Paxlovid, though safe, shows no benefit in long COVID treatment
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Key takeaways:
- Paxlovid made no significant improvement to long COVID symptoms, including fatigue, brain fog and body aches.
- The finding “does not rule out” Paxlovid as a therapy, the researchers wrote.
A 15-day course of Paxlovid demonstrated no significant benefit for patients with post-acute sequelae of SARS-CoV-2 infection, according to data published in JAMA Internal Medicine.
However, the researchers noted that Paxlovid (nirmatrelvir-ritonavir, Pfizer) was “generally safe” in the cohort of mostly vaccinated patients.
“SARS-CoV-2 virus or viral particle persistence is one of several proposed causal mechanisms for [post-acute sequelae of SARS-CoV-2 infection (PASC)],” Linda N. Geng, MD, PhD, clinical associate professor of medicine at Stanford University, and colleagues wrote. “Residual viral presence may trigger ongoing inflammation and immune dysregulation, resulting in a diverse array of symptoms. Thus, antiviral agents against SARS-CoV-2 present a therapeutic avenue for investigation to address a potential root cause of PASC.”
To examine the efficacy of Paxlovid in reducing the severity of long COVID symptoms, Geng and colleagues conducted a blinded, randomized, placebo-controlled trial dubbed the Selective Trial of Paxlovid for PASC (STOP-PASC). The study included 155 adults (median age, 43 years), of whom 153 were vaccinated, who self-reported at least two moderate or severe “core symptoms” of PASC, which included fatigue, brain fog, body aches, shortness of breath and gastrointestinal and cardiovascular symptoms.
Between November 2022 and September 2023, the researchers randomly assigned 102 participants to receive 300 mg of nirmatrelvir with 100 mg of ritonavir — and 53 to receive placebo with 100 mg of ritonavir — twice daily for 15 days. Participants were followed until 15 weeks from random assignment. The primary outcome was the pooled severity of the core symptoms based on a three-point Likert scale score at 10 weeks.
According to the researchers, there was no statistically significant difference between the groups’ pooled core symptom severity at 10 weeks, with severity lessening over time across symptoms in both groups. There were also no statistically significant between-group differences in a range of secondary outcomes, including Patient Global Impression of Severity, Patient Global Impression of Change, summative symptom scores or change in PROMIS scores for fatigue, dyspnea, or cognitive or physical function.
However, the 15-day Paxlovid course was generally well-tolerated, with a “safety profile similar to the 5-day acute treatment course,” the researchers wrote. Overall, 99% of patients treated with Paxlovid, and 92.5% of patients in the placebo group, reported at least one adverse event, nearly all grade 1 or 2. The most common were dysgeusia and diarrhea.
“Notably, both the intervention and control groups exhibited improvements in PASC symptoms over time,” Geng and colleagues wrote. “It is important to underscore that this study alone does not rule out [nirmatrelvir-ritonavir] 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.
“This randomized clinical trial demonstrated the overall safety of a 15-day course of [nirmatrelvir-ritonavir] in patients with PASC but did not find a significant benefit of this therapy for a subset of PASC symptoms among a mostly vaccinated cohort with prolonged PASC symptoms,” they added. “Ancillary analyses and evaluation for molecular and digital biomarkers from the STOP-PASC trial are forthcoming. Findings from this and other randomized clinical trials of [nirmatrelvir-ritonavir] will collectively determine whether this antiviral is beneficial for treating PASC.”
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