Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia

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Abstract:

Altered olfactory function is a common symptom of COVID-19, but its etiology is unknown. A key question is whether SARS-CoV-2 (CoV-2) – the causal agent in COVID-19 – affects olfaction directly, by infecting olfactory sensory neurons or their targets in the olfactory bulb, or indirectly, through perturbation of supporting cells. Here we identify cell types in the olfactory epithelium and olfactory bulb that express SARS-CoV-2 cell entry molecules. Bulk sequencing demonstrated that mouse, non-human primate and human olfactory mucosa expresses two key genes involved in CoV-2 entry, ACE2 and TMPRSS2. However, single cell sequencing revealed that ACE2 is expressed in support cells, stem cells, and perivascular cells, rather than in neurons. Immunostaining confirmed these results and revealed pervasive expression of ACE2 protein in dorsally-located olfactory epithelial sustentacular cells and olfactory bulb pericytes in the mouse. These findings suggest that CoV-2 infection of non-neuronal cell types leads to anosmia and related disturbances in odor perception in COVID-19 patients.

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Fiji: an open-source platform for biological-image analysis.

Johannes Schindelin, Ignacio Arganda-Carreras, Erwin Frise … (2020)

Fiji is a distribution of the popular open-source software ImageJ focused on biological-image analysis. Fiji uses modern software engineering practices to combine powerful software libraries with a broad range of scripting languages to enable rapid prototyping of image-processing algorithms. Fiji facilitates the transformation of new algorithms into ImageJ plugins that can be shared with end users through an integrated update system. We propose Fiji as a platform for productive collaboration between computer science and biology research communities.

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Clinical Characteristics of Coronavirus Disease 2019 in China

Wei-jie Guan, Zheng-yi Ni, Yu Hu … (2020)

Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)

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A Novel Coronavirus from Patients with Pneumonia in China, 2019

Na Zhu, Dingyu Zhang, Wenling Wang … (2020)

Summary In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)

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Author and article information

Journal

Journal ID (nlm-ta): Sci Adv

Journal ID (iso-abbrev): Sci Adv

Journal ID (publisher-id): SciAdv

Journal ID (hwp): advances

Title: Science Advances

Publisher: American Association for the Advancement of Science

ISSN (Electronic): 2375-2548

Publication date (Electronic): 31 July 2020

Publication date Collection: July 2020

Volume: 6

Issue: 31

Electronic Location Identifier: eabc5801

Affiliations

[1 ]Harvard Medical School Department of Neurobiology, Boston MA 02115 USA.

[2 ]Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London SE1 1UL, UK

[3 ]Department of Statistics, University of California, Berkeley, CA 94720

[4 ]Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium

[5 ]Division of Biostatistics, School of Public Health, University of California, Berkeley, CA 94720

[6 ]Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720

[7 ]Earlham Institute, Norwich Research Park, Norwich, NR4 7UZ, UK

[8 ]Present address: Surrozen, Inc., South San Francisco, CA 94080

[9 ]Berkeley Institute for Data Science, University of California, Berkeley

[10 ]Present address: Genentech, Inc., South San Francisco, CA 94080

[11 ]Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA

[12 ]Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA

[13 ]Center for Computational Biology, University of California, Berkeley, CA 94720

[14 ]QB3 Functional Genomics Laboratory, University of California, Berkeley, CA 94720

[15 ]Department of Statistical Sciences, University of Padova, Padova, Italy

[16 ]University of Exeter Medical School, College of Medicine & Health, University of Exeter, Exeter EX2 5DW, UK

[17 ]Duke University School of Medicine Department of Head and Neck Surgery & Communication Sciences, Durham, NC 27717 USA.

[18 ]Duke University School of Medicine Department of Molecular Genetics and Microbiology, Department of Neurobiology, Duke Institute for Brain Sciences, Durham, NC 27717 US

[19 ]Waltham Petcare Science Institute, Leicestershire LE14 4RT, UK.

[20 ]Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720

[21 ]Present address: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD

Author notes

[* ]To whom correspondence should be addressed: srdatta@ 123456hms.harvard.edu

[†]

These authors contributed equally to this work.

Author information

David H. Brann https://orcid.org/0000-0001-8844-8886

Tatsuya Tsukahara https://orcid.org/0000-0002-6928-8562

Caleb Weinreb https://orcid.org/0000-0001-6100-6084

Marcela Lipovsek https://orcid.org/0000-0001-9328-0328

Rebecca Chance https://orcid.org/0000-0001-7059-6119

Iain C. Macaulay https://orcid.org/0000-0002-6761-757X

Diya Das https://orcid.org/0000-0001-9646-8983

Kelly Street https://orcid.org/0000-0001-6379-5013

Hector Roux de Bezieux https://orcid.org/0000-0002-1489-8339

Davide Risso https://orcid.org/0000-0001-8508-5012

Elizabeth Purdom https://orcid.org/0000-0001-9455-7990

Jonathan Mill https://orcid.org/0000-0003-1115-3224

Hiroaki Matsunami https://orcid.org/0000-0002-8850-2608

Darren W. Logan https://orcid.org/0000-0003-1545-5510

Bradley J. Goldstein https://orcid.org/0000-0002-9612-1696

Matthew S. Grubb https://orcid.org/0000-0002-2673-274X

John Ngai https://orcid.org/0000-0002-1191-8971

Sandeep Robert Datta https://orcid.org/0000-0002-8068-3862

Article

Publisher ID: abc5801

DOI: 10.1126/sciadv.abc5801

PMC ID: 10715684

PubMed ID: 32937591

SO-VID: f7a14508-fe2e-4e29-b96d-e0fcc453fc08

Copyright © Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

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This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

History

Date received : 01 May 2020

Date accepted : 18 June 2020

Funding

Funded by: doi http://dx.doi.org/10.13039/100000002, National Institutes of Health;

Award ID: RO11DC016222

Funded by: doi http://dx.doi.org/10.13039/100000002, National Institutes of Health;

Award ID: U19NS112953

Funded by: doi http://dx.doi.org/10.13039/100000002, National Institutes of Health;

Award ID: RO1DC007235

Funded by: doi http://dx.doi.org/10.13039/100000002, National Institutes of Health;

Award ID: RO1DC016859

Funded by: doi http://dx.doi.org/10.13039/501100000275, Leverhulme Trust;

Award ID: RPG-2016-095

Funded by: doi http://dx.doi.org/10.13039/501100000781, European Research Council;

Award ID: 725729

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Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia

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Related collections

Novel Coronavirus Disease COVID-19

Most cited references 109

Fiji: an open-source platform for biological-image analysis.

Clinical Characteristics of Coronavirus Disease 2019 in China

A Novel Coronavirus from Patients with Pneumonia in China, 2019

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