Early corticosteroids are associated with lower mortality in critically ill patients with COVID-19: a cohort study
Pablo Monedero, Alfredo Gea, Pedro Castro, Angel M Candela-Toha, María L Hernández-Sanz, Egoitz Arruti, Jesús Villar, Carlos Ferrando, COVID-19 Spanish ICU Network, Pablo Monedero, Alfredo Gea, Pedro Castro, Angel M Candela-Toha, Pablo Monedero, Alfredo Gea, Pedro Castro, Angel M Candela-Toha, María L Hernández-Sanz, Egoitz Arruti, Jesús Villar, Carlos Ferrando, COVID-19 Spanish ICU Network, Pablo Monedero, Alfredo Gea, Pedro Castro, Angel M Candela-Toha
Abstract
Background: Critically ill patients with coronavirus disease 19 (COVID-19) have a high fatality rate likely due to a dysregulated immune response. Corticosteroids could attenuate this inappropriate response, although there are still some concerns regarding its use, timing, and dose.
Methods: This is a nationwide, prospective, multicenter, observational, cohort study in critically ill adult patients with COVID-19 admitted into Intensive Care Units (ICU) in Spain from 12th March to 29th June 2020. Using a multivariable Cox model with inverse probability weighting, we compared relevant outcomes between patients treated with early corticosteroids (before or within the first 48 h of ICU admission) with those who did not receive early corticosteroids (delayed group) or any corticosteroids at all (never group). Primary endpoint was ICU mortality. Secondary endpoints included 7-day mortality, ventilator-free days, and complications.
Results: A total of 691 patients out of 882 (78.3%) received corticosteroid during their hospital stay. Patients treated with early-corticosteroids (n = 485) had lower ICU mortality (30.3% vs. never 36.6% and delayed 44.2%) and lower 7-day mortality (7.2% vs. never 15.2%) compared to non-early treated patients. They also had higher number of ventilator-free days, less length of ICU stay, and less secondary infections than delayed treated patients. There were no differences in medical complications between groups. Of note, early use of moderate-to-high doses was associated with better outcomes than low dose regimens.
Conclusion: Early use of corticosteroids in critically ill patients with COVID-19 is associated with lower mortality than no or delayed use, and fewer complications than delayed use.
Keywords: COVID-19; Cohort study; Corticosteroids; Critically ill patient; Intensive Care Unit; Mortality; Outcomes; Ventilator-free days.
Conflict of interest statement
We declare no competing interests.
Figures
![Fig. 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7784014/bin/13054_2020_3422_Fig1_HTML.jpg)
![Fig. 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7784014/bin/13054_2020_3422_Fig2_HTML.jpg)
![Fig. 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7784014/bin/13054_2020_3422_Fig3_HTML.jpg)
References
- WHO. Clinical management of COVID-19. . Accessed 8 November 2020.
- Felsenstein S, Herbert JA, McNamara PS, Hedrich CM. COVID-19: immunology and treatment options. Clin Immunol. 2020;215:108448. doi: 10.1016/j.clim.2020.108448.
- Hodgens A, Sharman T. Corticosteroids. In: StatPearls. Treasure Island (FL): StatPearls Publishing; May 14, 2020.
- RECOVERY Collaborative Group, Horby P, Lim WS, et al. Dexamethasone in Hospitalized Patients with Covid-19-preliminary report. N Engl J Med. 2020 Jul 17:NEJMoa2021436.
- The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis. JAMA. 2020;324(13):1330–1341.
- 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. doi: 10.1001/jama.2020.17021.
- Centers for Disease Control Prevention. Clinical Care Guidance for Healthcare Professionals about Coronavirus (COVID-19). . Accessed 8 November 2020.
- WHO. Corticosteroids for COVID-19. . Accessed 8 November 2020.
- De Backer D, Azoulay E, Vincent J. Corticosteroids in severe COVID-19: a critical view of the evidence. Crit Care. 2020;24:627–629. doi: 10.1186/s13054-020-03360-0.
- Villar J, Ferrando C, Martínez D, et al. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. Lancet Respir Med. 2020;8(3):267–276. doi: 10.1016/S2213-2600(19)30417-5.
- Hernán MA, Hernández-Díaz S, Robins JM. A structural approach to selection bias. Epidemiology. 2004;15(5):615–625. doi: 10.1097/01.ede.0000135174.63482.43.
- 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. 2020;34(6):1503–1511. doi: 10.1038/s41375-020-0848-3.
- 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. 2018;197(6):757–767. doi: 10.1164/rccm.201706-1172OC.
- Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708–1720. doi: 10.1056/NEJMoa2002032.
- Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet. 2020;395(10223):473–475. doi: 10.1016/S0140-6736(20)30317-2.
- Alhazzani W, Møller MH, Arabi YM, et al. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19) Intensive Care Med. 2020;46(5):854–887. doi: 10.1007/s00134-020-06022-5.
- Johnson RM, Vinetz JM. Dexamethasone in the management of covid-19. BMJ. 2020;370:m2648. doi: 10.1136/bmj.m2648.
- Tang C, Wang Y, Lv H, Guan Z, Gu J. Caution against corticosteroid-based COVID-19 treatment. Lancet. 2020;395(10239):1759–1760. doi: 10.1016/S0140-6736(20)30749-2.
- 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(1):147–178.
- Jung J, Oh DK, Ahn JH, et al. Re: Low-dose corticosteroid therapy does not delay viral clearance in patients with COVID-19. J Infect. 2020;81(2):e79–e81. doi: 10.1016/j.jinf.2020.05.004.
- Ling Y, Xu SB, Lin YX, et al. Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients. Chin Med J (Engl) 2020;133(9):1039–1043. doi: 10.1097/CM9.0000000000000774.
- Zha L, Li S, Pan L, et al. Corticosteroid treatment of patients with coronavirus disease 2019 (COVID-19) Med J Aust. 2020;212(9):416–420. doi: 10.5694/mja2.50577.
- Steinberg KP, Hudson LD, Goodman RB, et al. Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med. 2006;354(16):1671–1684. doi: 10.1056/NEJMoa051693.
- Theoharides TC, Conti P. Dexamethasone for COVID-19? Not so fast. J Biol Regul Homeost Agents. 2020;34:3.
- Nicastri E, Petrosillo N, Ascoli Bartoli T, et al. National institute for the infectious diseases "L. Spallanzani", IRCCS recommendations for COVID-19 clinical management. Infect Dis Rep. 2020;12(1):8543. doi: 10.4081/idr.2020.8543.
- Xu X, Ong YK, Wang Y. Role of adjunctive treatment strategies in COVID-19 and a review of international and national clinical guidelines. Mil Med Res. 2020;7(1):22.
- 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. doi: 10.1186/s40560-018-0321-9.
Source: PubMed