No SARS-CoV-2 Neutralization by Intravenous Immunoglobulins Produced From Plasma Collected Before the 2020 Pandemic

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Abstract

The 2020 SARS-CoV-2 pandemic is caused by a zoonotic coronavirus transmitted to humans, similar to earlier events. Whether the other, seasonally circulating coronaviruses induce cross-reactive, potentially even cross-neutralizing, antibodies to the new species in humans is unclear. The question is particularly relevant for people with immune deficiencies, as their health depends on treatment with immunoglobulin preparations that need to contain neutralizing antibodies against the pathogens in their environment. Testing 54 intravenous immunoglobulin preparations, produced from plasma collected in Europe and the United States, confirmed highly potent neutralization of a seasonal coronavirus; however, no cross-neutralization of the new SARS-CoV-2 was seen.

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  1. SciScore for 10.1101/2020.07.30.228213: (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.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Detection of hCoV-229E neutralizing antibodies: The neutralization assay for hCoV-229E antibodies is essentially identical to the SARS-CoV-2, where samples were used undiluted or pre-diluted, then serially diluted in 2-fold steps and mixed 1:2 with 103.0 TCID50/mL hCoV-229E (ATCC, Cat. no. VR-740, Rockville, MD), incubated and titrated on MRC-5 cells (ATCC, Cat. no. CCL-171, Rockville, MD).
    hCoV-229E
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Equal volumes of sample dilutions were mixed with virus stock at 103.0 tissue culture infectious doses 50% per milliliter (TCID50/mL) SARS-CoV-2 (strain “BavPat1/2020”, kindly provided by C. Drosten and V. Corman, Charité Berlin, Germany) and incubated for 150min +/-15min, before titration on Vero cells (Cat. no. 84113001, ECACC, Porton Down, Salisbury, UK) in eight-fold replicates per dilution.
    Vero
    suggested: None
    Detection of hCoV-229E neutralizing antibodies: The neutralization assay for hCoV-229E antibodies is essentially identical to the SARS-CoV-2, where samples were used undiluted or pre-diluted, then serially diluted in 2-fold steps and mixed 1:2 with 103.0 TCID50/mL hCoV-229E (ATCC, Cat. no. VR-740, Rockville, MD), incubated and titrated on MRC-5 cells (ATCC, Cat. no. CCL-171, Rockville, MD).
    MRC-5
    suggested: None
    Software and Algorithms
    SentencesResources
    Human plasma pool samples were generated by combination of 6 individual donations obtained in the same calendar week (CW) at Austrian plasma donation centers (BioLife).
    BioLife
    suggested: None
    Graphs and statistical analysis: Graphical illustration and statistical analysis (paired t-tests) were done using GraphPad Prism v8.1.1 software (San Diego, CA).
    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: 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.

  2. SciScore for 10.1101/2020.07.30.228213: (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.Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Keywords Primary immunodeficiency; SARS-CoV-2; SARS coronavirus 2 antibody titer; neutralizing antibodies; COVID-19; intravenous immunoglobulin; plasma No SARS-CoV-2 neutralization by IVIGs SARS-COV-2 antibodies are presented.
    SARS coronavirus 2
    suggested: None
    Detection of hCoV-229E neutralizing antibodies The neutralization assay for hCoV-229E antibodies is essentially identical to the SARS-CoV-2 where samples were used undiluted or pre-diluted, then serially diluted in 2-fold steps and mixe 1:2 with 103.0 TCID50/mL hCoV-229E (ATCC, Cat. no. VR-740, Rockville, MD), incubated an titrated on MRC-5 cells (ATCC, Cat. no. CCL-171, Rockville, MD).
    hCoV-229E
    suggested: (Abcam Cat# ab28169, AB_777848)
    Thus, a higher infectio rate with hCoV-229E in elder people and consequently the generation of neutralizing hCoV- 229E-specific antibodies in the elder plasma donors would explain the higher hCoV-229E titers found in IVIG lots produced from recovered plasma.
    229E-specific
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Detection of hCoV-229E neutralizing antibodies The neutralization assay for hCoV-229E antibodies is essentially identical to the SARS-CoV-2 where samples were used undiluted or pre-diluted, then serially diluted in 2-fold steps and mixe 1:2 with 103.0 TCID50/mL hCoV-229E (ATCC, Cat. no. VR-740, Rockville, MD), incubated an titrated on MRC-5 cells (ATCC, Cat. no. CCL-171, Rockville, MD).
    MRC-5
    suggested: None
    Software and Algorithms
    SentencesResources
    Human plasma pool samples were generated by combination of 6 individual donations obtained in the same calendar week (CW) at Austrian plasma donation centers (BioLife).
    BioLife
    suggested: None
    Graphs and statistical analysis Graphical illustration and statistical analysis (paired t-tests) were done using GraphPad Prism v8.1.1 software (San Diego, CA).
    GraphPad Prism
    suggested: (GraphPad Prism, SCR_002798)

    Data from additional tools added to each annotation on a weekly basis.

    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 is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.