Obesity-Associated Hepatic Steatosis, Somatotropic Axis Impairment, and Ferritin Levels Are Strong Predictors of COVID-19 Severity.

The full spectrum of SARS-CoV-2-infected patients has not yet been defined. This study aimed to evaluate which parameters derived from CT, inflammatory, and hormonal markers could explain the clinical variability of COVID-19. We performed a retrospective study including SARS-CoV-2-infected patients hospitalized from March 2020 to May 2021 at the Umberto I Polyclinic of Rome. Patients were divided into four groups according to the degree of respiratory failure. Routine laboratory examinations, BMI, liver steatosis indices, liver CT attenuation, ferritin, and IGF-1 serum levels were assessed and correlated with severity. Analysis of variance between groups showed that patients with worse prognoses had higher BMI and ferritin levels, but lower liver density, albumin, GH, and IGF-1. ROC analysis confirmed the prognostic accuracy of IGF-1 in discriminating between patients who experienced death/severe respiratory failure and those who did not (AUC 0.688, CI: 0.587 to 0.789, p < 0.001). A multivariate analysis considering the degrees of severity of the disease as the dependent variable and ferritin, liver density, and the standard deviation score of IGF-1 as regressors showed that all three parameters were significant predictors. Ferritin, IGF-1, and liver steatosis account for the increased risk of poor prognosis in COVID-19 patients with obesity.

Increased Von Willebrand factor platelet-binding capacity is related to poor prognosis in COVID-19 patients.

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Interleukin 18 and IL-18 BP response to Sars-CoV-2 virus infection.

The immune response to the SARS-CoV-2 infection is crucial to the patient outcome. IL-18 is involved in the lymphocyte response to the disease and it is well established its important role in the complex developing of the host response to viral infection. This study aims at the analysis of the concentrations of IL-18, IL-18BP, INF-γ at the onset of the SARS-CoV-2 infection. The serum levels of measured interleukins were obtained through enzyme-linked immunosorbent assay. Furthermore, the free fraction of IL-18 was numerically evaluated. The enrolled patients were divided in two severity groups according to a threshold value of 300 for the ratio of arterial partial pressure of oxygen and fraction of inspired oxygen fraction and according to the parenchymal involvement as evaluated by computerized tomography at the admittance. In the group of patients with a more severe disease, a significant increase of the IL-18, INF-γ and IL-18BP levels have been observed, whereas the free IL-18 component values were almost constant. The results confirm that, at the onset of the disease, the host response keep the inflammatory cytokines in an equilibrium and support the hypothesis to adopt the IL-18BP modulation as a possible and effective therapeutic approach.

Anti-IFN-α/-ω neutralizing antibodies from COVID-19 patients correlate with downregulation of IFN response and laboratory biomarkers of disease severity.

A significant number of COVID-19 patients were shown to have neutralizing antibodies (NAB) against IFN; however, NAB specificity, fluctuation over time, associations with biochemical and hematological parameters, and IFN gene expression are not well characterized. Binding antibodies (BAB) to IFN-α/-ß were screened in COVID-19 patients' serum. All BAB positive sera, and a subset of respiratory samples, were tested for NAB against IFN-α/-ß/-ω, using an antiviral bioassay. Transcript levels of IFN-α/-ß/-ω and IFN-stimulated genes (ISGs) were quantified. Anti-IFN-I BAB were found in 61 out of 360 (17%) of patients. Among BAB positive sera, 21.3% had a high NAB titer against IFN-α. A total of 69.2% of anti-IFN-α NAB sera displayed cross-reactivity to IFN-ω. Anti-IFN-I NAB persisted in all patients. NAB to IFN-α were also detected in 3 out of 17 (17.6%) of respiratory samples. Anti-IFN-I NAB were higher in males (p = 0.0017), patients admitted to the ICU (p < 0.0001), and patients with a fatal outcome (p < 0.0001). NAB were associated with higher levels of CRP, LDH, d-Dimer, and higher counts of hematological parameters. ISG-mRNAs were reduced in patients with persistently NAB titer. NAB are detected in a significant proportion of severe COVID-19. NAB positive patients presented a defective IFN response and increased levels of laboratory biomarkers of disease severity.

Fibrosis-4 (FIB-4) Index and mortality in COVID-19 patients admitted to the emergency department.

Liver damage worsens the prognosis of coronavirus 19 disease (COVID-19). However, the best strategy to stratify mortality risk according to liver damage has not been established. The aim of this study is to test the predictive value of the validated Fibrosis-4 (FIB-4) Index and compared it to liver transaminases and to the AST-to-Platelet ratio index (APRI). Multicenter cohort study including 992 consecutive COVID-19 patients admitted to the Emergency Department. FIB-4 > 3.25 and APRI > 0.7 were used to define liver damage. Multivariable Cox regression and ROC curve analysis for mortality were performed. Secondary endpoints were (1) need for high-flow oxygen and (2) mechanical ventilation. 240 (24.2%) patients had a FIB-4 > 3.25. FIB-4 > 3.25 associated with an increased mortality (n = 119, log-rank test p < 0.001 and adjusted hazard ratio (HR) 1.72 (95% confidence interval [95%CI] 1.14-2.59, p = 0.010). ROC analysis for mortality showed that FIB-4 (AUC 0.734, 95% CI 0.705-0.761) had a higher predictive value than AST (p = 0.0018) and ALT (p < 0.0001). FIB-4 > 3.25 was also superior to APRI > 0.7 (AUC 0.58, 95% CI 0.553-0.615, p = 0.0008). Using an optimized cut-off > 2.76 (AUC 0.689, 95% CI 0.659-0.718, p < 0.0001), FIB-4 was superior to FIB-4 > 3.25 (p = 0.0302), APRI > 0.7 (p < 0.0001), AST > 51 (p = 0.0119) and ALT > 42 (p < 0.0001). FIB-4 was also associated with high-flow oxygen use (n = 255, HR 1.69, 95% CI 1.25-2.28, p = 0.001) and mechanical ventilation (n = 39, HR 2.07, 95% CI 1.03-4.19, p = 0.043). FIB-4 score predicts mortality better than liver transaminases and APRI score. FIB-4 score may be an easy tool to identify COVID-19 patients at worse prognosis in the emergency department.

Genetic Vaccination as a Flexible Tool to Overcome the Immunological Complexity of Invasive Fungal Infections.

The COVID-19 pandemic has highlighted genetic vaccination as a powerful and cost-effective tool to counteract infectious diseases. Invasive fungal infections (IFI) remain a major challenge among immune compromised patients, particularly those undergoing allogeneic hematopoietic bone marrow transplantation (HSCT) or solid organ transplant (SOT) both presenting high morbidity and mortality rates. Candidiasis and Aspergillosis are the major fungal infections among these patients and the failure of current antifungal therapies call for new therapeutic aids. Vaccination represents a valid alternative, and proof of concept of the efficacy of this approach has been provided at clinical level. This review will analyze current understanding of antifungal immunology, with a particular focus on genetic vaccination as a suitable strategy to counteract these diseases.

Ketogenic Diet as a Preventive and Supportive Care for COVID-19 Patients.

Severe obesity is associated with an increased risk of admission to intensive care units and need for invasive mechanical ventilation in patients with COVID-19. The association of obesity and COVID-19 prognosis may be related to many different factors, such as chronic systemic inflammation, the predisposition to severe respiratory conditions and viral infections. The ketogenic diet is an approach that can be extremely effective in reducing body weight and visceral fat in the short term, preserving the lean mass and reducing systemic inflammation. Therefore, it is a precious preventive measure for severely obese people and may be considered as an adjuvant therapy for patients with respiratory compromise.