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 10

SARS-CoV-2 is not replicated in oral squamous epithelial cells.

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SARS-CoV-2 is not replicated in oral squamous epithelial cells. (A) Repr...
(A) Representative images of en face view of ACE2 protein signal in human nasal respiratory, nasopharynx transitional, and oral squamous epithelia. Scale bars: 50 μm. Similar findings were observed in 2 normal tissues from 2 independent experiments. (B) Schematic diagram depicting a series of procedures of brushing cytology for nasal and oral epithelial cells of COVID-19 patients (n = 6) sampled on the first, third, and sixth days of hospitalization. (C and D) Representative images showing that SARS-CoV-2 NP is detected in nasal multiciliated epithelial cells but not in oral squamous epithelial cells on the indicated days of hospitalization. Box regions are magnified in lower panels. Scale bars: 20 μm (C); 50 μm (D). Similar findings were observed in 6 patients with COVID-19.