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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Self-citationEffect of Dexamethasone in Hospitalized Patients with COVID-19 – Preliminary Report
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Current COVID-19 treatments: Rapid review of the literature
Dong, Y., Shamsuddin, A., Campbell, H. J., & Τheodoratou, E. (2021) · Journal of Global Health · doi:10.7189/jogh.11.10003 · Cited by 37
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“In addition to the therapeutics described above, the use of glucocorticoid (dexamethasone) has been shown to be effective in reducing 28-day mortality in COVID-19 patients without significantly increasing the risk of adverse events [147].”
BackgroundAcute respiratory distress syndrome (ARDS): from mechanistic insights to therapeutic strategies
Xie, R., Tan, D., Liu, B., Xiao, G., Gong, F., Zhang, Q., Qi, L., Zheng, S., Yuan, Y., Yang, Z., et al. (2025) · MedComm · doi:10.1002/mco2.70074 · Cited by 43
“68 On the basis of the specificity of COVID-19, several novel treatment options are being explored.”
Immune Responses to SARS-CoV-2 in Solid Organ Transplant Recipients
Phadke, V. K., Scanlon, N., Jordan, S. C., & Rouphael, N. (2021) · Current Transplantation Reports · doi:10.1007/s40472-021-00322-5 · Cited by 38
Nanomedicine: A Diagnostic and Therapeutic Approach to COVID-19
Sharma, A., Kontodimas, K., & Bosmann, M. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.648005 · Cited by 39
Hamed, D. M., Belhoul, K. M., Maazmi, N. A. A., Farah, G., Moin, M., Suwaidi, M. A., Narainen, M., Makki, M., & Abdulrahman, M. (2021) · Journal of Infection and Public Health · doi:10.1016/j.jiph.2021.06.003 · Cited by 37
Dexamethasone for Severe COVID-19: How Does It Work at Cellular and Molecular Levels?
Kino, T., Burd, I. D., & Segars, J. H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22136764 · Cited by 36
Higashikuni, Y., Liu, W., Obana, T., & Sata, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222112081 · Cited by 38
Intensive care unit‐acquired weakness and the COVID ‐19 pandemic: A clinical review
Qin, E. S., Hough, C. L., Andrews, J. S., & Bunnell, A. E. (2022) · PM&R · doi:10.1002/pmrj.12757 · Cited by 37
Hoffman, K. L., Schenck, E. J., Satlin, M. J., Whalen, W., Pan, D., Williams, N., & Diaz, I. M. (2022) · JAMA Network Open · doi:10.1001/jamanetworkopen.2022.34425 · Cited by 36
Mondi, A., Lorenzini, P., Castilletti, C., Gagliardini, R., Lalle, E., Corpolongo, A., Valli, M. B., Taglietti, F., Cicalini, S., Loiacono, L., et al. (2021) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2021.02.117 · Cited by 36
Briggs, N., Gormally, M. V., Li, F., Browning, S. L., Treggiari, M. M., Morrison, A. R., Laurent-Rolle, M., Deng, Y., Hendrickson, J. E., Tormey, C. A., et al. (2021) · PLoS ONE · doi:10.1371/journal.pone.0254453 · Cited by 36
Goravey, W., Ali, G. A. M., Ali, M., Ibrahim, E. B., Maslamani, M. A. R. S. A., & Hadi, H. A. (2021) · Clinical Case Reports · doi:10.1002/ccr3.4827 · Cited by 35
Delanerolle, G., Zeng, Y., JIAN-QING, S., Yeng, X., Goodison, W., Shetty, A., Shetty, S., Haque, N., Elliot, K., Ranaweera, S., et al. (2022) · World Journal of Psychiatry · doi:10.5498/wjp.v12.i5.739 · Cited by 40
Barzegar, M., Houshi, S., Sadeghi, E., Hashemi, M. S., Pishgahi, G., Bagherieh, S., Afshari-Safavi, A., Mirmosayyeb, O., Shaygannejad, V., & Zabeti, A. (2022) · Multiple Sclerosis International · doi:10.1155/2022/9388813 · Cited by 35
Grainger, R., Machado, P., & Robinson, P. C. (2020) · Best Practice & Research Clinical Rheumatology · doi:10.1016/j.berh.2020.101657 · Cited by 39
COVID-19 Mortality Rates Among Nursing Home Residents Declined From March To November 2020
Kosar, C. M., White, E. M., Feifer, R. A., Blackman, C., Gravenstein, S., Panagiotou, O. A., McConeghy, K. W., & Mor, V. (2021) · Health Affairs · doi:10.1377/hlthaff.2020.02191 · Cited by 36
Pérez‐Martínez, A., Mora-Rillo, M., Ferreras, C., Guerra‐García, P., Pascual-Miguel, B., Mestre‐Durán, C., Borobia, A. M., Carcas, A. J., Queiruga‐Parada, J., Garcia, I., et al. (2021) · EClinicalMedicine · doi:10.1016/j.eclinm.2021.101086 · Cited by 36
Torres, A., Motos, A., Cillóniz, C., Ceccato, A., Fernández‐Barat, L., Gabarrús, A., Bermejo-Martín, J. F., Ferrer, R., Riera, J., Pérez-Arnal, R., et al. (2022) · Intensive Care Medicine · doi:10.1007/s00134-022-06726-w · Cited by 36
JAK inhibition as a new treatment strategy for patients with COVID-19
Huang, J., Zhou, C., Jinniu, D., & Zhou, J. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.115162 · Cited by 36
Could the fibromyalgia syndrome be triggered or enhanced by COVID-19?
Fialho, M. F. P., Brum, E. S., & Oliveira, S. M. (2023) · Inflammopharmacology · doi:10.1007/s10787-023-01160-w · Cited by 33
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“An important correlation between the administration of systemic GCs and reduced mortality was found among critically ill patients with COVID-19 (106).”
BackgroundSkaarup, K. G., Lassen, M. C. H., Modin, D., Johansen, N. D., Loiacono, M. M., Harris, R. C., Lee, J. K. H., Dufournet, M., Vardeny, O., Peikert, A., et al. (2024) · Journal of Infection · doi:10.1016/j.jinf.2024.106187 · Cited by 37
Knoll, R., Helbig, E. T., Dahm, K., Bolaji, O., Hamm, F., Dietrich, O., van Uelft, M., Müller, S. M., Bonaguro, L., Schulte-Schrepping, J., et al. (2024) · Cell · doi:10.1016/j.cell.2024.06.014 · Cited by 34
Hou, F., Shi, N., Yuan, H., LI, B. C., Xiao, J., Xiao, K., & Xie, L. (2025) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-025-00750-6 · Cited by 40
“Dexamethasone can reduce 28-day all-cause mortality in critically ill patients [104].”
Jaiswal, V., Nasa, P., Raouf, M. Y., Gupta, M., Dewedar, H., Mohammad, H., Rais, Z. A., Baqer, M. A., Alsabbah, A., Ibrahim, Y., et al. (2020) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2020.10.085 · Cited by 35
Feng, F., Chen, Y., Zhao, D., Tonglin, L., Huang, Y., Qiu, L., Hao, Y., Hu, X., Yin, W., Liu, Z., et al. (2020) · Frontiers in Pediatrics · doi:10.3389/fped.2020.553394 · Cited by 35
COVID19- clinical presentation and therapeutic considerations
Kenny, G., & Mallon, P. W. G. (2020) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2020.11.021 · Cited by 35
Efficacy and safety of steroid therapy in COVID-19: A rapid systematic review and Meta-analysis
Medhi, B., Sarma, P., Bhattacharyya, A., Kaur, H., Prajapat, M., Prakash, A., Kumar, S., Bansal, S., Kirubakaran, R., HariKrishnaReddy, D., et al. (2020) · Indian Journal of Pharmacology · doi:10.4103/ijp.ijp_1146_20 · Cited by 35
Shetty, G. M. (2021) · Indian Journal of Orthopaedics · doi:10.1007/s43465-021-00546-8 · Cited by 38
Kow, C. S., Ramachandram, D. S., & Hasan, S. S. (2021) · Journal of Infection and Chemotherapy · doi:10.1016/j.jiac.2021.11.008 · Cited by 35
Moreno, A. A., Carbonell, R., Martín‐Loeches, I., Solé‐Violán, J., Correig, E., Gómez, J., Ruíz-Botella, M., Trefler, S., Bodí, M. A., Payá, J. M., et al. (2021) · Annals of Intensive Care · doi:10.1186/s13613-021-00951-0 · Cited by 35
Shambat, S. M., Gómez-Mejía, A., Schweizer, T. A., Huemer, M., Chang, C., Acevedo, C., Bergadà-Pijuan, J., Vulin, C., Hofmaenner, D. A., Scheier, T., et al. (2022) · PLoS Pathogens · doi:10.1371/journal.ppat.1010176 · Cited by 34
Zeraatkar, D., Cusano, E., Martinez, J. P. D., Qasim, A., Mangala, S., Kum, E., Bartoszko, J. J., Devji, T., Agoritsas, T., Guyatt, G. H., et al. (2022) · BMJ Medicine · doi:10.1136/bmjmed-2021-000036 · Cited by 37
COVID-19 and Fungal infections: a double debacle
Mina, S., Yaakoub, H., Annweiler, C., Dubée, V., & Papon, N. (2022) · Microbes and Infection · doi:10.1016/j.micinf.2022.105039 · Cited by 35
Acute Respiratory Distress Syndrome
Gragossian, A., & Siuba, M. (2022) · Emergency Medicine Clinics of North America · doi:10.1016/j.emc.2022.05.002 · Cited by 39
Current Effective Therapeutics in Management of COVID-19
Atluri, K., Aimlin, I., & Arora, S. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11133838 · Cited by 37
Godolphin, P. J., White, I. R., Tierney, J. F., & Fisher, D. J. (2022) · Research Synthesis Methods · doi:10.1002/jrsm.1590 · Cited by 34
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“Despite the 28-day mortality benefit observed with corticosteroid use [4, 5] and controversies regarding tocilizumab use [6], both treatments were initiated prior to VAP occurrence, and often prior to ICU admission, and are independently associated with a higher risk of VAP.”
BackgroundClinical characteristics and risk factors for COVID-19-associated Candidemia
Omrani, A. S., Koleri, J., Abid, F. B., Daghfel, J., Odaippurath, T., Peediyakkal, M. Z. K., Baiou, A., Sarsak, E. W., Elayana, M., Kaleeckal, A. H., et al. (2021) · Medical Mycology · doi:10.1093/mmy/myab056 · Cited by 34
Human cardiac organoids to model COVID‐19 cytokine storm induced cardiac injuries
Arhontoulis, D. C., Kerr, C. M., Richards, D., Tjen, K., Hyams, N. A., Jones, J. A., DeLeon‐Pennell, K. Y., Menick, D. R., Bräuninger, H., Lindner, D., et al. (2022) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.3327 · Cited by 35
Kuperminc, E., Heming, N., Carlos, M., & Annane, D. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12093340 · Cited by 40
Self-citationImmunomodulation for Severe COVID-19 Pneumonia: The State of the Art
Zhang, Y., Chen, Y., & Meng, Z. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.577442 · Cited by 34
Lambermont, B. C., Rousseau, A., Seidel, L., Thys, M., Cavalleri, J., Delanaye, P., Chase, J. G., Gillet, P., & Misset, B. (2021) · Critical Care Explorations · doi:10.1097/cce.0000000000000438 · Cited by 31
Chong, W. H., Saha, B. K., & Chopra, A. (2021) · Heart & Lung · doi:10.1016/j.hrtlng.2021.04.009 · Cited by 33
Knight, S. R., Gupta, R. K., Ho, A. Y. W., Pius, R., Buchan, I. E., Carson, G., Drake, T. M., Dunning, J. W., Fairfield, C. J., Gamble, C. L., et al. (2021) · Thorax · doi:10.1136/thoraxjnl-2021-217629 · Cited by 35
Self-citationImmunosuppression and SARS-CoV-2 Infection in Kidney Transplant Recipients
Devresse, A., Greef, J. D., Yombi, J. C., Belkhir, L., Goffin, E., & Kanaan, N. (2022) · Transplantation Direct · doi:10.1097/txd.0000000000001292 · Cited by 33
Shiraki, K., Sato, N., Sakai, K., Matsumoto, S., Kaszynski, R. H., & Takemoto, M. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108121 · Cited by 33
Kidney Injury in COVID-19: Epidemiology, Molecular Mechanisms and Potential Therapeutic Targets
Teixeira, J. P., Barone, S., Zahedi, K. A., & Soleimani, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23042242 · Cited by 34
Hong, S., Wang, H., Zhang, Z., & Qiao, L. (2022) · Steroids · doi:10.1016/j.steroids.2022.109022 · Cited by 33
“Recently, a systematic review analyzed data from 7 randomized controlled trials (RCTs) to evaluate the effectiveness of glucocorticoids in 1703 critically ill patients with COVID-19 [11].”
BackgroundHohl, C. M., Rosychuk, R. J., Hau, J. P., Hayward, J., Landes, M., Yan, J. W., Ting, D. K., Welsford, M., Archambault, P. M., Mercier, É., et al. (2022) · Canadian Journal of Emergency Medicine · doi:10.1007/s43678-022-00275-3 · Cited by 33
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Esposito, S., Marchetti, F., Lanari, M., Caramelli, F., Fanti, A. D., Vergine, G., Iughetti, L., Fornaro, M., Suppiej, A., Zona, S., et al. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18083919 · Cited by 34
Bonet, D. B., Caguana-Vélez, O. A., Durán, X., Comas, M., Posso, M., Admetlló, M., Blasco, A. H., Cuadrado‐Godia, E., Marco, E., Martín‐Ezquerra, G., et al. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12124158 · Cited by 35
Lin, P., Zhao, Y., Li, X., Jiang, F., & Liang, Z. (2021) · Critical Care · doi:10.1186/s13054-021-03546-0 · Cited by 35
“Tomazini BM, Maia IS, Cavalcanti AB, Berwanger O, Rosa RG, Veiga VC, et al. Effect of Dexamethasone on days alive and ventilator-free in patients with moderate or severe acute respiratory distress syndrome and COVID-19: the CoDEX randomized clinical trial.”
BackgroundInfluentialCOVID-19 in Children: Respiratory Involvement and Some Differences With the Adults
Jurado, J. L., & Orozco, I. F. Á. (2021) · Frontiers in Pediatrics · doi:10.3389/fped.2021.622240 · Cited by 30
The effect of immunosuppressants on the prognosis of SARS-CoV-2 infection
Ward, D., Gørtz, S., Ernst, M. T., Andersen, N. N., Kjær, S. K., Hallas, J., Christensen, S., Christiansen, C. F., Israelsen, S. B., Benfield, T., et al. (2021) · European Respiratory Journal · doi:10.1183/13993003.00769-2021 · Cited by 32
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Self-citationPatel, C. A., Parmar, K., Patel, D., Patel, S. P., Sheth, D. B., & Beladiya, J. (2022) · Reviews in Medical Virology · doi:10.1002/rmv.2386 · Cited by 33
“Furthermore, meta‐analysis of seven RCTs involving 1703 disparagingly ill COVID‐19 patients also revealed that systemic corticosteroids therapy reduced 28‐day mortality when compared to standard care.(69) The RECOVERY trial found that dexamethasone therapy reduced 28‐day mortality in in-”
BackgroundUnmet needs in pneumonia research: a comprehensive approach by the CAPNETZ study group
Pletz, M. W., Jensen, A. V., Bahrs, C., Davenport, C., Rupp, J., Witzenrath, M., Barten-Neiner, G., Kolditz, M., Dettmer, S., Chalmers, J. D., et al. (2022) · Respiratory Research · doi:10.1186/s12931-022-02117-3 · Cited by 31
The Role of Cyclodextrins in COVID-19 Therapy—A Literature Review
Almeida, B. C., Domingues, C., Mascarenhas‐Melo, F., da Silva, I. S., Jarak, I., Veiga, F., & Figueiras, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032974 · Cited by 33
“Later, due to preliminary data demonstrating lower mortality in patients with COVID19 treated with corticosteroids, the use of corticosteroids for treating patients with severe or critical COVID-19 has been recommended [35].”
BackgroundA framework for prospective, adaptive meta-analysis (FAME) of aggregate data from randomised trials.
Tierney, J. F., Fisher, D. J., Vale, C. L., Burdett, S., Rydzewska, L. H., Rogozińska, E., Godolphin, P. J., White, I. R., & Parmar, M. K. B. (2021) · PLOS Medicine · doi:10.1371/journal.pmed.1003629 · Cited by 31
Self-citationPfeifer, M. A., & Hamer, O. W. (2020) · Der Internist · doi:10.1007/s00108-020-00854-5 · Cited by 31
Impact of late administration of corticosteroids in COVID-19 ARDS
COVADIS study group investigators, Mongardon, N., Piagnerelli, M., Grimaldi, D., Perrot, B., & Lascarrou, J.-B. (2020) · Intensive Care Medicine · doi:10.1007/s00134-020-06311-z · Cited by 31
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Nobile, B., Durand, M., Olié, É., Guillaume, S., Molès, J., Haffen, É., & Courtet, P. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.615695 · Cited by 31
IL-6 blockade for COVID-19: a global scientific call to arms
Murthy, S., & Lee, T. C. (2021) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(21)00127-2 · Cited by 30
Self-citationImpact of the COVID-19 pandemic on the management of chronic noninfectious respiratory diseases
Tiotiu, A. I., Chong‐Neto, H. J., Bikov, A., Kowal, K., Steiropoulos, P., Labor, M., Chérrez-Ojeda, I., Badellino, H., Emelyanov, A. V., Garcia, R., et al. (2021) · Expert Review of Respiratory Medicine · doi:10.1080/17476348.2021.1951707 · Cited by 30
Rhino-orbital mucormycosis following COVID-19 in previously non-diabetic, immunocompetent patients
Nair, A. G., Adulkar, N. G., D’Cunha, L., Rao, P. R., Bradoo, R. A., Bapaye, M. M., Kothari, A. R., Dave, T. V., & Shinde, C. A. (2021) · Orbit · doi:10.1080/01676830.2021.1960382 · Cited by 32
de Andrade, L. G. M., de Sandes‐Freitas, T. V., Requião‐Moura, L., Viana, L. A., Cristelli, M. P., Garcı́a, V. D., Alcántara, A., Esmeraldo, R. D. M., Abbud‐Filho, M., Pacheco‐Silva, Á., et al. (2021) · American Journal of Transplantation · doi:10.1111/ajt.16807 · Cited by 31
Host genetics of pediatric SARS-CoV-2 COVID-19 and multisystem inflammatory syndrome in children
Schulert, G. S., Blum, S. A., & Cron, R. Q. (2021) · Current Opinion in Pediatrics · doi:10.1097/mop.0000000000001061 · Cited by 31
“Glucocorticoids specifically, when given during hypoxic phases of the disease, have been demonstrated in randomized, blinded, placebo-controlled trials to improve mortality [2].”
BackgroundCOVID-19 Critical Illness: A Data-Driven Review
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“Dexamethasone, a preferred glucocorticoid, significantly reduces 28-day mortality in severe COVID-19 patients requiring respiratory support [260, 261].”
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A Timely Call to Arms: COVID-19, the Circadian Clock, and Critical Care
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“…Evidence Appraisal for COVID-19 Therapies (REACT) Working Group pooled data from seven trials totaling 1703 patients and showed that administration of systemic corticosteroids is associated with a lower 28-day mortality in critically ill COVID-19 patients (Horby et al., 2020; Sterne et al., 2020).”
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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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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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