Impaired function and delayed regeneration of dendritic cells in COVID-19
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Abstract
Disease manifestations in COVID-19 range from mild to severe illness associated with a dysregulated innate immune response. Alterations in function and regeneration of dendritic cells (DC) and monocytes may contribute to immunopathology and influence adaptive immune responses in COVID-19 patients. We analyzed circulating DC and monocyte subsets in 65 hospitalized COVID-19 patients with mild/moderate or severe disease from acute disease to recovery and in healthy controls. Persisting reduction of all DC subpopulations was accompanied by an expansion of proliferating Lineage - HLADR + cells lacking DC markers. Increased frequency of the recently discovered CD163 + CD14 + DC3 subpopulation in patients with more severe disease was associated with systemic inflammation, activated T follicular helper cells, and antibody-secreting cells. Persistent downregulation of CD86 and upregulation of PD-L1 in conventional DC (cDC2 and DC3) and classical monocytes associated with a reduced capacity to stimulate naïve CD4 + T cells correlated with disease severity. Long-lasting depletion and functional impairment of DCs and monocytes may have consequences for susceptibility to secondary infections and therapy of COVID-19 patients.
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SciScore for 10.1101/2021.05.26.445809: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: Written informed consent was received from participants prior to inclusion in the study and patient data were anonymized for analysis.
IRB: The study was approved by the local ethics committee (No. 20-245).Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources T cells were stained with Cell Trace Violet dye (ThermoFisher, cat. #C34557) washed twice with RPMI 1640 (10% FCS) and cocultured with DC3 or monocytes (APC:T 1:2 ratio) in 150 µl of RPMI 1640 (Biochrom, 10% FCS, 100 U/ml penicillin, 100 μg/ml streptomycin, 1% non-essential amino acids, 1 mM sodium pyruvate, 2 mM GlutaMAX™, … SciScore for 10.1101/2021.05.26.445809: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: Written informed consent was received from participants prior to inclusion in the study and patient data were anonymized for analysis.
IRB: The study was approved by the local ethics committee (No. 20-245).Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources T cells were stained with Cell Trace Violet dye (ThermoFisher, cat. #C34557) washed twice with RPMI 1640 (10% FCS) and cocultured with DC3 or monocytes (APC:T 1:2 ratio) in 150 µl of RPMI 1640 (Biochrom, 10% FCS, 100 U/ml penicillin, 100 μg/ml streptomycin, 1% non-essential amino acids, 1 mM sodium pyruvate, 2 mM GlutaMAX™, 0.05 mM β-mercaptoethanol) on a 96-well flat bottom plate coated with anti-CD3 antibody (10µg/ml, cat. # 317325, BioLegend). DC3suggested: (Novus Cat# NB 100-2694, RRID:AB_608325)anti-CD3suggested: NoneAnti-SARS-CoV-2 antibody detection assays: The following commercial CE in vitro diagnostics (IVD) marked assays were used to determine the presence of SARS-CoV-2-specific antibodies in serum specimens: Architect SARS-CoV-2 IgG (6R86, Abbott, Illinois, USA) detecting anti-nucleocapsid antibodies and Anti-SARS-CoV-2-ELISA IgG (EI 2606-9601 G, EuroImmun, Lübeck, Germany Anti-SARS-CoV-2suggested: (PhosphoSolutions Cat# CoV2-2G1, RRID:AB_2868397)anti-nucleocapsidsuggested: NoneAnti-SARS-CoV-2-ELISA IgGsuggested: NoneSoftware and Algorithms Sentences Resources FCS files were exported and analyzed with FlowJo software v10.7.1. FlowJosuggested: (FlowJo, RRID:SCR_008520)FlowJo workspace was imported with flowWorkspace::open_flowjo_xml (flowWorkspace version 4.2.0). flowWorkspacesuggested: (flowWorkspace, RRID:SCR_001155)Anti-SARS-CoV-2 antibody detection assays: The following commercial CE in vitro diagnostics (IVD) marked assays were used to determine the presence of SARS-CoV-2-specific antibodies in serum specimens: Architect SARS-CoV-2 IgG (6R86, Abbott, Illinois, USA) detecting anti-nucleocapsid antibodies and Anti-SARS-CoV-2-ELISA IgG (EI 2606-9601 G, EuroImmun, Lübeck, Germany Abbottsuggested: (Abbott, RRID:SCR_010477)Statistical analysis: Statistical analysis was performed using GraphPad Prism 9.1.0 and R 4.0.3 (packages used: ggplot2_3.3.3, ComplexHeatmap_2.4.3, ggstatsplot_0.6.8, bestNormalize_1.7.0, robustbase_0.93.7) GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)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: 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.
Results from scite Reference Check: We found no unreliable references.
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