Can These Drugs Stop a COVID Infection in Its Tracks? Seattle Researchers Are on the Forefront of New Treatments

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In a small research center nestled near the heart of Seattle's South Lake Union, Dr. Elizabeth Duke has been testing medicines to arm us in the fight against COVID-19.

Since the pandemic began, Duke and other infectious disease experts have led trial after trial at UW Medicine and, more recently, Fred Hutchinson Cancer Center's COVID-19 clinical research center, which was developed in October 2020 to treat outpatients with mild to moderate COVID.

The trials take time — and data analysis often takes longer — but as new virus variants emerge and the pandemic presses on, the clinic has remained on the forefront for testing many of the country's newest COVID therapeutics.

Now, Duke and her team are in the middle of taking a significant next step in the world of COVID drugs: figuring out how to prevent virus infections from happening in the first place.

"This is really exciting," Duke said. "If a person has been exposed to COVID, we currently don't have any approved treatments that are omicron-effective that can prevent an exposed person from going on to get infected. So that's the idea here — if we have an infected person in a household, can we treat the other people in the household and prevent them from getting sick?"

While state experts say COVID vaccines are still the best way to prevent infection and severe illness, interest in virus therapeutics has slowly been rising, said Dr. Bob Lutz, the state Department of Health's COVID medical adviser.

Duke's current clinical trial is analyzing the early effects of an existing COVID antiviral called molnupiravir, a pill from Merck that was granted emergency use authorization by the Food and Drug Administration in December. The oral pill was authorized to treat mild to moderate COVID in high-risk adults 18 and up — though it hasn't yet been approved as a medication to prevent COVID, or what's known as a post-exposure prophylaxis.

Results from Duke's trial could change that, and would make the pill the first FDA-approved COVID post-exposure prophylaxis available to the general public.

In the United States, the FDA has issued emergency use authorizations for four antiviral medications and monoclonal antibodies for those who have mild to moderate COVID and who are at high risk of getting sicker — all of which have considerably bolstered nationwide efforts to keep people with COVID out of the hospital and avoid severe illness or death. The problem is, local doctors say, many of their colleagues and patients still don't seem to know about them.

"There is a general lack of awareness among primary providers that these treatments exist," Duke said, which she attributed partially to changing eligibility requirements and partially to a lack of education from government agencies.

In Washington state, there's an "ample supply" of COVID drugs that could be going out to patients who ask for them, Cassie Sauer, president of the Washington State Hospital Association, said at a news briefing this week.

In addition to molnupiravir, doctors can prescribe another — generally more popular — antiviral pill called Paxlovid, developed by Pfizer, that can be given to adults and children 12 and older. While both have been authorized as medications to lessen people's COVID symptoms, the National Institutes of Health is prioritizing Paxlovid after clinical trials showed it had an 89% reduction in risk of hospitalization and death, compared to molnupiravir's 30% risk reduction, Lutz said.

But Lutz urged people to talk with their doctors first, since Paxlovid might not be the best fit for some people. Recently, for example, there have been reports in parts of the U.S. of a "rebound" of COVID symptoms in some people who have completed the five-day Paxlovid course. Other national experts have voiced concerns about potential "interactions" between Paxlovid and other medications people are taking.

"Remember, 30% is not that bad," Lutz said. "And when you look at all things considered, when you look at the fact that molnupiravir doesn't have the med-med interactions that Paxlovid does ... people need to realize that yes, the numbers sound better for Paxlovid, but you also may have more challenges in prescribing that medication."



As of this week, the state has almost 30,000 doses of Paxlovid available and about 25,000 doses of molnupiravir, Lutz said.

Remdesivir, the first COVID therapeutic that became available in the U.S. and only medication with full FDA approval, is also still a "very effective" option, he said. However, the drug can't be taken at home.

Unlike oral pills Paxlovid and molnupiravir, remdesivir is an intravenous drug — given through a needle or tube inserted into a vein — that has to be administered in a health care setting and is hard to give in post-exposure scenarios, Duke said.

The state also has a supply of monoclonal antibodies (known as Bebtelovimab) to treat mild to moderate COVID. Monoclonal antibodies also require an IV infusion.

Another drug called Evusheld does exist as a post-exposure prophylaxis — an exception to Duke's first-of-its-kind trial with molnupiravir — though it's primarily designed for those who are significantly immunocompromised, not anyone who's exposed.

"Therapeutics are much easier to get now," Sauer said at the news briefing. "... And this quick action to get these oral therapeutics, especially for high-risk individuals, could definitely be lifesaving and for sure will help keep you out of the hospital."

While any antiviral or antibody has the potential to work as a post-exposure preventative, Duke said, only antiviral medications have been able to keep up with the constant changes in the coronavirus' spike protein, the target of antibody treatments. New mutations on the spike protein were one of the main concerns that emerged with the omicron variant.

Antivirals, on the other hand, don't target the spike protein, but rather the virus's "replication machinery," Duke said.

"The concept would be just the same way we give post-exposure prophylaxis to people when they've been exposed to HIV," she said. "We give antivirals so that if there's any virus there ... that would stop it from replicating so that it couldn't go on to start a bigger chain of infection."

The relatively quick development of COVID drugs has excited doctors and scientists, but more work is needed to make them more accessible, Duke said.

"If your treatment is not a pill or something you can administer to yourself ... it means you need contact and staff time at a health care facility, and that is a problem right now," Duke said. "... We have staffing holes at every level. So if it's one more thing we need to staff for, it is bad."

Her trial for molnupiravir as a preventive drug is still underway and accepting participants through July — hopefully in time to get results by the fall, she said. For those interested in joining the study, Duke is looking for unvaccinated participants who have had a COVID exposure (but not a confirmed infection) with someone who tested positive for the virus within the past five days.

"I'm thrilled we've gotten as far as we have and we have antivirals available that are effective in preventing people from needing to go to the hospital which means also preventing deaths — and that we now have oral treatments available in pharmacies around the country," Duke said. "All of that is extremely encouraging and hopeful."