Scientists at Ohio State, Battelle and Nationwide Children's Hospital have launched an all-hands-on-deck quest to better understand and fight the spread of COVID-19.

Like many of us, Loren Wold found himself forced by the pandemic to work from home. Unlike many of us, he didn’t stay there.

In early April, after just a couple of frustrating weeks away from his laboratory at the Ohio State University Wexner Medical Center, Wold returned to campus. With the coronavirus wreaking havoc throughout Ohio, state health officials enlisted the university to help produce COVID-19 test kits, which were in critically short supply. Peter Mohler, the chief scientific officer at the med center, asked Wold to lead the effort. He gladly accepted the assignment, and the cardiovascular researcher and the rest of his team—three junior faculty members, four technicians and eight graduate and undergraduate students—snapped into action, converting his lab at the Davis Heart and Lung Research Institute into a test-kit assembly operation.

Within in a matter of days—and with the help of volunteers pulled from all over the med center—the group was producing up to 12,000 kits a day and sharing them with hospitals across Ohio and the country. “I’ve never done anything like this in my career as far as pivoting 180 degrees,” says Wold, a professor of nursing and medicine.

Wold has plenty of company. Faced with a medical crisis that has upended life throughout the world, scientists at Columbus’ three major research institutions—Ohio State, Nationwide Children’s Hospital and Battelle—are responding in an all-hands-on-deck manner. They’re breaking down barriers, redeploying resources and working around the clock to better understand and fight the spread of a maddeningly unpredictable virus that can be deadly and debilitating for some and a relatively minor nuisance for others. “In the 20 to 25 years that I’ve been doing science, I have never seen such collaboration and creativity, whether it’s across Ohio State or across the state or really around the world,” Mohler says. “It’s been very inspiring.”

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COVID-19 projects at the three institutions run the gamut, from exploring the most fundamental questions about the new coronavirus (how it affects the body, how to treat it) to more technical and diagnostic problem-solving (building ventilators with 3D printers, developing new tests and equipment). In early July, Columbus doctors weren’t testing any of the 18 COVID-19 vaccines in the clinical evaluation stage yet, but Dr. Hal Paz, Ohio State’s chancellor for health affairs and the CEO of the Wexner Medical Center, said at the time he’s “looking forward to a vaccine trial very soon.” Researchers are operating under a once-inconceivable timeline. Health officials hope to have a COVID-19 vaccine next year. In comparison, the current mumps vaccine, one of the fastest ever developed, took four years to create. “We’re moving at light speed compared to what we could do 10 to 20 years ago,” says Dr. John Barnard, president of the Abigail Wexner Research Institute at Nationwide Children’s Hospital.

Indeed, projects and collaborations that once might have taken months or even years to launch are coming together overnight. The breakneck pace has resulted in a slew of bold ideas, but the jury is still out on some projects. Recent media reports, for instance, question the value of one of the highest-profile COVID-19 technologies—a mask-decontamination system, developed by Battelle, that Gov. Mike DeWine and others have hailed as a game-changing development in the fight against the virus.

Regardless, Columbus researchers say this period could have lasting scientific benefits, raising the city’s profile as an innovation hub, creating a template for tackling other scientific challenges and preparing the city for the next medical crisis that comes its way. Most significant, perhaps, are the stronger ties that Ohio State and Battelle are developing as a result of their new COVID-19 partnerships. Columbus civic leaders have long believed that if the two research giants across the street from each other could ever figure out how to work together more effectively, then their combined efforts could result in an economic and scientific boom for the city.

“Through these tragic events, we’ve been able to accelerate some of the trust and partnerships that may have been much harder to do in the past,” says Battelle CEO Lou Von Thaer. “And I think we’re going to get long-term benefit from that.”

Ohio State: Breaking Down Barriers

Before he became the leader of the Wexner Medical Center, Hal Paz was a pulmonary and critical care physician who treated patients with infectious diseases. He’s plenty familiar with coronaviruses, a family of pathogens named for the crownlike spikes visible on their surfaces when viewed under a microscope. A coronavirus can cause the common cold, and most people are infected with one or more of these viruses during their lifetimes.

But SARS-CoV-2—the virus that causes the disease known as COVID-19—is much different than anything Paz has seen before. Like its common cold brethren, it’s extremely infectious. But it also has “an amazing ability” to attach itself to the cell linings of the lungs, Paz says, which can put some groups—particularly the elderly and people with weakened immune systems—at great risk. The result is the sweeping outbreak that has killed more than 550,000 people worldwide as of early July, including 431 in Franklin County. “It’s a unique set of circumstances that creates a pandemic like this,” Paz says.

Those unique circumstances, in turn, have inspired Ohio State’s all-encompassing scientific response. The $4 billion medical system—which includes seven hospitals, seven colleges and more than 20 research institutes—has launched about 100 COVID-19 research projects involving 20 academic departments and 60 laboratories, many of which retooled to fight the outbreak. “The pace and scale is like nothing I have ever seen,” Paz says.

Information is critical. Read our latest reporting on the coronavirus response here.

Naturally, OSU researchers are exploring ways to treat the disease. Paz says the university is a test site for a broad study of remdesivir, a promising antiviral drug for critically ill COVID-19 patients. Meanwhile, other studies are looking at whether antiviral HIV therapies can be repurposed to treat the new coronavirus, as well as whether transfusing plasma from recovered COVID-19 patients can help critically ill ones. (Recovered patients frequently have virus-fighting antibodies in their blood.)

Often, however, Ohio State scientists have focused on more immediate, pragmatic problems. For Wold to establish his test-kit operation, for instance, the university needed to find a sterile saline solution—called viral transport media, or VTM—to preserve samples. VTM was in high demand in early April when the test-kit facility was getting off the ground, so Jacob Yount, an Ohio State associate professor of microbial infection and immunity, developed in a day an in-house recipe for the liquid, which Wold and his team immediately started producing for their kits.

In addition to sharing the recipe with colleagues throughout the country so they could produce it themselves, university researchers shipped a large batch of VTM to New York City in the spring when it was the U.S. epicenter of the pandemic. “I received two letters of thanks already from the city of New York for what we were able to do right here in Columbus,” Paz says.

In March, when the pandemic was just beginning to hit Ohio, the university and Battelle combined forces to develop a rapid test for COVID-19. It filled a desperate need at the time, when diagnostic tools were scarce, as well as offering a quicker turnaround for results (as fast as five hours). Mohler, the med center’s chief science officer, says about 100 OSU and Battelle researchers—including engineers, chemists, molecular biologists and data scientists—worked 18- to 20-hour days for about two weeks to develop the test and establish a new lab in an empty room in the university’s Biomedical Research Tower, drawing plans on the walls “like you might see in a movie.”

The impact has been significant. Ohio State has gone from being able to do about 40 tests a day early in the pandemic to potentially as many as 4,000. As of early July, the new lab had administered more than 85,000 tests for individuals primarily from Central Ohio but also elsewhere in the state. What’s more, the project has deepened ties between the two neighboring scientific centers—one of the largest universities in the country and the largest private nonprofit research organization in the world. To be sure, Ohio State and Battelle have collaborated on research in the past. But community leaders have long believed there was plenty of room for growth.

While the pandemic has put on hold some ambitious ideas that leaders from the two institutions have discussed over the past six to eight months—including establishing joint research institutes—the test project, which is now expanding to include antibody testing, may offer a template for the future. “We believe this platform we’ve developed between our two groups will continue to expand, and people in Ohio will continue to see new and great things coming from these relationships going forward,” Mohler says.

Nationwide Children’s: In it for the Long Haul

Is it possible that we each have cells inside us that could keep COVID-19 at bay? That avenue of research is just one of many that Nationwide Children’s Hospital is examining as the virus continues to spread throughout the world.

“It’s a unique time, and there’s much to be learned from the coronavirus pandemic,” says Barnard, the head of the Research Institute at Nationwide Children’s. The hospital is involved in more than 30 research projects related to the novel coronavirus, including many that are offshoots of pre-pandemic research.

One is the study of so-called natural killer cells, or NK cells, which are in the body’s immune system and can seek out and destroy germs, cancer cells and viruses, says Dr. Dennis Durbin, chief scientific officer for the hospital. Researchers at Nationwide Children’s and Ohio State, led by Dr. Dean Lee at Children’s, are developing “ready-to-use” NK cells to fight cancer.

Early in the year, they began research to determine if they could repurpose the technology to fight COVID-19. Durbin says they plan to test whether giving extra NK cells to fight the virus can help adults at risk of severe complications from the disease. Then, a decision will be made about whether it also could help children.

Overall, Nationwide Children’s employees are responding to the pandemic with many types of research, Durbin says. That includes clinical studies, such as looking at how COVID-19 affects and manifests itself in different subgroups of pediatric patients with underlying conditions, such as those with heart problems or immune deficiencies. Those kinds of studies are important in the early days of a new disease because they can define how to care for different groups of children, he says.

Another is trying to identify new treatments by understanding the virus itself. And a third is looking at the body’s immune response to the virus, studying why children have such a different response than adults, Durbin says. One study will follow a large number of children for many years to understand, among other things, the virus’ long-term effects.

“As much as we want this virus to be here and gone quickly, it’s not going to be,” Durbin says. “It’s going to be with us now and into the future. We’re in this research for the long haul.”

Dr. Octavio Ramilo, chief of infectious diseases at Nationwide Children’s, says he’s especially intrigued by the question of why COVID-19 generally seems to affect children less. “This is the opposite of what we see with most viruses,” he says. “But maybe we have not seen all the complications these viruses can cause for kids, so we have to be very, very prudent.”

The hospital is also about to launch a study on how the virus affects pregnant women and their babies. OSU’s Wexner Medical Center, Jackson Laboratories in Connecticut, Cornell University in New York and Cevaxin in Panama are collaborating on the project, with funding from a $3 million federal grant, Ramilo says.

Durbin says that study is just one of several where Nationwide Children’s is working with researchers at other facilities to expand and accelerate results. “One of the wonderful things that’s happened in the scientific community during this is that there’s been an extraordinary amount of data sharing,” he says. “Some of our researchers are collaborating with institutions they’ve never worked with before.”

In another study, hospital researchers are examining how the social isolation of the pandemic and school shutdowns are affecting children. “There are real concerns in pediatrics about the impact of prolonged social isolation on long-term emotional and intellectual development,” Durbin says. “How does the effect of isolation manifest itself?”

Barnard expects additional research opportunities to emerge in the months ahead as the pandemic continues to evolve. What they’ll be isn’t clear, but he suspects one may be how colds, flu and the common childhood illness RSV, or respiratory syncytial virus, interact with COVID-19. Another will be what the pandemic means for children’s overall health in the years to come, since the virus has significantly interrupted preventive checkups.

“It’s a troubling time, but also a time of great opportunity to learn how we can improve health care in the unique way that researchers who study children’s health care can do,” he says.

Battelle: The Stopgap Solution

Early this year, the U.S. Department of Health and Human Services projected that health care workers would need 300 million N95 respirator masks per month to deal with the coronavirus, and 3.5 billion total during the pandemic. Yet the national stockpile held just 12 million, despite two decades of warnings. It’s as if the country readied for drought by saving a case of Evian.

Prompted by worries of a potential shortage, the Food and Drug Administration contracted Battelle in 2014 to study the decontamination and reuse of disposable N95s. The research organization investigated using vaporized hydrogen peroxide and found that its method—eventually known as the Critical Care Decontamination System, or CCDS—could clean masks up to 20 times without compromising filter efficiency or fit. Completed in 2016, the research was shelved for a time of need.

On March 13, Dr. Laurie Hommema was alarmed when her OhioHealth colleagues described how even a small surge of COVID-19 patients would deplete masks and other personal protective equipment, the scenario experts had warned about for years. Hommema, the medical director of well-being, mentioned her concern to her husband, Kevin, a Battelle engineer. He told her about the FDA study, which was led by his co-worker Will Richter. Within a week, Richter and his team had rigged a scaled-up version of their system into shipping containers, and OhioHealth had sent around 1,000 masks to test it.

Battelle was already pivoting many of its resources to help with the pandemic, says CEO Lou Von Thaer. Researchers and engineers dove into several projects, including a study to test how long the virus could survive on library books, the development of a sensor that can detect it in the air and a joint effort with Ohio State to ramp up testing. But no other project received the hype and scrutiny of CCDS.

The system vaporizes a hydrogen peroxide solution and pumps the gas into the sealed containers, where masks are hung by the hundreds or thousands. Once decontaminated, they’re aerated and returned to medical centers. The FDA gave emergency approval on March 28, initially for cleaning 10,000 masks daily and then for widespread use one day later. It was quickly hailed as a breakthrough.

But it also drew criticism, partially due to the FDA’s revised authorization, which came after Ohio Gov. DeWine and President Trump publicly urged the agency to discard the 10,000-unit limit. Reports from NBC and the Wall Street Journal speculated about political pressure leading to the about-face. Von Thaer says there was simply a misunderstanding between the two organizations—10,000 is the max for one machine’s cycle, not a systemwide limit, and that’s why the FDA modified it so quickly once they discussed it. “They didn’t make compromises on this,” Von Thaer says. “They didn’t bow to politics.”

The news reports also questioned CCDS’ costs, which NBC described as rising by hundreds of millions in just a few days. Von Thaer explains that there were two pieces to Battelle’s contracts with the Defense Logistics Agency. The first was $78 million for production of 60 machines, which has been completed. The other was to staff and run CCDS sites around the country, which Battelle hadn’t anticipated and required hiring 800 people. The contracts were capped at $413 million, with subsequent authorization for up to $600 million. Von Thaer says Battelle doesn’t know what the total cost will be because the timeline for operating the system is uncertain, so the final bill could fall below the ceiling.

The most serious concerns were related to safety. Some health care workers and unions expressed anxiety about the technology, which had never been deployed to decontaminate PPE intended for one-time use. The Centers for Disease Control and Prevention only recommends decontamination in a crisis, and its preferred method is to store masks in paper bags for five days between uses, though that assumes access to multiple masks.

Battelle stands by its original study. Richter says they’ve continued testing masks internally and from the field, and all have maintained the required filter efficiency. They’ve had some where fit has been compromised, and though deformed masks are supposed to be thrown out, Von Thaer acknowledges some have slipped through. By early July, CCDS had decontaminated 1.2 million masks at more than 40 sites around the country, and only seven had problems that required alerting the FDA, according to Battelle. None have undergone 20 cycles, but many have completed 10, and the most is 14. Although mask-maker 3M doesn’t recommend decontamination, the company evaluated two models that had gone through CCDS and verified that both passed 20 cycles for filter efficiency and fit.

Locally, Mount Carmel had 7,600 masks decontaminated by early July, and OSU had sent out 41,000 and received 38,000 back for reuse. Dr. Hommema says OhioHealth has had 127,486 masks returned as of July 1, many having undergone 10 or 11 cycles. Failures and problems have been infrequent, and when a mask is damaged or soiled, they instruct workers to throw it away. She says OhioHealth’s leaders have been mindful from the beginning that employees would have safety concerns, and they’ve tried to be transparent and share Battelle’s public research to alleviate them.

Von Thaer says he understands the emotion of health care workers who just want a new mask every time. “We completely agree with them and want them to get back to that, but until that reality is available, this is the next best thing.”

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