Corticosteroid use in viral pneumonia: experience so far and the dexamethasone breakthrough in coronavirus disease-2019
Publication: Journal of Comparative Effectiveness Research
Abstract
Dexamethasone was shown to decrease the mortality in coronavirus disease-2019 (COVID-19) recently. Use of corticosteroids was harmful in other coronavirus infections previously. WHO recommended against routine use of corticosteroids in COVID-19. In view of these, we reviewed the evidence about the use of corticosteroids in virus-induced acute respiratory distress syndrome (ARDS). Corticosteroids are beneficial in ARDS regardless of etiology. However, they increased the mortality rate in influenza-associated ARDS. In SARS and the Middle East respiratory syndrome, corticosteroids increased the mortality, delayed the viral clearance and increased the length of hospital stay. In the case of COVID-19, the available evidence from retrospective and observational studies is inconclusive about the corticosteroid use. Low-dose therapies appear to be effective. Evidence from a randomized control study found dexamethasone is effective in decreasing mortality in severe COVID-19 cases. More studies are needed to validate the benefit of corticosteroids in COVID-19.
Formats available
You can view the full content in the following formats:
References
Papers of special note have been highlighted as: • of interest; •• of considerable interest
1.
Guo Y-R, Cao Q-D, Hong Z-S et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak: an update on the status. Mil. Med. Res. 7(1), 1–10 (2020).
2.
Guan W, Ni Z, Hu Y et al. Clinical characteristics of coronavirus disease 2019 in China. N. Engl. J. Med. 382(18), 1708–1720 (2020).
3.
Li X, Ma X. Acute respiratory failure in COVID-19: is it “typical” ARDS? Crit. Care 24(1), 198 (2020).
4.
DeDiego ML, Nieto-Torres JL, Regla-Nava JA et al. Inhibition of NF-κB-mediated inflammation in severe acute respiratory syndrome coronavirus-infected mice increases survival. J. Virol. 88(2), 913–924 (2014).
5.
Chan JF-W, Yao Y, Yeung M-L et al. Treatment with lopinavir/ritonavir or interferon-β1b improves outcome of MERS-CoV infection in a nonhuman primate model of common marmoset. J. Infect. Dis. 212(12), 1904–1913 (2015).
6.
Arabi YM, Mandourah Y, Al-Hameed F et al. Corticosteroid therapy for critically ill patients with Middle East respiratory syndrome. Am. J. Respir. Crit. Care Med. 197(6), 757–767 (2018).
7.
Stockman LJ, Bellamy R, Garner P. SARS: systematic review of treatment effects. PLoS Med. 3(9), e343 (2006).
8.
Tran TH, Nguyen TL, Nguyen TD et al. Avian influenza A (H5N1) in 10 patients in Vietnam. N. Engl. J. Med. 350(12), 1179–1188 (2004).
9.
Wong SSY, Yuen K-Y. Avian influenza virus infections in humans. Chest 129(1), 156–168 (2006).
10.
Hui DS. Systemic corticosteroid therapy may delay viral clearance in patients with Middle East respiratory syndrome coronavirus infection. Am. J. Respir. Crit. Care Med. 197(6), 700–701 (2018).
11.
Auyeung TW, Lee JSW, Lai WK et al. The use of corticosteroid as treatment in SARS was associated with adverse outcomes: a retrospective cohort study. J. Infect. 51(2), 98–102 (2005).
12.
WHO. Clinical management of COVID-19 (2020). www.who.int/publications/i/item/clinical-management-of-covid-19
13.
Williams DM. Clinical pharmacology of corticosteroids. Respir. Care 63(6), 655–670 (2018).
14.
Shi Y, Wang Y, Shao C et al. COVID-19 infection: the perspectives on immune responses. Cell Death Differ. 27(5), 1451–1454 (2020).
15.
Georgiev T. Coronavirus disease 2019 (COVID-19) and anti-rheumatic drugs. Rheumatol. Int. 40(5), 825–826 (2020).
16.
Griffiths MJD, McAuley DF, Perkins GD et al. Guidelines on the management of acute respiratory distress syndrome. BMJ Open Respir. Res. 6(1), e000420 (2019).
• Provides basis for corticosteroid treatment in acute respiratory distress syndrome of any etiology.
17.
Mammen MJ, Aryal K, Alhazzani W, Alexander PE. Corticosteroids for patients with acute respiratory distress syndrome: a systematic review and meta-analysis of randomized trials. Polish Arch. Intern. Med. 130(4), 276–286 (2020).
18.
Sun S, Liu D, Zhang H, Zhang X, Wan B. Effect of different doses and time-courses of corticosteroid treatment in patients with acute respiratory distress syndrome: a meta-analysis. Exp. Ther. Med. 18(6), 4637–4644 (2019).
19.
Zhao Q, Shi J, Hu R, Li Q, Zhang C, Li J. Effect of glucocorticoids on mortality in patients with acute respiratory distress syndrome: a meta-analysis. Exp. Ther. Med. 18(6), 4913–4920 (2019).
20.
Yang ZG, Lei XL, Li XL. Early application of low-dose glucocorticoid improves acute respiratory distress syndrome: a meta-analysis of randomized controlled trials. Exp. Ther. Med. 13(4), 1215–1224 (2017).
21.
Zhou Y, Fu X, Liu X et al. Use of corticosteroids in influenza-associated acute respiratory distress syndrome and severe pneumonia: a systemic review and meta-analysis. Sci. Rep. 10(1), 1–10 (2020).
22.
Ni YN, Chen G, Sun J, Liang BM, Liang ZA. The effect of corticosteroids on mortality of patients with influenza pneumonia: a systematic review and meta-analysis. Crit. Care 23(1), 1–9 (2019).
23.
Yang JW, Fan LC, Miao XY et al. Corticosteroids for the treatment of human infection with influenza virus: a systematic review and meta-analysis. Clin. Microbiol. Infect. 21(10), 956–963 (2015).
24.
Lansbury L, Rodrigo C, Leonardi-Bee J, Nguyen-Van-Tam J, Lim WS. Corticosteroids as adjunctive therapy in the treatment of influenza. Cochrane Database Syst. Rev. 2(2), CD010406 (2019).
25.
Morens DM, Taubenberger JK, Fauci AS. Predominant role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness. J. Infect. Dis. 198(7), 962–970 (2008).
26.
Cao B, Gao H, Zhou B et al. Adjuvant corticosteroid treatment in adults with influenza A (H7N9) viral pneumonia. Crit. Care Med. 44(6), e318–328 (2016).
• Provides evidence for harmful effect of corticosteroids in influenza-associated acute respiratory distress syndrome.
27.
Li H, Chen C, Hu F et al. Impact of corticosteroid therapy on outcomes of persons with SARS-CoV-2, SARS-CoV, or MERS-CoV infection: a systematic review and meta-analysis. Leukemia 34(6), 1503–1511 (2020).
• Provides evidence for delayed viral clearance and increased length of hospital stay associated with corticosteroid treatment in SARS and Middle East respiratory syndrome infections.
28.
Yang Z, Liu J, Zhou Y, Zhao X, Zhao Q, Liu J. The effect of corticosteroid treatment on patients with coronavirus infection: a systematic review and meta-analysis. J. Infect. 81, 13–20 (2020).
• Gives evidence for increased secondary bacterial infections in SARS and Middle East respiratory syndrome patients who were on corticosteroid treatment.
29.
Lee N, Allen Chan KC, Hui DS et al. Effects of early corticosteroid treatment on plasma SARS-associated Coronavirus RNA concentrations in adult patients. J. Clin. Virol. 31(4), 304–309 (2004).
30.
Zhang JJY, Lee KS, Ang LW, Leo YS, Young BE. Risk factors of severe disease and efficacy of treatment in patients infected with COVID-19: a systematic review, meta-analysis and meta-regression analysis. Clin. Infect. Dis. (2020) (Epub ahead of print).
• Provides evidence for harms associated with corticosteroid use in coronavirus disease-2019 (COVID-19).
31.
Veronese N, Demurtas J, Yang L et al. Use of corticosteroids in coronavirus disease 2019 pneumonia: a systematic review of the literature. Front. Med. 7(April), 1–6 (2020).
32.
Zhong H, Wang Y, Zhang Z-L et al. Efficacy and safety of current therapeutic options for COVID-19 – lessons to be learnt from SARS and MERS epidemic: a systematic review and meta-analysis. Pharmacol. Res. 157, 104872 (2020).
33.
Fadel R, Morrison AR, Vahia A et al. Early short course corticosteroids in hospitalized patients with COVID-19. Clin. Infect. Dis. (2020) (Epub ahead of print).
• Provides evidence for the benefit of short-course corticosteroid in decreasing the mortality, respiratory failure and escalation to intensive care unit.
34.
Zha L, Li S, Pan L et al. Corticosteroid treatment of patients with coronavirus disease 2019 (COVID-19). Med. J. Aust. 212(9), 416–420 (2020).
35.
Gong Y, Guan L, Jin Z, Chen S, Xiang G, Gao B. Effects of methylprednisolone use on viral genomic nucleic acid negative conversion and CT imaging lesion absorption in COVID-19 patients under 50 years old. J. Med. Virol. (2020) (Epub ahead of print).
• Gives evidence for delayed viral clearance with the use of corticosteroid in COVID-19 patients.
36.
Fang X, Mei Q, Yang T et al. Low-dose corticosteroid therapy does not delay viral clearance in patients with COVID-19. J. Infect. 81(1), 147–178 (2020).
37.
Selvaraj V, Dapaah-Afriyie K, Finn A, Flanigan TP. Short-term dexamethasone in Sars-CoV-2 patients. R. I. Med. J. (2013) 103(6), 39–43 (2020).
38.
Li S, Hu Z, Song X. High-dose but not low-dose corticosteroids potentially delay viral shedding of patients with COVID-19. Clin. Infect. Dis. (2020) (Epub ahead of print).
39.
Yuan M, Xu X, Xia D et al. Effects of corticosteroid treatment for non-severe COVID-19 pneumonia: a propensity score-based analysis. Shock (2020) (Epub ahead of print).
40.
The RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19:preliminary report. N. Engl. J. Med. (2020) (Epub ahead of print).
•• Gives evidence for the benefit of corticosteroid use in severe COVID-19 cases.
41.
Mahase E. COVID-19: demand for dexamethasone surges as RECOVERY trial publishes preprint. BMJ 369, m2512 (2020).
42.
Zhu L, She ZG, Cheng X et al. Association of blood glucose control and outcomes in patients with COVID-19 and pre-existing Type 2 diabetes. Cell Metab. 31(6), 1068–1077.e3 (2020).
Information & Authors
Information
Published In
Pages: 1247 - 1254
PubMed: 33245242
Copyright
© 2020 Future Medicine Ltd.
History
Received: 11 July 2020
Accepted: 6 October 2020
Published online: 27 November 2020
Keywords:
Topics
Authors
Metrics & Citations
Metrics
Article Usage
Article usage data only available from February 2023. Historical article usage data, showing the number of article downloads, is available upon request.
Citations
How to Cite
Corticosteroid use in viral pneumonia: experience so far and the dexamethasone breakthrough in coronavirus disease-2019. (2020) Journal of Comparative Effectiveness Research. DOI: 10.2217/cer-2020-0146
Export citation
Select the citation format you wish to export for this article or chapter.
Citing Literature
- Xutao Ge, Sijia Yu, Shang Wu, Shujing Zhang, Ronghua Zhao, Lu Zhao, Multi-scale discovery of herbacetin as a macrophage-targeted SGK1-STAT1 signaling inhibitor alleviating lung inflammation and barrier dysfunction, Phytomedicine, 10.1016/j.phymed.2025.157489, 148, (157489), (2025).
- Katsuhiro Nakagawa, Shingo Ihara, Junko Yamaguchi, Tsukasa Kuwana, Kosaku Kinoshita, Steroid Pulse Therapy Leads to Secondary Infections and Poor Outcomes in Patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Intensive Care Units: A Retrospective Cohort Study, Viruses, 10.3390/v17060822, 17, 6, (822), (2025).
- Minji Kang, Chuanyu Zhuang, Jihun Oh, Minhyung Lee, Pulmonary Delivery of Anti-microRNA Oligonucleotide and Glycyrrhizic Acid Using Ternary Peptide Micelles for the Treatment of Acute Lung Injury, Biomaterials Research, 10.34133/bmr.0107, 28, (2024).
- Melissa González Ramírez, Jaime Andrés Hoyos Muñoz, Germán Alberto Moreno Gómez, Mateo Aguirre Flórez, José Fernando Gómez González, Relationship between steroid use and superinfections in SARS-CoV-2 patients. A systematic review and meta-analysis, Infection Ecology & Epidemiology, 10.1080/20008686.2023.2277000, 13, 1, (2023).
- Guangxu Bai, Yan Li, Yang Liu, Xinming Wang, Xuezhong Yu, Lili Ren, Jun Xu, Relationship between glucocorticoids and viral load during the Omicron wave in mainland China, Virology Journal, 10.1186/s12985-023-02235-4, 20, 1, (2023).
- Zahra Sahraei, Parnaz Panahi, Kouroush Solhjoukhah, Maryam Mesbah, Siamak Afaghi, Mahdi Amirdosara, Jamshid Salamzadeh, Farzad Esmaeili Tarki, Ilad Alavi Darazam, The Efficacy of High-Dose Pulse Therapy vs. Low-Dose Intravenous Methylprednisolone on Severe to Critical COVID-19 Clinical Outcomes: A Randomized Clinical Trial, Iranian Journal of Pharmaceutical Research, 10.5812/ijpr-137838, 22, 1, (2023).
- Laura Dormer, Journal of Comparative Effectiveness Research: 2022 year in review, Journal of Comparative Effectiveness Research, 10.57264/cer-2023-0026, 12, 4, (2023).
- Shu-Min Lin, Chung-Shu Lee, Allen Chung-Cheng Huang, Tzu-Hsuan Chiu, Ko-Wei Chang, Tse-Hung Huang, Tsung-Hsien Yang, Yi-Hsien Shiao, Fu-Tsai Chung, Chyi-Liang Chen, Cheng-Hsun Chiu, Effects of dexamethasone use on viral clearance among patients with COVID-19: a multicenter cohort study, International Journal of Infectious Diseases, 10.1016/j.ijid.2023.01.011, 128, (257-264), (2023).
- Anton V. Tyurin, Karina E. Akhiyarova, Damir A. Valishin, Lidiya D. Sadretdinova, Leonora N. Khusainova, Naufal S. Zagidullin, Khalida K. Gantseva, Valentin N. Pavlov, Comparative Analysis Of Immunosuppressive Therapy Effectiveness In COVID-19 Patients, Russian Open Medical Journal, 10.15275/rusomj.2022.0312, 11, 3, (2022).
- Stanley Calderwood, Aqsa Sabir, Latha Rao, Brian Baker, Vinod Balasa, Bindu K. Sathi, SARS-CoV-2 Infection Presenting as Acute Chest Syndrome in a Child With Hemoglobin SD-Los Angeles Disease: A Case Report and Review of Literature, Journal of Pediatric Hematology/Oncology, 10.1097/MPH.0000000000002546, 45, 2, (82-87), (2022).