The revolution in DIY testing that will outlive the Covid-19 pandemic

LONDON (FINANCIAL TIMES) – Imagine the scene: it’s 2023, everyone in north-west London wakes up to a text telling them that there are high levels of flu and norovirus in their area, as well as an outbreak of Covid-19. You feel a little unwell. You walk to your bathroom cabinet and take out a home test that can tell you whether you have Covid-19, flu or maybe just a common cold.

“The old world was you think ‘oh well, better go to work’ and by the end of the day you’ve infected 20 people,” says John Bell, regius professor of medicine at Oxford university, who has spearheaded the widespread rollout in the UK of so-called “lateral flow devices”, which can be used at home and give test results in 20 minutes.

“But now there’s a new world where you can test to see if you’re infectious and make sure you don’t pass it on.”

The pandemic has transformed the face of diagnostics, bringing testing into the home in a way many public health officials never imagined possible.

Ministers and scientists are beginning to focus on what sort of testing apparatus needs to be in place as the pandemic ebbs – and many hope that do-it-yourself tests will provide the backbone for a post-coronavirus revolution in diagnostics.

While the huge public expenditure – around £19 billion (S$35 billion) has been spent on all forms of Covid-19 testing so far in England alone – cannot continue, a system will be needed to quickly catch fresh outbreaks and to identify new variants. There is also huge demand for tools that can distinguish between Covid-19, flu and a common cold – so that a winter sniffle does not lead to a period of enforced self-isolation.

At the same time, the scientists behind the UK’s world-leading genomic testing, which has expanded rapidly during the pandemic, are looking for ways to apply the capabilities to new and different health threats.

Given the resources the UK has thrown at testing during the pandemic, the investment in home testing will be watched closely around the world.

“It is generally accepted that we have made a decade’s worth of progress in the space of a year,” says professor Chris Molloy, outgoing chief executive of the Medicines Discovery Catapult – a government-funded non-profit organisation. Molloy set up and led the UK’s network of huge pop-up testing laboratories, dubbed “Lighthouse Labs”.

“Diagnostics has historically been seen as a poor relation to drugs and healthcare… but now people are willing to use them in a home and work environment and change their behaviour on the back of the outcome.”

Yet, even after the huge investments of the past year and high hopes in the field, there are still fundamental questions about the basic efficacy of some of the take-at-home tests.

“We’re in this ridiculous state where people are being invited to test themselves twice a week with a test that’s really unreliable,” says Will Irving, professor of virology at Nottingham university, referring to the lateral flow devices.

“If you get a negative result it doesn’t mean you haven’t got it, if you get a positive result, it doesn’t mean you’ve got it.”

The legacy of testing infrastructure

After months of undersupply, delays and some shambolic errors, by December of last year the UK was able to boast one of the highest testing capacities in the developed world.

At its peak in January, it had the resources to run in excess of 800,000 gold-standard PCR tests a day, up from just 2,000 in February 2020. While highly accurate, they do take up to 24 hours to provide results as they need to be processed in a lab.

With infection rates in the UK lower due in part to the vaccination drive – even with the new variant first identified in India – a large chunk of investment this year is being thrown at the purchase and distribution of lateral flow devices. The UK has led the charge in deploying this diagnostic instrument, committing billions of pounds and offering them free of charge to every member of the public for twice-weekly testing.

As one government official put it, “they are basically displacing everything else where they can”, adding that the UK is currently running around 25 million LFD tests per week.

The widespread use of these tests in future will lie in whether they can be used to screen for several pathogens at the same time using one sample.

While these so-called “multiplex tests” already exist in the laboratory-processed PCR tests, there is still work needed to develop rapid assessments that can do the same thing. Diagnostics of this kind will be crucial when influenza re-emerges from the shadows to which it was confined by social restrictions in 2020, experts say.

“The flu season will probably come back to bite with a vengeance because everyone’s immune system hasn’t been primed,” says the NHS Test and Trace official.

“If you could distinguish early on whether it’s Covid or flu that would be a massive improvement, so it has to be the next frontier,” says Axel Heitmueller, who was director of strategy and innovation at NHS Test and Trace until recently.

But scientists continue to battle over the accuracy of the take-at-home tests. In 2020, the debate centred on whether these devices missed a large proportion of cases, with some studies indicating they picked up only between 40 and 60 per cent of active infections.

Proponents counter that they are good at picking up when individuals are actually “infectious”, rather than the periods pre and post infectiousness that PCR tests can also identify.

In recent months, as the prevalence of Covid-19 has decreased, attention has turned to whether these tests also tell people they have the disease when they do not – known as “false positives”.

Screening experts have expressed concern that the vast majority of positive results given by the tests in areas where the prevalence of the virus is low are likely to be inaccurate.

“In no other situation could you introduce a health tech or medicine without doing a health economic analysis,” says Irving at Nottingham university. “It might be costing £1m per case prevented – not only is that never calculated, but neither is any other alternative.”

But the government has so far made no indication that it will roll back the use of these devices, and has instead been desperately trying to shore up domestic supply.

In the early months of the pandemic, it outlined an ambitious plan to build and bolster a domestic diagnostics industry for rapid tests, and the optimistically named UK Rapid Testing Consortium (UK RTC) was born.

In spite of these plans, the government has been heavily reliant on a private equity-owned US company called Innova to support its testing vision. The Californian company has supplied over 1bn tests, worth over £3bn, to the UK, which is its biggest market for LFDs.

Innova recently told the FT it would begin manufacturing millions of tests a day in Wales from July 2021. The UK RTC has also built capacity to produce 2 million lateral flow devices a day, but this is yet to be fully used.

Prof Molloy, who has led the UK RTC for several months, says that critics of the speed of the programme need to take a “longer narrative”.

Once the consortium is up and running at full capacity, the UK will be “more than 20 times magnified in our ability to produce lateral flow”, he says.

These devices will be used to test for Covid-19 for years to come, he adds, as well as several other diseases the UK will “go to war on” to tackle the backlog of medical care that has built up over the past 15 months.

But as plans proliferate to enhance domestic production, one of the questions that Test and Trace has been grappling with for the past six months is how long the taxpayer is going to foot the bill for the rollout of this technology.

“What is really contested and not at all settled is the extent to which events testing, schools testing – LFDs dished out like confetti – how much of that is going to carry on from the summer and beyond?” asks the Track and Trace official.

The government is committed to offering these tests free of charge to local authorities and workplaces until at least the end of June.

But individuals have to buy their own to travel and the aim is to push the balance further in that direction. The government is seeking to “establish an effective private market for tests”, with the ultimate aim of using diagnostics to become a “viable alternative to self-isolation for contacts of infected people”.

The Department of Health and Social Care said in a statement that “with around one in three people showing no symptoms, regular testing is already playing a critical role in controlling the virus as society reopens, including variants of concern”.

Testing the limits of innovation

While the debate about at-home testing rages, researchers across academia and industry are also busily working on the next generation of testing solutions for Covid-19 and beyond.

Bees and sniffer dogs are being trained to smell out Covid-19 with a remarkably high level of accuracy. Researchers at Durham and the London School of Hygiene and Tropical Medicine found that trained dogs could be more effective at containing the spread of Covid-19 than most lateral flow devices.

Academics have also developed a method using technology called mass spectrometry that can give the molecular profile of a viral sample and can determine accurately whether someone is infected with Sars-Cov-2 for as little as £10 per test. It can be modified to add detection for influenza or any other virus for a fraction of a pence per test, say researchers from the University of Manchester and Waters Corporation, a US lab instruments company.

Germany, by contrast, had a strong regionalised diagnostics industry to start with, focused almost exclusively on PCR tests, which enabled it to offer consistent, fast tests to the public through the first wave of the pandemic – to the envy of the rest of the world.

“Germany played a wonderful piano concerto, they had one instrument, but they played it beautifully,” says Heitmueller. “Now, the UK is in a stronger position and the ‘orchestra’ is coming together Germany is struggling to innovate.”

British innovation is particularly visible in the celebrated field in which computers are used to break down and transcribe the exact genetic sequence of an organism – known as genomic sequencing.

Born out of Britain’s groundbreaking genetic discoveries of the last century – including Rosalind Franklin, James Watson and Francis Crick’s work on the double helix – the UK now has the most advanced genomics sequencing capability in the world.

In early March 2020, conscious of what might unfold over the course of the pandemic, Sharon Peacock, professor of public health and microbiology at Cambridge university, emailed five colleagues saying: “Can you call me, please?”.

Within weeks she had put together a consortium of the country’s leading genomic researchers and has since secured around £32 million in funding to map the genome of Sars-Cov-2 as it spreads across the UK. The Cog-UK consortium, comprised of 16 labs, has helped increase the amount of sequencing taking place in the UK from 50,000 genomes a year to over 30,000 a week.

“Here was a technology that was absolutely poised to make a big difference,” says Peacock. “But the scale and magnitude of change over the past year has been extraordinary.”

This genomics surveillance work will continue to be critical for determining changes to the severity of the virus and the effectiveness of vaccines.

“As long as vaccination is required, you’re going to need some level of sequencing,” says Peacock.

Once the pandemic is over, leading experts hope to ride the wave of public enthusiasm for the technology to apply it to other medical challenges. Peacock outlines ambitions to use sequencing to pick up changes in influenza strains faster and adapt vaccines to variants in circulation each year, as well as to detect new diseases in wastewater and track antimicrobial resistance (AMR).

“We’re already sequencing wastewater for Covid-19 – could we do the same for AMR?” she asks. “It’s the first time we have ever, as a nation or as a world, thought about sequencing like this proactively to get information.”

The majority of genomic sequencing machines around the world use large amounts of computer power and take several days to read out an entire genome, but new technology is emerging which makes the process much less cumbersome.

British company Oxford Nanopore has developed handheld devices that can read an entire viral sequence within hours, and have been used widely by UK officials to track the evolution of the Sars-Cov-2 genome.

“When you’re in a war, the cycle of innovation accelerates,” says Gordon Sanghera, Oxford Nanopore’s chief executive.

There is also the growing field of “pharmacogenomics” where scientists study the human genome – all 3bn letters – to work out if people have a predisposition to adverse reactions to certain medicines.

Blood samples of individuals who suffered severe blood clots after they received the Oxford/AstraZeneca vaccine have been sent for analysis to Genomics England, a government body. If a common genetic thread can be found those with the same characteristics could be offered an alternative, drastically reducing the risks associated with the vaccine.

But as Covid-19 shows tentative signs of slowing its spread in countries with high levels of vaccination, many in the world of diagnostics are wondering whether the same level of innovation and investment will be applied to the illnesses that have gone undiagnosed during the pandemic.

“The thing that worries me is the massive health emergency that’s looming,” says Heitmueller, who has returned to his role as managing director of Imperial College Health Partners. “We are going to have a massive backlog – for cancers like bowel, breast and lung – and we need to apply the same agility to identifying and diagnosing them.”

He adds: “Will we be willing to take the same kind of risks (as were taken during the pandemic) to invest in new technologies?”.

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