Nasal ciliated cells are primary targets for SARS-CoV-2 replication in the early stage of COVID-19
Ji Hoon Ahn, … , Chang-Seop Lee, Gou Young Koh
Ji Hoon Ahn, … , Chang-Seop Lee, Gou Young Koh
Published May 18, 2021
Citation Information: J Clin Invest. 2021;131(13):e148517. https://doi.org/10.1172/JCI148517.
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Research Article Infectious disease

Nasal ciliated cells are primary targets for SARS-CoV-2 replication in the early stage of COVID-19

Abstract

The upper respiratory tract is compromised in the early period of COVID-19, but SARS-CoV-2 tropism at the cellular level is not fully defined. Unlike recent single-cell RNA-Seq analyses indicating uniformly low mRNA expression of SARS-CoV-2 entry–related host molecules in all nasal epithelial cells, we show that the protein levels are relatively high and that their localizations are restricted to the apical side of multiciliated epithelial cells. In addition, we provide evidence in patients with COVID-19 that SARS-CoV-2 is massively detected and replicated within the multiciliated cells. We observed these findings during the early stage of COVID-19, when infected ciliated cells were rapidly replaced by differentiating precursor cells. Moreover, our analyses revealed that SARS-CoV-2 cellular tropism was restricted to the nasal ciliated versus oral squamous epithelium. These results imply that targeting ciliated cells of the nasal epithelium during the early stage of COVID-19 could be an ideal strategy to prevent SARS-CoV-2 propagation.

Authors

Ji Hoon Ahn, JungMo Kim, Seon Pyo Hong, Sung Yong Choi, Myung Jin Yang, Young Seok Ju, Young Tae Kim, Ho Min Kim, MD Tazikur Rahman, Man Ki Chung, Sang Duk Hong, Hosung Bae, Chang-Seop Lee, Gou Young Koh

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Figure 4

Comparison of cellular composition and SARS-CoV-2 entry molecular gene expression in nasal epithelial cells between healthy donors and patients with COVID-19.

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Comparison of cellular composition and SARS-CoV-2 entry molecular gene e...
(A) Schematic diagram depicting a series of procedures for scRNA-Seq of nasal epithelial cells from COVID-19 patients. (B) UMAP plot comparing unsupervised clustering of nasal epithelial cell subsets between healthy controls and patients with COVID-19. (C) List and proportion plots comparing proportion of each epithelial cell subset in total clustered epithelial cells between healthy controls and COVID-19 patients. (D) Unsupervised clustering projected on a 2D UMAP plot comparing distributions of ACE2+, ACE2+/TMPRSS2+, ACE2+/FURIN+, and ACE2+/TMPRSS2+/FURIN+ cells across total pooled nasal epithelial cells between healthy controls and COVID-19 patients. (E) Dot plot heatmap comparing expressions of SARS-CoV-2 entry molecule genes per each cell cluster between healthy controls and COVID-19 patients.