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

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.

The Infected Lungs and Brain Interface in COVID-19: The Impact on Cognitive Function

“…2 ). The first route of entry would be through the olfactory epithelium, crossing the cribriform plate of the ethmoid bone and reaching the olfactory bulb from which it could spread to different areas of the brain [ 81 ]. The second route would be through the activation of brain barriers, as already mentioned, which allows the action of a third route.…”

Mesenchymal stem cells and their derived small extracellular vesicles for COVID-19 treatment

“…SARS-CoV-2 can enter the central nervous system through olfactory mucosa [63] The hyperphosphorylation of Tau protein is one of the features of neuroinvasion of SARS-CoV-2. The S protein of SARS-CoV-2 interacts with amyloid proteins, such as Ab, a-synuclein, Tau, prion, and TDP-43 RRM [64], which lead to changes in distribution of Tau from axon to somatic cells, hyperphosphorylation, and apparent neuronal death [48].…”

Post-Intensive Care Unit Multidisciplinary Approach in Patients with Severe Bilateral SARS-CoV-2 Pneumonia

“…Coronavirus disease 2019 (COVID- 19) is a relatively new disease in the public health context, which was first notified in Wuhan (China) in December 2019. The WHO declared COVID-19 a pandemic on 11 March 2020 because of its alarming levels of propagation and severity [1,2]. The impact of this health emergency has increased the load on healthcare systems and the demand for rehabilitation during and after the disease [3].…”