Int J Med Sci 2021; 18(10):2102-2108. doi:10.7150/ijms.56324 This issue

Research Paper

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

Carlotta Pipolo1, Antonio Mario Bulfamante1✉, Andrea Schillaci2, Jacopo Banchetti2, Luca Castellani1, Alberto Maria Saibene1, Giovanni Felisati1*, Maurizio Quadrio2*

1. Unit of Otolaryngology, ASST Santi Paolo e Carlo, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.
2. Dept. of Aerospace Science and Technologies, Politecnico di Milano, Milan, Italy.
* These authors are both last co-authors

This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.
Pipolo C, Bulfamante AM, Schillaci A, Banchetti J, Castellani L, Saibene AM, Felisati G, Quadrio M. Through The Back Door: Expiratory Accumulation of SARS-Cov-2 in the Olfactory Mucosa as Mechanism for CNS Penetration. Int J Med Sci 2021; 18(10):2102-2108. doi:10.7150/ijms.56324. Available from

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Graphic abstract

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.

Keywords: Computational Fluid Dynamics, SARS-Cov-2, Olfactory Mucosa, Nose.