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.

It has been suggested that, by recruiting lung regions and enlarging the distribution volume of the cold indicator, increasing the positive end-expiratory pressure (PEEP) may lead to an artefactual overestimation of extravascular lung water (EVLW) by transpulmonary thermodilution (TPTD). In 60 ARDS patients, we measured EVLW (PiCCO2 device) at a PEEP level set to reach a plateau pressure of 30 cmH2O (HighPEEPstart) and 15 and 45 min after decreasing PEEP to 5 cmH2O (LowPEEP15′ and LowPEEP45′, respectively). Then, we increased PEEP back to the baseline level (HighPEEPend). Between HighPEEPstart and LowPEEP15′, we estimated the degree of lung derecruitment either by measuring changes in the compliance of the respiratory system (Crs) in the whole population, or by measuring the lung derecruited volume in 30 patients. We defined patients with a large derecruitment from the other ones as patients in whom the Crs changes and the measured derecruited volume were larger than the median of these variables observed in the whole population. Reducing PEEP from HighPEEPstart (14 ± 2 cmH2O) to LowPEEP15′ significantly decreased EVLW from 20 ± 4 to 18 ± 4 mL/kg, central venous pressure (CVP) from 15 ± 4 to 12 ± 4 mmHg, the arterial oxygen tension over inspired oxygen fraction (PaO2/FiO2) ratio from 184 ± 76 to 150 ± 69 mmHg and lung volume by 144 [68–420] mL. The EVLW decrease was similar in “large derecruiters” and the other patients. When PEEP was re-increased to HighPEEPend, CVP, PaO2/FiO2 and EVLW significantly re-increased. At linear mixed effect model, EVLW changes were significantly determined only by changes in PEEP and CVP (p < 0.001 and p = 0.03, respectively, n = 60). When the same analysis was performed by estimating recruitment according to lung volume changes (n = 30), CVP remained significantly associated to the changes in EVLW (p < 0.001). In ARDS patients, changing the PEEP level induced parallel, small and reversible changes in EVLW. These changes were not due to an artefact of the TPTD technique and were likely due to the PEEP-induced changes in CVP, which is the backward pressure of the lung lymphatic drainage. Trial registration ID RCB: 2015-A01654-45. Registered 23 October 2015

Background. SARS-CoV-2 is responsible for COVID-19, a clinically heterogeneous disease, ranging from being completely asymptomatic to life-threating manifestations. An unmet clinical need is the identification at disease onset or during its course of reliable biomarkers allowing patients’ stratification according to disease severity. In this observational prospective cohort study, patients’ immunologic and laboratory signatures were analyzed to identify independent predictors of unfavorable (either death or intensive care unit admission need) or favorable (discharge and/or clinical resolution within the first 14 days of hospitalization) outcome. Methods. Between January and May 2021 (third wave of the pandemic), we enrolled 139 consecutive SARS-CoV-2 positive patients hospitalized in Northern Italy to study their immunological and laboratory signatures. Multiplex cytokine, chemokine, and growth factor analysis, along with routine laboratory tests, were performed at baseline and after 7 days of hospital stay. Results. According to their baseline characteristics, the majority of our patients experienced a moderate to severe illness. At multivariate analysis, the only independent predictors of disease evolution were the serum concentrations of IP-10 (at baseline) and of C-reactive protein (CRP) after 7 days of hospitalization. Receiver-operating characteristic (ROC) curve analysis confirmed that baseline and at 7 days predict a worsening in clinical conditions (87% sensitivity, 66% specificity, area under the curve (AUC) 0.772, and 83% sensitivity, 73% specificity, AUC 0.826, , respectively). Conclusions. According to our results, baseline IP-10 and CRP after 7 days of hospitalization could be useful in driving clinical decisions tailored to the expected disease trajectory in hospitalized COVID-19 patients.