The role of immune suppression in COVID-19 hospitalization: clinical and epidemiological trends over three years of SARS-CoV-2 epidemic

Specific immune suppression types have been associated with a greater risk of severe COVID-19 disease and death. We analyzed data from patients >17 years that were hospitalized for COVID-19 at the “Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico” in Milan (Lombardy, Northern Italy). The study included 1727 SARS-CoV-2-positive patients (1,131 males, median age of 65 years) hospitalized between February 2020 and November 2022. Of these, 321 (18.6%, CI: 16.8–20.4%) had at least one condition defining immune suppression. Immune suppressed subjects were more likely to have other co-morbidities (80.4% vs. 69.8%, p < 0.001) and be vaccinated (37% vs. 12.7%, p < 0.001). We evaluated the contribution of immune suppression to hospitalization during the various stages of the epidemic and investigated whether immune suppression contributed to severe outcomes and death, also considering the vaccination status of the patients. The proportion of immune suppressed patients among all hospitalizations (initially stable at <20%) started to increase around December 2021, and remained high (30–50%). This change coincided with an increase in the proportions of older patients and patients with co-morbidities and with a decrease in the proportion of patients with severe outcomes. Vaccinated patients showed a lower proportion of severe outcomes; among non-vaccinated patients, severe outcomes were more common in immune suppressed individuals. Immune suppression was a significant predictor of severe outcomes, after adjusting for age, sex, co-morbidities, period of hospitalization, and vaccination status (OR: 1.64; 95% CI: 1.23–2.19), while vaccination was a protective factor (OR: 0.31; 95% IC: 0.20–0.47). However, after November 2021, differences in disease outcomes between vaccinated and non-vaccinated groups (for both immune suppressed and immune competent subjects) disappeared. Since December 2021, the spread of the less virulent Omicron variant and an overall higher level of induced and/or natural immunity likely contributed to the observed shift in hospitalized patient characteristics. Nonetheless, vaccination against SARS-CoV-2, likely in combination with naturally acquired immunity, effectively reduced severe outcomes in both immune competent (73.9% vs. 48.2%, p < 0.001) and immune suppressed (66.4% vs. 35.2%, p < 0.001) patients, confirming previous observations about the value of the vaccine in preventing serious disease

Neutralizing antibodies to Omicron after the fourth SARS-CoV-2 mRNA vaccine dose in immunocompromised patients highlight the need of additional boosters

IntroductionImmunocompromised patients have been shown to have an impaired immune response to COVID-19 vaccines.MethodsHere we compared the B-cell, T-cell and neutralizing antibody response to WT and Omicron BA.2 SARS-CoV-2 virus after the fourth dose of mRNA COVID-19 vaccines in patients with hematological malignancies (HM, n=71), solid tumors (ST, n=39) and immune-rheumatological (IR, n=25) diseases. The humoral and T-cell responses to SARS-CoV-2 vaccination were analyzed by quantifying the anti-RBD antibodies, their neutralization activity and the IFN-γ released after spike specific stimulation.ResultsWe show that the T-cell response is similarly boosted by the fourth dose across the different subgroups, while the antibody response is improved only in patients not receiving B-cell targeted therapies, independent on the pathology. However, 9% of patients with anti-RBD antibodies did not have neutralizing antibodies to either virus variants, while an additional 5.7% did not have neutralizing antibodies to Omicron BA.2, making these patients particularly vulnerable to SARS-CoV-2 infection. The increment of neutralizing antibodies was very similar towards Omicron BA.2 and WT virus after the third or fourth dose of vaccine, suggesting that there is no preferential skewing towards either virus variant with the booster dose. The only limited step is the amount of antibodies that are elicited after vaccination, thus increasing the probability of developing neutralizing antibodies to both variants of virus.DiscussionThese data support the recommendation of additional booster doses in frail patients to enhance the development of a B-cell response directed against Omicron and/or to enhance the T-cell response in patients treated with anti-CD20

Diversity of metallo-β-lactamase-encoding genes found in distinct species of Acinetobacter isolated from the Brazilian Amazon Region

Evandro Chagas Institute, CAPES grants to APS and CSN (DS-CAPES), CNPq (grant to ACG - Process nº 305535/2014-5).Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Universidade Federal de São Paulo. Instituto de Ciências Ambientais, Químicas e Farmacêuticas. Departamento de Ciências Biológicas. Setor de Biologia Molecular, Microbiologia e Imunologia. Diadema, SP, Brasil.Universidade Federal de São Paulo. Departamento de Medicina. Escola Paulista de Medicina. Laboratório Alerta. Disciplina de Infectologia. São Paulo, SP, Brasil.Universidade Federal de São Paulo. Departamento de Medicina. Escola Paulista de Medicina. Laboratório Alerta. Disciplina de Infectologia. São Paulo, SP, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Centro de Inovação Tecnológica. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Centro de Inovação Tecnológica. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Centro de Inovação Tecnológica. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Universidade Federal de São Paulo. Departamento de Medicina. Escola Paulista de Medicina. Laboratório Alerta. Disciplina de Infectologia. São Paulo, SP, Brasil.Hospital Fundação Santa Casa de Misericórdia do Pará. Belém, PA, Brasil.BACKGROUND: The multidrug resistance (MDR) phenotype is frequently observed in Acinetobacter baumannii, the most clinically relevant pathogenic species of its genus; recently, other species belonging to the A. calcoaceticus-A. baumannii complex have emerged as important MDR nosocomial pathogens. OBJECTIVES: The present study aimed to verify the occurrence of metallo-β-lactamase genes among distinct Acinetobacter species in a hospital located in the Brazilian Amazon Region. METHODS: Antimicrobial susceptibility profiles were determined by broth microdilution. The genetic relationships among these isolates were assessed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Pyrosequencing reads of plasmids carrying the bla NDM-1 gene were generated using the Ion Torrent™ platform sequencing. FINDINGS: A total of six isolates carried bla NDM-1: A. baumannii (n = 2), A. nosocomialis (n = 3), and A. pittii (n = 1); three carried bla IMP-1: A. baumannii, A. nosocomialis, and A. bereziniae. Resistance to colistin was observed for an NDM-1-producing A. nosocomialis isolate. Diverse PFGE patterns and sequence types were found among A. nosocomialis and A. baumannii isolates. The bla NDM-1 sequence was inserted in a Tn125 transposon, while the bla IMP-1 was found as a gene cassette of the class 1 integron In86. MAIN CONCLUSIONS: To the best of our knowledge, this is the first report describing the dissemination of bla NDM-1 among distinct Acinetobacter species recovered from the same hospital in South America

Prediction of Breast Cancer Histological Outcome by Radiomics and Artificial Intelligence Analysis in Contrast-Enhanced Mammography

Purpose: To evaluate radiomics features in order to: differentiate malignant versus benign lesions; predict low versus moderate and high grading; identify positive or negative hormone receptors; and discriminate positive versus negative human epidermal growth factor receptor 2 related to breast cancer. Methods: A total of 182 patients with known breast lesions and that underwent Contrast-Enhanced Mammography were enrolled in this retrospective study. The reference standard was pathology (118 malignant lesions and 64 benign lesions). A total of 837 textural metrics were extracted by manually segmenting the region of interest from both craniocaudally (CC) and mediolateral oblique (MLO) views. Non-parametric Wilcoxon–Mann–Whitney test, receiver operating characteristic, logistic regression and tree-based machine learning algorithms were used. The Adaptive Synthetic Sampling balancing approach was used and a feature selection process was implemented. Results: In univariate analysis, the classification of malignant versus benign lesions achieved the best performance when considering the original_gldm_DependenceNonUniformity feature extracted on CC view (accuracy of 88.98%). An accuracy of 83.65% was reached in the classification of grading, whereas a slightly lower value of accuracy (81.65%) was found in the classification of the presence of the hormone receptor; the features extracted were the original_glrlm_RunEntropy and the original_gldm_DependenceNonUniformity, respectively. The results of multivariate analysis achieved the best performances when using two or more features as predictors for classifying malignant versus benign lesions from CC view images (max test accuracy of 95.83% with a non-regularized logistic regression). Considering the features extracted from MLO view images, the best test accuracy (91.67%) was obtained when predicting the grading using a classification-tree algorithm. Combinations of only two features, extracted from both CC and MLO views, always showed test accuracy values greater than or equal to 90.00%, with the only exception being the prediction of the human epidermal growth factor receptor 2, where the best performance (test accuracy of 89.29%) was obtained with the random forest algorithm. Conclusions: The results confirm that the identification of malignant breast lesions and the differentiation of histological outcomes and some molecular subtypes of tumors (mainly positive hormone receptor tumors) can be obtained with satisfactory accuracy through both univariate and multivariate analysis of textural features extracted from Contrast-Enhanced Mammography images

Comparison of multiple definitions for Ventilator-Associated Pneumonia in patients requiring mechanical ventilation for non-pulmonary conditions: preliminary data from PULMIVAP, an Italian multicentre cohort study

Objectives: Compare intensivist-diagnosed VAP (iVAP) with four established definitions, assessing their agreement in detecting new episodes. Methods: Analysis from multicentric prospective study on pulmonary microbiota in patients requiring mechanical ventilation (MV). Data collected were used to compare hypothetical VAP onset according to iVAP with the study consensus criteria, the European Centre for Diseases Control and Prevention definition, and two versions of the latter adjusted for leukocyte count and fever. Results: In our cohort of 186 adult patients, iVAPs were 36.6% (68/186,95%CI=30.0%-44.0%), with an incidence rate of 4.64/100 patient-MVdays, and median MV-day at diagnosis of 6. Forty-seven percent of patients (87/186) were identified as VAP by at least one criterion, with a median MV-day at diagnosis of 5. Agreement between intensivist judgement (iVAP/no-iVAP) and the criteria was highest for the study consensus criteria (50/87, 57.4%), but still one-third of iVAP was not identified and 9% of patients were identified as VAP against intensivist diagnosis. VAP proportion differed among different criteria (25.2-30.1%). Conclusions: Caution is needed evaluating studies describing VAP incidence. Pre-agreed criteria and definitions that capture VAP's evolving nature provide greater consistency, but new clinically-driven definitions are needed to align surveillance and diagnostic criteria with clinical practice

GRAd-COV2 vaccine provides potent and durable humoral and cellular immunity to SARS-CoV-2 in randomized placebo-controlled phase 2 trial

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and heterologous immunization approaches implemented worldwide for booster doses call for diversified vaccine portfolios. GRAd-COV2 is a gorilla adenovirus-based COVID-19 vaccine candidate encoding prefusion-stabilized spike. The safety and immunogenicity of GRAd-COV2 is evaluated in a dose-and regimen-finding phase 2 trial (COVITAR study, ClinicalTrials.gov: NCT04791423) whereby 917 eligible participants are randomized to receive a single intramuscular GRAd-COV2 administration followed by placebo, or two vaccine injections, or two doses of placebo, spaced over 3 weeks. Here, we report that GRAd-COV2 is well tolerated and induces robust immune responses after a single immunization; a second administration increases binding and neutralizing antibody titers. Potent, variant of concern (VOC) cross-reactive spike-specific T cell response peaks after the first dose and is characterized by high frequencies of CD8s. T cells maintain immediate effector functions and high proliferative potential over time. Thus, GRAd vector is a valuable platform for ge-netic vaccine development, especially when robust CD8 response is needed

Clinical characteristics and outcomes of vaccinated patients hospitalised with SARS-CoV-2 breakthrough infection: Multi-IPV, a multicentre study in Northern Italy

Background: Despite the well-known efficacy of anti-COVID-19 vaccines in preventing morbidity and mortality, several vaccinated individuals are diagnosed with SARS-CoV-2 breakthrough infection, which might require hospitalisation. This multicentre, observational, and retrospective study aimed to investigate the clinical characteristics and outcomes of vaccinated vs. non-vaccinated patients, both hospitalised with SARS-CoV-2 infection in 3 major hospitals in Northern Italy. Methods: Data collection was retrospective, and paper and electronic medical records of adult patients with a diagnosed SARS-CoV-2 infection were pseudo-anonymised and analysed. Vaccinated and non-vaccinated individuals were manually paired, using a predetermined matching criterion (similar age, gender, and date of hospitalisation). Demographic, clinical, treatment, and outcome data were compared between groups differing by vaccination status using Pearson’s Chi-square and Mann-Whitney tests. Moreover, multiple logistic regression analyses were performed to assess the impact of vaccination status on ICU admission or intra-hospital mortality. Results: Data from 360 patients were collected. Vaccinated patients presented with a higher prevalence of relevant comorbidities, like kidney replacement therapy or haematological malignancy, despite a milder clinical presentation at the first evaluation. Non-vaccinated patients required intensive care more often than their vaccinated counterparts (8.8% vs. 1.7%, p = 0.002). Contrariwise, no difference in intra-hospital mortality was observed between the two groups (19% vs. 20%, p = 0.853). These results were confirmed by multivariable logistic regressions, which showed that vaccination was significantly associated with decreased risk of ICU admission (aOR=0.172, 95%CI: 0.039–0.542, p = 0.007), but not of intra-hospital mortality (aOR=0.996, 95%CI: 0.582–1.703, p = 0.987). Conclusions: This study provides real-world data on vaccinated patients hospitalised with COVID-19 in Northern Italy. Our results suggest that COVID-19 vaccination has a protective role in individuals with higher risk profiles, especially regarding the need for ICU admission. These findings contribute to our understanding of SARS-CoV-2 infection outcomes among vaccinated individuals and emphasise the importance of vaccination in preventing severe disease, particularly in those countries with lower first-booster uptake rates

Digital Modernism Heritage Lexicon

The book investigates the theme of Modernism (1920-1960 and its epigones) as an integral part of tangible and intangible cultural heritage which contains the result of a whole range of disciplines whose aim is to identify, document and preserve the memory of the past and the value of the future. Including several chapters, it contains research results relating to cultural heritage, more specifically Modernism, and current digital technologies. This makes it possible to record and evaluate the changes that both undergo: the first one, from a material point of view, the second one from the research point of view, which integrates the traditional approach with an innovative one. The purpose of the publication is to show the most recent studies on the modernist lexicon 100 years after its birth, moving through different fields of cultural heritage: from different forms of art to architecture, from design to engineering, from literature to history, representation and restoration. The book appeals to scholars and professionals who are involved in the process of understanding, reading and comprehension the transformation that the places have undergone within the period under examination. It will certainly foster the international exchange of knowledge that characterized Modernism