Extended Paxlovid Course Ineffective for Long COVID

A recent study published on June 7, 2024, in the journal *JAMA Internal Medicine* has revealed that an extended regimen of the antiviral drug Paxlovid does not alleviate Long COVID symptoms. The research indicates that taking Paxlovid for 15 days, which is three times longer than the standard prescription for an initial COVID-19 infection, offers no significant improvement compared to a placebo in treating Long COVID.

Dr. Upinder Singh, a senior researcher and chief of infectious disease and geographic medicine at Stanford University School of Medicine, emphasized the lack of FDA-approved treatments for Long COVID despite advancements in therapies for acute COVID-19. The condition, affecting an estimated 10% to 20% of COVID-19 patients, represents tens of millions of individuals in the United States. It manifests as a series of symptoms emerging three months or more after the initial infection, which can include fatigue, brain fog, shortness of breath, body aches, and heart or gastrointestinal issues.

A prevailing hypothesis suggests that Long COVID may result from residual virus or viral debris lingering in a person's tissues long after the infection has been cleared. "Some studies hint that viral particles and molecular debris might be driving the persistent symptoms in Long COVID sufferers," Singh explained in a statement from Stanford. "We thought if this were the case, then treating these patients with Paxlovid might alleviate some of their symptoms."

To investigate this theory, researchers enrolled 155 Long COVID patients between November 2022 and September 2023. These participants had been infected with COVID-19 over 16 months prior and reported experiencing at least two out of six prevalent Long COVID symptoms. The study randomly assigned half of the participants to a 15-day course of Paxlovid, while the other half received a placebo. The antiviral Paxlovid is typically administered for five days to combat an acute COVID-19 infection.

After 10 weeks, the findings showed no statistically significant difference in symptom relief between the Paxlovid and placebo groups. However, the study did yield a positive outcome: it demonstrated the safety of administering Paxlovid for an extended period. "One reasonable implication of our results is that Paxlovid can be safely prescribed for a longer duration," Singh noted, suggesting potential use in newly infected, immunocompromised patients.

Despite the discouraging results, Singh believes the study does not entirely rule out the possibility of Paxlovid being effective for Long COVID treatment. She posits that future research might explore the drug's efficacy in patients who recently developed Long COVID. "Should we have tested patients with symptoms appearing after only seven or eight months instead of 16 or 17? Should we have administered the treatment for a longer period? Were we even testing the right cohort? Perhaps only certain symptoms will respond to antiviral treatment," Singh conjectured.

The research team intends to continue analyzing the trial results to determine if specific subgroups of patients benefited more than others. Funded by Pfizer Inc., the manufacturer of Paxlovid, the trial underscores the ongoing challenge of finding effective treatments for Long COVID amidst the broader landscape of COVID-19 therapies.

This study's findings add to the growing body of research aimed at understanding and addressing the long-term impacts of COVID-19, highlighting the need for continued investigation and innovation in treating persistent post-infection symptoms.

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