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The Great Pandemic Stress Test

How emergency forces innovation & one Italian scientist advanced our understanding of COVID variants.


Photo by Fusion Medical Animation on Unsplash  

In February 2020, people all over the world watched with mounting anxiety as a novel coronavirus, then referred to as 2019-nCoV, began its unyielding spread across the globe. What at first seemed, to western eyes, like a worrying but well-contained viral outbreak on the other side of the world, had suddenly appeared in northern Italy and was crushing the country’s health system with the sheer number of patients needing intensive care. European and North American news cycles began to fill with countless stories of people desperate for treatment in overloaded hospitals, and soon after, Italy imposed a strict lockdown on the movement of its citizens in order to try to slow the exponential growth of coronavirus infections. Videos of Italians singing to each other across balconies and alleyways in an attempt to maintain some sort of interpersonal connection spread widely on social media as containment measures were put into place.

For Dr Gabriele Ibba, a postdoctoral researcher at the University of Sassari in Sardinia, Italy, lockdown was not an option. As a post-doctoral researcher working in a public-health oriented lab, his work was just beginning. In the early days of the pandemic, so little reliable information about the novel coronavirus was available that people simply didn’t know what to expect. This was especially stressful for scientists and physicians working on the front lines of the COVID response. Dr Ibba recalls the distinct anxiety of going to work in his basement testing lab, part of the hospital at the University. While he and his colleagues were working feverishly to develop effective coronavirus testing workflows, COVID patients were filling the wards a few floors above.

As if the pervasive sense of dread and personal danger weren’t enough, the scientists at the University of Sassari and other testing centers like it were grappling with even more basic problems: the novelty of the virus itself, coupled with the disruption of global supply chains that it caused, meant that simply getting one’s hands on the COVID testing kits—or even the basic ingredients that go into the kits—was incredibly difficult. Eventually, they were able to establish a steady supply of a particular kit, and were able to start pushing back against the tide of coronavirus infections. As it happens, though, this struggle to find a reliable supply of test kits ended up putting Dr Ibba and his team (led by Prof Sergio Uzzau) on the path to a discovery that could help scientists and clinicians better understand the way that viruses like SARS-CoV-2 spread—an invaluable tool in fighting future pandemics.

The Breakthrough

Most scientific discoveries, both big and small, start when a researcher notices something that just doesn’t quite fit. With a little bit of poking around, that little incongruity can sometimes turn out to be a sign of something much more interesting. For the COVID testing team at the University of Sassari, that first observation came when someone noticed that some of the amplification signals coming out of their testing machines didn’t look right. The tests were coming back positive, but the way they were doing so just seemed...odd. Instead of just filing that datapoint away and moving on, though, Dr. Ibba and his colleagues decided to dig a little deeper.

In order to do so, they would need to go back into their records of previous lab tests, which was key to solving this particular mystery. And because the lab had maintained digital records of all of the tests performed by their PCR machines, they could rapidly check the amplification curves from COVID tests going all the way back to the beginning of the pandemic. When they started looking closely, it turned out that a noticeable proportion of their tests were all showing that same funny amplification signal, but it wasn’t clear why. Only when they sequenced the suspected viral samples to analyze their entire genomes, everything started to make sense. The weird amplification signals they were seeing in their data were being caused by the mutations that have accumulated in the more infectious B.1.1.7 variant (now officially referred to as Alpha) that was originally discovered in Kent, UK. In a previous era, this sort of on-the-fly genetic sleuthing would not have been possible, but thanks to the rise of easy-to-use genetic analysis suites from companies like SOPHiA GENETICS, sorting through large collections of genetic data has become significantly easier for the average researcher. If it weren't for modern genetics suites' automated genetic lineaging, this work could have taken several days instead of a few hours of scientific labor allowing the clinicians to save an outstanding amount of time.

Because the standard PCR tests for detecting SARS-CoV-2 are really only able to provide a binary detected / not detected result, they can’t tell you much of anything about what particular variant of the virus a patient might be infected with. On top of that, if a variant has mutated enough, the genetic probes used to detect the virus might not work at all. Luckily, that was not the case here, and luck really did have a big role in this discovery: if the scramble to find a reliable source of SARS-CoV-2 testing kits hadn’t led so many labs in Dr. Ibba’s region to adopt the same test kits, there might not have been a noticeable pattern in the amplification curve data. Other kits might simply have returned no results or false negatives, which means no one would have noticed this little clue to the Alpha variant’s presence.

With the sequencing results in hand, the researchers realized they could take their analysis even further. As a public service, the lab Dr. Ibba works in was required to retain records and samples of all tests, which meant that they essentially had a historical record of B.1.1.7’s spread in southern Italy going back at least 6 months. With this data, they were able to show that the UK variant had actually spread to the area they monitored before January 15th 2021—much earlier than previously believed.

Now, Dr. Ibba and his extended team of epidemiologists, virologists and molecular biologists are trying to use this trove of data to better understand the dynamics of SARS-CoV-2 variant spread, and try to help get ahead of the curve in preparing for the next pandemic. No two pandemics are exactly the same, but the lessons learned in fighting one disease can often be applied to fighting another, so there’s reason to be optimistic about our chances next time around if humanity can maintain the pace of scientific and technological development that it set in responding to the coronavirus pandemic.

A Reason for Optimism

For Dr. Ibba, despite the dread of those early days of the pandemic—and the massive loss of life globally—the speed of the scientific response to the COVID crisis is a story of human technological and scientific triumph. The combined efforts of scientists around the globe, as well as huge improvements in technology and logistics, allowed for the development and testing of a highly effective vaccine within months of the public release of the virus’s genome. It wouldn’t have been possible to move this fast even 2 decades ago—when, notably, we experienced a pandemic of a related coronavirus, the original SARS.

“This pandemic was a stress test for humankind, and I think that we passed the stress test ... All of us fighting against SARS-CoV-2 absolutely passed the test, and I think we are even stronger and better than before the pandemic. We learned a lot about our potential and how to face new challenges and threats. I have a very positive view of how we performed.” What’s one thing that’s made him particularly optimistic for the future? The new technology that’s come his way as the lab has ramped up its testing and sequencing capabilities, from the brand new sequencers at his university’s core facility to genetic analysis software like the SOPHiA DDM™ platform.

Scientific research often involves long hours of careful, focused work, and a small mistake or lost data can destroy days or even weeks of effort. That can wear on a person under normal circumstances, but when it happens under the extreme pressure of a state of emergency due to a global pandemic, anything that makes the process of data collection and analysis even a little bit easier is a very welcome development. “I’m used to processing the data myself which is a very laborious and error-prone process—but these new devices make this processing much easier. When my boss told me that this part was going to be done by the SOPHiA GENETICS pipeline, I was so grateful.” The relief is palpable. This is one of the few upsides to a novel pandemic like COVID-19: it compels us to innovate, forcing progress that could stave off similar catastrophes in future.