What COVID-19 teaches us about diagnostic Whack-a-Mole  

Unfortunately, we all know what happened next: even though we knew how to test for the disease, we could not. There were public policy errors, like the guidance that restricted testing only to travelers coming into the US from Mainland China, which enabled undetected community spread. There were technical barriers, like the amplicon contamination at CDC’s production facility, which delayed the availability of testing kits. And there were logistical breakdowns, like the shortages of PPE and swabs, which forced further rationing of tests. Those links are all US-specific, but while the US’s inadequacies may have been unusually severe, they were not unique.

So, what should the diagnostics industry learn from this tragedy?

Start here: the global diagnostic response was reactive. Obviously, right? Diagnostic tests can’t be ready for a disease outbreak we don’t know is coming.

But what if they could? The diagnostic response was reactive because our gold-standard diagnostic methods are reactive. The gold standard for infectious disease testing is a nucleic acid amplification test (NAAT). And while NAATs are sensitive and specific, they require prior knowledge of the pathogen’s genome.

NAAT development is a game of whack-a-mole: the disease must emerge before a test can be developed to help suppress it. And after it is developed, that new test must be validated, manufactured, distributed, and implemented.

This isn’t true for other kinds of diagnostics. In the old days, COVID-19 would have just been “pneumonia,” and it would have been diagnosed using a stethoscope and an x-ray. In that sepia-toned scenario, deploying a diagnostic test is more dissemination than manufacturing or distribution.

The point is not to get nostalgic for a time where one pathogen could not be differentiated from another. The point is to ask,  is there a way to get back to a paradigm where the diagnostic tools are universal, even as the disease changes?

This is what sequencing-based diagnostics are all about. Today, sequencing remains expensive and complicated, so we only use it to learn about pathogens. If sequencing was cheap and ubiquitous, we could use it on every patient, all the time, whether they had a common cold, the flu, or COVID-19. Then when a new disease emerged, we wouldn’t be waiting for an unexplained rise in pneumonia, we’d see the novel sequence as a byproduct of routine testing. More importantly, we wouldn’t have to develop and deploy new tests, because the devices to diagnose the disease would already be installed and in use all around the world.

Think of it this way: if NAATs probe a pathogen 20-questions style (“Are you flu? Are you RSV? Are you SARS?”), sequencing simply asks, “What are you?”

Sequencing-based diagnostics is not a new idea. BARDA has been funding initiatives in this area for years, and sought out multiplexed molecular tests before that. Like any emerging technology, there is a gap between the promise and the reality—in particular, true unbiased sequencing is still a long way from being a commoditized assay. But if you’re not familiar with the field, now’s the time to start reading up.

If there’s one thing diagnostics developers should learn from the failure to deploy widespread COVID-19 tests, it’s that the mission of our industry is far from complete. Today, NAATs are our testing lifeline for triage, but we’ve seen that they make our response to new outbreaks shockingly brittle. It’s clear we have more building to do.

Redbud Labs is currently receiving inbound requests from teams with validated assays that need to move to point of care.  These development teams are seeking out new tools that will help make the transition to cartridge quickly and get new tests on the market soon.  Redbud manufacturers Cartridge-ready™ components that boost assay performance by tackling microscale fluidic challenges such as mixing and sample preparation. These components improve performance of microfluidic consumables used in basic research, diagnostics, drug discovery and development, biomanufacturing, and sequencing.  Connect anytime for a no-obligation consult.