Coronavirus disease-19 (COVID-19) has been regarded as an infective-inflammatory disease, which affects mainly lungs. More recently, a multi-organ involvement has been highlighted, with different pathways of injury. A hemoglobinopathy, hypoxia and cell iron overload might have a possible additional role. Scientific literature has pointed out two potential pathophysiological mechanisms: i) severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) interaction with hemoglobin molecule, through CD147, CD26 and other receptors located on erythrocyte and/or blood cell precursors; ii) hepcidin-mimetic action of a viral spike protein, inducing ferroportin blockage. In this translational medicine-based narrative review, the following pathologic metabolic pathways, deriving from hemoglobin denaturation and iron metabolism dysregulation, are highlighted: i) decrease of functioning hemoglobin quote; ii) iron overload in cell/tissue (hyperferritinemia); iii) release of free toxic circulating heme; iv) hypoxemia and systemic hypoxia; v) reduction of nitric oxide; vi) coagulation activation; vii) ferroptosis with oxidative stress and lipoperoxidation; viii) mitochondrial degeneration and apoptosis. A few clinical syndromes may follow, such as pulmonary edema based on arterial vasoconstriction and altered alveolo-capillary barrier, sideroblastic-like anemia, endotheliitis, vasospastic acrosyndrome, and arterio- venous thromboembolism. We speculated that in COVID-19, beyond the classical pulmonary immune-inflammation view, the occurrence of an oxygen-deprived blood disease, with iron metabolism dysregulation, should be taken in consideration. A more comprehensive diagnostic/therapeutic approach to COVID-19 is proposed, including potential adjuvant interventions aimed at improving hemoglobin dysfunction, iron over-deposit and generalized hypoxic state.

Traditionally, pneumonia has been classified as either community- or hospital-acquired. Although only limited data are available, health care–associated pneumonia has been recently proposed as a new category of respiratory infection. “Health care–associated pneumonia” refers to pneumonia in patients who have recently been hospitalized, had hemodialysis, or received intravenous chemotherapy or reside in a nursing home or long-term care facility. To ascertain the epidemiology and outcome of community-acquired, health care–associated, and hospital-acquired pneumonia in adults hospitalized in internal medicine wards. Multicenter, prospective observational study. 55 hospitals in Italy comprising 1941 beds. 362 patients hospitalized with pneumonia during two 1-week surveillance periods. Cases of radiologically and clinically assessed pneumonia were classified as community-acquired, health care–associated, or hospital-acquired and rates were compared. Of the 362 patients, 61.6% had community-acquired pneumonia, 24.9% had health care–associated pneumonia, and 13.5% had hospital-acquired pneumonia. Patients with health care–associated pneumonia had higher mean Sequential Organ Failure Assessment scores than did those with community-acquired pneumonia (3.0 vs. 2.0), were more frequently malnourished (11.1% vs. 4.5%, and had more frequent bilateral (34.4% vs. 19.7%) and multilobar (27.8% vs. 21.5%) involvement on a chest radiograph. Patients with health care–associated pneumonia also had higher fatality rates (17.8% [CI, 10.6% to 24.9%] vs. 6.7% [CI, 2.9% to 10.5%]) and longer mean hospital stay (18.7 days [CI, 15.9 to 21.5 days] vs. 14.7 days [CI, 13.4 to 15.9 days]). Logistic regression analysis revealed that depression of consciousness (odds ratio [OR], 3.2 [CI, 1.06 to 9.8]), leukopenia (OR, 6.2 [CI, 1.01 to 37.6]), and receipt of empirical antibiotic therapy not recommended by international guidelines (OR, 6.4 [CI, 2.3 to 17.6]) were independently associated with increased intrahospital mortality. The number of patients with health care–associated pneumonia was relatively small. Microbiological investigations were not always homogeneous. The study included only patients with pneumonia that required hospitalization; results may not apply to patients treated as outpatients. Health care–associated pneumonia should be considered a distinct subset of pneumonia associated with more severe disease, longer hospital stay, and higher mortality rates. Physicians should differentiate between patients with health care–associated pneumonia and those with community-acquired pneumonia and provide more appropriate initial antibiotic therapy. None.

In the last decade, an increasing awareness was directed to the role of Vitamin D in non-skeletal and preventive roles for chronic diseases. Vitamin D is an essential hormone in regulating calcium/phosphorous balance and in the pathogenesis of inflammation, insulin resistance, and obesity. The main forms of vitamin D, Cholecalciferol (Vitamin D3) and Ergocalciferol (Vitamin D2) are converted into the active form (1,25-dihydroxyvitamin D) thanks to two hydroxylations in the liver, kidney, pancreas, and immune cells. Some anti-inflammatory cytokines are produced at higher levels by vitamin D, while some pro-inflammatory cytokines are released at lower levels. Toll-Like Receptor (TLR) expression is increased, and a pro-inflammatory state is also linked to low levels of vitamin D. Regardless of how it affects inflammation, various pathways suggest that vitamin D directly improves insulin sensitivity and secretion. The level of vitamin D in the body may change the ratio of pro- to anti-inflammatory cytokines, which would impact insulin action, lipid metabolism, and the development and function of adipose tissue. Many studies have demonstrated an inverse relationship between vitamin D concentrations and pro-inflammatory markers, insulin resistance, glucose intolerance, metabolic syndrome, obesity, and cardiovascular disease. It is interesting to note that several long-term studies also revealed an inverse correlation between vitamin D levels and the occurrence of diabetes mellitus. Vitamin D supplementation in people has controversial effects. While some studies demonstrated improvements in insulin sensitivity, glucose, and lipid metabolism, others revealed no significant effect on glycemic homeostasis and inflammation. This review aims to provide insight into the molecular basis of the relationship between vitamin D, insulin resistance, metabolic syndrome, type 1 and 2 diabetes, gestational diabetes, and cardiovascular diseases.

Our aim was to analyze mortality attributable to carbapenem-resistant (CR) Gram-negative bacilli (GNB) in patients with bloodstream infections (BSIs). Prospective multicentric study including patients with GNB-BSI from19 Italian hospitals (June 2018-January 2020). Patients were followed-up to 30 days. Primary outcomes were 30-day mortality and attributable mortality. Attributable mortality was calculated in the following groups: KPC-producing Enterobacterales, metallo-β-lactamases (MBL)-producing Enterobacterales, CR-Pseudomonas aeruginosa (CRPA), CR-Acinetobacter baumannii (CRAB). A multivariable analysis with hospital fixed-effect was built to identify factors associated with 30-day mortality. Adjusted OR (aOR) were reported. Attributable mortality was calculated according to the DRIVE-AB Consortium. Overall,1276 patients with monomicrobial GNB BSI were included: 723/1276 (56.7%) carbapenem-susceptible (CS)-GNB, 304/1276 (23.8%) KPC-, 77/1276 (6%) MBL-producing CRE, 61/1276 (4.8%) CRPA, and 111/1276 (8.7%) CRAB BSI. Thirty-day mortality in patients with CS-GNB BSI was 13.7% compared to 26.6%, 36.4%, 32.8% and 43.2% in patients with BSI by KPC-CRE, MBL-CRE, CRPA and CRAB, respectively (p<0.001). On multivariable analysis, age, ward of hospitalization, SOFA score, and Charlson Index were factors associated with 30-day mortality, while urinary source of infection and early appropriate therapy resulted protective factors. Compared to CS-GNB, MBL-producing CRE (aOR 5.86, 95% CI 2.72-12.76), CRPA (aOR 1.99, 95% CI 1.48-5.95) and CRAB (aOR 2.65, 95% CI 1.52-4.61) were significantly associated with 30-day mortality. Attributable mortality rates were 5% for KPC-, 35% for MBL, 19% for CRPA, and 16% for CRAB. In patients with BSIs, carbapenem-resistance is associated with an excess of mortality, with MBL-producing CRE carrying the highest risk of death.