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J Allergy Clin Immunol ; 2022 Jul 11.
Article in English | MEDLINE | ID: covidwho-1926575


BACKGROUND: SARS-CoV-2 infection may result in a severe pneumonia associated to elevation of blood inflammatory parameters, reminiscent of cytokine storm syndrome. Steroidal anti-inflammatory therapies have shown efficacy in reducing mortality in critically ill patients, however the mechanisms by which SARS-CoV2 virus triggers such an extensive inflammation remain unexplained. OBJECTIVES: To dissect the mechanisms underlying SARS-CoV-2 associated inflammation in severe COVID-19 patients we studied the role of IL-1ß, a pivotal cytokine driving inflammatory phenotypes, whose maturation and secretion are regulated by inflammasomes. METHODS: We analyzed NLRP3 pathway activation by means of confocal microscopy, plasma cytokine measurement, cytokine secretion following in vitro stimulation of blood circulating monocytes and whole blood RNA sequencing. The role of ORF3a SARS-CoV2 protein was assessed by confocal microscopy analysis following nucleofection of a monocytic cell line. RESULTS: We found that circulating monocytes from COVID-19 patients display ASC specks that colocalize with NLRP3 inflammasome and spontaneously secrete IL-1ß in vitro. This spontaneous activation reverts following patient's treatment with the IL-1 receptor antagonist anakinra. Transfection of a monocytic cell line with cDNA coding for the ORF3a SARS-CoV2 protein, resulted in ASC speck formation CONCLUSIONS: These results provide further evidence that IL-1ß targeting could represent an effective strategy in this disease and suggest a mechanistic explanation for the strong inflammatory manifestations associated to COVID-19.

BMC Bioinformatics ; 22(Suppl 15): 544, 2021 Nov 08.
Article in English | MEDLINE | ID: covidwho-1506889


BACKGROUND: Improving the availability and usability of data and analytical tools is a critical precondition for further advancing modern biological and biomedical research. For instance, one of the many ramifications of the COVID-19 global pandemic has been to make even more evident the importance of having bioinformatics tools and data readily actionable by researchers through convenient access points and supported by adequate IT infrastructures. One of the most successful efforts in improving the availability and usability of bioinformatics tools and data is represented by the Galaxy workflow manager and its thriving community. In 2020 we introduced Laniakea, a software platform conceived to streamline the configuration and deployment of "on-demand" Galaxy instances over the cloud. By facilitating the set-up and configuration of Galaxy web servers, Laniakea provides researchers with a powerful and highly customisable platform for executing complex bioinformatics analyses. The system can be accessed through a dedicated and user-friendly web interface that allows the Galaxy web server's initial configuration and deployment. RESULTS: "Laniakea@ReCaS", the first instance of a Laniakea-based service, is managed by ELIXIR-IT and was officially launched in February 2020, after about one year of development and testing that involved several users. Researchers can request access to Laniakea@ReCaS through an open-ended call for use-cases. Ten project proposals have been accepted since then, totalling 18 Galaxy on-demand virtual servers that employ ~ 100 CPUs, ~ 250 GB of RAM and ~ 5 TB of storage and serve several different communities and purposes. Herein, we present eight use cases demonstrating the versatility of the platform. CONCLUSIONS: During this first year of activity, the Laniakea-based service emerged as a flexible platform that facilitated the rapid development of bioinformatics tools, the efficient delivery of training activities, and the provision of public bioinformatics services in different settings, including food safety and clinical research. Laniakea@ReCaS provides a proof of concept of how enabling access to appropriate, reliable IT resources and ready-to-use bioinformatics tools can considerably streamline researchers' work.

COVID-19 , Cloud Computing , Computational Biology , Humans , SARS-CoV-2 , Software