1. In this randomized controlled trial, patients experiencing symptomatic coronavirus disease 2019 (COVID-19) saw significant improvement in symptom resolution times compared to the placebo group.

2. Further investigation is needed to specifically delineate the impact of simnotrelvir on older COVID-19 patients. 

Evidence Rating Level: 1 (Excellent)

Study Rundown: COVID-19 has been a major public health concern since the initial pandemic occurrence in 2020. Though vaccinations are beneficial, they have not been completely effective at preventing the more recent strains of COVID-19. The new variants have strong immune evasion, thus warranting the search for a new drug affecting these variants. Simnotrelvir (SIM0417), an oral small-molecule antiviral agent targeting the SARS-CoV-2 3CLpro, has been proposed as a treatment. When used against the omicron variant of SARS-CoV-2 in vitro, simnotrelvir showed antiviral activity with acceptable side effects. In this double-blind randomized control trial, patients with mild-to-moderate COVID-19 had shorter-lasting symptoms after receiving simnotrelvir plus ritonavir.  In the study, those experiencing respiratory symptoms showed more benefits from Simnotrelvir when compared to the placebo. Those in the treatment group had a decrease in their viral load until day nine when compared to those in the placebo group. The placebo group could have experienced unblinding due to the unique taste of the placebo drug, as it only contained excipients. This study only included younger individuals, so the safety and efficacy of this drug on the elderly remains unclear. Overall, early intervention with simnotrelvir plus ritonavir safely showed reduced length of symptoms in patients with COVID-19.

Click here to read the study in NEJM

In-Depth [randomized controlled trial]: A randomized controlled trial in China examined the effects of simnotrelvir on COVID-19 patients. The eligibility criteria included being 18 or older, having signs or symptoms of COVID-19 within three days before the first dose, having at least one symptom before the first dose, and having a mild or moderate severity of the illness. To determine the severity levels, the Food and Drug Administration provided definitions to help classify the participants in the study. The study provided exclusion criteria, including serious kidney, liver, or heart disease, along with the use or expected use of medications that interfere with cytochrome P-450 3A4. The symptoms of COVID-19 most commonly found in participants were dry throat (76.2%), cough (73.4%), and stuffy or runny nose (55.9%). The simnotrelvir group had a significantly shorter time for symptom resolution (180.1 hours; 95% Confidence Interval [CI], 162.1 to 201.6) than the placebo group did (216.0 hours; 95% CI, 203.4 to 228.1). The fever and systemic symptoms resolution times were similar in both groups. However, the simnotrelvir group experienced significantly faster resolution of respiratory symptoms (-41.4 hours; 95% CI, -70.7 to -13.3). From the time of receiving the first dose until day 29, there was a lower incidence of adverse events in the placebo group than in the simnotrelvir group (21.6% vs. 29.0%). The placebo group experienced two serious adverse events, whereas the simnotrelvir group did not experience any. In summary, this study’s results suggest that simnotrelvir plus ritonavir is an effective and safe treatment for COVID-19, resulting in earlier respiratory symptom resolution.

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