Effectiveness and safety of glucocorticoids to treat COVID-19: a rapid review and meta-analysis

doi:10.21037/atm-20-3307

. 2020 May;8(10):627.

doi: 10.21037/atm-20-3307.

Effectiveness and safety of glucocorticoids to treat COVID-19: a rapid review and meta-analysis

Shuya Lu^{1

2

3}, Qi Zhou^{3

4}, Liping Huang^{5

6

7}, Qianling Shi^{3

4}, Siya Zhao⁸, Zijun Wang³, Weiguo Li^{5

6

7}, Yuyi Tang^{5

6

7}, Yanfang Ma³, Xufei Luo^{3

8}, Toshio Fukuoka^{9

10}, Hyeong Sik Ahn^{11

12}, Myeong Soo Lee^{13

14}, Zhengxiu Luo^{5

6

7}, Enmei Liu^{5

6

7}, Yaolong Chen^{3

15

16

17}, Chenyan Zhou^{1

2}, Donghong Peng^{5

6

7}

Affiliations

¹ Department of Pediatric, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 611731, China.
² Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu 610072, China.
³ Evidence-based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
⁴ The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China.
⁵ Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
⁶ National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
⁷ Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China.
⁸ School of Public Health, Lanzhou University, Lanzhou 730000, China.
⁹ Emergency and Critical Care Center, the Department of General Medicine, Department of Research and Medical Education at Kurashiki Central Hospital, Kurashiki, Japan.
¹⁰ Advisory Committee in Cochrane Japan, Tokyo, Japan.
¹¹ Department of Preventive Medicine, Korea University College of Medicine, Seoul, Korea.
¹² Korea Cochrane Centre, Seoul, Korea.
¹³ Korea Institute of Oriental Medicine, Daejeon, Korea.
¹⁴ University of Science and Technology, Daejeon, Korea.
¹⁵ Lanzhou University, an Affiliate of the Cochrane China Network, Lanzhou 730000, China.
¹⁶ Chinese GRADE Center, Lanzhou 730000, China.
¹⁷ Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu Province, Lanzhou University, Lanzhou 730000, China.

PMID: 32566564
PMCID: PMC7290628
DOI: 10.21037/atm-20-3307

Effectiveness and safety of glucocorticoids to treat COVID-19: a rapid review and meta-analysis

Shuya Lu et al. Ann Transl Med. 2020 May.

. 2020 May;8(10):627.

doi: 10.21037/atm-20-3307.

Authors

Affiliations

¹ Department of Pediatric, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 611731, China.
² Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu 610072, China.
³ Evidence-based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
⁴ The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China.
⁵ Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
⁶ National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
⁷ Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China.
⁸ School of Public Health, Lanzhou University, Lanzhou 730000, China.
⁹ Emergency and Critical Care Center, the Department of General Medicine, Department of Research and Medical Education at Kurashiki Central Hospital, Kurashiki, Japan.
¹⁰ Advisory Committee in Cochrane Japan, Tokyo, Japan.
¹¹ Department of Preventive Medicine, Korea University College of Medicine, Seoul, Korea.
¹² Korea Cochrane Centre, Seoul, Korea.
¹³ Korea Institute of Oriental Medicine, Daejeon, Korea.
¹⁴ University of Science and Technology, Daejeon, Korea.
¹⁵ Lanzhou University, an Affiliate of the Cochrane China Network, Lanzhou 730000, China.
¹⁶ Chinese GRADE Center, Lanzhou 730000, China.
¹⁷ Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu Province, Lanzhou University, Lanzhou 730000, China.

PMID: 32566564
PMCID: PMC7290628
DOI: 10.21037/atm-20-3307

Abstract

Background: Glucocorticoids are widely used in the treatment of various pulmonary inflammatory diseases, but they are also often accompanied by significant adverse reactions. Published guidelines point out that low dose and short duration systemic glucocorticoid therapy may be considered for patients with rapidly progressing coronavirus disease 2019 (COVID-19) while the evidence is still limited.

Methods: We comprehensively searched electronic databases and supplemented the screening by conducting a manual search. We included randomized controlled trials (RCTs) and cohort studies evaluating the effectiveness and safety of glucocorticoids in children and adults with COVID-19, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and conducted meta-analyses of the main indicators that were identified in the studies.

Results: Our search retrieved 23 studies, including one RCT and 22 cohort studies, with a total of 13,815 patients. In adults with COVID-19, the use of systemic glucocorticoid did not reduce mortality [risk ratio (RR) =2.00, 95% confidence interval (CI): 0.69 to 5.75, I²=90.9%] or the duration of lung inflammation [weighted mean difference (WMD) =-1 days, 95% CI: -2.91 to 0.91], while a significant reduction was found in the duration of fever (WMD =-3.23 days, 95% CI: -3.56 to -2.90). In patients with SARS, glucocorticoids also did not reduce the mortality (RR =1.52, 95% CI: 0.89 to 2.60, I²=84.6%), duration of fever (WMD =0.82 days, 95% CI: -2.88 to 4.52, I²=97.9%) or duration of lung inflammation absorption (WMD =0.95 days, 95% CI: -7.57 to 9.48, I²=94.6%). The use of systemic glucocorticoid therapy prolonged the duration of hospital stay in all patients (COVID-19, SARS and MERS).

Conclusions: Glucocorticoid therapy was found to reduce the duration of fever, but not mortality, duration of hospitalization or lung inflammation absorption. Long-term use of high-dose glucocorticoids increased the risk of adverse reactions such as coinfections, so routine use of systemic glucocorticoids for patients with COVID-19 cannot be recommend.

Keywords: Coronavirus disease 2019 (COVID-19); glucocorticoids; meta-analysis; rapid review.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-3307). MSL serves as the unpaid editorial board member of Annals of Translational Medicine from Nov 2019 to Oct 2021. The other authors have no conflicts of interest to declare.

Figures

**Figure 1**
PRISMA flow chart. RCT, randomized controlled trial.

**Figure 2**
Relative risk of death in patients receiving versus not receiving glucocorticoid therapy: all patients. RR, risk ratio; CI, confidence interval.

**Figure 3**
Relative risk of death in patients receiving versus not receiving glucocorticoid therapy: subgroup analyses of patients with mild and severe SARS. RR, risk ratio; CI, confidence interval.

**Figure 4**
Relative risk of death in patients receiving versus not receiving glucocorticoid therapy: subgroup analyses of adult patients with SARS. RR, risk ratio; CI, confidence interval.

**Figure 5**
Duration of fever in patients receiving versus not receiving glucocorticoid therapy: all patients. WMD, weighted mean difference; CI, confidence interval; SD, standard deviation.

**Figure 6**
Duration of fever in patients receiving versus not receiving glucocorticoid therapy: subgroup analyses of patients with mild and severe SARS. WMD, weighted mean difference; CI, confidence interval; SD, standard deviation.

**Figure 7**
Lung inflammation absorption time in patients receiving versus not receiving glucocorticoid therapy: all patients. WMD, weighted mean difference; CI, confidence interval; SD, standard deviation.

**Figure 8**
Lung inflammation absorption time in patients receiving versus not receiving glucocorticoid therapy: subgroup analyses of patients with mild and severe SARS. WMD, weighted mean difference; CI, confidence interval; SD, standard deviation.

**Figure 9**
Length of stay in patients receiving versus not receiving glucocorticoid therapy: all patients. WMD, weighted mean difference; CI, confidence interval; SD, standard deviation.

**Figure 10**
Relative risk of adverse events in patients receiving versus not receiving glucocorticoid therapy. RR, risk ratio; CI, confidence interval.

**Figure 11**
Sensitivity analysis of mortality in SARS patients.

**Figure 12**
Publication bias (Egger test). SND, standard normal deviate; CI, confidence interval.

See this image and copyright information in PMC

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[1] Phelan AL, Katz R, Gostin LO. The Novel Coronavirus Originating in Wuhan, China: Challenges for Global Health Governance. JAMA 2020. [Epub ahead of print]. doi:.10.1001/jama.2020.1097 - DOI - PubMed

[2] Phelan AL, Katz R, Gostin LO. The Novel Coronavirus Originating in Wuhan, China: Challenges for Global Health Governance. JAMA 2020. [Epub ahead of print]. doi:.10.1001/jama.2020.1097 - DOI - PubMed

[3] WHO Director-General's remarks at the media briefing on 2019-nCoV on 11 February 2020[Internet]. World Health Organization 2020 [cited 2020 Apr 13]. Available online: https://www.who.int/dg/speeches/detail/who-director-general-s-remarks-at...

[4] WHO Director-General's remarks at the media briefing on 2019-nCoV on 11 February 2020[Internet]. World Health Organization 2020 [cited 2020 Apr 13]. Available online: https://www.who.int/dg/speeches/detail/who-director-general-s-remarks-at...

[5] WHO characterizes COVID-19 as a pandemic. March 12, 2020[Internet]. World Health Organization 2020 [cited 2020 Apr 13]. Available online: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/events-a...

[6] WHO characterizes COVID-19 as a pandemic. March 12, 2020[Internet]. World Health Organization 2020 [cited 2020 Apr 13]. Available online: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/events-a...

[7] Coronavirus (COVID-19) [Internet]. World Health Organization 2020 [cited 2020 Apr 13]. Available online: https://who.sprinklr.com/

[8] Coronavirus (COVID-19) [Internet]. World Health Organization 2020 [cited 2020 Apr 13]. Available online: https://who.sprinklr.com/

[9] Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020;395:565-74. 10.1016/S0140-6736(20)30251-8 - DOI - PMC - PubMed

[10] Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020;395:565-74. 10.1016/S0140-6736(20)30251-8 - DOI - PMC - PubMed

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Effectiveness and safety of glucocorticoids to treat COVID-19: a rapid review and meta-analysis

Affiliations

Effectiveness and safety of glucocorticoids to treat COVID-19: a rapid review and meta-analysis

Authors

Affiliations

Abstract

Conflict of interest statement

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