Single cell RNA sequencing of blood antigen-presenting cells in severe Covid-19 reveals multi-process defects in antiviral immunity
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Abstract
COVID-19 can lead to life-threatening acute respiratory failure, characterized by simultaneous increase in inflammatory mediators and viral load. The underlying cellular and molecular mechanisms remain unclear. We performed single-cell RNA-sequencing to establish an exhaustive high-resolution map of blood antigen-presenting cells (APC) in 7 COVID-19 patients with moderate or severe pneumonia, at day-1 and day-4 post-admission, and two healthy donors. We generated a unique dataset of 31,513 high quality APC, including monocytes and rare dendritic cell (DC) subsets. We uncovered multiprocess and previously unrecognized defects in anti-viral immune defense in specific APC compartments from severe patients: i) increase of pro-apoptotic genes exclusively in pDC, which are key effectors of antiviral immunity, ii) sharp decrease of innate sensing receptors, TLR7 and DHX9, in pDC and cDC1, respectively, iii) down-regulation of antiviral effector molecules, including Interferon stimulated genes (ISG) in all monocyte subsets, and iv) decrease of MHC class II-related genes, and MHC class II transactivator (CIITA) activity in cDC2, suggesting a viral inhibition of antigen presentation. These novel mechanisms may explain patient aggravation and suggest strategies to restore defective immune defense.
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SciScore for 10.1101/2020.07.20.212837: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The study was approved by the appropriate institutional review board and independent ethics committee (CPP #2018-A01934-51).
Consent: Informed consent was obtained from patients or next-of-kin.Randomization For each cell-type signature, enrichment scores were computed using “AddModuleScore()” function per cell with 100 randomly selected control genes, split on 25 bins. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources The signature construction relied on a thorough mining of existence literature, using a combination of MeSH terms and keywords on the PubMed search … SciScore for 10.1101/2020.07.20.212837: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The study was approved by the appropriate institutional review board and independent ethics committee (CPP #2018-A01934-51).
Consent: Informed consent was obtained from patients or next-of-kin.Randomization For each cell-type signature, enrichment scores were computed using “AddModuleScore()” function per cell with 100 randomly selected control genes, split on 25 bins. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources The signature construction relied on a thorough mining of existence literature, using a combination of MeSH terms and keywords on the PubMed search tool. MeSHsuggested: (MeSH, RRID:SCR_004750)PubMedsuggested: (PubMed, RRID:SCR_004846)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: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04386252 Not yet recruiting Phase I-II Trial of Dendritic Cell Vaccine to Prevent COVID-… 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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