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      Convalescent serum-derived exosomes: Attractive niche as COVID-19 diagnostic tool and vehicle for mRNA delivery

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          Abstract

          The spread of SARS-CoV-2 over the entire world is more commonly known as COVID-19. COVID-19 has impacted society in every aspect of routine life. SARS-CoV-2 infection is often misdiagnosed as influenza or seasonal upper respiratory tract viral infections. General diagnostic tools can detect the viral antigen or isotypes of antibodies. However, inter- and intraindividual variations in antibody levels can cause false negatives in antibody immunoassays. On the contrary, the false-positive test results can also occur due to either cross-reactivity of the viral antigens or some other patient-related autoimmune factors. There is need for a cogent diagnostic tool with more specificity, selectivity, and reliability. Here, we have described the potential of convalescent serum-derived exosome as a diagnostic tool for the detection of SARS-CoV-2, even in asymptomatic patients, which is a limitation for currently practiced diagnostic tests throughout the globe. In addition, its potential as a vehicle for messenger RNA (mRNA) delivery is also emphasized.

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          Most cited references67

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          Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China

          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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            An interactive web-based dashboard to track COVID-19 in real time

            In December, 2019, a local outbreak of pneumonia of initially unknown cause was detected in Wuhan (Hubei, China), and was quickly determined to be caused by a novel coronavirus, 1 namely severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The outbreak has since spread to every province of mainland China as well as 27 other countries and regions, with more than 70 000 confirmed cases as of Feb 17, 2020. 2 In response to this ongoing public health emergency, we developed an online interactive dashboard, hosted by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University, Baltimore, MD, USA, to visualise and track reported cases of coronavirus disease 2019 (COVID-19) in real time. The dashboard, first shared publicly on Jan 22, illustrates the location and number of confirmed COVID-19 cases, deaths, and recoveries for all affected countries. It was developed to provide researchers, public health authorities, and the general public with a user-friendly tool to track the outbreak as it unfolds. All data collected and displayed are made freely available, initially through Google Sheets and now through a GitHub repository, along with the feature layers of the dashboard, which are now included in the Esri Living Atlas. The dashboard reports cases at the province level in China; at the city level in the USA, Australia, and Canada; and at the country level otherwise. During Jan 22–31, all data collection and processing were done manually, and updates were typically done twice a day, morning and night (US Eastern Time). As the outbreak evolved, the manual reporting process became unsustainable; therefore, on Feb 1, we adopted a semi-automated living data stream strategy. Our primary data source is DXY, an online platform run by members of the Chinese medical community, which aggregates local media and government reports to provide cumulative totals of COVID-19 cases in near real time at the province level in China and at the country level otherwise. Every 15 min, the cumulative case counts are updated from DXY for all provinces in China and for other affected countries and regions. For countries and regions outside mainland China (including Hong Kong, Macau, and Taiwan), we found DXY cumulative case counts to frequently lag behind other sources; we therefore manually update these case numbers throughout the day when new cases are identified. To identify new cases, we monitor various Twitter feeds, online news services, and direct communication sent through the dashboard. Before manually updating the dashboard, we confirm the case numbers with regional and local health departments, including the respective centres for disease control and prevention (CDC) of China, Taiwan, and Europe, the Hong Kong Department of Health, the Macau Government, and WHO, as well as city-level and state-level health authorities. For city-level case reports in the USA, Australia, and Canada, which we began reporting on Feb 1, we rely on the US CDC, the government of Canada, the Australian Government Department of Health, and various state or territory health authorities. All manual updates (for countries and regions outside mainland China) are coordinated by a team at Johns Hopkins University. The case data reported on the dashboard aligns with the daily Chinese CDC 3 and WHO situation reports 2 for within and outside of mainland China, respectively (figure ). Furthermore, the dashboard is particularly effective at capturing the timing of the first reported case of COVID-19 in new countries or regions (appendix). With the exception of Australia, Hong Kong, and Italy, the CSSE at Johns Hopkins University has reported newly infected countries ahead of WHO, with Hong Kong and Italy reported within hours of the corresponding WHO situation report. Figure Comparison of COVID-19 case reporting from different sources Daily cumulative case numbers (starting Jan 22, 2020) reported by the Johns Hopkins University Center for Systems Science and Engineering (CSSE), WHO situation reports, and the Chinese Center for Disease Control and Prevention (Chinese CDC) for within (A) and outside (B) mainland China. Given the popularity and impact of the dashboard to date, we plan to continue hosting and managing the tool throughout the entirety of the COVID-19 outbreak and to build out its capabilities to establish a standing tool to monitor and report on future outbreaks. We believe our efforts are crucial to help inform modelling efforts and control measures during the earliest stages of the outbreak.
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              Is Open Access

              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
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                Journal
                Experimental Biology and Medicine
                Exp Biol Med (Maywood)
                SAGE Publications
                1535-3702
                1535-3699
                July 2022
                May 13 2022
                July 2022
                : 247
                : 14
                : 1244-1252
                Affiliations
                [1 ]Department of Chemical Pathology, School of Pathology, Faculty of Health Sciences, University of the Free State, Bloemfontein 9300, South Africa
                [2 ]Department of Chemical Pathology, School of Pathology, National Health Laboratory Services, Bloemfontein 9301, South Africa
                [3 ]BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea
                [4 ]Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Republic of Korea
                [5 ]Department of Pharmaceutics and Pharmaceutical Technology, L. M. College of Pharmacy, Ahmedabad 380009, India
                [6 ]Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94158, USA
                [7 ]Department of Pharmaceutical Analysis, Omega College of Pharmacy, Hyderabad 501301, India
                [8 ]Research and Development, Intas Pharmaceuticals Ltd. (Biopharma Division), Ahmedabad 382213, India
                [9 ]Molecular Cell Physiology Laboratory, Department of Biochemistry, School of Medicine, AKFA University, Tashkent 100042, Uzbekistan
                [10 ]Dhanvanthri Lab, Department of Sciences, Amrita School of Engineering, Amrita Vishwa Vidyapeetham, Coimbatore 641112, India
                [11 ]Center of Excellence in Advanced Materials & Green Technologies (CoE–AMGT), Amrita School of Engineering, Amrita Vishwa Vidyapeetham, Coimbatore 641112, India
                [12 ]Federal Research Center—All-Russian Scientific Research Institute of Experimental Veterinary Medicine named after K.I. Skryabin and Y.R. Kovalenko of the Russian Academy of Sciences, Moscow 117218, Russia
                [13 ]Laboratory of Biocontrol and Antimicrobial Resistance, Orel State University named after I.S. Turgenev, Orel 302026, Russia
                [14 ]Department of Chemistry, GITAM (Deemed to be University), Hyderabad 502329, India
                Article
                10.1177/15353702221092984
                35549570
                ac779c05-9aeb-4ab2-9fac-fcccf13a1f15
                © 2022

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