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, M D Tazikur Rahman, Man Ki Chung, Sang Duk Hong, Hosung Bae, Chang-Seop Lee, Gou Young Koh
Author Information
  1. Ji Hoon Ahn: Center for Vascular Research, Institute for Basic Science (IBS), Daejeon, Republic of Korea.
  2. JungMo Kim: Center for Vascular Research, Institute for Basic Science (IBS), Daejeon, Republic of Korea.
  3. Seon Pyo Hong: Center for Vascular Research, Institute for Basic Science (IBS), Daejeon, Republic of Korea.
  4. Sung Yong Choi: Department of Otorhinolaryngology - Head and Neck Surgery, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Daejeon, Republic of Korea.
  5. Myung Jin Yang: Center for Vascular Research, Institute for Basic Science (IBS), Daejeon, Republic of Korea.
  6. Young Seok Ju: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
  7. Young Tae Kim: Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul, Republic of Korea.
  8. Ho Min Kim: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
  9. M D Tazikur Rahman: Department of Medical Science, Jeonbuk National University Medical School, Jeonju, Republic of Korea.
  10. Man Ki Chung: Department of Otorhinolaryngology - Head and Neck Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
  11. Sang Duk Hong: Department of Otorhinolaryngology - Head and Neck Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
  12. Hosung Bae: Center for Vascular Research, Institute for Basic Science (IBS), Daejeon, Republic of Korea.
  13. Chang-Seop Lee: Research Institute of Clinical Medicine of Jeonbuk National University - Biomedical Research Institute of Jeonbuk, National University Hospital, Jeonju, Republic of Korea.
  14. Gou Young Koh: Center for Vascular Research, Institute for Basic Science (IBS), Daejeon, Republic of Korea.

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.

Keywords

References

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MeSH Term

Angiotensin-Converting Enzyme 2
Animals
COVID-19
Cell Differentiation
Cilia
Furin
Host Microbial Interactions
Humans
Macaca
Models, Biological
Nasal Mucosa
Pandemics
RNA, Messenger
RNA-Seq
SARS-CoV-2
Serine Endopeptidases
Stem Cells
Virus Internalization
Virus Replication

Chemicals

RNA, Messenger
ACE2 protein, human
Angiotensin-Converting Enzyme 2
Serine Endopeptidases
TMPRSS2 protein, human
FURIN protein, human
Furin

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