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SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes
Open accessAbstract
We investigated SARS-CoV-2 potential tropism by surveying expression of viral entry-associated genes in single-cell RNA-sequencing data from multiple tissues from healthy human donors. We co-detected these transcripts in specific respiratory, corneal and intestinal epithelial cells, potentially explaining the high efficiency of SARS-CoV-2 transmission. These genes are co-expressed in nasal epithelial cells with genes involved in innate immunity, highlighting the cells’ potential role in initial viral infection, spread and clearance. The study offers a useful resource for further lines of inquiry with valuable clinical samples from COVID-19 patients and we provide our data in a comprehensive, open and user-friendly fashion at www.covid19cellatlas.org . An analysis of single-cell transcriptomics datasets from different tissues shows that ACE2 and TMPRSS2 are co-expressed in respiratory, corneal and intestinal epithelial cell populations, and that respiratory expression of ACE2 is associated with genes involved in innate immunity.
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“Although scSeq revealed ACE2 transcripts in only a subset of OE cells, this low level of observed expression matches or exceeds that observed in respiratory cells types that are infected by CoV-2 in COVID-19 patients (39) (Fig. 3).”
From Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia (2020) · cites this paper as [39]
Experimental — accuracy not yet measuredIn the citing paper
“Probably most important for the high efficacy of SARS-CoV-2 transmission is the high co-expression of ACE2 and TMPRSS2 in nasal epithelial cells, particularly in two types of goblet cells and a subset of ciliated cells, showing the highest expression among all cells in the respiratory tree (Figure 2 A).”
From COVID-19 and the human innate immune system (2021) · cites this paper as Sungnak et al., 2020
In the citing paper
“An interesting observation of this study was the high co-expression of genes involved in early steps of antiviral immune responses in these epithelial cells, which indicated the potential for these specialized nasal cells to play an important role in the initial viral infection, spread, but potentially also, clearance.”
From COVID-19 and the human innate immune system (2021) · cites this paper as Sungnak et al., 2020
In the citing paper
“TMPRSS2 is more widely expressed than ACE2, and cells with simultaneous expression were identified in the respiratory tree, the cornea, esophagus, ileum, colon, gallbladder, and common bile duct (Sungnak et al., 2020), yet there was no evidence for simultaneous expression in immune cells.”
From COVID-19 and the human innate immune system (2021) · cites this paper as Sungnak et al., 2020
In the citing paper
“It has recently been demonstrated through single cell RNA sequencing analysis (referred to herein as scSeq) that cells from the human upper airway — including nasal RE goblet and ciliated cells —express high levels of ACE2 and TMPRSS2, suggesting that these RE cell types may serve as a viral reservoir during CoV-2 infection (39, 40).”
From Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia (2020) · cites this paper as [39]
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Metadata
- Authors
- HCA Lung Biological Network, Sungnak, W., Huang, N., Bécavin, C., Berg, M., Queen, R., Litvinukova, M., Talavera-López, C., Maatz, H., Reichart, D., Sampaziotis, F., Worlock, K. B., Yoshida, M., & Barnes, J. L.
- Affiliations
- Wellcome Sanger Institute (GB)
- Centre National de la Recherche Scientifique (FR)
- University Medical Center Groningen (NL)
- Max Delbrück Center (DE)
- Harvard University (US)
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- University College London (GB)
- Corresponding author
- Sungnak, Waradon
- ORCID
- Venue
- Nature Medicine
- Published
- 2020-04-23
- Volume
- 26
- Issue
- 5
- Pages
- 681-687
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC8637938
- OpenAlex
- W3011483298
- Cited by
- 2,501
- References
- 59
- Citations by year
- 2026: 53 · 2025: 105 · 2024: 140 · 2023: 265 · 2022: 454 · 2021: 814 · 2020: 664
- FWCI
- 71.69
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- en
- Open access
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- PubMed (publishedVersion)
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- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Apollo
- Funders
- U.S. Department of Defense (W81XWH1910416)
- Howard Hughes Medical Institute
- U.S. Department of Veterans Affairs
- Bill and Melinda Gates Foundation
- Richard and Susan Smith Family Foundation
- Massachusetts General Hospital
- Yale University
- Vanderbilt University
- Massachusetts Institute of Technology
- Memorial Sloan-Kettering Cancer Center
- Northwestern University
- School of Medicine, Boston University
- Arizona State University
- Helsingin Yliopisto
- University of Washington
- Deutsches Zentrum für Infektionsforschung
- Wellcome Trust (211276/Z/18/Z, 211276/D/18/Z, 108082/A/15/Z, #MR/R006237/1, WT206194, 107931/Z/15/Z, GINOP-2.3.2-15-2016-00026, WT211276/Z/18/Z)
- Deutsches Zentrum für Herz-Kreislaufforschung
- European Bioinformatics Institute
- National Jewish Health
- Vanderbilt University Medical Center
- European Molecular Biology Laboratory
- Broad Institute
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
- Manton Foundation
- University of Alberta
- Cancer Research UK
- National Institute for Health and Care Research (PB-PG-1215-20037, CL-2017-14-001)
- British Heart Foundation (SP/19/1/34461, PG/16/47/32156)
- Cystic Fibrosis Trust (VIA 028)
- Academy of Medical Sciences (SGL019\1071)
- Imperial College London (H2020)
- University College London
- Newcastle University
- European Commission (2018-342, GINOP‐2.3.2‐15‐2016‐00037, 874656, GINOP-2.3.2-15-2016-00006, H2020)
- Rosetrees Trust
- National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC/T2T0419, NC/N001540/1)
- National Research Foundation
- Deutsche Forschungsgemeinschaft (347286815, DK043351, EXC2151/1, EXC 2151, 329123747, 390873048)
- Agence Nationale de la Recherche (ANR‐10‐INBS‐09‐03, ANR- 10-INBS-09, ANR‐19, ANR-19-CE14, ANR-19-CE14-0027, ANR-10, 10-INBS-09, -15-IDEX-01, ANR‐15‐IDEX‐01)
- Fondation Leducq
- Rijksuniversiteit Groningen
- University of New South Wales
- National Natural Science Foundation of China (31871370)
- Catholic University of Korea
- Cancerfonden (2019-)
- Fondation pour la Recherche Médicale (DEQ20180339158)
- National Research Foundation of Korea
- Karolinska Institutet
- National Science and Technology Development Agency
- Kungliga Tekniska Högskolan
- Vetenskapsrådet (2018-)
- Thailand Research Fund
- Centre National de la Recherche Scientifique
- Universitair Medisch Centrum Groningen
- Deutsches Zentrum für Neurodegenerative Erkrankungen
- Medizinischen Hochschule Hannover
- Rheinische Friedrich-Wilhelms-Universität Bonn
- Stockholms Universitet
- Science for Life Laboratory
- Conseil Départemental des Alpes Maritimes (2016-294DGADSH-CV)
- Deutsches Zentrum für Lungenforschung
- National Centre for the Replacement Refinement and Reduction of Animals in Research (NC/N001540/1)
- Ministerie van Economische Zaken en Klimaat
- Berlin Institute of Health
- National Institutes of Health (1r56hl135124-01, H2020, AG‐049665, DK 043351, AI135964)
- Directorate for Biological Sciences
- School of Medicine, Duke University
- School of Medicine, Stanford University
- University of California, San Diego
- Harvard Stem Cell Institute
- Feinberg School of Medicine
- Medical School, University of Michigan
- Horizon 2020 Framework Programme (874656, GINOP-2.3.2)
- Klarman Cell Observatory, Broad Institute
- Medical Research Council (MC_PC_17230, MR/R015635/1, MR/P009581/1, MC_PC_12009, MR/R006237/1, MR/K017047/1, MR/S005579/1)
- Engineering and Physical Sciences Research Council (TS/H001220/1)
- Biotechnology and Biological Sciences Research Council (BB/T004460/1, BB/V01126X/1)
- National Health and Medical Research Council
- Faculty of Medical Sciences, Newcastle University
- European Regional Development Fund (GINOP‐2.3.2‐15‐2016‐00006, H2020, GINOP-2.3.2-15-2016-00037, GINOP-2.3.2-15-2016-00026)
- NIHR Newcastle Biomedical Research Centre
- Helmholtz Zentrum München
- NIHR Cambridge Biomedical Research Centre
- National Institute on Aging (P01AG049665)
- National Heart, Lung, and Blood Institute (HL135124, R01HL146557, U01HL148856, R56 HL135124, K08HL130595, K08HL146943, HL148856, U01HL145567, R01HL145372, R01HL127349)
- National Institute of Allergy and Infectious Diseases (U24AI118672, U19AI135964)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK043351)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R24HD000836)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Keywords
- SARS-CoV-2, viral entry factors, ACE2, TMPRSS2, nasal epithelial cells, innate immunity, respiratory epithelium, corneal epithelium, intestinal epithelium, tissue tropism, COVID-19 pandemic, single-cell transcriptomics, gene co-expression
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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