The Push for Off-Label Rx to Treat Long COVID: What Works?

Charlie McCone, a San Francisco marketer, contracted long COVID in 2020, recovered and developed it again in 2021. Since then he has suffered from fatigue and shortness of breath and spends many hours in bed every day.

Only one medication helped with his shortness of breath, he said. But one doctor after another refused to prescribe the drug Plavix, which was approved by the U.S. Food and Drug Administration (FDA) to prevent blood clots. McCone started asking about it after doing his own research and finding that it held promise. When he finally found a doctor who could authorize a prescription, he began breathing easier again, McCone said.

McCone, who now advocates for long-term COVID patients as part of the Patient-Led Research Collaborative, a group of researchers and patients with long-term COVID, felt he needed to take alternative steps. Because there are no federally approved treatments for the millions of Americans suffering from long-term COVID, some patients and doctors are turning to off-label medications to treat the condition.

But patients say it’s not always easy to find a doctor who will prescribe them. And in some cases, insurance won’t cover the cost of the drugs because they’re classified as experimental.

In the case of Plavix, researchers at Stellenbosch University in South Africa published results of a blood plasma analysis that found patients with long-COVID had microclots – and Plavix could help relieve them.

McCone and others are urging doctors to learn about and use off-label medications that have been shown to help long COVID symptoms. Including:

• Low-dose naltrexone for fatigue
• Nicotine patches for fatigue
• Rapamycin for immune function
• Triptans for headaches
• Beta blockers for postural orthostatic tachycardia syndrome, dizziness
• Paxlovid for viral persistence
• Plavix and other blood thinners for blood clots

“We don’t believe any of these drugs will cure patients, but (taking them off-label) can make the difference in whether a patient can keep their job,” McCone said. “It could be that a patient goes from being stuck in a dark room to being able to socialize and enjoy their day again. That can make the difference in whether a parent is able to care for their children.”

Not every doctor will be comfortable prescribing Plavix, McCone said. But there is some solid evidence to support the idea that low-risk drugs like this can provide great relief to patients with long-term COVID illness, he said.

The case for more aggressive off-label prescribing

Julia Moore Vogel, PhD, senior program director at Scripps Research in La Jolla, California, co-authored an article published last month in cell calls for greater funding of long-term COVID treatments. The paper states: “While patients wait for evidence-based care, many are conducting self-experimentation on the fringes of medical science.”

Moore Vogel and others say people don’t need to experiment. They can use safe, existing treatments if they know about them and a doctor agrees that a prescription is warranted. She would like to see more medical groups conduct more training on long-COVID so doctors can learn more about the best off-label options.

Groups such as the American Academy of Physical Medicine and Rehabilitation have created a guide for treating cardiac, respiratory and other symptoms in patients with long COVID. But Moore Vogel believes primary care physicians should take the lead.

“Part of what we’re saying is that a lot of this falls to primary care physicians right now because people are waiting so long to get into these subspecialties,” she said.

She would like the recommendations for primary care providers to be summarized in simple terms about the current status of first-line and off-label therapies.

Sterling Ransone, MD, a family doctor in coastal Virginia, agrees that primary care specialists need to be trained on how to recognize and treat long COVID.

He says he sees about one long COVID case a week, and sometimes his patients don’t know they have it. Patients will come a month after symptoms and he will ask them if they are sick and have been tested for COVID.

“A patient literally said to me, ‘Does this still exist?'” he said.

He suggests that doctors add long COVID to the list of conditions they rule out when confusing symptoms are present.

“What we need to do is make sure that we always ask about the possibility of long COVID infection with this variety of symptoms,” Ransone said.

He prescribes off-label medications after research when a patient asks, he said.

“If it’s someone I know well and they have questions about something, I make sure to sit down and talk to them and tell them about the research I’ve done,” he said. “I mean, you know, from a medical perspective, the main thing is to do no harm, right?”

Once patients and doctors decide to try something, they must get insurance approval. Some of the drugs don’t have insurance coverage and are expensive, Ransone said.

“We have to go through prior approval processes and that’s just another hurdle that these folks unfortunately have to overcome,” he said.

One reason patient advocates say off-label drugs are crucial is that clinical trials take too long, McCone said. There are many studies underway on long-term COVID treatments, but none have produced conclusive results that could identify effective standardized treatments for the disease. For this reason, the FDA has not approved standard long-term treatments for COVID, just as treatments for other viral diseases and illnesses have been approved and are widely used.

Patient advocacy by patients

McCone is a patient representative in the National Institutes of Health’s RECOVER-TLC research program, which met this summer to launch a series of clinical trials. He said the organization is making progress, but clinical trial results are not expected until 2028 – a long time for patients with long COVID to wait.

He pointed to the upcoming trial of low-dose rapamycin, which researchers hope will reverse some of the immune or infection-related dysfunctions that lead to long COVID.

After spending hours in bed for over a year, McCone can now work on the computer for about two hours a day. His shortness of breath improved after he started taking Plavix.

“That’s an increase of about 30 minutes. I can leave the house occasionally, once or twice a week depending on the week,” he said.

McCone and others are calling for better training for doctors on long-COVID and more publicly available information so patients know what medications are already available and could help them.

“Read the research, offer your patients some low-risk treatment options and let your patient decide,” he advised doctors. “I don’t think that’s too much to ask. This is a health crisis that affects every aspect of society.”