COVID-19 patients upregulate toll-like receptor 4-mediated inflammatory signaling that mimics bacterial sepsis
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Abstract
Observational studies of the ongoing coronavirus disease 2019 (COVID-19) outbreak suggest that a cytokine storm is involved in the pathogenesis of severe illness. However, the molecular mechanisms underlying the altered pathological inflammation in COVID-19 are largely unknown. We report here that toll-like receptor (TLR) 4-mediated inflammatory signaling molecules are upregulated in peripheral blood mononuclear cells (PBMCs) from COVID-19 patients, compared with healthy controls. Among the most highly increased inflammatory mediators in severe/critically ill patients, S100A9, an alarmin and TLR4 ligand, was found as a noteworthy biomarker, because it inversely correlated with the serum albumin levels. These data support a link between TLR4 signaling and pathological inflammation during COVID-19 and contribute to develop therapeutic approaches through targeting TLR4-mediated inflammation.
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SciScore for 10.1101/2020.07.17.207878: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: Twenty-eight COVID-19 patients (8 SEVERE versus 20 MILD) admitted to Chungnam National University Hospital, and age/sex-matched 20 healthy controls, giving specific informed consent were included in the study.
IRB: Ethics statement: This study was approved by the Institutional Research and Ethics Committee at Chungnam National University HospitalRandomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Differentially expressed immune genes (DEiGs) among HC, SEVERE and MILD patients, were satisfied false discovery rate (FDR) < 0.05 which is … SciScore for 10.1101/2020.07.17.207878: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: Twenty-eight COVID-19 patients (8 SEVERE versus 20 MILD) admitted to Chungnam National University Hospital, and age/sex-matched 20 healthy controls, giving specific informed consent were included in the study.
IRB: Ethics statement: This study was approved by the Institutional Research and Ethics Committee at Chungnam National University HospitalRandomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Differentially expressed immune genes (DEiGs) among HC, SEVERE and MILD patients, were satisfied false discovery rate (FDR) < 0.05 which is analyzed and corrected by wilcox.test and p.adjust functions, respectively, implemented in stat package of R (v. 3.6.2). MILDsuggested: (MILD, RRID:SCR_003335)The KEGG pathway enrichment analysis was performed using DAVID (version 6.8, https://david.ncifcrf.gov) with a human reference gene set. KEGGsuggested: (KEGG, RRID:SCR_012773)DAVIDsuggested: (DAVID, RRID:SCR_001881)To identify chemokine, interleukin, TNF, interferon and those receptor gene families, we downloaded gene family annotations from HUGO Gene Nomenclature Committee (https://www.genenames.org) (38). https://www.genenames.orgsuggested: (HGNC, RRID:SCR_002827)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.
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