Early Short-Course Corticosteroids in Hospitalized Patients With COVID-19

  1. Raef Fadel
  2. Austin R Morrison
  3. Amit Vahia
  4. Zachary R Smith
  5. Zohra Chaudhry
  6. Pallavi Bhargava
  7. Joseph Miller
  8. Rachel M Kenney
  9. George Alangaden
  10. Mayur S Ramesh
  11. Henry Ford COVID-19 Management Task Force
  12. Varidhi Nauriyal
  13. Jayanth Lakshmikanth
  14. Asif Abdul Hamed
  15. Owais Nadeem
  16. Kristin Griebe
  17. Joseph M Johnson
  18. Patrick Bradley
  19. Junior Uduman
  20. Sara Hegab
  21. Jennifer Swiderek
  22. Amanda Godfrey
  23. Jeffrey Jennings
  24. Jayna Gardner-Gray
  25. Adam Ackerman
  26. Jonathan Lezotte
  27. Joseph Ruhala
  28. Linoj Samuel
  29. Robert J Tibbetts
  30. Indira Brar
  31. John McKinnon
  32. Geehan Suleyman
  33. Nicholas Yared
  34. Erica Herc
  35. Jonathan Williams
  36. Odaliz Abreu Lanfranco
  37. Anne Chen
  38. Marcus Zervos
  39. Eric Scher

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Abstract

Background

There is no proven antiviral or immunomodulatory therapy for coronavirus disease 2019 (COVID-19). The disease progression associated with the proinflammatory host response prompted us to examine the role of early corticosteroid therapy in patients with moderate to severe COVID-19.

Methods

We conducted a single pretest, single posttest quasi-experiment in a multicenter health system in Michigan from 12 March to 27 March 2020. Adult patients with confirmed moderate to severe COVID were included. A protocol was implemented on 20 March 2020 using early, short-course, methylprednisolone 0.5 to 1 mg/kg/day divided in 2 intravenous doses for 3 days. Outcomes of standard of care (SOC) and early corticosteroid groups were evaluated, with a primary composite endpoint of escalation of care from ward to intensive care unit (ICU), new requirement for mechanical ventilation, and mortality. All patients had at least 14 days of follow-up.

Results

We analyzed 213 eligible subjects, 81 (38%) and 132 (62%) in SOC and early corticosteroid groups, respectively. The composite endpoint occurred at a significantly lower rate in the early corticosteroid group (34.9% vs 54.3%, P = .005). This treatment effect was observed within each individual component of the composite endpoint. Significant reduction in median hospital length of stay was also observed in the early corticosteroid group (5 vs 8 days, P < .001). Multivariate regression analysis demonstrated an independent reduction in the composite endpoint at 14-days controlling for other factors (adjusted odds ratio: 0.41; 95% confidence interval, .22 – .77).

Conclusions

An early short course of methylprednisolone in patients with moderate to severe COVID-19 reduced escalation of care and improved clinical outcomes.

Clinical Trials Registration

NCT04374071.

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  1. ScreenIT

    SciScore for 10.1101/2020.05.04.20074609: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: The study was approved by the institution’s Investigational Review Board (#13739) with waiver of consent.
    Consent: The study was approved by the institution’s Investigational Review Board (#13739) with waiver of consent.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    This study has several limitations. Given the pandemic nature of the disease a pragmatic quasi-experimental design was used. The potential for regression to the mean and maturation is an inherent limitation to all quasi-experiments. On March 16, 2020 rapid on-site RT-PCR testing for SARS-CoV-2 testing was implemented, and some of the pre-steroid group experienced delayed diagnosis and treatment. However, the observed association was unchanged in the sensitivity analysis. A non-equivalent dependent variable, empiric antibiotic therapy for pneumonia, suggested no difference in management of COVID-19. Some of the precorticosteroid protocol group received corticosteroids after initiation of the updated COVID-19 institutional treatment protocol. Steroids initiated in this group were started significantly later. Additionally, guideline adherence in the corticosteroid protocol group was not universal. Finally, the study has a limited follow up period of 14 days, similar to other recent reports. As of April 9, 2020, 51 (62.9%) of patients in the pre-steroid cohort and 88 (66.7%) of patients in the post-steroid cohort were discharged from the hospital. As a result, outcomes for those patients are not known. Anecdotally, we observed hyperglycemia, but no severe corticosteroid related adverse effects (i.e. gastrointestinal hemorrhage), and data collection is ongoing. In conclusion, early use of a short course of methylprednisolone, an inexpensive and readily available agent, in patients...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04374071CompletedEarly Short Course Corticosteroids in COVID-19

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  2. Version published to 10.1093/cid/ciaa601
  3. Version published to 10.1101/2020.05.04.20074609v1 on medRxiv