SARS-CoV-2 induces inflammation and intracranial infection through the olfactory epithelium-olfactory bulb pathway in non-human primates

• Published in: Journal of neuroimmunology 2024-02, Vol.387, p.578288-578288, Article 578288
• Main Authors: Shimizu, Shino, Nakayama, Misako, Nguyen, Cong Thanh, Ishigaki, Hirohito, Kitagawa, Yoshinori, Yasui, Fumihiko, Yagi, Yoshiki, Kusayanagi, Tomoe, Kohara, Michinori, Itoh, Yasushi, Tojima, Ichiro, Kouzaki, Hideaki, Shimizu, Takeshi
• Format: Article
• Language: English
• Subjects: cynomolgus and rhesus macaque; Nose-associated lymphoid tissue; Olfactory bulb; Olfactory neuron; SARS-CoV-2; Supporting cell
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2024.578288

We examined the histopathological changes in the olfactory mucosa of cynomolgus and rhesus macaque models of SARS-CoV-2 infection. SARS-CoV-2 infection induced severe inflammatory changes in the olfactory mucosa. A major histocompatibility complex (MHC) class II molecule, HLA-DR was expressed in macrophage and supporting cells, and melanocytes were increased in olfactory mucosa. Supporting cells and olfactory neurons were infected, and SARS-CoV-2 N protein was detected in the axons of olfactory neurons and in olfactory bulbs. Viral RNA was detected in olfactory bulbs and brain tissues. The olfactory epithelium-olfactory bulb pathway may be important as a route for intracranial infection by SARS-CoV-2. •SARS-CoV-2 infection induces severe inflammatory changes in olfactory mucosa.•Supporting cells, olfactory neurons and olfactory bulbs are infected.•Supporting cells and macrophages express HLA-DR as antigen presenting cells.•Melanocytes increase in the infected olfactory mucosa.•Olfactory epithelium-olfactory bulb pathway as a route for intracranial infection.