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 COVID-19 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 7

Nucleocapsid protein of SARS-CoV-2 is detected exclusively in multiciliated epithelial cells of patients with COVID-19.

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Nucleocapsid protein of SARS-CoV-2 is detected exclusively in multicilia...
(A) Schematic diagram of a series of procedures for human nasal cytology by nasal brushing and preparation of nasal cell smear onto slide. (B–E) Representative images showing detection of SARS-CoV-2 nucleocapsid protein (NP) in acetylated-α-tubulin+ multiciliated epithelial cells (yellow arrowheads) (B–D) and SARS-CoV-2–infected dead cells (E). Box regions are magnified in right panels. Note cell shrinkage (yellow arrow) and loss of cilia and nucleus (white arrow). Scale bars: 200 μm (B); 20 μm (C–E). Similar findings were observed in n = 6 COVID-19 patients. (F and G) Representative images showing no SARS-CoV-2 NP in MUC5AC+ goblet cells. Box region is magnified and displayed as G. Scale bars: 200 μm (F); 20 μm (G). Similar findings were observed in 6 patients with COVID-19. (H) Donut plots presenting proportion of indicated cell subtypes in about 2449 pooled epithelial cells and 1606 pooled infected cells from 3 patients with COVID-19. (I–K) Representative images showing no SARS-CoV-2 NP (yellow arrowheads) in KRT7hi secretory or differentiating cells. Box regions are magnified and displayed as J and K. Scale bars: 500 μm (I); 50 μm (J and K). (L) Comparison of KRT7 intensity between secretory cells and SARS-CoV-2–infected cells. Each dot indicates a value obtained from 1 smear sample in 5 patients (4 smeared slides per patient) from 2 independent experiments. Horizontal bars indicate mean ± SD. P value versus secretory cells was obtained by 2-tailed Mann-Whitney U test.