Nine months in, Denver hospitals can better help COVID-19 patients thanks to “unprecedented” advances in care

In March, doctors at hospitals around the world tried anything that seemed like it might work against a new virus that was killing their patients.

Nine months later, physicians in Denver and elsewhere have a few tools that improve the odds of surviving COVID-19.

While much is still unknown and too many people don’t survive the virus, it’s “unprecedented” for frontline care to change this quickly, said Dr. Michelle Barron, senior medical director of infection prevention and control at UCHealth.

“It’s really, truly remarkable that we have these options,” she said.

When COVID-19 was found in December 2019 in China, doctors and scientists had to make guesses about what treatments might help, said Dr. Ivor Douglas, a pulmonologist and intensive care specialist at Denver Health. Usually, that meant trying drugs that worked against similar conditions, he said.

In the summer and early fall, the first large-scale studies started showing which drugs worked for COVID-19, said Dr. Joe Forrester, director of pulmonology and critical care services for a physician practice that works in three HealthOne hospitals and UCHealth Highlands Ranch Hospital.

Some ideas, like the anti-malaria drug hydroxychloroquine and pneumonia treatment azithromycin, turned out to be disappointments. Studies found no evidence they decreased the odds of severe illness or deaths.

A few drugs, like corticosteroids, showed clear benefits. It’s still unclear whether many other treatments work, though, leaving doctors to weigh the little evidence that’s available.

Fighting the immune overreaction

Federal agencies initially advised doctors not to use corticosteroids to treat patients, because prior studies had found they didn’t help patients who had severe influenza, said Dr. John Hammer, an infectious disease specialist at Rose Medical Center. A few months later, however, a large trial in the United Kingdom found the drugs had clear benefits for people who were seriously ill with COVID-19, and nearly all hospitalized patients now get them.

Unlike anabolic steroids, which are misused to build muscle, corticosteroids lower inflammation in the body. That makes them helpful for treating conditions where the immune system attacks the body, though long-term use makes patients more vulnerable to infections.

The most severe complications of COVID-19 are caused by the body’s efforts to fight the virus, so lowering inflammation is important, Hammer said. A person who’s doing well fighting the virus shouldn’t take corticosteroids, he said.

Initially, only the most seriously ill patients received corticosteroids, but now doctors in the emergency department at UCHealth also sometimes prescribe them when they send COVID-19 patients home with supplemental oxygen, Barron said.

“If they’re requiring oxygen, the level of inflammation in the lungs is quite high,” she said. “The concern was that it would cause the virus to go crazy, and it doesn’t.”

Denver doctors also prescribe an antiviral drug, remdesivir, to most COVID-19 patients in the hospital, even though the benefits are less clear.

The World Health Organization recommended against using remdesivir in November, after four studies didn’t find any benefit. Many hospitals continue to use it, however, based on a study from the National Institutes of Health showing it “modestly” reduced the time it took patients to recover, Hammer said.

Remdesivir is safe, except for patients with liver problems, and it’s also not particularly expensive, Douglas said. That makes it worth a try, even if benefits may be modest, he said.

“What we’re trying to do is balance benefits with potential costs,” he said.

Those drugs don’t help everyone, though. The Colorado Department of Public Health and Environment reports about one in five patients admitted to an intensive-care unit still dies.

Few risks, unknown benefits

Doctors are divided on other possible treatments for COVID-19. In the spring and summer, there was a push to collect plasma, the liquid part of blood, from people who’d survived the new virus. The hope was that antibodies in their blood would help seriously ill patients to fight the virus.

Antibodies are a kind of first responder in the immune system. When they recognize an invader, they then block it from entering cells, or signal other cells in the immune system to destroy it.

In theory, giving antibodies to patients should give the body a better chance to fight back. But the evidence that it works is lacking. Douglas said he rarely gives convalescent plasma anymore, because it doesn’t appear to help. Barron said UCHealth doctors offer it as an option, but not one they recommend strongly.

Forrester thinks it’s too early to give up on plasma, though. There’s some evidence it may benefit patients if given early, and if the donor had a high level of antibodies, he said. But donor plasma isn’t regularly screened for specific antibody levels.

“It’s not always clear, when giving it to the patient, if they’re getting serum with a high level of COVID antibodies,” he said.

The U.S. Food and Drug Administration has given an emergency use authorization to two drugs that try to solve the variability problem. Both produced copies of antibodies for COVID-19, so doctors know how much they’re giving patients. The drugs are targeted to people who aren’t severely sick, but are at risk of being hospitalized, such as those who are older than 65 or have other health conditions. It’s not clear yet if they work, though.

Nationwide, demand for the antibody drugs has been modest, according to The Associated Press. It can be a challenge getting people to infusion centers to take the medication intravenously, Douglas said. At UCHealth, they’ve seen relatively high interest among older patients who’ve been offered the drug, though, Barron said.

We may never have a clear answer about whether antibody drugs work, because patients don’t have to get them through a clinical trial with a comparison group, Hammer said. Without comparing people who got the drug and those who didn’t, there’s no way to tell if those patients would have gotten sicker without it, he said.

“It makes it difficult to study if they’re actually effective,” he said. “We don’t really know if either of those antibody products are better than placebo.”

At Denver Health, doctors continue to encourage seriously ill patients and their families to consider clinical trials, Douglas said. Hospitals are testing drugs to stop the virus from hijacking cells and to tamp down part of the immune system’s overreaction, while not suppressing it as fully as steroids do.

Without trials, it won’t be clear if those drugs are worth using, he said.

“Every therapy that patients benefit from was tested in a clinical trial with someone else’s family member,” he said.

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