Preparedness and activities of the anti-SARS-CoV-2 convalescent plasma bank in the Veneto region (Italy): An organizational model for future emergencies.

BACKGROUND: Convalescent plasma (CP) has been used in the past in various pandemics, in particular in H1N1, SARS and MERS infections. In Spring 2020, when ongoing the SARS-CoV-2 pandemics, the Veneto Region (V-R) has proposed setting-up an anti-SARS-CoV-2 CP (CCP) Bank, with the aim of preparing a supply of CCP immediately available in case of subsequest epidemic waves. MATERIALS AND METHODS: Key-points to be developed for a quick set-up of the V-R CCP Bank have been recruitment of donors recovered from COVID-19 infection, laboratory analysis for the biological qualification of the CCP units, including titre of neutralizing antibodies and reduction of pathogens, according to National Blood Centre (CNS) Directives, adaptation of the V-R Information Technology systems and cost analysis. Some activities, including diagnostic and viral inactivation processes, have been centralized in 2 or 3 sites. Laboratory analysis upon preliminary admission of the donor included all tests required by the Italian laws and the CNS directives. RESULTS: From April to August 2020, 3,298 people have contacted the V-R Blood Transfusion Services: of these, 1,632 have been evaluated and examined as first time donors and those found to be suitable have carried out 955 donations, from which 2,626 therapeutic fractions have been obtained, at a cost around 215,00 Euro. Since October 2020, the number of COVID-19 inpatients has had a surge with a heavy hospital overload. Moreover, the high request of CCP therapy by clinicians has been just as unexpected, showing a wide therapeutic use. CONCLUSIONS: The organizational model here presented, which has allowed the rapid collection of a large amount of CCP, could be useful when facing new pandemic outbreaks, especially in low and middle income countries, with generally acceptable costs.

Identification of new BMP6 pro-peptide mutations in patients with iron overload.

Hereditary Hemochromatosis (HH) is a genetically heterogeneous disorder caused by mutations in at least five different genes (HFE, HJV, TFR2, SLC40A1, HAMP) involved in the production or activity of the liver hormone hepcidin, a key regulator of systemic iron homeostasis. Nevertheless, patients with an HH-like phenotype that remains completely/partially unexplained despite extensive sequencing of known genes are not infrequently seen at referral centers, suggesting a role of still unknown genetic factors. A compelling candidate is Bone Morphogenetic Protein 6 (BMP6), which acts as a major activator of the BMP-SMAD signaling pathway, ultimately leading to the upregulation of hepcidin gene transcription. A recent seminal study by French authors has described three heterozygous missense mutations in BMP6 associated with mild to moderate late-onset iron overload (IO). Using an updated next-generation sequencing (NGS)-based genetic test in IO patients negative for the classical HFE p.Cys282Tyr mutation, we found three BMP6 heterozygous missense mutations in four patients from three different families. One mutation (p.Leu96Pro) has already been described and proven to be functional. The other two (p.Glu112Gln, p.Arg257His) were novel, and both were located in the pro-peptide domain known to be crucial for appropriate BMP6 processing and secretion. In silico modeling also showed results consistent with their pathogenetic role. The patients' clinical phenotypes were similar to that of other patients with BMP6-related IO recently described. Our results independently add further evidence to the role of BMP6 mutations as likely contributing factors to late-onset moderate IO unrelated to mutations in the established five HH genes.

An Integrated Management System for Noncommunicable Diseases Program Implementation in a Sub-Saharan Setting.

Morbidity and mortality due to noncommunicable diseases (NCDs) are growing exponentially across Tanzania. The limited availability of dedicated services and the disparity between rural and urban areas represent key factors for the increased burden of NCDs in the country. From March 2019, an integrated management system was started in the Iringa District Council. The system implements an integrated management of hypertension and diabetes between the hospital and the peripheral health centers and introduces the use of paper-based treatment cards. The aim of the study was to present the results of the first 6 months' roll-out of the system, which included 542 patients. Data showed that 46.1% of patients returned for the reassessment visit (±1 month), more than 98.4% of patients had blood pressure measured and were checked for complication, more than 88.6% of patients had blood sugar tested during follow-up visit, and blood pressure was at target in 42.8% of patients with hypertension and blood sugar in 37.3% of diabetic patients. Most patients who were lost to follow-up or did not reach the targets were those without medical insurance or living in remote peripheries. Our findings suggest that integrated management systems connecting primary health facilities and referral hospitals may be useful in care and follow-up of patients with hypertension and diabetes.

Gene expression profiling in peripheral blood mononuclear cells of patients with common variable immunodeficiency: modulation of adaptive immune response following intravenous immunoglobulin therapy.

BACKGROUND: Regular intravenous immunoglobulin treatment is used to replace antibody deficiency in primary immunodeficiency diseases; however the therapeutic effect seems to be related not only to antibody replacement but also to an active role in the modulation of the immune response. Common variable immunodeficiency is the most frequent primary immunodeficiency seen in clinical practice. METHODS: We have studied the effect of intravenous immunoglobulin replacement in patients with common variable immunodeficiency by evaluating the gene-expression profiles from Affimetrix HG-U133A. Some of the gene array results were validated by real time RT-PCR and by the measurement of circulating cytokines and chemokines by ELISA. Moreover we performed FACS analysis of blood mononuclear cells from the patients enrolled in the study. RESULTS: A series of genes involved in innate and acquired immune responses were markedly up- or down-modulated before therapy. Such genes included CD14, CD36, LEPR, IRF-5, RGS-1, CD38, TNFRSF25, IL-4, CXCR4, CCR3, IL-8. Most of these modulated genes showed an expression similar to that of normal controls after immunoglobulin replacement. Real time RT-PCR of selected genes and serum levels of IL-4, CXCR4 before and after therapy changed accordingly to gene array results. Interestingly, serum levels of IL-8 remained unchanged, as the corresponding gene, before and after treatment. FACS analysis showed a marked decrease of CD8+T cells and an increase of CD4+T cells following treatment. Moreover we observed a marked increase of CD23⁻CD27⁻IgM⁻IgG⁻ B cells (centrocytes). CONCLUSIONS: Our results are in accordance with previous reports and provide further support to the hypothesis that the benefits of intravenous immunoglobulin therapy are not only related to antibody replacement but also to its ability to modulate the immune response in common variable immunodeficiency.