Worth a Long Look for Easing Long COVID

Paxlovid, one of the most well-known treatments for COVID-19, has also been shown to ease symptoms of some patients with long COVID — and new research suggests the antiviral medication could prove to be an important treatment for some with the condition.

A study published in Communication Medicine found that some patients experienced improvement in their long COVID symptoms after taking the medication for a longer period, up to 30 days in some cases. The most common symptom improvements included a decrease in fatigue and neurocognitive symptoms like brain fog and memory loss.

“This is all observational data, so we weren’t able to make causal claims, but what we can say is that extended use of the medication may have meaningful benefits for some people with long COVID but not others,” said lead study author Alison Cohen, PhD, an epidemiologist at the University of California, San Francisco.

Commonly prescribed to treat acute COVID and for the prevention of long COVID, the data are less clear on whether Paxlovid is effective at treating patients who already have the condition, but it has been shown to help some patients, but not others with the condition.

Prevention but Not Necessarily a Cure

Paxlovid has a clear role in preventing long COVID in patients with acute COVID, which has been shown in the data, said Ziyad Al-Aly, MD, a global expert on long COVID and chief of Research and Development at the Veterans Affairs St. Louis Health Care System. A study led by Al-Aly in JAMA Internal Medicine found that Paxlovid was tied to a 26% reduced risk of developing long COVID over a 6-month period.

“It’s good for prevention, but in those who already have it, the evidence is very preliminary,” said Al-Aly. “Some people did improve, but we can’t draw broad conclusions from the study about whether they would have improved anyway without taking the medication.”

Nisha Viswanathan, MD, director of the University of California, Los Angeles long COVID program, agrees. While she has prescribed it for use in treating acute COVID, she’s never prescribed it for long COVID and notes that while a shorter 15-day course of the antiviral was found safe, it was ineffective at treating patients with long COVID, as documented in a study published last June in JAMA Internal Medicine.

“The reason that we haven’t been seeing success with using any one intervention is likely because different patients have different root causes of long COVID, which is why some might be responding well to Paxlovid and others not,” said Viswanathan.

By shutting down the viral reservoir that, in some patients with long COVID, causes the condition, some may experience symptom improvement. “But it’s still a matter of targeting the right patients,” adds Viswanathan.

Paxlovid’s Severe Side Effects

Ritonavir was previously used as an HIV medication that lessened the viral load in the blood of patients, reducing their likelihood of developing AIDS. It may have a similar effect in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19. But according to Viswanathan, this powerful antiviral also comes with a heavy set of side effects, most of which are gastrointestinal and include diarrhea, abdominal pain, and pancreatitis.

Still, for many patients, the severity of their long COVID symptoms makes some side effects more tolerable and even worth it, adds David Putrino, the Nash Family Director of the Cohen Center for Recovery from Complex Chronic Illness and a national leader in the treatment of long COVID. Not only does it have numerous side effects, but it can also have serious and sometimes life-threatening interactions with other medications that patients may be taking. This means patients absolutely must consult with their doctor before trying the medication.

There’s also a concern that some pathogens, potentially including SARS-CoV-2, hide in tissue and in the gut rather than the bloodstream, and many antivirals are not good at penetrating tissue, another reason why Paxlovid seems to work inconsistently.

Additionally, added Putrino, “It doesn’t eradicate the virus and instead only stops it from replicating, which means it might not be the best approach to solving the problem of persistent virus in the body.”

Alternative Treatments for Persistent Virus

Instead, Putrino thinks that we should be using monoclonal antibodies that are capable of reversing severe long COVID in more patients. A study published last year in The American Journal of Emergency Medicine found “the striking rapid and complete remissions” of a small number of patients with severe long COVID symptoms.

A larger trial led by Michael Peluso also at the University of California, San Francisco, is currently underway looking at the potential for the use of monoclonal antibodies for the treatment of persistent virus in the body. The study will be completed in July of 2025.

Still, we’re 5 years into the COVID-19 pandemic with no US Food and Drug Administration–approved treatments for long COVID. And as a result, patients with the condition are desperate for treatments. This most recent research was an observational study of people who were already taking the medication. They were looking for anything that might work on their symptoms, and some found that it did, said Cohen. She added that the next step needs to be trials that show how and why it worked for some and why it didn’t for others, as well as the course length that’s most effective for patients.

“Patients are eager for rigorous and accessible clinical trials that can test medications to meaningfully improve symptoms and address the underlying root causes of the condition,” said Cohen.