COVID-19 drugs that work (or not)

With names like Evusheld, remdesivir, and Paxlovid, today’s COVID-19 therapies sound like the typical pharmaceutical alphabet soup you see on glossy TV commercials.

Those three are among the most commonly used treatments authorized by the U.S. Food and Drug Administration to combat COVID-19 today. Regrettably, just like their convoluted names, there’s confusion about these drugs’ effectiveness, proper usage, and availability. Are they equally potent, and can any patient get them?

One source of the confusion has become clear: As the COVID-19 virus changes, so have the treatments, and the medical field is often playing catch-up.

“We need to be very much on our toes,” said Dr. Christian Ramers, an infectious disease specialist at Family Health Centers of San Diego.

Back in January, Ramers’ lab was among the few that could distinguish whether someone was positive for the omicron or delta coronavirus variant. People with omicron could get sotrovimab, a monoclonal antibody treatment. The lab-created antibodies are administered intravenously to sick patients.

But Ramers says his lab cannot tell the difference between omicron and the BA.2 subvariant, which is now the dominant strain across the United States. In fact, the variant is different enough that the drugs that worked well on the earlier omicron strain won’t work on BA.2.

Federal guidelines continue shifting as a result. Just two months ago, sotrovimab was a top recommendation by the National Institutes of Health’s COVID-19 Treatment Guidelines Panel. But a late March Nature article showed sotrovimab, while 63 percent effective at reducing hospitalization for the original omicron strain, is much less effective against the BA.2 variant. On Tuesday, the FDA revoked its emergency authorization of sotrovimab, citing the drug’s ineffectiveness against BA.2.

Currently, NIH recommends Paxlovid and remdesivir, two antiviral drugs that appear to be resilient against omicron and its subvariants in lab tests. In patient studies involving earlier COVID-19 strains, the two drugs significantly reduced the risk of hospitalization and death, remdesivir by 87 percent, and Paxlovid by 89 percent, according to Pfizer. (Evusheld, a preventive treatment for immunocompromised individuals, was shown to be effective at preventing symptomatic COVID-19 in early trials.)

Other drugs besides sotrovimab have had their five minutes of fame before succumbing to variants or prevailing research data. Last year, the antiparasitic drug ivermectin was all the rage as an unofficial treatment for COVID-19, winning the attention of media personalities including popular podcaster Joe Rogan, even though FDA officials warned it was not authorized for such use. But recent studies involving hundreds of patients have effectively squashed ivermectin as a COVID-19 treatment. An earlier paper showing ivermectin’s effectiveness was based on potentially fraudulent or flawed data, and when subsequent studies removed questionable data, ivermectin didn’t improve patient outcomes.

Remembering the names of these drugs may be tough. (Hint: Anything that ends in “-MAB” is a monoclonal antibody treatment, and everything else is likely antiviral.) But figuring out who gets the drugs is fairly straightforward.

After seeing young, vaccinated patients with mild COVID-19 symptoms this week, Craig Spencer, a New York City emergency room doctor and associate professor of emergency medicine at the Columbia University Medical Center, tweeted his refusal to prescribe any treatments to them because they’re not likely to need hospitalization. “Even if the pills are well-tolerated with few side effects for most, they are still in short-supply [in] many places,” he wrote. Spencer is justified in turning away the patients. NIH guidelines prioritize COVID-19 therapeutics to high-risk patients, including people over age 65 or the immunocompromised.

But the drugs are not in short supply, not anymore at least. A March NPR report revealed that millions of doses of COVID-19 treatments, including top-ranked Paxlovid, are sitting on shelves unused. The U.S. Department of Health and Human Services, which regularly publishes distribution numbers, shows Paxlovid and other drugs being allocated at a steady rate. A quick search on the federal website COVID.gov shows thousands of treatment locations dotting the country.

Still, this doesn’t mean anyone can or should obtain prescriptions. Ramers says most COVID-19 therapeutics are under FDA emergency use authorization, which means doctors will be stricter about who gets them. His lab has treated 4,000 patients with antivirals and monoclonal antibodies, and the large majority of patients getting them are high-risk—they’re either unvaccinated or vaccinated with health problems.

After putting too many unvaccinated patients in body bags, Ramers says these therapeutics are not a substitute for vaccines, and should be treated more like an emergency crutch than a first line of defense. In the end, it’s better to prevent illness than to treat it.