The use of corticosteroid therapy for COVID-19 patients: an evidence-based overview
Article Sidebar
Main Article Content
Abstract
Since the World Health Organization declared COVID-19 as a pandemic, huge efforts to promote better treatment for the patients raised from the scientific community. One of the most effective treatment is the administration of corticosteroid in specific stages of the disease, once that severe COVID-19 pathophysiology evolves an exuberant inflammatory response, resulting in uncontrolled pulmonary inflammation and multisystem damage. However, it is still discussed whether some drugs, such as dexamethasone, are more effective than others, such as hydrocortisone and methylprednisolone. Therefore, we constructed here a comprehensive overview, based on clinical studies with detailed methodological procedures, regarding the role of corticosteroids in COVID-19 treatment. We aimed to address how the current evidence support their use in this scenario.
Article Details
Authors maintain copyright and grant the HSJ the right to first publication. From 2024, the publications wiil be licensed under Attribution 4.0 International 
, allowing their sharing, recognizing the authorship and initial publication in this journal.
Authors are authorized to assume additional contracts separately for the non-exclusive distribution of the version of the work published in this journal (e.g., publishing in an institutional repository or as a book chapter), with acknowledgment of authorship and initial publication in this journal.
Authors are encouraged to publish and distribute their work online (e.g., in institutional repositories or on their personal page) at any point after the editorial process.
Also, the AUTHOR is informed and consents that the HSJ can incorporate his article into existing or future scientific databases and indexers, under the conditions defined by the latter at all times, which will involve, at least, the possibility that the holders of these databases can perform the following actions on the article.
References
World Health Organization. Director-General's opening remarks at the media briefing on COVID-19 [Internet] 2020 Mar 11 [cited 2022 Aug 15]. Available from: https://bit.ly/3C65GSG
Food and Drug Administration. FDA Takes Key Action in Fight Against COVID-19 By Issuing Emergency Use Authorization for First COVID-19 Vaccine [Internet]. 2020 Dec 11[cited 2022 Aug 15]. Available from: https://bit.ly/3Ao1dJP
Del Sole F, Farcomeni A, Loffredo L, Carnevale R, Menichelli D, Vicario T, et al. Features of severe COVID-19: A systematic review and meta-analysis. Eur J Clin Invest. 2020;50(10):e13378. https://doi.org/10.1111/eci.13378 DOI: https://doi.org/10.1111/eci.13378
Fu Y, Cheng Y, Wu Y. Understanding SARS-CoV-2-mediated inflammatory responses: from mechanisms to potential therapeutic tools. Virol Sin. 2020;35(3):266-71. https://doi.org/10.1007/s12250-020-00207-4 DOI: https://doi.org/10.1007/s12250-020-00207-4
Perico L, Benigni A, Casiraghi F, Ng LFP, Renia L, Remuzzi G. Immunity, endothelial injury and complement-induced coagulopathy in COVID-19. Nat Rev Nephrol. 2021;17(1):46-64. https://doi.org/10.1038/s41581-020-00357-4 DOI: https://doi.org/10.1038/s41581-020-00357-4
Lee KH, Yoon S, Jeong GH, Kim JY, Han YJ, Hong SH, et al. Efficacy of Corticosteroids in Patients with SARS, MERS and COVID-19: A Systematic Review and Meta-Analysis. J Clin Med. 2020;9(8):2392. https://doi.org/10.3390/jcm9082392 DOI: https://doi.org/10.3390/jcm9082392
Kapugi M, Cunningham K. Corticosteroids. Orthop Nurs. 2019;38(5):336-9. https://doi.org/10.1097/NOR.0000000000000595 DOI: https://doi.org/10.1097/NOR.0000000000000595
Lam CW, Chan MH, Wong CK. Severe acute respiratory syndrome: clinical and laboratory manifestations. Clin Biochem Rev. 2004;25(2):121-32. PMCId:PMC1904416.
van Paassen J, Vos JS, Hoekstra EM, Neumann KMI, Boot PC, Arbous SM. Corticosteroid use in COVID-19 patients: a systematic review and meta-analysis on clinical outcomes. Crit Care. 2020;24(1):696. https://doi.org/10.1186/s13054-020-03400-9 DOI: https://doi.org/10.1186/s13054-020-03400-9
Yang JW, Yang L, Luo RG, Xu JF. Corticosteroid administration for viral pneumonia: COVID-19 and beyond. Clin Microbiol Infect. 2020;26(9):1171-7. https://doi.org/10.1016/j.cmi.2020.06.020 DOI: https://doi.org/10.1016/j.cmi.2020.06.020
Peiris M. Respiratory tract viruses. In: Warrell DA, Cox TM, Firth JD. Oxford Textbook of Medicine. 4th ed. Oxford:Oxford Press, 2003. p. 363-68.
Huppert LA, Matthay MA, Ware LB. Pathogenesis of acute respiratory distress syndrome. Semin Respir Crit Care Med. 2019;40(1):31-39. https://doi.org/10.1055/s-0039-1683996 DOI: https://doi.org/10.1055/s-0039-1683996
Swartz SL, Dluhy RG. Corticosteroids: clinical pharmacology and therapeutic use. Drugs. 1978;16(3):238-55. https://doi.org/10.2165/00003495-197816030-00006 DOI: https://doi.org/10.2165/00003495-197816030-00006
Annane D, Sébille V, Bellissant E. Effect of low doses of corticosteroids in septic shock patients with or without early acute respiratory distress syndrome. Crit Care Med. 2006; 34(1):22-30. https://doi.org/10.1097/01.CCM.0000194723.78632.62 DOI: https://doi.org/10.1097/01.CCM.0000194723.78632.62
Samuel S, Nguyen T, Choi HA. Pharmacologic characteristics of corticosteroids. J Neurocrit Care. 2017;10(2):53-59. https://doi.org/10.18700/jnc.170035 DOI: https://doi.org/10.18700/jnc.170035
Mokra D, Mikolka P, Kosutova P, Mokry J. Corticosteroids in acute lung injury: the dilemma continues. Int J Mol Sci. 2019;20(19):4765. https://doi.org/10.3390/ijms20194765 DOI: https://doi.org/10.3390/ijms20194765
Li H, Yang SG, Gu L, Zhang Y, Yan XX, Liang ZA, et al. Effect of low‐to‐moderate‐dose corticosteroids on mortality of hospitalized adolescents and adults with influenza A(H1N1) pdm09 viral pneumonia. Influenza Other Respir Viruses. 2017;11(4):345-54. https://doi.org/10.1111/irv.12456 DOI: https://doi.org/10.1111/irv.12456
Meduri GU, Siemieniuk RAC, Ness RA, Seyler SJ. Prolonged low-dose methylprednisolone treatment is highly effective in reducing duration of mechanical ventilation and mortality in patients with ARDS. J Intensive Care. 2018;6:53. https://doi.org/10.1186/s40560-018-0321-9 DOI: https://doi.org/10.1186/s40560-018-0321-9
Villar J, Ferrando C, Martínez D, Ambrós A, Muñoz T, Soler JA, et al. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. Lancet Respir Med. 2020;8(3):267-76. https://doi.org/10.1016/S2213-2600(19)30417-5 DOI: https://doi.org/10.1016/S2213-2600(19)30417-5
Rong CC, Xiao PT, Shou YT, Bi LL, Zhuo YW, Ji QF et al. Treatment of severe acute respiratory syndrome with glucosteroids. Chest J. 2006;129(6):1441-52. https://doi.org/10.1378/chest.129.6.1441 DOI: https://doi.org/10.1378/chest.129.6.1441
Lee N, Leo YS, Cao B, Chan PK, Kyaw WM, Uyeki TM, et al. Neuraminidase inhibitors, superinfection and corticosteroids affect survival of influenza patients. Eur Respir J. 2015;45(6):1642-52. https://doi.org/10.1183/09031936.00169714 DOI: https://doi.org/10.1183/09031936.00169714
Rodrigo C, Leonardi-Bee J, Nguyen-Van-Tam JS, Lim WS. Effect of corticosteroid therapy on influenza-related mortality: a systematic review and meta-analysis. J Infect Dis. 2015;212(2):183-94. https://doi.org/10.1093/infdis/jiu645 DOI: https://doi.org/10.1093/infdis/jiu645
Shang L, Zhao J, Hu Y, Du R, Cao B. On the use of corticosteroids for 2019-nCoV pneumonia. Lancet. 2020;395(10225):683-4. https://doi.org/10.1016/S0140-6736(20)30361-5 DOI: https://doi.org/10.1016/S0140-6736(20)30361-5
Vichyanond P, Irvin CG, Larsen GL, Szefler SJ, Hill MR. Penetration of corticosteroids into the lung: evidence for a difference between methylprednisolone and prednisolone. J Allergy Clin Immunol. 1989;84(6 Pt 1):867-73. https://doi.org/10.1016/0091-6749(89)90381-3 DOI: https://doi.org/10.1016/0091-6749(89)90381-3
Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet. 2020;395(10223):473-5. https://doi.org/10.1016/S0140-6736(20)30317-2 DOI: https://doi.org/10.1016/S0140-6736(20)30317-2
Tlayjeh H, Mhish OH, Enani MA, Alruwaili A, Tleyjeh R, Thalib L, et al. Association of corticosteroids use and outcomes in COVID-19 patients: A systematic review and meta-analysis. J Infect Public Health. 2020;13(11):1652-63. https://doi.org/10.1016/j.jiph.2020.09.008 DOI: https://doi.org/10.1016/j.jiph.2020.09.008
Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020;180(7):934-43. https://doi.org/10.1001/jamainternmed.2020.0994 DOI: https://doi.org/10.1001/jamainternmed.2020.0994
Wang Y, Jiang W, He Q, Wang C, Wang B, Zhou P, et al. A retrospective cohort study of methylprednisolone therapy in severe patients with COVID-19 pneumonia. Signal Transduct Target Ther. 2020;5(1):57. https://doi.org/10.1038/s41392-020-0158-2 DOI: https://doi.org/10.1038/s41392-020-0158-2
Angus DC, Derde L, Al-Beidh F, Annane D, Arabi Y, Beane A, 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):1317-29. https://doi.org/10.1001/jama.2020.17022 DOI: https://doi.org/10.1001/jama.2020.17022
Dequin P, Heming N, Meziani F, Plantefève G, Voiriot G, Badié J, 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):1298-306. https://doi.org/10.1001/jama.2020.16761 DOI: https://doi.org/10.1001/jama.2020.16761
Jeronimo CMP, Farias MEL, Val FFA, Sampaio VS, Alexandre MAA, Melo GC, 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. https://doi.org/10.1093/cid/ciaa1177 DOI: https://doi.org/10.1093/cid/ciaa1177
Ranjbar K, Moghadami M, Mirahmadizadeh A, Fallahi MJ, Khaloo V, Shahriarirad R, et al. Methylprednisolone or dexamethasone, which one is superior corticosteroid in the treatment of hospitalized COVID-19 patients: a triple-blinded randomized controlled trial. BMC Infect Dis. 2021;21(1):337. https://doi.org/10.1186/s12879-021-06045-3 DOI: https://doi.org/10.1186/s12879-021-06045-3
Liu D, Ahmet A, Ward L, Krishnamoorthy P, Mandelcorn ED, Leigh R, et al. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin Immunol. 2013;9(1):30. https://doi.org/10.1186/1710-1492-9-30 DOI: https://doi.org/10.1186/1710-1492-9-30
Ahmed MH, Hassan A. Dexamethasone for the treatment of coronavirus disease (COVID-19): a Review. SN Compr Clin Med. 2020;2(12):2637-46. https://doi.org/10.1007/s42399-020-00610-8 DOI: https://doi.org/10.1007/s42399-020-00610-8
RECOVERY Collaborative Group, Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, et al. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384(8):693-704. https://doi.org/10.1056/NEJMoa2021436 DOI: https://doi.org/10.1056/NEJMoa2021436
Tomazini BM, Maia IS, Cavalcanti AB, Berwanger O, Rosa RG, Veiga VC, 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):1307-16. https://doi.org/10.1001/jama.2020.17021 DOI: https://doi.org/10.1001/jama.2020.17021
COVID STEROID 2 Trial Group, Munch MW, Myatra SN, Vijayaraghavan BKT, Saseedharan S, Benfield T, Wahlin RR, et al. Effect of 12 mg vs 6 mg of dexamethasone on the number of days alive without life support in adults with COVID-19 and severe hypoxemia: The COVID STEROID 2 Randomized Trial. JAMA. 2021;326(18):1807-17. https://doi.org/10.1001/jama.2021.18295 DOI: https://doi.org/10.1001/jama.2021.18295
Johns M, George S, Taburyanskaya M, Poon YK. A review of the evidence for corticosteroids in COVID-19. J Pharm Pract. 2022;35(4):626-37. https://doi.org/10.1177/0897190021998502 DOI: https://doi.org/10.1177/0897190021998502
Prakash H, Chakrabarti A. Epidemiology of mucormycosis in India. Microorganisms. 2021;9(3):523. https://doi.org/10.3390/microorganisms9030523 DOI: https://doi.org/10.3390/microorganisms9030523
Silva DL, Lima CM, Magalhães VCR, et al. Fungal and bacterial coinfections increase mortality of severely ill COVID-19 patients. J Hosp Infect. 2021;113:145-54. https://doi.org/10.1016/j.jhin.2021.04.001 DOI: https://doi.org/10.1016/j.jhin.2021.04.001
Chong WH, Neu KP. Incidence, diagnosis and outcomes of COVID-19-associated pulmonary aspergillosis (CAPA): a systematic review. J Hosp Infect. 2021;113:115-29. https://doi.org/10.1016/j.jhin.2021.04.012 DOI: https://doi.org/10.1016/j.jhin.2021.04.012
Raut A, Huy NT. Rising incidence of mucormycosis in patients with COVID-19: another challenge for India amidst the second wave?. Lancet Respir Med. 2021;9(8):e77. https://doi.org/10.1016/S2213-2600(21)00265-4 DOI: https://doi.org/10.1016/S2213-2600(21)00265-4
Patterson TF, Thompson GR 3rd, Denning DW, et al. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;63(4):e1-e60. https://doi.org/10.1093/cid/ciw326 DOI: https://doi.org/10.1093/cid/ciw326
Ullmann AJ, Aguado JM, Arikan-Akdagli S, et al. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin Microbiol Infect. 2018;24 Suppl 1:e1-e38. https://doi.org/10.1016/j.cmi.2018.01.002 DOI: https://doi.org/10.1016/j.cmi.2018.01.002
Prattes J, Wauters J, Giacobbe DR, Lagrou K, Hoenigl M; ECMM-CAPA Study Group. Diagnosis and treatment of COVID-19 associated pulmonary apergillosis in critically ill patients: results from a European confederation of medical mycology registry. Intensive Care Med. 2021;47(10):1158-60. https://doi.org/10.1007/s00134-021-06471-6 DOI: https://doi.org/10.1007/s00134-021-06471-6
Skiada A, Pagano L, Groll A, et al. Zygomycosis in Europe: analysis of 230 cases accrued by the registry of the European Confederation of Medical Mycology (ECMM) Working Group on Zygomycosis between 2005 and 2007. Clin Microbiol Infect. 2011;17(12):1859-67. https://doi.org/10.1111/j.1469-0691.2010.03456.x DOI: https://doi.org/10.1111/j.1469-0691.2010.03456.x
Kontoyiannis DP, Yang H, Song J, et al. Prevalence, clinical and economic burden of mucormycosis-related hospitalizations in the United States: a retrospective study. BMC Infect Dis. 2016;16(1):730. https://doi.org/10.1186/s12879-016-2023-z DOI: https://doi.org/10.1186/s12879-016-2023-z
Chakrabarti A, Chatterjee SS, Das A, et al. Invasive zygomycosis in India: experience in a tertiary care hospital. Postgrad Med J. 2009;85(1009):573-81. https://doi.org/10.1136/pgmj.2008.076463 DOI: https://doi.org/10.1136/pgmj.2008.076463
Colombo AL, Guimarães T, Camargo LF, et al. Brazilian guidelines for the management of candidiasis - a joint meeting report of three medical societies: Sociedade Brasileira de Infectologia, Sociedade Paulista de Infectologia and Sociedade Brasileira de Medicina Tropical. Braz J Infect Dis. 2013;17(3):283-312. https://doi.org/10.1016/j.bjid.2013.02.001 DOI: https://doi.org/10.1016/j.bjid.2013.02.001
Pappas PG, Kauffman CA, Andes DR, et al. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62(4):e1-e50. https://doi.org/10.1093/cid/civ933 DOI: https://doi.org/10.1093/cid/civ933
Cornely OA, Bassetti M, Calandra T, et al. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect. 2012;18 Suppl 7:19-37. https://doi.org/10.1111/1469-0691.12039 DOI: https://doi.org/10.1111/1469-0691.12039
Ganesh R, et al. Intravenous bamlanivimab use associates with reduced hospitalization in high-risk patients with mild to moderate COVID-19. J Clin Invest. 2021;131(19):e151697. https://doi.org/10.1172/JCI151697 DOI: https://doi.org/10.1172/JCI151697
Gupta A, Gonzalez-Rojas Y, Juarez E, et al. Effect of Sotrovimab on hospitalization or death among high-risk patients with mild to moderate COVID-19: A Randomized Clinical Trial. JAMA. 2022;327(13):1236-46. https://doi.org/10.1001/jama.2022.2832 DOI: https://doi.org/10.1001/jama.2022.2832
Gupta A, Gonzalez-Rojas Y, Juarez E, et al. Early treatment for Covid-19 with SARS-CoV-2 neutralizing antibody sotrovimab. N Engl J Med. 2021;385(21):1941-50. https://doi.org/10.1056/NEJMoa2107934 DOI: https://doi.org/10.1056/NEJMoa2107934
Montgomery H, Hobbs FDR, Padilla F, et al. Efficacy and safety of intramuscular administration of tixagevimab-cilgavimab for early outpatient treatment of COVID-19 (TACKLE): a phase 3, randomised, double-blind, placebo-controlled trial [ahead of print]. Lancet Respir Med. 2022 [published online 2022 Jun 7]. https://doi.org/10.1016/S2213-2600(22)00180-1 DOI: https://doi.org/10.1016/S2213-2600(22)00180-1
Dougan M, Nirula A, Azizad M, et al. Bamlanivimab plus Etesevimab in Mild or Moderate Covid-19. N Engl J Med. 2021;385(15):1382-92. https://doi.org/10.1056/NEJMoa2102685 DOI: https://doi.org/10.1056/NEJMoa2102685
Ramakrishnan S, Nicolau DV Jr, Langford B, Mahdi M, Jeffers H, Mwasuku C, Krassowska K, et al. Inhaled budesonide in the treatment of early COVID-19 (STOIC): a phase 2, open-label, randomised controlled trial. Lancet Respir Med. 2021;9(7):763-72. https://doi.org/10.1016/S2213-2600(21)00160-0 DOI: https://doi.org/10.1016/S2213-2600(21)00160-0