A time-resolved proteomic and prognostic map of COVID-19

COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease

Clinical and virological characteristics of hospitalised COVID-19 patients in a German tertiary care centre during the first wave of the SARS-CoV-2 pandemic: a prospective observational study

Purpose: Adequate patient allocation is pivotal for optimal resource management in strained healthcare systems, and requires detailed knowledge of clinical and virological disease trajectories. The purpose of this work was to identify risk factors associated with need for invasive mechanical ventilation (IMV), to analyse viral kinetics in patients with and without IMV and to provide a comprehensive description of clinical course. Methods: A cohort of 168 hospitalised adult COVID-19 patients enrolled in a prospective observational study at a large European tertiary care centre was analysed. Results: Forty-four per cent (71/161) of patients required invasive mechanical ventilation (IMV). Shorter duration of symptoms before admission (aOR 1.22 per day less, 95% CI 1.10-1.37, p < 0.01) and history of hypertension (aOR 5.55, 95% CI 2.00-16.82, p < 0.01) were associated with need for IMV. Patients on IMV had higher maximal concentrations, slower decline rates, and longer shedding of SARS-CoV-2 than non-IMV patients (33 days, IQR 26-46.75, vs 18 days, IQR 16-46.75, respectively, p < 0.01). Median duration of hospitalisation was 9 days (IQR 6-15.5) for non-IMV and 49.5 days (IQR 36.8-82.5) for IMV patients. Conclusions: Our results indicate a short duration of symptoms before admission as a risk factor for severe disease that merits further investigation and different viral load kinetics in severely affected patients. Median duration of hospitalisation of IMV patients was longer than described for acute respiratory distress syndrome unrelated to COVID-19

Near-surface Iron Cation Transport in Magnetite

Magnetite ($\text{Fe}_3\text{O}_4$), one of the first known magnetic materials, has multiple applications as for example as a catalyst or catalyst component. Magnetite nanoparticles are used as contrast agents in medicine or building blocks in novel hierarchical materials with outstanding mechanical properties. Magnetite thin-films are promising for the development of spintronic devices. For all these applications the surface structure and the processes in the near-surface region of magnetite are crucial.On the magnetite (001) surface a non-stoichiometric $(\sqrt{2} × \sqrt{2}) R45^\circ$ reconstruction is observed after preparation in ultra-high vacuum (UHV). The reconstruction’s structural motif was found to be the combination of a tetrahedrally coordinated interstitial cation and two octahedrally coordinated vacancies in the subjacent layer. Lifting of the reconstruction by adsorption of molecules or annealing therefore requires cation transport processes to fill the vacancies with cations from the bulk. During annealing to 900 K at $1.3 × 10^{−6}$ mbar oxygen an oxidative regrowth of new magnetite layers was observed on the (001) surface. The cations forming the new layers are supplied by the oxidation of magnetite to haematite deep in the bulk.Transport processes involved in the lifting of the reconstruction or the regrowth phenomenon were monitored under UHV conditions in the temperature range from 470-770 K relevant for catalysis applications and the manufacturing of magnetite-based materials and devices. Under these conditions, magnetite is thermodynamically unstable, but the phase transfer to thermodynamically stable haematite is kinetically hindered due to the energy needed to transform the cubic magnetite to the hexagonal haematite structure and the low energy gain of the phase transformation. Oxidation instead leads to the formation of a kinetically stabilised cubic maghemite phase.Cation transport was observed at the interface of isotopically labelled $^{57}\text{Fe}_3\text{O}_4$ thin-films and magnetite substrates by neutron reflectivity (NR), nuclear forward scattering (NFS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). The growth, structure and surface morphology of the thin-films were studied by surface X-ray diffraction (SXRD), low-energy electron diffraction (LEED), Auger electron spectroscopy (AES), X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). Magnetite thin-films were homoepitaxially grown by reactive molecular beam epitaxy. Chemical characterisation by AES and XPS showed that the prepared thin-films had a close to perfect magnetite stoichiometry. The thin-film structures were characterised by SXRD, LEED and XRR indicating a slightly reduced density of the thin-films and a minor contraction of their structure along the surface normal, otherwise being in good agreement with the structure of magnetite. X-ray growth intensity oscillations observed during the deposition indicated an ordered layer-by-layer growth of magnetite. Modelling the oscillations with the birth-death model of epitaxy indicated a slightly reduced order of the growth process for increasing growth rates. The modelled growth unit corresponds to 1/4 of the unit cell of magnetite. AFM images of the thin-films but also of substrates heated under growth conditions at 420 K in $8 × 10^{−7}$ mbar oxygen showed large flat islands covering the surface. The islands result most likely from the regrowth process described above. They seem to be formed in parallel to the homoepitaxial growth process and might partly explain the deviations of the thin-film and the bulk magnetite structure discussed above.Cation transport in the near-surface region was observed by monitoring the interface of a $^{57}\text{Fe}_3\text{O}_4$ thin-film and its magnetite substrate. A considerable intermixing at the isotopic interface resulting from the growth procedure was already observed before the actual transport experiment. Cation transport was induced by annealing the thin-films in UHV. Changes of the $^{57}\text{Fe}$ distribution were found by NR, NFS and ToF-SIMS starting at 470 K. Using NFS, the changes could be attributed predominantly to the octahedrally coordinated cations. Under the given slightly oxidising conditions, cation transport via the octahedral sublattice is also predicted by the point defect model developed for the cation transport in the volume of thermodynamically stable magnetite. The diffusion coefficients estimated from NR and NFS are, however, four to five orders of magnitude smaller than expected from the point defect model. The discrepancy might be explained partly by the defect structure and the complex surface morphology of the thin-films. As the experiments were carried out outside the thermodynamic stability range of magnetite side effects may have taken place slowing down the statistical transport of $^{57}\text{Fe}$ along the surface normal.The observation of cation migration in the near-surface region of magnetite at only 470 K clearly shows that growth and transport processes are non-negligible for the manufacturing process and the application of magnetite based structures

Size-Dependent Phase Transfer Functionalization of Gold Nanoparticles To Promote Well-Ordered Self-Assembly

We present a route for the functionalization of gold nanoparticles (AuNP) based on phase transfer functionalization in order to optimize the stability and the potential for self-assembly. Depending on the desired size, different ligand exchanges have to be employed: The maximum AuNP size that can be stabilized without concentration loss is 46 nm for polystyrene-based ligands with 5 and 10 kDa. Small particles <12 nm are better stabilized by smaller ligands. We are able to demonstrate that well-ordered close-packed monolayers of 28 nm AuNP covering at least 400 μm² are possible with a potential for much larger areas. Such monolayers are of great interest for various fundamental experiments in the context of plasmonics and SERS and for sensor applications