Nirmatrelvir-ritonavir misses mark in postacute sequelae of SARS-CoV-2 infection

A 15-day treatment course of nirmatrelvir-ritonavir appears to be safe but falls short of improving symptoms of postacute sequelae of SARS-CoV-2 infection (PASC) in a mostly vaccinated cohort, as shown in the results of the STOP-PASC trial.

STOP-PASC included 155 adults (median age, 43 years; 92 [59 percent] females) with moderate to severe PASC symptoms persisting for at least 3 months. Nearly all participants (n=153) were fully vaccinated against COVID-19. The mean time between index SARS-CoV-2 infection and randomization was 17.5 months.

The participants were randomly assigned to receive nirmatrelvir 300 mg plus ritonavir 100 mg (NMV/r group, n=102) or placebo plus ritonavir (PBO/r group, n=53) orally twice daily for 15 days. The pooled severity of six PASC symptoms (fatigue, brain fog, shortness of breath, body aches, gastrointestinal symptoms, and cardiovascular symptoms) at 10 weeks was evaluated on a Likert scale as the primary outcome. Secondary outcomes included symptom severity at different time points, symptom burden and relief, patient global measures, Patient-Reported Outcomes Measurement Information System (PROMIS) measures, orthostatic vital signs, and sit-to-stand test change from baseline.

At 10 weeks, NMV/r did not produce a significant improvement in the model-derived severity outcome pooled across the six core symptoms of PASC compared with PBO/r.

Likewise, there were no significant between-group differences seen in the Patient Global Impression of Severity or Patient Global Impression of Change scores, summative symptom scores, and change from baseline to 10 weeks in PROMIS fatigue, dyspnea, cognitive function, and physical function measures.

Adverse event rates were comparable between the NMV/r and PBO/r groups, with most events being of low grade.