Background. COVID-19 patients develop pneumonia generally associated to lymphopenia and severe inflammatory response due to uncontrolled cytokine release. These mediators are transcriptionally regulated by the JAK-STAT signaling pathways, which can be disabled by small molecules. Methods. A group of subjects (n = 20) was treated with baricitinib according to an offlabel use of the drug. The study was designed as an observational longitudinal trial and approved by the local ethical committee. The patients were treated with baricitinib 4 mg twice daily for 2 days, followed by 4 mg per day for the remaining 7 days. Changes in the immune phenotype and expression of pSTAT3 in blood cells were evaluated and correlated with serum-derived cytokine levels and antibodies anti-SARS-CoV-2. In a single treated patient, we evaluated also the alteration of myeloid cell functional activity. Results. We provided evidence that baricitinib-treated patients have a marked reduction in serum levels of interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-a, a rapid recovery in circulating T and B cell frequencies, and increased antibody production against SARS-CoV-2 spike protein, which were clinically associated with a reduction in oxygen flow need and progressive increase in the P/F. Conclusion. These data suggest that Baricitinib prevented the progression towards a severe/extreme form of the viral disease by modulating the patients' immune landscape and these changes were associated with a safer and favorable clinical outcome of patients with COVID-19 pneumonia. Trial registration. The ClinicalTrials.gov identifier of this project is protocol NCT04438629.

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Objectives To assess risk factors for a first thrombotic event in confirmed antiphospholipid (aPL) antibody carriers and to evaluate the efficacy of prophylactic treatments.Methods Inclusion criteria were age 18-65 years, no history of thrombosis and two consecutive positive aPL results.Demographic, laboratory and clinical parameters were collected at enrolment, once a year during the follow-up and at the time of the thrombotic event, whenever that occurred.Results 258 subjects were prospectively observed between October 2004 and October 2008. The mean±SD follow-up was 35.0±11.9 months (range 1-48). A first thrombotic event (9 venous, 4 arterial and 1 transient ischaemic attack) occurred in 14 subjects (5.4%, annual incidence rate 1.86%). Hypertension and lupus anticoagulant (LA) were significantly predictive of thrombosis (both at p<0.05) and thromboprophylaxis was significantly protective during high-risk periods (p<0.05) according to univariate analysis. Hypertension and LA were identified by multivariate logistic regression analysis as independent risk factors for thrombosis (HR 3.8, 95% CI 1.3 to 11.1, p<0.05, and HR 3.9, 95% CI 1.1 to 14, p<0.05, respectively).Conclusions Hypertension and LA are independent risk factors for thrombosis in aPL carriers. Thromboprophylaxis in these subjects should probably be limited to high-risk situations.

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