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

Human nasal cytology reveals that SARS-CoV-2 entry molecules are located at the apical side of multiciliated cells.

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Human nasal cytology reveals that SARS-CoV-2 entry molecules are located...
(A) Schematic diagram of a series of procedures for human nasal cytology by nasal brushing and preparation of nasal cell smear onto slide. (B–G) Representative images showing that ACE2, TMPRSS2, and FURIN are abundant in the apical side of acetylated α-tubulin+ multiciliated cells, but very limited or absent in MUC5AC+ goblet cells in the smeared nasal cells. Scale bars: 25 μm. Similar findings were observed in 3 healthy volunteers from 2 independent experiments.