Gold Nanoparticle-Based Plasmonic Biosensors.

One of the emerging technologies in molecular diagnostics of the last two decades is the use of gold nanoparticles (AuNPs) for biosensors. AuNPs can be functionalized with various biomolecules, such as nucleic acids or antibodies, to recognize and bind to specific targets. AuNPs present unique optical properties, such as their distinctive plasmonic band, which confers a bright-red color to AuNP solutions, and their extremely high extinction coefficient, which makes AuNPs detectable by the naked eye even at low concentrations. Ingenious molecular mechanisms triggered by the presence of a target analyte can change the colloidal status of AuNPs from dispersed to aggregated, with a subsequent visible change in color of the solution due to the loss of the characteristic plasmonic band. This review describes how the optical properties of AuNPs have been exploited for the design of plasmonic biosensors that only require the simple mixing of reagents combined with a visual readout and focuses on the molecular mechanisms involved. This review illustrates selected examples of AuNP-based plasmonic biosensors and promising approaches for the point-of-care testing of various analytes, spanning from the viral RNA of SARS-CoV-2 to the molecules that give distinctive flavor and color to aged whisky.

Risk stratification of patients with SARS-CoV-2 by tissue factor expression in circulating extracellular vesicles.

Inflammatory response following SARS-CoV-2 infection results in substantial increase of amounts of intravascular pro-coagulant extracellular vesicles (EVs) expressing tissue factor (CD142) on their surface. CD142-EV turned out to be useful as diagnostic biomarker in COVID-19 patients. Here we aimed at studying the prognostic capacity of CD142-EV in SARS-CoV-2 infection. Expression of CD142-EV was evaluated in 261 subjects admitted to hospital for pneumonia and with a positive molecular test for SARS-CoV-2. The study population consisted of a discovery cohort of selected patients (n = 60) and an independent validation cohort including unselected consecutive enrolled patients (n = 201). CD142-EV levels were correlated with post-hospitalization course of the disease and compared to the clinically available 4C Mortality Score as referral. CD142-EV showed a reliable performance to predict patient prognosis in the discovery cohort (AUC = 0.906) with an accuracy of 81.7%, that was confirmed in the validation cohort (AUC = 0.736). Kaplan-Meier curves highlighted a high discrimination power in unselected subjects with CD142-EV being able to stratify the majority of patients according to their prognosis. We obtained a comparable accuracy, being not inferior in terms of prediction of patients' prognosis and risk of mortality, with 4C Mortality Score. The expression of surface vesicular CD142 and its reliability as prognostic marker was technically validated using different immunocapture strategies and assays. The detection of CD142 on EV surface gains considerable interest as risk stratification tool to support clinical decision making in COVID-19.

Modelling the adsorption of proteins to nanoparticles at the solid-liquid interface.

HYPOTHESIS: We developed a geometrical model to determine the theoretical maximum number of proteins that can pack as a monolayer surrounding a spherical nanoparticle. We applied our new model to study the adsorption of receptor binding domain (RBD) of the SARS-CoV-2 spike protein to silica nanoparticles. Due to its abundance and extensive use in manufacturing, silica represents a reservoir where the virus can accumulate. It is therefore important to study the adsorption and the persistence of viral components on inanimate surfaces. EXPERIMENTS: We used previously published datasets of nanoparticle-adsorbed proteins to validate the new model. We then used integrated experimental methods and Molecular Dynamics (MD) simulations to characterise binding of the RBD to silica nanoparticles and the effect of such binding on RBD structure. FINDINGS: The new model showed excellent fit with existing datasets and, combined to new RBD-silica nanoparticles binding data, revealed a surface occupancy of 32% with respect to the maximum RBD packing theoretically achievable. Up to 25% of RBD's secondary structures undergo conformational changes as a consequence of adsorption onto silica nanoparticles. Our findings will help developing a better understanding of the principles governing interaction of proteins with surfaces and can contribute to control the spread of SARS-CoV-2 through contaminated objects.

Initiation of an inter-hospital extracorporeal membrane oxygenation transfer programme for critically ill patients with coronavirus disease 2019: bringing extracorporeal membrane oxygenation support to peripheral hospitals.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) is a resource-intensive, highly specialized and expensive therapy that is often reserved for high-volume centres. In recent years, we established an inter-hospital ECMO transfer programme that enables ECMO implants in peripheral hospitals. During the pandemic, the programme was expanded to include ECMO support in selected critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: This retrospective single-centre study reports the technical details and challenges encountered during our initial experience with ECMO implants in peripheral hospitals for patients with COVID-19. RESULTS: During March and April 2020, our team at the University Hospital of Zurich performed 3 out-of-centre ECMO implants at different peripheral hospitals. The implants were performed without any complications. The patients were transported by ambulance or helicopter. Good preparation and selection of the required supplies are the keys to success. The implant should be performed by a well-trained, seasoned ECMO team, because options are limited in most peripheral hospitals. CONCLUSIONS: Out-of-centre ECMO implants in well-selected patients with COVID-19 is feasible and safe if a well-established organization is available and if the implantation is done by an experienced and regularly trained team.