Single cell resolution of SARS-CoV-2 tropism, antiviral responses, and susceptibility to therapies in primary human airway epithelium
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Abstract
The human airway epithelium is the initial site of SARS-CoV-2 infection. We used flow cytometry and single cell RNA-sequencing to understand how the heterogeneity of this diverse cell population contributes to elements of viral tropism and pathogenesis, antiviral immunity, and treatment response to remdesivir. We found that, while a variety of epithelial cell types are susceptible to infection, ciliated cells are the predominant cell target of SARS-CoV-2. The host protease TMPRSS2 was required for infection of these cells. Importantly, remdesivir treatment effectively inhibited viral replication across cell types, and blunted hyperinflammatory responses. Induction of interferon responses within infected cells was rare and there was significant heterogeneity in the antiviral gene signatures, varying with the burden of infection in each cell. We also found that heavily infected secretory cells expressed abundant IL-6, a potential mediator of COVID-19 pathogenesis.
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SciScore for 10.1101/2020.10.19.343954: (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
Experimental Models: Organisms/Strains Sentences Resources Abs used include the following: CD66c (B6.2/CD66) (BD Biosciences); CD271 (ME20.4) (Biolegend); and TSPAN8 (458811) (Biotechne). B6.2/CD66suggested: NoneSoftware and Algorithms Sentences Resources Abs used include the following: CD66c (B6.2/CD66) (BD Biosciences); CD271 (ME20.4) (Biolegend); and TSPAN8 (458811) (Biotechne). BD Biosciences)suggested: NoneThe resulting raw count matrix for each experimental data set was imported into an R pipeline using Seurat 2.3.4 [40], where the filter criteria for empty droplets are minimum 1000 genes per cell, for genes that are presented in … SciScore for 10.1101/2020.10.19.343954: (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
Experimental Models: Organisms/Strains Sentences Resources Abs used include the following: CD66c (B6.2/CD66) (BD Biosciences); CD271 (ME20.4) (Biolegend); and TSPAN8 (458811) (Biotechne). B6.2/CD66suggested: NoneSoftware and Algorithms Sentences Resources Abs used include the following: CD66c (B6.2/CD66) (BD Biosciences); CD271 (ME20.4) (Biolegend); and TSPAN8 (458811) (Biotechne). BD Biosciences)suggested: NoneThe resulting raw count matrix for each experimental data set was imported into an R pipeline using Seurat 2.3.4 [40], where the filter criteria for empty droplets are minimum 1000 genes per cell, for genes that are presented in a minimum of three cells and for mitochondria genes percentage is no more than 30%. Seuratsuggested: (SEURAT, RRID:SCR_007322)Results from OddPub: Thank you for sharing your code and data.
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 found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
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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