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The UK government’s announcement on January 10 that regular targeted testing of asymptomatic individuals would be expanded across all local authorities in England fueled debate within the scientific community. Supporters of the ambitious project saw it as long overdue and a vital tool to help break chains of SARS-CoV-2 transmission.
“Mass regular SARS-CoV-2 screening must be rolled out without further delay, across the whole UK in a coordinated effort, to focus interventions only on asymptomatic transmitters and avoid the ill effects of indiscriminate restriction measures in society and the economy,” said Professor Jose Vazquez-Boland, chair of infectious diseases, Edinburgh Medical School, University of Edinburgh.
“Early detection of emerging cases can have a significant impact so having this rolled out country-wide is a positive step,” commented Dr Shaun Fitzgerald, director, Centre for Climate Repair at the University of Cambridge. Around 20% of SARS-CoV-2 infections are estimated to be asymptomatic, so identifying and isolating these individuals sooner is seen by many as an important additional means of reducing spread of the virus.
However, several scientists expressed their concerns about the plans, suggesting that they could create more problems than they solve. Questions have been raised over the accuracy of the tests, which are based on lateral flow technology, and the effects that false negative results could have.
What is a lateral flow test?
“Any benefit from finding symptomless cases will be outweighed by the many more infectious cases that are missed by these tests,” said Dr Angela Raffle, honorary senior lecturer at the University of Bristol Medical School. “Already outbreaks are known to have occurred because people have been falsely reassured by a negative lateral flow result, leading them to attend work whilst having symptoms.”
Government urged to rethink plans
In a letter in the BMJ, Raffle, along with Jon Deeks, professor of biostatistics at the University of Birmingham, and Mike Gill, former regional director of public health, advised that the government urgently rethink the rollout of lateral flow testing. They argued that the tests don’t detect SARS-CoV-2 in a substantial proportion of symptomless people, citing figures from the Liverpool pilot study where a reported 60% of infected people went undetected.
The scientists also highlighted issues in test performance when not used in line with the manufacturer’s instructions, such as being performed by untrained users and in symptomless people. They suggested that the problem of low test accuracy would be “less dangerous if people being tested and the public at large received accurate information about the risks and implications of a false negative result. Instead they are being misled.” In their closing remarks, they recommended that the stockpiled tests are donated to another country without PCR testing capacity and called on the government to pause the rollout of asymptomatic testing.
Scientists reject assertions of harm
In response, a group of scientists issued a counter statement on January 22, citing that the “letter is full of bold allegations supported by neither observation data nor experimental work in the field,” and suggested that the assertion of serious harm highlighted in the letter was “irresponsible” with potential to harm public trust. The signatories, including Professor Matthew Ashton, Liverpool Director of Public Health, Dr Rupert Beale, a group leader at The Francis Crick Institute and Professor Sir John Bell, Regius Professor of Medicine, Oxford University, argued that the authors quoted selectively and ignored evidence evaluating the roll out of lateral flow testing, such as that from a study from Boston.
Critically, they proposed that the authors “do not appear to be addressing the fundamental and important difference between ‘infectiousness’ and ‘recent or current infection.’” They highlighted that lateral flow testing detects live virus, allowing identification of infectious individuals, and therefore those most likely to pass on the virus. Whereas PCR detects non-viable RNA fragments in addition to viable virus, so consequently some PCR positive individuals will not be infectious. “The ideal test for infectiousness would be negative among many of the PCR positive individuals,” they said.
Call for clear messaging
Several other scientists have acknowledged the potential benefits that asymptomatic mass testing could offer, if messaging is clear about what the results mean and how they should be interpreted by the patient. With some studies indicating that only around half of infected individuals will be detected, they advise that a negative lateral flow result is not used to reassure someone that they do not have the virus and have no need to take precautions. Instead, the tests should be used to help quickly identify positive cases that otherwise might have been missed.
“These are ‘red light’ tests. If they come positive that means you are potentially infectious to others and must self-isolate. They are not ‘green light’ tests. You cannot be sure that if the test is negative you are not infectious and you must continue to take the usual precautions,” commented Adam Finn, professor of paediatrics at the University of Bristol.
Detecting the most infectious individuals
In a preprint published on January 20, Professor Tim Peto and colleagues from Oxford University suggest that lateral flow testing could have value particularly in rapidly identifying the most infectious individuals. As the largest analysis of contacts following exposure to SARS-CoV-2 to date, the study provides evidence indicating that SARS-CoV-2 infectivity varies by case viral load, with those with high viral loads being the most infectious. As these individuals are more likely to pass the infection on, identifying them rapidly could help them to take precautions such as self-isolation sooner.
Using modeling, the authors suggest that the best performing lateral flow devices are sensitive enough to detect between 83.7% and 90.5% of cases leading to onward transmission. They highlight that although not a substitute for PCR, lateral flow devices could be a useful complementary tool in the pandemic to identify the most infectious individuals earlier, with the added advantages of being lower cost, rapid and with no requirement for laboratory or logistics infrastructure.
Real world validation vital
However, the study focused on individuals who were symptomatic when tested, so there are uncertainties about how the findings will translate into asymptomatic mass screening. Also, “the predicted sensitivities of the lateral flow tests should be considered as ‘best case estimates,’” noted Deeks, to account for the reduction in performance seen in the tests when used outside of laboratories. The need for evaluation in real world settings is a point that the study authors acknowledged, and one that is highlighted by many scientists when discussing the use of rapid mass testing.
“It remains vital to keep working hard to make best use of all options including lateral flow tests, but we must continue to evaluate how well tests work in different settings, and to make sure new testing systems are checked to confirm they do reduce transmission,” stated Alexander Edwards, associate professor at the University of Reading.
At present, targeted testing of asymptomatic individuals is continuing in a range of community and business settings, with the government announcing on January 24 that several more employers had signed up to the scheme.