Markers of Polyfunctional SARS-CoV-2 Antibodies in Convalescent Plasma
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Abstract
Convalescent plasma has been deployed globally as a treatment for COVID-19, but efficacy has been mixed. Better understanding of the antibody characteristics that may contribute to its antiviral effects is important for this intervention as well as offer insights into correlates of vaccine-mediated protection.
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SciScore for 10.1101/2020.09.16.20196154: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Human subject research was approved by both the Johns Hopkins University School of Medicine’s Institutional Review Board and the Dartmouth-Hitchcock Medical Center Committee for the Protection of Human Subjects.
Consent: All participants provided informed written consent.Randomization Upon log transformation, default UMAP parameters were used with the following exceptions: random_state = 45, min_dist = 1E-9, knn_repeats: -1, set_op_mix_ratio= 1. k-means was tested with a range of k = 1:15 to identify an optimal number of clusters as defined by a visual identification of an “elbow” in a plot of variance versus number of clusters. Blinding not detected. Power … SciScore for 10.1101/2020.09.16.20196154: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Human subject research was approved by both the Johns Hopkins University School of Medicine’s Institutional Review Board and the Dartmouth-Hitchcock Medical Center Committee for the Protection of Human Subjects.
Consent: All participants provided informed written consent.Randomization Upon log transformation, default UMAP parameters were used with the following exceptions: random_state = 45, min_dist = 1E-9, knn_repeats: -1, set_op_mix_ratio= 1. k-means was tested with a range of k = 1:15 to identify an optimal number of clusters as defined by a visual identification of an “elbow” in a plot of variance versus number of clusters. Blinding not detected. Power Analysis not detected. Sex as a biological variable The cohort was composed of 68 males (54.0%) and 58 females (46.0%). Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources VeroE6-TMPRSS2 cells were used to propagate the virus and to determined infectious virus titers using a 50% tissue culture infectious dose (TCID50) assay as previously described for SARS-CoV8,58 using Institutional Biosafety Committee approved protocols in Biosafety Level 3 containment. VeroE6-TMPRSS2suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)) covalently conjugated with recombinant RBD were incubated for 3 hrs with dilute plasma specimens and the human monocytic THP-1 cell line (ATCC, TIB-202). THP-1suggested: NoneSoftware and Algorithms Sentences Resources Data analysis and visualization: Basic analysis and visualization were performed using GraphPad Prism. GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Heatmaps, correlation plots, and boxplots were generated in R (supported by R packages pheatmap, corrplot, and ggplot2). ggplot2suggested: (ggplot2, RRID:SCR_014601)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 this study range from cohort composition to the experimental and analytical approaches employed. Individuals in the naïve control cohort were generally younger and sourced from a different geographic location, which may impact our observation of apparent boosting of responses toward endemic CoV. Additionally, the convalescent and naïve subjects enrolled in the DHMC cohort provided serum samples, whereas the convalescent subjects in the JHMI cohort contributed plasma, which could result in differences in antibody detection and functional activity. Nevertheless, the model trained on convalescent plasma samples was able to make accurate predictions on convalescent serum samples. Recombinant antigen and lab-adapted cell lines were employed for several of the functional assays, and the substitution of surrogate measurements such as FcγRIIIa activation was made in place of target cell death. Thus, in vitro function may differ substantially from the in vivo processes these assays are meant to mimic. Given high feature dimensionality and relatively fewer subjects, LASSO regularization was used to increase the quality of prediction. This approach simplified the resulting models and improved interpretability of the selected variables, but tends to eliminate features that are highly correlated to selected variables in the established model, which can result in a trade-off between model simplification and obscuring potential biological mechanisms. In summary, this study es...
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.
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