Extended Paxlovid course safe but ineffective for long COVID symptoms, shows study

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A recent clinical trial by Stanford Medicine researchers has found that while a 15-day course of Paxlovid, an antiviral drug for COVID-19, is safe, it does not reduce symptoms of long COVID.

These findings were published in JAMA Internal Medicine.

Paxlovid is widely known for its effectiveness in treating acute COVID-19, significantly reducing the risk of hospitalization and death when taken for five days.

The drug, approved by the FDA, is used to treat adults newly infected with COVID-19 who have mild to moderate symptoms and are at high risk due to age or other health conditions.

The Stanford trial, however, aimed to see if extending the Paxlovid treatment to 15 days could help alleviate long COVID symptoms.

Long COVID refers to the persistence or reappearance of COVID-related symptoms three months or more after the initial infection. Despite the trial showing that a longer course of Paxlovid is safe, it did not show any improvement in long COVID symptoms.

Dr. Linda Geng, co-principal investigator and lead author of the study, emphasized the importance of these findings.

“We’ve demonstrated that a 15-day course of Paxlovid is safe,” she said. “But unfortunately, it didn’t lessen the symptoms of long COVID.”

Dr. Upinder Singh, the trial’s other co-principal investigator, highlighted the ongoing challenge. “While there are improved therapies for acute COVID, there is still no FDA-approved treatment for long COVID, and many people continue to suffer,” she said.

Long COVID affects an estimated 10% to 20% of people who contract COVID-19, amounting to tens of millions in the United States alone.

The condition is difficult to define and diagnose because it includes over 200 symptoms that overlap with other illnesses.

The trial, named STOP-PASC, was a double-blind, placebo-controlled study involving 155 participants who had tested positive for COVID-19. Most had been vaccinated, and their median age was 43.

Participants reported moderate to severe cases of at least two out of six common long COVID symptoms: fatigue, brain fog, shortness of breath, body aches, cardiovascular issues, and gastrointestinal problems.

Participants were randomly assigned to receive either a 15-day course of Paxlovid or a placebo. The researchers used various tests, including ultrasound and functional MRI scans, to evaluate the effects of the drugs.

Key findings from the trial include:

  • Paxlovid increased blood flow in both large and small brain vessels.
  • Paxlovid improved the blood flow response to carbon dioxide.
  • Both Paxlovid and cilostazol reduced blood vessel resistance in the brain.
  • Paxlovid caused fewer side effects compared to cilostazol.

However, at the 10-week mark, there was no significant difference between the two groups in reducing the severity of long COVID symptoms. The trial did show that a longer course of Paxlovid is safe, with no major adverse effects directly linked to the drug.

Dr. Singh noted that the lack of clinical response in this trial does not rule out the possibility that Paxlovid might help some people with long COVID. “We still have many questions to answer,” she said. “Should we have tested patients sooner after their initial infection? Should the treatment have been longer? Were we testing the right patients?”

Interestingly, both the treatment and placebo groups reported an overall improvement in symptoms over the course of the study, which might indicate that long COVID symptoms generally improve with time or could be influenced by the placebo effect.

The Stanford Medicine team is analyzing further data from chemical and immunological tests conducted during the trial to understand better who might benefit from Paxlovid. They hope to share these results in the coming months.

Researchers from Kaiser Permanente Northern California and Pfizer also contributed to the study. These findings will inform future clinical trials aimed at countering long COVID symptoms.

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