HIGH VERSUS STANDARD DOSES OF CORTICOSTEROIDS IN COVID-19 PATIENTS WITH AN ACUTE RESPIRATORY DISTRESS SYNDROME: a controlled observational comparative study

  1. Enric Monreal
  2. Susana Sainz de la Maza
  3. Elena Natera-Villalba
  4. Álvaro Beltrán-Corbellini
  5. Fernando Rodríguez-Jorge
  6. Jose Ignacio Fernández-Velasco
  7. Paulette Walo-Delgado
  8. Alfonso Muriel
  9. Javier Zamora
  10. Araceli Alonso-Canovas
  11. Jesús Fortún
  12. Luis Manzano
  13. Beatriz Montero-Errasquín
  14. Lucienne Costa-Frossard
  15. Jaime Masjuan
  16. Luisa María Villar
  17. for the COVID-HRC group

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Abstract

INTRODUCTION

Despite the increasing evidence of the benefit of corticosteroids for the treatment of moderate-severe Coronavirus disease 2019 (COVID-19) patients, no data are available about the potential role of high doses of steroids for these patients.

METHODS

All consecutive confirmed COVID-19 patients admitted to a single center were selected, including those treated with steroids and an acute respiratory distress syndrome (ARDS). Patients were allocated to the high doses (HD, ≥250mg/day of methylprednisolone) of corticosteroids or the standard doses (SD, ≤1.5mg/kg/day of methylprednisolone) at discretion of treating physician. The primary endpoint was the mortality between both cohorts and secondary endpoints were the risk of need for mechanical ventilation (MV) or death and the risk of developing a severe ARDS.

RESULTS

573 patients were included: 428 (74.7%) men, with a median (IQR) age of 64 (54–73) years. In HD cohort, a worse baseline respiratory situation was observed and male sex, older age and comorbidities were significantly more common. After adjusting by baseline characteristics, HD were associated with a higher mortality than SD (adjusted-OR 2.46, 95% CI 1.58 – 3.83, p<0.001) and with an increased risk of needing MV or death (adjusted-OR 2.50, p=0.001). Conversely, the risk of developing a severe ARDS was similar between groups. Interaction analysis showed that HD increased mortality exclusively in elderly patients.

CONCLUSION

Our real-world experience advises against exceeding 1-1.5mg/kg/day of corticosteroids for severe COVID-19 with an ARDS, especially in older subjects. This reinforces the rationale of modulating rather than suppressing immune responses in these patients.

SUMMARY

In patients with severe COVID-19, high doses of corticosteroids are associated with a higher mortality and risk of need for mechanical ventilation or death compared to standard doses. This deleterious effect is mainly observed in the elderly.

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  1. ScreenIT

    SciScore for 10.1101/2020.07.17.20156315: (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 institutional ethics board of HRC.
    Consent: The need for informed consent from individual patients was waived due to its retrospective design.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    All analyses were conducted using Stata® 14 (StataCorp, College Station, TX, USA) and were two-tailed, with P <0.05 as the level of significance.
    StataCorp
    suggested: (Stata, RRID:SCR_012763)

    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:
    There are obvious limitations in a single-center study of this type. First, due to the observational character of the current work, potential confounding factors might have not been controlled and, therefore, conclusions must be taken with caution. In addition, the lack of randomization could have introduced indication bias, using HD of corticosteroids for more severe patients. Second, the range of doses used in the HD cohort contributed to some heterogeneity within this group. And finally, standardized care pathways and evidence-based treatment protocols for COVID-19 have not been established, and management might have been different between patients, introducing potential bias. Despite these limitations, these results could have direct relevance to the evolving management of COVID-19 for treating physicians. In addition to the contribution made by the first clinical trial of dexamethasone at moderate doses [7], we add robust evidence to prevent from using high doses of corticosteroids for moderate or severe COVID-19 patients in order to avoid harmful effects. In conclusion, among hospitalized patients with COVID-19 developing an ARDS, the administration of high doses of corticosteroids are associated with increased mortality and a higher risk of need for MV or death compared to standard doses. Thus, corticosteroids at 1 mg/kg/day of methylprednisolone-equivalent given for a short period might be more beneficial for these patients. Nevertheless, randomized, double-blind, con...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    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 10.1101/2020.07.17.20156315v1 on medRxiv