Nirmatrelvir–ritonavir combo not better than ritonavir alone in adults with long COVID

For individuals with long COVID, treatment with nirmatrelvir plus ritonavir does not appear to yield improvements in health outcomes when compared with ritonavir alone, according to a phase II study.

The study included 100 adults (66 percent female) with previous documented SARS-CoV-2 infection and long COVID symptoms starting within 4 weeks of initial infection and persisting for at least 12 weeks. These participants were randomly assigned to receive either two tablets of nirmatrelvir at 150 mg each plus one tablet of ritonavir at 100 mg (n=49, mean age 42 years) or placebo and one tablet of ritonavir 100 mg (n=51, mean age 43.1 years). Treatment was administered orally, twice daily for 15 days.

Researchers assessed the change in the Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Physical Health Summary Score (PHSS), from baseline to day 28, as the primary efficacy endpoint. Safety was also evaluated.

At day 28, the mean PROMIS-29 PHSS increased by 0.45 points in the nirmatrelvir–ritonavir group and by 1.01 points in the placebo–ritonavir group. The adjusted mean difference of –0.55 points was not significant (p=0.54).

In terms of safety, none of the participants died or experienced any serious adverse events (AEs) between baseline and week 6. Drug-related treatment-emergent AEs occurred more frequently in the nirmatrelvir–ritonavir group than in the placebo–ritonavir group (76 percent vs 55 percent), with the most common being dysgeusia. AEs led to early treatment termination in two participants in the nirmatrelvir–ritonavir group and one in the placebo–ritonavir group.