Elevated Anti-SARS-CoV-2 Antibodies and IL-6, IL-8, MIP-1β, Early Predictors of Severe COVID-19

  1. Helena Codina
  2. Irene Vieitez
  3. Alicia Gutierrez-Valencia
  4. Vasso Skouridou
  5. Cristina Martínez
  6. Lucía Patiño
  7. Mariluz Botero-Gallego
  8. María Trujillo-Rodríguez
  9. Ana Serna-Gallego
  10. Esperanza Muñoz-Muela
  11. María M. Bobillo
  12. Alexandre Pérez
  13. Jorge Julio Cabrera-Alvar
  14. Manuel Crespo
  15. Ciara K. O’Sullivan
  16. Ezequiel Ruiz-Mateos
  17. Eva Poveda

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Abstract

Viral and host immune kinetics during acute COVID-19 and after remission of acute symptoms need better characterization. SARS-CoV-2 RNA, anti-SARS-CoV-2 IgA, IgM, and IgG antibodies, and proinflammatory cytokines were measured in sequential samples from hospitalized COVID-19 patients during acute infection and six months following diagnosis. Twenty four laboratory confirmed COVID-19 patients with mild/moderate and severe COVID-19 were included. Most were males (83%) with a median age of 61 years. Twenty one percent were admitted to the intensive care unit (ICU) and eight of them (33.3%) met the criteria for severe COVID-19 disease. A delay in SARS-CoV-2 levels’ decline during the first six days of follow up, and viral load persistence until month 3 were related to severe COVID-19, but not viral load levels at the diagnosis. Higher levels of anti-SARS-CoV-2 IgA, IgM, IgG and the cytokines IL-6, IL-8 and MIP-1β at the diagnosis time were related to the severe COVID-19 outcome. Higher levels of MIP-1β, IL-1β, MIP-1α and IFN-γ were observed at month 1 and 3 during mild/moderate disease, compared to severe COVID-19. IgG persisted at low levels after six months of diagnosis. In conclusion, higher concentrations of IgA, IgM, and IgG, and IL-6, IL-8 and MIP-1β are identified as early predictors of COVID-19 severity, whereas no significant association is found between baseline SARS-COV-2 viral load and COVID-19 severity.

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  1. Version published to 10.3390/microorganisms9112259
  2. ScreenIT

    SciScore for 10.1101/2021.04.13.439586: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Written informed consent was obtained from each individual enrolled in the COHVID-GS.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The levels of IgA, IgM and IgG antibodies in each sample were estimated using standard antibody calibration curves performed in parallel in each plate as detailed in the supplementary information.
    IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    Droplet digital PCR analysis: SARS-CoV-2 viral load was quantified by reverse transcriptase droplet digital PCR (RT-ddPCR), including the one-step reverse transcription (One-Step RT-ddPCR Advanced Kit for Probes, Bio-Rad Laboratories) and the triplex probe assay for PCR amplification (2019-nCoV CDC ddPCR Triplex Probe Assay, Bio-Rad Laboratories).
    Bio-Rad Laboratories
    suggested: (Bio-Rad Laboratories, RRID:SCR_008426)
    Data analysis was performed using the QuantaSoft Analysis Pro Software (Bio-Rad Laboratories) which showed the results as copies per microliter of 1x ddPCR reaction.
    QuantaSoft Analysis Pro
    suggested: None
    Statistical analyses were done with SPSS version 19 and GraphPad Prism 8.2.1 and a p value less than 0.05 was considered statistical significance.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)
    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:
    This study presents some limitations. First, the relatively small size of the study population mainly represented by men as during the first wave of COVID-19 in our institution 86% of hospitalized patients were men. However, we were able to accomplish a very close follow-up of the clinical outcomes, viral and host immune factors in this population allowing interesting observations. Although we have identified IgG after 6 months of SARS-CoV-2 infection we did not assess their neutralization activity and therefore the risk upon new SARS-CoV-2 re-infections. External validation should be assessed to confirm the predictive value of our findings. In conclusion, in a well-characterized cohort of hospitalized COVID-19 with mild/moderate and severe disease and close clinical follow-up during and after 6 months of SARS-CoV-2 infection we have recognized early host immune predictors of severity. Higher levels of IgA, IgM, and IgG and the specific cytokines IL-6, IL-8, and MIP-1β during acute infection were observed in those patients with a severe COVID-19 outcome. Conversely, higher levels of IL-1β and IFN-γ and at month 1 and MIP-1β, IL-1β, MIP-1α and IFN-γ month 3 were observed among patients with mild/moderate diseases compared to those with severe COVID-19. IgG against SARS-CoV-2 persisted after 6 months of the diagnosis.

    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.

  3. Version published to 10.1101/2021.04.13.439586v1 on bioRxiv