Evidence map›Paper›PMID 33767405›Full record

ArticleNature medicine2021

SARS-CoV-2 infection of the oral cavity and saliva.

Ni Huang, Paola Pérez, Takafumi Kato, Yu Mikami, Kenichi Okuda, Rodney C Gilmore, Cecilia Domínguez Conde, Billel Gasmi, Sydney Stein, Margaret Beach and 44 more

Open access · bronzeAbstract read
In one paragraph

Article in Nature medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 473 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
473citing papers in PubMed, 1 pooled it
145.7field-weighted citation impact, top 1% 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

473 citing papers in PubMed, 1 synthesis or guideline pooled it, 807 citations in OpenAlex.

  1. Pooled it
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  17. Ascl3The Journal of physiology · 2026
    Article
  18. Post-COVID-19 Jaw Osteonecrosis: A Narrative Review.Medicina (Kaunas, Lithuania) · 2026
    Review
  19. Article
  20. Article

413 more citing papers are in PubMed but not listed here.

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

54 authors at 10 institutions in 3 countries.

Ni Huang *Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
Paola Pérez *Salivary Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Takafumi Kato *Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0003-2248-3376
Yu Mikami *Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0003-3262-2958
Kenichi OkudaMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0001-9341-2730
Rodney C GilmoreMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Cecilia Domínguez CondeWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.ORCID http://orcid.org/0000-0002-8684-4655
Billel GasmiSalivary Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Sydney SteinEmerging Pathogens Section, Department of Critical Care Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-0259-4485
Margaret BeachSalivary Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Eileen PelayoSalivary Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Jose O MaldonadoSalivary Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-1226-7119
Bernard A LafontSARS-CoV-2 Virology Core, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-2140-6205
Shyh-Ing JangSalivary Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Nadia NasirLaboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Ricardo J PadillaDivision of Diagnostic Sciences, University of North Carolina Adams School of Dentistry, Chapel Hill, NC, USA.
Valerie A MurrahDivision of Diagnostic Sciences, University of North Carolina Adams School of Dentistry, Chapel Hill, NC, USA.
Robert MaileDepartment of Microbiology & Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
William LovellDivision of Oral & Craniofacial Health Sciences, University of North Carolina Adams School of Dentistry, Chapel Hill, NC, USA.
Shannon M WalletDepartment of Microbiology & Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Natalie M BowmanDepartment of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Suzanne L MeinigMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Matthew C WolfgangMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Saibyasachi N ChoudhuryDepartment of Genomic Medicine and Infectious Disease, J. Craig Venter Institute, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-7299-5540
Mark NovotnyDepartment of Infectious Disease, J. Craig Venter Institute, La Jolla, CA, USA.
Brian D AevermannDepartment of Infectious Disease, J. Craig Venter Institute, La Jolla, CA, USA.
Richard H ScheuermannDepartment of Informatics, J. Craig Venter Institute, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-1355-892X
Gabrielle CannonThe Advanced Analytics Core, Center for Gastrointestinal Biology and Disease, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Carlton W AndersonThe Advanced Analytics Core, Center for Gastrointestinal Biology and Disease, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Rhianna E LeeMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0003-2039-1304
Julie T MarchesanDivision of Comprehensive Oral Health, University of North Carolina Adams School of Dentistry, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0003-0610-3193
Mandy BushDivision of Comprehensive Oral Health, University of North Carolina Adams School of Dentistry, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0002-4381-2354
Marcelo FreireDepartment of Genomic Medicine and Infectious Disease, J. Craig Venter Institute, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-4906-7698
Adam J KimpleMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Daniel L HerrDepartment of Shock Trauma Critical Care, University of Maryland School of Medicine, Baltimore, MD, USA.
Joseph RabinDepartment of Surgery, R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, MD, USA.
Alison GrazioliKidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Sanchita DasDivision of Microbiology, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
Benjamin N FrenchAAV Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Thomas PranzatelliAAV Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
John A ChioriniAAV Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
David E KleinerLaboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-3442-4453
Stefania PittalugaLaboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Stephen M HewittLaboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-8283-1788
Peter D BurbeloAAV Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Daniel ChertowEmerging Pathogens Section, Department of Critical Care Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-1675-1728
NIH COVID-19 Autopsy Consortium
HCA Oral and Craniofacial Biological Network
Karen FrankDivision of Microbiology, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
Janice LeeCraniofacial Anomalies & Regeneration Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-5164-5958
Richard C BoucherMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Sarah A TeichmannWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.ORCID http://orcid.org/0000-0002-6294-6366
Blake M WarnerSalivary Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA. blake.warner@nih.gov.ORCID http://orcid.org/0000-0002-4961-018X
Kevin M ByrdDivision of Oral & Craniofacial Health Sciences, University of North Carolina Adams School of Dentistry, Chapel Hill, NC, USA. kevinmbyrd@gmail.com.
University of Maryland, Baltimore · USNational Institutes of Health · USUniversity of North Carolina at Chapel Hill · USNational Institutes of Health Clinical Center · USJ. Craig Venter Institute · USQueen Mary University of London · GBWellcome Sanger Institute · GBNational Institute of Dental and Craniofacial Research · USPeninsula Regional Medical Center · USSt. Joseph Medical Center · US

Funding

NIDCR DIR Clinical Support ServicesZIDDE000728 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI LEE, JANICE · 2009 to 2025
$76.2M
Adeno-associated Virus Biology And Utilization For Gene TransferZIADE000695 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI CHIORINI, JAY · 2009 to 2025
$36.6M
PILOT AND FEASIBILITY STUDIESP30DK034987 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ROBERT S. SANDLER · 1985 to 2026
$30.5M
Anatomic Pathology Residency ProgramZIEBC011384 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI BARR, FREDERIC · 2011 to 2025
$26.8M
Clinical Investigations of Sjogren's SyndromeZIADE000704 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI WARNER, BLAKE · 2009 to 2025
$22.3M
Experimental Pathology Laboratory (EPL)ZICBC011638 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HEWITT, STEPHEN · 2015 to 2025
$16.6M
Postmortem PathologyZICBC010685 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI KLEINER, DAVID ERWIN · 2009 to 2025
$14.3M
Craniofacial Anomalies and RegenerationZIADE000746 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI LEE, JANICE · 2015 to 2025
$12.3M
North Carolina Translational and Clinical Science Institute (NC TraCS) KL2KL2TR002490 · NCATS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WEINBERGER, MORRIS · 2018 to 2022
$11.0M
Clinical Investigations Of Sjogren's SyndromeZ01DE000704 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI ILLEI, GABOR · 2002 to 2008
$3.0M
Training Program in Cellular Systems and Integrative PhysiologyT32GM133364 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Kathleen M Caron, Natasha T Snider · 2020 to 2026
$1.4M
IFI16 is a Periodontitis Modulating ProteinK01DE027087 · NIDCR · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MARCHESAN, JULIE TERESA · 2017 to 2022
$833k
Cystic Fibrosis Foundation (CF Foundation) KATO20F0Cystic Fibrosis Foundation (CF Foundation) MIKAMI19XX0Intramural NIH HHS Z01 DE000704Intramural NIH HHS ZIA DE000704NCATS NIH HHS KL2 TR002490NIDCR NIH HHS K01 DE027087NIDCR NIH HHS K08 DE026537NIDCR NIH HHS L30 DE029055NIDDK NIH HHS P30 DK034987NIGMS NIH HHS T32 GM133364U.S. Department of Health & Human Services | National Institutes of Health (NIH) K08-DE026537 (Byrd)U.S. Department of Health & Human Services | National Institutes of Health (NIH) NIDCR K01-DE027087U.S. Department of Health & Human Services | National Institutes of Health (NIH) NIDCR Z01-DE000704U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) NIDDK P30-DK034987
6 · The paper itself

Abstract

Despite signs of infection-including taste loss, dry mouth and mucosal lesions such as ulcerations, enanthema and macules-the involvement of the oral cavity in coronavirus disease 2019 (COVID-19) is poorly understood. To address this, we generated and analyzed two single-cell RNA sequencing datasets of the human minor salivary glands and gingiva (9 samples, 13,824 cells), identifying 50 cell clusters. Using integrated cell normalization and annotation, we classified 34 unique cell subpopulations between glands and gingiva. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral entry factors such as ACE2 and TMPRSS members were broadly enriched in epithelial cells of the glands and oral mucosae. Using orthogonal RNA and protein expression assessments, we confirmed SARS-CoV-2 infection in the glands and mucosae. Saliva from SARS-CoV-2-infected individuals harbored epithelial cells exhibiting ACE2 and TMPRSS expression and sustained SARS-CoV-2 infection. Acellular and cellular salivary fractions from asymptomatic individuals were found to transmit SARS-CoV-2 ex vivo. Matched nasopharyngeal and saliva samples displayed distinct viral shedding dynamics, and salivary viral burden correlated with COVID-19 symptoms, including taste loss. Upon recovery, this asymptomatic cohort exhibited sustained salivary IgG antibodies against SARS-CoV-2. Collectively, these data show that the oral cavity is an important site for SARS-CoV-2 infection and implicate saliva as a potential route of SARS-CoV-2 transmission.

Indexed as

Angiotensin-Converting Enzyme 2Asymptomatic InfectionsCOVID-19HumansMouthSalivaSARS-CoV-2Serine EndopeptidasesTaste DisordersVirus ReplicationACE2 protein, humanAngiotensin-Converting Enzyme 2Serine EndopeptidasesTMPRSS2 protein, human

Identifiers

PMID33767405
PMCPMC8240394
OpenAlexW3137107306

What OpenQuestion holds

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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.