Long-term corticosteroid therapy for patients with severe coronavirus disease 2019 (COVID-19)

  1. George Calcaianu
  2. Samuel Degoul
  3. Thibault Payen
  4. Bénédicte Michau
  5. Mihaela Calcaianu
  6. Bree Lawson
  7. Didier Bresson
  8. Didier Debieuvre

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Abstract

earlier and longer corticosteroid therapy with methylprednisolone could reduce the mortality and/or rate of ICU admission by 26% in patients with severe COVID-19, hospitalized in conventional medical ward.

Background

Low dose of dexamethasone reduced mortality in hospitalized COVID-19 patients who required respiratory support. Less is known about the efficacy of other corticosteroids in severe COVID-19 patients. This study was designed to determine if longer and earlier corticoid therapy in severe COVID-19 patients is associated with reduced mortality and/or reduced rate of ICU admission for worsening of respiratory state.

Methods

We performed a retrospective study with patients aged ≥ 18 years, with epidemiological and/or radiological suspected COVID-19, hospitalized in a regional hospital GHRMSA Mulhouse, France. Twenty-three patients received methylprednisolone (MP) as compassionate use, 1 mg/kg/day for seven days followed by prednisolone at a gradually reduced dosage, for 4 to 6 weeks. MP was started one week after COVID-19 symptoms first appeared. The primary composite outcome was mortality and/or ICU admission during hospitalisation.

Results

Between March 14 th to June 5 th 2020, 255 patients were screened, 181 were included, and 92 were analysed, 23 patients treated with MP and 69 received standard care. SARS-CoV2 infection was confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) in 82.3%. The overall composite outcome was higher in the control group: 42/69 patients (60.9%) versus 8/23 (34.8%) in the interventional group (p= 0.018). The correction of lymphopenia between days 1 to 7 was associated with better outcome (p=0.006).

Conclusion

These results suggest that earlier and longer corticosteroid therapy with methylprednisolone could reduce the mortality and/or rate of ICU admission in patients with severe COVID-19, hospitalized in conventional medical ward.

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  1. ScreenIT

    SciScore for 10.1101/2021.08.30.21262824: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: This study complied with the Declaration of Helsinki and was approved by the Institutional Review Board of the French Learned Society for Respiratory Medicine – “Société de Pneumologie de Langue Française” (CEPRO 2020-055).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot 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 had several limitations. Our study analyses retrospectively a small sample size and therefore it is subject to confounding and bias. Since this study was done in a single center, these results cannot be generalized. However, we tried to reduce the bias and confounders by restoring comparability between the two groups, by 1:3 nearest neighbour propensity score, based on three covariates: age, hypertension or diabetes comorbidity, and maximal dose of maximal oxygen therapy in first 48 hours. Moreover, the patients treated by MP were more likely to have cardiovascular comorbidities. During the first 2 months of pandemic in France, we used this corticosteroid regime as a compassionate use and therefore this analysis is not based on a randomized allocation of therapy. Therefore, these results need to be confirmed in a larger, prospective study. Last, due to limited number of patients we could not assess the effect of corticosteroid treatment on the respiratory functional recovery. In conclusion, the use of methylprednisolone, at 1-2 mg/kg/day during 7 days followed by prednisolone at a gradually reduced dosage for 4 to 6 weeks, seemed to improve the prognosis (the mortality and/or ICU transfer) in COVID-19 patients, hospitalized in a conventional medical ward. Our exploratory analysis showed that the correction of lymphopenia during the first week could be a prognostic marker of a better evolution of the disease.

    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.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2021.08.30.21262824v1 on medRxiv