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      Distinct expression of SARS‐CoV‐2 receptor ACE2 correlates with endotypes of chronic rhinosinusitis with nasal polyps

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          Abstract

          Background

          Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) entry factors, ACE2 and TMPRSS2, are highly expressed in nasal epithelial cells. However, the association between SARS‐CoV‐2 and nasal inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) has not been investigated. We thus investigated the expression of SARS‐CoV‐2 entry factors in nasal tissues of CRSwNP patients, and their associations with inflammatory endotypes of CRSwNP.

          Methods

          The expression of ACE2 and TMPRSS2 was assessed in nasal tissues of control subjects and eosinophilic CRSwNP (ECRSwNP) and nonECRSwNP patients. The correlations between ACE2/TMPRSS2 expression and inflammatory indices of CRSwNP endotypes were evaluated. Regulation of ACE2/TMPRSS2 expression by inflammatory cytokines and glucocorticoids was investigated.

          Results

          ACE2 expression was significantly increased in nasal tissues of nonECRSwNP patients compared to ECRSwNP patients and control subjects, and positively correlated with the expression of IFN‐γ, but negatively correlated with tissue infiltrated eosinophils, and expression of IL5 and IL13. IFN‐γ up‐regulated ACE2 expression while glucocorticoid attenuated this increase in cultured nasal epithelial cells. Genes co‐expressed with ACE2 were enriched in pathways relating to defence response to virus in nasal tissue. TMPRSS2 expression was decreased in nasal tissues of CRSwNP patients compared to control subjects and not correlated with the inflammatory endotypes of CRSwNP. Glucocorticoid treatment decreased ACE2 expression in nasal tissues of nonECRSwNP patients, but not in ECRSwNP patients, whereas TMPRSS2 expression was not affected.

          Conclusion

          These findings indicate that ACE2 expression, regulated by IFN‐γ, is increased in nasal tissues of nonECRSwNP patients and positively correlates with type 1 inflammation.

          Abstract

          • The expression of SARS‐CoV‐2 receptor ACE2 is significantly increased in nasal tissues of nonECRSwNP patients compared to ECRSwNP patients and control subjects.

          • ACE2 expression is increased in nasal tissues of type 1 endotype of CRSwNP and positively correlated with the expression of IFN‐γ.

          • IFN‐γ up‐regulates ACE2 expression while glucocorticoids attenuate this increase in cultured nasal epithelial cells

          Abbreviations: ACE2, angiotensin‐converting enzyme 2; ECRSwNP, eosinophilic chronic rhinosinusitis with nasal polyps; nonECRSwNP, noneosinophilic chronic rhinosinusitis with nasal polyps; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2

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          Most cited references61

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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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              Is Open Access

              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.
              Article 0 comments Cited 10097 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Chengshuo Wang:
                ORCID: https://orcid.org/0000-0003-0646-5135
                wangcs830@126.com
                Luo Zhang:
                ORCID: https://orcid.org/0000-0002-0910-9884
                dr.luozhang@139.com
                Journal
                Journal ID (nlm-ta): Allergy
                Journal ID (iso-abbrev): Allergy
                Journal ID (doi): 10.1111/(ISSN)1398-9995
                Journal ID (publisher-id): ALL
                Title: Allergy
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Print): 0105-4538
                ISSN (Electronic): 1398-9995
                Publication date (Electronic): 29 November 2020
                Electronic Location Identifier: 10.1111/all.14665
                Affiliations
                [ 1 ] Department of Otolaryngology, Head and Neck Surgery Beijing TongRen Hospital Capital Medical University Beijing China
                [ 2 ] Beijing Key Laboratory of Nasal Diseases Beijing Institute of Otolaryngology Beijing China
                [ 3 ] Department of Allergy Beijing TongRen Hospital Capital Medical University Beijing China
                [ 4 ] Department of Otolaryngology, Head and Neck Surgery Beijing Ditan Hospital Capital Medical University Beijing China
                [ 5 ] Swiss Institute of Allergy and Asthma Research (SIAF) University of Zurich Davos Switzerland
                [ 6 ] Christine Kühne – Center for Research and Education (CK‐CARE) Davos Switzerland
                Author notes
                [*] [* ] Correspondence

                Luo Zhang and Chengshuo Wang, Beijing TongRen Hospital, Capital Medical University, No. 1, DongJiaoMinXiang, DongCheng District, Beijing, China.

                Emails: dr.luozhang@ 123456139.com (L.Z.); wangcs830@ 123456126.com (C.W.)

                Author information
                https://orcid.org/0000-0002-8560-3964
                https://orcid.org/0000-0001-5755-7684
                https://orcid.org/0000-0001-8020-019X
                https://orcid.org/0000-0003-0646-5135
                https://orcid.org/0000-0002-0910-9884
                Article
                Publisher ID: ALL14665
                DOI: 10.1111/all.14665
                PMC ID: 7753806
                PubMed ID: 33210729
                SO-VID: fa3c55ad-3575-4e92-b3c5-f4b6e58d4f95
                Copyright © © 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
                License:

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                History
                Date received : 01 June 2020
                Date revision received : 02 November 2020
                Date accepted : 15 November 2020
                Page count
                Figures: 8, Tables: 0, Pages: 15, Words: 19288
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 81800882
                Award ID: 81630023
                Award ID: 81870698
                Funded by: Beijing municipal administration of hospitals’ mission plan
                Award ID: SML20150203
                Funded by: national key R&D program of China
                Award ID: 2018YFC0116800
                Award ID: 2016YFC0905200
                Funded by: program for the Changjiang scholars and innovative research team
                Award ID: IRT13082
                Funded by: Beijing municipal administration of hospitals’ Dengfeng plan
                Award ID: DFL20190202
                Funded by: Beijing municipal administration of hospitals clinical medicine development of special funding support
                Award ID: XMLX201816
                Categories
                Subject: Original Article
                Subject: ORIGINAL ARTICLES
                Subject: Rhinitis, Sinusitis, and Upper Airway Disease
                Custom metadata
                source-schema-version-number 2.0
                edited-state corrected-proof
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.6 mode:remove_FC converted:22.12.2020

                ScienceOpen disciplines: Immunology
                Keywords: ace2,chronic rhinosinusitis with nasal polyps,inflammatory endotype,sars‐cov‐2,tmprss2
                Data availability:
                ScienceOpen disciplines: Immunology
                Keywords: ace2, chronic rhinosinusitis with nasal polyps, inflammatory endotype, sars‐cov‐2, tmprss2

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