PMC:7235801 / 1410-18368 JSONTXT 11 Projects

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Id Subject Object Predicate Lexical cue
T13 0-285 Sentence denotes SARS-CoV-2 is a large positive-sense single-stranded ribonucleic acid (RNA) virus that comprises of four structural proteins, i.e., nucleocapsid protein (NP) that holds the viral RNA, spike protein (SP), envelope protein (EP), and membrane protein (MP), that create the viral envelope.
T14 286-461 Sentence denotes It has a diameter of 50–200 nm and possesses spikes on its surface (up to 20 nm in length) that provide it the crown-like appearance, a characteristic of coronaviruses (CoVs).
T15 462-586 Sentence denotes The lung disease caused by SARS-CoV-2 was given the name of COVID-19 by the World Health Organisation (WHO) on Feb 11, 2020.
T16 587-724 Sentence denotes WHO declared COVID-19 as a public health emergency of international concern (PHEIC) on January 30, 2020 and a pandemic on March 11, 2020.
T17 725-918 Sentence denotes Although China was the epicenter of the pandemic in the beginning, Europe was declared as the new epicenter on March 13, 2020 as the number of cases and deaths in Europe exceeded that of China.
T18 919-1108 Sentence denotes However, as the number of COVID-19 cases has increased significantly in the United States recently, it could become the new epicenter of COVID-19, as mentioned by the WHO on March 24, 2020.
T19 1109-1389 Sentence denotes Since its discovery in the Hubei province of Wuhan city in China in late December 2019, SARS-CoV-2 has now spread to 204 countries worldwide and also affecting two international conveyances, i.e., the Diamond Princess cruise ship, and the Holland America’s MS Zaandam cruise ship.
T20 1390-1512 Sentence denotes The number of confirmed COVID-19 cases worldwide exceeds 1 million [1,2] while the number of global deaths exceeds 53,000.
T21 1513-1653 Sentence denotes The United States of America (USA) has the most COVID-19 cases with over 245,000 cases, representing about 24% of the global COVID-19 cases.
T22 1654-1750 Sentence denotes Italy, Spain, and Germany follow it, with over 115,000, 112,000, and 84,000 cases, respectively.
T23 1751-1974 Sentence denotes However, Italy is the most affected country, as evident from the high mortality rate due to COVID-19 of over 14,000 deaths, while Spain and the USA are also seriously impacted with over 10,000 and 6000 deaths, respectively.
T24 1975-2103 Sentence denotes The last few weeks have led to an exponential increase in the number of cases in the USA, UK, Iran, and the European Union (EU).
T25 2104-2266 Sentence denotes However, Singapore, South Korea, and China have managed to successfully contain the spread of COVID-19 by taking all essential measures to deal with the pandemic.
T26 2267-2400 Sentence denotes SARS-CoV-2 was transmitted to humans via human–animal contact at the live animals market in Wuhan, China, in late December, 2019 [3].
T27 2401-2522 Sentence denotes Chinese researchers found its origin in bats, but the intermediate hosts for SARS-CoV-2 have not yet been identified [4].
T28 2523-2658 Sentence denotes The genomic sequence of SARS-CoV-2 has about 82% sequence homology to the human SARS-CoV and about 89% with bat SARS-like-CoVZXC21 [5].
T29 2659-2933 Sentence denotes The aged population (age above 65 years), and persons having decreased immunity or chronic diseases, such as hypertension, diabetes mellitus, cardiovascular diseases, and lung disease, are at a higher risk for developing severe COVID-19 if they are infected with SARS-CoV-2.
T30 2934-3005 Sentence denotes Therefore, they must take special precautions to prevent the infection.
T31 3006-3201 Sentence denotes The WHO has stressed the need for more intensive testing of suspected cases to identify COVID-19 infected people so that they can be quarantined in order to avoid the further spread of infection.
T32 3202-3467 Sentence denotes It is also evident that the existing real-time reverse transcriptase polymerase chain (RT-PCR) assays are unable to detect the COVID-19 in the early stages of infection, and there are reports where it has given false negatives in subjects for up to two weeks [6,7].
T33 3468-3644 Sentence denotes The reason of false negative results by RT-PCR could be due to the improper extraction of nucleic acid from clinical materials and insufficient cellular material for detection.
T34 3645-3841 Sentence denotes A chest computerized tomography (CT) scan act as a complementary diagnostic tool that enables physicians to effectively detect COVID-19 infection in several such RT-PCR false-negative cases [8,9].
T35 3842-4011 Sentence denotes Therefore, there is a need for developing better in vitro diagnostic (IVD) assays that can detect the SARS-CoV-2 infection reliably in persons even at the initial stage.
T36 4012-4161 Sentence denotes The specific biomarkers involved during the early stage of COVID-19 infection should be investigated and employed for the development of diagnostics.
T37 4162-4249 Sentence denotes The structure of SARS-CoV-2 comprises of spikes, which are formed by the SP (Figure 1).
T38 4250-4282 Sentence denotes SP is a major glycoprotein (Mol.
T39 4283-4349 Sentence denotes Wt. ~180 kDa) that consists of two subunits, i.e., S1 and S2 [10].
T40 4350-4569 Sentence denotes S1 contains a receptor binding domain (RBD), which is responsible for recognizing and binding with the host cell receptor, i.e., angiotensin converting enzyme 2 receptor (ACE2) found in the lower respiratory tract [11].
T41 4570-4653 Sentence denotes On the other hand, S2 contains other basic elements needed for the membrane fusion.
T42 4654-4803 Sentence denotes SP is the common target for neutralizing antibodies and vaccines, while the amino-terminal S1 subunit of SP is the most variable immunogenic antigen.
T43 4804-4841 Sentence denotes Additionally, SARS-CoV-2 has NP (Mol.
T44 4842-4930 Sentence denotes Wt. ~40 kDa), the most abundant viral phosphoprotein produced and shed during infection.
T45 4931-4991 Sentence denotes The template mRNA of NP is the most abundant subgenomic RNA.
T46 4992-5179 Sentence denotes NP exhibits high immunogenicity and can be detected in either serum or urine samples during the first two weeks of infection with peak viral shedding around ten days after infection [12].
T47 5180-5249 Sentence denotes Being a large protein, it can be detected via a sandwich immunoassay.
T48 5250-5354 Sentence denotes Furthermore, SARS-CoV-2 contains MP, which is the most abundant protein on the complete virion particle.
T49 5355-5492 Sentence denotes The EP is the smallest major structural protein of SARS-CoV-2, which is involved in viral assembly, release of virions, and pathogenesis.
T50 5493-5648 Sentence denotes Several serological immunoassays have been developed by IVD companies for the detection of SARS-CoV-2 viral proteins and antibodies in the serum or plasma.
T51 5649-5962 Sentence denotes The most widely used biomarkers for the detection of SARS-CoV-2 infection in commercial immunoassays (rapid lateral flow immunoassay (LFIA) tests, automated chemiluminescence immunoassay (CLIA), manual ELISA, and other formats) are IgM and IgG antibodies produced in suspects from the 2nd week of viral infection.
T52 5963-6105 Sentence denotes IgM can be detected in the patient samples from 10 to 30 days after SARS-CoV-2 infection, while IgG can be detected from 20 days onwards [13].
T53 6106-6193 Sentence denotes The IgM response occurs earlier than that of IgG, but it then decreases and disappears.
T54 6194-6292 Sentence denotes On the other hand, IgG can persist after infection for a long time and may have a protective role.
T55 6293-6422 Sentence denotes Several manual ELISA kits are also commercially available for the detection of NP and SP, but these are used mainly for research.
T56 6423-6577 Sentence denotes The most widely used IVD assays for the confirmatory diagnosis of COVID-19 are based on RT-PCR that have been employed globally to deal with the pandemic.
T57 6578-6735 Sentence denotes A novel and robust real-time RT-PCR assay was developed by Tib-Molbiol, Germany, in collaboration with various partners by the 2nd week of January 2020 [14].
T58 6736-6827 Sentence denotes It was highly specific for SARS-CoV-2 RNA and did not cross-react with other coronaviruses.
T59 6828-6933 Sentence denotes The test detects the SARS-CoV-2 RNA via envelope (E) and RNA-dependent RNA polymerase (RdRp) gene assays.
T60 6934-7050 Sentence denotes The E-gene assay was used for first line screening, while the RdRp gene assay was employed for confirmatory testing.
T61 7051-7188 Sentence denotes In another approach, the researchers developed one-step RT-PCR assays to detect ORF1b and N regions of SARS-CoV-2 in 1 h and 15 min [15].
T62 7189-7272 Sentence denotes The N gene assay was used for screening, while Orf1b was used as confirmatory test.
T63 7273-7454 Sentence denotes However, as the assay involved the detection of ORF1b and N regions that are highly conserved among sarbecoviruses, it could also bind to SARS-CoV and other closely-related viruses.
T64 7455-7613 Sentence denotes The authors mentioned that they could distinguish the SARS-CoV-2 from SARS-CoV via sequence analysis of positive amplicons if the RT-PCR results are positive.
T65 7614-7818 Sentence denotes Of interest was the development of real-time RT-PCR assay for the detection of RdRp/helicase (H) genes of SARS-CoV-2, which did not cross-react with other human coronaviruses and respiratory viruses [16].
T66 7819-7991 Sentence denotes Due to its high sensitivity, it can be used for COVID-19 detection in samples that have low viral loads and for testing saliva, plasma, and upper respiratory tract samples.
T67 7992-8083 Sentence denotes Many RT-PCR assays have already been developed by many companies and researchers worldwide.
T68 8084-8259 Sentence denotes The most prominent real-time RT-PCR rapid test is the Xpert® Xpress SARS-CoV-2 test by Cepheid, USA, which provides results in just 45 min using GenXpert benchtop system [17].
T69 8260-8448 Sentence denotes It is a rapid and automated point-of-care (POC) molecular test that enables the qualitative detection of SARS-CoV-2 in nasopharyngeal swab, nasal wash, or aspirate specimens from suspects.
T70 8449-8608 Sentence denotes The test requires only a minute for sample preparation, employs Cepheid’s Xpert® Xpress cartridge technology, and targets multiple regions of the viral genome.
T71 8609-8699 Sentence denotes It has also received Food and Drug Administration (FDA) emergency use authorization (EUA).
T72 8700-8847 Sentence denotes Another prominent advance is the Vivalytic COVID-19 test by Bosch, Germany [18], which detects SARS-CoV-2 infection in suspects in less than 2.5 h.
T73 8848-8926 Sentence denotes The test was developed by Bosch in collaboration with Randox Laboratories, UK.
T74 8927-9086 Sentence denotes It is a fully automated and rapid POC molecular test that can simultaneously detect SARS-CoV-2 and nine other respiratory viruses, including influenza A and B.
T75 9087-9229 Sentence denotes The sample is taken from the nose or throat of suspect using a swab and placed inside a Vivalytic cartridge containing all the assay reagents.
T76 9230-9301 Sentence denotes The cartridge is then plugged into a small benchtop Vivalytic analyzer.
T77 9302-9419 Sentence denotes Abbott ID Now™ COVID-19 test is the most recent breakthrough IVD assay that detects SARS-CoV-2 in just 5 min [19,20].
T78 9420-9573 Sentence denotes It is a molecular POC test that utilizes the isothermal nucleic acid amplification technology for the qualitative detection of viral RNA from SARS-CoV-2.
T79 9574-9697 Sentence denotes The test can be used in any location, such as hospitals, clinics, physicians’ offices, or in outbreak hotspots of COVID-19.
T80 9698-9849 Sentence denotes It requires just a portable touchscreen-operated instrument, i.e., ID Now, which is lightweight (6.6 pounds) and compact (the size of a small toaster).
T81 9850-9975 Sentence denotes It employs a molecular test for the RdRp gene, and can take throat, nasal, nasopharyngeal and oropharyngeal swabs as samples.
T82 9976-10077 Sentence denotes The kit contains 24 tests, positive and negative controls, swabs for sample collection, and pipettes.
T83 10078-10167 Sentence denotes It has just received the FDA EUA and is being seen as a remarkable achievement worldwide.
T84 10168-10394 Sentence denotes Apart from the molecular diagnostics, numerous LFIA based rapid POC tests have been developed by several companies, which enable the detection of IgM and IgG antibodies produced in suspects in response to SARS-COV-2 infection.
T85 10395-10554 Sentence denotes One of the most prominent rapid tests is the COVID-19 test developed by BioMedomics, USA, which detects IgM and IgG antibodies in suspects in just 10 min [21].
T86 10555-10651 Sentence denotes It requires minimal sample volume, i.e., 20 µL of finger-pricked blood or 10 µL of serum/plasma.
T87 10652-10844 Sentence denotes It does not require any instrument or trained staff and, thus, it can be employed at any place and time, especially in developing nations with limited healthcare resources and remote settings.
T88 10845-10938 Sentence denotes The assay is ideal for primary healthcare workers for the rapid testing of COVID-19 suspects.
T89 10939-11131 Sentence denotes Another prospective test is the SARS-CoV-2 rapid by Pharmacyt AG, Germany [22], which employs only two drops of finger-pricked blood sample from the suspects and can provide results in 20 min.
T90 11132-11217 Sentence denotes The results obtained by the rapid test correlated well with those achieved by RT-PCR.
T91 11218-11359 Sentence denotes The most exciting advance is the DPP COVID-19 IgM/IgG test launched recently by Chembio Diagnostics, USA, which has already received FDA EUA.
T92 11360-11459 Sentence denotes It is a POC rapid LFIA test that provides results in just 15 min using finger-pricked blood sample.
T93 11460-11660 Sentence denotes However, the distinct feature of the test is that it does not rely on the visual detection by naked eye but employs optical readout via MicroReader 1 and 2 analyzers produced by Chembio, Germany [23].
T94 11661-12031 Sentence denotes A large number of rapid IgM/IgG tests have been developed by several IVD companies, such as Beijing Lepu Medical Technology, Sona Nanotech, Jiangsu Medomics Medical Technologies, Innovita Biological Technology, Guangzhou Wondfo Biotech, Zhejiang Orient Gene Biotech, Biomerica, Xiamen AmonMed Biotechnology, Sugentech, CHIL, Zhenjiang Orient Gene Biotech, Sure Bio-Tech.
T95 12032-12207 Sentence denotes However, there are very few peer-reviewed publications [24] that show the accuracy of the COVID-19 diagnostic results obtained by the rapid tests with respect to RT-PCR tests.
T96 12208-12423 Sentence denotes Rapid tests could be used as a complementary IVD assay to the existing RT-PCR assays, which could lead to much better diagnosis of COVID-19 and provide additional information about the immune status of the suspects.
T97 12424-12566 Sentence denotes However, the clinical accuracy of rapid tests needs to be stringently evaluated before they are authorized for the mass screening of COVID-19.
T98 12567-12788 Sentence denotes The recent reports from many European countries suggest that most of the rapid tests for COVID-19 procured from China did not show good analytical performance and did not work for over 70% of COVID-19 cases [25,26,27,28].
T99 12789-13039 Sentence denotes Furthermore, as IgM and IgG could only be detected in suspects about two weeks after the onset of infection, there is an immense need to include other biomarkers of the early stage of SARS-CoV-2 infection for developing improved COVID-19 rapid tests.
T100 13040-13172 Sentence denotes An exciting development is the DZ-Lite SARS-CoV-2 CLIA IgM and IgG tests developed by Diazyme, USA, that have received FDA EUA [29].
T101 13173-13359 Sentence denotes The tests are based on the principle of chemiluminescence immunoassay (CLIA) and run on an automated Diazyme DZ-Lite 3000 Plus chemiluminescence analyzer with a throughput of 50 tests/h.
T102 13360-13516 Sentence denotes Similarly, Snibe, China, has developed automated CLIA tests on MAGLUMI CLIA analyzers for the detection of IgG and IgM in the patient sample in 30 min [30].
T103 13517-13832 Sentence denotes The main advantages of automated CLIA analyzers based COVID-19 assays compared to rapid LFIA tests is the very high throughput of samples that can be analyzed and the ability to perform more clinical tests for other biomarkers, such as C-reactive protein (CRP), which also need to be monitored in COVID-19 suspects.
T104 13833-14008 Sentence denotes Several CE marked manual ELISA kits have also been developed by various IVD manufacturers, such as Euroimmun, IBL International, DRG Diagnostics GmbH, and Epitope Diagnostics.
T105 14009-14102 Sentence denotes Most of them target the IgG and IgM produced in subjects in response to SARS-CoV-2 infection.
T106 14103-14337 Sentence denotes Other prospective IVD assay formats, such as those based on reverse transcription loop-mediated isothermal amplification (RT-LAMP), lab-on-a-chip, microfluidics, and multiplex detection are currently being investigated by researchers.
T107 14338-14506 Sentence denotes It would also be useful to develop an automated and fully integrated POC IVD assay that can perform molecular and immunological testing on a single analytical platform.
T108 14507-14775 Sentence denotes An ideal IVD assay for the POC detection of COVID-19 in the near future would be the smartphone-based POC electrochemical test for SARS-CoV-2 biomarkers, similar to the iHealth Align device developed by iHealth, USA, for smartphone-based blood glucose monitoring [31].
T109 14776-14929 Sentence denotes Smartphones are omnipresent, powered by internal battery, and equipped with large storage capacity, advanced processing power and a large screen display.
T110 14930-15146 Sentence denotes Moreover, they have global positioning system (GPS) for spatiotemporal tagging of data, internet connectivity, and capability to store the processed results in the internal device memory as well as to a secure Cloud.
T111 15147-15342 Sentence denotes Therefore, smartphone-based POC electrochemical device for the detection of SARS-CoV-2 biomarkers could be very useful for the large-scale rapid testing of COVID-19 suspects at the point-of-need.
T112 15343-15456 Sentence denotes The accurate diagnosis of people infected with the SARS-CoV-2 is essential to curb the global spread of COVID-19.
T113 15457-15582 Sentence denotes However, the current RT-PCR based diagnostic assays are not robust, as they are still missing several infected cases [6,8,9].
T114 15583-15685 Sentence denotes Moreover, they can only be performed in well-equipped central laboratories by highly skilled analysts.
T115 15686-15849 Sentence denotes Therefore, they are of limited utility and cannot be deployed widely, such as in developing nations, remote locations, and regions with decentralized laboratories.
T116 15850-15998 Sentence denotes The delay in diagnosing people until after they have passed the disease onto many others is contributing to the continued global spread of COVID-19.
T117 15999-16112 Sentence denotes The rapid LFIA and automated CLIA tests for IgM and IgG could complement the existing COVID-19 testing by RT-PCR.
T118 16113-16258 Sentence denotes However, there is a need to stringently evaluate the clinical performance of commercial tests before they are used for the diagnosis of COVID-19.
T119 16259-16404 Sentence denotes The biomarker discovery could also play a key role in identifying novel biomarkers that are involved in the early stages of SARS-CoV-2 infection.
T120 16405-16567 Sentence denotes The recently developed Abbott ID Now™ COVID-19 test that detects SARS-CoV-2 in 5 min is a remarkable achievement [19,20] and could revolutionize COVID-19 testing.
T121 16568-16702 Sentence denotes The ongoing efforts will further lead to reliable, robust, rapid, and easy-to-implement IVD assays and smart diagnostics for COVID-19.
T122 16703-16847 Sentence denotes There are still significant knowledge gaps in health research that are crucial for an effective public health response in the case of epidemics.
T123 16848-16958 Sentence denotes It signifies the need for all nations to invest in health research and make it an integral part of healthcare.