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

Angiotensin-Converting Enzyme 2 / analysis Asymptomatic Infections COVID-19 / etiology Humans Mouth / virology SARS-CoV-2 / isolation & purification Saliva / virology Serine Endopeptidases / analysis Taste Disorders / etiology Virus Replication

Journal

Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015

Informations de publication

Date de publication:
05 2021
Historique:
received: 20 10 2020
accepted: 26 02 2021
pubmed: 27 3 2021
medline: 25 5 2021
entrez: 26 3 2021
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1038/s41591-021-01296-8 PMID: 33767405 PMC: PMC8240394
pubmed: 33767405
doi: 10.1038/s41591-021-01296-8
pii: 10.1038/s41591-021-01296-8
pmc: PMC8240394
mid: NIHMS1716445
doi:

Substances chimiques

ACE2 protein, human EC 3.4.17.23
Angiotensin-Converting Enzyme 2 EC 3.4.17.23
Serine Endopeptidases EC 3.4.21.-
TMPRSS2 protein, human EC 3.4.21.-

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

892-903

Subventions

Organisme : Cystic Fibrosis Foundation (CF Foundation)
ID : MIKAMI19XX0
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)
ID : NIDDK P30-DK034987
Organisme : NIDCR NIH HHS
ID : L30 DE029055
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM133364
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR002490
Pays : United States
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : NIDCR Z01-DE000704
Organisme : Intramural NIH HHS
ID : Z01 DE000704
Pays : United States
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : NIDCR K01-DE027087
Organisme : Intramural NIH HHS
ID : ZIA DE000704
Pays : United States
Organisme : Cystic Fibrosis Foundation (CF Foundation)
ID : KATO20F0
Organisme : NIDDK NIH HHS
ID : P30 DK034987
Pays : United States
Organisme : NIDCR NIH HHS
ID : K01 DE027087
Pays : United States
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : K08-DE026537 (Byrd)
Organisme : NIDCR NIH HHS
ID : K08 DE026537
Pays : United States

Investigateurs

David E Kleiner (DE)
Michelly Sampaio De Melo (MS)
Esra Dikoglu (E)
Sabina Desar (S)
Kris Ylaya (K)
Joon-Yong Chung (JY)
Grace Smith (G)
Daniel S Chertow (DS)
Kevin M Vannella (KM)
Marcos Ramos-Benitez (M)
Sabrina C Ramelli (SC)
Shelly J Samet (SJ)
Ashley L Babyak (AL)
Luis Perez Valenica (LP)
Mary E Richert (ME)
Nicole Hays (N)
Madeleine Purcell (M)
Shreya Singireddy (S)
Jocelyn Wu (J)
Jean Chung (J)
Amy Borth (A)
Kimberly Bowers (K)
Anne Weichold (A)
Douglas Tran (D)
Ronson J Madathil (RJ)
Eric M Krause (EM)
Daniel L Herr (DL)
Joseph Rabin (J)
Joseph A Herrold (JA)
Ali Tabatabai (A)
Eric Hochberg (E)
Christopher Cornachione (C)
Andrea R Levine (AR)
Michael T McCurdy (MT)
Kapil K Saharia (KK)
Zack Chancer (Z)
Michael A Mazzeffi (MA)
Justin E Richards (JE)
James W Eagan (JW)
Yashvir Sangwan (Y)
Inês Sequeira (I)
Sarah A Teichmann (S)
Adam J Kimple (A)

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Auteurs

Ni Huang (N)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.

Paola Pérez (P)

Salivary Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.

Takafumi Kato (T)

Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
ORCID: 0000-0003-2248-3376

Yu Mikami (Y)

Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
ORCID: 0000-0003-3262-2958

Kenichi Okuda (K)

Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
ORCID: 0000-0001-9341-2730

Rodney C Gilmore (RC)

Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Cecilia Domínguez Conde (CD)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
ORCID: 0000-0002-8684-4655

Billel Gasmi (B)

Salivary Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Sydney Stein (S)

Emerging Pathogens Section, Department of Critical Care Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, MD, USA.
ORCID: 0000-0002-0259-4485

Margaret Beach (M)

Salivary Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.

Eileen Pelayo (E)

Salivary Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.

Jose O Maldonado (JO)

Salivary Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
AAV Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
ORCID: 0000-0003-1226-7119

Bernard A Lafont (BA)

SARS-CoV-2 Virology Core, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
ORCID: 0000-0003-2140-6205

Shyh-Ing Jang (SI)

Salivary Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.

Nadia Nasir (N)

Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Ricardo J Padilla (RJ)

Division of Diagnostic Sciences, University of North Carolina Adams School of Dentistry, Chapel Hill, NC, USA.

Valerie A Murrah (VA)

Division of Diagnostic Sciences, University of North Carolina Adams School of Dentistry, Chapel Hill, NC, USA.

Robert Maile (R)

Department of Microbiology & Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

William Lovell (W)

Division of Oral & Craniofacial Health Sciences, University of North Carolina Adams School of Dentistry, Chapel Hill, NC, USA.

Shannon M Wallet (SM)

Department of Microbiology & Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Division of Oral & Craniofacial Health Sciences, University of North Carolina Adams School of Dentistry, Chapel Hill, NC, USA.

Natalie M Bowman (NM)

Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Suzanne L Meinig (SL)

Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Matthew C Wolfgang (MC)

Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Microbiology & Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.

Saibyasachi N Choudhury (SN)

Department of Genomic Medicine and Infectious Disease, J. Craig Venter Institute, La Jolla, CA, USA.
ORCID: 0000-0002-7299-5540

Mark Novotny (M)

Department of Infectious Disease, J. Craig Venter Institute, La Jolla, CA, USA.

Brian D Aevermann (BD)

Department of Infectious Disease, J. Craig Venter Institute, La Jolla, CA, USA.

Richard H Scheuermann (RH)

Department of Informatics, J. Craig Venter Institute, La Jolla, CA, USA.
Department of Pathology, University of California San Diego, La Jolla, CA, USA.
ORCID: 0000-0003-1355-892X

Gabrielle Cannon (G)

The Advanced Analytics Core, Center for Gastrointestinal Biology and Disease, University of North Carolina School of Medicine, Chapel Hill, NC, USA.

Carlton W Anderson (CW)

The Advanced Analytics Core, Center for Gastrointestinal Biology and Disease, University of North Carolina School of Medicine, Chapel Hill, NC, USA.

Rhianna E Lee (RE)

Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Cell Biology & Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
ORCID: 0000-0003-2039-1304

Julie T Marchesan (JT)

Division of Comprehensive Oral Health, University of North Carolina Adams School of Dentistry, Chapel Hill, NC, USA.
ORCID: 0000-0003-0610-3193

Mandy Bush (M)

Division of Comprehensive Oral Health, University of North Carolina Adams School of Dentistry, Chapel Hill, NC, USA.
ORCID: 0000-0002-4381-2354

Marcelo Freire (M)

Department of Genomic Medicine and Infectious Disease, J. Craig Venter Institute, La Jolla, CA, USA.
Department of Infectious Disease, J. Craig Venter Institute, La Jolla, CA, USA.
ORCID: 0000-0003-4906-7698

Adam J Kimple (AJ)

Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Otolaryngology-Head and Neck Surgery, University of North Carolina School of Medicine, Chapel Hill, NC, USA.

Daniel L Herr (DL)

Department of Shock Trauma Critical Care, University of Maryland School of Medicine, Baltimore, MD, USA.

Joseph Rabin (J)

Department of Surgery, R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, MD, USA.

Alison Grazioli (A)

Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.

Sanchita Das (S)

Division of Microbiology, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA.

Benjamin N French (BN)

AAV Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.

Thomas Pranzatelli (T)

AAV Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.

John A Chiorini (JA)

AAV Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.

David E Kleiner (DE)

Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
ORCID: 0000-0003-3442-4453

Stefania Pittaluga (S)

Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Stephen M Hewitt (SM)

Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
ORCID: 0000-0001-8283-1788

Peter D Burbelo (PD)

AAV Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.

Daniel Chertow (D)

Emerging Pathogens Section, Department of Critical Care Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, MD, USA.
ORCID: 0000-0002-1675-1728

Karen Frank (K)

Division of Microbiology, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA.

Janice Lee (J)

Craniofacial Anomalies & Regeneration Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
ORCID: 0000-0001-5164-5958

Richard C Boucher (RC)

Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Sarah A Teichmann (SA)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
Department of Physics, Cavendish Laboratory, Cambridge, UK.
ORCID: 0000-0002-6294-6366

Blake M Warner (BM)

Salivary Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA. blake.warner@nih.gov.
ORCID: 0000-0002-4961-018X

Kevin M Byrd (KM)

Division of Oral & Craniofacial Health Sciences, University of North Carolina Adams School of Dentistry, Chapel Hill, NC, USA. kevinmbyrd@gmail.com.
Department of Innovation & Technology Research, ADA Science & Research Institute, Gaithersburg, MD, USA. kevinmbyrd@gmail.com.

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Classifications MeSH

questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Peptide hydrolases › Exopeptidases › Carboxypeptidases › Angiotensin-converting enzyme 2 › SARS-CoV-2 infection of the oral cavity and saliva.
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Maladies asymptomatiques › Infections asymptomatiques › SARS-CoV-2 infection of the oral cavity and saliva.
questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Pneumopathie infectieuse › Pneumopathie virale › COVID-19 › SARS-CoV-2 infection of the oral cavity and saliva.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › SARS-CoV-2 infection of the oral cavity and saliva.
questionsmedicales.fr › Système stomatognathique › Bouche › SARS-CoV-2 infection of the oral cavity and saliva.
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN à brin positif › Nidovirales › Coronaviridae › Coronavirus › Betacoronavirus › Virus du SRAS › SARS-CoV-2 › SARS-CoV-2 infection of the oral cavity and saliva.
questionsmedicales.fr › Liquides et sécrétions biologiques › Sécrétions corporelles › Salive › SARS-CoV-2 infection of the oral cavity and saliva.
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Peptide hydrolases › Protéases à sérine › Serine endopeptidases › SARS-CoV-2 infection of the oral cavity and saliva.
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Manifestations neurologiques › Troubles sensitifs › Troubles du goût › SARS-CoV-2 infection of the oral cavity and saliva.
questionsmedicales.fr › Phénomènes microbiologiques › Phénomènes physiologiques viraux › Réplication virale › SARS-CoV-2 infection of the oral cavity and saliva.