The prescription drug hydroxychloroquine has been in the news in recent months, thanks to the COVID-19 global pandemic.
Hydroxychloroquine has been used successfully to treat lupus and rheumatoid arthritis and to prevent and treat malaria by killing the parasites that cause that disease. Since the drug has been beneficial in fighting off other viral illnesses, there was some thought that it also could combat SARS-CoV-2—the specific name for this coronavirus.
According to a researcher who spent his undergraduate years at the University of Tennessee at Chattanooga, the answer to the hydroxychloroquine question is no.
“There has been a lot of prior work on similar viruses showing hydroxychloroquine can inhibit viral replication. The thought is that if you slow down the replication after exposure, it allows your body to naturally handle and clear out the virus,” said Dr. Matthew Pullen, who received a degree in molecular biology from UTC in 2007. “Unfortunately, as you can see in our paper, that was not the case.”
Pullen was referring to “A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for COVID-19,” a paper published this month in the New England Journal of Medicine. Pullen, chief fellow in the infectious diseases and international medicine division of the Department of Medicine at the University of Minnesota, was one of the investigators on the recent hydroxychloroquine prophylaxis trial. He was the second author on the piece describing the research team’s running of the first randomized clinical trial of hydroxychloroquine for the post-exposure prevention of this virus.
Done in collaboration with McGill University, the University of Manitoba and the University of Alberta, the trial enrolled 821 asymptomatic, non-hospitalized adults from across the U.S. and Canada exposed to the coronavirus from someone living in their same households or as a health care worker or first responder. Half of the participants received hydroxychloroquine; half received a placebo. Participants were followed for two weeks to see who developed symptomatic COVID-19.
Pullen has multiple published papers on his resume, but this was the first time his work has been featured in the New England Journal of Medicine. As this trial study’s subject matter is topical, it makes that placement even more special.
To have a paper appear in the New England Journal of Medicine is “a really nice feather in your cap,” Pullen said. “This is the preeminent medical journal, so it feels good to see your name on a publication that appears in the journal. It validates that the work you’re doing is important and well-done, and it makes a lot of the long, long, long days worth it. The huge readership of the Journalmeans that our research is getting out there to a lot of researchers and clinicians, which is nice.”
Pullen said the idea for the study came about quickly. It was a double-blind, randomized controlled trial, considered the gold standard for any scientific or medical testing; neither the participants nor the researchers knew what the participants received. Through randomization, they were trying to eliminate any bias for who got what.
“This started in early March when the head of our lab, Dr. David Boulware, emailed us one night and said, ‘Hey, I have an idea for a trial.’ Dr. Boulware had some experience working with hydroxychloroquine before as an anti-HIV agent that didn’t work, but there was still a lot of research showing it was good for coronaviruses,” Pullen said. “We thought this might show some promise and was worth the trial. In the span of about eight days—which is more than light speed for clinical trials—we went from the initial idea to having institutional approval, FDA approval, having a design drawn up, having it submitted. And then, March 16—eight days after we initially conceived of the study—we recruited our first participant.
“The randomized part means when we recruited people, they were given either placebo or the medication in random order. It ensured that about 50% of people got one or the other; and that randomization also means that if there’s any confounding variable, randomization solves that because it’s completely random which group you get sorted in to. The postexposure prophylaxis part is we were following people that had exposure to someone with coronavirus. If they enrolled within the first four days after that exposure, we would give them either the placebo or medication and then follow them for two weeks to see if they then went on to develop the infection themselves.”
While the study showed that hydroxychloroquine was not beneficial in preventing illness compatible with COVID-19, Pullen stressed the importance of finding out that a specific drug has no benefit.
“It’s twofold why that’s important,” he said. “For instance, if you don’t have cancer but you decide to take a chemotherapy agent, you’re not receiving any benefit from that; you’re only accepting the risk of that drug, and no drug is really benign. Our study is showing pretty solidly that for postexposure prophylaxis, hydroxychloroquine does not help you.
“The other part of why it’s important is that hydroxychloroquine is very effective for lupus and rheumatoid arthritis. When a lot of the big media attention was on this drug in late March and early April, there were a lot of doctors prescribing it for themselves or family members thinking was going to be a cure or preventative. It put shortages across the country, and people with lupus and rheumatoid arthritis were not able to get a drug they needed for quality of life. We need to reserve this drug for people with conditions that it is beneficial for.”
Pullen, whose research interests center on epidemiology and virology, has had a fascinating career since first arriving at UTC. One of the highlights of his time in Chattanooga included learning about—and landing—a coveted molecular genetic research internship at the FBI laboratory in Quantico, Virginia.
Pullen’s time as a researcher has taken him around the world, as he has spent significant time studying infectious diseases while working abroad in Kenya and Uganda. He said his eyes were opened to the world of research during his time in the UTC Honors program.
“When I came and interviewed for the program, I was just blown away by the people, by the opportunities, the campus, everything. I had a phenomenal four years there, and I’m still close friends with a lot of the faculty and classmates,” Pullen said. “Margaret Kovach in the department of biology was a wonderful mentor. She helped me dip my toes into research for the first time as an undergraduate. And then all the Honors College faculty—Greg O’Dea, Joanie Sompayrac, Debbie Bell, Dr. (Gavin) Townsend, who unfortunately has passed—they were wonderful influences. They worked tirelessly to open people’s eyes to the world out there and expand your horizons.”
The New England Journalpaper on hydroxychloroquine has been published, but Pullen and the members of the research team don’t have time to rest on their laurels.
“We have one study that’s being written right now on early treatment of people with coronavirus symptoms. And then we have another trial that’s preexposure prophylaxis,” Pullen said, giving a sneak preview. “That study should wrap up by the end of the month and hopefully get published a few weeks after that.”