Association of inflammatory markers with severity of disease and mortality in COVID-19 patients: a systematic review and meta-analysis

  1. Sara Khan
  2. Pinki Mishra
  3. Rizwana Parveen
  4. Ram Bajpai
  5. Mohd Ashif Khan
  6. Nidhi Bharal Agarwal

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Abstract

Purpose

Literature suggests association of inflammatory markers with the severity and mortality related to COVID-19, but there are varying conclusions available. We aimed to provide an overview of the association of inflammatory markers with the severity and mortality of COVID-19 patients.

Methods

We searched Medline (via PubMed), Cochrane, Clinicaltrials.gov databases until Sept 1, 2020.

Results

A total of 21 studies comprising 4023 patients with COVID-19 were included in our analysis. Levels of IL-6 (WMD=18.17 95%CI 3.38 to 32.96, p=0.016), IL-8 (WMD=12.09 95%CI 4.41 to 19.77, p=0.002), MCP-1 (WMD=146.66 95%CI 88.16 to 205.16, p<0.001), CRP (WMD=31.09 95%CI 10.08 to 52.10, p=0.004), PCT (WMD= -31.23 95%CI -37.70 to -24.76, p<0.001), IL-2R (WMD=861.93 95%CI 275.45 to 1448.41, p=0.004), ferritin (WMD= 1083.34 95%CI 431.99 to 1734.70, p=0.001) were found significantly higher in the severe group compared with the non-severe group of COVID-19 patients. Moreover, non-survivors had a higher levels of IL-2R (WMD= -666.06 95%CI -782.54 to -549.59, p<0.001), IL-8 (WMD= -26.63 95%CI -33.031 to -20.236, p<0.001), IL-10 (WMD= -7.60 95%CI -8.93 to -6.26, p<0.001), TNF-α (WMD= -4.60 95%CI -5.71 to -3.48, p<0.001), IL-1β (WMD=22.66 95%CI 8.13 to 37.19, p=0.002), CRP (WMD= -96.40 95%CI -117.84 to -74.97, p<0.001), and ferritin (WMD= -937.60 95%CI -1084.15 to -791.065, p<0.001) when compared to the non-survivor group.

Conclusion

This meta-analysis highlights the association of inflammatory markers with the severity and mortality of COVID-19 patients. Measurement of these inflammatory markers may assist clinicians to monitor and evaluate the severity and prognosis of COVID-19 thereby reducing the mortality rate.

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  1. ScreenIT

    SciScore for 10.1101/2021.09.16.21263678: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Data sources and searches: A systematic literature search was performed using Medline (via PubMed), The Cochrane Central Register of Controlled Trials (CENTRAL) and Clinicaltrials.gov until September 1, 2020 using the keywords “SARS CoV-2”, “Interleukins”, “Cytokines”, “COVID-19”, “Cytokine storm”, “Inflammatory markers”, “laboratory findings”.
    Medline
    suggested: (MEDLINE, RRID:SCR_002185)
    Cochrane Central Register of Controlled Trials
    suggested: (Cochrane Central Register of Controlled Trials, RRID:SCR_006576)
    We also searched grey literature using Google Scholar and reference list of eligible articles with the aim of identifying additional potential eligible studies.
    Google Scholar
    suggested: (Google Scholar, RRID:SCR_008878)

    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:
    There are several limitations that needs to be mentioned. The number of studies included in the meta-analysis is small. There was heterogeneity amongst individual studies because of which there was a deviation of some of our results from usual findings. Additionally, case-series were included in the present meta-analysis. Although we did an extensive search, we may have inadvertently missed relevant studies. Exclusion of studies in languages other than English may have resulted in missing of relevant studies.

    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.

    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.

  2. Version published to 10.1101/2021.09.16.21263678v1 on medRxiv