Rapid synchronous type 1 IFN and virus-specific T cell responses characterize first wave non-severe SARS-CoV-2 infections
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SciScore for 10.1101/2021.03.30.21254540: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
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Software and Algorithms Sentences Resources RNAseq data were mapped to the reference transcriptome (Ensembl Human GRCh38 release 100) using Kallisto.28 The transcript-level output counts and transcripts per million (TPM) values were summed on gene level and annotated with Ensembl gene ID, gene name, and gene biotype using the R/Bioconductor packages tximport and BioMart.29,30 Blood RNA sequencing data analysis: Sample processing batch effects were evaluated by principle component analysis at genome wide level (Supplementary Figure 2a) and among the intersect of the 10% genes with least variable expression in each sample … SciScore for 10.1101/2021.03.30.21254540: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources RNAseq data were mapped to the reference transcriptome (Ensembl Human GRCh38 release 100) using Kallisto.28 The transcript-level output counts and transcripts per million (TPM) values were summed on gene level and annotated with Ensembl gene ID, gene name, and gene biotype using the R/Bioconductor packages tximport and BioMart.29,30 Blood RNA sequencing data analysis: Sample processing batch effects were evaluated by principle component analysis at genome wide level (Supplementary Figure 2a) and among the intersect of the 10% genes with least variable expression in each sample processing batch (Supplementary Figure 2b). Ensemblsuggested: (Ensembl, RRID:SCR_002344)R/Bioconductorsuggested: NoneA batch effect evident in the least variant gene expression analysis was corrected using the ComBat function in the sva package in R, allocating samples with PC2 score <0 and >0 (in Supplementary Figure 2b) to separate batches31. ComBatsuggested: (ComBat, RRID:SCR_010974)Analysis of upstream transcriptional regulation of the differentially expressed genes was performed using Ingenuity Pathway Analysis (Qiagen, Venlo, The Netherlands) and visualised as network diagram using the Force Atlas 2 algorithm in Gephi v0.9.233. Ingenuity Pathway Analysissuggested: (Ingenuity Pathway Analysis, RRID:SCR_008653)Gephisuggested: (Gephi, RRID:SCR_004293)Samples were acquired in PBS on LSR II flow cytometer (BD biosciences) and were analyzed using FlowJo (version 10.7.1 for mac, Tree Star). FlowJosuggested: (FlowJo, RRID:SCR_008520)Full details for both the experimental TCRseq library preparation and the subsequent TCR annotation (V, J and CDR3 annotation) using Decombinator V4 have been described previously40–42 The Decombinator software is freely available at https://github.com/innate2adaptive/Decombinator. Decombinatorsuggested: (Decombinator, RRID:SCR_006732)Results from OddPub: Thank you for sharing your code and data.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Our study has some important limitations. The precise time of exposure to SARS-CoV-2 or transmission of infection was not possible to determine. This was offset by including longitudinal samples in 12 subjects before detection of incident infection by PCR, providing enough statistical power to show that both type 1 IFN and cell proliferation responses were statistically enriched in the week before the first positive PCR result. We had limited access to PBMC to assess frequency, phenotypic and functional characteristics of SARS-CoV-2 reactive T cells. The accumulating database of SARS-CoV-2 specific TCR sequences allowed us to relate clonal T cell expansion with antigen-specificity. This only accounted for an extremely small fraction of expanded sequences and does not exclude proliferation of bystander T cells. However, substantially lower levels of enrichment of CMV or EBV specific TCRs among expanded clones, and the lack of enrichment for IFNγ activity or other signatures of T cell activation in the blood transcriptome argue against generalised bystander T cell activation. Future re-analysis of the data (as more sequences across a wider range of HLA haplotypes are reported) will be necessary to evaluate whether the majority of expanded TCRs are ultimately found to recognise SARS-CoV-2. The focus on the blood compartment meant that we do not have direct measurements of responses at the site of host-pathogen interactions. Analysis of bulk RNA samples for transcriptional profil...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04318314 Recruiting COVID-19: Healthcare Worker Bioresource: Immune Protection a… 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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