Can Columbus Stay Ahead of the COVID-19 Variants?
As others celebrate a return to normalcy, Ohio State, Battelle and Nationwide Children’s Hospital researchers try to keep up with a relentless and evolving foe.
While many cocooned at home as the pandemic raged, Dr. Dan Jones spent his days doing something few paid much attention to before the coronavirus emerged: genomic sequencing. In a nondescript building on Columbus’ Far North Side, the Ohio State genetic pathologist led a team of researchers that placed samples of SARS-CoV-2, the virus that causes COVID-19, into machines that resemble giant microwaves. Not that long ago, it took two weeks to determine the order of the chemical building blocks that make up a virus’ DNA. With these machines, however, the results can come overnight, substantially speeding up essential research.
Jones’ project was a part of the unprecedented, worldwide, scientific response to the once-in-a-century global health crisis. That effort’s crowning achievement, of course, was the rapid development of the Pfizer, Moderna and Johnson & Johnson vaccines. Thanks to these life-saving inoculations, Columbus and many other parts of the world have begun to reopen in recent months: ditching masks, returning to offices, gathering again in bars, restaurants, theaters and sports arenas.
Yet for Jones and other researchers in Columbus, their work continues—as does their sense of urgency. While others may celebrate a return to normalcy, these scientists remain locked in a race against a relentless foe—a constantly evolving pathogen that still poses a serious threat, especially to the large percentage of the population in Ohio and elsewhere that remains unvaccinated. Just as they have since the novel coronavirus upended life in 2020, Jones and his colleagues at Ohio State and other Columbus research and medical institutions are staying focused. They’re quietly building upon the work they began last year—and keeping close tabs on the new viral strains developing both here and around the globe, including the delta variant, now the most common coronavirus strain in the United States.
The result has been a plethora of projects across multiple disciplines that have combined to advance the understanding of not only how to successfully treat those who get COVID-19, but how to protect against its transmission, keep it in check and lay a pathway to prevent future outbreaks from morphing into pandemics. And, most of all, to win the race against the virus.
“What’s most concerning is the next variant,” says Dr. Mysheika Roberts, the Columbus health commissioner. “The more unvaccinated people we have, the greater the chance the virus could mutate.”
Last fall, scientists and health officials issued several dire warnings. In those pre-vaccine days, they feared what might happen if people gathered en masse with friends and family to celebrate Thanksgiving, Hanukkah and Christmas.
Despite the urgent public statements, many folks chose to ignore the message, eager for a few days of togetherness after months of pandemic isolation. During this time, the wily coronavirus passed from person to person to person, from a Texan to an Ohioan, a Californian to a Coloradan, a New Yorker to a Floridian. By then, the virus had begun to evolve ever so slightly into an explosion of variants, a complex mixture that spread over turkey dinners and gift exchanges and cocktails.
All the while, Jones and his staff at Ohio State continued to doggedly pick apart those strains, inside and out, sequencing their genetic material to determine which variants were swirling through the human population and, through analysis, what kind of threats they posed.
One of their findings grabbed worldwide attention: the discovery of two new variant strains of SARS-CoV-2 late last year. One carried the mutation that was identical to a strain found in the United Kingdom and South Africa, while the other was a completely new virus strain, then called the Columbus strain, as Peter Mohler, chief scientific officer at the OSU Wexner Medical Center, explained in January.
By then, Jones realized that the Columbus virus, which he now calls the Midwestern variant because researchers determined it likely originated in Wisconsin, had been dominant in Columbus in late December 2020 and early January. With three mutations, it represented a significant evolution of the virus, Jones says.
But as is the way with viruses, the strain that put Columbus on the map for a few weeks petered out, bested by variants first detected in the U.K. (alpha), South Africa (beta) and Brazil (gamma). More recently, the delta variant, first discovered in India, is causing the most concern in the United States.
The Centers for Disease Control and Prevention announced that the delta variant had become dominant in the country as of July 3, identified in 52 percent of new COVID-19 cases. The variant is considered much more contagious than the original. In Ohio, the variant represented just 1 percent of new cases by July 2, but that percentage was expected to climb.
Having their variant knocked out hasn’t stopped Jones’ work to help control the pandemic, a job he’s doing on top of his regular full-time gig as director of molecular pathology for the OSU Comprehensive Cancer Center, which includes the James Cancer Hospital and Solove Research Institute. When it became apparent in January 2020 that the virus would spread across the globe, scientists such as Jones—who last worked with viruses 20 years ago but understood the danger posed by the so-called novel coronavirus—had urgent discussions with colleagues about how they could help.
Now, his genomics lab is working on other major SARS-CoV-2-related projects: the OSU Center to STOP-COVID, which is following the long-term effect of COVID-19 on Columbus first responders and the durability of immunity from vaccination and natural infections; tracking large community shifts of SARS-CoV-2 with DNA sequencing of wastewater; and designing and launching rapid sequencing diagnostics that measure multiple respiratory viruses and immune parameters at the same time.
Other Columbus researchers, like Battelle, are trying to stay ahead
Ohio State isn’t the only institution in town trying to stay ahead of COVID-19. Battelle, the nonprofit research giant located across the street from the university’s medical campus, has several projects underway.
Working with scary diseases like COVID-19 is nothing new for Dan Sanford, a senior research leader and study director at the Battelle Biomedical Research Center. He’s led studies involving anthrax, botulism and bubonic plague, as well as biological warfare agents.
He remembers well when he first became truly alarmed about the novel coronavirus: during a late January 2020 scientific conference featuring Dr. Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases, who abruptly switched his speech topic from Ebola to the novel coronavirus. “He talked about how it started in China and showed us maps and up-to-date data and alluded to the fact that his biggest fear—a respiratory virus that spread easily—was coming true right in front of him.” Battelle already had begun some research related to the virus, but Sanford says the speech added urgency to the work.
A current effort revolves around how long COVID-19 vaccines will last: Will they be required annually, like flu shots? Will they last 10 years, like the tetanus vaccine? Will they protect against variants?
One way to answer some of these questions is to follow vaccinated people and determine a correlate of protection (an immune response that is responsible for and statistically interrelated with protection). First, researchers identify an immune marker (such as an antibody or memory cell response) that is linked with protection. Next, researchers must determine the body’s threshold of protection from the virus. For instance, is someone still protected if the immune marker response is just 50 percent? Then, researchers must determine how quickly that happens, Sanford explains. “You’re trying to identify the time that your immune response drops so low that you’re not protected anymore,” he says.
Rather than wait months and years to determine the immune response marker by studying those results in vaccinated individuals, Sanford and his team are trying to speed up the process by diluting vaccine samples in their lab and testing them against the virus to figure out when the diluted vaccine no longer offers protection. “You take the data from our study and then we know what the immune marker is,” Sanford says. “Then we look at the people being followed in the clinical vaccine studies and determine when their protection dropped below a certain point.”
The results, not yet publicly released, can help determine if and when booster vaccines would be needed.
Researchers use wastewater to determine which variants are spreading
Rachel Spurbeck, another Battelle researcher, has a much different COVID battleground: sewers. The senior genomics research scientist found her niche in the fight against the pandemic when she learned in early 2020 that the coronavirus that causes COVID-19 was found in fecal matter. Spurbeck knew that wastewater had been used to study stomach flu outbreaks in the Netherlands decades ago and, more recently, to monitor for illegal drug use in the United States. “I’m interested in analyzing different types of materials to help understand things, and one avenue of research is what we can learn about the health of a population from wastewater,” she says.
Spurbeck and her team developed techniques to pull the virus out of wastewater samples. Linking up with the Great Lakes Environmental Center, they used 24-hour automatic samplers in Toledo to collect effluent from manholes in a neighborhood, a nursing home and two hospitals in July 2020. The researchers then tested how much SARS-CoV-2 was in the samples and sequenced them to determine which variants were circulating in the community.
In part, Spurbeck’s study has spurred the establishment of the Ohio Coronavirus Wastewater Monitoring Network, a collaboration between the Ohio Department of Health, other state agencies and a number of universities statewide, including OSU. The network, which started in 2020, samples raw wastewater at specific locations across the state to detect SARS-CoV-2 in communities before it shows up through individual testing or hospitalizations.
“We can see where we need more resources and get those resources,” Spurbeck says. “What concerns me is that the rates have not dropped considerably, not enough to reduce COVID-19 to the point where it’s no longer a threat.”
Battelle is also part of a new nationwide COVID-19 testing program that is keeping an eye on that threat. The voluntary program aims to keep schools open and tamp down the virus by organizing widespread testing across the country at K–12 public and private schools and in congregate care settings such as homeless shelters and prisons. Battelle is managing one of three Department of Health and Human Services hubs for the work, coordinating a 16-state swath of testing known as the Midwest Coordination Center.
Justin Sanchez, a fellow at Battelle, says the tests are being given proactively—not necessarily as the result of a diagnosed case of COVID-19—to identify cases quickly and keep the virus from spreading. “We know this testing can help keep kids in school,” Sanchez says. “Kids need to be in school, and their parents need to be at work. If we can inform people [about COVID cases] earlier and with precision, administrators and parents can make decisions on how to keep kids in school. It’s about knowledge and empowerment, and it’s also about speed.”
The program began ramping up in June with a goal of 750,000 tests performed per week in the Midwest once everything is in place. It’s considered a pilot at the moment, running from May 25–Nov. 24, but could be extended for six months after that. “This infrastructure didn’t exist in this country before,” Sanchez says. “It will pay dividends in the future if we want to use an infrastructure like this again. Right now, we’re testing for COVID, but in the future we can think about this for other infectious diseases.”
Do we need another COVID-19 vaccine?
Meanwhile, scientists from Columbus’ third major research institution, Nationwide Children’s Hospital, are exploring whether there is a need for another COVID-19 vaccine. Since March 2020, that team and its partners at Ohio State have been repurposing research developed to create a vaccine against another virus—respiratory syncytial virus, or RSV, which can be deadly for infants and older adults.
RSV kills more than 80,000 children worldwide each year, and by January 2020, their new discoveries had resulted in publication of their first RSV vaccine candidate. But when it became clear a few months later that SARS-CoV-2 was a dramatic threat, the RSV team shifted to apply the processes they had developed to the novel coronavirus.
Mark Peeples, a principal investigator in the Center for Vaccines and Immunity at Nationwide Children’s Hospital and professor of pediatrics at OSU, had long been working with Jianrong Li and Stefan Niewiesk, professors of virology in OSU’s veterinary biosciences department, on the RSV vaccine. Li used the measles virus vaccine as a means for delivering a stabilized version of the SARS-CoV-2 spike protein, thereby causing a strong, protective immune response in lab animals.
Using the measles vaccine as a delivery conduit could have major benefits over the current vaccines. It’s inexpensive to produce, easy to ship and can be stored in a refrigerator, Li says. The hope, Peeples says, is that their vaccine might also provide longer immunity against SARS-CoV-2 because the measles vaccine protects for life. It’s unknown how long current vaccines for COVID-19 will protect vaccinated people, but Peeples says it appears the protection will not be permanent, and those vaccines would have to be given every year or two.
The vaccine candidate has been licensed to a company based in India, Biological E. Limited, and Columbus researchers hope it will be developed and tested in clinical trials.
Are scientists staying ahead of the virus?
Opinions vary. “We’re keeping pace with it,” says Dr. Susan Koletar, director of the division of infectious diseases at the Wexner Medical Center. “Viruses by their nature mutate, and the fact that we’re able to detect variants at such a quick pace with reproducible precision, one might argue we are trying to stay ahead of it. But if we were really ahead of it, we’d stop it from mutating.”
Koletar sees just one way to accomplish that goal: More people need to get vaccinated so the virus can’t spread. Roberts, the Columbus health commissioner, estimates that herd immunity could be reached if about 70 percent of people are either vaccinated or have had COVID-19 (though she would be more comfortable if the 70 percent figure consisted entirely of vaccinated people; immunity gained by having the virus may last only three to six months, Roberts says).
By early July, 44.9 percent of Ohioans and 48.9 percent of Franklin County residents had been fully vaccinated. Among those 12 and older in Franklin County, 58.3 percent had been fully vaccinated. Nationwide, Roberts says, recent data shows that 99 percent of those who have died or been hospitalized with COVID-19 were unvaccinated. And while current vaccines appear to protect against the spreading delta variant, that might not be the case with another variant, she says.
The pandemic, she says, is far from over. “We could see a surge; people need to be on guard. There is no ‘post pandemic’ yet.”
Koletar is surprised that many Americans don’t see the benefit of getting vaccinated; she wonders if the resistance is because many people have never personally experienced the effects of diseases such as polio, measles or tetanus.
“It’s our job to keep pushing the message of the safety of the vaccines,” she says. “It has to start with people understanding the origins of the vaccines and being very clear in terms of language they can understand. And the information has to be aimed toward the group you’re talking to and knowing what is motivating their distrust.”
Koletar points out that while medical professionals have found ways to help those with COVID-19, there still are no good therapies to manage it on an outpatient basis. “It’s scary, especially for those of us in the hospital taking care of people.”
Gabe Meister, research leader at Battelle’s state-of-the-art biocontainment research facilities, believes new technologies will help science stay ahead of SARS-CoV-2 variants. He says researchers can adapt vaccines to the new strains using the new vaccine technologies developed in recent months and the coordinated work of scientists worldwide. Koletar says research on mRNA technology, which two of the vaccines use, had been going on for years, enabling the quick turnaround. Messenger RNA vaccines carry instructions that prompt the body’s cells to create a harmless piece of the spike protein found on the virus that causes, in this case, COVID-19. That prompts the immune system to make antibodies against the disease.
Peeples says the pandemic has pushed scientists to cooperate with each other in ways he hasn’t seen in nearly 50 years as a researcher, both within institutions and between them. “We’ve all gotten to know each other better, and people will say, ‘Can you help us with this or that?’ We have a network, a lot of it informal, and we have become much more informed about what else is going on at our institutions and about people who know the people who might be of help. Labs are helping other labs, and it’s a really good thing. I think these networks are going to last.”
Jones says those collaborations extend to public health departments, and he’s hopeful that the bridges that have been built between researchers in organized lab programs and health officials will continue. But the infrastructure supporting those collaborations hasn’t been funded in the past, and he fears it may fall away in the future.
“It was a worldwide lesson on the importance of organized lab programs, and I worry we’re not going to keep that structure in place, between diagnostics and public health. We need to keep this alive. The challenge is, how do we keep all the useful resources that were built here together? How do we build more resiliency into the system?”
The pandemic, Meister says, created a scientific awakening that he believes will fuel the fight against infectious disease into the future. “Every day there seemed to be new knowledge gained, as scientists were shaking every bush and every tree. That’s demonstrated to me the resolve of an entire community to work together to produce a phenomenal amount of data and information. We have learned a lot across many, many disciplines, and I feel strongly that’s going to be applied to infectious disease. There are real possibilities coming out of this, because every new learning opportunity prepares us for the next challenge.”
This story is from the August 2021 issue of Columbus Monthly.