Eosinopenia is a reliable marker of severe disease and unfavourable outcome in patients with COVID-19 pneumonia.

BACKGROUND AND AIM: Viral pneumonia is the most relevant clinical presentation of COVID-19 which may lead to severe acute respiratory syndrome and even death. Eosinopenia was often noticed in patients with COVID-19 pneumonia, but its role is poorly investigated. The aim of the present study was to investigate the characteristics and clinical outcomes of patients with COVID-19 pneumonia and eosinopenia. METHODS: We revised the records of consecutive patients with COVID-19 pneumonia admitted to our ER-COVID-19 area in order to compare clinical characteristics and outcomes of patients with and without eosinopenia. We considered the following clinical outcomes: 4-weeks survival; need for intensive respiratory support; and hospital discharge. RESULTS: Out of first 107 consecutive patients with pneumonia and a positive COVID-19 nasopharyngeal swab, 75 patients showed undetectable eosinophil count (absolute eosinopenia). At 4 weeks, 38 patients (38.4%) had required intensive respiratory treatment, 25 (23.4%) deceased and 42 (39.2%) were discharged. Compared with patients without absolute eosinopenia, patients with absolute eosinopenia showed higher need of intensive respiratory treatment (49.3% vs 13.3%, P < .001), higher mortality (30.6% vs 6.2%, P .006) and lower rate of hospital discharge (28% vs 65.6%, P < .001). Binary logistic regression analyses including neutrophil, lymphocyte, eosinophil, basophil and monocyte counts showed that absolute eosinopenia was an independent factor associated with 4-weeks mortality, need for intensive respiratory support and hospital discharge. CONCLUSIONS: Absolute eosinopenia is associated with clinical outcomes in patients with COVID-19 pneumonia and might be used as a marker to discriminate patients with unfavourable prognosis.

Blood cell differential count discretisation modelling to predict survival in adults reporting to the emergency room: a retrospective cohort study.

OBJECTIVES: To assess the survival predictivity of baseline blood cell differential count (BCDC), discretised according to two different methods, in adults visiting an emergency room (ER) for illness or trauma over 1 year. DESIGN: Retrospective cohort study of hospital records. SETTING: Tertiary care public hospital in northern Italy. PARTICIPANTS: 11 052 patients aged >18 years, consecutively admitted to the ER in 1 year, and for whom BCDC collection was indicated by ER medical staff at first presentation. PRIMARY OUTCOME: Survival was the referral outcome for explorative model development. Automated BCDC analysis at baseline assessed haemoglobin, mean cell volume (MCV), red cell distribution width (RDW), platelet distribution width (PDW), platelet haematocrit (PCT), absolute red blood cells, white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, basophils and platelets. Discretisation cut-offs were defined by benchmark and tailored methods. Benchmark cut-offs were stated based on laboratory reference values (Clinical and Laboratory Standards Institute). Tailored cut-offs for linear, sigmoid-shaped and U-shaped distributed variables were discretised by maximally selected rank statistics and by optimal-equal HR, respectively. Explanatory variables (age, gender, ER admission during SARS-CoV2 surges and in-hospital admission) were analysed using Cox multivariable regression. Receiver operating curves were drawn by summing the Cox-significant variables for each method. RESULTS: Of 11 052 patients (median age 67 years, IQR 51-81, 48% female), 59% (n=6489) were discharged and 41% (n=4563) were admitted to the hospital. After a 306-day median follow-up (IQR 208-417 days), 9455 (86%) patients were alive and 1597 (14%) deceased. Increased HRs were associated with age >73 years (HR=4.6, 95% CI=4.0 to 5.2), in-hospital admission (HR=2.2, 95% CI=1.9 to 2.4), ER admission during SARS-CoV2 surges (Wave I: HR=1.7, 95% CI=1.5 to 1.9; Wave II: HR=1.2, 95% CI=1.0 to 1.3). Gender, haemoglobin, MCV, RDW, PDW, neutrophils, lymphocytes and eosinophil counts were significant overall. Benchmark-BCDC model included basophils and platelet count (area under the ROC (AUROC) 0.74). Tailored-BCDC model included monocyte counts and PCT (AUROC 0.79). CONCLUSIONS: Baseline discretised BCDC provides meaningful insight regarding ER patients' survival.

Microvesicles in haemoglobinopathies offer insights into mechanisms of hypercoagulability, haemolysis and the effects of therapy.

Levels of circulating red blood cell (RBC)-derived vesicles are increased in sickle cell anaemia (SCA) and thalassaemia intermedia (TI) but the mechanisms, effects and controlling factors may differ. This study found that levels of vesicles and intravascular haemolysis were linked as shown by the correlation between levels of vesicles and plasma Hb. Vesicle levels were 6-fold greater in SCA and 4-fold greater in TI than in controls. The proportion of plasma Hb within vesicles was increased in SCA and TI with a significantly higher proportion in TI. We examined whether subpopulations of RBC expressing phosphatidylserine (PS) were a source of PS(+) vesicles and observed a significant association. Thrombin generation was promoted by the vesicles in which 40-50% expressed PS. In TI, markers of thrombin generation were significantly related to PS(+) RBC. Splenectomy in TI had significant effects including greater increases in vesicle levels, plasma Hb, PS(+) RBCs and thrombin generation markers than in unsplenectomised patients. In hydroxycarbamide (HC)-treated SCA patients these measures were decreased compared with untreated controls. The relationship between vesicle levels and plasma Hb suggests a mechanism linking vesiculation to haemolysis and consequently nitric oxide (NO) bioavailability and suggests a means by which HC treatment improves NO bioavailability.

Clinical and histological characterization of liver disease in patients with transfusion-dependent beta-thalassemia. A multicenter study of 117 cases.

BACKGROUND AND OBJECTIVES: Updated information on liver disease in transfusion-dependent beta-thalassemia is lacking. We conducted a multicenter study within the Cooleycare Group to describe the clinical and histopathological features of liver disease in currently treated thalassemics. DESIGN AND METHODS: Two-hundred and three thalassemics with laboratory signs of liver disease were eligible. Liver biopsy was performed in the 129 (63.5%) who consented (age 26+/-7 years). Biological samples were sent to the central laboratory. RESULTS: Anti-hepatitis C virus (HCV) antibodies were found in 118 patients (91%), 85 (72%) of whom were viremic. Ninety-one patients (70%) had abnormal aminotransferase concentrations. In the 117 liver biopsies that met the criteria for evaluation (88%), the median Ishak's necroinflammatory and fibrosis scores were 4 (range, 0-9) and 2 (range, 0-6), respectively. Significant fibrosis (score >or=3) was found in 53 (45%); 9 (8%) had cirrhosis. At multivariate analysis, necroinflammation was related to HCV viremia, and fibrosis to increased serum aminotransferases, higher iron stores (including serum ferritin, Deugnier's total iron score, and liver iron content) and male gender (p<0.05). In HCV-RNA negative subjects, the median total iron score was 27 (range, 0-52). Iron accumulated in both mesenchymal cells and hepatocytes, and the presence of a lobular gradient was interpreted to indicate intestinal hyperabsorption. INTERPRETATION AND CONCLUSIONS: Transfusion-dependent thalassemics have mild liver necroinflammation, mainly attributable to HCV infection. Significant fibrosis is frequent, and its progression is mostly influenced by iron overload which, with current therapy regimens, may be attributable to both erythrocyte catabolism and iron hyperabsorption.

Exercise capacity in patients with beta-thalassaemia intermedia.

Thalassaemia intermedia patients can suffer fatigue and exercise capacity reduction, possibly because of anaemia, deconditioning and lack of exercise-induced haemoconcentration. We studied 21 beta-thalassaemia intermedia patients, 10 splenectomised (group A) and 11 not splenectomised (group B). Patients were evaluated by cardiopulmonary exercise test with blood sampling for haemoglobin and plasma protein measurements at rest and peak. During exercise, an isolated increase of haemoglobin suggested spleen contraction while a parallel increase of haemoglobin and proteins suggested fluid filtration through capillary wall. Groups were homogeneous for age and gender. Peak oxygen consumption (VO2) was 22.5 +/- 4.4 ml/min/kg (51 +/- 14%) and 24.3 +/- 7.0 (53 +/- 12%) in groups A and B respectively [not significant (NS)]. At rest, haemoglobin was 8.8 g/dl in both groups. Exercise-induced increment was 0.4 +/- 0.2 and 1.0 +/- 0.4 g/dl (P < 0.001) for haemoglobin and 4.0 +/- 3.0 and 5.0 +/- 4.0 g/l (NS) for proteins, in groups A and B respectively. Anaemia was the major cause of peak VO2 reduction (1097 +/- 260 ml/min). However, anaemia did not explain the entire exercise capacity reduction, suggesting the presence of muscular deconditioning. Exercise capacity is reduced in beta-thalassaemia intermedia because of anaemia and muscular deconditioning. Spleen contraction does not significantly influence exercise capacity although exercise-induced haemoconcentration was greater in patients with spleen.