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 3

SARS-CoV-2 entry molecule proteins are highly present in fully differentiated multiciliated cells, but not in secretory or differentiating cells.

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SARS-CoV-2 entry molecule proteins are highly present in fully different...
(A–C) Representative images showing subtypes of human nasal epithelial cells. White-dashed boxes in A are magnified in B and C. Scale bar in A: 100 μm. (B) Image showing KRT7hi secretory- or differentiating-type cells (yellow arrowhead) and KRT5lo/KRT7lo fully differentiated multiciliated cells (white arrowhead). Scale bar: 50 μm. (C) Image showing KRT5hi basal type cells (white arrow). Scale bar: 50 μm. (D) Donut plot showing subtype proportions in 1538 pooled smeared nasal epithelial cells of healthy volunteers (n = 3). (E–J) Representative images and comparisons of relative ACE2, TMPRSS2, and FURIN intensity in the smeared nasal cells, showing high in KRT7lo fully differentiated multiciliated cells (yellow arrowheads) but very low in KRT7hi secretory or differentiating cells (white arrowheads). Scale bars: 50 μm. (F, H, and J) Each dot indicates a value obtained from 1 smear sample in 3 volunteers (3 smeared slides per volunteer) from 2 independent experiments. Horizontal bars indicate the mean ± SD. P value versus ciliated cells was obtained by 2-tailed Mann-Whitney U test.