Halting the spread

It was New Year’s Eve 2020, the last day of another tumultuous year, when Tom Gallagher first heard about a concerning outbreak in China. He woke up the following morning with a fresh email from a virologist colleague at the University of Iowa. What little the pair could piece together pointed to a novel coronavirus, a single-stranded RNA virus that can cause a variety of diseases, and one that seemed transmittable between humans. This was disturbing, to say the least. 

For three decades, Gallagher—a professor of microbiology and immunology at Loyola University Chicago’s Stritch School of Medicine—has studied how coronaviruses infect different cell types or tissues. (The technical term is viral tropism.) That January email jogged a memory from years back, about a conversation he’d had with another well-known investigator who’d examined coronavirus strands in cows and pigs: “If you saw what these animal viruses do to domesticated livestock, and you thought a similar virus could get to humans? You’d be really alarmed.” 

Like Gallagher, Susan Baker has spent 30 years trying to understand the sacks of code that make up coronaviruses; her life’s work was rarely at the center of global conversation. As winter gave way to spring and the coronavirus skipped around the world with bracing speed, Baker—also a professor of microbiology and immunology at Stritch—found herself playing a little game: she’d flip on NPR and start counting. “Every time I turned on the radio, no matter what time of day, I’d hear the words COVID-19 or coronavirus before I got to 10 seconds,” she says. “That’s not my typical experience.” 

What came to be called SARS-CoV-2 had forced Chinese lockdowns before it brutalized Iran and northern Italy. By mid-March, it had penetrated American life so deeply that Loyola, like colleges everywhere, was forced to suspend its in-person operations for the safety of its community. While students and colleagues dispersed, a handful of brave and resourceful researchers at the Center For Translational Research and Education (CTRE), on the Health Sciences Campus (HSC), secured an exemption from the University administration to access their labs. 

Inside, they buckled down. Chinese scientists had publicly released the complete genome of the virus two months prior, data that could be simulated and synthesized in a lab. “Just like the rest of the world, I was hoping the virus would be quickly extinguished,” Gallagher remembers. “But once we had the sequence for the virus and the tools to study it, I thought there was a possibility we could be of service.” 

There are thousands of coronaviruses circulating every day. Some pester animals we bump up against, like cats, chickens, and (especially) bats. Only about 250 have the mechanics to infect humans. Most of those prompt nothing more than a common cold. But all of them are RNA viruses, complex in the way they can get around and take over a cell. 

SARS-CoV-2 replicates and spreads quietly. Early research suggests that it’s 10 times more efficient at binding to a cell’s enzyme than its cousin, which caused the dangerous SARS outbreak in 2003 and 2004. And its aptitude at transmitting between humans—particularly those who aren’t yet exhibiting symptoms—would be impressive if it wasn’t so devastating. 

Once locked in, the virus overloads the gene’s machinery. The disease it causes, COVID-19, is vascular in nature, bombarding the body’s circulatory system. COVID-19’s range of severity is vexing—some don’t even know they have it, while others experience a dangerous immune response. If it settles, the virus can attack the lining of the blood vessels; shred the muscular walls of the heart; trigger acute respiratory distress or pneumonia; and prompt strokes, seizures, and inflammation of the brain. The global death toll, through July, has eclipsed 650,000. 

For months, medical workers have risked their own lives to tend to the ill. And in laboratories across the world, scientists are racing to understand the virus’s weaknesses. From the earliest stages of the pandemic, Loyola was well-positioned to contribute. 

There’s physical infrastructure in place at CTRE, including a biosafety level two lab, that allows for high-impact and socially distanced experimentation and analysis. Thanks to Loyola’s Infectious Disease and Immunology Research Institute (InDIRI), there’s ongoing interaction and collaboration between basic scientists who specialize in infectious diseases and the clinicians at Loyola University Medical Center (LUMC) who treat afflicted patients. Baker and Gallagher, meanwhile, are two of the only coronavirus virologists in the region; as InDIRI collaborators, they represent a deep well of expertise on which Loyola’s entire research team draws. 

Senior leaders at Loyola, including Vice Provost for Research Meharvan Singh, made a strategic decision in March allowing those whose research intersected with coronaviruses to continue working at HSC, in spite of Illinois’s statewide lockdown. The thinking was simple: it’d be ironic and short-sighted to clamp down on research targeting the very pandemic that caused the shutdown in the first place. “It’s a matter of applying what we already know and leveraging our resources to attack the problem,” Baker adds, “and using everything we’ve learned in order to attack it more efficiently.”  

Collectively, Loyola scientists have kickstarted projects that fall into a broad range of categories. Gallagher’s lab has taken up that question of tropism: how the virus enters into cells, which in turn sheds light on the path by which it spreads. Some of the assays Gallagher has developed can be adjusted to identify and evaluate antibodies in a patient’s blood. (The presence of antibodies in one’s serum should confer immunity.) 

Baker, for her part, has leaned into her longstanding interest in how coronaviruses replicate and how the host organism defends against a subsequent infection. (In biology, it’s known as pathogenesis.) SARS-CoV-2 creates enzymes called proteases that act like scissors, slicing the virus’s own proteins into smaller, functional pieces. The main protease, then, makes for an attractive drug target; disrupting that scissor snipping would, in theory, prevent the virus from copying. (There’s precedence for proteases inhibitors slowing virus replication in people with HIV, for example.)

That’s where Baker and her team have devoted a lot of their energy—developing rapid tests that can determine if a drug actually blocks a coronavirus protease: “We appreciated that if we could impede those or knock those out, that would be one way you can make the virus more vulnerable to the immune response.” 

Arguably the largest bucket of research supports antiviral drug and vaccine development. InDIRI is critical to the organization and execution of these initiatives. Associate Professor Prakasha Kempaiah’s lab is performing in silico drug screening, canvassing existing approved drugs for their potential as a repurposed COVID-19 therapy. Another, led by Dr. Ravi Durvasula, is attempting to produce designer antibodies, burrowing into the medical chemistry to learn how to create the strongest bond. Assistant Professor Brian Mounce is identifying broad-acting antivirals that could inhibit not only this virus, but subsequent viral outbreaks. Baker is studying whether a live attenuated coronavirus vaccine for pigs that she’d previously developed with the USDA has any crossover potential.

Loyola’s emphasis is on what InDIRI co-director Susan Uprichard calls “strategic types of vaccines.” They may not be the first to market, but Loyolan research can help pinpoint more effective longer-term approaches, pushing our collective understanding forward.  

Over on the hospital side, doctors affiliated with InDIRI have been collecting serology samples of health care workers for months, in an effort to understand how long antibodies last and how long they’re functionally protective. Early in the spring, it occurred to Gail Reid, an infectious disease specialist at LUMC, that the virus might have been circulating far longer than people realized—she’d noticed plenty of respiratory illnesses surfacing in December and January. Those samples (along with periodic symptom tracking) are forming the backbone of a longitudinal study. Uprichard processes the samples in her Clinical Research Office Biobank, which houses equipment for clinical sample processing and storage. Baker’s lab tests to see if there are antibodies present in those samples. If there are, Gallagher can determine if those antibodies actually neutralize SARS-2 pseudo-particles.

The collected data should allow Loyola to correlate health care professionals who were sick in the winter and have not fallen victim in the spring and summer. They’ll also try to identify the prevalence of specific antibody responses in folks who had minimal symptoms or asymptomatic infections. “We’re smack in the middle of it,” Uprichard says, “and I think we’ll be going for a while.” 

For the intellectually curious, viruses present fertile ground for inquiry. Nina Clark,  InDIRI’s co-director, entered the field during the AIDS epidemic, when questions about transmission and treatment for that hellacious viral disease were unsettled. Gallagher similarly saw something appealing about specializing in coronaviruses, which were prevalent in agricultural and domesticated animals but had not caused anything more serious than a cold in humans, and which reproduced in unexpected ways. (The New York Times recently described the study of coronaviruses, before the emergence of the original SARS, as a “professional backwater.”) “It was all relatively new,” adds Baker, about her equivalent motivation, in the early 1990s. “I looked at it as a really exciting opportunity, because you could be on the ground floor.” 

For those steeped in the science, the potential for a pandemic was never far from mind, either. Over the years, that looming threat underpinned many coronavirus grant requests and subsequent fact-finding. And in the spring of 2020, as SARS-CoV-2 mushroomed out of control, what for many had started as an intellectual pursuit took on dramatic new urgency. 

Singh, Loyola’s vice provost for research, was confident that his front-line researchers could get to work quickly, “finding a way to be functional in this new normal.” Initial capacity restrictions mandated that only one investigator could occupy each research bay at any given time, in a space of about 500 square feet. Everyone at CTRE wore masks at all times and kept at least six feet apart from colleagues. The former is par for the course in wet labs, while the latter took some getting used to. “Sometimes we have our Zoom lab meetings with people in very different areas of the CTRE, so that we’re not all in the same room,” Baker says. “You feel almost like The Twilight Zone: Where are the other people? Where did they go?” 

More stressful than adhering to tightened safety measures was the sheer volume and intensity of the tasks at hand, when the entire world was desperate for progress. At the hospital, Clark was forced to treat a flood of COVID-19 patients, all in various states of distress. “There’s a lot of anxiety on the part of people working in the hospital that you have to manage,” she says. “There’s intense communications that have to be addressed every day.” 

At the research center, projects needed organizing, clinical studies and trials needed lining up, papers and grants needed review, administrative hurdles needed clearing. Securing adequate funding was another question entirely. Few expected they’d be studying coronaviruses so deeply six months ago; now, Uprichard and others had to launch studies and then scramble to figure out how to pay for them. 

The warming summer weather was of great help to Baker, who managed her inevitable anxiety by taking long walks with her dog. Uprichard and Clark both joked of napping occasionally (and unwittingly) on their computers. While exhausted, the Ramblers at CTRE are equally energized by the challenge of figuring out what’s going on, and by their ability to leverage that expertise to help solve a global crisis. “It’s their privilege and not their prerogative to do the science they get to do,” Singh says. “And in this environment, where the stakes are so high, they are upping their game.” 

For all that dedicated focus these past six months, the pernicious virus is still new to science, with ample unknowns. That lack of clarity is precisely why researchers at Loyola and around the world are pooling their resources and know-how and working every conceivable angle—a clearer understanding of the viruses’ mechanics is a prerequisite for successful diagnostic tests, antibody tests, contact tracing, vaccine development, and, ultimately, the resumption of life as we once knew it. Baker and others realize the world will need many solutions to control the virus.

Gallagher, for his part, finds it “tremendously uplifting” to see so many competent investigators affixing their PPE and weighing in. “The public sees just a little, teeny slice of the iceberg of what is actually going on in research labs around the world,” adds Uprichard. “And even if the antivirals or vaccines aren’t perfect in the end, they’re going to mitigate this really extreme and deadly response.” 

When Illinois moved to phase four of its Restore Illinois reopening plan, in June, the CTRE cracked open its doors to a wider range of researchers eager to contribute however they could. They’ll keep chipping away as the year moves along and the threat of additional surges hangs in the air.

When he (safely and considerately) visits with neighbors or loved ones, the questions Gallagher fields are more practical than theoretical, less about science and more about aerosols and gathering sizes. Everyone wants to know when it’s all going to end, and how they can reduce their risk in the meantime. While the expert can’t offer immediately satisfying answers, he and his coworkers push for them day after tiring day, inside their lab coats and behind their trusty masks.