Despite recent promising signs, a vaccine might not work at all against the novel coronavirus. If it does work, it could take many months to pass large-scale trials and get approval from the U.S. Food and Drug Administration. And even if it gets the FDA’s nod, a vaccine might not work for everyone.
All of which is to say that new treatment regimens—which the federal government is suggesting could be months away—are as important as ever as the United States registers more than 3.4 million SARS-CoV-2 infections and 136,000 deaths.
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Janet Woodcock, the director of the FDA’s Center for Drug Evaluation and Research and a senior member of the federal government's vaccine-hunting task force Operation Warp Speed, has stressed that a vaccine remains “the permanent hope for controlling an outbreak.” To that end, Operation Warp Speed has handed billions of dollars to five companies with apparently viable vaccine-candidates. The goal is to get one or more vaccines past the FDA by the end of the year, and produce 300 million doses by January.
But it would be unwise to bet solely on vaccines, Woodcock told reporters on Monday. “Even with success, some people may not respond to vaccines and some might not get vaccinated at all, so you always need therapeutics.”
Therapies take a lot of different forms, as Woodcock and other Operation Warp Speed officials explained.
They include prophylactics that can boost the immune system and help ward off coronavirus infections. Other therapies can help to calm the hyperactive immune response—the so-called “cytokine storm”—that has proved to be one of the most lethal aspects of a serious case of COVID-19. Some therapies can protect patients on ventilators. Others help recovering COVID patients with the long-term complications that can result from the disease.
“COVID-19 is a complex illness and there are multiple clinical scenarios where we need to address therapeutics,” Woodcock said.
Therapies can be developed and fielded in mere months, as opposed to the year or more it can take to invent, test, and deploy a vaccine. Operation Warp Speed officials said they want to produce hundreds of thousands of doses of new therapies by the fall.
But the quickest and easiest way to develop a COVID therapy is to repurpose an existing drug. There are lots of candidates. “We have data showing that usage of certain drugs, over-the-counter and prescription, are correlated with protection from COVID-19,” David Ostrov, a professor in the Department of Pathology, Immunology, and Laboratory Medicine at the University of Florida College of Medicine, told The Daily Beast.
The antiviral drug Remdesivir is the poster-child of COVID-19 repurposing. California pharma company Gilead Sciences developed Remdesivir in the early 2000s as a treatment for hepatitis C. As the novel coronavirus began spreading across Asia and Europe back in January, scientists discovered the drug also seemed to help shorten hospital stays and showed signs of reducing mortality.
The federal government quickly bought 500,000 doses—essentially all of the drug Gilead could manufacture through the fall—and began distributing it to the states the feds determined were most in need.
Compare that to the malaria drugs chloroquine and hydroxychloroquine. Those drugs became objects of intense scrutiny—and runaway bestsellers at pharmacies—after President Donald Trump touted them as effective COVID therapies and even claimed that he was taking hydroxychloroquine as a preventative.
But then multiple studies cast doubt on chloroquine and hydroxychloroquine as effective COVID treatments. In early June, The New England Journal of Medicine published a study of more than 800 COVID-19 patients who received the malaria drugs. “Hydroxychloroquine did not prevent illness compatible with COVID-19 or confirmed infection when used as postexposure prophylaxis,” the study found.
The Lancet, a top scientific journal, recently pulled a major paper questioning the effectiveness of chloroquine and hydroxychloroquine in the treatment of COVID after one of the authors declined to make available his full data-set. Still, concerns over the drugs linger. In mid-June, the FDA revoked its approval of chloroquine and hydroxychloroquine for emergency use in COVID cases.
Other once-promising therapies have run into their own obstacles. Working on some early research indicating that “convalescent” blood-plasma from recovered COVID patients might help current patients develop antibodies, the Mayo Clinic in Minnesota teamed up with the federal government to develop standards for collecting and administering plasma. Initial indications from a tiny—just five patients—sample in China suggested the treatment could help stabilize body temperatures and cut down viral load.
The ensuing treatment effort has produced 40,000 doses of convalescent plasma, though Woodcock said demand for plasma greatly exceeds supply. She urged the media to encourage recovered COVID-19 patients to donate their plasma.
“My hunch is that convalescent plasma is going to continue to be our best bet,” Stephen Jameson, a University of Minnesota immunologist, told The Daily Beast.
But the Mayo Clinic told The Daily Beast in a statement that there’s “no conclusion on efficacy” in the latest research on convalescent plasma. “Ongoing data are being studied.”
Ostrov argued that, when it comes to convalescent plasma, research hasn’t kept up with deployment. While the plasma is apparently safe to administer, there isn’t a lot of hard science to prove it actually works to reduce the severity of COVID cases. “I am not that optimistic about convalescent serum because we have not heard convincing positive results yet,” Ostrov said. “If there were clear benefits, we likely would have heard about it by now.”
Then there’s the cheap, widely available steroid dexamethasone, which British scientists last month announced was linked to a significant mortality reduction in a major trial of some 6,000 COVID-19 patients. The drug seemed to be especially helpful to patients on ventilators, though it was less clear how it helped infected people who were not having oxygen problems. There were also questions about the dangers posed to patients by steroids that effectively serve to discourage the immune system from overreacting to an invading virus.
The scramble to repurpose existing drugs could result in a lot of disappointment. A research team centered around New York University’s Grossman School of Medicine is pushing PT150, an antidepressant, as a COVID therapy. Initial testing on cell cultures indicates the drug might have “potent immunomodulatory effects” and could help suppress SARS-CoV-2 and calm the cytokine storm, the team wrote in a paper it provided to The Daily Beast this week.
Jameson said he’s skeptical. “Lots of things work beautifully in cell-culture assays, but are disappointing in vivo,” Jameson said, using the scientific term for live patients.
Randi Altschul, the founder of New Jersey-based Pop Test, one of the companies behind the PT150 research, objected to Jameson’s characterization. “We used normal human airway cells, making our test a closer correlate to effects in humans.”
But Altschul said he and Jameson see eye-to-eye on at least one thing. “We agree that imagination and scientific insight will be useful in identifying and developing new antivirals.”
The risk of therapeutic dead-ends could increase as the sense of urgency surrounding COVID-19 deepens and more and more government money flows into the pharmaceutical industry. And those dead-ends in turn could undermine public confidence in the scientific process that proves out potential therapies.
It certainly doesn’t help when Trump and other politicians embrace, over the advice of experts, drugs that demonstrably don’t work.
“Science by nature is uncertain,” Jeffrey Klausner, a professor of medicine and public health at UCLA, told The Daily Beast. “But in the current political climate, any uncertainty is seized upon to undermine scientific credibility.”
