Adjunctive Corticosteroids for COVID-19: A Retrospective Cohort Study

  1. Ooi Say Tat
  2. Purnima Parthasarathy
  3. Lin Yi
  4. Valliammai D/O Nallakaruppan
  5. Shereen Ng Jia Huey
  6. Tan Teck Choon
  7. Low Serena
  8. Tang Terence

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Abstract

Background

Coronavirus disease 2019 (COVID-19) is associated with severe pneumonia, respiratory failure and death. We aim to evaluate the efficacy of adjunctive corticosteroids in the management of COVID-19.

Methods

This is a retrospective cohort study of hospitalized adults (≥18 years) who were diagnosed with COVID-19 and were given treatment. Treatment included hydroxycholoroquine and lopinavir-ritonavir. Corticosteroids were included as adjunctive therapy in mid-April, 2020. We compared composite outcomes of clinical progression and invasive mechanical ventilation (MV) or death between group that received treatment only (Group A) versus group that received adjunctive corticosteroids (Group B). Entropy balancing was used to generate stabilized weight for covariates between treatment groups. Unweighted Kaplan-Meir curves, weighted and adjusted Cox regression analysis were used to estimate effect of adjunctive corticosteroids on composite outcomes. Subgroup analysis was performed on those with pneumonia.

Results

Of 1046 patients with COVID-19, 57 received treatment alone (Group A) and 35 received adjunctive corticosteroids in addition to treatment (Group B). Median day of illness at treatment initiation was 5 day. There were 44 patients with pneumonia; 68.9% of them were not requiring supplemental oxygen at treatment initiation. Overall, 17 (18.5%) of 92 patients had clinical progression including 13 (22.8%) of 57 patients in Group A versus 4 (11.4%) of 35 patients in Group B (p=0.172). Unweighted Kaplan-Meier estimates showed no significant difference in the proportion of patients who had clinical progression or invasive MV or death between the 2 treatment groups. However in those with pneumonia, there were lower proportions of patients in Group B with clinical progression (11.1%, 95% CI 0.0 - 22.2 versus 58.8%, 95% CI 27.3 - 76.7, log rank p<0.001); and invasive MV or death (11.3%, 95% CI 0.0 - 22.5 versus 41.2%, 95% CI 12.4. - 60.5, log rank p=0.016). In weighted and adjusted cox regression analysis, patients in Group B were less likely to have clinical progression, (adjusted HR [aHR] 0.08, 95% CI 0.01-0.99, p=0.049) but there was no statistical significant difference in risk of requiring invasive MV or death (aHR 0.22, 95%CI 0.02 - 2.54, p=0.22). In subgroup with pneumonia, patients in Group B were significantly at lower risk of clinical progression (aHR 0.15, 95% CI 0.06 - 0.39, p<0.001) and requiring invasive MV compared to Group A (aHR 0.30, 0.10-0.87, p=0.029).

Conclusions

Use of adjunctive corticosteroids is associated with lower risk of clinical progression and invasive MV or death, especially in those with pneumonia. Concurrent use of antivirals and corticosteroids should be considered in the management of COVID-19 related pneumonia.

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  1. ScreenIT

    SciScore for 10.1101/2020.07.18.20157008: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: This study was approved by Domain Specific Review Board.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Comparison of baseline characteristics by treatment group, patterns of fever and CRP changes following treatment was performed using STATA version 15 (STATA Corp., Texas, USA)
    STATA
    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:
    Our study has several limitations. Without a placebo arm, we are unable to conclude if the protective effect observed in our study was directly due to corticosteroids alone or in combination with a treatment agent, mostly HCQ. Non-randomized treatment selection and small sample size could have biased estimates and limit our subgroup analysis. The estimates in weighted regression are dependent on balancing of covariates and confounders. Despite non-parametric method of covariate balancing, there were some imbalances that required further covariate adjustment in regression models. Our estimates could subject to possible model misspecification and are based on assumption that all confounders are controlled. In a conservative view, estimates in unadjusted cox regression did not show an increased risk of composite outcomes despite seemingly more severe disease in group that received adjunctive corticosteroids. Having said that, risk of secondary infection and other adverse outcomes associated with corticosteroids were not evaluated. Our analysis could not account for change in clinical practice and experience gained in managing COVID-19 over time that might affect better outcome in the later stage. However, it is unlikely to account for lower risk of clinical progression of requiring oxygen in those with pneumonia on adjunctive corticosteroids. Lastly, younger population in our cohort and single center design may limit generalizability of these results to other populations. In sum...

    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

    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 10.1101/2020.07.18.20157008 on medRxiv