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Review
. 2021 Aug 16;8(8):CD014963.
doi: 10.1002/14651858.CD014963.

Systemic corticosteroids for the treatment of COVID-19

Carina Wagner  1 , Mirko Griesel  2 , Agata Mikolajewska  3 , Anika Mueller  4 , Monika Nothacker  5 , Karoline Kley  2 , Maria-Inti Metzendorf  6 , Anna-Lena Fischer  7 , Marco Kopp  1 , Miriam Stegemann  3 , Nicole Skoetz  8 , Falk Fichtner  2
Affiliations
Review

Systemic corticosteroids for the treatment of COVID-19

Carina Wagner et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: Systemic corticosteroids are used to treat people with COVID-19 because they counter hyper-inflammation. Existing evidence syntheses suggest a slight benefit on mortality. So far, systemic corticosteroids are one of the few treatment options for COVID-19. Nonetheless, size of effect, certainty of the evidence, optimal therapy regimen, and selection of patients who are likely to benefit most are factors that remain to be evaluated.

Objectives: To assess whether systemic corticosteroids are effective and safe in the treatment of people with COVID-19, and to keep up to date with the evolving evidence base using a living systematic review approach.

Search methods: We searched the Cochrane COVID-19 Study Register (which includes PubMed, Embase, CENTRAL, ClinicalTrials.gov, WHO ICTRP, and medRxiv), Web of Science (Science Citation Index, Emerging Citation Index), and the WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies to 16 April 2021.

Selection criteria: We included randomised controlled trials (RCTs) that evaluated systemic corticosteroids for people with COVID-19, irrespective of disease severity, participant age, gender or ethnicity. We included any type or dose of systemic corticosteroids. We included the following comparisons: systemic corticosteroids plus standard care versus standard care (plus/minus placebo), dose comparisons, timing comparisons (early versus late), different types of corticosteroids and systemic corticosteroids versus other active substances. We excluded studies that included populations with other coronavirus diseases (severe acute respiratory syndrome or Middle East respiratory syndrome), corticosteroids in combination with other active substances versus standard care, topical or inhaled corticosteroids, and corticosteroids for long-COVID treatment.

Data collection and analysis: We followed standard Cochrane methodology. To assess the risk of bias in included studies, we used the Cochrane 'Risk of bias' 2 tool for RCTs. We rated the certainty of evidence using the GRADE approach for the following outcomes: all-cause mortality, ventilator-free days, new need for invasive mechanical ventilation, quality of life, serious adverse events, adverse events, and hospital-acquired infections.

Main results: We included 11 RCTs in 8075 participants, of whom 7041 (87%) originated from high-income countries. A total of 3072 participants were randomised to corticosteroid arms and the majority received dexamethasone (n = 2322). We also identified 42 ongoing studies and 16 studies reported as being completed or terminated in a study registry, but without results yet. Hospitalised individuals with a confirmed or suspected diagnosis of symptomatic COVID-19 Systemic corticosteroids plus standard care versus standard care plus/minus placebo We included 10 RCTs (7989 participants), one of which did not report any of our pre-specified outcomes and thus our analysis included outcome data from nine studies. All-cause mortality (at longest follow-up available): systemic corticosteroids plus standard care probably reduce all-cause mortality slightly in people with COVID-19 compared to standard care alone (median 28 days: risk difference of 30 in 1000 participants fewer than the control group rate of 275 in 1000 participants; risk ratio (RR) 0.89, 95% confidence interval (CI) 0.80 to 1.00; 9 RCTs, 7930 participants; moderate-certainty evidence). Ventilator-free days: corticosteroids may increase ventilator-free days (MD 2.6 days more than control group rate of 4 days, 95% CI 0.67 to 4.53; 1 RCT, 299 participants; low-certainty evidence). Ventilator-free days have inherent limitations as a composite endpoint and should be interpreted with caution. New need for invasive ventilation: the evidence is of very low certainty. Because of high risk of bias arising from deaths that occurred before ventilation we are uncertain about the size and direction of the effects. Consequently, we did not perform analysis beyond the presentation of descriptive statistics. Quality of life/neurological outcome: no data were available. Serious adverse events: we included data on two RCTs (678 participants) that evaluated systemic corticosteroids compared to standard care (plus/minus placebo); for adverse events and hospital-acquired infections, we included data on five RCTs (660 participants). Because of high risk of bias, heterogeneous definitions, and underreporting we are uncertain about the size and direction of the effects. Consequently, we did not perform analysis beyond the presentation of descriptive statistics (very low-certainty evidence). Different types, dosages or timing of systemic corticosteroids We identified one study that compared methylprednisolone with dexamethasone. The evidence for mortality and new need for invasive mechanical ventilation is very low certainty due to the small number of participants (n = 86). No data were available for the other outcomes. We did not identify comparisons of different dosages or timing. Outpatients with asymptomatic or mild disease Currently, there are no studies published in populations with asymptomatic infection or mild disease.

Authors' conclusions: Moderate-certainty evidence shows that systemic corticosteroids probably slightly reduce all-cause mortality in people hospitalised because of symptomatic COVID-19. Low-certainty evidence suggests that there may also be a reduction in ventilator-free days. Since we are unable to adjust for the impact of early death on subsequent endpoints, the findings for ventilation outcomes and harms have limited applicability to inform treatment decisions. Currently, there is no evidence for asymptomatic or mild disease (non-hospitalised participants). There is an urgent need for good-quality evidence for specific subgroups of disease severity, for which we propose level of respiratory support at randomisation. This applies to the comparison or subgroups of different types and doses of corticosteroids, too. Outcomes apart from mortality should be measured and analysed appropriately taking into account confounding through death if applicable. We identified 42 ongoing and 16 completed but not published RCTs in trials registries suggesting possible changes of effect estimates and certainty of the evidence in the future. Most ongoing studies target people who need respiratory support at baseline. With the living approach of this review, we will continue to update our search and include eligible trials and published data.

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Conflict of interest statement

CW: is funded by the Federal Ministry of Education and Research, Germany (NaFoUniMedCovid19, funding number: 01KX2021; part of the project 'CEOSys', which was paid to the institution).

MG: is funded by the Federal Ministry of Education and Research, Germany (NaFoUniMedCovid19, funding number: 01KX2021; part of the project 'CEOSys', which was paid to the institution); works as a resident with the Department of Anaesthesiology and Intensive Care at the University of Leipzig Medical Center; is member of the German Society for Anaesthesia and Intensive Care.

AM: works as a physician at the Department of Infectious Diseases and Respiratory Medicine at Charité University medicine Berlin; is a member of the German Society for Infectious Diseases; works in the office of STAKOB at Robert Koch‐Institut; coordinates the work of the specialist group COVRIIN.

AMu: none known.

MM: is funded by the Federal Ministry of Education and Research, Germany (NaFoUniMedCovid19, funding number: 01KX2021; part of the project 'CEOSys', which was paid to the institution).

AF: is funded by the Federal Ministry of Education and Research, Germany (NaFoUniMedCovid19, funding number: 01KX2021; part of the project 'CEOSys', which was paid to the institution) and works as a resident with the Department of Anaesthesiology and Intensive Care at the University of Leipzig Medical Center.

MK: is funded by the Federal Ministry of Education and Research, Germany (NaFoUniMedCovid19, funding number: 01KX2021; part of the project 'CEOSys', which was paid to the institution).

MN: works as a health professional; Leadership or other fiduciary role in other board, society, committee, or advocacy group; Published opinions in medical journals, the public press, broadcast and social media relevant to the interventions in the work.

MS: none known.

KK: is funded by the Federal Ministry of Education and Research, Germany (NaFoUniMedCovid19, funding number: 01KX2021; part of the project 'CEOSys', which was paid to the institution); works as an intensive care specialist with the Department of Anaesthesiology and Intensive Care at the University of Leipzig Medical Center; is a member of the German Society for Anaesthesia and Intensive Care.

NS: none known.

FF: works as an intensive care consultant with the Department of Anaesthesiology and Intensive Care at the University of Leipzig Medical Center and is a member of the CEOsys project (no direct funding), the German Society for Anaesthesia and Intensive Care (DGAI), and the German Interdisciplinary Association for Intensive and Emergency Medicine (DIVI). Leading role in German guideline on respiratory failure and invasive mechanical ventilation.

Figures

1
1
WHO Clinical Progression Scale (Marshall 2020). Copyright © 2020 Elsevier Ltd. All rights reserved: reproduced with permission. ECMO = extracorporeal membrane oxygenation; FiO2 = fraction of inspired oxygen; NIV = non‐invasive ventilation; pO2 = partial pressure of oxygen; RNA = ribonucleic acid; SpO2 = oxygen saturation. *If hospitalised for isolation only, record status for ambulatory patients.
2
2
PRISMA flow diagram illustrating our study selection process.
1.1
1.1. Analysis
Comparison 1: Systemic corticosteroids plus standard care versus standard care (plus/minus placebo), Outcome 1: All‐cause mortality
1.2
1.2. Analysis
Comparison 1: Systemic corticosteroids plus standard care versus standard care (plus/minus placebo), Outcome 2: Clinical improvement: Liberation from IMV
1.3
1.3. Analysis
Comparison 1: Systemic corticosteroids plus standard care versus standard care (plus/minus placebo), Outcome 3: Clinical improvement: Ventilator‐free days
1.4
1.4. Analysis
Comparison 1: Systemic corticosteroids plus standard care versus standard care (plus/minus placebo), Outcome 4: Clinical worsening: New need for IMV
1.5
1.5. Analysis
Comparison 1: Systemic corticosteroids plus standard care versus standard care (plus/minus placebo), Outcome 5: Serious adverse events
1.6
1.6. Analysis
Comparison 1: Systemic corticosteroids plus standard care versus standard care (plus/minus placebo), Outcome 6: Adverse events
1.7
1.7. Analysis
Comparison 1: Systemic corticosteroids plus standard care versus standard care (plus/minus placebo), Outcome 7: Hospital‐acquired infections
1.8
1.8. Analysis
Comparison 1: Systemic corticosteroids plus standard care versus standard care (plus/minus placebo), Outcome 8: Need for dialysis
1.9
1.9. Analysis
Comparison 1: Systemic corticosteroids plus standard care versus standard care (plus/minus placebo), Outcome 9: Viral clearance
2.1
2.1. Analysis
Comparison 2: Subgroup analysis: respiratory support for the comparison of corticosteroids plus standard care versus standard care (plus/minus placebo), Outcome 1: All‐cause mortality
3.1
3.1. Analysis
Comparison 3: Subgroup analysis: dexamethasone versus methylprednisolone versus hydrocortisone for the comparison of corticosteroids plus standard care versus standard care (plus/minus placebo), Outcome 1: All‐cause mortality
4.1
4.1. Analysis
Comparison 4: Methylprednisolone versus dexamethasone, Outcome 1: All‐cause mortality
4.2
4.2. Analysis
Comparison 4: Methylprednisolone versus dexamethasone, Outcome 2: Clinical worsening: New need for IMV
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    1. IRCT20160118026097N4. The effect of dexamethasone in the treatment of high-risk COVID-19 patients. irct.ir/trial/48310 (first received 13 September 2020).
IRCT20200611047727N3 {published data only}
    1. IRCT20200611047727N3. Evaluation of efficacy and safety of low dose corticosteroid with severe pneumonia COVID-19. irct.ir/trial/49116 (first received 3 January 2021).
IRCT20201015049030N1 {published data only}
    1. IRCT20201015049030N1. Effect of dexamethasone on treatment of COVID-19. www.irct.ir/trial/51736 (first received 7 November 2020).
ISRCTN33037282 {published data only}
    1. ISRCTN33037282. Comparing two medications (dexamethasone and methylprednisolone high dose) for the treatment of pneumonia in patients with COVID-19. www.isrctn.com/ISRCTN33037282 (first received 26 November 2020).
Munch 2021 {published data only}
    1. Munch MW, Meyhoff TS, Helleberg M, Kjær M-BN, Granholm A, Hjortsø CJ, et al. Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia: the COVID STEROID randomised, placebo-controlled trial. Acta Anaesthesiologica Scandinavica 2021 Jun 17 [Epub ahead of print]. [DOI: 10.1111/aas.13941] - DOI - PMC - PubMed
    1. NCT04348305. Hydrocortisone for COVID-19 and severe hypoxia. clinicaltrials.gov/show/NCT04348305 (first received 16 April 2020).
    1. Petersen MW, Meyhoff TS, Helleberg M, Nørregaard Kjær MB, Granholm A, Steensen Hjortsø CJ, et al. Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia (COVID STEROID) trial-protocol and statistical analysis plan. Acta Anaesthesiologica Scandinavica 2020;64(9):1365-75. [DOI: 10.1111/aas.13673] - DOI - PMC - PubMed
NCT03852537 {published data only}
    1. NCT03852537. Steroid dosing by biomarker guided titration in critically ill patients with pneumonia. clinicaltrials.gov/show/NCT03852537 (first received 25 February 2019).
NCT04244591 {published data only}
    1. NCT04244591. Glucocorticoid therapy for novel coronavirus critically ill patients with severe acute respiratory failure. www.clinicaltrials.gov/ct2/show/NCT04244591 (first received 28 January 2020).
NCT04325061 {published data only}
    1. NCT04325061. Efficacy of dexamethasone treatment for patients with ARDS caused by COVID-19. clinicaltrials.gov/ct2/show/NCT04325061 (first received 27 March 2020).
NCT04746430 {published data only}
    1. NCT04746430. COVID-19 primary care platform for early treatment and recovery (COPPER) study. clinicaltrials.gov/show/NCT04746430 (first received 9 February 2021).
Rashad 2021 {unpublished data only}
    1. NCT04519385. Tocilizumab versus dexamethasone in severe COVID19 cases. clinicaltrials.gov/show/NCT04519385 (first received 19 August 2020).
    1. Rashad A, Mousa S, Nafady‑Hego H, Nafady A, Elgendy H. Short term survival of critically ill COVID‑19 Egyptian patients on assisted ventilation treated by either dexamethasone or tocilizumab. Scientific Reports 2021;11(8816):1-7. - PMC - PubMed

References to ongoing studies

ChiCTR2000029386 {published data only}
    1. Qin YY, Zhou YH, Lu YQ, Sun F, Yang S, Harypursat V, et al. Effectiveness of glucocorticoid therapy in patients with severe novel coronavirus pneumonia: protocol of a randomised controlled trial. Chinese Medical Journal 2020;133(9):1080-6. [DOI: 10.1097/CM9.0000000000000791] [ChiCTR2000029386] - DOI - PMC - PubMed
ChiCTR2000029656 {published data only}
    1. ChiCTR2000029656. A randomised, open-label study to evaluate the efficacy and safety of low-dose corticosteroids in hospitalised patients with novel coronavirus pneumonia (COVID-19). www.chictr.org.cn/showprojen.aspx?proj=49086 (first received 9 February 2020).
ChiCTR2000030481 {published data only}
    1. ChiCTR2000030481. The clinical value of corticosteroid therapy timing in the treatment of novel coronavirus pneumonia (COVID-19): a prospective randomised controlled trial. www.chictr.org.cn/showprojen.aspx?proj=50453 (first received 3 March 2020).
CTRI/2020/07/026608 {published data only}
    1. CTRI/2020/07/026608. A clinical trial to study the effects of two drugs methylprednisolone and dexamethasone in patients with severe COVID-19. www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=45638 (first received 15 July 2020).
CTRI/2020/10/028731 {published data only}
    1. CTRI/2020/10/028731. Higher vs. lower doses of dexamethasone in patients with COVID-19 and severe hypoxia. ctri.nic.in/Clinicaltrials/showallp.php?mid1=46442&EncHid=&userName=28731 (first received 29 October 2020).
    1. CTRI/2020/10/028731. Higher vs. lower doses of steroids in patients with COVID-19. www.who.int/trialsearch/Trial2.aspx?TrialID=CTRI/2020/10/028731 (first received 29 October 2020).
CTRI/2020/12/029894 {published data only}
    1. Comparing the effectiveness of dexamethasone versus methylprednisolone in patients with moderate COVID 19 - a randomised controlled trial. ctri.nic.in/Clinicaltrials/showallp.php?mid1=49273&EncHid=&userName=029894 (first received 18 December 2020).
    1. CTRI/2020/12/029894. A study to compare the effectiveness of two drugs, dexamethasone versus methylprednisolone in the treatment of moderate Covid 19 patients. www.who.int/trialsearch/Trial2.aspx?TrialID=CTRI/2020/12/029894.
CTRI/2020/12/030143 {published data only}
    1. CTRI/2020/12/030143. Comparison of different steroid regimes in critically ill adult patients of COVID-19. www.who.int/trialsearch/Trial2.aspx?TrialID=CTRI/2020/12/030143.
    1. Evaluation of different steroid regimes in critically ill adult patients of COVID-19 admitted to intensive care units. ctri.nic.in/Clinicaltrials/showallp.php?mid1=50886&EncHid=&userName=30143 (first received 31 December 2020).
EUCTR2020‐001413‐20‐ES {published data only}
    1. EUCTR2020-001413-20-ES. Efficacy and safety of siltuximab vs. corticosteroids in hospitalized patients with COVID-19 pneumonia. www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:202... (first received 7 April 2020).
EUCTR2020‐001457‐43‐FR {published data only}
    1. EUCTR2020-001457-43-FR. Dexamethasone and oxygen support strategies in ICU patients with COVID-19 pneumonia. www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:202... (first received 10 April 2020).
EUCTR2020‐001622‐64‐ES {published data only}
    1. EUCTR2020-001622-64-ES. Outpatient treatment of COVID-19 with early pulmonary corticosteroids as an opportunity to modify the course of the disease. www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:202... (first received 19 April 2020).
    1. Saiz-Rodríguez M, Peña T, Lázaro L, González A, Martínez A, Cordero JA, et al. Outpatient treatment of COVID-19 with steroids in the phase of mild pneumonia without the need for admission as an opportunity to modify the course of the disease: a structured summary of a randomised controlled trial. Trials 2020;21(632):1-3. [DOI: 10.1186/s13063-020-04575-w] - DOI - PMC - PubMed
EUCTR2020‐001707‐16‐ES {published data only}
    1. EUCTR2020-001707-16-ES. Phase III randomised, unicentric open, controlled clinical trial to demonstrate the effectiveness of tocilizumab against systemic corticotherapy in patients entered by COVID-19 with bilateral pneumonia and bad evolution. www.clinicaltrialsregister.eu/ctr-search/trial/2020-001707-16/ES (first received 25 June 2020).
EUCTR2020‐001921‐30 {published data only}
    1. Busani S, Tosi M, Mighali P, Vandelli P, D'Amico R, Marietta M, et al. Multi-centre, three arm, randomised controlled trial on the use of methylprednisolone and unfractionated heparin in critically ill ventilated patients with pneumonia from SARS-CoV-2 infection: a structured summary of a study protocol for a randomised controlled trial. Trials 2020;21(1):724. [DOI: 10.1186/s13063-020-04645-z] - DOI - PMC - PubMed
    1. EUCTR2020-001921-30. Steroids and unfractionated heparin in critically-ill patients with pneumonia from COVID-19 infection. A multicenter, interventional, randomised, three arms study design. www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:202... (first received 26 June 2020).
EUCTR2020‐002186‐34‐ES {published data only}
    1. EUCTR2020-002186-34-ES. Efficacy of the early use of corticotherapy in CoV-2 infection to prevent the progression of acute respiratory distress syndrome (ARDS). www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:202... (first received 22 July 2020).
EUCTR2020‐003363‐25‐DK {published data only}
    1. EUCTR2020-003363-25-DK. Higher vs. lower doses of dexamethasone in patients with COVID-19 and severe oxygen deficiency: the COVID STEROID 2 trial. www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:202... (first received 18 August 2020).
EUCTR2020‐004323‐16 {published data only}
    1. EUCTR2020-004323-16. Evaluation of the efficacy of high doses of methylprednisolone in SARS-CoV2 pneumonia patients. www.clinicaltrialsregister.eu/ctr-search/trial/2020-004323-16/IT (first received 23 November 2020).
NCT04329650 {published data only}
    1. NCT04329650. Efficacy and safety of siltuximab vs. corticosteroids in hospitalised patients with COVID19 pneumonia. clinicaltrials.gov/show/NCT04329650 (first received 1 April 2020).
NCT04344730 {published data only}
    1. NCT04344730. Dexamethasone and oxygen support strategies in ICU patients with COVID-19 pneumonia. clinicaltrials.gov/show/NCT04344730 (first received 14 April 2020).
NCT04345445 {published data only}
    1. NCT04345445. Study to evaluate the efficacy and safety of tocilizumab versus corticosteroids in hospitalised COVID-19 patients with high risk of progression. clinicaltrials.gov/show/NCT04345445 (first received 14 April 2020).
NCT04347980 {published data only}
    1. NCT04347980. Dexamethasone treatment for severe acute respiratory distress syndrome. clinicaltrials.gov/show/NCT04347980 (first received 15 April 2020).
NCT04377503 {published data only}
    1. NCT04377503. Tocilizumab versus methylprednisolone in the cytokine release syndrome of patients with COVID-19. clinicaltrials.gov/show/NCT04377503 (first received 6 May 2020).
NCT04395105 {published data only}
    1. Maskin LP, Olarte GL, Palizas F Jr, Velo AE, Lurbet MF, Bonelli I, et al. High dose dexamethasone treatment for acute respiratory distress syndrome secondary to COVID-19: a structured summary of a study protocol for a randomised controlled trial. Trials 2020;21(1):743. [DOI: 10.1186/s13063-020-04646-y] - DOI - PMC - PubMed
    1. NCT04395105. Dexamethasone for COVID-19 related ARDS: a multicenter, randomised clinical trial. clinicaltrials.gov/show/NCT04395105 (first received 20 May 2020).
NCT04438980 {published data only}
    1. Les Bujanda I, Loureiro-Amigo J, Capdevila Bastons F, Elejalde Guerra I, Anniccherico Sánchez J, Murgadella-Sancho A, et al. Treatment of COVID-19 pneumonia with glucocorticoids (CORTIVID): a structured summary of a study protocol for a randomised controlled trial. Trials 2021;22(1):43. [DOI: 10.1186/s13063-020-04999-4] - DOI - PMC - PubMed
    1. NCT04438980. Glucocorticoids in COVID-19 (CORTIVID). clinicaltrials.gov/show/NCT04438980 (first received 19 June 2020).
NCT04451174 {published data only}
    1. NCT04451174. Early use of corticosteroids in hospitalised patients with moderate COVID19 pneumonia. clinicaltrials.gov/show/NCT04451174 (first received 30 June 2020).
    1. Salinas M, Andino P, Palma L, Valencia J, Figueroa E, Ortega J. Early use of corticosteroids in non-critical patients with COVID-19 pneumonia (PREDCOVID): a structured summary of a study protocol for a randomised controlled trial. Trials 2021;22(1):92. [DOI: 10.1186/s13063-021-05046-6.] - DOI - PMC - PubMed
NCT04452565 {published data only}
    1. NCT04452565. NA-831, atazanavir and dexamethasone in the treatment of SARSCov-2 infection (NATADEX). clinicaltrials.gov/show/NCT04452565 (first received 30 June 2020).
NCT04485429 {published data only}
    1. NCT04485429. Efficacy assessment of methylprednisolone and heparin in patients with COVID-19 pneumonia. clinicaltrials.gov/show/NCT04485429 (first received 24 July 2020).
NCT04499313 {published data only}
    1. NCT04499313. Dexamethasone versus methylprednisolone for the treatment of patients with ARDS caused by COVID-19. clinicaltrials.gov/show/NCT04499313 (first received 5 August 2020).
NCT04509973 {published data only}
    1. Munch MW, Granholm A, Myatra SN, Vijayaraghavan BK, Cronhjort M, Wahlin RR, et al. Higher vs. lower doses of dexamethasone in patients with COVID-19 and severe hypoxia (COVID STEROID 2) trial: protocol and statistical analysis plan. Acta Anaesthesiologica Scandinavica 2021;00:1-12. [DOI: 10.1111/aas.13795] - DOI - PMC - PubMed
    1. NCT04509973. Higher vs. lower doses of dexamethasone for COVID-19 and severe hypoxia. clinicaltrials.gov/show/NCT04509973 (first received 12 August 2020).
NCT04513184 {published data only}
    1. NCT04513184. Randomised clinical trial of nasal dexamethasone as an adjuvant in patients with COVID-19. clinicaltrials.gov/show/NCT04513184 (first received 14 August 2020).
NCT04528329 {published data only}
    1. NCT04528329. Anosmia and / or ageusia and early corticosteroid use. clinicaltrials.gov/show/NCT04528329 (first received 27 August 2020).
NCT04528888 {published data only}
    1. NCT04528888. Steroids and unfractionated heparin in critically ill patients with pneumonia from COVID-19 infection. clinicaltrials.gov/show/NCT04528888 (first received 27 August 2020). [EUDRA-CT: https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001921-30/IT] [NCT: https://clinicaltrials.gov/ct2/show/study/NCT04528888]
NCT04530409 {published data only}
    1. NCT04530409. Timing of corticosteroids in COVID-19. clinicaltrials.gov/show/NCT04530409 (first received 28 August 2020).
NCT04545242 {published data only}
    1. NCT04545242. Efficacy of dexamethasone in patients with acute hypoxemic respiratory failure caused by infections. clinicaltrials.gov/show/NCT04545242 (first received 10 September 2020).
NCT04636671 {published data only}
    1. NCT04636671. Methylprednisolone vs. dexamethasone in COVID-19 pneumonia (MEDEAS RCT). clinicaltrials.gov/show/NCT04636671 (first received 19 November 2020).
NCT04663555 {published data only}
    1. NCT04663555. Effect of two different doses of dexamethasone in patients with ARDS and COVID-19. clinicaltrials.gov/show/NCT04663555 (first received 11 December 2020).
NCT04673162 {published data only}
    1. NCT04673162. Evaluation of the efficacy of high doses of methylprednisolone in SARS-CoV2 ( COVID-19) pneumonia patients. clinicaltrials.gov/show/NCT04673162 (first received 17 December 2020).
NCT04707534 {published data only}
    1. NCT04707534. Dexamethasone for COVID-19. clinicaltrials.gov/show/NCT04707534 (first received 13 January 2021).
NCT04726098 {published data only}
    1. NCT04726098. Low or high dose of dexamethasone in patients with respiratory failure by COVID-19. clinicaltrials.gov/ct2/show/record/NCT04726098 (first received 27 January 2021).
NCT04765371 {published data only}
    1. NCT04765371. Comparison between prednisolone and dexamethasone on mortality in patients on oxygen therapy, with COVID-19. clinicaltrials.gov/ct2/show/NCT04765371 (first received 21 February 2021).
NCT04780581 {published data only}
    1. NCT04780581. Glucocorticoid therapy in coronavirus disease COVID-19 patients. clinicaltrials.gov/show/NCT04780581 (first received 3 March 2021).
NCT04795583 {published data only}
    1. NCT04795583. Corticosteroids for COVID-19. clinicaltrials.gov/show/NCT04795583 (first received 12 March 2021).
NCT04834375 {published data only}
    1. NCT04834375. Randomised open investigation determining steroid dose. clinicaltrials.gov/show/NCT04834375 (first received 8 April 2021).
NCT04836780 {published data only}
    1. NCT04836780. Dexamethasone early administration in hospitalised patients with COVID-19 pneumonia. clinicaltrials.gov/show/NCT04836780 (first received 8 April 2021).

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