Background Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. Results In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Conclusions Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).

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.

In this cross-sectional study, we evaluate potential predictors of Metabolic Syndrome (MS) in a group of 54 Caucasian chronically HI V-infected patients with lipodystrophy. According to ATP-III criteria, 22 patients were affected by MS and 32 were not. The mean age of the sample was 41.2 ± 8.6 years, and most patients were males (74.1%); the two groups were homogeneous for gender, age, viroimmunologic status and the duration of antiviral therapy. The independent association between MS and several factors including demographic characteristics, type of highly-active antiviral therapy (HAART), viro-immunologic response, common cardiovascular risk factors (including Framingham scores), and selected cytokines (IFN-y, TNF-a, IL-2, IL-4, IL-6, IL-I0 and IL-18), was investigated using stepwise forward logistic regression. At multivariate analysis, the only independent predictors of the metabolic syndrome were trjglycerldes and IL-18. A 10 mg/dL increase in triglycerides corresponds to an adjusted risk ratio for MS of 1.11 (95% IC: 1.04-1.19); and patients in the top tertile of IL-18 (those with IL-18 530 pglL) had more than three times the likelihood of MS, as compared to the bottom and medium tertiles of IL-18 (patients with IL-18 < 530 pg/L), This relationship was not attenuated by the inclusion of any other variable in the multivariate model. However, the association between metabolic syndrome and IL-18 is no longer significant when IL-18 is treated as a continuous variable (trend p = 0.087). Our results on HIV patients with lipodystrophy confirm previous findings on a strong independent association between IL-18 and MS in the general population. Further research is needed to clarify the mechanism of this association and its role in the development of cardiovascular disease in HIV patients.

Objective: To investigate a predictive role for the protein S-100b and serum circulating levels of Th1/Th2 cytokines in patients with chronic hepatitis C virus (HCV) infection with and without mixed cryoglobulinemia (MC). Methods: Sixty chronically HCV-infected patients were divided into two groups: 30 with and 30 without MC. Patients with MC presented detectable mixed cryoglobulins and clinical weakness, purpura and arthralgias. HCV-RNA and genotype, serum levels of cryoglobulins, principal hepatic indexes and levels of IL-6, IL-18 and S-100b protein were evaluated. Twenty uninfected healthy subjects were a control group to evaluate serum levels of S-100b protein. Results: IL-6 and IL-18 serum levels were higher in the MC+ group than the MC- group (8.7 ± 4.5 pg/mL versus 4.6 ± 2.3 pg/mL P < 0.0001 and 743.5 ± 128.2 pg/mL versus 578.5 ± 296.5 pg/mL P < 0.001 respectively). S-100b serum levels were higher in HCV+ with MC (0.23 ± 0.07 microg/L) respect to HCV+ patients without MC (0.17 ± 0.05 microg/L, P < 0.0001) and were statistically higher than in the control group (0.08 ± 0.03 microg/L, P < 0.0001 and P < 0.0001, respectively). A positive correlation was shown between serum levels of S-100b protein and levels of cryoglobulins in the group of HCV+ patients MC+ (r=0.72 and P < 0.0001). Conclusion: HCV patients with MC have a worse inflammatory condition than those without MC. Moreover, S-100b protein seems to be a sensitive marker of endothelial and tissue damage in chronic HCV hepatitis with cryoglobulinemia.