The identification of patients with coronavirus disease 2019 and high risk of severe disease is a challenge in routine care. We performed cell phenotypic, serum, and RNA sequencing gene expression ...analyses in severe hospitalized patients (n = 61). Relative to healthy donors, results showed abnormalities of 27 cell populations and an elevation of 42 cytokines, neutrophil chemo-attractants, and inflammatory components in patients. Supervised and unsupervised analyses revealed a high abundance of CD177, a specific neutrophil activation marker, contributing to the clustering of severe patients. Gene abundance correlated with high serum levels of CD177 in severe patients. Higher levels were confirmed in a second cohort and in intensive care unit (ICU) than non-ICU patients (P < 0.001). Longitudinal measurements discriminated between patients with the worst prognosis, leading to death, and those who recovered (P = 0.01). These results highlight neutrophil activation as a hallmark of severe disease and CD177 assessment as a reliable prognostic marker for routine care.
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•Increase in B cells, activated CD8 T cells, NKT, and γδ T NKG2A + cells in severe COVID-19•Severe COVID-19 is characterized by an increase of neutrophil and inflammatory markers•Serum CD177 protein levels are increased in patients with COVID-19 in ICU•Sustained high levels of CD177 discriminated recovery and death of patients with COVID-19
Immunology; Virology
A better understanding of the immunological markers associated with long-lasting immune responses to SARS-CoV-2 infection is of paramount importance. In the present study, we characterized ...SARS-CoV-2-specific humoral responses in hospitalized (ICU and non-ICU) and non-hospitalized individuals at six months post-onset of symptoms (POS) (N = 95). We showed that the proportion of individuals with detectable anti-SARS-CoV-2 IgG or neutralizing (NAb) responses and the titers of antibodies were significantly reduced in non-hospitalized individuals, compared to ICU- or non-ICU-hospitalized individuals at 6 months POS. Interestingly, SARS-CoV-2-specific memory B cells persist at 6 months POS in both ICU and non-ICU patients and were enriched in cells harboring an activated and/or exhausted phenotype. The frequency/phenotype of SARS-CoV-2-specific memory B cells and the magnitude of IgG or NAb responses at 6 months POS correlated with the serum immune signature detected at patient admission. In particular, the serum levels of CXCL13, IL-1RA, and G-CSF directly correlated with the frequency of Spike-specific B cells and the magnitude of Spike-specific IgG or NAb, while the serum levels of CXCL12 showed an antagonizing effect. Our results indicate that the balance between CXCL12 and CXCL13 is an early marker associated with the magnitude and the quality of the SARS-CoV-2 humoral memory.
Following the Swiss Federal Office of Public Health (FOPH) authorization of the rapid antigen test (RAT), we implemented the use of the RAT in the emergency ward of our university hospital for ...patients' cohorting. RAT triaging in association with RT-PCR allowed us to promptly isolate positive patients and save resources. Among 532 patients, overall sensitivities were 48.3% for Exdia and 41.2% for Standard Q
, Panbio
and BD Veritor™. All RATs exhibited specificity above 99%. Sensitivity increased to 74.6%, 66.2%, 66.2% and 64.8% for Exdia, Standard Q
, Panbio
and BD Veritor™, respectively, for viral loads above 10
copies/mL, to 100%, 97.8%, 96.6% and 95.6% for viral loads above 10
copies/mL and 100% for viral loads above 10
copies/mL. Sensitivity was significantly higher for patients with symptoms onset within four days (74.3%, 69.2%, 69.2% and 64%, respectively) versus patients with the evolution of symptoms longer than four days (36.8%, 21.1%, 21.1% and 23.7%, respectively). Among COVID-19 asymptomatic patients, sensitivity was 33%. All Immunoglobulin-A-positive patients resulted negative for RAT. The RAT might represent a useful resource in selected clinical settings as a complementary tool in RT-PCR for rapid patient triaging, but the lower sensitivity, especially in late presenters and COVID-19 asymptomatic subjects, must be taken into account.
The aim of this retrospective single-cohort study was to evaluate the clinical outcome of four-to-five implants immediately restored with metal-resin screw-retained cross-arch fixed prostheses in ...edentulous jaws 10 years after loading. One-hundred-and-four consecutive patients received four to five implants placed with a torque superior 35 Ncm. One-hundred-and-twenty-seven metal-resin screw-retained fixed prostheses (59 mandibular and 68 maxillary) were to be delivered within 3 days. Outcome measures, evaluated by the treating clinician, were: prosthesis and implant failures, prosthetic modifications, peri-implant mucositis, and biological and prosthetic complications. A total of 549 implants were placed. Twenty-one implants failed in 14 patients and 102 prostheses were remade, at least once, in 81 patients: 2 due to implant failures and 33 because of fractures of the prostheses. In particular, 25 original metal-resin prostheses had to be remade because of fractures versus only eight of the replacement monolithic metal-resin prostheses. All patients were wearing fixed prostheses at the end of the follow-up. Thirty-six biological complications occurred in 22 patients. Eighty-six prosthetic complications occurred in 42 patients. In conclusion, immediately loaded cross-arch prostheses supported by four-to-five immediately placed implants are a viable therapeutic option if robust prostheses are made.
LaMnO3 (LM) catalysts with a molar ratio of citric acid (CA) to metal (La3+ + Mn2+) nitrates ranging from 0.5 to 2 (LM0.5 to LM2) were synthesized by the citrate sol–gel method with the aim of ...studying the effect of the citric acid ratio on the physicochemical properties and the catalytic performance in hydrocarbon oxidation. Structural and morphological properties of these catalysts were characterized by X-ray diffraction (XRD) and specific surface area (N2 adsorption) measurements, while the chemical composition was determined by inductively coupled plasma atomic emission spectroscopy (ICP-OES). In the selected samples, additional characterizations were carried out by thermogravimetric and differential thermal analysis (TGA/DTA), Fourier Transform Infrared Spectroscopy (FT-IR), temperature-programmed reduction by hydrogen (H2-TPR), and X-ray photoelectron spectroscopy (XPS). The results showed that the amount of citric acid used significantly influenced the TGA/DTA profile of gels along with the physicochemical properties of the catalysts. The XRD patterns are consistent with the perovskite formation as the main phase. The segregation of a small amount of Mn3O4, detected for molar ratios ranging between 0.5 and 1.5, suggested the formation of a slightly nonstoichiometric LaMn1−xO3 phase with a relatively high content of Mn4+. The catalytic performance was evaluated in the total oxidation of two selected hydrocarbons, toluene and propene, which represent typical volatile organic compounds (VOCs). Typically, three consecutive catalytic cycles were performed in order to reach steady-state performance in toluene and propene oxidation. Moreover, the stability of the catalysts under reaction conditions was investigated through 24-h experiments at 17% of toluene conversion. The catalysts LM1.2, LM1.3, and LM1.5 showed the best catalytic performance in both hydrocarbon oxidations, well comparing with the Pd/Al2O3 used as a reference.
For more than five years, high-dimensional mass cytometry has been employed to study immunology. However, these studies have typically been performed in one laboratory on one or few instruments.
We ...present the results of a six-center study using healthy control human peripheral blood mononuclear cells (PBMCs) and commercially available reagents to test the intra-site and inter-site variation of mass cytometers and operators. We used prestained controls generated by the primary center as a reference to compare against samples stained at each individual center. Data were analyzed at the primary center, including investigating the effects of two normalization methods.
All six sites performed similarly, with CVs for both Frequency of Parent and median signal intensity (MSI) values<30%. Increased background was seen when using the premixed antibody cocktail aliquots at each site, suggesting that cocktails are best made fresh. Both normalization methods tested performed adequately for normalizing MSI values between centers. Clustering algorithms revealed slight differences between the prestained and the sites-stained samples, due mostly to the increased background of a few antibodies. Therefore, we believe that multicenter mass cytometry assays are feasible.
•A multicenter mass cytometry study was performed among six international centers.•A premixed antibody cocktail resulted in higher background for a few antibodies.•Manual gating and clustering algorithms demonstrate that all sites were adequately consistent in performance.
Functional and phenotypic characterization of virus-specific CD8 T cells against cytomegalovirus, Epstein-Barr virus, influenza (flu), and HIV-1 were performed on the basis of the ability of CD8 T ...cells to secrete IFN-γ and IL-2, to proliferate, and to express CD45RA and CCR7. Two functional distinct populations of CD8 T cells were identified: (i) dual IFN-γ/IL-2-secreting cells and (ii) single IFN-γ-secreting cells. Virus-specific IFN-γ/IL-2-secreting CD8 T cells were CD45 RA-CCR7-, whereas single IFN-γ CD8 T cells were either CD45 RA-CCR7-or CD45 RA+CCR7-. The proportion of virus-specific IFN-γ/IL-2-secreting CD8 T cells correlated with that of proliferating CD8 T cells, and the loss of HIV-1-specific IL-2-secreting CD8 T cells was associated with that of HIV-1-specific CD8 T cell proliferation. Substantial proliferation of virus-specific CD8 T cells (including HIV-1-specific CD8 T cells) was also observed in CD4 T cell-depleted populations or after stimulation with MHC class I tetramer-peptide complexes. IL-2 was the factor responsible for the CD4-independent CD8 T cell proliferation. These results indicate that IFN-γ/IL-2-secreting CD8 T cells may promote antigen-specific proliferation of CD8 T cells even in the absence of helper CD4 T cells.
The international shipping industry is facing increasingly stringent limitations on nitrogen oxide (NOx) emissions. New solutions for reducing NOx emitted by marine engines need to be investigated to ...find the best technology. Selective Catalytic Reduction (SCR) is an advanced active emissions control technology successfully used in automotive diesel engines; it could be applied to marine engines with ad-hoc solutions to integrate it in the exhaust of large engines. In this study, a commercial SCR was tested at the exhaust of a diesel engine in inlet gas conditions typical of a marine engine. The SCR system consisted of a custom monolith (provided by Hug-Engineering AG) that enabled seamless integration for a broad range of engine sizes; the active phases were V2O5 (3 wt%)-WO3 (7 wt%)-TiO2 (75 wt%). The monolith was studied at the laboratory scale for its in-depth chemical/physical characterization and by means of an intermediate-scale engine, reproducing the exhaust gas conditions of a full-scale marine engine. The system’s effectiveness in terms of NOx removal for the selected engine operating conditions was evaluated in a wide range of temperature and NOx emissions values and for different quantities of the reduction agent (AdBlue or ammonia) added to exhaust gases. The investigated technological solution resulted in efficient NOx emission control from a marine engine.
Coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 is associated with a wide spectrum of disease, ranging from asymptomatic infection to acute respiratory distress syndrome. Some biomarkers may ...predict disease severity. Among them, the anti-SARS-CoV-2 antibody response has been related to severe disease. The aim of this study was to assess the correlation between the anti-SARS-CoV-2 serological response and COVID-19 outcome. Demographic, clinical, and biological data from nasopharyngeal-PCR confirmed COVID-19 hospitalized patients were prospectively collected between April and August 2020 at our institution. All patients had serial weekly serology testing for a maximum of three blood samples or until discharge. Two different serological assays were used: a chemiluminescent assay and an in-house developed Luminex immunoassay. Kinetics of the serological response and correlation between the antibody titers and outcome were assessed. Among the 70 patients enrolled in the study, 22 required invasive ventilation, 29 required non-invasive ventilation or oxygen supplementation, and 19 did not require any oxygen supplementation. Median duration of symptoms upon admission for the three groups were 13, 8, and 9 days, respectively. Antibody titers gradually increased for up to 3 weeks since the onset of symptoms for patients requiring oxygen supplementation with significantly higher antibody titers for patients requiring invasive ventilation. Antibody titers on admission were also significantly higher in severely ill patients and serology performed well in predicting the necessity of invasive ventilation (AUC: 0.79, 95% CI: 0.67-0.9). Serology testing at admission may be a good indicator to identify severe COVID-19 patients who will require invasive mechanical ventilation.
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