CovidNudge: diagnostic accuracy of a novel lab free point of care diagnostic for SARS CoV 2

Background Access to rapid diagnosis is key to the control and management of SARS-CoV-2. Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) testing usually requires a centralised laboratory and significant infrastructure. We describe the development and diagnostic accuracy assessment of a novel, rapid point-of-care RT-PCR test, the DnaNudge® platform CovidNudge test, which requires no laboratory handling or sample pre-processing. Methods Nasopharyngeal swabs are inserted directly into a cartridge which contains all reagents and components required for RT-PCR reactions, including multiple technical replicates of seven SARS-CoV-2 gene targets (rdrp1, rdrp2, e -gene, n -gene, n1, n2 and n3) and human ribonuclease P (RNaseP) as positive control. Between April and May 2020, swab samples were tested in parallel using the CovidNudge direct-to-cartridge platform and standard laboratory RT-PCR using swabs in viral transport medium. Samples were collected from three groups: self-referred healthcare workers with suspected COVID-19 (Group 1, n=280/386; 73%); patients attending the emergency department with suspected COVID-19 (Group 2, n=15/386; 4%) and hospital inpatient admissions with or without suspected COVID-19 (Group 3, n=91/386; 23%). Results Of 386 paired samples tested across all groups, 67 tested positive on the CovidNudge platform and 71 with standard laboratory RT-PCR. The sensitivity of the test varied by group (Group 1 93% [84-98%], Group 2 100% [48-100%] and Group 3 100% [29-100%], giving an average sensitivity of 94.4% (95% confidence interval 86-98%) and an overall specificity of 100% (95%CI 99-100%; Group 1 100% [98-100%]; Group 2 100% [69-100%] and Group 3 100% [96-100%]). Point of care testing performance was comparable during a period of high (25%) and low (3%) background prevalence. Amplification of the viral nucleocapsid (n1, n2, n3) targets were most sensitive for detection of SARS-CoV2, with the assay able to detect 1×10[4][1] viral particles in a single swab. Conclusions The CovidNudge platform offers a sensitive, specific and rapid point of care test for the presence of SARS-CoV-2 without laboratory handling or sample pre-processing. The implementation of such a device could be used to enable rapid decisions for clinical care and testing programs. Evidence before this study The WHO has highlighted the development of rapid, point-of-care diagnostics for detection of SARS-CoV-2 as a key priority to tackle COVID-19. The Foundation for Innovative Diagnostics (FIND) has identified over 90 point-of-care, near patient or mobile tests for viral detection of SARS-CoV-2. However, the most widely available rapid tests to date require some sample handling which limits their use at point-of-care. In addition, pressure on supply chains is restricting access to current diagnostics and alternatives are needed urgently. Added value of this study We describe the development and clinical validation of COVID nudge, a novel point-of-care RT-PCR diagnostic, evaluated during the first wave of the SARS-CoV-2 epidemic. The platform is able to achieve high analytic sensitivity and specificity from dry swabs within a self-contained cartridge. The lack of downstream sample handling makes it suitable for use in a range of clinical settings, without need for a laboratory or specialized operator. Multiplexed assays within the cartridge allow inclusion of a positive human control, which reduces the false negative testing rate due to insufficient sampling. Implication of the available evidence Point-of-care testing can relieve pressure on centralized laboratories and increase overall testing capacity, complementing existing approaches. These findings support a role for COVID Nudge as part of strategies to improve access to rapid diagnostics to SARS-CoV-2. Since May 2020, the system has been implemented in UK hospitals and is being rolled out nationwide. ### Competing Interest Statement CT, RS, MS, CI, MK, TH, SDM, FL, JB and AO are employees of DnaNudge. CT is named on the patent for method and apparatus for analyzing biological specimens on the DnaNudge platform (US Patent No: US 10,093,965 B216. LSPM has consulted for bioMerieux (2013 to 2020), DNAelectronics (2015), Dairy Crest (2017 to 2018), Pfizer (2018-2020), and Umovis Lab (2020), received speaker fees from Profile Pharma (2018), received research grants from the National Institute for Health Research (2013 to 2019), Leo Pharma (2016), and CW+ Charity (2018 to 2019), and received educational support from Eumedica (2016 to 2017). NM has received speaker fees from Beyer (2016) and Pfizer (2019) and received educational support from Eumedica (2016) and Baxter (2017). All other authors have no conflicts of interest to declare. ### Funding Statement The work was supported by the Biomedical Research Centre of Imperial College NHS Trust. M.M.G. is supported in part by the NIHR Imperial Biomedical Research Centre. GC is an NIHR Research Professor and Investigator within the NIHR London In-vitro Diagnostic Collaborative. Part of this work was supported by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Healthcare Associated Infections and Antimicrobial Resistance at Oxford University in partnership with Public Health England (PHE) [grant HPRU-2012-10041] and the NIHR Biomedical Research Centre, Oxford. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, the Department of Health or Public Health England. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Participants in Group 2 were consented as part of the communicable disease research tissue bank (ethical approval ref 15/SC/0089). Following derogation from the Medicines and Healthcare Regulatory Agency (MHRA) evaluation within staff testing at all three sites was performed as a service evaluation in parallel with routine SARS-CoV-2 RT-PCR testing. Verbal or written consent for an additional swab was obtained from each participant and results from POC testing were not fed back to the individual participants. Analysis of Group 3 was conducted as a service evaluation approved by the Point of Care Committee at Chelsea & Westminster NHS Foundation Trust and results were used to inform patient care. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes De-identified study data are available from the corresponding author upon reasonable request. [1]: #ref-4