Feb. 24, 2022 -- These days, when doctors prescribe a treatment for a patient who's positive for COVID-19, their list of options is longer than ever. That's the good news.
But the abundance of options comes with many questions. Before deciding which of those treatments is best to keep you alive and perhaps even out of the hospital, it's crucial for your doctor to consider many things, says Daniel C. DeSimone, MD, a consultant in infectious diseases and associate professor of medicine at Mayo Clinic.
First, how sick are you?
"Are they inpatient or outpatient?" he asks. "Symptomatic or asymptomatic? And what are their underlying risk factors that could put them at high risk of progression to severe disease?"
Is the drug available in the community, or scarce? And does the latest research suggest it's working well against the latest COVID-19 variant?
"I wish it was easier," DeSimone says of deciding which COVID-19 treatment is best, "but also wish I had the list about 2 years ago."
"Finding the right fit is like the Goldilocks [principle]," agrees Katherine Yang, PharmD, a professor of pharmacy at the University of California, San Francisco. "Compared to 2 years ago, yes, we have more tools in our toolkit, which is great. But we still have to find the right drugs [for the right patient]."
Besides the patient's condition, Yang says, prescribers have to consider drug interactions, among many other things. Will a drug the patient is on interfere with the COVID drug?
Research has been brisk to detail how effective numerous COVID treatments are, but so has unsubstantiated buzz about unproven, untested treatments, from azithromycin to hydroxychloroquine to chloroquine.
"I think the enthusiasm for a treatment should be commensurate with the evidence that supports its use," says Rajesh Tim Gandhi, MD, a professor of medicine at Harvard Medical School, who spoke at a recent briefing on COVID treatments hosted by the Infectious Diseases Society of America. "We now have several medications proven to prevent hospitalization and death."
Among the options to treat COVID-19 are:
- Monoclonal antibody drugs, laboratory-made molecules that imitate the immune system's ability to fight off the virus
- Antiviral drugs, which stop the virus from replicating
- Drugs that reduce inflammation, such as corticosteroids
Only one treatment, remdesivir (Veklury), has the full approval of the FDA. It works by blocking reproduction of the virus. But Many other treatments have emergency use authorizations from the FDA. The FDA has the authority to authorize the use of an unapproved product to treat a life-threatening disease.
COVID-19 Drug Decision Processes
Not everyone will need treatment, DeSimone says. Suppose a 20-year-old patient, healthy and vaccinated, has no other conditions and tests positive but has no symptoms or mild ones.
"More often than not, we would say hold off," he says. "The patients we need to focus on [for treatment] are older age, with multiple risk factors for progression to severe disease, are immunocompromised, and have coexisting medical conditions."
Guidelines from the Infectious Diseases Society of America, the National Institutes of Health, and other organizations recommend when treatments should be used, which ones, and in whom. The guidelines are updated as research emerges or as the FDA grants new emergency use authorizations or limits others.
"If you look at the NIH treatment guidelines, they lay out recommendations different than IDSA," says Yang of UCSF.
But "both use a grading scale," which recommends treatments backed by the most evidence. Beyond the guidelines, "which [treatment] a patient gets depends on their underlying disease, and whether or not they have potential drug interactions," which is a constant concern, Yang says.
"The drug interactions are complicated," she says, as there is a long list of medications (such as heart medicines and immune suppressants) that can adversely affect the way the COVID-19 treatments work.
Treatment guidelines take into account how severe the illness is and whether patients need to be in the hospital.
Drug Therapies: Outpatients
For a patient with mild to moderate symptoms and some risk factors, DeSimone says, "what would be offered is a monoclonal antibody or, if not available, the alternative would be Paxlovid, " which is a pill that works as an antiviral.
Paxlovid reduced the risk of hospitalization or death by nearly 90%, one study found.
Two monoclonal antibody treatments are now seen as effective against the Omicron variant that's now causing the majority of COVID-19 cases -- sotrovimab and a newer one, bebtelovimab. But because bebtelovimab just received its emergency use authorization, supplies of it are expected to be limited at least for a few weeks, DeSimone says.
Meanwhile, the FDA revised its emergency use authorization for two other monoclonal antibodies, limiting their use to COVID-19 infections not caused by the Omicron variant, saying they are highly unlikely to be effective for Omicron infections. These are REGEN-COV and bamlanivimab/etesevimab. The FDA said that other treatments, including Paxlovid, sotrovimab, and remdesivir, are expected to work against Omicron.
One other plus, according to Gandhi, is that "monoclonal antibodies in general are thought to be safe in pregnancy." Monoclonal antibodies are given by IV.
A new option for outpatients is the antiviral drug remdesivir (Veklury), which already was authorized for hospitalized patients. It was authorized in late January by the FDA for outpatient use. Researchers found that patients getting the drug within 7 days of symptoms starting were 87% less likely to need hospitalization or to die.
Drug Therapies: Inpatients
For patients sick enough with COVID-19 to be hospitalized, DeSimone says, a 5-day course of IV remdesivir is often given.
"If you are requiring oxygen, that ups the stakes a little bit,” he says.
In those, he says, a corticosteroid such as dexamethasone, given for up to10 days, could be added.
As infection worsens, inflammation increases. In some cases, DeSimone says, one dose of an immune suppressant drug, tocilizumab, is given. A recent study shows a modest decrease in the risk of death with its use. The patients given this are seriously ill, about to be intubated or already intubated, DeSimone says.
After the study was published, there were issues with supply, he says, so another option to reduce inflammation is baricitinib (Olumiant), an oral drug used in rheumatoid arthritis that can be given for 14 days.
Timing Is Critical
Regardless of the drugs used, it's important, DeSimone says, to seek treatment as soon as possible, as some drugs have a window in which they work best.
"The quicker the access, the better," he says. That's especially true, he says, in those who have symptoms and are at higher risk for getting severe disease. That's a long list, he says, including older adults as well as those with cancer, kidney disease, lung disease, obesity, and HIV.
Last Resort List, Special Cases
Convalescent plasma, which first showed promise, is used less now. It involves using blood from people who have recovered from COVID-19 to help those infected recover. But the Infectious Diseases Society of America says it shouldn’t be used on hospitalized patients, and it also shouldn’t be used on non-hospitalized patients unless they are in a clinical trial.
"Early on, it showed promise," DeSimone says. Now, "the thought is, now that we have these other therapies, it may not be adding much." But in a small group, such as those who can't make antibodies to a vaccine or infection, it can help, he says.
Another option for a small group of people is what's known as "pre-exposure" treatment. The treatment, EvuSheld, combines two monoclonal antibodies (tixagevimab and cilgavimab). It is given to high-risk people before exposure, every 6 months. "This gives hope for those severely immunocompromised," DeSimone says, the people who "have nothing to protect themselves and have a hard time fighting it off."