Treatments for COVID-19 are taking on new importance as the highly transmissible BA.2 Omicron variant continues to be the predominant SARS-CoV-2 strain with new BA.2 subvariants emerging, and governments and institutions relax or eliminate their COVID-19-related mitigation strategies such as masking in indoor public gatherings.

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The Centers for Disease Control and Prevention (CDC) has issued a health advisory with updates on the availability and use of treatments for outpatients who have mild or moderate COVID-19 and also are at higher risk for severe outcomes from the disease.

Physicians and health care organizations should be doing everything they can to avoid COVID-19 disease progression in patients with risk factors, according to Nancy Crum, MD, MPH, an infectious disease physician with Avita Health System, in Galion, Ohio, and alternate delegate representing the Infectious Diseases Society of America in the AMA House of Delegates

“If we can get patients rapidly tested and treated, we can prevent hospitalizations and deaths and improve outcomes among both vaccinated and unvaccinated patients who are at high risk of progressive severe disease,” said Dr. Crum, an AMA member.

Physicians should refer any patient with high risk factors for treatment, even if they have mild symptoms, Dr. Crum said. This includes patients with heart or lung disease, obesity, cancer, kidney disease, transplant recipients, poorly controlled HIV, or those over 65.

“I’ve known hundreds of people who start out with mild symptoms, and the next week end up hypoxic and requiring oxygen support,” she said. “We know the risk factors that lead to poor prognosis, and we should use that experience to administer these novel COVID-19 treatments.”

Read this JAMA Patient Page, “Oral Antiviral Medications for COVID-19.”

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Patients with any respiratory symptoms, including cough or sore throat, should go and get tested. “It’s true that it could be another type of respiratory virus, but there’s no specific clinical symptom that distinguishes COVID-19 from other viruses,” said Dr. Crum. “COVID-19, including mild to moderate cases, has specific therapy now available, so differentiating is important.”

PCR tests are widely available at physician offices and other locations, and there’s also the option to do a rapid test at home. The earlier the diagnosis, the earlier patients can start these medications, which are most effective in the first few days of illness, she said.

Testing earlier also can be a boon to public health, added Dr. Crum. “If you’re positive, you should isolate to protect people out there who aren’t vaccinated, are at increased risk for severe COVID-19 outcomes, or are immunocompromised.”

Find out what doctors wish patients knew about which COVID-19 test is best.

Physicians currently have several therapies for mild to moderate COVID-19 at their disposal.

Paxlovid (PDF), an oral antiviral combined with an HIV drug, and remdesivir (marketed as Veklury) are the top two recommended by the CDC due to strong efficacy data, said Dr. Crum.

A New England Journal of Medicine study showed Paxlovid was 89% effective at preventing severe progressive disease. “It’s an oral drug, so it’s easy in terms of taking a pill for five days and not needing an infusion,” said Dr. Crum. Ashish Jha, MD, the White House COVID-19 response coordinator, has advised that people at high risk for COVID-19 complications should be prioritized for Paxlovid.

Use of remdesivir is moving beyond severe hospitalized cases, as data shows it’s effective for treating mild-to-moderate disease in the outpatient setting and can be given as a three-day course.

Other options if Paxlovid or remdesivir are not available, feasible or clinically appropriate include a monoclonal antibody infusion known as bebtelovimab and an antiviral known as molnupiravir.

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Bebtelovimab has demonstrated in vitro effectiveness against BA.2 variants. Although there is insufficient data on hospitalization and mortality outcomes for patients with COVID-19 who received bebtelovimab, this agent has a mechanism of action that is similar to other anti-SARS-CoV-2 monoclonal antibodies that have been shown to cut hospitalization or death among high-risk patients.

Molnupiravir (PDF) is another five-day oral antiviral medication regimen, although its efficacy data isn’t as strong and mutagenicity remains a concern.  

The treatment course for all these therapies is very short, just a few days or a one-time infusion, noted Dr. Crum. Antivirals should be given within five days of symptom onset. Remdesivir and monoclonal antibodies should be started within seven days of when symptoms start.

Learn what doctors wish patients knew about COVID-19 antivirals.

Access to treatments has been a problem, especially with respect to Paxlovid. The Biden administration announced plans to nearly double the number of places where antivirals are available in the U.S., to 40,000. Locations include pharmacies, community health centers, hospitals, urgent care centers, Veterans Affairs clinics, and Department of Defense facilities.

Dr. Crum’s own pharmacy at Avita Health has been working with the state to get oral antivirals and distribute them, putting out regular bulletins to providers about “what is available and how to get it.”

Visit the AMA COVID-19 resource center for physicians for clinical information, guides and resources, and updates on advocacy and medical ethics.

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