Effect of Lactoferrin on Clinical Outcomes of Hospitalized Patients with COVID-19: The LAC Randomized Clinical Trial.

As lactoferrin is a nutritional supplement with proven antiviral and immunomodulatory abilities, it may be used to improve the clinical course of COVID-19. The clinical efficacy and safety of bovine lactoferrin were evaluated in the LAC randomized double-blind placebo-controlled trial. A total of 218 hospitalized adult patients with moderate-to-severe COVID-19 were randomized to receive 800 mg/die oral bovine lactoferrin (n = 113) or placebo (n = 105), both given in combination with standard COVID-19 therapy. No differences in lactoferrin vs. placebo were observed in the primary outcomes: the proportion of death or intensive care unit admission (risk ratio of 1.06 (95% CI 0.63-1.79)) or proportion of discharge or National Early Warning Score 2 (NEWS2) ≤ 2 within 14 days from enrollment (RR of 0.85 (95% CI 0.70-1.04)). Lactoferrin showed an excellent safety and tolerability profile. Even though bovine lactoferrin is safe and tolerable, our results do not support its use in hospitalized patients with moderate-to-severe COVID-19.

Improvements throughout the Three Waves of COVID-19 Pandemic: Results from 4 Million Inhabitants of North-West Italy.

At the very beginning of the European spread of SARS-CoV-2, Piedmont was one of the most affected regions in Italy, with a strong impact on healthcare organizations. In this study, we evaluated the characteristics and outcomes of the COVID-19 patients in an entire region during the first three pandemic waves, identifying similarities and differences in the SARS-CoV-2 epidemic's timeline. We collected the health-administrative data of all the Piedmont COVID-19 patients infected during the first three pandemic waves (1 March 2020-15 April 2020; 15 October 2020-15 December 2020; 1 March 2021-15 April 2021, respectively). We compared differences among the waves in subjects positive for SARS-CoV-2 and in patients admitted to ICU. Overall, 18.621 subjects tested positive during the first wave (405 patients/day), 144.350 (2366.4 patients/day) in the second, and 81.823 (1778.8 patients/day) in the third. In the second and third waves, we observed a reduction in median age, comorbidity burden, mortality in outpatients, inpatients, and patients admitted to ICU, in intubation, invasive ventilation and tracheostomy, and a parallel increase in the use of CPAP. Our study confirmed a trend towards younger and healthier patients over time but also showed an independent effect of the period on mortality and ICU admission. The appearance of new viral variants, the starting of vaccination, and organizational improvements in tracking, outpatients and inpatients management could have influenced these trends.

Hemostasis and cancer: tumor cells induce the expression of tissue factor-like procoagulant activity on endothelial cells.

BACKGROUND AND OBJECTIVES: Clotting activation and thromboembolic manifestations are common features in patients with cancer. The two-way interaction between tumor cells and host cells is of crucial importance in this context. In the present study we investigated the effect of tumor cell-endothelial cell co-culture on the expression of procoagulant activity in the mixed cell populations. DESIGN AND METHODS: Human tumor cell lines (HL60 promyelocytic leukemia and HeLa uterine cervical cancer) and human umbilical vein endothelial cells (HUVEC) were cultured in vitro according to standard procedures. Procoagulant activity was studied in a coagulometer and was found to be tissue factor-like. A calibration curve was obtained with decreasing concentrations of rabbit brain thromboplastin (RBT) and the procoagulant activity of both tumor cells and HUVEC was expressed as RBT U/10(5) cells. RESULTS: Before incubation procoagulant activity (means S.E.) was found to be 0.18 +/- 0.04 U in HUVEC, 9.8 +/- 1.9 U in HL60 cells, 11.9 +/- 2.2 U in HeLa cells, 7.2 +/- 1.4 U in a mixed HL60 cell-HUVEC population (ratio 2:1) and 8.5 +/- 2.0 in a mixed HeLa cell-HUVEC population (ratio 2:1). Incubation at 37 degrees C for up to 4 hours of tumor cells or HUVEC alone did not produce any change in procoagulant activity. In contrast, co-incubation of tumor cells with HUVEC for 4 hours was followed by a significant increase in procoagulant activity of the mixed cell populations. Addition of supernatants from tumor cells, HUVEC or tumor cell-HUVEC co-cultures to HUVEC or tumor cells showed that the tissue factor-like procoagulant activity generated during coincubation was localized on HUVEC. INTERPRETATION AND CONCLUSIONS: Our results show that the close interaction of tumor cells with endothelial cells may induce surface expression of tissue factor in the latter. This effect could represent an additional mechanism of clotting activation in patients with cancer.