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Analysis of SARS-CoV-2 replication using human nasal organoids comprising olfactory and respiratory epithelium

ABSTRACT: SARS-CoV-2 infects the nasal epithelium (NE) and can cause olfactory dysfunction. Because the virus cannot infect olfactory sensory neurons (OSNs) which detect odorants, the underlying mechanisms remain unknown. Here, using human embryonic stem cells, we were the first to develop human NE organoids comprising both olfactory neuroepithelia (OE) and nasal respiratory epithelia (NRE). SARS-CoV-2 initially replicated in the NRE and then spread to the OE where angiotensin converting enzyme 2 was expressed after virus replication in NRE. Importantly, a significant proportion of neural precursor cells (NPCs) and basal stem cells in the OE, both of which constantly differentiate into OSNs, were infected. Viral infection upregulated cell death-associated genes in the NPCs and basal stem cells, suggesting that SARS-CoV-2 infection disrupts the repair and renewal of OSNs. Taken together, our human nasal organoid model would be useful for the investigation of a potential mechanism underlying olfactory dysfunction in COVID-19 patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE309325 | GEO | 2025/10/06

REPOSITORIES: GEO

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