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Comment & Response
August 3, 2020

The Uncertain Role of Corticosteroids in the Treatment of COVID-19

Author Affiliations
  • 1Weill Cornell Medicine, New York, New York
JAMA Intern Med. 2021;181(1):140. doi:10.1001/jamainternmed.2020.2444

To the Editor We question the conclusion of Wu et al1 about the benefit of corticosteroid use in the treatment of coronavirus disease 2019 (COVID-19). The World Health Organization and the US Centers for Disease Control and Prevention have issued clinical guidance against the use of corticosteroids in the treatment of COVID-19 unless another indication is present, such as a chronic obstructive pulmonary disease exacerbation, or as adjunct treatment of septic shock. This guidance was made on the basis of systematic reviews of observational studies of corticosteroids that demonstrated an association with increased mortality and secondary infections in influenza2 and no benefit with possible harms in severe acute respiratory syndrome.3 A retrospective cohort study of Middle East respiratory syndrome showed that corticosteroids were associated with no difference in mortality and prolonged respiratory viral shedding.4

It is unclear that the proportional hazards analysis in the study modeled methylprednisolone administration as a time-dependent covariate, which is necessary to mitigate what has been termed survivor treatment selection bias.5 Stated simply, patients who died rapidly may have been less likely to receive methylprednisolone, leading to an observed difference in mortality that was incorrectly associated with this intervention. Mortality was 23 of 50 (46%) among those with acute respiratory distress syndrome who received methylprednisolone vs 21 of 34 (62%) among those who did not. Even if there were no bias present and methylprednisolone provided some short-term survival benefit, the end point difference of 16% less mortality in those who received corticosteroids is not significant (95% CI, −40% to 8%; P = .23). From the Kaplan-Meier curves, the ultimate mortality rate was roughly similar in both groups—around 60%.

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Article Information

Corresponding Author: Grant B. Ellsworth, MD, MS, Weill Cornell Medicine, 53 W 23rd St, 6th Floor, New York, NY 10010 (gre9006@med.cornell.edu).

Published Online: August 3, 2020. doi:10.1001/jamainternmed.2020.2444

Conflict of Interest Disclosures: Dr Ellsworth reported grants from the AIDS Malignancy Consortium and the National Institute of Allergy and Infectious Diseases, as well as nonfinancial support from Weill Cornell Clinical & Translational Science Center. Dr Glesby reported grants from Gilead Sciences and royalties from UpToDate and Springer. No other disclosures were reported.

Wu  C, Chen  X, Cai  Y,  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. Published online March 13, 2020. doi:10.1001/jamainternmed.2020.0994PubMedGoogle Scholar
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. 2019;2:CD010406. doi:10.1002/14651858.CD010406.pub3PubMedGoogle Scholar
Stockman  LJ, Bellamy  R, Garner  P.  SARS: systematic review of treatment effects.   PLoS Med. 2006;3(9):e343. doi:10.1371/journal.pmed.0030343PubMedGoogle Scholar
Arabi  YM, Mandourah  Y, Al-Hameed  F,  et al; Saudi Critical Care Trial Group.  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.201706-1172OCPubMedGoogle ScholarCrossref
Glesby  MJ, Hoover  DR.  Survivor treatment selection bias in observational studies: examples from the AIDS literature.   Ann Intern Med. 1996;124(11):999-1005. doi:10.7326/0003-4819-124-11-199606010-00008PubMedGoogle ScholarCrossref
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