sMAdCAM: IL-6 Ratio Influences Disease Progression and Anti-Viral Responses in SARS-CoV-2 Infection

  1. Dhanashree Jagtap
  2. Vikrant M. Bhor
  3. Shilpa Bhowmick
  4. Nandini Kasarpalkar
  5. Pooja Sagvekar
  6. Bhalchandra Kulkarni
  7. Manish Pathak
  8. Nirjhar Chatterjee
  9. Pranam Dolas
  10. Harsha Palav
  11. Snehal Kaginkar
  12. Sharad Bhagat
  13. Itti Munshi
  14. Swapneil Parikh
  15. Sachee Agrawal
  16. Chandrakant Pawar
  17. Mala Kaneria
  18. Smita D. Mahale
  19. Jayanthi Shastri
  20. Vainav Patel

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Abstract

The role of sMAdCAM, an important gut immune migratory marker, remains unexplored in COVID-19 pathogenesis considering recent studies positing the gut as a sanctuary site for SARS-CoV-2 persistence. Thus, assimilating profiles of systemic inflammatory mediators with sMAdCAM levels may provide insights into the progression of COVID-19 disease. Also, the role of these markers in governing virus specific immunity following infection remains largely unexplored. A cohort (n = 84) of SARS-C0V-2 infected individuals included a group of in-patients (n = 60) at various stages of disease progression together with convalescent individuals (n = 24) recruited between April and June 2020 from Mumbai, India. Follow-up of 35 in-patients at day 7 post diagnosis was carried out. Th1/Th2/Th17 cytokines along with soluble MAdCAM (sMAdCAM) levels in plasma were measured. Also, anti-viral humoral response as measured by rapid antibody test (IgG, IgM), Chemiluminescent Immunoassay (IgG), and antibodies binding to SARS-CoV-2 proteins were measured by Surface Plasmon Resonance (SPR) from plasma. IL-6 and sMAdCAM levels among in-patients inversely correlated with one another. When expressed as a novel integrated marker—sMIL index (sMAdCAM/IL-6 ratio)—these levels were incrementally and significantly higher in various disease states with convalescents exhibiting the highest values. Importantly, sMAdCAM levels as well as sMIL index (fold change) correlated with peak association response units of receptor binding domain and fold change in binding to spike respectively as measured by SPR. Our results highlight key systemic and gut homing parameters that need to be monitored and investigated further to optimally guide therapeutic and prophylactic interventions for COVID-19.

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  1. Version published to 10.3389/fimmu.2021.619906
  2. Version published to 10.1101/2020.10.13.20182949v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2020.10.13.20182949: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Study population, setting, and data collection: A total of 36 in-patients and 22 convalescent individuals were recruited (from April-June, 2020), following informed consent, for the study from the isolation ward at Kasturba Hospital for Infectious Diseases (Municipal Corporation of Greater Mumbai).
    IRB: The Kasturba Hospital and ICMR-NIRRH institutional ethics committees approved this study.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablePregnant women, prisoners, and children (less than 18 years of age) were excluded from the study.

    Table 2: Resources

    Antibodies
    SentencesResources
    IgG and IgM antibodies against SARS-CoV-2 were detected in fresh plasma samples using Rapid test from either Voxpress (Voxtur Bio LTD, India) or Tell me fast (Biocan Diagnostics Inc., Canada) kits and also by ARCHITECT™ Abbott™ (Abbott Diagnostics, USA) chemiluminescence immunoassay (CLIA) directed against SARS -CoV-2 anti-NC IgG.
    SARS-CoV-2
    suggested: None
    anti-NC IgG
    suggested: None
    Remaining plasma samples were aliquoted and stored at −80°C until batch analysis of cytokines, soluble mucosal addressin cell adhesion molecule (sMAdCAM) and antibody binding profile using surface plasmon resonance (SPR).
    SPR
    suggested: None
    Software and Algorithms
    SentencesResources
    IgG and IgM antibodies against SARS-CoV-2 were detected in fresh plasma samples using Rapid test from either Voxpress (Voxtur Bio LTD, India) or Tell me fast (Biocan Diagnostics Inc., Canada) kits and also by ARCHITECT™ Abbott™ (Abbott Diagnostics, USA) chemiluminescence immunoassay (CLIA) directed against SARS -CoV-2 anti-NC IgG.
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    GraphPad Prism was used to extrapolate individual cytokine concentrations from a standard curve.
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Statistical analysis: Statistical analysis was performed in GraphPad Prism 8 using non parametric tests.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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:
    Limitations: The limitations of this study include a modest sized cohort that may reduce the impact of the observations and requires validation through larger prospective studies. Also, the follow-up data was based on 11 of 36 in-patients due to limited availability of sequential samples. With respect to sMAdCAM levels there is a lack of robust data for healthy individuals. Further, the date of diagnosis was considered as the onset of disease progression which may not have been the case for all the study participants.

    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 10.1101/2020.10.13.20182949v1 on medRxiv