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      SARS-CoV-2 infection in the mouse olfactory system

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          Abstract

          SARS-CoV-2 infection causes a wide spectrum of clinical manifestations in humans, and olfactory dysfunction is one of the most predictive and common symptoms in COVID-19 patients. However, the underlying mechanism by which SARS-CoV-2 infection leads to olfactory disorders remains elusive. Herein, we demonstrate that intranasal inoculation with SARS-CoV-2 induces robust viral replication in the olfactory epithelium (OE), not the olfactory bulb (OB), resulting in transient olfactory dysfunction in humanized ACE2 (hACE2) mice. The sustentacular cells and Bowman’s gland cells in the OE were identified as the major target cells of SARS-CoV-2 before invasion into olfactory sensory neurons (OSNs). Remarkably, SARS-CoV-2 infection triggers massive cell death and immune cell infiltration and directly impairs the uniformity of the OE structure. Combined transcriptomic and quantitative proteomic analyses revealed the induction of antiviral and inflammatory responses, as well as the downregulation of olfactory receptor (OR) genes in the OE from the infected animals. Overall, our mouse model recapitulates olfactory dysfunction in COVID-19 patients and provides critical clues for understanding the physiological basis for extrapulmonary manifestations of COVID-19.

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Chaolin Huang, Yeming Wang, Xingwang Li … (2020)
          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China

            Dawei Wang, Bo Hu, Fangfang Zhu … (2020)
            In December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited.
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              A pneumonia outbreak associated with a new coronavirus of probable bat origin

              Peng Zhou, Xing-Lou Yang, Xian-Guang Wang … (2020)
              Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.
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                Author and article information

                Contributors
                Ping Xu: xuping_bprc@126.com
                Xiao Yang: yangx@bmi.ac.cn
                Cheng-Feng Qin:
                ORCID: http://orcid.org/0000-0002-0632-2807
                qincf@bmi.ac.cn
                Journal
                Journal ID (nlm-ta): Cell Discov
                Journal ID (iso-abbrev): Cell Discov
                Title: Cell Discovery
                Publisher: Springer Singapore (Singapore )
                ISSN (Electronic): 2056-5968
                Publication date (Electronic): 6 July 2021
                Publication date PMC-release: 6 July 2021
                Publication date Collection: 2021
                Volume: 7
                Electronic Location Identifier: 49
                Affiliations
                [1 ]GRID grid.410740.6, ISNI 0000 0004 1803 4911, State Key Laboratory of Pathogen and Biosecurity, , Beijing Institute of Microbiology and Epidemiology, ; Beijing, China
                [2 ]GRID grid.419611.a, ISNI 0000 0004 0457 9072, State Key Laboratory of Proteomics, National Center for Protein Science (Beijing), , Beijing Institute of Lifeomics, ; Beijing, China
                [3 ]GRID grid.415954.8, ISNI 0000 0004 1771 3349, Department of Otorhinolaryngology, , China-Japan Friendship Hospital, ; Beijing, China
                [4 ]GRID grid.506261.6, ISNI 0000 0001 0706 7839, Research Unit of Discovery and Tracing of Natural Focus Diseases, , Chinese Academy of Medical Sciences, ; Beijing, China
                Author information
                http://orcid.org/0000-0002-2306-1039
                http://orcid.org/0000-0002-0632-2807
                Article
                Publisher ID: 290
                DOI: 10.1038/s41421-021-00290-1
                PMC ID: 8260584
                PubMed ID: 34230457
                SO-VID: 4e72d545-5d37-4fc4-a142-ec42fabaeaec
                Copyright © © The Author(s) 2021
                License:

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                Date received : 15 January 2021
                Date accepted : 9 June 2021
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);
                Award ID: 81925025
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100005150, Chinese Academy of Medical Sciences (CAMS);
                Award ID: 2019RU040
                Award Recipient :
                Funded by: The National Key Research and Development Project of China (2016YFD0500304, 2020YFC0842200, and 2020YFA0707801) The National Science Fund for Distinguished Young Scholar (No. 81925025) The Innovative Research Group (No. 81621005) from the NSFC The Innovation Fund for Medical Sciences (No.2019RU040) from the Chinese Academy of Medical Sciences (CAMS)
                Funded by: Youth Program of National Natural Science Foundation of China (No.82002148) from NSFC, and the China Postdoctoral Science Fund (No. 2020T130134ZX and No.2020M673685).
                Funded by: the China Postdoctoral Science Fund (No.2019M664012 and No. 2020T130135ZX).
                Funded by: Natural Science Foundation of Beijing (7212090)
                Categories
                Subject: Article
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                issue-copyright-statement © The Author(s) 2021

                Keywords: mechanisms of disease,cell signalling
                Data availability:
                Keywords: mechanisms of disease, cell signalling

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