Multi-omics Characterization of Neutrophil Extracellular Trap Formation in Severe and Mild COVID-19 Infections
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Abstract
The detailed mechanisms of COVID-19 infection pathology remain poorly understood. To improve our understanding of SARS-CoV-2 pathology, we performed a multi-omics analysis of an immunologically naïve SARS-CoV-2 clinical cohort from the plasma of uninfected controls, mild, and severe infections. A comparison of healthy controls and patient samples showed activation of neutrophil degranulation pathways and formation of neutrophil extracellular trap (NET) complexes that were activated in a subset of the mild infections and more prevalent in severe infections (containing multiple NET proteins in individual patient samples). As a potential mechanism to suppress NET formation, multiple redox enzymes were elevated in the mild and severe symptom population. Analysis of metabolites from the same cohort showed a 24- and 60-fold elevation in plasma L-cystine, the oxidized form of cysteine, which is a substrate of the powerful antioxidant glutathione, in mild and severe patients, respectively. Unique to patients with mild infections, the carnosine dipeptidase modifying enzyme (CNDP1) was up-regulated. The strong protein and metabolite oxidation signatures suggest multiple compensatory pathways working to suppress oxidation and NET formation in SARS-CoV-2 infections.
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SciScore for 10.1101/2022.04.26.22274196: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Experimental Model and Subject Details: Study design and participation were approved by the University of Wisconsin Health Sciences review board under IRB protocol # 2015-0802-CR006.
Consent: Consent was obtained for all participants prior to enrolment.Sex as a biological variable not detected. Randomization Briefly, plasma samples were prepared and batched in a random order placing National Institute of Standards and Technology (NIST) Standard Reference Material (SRM) for Human Plasma (SRM 1950) (NIST Office of Reference Materials, Gaithersburg, MD) aliquots at the beginning and end of each batch (58). Blinding not detected. Power Analysis not detected. Table 2: Resources
… SciScore for 10.1101/2022.04.26.22274196: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Experimental Model and Subject Details: Study design and participation were approved by the University of Wisconsin Health Sciences review board under IRB protocol # 2015-0802-CR006.
Consent: Consent was obtained for all participants prior to enrolment.Sex as a biological variable not detected. Randomization Briefly, plasma samples were prepared and batched in a random order placing National Institute of Standards and Technology (NIST) Standard Reference Material (SRM) for Human Plasma (SRM 1950) (NIST Office of Reference Materials, Gaithersburg, MD) aliquots at the beginning and end of each batch (58). Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources Data and Code Availability: All mass spectrometry datasets generated during this study have been deposited at the Mass Spectrometry Interactive Virtual Environment (MassIVE) under code XXXX. MassIVEsuggested: NoneProtein identifications were made by searching the SwissProt version of Uniprot Human Database (Release November 2019) using MS-GF+ combined to mzRefinery to recalibrate the mass spectra (69). MS-GF+suggested: (MS-GF+, RRID:SCR_015646)All visualizations were generated using the ggplot2 (78) and trelliscopejs R packages. ggplot2suggested: NoneResults 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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