Calprotectin and Imbalances between Acute-Phase Mediators Are Associated with Critical Illness in COVID-19
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Abstract
The trajectory from moderate and severe COVID-19 into acute respiratory distress syndrome (ARDS) necessitating mechanical ventilation (MV) is a field of active research. We determined serum levels within 24 h of presentation of 20 different sets of mediators (calprotectin, pro- and anti-inflammatory cytokines, interferons) of patients with COVID-19 at different stages of severity (asymptomatic, moderate, severe and ARDS/MV). The primary endpoint was to define associations with critical illness, and the secondary endpoint was to identify the pathways associated with mortality. Results were validated in serial measurements of mediators among participants of the SAVE-MORE trial. Levels of the proinflammatory interleukin (IL)-8, IL-18, matrix metalloproteinase-9, platelet-derived growth factor (PDGF)-B and calprotectin (S100A8/A9) were significantly higher in patients with ARDS and MV. Levels of the anti-inflammatory IL-1ra and IL-33r were also increased; IL-38 was increased only in asymptomatic patients but significantly decreased in the more severe cases. Multivariate ordinal regression showed that pathways of IL-6, IL-33 and calprotectin were associated with significant probability for worse outcome. Calprotectin was serially increased from baseline among patients who progressed to ARDS and MV. Further research is needed to decipher the significance of these findings compared to other acute-phase reactants, such as C-reactive protein (CRP) or ferritin, for the prognosis and development of effective treatments.
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SciScore for 10.1101/2022.01.28.22270001: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Patients have already participated as comparators receiving usual care in the studies ACHIEVE33, SAVE32 and ESCAPE34 that have been approved by the National Ethics Committee of Greece and by the National Organization for Medicines of Greece (approval numbers 45/20 and IS 36/20 respectively for ACHIEVE; approval numbers 38/20 and IS 28/20 for SAVE; and approval numbers approval 30/20 and IS 021-20 respectively for ESCAPE).
Consent: Patients were enrolled after written informed consent provided by themselves or legal representatives.Sex as a biological variable not detected. Randomization SAVE-MORE is a double-blind randomized clinical trial where patients were allocated to treatment with … SciScore for 10.1101/2022.01.28.22270001: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Patients have already participated as comparators receiving usual care in the studies ACHIEVE33, SAVE32 and ESCAPE34 that have been approved by the National Ethics Committee of Greece and by the National Organization for Medicines of Greece (approval numbers 45/20 and IS 36/20 respectively for ACHIEVE; approval numbers 38/20 and IS 28/20 for SAVE; and approval numbers approval 30/20 and IS 021-20 respectively for ESCAPE).
Consent: Patients were enrolled after written informed consent provided by themselves or legal representatives.Sex as a biological variable not detected. Randomization SAVE-MORE is a double-blind randomized clinical trial where patients were allocated to treatment with placebo or anakinra plus standard-of-care to prevent progression into severe respiratory failure12 (approval 161/20 by the National Ethics Committee of Greece; approval 01.02.2021 by the Ethics Committee of the National Institute for Infectious Diseases Lazzaro Spallanzani, IRCCS in Rome; EudraCT number, 2020-005828-11; ClinicalTrials.gov NCT04680949). Blinding not detected. Power Analysis not detected. Cell Line Authentication Authentication: The value of this cut-off was further validated by forward step-wise Cox regression analysis. 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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04680949 Active, not recruiting suPAR-Guided Anakinra Treatment for Management of Severe Res… 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.
Results from scite Reference Check: We found no unreliable references.
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