Observational cohort study of IP-10’s potential as a biomarker to aid in inflammation regulation within a clinical decision support protocol for patients with severe COVID-19

  1. Shaul Lev
  2. Tamar Gottesman
  3. Gal Sahaf Levin
  4. Doron Lederfein
  5. Evgeny Berkov
  6. Dror Diker
  7. Aliza Zaidman
  8. Amir Nutman
  9. Tahel Ilan Ber
  10. Alon Angel
  11. Lior Kellerman
  12. Eran Barash
  13. Roy Navon
  14. Olga Boico
  15. Yael Israeli
  16. Michal Rosenberg
  17. Amir Gelman
  18. Roy Kalfon
  19. Einav Simon
  20. Noa Avni
  21. Mary Hainrichson
  22. Oren Zarchin
  23. Tanya M. Gottlieb
  24. Kfir Oved
  25. Eran Eden
  26. Boaz Tadmor

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Abstract

Treatment of severely ill COVID-19 patients requires simultaneous management of oxygenation and inflammation without compromising viral clearance. While multiple tools are available to aid oxygenation, data supporting immune biomarkers for monitoring the host-pathogen interaction across disease stages and for titrating immunomodulatory therapy is lacking.

Methods

In this single-center cohort study, we used an immunoassay platform that enables rapid and quantitative measurement of interferon γ-induced protein 10 (IP-10), a host protein involved in lung injury from virus-induced hyperinflammation. A dynamic clinical decision support protocol was followed to manage patients infected with severe acute respiratory syndrome coronavirus 2 and examine the potential utility of timely and serial measurements of IP-10 as tool in regulating inflammation.

Results

Overall, 502 IP-10 measurements were performed on 52 patients between 7 April and 10 May 2020, with 12 patients admitted to the intensive care unit. IP-10 levels correlated with COVID-19 severity scores and admission to the intensive care unit. Among patients in the intensive care unit, the number of days with IP-10 levels exceeding 1,000 pg/mL was associated with mortality. Administration of corticosteroid immunomodulatory therapy decreased IP-10 levels significantly. Only two patients presented with subsequent IP-10 flare-ups exceeding 1,000 pg/mL and died of COVID-19-related complications.

Conclusions

Serial and readily available IP-10 measurements potentially represent an actionable aid in managing inflammation in COVID-19 patients and therapeutic decision-making.

Trial registration

Clinicaltrials.gov, NCT04389645 , retrospectively registered on May 15, 2020.

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  1. Version published to 10.1371/journal.pone.0245296
  2. ScreenIT

    SciScore for 10.1101/2020.07.21.20158782: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    25 The analysis was performed using Python 3.7.6.
    Python
    suggested: (IPython, RRID:SCR_001658)

    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:
    The main limitation of our study is that the study design was not a randomized controlled trial, which limits the ability to estimate the magnitude of improvement in patient outcome that is attributable to implementation of the dynamic clinical decision support protocol. Moreover, the cohort study design does not allow evaluation of the contribution of different elements of the protocol, in particular, the personalized corticosteroid regimens. In addition, this is a single-center study; application of the protocol at additional sites and across multiple cohorts is warranted. The pivotal strength of our study is that it is the first prospective investigation of the potential value of serial and rapid IP-10 measurements as an indicator of the inflammatory status of COVID-19 patients. In addition, preliminary data was collected suggesting that low TRAIL levels, reported as an indicator of infection severity29, when sustained may flag failure to clear the virus. Further studies of TRAIL and its prognostic value are required. In conclusion, our study supports the utility of using serial and rapid IP-10 measurements as a practical new tool in management of COVID-19 patients. Future studies are warranted to establish the contribution of IP-10 within a clinical decision support protocol to improved COVID-19 patient outcome.

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

    IdentifierStatusTitle
    NCT04389645CompletedInterferon Gamma Induced Protein 10 (IP-10) in a Clinical De…

    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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  3. Version published to 10.1101/2020.07.21.20158782v1 on medRxiv