PCR-4-ALL: Rethinking pandemic response through mass testing

The PCR-4-ALL project is exploring whether a fundamentally different approach to diagnostics could transform how Europe responds to future pandemics – detecting infections earlier, reducing transmission and avoiding the societal and economic disruption of lockdowns. We speak to several partners about the project and the impact it could have on future pandemics.

At the start of the COVID-19 pandemic, the science moved fast. Within weeks of the virus being sequenced, PCR tests were developed that could detect infection with remarkable accuracy. And yet, despite this scientific success, the virus spread rapidly across the globe, overwhelming health systems and forcing governments into blunt, disruptive measures like full lockdowns and school closures.

For the researchers behind PCR-4-ALL, this disconnect pointed to a critical gap, not in scientific capability, but in how that capability was translated into real-world response. Xevi Casadevall i Solvas, project coordinator and PI at KU Leuven , the issue was not whether testing worked, but whether it could be deployed at the scale and speed required to make a meaningful difference.

“Everything started with the sequencing of the virus in early January,” he says. “Then a couple of weeks later, there was already a PCR protocol to detect that virus and a few weeks after that, the pandemic was declared. Just a few weeks later, we had half the world in lockdown. And then after practically a full year, rapid tests started to become widely available.”

By that point, the damage had already been done. “Vaccination began and somebody like me got the first shot after 3.8 million people had died.”

The question that sits at the heart of PCR-4-ALL is, therefore, a simple one: what if large-scale, systematic testing had been available much earlier?

Proactive testing
During COVID-19, testing strategies were largely reactive. Individuals were tested once they developed symptoms, followed up by contact tracing and isolation. While effective to a degree, this approach struggled to keep pace with a rapidly spreading virus, particularly one capable of asymptomatic transmission.

“People who had symptoms were tested. If they turned out to be positive, then contact tracing followed and people stayed at home,” says Casadevall i Solvas. “At some point, everybody was at home. This was not an effective way to manage transmission.”

PCR-4-ALL proposes a fundamentally different model: population-wide, routine testing carried out early and systematically, rather than selectively and reactively. “Our idea is to implement population-wide testing early on,” says Casadevall i Solvas. “That would allow us to isolate those who are actually infectious and maintain normal activity across society.”

The implications of this shift are significant. Rather than relying on broad restrictions such as lockdowns, public health responses could become more targeted, isolating only those who are infectious while allowing society and the economy to continue functioning.

The limitations of PCR
At first glance, PCR may seem an obvious candidate for such a strategy. It is widely regarded as the gold standard for diagnostic testing, offering high sensitivity and specificity. But as the pandemic revealed, its strengths at the individual level do not easily translate to population scale. “It’s very simple,” says Javier Martinez-Picado of IrsiCaixa and principle investigator. “PCR is not a test that has been designed to test a lot of people. It’s more of a clinical test that helps diagnose individuals.”

This limitation becomes stark when viewed in operational terms. As Martinez-Picado explains, even well-equipped hospital laboratories struggled to process sufficient volumes during the pandemic. “Most of the machines we have in hospitals to do PCR diagnostics cannot run more than 96 samples at once,” he says. “Even if you run multiple cycles per day, it’s not going to be more than 300 samples overall and that is nowhere near the scale of testing we need.”

Faced with this constraint, the response during COVID-19 was to scale up existing infrastructure – buying more machines, expanding laboratory capacity – but without fundamentally changing the underlying model. “It was the best we had,” he concludes. “But it was still not good enough for mass testing.”

A new testing paradigm
PCR-4-ALL seeks to overcome these limitations by rethinking the entire testing pipeline – from the collection of samples to processing and analysis. The project is built around three interconnected technological innovations, designed to work as a coherent system, with each addressing a different bottleneck in scaling PCR.

The first focuses on sample collection. Rather than relying on clinical settings and trained personnel, PCR-4-ALL focuses on developing saliva-based self-sampling strategies, enabling individuals to collect samples at home. “If we are talking about mass testing, people should be able to collect samples by themselves,” Dragana Spasic of KU Leuven explains. “We opted for saliva because it is non-invasive, and it contains the targets we need to detect respiratory infections.”

But the innovation goes beyond this convenience. The collection device is designed not only to stabilise the sample, but to prepare it for immediate integration into an automated processing system—removing the need for manual handling in laboratories and enabling the kind of scale PCR has traditionally struggled to achieve.

It is this seamless transition from collection to processing that underpins the second core component of PCR-4-ALL: a highly automated pipeline capable of analysing vast numbers of samples in parallel. Central to this is the concept of pooling, combining multiple samples into a single test within standard laboratory plates made up of multiple small compartments. “Each well would not contain one single sample,” says Casadevall i Solvas. “It would contain, we estimate, around 30 samples. And by doing this repeatedly, we can process up to 100,000 samples in a short period of time, dramatically increasing throughput while reducing both time and cost.”

The third innovative element of PCR-4-ALL addresses one of the key challenges created by pooling: how to retain individual results when multiple samples are analysed together. To solve this, the project has developed a novel reagent system that effectively labels each sample before processing and compartmentalizes them in small picolitre-sized droplets, allowing them to be combined without losing traceability.

“You have to imagine combinations of fluorochromes like a barcode that identifies each individual sample,” explains Javier Martinez-Picado. “Once we run the PCR, we can determine the result for each person based on that barcode.”

In practice, this means that even when dozens of samples are tested simultaneously within a single reaction, positive cases can still be traced back to the individual with precision. The approach preserves the sensitivity and reliability of PCR while enabling the scale and efficiency required for population-level testing – turning what is traditionally a one-sample, one-test system into a high-throughput, multiplexed process.

Together, these innovations create a system designed not only for scale but for rapid, actionable insight, enabling large populations to be screened in a matter of hours rather than days. The ambition is to process samples overnight, with results delivered the following morning, allowing potential cases to be identified before further transmission occurs.

“The goal would be that when you wake up, you get a message saying you have tested positive,” says Casadevall i Solvas. “At that point, you would go for a confirmatory test.”

This two-step approach is central to the PCR-4-ALL strategy. The initial test is designed as a high-throughput screening tool – fast, cost-effective and sensitive enough to identify likely infectious individuals at scale. Any positive result can then be verified using a conventional, highly sensitive PCR test, ensuring accuracy while avoiding the cost and complexity of applying gold-standard diagnostics to entire populations.

Balancing act
One of the more nuanced aspects of the PCR-4-ALL approach lies in how it redefines the role of diagnostic accuracy. While traditional PCR testing is designed for maximum sensitivity, detecting even very low levels of viral material, this level of precision is not always aligned with the needs of large-scale public health response.

“PCR is extremely sensitive,” Casadevall i Solvas explains. “It can detect the virus at levels where you are not infectious and not sick, so you do not present a problem.”

In a mass testing context, the priority shifts from detecting every trace of the virus to identifying those individuals most likely to transmit it. Rather than maximising sensitivity, PCR-4-ALL focuses on achieving the level of detection needed to act quickly and effectively at population scale. Crucially, this approach is not defined by a single test result, but by repetition. As Spasic notes, frequency can compensate for lower sensitivity. “If you have the capacity to do mass testing with a certain frequency, then you can compromise to some extent on sensitivity,” she says. “You will still catch enough people who are infectious.”

This balance between sensitivity, speed and frequency is central to making large-scale PCR testing both practical and sustainable.

Cost and resilience
Beyond technology, PCR-4-ALL also addresses one of the most pressing challenges exposed during the pandemic: dependence on global supply chains. “In the worst months of the pandemic, it was very difficult to get enough reagents,” says Mari Carmen Puertas, an immunobiologist at IrsiCaixa. “We were dependent on big companies, and the reagents were very expensive. To address this, we have developed our own reagent formulations using patent-free components, significantly reducing costs. The idea is to reduce cost and to be independent of these big companies.”

Early estimates suggest that these reagents could be up to 13 times cheaper than commercial alternatives. “And this is at a very early stage,” adds Martinez-Picado. “We haven’t even optimised production yet.”

This combination of cost reduction and supply chain independence is central to the project’s broader ambition: making mass PCR testing economically viable at national and European scale. It is also what begins to shift PCR-4-ALL from a technological concept to a realistic public health strategy, one that can be implemented and scaled up.

With these technological foundations in place, attention turns to how such a system could be implemented in practice. PCR-4-ALL recognises that real-world impact will ultimately depend on policy decisions and system-level adoption. To address this, epidemiological modelling has been integrated by project partners at the Helmholtz Centre for Infection Research in Germany (Berit Lange and Carolina Klett-Tammen) and economic modelling by the University of Verona in Italy (Stefano Landi) and IDIAP JordiGol in Spain (Catia Nicodemo). This activity assesses not only whether mass testing is technically feasible, but whether it delivers measurable benefits and can be sustained over time.

A key output will be a comprehensive white paper, bringing together these findings. “We want to show that with this implementation, and with certain policies, this should work,” says Casadevall i Solvas. “And that the cost is compatible with the economic model.”

The project is also drawing on real-world experience from the COVID-19 pandemic to inform these models. One example is Luxembourg, which implemented large-scale testing with notable success. “Luxembourg had one of the lowest excess mortalities and avoided prolonged lockdowns,” adds Puertas. “The idea is that what Luxembourg did, we could make every country look like that.”

Luxembourg was able to sustain its strategy in part because of its size and resources, conditions not easy to replicate across larger or less well-resourced countries. PCR-4-ALL is designed to bridge that gap. “By dramatically increasing testing throughput while reducing cost and reliance on constrained supply chains, we aim to make this kind of proactive, large-scale testing strategy feasible across Europe,” continues Puertas. “This will help transform what was, in Luxembourg, an exceptional case into a scalable model for pandemic response.”

Beyond pandemics
Although PCR-4-ALL is rooted in pandemic preparedness, its potential applications extend far beyond crisis response. One area of interest is surveillance, not only in human populations, but also in animal reservoirs where new pathogens may emerge. “This could be useful not just for pandemics, but for surveillance of zoonotic viruses,” says Casadevall i Solvas “Testing birds, pigs and other wild animals will help us detect threats before they jump to humans.”

By enabling high-volume, cost-effective testing, the platform could support continuous monitoring at a scale that is currently impractical, providing early warning signals and enabling health authorities to act before outbreaks take hold.

There is also growing interest within the consortium in how the same technological principles could be applied to broader health screening. As Spasic explains: “The combination of speed and affordability opens up new possibilities for earlier intervention. Imagine using the same platform for mass screening of other diseases, catching biomarkers early, before symptoms appear.” This points to a longer-term vision in which testing is no longer triggered solely by illness, but becomes part of a more preventative, system-wide approach to health. Population-level screening could help identify changes in health status earlier, shifting the emphasis from treatment to timely intervention. “We have been discussing how this could be used more broadly,” Casadevall i Solvas adds, “not just for infectious diseases, but as a way of monitoring health more generally.”

While these applications remain at an exploratory stage, they highlight the versatility of the platform. The same characteristics that underpin PCR-4-ALL – scale, speed and affordability – could support a transition toward more proactive, data-driven models of healthcare, moving from reactive response to continuous population-level monitoring.

A uniquely interdisciplinary effort
Underlying the PCR4ALL project is an unusually diverse consortium, bringing together expertise from biology, engineering, epidemiology and economics. “This is a very comprehensive study,” says Casadevall i Solvas. “We are trying to do something that is logistically and economically viable. And to achieve that, we need people from very different areas. “It’s not easy to coordinate such a spread-out consortium,” he admits. “But hopefully we will make something that can help us continue and further validate that this can work.”

And if this diverse consortium does succeed, its impact could be transformative. By enabling early, large-scale detection of infectious individuals, it offers a pathway to managing pandemics without resorting to the disruptive measures that defined COVID-19. This could reduce transmission, ease pressure on health systems and ultimately save lives. In addition to this, it could also deliver the possibility of countries being able to maintain economic and social activity even in the face of a new outbreak. As Casadevall i Solvas reflects, “The idea is to implement large-scale testing much earlier, so that next time, we are ready.”