Molecular markers for early stratification of disease severity and progression in COVID-19

  1. Anusha
  2. Savitha Anne Sebastian
  3. N. Raksha
  4. K. Raksha
  5. H. Krishnamurthy
  6. Bhuvana Krishna
  7. George D’Souza
  8. Jyothi Idiculla
  9. Neha Vyas

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Abstract

COVID-19 infections have imposed immense pressure on the healthcare system of most countries. While the initial studies have identified better therapeutic and diagnostic approaches, the disease severity is still assessed by close monitoring of symptoms by healthcare professionals due to the lack of biomarkers for disease stratification. In this study, we have probed the immune and molecular profiles of COVID-19 patients at 48-hour intervals after hospitalization to identify early markers, if any, of disease progression and severity. Our study reveals that the molecular profiles of patients likely to enter the host-immune response mediated moderate or severe disease progression are distinct even in the early phase of infection when severe symptoms are not yet apparent. Our data from 37 patients suggest that at hospitalization, IL6 (>300pg/ml) and IL8 levels (>200pg/ml) identify cytokine-dependent disease progression. Monitoring their levels will facilitate timely intervention using available immunomodulators or precision medicines in those likely to progress due to cytokine storm and help improve outcomes. Additionally, it will also help identify cytokine-independent progressive patients, not likely to benefit from immuno-modulators or precision drugs.

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  1. ScreenIT

    SciScore for 10.1101/2022.02.06.22270355: (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

    Antibodies
    SentencesResources
    Cell Staining for Flow Cytometric analysis: The antibody capture beads Unstained beads (Negative beads and Positive beads), single stained(negative beads + positive beads) were used for color compensation as per manufacturer’s protocol (552843 BD™ CompBead, Anti-Mouse)
    Anti-Mouse
    suggested: None
    Antibody mix includes CD45 (563204, Mouse, BD Biosciences), CD38 (555462, Mouse, BD Biosciences), CD24 (Mouse, 555427, BD Biosciences), CD66B
    CD45
    suggested: (BD Biosciences Cat# 563204, RRID:AB_2738067)
    CD38
    suggested: (BD Biosciences Cat# 555462, RRID:AB_398599)
    CD24
    suggested: (BD Biosciences Cat# 555427, RRID:AB_395821)
    Antibodies mix includes CD45, CD3, CD4, CD8 (Mouse, 340499, BD Biosciences).
    CD3
    suggested: (BD Biosciences Cat# 340499, RRID:AB_400472)
    CD4
    suggested: (BD Biosciences Cat# 340499, RRID:AB_400472)
    CD8
    suggested: (BD Biosciences Cat# 340499, RRID:AB_400472)
    Software and Algorithms
    SentencesResources
    , TNF-a (550610, BD Biosciences), and IL10 (550613, BD Biosciences) and Lung markers include Uteroglobin (DUGB00, R&D Systems), SP-D (DSFPD0, R&D Systems) and sRAGE (DRG00, R&D Systems).
    BD Biosciences
    suggested: (BD Biosciences, RRID:SCR_013311)

    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: 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 10.1101/2022.02.06.22270355 on medRxiv
  3. Version published to 10.1093/biomethods/bpac028