Long COVID Treatments: What Medications Are Being Tested and What Safety Risks You Need to Know

More than 15 million people in the U.S. alone are living with Long COVID - symptoms that won’t go away weeks or months after the initial infection. Fatigue, brain fog, heart palpitations, shortness of breath, and muscle pain aren’t just lingering side effects. For many, they’re life-altering. And right now, there’s no FDA-approved treatment for it. That’s why doctors, researchers, and patients are turning to existing medications - repurposing drugs meant for other conditions - in hopes of finding relief. But here’s the catch: we don’t fully know what these drugs do to people with Long COVID. Safety signals are emerging, and some are worrying.

What’s Actually Being Tried Right Now?

The biggest research effort in the world for Long COVID is the NIH’s RECOVER initiative. It’s spent over $1 billion since 2021, funding dozens of trials. Among the most studied drugs are baricitinib, metformin, low-dose naltrexone (LDN), and Paxlovid - all repurposed from other uses.

Baricitinib, a JAK inhibitor approved for rheumatoid arthritis and alopecia, is being tested in a phase 3 trial called REVERSE-LC. It worked in severe acute COVID by calming an overactive immune system. Early data suggested it might help with Long COVID fatigue and brain fog. But here’s what we know about safety: in arthritis patients, it raised the risk of serious infections by 10-20%, increased heart attacks and strokes, and showed a small but real link to lymphoma. Long COVID patients are often younger and healthier than rheumatoid arthritis patients. So does that mean baricitinib is safer for them? Maybe. But we don’t have the data yet. Results from this trial won’t be out until late 2026.

Metformin, a cheap, widely used diabetes drug, has the strongest evidence so far. A 2023 University of Minnesota trial found it cut the risk of developing Long COVID by 41% when taken within the first week of infection. That’s huge. But the side effects? Rough. Over a third of people had nausea, diarrhea, or stomach pain. For someone already dealing with fatigue and digestive issues from Long COVID, that’s a tough trade-off. It’s not a cure, but it’s one of the few drugs with real clinical trial backing.

Low-dose naltrexone (LDN) is being used off-label by many patients. Typically, naltrexone is given at 50 mg for opioid addiction. LDN uses 1-5 mg daily - a tiny fraction. In a 2024 patient survey from Nova Southeastern University, 62% reported less fatigue. But 28% had trouble sleeping, and 19% got headaches. These aren’t lab results - they’re real people reporting how they feel. That’s valuable, but it’s not proof. No large, controlled trial has confirmed these benefits yet.

Paxlovid, the antiviral combo of nirmatrelvir and ritonavir, was a game-changer for acute COVID. But for Long COVID? The data is mixed. One small UCSF study found symptom improvement in 38% of people taking a 15-day course. But a much larger NIH trial found no difference compared to placebo. And the side effects? A bitter taste affected nearly 80% of users. Ritonavir also interferes with dozens of common medications - statins, blood thinners, even some anxiety drugs. For someone already on multiple prescriptions, that’s a red flag.

What’s Failing - and Why It Matters

Not every drug being tested works. In March 2025, the BC007 trial was stopped. It was designed to neutralize autoantibodies thought to drive Long COVID symptoms. But it didn’t beat placebo. Worse, three people in the treatment group had serious infusion reactions - compared to just one in the placebo group. That’s a red flag. When a drug looks promising in theory but fails in practice, it tells us something: Long COVID isn’t one disease. It’s many.

Another drug, AER002, a human immunoglobulin, is still in phase 2. So far, mild infusion reactions happened in 18% of patients. No serious events. That’s promising. But we’re still in early stages. And then there’s polymerized type I collagen, tested in a small Johns Hopkins pilot. Only 12% reported injection site pain. No serious side effects. It’s a novel approach - trying to repair damaged tissue. But it’s only been tested in 40 people. Too early to call it a breakthrough.

The Big Unknowns

We don’t know who will respond to what. That’s the biggest problem. Long COVID isn’t a single condition. The NIH now recognizes at least four different types - some driven by lingering virus, others by autoimmunity, nerve damage, or mitochondrial dysfunction. One drug might help one group and hurt another.

There’s also no lab test to confirm Long COVID. No blood marker. No scan. No clear way to tell if a treatment is working. Doctors are guessing. Patients are guessing. That makes clinical trials harder. If you can’t measure improvement, how do you prove a drug works?

And then there’s the safety gap. Most of these drugs were tested in older, sicker populations - people with rheumatoid arthritis, diabetes, or cancer. Long COVID patients are often younger, previously healthy, and not on other immunosuppressants. Does baricitinib’s infection risk apply the same way? Maybe not. But we don’t know. We’re using drugs designed for different people, in different bodies, for different reasons.

What About New Drugs?

Some researchers are looking beyond repurposing. The WEHI Institute in Australia found a new antiviral compound in mice that prevented Long COVID symptoms entirely. But it’s not tested in humans yet. Toxicity studies start in early 2026. That’s years away from being available.

Other experimental ideas include GLP-1 receptor agonists like tirzepatide (Mounjaro), approved for diabetes and weight loss. These drugs reduce inflammation and may help with brain fog and fatigue. But they cause nausea, vomiting, and diarrhea - side effects that could make Long COVID worse, not better. Trials are just beginning.

Then there’s the stellate ganglion block - a nerve injection used for chronic pain. Some patients report relief from anxiety, heart palpitations, and sweating. But the procedure carries risks: hoarseness in 15% of cases, bleeding in 5%. No large study has looked at safety in Long COVID patients. It’s being tested now, but it’s still experimental.

What Are Patients Actually Doing?

While trials are ongoing, people aren’t waiting. The Body Politic Long COVID Support Group - with over 15,000 members - surveyed its community in 2025. Sixty-eight percent have tried at least one medication off-label. The top three? Metformin (32%), LDN (29%), and Paxlovid (24%).

But here’s the sobering part: 57% said they didn’t get enough relief. And 41% said the side effects were worse than their symptoms. For metformin, stomach issues were the main complaint. For LDN, sleep problems. For Paxlovid, the bitter taste and drug interactions made it hard to keep taking.

One patient in Brisbane told me: “I took metformin for three weeks. I lost five pounds. My brain fog didn’t change. But I couldn’t eat without feeling sick. I stopped.”

Another said: “LDN gave me back energy. But I couldn’t sleep. I felt like I was on a rollercoaster. I’m still trying to figure out if it’s worth it.”

What Should You Do?

If you have Long COVID and are considering medication, here’s what you need to know:

• Don’t self-prescribe. Even “safe” drugs like LDN or metformin can interact with other meds or worsen symptoms.
• Track your symptoms. Use a journal or app. Note when you start a drug, what you feel, and how you sleep, eat, and think. This helps your doctor spot patterns.
• Ask about clinical trials. RECOVER has sites across the U.S. and Australia. You might get access to drugs before they’re widely available - and you’ll be monitored closely.
• Be patient with uncertainty. We’re learning as we go. What works for one person may not work for you. That doesn’t mean you’re failing. It means the science is still evolving.

The FDA won’t approve a Long COVID treatment until we have clear evidence of benefit - and a solid understanding of risk. That’s coming. But not yet. In the meantime, the best thing you can do is stay informed, work with a doctor who understands Long COVID, and avoid treatments that promise miracles.

The path forward isn’t about one magic pill. It’s about matching the right treatment to the right person - and knowing when not to use a drug, even if it seems like it should help.