The STOP-PASC (Selective Trial of Paxlovid for PASC) randomized clinical trial evaluated the efficacy of a 15-day course of nirmatrelvir-ritonavir (NMV/r) in reducing the severity of select postacute sequelae of SARS-CoV-2 infection (PASC) symptoms in adults. The study was conducted from November 2022 to September 2023 at Stanford University and included 155 participants with moderate to severe PASC symptoms lasting 3 months or longer. Participants were randomized 2:1 to receive NMV/r or placebo-ritonavir (PBO/r) twice daily for 15 days. The primary outcome was the pooled severity of six PASC symptoms (fatigue, brain fog, shortness of breath, body aches, gastrointestinal symptoms, and cardiovascular symptoms) based on a Likert scale score at 10 weeks. Secondary outcomes included symptom severity at different time points, symptom burden and relief, patient global measures, PROMIS measures, orthostatic vital signs, and sit-to-stand test change from baseline. The results showed no statistically significant difference in symptom severity between the NMV/r and PBO/r groups at 10 weeks. Adverse event rates were similar in both groups, mostly of low grade. The study concluded that while NMV/r was generally safe, it did not demonstrate a significant benefit in improving select PASC symptoms in a mostly vaccinated cohort with prolonged symptom duration. Further studies are needed to determine the role of antivirals in treating PASC.The STOP-PASC (Selective Trial of Paxlovid for PASC) randomized clinical trial evaluated the efficacy of a 15-day course of nirmatrelvir-ritonavir (NMV/r) in reducing the severity of select postacute sequelae of SARS-CoV-2 infection (PASC) symptoms in adults. The study was conducted from November 2022 to September 2023 at Stanford University and included 155 participants with moderate to severe PASC symptoms lasting 3 months or longer. Participants were randomized 2:1 to receive NMV/r or placebo-ritonavir (PBO/r) twice daily for 15 days. The primary outcome was the pooled severity of six PASC symptoms (fatigue, brain fog, shortness of breath, body aches, gastrointestinal symptoms, and cardiovascular symptoms) based on a Likert scale score at 10 weeks. Secondary outcomes included symptom severity at different time points, symptom burden and relief, patient global measures, PROMIS measures, orthostatic vital signs, and sit-to-stand test change from baseline. The results showed no statistically significant difference in symptom severity between the NMV/r and PBO/r groups at 10 weeks. Adverse event rates were similar in both groups, mostly of low grade. The study concluded that while NMV/r was generally safe, it did not demonstrate a significant benefit in improving select PASC symptoms in a mostly vaccinated cohort with prolonged symptom duration. Further studies are needed to determine the role of antivirals in treating PASC.