Relative Importance of Various Inflammatory Markers and Their Critical Thresholds for COVID-19 Mortality

  1. Sandeep Budhiraja

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Abstract

Background: The management of COVID-19 patients often involves assessing various inflammatory markers. However, it is unclear how the different levels of these markers correlate with mortality risk and which markers are more critical. This study aims to analyse the levels of eight inflammatory markers— C-reactive protein (CRP), D-dimer, ferritin, interlukin-6 (IL-6), lactate dehydrogenase (LDH), creatine phosphokinase (CPK), troponin-I, and absolute lymphocyte count (ALC)—and their association with COVID-19 mortality. Methods: Data from 19,852 COVID-19 patients admitted to a hospital chain in North India from March 2020 to July 2021 were analysed. Inflammatory marker levels were divided into quintiles for mortality pattern analysis and logistic regression. The distribution of marker levels was compared using the Mann-Whitney test. The relative importance of each marker was evaluated using mortality rates, area under the ROC curves (AUROCs), and odds ratios. Results: Mortality increased with decreasing ALC and rising levels of all other markers, though over 70% survived even with extreme quintile levels. IL-6 had the highest adjusted odds ratio (7.62) at the highest quintile, followed by D-dimer (OR=6.04). LDH had the highest AUROC (0.817), while CPK had the lowest (0.612). No single marker could classify more than 80% of deaths correctly, and multivariable logistic regression only correctly classified mortality in less than 24% of cases. Conclusion: Elevated levels of inflammatory markers and low ALC values were significant risk factors for COVID-19 mortality. However, no single marker was a definitive predictor of mortality without reaching critical thresholds. Among the markers studied, D-dimer (>192 ng/mL) and IL-6 (>4.5 pg/mL) were most strongly associated with mortality even at moderately elevated levels, while LDH (>433 U/L) and troponin-I (>0.002 ng/mL) were associated with mortality only at high levels. Ferritin showed a modest association, and CPK, CRP, and ALC were relatively poor indicators of mortality risk.

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  1. Version published to 10.62830/mmj1-3-6a
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    SciScore for 10.1101/2021.12.24.21268371: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variableMost common age-group was 40-59 years (38.6%) and 33.6% of all patients were females.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    SPSS 21 was used for calculations.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    Results from OddPub: Thank you for sharing your data.

    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: 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.

    Results from scite Reference Check: We found no unreliable references.

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  3. Version published to 10.1101/2021.12.24.21268371v1 on medRxiv