Scientists launch wide dragnet against elusive killer

Although scientists have celebrated the approval for emergency use of remdesivir to treat COVID-19, a cure remains a long way off — and might never arrive.

Hundreds of drugs are being studied around the world, but "I don't see a lot of home runs right now," said Dr. Carlos del Rio, a professor of infectious diseases at the Emory University Rollins School of Public Health. "I see a lot of strikeouts."

The coronavirus is an elusive enemy.

Doctors say they're fighting a war on multiple fronts, battling a virus that batters organs throughout the body, causes killer blood clots and prompts an immune system overreaction. With so many parts of the body under siege, scientists say, improving survival rates will require multiple routes of attack — and more than one drug.

"There are so many pieces of this, and they will all require different therapies," said Dr. Lewis Kaplan, president of the Society of Critical Care Medicine.

High-tech approaches include using stem cells, virus-specific T cells and synthetic antibodies to neutralize the coronavirus.

Scientists are also taking a fresh look at existing medications that might be repurposed, including antivirals for influenza, arthritis drugs, estrogen patches and even antacids. If repurposed drugs are successful, they could reach patients relatively quickly, because doctors are already familiar with their side effects and safety concerns.

Dr. Steven Nissen, chair of cardiovascular medicine at the Cleveland Clinic, said he fears that hype over unproven products could harm patients. Patients who demand antacids or antimalarial drugs being studied in COVID-19 could suffer from side effects, for example. Those who hoard drugs — on the hope of protecting themselves — could deprive other patients of medications they need. "This rush to get every imaginable treatment into a study, it's not prudent," Nissen said. "It's not good medicine. It's an act of desperation."

Other experts say scientists should cast a wide net. "I don't think we want to rule anything out because it sounds out of the ordinary," said Dr. Walid Gellad, director of the Center for Pharmaceutical Policy and Prescribing at the University of Pittsburgh.

Antivirals such as remdesivir aim to prevent viruses from replicating, said Dr. Peter Hotez, a professor at Baylor College of Medicine in Houston. But a Chinese study, published in the Lancet, found no benefit to severely ill COVID-19 patients. Remdesivir had failed when tested against Ebola.

Antivirals tend to be most helpful in the early stages of infection, Hotez said.

International researchers also are studying the antiviral favipiravir, developed to fight the flu. The antimalarial drugs chloroquine and hydroxychloroquine — heavily touted by President Donald Trump — also have antiviral effects. Although the Food and Drug Administration approved forms of those drugs for emergency use against COVID-19, it later warned that they could cause dangerous heart rhythm problems.

Donated antibodies — and any immunity they might provide — don't last forever, said Dr. William Schaffner, a professor at the Vanderbilt University Medical Center. The body destroys aging antibodies as part of its routine maintenance, he said. In general, half of donated antibodies are eliminated in about three weeks. The use of convalescent plasma goes back more than a century, but doctors don't know yet whether it will work for COVID-19.

Researchers are also studying the use of prepackaged plasma, called intravenous immunoglobulin. This product, known as IVIG and already in stock in hospitals, is taken from healthy donors in the general population and has been used to help patients with weakened immune systems fight infections.

In a third form of immune therapy, researchers are trying to identify the antibodies that are most important for neutralizing the coronavirus, then reproduce them as drugs called monoclonal antibodies. Monoclonal antibodies are used to treat a variety of conditions, from cancer to rheumatoid arthritis and migraines.

"When we give people an antibody, they are immediately at least partially immune to that specific virus," said Dr. James Crowe, director of the Vanderbilt Vaccine Center, who hopes to have antibodies ready for a clinical trial in a few months. "We're moving the immune system from one person to another."

Ideally, doctors would develop a very potent monoclonal antibody or a cocktail of antibodies, but manufacturing that can be complicated, expensive and time-consuming. "A cocktail might be preferred," he said, "but cocktails are harder to move quickly."

But some patients' immune systems becomes hyperactive, attacking not just the virus but the patient's cells. A "cytokine storm," in which the immune system floods the body with inflammatory chemicals, can do more damage than the virus itself.

In an effort to calm the immune system, researchers are testing immune-suppressing drugs, said Dr. Amesh Adalja of Johns Hopkins Center for Health Security.

Health care giant Roche is conducting large clinical trials of its drug, Actemra, which is designed to lower levels of an inflammatory chemical, interleukin-6, which has been elevated in some patients.

Scientists are also studying similar drugs, anakinra and siltuximab.

Another immune suppressant from Regeneron and Sanofi, called Kevzara, has had disappointing results in clinical trials. The manufacturers plan to continue to see whether it can help certain types of patients.