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      Welche Bedeutung hat die Bindehaut als möglicher Übertragungsweg für eine SARS-CoV-2-Infektion? Translated title: What is the importance of the conjunctiva as a potential transmission pathway for SARS-CoV-2 infections?

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          Abstract

          Aktuelle Studien haben bei ca. 1 % aller COVID-19-Patienten eine Bindehautentzündung beschrieben und spekuliert, dass SARS-CoV‑2 über die Bindehaut übertragen werden kann. In der vorliegenden Arbeit rekapitulieren wir die molekularen Mechanismen des Eintritts von SARS-CoV‑2 in die Wirtszelle und diskutieren die aktuelle Studienlage zu einer möglichen konjunktivalen Transmission. Derzeit geht man davon aus, dass SARS-CoV‑2 das membrangebundene Angiotensin-konvertierende Enzym 2 (ACE2) sowie die Membran-gebundene Serinprotease TMPRSS2 benötigt, um in die Wirtszelle einzudringen. Aktuelle Studien weisen darauf hin, dass COVID-19-Patienten nur sehr selten Virus-RNA im Tränenfilm und Bindehautabstrichen aufweisen und dass ACE2 und TMPRSS2 in der Bindehaut nur in sehr geringen Mengen gebildet werden, was eine konjunktivale Infektion durch SARS-CoV‑2 über diese Mediatoren wenig wahrscheinlich macht. Dennoch halten wir die derzeitige Studienlage für zu begrenzt, um eine abschließende Aussage treffen zu können, und empfehlen konsequente und adäquate Schutzmaßnahmen für medizinisches Personal, das in engem Kontakt mit verdächtigen und bestätigten COVID-19-Patienten steht.

          Translated abstract

          Recent studies have described conjunctivitis in approximately 1% of COVID-19 patients and speculated that SARS-CoV‑2 can be transmitted via the conjunctiva. In this article we recapitulate the molecular mechanisms of host cell entry of SARS-CoV‑2 and discuss the current evidence for a potential conjunctival transmission of SARS-CoV‑2. The current body of evidence indicates that SARS-CoV‑2 requires the membrane-bound angiotensin-converting enzyme 2 (ACE2) and the membrane-bound serine protease TMPRSS2 to enter cells. Recent studies suggest that COVID-19 patients rarely exhibit viral RNA in tear film and conjunctival smears and that, ACE2 and TMPRSS2 are only expressed in very small amounts in the conjunctiva, making conjunctival infection with SARS-CoV‑2 via these mediators unlikely. Nevertheless, we consider the current evidence to be still too limited to provide a conclusive statement and recommend appropriate protective measures for healthcare personnel who are in close contact with suspected and confirmed COVID-19 patients.

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          Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection

          It has been known that, the novel Coronavirus, 2019-nCoV, which is considered similar to SARS-CoV and originated from Wuhan (China), invades human cells via the receptor angiotensin converting enzyme II (ACE2). Moreover, lung cells that have ACE2 expression may be the main target cells during 2019-nCoV infection. However, some patients also exhibit non-respiratory symptoms, such as kidney failure, implying that 2019-nCoV could also invade other organs. To construct a risk map of different human organs, we analyzed the single-cell RNA sequencing (scRNA-seq) datasets derived from major human physiological systems, including the respiratory, cardiovascular, digestive, and urinary systems. Through scRNA-seq data analyses, we identified the organs at risk, such as lung, heart, esophagus, kidney, bladder, and ileum, and located specific cell types (i.e., type II alveolar cells (AT2), myocardial cells, proximal tubule cells of the kidney, ileum and esophagus epithelial cells, and bladder urothelial cells), which are vulnerable to 2019-nCoV infection. Based on the findings, we constructed a risk map indicating the vulnerability of different organs to 2019-nCoV infection. This study may provide potential clues for further investigation of the pathogenesis and route of 2019-nCoV infection. Electronic Supplementary Material Supplementary material is available for this article at 10.1007/s11684-020-0754-0 and is accessible for authorized users.
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            Evaluation of coronavirus in tears and conjunctival secretions of patients with SARS‐CoV‐2 infection

            Abstract Objective This study aimed to assess the presence of novel coronavirus in tears and conjunctival secretions of SARS–CoV‐2‐infected patients. Methods A prospective interventional case series study was performed, and 30 confirmed novel coronavirus pneumonia (NCP) patients were selected at the First Affiliated Hospital of Zhejiang University from 26 January 2020 to 9 February 2020. At an interval of 2 to 3 days, tear and conjunctival secretions were collected twice with disposable sampling swabs for reverse‐transcription polymerase chain reaction (RT‐PCR) assay. Results Twenty‐one common‐type and nine severe‐type NCP patients were enrolled. Two samples of tear and conjunctival secretions were obtained from the only one patient with conjunctivitis yielded positive RT‐PCR results. Fifty‐eight samples from other patents were all negative. Conclusion We speculate that SARS‐CoV‐2 may be detected in the tears and conjunctival secretions in NCP patients with conjunctivitis.
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              Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses

              The new coronavirus (SARS-CoV-2) outbreak from December 2019 in Wuhan, Hubei, China, has been declared a global public health emergency. Angiotensin I converting enzyme 2 (ACE2), is the host receptor by SARS-CoV-2 to infect human cells. Although ACE2 is reported to be expressed in lung, liver, stomach, ileum, kidney and colon, its expressing levels are rather low, especially in the lung. SARS-CoV-2 may use co-receptors/auxiliary proteins as ACE2 partner to facilitate the virus entry. To identify the potential candidates, we explored the single cell gene expression atlas including 119 cell types of 13 human tissues and analyzed the single cell co-expression spectrum of 51 reported RNA virus receptors and 400 other membrane proteins. Consistent with other recent reports, we confirmed that ACE2 was mainly expressed in lung AT2, liver cholangiocyte, colon colonocytes, esophagus keratinocytes, ileum ECs, rectum ECs, stomach epithelial cells, and kidney proximal tubules. Intriguingly, we found that the candidate co-receptors, manifesting the most similar expression patterns with ACE2 across 13 human tissues, are all peptidases, including ANPEP, DPP4 and ENPEP. Among them, ANPEP and DPP4 are the known receptors for human CoVs, suggesting ENPEP as another potential receptor for human CoVs. We also conducted “CellPhoneDB” analysis to understand the cell crosstalk between CoV-targets and their surrounding cells across different tissues. We found that macrophages frequently communicate with the CoVs targets through chemokine and phagocytosis signaling, highlighting the importance of tissue macrophages in immune defense and immune pathogenesis.
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                Author and article information

                Contributors
                clemens.lange@uniklinik-freiburg.de
                guenther.schlunck@uniklinik-freiburg.de
                Journal
                Ophthalmologe
                Ophthalmologe
                Der Ophthalmologe
                Springer Medizin (Heidelberg )
                0941-293X
                1433-0423
                22 June 2020
                22 June 2020
                : 1-5
                Affiliations
                [1 ]GRID grid.7708.8, ISNI 0000 0000 9428 7911, Klinik für Augenheilkunde, , Universitätsklinikum Freiburg, ; Killianstr. 5, 79106 Freiburg, Deutschland
                [2 ]GRID grid.5963.9, Medizinische Fakultät, , Universität Freiburg, ; Breisacher Str. 153, 79110 Freiburg, Deutschland
                Article
                1150
                10.1007/s00347-020-01150-1
                7306648
                32572552
                fa8e2e90-c1ed-4236-9617-f4c981376382
                © The Author(s) 2020

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                History
                Categories
                Leitthema

                sars-cov‑2,covid-19,ace2,tmprss2,bindehaut,conjunctiva
                sars-cov‑2, covid-19, ace2, tmprss2, bindehaut, conjunctiva

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