved viral clearance may translate into lower mortality in a high-risk population. Different studies may report lower severity, improved recovery, and lower mortality, and the significance may be very high when combining the results. "The studies reported different outcomes" is not a good reason for disregarding results. Pooling the results of studies reporting different outcomes allows us to use more of the available information. Logically we should, and do, use additional information when evaluating treatments—for example dose-response and treatment delay-response relationships provide additional evidence of efficacy that is considered when reviewing the evidence for a treatment.
We present both specific outcome and pooled analyses. In order to combine the results of studies reporting different outcomes we use the most serious outcome reported in each study, based on the thesis that improvement in the most serious outcome provides comparable measures of efficacy for a treatment. A critical advantage of this approach is simplicity and transparency. There are many other ways to combine evidence for different outcomes, along with additional evidence such as dose-response relationships, however these increase complexity.
Trials with high-risk patients may be restricted due to ethics for treatments that are known or expected to be effective, and they increase difficulty for recruiting. Using less severe outcomes as a proxy for more serious outcomes allows faster and safer collection of evidence.
For many COVID-19 treatments, a reduction in mortality logically follows from a reduction in hospitalization, which follows from a reduction in symptomatic cases, which follows from a reduction in PCR positivity. We can directly test this for COVID-19.
Analysis of the the association between different outcomes across studies from all 172 treatments we cover confirms the validity of pooled outcome analysis for COVID-19. Figure 16 shows that lower hospitalization is very strongly associated with lower mortality (p < 0.000000000001). Similarly, Figure 17 shows that improved recovery is very strongly associated with lower mortality (p < 0.000000000001). Considering the extremes, Singh et al. show an association between viral clearance and hospitalization or death, with p = 0.003 after excluding one large outlier from a mutagenic treatment, and based on 44 RCTs including 52,384 patients. Figure 18 shows that improved viral clearance is strongly associated with fewer serious outcomes. The association is very similar to Singh et al., with higher confidence due to the larger number of studies. As with Singh et al., the confidence increases when excluding the outlier treatment, from p = 0.00000009 to p = 0.0000000039.
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Figure 16. Lower hospitalization is associated with lower mortality, supporting pooled outcome analysis.
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Figure 17. Improved recovery is associated with lower mortality, supporting pooled outcome analysis.
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Figure 16. Improved viral clearance is associated with fewer serious outcomes, supporting pooled outcome analysis.
Currently, 54 of the treatments we analyze show statistically significant efficacy or harm, defined as ≥10% decreased risk or >0% increased risk from ≥3 studies. 90% of these have been confirmed with one or more specific outcomes, with a mean delay of 4.9 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 7.3 months. Figure 19 shows when treatments were found effective during the pandemic. Pooled outcomes often resulted in earlier detection of efficacy.
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Figure 19. 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.
Pooled analysis could hide efficacy, for example a treatment that is beneficial for late stage patients but has no effect on viral clearance may show no efficacy if most studies only examine viral clearance. In practice, it is rare for a non-antiviral treatment to report viral clearance and to not report clinical outcomes; and in practice other sources of heterogeneity such as difference in treatment delay is more likely to hide efficacy.
Analysis validates the use of pooled effects and shows significantly faster detection of efficacy on average. However, as with all meta analyses, it is important to review the different studies included. We also present 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 results69-72. For dexamethasone, there is currently not enough data to evaluate publication bias with high confidence.
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 < 0.0573-80. 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.
Log Risk Ratio Standard Error 1.406 1.055 0.703 0.352 0 -3 -2 -1 0 1 2 A: Simulated perfect trials p > 0.05 Log Risk Ratio Standard Error 1.433 1.074 0.716 0.358 0 -4 -3 -2 -1 0 1 2 B: Simulated perfect trials with varying treatment delay p < 0.0001
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. Dexamethasone for COVID-19 lacks this because it is off-patent, has multiple manufacturers, and is very low cost. In contrast, most COVID-19 dexamethasone 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 dexamethasone 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 for 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 with conflicts of interest 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 alone51-67. 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 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.
Currently all studies are peer-reviewed. While overall meta-analysis shows poor results, dexamethasone may reduce risk for a subgroup of later stage patients1,2.
Additional preclinical or review papers suggesting potential benefits of dexamethasone for COVID-19 include89-124. We have not reviewed these studies in detail.
SARS-CoV-2 infection and replication involves a complex interplay of 100+ host and viral proteins and other factors23-30, providing many therapeutic targets. Over 9,000 compounds have been predicted to reduce COVID-19 risk31, either by directly minimizing infection or replication, by supporting immune system function, or by minimizing secondary complications. Figure 21 shows an overview of the results for dexamethasone in the context of multiple COVID-19 treatments, and Figure 22 shows a plot of efficacy vs. cost for COVID-19 treatments.
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Figure 21. Scatter plot showing results within the context of multiple COVID-19 treatments. Diamonds shows the results of random effects meta-analysis. 0.6% of 9,000+ proposed treatments show efficacy125.
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Figure 22. Efficacy vs. cost for COVID-19 treatments.
Meta analysis using the most serious outcome reported shows 12% [-7‑34%] higher risk, without reaching statistical significance.
While overall meta-analysis shows poor results, dexamethasone may reduce risk for a subgroup of later stage patients1,2.
Mortality -104% Improvement Relative Risk Dexamethasone  Bepouka et al.  LATE TREATMENT Is late treatment with dexamethasone beneficial for COVID-19? Retrospective 410 patients in DR Congo (March 2020 - January 2022) Higher mortality with dexamethasone (not stat. sig., p=0.55) c19early.org Bepouka et al., Infection and Drug Res.., May 2025 Favorsdexamethasone Favorscontrol 0 0.5 1 1.5 2+
Retrospective 410 hospitalized COVID-19 patients in the Democratic Republic of Congo showing significantly lower mortality with vitamin C treatment. Submit Corrections or Updates.
Mortality -35% Improvement Relative Risk Improvement -46% Dexamethasone  Bhat et al.  LATE TREATMENT Is late treatment with dexamethasone beneficial for COVID-19? PSM retrospective 1,058 patients in the USA (Mar 2020 - Jun 2022) Worse improvement with dexamethasone (p=0.023) c19early.org Bhat et al., The J. Clinical Endocrino.., Oct 2024 Favorsdexamethasone Favorscontrol 0 0.5 1 1.5 2+
Retrospective propensity score matched study of 529 hospitalized diabetic COVID-19 patients showing no significant difference in mortality or clinical improvement with dexamethasone treatment. Submit Corrections or Updates.
Ventilation -134% Improvement Relative Risk ICU admission -217% ARDS -17% Hospitalization time 3% Dexamethasone  EARLY-DEX  LATE TREATMENT  RCT Is late treatment with dexamethasone beneficial for COVID-19? RCT 126 patients in Spain (June 2021 - January 2022) Higher ventilation (p=0.41) and ICU admission (p=0.46), not sig. c19early.org Franco-Moreno et al., Frontiers in Med.., Jul 2024 Favorsdexamethasone Favorscontrol 0 0.5 1 1.5 2+
RCT 126 hospitalized COVID-19 pneumonia patients not requiring oxygen at admission, showing no significant difference in outcomes with dexamethasone treatment. Submit Corrections or Updates.
Mortality -31% Improvement Relative Risk ICU admission -423% Hospitalization time -155% Dexamethasone  Garneau et al.  LATE TREATMENT Is late treatment with dexamethasone beneficial for COVID-19? Retrospective 30 patients in the USA (June 2020 - June 2022) Higher ICU admission (p=0.14) and longer hospitalization (p=0.063), not sig. c19early.org Garneau et al., PLOS ONE, November 2024 Favorsdexamethasone Favorscontrol 0 0.5 1 1.5 2+
Retrospective 30 hospitalized patients with sickle cell disease (SCD) showing increased risk of venous thromboembolism (VTE) with dexamethasone treatment for COVID-19. There were also trends towards increased ICU admission and longer hospital stays with dexamethasone, without statistical significance. Submit Corrections or Updates.
Mortality 17% Improvement Relative Risk Ventilation 21% Discharge 9% Dexamethasone  RECOVERY  LATE TREATMENT  RCT Is late treatment with dexamethasone beneficial for COVID-19? RCT 6,425 patients in the United Kingdom (March - June 2020) Lower mortality (p=0.00072) and ventilation (p=0.026) c19early.org Horby et al., New England J. Medicine, Feb 2021 Favorsdexamethasone Favorscontrol 0 0.5 1 1.5 2+
RCT 6,425 hospitalized COVID-19 patients showing lower 28-day mortality with dexamethasone treatment. The benefit was most pronounced in patients who had symptoms for more than 7 days at randomization, suggesting dexamethasone is most effective when the disease is dominated by inflammatory processes rather than viral replication. Submit Corrections or Updates.
Hospitalization -300% Improvement Relative Risk Severe case -450% Recovery -600% Dexamethasone  COPPER  EARLY TREATMENT  DB RCT Is early treatment with dexamethasone beneficial for COVID-19? Double-blind RCT 6 patients in Netherlands Higher hospitalization (p=0.47) and severe cases (p=0.4), not sig. c19early.org Kocks et al., ERJ Open Research, April 2022 Favorsdexamethasone Favorscontrol 0 0.5 1 1.5 2+
Pilot RCT of 7 outpatients with non-severe COVID-19 suggesting potential harmful effects of dexamethasone treatment. Time to recovery was significantly longer in the dexamethasone group compared to controls (p=0.03). Authors note that systemic corticosteroids, while beneficial for hospitalized COVID-19 patients requiring oxygen, may be harmful in non-severe cases by potentially inhibiting normal immune response when administered too early. Submit Corrections or Updates.
Mortality -130% Improvement Relative Risk Dexamethasone  Madamombe et al.  EARLY TREATMENT Is early treatment with dexamethasone beneficial for COVID-19? Retrospective 672 patients in Zimbabwe (April 2020 - April 2022) Higher mortality with dexamethasone (p=0.000018) c19early.org Madamombe et al., Pan African Medical J., Mar 2023 Favorsdexamethasone Favorscontrol 0 0.5 1 1.5 2+
Retrospective 672 COVID-19 patients in Zimbabwe, showing higher mortality with dexamethasone treatment. Submit Corrections or Updates.
Mortality, all patients 10% Improvement Relative Risk Mortality, no oxygen 10% Mortality, supplement.. 8% Mortality, NIPPV 13% Mortality, MV/ECMO 18% Dexamethasone  Mourad et al.  LATE TREATMENT Is late treatment with dexamethasone beneficial for COVID-19? Retrospective 56,368 patients in the USA (July 2020 - October 2021) Lower mortality with dexamethasone (p=0.00024) c19early.org Mourad et al., JAMA Network Open, April 2023 Favorsdexamethasone Favorscontrol 0 0.5 1 1.5 2+
PSM retrospective 80,699 hospitalized COVID-19 patients showing reduced mortality or discharge to hospice with dexamethasone in patients requiring supplemental oxygen or mechanical ventilation/ECMO, but no significant difference in patients not requiring supplemental oxygen or on NIPPV. Submit Corrections or Updates.
Mortality 3% Improvement Relative Risk 6-point scale 34% Dexamethasone  CoDEX  LATE TREATMENT  RCT Is late treatment with dexamethasone beneficial for COVID-19? RCT 299 patients in Brazil (April - June 2020) No significant difference in mortality c19early.org Tomazini et al., JAMA, October 2020 Favorsdexamethasone Favorscontrol 0 0.5 1 1.5 2+
RCT 299 patients with moderate or severe COVID-19-related ARDS showing increased ventilator-free days with dexamethasone treatment. There was no significant difference in 28-day mortality (56.3% vs 61.5%), ICU-free days, or mechanical ventilation duration. Submit Corrections or Updates.
Mortality -103% Improvement Relative Risk Dexamethasone for COVID-19  Yen et al.  LATE TREATMENT Is late treatment with dexamethasone beneficial for COVID-19? Retrospective 2,196 patients in Taiwan (January - July 2022) Higher mortality with dexamethasone (p=0.0002) c19early.org Yen et al., BMC Infectious Diseases, Aug 2024 Favorsdexamethasone Favorscontrol 0 0.5 1 1.5 2+
Retrospective 2,196 COVID-19 patients in Taiwan (49% mild cases, 44% moderate, 7% severe) showing significantly higher mortality with dexamethasone. Submit Corrections or Updates.
Mortality, day 365 34% Improvement Relative Risk Mortality, day 28 33% Dexamethasone  Zhao et al.  LATE TREATMENT Is late treatment with dexamethasone beneficial for COVID-19? PSM retrospective 576 patients in the USA Lower mortality with dexamethasone (p=0.014) c19early.org Zhao et al., BMC Infectious Diseases, Nov 2024 Favorsdexamethasone Favorscontrol 0 0.5 1 1.5 2+
Retrospective 576 hospitalized COVID-19 patients showing lower mortality with dexamethasone treatment. Submit Corrections or Updates.
We perform ongoing searches of PubMed, medRxiv, Europe PMC, ClinicalTrials.gov, The Cochrane Library, Google Scholar, Research Square, ScienceDirect, Oxford University Press, the reference lists of other studies and meta-analyses, and submissions to the site c19early.org. Search terms are dexamethasone and COVID-19 or SARS-CoV-2. Automated searches are performed twice daily, with all matches reviewed for inclusion. All studies regarding the use of dexamethasone 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. Studies with major unexplained data issues, for example major outcome data that is impossible to be correct with no response from the authors, are excluded. This is a living analysis and is updated regularly.
Figure 23. Mid-recovery results can more accurately reflect efficacy when almost all patients recover. Mateja et al. confirm that intermediate viral load results more accurately reflect hospitalization/death.
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 reported then they are both used in specific outcome analyses, while mortality is used for pooled analysis. If symptomatic results are reported at multiple times, we use the latest time, for example if mortality results are provided at 14 days and 28 days, the results at 28 days have preference. Mortality alone is preferred over combined outcomes. Outcomes with zero events in both arms are not used, the next most serious outcome with one or more events is used. 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 outcomes are considered more important than viral outcomes. 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 little or no room for an effective treatment to do better, however faster recovery is valuable. An IPD meta-analysis confirms that intermediate viral load reduction is more closely associated with hospitalization/death than later viral load reduction126. 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 compute the relative risk when possible, or convert to a relative risk according to Zhang et al. Reported confidence intervals and p-values are used when available, and adjusted values are used when provided. If multiple types of adjustments are reported propensity score matching and multivariable regression has preference over propensity score matching or weighting, which has preference over multivariable regression. Adjusted 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 1130. 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 (3.13.4) with scipy (1.15.3), pythonmeta (1.26), numpy (2.3.0), statsmodels (0.14.4), and plotly (6.1.2).
Forest plots are computed using PythonMeta131 with the DerSimonian and Laird random effects model (the fixed effect assumption is not plausible in this case) and inverse variance weighting. Results are presented with 95% confidence intervals. Heterogeneity among studies was assessed using the I2 statistic. Mixed-effects meta-regression results are computed with R (4.4.0) using the metafor (4.6-0) and rms (6.8-0) packages, and using the most serious sufficiently powered outcome. For all statistical tests, a p-value less than 0.05 was considered statistically significant. Grobid 0.8.2 is used to parse PDF documents.
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 effective36,37.
We received no funding, this research is done in our spare time. We have no affiliations with any pharmaceutical companies or political parties.
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/dexmeta.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.
Kocks, 4/30/2022, Double Blind Randomized Controlled Trial, Netherlands, peer-reviewed, 9 authors, trial NCT04746430 (history) (COPPER). risk of hospitalization, 300.0% higher, RR 4.00, p = 0.47, treatment 2 of 4 (50.0%), control 0 of 2 (0.0%), continuity correction due to zero event (with reciprocal of the contrasting arm).
risk of severe case, 450.0% higher, RR 5.50, p = 0.40, treatment 3 of 4 (75.0%), control 0 of 2 (0.0%), continuity correction due to zero event (with reciprocal of the contrasting arm).
risk of no recovery, 600.0% higher, RR 7.00, p = 0.07, treatment 4 of 4 (100.0%), control 0 of 2 (0.0%), continuity correction due to zero event (with reciprocal of the contrasting arm).
Madamombe, 3/21/2023, retrospective, Zimbabwe, peer-reviewed, 9 authors, study period April 2020 - April 2022, excluded in exclusion analyses: substantial unadjusted confounding by indication possible. risk of death, 130.0% higher, OR 2.30, p < 0.001, treatment 245, control 427, adjusted per study, multivariable, RR approximated with OR.
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.
Bepouka, 5/14/2025, retrospective, DR Congo, peer-reviewed, 14 authors, study period 20 March, 2020 - 2 January, 2022. risk of death, 104.1% higher, OR 2.04, p = 0.55, treatment 70, control 340, adjusted per study, inverted to make OR<1 favor treatment, multivariable, RR approximated with OR.
Bhat, 10/17/2024, retrospective, USA, peer-reviewed, 7 authors, study period 4 March, 2020 - 25 June, 2022. risk of death, 35.3% higher, RR 1.35, p = 0.20, treatment 46 of 529 (8.7%), control 34 of 529 (6.4%), propensity score matching, day 28.
risk of no improvement, 45.6% higher, RR 1.46, p = 0.02, treatment 83 of 529 (15.7%), control 57 of 529 (10.8%), propensity score matching, day 28.
Franco-Moreno, 7/17/2024, Randomized Controlled Trial, Spain, peer-reviewed, mean age 48.8, 14 authors, study period June 2021 - January 2022, average treatment delay 9.0 days, trial NCT04836780 (history) (EARLY-DEX). risk of mechanical ventilation, 134.5% higher, RR 2.34, p = 0.41, treatment 4 of 58 (6.9%), control 2 of 68 (2.9%).
risk of ICU admission, 217.2% higher, RR 3.17, p = 0.46, treatment 1 of 58 (1.7%), control 0 of 68 (0.0%), continuity correction due to zero event (with reciprocal of the contrasting arm).
risk of ARDS, 17.2% higher, RR 1.17, p = 0.81, treatment 10 of 58 (17.2%), control 10 of 68 (14.7%).
hospitalization time, 3.0% lower, relative time 0.97, p = 0.88, treatment mean 6.4 (±5.0) n=58, control mean 6.6 (±8.7) n=68.
Garneau, 11/26/2024, retrospective, USA, peer-reviewed, median age 33.7, 6 authors, study period 1 June, 2020 - 26 June, 2022. risk of death, 30.8% higher, RR 1.31, p = 1.00, treatment 1 of 13 (7.7%), control 1 of 17 (5.9%).
risk of ICU admission, 423.1% higher, RR 5.23, p = 0.14, treatment 4 of 13 (30.8%), control 1 of 17 (5.9%).
hospitalization time, 154.5% higher, relative time 2.55, p = 0.06, treatment 13, control 17.
Horby, 2/25/2021, Randomized Controlled Trial, United Kingdom, peer-reviewed, mean age 66.1, 26 authors, study period 19 March, 2020 - 8 June, 2020, trial NCT04381936 (history) (RECOVERY). risk of death, 17.0% lower, RR 0.83, p < 0.001, treatment 482 of 2,104 (22.9%), control 1,110 of 4,321 (25.7%), NNT 36, adjusted per study.
risk of mechanical ventilation, 21.0% lower, RR 0.79, p = 0.03, treatment 110 of 1,780 (6.2%), control 298 of 3,638 (8.2%), NNT 50, adjusted per study.
risk of no hospital discharge, 9.1% lower, RR 0.91, p = 0.003, treatment 2,104, control 4,321, adjusted per study, inverted to make RR<1 favor treatment.
Mourad, 4/17/2023, retrospective, USA, peer-reviewed, median age 64.0, 7 authors, study period 1 July, 2020 - 31 October, 2021. risk of death, 9.6% lower, RR 0.90, p < 0.001, treatment 48,579, control 7,789, adjusted per study, all patients.
risk of death, 10.0% lower, OR 0.90, p = 0.14, treatment 7,537, control 5,503, adjusted per study, no oxygen, mortality or discharge to hospice, RR approximated with OR.
risk of death, 8.0% lower, OR 0.92, p = 0.01, treatment 48,579, control 7,789, adjusted per study, supplemental oxygen, mortality or discharge to hospice, RR approximated with OR.
risk of death, 13.0% lower, OR 0.87, p = 0.12, treatment 6,826, control 792, adjusted per study, NIPPV, mortality or discharge to hospice, RR approximated with OR.
risk of death, 18.0% lower, OR 0.82, p = 0.04, treatment 2,660, control 1,013, adjusted per study, MV/ECMO, mortality or discharge to hospice, RR approximated with OR.
Tomazini, 10/6/2020, Randomized Controlled Trial, Brazil, peer-reviewed, 34 authors, study period 17 April, 2020 - 23 June, 2020, trial NCT04327401 (history) (CoDEX). risk of death, 3.0% lower, HR 0.97, p = 0.85, treatment 85 of 151 (56.3%), control 91 of 148 (61.5%), NNT 19, adjusted per study, day 28.
6-point scale, 34.0% lower, OR 0.66, p = 0.07, treatment 151, control 148, day 15, RR approximated with OR.
Yen, 8/20/2024, retrospective, Taiwan, peer-reviewed, 6 authors, study period 1 January, 2022 - 31 July, 2022. risk of death, 103.0% higher, HR 2.03, p < 0.001, treatment 572, control 1,624, adjusted per study, multivariable, Cox proportional hazards.
Zhao, 11/25/2024, retrospective, USA, peer-reviewed, 7 authors. risk of death, 34.0% lower, HR 0.66, p = 0.01, treatment 288, control 288, propensity score matching, day 365.
risk of death, 33.0% lower, HR 0.67, p = 0.01, treatment 288, control 288, propensity score matching, day 28.
Viral infection and replication involves attachment, entry, uncoating and release, genome replication and transcription, translation and protein processing, assembly and budding, and release. Each step can be disrupted by therapeutics.
Please send us corrections, updates, or comments. c19early involves the extraction of 200,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. 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. IMA and WCH provide treatment protocols.
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