Optimism on outpatient COVID-19 treatment options

The seventh ACP and Annals of Internal Medicine forum on COVID-19 landed amid a flurry of concerning coronavirus news in early December 2021, including spread of the omicron variant and rising case rates in a number of states.

“This is a very difficult time,” said Deborah Cotton, MD, MPH, FACP, moderator of the Dec. 8 forum and deputy editor of Annals. However, she and her co-panelists found some good news to highlight—specifically advances in outpatient treatment—as they answered challenging clinical questions about COVID-19.

The questions were submitted in advance by ACP members and Annals subscribers. A video recording of the forum is available on Annals' website, along with an article summarizing the discussion.

At the time of the forum, three monoclonal antibody formulations had received emergency use authorization (EUA) for high-risk patients with SARS-CoV-2 infection. Their arrival as cases surged in 2021 was very exciting, noted Jeanne Marrazzo, MD, MPH, FACP, professor of medicine and director of the infectious diseases (ID) division at the University of Alabama at Birmingham.

“This is something we jumped on very early, because we were completely freaked out by what was going on and we knew that we were not going to be able to stem the tide of hospitalizations,” she said. “We mostly had volunteer faculty who staffed these clinics, largely ID. We have gotten support from the hospital, but it's taken some time.”

That was a common issue around the country, agreed Judith S. Currier, MD, MSc, professor of medicine and division chief of ID at the University of California, Los Angeles. “The infrastructure had to be created in every location,” she said. “It really led to incredible disparity in availability of a very effective treatment.”

A number of factors added challenges, including the short time window for treatment. “You have to get them really fast, really within the first five to seven days of infection. Early on, people were taking that long to even get a test done,” said Dr. Currier, who noted that she worked on a study looking at use of another antibody candidate within 10 days of symptoms. “That will potentially, if it receives a EUA, be another option that might not have the same cutoff,” she added.

Having enough expert staff to provide antibodies was another issue. “You need somebody who can administer this—even if it's [subcutaneous], you don't get away from that—and we're having shortages of personnel, and that's making it hard to staff these operations,” Dr. Currier said.

“It also comes down to triage,” added Dr. Marrazzo. “It's talking to the patient and figuring out: Do they really qualify? Are they too sick to get the antibody? Because remember, you can't get it if you have an oxygen level below the threshold.”

Even clinicians who aren't going to administer the treatments needed to be educated about them, so they can tell their patients in turn, said Sabrina A. Assoumou, MD, MPH, assistant professor of medicine at Boston University, citing “stories of patients who were called and asked to come in for monoclonals who had never heard of it, and decided that they were not interested in it and were going to talk with a health care professional about it.”

Often by the time that conversation was complete, “it was too late,” said Dr. Assoumou. “So we focused on educating health care providers in general.”

Just as these obstacles are overcome, at least at the experts' large academic centers, more have appeared on the horizon, attached to two oral antivirals for COVID-19 that were under FDA consideration at the time of the forum.

“Maybe we are on the brink of something really fantastic,” said Dr. Cotton. “I think a lot of the logistic questions are going to be the same, aren't they? How are we going to get people tested and get the drugs to them?”

That will be complicated, agreed Dr. Marrazzo. “The real trick is going to be figuring out: Do you have influenza and should you get oseltamivir? Do you have COVID and should you get molnupiravir? Or do you have a virus that isn't treatable by current antivirals?” she said.

As with the monoclonal antibodies, speed will be an issue, said Dr. Assoumou, noting that current data suggest molnupiravir (from Merck) needs to be started within five days and the antiviral under development by Pfizer within three days. “Is there a way that we can set up clinics, or use of pharmacies where you get your test, or rapid test, and as soon as you get your results, you're starting on one of these drugs?”

The experts also expressed some concern about the risks of molnupiravir, specifically the chance of birth defects if a patient is or becomes pregnant while taking it. “All reproductive-age women who are sexually active with the possibility of getting pregnant—that's a lot,” said Dr. Marrazzo.

It is not the population most likely to be targeted for the medication, though. “One of the things that helps us is that the people most at risk [for severe COVID-19] are generally older,” noted Dr. Cotton.

With the Pfizer antiviral, a concern is that it contains ritonavir, according Dr. Currier. “Apparently there's no issues with tolerability, which was good to see, but there are some drug interactions that folks have to watch out for,” she said.

All four experts agreed that they'd be eagerly watching for more efficacy data on both antivirals. A concern with molnupiravir is the difference between interim and final analysis data on how often it prevented hospitalization and death, according to Dr. Marrazzo. “For the Pfizer drug, we've seen a press release,” said Dr. Currier. “And that's it.”

The drugs may have limitations, but there's potential for them to be the first of many, Dr. Cotton added. “I must say I'm feeling very hopeful that if we've made this much progress with these two drugs, we may see more,” she said.

While internists are waiting for these advances, they shouldn't forget the basics of good care, reminded Dr. Marrazzo, who offered a report from her COVID-19 respiratory clinic: “Everyone we saw—literally, I'm not kidding—was on antibiotics and steroids.” She urged forum attendees to “please, please” spread the word about avoiding such inappropriate use of these drugs. “Steroids are harmful when you give them in the first seven days of COVID.”