Unique inflammatory profile is associated with higher SARS-CoV-2 acute respiratory distress syndrome (ARDS) mortality

  1. Joseph Balnis
  2. Alejandro P. Adam
  3. Amit Chopra
  4. Hau C. Chieng
  5. Lisa A. Drake
  6. Nina Martino
  7. Ramon Bossardi Ramos
  8. Paul J. Feustel
  9. Katherine A. Overmyer
  10. Evgenia Shishkova
  11. Joshua J. Coon
  12. Harold A. Singer
  13. Marc A. Judson
  14. Ariel Jaitovich

Reviewed by

Read the full article

Listed in

Log in to save this article

Abstract

The COVID19 pandemic has caused more than a million of deaths worldwide, primarily due to complications from COVID19-associated acute respiratory distress syndrome (ARDS). Controversy surrounds the circulating cytokine/chemokine profile of COVID19-associated ARDS, with some groups suggesting that it is similar to patients without COVID19 ARDS and others observing substantial differences. Moreover, although a hyperinflammatory phenotype associates with higher mortality in non-COVID19 ARDS, there is little information on the inflammatory landscape’s association with mortality in patients with COVID19 ARDS. Even though the circulating leukocytes’ transcriptomic signature has been associated with distinct phenotypes and outcomes in critical illness including ARDS, it is unclear whether the mortality-associated inflammatory mediators from patients with COVID19 are transcriptionally regulated in the leukocyte compartment. Here, we conducted a prospective cohort study of 41 mechanically ventilated patients with COVID19 infection using highly calibrated methods to define the levels of plasma cytokines/chemokines and their gene expressions in circulating leukocytes. Plasma IL1RA and IL8 were found positively associated with mortality, whereas RANTES and EGF negatively associated with that outcome. However, the leukocyte gene expression of these proteins had no statistically significant correlation with mortality. These data suggest a unique inflammatory signature associated with severe COVID19.

Article activity feed

  1. Version published to 10.1152/ajpregu.00324.2020
  2. Version published to 10.1101/2020.05.21.20051300v3 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2020.05.21.20051300: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethical approval was obtained from Albany Medical College Committee on Research Involving Human Subjects (IRB# 5670-20).
    Consent: Exclusion criteria included likely imminent death or inability to provide consent.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Our study has some limitations. First, this is a single-center study that may not be universally reflective of COVID19 ARDS patients. Second, we did not have access to an external validation cohort. However, the associations between IL1RA and worse outcomes and RANTES with better outcomes in COVID-ARDS have been replicated by two recently published studies3,17. Third, while we enrolled the patients at the time of hospital admission, we had no control over the period elapsed between the disease development and the blood sampling, which may have affected the inflammatory landscape. Fourth, we had no control of different drugs administered to the patients which could have impacted their inflammatory profile.

    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.

  4. Version published to 10.1101/2020.05.21.20051300v1 on medRxiv
  5. Version published to 10.1101/2020.05.21.20051300v2 on medRxiv