The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index; none of the 8 sources its claims cite is checked for support yet.
Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis
Open accessAbstract
Importance: Effective therapies for patients with coronavirus disease 2019 (COVID-19) are needed, and clinical trial data have demonstrated that low-dose dexamethasone reduced mortality in hospitalized patients with COVID-19 who required respiratory support. Objective: To estimate the association between administration of corticosteroids compared with usual care or placebo and 28-day all-cause mortality. Design, Setting, and Participants: Prospective meta-analysis that pooled data from 7 randomized clinical trials that evaluated the efficacy of corticosteroids in 1703 critically ill patients with COVID-19. The trials were conducted in 12 countries from February 26, 2020, to June 9, 2020, and the date of final follow-up was July 6, 2020. Pooled data were aggregated from the individual trials, overall, and in predefined subgroups. Risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance-weighted fixed-effect meta-analysis of overall mortality, with the association between the intervention and mortality quantified using odds ratios (ORs). Random-effects meta-analyses also were conducted (with the Paule-Mandel estimate of heterogeneity and the Hartung-Knapp adjustment) and an inverse variance-weighted fixed-effect analysis using risk ratios. Exposures: Patients had been randomized to receive systemic dexamethasone, hydrocortisone, or methylprednisolone (678 patients) or to receive usual care or placebo (1025 patients). Main Outcomes and Measures: The primary outcome measure was all-cause mortality at 28 days after randomization. A secondary outcome was investigator-defined serious adverse events. Results: A total of 1703 patients (median age, 60 years [interquartile range, 52-68 years]; 488 [29%] women) were included in the analysis. Risk of bias was assessed as "low" for 6 of the 7 mortality results and as "some concerns" in 1 trial because of the randomization method. Five trials reported mortality at 28 days, 1 trial at 21 days, and 1 trial at 30 days. There were 222 deaths among the 678 patients randomized to corticosteroids and 425 deaths among the 1025 patients randomized to usual care or placebo (summary OR, 0.66 [95% CI, 0.53-0.82]; P < .001 based on a fixed-effect meta-analysis). There was little inconsistency between the trial results (I2 = 15.6%; P = .31 for heterogeneity) and the summary OR was 0.70 (95% CI, 0.48-1.01; P = .053) based on the random-effects meta-analysis. The fixed-effect summary OR for the association with mortality was 0.64 (95% CI, 0.50-0.82; P < .001) for dexamethasone compared with usual care or placebo (3 trials, 1282 patients, and 527 deaths), the OR was 0.69 (95% CI, 0.43-1.12; P = .13) for hydrocortisone (3 trials, 374 patients, and 94 deaths), and the OR was 0.91 (95% CI, 0.29-2.87; P = .87) for methylprednisolone (1 trial, 47 patients, and 26 deaths). Among the 6 trials that reported serious adverse events, 64 events occurred among 354 patients randomized to corticosteroids and 80 events occurred among 342 patients randomized to usual care or placebo. Conclusions and Relevance: In this prospective meta-analysis of clinical trials of critically ill patients with COVID-19, administration of systemic corticosteroids, compared with usual care or placebo, was associated with lower 28-day all-cause mortality.
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In the paper
“There were 222 deaths among 678 patients randomized to corticosteroids and 425 deaths among 1025 patients randomized to usual care or placebo.”
§ The WHO Rapid Evidence Appraisal > Association Between Corticosteroids and 28-Day All-Cause Mortality
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In the paper
“the OR was 0.64 (95% CI, 0.49-0.83) among 1111 patients who were sympto- matic for more than 7 days prior to randomization”
§ The WHO Rapid Evidence Appraisal > Association Between Corticosteroids and 28-Day All-Cause Mortality Within Subgroups
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In the paper
“For the association be- tween corticosteroids and mortality, the OR was 1.05 (95% CI, 0.65-1.69) among patients who were receiving vasoactive agents at randomization (an absolute risk of 48% for cortico- steroids vs 47% for usual care or placebo)”
§ The WHO Rapid Evidence Appraisal > Association Between Corticosteroids and 28-Day All-Cause Mortality Within Subgroups
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In the paper
“the OR was 0.55 (95% CI, 0.34-0.88) among patients who were not receiving vasoactive agents at randomization (an absolute risk of 24% for corticosteroids vs 37% for usual care or placebo).”
§ The WHO Rapid Evidence Appraisal > Association Between Corticosteroids and 28-Day All-Cause Mortality Within Subgroups
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In the paper
“49.8 76/169 74/158 Yes (I 2 = 0%) 1.05 (0.65-1.69)”
§ The WHO Rapid Evidence Appraisal > Association Between Corticosteroids and 28-Day All-Cause Mortality Within Subgroups
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In the paper
“which was consistent with the corresponding result based on patients in the RECOVERY trial who were receiving invasive mechanical ventilation at randomization (OR, 0.59 [95% CI, 0.44-0.78]).”
§ The WHO Rapid Evidence Appraisal > Association Between Corticosteroids and 28-Day All-Cause Mortality
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In the paper
“Age, y 42.7 72/338 141/483 ≤60 (I 2 = 0%) 0.67 (0.48-0.94)”
§ The WHO Rapid Evidence Appraisal > Association Between Corticosteroids and 28-Day All-Cause Mortality Within Subgroups
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In the paper
“72.6 162/476 319/739 Male (I 2 = 14.7%) 0.66 (0.51-0.84)”
§ The WHO Rapid Evidence Appraisal > Association Between Corticosteroids and 28-Day All-Cause Mortality Within Subgroups
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For the association between methylprednisolone and 28-day mortality, the fixed-effect OR was 0.80 (95% CI, 0.40-1.63;P = .54).”
§ The WHO Rapid Evidence Appraisal > Association Between Corticosteroids and 28-Day All-Cause Mortality
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In the paper
“Among the 6 trials that reported serious adverse events, 64 events occurred among 354 patients randomized to corticosteroids and 80 events occurred among 342 patients randomized to usual care or placebo.”
§ The WHO Rapid Evidence Appraisal > Abstract
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- Probably not a substantial claim. 27
- It may state two separate claims as one. 16
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“The extent of concurrent treatment with antiviral agents or azithromycin varied substantially among the trials (Table 2).”
§ The WHO Rapid Evidence Appraisal > Results
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In the paper
“A total of 1703 patients were randomized (678 to corticosteroids and 1025 to usual care or placebo) in the 7 trials, the median age was 60 years (interquartile range, 52-68 years), and 488 patients (29%) were women (Table 2).”
§ The WHO Rapid Evidence Appraisal > Results
Strength:plain· not yet calibratedn = 1,703Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
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In the paper
“Five trials reported mortality at 28 days, 1 trial at 21 days, and 1 trial at 30 days.”
§ The WHO Rapid Evidence Appraisal > Abstract
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“The larger number of patients randomized to usual care or placebo was due to randomization in the RECOVERY trial (contributed 1007 [59.1%] patients to this analysis) in which patients were assigned to corticosteroid or usual care in a ratio of 1:2.”
§ The WHO Rapid Evidence Appraisal > Results
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“In all trials, the majority of patients were male.”
§ The WHO Rapid Evidence Appraisal > Results
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In the paper
“the proportions of patients with SARS-CoV-2 infection confirmed by polymerase chain reaction ranged from 78.7% to 100% across trials.”
§ The WHO Rapid Evidence Appraisal > Results
Strength:plain· not yet calibratedn = 1,703Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“Among 695 patients from 6 trials for whom data were avail- able, 327 (47.0%) were receiving vasoactive agents for blood pressure support at randomization.”
§ The WHO Rapid Evidence Appraisal > Association Between Corticosteroids and 28-Day All-Cause Mortality Within Subgroups
Strength:plain· not yet calibratedn = 695Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“The ORs for the association between corticosteroids and mortality appeared similar for older and younger individuals, men and women, and for longer and shorter durations of symptoms before randomization.”
§ The WHO Rapid Evidence Appraisal > Discussion
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In the paper
“The trial for which the risk of bias was assessed as “some concerns” (Steroids-SARI; NCT04244591) was relatively small (47 patients and 26 deaths) and contributed only 3.5% of the weight in the primary meta-analysis.”
§ The WHO Rapid Evidence Appraisal > Limitations
Strength:plain· not yet calibratedn = 47Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“the trials were mainly conducted in high-income settings”
§ The WHO Rapid Evidence Appraisal > Limitations
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In the paper
“The trial for which the risk of bias was assessed as “some concerns” (Steroids-SARI; NCT04244591) was relatively small (47 patients and 26 deaths) and contributed only 3.5% of the weight in the primary meta-analysis.”
§ The WHO Rapid Evidence Appraisal > Limitations
Strength:plain· not yet calibratedn = 47Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
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In the paper
“Adverse events varied across trials but there was no suggestion that the risk of serious adverse events was higher in patients assigned to corticosteroids except for the 2 smallest trials, in which the total number of serious adverse events was 1 and 3.”
§ The WHO Rapid Evidence Appraisal > Serious Adverse Events
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In the paper
“Inclusion of data from the Metcovid trial did not materially change the results other than reducing the inconsistency among the trials.”
§ The WHO Rapid Evidence Appraisal > Discussion
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
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In the paper
“All trials contributed data according to age group and sex.”
§ The WHO Rapid Evidence Appraisal > Association Between Corticosteroids and 28-Day All-Cause Mortality Within Subgroups
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In the paper
“All trials secured institutional review board approval, but approval was not required for the secondary data analysis reported here.Informed consent for participation in each trial was obtained and was consistent with local institutional review board requirements.”
§ The WHO Rapid Evidence Appraisal > Development of Prospective Meta-analysis
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In the paper
“Comparisons between subgroups defined by trial characteristics were made using randomeffects meta-regression and interpreted as exploratory because of the small number of trials and the potential for confounding by other characteristics.”
§ The WHO Rapid Evidence Appraisal > Data Analysis
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In the paper
“The fifth subgroup was specified post hoc based on results from the RECOVERY trial.All other subgroup analyses were prespecified before any outcome data became available.”
§ The WHO Rapid Evidence Appraisal > Data Aggregation
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In the paper
“Because the definitions of serious adverse events varied among the trials, a meta-analysis of this outcome was not conducted.”
§ The WHO Rapid Evidence Appraisal > Data Analysis
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In the paper
“Risk of bias assessments were done independently by 4 of the investigators (A.G., J.P.T.H., M.H.M., and J.S.), with disagreements resolved through discussion.”
§ The WHO Rapid Evidence Appraisal > Risk of Bias Assessment
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In the paper
“The primary analysis was an inverse variance-weighted fixed-effect meta-analysis of odds ratios (ORs) for overall mortality”
§ The WHO Rapid Evidence Appraisal > Data Analysis
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In the paper
“There were minimal missing outcome data.Follow-up was complete for both mortality and serious adverse events for 4 of the 7 trials.”
§ The WHO Rapid Evidence Appraisal > Results
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In the paper
“The Steroids-SARI trial (NCT04244591) recorded adverse events but did not categorize them as serious or nonserious adverse events.”
§ The WHO Rapid Evidence Appraisal > Serious Adverse Events
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In the paper
“Data were pooled from patients recruited to the participating trials through June 9, 2020, because patient management after that date was likely to be affected by the release of results of the RECOVERY trial on June 16, 2020.”
§ The WHO Rapid Evidence Appraisal > Development of Prospective Meta-analysis
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- Rests on an assumption: Patient management after June 9, 2020 was likely affected by the release of the RECOVERY trial results.
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In the paper
“The protocol was registered and made publicly avail-able on the PROSPERO database (CRD42020197242) on July 6, 2020”
§ The WHO Rapid Evidence Appraisal > Development of Prospective Meta-analysis
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In the paper
“This was regarded as reflecting usual practice, 22 and was not considered to introduce a risk of bias in the effect of assignment to the intervention.”
§ The WHO Rapid Evidence Appraisal > Association Between Corticosteroids and 28-Day All-Cause Mortality
What the sources say
- Not checked yetcites [22] source
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In the paper
“The optimal dose and duration of treatment could not be assessed in this analysis”
§ The WHO Rapid Evidence Appraisal > Discussion
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In the paper
“The protocol and analysis plan, including specification of subgroup analyses, was registered and made publicly available on the PROSPERO database prior to data analysis or receipt of outcome data.”
§ The WHO Rapid Evidence Appraisal > Discussion
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In the paper
“Third, there were only limited missing outcome data”
§ The WHO Rapid Evidence Appraisal > Limitations
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In the paper
“Data from the Metcovid trial were not included in the primary meta-analysis because this trial was registered after the searches of the trial registries were conducted.”
§ The WHO Rapid Evidence Appraisal > Discussion
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In the paper
“in many trials, follow-up was censored when participants were discharged from the hospital.”
§ The WHO Rapid Evidence Appraisal > Limitations
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“The other 4 trials had unblinded outcome assessment, and the risk of bias was assessed as “some concerns” based on subjectivity implying that classification of serious adverse events could differ between intervention groups.”
§ The WHO Rapid Evidence Appraisal > Serious Adverse Events
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
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In the paper
“All subgroup analyses other than that comparing longer with shorter duration of symptoms at randomization were prespecified.”
§ The WHO Rapid Evidence Appraisal > Discussion
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“As is standard in meta-analyses, patients were compared only with other patients randomized in the same trial.”
§ The WHO Rapid Evidence Appraisal > Discussion
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In the paper
“This prospective meta-analysis was based on a relatively large number of critically ill patients with COVID-19 from geographically diverse sites who were randomized to receive corticosteroids or to receive usual care or placebo.”
§ The WHO Rapid Evidence Appraisal > Discussion
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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In the paper
“Nonetheless, the number of patients randomized in eligible trials who did not participate is likely to be smaller than the number of patients included in this meta-analysis.”
§ The WHO Rapid Evidence Appraisal > Limitations
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None of the sources cited for this claim have been checked yet.
In the paper
“Nonetheless, the substantial risk of death in these patients (682/2604 [26.1%] in the control group) is consistent with mortality in critically ill patients with COVID-19.24,25”
§ The WHO Rapid Evidence Appraisal > Discussion
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In the paper
“The protocol also has been published along with a structured abstract.8”
§ The WHO Rapid Evidence Appraisal > Discussion
What the sources say
- Not checked yetcites [8]
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The authors state this as an assumption.
For illustrative absolute risk estimates, the mortality risk without corticosteroids was assumed to be 40%.
“we assumed a mortality risk without corticosteroids of 40% (approximately, the risk among all patients allocated to usual care or placebo)”
The authors state this as an assumption.
For subgroup absolute risk estimates, the mortality risk without corticosteroids was assumed to equal the observed risk among patients in that subgroup randomized to usual care or placebo.
“we assumed a mortality risk equal to the observed risk across patients in that subgroup who were randomized to usual care or placebo”
The paper relies on this without support.
Patient management after June 9, 2020 was likely affected by the release of the RECOVERY trial results.
“because patient management after that date was likely to be affected by the release of results of the RECOVERY trial on June 16, 2020”
The paper relies on this without support.
The effect of corticosteroids on 28-day mortality after discharge does not differ from the effect before discharge.
“We are aware of no reason that the effect of corticosteroids on postdischarge 28-day mortality would differ from that on predischarge mortality”
Claims other papers make about this one
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In the citing paper
“However, the trials of sarilumab were generally done earlier in the pandemic than those of tocilizumab and before corticosteroids became the standard of care.7”
From Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19: A Meta-analysis (2021) · cites this paper as [7]
In the citing paper
“The tools varied by the type of reporting bias (publication bias or selective nonreporting bias) assessed; the target of assessment (e.g. an individual study or a meta-analysis of studies); and the criteria used to designate a study or meta-analysis as at risk of bias.”
From Investigating and dealing with publication bias and other reporting biases in meta-analyses of health research: a review (2021) · cites this paper as [42]
In the citing paper
“Various tools have been developed to assess selective nonreporting of results 42 .”
From Investigating and dealing with publication bias and other reporting biases in meta-analyses of health research: a review (2021) · cites this paper as [42]
In the citing paper
“All emphasize the importance of retrieving the study's protocol, registration record, or statistical analysis plan so that the planned outcomes and analyses can be compared with those that were reported 42 .”
From Investigating and dealing with publication bias and other reporting biases in meta-analyses of health research: a review (2021) · cites this paper as [42]
In the citing paper
“Some tools for assessing risk of reporting biases guide users to consider various qualitative signals that suggest additional results may be missing from studies that have not been identified 42 .”
From Investigating and dealing with publication bias and other reporting biases in meta-analyses of health research: a review (2021) · cites this paper as [42]
In the citing paper
“A systematic search for scales and checklists designed to help authors make a qualitative judgement about the risk of reporting biases identified 15 tools published up to February 2017 42 .”
From Investigating and dealing with publication bias and other reporting biases in meta-analyses of health research: a review (2021) · cites this paper as [42]
In the citing paper
“A meta-analysis of seven randomized trials showed that 28-day all-cause mortality in critically ill patients with Covid-19 was lower among those who were treated with glucocorticoids than among those who received usual care or placebo.100”
From Cytokine storm (2020) · cites this paper as [100]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Nonventilated control-group risk uses the wrong percentage
MinorThe figure gives 28 deaths among 74 nonventilated control patients, an observed risk of 37.8%, not 42%. The stated 38% and 42% control risks appear to have been exchanged between the ventilation subgroups.
Reported 42 · recomputed 37.837838
“among patients who were not receiving invasive mechanical ventilation at randomization (corresponding to an absolute risk of 23% for corticosteroids vs 42% for usual care or placebo).”
Ventilated patient count is 100 too low
MinorThe subgroup figure lists 608 corticosteroid patients and 951 control patients receiving invasive mechanical ventilation, totaling 1559 rather than 1459.
Reported 1459 · recomputed 1559
“Among critically ill patients, many more were receiving invasive mechanical ventilation at randomization (1459 patients and 604 deaths) than were not (144 patients and 42 deaths).”
Citations
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Dexamethasone in Hospitalized Patients with Covid-19
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Acute Respiratory Distress Syndrome
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Research works printed but not linked: 3
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- Langan, 2017, Comparative performance of heterogeneity variance estimators in meta-analysis., Res Synth Methods, 8, 181, 10.1002/jrsm.v8.2 · DOI
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Items 501–600 of 1,001
Dexamethasone for Inpatients With COVID-19 in a National Cohort
Mourad, A., Thibault, D. P., Holland, T. L., Yang, S., Young, A. R., Egloff, S. A. A., & Thomas, L. E. (2023) · JAMA Network Open · doi:10.1001/jamanetworkopen.2023.8516 · Cited by 30
Sepsis in the critically ill patient: current and emerging management strategies
Heming, N., Azabou, É., Cazaumayou, X., Moine, P., & Annane, D. (2020) · Expert Review of Anti-infective Therapy · doi:10.1080/14787210.2021.1846522 · Cited by 32
Self-citationden Eynde, E. V., Gasch, O., Oliva, J. C., García-Prieto, E., Calzado, S., Grange, A. G., Machado, M. L., Falgueras, L., Roig, S. O., Morón, A., et al. (2021) · Scandinavian Journal of Infectious Diseases · doi:10.1080/23744235.2021.1884286 · Cited by 28
Targeting Microbiome: An Alternative Strategy for Fighting SARS-CoV-2 Infection
Spagnolello, O., Pinacchio, C., Santinelli, L., Vassalini, P., Innocenti, G. P., Girolamo, G. D., Fabris, S., Giovanetti, M., Angeletti, S., Russo, A., et al. (2021) · Chemotherapy · doi:10.1159/000515344 · Cited by 29
COVID-19 and Indirect Liver Injury: A Narrative Synthesis of the Evidence
Idalsoaga, F. J., Ayares, G., Arab, J. P., & Díaz, L. A. (2021) · Journal of Clinical and Translational Hepatology · doi:10.14218/jcth.2020.00140 · Cited by 29
“[118] Group WHOREAfC-TW, Sterne JAC, Murthy S, Diaz JV, Slutsky AS, Villar J, et al.”
BackgroundCurrent systematic reviews and meta-analyses of COVID-19
Nassar, M., Nso, N., Alfishawy, M., Novikov, A., Yaghi, S., Medina, L., Toz, B., Lakhdar, S., Idrees, Z., Kim, Y., et al. (2021) · World Journal of Virology · doi:10.5501/wjv.v10.i4.182 · Cited by 29
Adverse Cardiovascular Effects of Anti-COVID-19 Drugs
Liu, D., Zeng, X., Ding, Z., Lv, F., Mehta, J. L., & Wang, X. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.699949 · Cited by 29
“…could only reduce the mortality of patients with severe COVID-19, but had no effect on the mortality of patients with mild and moderate COVID-19 patients; while high doses of dexamethasone contributed to more harm than good (Ahmed and Hassan, 2020; Prescott and Rice, 2020; Sterne et al., 2020).”
BackgroundFocused Management of Patients With Severe Acute Brain Injury and ARDS
Kim, J. A., Wahlster, S., LaBuzetta, J. N., Nobleza, C. O. S., Johnson, N. J., Rubiños, C., Malaiyandi, D. P., O’Phelan, K. H., Mainali, S., Sarwal, A., et al. (2021) · CHEST Journal · doi:10.1016/j.chest.2021.08.066 · Cited by 30
Stem cell-based therapy for COVID-19 and ARDS: a systematic review
Zanirati, G., Provenzi, L., Libermann, L. L., Bizotto, S. C., Ghilardi, I. M., Marinowic, D. R., Shetty, A. K., & da Costa, J. C. (2021) · npj Regenerative Medicine · doi:10.1038/s41536-021-00181-9 · Cited by 29
Xie, L., Zhang, Z., Wang, Q., Chen, Y., Lu, D., & Wu, W. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.772865 · Cited by 30
Remdesivir for pregnancy: A systematic review of antiviral therapy for COVID-19
Budi, D. S., Pratama, N. R., Wafa, I. A., Putra, M., Wardhana, M. P., & Wungu, C. D. K. (2022) · Heliyon · doi:10.1016/j.heliyon.2022.e08835 · Cited by 30
Hospitalization burden and epidemiology of the COVID-19 pandemic in Spain (2020–2021)
Carretero, R. G., Gómez, O. V., Gil-Prieto, R., & de Miguel, Á. G. (2023) · BMC Infectious Diseases · doi:10.1186/s12879-023-08454-y · Cited by 27
Delirium and Associated Factors in a Cohort of Hospitalized Patients With Coronavirus Disease 2019
Garcia-Grimshaw, M. A., Chiquete, E., Jiménez‐Ruiz, A., Vidal-Mayo, J. D. J., Grajeda-González, S. L., Vargas-Martínez, M. D. L. Á., Toapanta-Yanchapaxi, L. N., Valdés‐Ferrer, S. I., Chávez-Martínez, O. A., Fernández, O. A. M., et al. (2021) · Journal of the Academy of Consultation-Liaison Psychiatry · doi:10.1016/j.jaclp.2021.06.008 · Cited by 29
Nagarkatti, P. S., Miranda, K., & Nagarkatti, M. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.589438 · Cited by 29
Lariccia, V., Magi, S., Serfilippi, T., Toujani, M., Gratteri, S., & Amoroso, S. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9124021 · Cited by 28
Remdesivir and systemic corticosteroids for the treatment of COVID-19: A Bayesian re-analysis
Lee, T. C., McDonald, E. G., Butler‐Laporte, G., Harrison, L. B., Cheng, M. P., & Brophy, J. M. (2021) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2021.01.065 · Cited by 29
“For corticosteroids, results were extracted for patients from the RECOVERY (RECOVERY Collaborative Group, 2020), METCOVID (Jeronimo et al., 2020) and CODEX (Tomazini et al., 2020) trials, and the remainder of the data were extracted from the WHO metaanalysis of corticosteroids [WHO Rapid Evidence…”
InfluentialLin, W., Hung, S., Lai, C., Wang, C., & Chen, C. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.107602 · Cited by 28
Combination therapy of tocilizumab and steroid for COVID‐19 patients: A meta‐analysis
Moosazadeh, M., & Mousavi, T. (2021) · Journal of Medical Virology · doi:10.1002/jmv.27489 · Cited by 27
Outcomes of Barotrauma in Critically Ill COVID-19 Patients With Severe Pneumonia
Gazivoda, V. P., Ibrahim, M., Kangas-Dick, A. W., Sun, A. J., Silver, M. P., & Wiesel, O. (2021) · Journal of Intensive Care Medicine · doi:10.1177/08850666211023360 · Cited by 28
“581 Total LOS (days) 17 (7-31) 14 (8-25) 0.”
Ali, G. A. M., Husain, A., Salah, H., & Goravey, W. (2021) · IDCases · doi:10.1016/j.idcr.2021.e01244 · Cited by 28
“asahii fungemia as in our patient [1,3].”
Yaqoob, H., Greenberg, D. J., Hwang, F., Lee, C. D., Vernik, D., Manglani, R., Wang, Z., Murad, M., Chandy, D., & Epelbaum, O. (2021) · Journal of Medical Virology · doi:10.1002/jmv.27351 · Cited by 28
Stasko, N., Kocher, J., Annas, A., Henson, I., Seitz, T. S., Miller, J. M., Arwood, L., Roberts, R. C., Womble, T. M., Keller, E. G., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-99917-2 · Cited by 28
Real-world corticosteroid use in severe pneumonia: a propensity-score-matched study
Ceccato, A., Russo, A., Barbeta, E., Oscanoa, P., Tiseo, G., Gabarrús, A., Giannatale, P. D., Nogas, S., Cillóniz, C., Menichetti, F., et al. (2021) · Critical Care · doi:10.1186/s13054-021-03840-x · Cited by 28
Kalyanaraman, M., & Anderson, M. R. (2022) · Pediatric Clinics of North America · doi:10.1016/j.pcl.2022.01.013 · Cited by 30
Peng, H. T., Rhind, S. G., & Beckett, A. (2021) · JMIR Public Health and Surveillance · doi:10.2196/25500 · Cited by 29
The role of cytokines and their antagonists in the treatment of COVID‐19 patients
Afshar, Z. M., Barary, M., Babazadeh, A., Pirzaman, A. T., Hosseinzadeh, R., Alijanpour, A., Allahgholipour, A., Miri, S. R., Sio, T. T. W., Sullman, M. J. M., et al. (2022) · Reviews in Medical Virology · doi:10.1002/rmv.2372 · Cited by 29
HIV and COVID-19 Co-Infection: Epidemiology, Clinical Characteristics, and Treatment
Basoulis, D., Mastrogianni, E., Voutsinas, P.-M., & Psichοgiou, M. (2023) · Viruses · doi:10.3390/v15020577 · Cited by 29
Dexamethasone attenuates interferon-related cytokine hyperresponsiveness in COVID-19 patients
Engel, J. J., van der Made, C. I., Keur, N., Setiabudiawan, T. P., Röring, R. J., Damoraki, G., Dijkstra, H., Lemmers, H., Ioannou, S., Poulakou, G., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1233318 · Cited by 33
Navigating the Post-COVID-19 Immunological Era: Understanding Long COVID-19 and Immune Response
Mohan, A., Iyer, V. A., Kumar, D., Batra, L., & Dahiya, P. (2023) · Life · doi:10.3390/life13112121 · Cited by 31
“Before taking any drug, speaking to a The consequences of COVID-19 and the methods used to combat such problems are represented in Figure 2. healthcare provider is recommended [93].”
BackgroundMethodSilva, P. G. O. E., Filho, L. A. C. B., Flores, I. P., Silva, V. V. E., Maciel, A. T., & Medeiros, L. S. (2023) · Medwave · doi:10.5867/medwave.2023.11.2719 · Cited by 31
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Beneficial and Detrimental Effects of Cytokines during Influenza and COVID-19
Chang, D., Cruz, C. S. D., & Sharma, L. (2024) · Viruses · doi:10.3390/v16020308 · Cited by 33
“Inhibiting the persistent effect of cytokines is another challenge, as the cells that secrete cytokines remain active and their elimination remains a challenge.”
BackgroundOng, E. Z., Kalimuddin, S., Chia, W. C., Ooi, S. H., Koh, C. W., Tan, H. C., Zhang, S. L.-X., Low, J. G. H., Ooi, E. E., & Chan, K. R. (2021) · EBioMedicine · doi:10.1016/j.ebiom.2021.103262 · Cited by 25
“In contrast, host targets of a different cortico-steroid, methylprednisolone [12,31], and other drugs such as azithromycin, lopinavir-ritonavir and hydroxychloroquine [31 (cid:1) 34], all of which have shown no ef fi cacy in improving clinical outcomes in COVID-19 patients, were absent from the hits…”
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Clinical evidence of an interferon–glucocorticoid therapeutic synergy in COVID-19
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Alterations in platelets during SARS-CoV-2 infection
Brambilla, M., Canzano, P., Becchetti, A., Tremoli, E., & Camera, M. (2021) · Platelets · doi:10.1080/09537104.2021.1962519 · Cited by 27
Foulkes, A. S., Selvaggi, C. A., Shinnick, D. J., Lumish, H. S., Kim, E. Y., Cao, T., Thaweethai, T., Qian, J., Lu, F., Yan, J., et al. (2021) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgab629 · Cited by 30
Pharmacologic Treatments for Acute Respiratory Distress Syndrome
Qadir, N., & Chang, S. Y. (2021) · Critical Care Clinics · doi:10.1016/j.ccc.2021.05.009 · Cited by 28
Triple jeopardy in ageing: COVID-19, co-morbidities and inflamm-ageing
Rea, I. M., & Alexander, H. D. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101494 · Cited by 27
“Dexamethasone, a corticosteroid used in a wide range of conditions for its anti-inflammatory and immunosuppressant effects is effective in COVID-19 and reduces the risk of death by approximately 25% in seriously ill patients at risk of, or requiring mechanical ventilation (RECOVERY Collaborative Group, 2021b; WHO Rapi…”
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“NRBM (days) Median (IQR) 13 (12, 14) 13 (12, 14) ND”
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Steroids for sepsis and ARDS: this eternal controversy remains with COVID-19
Carlet, J. M., Payen, D. M., & Opal, S. M. (2020) · The Lancet · doi:10.1016/s0140-6736(20)32132-2 · Cited by 28
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B cells modulate lung antiviral inflammatory responses via the neurotransmitter acetylcholine
Prieto, A. C., Luo, Z. L., Kulaga, H. M., & Baumgarth, N. (2025) · Nature Immunology · doi:10.1038/s41590-025-02124-8 · Cited by 27
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Estado actual de los tratamientos para la COVID-19
Llover, M. N., & Jiménez, M. C. (2021) · FMC - Formación Médica Continuada en Atención Primaria · doi:10.1016/j.fmc.2020.10.005 · Cited by 34
Clinical features of 47 patients infected with COVID-19 admitted to a Regional Reference Center
Olivares, F., Muñoz, D. L., Fíca, A., Delama, I., Alvarez, I., Maritza Navarrete, C., Blackburn, E., Garrido, P., Wenger, R., & Grandjean, J. (2020) · Revista médica de Chile · doi:10.4067/s0034-98872020001101577 · Cited by 26
Human coronaviruses and therapeutic drug discovery
Song, L., Xie, Q.-X., Lao, H., & Lv, Z. (2021) · Infectious Diseases of Poverty · doi:10.1186/s40249-021-00812-9 · Cited by 28
Post COVID-19 Organizing Pneumonia: The Right Time to Interfere
Biekšienė, K., Zaveckienė, J., Malakauskas, K., Vagulienė, N., Žemaitis, M., & Miliauskas, S. (2021) · Medicina · doi:10.3390/medicina57030283 · Cited by 26
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Repurposing Colchicine in Treating Patients with COVID-19: A Systematic Review and Meta-Analysis
Lien, C.-H., Lee, M.-D., Weng, S.-L., Lin, C., Lin, C., Tai, Y., Lei, W.-T., Liu, J., Huang, Y.-N., Chi, H., et al. (2021) · Life · doi:10.3390/life11080864 · Cited by 26
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“Dex treatment, a potent suppressor of systemic inflammation including IL-6, has been shown to reduce mortality in hospitalized COVID-19 patients under oxygen supplementation treatment or mechanical ventilation [34,35].”
BackgroundRajajee, V., Fung, C., Seagly, K., Park, P. K., Raghavendran, K., Machado-Aranda, D., Scott, J. W., Delano, M. J., Ela, A. S. A. A. A. E., Haft, J. W., et al. (2021) · Critical Care Explorations · doi:10.1097/cce.0000000000000537 · Cited by 26
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Characteristics and Outcomes of US Patients Hospitalized With COVID-19
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Lakota, K., Pirkmajer, K. P., Hočevar, A., Sodin‐Šemrl, S., Rotar, Ž., Čučnik, S., & Žigon, P. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.611318 · Cited by 26
“In recent metaanalysis of clinical trials of critically ill COVID-19 patients showed that the administration of systemic corticosteroids led to lower 28-day all-cause mortality compared to usual care (88) and retrospective analysis of health records of 5776 patients”
BackgroundMunch, M. W., Granholm, A., Myatra, S. N., Vijayaraghavan, B., Cronhjort, M., Wahlin, R. R., Jakob, S. M., Cioccari, L., Kjær, M. N., Vesterlund, G. K., et al. (2021) · Acta Anaesthesiologica Scandinavica · doi:10.1111/aas.13795 · Cited by 24
Self-citationCorticosteroid Pulses for Hospitalized Patients with COVID-19: Effects on Mortality
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“Only a few studies demonstrate the bene fi ts of corticosteroids on mortality [15, 16, 27, 28].”
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COVID-19 and Disease-Modifying Anti-rheumatic Drugs
D’Silva, K. M., & Wallace, Z. S. (2021) · Current Rheumatology Reports · doi:10.1007/s11926-021-00998-9 · Cited by 25
Reducing the global burden of sepsis: a positive legacy for the COVID-19 pandemic?
The European Society of Intensive Care Medicine (ESICM), The Global Sepsis Alliance (GSA), Reinhart, K., The Society of Critical Care Medicine (SCCM), Levy, M. M., Finfer, S. R., Machado, F. R., Kaplan, L., Kesecioğlu, J., Rhodes, A., et al. (2021) · Intensive Care Medicine · doi:10.1007/s00134-021-06409-y · Cited by 27
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Zarębska‐Michaluk, D., Jaroszewicz, J., Rogalska, M., Martonik, D., Pabjan, P., Berkan‐Kawińska, A., Bolewska, B., Oczko-Grzesik, B., Kozielewicz, D., Tudrujek‐Zdunek, M., et al. (2021) · Journal of Inflammation Research · doi:10.2147/jir.s322645 · Cited by 25
DrugWAS: Drug‐wide Association Studies for COVID‐19 Drug Repurposing
Bejan, C. A., Cahill, K. N., Staso, P. J., Choi, L., Peterson, J. F., & Phillips, E. J. (2021) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.2376 · Cited by 24
Do high‐dose corticosteroids improve outcomes in hospitalized COVID‐19 patients?
Kumar, G., Patel, D., Herrera, M., Jefferies, D., Sakhuja, A., Meersman, M., Dalton, D., Nanchal, R. S., & Guddati, A. K. (2021) · Journal of Medical Virology · doi:10.1002/jmv.27357 · Cited by 25
Complications of Critical COVID-19
Maslove, D. M., Sibley, S. R., Boyd, J. G., Goligher, E. C., Munshi, L., Bogoch, I. I., & Rochwerg, B. N. (2021) · CHEST Journal · doi:10.1016/j.chest.2021.10.011 · Cited by 27
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Villar, J., Ferrando, C., Tusman, G., Berra, L. M., Rodríguez, P., & Suárez-Sipmann, F. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.774025 · Cited by 26
Self-citationReverse‐Bayes methods for evidence assessment and research synthesis
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Postacute Sequelae of COVID-19 Critical Illness
Schwab, K. E., Schwitzer, E., & Qadir, N. (2022) · Critical Care Clinics · doi:10.1016/j.ccc.2022.01.001 · Cited by 26
“Corticosteroids and prolonged used of neuromuscular blocking agents, which are prescribed to treat COVID-19 pneumonia and manage severe acute respiratory distress syndrome, respectively, further increase the risk of CIM when used in combination.(42,43)”
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“Various drugs have been proven effective against COVID-19 in controlled clinical trials, including remdesivir (Beigel et al., 2020), corticosteroids (Sterne et al., 2020), and a few monoclonal antibodies (Marovich et al., 2020; Taylor et al., 2021).”
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van Grootveld, R., van der Beek, M. T., Janssen, N. A. F., Ergün, M., van Dijk, K., Bethlehem, C., Stads, S., van Paassen, J., Heunks, L. M. A., Bouman, C. S. C., et al. (2023) · Journal of Critical Care · doi:10.1016/j.jcrc.2023.154272 · Cited by 26
“After the RECOVERY trial and a meta-analysis showed that patients with COVID-19 receiving either invasive mechanical ventilation or oxygen alone benefited from treatment with systemic corticosteroids this became the mainstay of treatment [4,5].”
MethodHong, S., Wang, H., Li, S., Liu, J., & Qiao, L. (2023) · BMC Infectious Diseases · doi:10.1186/s12879-023-08280-2 · Cited by 25
“A meta-analysis collected data from 7 randomized clinical trials to evaluate the effectiveness of glucocorticoids in 1703 critically ill patients with COVID-19 [44].”
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Targeting Sepsis: Disease Tolerance, Immune Resilience, and Compartmentalized Immunity
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Liver Injury in Patients Hospitalized for COVID-19: Possible Role of Therapy
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Metadata
- Authors
- The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, Sterne, J. A. C., Murthy, S., Diaz, J. V., Slutsky, A. S., Villar, J., Angus, D. C., Annane, D., Azevedo, L. C. P., Berwanger, O., Cavalcanti, A. B., Dequin, P.-F., Du, B., Emberson, J., Fisher, D., Giraudeau, B., Gordon, A. C., Granholm, A., Green, C., Haynes, R., Heming, N., Higgins, J. P. T., Horby, P., Jüni, P., Landray, M. J., Le Gouge, A., Leclerc, M., Lim, W. S., Machado, F. R., McArthur, C., Meziani, F., Møller, M. H., Perner, A., Petersen, M. W., Savovic, J., Tomazini, B., Veiga, V. C., Webb, S., & Marshall, J. C.
- Affiliations
- University of Bristol (GB)
- University of British Columbia (CA)
- St. Michael's Hospital (CA)
- University of Pittsburgh (US)
- Universidade de São Paulo (BR)
- Hospital Sírio-Libanês, São Paulo, Brazil
- Hospital Israelita Albert Einstein (BR)
- Université de Tours (FR)
- Médecine Intensive-Réanimation, INSERM CIC1415, CHRU de Tours, Tours, France
- Peking Union Medical College Hospital (CN)
- University of Oxford (GB)
- Inserm (FR)
- University of Copenhagen (DK)
- Université de Versailles Saint-Quentin-en-Yvelines (FR)
- CIC INSERM 1415-CHRU de Tours, Tours, France
- Nottingham University Hospitals NHS Trust (GB)
- Anesthesiology, Pain, and Intensive Care Department, Federal University of São Paulo, São Paulo, Brazil
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, England
- St John of God Subiaco Hospital (AU)
- Corresponding author
- Sterne, Jonathan A. C.
- ORCID
- Sterne, Jonathan A. C.
- Murthy, Srinivas
- Diaz, Janet V.
- Slutsky, Arthur S.
- Villar, Jesús
- Angus, Derek C.
- Annane, Djillali
- Berwanger, Otavio
- Cavalcanti, Alexandre B.
- Du, Bin
- Emberson, Jonathan
- Fisher, David
- Giraudeau, Bruno
- Gordon, Anthony C.
- Granholm, Anders
- Green, Cameron
- Haynes, Richard
- Heming, Nicholas
- Higgins, Julian P. T.
- Horby, Peter
- Jüni, Peter
- Landray, Martin J.
- Lim, Wei Shen
- McArthur, Colin
- Meziani, Ferhat
- Møller, Morten Hylander
- Perner, Anders
- Tomazini, Bruno
- Veiga, Viviane C.
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2020-10-06
- Volume
- 324
- Issue
- 13
- Pages
- 1330
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC7489434
- OpenAlex
- W3082355253
- Semantic Scholar
- c40537695ad1c573a608449e4ff9bb6bc94c3dab
- Cited by
- 2,257
- References
- 30
- Citations by year
- 2026: 39 · 2025: 92 · 2024: 175 · 2023: 302 · 2022: 538 · 2021: 906 · 2020: 204
- FWCI
- 63.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Bristol Research (University of Bristol) (acceptedVersion, other-oa)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- HAL (submittedVersion)
- Funders
- Amgen
- Pfizer
- AstraZeneca
- World Health Organization
- Nottingham University Hospitals NHS Trust
- University Hospitals Bristol NHS Foundation Trust
- UK Research and Innovation
- Medicines Company
- National Institute for Health and Care Research (11/46/14, NF-SI-0616-10111, COVID-19, NF-SI-0617-10145, RP-2015-06-018)
- University of Oxford
- University of Nottingham
- Institut National de la Santé et de la Recherche Médicale
- Monash University
- University of Toronto
- Novo Nordisk
- Rigshospitalet
- Universidade de São Paulo
- Oxford University Hospitals NHS Foundation Trust
- Novo Nordisk Fonden (NNF20SA0062998)
- Universidade do Estado do Amazonas
- Minderoo Foundation
- Abbott Vascular
- Canadian Institutes of Health Research
- Medical Research Council (MC_UU_12023/22, MC_UU_12023/21, MC_UU_00017/3, MC_PC_20062)
- National Health and Medical Research Council
- Health Research Council of New Zealand
- NIHR Oxford Biomedical Research Centre
- Health Data Research UK
- Topics
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- COVID-19 pandemic, systemic corticosteroids, dexamethasone, cortisol, methylprednisolone, 28-day mortality, critically ill patients, serious adverse events, corticosteroid therapy, risk of bias, subgroup analysis, risk of bias assessment
- MeSH terms
- Betacoronavirus, COVID-19, SARS-CoV-2, COVID-19 Drug Treatment, Adrenal Cortex Hormones, Cause of Death, Dexamethasone, Glucocorticoids, Humans, Hydrocortisone, Methylprednisolone, Pneumonia, Viral, Randomized Controlled Trials as Topic, Critical Illness, Coronavirus Infections, Pandemics
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