Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
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.
View: Text | PDF
Research Article Infectious disease Article has an altmetric score of 250

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

  • Text
  • PDF
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

×

Figure 7

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

Options: View larger image (or click on image) Download as PowerPoint
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.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Picked up by 17 news outlets
Blogged by 3
Posted by 176 X users
Referenced in 2 patents
253 readers on Mendeley
See more details