Therapeutic plasma exchange for coronavirus disease-2019 triggered cytokine release syndrome; a retrospective propensity matched control study

  1. Sultan Mehmood Kamran
  2. Zill-e-Humayun Mirza
  3. Arshad Naseem
  4. Jahanzeb Liaqat
  5. Imran Fazal
  6. Wasim Alamgir
  7. Farrukh Saeed
  8. Salman Saleem
  9. Shazia Nisar
  10. Muhammad Ali Yousaf
  11. Asad Zaman Khan
  12. Mehmood Hussain
  13. Rizwan Azam
  14. Maryam Hussain
  15. Kumail Abbas Khan
  16. Yousaf Jamal
  17. Raheel Iftikhar

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Abstract

Cytokine release syndrome (CRS) plays a pivotal role in the pathophysiology and progression of Coronavirus disease-2019 (COVID-19). Therapeutic plasma exchange (TPE) by removing the pathogenic cytokines is hypothesized to dampen CRS.

Objective

To evaluate the outcomes of the patients with COVID-19 having CRS being treated with TPE compared to controls on the standard of care.

Methodology

Retrospective propensity score-matched analysis in a single centre from 1st April to 31st July 2020. We retrospectively analyzed data of 280 hospitalized patients developing CRS initially. PSM was used to minimize bias from non-randomized treatment assignment. Using PSM 1:1, 90 patients were selected and assigned to 2 equal groups. Forced matching was done for disease severity, routine standard care and advanced supportive care. Many other Co-variates were matched. Primary outcome was 28 days overall survival. Secondary outcomes were duration of hospitalization, CRS resolution time and timing of viral clearance on Polymerase chain reaction testing.

Results

After PS-matching, the selected cohort had a median age of 60 years (range 32–73 in TPE, 37–75 in controls), p = 0.325 and all were males. Median symptoms duration was 7 days (range 3–22 days’ TPE and 3–20 days controls), p = 0.266. Disease severity in both groups was 6 (6.6%) moderate, 40 (44.4%) severe and 44 (49%) critical. Overall, 28-day survival was significantly superior in the TPE group (91.1%), 95% CI 78.33–97.76; as compared to PS-matched controls (61.5%), 95% CI 51.29–78.76 (log rank 0.002), p<0.001. Median duration of hospitalization was significantly reduced in the TPE treated group (10 days vs 15 days) (p< 0.01). CRS resolution time was also significantly reduced in the TPE group (6 days vs. 12 days) (p< 0.001). In 71 patients who underwent TPE, the mortality was 0 (n = 43) if TPE was done within the first 12 days of illness while it was 17.9% (deaths 5, n = 28 who received it after 12 th day (p = 0.0045).

Conclusion

An earlier use of TPE was associated with improved overall survival, early CRS resolution and time to discharge compared to SOC for COVID-19 triggered CRS in this selected cohort of PS-matched male patients from one major hospital in Pakistan.

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  1. Version published to 10.1371/journal.pone.0244853
  2. ScreenIT

    SciScore for 10.1101/2020.07.23.20160796: (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 Institutional Review Board.
    Consent: Written consent was taken from those who agreed for this treatment.
    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:
    Nonetheless, our study had few limitations. Firstly, it was retrospective study which in itself has weaker evidence as compared to prospective trials. Secondly, although a strict PSM analysis was done, but still all biases cannot be neutralized. Thirdly, we did not follow up patients after discharge, due to lack of resources. Fourthly, in TPE procedure, we used centrifugation TPE machine rather than continuous hemofiltration (CHF) which is known to remove IL-6 and similar cytokines molecular mass of 21 to 54.1 kDa24, due to lack of availability of filters. Nevertheless, even after considering such limitations, using TPE early, in addition to standard treatment in patients with COVID-19 can mitigate the cytokine storm. TPE shows promise, and we propose that large, multi-centric, randomized trials be designed to further investigate its role.

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

    IdentifierStatusTitle
    NCT04485169CompletedTherapeutic Plasma Exchange for Coronavirus Disease-2019 Tri…

    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.

  3. ScreenIT

    SciScore for 10.1101/2020.07.23.20160796: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementThe study was approved by Institutional Review Board.RandomizationTPE shows promise, and we propose that large, multi-centric, randomized trials be designed to further investigate its role.Blindingnot detected.Power Analysisnot detected.Sex as a biological variableThe overall eligible cohort was 245/280 (87.5%) males and 35/280 (12.5%) females, with a median age of 62 years (range 20-80 years) p-value 0.05.

    Table 2: Resources

    Data from additional tools added to each annotation on a weekly basis.

    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 is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.

  4. Version published to 10.1101/2020.07.23.20160796v1 on medRxiv