Through The Back Door: Expiratory Accumulation of SARS-Cov-2 in the Olfactory Mucosa as Mechanism for CNS Penetration.

Introduction: SARS-CoV-2 is a respiratory virus supposed to enter the organism through aerosol or fomite transmission to the nose, eyes and oropharynx. It is responsible for various clinical symptoms, including hyposmia and other neurological ones. Current literature suggests the olfactory mucosa as a port of entry to the CNS, but how the virus reaches the olfactory groove is still unknown. Because the first neurological symptoms of invasion (hyposmia) do not correspond to first signs of infection, the hypothesis of direct contact through airborne droplets during primary infection and therefore during inspiration is not plausible. The aim of this study is to evaluate if a secondary spread to the olfactory groove in a retrograde manner during expiration could be more probable. Methods: Four three-dimensional virtual models were obtained from actual CT scans and used to simulate expiratory droplets. The volume mesh consists of 25 million of cells, the simulated condition is a steady expiration, driving a flow rate of 270 ml/s, for a duration of 0.6 seconds. The droplet diameter is of 5 µm. Results: The analysis of the simulations shows the virus to have a high probability to be deployed in the rhinopharynx, on the tail of medium and upper turbinates. The possibility for droplets to access the olfactory mucosa during the expiratory phase is lower than other nasal areas, but consistent. Discussion: The data obtained from these simulations demonstrates the virus can be deployed in the olfactory groove during expiration. Even if the total amount in a single act is scarce, it must be considered it is repeated tens of thousands of times a day, and the source of contamination continuously acts on a timescale of several days. The present results also imply CNS penetration of SARS-CoV-2 through olfactory mucosa might be considered a complication and, consequently, prevention strategies should be considered in diseased patients.

An adjoint-based approach for the surgical correction of nasal septal deviations.

Deviations of the septal wall are widespread anatomic anomalies of the human nose; they vary significantly in shape and location, and often cause the obstruction of the nasal airways. When severe, septal deviations need to be surgically corrected by ear-nose-throat (ENT) specialists. Septoplasty, however, has a low success rate, owing to the lack of suitable standardized clinical tools for assessing type and severity of obstructions, and for surgery planning. Moreover, the restoration of a perfectly straight septal wall is often impossible and possibly unnecessary. This paper introduces a procedure, based on advanced patient-specific Computational Fluid Dynamics (CFD) simulations, to support ENT surgeons in septoplasty planning. The method hinges upon the theory of adjoint-based optimization, and minimizes a cost function that indirectly accounts for viscous losses. A sensitivity map is computed on the mucosal wall to provide the surgeon with a simple quantification of how much tissue removal at each location would contribute to easing the obstruction. The optimization procedure is applied to three representative nasal anatomies, reconstructed from CT scans of patients affected by complex septal deviations. The computed sensitivity consistently identifies all the anomalies correctly. Virtual surgery, i.e. morphing of the anatomies according to the computed sensitivity, confirms that the characteristics of the nasal airflow improve significantly after small anatomy changes derived from adjoint-based optimization.