Chagas Disease and Transfusion Risk in Italy: The Results of a National Survey.

BACKGROUND: Universal serological screening in endemic areas is essential for preventing Chagas disease transmission by transfusions, while in non-endemic areas, screening is provided only to donors exposed to the infection risk. In this respect, in order to ensure high and uniform standards of quality and safety of blood components, the Italian National Blood Centre conducted a survey to detect information on management of donors at risk of Chagas disease and on the current transfusion risk. METHODS: The National Blood Centre conducted a survey on preventive measures for Chagas disease in the years 2020-2021. RESULTS: Survey results are broadly representative of the national situation; out of 24,269 tested donors, only 15 donors were confirmed positive (0.4 out of 100,000 donors). This rate is lower than the number of positive donors (72/100,000) for transfusion transmissible infections (HIV, HBV, HCV, and T. pallidum) in the same period. Furthermore, the number of T. cruzi positive blood donors is lower than the T. cruzi positive subjects in the general population. CONCLUSIONS: In Italy, T. cruzi infection transfusion risk may be considered still very low, and this is confirmed by the absence of documented transfusion transmission.

Neutralizing Antibody Responses to SARS-CoV-2 in Recovered COVID-19 Patients Are Variable and Correlate With Disease Severity and Receptor-Binding Domain Recognition.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) caused outbreaks of the pandemic starting from the end of 2019 and, despite ongoing vaccination campaigns, still influences health services and economic factors globally. Understanding immune protection elicited by natural infection is of critical importance for public health policy. This knowledge is instrumental to set scientific parameters for the release of "immunity pass" adopted with different criteria across Europe and other countries and to provide guidelines for the vaccination of COVID-19 recovered patients. Here, we characterized the humoral response triggered by SARS-CoV-2 natural infection by analyzing serum samples from 94 COVID-19 convalescent patients with three serological platforms, including live virus neutralization, pseudovirus neutralization, and ELISA. We found that neutralization potency varies greatly across individuals, is significantly higher in severe patients compared with mild ones, and correlates with both Spike and receptor-binding domain (RBD) recognition. We also show that RBD-targeting antibodies consistently represent only a modest proportion of Spike-specific IgG, suggesting broad specificity of the humoral response in naturally infected individuals. Collectively, this study contributes to the characterization of the humoral immune response in the context of natural SARS-CoV-2 infection, highlighting its variability in terms of neutralization activity, with implications for immune protection in COVID-19 recovered patients.

Outcome of SARS CoV-2 inpatients treated with convalescent plasma: One-year of data from the Veneto region (Italy) Registry.

OBJECTIVES AND BACKGROUND: Convalescent plasma (CP) has been used worldwide to contrast SARS-CoV-2 infection. Since April 2020, it has also been used in the treatment of patients with COVID-19 in the Veneto region (Italy), along with all the other available drugs and therapeutic tools. Here we report data analysis and clinical results in 1,517 COVID-19 inpatients treated with CP containing high-titre neutralizing anti-SARS-CoV-2 antibodies (CCP). Mortality after 30 days of hospitalization has been considered primary outcome, by comparing patients treated with CCP vs all COVID-19 patients admitted to hospitals of the Veneto region in a one-year period (from April 2020 to April 2021). PATIENTS AND METHODS: Adult inpatients with a severe form of COVID-19 have been enrolled, with at least one of the following inclusion criteria: 1) tachypnea with respiratory rate (RR) ≥ 30 breaths/min; 2) oxygen saturation (SpO2) ≤ 93% at rest and in room air; 3) partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ≤ 200 mmHg, 4) radiological picture and/or chest CT scan showing signs of interstitial disease and/or rapid progression of lung involvement. Patients received a maximum of three therapeutic fractions (TFs) of CCP with a neutralizing antibody titre of ≥ 1:160, administered over a period of 3-5 days. If TFs of CCP with titre ≥ 1:160 were unavailable, 2 with antibody titre of ≥ 1:80 have been administered. RESULTS: Of the 1,517 patients treated with CCP, 209 deceased at the 30-day follow-up (14%). Death was significantly associated with an older age (p<0.001), a longer time of hospitalization before CCP infusion (p<0.001), a greater number of inclusion criteria (p<0.001) and associated comorbidities (p<0.001). Conditions significantly associated with an increased frequency of death were PaO2/FiO2 ≤ 200 (p<0.001) and tachypnea with RR>30 (p<0.05) at entry, concurrent arterial hypertension (p<0.001), cardiovascular disease (p<0.001), chronic kidney disease (p<0.001), dyslipidemia (p<0.05) and cancer (p<0.05). Moreover, factors leading to an unfavorable prognosis were a life-threatening disease (p<0.001), admission to Intensive Care Unit (p<0.001), high flow oxygen therapy or mechanical ventilation (p<0.05) and a chest X-ray showing consolidation area (p<0.001). By analyzing the regional report of hospitalized patients, a comparison of mortality by age group, with respect to our series of patients treated with CCP, has been made. Mortality was altogether lower in patients treated with CCP (14% v. 25%), especially in the group of the elderly patients (23% vs 40%,), with a strong significance (p<0.001). As regards the safety of CCP administration, 16 adverse events were recorded out of a total of 3,937 transfused TFs (0,4%). CONCLUSIONS: To overcome the difficulties of setting up a randomized controlled study in an emergency period, a data collection from a large series of patients with severe COVID-19 admitted to CCP therapy with well-defined inclusion criteria has been implemented in the Veneto region. Our results have shown that in patients with severe COVID-19 early treatment with CCP might contribute to a favourable outcome, with a reduced mortality, in absence of relevant adverse events.

Emerging role of monocytes and their intracellular calcium pattern in spondyloarthritis.

Spondyloarthritis (SpA) comprises multifactorial diseases characterized by a complex interplay between an inherited background and environmental factors that lead to immune response dysregulation and inflammation. Unlike for other rheumatic diseases, no specific biomarkers are available in clinical practice for diagnosing SpA. The aim of the present study was to search new potential biomarkers for SpA diagnosis by focusing on the innate immune response. An evaluation was made of the mRNA expression levels of inflammatory cytokines (TNF-α, IL-1ß, TGF-ß1, S100A8, S100A9) and matrix metalloproteinases (MMP3, MMP8, MMP9) in blood mononuclear cells of SpA patients (n = 64) with respect to controls (n = 100). In parallel, the pattern of intracellular calcium flows of blood monocytes was verified in order to ascertain whether any specific fingerprint characterizes innate immune cells in SpA patients. Inflammatory cytokines and MMPs expression levels were not correlated with SpA, while in this disease a reduced expression of the S100A8 and a decreased frequency of monocytes showing intracellular calcium flows were observed. In conclusion, no specific signs of systemic inflammation are detectable in SpA, but the disease affects the "on-off" mechanisms that regulate the concentration of intracellular calcium and calcium-related proteins. This potentially pave the way for the discovery of new biomarkers.

Incidental finding of monoclonal gammopathy in blood donors: a follow-up study.

BACKGROUND: The incidental finding of monoclonal immunoglobulin in the sera of healthy blood donors is a relatively frequent event and in such cases the subjects are commonly deferred permanently from donating blood. However, no follow-up studies of these cases have been published so far. MATERIALS AND METHODS: Since 2000, all regular blood donors at Trieste Blood Bank have undergone annual screening by serum protein electrophoresis. Cases presenting with monoclonal gammopathy between January 2000 and December 2008 were registered and follow-up was performed until December 2010. RESULTS: Out of 8,197 regular blood donors, monoclonal gammopathy was detected in 104 subjects (1.3%). The median age at detection was 53 years, the median monoclonal protein concentration was 0.2 g/dL and the cumulative follow-up of these cases amounted to 763 person/years. In two cases asymptomatic multiple myeloma was diagnosed within 6 months of detection of the gammopathy and in 14 cases, the monoclonal gammopathy was transient. The remaining 88 cases were classified as having monoclonal gammopathy of undetermined significance (MGUS). Out of these, two events related to monoclonal gammopathy were observed during the follow up: one lymphoma and one light chain deposition nephropathy. DISCUSSION: According to current prognostic staging systems, the majority of blood donors with monoclonal gammopathy were classified as having low-risk MGUS and had a very low incidence of lymphoproliferative diseases. Permanent deferral of blood donors with stable MGUS causes about a 1% loss of potential blood donations and it represents a "precautionary measure" that needs to be substantiated and validated.