Clinical characteristics and outcomes among hospitalized adults with severe COVID-19 admitted to a tertiary medical center and receiving antiviral, antimalarials, glucocorticoids, or immunomodulation with tocilizumab or cyclosporine: A retrospective observational study (COQUIMA cohort).

BACKGROUND: The COVID-19 outbreak challenges the Spanish health system since March 2020. Some available therapies (antimalarials, antivirals, biological agents) were grounded on clinical case observations or basic science data. The aim of this study is to describe the characteristics and impact of different therapies on clinical outcomes in a cohort of severe COVID-19 patients. METHODS: In this retrospective, single-center, observational study, we collected sequential data on adult patients admitted to Hospital Universitario Quironsalud Madrid. Eligible patients should have a microbiological (positive test on RT-PCR assay from a nasal swab) or an epidemiological diagnosis of severe COVID-19. Demographic, baseline comorbidities, laboratory data, clinical outcomes, and treatments were compared between survivors and non-survivors. We carried out univariate and multivariate logistic regression models to assess potential risk factors for in-hospital mortality. FINDINGS: From March 10th to April 15th, 2020, 607 patients were included. Median age was 69 years [interquartile range, {IQR} 22; 65% male). The most common comorbidities were hypertension (276 [46·94%]), diabetes (95 [16·16%]), chronic cardiac (133 [22·62%]) and respiratory (114 [19·39%]) diseases. 141 patients (23·2%) died. In the multivariate model the risk of death increased with older age (odds ratio, for every year of age, 1·15, [95% CI 1·11 - 1·2]), tocilizumab therapy (2·4, [1·13 - 5·11]), C-reactive protein at admission (1·07, per 10 mg/L, [1·04 - 1·10]), d-dimer > 2·5 µg/mL (1·99, [1·03 - 3·86]), diabetes mellitus (2·61, [1·19 - 5·73]), and the PaO2/FiO2 at admission (0·99, per every 1 mmHg, [0·98 - 0·99]). Among the prescribed therapies (tocilizumab, glucocorticoids, lopinavir/ritonavir, hydroxychloroquine, cyclosporine), only cyclosporine was associated with a significant decrease in mortality (0·24, [0·12 - 0·46]; p<0·001). INTERPRETATION: In a real-clinical setting, inhibition of the calcineurin inflammatory pathway, NF-κΒ, could reduce the hyperinflammatory phase in COVID-19. Our findings might entail relevant implications for the therapy of this disease and could boost the design of new clinical trials among subjects affected by severe COVID-19. FUNDING: Hospital Universitario Quironsalud Madrid. Own fundings for COVID-19 research.

Size-dependent and step-modulated supramolecular electrochemical properties of catechol-derived adlayers at Pt(hkl) surfaces.

The electrochemical reactivity of catechol-derived adlayers is reported at platinum (Pt) single-crystal electrodes. Pt(111) and stepped vicinal surfaces are used as model surfaces possessing well-ordered nanometer-sized Pt(111) terraces ranging from 0.4 to 12 nm. The electrochemical experiments were designed to probe how the control of monatomic step-density and of atomic-level step structure can be used to modulate molecule-molecule interactions during self-assembly of aromatic-derived organic monolayers at metallic single-crystal electrode surfaces. A hard sphere model of surfaces and a simplified band formation model are used as a theoretical framework for interpretation of experimental results. The experimental results reveal (i) that supramolecular electrochemical effects may be confined, propagated, or modulated by the choice of atomic level crystallographic features (i.e.monatomic steps), deliberately introduced at metallic substrate surfaces, suggesting (ii) that substrate-defect engineering may be used to tune the macroscopic electronic properties of aromatic molecular adlayers and of smaller molecular aggregates.

Electrochemical reactivity of aromatic molecules at nanometer-sized surface domains: from Pt(hkl) single crystal electrodes to preferentially oriented platinum nanoparticles.

This manuscript compares the electrochemically controlled adsorption of hydroquinone-derived adlayers and their reductive desorption from nanometer-sized Pt(111) domains present on the surface (i) of model stepped single-crystal electrodes and (ii) of preferentially oriented Pt nanoparticles. The results obtained using a stepped surface series, i.e., Pt(S)[(n - 1)(111)x(110)], suggest that in the presence of 2 mM H(2)Q((aq)) the electrochemically detected desorption-adsorption process takes place selectively from ordered Pt(111) domains present as terraces, while being precluded at other available surface sites, i.e., Pt(110) steps, where adsorption takes place irreversibly. This domain-selective electroanalytical detection scheme is employed later to selectively monitor desorption-adsorption of hydroquinone-derived adlayers from ordered, nanometer-scaled Pt(111) domains on the surface of preferentially oriented Pt nanoparticles, confirming the existence of well-ordered (111) domains on the surface of the Pt nanoparticles. A good correlation is noted between the electrochemical behavior at well-ordered Pt(hkl) surfaces and at preferentially oriented Pt nanoparticles. Key learnings and potential applications are discussed. The results demonstrate the technical feasibility of performing domain-selective decapping of nanoparticles by handle of an externally controlled parameter, i.e., the applied potential.

Use of model Pt(111) single crystal electrodes under HMRDE configuration to study the redox mechanism for charge injection at aromatic/metal interfaces.

The electrochemical reactivity of hydroquinone-derived, catechol-derived and benzene-derived adlayers is compared at Pt(111) single-crystal surfaces (i) under stagnant hanging meniscus (HM) configuration and (ii) under hydrodynamic conditions imposed by combining the HM configuration with the rotating disk electrode (RDE) that merge in the so-called HMRDE technique. For the three cases studied, the results suggest that reductive desorption of the adlayers can be accomplished in aqueous 0.5 M H(2)SO(4) solutions within the time frame of a single cathodic scan, i.e. the first half of a single CV experiment. The results highlight the simplicity of exploiting the hydrodynamic conditions imposed by RDE as a convenient electroanalytical strategy to elucidate controversies regarding whether desorption takes place or not during electrode processes studied under the HM configuration.

Domain-selective reactivity of hydroquinone-derived adlayers at basal Pt(hkl) single-crystal electrodes.

The electrochemical reactivity of hydroquinone-derived adlayers (Q((ads))) is compared at basal Pt(hkl) single-crystal surfaces, revealing that the electrochemically controlled desorption of Q((ads)) is a highly selective surface reaction. At well-ordered Pt(111) single-crystal surfaces, classical electrochemical methods are combined with in situ SNIFTIRS measurements to demonstrate that the reductive desorption of Q((ads)) and their full oxidative readsorption can be achieved, even in the presence of hydroquinone solution (H(2)Q(aq)), by controlling the potential of Pt(111) electrodes. At well-ordered Pt(111) domains, the presence of vertically adsorbed molecules within the Q((ads)) adlayer is deduced from the spectroelectrochemical SNIFTIRS measurements. The desorption mechanism, detected voltammetrically at Pt(111) electrodes, is precluded at well-ordered Pt(110) and Pt(100) single-crystal electrodes immersed in hydroquinone-containing solutions, requiring the presence of well-ordered Pt(111) surface domains in order to be detected. In clean supporting electrolyte, the partial desorption of Q((ads)) layers may take place, but predominantly from minority surface imperfections at Pt(110) and Pt(100) via a different mechanism than at Pt(111) surface domains.

Model system for the study of 2D phase transitions and supramolecular interactions at electrified interfaces: hydrogen-assisted reductive desorption of catechol-derived adlayers from Pt(111) single-crystal electrodes.

Classical electroanalytical techniques and in situ FTIR are used to study the oxidative chemisorption of catechol (o-H(2)Q) and the hydrogen-assisted reductive desorption of catechol-derived adlayers (o-Q((ads))) at nearly defect-free Pt(111) single-crystal electrodes in 0.5 M H(2)SO(4). At near equilibrium conditions (lim(upsilon-->0)) the cyclic voltammetric response does not conform to the behavior expected from classical models of molecular adsorption at electrochemical interfaces. Instead, attractive interactions play a controlling role, i.e., hydrogen-assisted displacement of o-Q((ads)) takes place as an electrochemically reversible two-dimensional (2D) phase transition controlled by collision-nucleation-growth phenomena in the presence of 2 mM o-H(2)Q((aq)). In contrast, different desorption dynamics are observed when the reductive desorption of the adlayers is carried out in clean (0 mM o-H(2)Q((aq)) supporting electrolyte. Donor-acceptor (DA) interactions between the Pt(111)/o-Q((ads)) surface adduct and o-H(2)Q((aq)) are postulated as a possible intervening mechanism leading to the observed differences in the macroscopic electrochemical responses. The results also demonstrate that in aqueous solutions it is thermodynamically feasible to shift the formal oxidation potential of catechol-metal adducts to potentials near those of molecular hydrogen via chemically reversible, nondissociative interactions, taking place as a 2D phase transition.