The role of corticosteroids in the management of critically ill patients with coronavirus disease 2019 (COVID-19): A meta-analysis

  1. Kalyan Kumar Gangopadhyay
  2. Jagat J Mukherjee
  3. Binayak Sinha
  4. Samit Ghosal

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Abstract

Objective

There are no controlled studies on the role of systemic corticosteroids (CS) in patients with coronavirus disease 2019 (COVID-19). In the absence of high-quality evidence, understandably the recommendations from various organizations are cautious. Several randomized controlled trials are underway but shall take time to conclude. We therefore undertook a meta-analysis to ascertain the role of CS in the management of critically ill patients with COVID-19.

Data Sources

Electronic databases, including Pubmed, Cochrane library and Embase, were searched, using the keywords of interest and the PICO search technique, from inception to 12th April 2020.

Study Selection

Studies highlighting the use of CS in coronavirus infection with severe acute respiratory syndrome (SARS), Middle East Respiratory Syndrome (MERS) and COVID-19 were selected based on pre-determined inclusion criteria.

Data extraction

Data was extracted into an excel sheet and transferred to comprehensive meta-analysis software version 3, Biostat Inc., Englewood, NJ, USA, for analysis.

Data synthesis

Five studies with SARS-CoV-2 infection were included in the meta-analysis. The rate ratio (RR) for mortality in patients with SARS-CoV-2 infection was 1.26 (95% CI: 0.96-1.65, I 2 : 74.46), indicating lack of benefit of CS therapy on mortality in critically ill patients with COVID-19. The RR for mortality on analysis of the three studies that particularly reported on patients with significant pulmonary compromise secondary to SARS-CoV-2 infection was neutral (RR: 0.91, 95% CI: 0.63-1.33, I 2 : 63.38).

Conclusions

The use of CS in critically ill patients with COVID-19 did not improve or worsen mortality. Pending further information from controlled studies, CS can be used in critically ill patients with COVID-19 with ‘critical illness related corticosteroid insufficiency’ and moderate to severe ARDS without the risk of increased mortality.

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  1. ScreenIT

    SciScore for 10.1101/2020.04.17.20069773: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomization[Figure 1] Due to a dearth of well-designed randomized prospective studies on the topic under consideration, a wide-angle search was conducted with the following inclusion criteria: 2.2 Process of study selection: The study was conceptualized by KKG.
    Blinding2.3 Study quality assessment: Quality of individual studies were assessed using the Cochrane collaboration tool using random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcomes assessment, incomplete outcome data, selective reporting and other bias as assessment attributes.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    An electronic database search was conducted using the Cochrane library, PubMed and Medline.
    Cochrane library
    suggested: (Cochrane Library, RRID:SCR_013000)
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    Medline
    suggested: (MEDLINE, RRID:SCR_002185)
    2.3 Study quality assessment: Quality of individual studies were assessed using the Cochrane collaboration tool using random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcomes assessment, incomplete outcome data, selective reporting and other bias as assessment attributes.
    Cochrane collaboration tool
    suggested: None
    Heterogeneity was assessed using the Cochrane Q and Higgin’s I2 test, and publication bias was assessed by funnel plots.
    Cochrane Q
    suggested: None
    Where relative-risk or odds-ratio were not reported, rate-ratio was calculated from the reported events using Medcalc statistical software, © 2020 MedCalc Software Ltd, Ostend, Belgium.
    Medcalc
    suggested: (MedCalc, RRID:SCR_015044)

    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 a number of limitations in our meta-analysis. Firstly, the studies included for analysis used different primary and secondary criteria as aims for their respective studies resulting in a moderate degree of heterogeneity. Secondly, there were significant differences in the types of steroids used in the individual studies. This could have an impact on the final analysis. Thirdly, we are in the midst of a pandemic, and new data is being accrued constantly, which might impact our results. Fourthly, we have used rate ratio over hazard ratio to report mortality outcomes as it is a better index for assessing mortality over time. Majority of the trials included in the meta-analysis did not report a hazard ratio or mortality events over a period of time. We therefore took the cumulative events as reported at the end of the study period, ignoring time frame, for calculations. [Supplementary table 1] The strength of our meta-analysis lies in the fact that in an evolving infectious disease pandemic with acute consequences, the best way to increase the predictability of the question in focus is to perform pooled analysis. By pooling data and performing a systematic review and meta-analysis we have circumvented the problems associated with individual studies that have very divergent results as noted above; this shall help guide physicians till further information becomes available in the future. Secondly, to bring in some degree of uniformity, we created a stringent inclusion cri...

    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 10.1101/2020.04.17.20069773 on medRxiv