Current best evidence for clinical care (more info)
Background: Access to rapid diagnosis is key to the control and management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Laboratory RT-PCR testing is the current standard of care but usually requires a centralised laboratory and significant infrastructure. We describe our diagnostic accuracy assessment of a novel, rapid point-of-care real time RT-PCR CovidNudge test, which requires no laboratory handling or sample pre-processing.
Methods: Between April and May, 2020, we obtained two nasopharyngeal swab samples from individuals in three hospitals in London and Oxford (UK). Samples were collected from three groups: self-referred health-care workers with suspected COVID-19; patients attending emergency departments with suspected COVID-19; and hospital inpatient admissions with or without suspected COVID-19. For the CovidNudge test, nasopharyngeal swabs were 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 sample adequacy control. Swab samples were tested in parallel using the CovidNudge platform, and with standard laboratory RT-PCR using swabs in viral transport medium for processing in a central laboratory. The primary analysis was to compare the sensitivity and specificity of the point-of-care CovidNudge test with laboratory-based testing.
Findings: We obtained 386 paired samples: 280 (73%) from self-referred health-care workers, 15 (4%) from patients in the emergency department, and 91 (23%) hospital inpatient admissions. Of the 386 paired samples, 67 tested positive on the CovidNudge point-of-care platform and 71 with standard laboratory RT-PCR. The overall sensitivity of the point-of-care test compared with laboratory-based testing was 94% (95% CI 86-98) with an overall specificity of 100% (99-100). The sensitivity of the test varied by group (self-referred healthcare workers 93% [95% CI 84-98]; patients in the emergency department 100% [48-100]; and hospital inpatient admissions 100% [29-100]). Specificity was consistent between groups (self-referred health-care workers 100% [95% CI 98-100%]; patients in the emergency department 100% [69-100]; and hospital inpatient admissions 100% [96-100]). Point of care testing performance was similar during a period of high background prevalence of laboratory positive tests (25% [95% 20-31] in April, 2020) and low prevalence (3% [95% 1-9] in inpatient screening). Amplification of viral nucleocapsid (n1, n2, and n3) and envelope protein gene (e-gene) were most sensitive for detection of spiked SARS-CoV-2 RNA.
Interpretation: The CovidNudge platform was a sensitive, specific, and rapid point of care test for the presence of SARS-CoV-2 without laboratory handling or sample pre-processing. The device, which has been implemented in UK hospitals since May, 2020, could enable rapid decisions for clinical care and testing programmes.
Funding: National Institute of Health Research (NIHR) Imperial Biomedical Research Centre, NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at Oxford University in partnership with Public Health England, NIHR Biomedical Research Centre Oxford, and DnaNudge.
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This RCT conducted in the UK evaluated a point-of-care test (CovidNudge test) for diagnosis of COVID-19. Two nasopharyngeal swabs were obtained from each patient from 3 separate hospitals. Three groups were included: self-referred healthcare workers with suspected infection, patients in the ED with suspected infection, and admitted patients with or without suspected COVID-19. The CovidNudge test utilizes a cartridge that contains all reagents and components for PCR reactions, based on seven gene targets for SARS-CoV-2. This was compared with standard RT-PCR. There were 386 paired samples. The sensitivity was 94% (95% CI 86-98%), with a 100% specificity (95% CI 99-100%). There are several limitations. First, there was no single laboratory platform used for comparison. Infection rates fell during the study period. The testing platform can only process one cartridge at a time. This testing platform has promise, and further studies may validate the utility of this modality.
Point-of-care testing without handling delays for SARS-CoV-2 will be essential when the next phase of COVID-19 emerges in the northern hemisphere with influenza season. This diagnostic accuracy study provides encouraging preliminary evidence of one such test. In my opinion, the quality of this study would have been enhanced by strict adherence to (and citation of) the STARD criteria (https://www.equator-network.org/reporting-guidelines/stard/), which is too often neglected in emergency medicine diagnostic research (https://onlinelibrary.wiley.com/doi/full/10.1111/acem.13233 and https://onlinelibrary.wiley.com/doi/full/10.1111/acem.13225). Some contemplation beyond "additional research required" about how this test might add to history/physical exam/imaging (https://onlinelibrary.wiley.com/doi/full/10.1111/acem.14048) would also have been additive. In addition, the cost of this test is not reported.
Clearly an area of growing importance to emergency physicians as rapid testing will become central to the evaluation of patients with suspected infection. While this technology is not ready for prime time, it is important that ED providers begin to familiarize themselves with this literature.
This paper describes a point-of-care test that compares well with the "gold standard" of PCR. However, both still require a nasopharyngeal swab, which may limit acceptability.
Looks good in higher risk groups, but the certainty in low-risk groups is unclear.
Problematic in the use of the terms "sensitivity" and "specificity" when it really probably reports "reproducibility" vs a somewhat flawed gold standard. Still, quite important in terms of short turnaround.
The CovidNudge point of care system for detecting COVID appears to be quite accurate with "compartmentalized" sample handling, controls to detect invalid results, and a run-time of around 90 minutes. Though the throughput is low (one cartridge only per run), the portability and rapid test results obtained by the system would seem to be quite useful for contact tracing purposes.