SARS-CoV-2-Specific Antibody Profiles Distinguish Patients with Moderate from Severe COVID-19

  1. Leire de Campos Mata
  2. Janet Piñero
  3. Sonia Tejedor Vaquero
  4. Roser Tachó-Piñot
  5. Maria Kuksin
  6. Itziar Arrieta Aldea
  7. Natalia Rodrigo Melero
  8. Carlo Carolis
  9. Laura Furlong
  10. Andrea Cerutti
  11. Judit Villar-García
  12. Giuliana Magri

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Abstract

The production of SARS-CoV-2-specific neutralizing antibodies is widely considered as a key mechanism for COVID-19 resolution and protection. However, beyond their protective function, antibodies to SARS-CoV-2 may also participate in disease pathogenesis. To explore the potential relationship between virus-specific humoral responses and COVID-19 immunopathology, we measured serum antibody classes and subclasses to the receptor-binding domain of the SARS-CoV-2 spike protein and the nucleoprotein in a cohort of hospitalized COVID-19 patients with moderate to severe disease. We found that RBD-specific IgG1 and IgG3 dominated the humoral response to SARS-CoV-2, were more abundant in severe patients, and positively correlated with several clinical parameters of inflammation. In contrast, a virus-specific IgA2 response skewed toward RBD rather than NP associated with a more favorable clinical course. Interestingly, RBD-dominant IgA2 responses were mostly detected in patients with gastrointestinal symptoms, suggesting the possible involvement of intrinsically tolerogenic gut immune pathways in the attenuation of virus-induced inflammation and disease resolution.

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  1. ScreenIT

    SciScore for 10.1101/2020.12.18.20248461: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Vienna, Austria: R Foundation for Statistical Computing; https://www.R-project.org/.) and GraphPad Prism (version 8.0).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    The heatmaps were created using R package ComplexHeatmap (10.1093/bioinformatics/btw313), and row and column clustering were performed with complete cluster method and euclidean distance metric.
    ComplexHeatmap
    suggested: (ComplexHeatmap, RRID:SCR_017270)

    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 of the study: There are a number of limitations in this study. First of all, it includes a limited number of COVID-19 patients (n=38) and presence of co-morbidities were not taken into consideration, thus our results should be confirmed in future studies in a larger cohort of SARS-CoV-2-infected patients. Our serologic analysis has been performed only on COVID-19 hospitalized patients ranging from moderate to severe COVID-19. Although previous reports (Guthmiller et al., 2020; Long et al., 2020b; Robbiani et al., 2020) have described striking differences in the magnitude of virus-specific humoral responses between asymptomatic and hospitalized individuals, mild patients may be analyzed in future studies to confirm the association between antibody profiles (i.e. RBD-specific IgA2) and intestinal symptoms or time of disease resolution. Finally, the time from symptom onset to blood sampling should be also considered as a possible confounder as for some patients with low virus-specific antibody titers, serologic analysis may have been performed before the subject had mounted a significant humoral response.

    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.

  2. Version published to 10.1101/2020.12.18.20248461 on medRxiv