Article Impact Level: HIGH Data Quality: STRONG Summary of JAMA Internal Medicine. https://doi.org/10.1001/jamainternmed.2024.2007 Dr. Linda N. Geng et al.
Points
- The 15-week blinded, placebo-controlled, randomized clinical trial evaluated the efficacy of nirmatrelvir-ritonavir in treating persistent symptoms of PASC, involving 155 adult participants who had been experiencing moderate to severe PASC symptoms for at least three months.
- Participants were assigned in a 2:1 ratio to receive either nirmatrelvir-ritonavir (300 mg nirmatrelvir and 100 mg ritonavir) or a placebo-ritonavir twice daily for 15 days, aiming to assess symptom changes across multiple health dimensions.
- The primary outcome measured was the pooled severity of six specific PASC symptoms at ten weeks post-treatment using a Likert scale score. Secondary outcomes included evaluations of symptom severity at various time points, overall symptom burden, global patient assessments, and physical function changes from baseline.
- The study found no statistically significant differences between the treatment and placebo groups regarding symptom improvement at the 10-week mark nor in any secondary patient-reported outcomes or physical function tests.
- Although nirmatrelvir-ritonavir was found to be generally safe for individuals with PASC, it did not significantly alleviate symptoms in a predominantly vaccinated cohort with long-term PASC manifestations, highlighting the need for ongoing research into effective treatments for this condition.
Summary
In a rigorous investigation at Stanford University, researchers conducted a 15-week blinded, placebo-controlled, randomized clinical trial from November 2022 to September 2023 to evaluate the efficacy of nirmatrelvir-ritonavir in treating persistent symptoms of post-acute sequelae of SARS-CoV-2 infection (PASC). The study enrolled 155 adult participants suffering from moderate to severe PASC symptoms for three months or more. Participants were randomized in a 2:1 ratio to receive either a combination of oral nirmatrelvir-ritonavir (300 mg and 100 mg) or a placebo-ritonavir twice daily for 15 days, aiming to assess changes in symptom severity across multiple health dimensions.
The study’s primary outcome was to measure the pooled severity of six specific PASC symptoms—fatigue, brain fog, shortness of breath, body aches, gastrointestinal symptoms, and cardiovascular symptoms—using a Likert scale score at 10 weeks post-treatment. Secondary outcomes included an evaluation of symptom severity at various time points, overall symptom burden and relief, global patient assessments, and changes in physical function metrics from baseline. Despite thorough assessments, the trial found no statistically significant differences between the nirmatrelvir-ritonavir and placebo groups regarding symptom improvement at the 10-week mark, nor in patient-reported outcomes or physical function tests.
The trial demonstrated that while a 15-day course of nirmatrelvir-ritonavir is generally safe for individuals with PASC, it does not significantly alleviate symptoms in a predominantly vaccinated cohort with long-term PASC manifestations. The median age of participants was 43 years, with a significant majority being female (59%), and nearly all had received COVID-19 vaccinations. Given these outcomes, further research is crucial to explore the potential role of antivirals in managing PASC, indicating a need for continued investigation into effective treatments for this prolonged condition.
Link to the article: https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2819901
References Geng, L. N., Bonilla, H., Hedlin, H., Jacobson, K. B., Tian, L., Jagannathan, P., Yang, P. C., Subramanian, A. K., Liang, J. W., Shen, S., Deng, Y., Shaw, B. J., Botzheim, B., Desai, M., Pathak, D., Jazayeri, Y., Thai, D., O’Donnell, A., Mohaptra, S., … Singh, U. (2024). Nirmatrelvir-Ritonavir and Symptoms in Adults With Postacute Sequelae of SARS-CoV-2 Infection: The STOP-PASC Randomized Clinical Trial. JAMA Internal Medicine. https://doi.org/10.1001/jamainternmed.2024.2007
