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      Detection of COVID-19: A review of the current literature and future perspectives

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          Abstract

          The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the coronavirus disease 2019 (COVID-19) worldwide pandemic. This unprecedented situation has garnered worldwide attention. An effective strategy for controlling the COVID-19 pandemic is to develop highly accurate methods for the rapid identification and isolation of SARS-CoV-2 infected patients. Many companies and institutes are therefore striving to develop effective methods for the rapid detection of SARS-CoV-2 ribonucleic acid (RNA), antibodies, antigens, and the virus. In this review, we summarize the structure of the SARS-CoV-2 virus, its genome and gene expression characteristics, and the current progression of SARS-CoV-2 RNA, antibodies, antigens, and virus detection. Further, we discuss the reasons for the observed false-negative and false-positive RNA and antibody detection results in practical clinical applications. Finally, we provide a review of the biosensors which hold promising potential for point-of-care detection of COVID-19 patients. This review thereby provides general guidelines for both scientists in the biosensing research community and for those in the biosensor industry to develop a highly sensitive and accurate point-of-care COVID-19 detection system, which would be of enormous benefit for controlling the current COVID-19 pandemic.

          Highlights

          • The viral particles structure, genome and gene expression characteristics of SARS-CoV-2 are described.

          • The current SARS-CoV-2 viral particles, RNA, antigens, and antibody detection methods are reviewed.

          • The clinical performance and unmet problems associated with SARS-CoV-2 RNA antigen, and antibody detection are highlighted.

          • Potential biosensors for use in developing point-of-care, rapid, high-sensitivity SARS-CoV-2 detection methods are discussed.

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          Most cited references105

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          A pneumonia outbreak associated with a new coronavirus of probable bat origin

          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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            SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

            Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
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              Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR

              Background The ongoing outbreak of the recently emerged novel coronavirus (2019-nCoV) poses a challenge for public health laboratories as virus isolates are unavailable while there is growing evidence that the outbreak is more widespread than initially thought, and international spread through travellers does already occur. Aim We aimed to develop and deploy robust diagnostic methodology for use in public health laboratory settings without having virus material available. Methods Here we present a validated diagnostic workflow for 2019-nCoV, its design relying on close genetic relatedness of 2019-nCoV with SARS coronavirus, making use of synthetic nucleic acid technology. Results The workflow reliably detects 2019-nCoV, and further discriminates 2019-nCoV from SARS-CoV. Through coordination between academic and public laboratories, we confirmed assay exclusivity based on 297 original clinical specimens containing a full spectrum of human respiratory viruses. Control material is made available through European Virus Archive – Global (EVAg), a European Union infrastructure project. Conclusion The present study demonstrates the enormous response capacity achieved through coordination of academic and public laboratories in national and European research networks.
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                Author and article information

                Contributors
                Journal
                Biosens Bioelectron
                Biosens Bioelectron
                Biosensors & Bioelectronics
                Published by Elsevier B.V.
                0956-5663
                1873-4235
                21 July 2020
                21 July 2020
                : 112455
                Affiliations
                [a ]Department of Clinical Laboratory Medicine, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, PR China
                [b ]Guangzhou Institute of Respiratory Medicine Company Limited, Guangzhou, 510535, PR China
                [c ]Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, PR China
                [d ]Department of Clinical Laboratory Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, PR China
                [e ]Laboratory of Pathology, Department of Pathobiology, University of Poonch Rawalakot, Rawala Kot, 12350, Pakistan
                [f ]Department of Clinical Laboratory, Maoming People's Hospital, Maoming, 525000, PR China
                [g ]School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, HongKong, PR China
                Author notes
                []Corresponding author. jitianxing7021@ 123456163.com
                [∗∗ ]Corresponding author. qiangzhou70@ 123456163.com
                [∗∗∗ ]Corresponding author. yangchaochen@ 123456cuhk.edu.hk
                [1]

                These authors contributed equally to this work.

                Article
                S0956-5663(20)30449-8 112455
                10.1016/j.bios.2020.112455
                7371595
                32739797
                bbb7550e-1fd1-482f-a78c-0ba1c8e3bada
                © 2020 Published by Elsevier B.V.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 31 March 2020
                : 13 July 2020
                : 14 July 2020
                Categories
                Article

                Biomedical engineering
                point-of-care testing,covid-19,sars-cov-2
                Biomedical engineering
                point-of-care testing, covid-19, sars-cov-2

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