Evidence map›Paper›PMID 34604819›Full record

ArticleCell reports. Medicine2021

Determinants of SARS-CoV-2 entry and replication in airway mucosal tissue and susceptibility in smokers.

Tsuguhisa Nakayama, Ivan T Lee, Sizun Jiang, Matthias S Matter, Carol H Yan, Jonathan B Overdevest, Chien-Ting Wu, Yury Goltsev, Liang-Chun Shih, Chun-Kang Liao and 33 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 2 pooled it
1.3field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 27 citations in OpenAlex.

  1. Mucosal immune response in biology, disease prevention and treatment.Signal transduction and targeted therapy · 2025
    Pooled it
  2. Pooled it
  3. Article
  4. Article
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  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Identification of Z-Tyr-Ala-CHNMicroorganisms · 2023
    Article
  13. Article
  14. Article
  15. Organ manifestations of COVID-19: what have we learned so far (not only) from autopsies?Virchows Archiv : an international journal of pathology · 2022
    Review
  16. Article
  17. Observational
  18. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

43 authors at 13 institutions in 4 countries.

Tsuguhisa NakayamaDepartment of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA.
Ivan T LeeDepartment of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA.
Sizun JiangDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Matthias S MatterPathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.
Carol H YanDivision of Otolaryngology - Head and Neck Surgery, Department of Surgery, University of California San Diego School of Medicine, University of California, San Diego, La Jolla, CA, USA.
Jonathan B OverdevestDepartment of Otolaryngology-Head and Neck Surgery, Columbia University School of Medicine, New York, NY, USA.
Chien-Ting WuBaxter Laboratory, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, USA.
Yury GoltsevDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Liang-Chun ShihDepartment of Otorhinolaryngology, China Medical University Hospital, Taichung, Taiwan.
Chun-Kang LiaoDepartment of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan.
Bokai ZhuDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Yunhao BaiDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Peter LidskyDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
Yinghong XiaoDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
David ZarabandaDepartment of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA.
Angela YangDepartment of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA.
Meena EaswaranDepartment of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA.
Christian M SchürchDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Pauline ChuDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Han ChenDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Anna K StalderPathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.
David R McIlwainDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Nicole A BorchardDepartment of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA.
Phillip A GallDepartment of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA.
Sachi S DholakiaDepartment of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA.
Wei LeDepartment of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA.
Le XuDepartment of Pediatrics, University of California San Diego School of Medicine, University of California, San Diego, La Jolla, CA, USA.
Chih-Jaan TaiDepartment of Otorhinolaryngology, China Medical University Hospital, Taichung, Taiwan.
Te-Huei YehDepartment of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan.
Elizabeth Erickson-DirenzoDepartment of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA.
Jason M DuranDivision of Cardiovascular Medicine, Department of Medicine, University of California San Diego School of Medicine, University of California, San Diego, La Jolla, CA, USA.
Kirsten D MertzInstitute of Pathology, Cantonal Hospital Baselland, Liestal, Switzerland.
Peter H HwangDepartment of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA.
Jasmin D HaslbauerPathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.
Peter K JacksonBaxter Laboratory, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, USA.
Thomas MenterPathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.
Raul AndinoDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
Peter D CanollDepartment of Pathology and Cell Biology, Columbia University Medical Center, Irving Cancer Research Center, New York, NY, USA.
Adam S DeCondeDivision of Otolaryngology - Head and Neck Surgery, Department of Surgery, University of California San Diego School of Medicine, University of California, San Diego, La Jolla, CA, USA.
Zara M PatelDepartment of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA.
Alexandar TzankovPathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.
Garry P NolanDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Jayakar V NayakDepartment of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA.
Stanford Medicine · USStanford University · USUniversity of Basel · CHUniversity of California San Diego · USUniversity of California, San Francisco · USChina Medical University · TWBeth Israel Deaconess Medical Center · USColumbia University · USColumbia University Irving Medical Center · USJikei University School of Medicine · JPNational Taiwan University · TWNational Taiwan University Hospital · TWVA Palo Alto Health Care System · US

Funding

Spatial-Genomic Integrative Multi-Species Analysis of Lymph Node MetastasisU54CA209971 · NCI · STANFORD UNIVERSITY · PI NOLAN, GARRY P, PLEVRITIS, SYLVIA KATINA · 2016 to 2021
$11.0M
Defining Mechanisms of Viral Persistence in Situ at the Single-Cell LevelR01AI149672 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI ESTES, JACOB D · 2020 to 2024
$4.0M
Optimizing Surgical Transplant of CFTR Gene-Corrected Human Basal Stem Cells to the Upper AirwayR01HL151677 · NHLBI · STANFORD UNIVERSITY · PI NAYAK, JAYAKAR V · 2021 to 2025
$2.4M
NCI NIH HHS U54 CA209971NHLBI NIH HHS R01 HL151677NIAID NIH HHS R01 AI149672
6 · The paper itself

Abstract

Understanding viral tropism is an essential step toward reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, decreasing mortality from coronavirus disease 2019 (COVID-19) and limiting opportunities for mutant strains to arise. Currently, little is known about the extent to which distinct tissue sites in the human head and neck region and proximal respiratory tract selectively permit SARS-CoV-2 infection and replication. In this translational study, we discover key variabilities in expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), essential SARS-CoV-2 entry factors, among the mucosal tissues of the human proximal airways. We show that SARS-CoV-2 infection is present in all examined head and neck tissues, with a notable tropism for the nasal cavity and tracheal mucosa. Finally, we uncover an association between smoking and higher SARS-CoV-2 viral infection in the human proximal airway, which may explain the increased susceptibility of smokers to developing severe COVID-19. This is at least partially explained by differences in interferon (IFN)-β1 levels between smokers and non-smokers.

Indexed as

SmokersViral TropismAgedAged, 80 and overAngiotensin-Converting Enzyme 2COVID-19FemaleGene Expression RegulationHumansMaleMiddle AgedNasal CavityRespiratory MucosaSARS-CoV-2Serine EndopeptidasesTracheaACE2 protein, humanAngiotensin-Converting Enzyme 2Serine EndopeptidasesTMPRSS2 protein, humanACE2ciliated epithelial cellCOVID-19IFN-β1nasal cavitySARS-CoV-2smokingTMPRSS2tracheaupper airway

Identifiers

PMID34604819
PMCPMC8479532
OpenAlexW3204417766

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.