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      Current status, advances, challenges and perspectives on biosensors for COVID-19 diagnosis in resource-limited settings

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          Highlights

          • Urgent need for affordable, rapid and robust COVID-19 diagnostics is underscored.

          • Biomarkers and working principles for the COVID-19 diagnosis are reviewed.

          • Advances, challenges, perspectives of COVID-19 point-of-care diagnosis discussed.

          • Research and commercial products based on different bio/markers presented.

          • Key specifications for US-FDA approved and lab-based biosensors summarized.

          Abstract

          As the COVID-19 pandemic has profoundly impacted human life, prompt diagnostic tests are becoming an essential part of the social activities. However, the expensive and time-consuming laboratory-based traditional methods do not suffice the enormous needs for massive number of tests, especially in resource-limited settings. Therefore, more affordable, rapid, sensitive and specific field-practical diagnostic devices play an important role in the fight against the disease. In this review, we present the current status and advances in the biosensing technologies for diagnosing COVID-19, ranging from commercial achievements to research developments. Starting from a brief introduction to the disease biomarkers, this review summarizes the working principles of the biosensing technologies, followed by a review of the commercial products and research advances in academia. We recapitulate the literatures with a wide scope of bio/marker detections, embracing nucleic acids, viral proteins, human immune responses, and other potential bio/markers. Further, the challenges and perspectives for their employment in future point-of-care applications are discussed, with an extended appraisal on the practical strategies to enlarge the testing capability without high cost. This critical review provides a comprehensive insight into the diagnostic tools for COVID-19 and will encourage the industry and academia in the field of diagnostic biosensing for future evolvement to large-scale point-of-care screening of COVID-19.

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          Most cited references123

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          Is Open Access

          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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            Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

            Summary Background In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. Methods In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. Findings Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. Interpretation The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. Funding National Key R&D Program of China.
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              Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein

              Summary The emergence of SARS-CoV-2 has resulted in >90,000 infections and >3,000 deaths. Coronavirus spike (S) glycoproteins promote entry into cells and are the main target of antibodies. We show that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, correlating with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S1/S2 subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and SARS-related CoVs. We determined cryo-EM structures of the SARS-CoV-2 S ectodomain trimer, providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S murine polyclonal antibodies potently inhibited SARS-CoV-2 S mediated entry into cells, indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.
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                Author and article information

                Journal
                Sensors and Actuators Reports
                The Authors. Published by Elsevier B.V.
                2666-0539
                2666-0539
                7 January 2021
                November 2021
                7 January 2021
                : 3
                : 100025
                Affiliations
                [a ]Chemical and Environmental Engineering Department, University of California Riverside, Riverside, CA, 92521 USA
                [b ]Center for Environmental Research and Technology (CE-CERT), University of California Riverside, Riverside, CA, 92507 USA
                Author notes
                [* ]Corresponding author.
                [#]

                These authors contributed equally.

                Article
                S2666-0539(21)00001-1 100025
                10.1016/j.snr.2021.100025
                7831652
                e6d2357f-cdc4-407d-92b6-e6198b7f773c
                © 2021 The Authors

                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
                : 6 December 2020
                : 28 December 2020
                : 29 December 2020
                Categories
                Article

                covid-19,point-of-care,biosensors,diagnostics,assured criteria,healthcare

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