Severe acute respiratory syndrome coronavirus ORF3a protein activates the NLRP3 inflammasome by promoting TRAF3dependent ubiquitination of ASC.
Background Clinicians all around the world are currently experiencing a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Several therapeutic strategies have been used until now but, to date, there is no specific therapy to treat SARS‐CoV‐2 infection. In this study, we used canakinumab, a human monoclonal antibody targeting interleukin‐1 beta to improve respiratory function and laboratory parameters compared with standard therapy (hydroxycloroquine plus lopinavir/ritonavir). Methods We enrolled 34 patients with mild or severe non intensive care unit (ICU) coronavirus disease 2019 (COVID‐19): 17 patients treated with standard therapy and 17 patients treated with a subcutaneous single dose of canakinumab 300 mg. We collected data about oxygen supports and laboratory parameters such as inflammation indices and hemogasanalysis. We compared the data collected before the administration of canakinumab (T0), 3 days after T0 (T1) and 7 days after T0 (T2) with the same data from patients taking the standard therapy. Results We observed a reduction in inflammation indices and a significant and rapid increase in P/F ratio in canakinumab group, with improvement of 60.3% after the administration. We reported a significant reduction in oxygen flow in patients treated with canakinumab (−28.6% at T1 vs. T0 and −40.0% at T2 vs. T1). Conversely, the standard group increased the supply of high oxygen at T1 versus T0 (+66.7%), but reduced oxygen flows at T2 versus T1 (−40.0%). Conclusion In hospitalized adult patients with mild or severe non ICU COVID‐19, canakinumab could be a valid therapeutic option. Canakinumab therapy causes rapid and long‐lasting improvement in oxygenation levels in the absence of any severe adverse events.
Background: Extracellular vesicles, released by cell pullulation, are surrounded by a phospholipid bilayer and carry proteins as well and genetic material. It has been shown that extracellular vesicles mediate intercellular communication in several conditions, such as inflammation, immunodeficiency, tumor growth, and viral infections. Here, we analyzed circulating levels of extracellular vesicles in order to clarify their role in chronic inflammation mechanisms characterizing HIV patients. Methods: We analyzed and subtyped circulating levels of extracellular vesicles, through a recently developed flow cytometry method. In detail, endothelial-derived extracellular vesicles (CD31+/CD41a−/CD45−, EMVs), extracellular vesicles stemming from leukocytes (CD45+, LMVs) and platelets (CD41a+/CD31+) were identified and enumerated. Moreover, we analyzed the extracellular vesicle protein cargo with proteomic analysis. Results: Circulating levels of total extracellular vesicles, EMVs and LMVs were significantly lower in the HIV+ patients than in healthy subjects, whereas platelet-derived extracellular vesicles resulted higher in patients than in the healthy population. Proteomic analysis showed the upregulation of gammaIFN and IL1α, and down-regulation of OSM, NF-kB, LIF, and RXRA signaling resulted activated in this patients. Conclusion: These data demonstrate, for the first time that HIV infection induces the production of extracellular vesicles containing mediators that possibly feed the chronic inflammation and the viral replication. These two effects are connected as the inflammation itself induces the viral replication. We, therefore, hypothesize that HIV infection inhibits the production of extracellular vesicles that carry anti-inflammatory molecules.
Recent studies have focused their attention on conjunctivitis as one of the symptoms of coronavirus disease 2019 (COVID-19). Therefore, tear samples were taken from COVID-19 patients and the presence of SARS-CoV-2 was evidenced using Real Time reverse transcription polymerase chain reaction. The main aim of this study was to analyze mRNA expression in the tears of patients with COVID-19 compared with healthy subjects using Next Generation Sequencing (NGS). The functional evaluation of the transcriptome highlighted 25 genes that differ statistically between healthy individuals and patients affected by COVID-19. In particular, the NGS analysis identified the presence of several genes involved in B cell signaling and keratinization. In particular, the genes involved in B cell signaling were downregulated in the tears of COVID-19 patients, while those involved in keratinization were upregulated. The results indicated that SARS-CoV-2 may induce a process of ocular keratinization and a defective B cell response.
Objectives We designed this study to identify laboratory and radiological parameters, which could be useful to guide the clinician, in the evaluation of a suspected case of coronavirus disease 19 (COVID‐19). Methods This retrospective, observational, single‐center‐study recruited patients with a suspect of COVID‐19 data were extracted from electronic medical records using a standardized data collection form. Results A total of 566 patients with suspect COVID‐19 infection were enrolled (280 were COVID‐19+). The COVID‐19 population was characterized with bilateral‐pneumonia, a lower count of neutrophil, lymphocyte and monocyte, a lower neutrophil to lymphocyte‐ratio (NLR). Lower of platelet count, d ‐dimer, troponin I, and serum calcium were in COVID‐19 patients. The occurrence of COVID‐19 diagnosis increased, independently of other variables, with pneumonia (odds ratio [OR]: 3.60; p < .001), neutrophil below normal range (OR: 4.15; p < .05), lactate dehydrogenase (OR: 2.09; p < .01) and sodium above normal range (OR: 2.34; p < .01). In patients with possible respiratory acute affections we found a higher neutrophil, higher monocyte, a higher NLR and a more elevation in d ‐dimer. In the Sepsis group showed higher level of white blood cell, C‐reactive protein, d ‐dimer, and procalcitonin. Conclusions Our study confirms that patients with COVID‐19 have typical radiological and laboratory characteristics. The parameters highlighted in the study can help identify COVID‐19 patients, also highlighting which are the main differential diagnoses to be made and the parameters that facilitate the differential diagnosis.
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