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

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.

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Affiliated Institutions

• Freie Universität Berlin DE
• Universitätsmedizin Göttingen DE
• Charité - Universitätsmedizin Berlin DE
• Otto-von-Guericke University Magdeburg DE
• Humboldt-Universität zu Berlin DE
• Deutschen Konsortium für Translationale Krebsforschung
• Robert Koch Institute DE
• Saarland University DE
• Berlin Institute of Health at Charité - Universitätsmedizin Berlin DE
• DRK Kliniken Berlin DE
• University of Göttingen DE

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