255 research outputs found

    SARS-CoV-2 antibodies protect against reinfection for at least 6 months in a multicentre seroepidemiological workplace cohort

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    dentifying the potential for SARS-CoV-2 reinfection is crucial for understanding possible long-term epidemic dynamics. We analysed longitudinal PCR and serological testing data from a prospective cohort of 4,411 United States employees in 4 states between April 2020 and February 2021. We conducted a multivariable logistic regression investigating the association between baseline serological status and subsequent PCR test result in order to calculate an odds ratio for reinfection. We estimated an odds ratio for reinfection ranging from 0.14 (95% CI: 0.019 to 0.63) to 0.28 (95% CI: 0.05 to 1.1), implying that the presence of SARS-CoV-2 antibodies at baseline is associated with around 72% to 86% reduced odds of a subsequent PCR positive test based on our point estimates. This suggests that primary infection with SARS-CoV-2 provides protection against reinfection in the majority of individuals, at least over a 6-month time period. We also highlight 2 major sources of bias and uncertainty to be considered when estimating the relative risk of reinfection, confounders and the choice of baseline time point, and show how to account for both in reinfection analysis.The authors received funding from the following sources: EF was funded by the Medical Research Council (MR/N013638/1); AJK was supported by Wellcome Trust (206250/Z/17/Z) and National Institute for Health Research (NIHR200908); RL was funded by a Royal Society Dorothy Hodgkin Fellowship (https://royalsociety.org). EN was supported by the US Centers for Disease Control and Prevention (U01 U01GH002238). AM was supported by the Translational Research Institute for Space Health through NASA Cooperative Agreement (https://www.nasa.gov/hrp/tri; NNX16AO69A). GA was supported by the Massachusetts Consortium on Pathogen Readiness (https://masscpr.hms.harvard.edu/; MassCPR), the National Institutes of Health (3R37AI080289-11S1, R01AI146785, U19AI42790-01, U19AI135995-02, 1U01CA260476-01) and the Musk Foundation (http://www.muskfoundation.org/). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript."Article signat per 18 autors/es: Emilie Finch ,Rachel Lowe,Stephanie Fischinger,Michael de St Aubin,Sameed M. Siddiqui,Diana Dayal,Michael A. Loesche,Justin Rhee,Samuel Beger,Yiyuan Hu,Matthew J. Gluck,Benjamin Mormann,Mohammad A. Hasdianda,Elon R. Musk,Galit Alter,Anil S. Menon ,Eric J. Nilles ,Adam J. Kucharski ,on behalf of the CMMID COVID-19 working group and the SpaceX COVID-19 Cohort Collaborative"Postprint (author's final draft

    Organische Dünger in Topfkulturen auf dem Prüfstand - wie steht es mit der Stickstofffreisetzung?

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    Matching nitrogen demand of plants and N release of organic fertilizers with respect to amount and timing is one key for successful cultivation of organic ornamentals. Thereby for plants with a low to moderate N demand growers can add the fertilizer as complete preplant application (CPA). For plants with a high N demand splitting fertilization in a reduced preplant application combined with an additional fertigation (RPA+F) is preferable. Aim of the current research was the investigation of N release of organic fertilizers in incubation experiments. Results of the incubation experiment were linked to a pot trial with pelargonium. Incubation experiments reveal that most fertilizers release about 40 to 50 % of total N and most nitrogen is released within the first 21 days. Only for sheep wool a delay of N release up to ten days was found. CPA using sheep wool and RPA+F (irrespective of fertilizer) give the best results. The delayed release pattern of sheep wool seems to match best N demand of plants

    Numerical modelling for earthquake engineering: the case of lightly RC structural walls

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    Different types of numerical models exist to describe the non‐linear behaviour of reinforced concrete structures. Based on the level of discretization they are often classified as refined or simplified ones. The efficiency of two simplified models using beam elements and damage mechanics in describing the global and local behaviour of lightly reinforced concrete structural walls subjected to seismic loadings is investigated in this paper. The first model uses an implicit and the second an explicit numerical scheme. For each case, the results of the CAMUS 2000 experimental programme are used to validate the approaches

    Cyclic shear tests on RC precast beam-to-column connections retrofitted with a three-hinged steel device

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    Recent European earthquakes demonstrated that the seismic response of RC precast structures can be significantly influenced by the connection systems. Moreover, during past seismic events, many failures of the beam-to-column connections occurred due to their inadequate strength under seismic loads. The seismic safety of these connections has a crucial role in the overall seismic capacity of existing precast structures. A new connection system is employed as a retrofitting solution for a damaged beam-to-column connection and its cyclic shear performance is investigated by means of two cyclic shear tests on two different configurations. In both the experimental tests, the results demonstrate an efficient behavior of the retrofitted connections under horizontal cyclic loads. The comparison between the performance of the investigated connection and the response of a typical beam-to-column dowel connection allows to discuss the main critical features of the dowel connection system

    Measurement of sulfatides in the amniotic fluid supernatant : a useful tool in the prenatal diagnosis of metachromatic leukodystrophy

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    Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal disorder caused by deficiency of arylsulfatase A (ARSA), leading to an accumulation of sulfatides. Sulfatides have been quantified in urine, dried blood spots (DBS), and tissues of patients with MLD. Newborn screening (NBS) for MLD has already been proposed based on a two-tier approach with the quantification of sulfatides in DBS followed by the quantification of ARSA by liquid chromatography–tandem mass spectrometry (LC–MS/MS). Prenatal screening for MLD is also crucial, and sulfatide quantification in amniotic fluid (AF) can aid diagnosis. The prenatal study was initiated due to a family history of MLD at 19 weeks of gestation. ARSA was quantified in cultured amniocytes. C16:0 sulfatide was quantified by LC-MS/MS in the supernatant of AF. Molecular analysis of the ARSA gene was performed in cultured amniocytes. ARSA was deficient in fetal cells, and C16:0 sulfatides were significantly elevated in comparison to age-matched controls (3-fold higher). Genetic studies identified the c.465+1G>A variant in homozygosis in the ARSA gene. Our study shows that sulfatides can be quantified in the supernatant of AF of MLD fetuses, and it could potentially aid in a faster and more accurate diagnosis of MLD patients

    Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques

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    A safe and effective vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be required to end the coronavirus disease 2019 (COVID-19) pandemic1–8. For global deployment and pandemic control, a vaccine that requires only a single immunization would be optimal. Here we show the immunogenicity and protective efficacy of a single dose of adenovirus serotype 26 (Ad26) vector-based vaccines expressing the SARS-CoV-2 spike (S) protein in non-human primates. Fifty-two rhesus macaques (Macaca mulatta) were immunized with Ad26 vectors that encoded S variants or sham control, and then challenged with SARS-CoV-2 by the intranasal and intratracheal routes9,10. The optimal Ad26 vaccine induced robust neutralizing antibody responses and provided complete or near-complete protection in bronchoalveolar lavage and nasal swabs after SARS-CoV-2 challenge. Titres of vaccine-elicited neutralizing antibodies correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate robust single-shot vaccine protection against SARS-CoV-2 in non-human primates. The optimal Ad26 vector-based vaccine for SARS-CoV-2, termed Ad26.COV2.S, is currently being evaluated in clinical trials

    Dissecting strategies to tune the therapeutic potential of SARS-CoV-2–specific monoclonal antibody CR3022

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    The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coupled with a lack of therapeutics, has paralyzed the globe. Although significant effort has been invested in identifying antibodies that block infection, the ability of antibodies to target infected cells through Fc interactions may be vital to eliminate the virus. To explore the role of Fc activity in SARS-CoV-2 immunity, the functional potential of a cross–SARS-reactive antibody, CR3022, was assessed. CR3022 was able to broadly drive antibody effector functions, providing critical immune clearance at entry and upon egress. Using selectively engineered Fc variants, no protection was observed after administration of WT IgG1 in mice or hamsters. Conversely, the functionally enhanced Fc variant resulted in increased pathology in both the mouse and hamster models, causing weight loss in mice and enhanced viral replication and weight loss in the more susceptible hamster model, highlighting the pathological functions of Fc-enhancing mutations. These data point to the critical need for strategic Fc engineering for the treatment of SARS-CoV-2 infection

    SARS-CoV-2 RBD trimer protein adjuvanted with Alum-3M-052 protects from SARS-CoV-2 infection and immune pathology in the lung

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    There is a great need for the development of vaccines that induce potent and long-lasting protective immunity against SARS-CoV-2. Multimeric display of the antigen combined with potent adjuvant can enhance the potency and longevity of the antibody response. The receptor binding domain (RBD) of the spike protein is a primary target of neutralizing antibodies. Here, we developed a trimeric form of the RBD and show that it induces a potent neutralizing antibody response against live virus with diverse effector functions and provides protection against SARS-CoV-2 challenge in mice and rhesus macaques. The trimeric form induces higher neutralizing antibody titer compared to monomer with as low as 1μg antigen dose. In mice, adjuvanting the protein with a TLR7/8 agonist formulation alum-3M-052 induces 100-fold higher neutralizing antibody titer and superior protection from infection compared to alum. SARS-CoV-2 infection causes significant loss of innate cells and pathology in the lung, and vaccination protects from changes in innate cells and lung pathology. These results demonstrate RBD trimer protein as a suitable candidate for vaccine against SARS-CoV-2
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