Hydroxychloroquine Inhibits the Trained Innate Immune Response to Interferons

Rother, Nils; Yanginlar, Cansu; Lindeboom, R.G.H.; Bekkering, Siroon; Leent, Mandy M. T. van; Buijsers, Baranca; Jonkman, Inge; Graaf, Mark de; Baltissen, Marijke P; Lamers, Lieke A.; Riksen, Niels P.; Fayad, Zahi A.; Mulder, Willem J. M.; Hilbrands, Luuk B.; Joosten, Leo A. B.; Netea, Mihai G.; Vermeulen, Michiel; Vlag, Johan van der; Duivenvoorden, Raphaël

doi:10.1016/j.xcrm.2020.100146

Cited by 27 publications

(25 citation statements)

References 64 publications

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“…Chloroquine, an antimalarial drug, was proposed as therapeutic agent for COVID-19 because they were observed to inhibit SARS-CoV-2 viral replication in vitro in primate cells [ 5 ]; however, a later study found that chloroquine did not inhibit infection of human lung cells with SARS-CoV-2 [ 34 ]. HCQ, a less toxic derivative of chloroquine, inhibits trained immunity in vitro in peripheral blood mononuclear cells, which may not be beneficial for the antiviral innate immune response to SARS-CoV-2 infection in patients [ 35 ]. Chloroquine also has been investigated in vitro as potential treatment for other viruses such as human immunodeficiency virus [ 36 ], human coronavirus OC43, enterovirus EV-A71, Zika virus, influenza A H5N1, hepatitis C virus and chikungunya virus [ 37 ]; however, these studies did not show beneficial effects.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Hydroxychloroquine for Hospitalized COVID-19 Patients: A Systematic Review and Meta-Analysis

Hernandez

Phan

Rocco

et al. 2021

JCM

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We systematically reviewed the efficacy and safety of hydroxychloroquine as treatment for hospitalized COVID-19. Randomized controlled trials (RCTs) evaluating hydroxychloroquine as treatment for hospitalized COVID-19 patients were searched until 2nd of December 2020. Primary outcomes were all-cause mortality, need of mechanical ventilation, need of non-invasive ventilation, ICU admission and oxygen support at 14 and 30 days. Secondary outcomes were clinical recovery and worsening, discharge, radiological progression of pneumonia, virologic clearance, serious adverse events (SAE) and adverse events. Inverse variance random effects meta-analyses were performed. Thirteen RCTs (n=18,540) were included. Hydroxychloroquine total doses ranged between 2000 and 12,400 mg; treatment durations were from 5 to 16 days and follow up times between 5 and 30 days. Compared to controls, hydroxychloroquine non-significantly increased mortality at 14 days (RR 1.07, 95%CI 0.92–1.25) or 30 days (RR 1.08, 95%CI 1.00–1.16). Hydroxychloroquine did not affect other primary or secondary outcomes, except SAEs that were significantly higher than the control (RR 1.24, 95%CI 1.05–1.46). Eleven RCTs had high or some concerns of bias. Subgroup analyses were consistent with main analyses. Hydroxychloroquine was not efficacious for treating hospitalized COVID-19 patients and caused more severe adverse events. Hydroxychloroquine should not be recommended as treatment for hospitalized COVID-19 patients.

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Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Hydroxychloroquine for Hospitalized COVID-19 Patients: A Systematic Review and Meta-Analysis

Hernandez

Phan

Rocco

et al. 2021

JCM

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“…The monocyte COVID-19 RNA-Seq data, published under the accession GSE159678 (Rother et al, 2020), was downloaded from SRA and gene expression was quantified using Salmon's selective alignment approach (Srivastava et al, 2020). The RNA-Seq processing pipeline was implemented using pyrpipe (Singh et al, 2021) (https://github.com/urmi-21/pyrpipe/tree/master/case_studies/ Covid_RNA-Seq).…”

Section: Star+methodsmentioning

confidence: 99%

Role of miR-2392 in driving SARS-CoV-2 infection

et al. 2021

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MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation that have a major impact on many diseases and provides an exciting avenue towards antiviral therapeutics. From patient transcriptomic data, we determined a circulating miRNA, miR-2392, is directly involved with SARS-CoV-2 machinery during host infection. Specifically, we show that miR-2392 is key in driving downstream suppression of mitochondrial gene expression, increasing inflammation, glycolysis, and hypoxia as well as promoting many symptoms associated with COVID-19 infection. We demonstrate miR-2392 is present in the blood and urine of patients positive for COVID-19, but not present in patients negative for COVID-19. These findings indicate the potential for developing a minimally invasive COVID-19 detection method. Lastly, using in vitro human and in vivo hamster models, we design a miRNA-based antiviral therapeutic that targets miR-2392, significantly reduces SARS-CoV-2 viability in hamsters and may potentially inhibit a COVID-19 disease state in humans.

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“…We used this pipeline to quantify RNA-Seq data from a COVID-19 study of circulating monocytes ( 28 ), and provide output that can be directly analyzed by biologists, using the versatile Java software for exploratory analysis of large datasets, MetaOmGraph (MOG).…”

Section: Resultsmentioning

confidence: 99%

`pyrpipe`: a Python package for RNA-Seq workflows

Singh

Seetharam

et al. 2021

NAR Genomics and Bioinformatics

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The availability of terabytes of RNA-Seq data and continuous emergence of new analysis tools, enable unprecedented biological insight. There is a pressing requirement for a framework that allows for fast, efficient, manageable, and reproducible RNA-Seq analysis. We have developed a Python package, (pyrpipe), that enables straightforward development of flexible, reproducible and easy-to-debug computational pipelines purely in Python, in an object-oriented manner. pyrpipe provides access to popular RNA-Seq tools, within Python, via high-level APIs. Pipelines can be customized by integrating new Python code, third-party programs, or Python libraries. Users can create checkpoints in the pipeline or integrate pyrpipe into a workflow management system, thus allowing execution on multiple computing environments, and enabling efficient resource management. pyrpipe produces detailed analysis, and benchmark reports which can be shared or included in publications. pyrpipe is implemented in Python and is compatible with Python versions 3.6 and higher. To illustrate the rich functionality of pyrpipe, we provide case studies using RNA-Seq data from GTEx, SARS-CoV-2-infected human cells, and Zea mays. All source code is freely available at https://github.com/urmi-21/pyrpipe; the package can be installed from the source, from PyPI (https://pypi.org/project/pyrpipe), or from bioconda (https://anaconda.org/bioconda/pyrpipe). Documentation is available at (http://pyrpipe.rtfd.io).

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Hydroxychloroquine Inhibits the Trained Innate Immune Response to Interferons

Cited by 27 publications

References 64 publications

Efficacy and Safety of Hydroxychloroquine for Hospitalized COVID-19 Patients: A Systematic Review and Meta-Analysis

Efficacy and Safety of Hydroxychloroquine for Hospitalized COVID-19 Patients: A Systematic Review and Meta-Analysis

Role of miR-2392 in driving SARS-CoV-2 infection

`pyrpipe`: a Python package for RNA-Seq workflows

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Hydroxychloroquine Inhibits the Trained Innate Immune Response to Interferons

Cited by 27 publications

References 64 publications

Efficacy and Safety of Hydroxychloroquine for Hospitalized COVID-19 Patients: A Systematic Review and Meta-Analysis

Efficacy and Safety of Hydroxychloroquine for Hospitalized COVID-19 Patients: A Systematic Review and Meta-Analysis

Role of miR-2392 in driving SARS-CoV-2 infection

pyrpipe: a Python package for RNA-Seq workflows

Contact Info

Product

Resources

About

`pyrpipe`: a Python package for RNA-Seq workflows