SARS-CoV-2 viremia is associated with distinct proteomic pathways and predicts COVID-19 outcomes

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Abstract

No abstract available

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  1. SciScore for 10.1101/2021.02.24.21252357: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Briefly, participants were enrolled in the Emergency Department (ED) from Massachusetts General Hospital, Boston MA, from 3/24/2020 to 4/30/2020 during the first peak of the COVID-19 surge, with an institutional IRB-approved waiver of informed consent.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    (Addgene plasmid #86677), and pTRIP-SFFV-Hygro-2ATMPRSS2 were described in our recent publication 15. 293T ACE2/TMPRESS2 cell line was generated as described in our recent publication 15
    ACE2/TMPRESS2
    suggested: None
    . 293T cells were seeded at 0.8 x 106 cells per well in a 6-well plate and were transfected the same day with a mix of DNA containing 1 μg psPAX, 1.6 μg pTRIP-SFFV-EGFP-NLS, and 0.4 μg pCMV-SARS2ΔC-gp41 using TransIT®-293 Transfection Reagent.
    293T
    suggested: None
    To transduce 293T ACE2 cells, the same protocol was followed, with a mix containing 1 μg psPAX, 1.6 μg pTRIPSFFV-Hygro-2A-TMPRSS2, and 0.4 μg pCMV-VSV-G.
    ACE2
    suggested: RRID:CVCL_DR94)
    Medium was then removed from 293T ACE2/TMPRSS2 cells and replaced with 150 μl of the mix of plasma and pseudotyped lentivirus.
    ACE2/TMPRSS2
    suggested: None
    Software and Algorithms
    SentencesResources
    Percentage GFP was quantified on a Cytoflex LX (Beckman Coulter), and data was analyzed with FlowJo.
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Clinical data analyses, logistic regression and Cox proportion regression were performed on Stata (version 13.1) and figures were generated by Stata and GraphPad (Prism, version 9.0).
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Prism
    suggested: (PRISM, RRID:SCR_005375)

    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:
    Our study also has a few notable limitations. Although quite comprehensive, our proteomic database does not cover all the cytokines and proteins of interest in COVID-19 pathogenesis. We rely on a pre- existing proteomic database 17 and peripheral blood databases 26,28 to infer the origin of differentially expressed proteins, but do not have data on scRNA-Seq from this cohort to confirm the cellular source of some differentially expressed protein. Given the relatively high limits of detection of culture-based assays, we are unable to confirm whether the RNA detected in plasma samples are from viable, infective SARS-CoV-2 virions. In summary, we report the largest study to date that demonstrates SARS-CoV-2 viremia predicts severe COVID-19 disease outcomes and the likely role of systemic viral dissemination in mediating tissue damage, tissue fibrosis, hypercoagulable state, persistent elevation of proinflammatory markers, and higher viral entry factor expression. Our findings provide key insights into SARS-CoV-2 pathogenesis and identify potential therapeutic targets to mitigate COVID-19 disease severity. Methods Study participants Participant enrollment was described in our prior report 15. Briefly, participants were enrolled in the Emergency Department (ED) from Massachusetts General Hospital, Boston MA, from 3/24/2020 to 4/30/2020 during the first peak of the COVID-19 surge, with an institutional IRB-approved waiver of informed consent. Symptomatic participants of 18 years or...

    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.
    • Thank you for including a protocol registration statement.

    About SciScore

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