Background Coronavirus Disease 2019 (COVID-19) is primarily an acute respiratory tract infection. Distinctively, a substantial proportion of COVID-19 patients develop olfactory dysfunction of uncertain underlying mechanism which can be severe and prolonged. The roles of inflammatory obstruction of the olfactory clefts leading to conductive impairment, inflammatory cytokines affecting olfactory neuronal function, destruction of olfactory neurons or their supporting cells, and direct invasion of olfactory bulbs, in causing olfactory dysfunction are uncertain. Methods In this study, we investigated the location for the pathogenesis of SARS-CoV-2 from the olfactory epithelium (OE) of the nasopharynx to the olfactory bulb of golden Syrian hamsters. Results After intranasal inoculation with SARS-CoV-2, inflammatory cell infiltration and proinflammatory cytokine/chemokine responses were detected in the nasal turbinate tissues which peaked between 2 to 4 days post-infection with the highest viral load detected at day 2 post-infection. Besides the nasopharyngeal pseudo-columnar ciliated respiratory epithelial cells, SARS-CoV-2 viral antigens were also detected in the more superficial mature olfactory sensory neurons labeled by olfactory marker protein (OMP), the less mature olfactory neurons labelled by Tuj1 at more basal position, and the sustentacular cells which provide metabolic and physical support for the olfactory neurons, resulting in apoptosis and severe destruction of the OE. During the whole course of infection, SARS-CoV-2 viral antigens were not detected in the olfactory bulb. Conclusions Besides acute inflammation at OE, infection of mature and immature olfactory neurons, and the supporting sustentacular cells by SARS-CoV-2 may contribute to the unique olfactory dysfunction of COVID-19 which is not reported with SARS-CoV.

3D printing in the context of medical application can allow for visualization of patient-specific anatomy to facilitate surgical planning and execution. Intra-operative usage of models and guides allows for real time feedback but ensuring sterility is essential to prevent infection. The additive manufacturing process restricts options for sterilisation owing to temperature sensitivity of thermoplastics utilised for fabrication. Here, we review one of the largest single cohorts of 3D models and guides constructed from Acrylonitrile butadiene styrene (ABS) and utilized intra-operatively, following terminal sterilization with hydrogen peroxide plasma. We describe our work flow from initial software rendering to printing, sterilization, and on-table application with the objective of demonstrating that our process is safe and can be implemented elsewhere. Overall, 7% (8/114 patients) of patients developed a surgical site infection, which was not elevated in comparison to related studies utilizing traditional surgical methods. Prolonged operation time with an associated increase in surgical complexity was identified to be a risk factor for infection. Low temperature plasma-based sterilization depends upon sufficient permeation and contact with surfaces which are a particular challenge when our 3D-printouts contain diffusion-restricted luminal spaces as well as hollows. Application of printouts as guides for power tools may further expose these regions to sterile bodily tissues and result in generation of debris. With each printout being a bespoke medical device, it is important that the multidisciplinary team involved in production and application understand potential pitfalls to ensuring sterility as to minimize infection risk.

Myelin, the structure that surrounds and insulates neuronal axons, is an important component of the central nervous system. The visualization of the myelinated fibers in brain tissues can largely facilitate the diagnosis of myelin-related diseases and understand how the brain functions. However, the most widely used fluorescent probes for myelin visualization, such as Vybrant DiD and FluoroMyelin, have strong background staining, low-staining contrast, and low brightness. These drawbacks may originate from their self-quenching properties and greatly limit their applications in three-dimensional (3D) imaging and myelin tracing. Chemical probes for the fluorescence imaging of myelin in 3D, especially in optically cleared tissue, are highly desirable but rarely reported. We herein developed a near-infrared aggregation-induced emission (AIE)-active probe, PM-ML, for high-performance myelin imaging. PM-ML is plasma membrane targeting with good photostability. It could specifically label myelinated fibers in teased sciatic nerves and mouse brain tissues with a high–signal-to-background ratio. PM-ML could be used for 3D visualization of myelin sheaths, myelinated fibers, and fascicles with high-penetration depth. The staining is compatible with different brain tissue–clearing methods, such as ClearT and ClearT2. The utility of PM-ML staining in demyelinating disease studies was demonstrated using the mouse model of multiple sclerosis. Together, this work provides an important tool for high-quality myelin visualization across scales, which may greatly contribute to the study of myelin-related diseases.