Efficacy and safety of glucocorticoids for severe COVID-19 patients: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

LIU Min ^1,2 , YANG Cheng ^2,3 , FENG Chunlu ^2,3 , TUO Lin ² , GENG Xiaoxia ² ,  YANG Xingxiang ²

1. Chengdu Medical College, Chengdu 610500, P. R. China;
2. Department of Infectious Disease, Sichuan Academy of Medical Sciences·Sichuan Provincial People's Hospital, Chengdu 610072, P. R. China;
3. School of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, P. R. China;

Corresponding author：

YANG Xingxiang, Email: 719525383@qq.com

Keywords：

Glucocorticoids; COVID-19; Efficacy; Safety; Meta-analysis

DOI：

10.7507/1672-2531.202112067

Video：

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Objective To systematically review the efficacy and safety of glucocorticoids for severe COVID-19 and to provide references for the treatment strategy of severe COVID-19 patients. Methods PubMed, EMbase, The Cochrane Library, Web of Science, ClinicalTrials.gov, WanFang Data and CNKI databases were electronically searched to collect randomized controlled trials (RCTs) that reported glucocorticoid therapy for severe COVID-19 patients from inception to August 26^th, 2021. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. Meta-analysis was then performed using RevMan 5.3 software. Results A total of 7 RCTs involving 6 236 patients were included. The meta-analysis results showed that compared with usual care, glucocorticoids significantly reduced the all-cause mortality of severe COVID-19 (RR=0.84, 95%CI 0.77 to 0.91, P<0.000 1), whereas no significant difference was found in the progression of complex diseases between the two groups (RR=0.84, 95%CI 0.69 to 1.01, P=0.06). Glucocorticoids did not increase adverse effects in severe COVID-19 compared with usual care (general adverse events: RR=1.15, 95%CI 0.66 to 2.03, P=0.62; serious adverse events: RR=1.13, 95%CI 0.54 to 2.38, P=0.75). Conclusion Current evidence suggests that glucocorticoids are effective in treating severe COVID-19 without significantly increasing adverse events. However, due to the limited quantity and quality of the included studies, more high-quality studies are needed to verify the conclusion.

Citation： LIU Min, YANG Cheng, FENG Chunlu, TUO Lin, GENG Xiaoxia, YANG Xingxiang. Efficacy and safety of glucocorticoids for severe COVID-19 patients: a meta-analysis. Chinese Journal of Evidence-Based Medicine, 2022, 22(4): 387-393. doi: 10.7507/1672-2531.202112067 Copy

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2.	Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: a clinical-therapeutic staging proposal. J Heart Lung Transplant, 2020, 39(5): 405-407.
3.	马文君, 贾换. 丙种球蛋白联合地塞米松治疗重症肺炎的效果. 河南医学研究, 2020, 29(7): 1259-1260.
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5.	Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet, 2020, 395(10223): 473-475.
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7.	Fadel R, Morrison AR, Vahia A, et al. Early short-course corticosteroids in hospitalized patients with COVID-19. Clin Infect Dis, 2020, 71(16): 2114-2120.
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14.	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(13): 1317-1329.
15.	Dequin PF, 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(13): 1298-1306.
16.	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(13): 1307-1316.
17.	Jeronimo CMP, Farias MEL, Val FFA, et al. Methylprednisolone as adjunctive therapy for patients hospitalized with coronavirus disease 2019 (COVID-19; Metcovid): a randomized, double-blind, phase IIb, placebo-controlled trial. Clin Infect Dis, 2021, 72(9): e373-e381.
18.	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(6): 2002808.
19.	Cain DW, Cidlowski JA. After 62 years of regulating immunity, dexamethasone meets COVID-19. Nat Rev Immunol, 2020, 20(10): 587-588.
20.	Veronese N, Demurtas J, Yang L, et al. Use of corticosteroids in coronavirus disease 2019 pneumonia: a systematic review of the literature. Front Med (Lausanne), 2020, 7: 170.
21.	高安, 陆圣威, 陈丽, 等. 糖皮质激素在重症新型冠状病毒肺炎治疗中的安全性荟萃分析. 中国感染与化疗杂志, 2021, 21(4): 411-417.
22.	Cheng W, Li Y, Cui L, et al. Efficacy and safety of corticosteroid treatment in patients with COVID-19: a systematic review and meta-analysis. Front Pharmacol, 2020, 11: 571156.
23.	Gangopadhyay KK, Mukherjee JJ, Sinha B, et al. The role of corticosteroids in the management of critically ill patients with coronavirus disease 2019 (COVID-19): a meta-analysis. Available at: https://www.medrxiv.org/content/10.1101/2020.04.17.20069773v1.
24.	Lu S, Zhou Q, Huang L, et al. Effectiveness and safety of glucocorticoids to treat COVID-19: a rapid review and meta-analysis. Ann Transl Med, 2020, 8(10): 627.
25.	WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, Sterne JAC, Murthy S, et al. Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis. JAMA, 2020, 324(13): 1330-1341.

1. Gorbalenya AE, Baker SC, Baric RS, et al. Severe acute respiratory syndrome-related coronavirus: the species and its viruses – a statement of the Coronavirus Study Group. 2020: 2020.02. 07.937862.
2. Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: a clinical-therapeutic staging proposal. J Heart Lung Transplant, 2020, 39(5): 405-407.
3. 马文君, 贾换. 丙种球蛋白联合地塞米松治疗重症肺炎的效果. 河南医学研究, 2020, 29(7): 1259-1260.
4. Yang Z, Liu J, Zhou Y, et al. The effect of corticosteroid treatment on patients with coronavirus infection: a systematic review and meta-analysis. J Infect, 2020, 81(1): e13-e20.
5. Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet, 2020, 395(10223): 473-475.
6. Hazbun ME, Faust AC, Ortegon AL, et al. The combination of tocilizumab and methylprednisolone along with initial lung recruitment strategy in coronavirus disease 2019 patients requiring mechanical ventilation: a series of 21 consecutive cases. Crit Care Explor, 2020, 2(6): e0145.
7. Fadel R, Morrison AR, Vahia A, et al. Early short-course corticosteroids in hospitalized patients with COVID-19. Clin Infect Dis, 2020, 71(16): 2114-2120.
8. Moher D, Shamseer L, Clarke M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev, 2015, 4(1): 1.
9. 姜利, 潘纯, 桑岭, 等. 重症新型冠状病毒肺炎管理专家推荐意见. 中华重症医学电子杂志, 2020, 6(1): 1-11.
10. Sterne JAC, Savović J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ, 2019, 366: l4898.
11. Higgins JP, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses. BMJ, 2003, 327(7414): 557-560.
12. RECOVERY Collaborative Group, Horby P, Lim WS, et al. Dexamethasone in hospitalized patients with COVID-19. N Engl J Med, 2021, 384(8): 693-704.
13. Corral-Gudino L, Bahamonde A, Arnaiz-Revillas F, et al. Methylprednisolone in adults hospitalized with COVID-19 pneumonia: an open-label randomized trial (GLUCOCOVID). Wien Klin Wochenschr, 2021, 133(7-8): 303-311.
14. 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(13): 1317-1329.
15. Dequin PF, 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(13): 1298-1306.
16. 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(13): 1307-1316.
17. Jeronimo CMP, Farias MEL, Val FFA, et al. Methylprednisolone as adjunctive therapy for patients hospitalized with coronavirus disease 2019 (COVID-19; Metcovid): a randomized, double-blind, phase IIb, placebo-controlled trial. Clin Infect Dis, 2021, 72(9): e373-e381.
18. 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(6): 2002808.
19. Cain DW, Cidlowski JA. After 62 years of regulating immunity, dexamethasone meets COVID-19. Nat Rev Immunol, 2020, 20(10): 587-588.
20. Veronese N, Demurtas J, Yang L, et al. Use of corticosteroids in coronavirus disease 2019 pneumonia: a systematic review of the literature. Front Med (Lausanne), 2020, 7: 170.
21. 高安, 陆圣威, 陈丽, 等. 糖皮质激素在重症新型冠状病毒肺炎治疗中的安全性荟萃分析. 中国感染与化疗杂志, 2021, 21(4): 411-417.
22. Cheng W, Li Y, Cui L, et al. Efficacy and safety of corticosteroid treatment in patients with COVID-19: a systematic review and meta-analysis. Front Pharmacol, 2020, 11: 571156.
23. Gangopadhyay KK, Mukherjee JJ, Sinha B, et al. The role of corticosteroids in the management of critically ill patients with coronavirus disease 2019 (COVID-19): a meta-analysis. Available at: https://www.medrxiv.org/content/10.1101/2020.04.17.20069773v1.
24. Lu S, Zhou Q, Huang L, et al. Effectiveness and safety of glucocorticoids to treat COVID-19: a rapid review and meta-analysis. Ann Transl Med, 2020, 8(10): 627.
25. WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, Sterne JAC, Murthy S, et al. Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis. JAMA, 2020, 324(13): 1330-1341.

Chinese Journal of Evidence-Based Medicine

Efficacy and safety of glucocorticoids for severe COVID-19 patients: a meta-analysis

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