September 17, 2020

expert reaction to study assessing accuracy of rapid 90-minute COVID-19 test, CovidNudge

Research, published in the Lancet Microbe, has looked at the accuracy of the rapid 90-minute COVID-19 test, CovidNudge.

This Roundup was accompanied by an SMC Briefing.

Prof Terry Wilkins FREng, Emeritus Professor of Nanomanufacturing Innovation at the University of Leeds, and a Fellow of the Royal Academy of Engineering, said:

Is this robust science?

“The answer is yes.  The underpinning science and technologies of the clinical diagnostic testing methodology are well thought out and robust with many sensible checks and balances throughout.  I particularly commend the use of an “on board” reference DNA sample in each test unit.  The basic nudge platform was developed from an already proven and robust DNA sequencing platform.  The pairwise comparison of samples using DNA Nudge and PHE/NHS high-throughput laboratories is very sensible and has good statistical power to support the authors conclusions.

Does the press release accurately reflect the research?

“Yes.  In all aspects.  I note that the Cloud data storage capability also offers the option of rapid reporting to mobile phones, which I approve.

Is this convincing evidence of accuracy of the test?

“Yes.  For the reasons I note above.  The authors have studied both analytical and clinical accuracy.  The former covers detection limits and dynamic range.  The latter studies clinical sensitivity and specificity.  There is good agreement between the DNA nudge and the reference methods.  The number of hospitals and subjects studied equates to stage-1 clinical trial and is sufficient for a good Lancet publication.  The authors note that a 2^nd much larger study (stage-2 clinical trial) has been underway since May.  This is essential for gaining US FDA and EU CE regulatory approvals.  Given the quality of the stage-1 study, I would expect the stage-2 study’s results to compare well with those from stage-1.

What are the implications for testing in the UK?

“The UK must focus on operational matters asap.  At the start of the pandemic it made very good sense to set up large central reference laboratories using pre-existing DNA technologies and with essential GLP and QA practices needed.  But these can lead to bottle necks and logistical problems.  The normal practice is clinical diagnostics is to have a tiered approach.  Initial screening tests available widely and locally (Tier-1).  A positive result triggers secondary tests in a reference laboratory or hospital (Tier-2).  It is possible to consider a further (Tier-zero) test done by individuals with an over-the-counter (OTC) test.  The latter would be quick and cheap like the “Clear Blue “ pregnancy tests.  The DNA Nudge test would make a good candidate for Tier-1.  It has sensitivity, precision and clinical accuracies similar to the Tier-2 reference methods.

Any other comments?

“The core RT-PCR nudge technology is potentially future proof and could easily be re-configured in response to a virus that will continuously change and mutate, as viruses do.”

Prof Paul Hunter, Professor in Medicine, UEA, said:

“The point of use test described in the paper by Gibani and colleagues looks to be a promising development towards improving availability of tests for COVID-19.  This is a test for the virus RNA and not a test for antibodies so would be a replacement for the standard PCR tests currently done on nose and throat swabs.  The reported sensitivity and specificity of the test look very good and are sufficient for its use in diagnosis.

“However, there are a few issues that need to be considered before the tests could be rolled out for near patient testing.  It is not entirely clear who processed the CovidNudge tests that were undertaken and what training they received.  Also there is the need for a testing machine but it is not clear how many tests could be processed at any one time.  If as it appears on the image only a single specimen could be analysed as a single time then multiple units may need to be purchased for any busy clinic.

“Use of all point of care testing such as this does need to be done safely and following appropriate guidance such as that issued by The Royal College of Pathologists.  The operator would need some training in operation of the machine and in the safe handling of specimens and disposal of used materials.

“Another point is that although the sensitivity and specificity look very good this is based on initial testing in centres of excellence.  Whether this degree of accuracy could be maintained during routine use in the real world is a big question and needs to be monitored during any roll out of the technology.

“Whether this new technology would be of value on the UK government’s Moonshot testing strategy is uncertain.  The big worry is with use of any testing in asymptomatic individuals, a reported feature of this strategy.  Any testing of asymptomatic individuals is likely to yield very low numbers of true positives, probably less than 1 in 10,000 tests.  When the true incidence is so low then even a small number of false positives from a test could mean that the majority of positive results are false.  We would need to see much larger evaluation studies to get a better understanding of the real specificity.

“Providing the results of further evaluations during roll out remain good I can certainly see this test finding a place in clinics and hospitals (and this is essentially what the authors are saying) where there is no immediate access to laboratory facilities.  The main time saving is probably going to come from not having to transport swabs from one place to another.  At present though it does not look like this will be the in home test that would be what was needed for the “Moonshot strategy” as currently reported.”

Prof Lawrence Young, Professor of Molecular Oncology, University of Warwick, said:

“This paper provides important validation of a point-of-care test for rapid detection of SARS-CoV-2.  It uses innovative technology in a lab-on-a-chip format that removes the need for complex laboratory processing of swab samples and has in-built quality controls to ensure that the sample is adequate for testing.  The CovidNudge test was evaluated on nasopharyngeal swab samples taken from healthcare workers and patients at the height of the pandemic and shows that the test compares very well in terms of sensitivity and specificity with standard laboratory (RT-PCR) approaches.  Aside from the ease of use of the CovidNudge platform, this approach could also be easily adapted to incorporate testing for other respiratory infections (influenza, respiratory syncytial virus) which would be very useful as we head into the winter.

“The CovidNudge test, like other point-of-care diagnostics, could have an important role where near-patient real-time decision making is necessary such as screening patients for admission to hospital or for surgery.  However, this test is not currently useful for high throughput analysis as only a single sample can be analysed at a time.  So this is not the answer to universal mass testing.  Also the test needs further evaluation in comparison with standard laboratory tests to determine whether it can be reliably used to measure the level of virus infection in an infected individual.  According to the recent press release (3rd August) from the Department of Health and Social Care, 5000 of the Nudgebox machines required for the CovidNudge test are being rolled out across NHS hospitals and each machine can ‘process up to 15 tests on the spot each day without the need for a laboratory.’  This press release also suggests that CovidNudge will ‘provide 5.8 million tests in the coming months’.”

‘Assessing a novel, lab-free, point-of-care test for SARS-CoV-2 (CovidNudge): a diagnostic accuracy study’ by Malick M Gibani et al. was published in the Lancet Microbe at 23:30 UK time on Thursday 17 September 2020.

DOI: 10.1016/S2666-5247(20)30121-X

Declared interests

Prof Terry Wilkins: “1. The subject matter is well within my decades of industrial and academic experience in clinical diagnostics.  2. I have no personal or business connections with the authors or organisations involved in this research and innovation.”

Prof Lawrence Young: “I have no conflicts.”

None others received.