Activin A correlates with the worst outcomes in COVID-19 patients, and can be induced by cytokines via the IKK/NF-kappa B pathway
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Abstract
A fraction of COVID-19 patients develop the most severe form, characterized by Acute Respiratory Disease Syndrome (ARDS). The molecular mechanisms causing COVID-19-induced ARDS have yet to be defined, though many studies have documented an increase in cytokines known as a “cytokine storm.” Here, we demonstrate that cytokines that activate the NF-kappaB pathway can induce Activin A and its downstream marker, FLRG. In hospitalized COVID-19 patients elevated Activin A/FLRG at baseline were predictive of the most severe longitudinal outcomes of COVID-19, including the need for mechanical ventilation, lack of clinical improvement and all-cause mortality. Patients with Activin A/FLRG above the sample median were 2.6/2.9 times more likely to die, relative to patients with levels below the sample median, respectively. The study indicates high levels of Activin A and FLRG put patients at risk of ARDS, and blockade of Activin A may be beneficial in treating COVID-19 patients experiencing ARDS.
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SciScore for 10.1101/2021.02.04.429815: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: COVID-19 Samples and informed consent: Samples were collected from subjects who consented to participate in an adaptive, phase 2/3, randomized, double-blind, placebo-controlled trial of intravenous (IV) sarilumab in adults hospitalized with severe or critical COVID-19.
IRB: The local institutional review board or ethics committee at each study center oversaw trial conduct and documentation.Randomization COVID-19 Samples and informed consent: Samples were collected from subjects who consented to participate in an adaptive, phase 2/3, randomized, double-blind, placebo-controlled trial of intravenous (IV) sarilumab in adults hospitalized with severe or … SciScore for 10.1101/2021.02.04.429815: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: COVID-19 Samples and informed consent: Samples were collected from subjects who consented to participate in an adaptive, phase 2/3, randomized, double-blind, placebo-controlled trial of intravenous (IV) sarilumab in adults hospitalized with severe or critical COVID-19.
IRB: The local institutional review board or ethics committee at each study center oversaw trial conduct and documentation.Randomization COVID-19 Samples and informed consent: Samples were collected from subjects who consented to participate in an adaptive, phase 2/3, randomized, double-blind, placebo-controlled trial of intravenous (IV) sarilumab in adults hospitalized with severe or critical COVID-19. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
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 NCT04315298 Completed Evaluation of the Efficacy and Safety of Sarilumab in Hospit… 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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