Plasmin cascade mediates thrombolytic events in SARS-CoV-2 infection via complement and platelet-activating systems
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Abstract
Recently emerged beta-coronavirus, SARS-CoV-2 has resulted in the current pandemic designated COVID-19. COVID-19 manifests as severe illness exhibiting systemic inflammatory response syndrome, acute respiratory distress syndrome (ARDS), thrombotic events, and shock, exacerbated further by co-morbidities and age 1–3 . Recent clinical reports suggested that the pulmonary failure seen in COVID-19 may not be solely driven by acute ARDS, but also microvascular thrombotic events, likely driven by complement activation 4,5 . However, it is not fully understood how the SARS-CoV-2 infection mechanisms mediate thrombotic events, and whether such mechanisms and responses are unique to SARS-CoV-2 infection, compared to other respiratory infections. We address these questions here, in the context of normal lung epithelia, in vitro and in vivo , using publicly available data. Our results indicate that plasmin is a crucial mediator which primes interactions between complement and platelet-activating systems in lung epithelia upon SARS-CoV-2 infection, with a potential for therapeutic intervention.
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SciScore for 10.1101/2020.05.28.120162: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources The published dataset contained multiple cell lines treated with SARS-CoV-2 including NHBE, Calu-3, A529 (with and without exogenous expression of ACE2) in addition to COVID-19 lung and normal tissue samples (available via GSE147507). Calu-3suggested: NoneWe, however, did not find studies on related beta-coronaviruses in NHBE/BEAS-2B cell lines which matched our inclusion criterion. NHBE/BEAS-2Bsuggested: NoneSoftware and Algorithms Sente… SciScore for 10.1101/2020.05.28.120162: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources The published dataset contained multiple cell lines treated with SARS-CoV-2 including NHBE, Calu-3, A529 (with and without exogenous expression of ACE2) in addition to COVID-19 lung and normal tissue samples (available via GSE147507). Calu-3suggested: NoneWe, however, did not find studies on related beta-coronaviruses in NHBE/BEAS-2B cell lines which matched our inclusion criterion. NHBE/BEAS-2Bsuggested: NoneSoftware and Algorithms Sentences Resources We utilized the same pipeline implemented in GEO2R to call DEGs from CoV-2 data (using the limma-voom pipeline in R). GEO2Rsuggested: (GEO2R, RRID:SCR_016569)Low counts were filtered using the “FilterByExpression” feature available through the edgeR package. edgeRsuggested: (edgeR, RRID:SCR_012802)We would additionally like to point out that we reanalyzed the CoV-2 data using the DESeq2 protocol as described in the original publication consistently identified similar number of DEGs as detected through limma-voom. DESeq2suggested: (DESeq, RRID:SCR_000154)All visualizations were generated via the ClusterProfiler library58 available through R/Bioconductor. ClusterProfilersuggested: (clusterProfiler, RRID:SCR_016884)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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