Limited intestinal inflammation despite diarrhea, fecal viral RNA and SARS-CoV-2-specific IgA in patients with acute COVID-19

  1. Graham J. Britton
  2. Alice Chen-Liaw
  3. Francesca Cossarini
  4. Alexandra E. Livanos
  5. Matthew P. Spindler
  6. Tamar Plitt
  7. Joseph Eggers
  8. Ilaria Mogno
  9. Ana S. Gonzalez-Reiche
  10. Sophia Siu
  11. Michael Tankelevich
  12. Lauren Tal Grinspan
  13. Rebekah E. Dixon
  14. Divya Jha
  15. Adriana van de Guchte
  16. Zenab Khan
  17. Gustavo Martinez-Delgado
  18. Fatima Amanat
  19. Daisy A. Hoagland
  20. Benjamin R. tenOever
  21. Marla C. Dubinsky
  22. Miriam Merad
  23. Harm van Bakel
  24. Florian Krammer
  25. Gerold Bongers
  26. Saurabh Mehandru
  27. Jeremiah J. Faith

Reviewed by

Read the full article

Listed in

Log in to save this article

Abstract

Gastrointestinal symptoms are common in COVID-19 patients but the nature of the gut immune response to SARS-CoV-2 remains poorly characterized, partly due to the difficulty of obtaining biopsy specimens from infected individuals. In lieu of tissue samples, we measured cytokines, inflammatory markers, viral RNA, microbiome composition, and antibody responses in stool samples from a cohort of 44 hospitalized COVID-19 patients. SARS-CoV-2 RNA was detected in stool of 41% of patients and more frequently in patients with diarrhea. Patients who survived had lower fecal viral RNA than those who died. Strains isolated from stool and nasopharynx of an individual were the same. Compared to uninfected controls, COVID-19 patients had higher fecal levels of IL-8 and lower levels of fecal IL-10. Stool IL-23 was higher in patients with more severe COVID-19 disease, and we found evidence of intestinal virus-specific IgA responses associated with more severe disease. We provide evidence for an ongoing humeral immune response to SARS-CoV-2 in the gastrointestinal tract, but little evidence of overt inflammation.

Article activity feed

  1. Version published to 10.1038/s41598-021-92740-9
  2. ScreenIT

    SciScore for 10.1101/2020.09.03.20183947: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The study was reviewed and approved by the institutional review board at our medical center (Protocol #: HS# 16-00512/ GCO# 16-0583).
    Consent: We enrolled patients who were able to give informed consent and were able to provide a stool sample.
    Randomizationnot detected.
    BlindingInformation regarding subject’s participation on double blinded clinical trials was recorded.
    Power Analysisnot detected.
    Sex as a biological variableThe mean (SD) age in the control group was 52.1 (11.3) compared to 55.9 (15.1) of the COVID-19 cohort (p=0.3, t-test) and 9 healthy donors were male (40.9%) compared with 47.7% of the COVID-19 cohort.

    Table 2: Resources

    Antibodies
    SentencesResources
    Laboratory data were also collected via chart review, we included results for: SARS-CoV-2 nasal PCR, SARS-CoV-2 antibodies, peripheral WBC and lymphocyte percentage, Aspartate Aminotransferase (AST)
    SARS-CoV-2
    suggested: None
    Software and Algorithms
    SentencesResources
    Amplicon Sequence Variants (ASVs) were classified using the Scikit-Learn plugin [50] using the Naive Bayes classifiers trained on the silva-132-99-515-806-nb-classifier.
    Scikit-Learn
    suggested: (scikit-learn, RRID:SCR_002577)
    Reads were trimmed with Trimmomatic [52] and taxonomic assignments were generated with MetaPhlAn2[53].
    Trimmomatic
    suggested: (Trimmomatic, RRID:SCR_011848)
    MetaPhlAn2
    suggested: None
    Data is deposited to NCBI under BioProject PRJNA660883.
    BioProject
    suggested: (NCBI BioProject, RRID:SCR_004801)

    Results from OddPub: Thank you for sharing your data.

    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.

    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 10.1101/2020.09.03.20183947v2 on medRxiv
  4. Version published to 10.1101/2020.09.03.20183947v1 on medRxiv