Decidual immune response following COVID-19 during pregnancy varies by timing of maternal SARS-CoV-2 infection

  1. Lillian J. Juttukonda
  2. Elisha M. Wachman
  3. Jeffery Boateng
  4. Mayuri Jain
  5. Yoel Benarroch
  6. Elizabeth S. Taglauer

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Abstract

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  1. Version published to 10.1016/j.jri.2022.103501
  2. ScreenIT

    SciScore for 10.1101/2021.11.20.469369: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: All patient enrollment and tissue collection was approved by the Boston University Medical Campus Institutional Review Board.
    Consent: For this cohort, informed consent was waived, and samples were accompanied by limited demographic data available from chart review.
    Sex as a biological variablecohort (April-May 2020) involved tissue collection from placentas designated for pathology analysis either from women who tested positive via SARS-CoV-2 nasopharyngeal PCR testing at the time of delivery or from contemporary controls who tested negative.
    RandomizationDecidua basalis areas were manually surveyed at 100× followed by automated acquisition at 200× of 4 tiled images from 5 randomized areas per slide.
    BlindingAll ImageJ analysis and calculations were performed on blinded samples.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Primary antibodies were diluted 1:100 in PBS-T as follows: single labeling: CD14 (mouse anti-human, 14-149-82, Invitrogen), CD56 (mouse anti-human, 14-0567-82, Invitrogen); double labeling: SARS CoV-2 spike glycoprotein (rabbit anti-human, ab272504 Abcam), CD3 (mouse anti-human, 14-0038-82, Invitrogen)
    CD14
    suggested: (BioLegend Cat# 348805, RRID:AB_2889063)
    anti-human , 14-149-82 , Invitrogen) , CD56
    suggested: None
    anti-human ,
    suggested: None
    anti-human , ab272504 Abcam) , CD3
    suggested: None
    anti-human , 14-0038-82 , Invitrogen
    suggested: None
    Fluorescently labeled secondary antibodies were diluted 1:500 in PBS-T as follows: single labeling: Alexa 594 (anti-mouse, ab150108 Abcam); double labeling: AlexaFluor 594 (anti-mouse, ab150108 Abcam)
    anti-mouse
    suggested: (Abcam Cat# ab150108, RRID:AB_2732073)
    anti-mouse ,
    suggested: None
    Software and Algorithms
    SentencesResources
    Data collection: Demographic and clinical variables (as summarized in Tables 1 and 2) were obtained from the electronic medical record (EMR) and recorded in a secure, de-identified RedCap Database (https://www.project-redcap.org).
    RedCap
    suggested: (REDCap, RRID:SCR_003445)
    Quantitative Image Analysis: Image area and integrated density were measured via ImageJ software (imagej.net) for each immunofluorescent 200× image (n=5/slide) along with mean fluorescence values from 5 randomly selected background readings per image cohort were used to calculate a corrected total cell fluorescence (CTCF) per published protocols (Taglauer et al., 2020; Benarroch et al., 2021; Kenan et al., 2020).
    ImageJ
    suggested: (ImageJ, RRID:SCR_003070)
    Analyses were conducted using R version 3.6.1 (https://www.r-project.org).
    https://www.r-project.org
    suggested: (R Project for Statistical Computing, RRID:SCR_001905)
    All laboratory statistical analysis was performed using Prism 9 software (GraphPad).
    GraphPad
    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:
    The current study has several limitations. First, we only had access to basic clinical demographic data from the retrospective cohort, and it is possible that the women had severe COVID-19 disease as these tissues were collected during the first-wave of COVID-19, limiting the generalizability of these results. Importantly, the findings of increased macrophages and NK cells were replicated in our third-trimester group in the prospective, fully-consented cohort study with contemporary controls. A limitation in the prospective cohort study is the small sample size collected from a single clinical site. Taken as a whole, these results demonstrate that immune cell infiltrates in the placenta following COVID-19 are driven by timing of infection during gestation. While additional studies are required to more fully evaluate the immune profile in pregnancies affected by maternal COVID-19, these data provide early evidence supporting the role of decidual leukocytes in the physiologic response against SARS-CoV-2 at the maternal-fetal interface.

    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: Please consider improving the rainbow (“jet”) colormap(s) used on page 21. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.

    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.

  3. Version published to 10.1101/2021.11.20.469369 on bioRxiv