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DON’T Count on Paxlovid to Treat Long COVID – Study Disappoints!

Is there anything that can help PASC (post-acute sequelae of COVID-19)? A new study suggests: DON'T rely on Paxlovid to treat long COVID.

Most people want to put COVID behind them. But over 17 million Americans can’t do that. They are the victims of long COVID. The medical term for this condition is PASC or “postacute sequelae of SARS-CoV-2.” There are over 200 symptoms associated with this chronic condition. The most common is “post-exertional malaise.” That means that whenever someone does something physical or mental that requires effort, there is a rebound exhaustion. Other frequent complaints include general fatigue, brain fog, cough, palpitations, chest pain, tinnitus, dizziness, GI problems, smell/taste troubles, thirst and reduced libido. Read more at this link. Researchers wondered if patients taking Paxlovid to treat long COVID symptoms would fare better. A new study (JAMA Internal Medicine, June 7, 2024) says it did not!

Early Optimism About Paxlovid to Prevent Long COVID:

Last April we received this comment from a visitor to this website:

“I took Paxlovid and I am glad I did. I am 63, and I have diabetes and hypertension, perhaps because I am overweight.

“The day that I tested positive for COVID-19, I started taking medication. My fever was gone, and I felt better in two days. However, I was still fatigued for the rest of the month. I cannot imagine what my bout with COVID-19 would have been like without Paxlovid.

We responded to her enthusiastic support of Paxlovid to prevent long COVID this way:

“A recent study looked at COVID outcomes for people like you with one or more risk factors such as overweight or diabetes (JAMA Internal Medicine, March 23, 2023). Those who took Paxlovid (nirmatrelvir + ritonavir) were about 25 percent less likely to develop long COVID. Even more impressive, they were only about half as likely to die from COVID.”

A Reversal from the VHA (Veterans Health Administration):

A study published in the Annals of Internal Medicine (Oct. 31, 2023) contradicted the earlier research when it comes to relying on Paxlovid to prevent long COVID. The researchers wondered if using the antiviral medicine Paxlovid during the acute phase of COVID would reduce the likelihood of post-COVID conditions.

To find out, they compared the health records of patients treated for COVID at the Veterans Health Administration in 2022. More than 9500 were treated with Paxlovid within 5 days of symptom onset.

Their subsequent health problems were compared to those who did not receive Paxlovid though they were similar in other ways. The investigators were disappointed to find that Paxlovid reduced the chance of only one type of complication: blood clots in the legs or in the lungs. Other post-COVID problems did not respond.

The investigators described the outcome of their study using Paxlovid to prevent long COVID:

“In this emulated target trial of nirmatrelvir–ritonavir [Paxlovid] versus no treatment among outpatient U.S. veterans testing positive for SARS-CoV-2 during January through July 2022, nirmatrelvir–ritonavir was not effective at reducing risk for many of the PCCs [post-COVID-19 conditions] that were examined, including cardiac, pulmonary, renal, gastrointestinal, neurologic, mental health, musculoskeletal, endocrine, and general conditions and symptoms.”

In other words, Paxlovid did not work to prevent most symptoms of long COVID.

A New Study of Paxlovid to Treat Long COVID Symptoms:

The study (called STOP-PASC) just published in JAMA Internal Medicine, June 7, 2024 tested the anti-COVID drug PAXLOVID (nirmatrelvir-ritonavir) in a 15-week randomized clinical trial. The investigators recruited 155 long COVID patients suffering from moderate to severe symptoms. These included brain fog, fatigue, shortness of breath, digestive distress, cardiovascular symptoms and body aches.

The researchers report that a 15-day course of Paxlovid was generally safe but ineffective.


“…did not improve select PASC symptoms (fatigue, brain fog, body aches, cardiovascular symptoms, shortness of breath, and gastrointestinal symptoms) or other health outcomes…”

The investigators are quick to add that:

“It is important to underscore that this study alone does not rule out NMV/r [Paxlovid] as a potential therapy for PASC. There are multiple reasons that would explain why this trial did not detect a benefit for the selected outcomes, and several key themes warrant further discussion to inform future trials in PASC.”

In other words, there may yet be evidence that patients could use Paxlovid to treat long COVID symptoms. The authors point out that PASC is “not a single entity.” There may be some patients who do benefit from the antiviral drug(s). They also point out that their average patient had been suffering for more than 16 months and that treatment might need to be started earlier in the course of the ailment(s).

They conclude that further studies are needed to determine the role of antivirals like Paxlovid to treat long COVID.

We will shortly be interviewing two long COVID experts on our nationally syndicated public radio show. They will discuss up-to-date information on the possible causes of long COVID and some of the treatments that are being tried to ease symptoms. Please encourage friends and family to sign up for our newsletter so that they won’t miss this important podcast about long COVID. Here is a link.

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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.”.
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  • Ioannou, G.N., et al, "Effectiveness of Nirmatrelvir–Ritonavir Against the Development of Post–COVID-19 Conditions Among U.S. Veterans," Annals of Internal Medicine, October 31, 2023, https://doi.org/10.7326/M23-1394
  • Geng, L.N., et al, "Nirmatrelvir-Ritonavir and Symptoms in Adults With Postacute Sequelae of SARS-CoV-2 Infection," JAMA Internal Medicine, June 7, 2024, doi: 10.1001/jamainternmed.2024.2007
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