15-day Paxlovid regimen safe but adds no clear long-COVID benefit

A clinical trial led by Stanford Medicine researchers has found that a 15-day course of Paxlovid, an antiviral drug targeting the virus that causes COVID-19, is safe as an extended treatment but does not alleviate select symptoms of long COVID. The findings, described in a paper published June 7 in JAMA Internal Medicine, offer a glimpse into the complex nature of the syndrome that affects an estimated 10% to 20% of people infected with SARS-CoV-2.

Paxlovid has proven highly effective in treating acute COVID-19, reducing the risk of hospitalization and death by more than 85% in adults who are newly infected and at high risk of complications. But for the millions of people grappling with the persistent or recurring symptoms of long COVID, there are no FDA-approved treatments.

A Test of the Viral Reservoir Hypothesis

The Stanford trial, known as STOP-PASC, is the first randomized, controlled, double-blinded study to test Paxlovid as a treatment for long COVID. The researchers aimed to explore the viral reservoir hypothesis, which suggests that even after initial symptoms subside and measured viral counts drop to zero, the virus or its remnants may linger in deep tissues, potentially causing ongoing symptoms.

“Some studies suggest that viral particles and molecular debris could be responsible for some long-COVID sufferers’ ongoing symptoms,” said Upinder Singh, MD, professor and chief of infectious disease and geographic medicine and of microbiology and immunology, who co-led the trial. “We figured if that’s the case, maybe treating them with Paxlovid could relieve some of these symptoms.”

No Significant Difference in Symptom Severity

The trial enrolled 155 participants who had tested positive for SARS-CoV-2 and reported moderate to severe cases of at least two out of six common long COVID symptoms. Half were randomized to a 15-day course of Paxlovid, while the others received a placebo.

At the 10-week mark, there was no statistically significant difference between the two groups in the severity of the six core symptoms. Nor was there any detectable divergence in various secondary outcomes, such as blood pressure, heart rate, and performance on a physical test.

The 15-day drug regimen was, however, safe. While there were a few serious adverse events among participants, most were judged to be unrelated to the treatment.

“One reasonable implication of our results is that Paxlovid can be given safely for a longer period of time,” Singh said, “for example, in instances where a newly infected patient is immunocompromised.”

The absence of a clear clinical response in the trial doesn’t rule out the possibility that Paxlovid might help some people with long COVID, the researchers noted. Many questions remain about the optimal timing, duration, and patient selection for treatment.

“We hope to report on our analyses of these measurements in four to six months,” Singh said. The results may inform other ongoing and planned clinical trials of Paxlovid and other drugs’ potential to counter long COVID symptoms.

The trial was funded by Pfizer, the developer and manufacturer of Paxlovid.

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