Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19

TLDR

SARS‑CoV‑2, the agent of the COVID‑19 pandemic, has been linked to widespread thromboembolic events, including in the central nervous system, and neurological symptoms are common, suggesting likely viral penetration of the CNS. The virus gains access to the nervous system by traversing the neural‑mucosal interface of the olfactory mucosa, exploiting its proximity to endothelial and neural tissues, and then follows neuroanatomical pathways to reach the medulla oblongata. We detected SARS‑CoV‑2 RNA and protein in distinct regions of the nasopharynx and brain, observed thromboembolic ischemic infarcts, and provided evidence of viral neurotropism.

Abstract

The newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a pandemic respiratory disease. Moreover, thromboembolic events throughout the body, including in the CNS, have been described. Given the neurological symptoms observed in a large majority of individuals with COVID-19, SARS-CoV-2 penetrance of the CNS is likely. By various means, we demonstrate the presence of SARS-CoV-2 RNA and protein in anatomically distinct regions of the nasopharynx and brain. Furthermore, we describe the morphological changes associated with infection such as thromboembolic ischemic infarction of the CNS and present evidence of SARS-CoV-2 neurotropism. SARS-CoV-2 can enter the nervous system by crossing the neural-mucosal interface in olfactory mucosa, exploiting the close vicinity of olfactory mucosal, endothelial and nervous tissue, including delicate olfactory and sensory nerve endings. Subsequently, SARS-CoV-2 appears to follow neuroanatomical structures, penetrating defined neuroanatomical areas including the primary respiratory and cardiovascular control center in the medulla oblongata.