WHERE LATERAL FLOW TESTS HAVE THE UPPER HAND OVER PCR

Updated: Dec 9, 2020



We know that SARS-CoV-2 can be transmitted whilst the host is unaware of infection, which has probably been a larger driver of the epidemic (1). Around 20-40 % of infected individuals can be asymptomatic but have enough virus to potentially spread the disease. Detecting those people may help us to contain the disease, whilst getting us back to some sort of normality, hence the recent introduction of cheap and rapid tests, like lateral flow tests. Lateral flow tests are being used for mass population screening, testing of students and, now, care home visitors. Yet, some recent headlines suggest they should not be used and are inaccurate in over 50% (2). Why then, have governments around the world promoted their use? We aim to answer some of these questions and clarify some mis-reporting and mis-interpretation of the existing evidence.


Lateral Flow Test (LFT)

Samples are usually obtained by swabbing of the back of the throat and/or the nose by a healthcare professional. Sometimes saliva samples can be used. The sample is mixed with a special fluid that allows the viral proteins to be detected by way of a dark band on the test cartridge – much like a pregnancy test. Results on the presence of Covid antigen can be obtained in 15 minutes or less. When compared to the gold-standard PCR test (see below) the lateral flow test has reported a 95% sensitivity when used by a trained healthcare professional. This accuracy is seen with high viral loads of 100,000 RNA copies/ml. With lower viral loads between 1,000 and 100,000 RNA copies/ml, when used by a trained healthcare professional, a recent study reported 78% sensitivity (3). This difference in sensitivity for differing viral loads is important, as detailed below.

The accuracy is dependent on an adequate sample, hence lateral flow tests are only licensed for use by a health care professional. If the public self-test, the accuracy drops by 25% (3).


Polymerase Chain Reaction (PCR) Test

PCR tests are regarded as the gold-standard – though the accuracy of these also depends on good sampling technique. Samples are usually obtained by swabbing of the back of the throat and the nose by a healthcare professional, or using home kits. The samples are then sent to a lab, the results are obtained within 48-72 hours. The PCR test is highly sensitive, picking up the presence of a tiny amount of viral RNA (genetic material) by amplifying it, and can deliver a positive result several weeks after infection.

PCR testing can take a few days to report, but is clearly only accurate on the day it was taken. By the time a positive result is obtained, a person may have been unwittingly spreading virus. If a negative result is obtained, they may have been isolating for no good reason. And, of course, that result, whatever it was, is now outdated.


PCR tests are usually only available to those who are symptomatic. Lateral flow tests are often used in asymptomatic screening. Many recent comparisons with PCR tests are usually, therefore, comparing different populations, with different aims, and are hence flawed.



The right test for the right job

Whilst PCR tests have a greater overall sensitivity for detecting viral material, that has its downside too, as people may no longer be infectious – see graph above (4). As a recent article in the New England Journal of Medicine states, “the long duration of the RNA-positive tail suggests that most infected people are being identified after the infectious period has passed. Crucially for the economy, it also means that thousands of people are being sent to 10-day quarantines after positive RNA tests despite having already passed the transmissible stage of infection.” (4)


Instead, for mass screening of asymptomatic individuals who want to get back to work, to socialising or visiting loved ones, you may need a different tool that is less sensitive, but cheap and quick to perform on multiple occasions. Such a test would also need to provide immediate results that relate to your current Covid status and likelihood of having enough viral load to transmit.


As Professor Jonathan Ball, Professor of Molecular Virology, University of Nottingham, said: “Whilst the lateral flow assay lacks the sensitivity of the PCR test, its rapidity and ease of use makes it a pragmatic test for community surveillance, where you want to quickly identify then isolate infected people. Even though it won’t detect as many infected individuals as the PCR test, it will identify those with the highest viral loads, and it’s those people who are most likely to go onto infect others. It won’t replace other tests like PCR, but it is a useful additional tool for coronavirus control.”


So how should we use LFTs?

A positive lateral flow test pretty much means you have Covid and certainly shouldn’t be visiting vulnerable people…or anyone, for that matter. Self-isolation, and informing test and trace is the order of the day.


In contrast, a negative lateral flow test doesn’t mean you can just throw caution to the wind, along with your mask. Because around 4 in 100 may be carrying Covid, despite a negative test. Standard safety measures should therefore still apply – for your own protection as well as others around you. But it does provide added reassurance. Nothing is without risk, but lateral flow tests to screen for example, care home visitors, will considerably reduce the chance of introducing infection compared to simply checking their temperature and asking about symptoms or contacts. This risk is likely to be far outweighed by the mental health benefits of allowing residents to connect with family and friends again


As recently highlighted in JAMA “testing in the absence of other proven prevention strategies is unable to prevent outbreaks...although the evidence is growing that widespread access to rapid antigen testing may be a pragmatic tool to interrupt the community transmission of SARS-CoV-2, what will remain equally important to prevent spread of infection to others is what happens before and after test results are delivered. Even the perfect test cannot go it alone (5).”


They have limitations which need to be understood. They do not replace other guidance or advice, but they are an adjunct to what we currently have. It is important to educate the community of the advantages and limitations, but not throw the tests out because they are not 100% sensitive, or because the full scientific studies have yet to be performed. We have to remember, residents who belong to the frail elderly group in our society, have been isolating for over 9 months. It would be interesting to know how they would view the risks versus benefits of performing this additional screening, which could give them the opportunity of seeing their family without the use of a Perspex or computer screen.


References


1. Ferretti L, Wymant C, Kendall M, et al. Quantifying SARS-CoV-2 transmission suggests epidemic control with digital contact tracing.  Science. 2020;368(6491):eabb6936. doi:10.1126/science.abb6936


2. Covid-19: Safety of lateral flow tests questioned after they are found to miss half of cases BMJ 2020; 371 doi: https://doi.org/10.1136/bmj.m4744 (Published 04 December 2020)


3. Preliminary report from the Joint PHE Porton Down and University of Oxford SARS-CoV-2 test development and validation cell: rapid evaluation of lateral flow viral antigen detection devices (LFDs) for mass community testing. 8 November 2020. www.ox.ac.uk/sites/files/oxford/media_wysiwyg/UK%20evaluation_PHE%20Porton%20Down%20%20University%20of%20Oxford_final.pdf.


4. Michael J. Mina, M.D., Ph.D., Roy Parker, Ph.D., Daniel B. Larremore, Ph.D.

Rethinking Covid-19 Test Sensitivity — A Strategy for Containment. N Engl J Med 2020; 383:e120DOI: 10.1056/NEJMp2025631


5. Manabe YC, Sharfstein JS, Armstrong K. The Need for More and Better Testing for COVID-19. JAMA. 2020;324(21):2153–2154. doi:10.1001/jama.2020.21694

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