Steroid therapy for COVID-19: A systematic review and meta-analysis of randomized controlled trials

Submitted: December 5, 2020
Accepted: June 8, 2021
Published: July 21, 2021
Abstract Views: 1792
PDF: 686
Supplementary: 0
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

There is an urgent need for effective treatment modalities for coronavirus disease 2019 (COVID-19). Data for the use of steroids in COVID-19 is emerging. We conducted this systematic review and meta-analysis to estimate the effectiveness of steroid administration in mortality reduction due to COVID-19 compared to the control group. A systematic search of the Pubmed and Embase databases was performed to extract randomized controlled trials (RCTs) regarding the use of steroid therapy for COVID-19. An overall and subgroup (based upon the type of steroid) pooled mortality analysis was performed, and odds ratios were reported. Cochrane risk of bias assessment tool was used to assess the risk of bias. Heterogeneity was assessed using the I2 statistic. Six RCTs, including 7707 patients, were selected for review. Three trials reported 28-day mortality, and two trials reported 21-day mortality, and one trial reported in-hospital mortality. There were 730 deaths among 2837 participants in the steroid group while 1342 deaths among 4870 patients randomized to the control group (Odds ratio 0.76, 95% confidence interval 0.58-1.00, p=0.05). The effect was significant in patients on oxygen or mechanical ventilation. There was no difference in the various preparations and doses of the steroids. There was heterogeneity among the trials as the I2 value was 53%, with a p-value of 0.06. There was no indication of increased serious adverse events. This meta-analysis of RCTs demonstrated that the use of systemic corticosteroids is associated with a reduction in all-cause mortality in patients with COVID-19 on oxygen or mechanical ventilation.

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.

Citations

Hussain MA, Yadav S, Hadda V, et al. Covid-19: a comprehensive review of a formidable foe and the road ahead. Expert Rev Respir Med 2020;14:869-79. DOI: https://doi.org/10.1080/17476348.2020.1782198
Mohan A, Tiwari P, Bhatnagar S, et al. Clinico-demographic profile & hospital outcomes of COVID-19 patients admitted at a tertiary care centre in north India. Indian J Med Res 2020;152:61–9. DOI: https://doi.org/10.4103/ijmr.IJMR_1788_20
Tyagi R, Mittal S, Madan K, et al. Assessment of the impact and reorganization of interventional pulmonology services at a tertiary care centre during nationwide lockdown for COVID-19 pandemic. Monaldi Arch Chest Dis 2021;91:1615. DOI: https://doi.org/10.4081/monaldi.2021.1615
Aggarwal N, Boppana TK, Mittal S. COVID-19 pandemic: The testing times for healthcare workers. Monaldi Arch Chest Dis 2021;91:1515. DOI: https://doi.org/10.4081/monaldi.2021.1515
Madan M, Pahuja S, Tyagi R, et al. Ambient temperature and COVID-19 outcomes. Adv Respir Med 2021;89:341-3. DOI: https://doi.org/10.5603/ARM.a2021.0021
Pahuja S, Madan M, Mittal S, et al. Weather parameters and COVID-19: A correlational analysis. J Occup Environ Med 2021;63:69-73. DOI: https://doi.org/10.1097/JOM.0000000000002082
Madan M, Mohan A, Madan K, et al. Timing of anti-viral therapy in COVID-19: Key to success. Adv Respir Med 2021;89:237-9. DOI: https://doi.org/10.5603/ARM.a2021.0020
Singh Sehgal I, Guleria R, Singh S, et al. A randomised trial of Mycobacterium w in critically ill patients with COVID-19 (ARMY-1). ERJ Open Res 2021;7:00059-2021. DOI: https://doi.org/10.1183/23120541.00059-2021
Sryma PB, Mittal S, Madan K, et al. Reinventing the wheel in ARDS: Awake poning in COVID-19. Arch Bronconeumol 2020;56:747–9. DOI: https://doi.org/10.1016/j.arbres.2020.06.002
Mittal S, Pb S, Madan K, et al. Awake proning in COVID-19 - does CPAP make a difference? Adv Respir Med 2020;89:82. DOI: https://doi.org/10.5603/ARM.a2020.0179
Pb S, Mittal S, Madan K, et al. Awake prone positioning in non-intubated patients for the management of hypoxemia in COVID-19: A systematic review and meta-analysis. Monaldi Arch Chest Dis 2021;91:1623. DOI: https://doi.org/10.4081/monaldi.2021.1623
Sryma PB, Mittal S, Mohan A, et al. Effect of proning in patients with COVID-19 acute hypoxemic respiratory failure receiving noninvasive oxygen therapy. Lung India 2021;38:S6–10. DOI: https://doi.org/10.4103/lungindia.lungindia_794_20
Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of Covid-19 - Final report. N Engl J Med 2020;383:1813-26. DOI: https://doi.org/10.1056/NEJMc2022236
Huang J, Guo J, Li H, et al. Efficacy and safety of adjunctive corticosteroids therapy for patients with severe community-acquired pneumonia: A systematic review and meta-analysis. Medicine (Baltimore) 2019;98:e14636. DOI: https://doi.org/10.1097/MD.0000000000014636
RECOVERY Collaborative Group, Horby P, Lim WS, et al. Dexamethasone in hospitalized patients with Covid-19 - Preliminary report. N Engl J Med 2021;384:693-704. DOI: https://doi.org/10.1056/NEJMoa2021436
Tomazini BM, Maia IS, Cavalcanti AB, 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. JAMA 2020;324:1307-16. DOI: https://doi.org/10.1001/jama.2020.17021
Angus DC, Derde L, Al-Beidh F, et al. Effect of hydrocortisone on mortality and organ support in patients with severe COVID-19: The REMAP-CAP COVID-19 corticosteroid domain randomized clinical trial. JAMA 2020;324:1317-29. DOI: https://doi.org/10.1001/jama.2020.17022
Dequin P-F, Heming N, Meziani F, et al. Effect of hydrocortisone on 21-day mortality or respiratory support among critically ill patients with COVID-19: A randomized clinical trial. JAMA 2020;324:1298-306. DOI: https://doi.org/10.1001/jama.2020.16761
Edalatifard M, Akhtari M, Salehi M, et al. Intravenous methylprednisolone pulse as a treatment for hospitalised severe COVID-19 patients: results from a randomised controlled clinical trial. Eur Respir J 2020;56:2002808. DOI: https://doi.org/10.1183/13993003.02808-2020
Jeronimo CMP, Farias MEL, Val FFA, et al. Methylprednisolone as adjunctive therapy for patients hospitalized with COVID-19 (Metcovid): A randomised, double-blind, phase IIb, placebo-controlled trial. Clin Infect Dis 2020;72:e373-81.
Bani-Sadr F, Hentzien M, Pascard M, et al. Corticosteroid therapy for patients with COVID-19 pneumonia: a before-after study. Int J Antimicrob Agents 2020;56:106077. DOI: https://doi.org/10.1016/j.ijantimicag.2020.106077
Bartoletti M, Marconi L, Scudeller L, et al. Efficacy of corticosteroid treatment for hospitalized patients with severe COVID-19: a multicenter study. Clin Microbiol Infect 2020;27:105-11. DOI: https://doi.org/10.1016/j.cmi.2020.09.014
Cruz AF, Ruiz-Antorán B, Múñez Rubio E, et al. The right time for steroids in COVID-19. Clin Infect Dis 2020;72:1486-7. DOI: https://doi.org/10.1093/cid/ciaa865
Fadel R, Morrison AR, Vahia A, et al. Early short course corticosteroids in hospitalized patients with COVID-19. Clin Infect Dis 2020;71:2144-20. DOI: https://doi.org/10.1101/2020.05.04.20074609
Fang X, Mei Q, Yang T, et al. Low-dose corticosteroid therapy does not delay viral clearance in patients with COVID-19. J Infect 2020;81:147–78. DOI: https://doi.org/10.1016/j.jinf.2020.03.039
Sarkar S, Khanna P, Soni KD. Are the steroids a blanket solution for COVID-19? a systematic review and meta-analysis. J Med Virol 2021;93:1538-47. DOI: https://doi.org/10.1002/jmv.26483
Sterne JAC, Murthy S, Diaz JV, et al. Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: A meta-analysis. JAMA 2020;324:1330-41. DOI: https://doi.org/10.1001/jama.2020.17023
Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 2009;339:b2700. DOI: https://doi.org/10.1136/bmj.b2700
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629–34. DOI: https://doi.org/10.1136/bmj.315.7109.629
Khilnani GC, Hadda V. Corticosteroids and ARDS: A review of treatment and prevention evidence. Lung India 2011;28:114–9. DOI: https://doi.org/10.4103/0970-2113.80324
Stone JH, Frigault MJ, Serling-Boyd NJ, et al. Efficacy of tocilizumab in patients hospitalized with Covid-19. N Engl J Med 2020;383:233-44. DOI: https://doi.org/10.1056/NEJMoa2028836
Lansbury LE, Rodrigo C, Leonardi-Bee J, et al. Corticosteroids as adjunctive therapy in the treatment of influenza: An updated Cochrane systematic review and meta-analysis. Crit Care Med 2020;48:e98-106. DOI: https://doi.org/10.1097/CCM.0000000000004093
Mittal S, Madan K, Mohan A, et al. Diabetes in COVID-19: Steroid effect. J Med Virol 2021;93:4166. DOI: https://doi.org/10.1002/jmv.26457
Mittal S, Madan K, Mohan A. COVID-19 and steroid therapy: Impact on diabetes. Prim Care Diabetes 2020;14:568. DOI: https://doi.org/10.1016/j.pcd.2020.07.013

How to Cite

Boppana, Tarun Krishna, Saurabh Mittal, Karan Madan, Anant Mohan, Vijay Hadda, Pawan Tiwari, and Randeep Guleria. 2021. “Steroid Therapy for COVID-19: A Systematic Review and Meta-Analysis of Randomized Controlled Trials”. Monaldi Archives for Chest Disease 91 (4). https://doi.org/10.4081/monaldi.2021.1716.