Metabolic stress and disease-stage specific basigin expression of peripheral blood immune cell subsets in COVID-19 patients
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Abstract
Coronavirus disease 2019 (COVID-19) is driven by dysregulated immune responses yet the role of immunometabolism in COVID-19 pathogenesis remains unclear. By investigating 47 patients with confirmed SARS-CoV-2 infection and 16 uninfected controls, we found an immunometabolic dysregulation specific for patients with progressed disease that was reversible in the recovery phase. Specifically, T cells and monocytes exhibited increased mitochondrial mass, accumulated intracellular ROS and these changes were accompanied by disrupted mitochondrial architecture. Basigin (CD147), but not established markers of T cell activation, was up-regulated on T cells from progressed COVID-19 patients and correlated with ROS accumulation, reflected in the transcriptome. During recovery, basigin and ROS decreased to match the uninfected controls. In vitro analyses confirmed the correlation and showed a down-regulation of ROS by dexamethasone treatment. Our findings provide evidence of a basigin-related and reversible immunometabolic dysregulation in COVID-19.
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SciScore for 10.1101/2020.09.18.20194175: (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 (University Hospital Regensburg, No. 20-1785-101) and conformed to the principles outlined in the Declaration of Helsinki. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Controls were asymptomatic healthy individuals with age median of 46.7 (IQR 37.25-46.7) and male sex in 47%. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Antibody response was defined by presence of SARS-CoV-2 specific IgG antibodies in serum. SARS-CoV-2 specific IgGsuggested: NoneCells were stained with surface antibodies as … SciScore for 10.1101/2020.09.18.20194175: (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 (University Hospital Regensburg, No. 20-1785-101) and conformed to the principles outlined in the Declaration of Helsinki. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Controls were asymptomatic healthy individuals with age median of 46.7 (IQR 37.25-46.7) and male sex in 47%. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Antibody response was defined by presence of SARS-CoV-2 specific IgG antibodies in serum. SARS-CoV-2 specific IgGsuggested: NoneCells were stained with surface antibodies as described above and incubated in with 2-NBDG (45 min) or BODIPY 500/510 C1, C12 (20 min). C12suggested: NoneExperimental Models: Cell Lines Sentences Resources SARS-CoV-2 infection of A549 cells was performed and published by Blanco-Melo et al (Blanco-Melo et al., 2020). A549suggested: NoneSoftware and Algorithms Sentences Resources Tables of raw uniquely mapped read counts per human gene were generated during mapping using the built-in --quantMode GeneCounts option in STAR. STARsuggested: (STAR, RRID:SCR_015899)Differential expression analysis was carried out on raw gene counts using edgeR 3.20.8 (Robinson et al., 2009) in R (3.4.3). edgeRsuggested: (edgeR, RRID:SCR_012802)Volcano plots were generated using the ggplot2 (v3.1.0) package in R. ggplot2suggested: (ggplot2, RRID:SCR_014601)The rank-based gene set enrichment tests in Figure 5 were done using the fry function of the limma package (Ritchie et al., 2015) and plotted using the barcodeplot function in R. limmasuggested: (LIMMA, RRID:SCR_010943)Gene-sets were defined in the hallmark gene set collection (Liberzon et al., 2015) and basigin interaction partners were defined by STRING (Szklarczyk et al., 2019). STRINGsuggested: (STRING, RRID:SCR_005223)Statistics: GraphPad Prism was used for statistical analyses, using ANOVA with post-hoc Bonferroni test and Mann-Whitney U test. GraphPadsuggested: (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: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04275245 Recruiting Clinical Study of Anti-CD147 Humanized Meplazumab for Inject… Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on page 26. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.
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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