CORD-19-Sentences  

CORD-19:5a51f0a5a8d59d0e6598256bbb2a411196bd2d72 JSONTXT 7 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
TextSentencer_T1 0-106 Sentence denotes Rapid Detection of 2019 Novel Coronavirus SARS-CoV-2 Using a CRISPR-based 1 DETECTR Lateral Flow Assay 2 3
TextSentencer_T2 108-116 Sentence denotes Abstract
TextSentencer_T3 118-120 Sentence denotes 33
TextSentencer_T4 123-171 Sentence denotes virus (ZIKV), and most recently SARS-CoV-2 1,2 .
TextSentencer_T5 172-365 Sentence denotes All of these epidemics presumably 46 resulted from an initial zoonotic animal-to-human transmission event, with either 47 clinically apparent or occult spread into vulnerable human populations.
TextSentencer_T6 366-523 Sentence denotes Each time, a 48 lack of rapid, accessible, and accurate molecular diagnostic testing has hindered the 49 public health response to the emerging viral threat.
TextSentencer_T7 524-526 Sentence denotes 50
TextSentencer_T8 527-691 Sentence denotes In early January 2020, a cluster of cases of pneumonia from a novel coronavirus, 51 SARS-CoV-2 (with the disease referred to as COVID-19), was reported in Wuhan, 52
TextSentencer_T9 692-703 Sentence denotes China 1,2 .
TextSentencer_T10 704-815 Sentence denotes This outbreak has spread rapidly, with over 90,000 reported cases and 3,000 53 deaths as of March 4th, 2020 3 .
TextSentencer_T11 816-923 Sentence denotes Person-to-person transmission from infected individuals 54 with no or mild symptoms has been reported 4,5 .
TextSentencer_T12 924-1125 Sentence denotes Assays using quantitative reverse 55 transcription-polymerase chain reaction (qRT-PCR) approaches for detection of the 56 virus in 4-6 hours have been developed by several laboratories, including an 57
TextSentencer_T13 1126-1202 Sentence denotes Emergency Use Authorization (EUA)-approved assay developed by the US CDC 6 .
TextSentencer_T14 1203-1205 Sentence denotes 58
TextSentencer_T15 1206-1399 Sentence denotes However, the typical turnaround time for screening and diagnosing patients with 59 suspected SARS-CoV-2 has been >24 hours given the need to ship samples overnight 60 to reference laboratories.
TextSentencer_T16 1400-1704 Sentence denotes To accelerate clinical diagnostic testing for COVID-19 in the 61 United States, the FDA on February 28th, 2020 permitted individual clinically licensed 62 laboratories to report the results of in-house developed SARS-CoV-2 diagnostic assays 63 while awaiting results of an EUA submission for approval 7 .
TextSentencer_T17 1705-1707 Sentence denotes 64
TextSentencer_T18 1708-1966 Sentence denotes Here we report the development and initial validation of a CRISPR (clustered 65 regularly interspaced short palindromic repeats)-Cas12 based assay 8-11 for detection of 66 SARS-CoV-2 from extracted patient sample RNA in ~30 min, called SARS-CoV-2 67 DETECTR.
TextSentencer_T19 1967-2041 Sentence denotes This assay performs simultaneous reverse transcription and isothermal 68 .
TextSentencer_T20 2042-2196 Sentence denotes CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
TextSentencer_T21 2197-2499 Sentence denotes is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.06.20032334 doi: medRxiv preprint target region for the CDC assay is no longer being used due to concerns regarding 92 flaws in manufacturing reagents and potential decreased sensitivity) 14 .
TextSentencer_T22 2500-2502 Sentence denotes 93
TextSentencer_T23 2503-2724 Sentence denotes We next compared the analytic limits of detection (LoD) of the RT-LAMP/Cas12 94 DETECTR assay relative to the US FDA Emergency Use Authorization (EUA)-approved 95 CDC assay for detection of SARS-CoV-2 (Table 1; Fig. 2d) .
TextSentencer_T24 2725-2944 Sentence denotes A standard curve for 96 quantitation was constructed using 7 dilutions of a control IVT viral nucleoprotein RNA 97 ("CDC VTC nCoV Transcript") 6 , with 3 replicates at each dilution (Fig. 2d, left; 98 Extended Data 1).
TextSentencer_T25 2945-3015 Sentence denotes Ten two-fold serial dilutions of the same control nucleoprotein RNA 99
TextSentencer_T26 3016-3137 Sentence denotes were then used to run the DETECTR assay, with 6 replicates at each dilution (Fig. 2d, 100 right; Supplementary Fig. 3) .
TextSentencer_T27 3138-3187 Sentence denotes The estimated LoD for the CDC assay tested by 101
TextSentencer_T28 3188-3378 Sentence denotes California Department of Public Health was 1 copy/µL reaction, consistent with the 102 analytic performance in the FDA package insert, versus 10 copies/µL reaction for the 103 DETECTR assay.
TextSentencer_T29 3379-3382 Sentence denotes 104
TextSentencer_T30 3383-3695 Sentence denotes We then assessed the capability of the RT-LAMP assay to amplify SARS-CoV-2 105 nucleic acid directly from raw sample matrix consisting of nasopharyngeal swabs from 106 asymptomatic donors placed in universal transport medium (UTM) or phosphate 107 buffered saline (PBS) and spiked with SARS-CoV-2 IVT target RNA.
TextSentencer_T31 3696-3914 Sentence denotes Assay 108 performance was degraded at reaction concentration of ≥ 10% UTM and ≥ 20% PBS by 109 volume, with estimated limits of detection decreasing to 500 and 1,500 copies/µL, 110 respectively (Supplementary Fig. 4) .
TextSentencer_T32 3915-3918 Sentence denotes 111
TextSentencer_T33 3919-4077 Sentence denotes Finally, we tested extracted RNA from 11 respiratory swab samples collected 112 from 6 PCR-positive COVID-19 patients (COVID19-1A/B to COVID19-5A/B, where 113
TextSentencer_T34 4078-4154 Sentence denotes A=nasopharyngeal swab and B=oropharyngeal swab and COVID19-6, a single 114 .
TextSentencer_T35 4155-4309 Sentence denotes CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
TextSentencer_T36 4310-4698 Sentence denotes is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.06.20032334 doi: medRxiv preprint nasopharyngeal swab) and 12 nasopharyngeal swab samples from patients with 115 influenza (n=4), common human seasonal coronavirus infections (n=3, representing 116 OC43, HKU1, NL63), and healthy donors (n=5) (Fig. 2e, f; Supplementary Fig. 5) .
TextSentencer_T37 4699-4702 Sentence denotes 117
TextSentencer_T38 4703-4957 Sentence denotes Relative to the CDC qRT-PCR, SARS-CoV-2 DETECTR was 90% sensitive and 100% 118 specific for detection of the coronavirus in respiratory swab samples, corresponding to 119 positive and negative predictive values of 100% and 91.7%, respectively (Fig. 2g) .
TextSentencer_T39 4958-4961 Sentence denotes 120
TextSentencer_T40 4962-5123 Sentence denotes Here we combined isothermal amplification with CRISPR-Cas12 DETECTR 121 technology to develop a rapid (~30 min) and low-cost test for detection of SARS-CoV-2 122
TextSentencer_T41 5124-5144 Sentence denotes in clinical samples.
TextSentencer_T42 5145-5324 Sentence denotes The use of existing qRT-PCR based assays is hindered by the need 123 for expensive lab instrumentation, and availability is currently restricted to public health 124 laboratories.
TextSentencer_T43 5325-5527 Sentence denotes Importantly, the DETECTR assays developed here have comparable 125 accuracy to qRT-PCR and are broadly accessible, as they use routine protocols and 126 commercially available, "off-the-shelf" reagents.
TextSentencer_T44 5528-6078 Sentence denotes Key advantages of our approach over 127 existing methods such as qRT-PCR include (1) isothermal signal amplification for rapid 128 target detection obviating the need for thermocycling, (2) single nucleotide target 129 specificity (guide RNAs at the N2 site can distinguish SARS-CoV-2 from SARS-CoV 130 and MERS-CoV), (3) integration with portable, low-cost reporting formats such as lateral 131 flow strips, and (4) quick development cycle to address emerging threats from novel 132 zoonotic viruses (<2 weeks for SARS-CoV-2, Supplementary Fig. 6) .
TextSentencer_T45 6079-6082 Sentence denotes 133
TextSentencer_T46 6083-6331 Sentence denotes Although most of the cases of COVID-19 infection during the first month of the 134 epidemic were traced to the city of Wuhan and Hubei province in China, the ongoing 135 rise in cases now appears to be driven to local community transmission 15,16 .
TextSentencer_T47 6332-6435 Sentence denotes For a 136 number of reasons, there is an urgent public health need for rapid diagnostic tests for 137 .
TextSentencer_T48 6436-6592 Sentence denotes CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. .
TextSentencer_T49 6593-6747 Sentence denotes CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
TextSentencer_T50 6748-6891 Sentence denotes is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.06.20032334 doi: medRxiv preprint
TextSentencer_T51 6892-6897 Sentence denotes 162 .
TextSentencer_T52 6898-7052 Sentence denotes CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
TextSentencer_T53 7053-7351 Sentence denotes is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.06.20032334 doi: medRxiv preprint CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
TextSentencer_T54 7352-7501 Sentence denotes is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.06.20032334 doi: medRxiv preprint 181 .
TextSentencer_T55 7502-7656 Sentence denotes CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
TextSentencer_T56 7657-7810 Sentence denotes is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.06.20032334 doi: medRxiv preprint interest.
TextSentencer_T57 7811-7928 Sentence denotes First a PCR step was performed on the synthetic gene fragment with a forward 232 primer that contained a T7 promoter.
TextSentencer_T58 7929-7979 Sentence denotes Next, the PCR product was used as the template 233
TextSentencer_T59 7980-8045 Sentence denotes for an in-vitro transcription (IVT) reaction at 37°C for 2 hours.
TextSentencer_T60 8046-8190 Sentence denotes The IVT reaction was then 234 treated with TURBO DNase (Thermo) for 30 min at 37°C, followed by a heat-235 denaturation step at 75°C for 15 min.
TextSentencer_T61 8191-8231 Sentence denotes RNA was purified using RNA Clean and 236
TextSentencer_T62 8232-8293 Sentence denotes and diluted in nuclease-free water to working concentrations.
TextSentencer_T63 8294-8303 Sentence denotes 238 239 .
TextSentencer_T64 8304-8460 Sentence denotes CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. .
TextSentencer_T65 8461-8615 Sentence denotes CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
TextSentencer_T66 8616-8770 Sentence denotes CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
TextSentencer_T67 8771-8956 Sentence denotes is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.06.20032334 doi: medRxiv preprint Extended Data 1 ("Extended_Data_1.xlsx").
TextSentencer_T68 8957-9091 Sentence denotes Standard curve generated by running 361 seven 5-or 10-fold dilutions of the CDC N2 qRT-PCR assay, with 3 replicates each 362 dilution.
TextSentencer_T69 9092-9161 Sentence denotes The R-squared measure corresponding to the regression line is 0.9981.
TextSentencer_T70 9162-9171 Sentence denotes 363 364 .
TextSentencer_T71 9172-9326 Sentence denotes CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
TextSentencer_T72 9327-9512 Sentence denotes is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.06.20032334 doi: medRxiv preprint Extended Data 2 ("Extended_Data_2.xlsx").
TextSentencer_T73 9513-9602 Sentence denotes Primer, reporter molecules, target gene 365 fragments, and guide RNAs used in this study.
TextSentencer_T74 9603-9620 Sentence denotes 366 367 368 369 .
TextSentencer_T75 9621-9775 Sentence denotes CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
TextSentencer_T76 9776-9921 Sentence denotes is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.06.20032334 doi: medRxiv preprint .
TextSentencer_T77 9922-10076 Sentence denotes CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
TextSentencer_T78 10077-10220 Sentence denotes is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.06.20032334 doi: medRxiv preprint