Comparative study of ensitrelvir and symptomatic therapy in healthcare workers with mild COVID-19: A single center retrospective analysis in Chiba, Japan.

Background: Ensitrelvir, a novel oral antiviral targeting the 3CL protease of SARS-CoV-2, has demonstrated efficacy in reducing viral load in clinical trials. Rapid viral clearance in healthcare workers (HCWs) with mild COVID-19 is critical for symptom relief and minimizing secondary transmission. However, real-world evidence on ensitrelvir's effectiveness in this population is limited.

Methods: This single-center retrospective study analyzed 407 HCWs with mild COVID-19 treated with either ensitrelvir or symptomatic therapy. Viral load was assessed using reverse transcription-polymerase chain reaction cycle threshold (Ct) values. The primary endpoint was achieving a Ct > 30, indicating low infectivity, on days 5-8 or 9-12. Secondary endpoints included adverse events, hospitalization, disease progression, and all-cause mortality within 30 days of symptom onset. Multivariate logistic regression identified factors associated with achieving Ct > 30.

Results: Patients in the ensitrelvir group had significantly higher rates of achieving Ct > 30 on days 5-8 (38.0 % vs. 9.9 %, p < 0.01) and days 9-12 (77.8 % vs. 42.3 %, p < 0.01). Treatment with ensitrelvir was associated with a significantly higher likelihood of symptom improvement within 5-8 days compared to symptomatic therapy (p < 0.01). Multivariate analysis confirmed ensitrelvir as independently associated with Ct > 30 (adjusted odds ratio: 6.498; p < 0.01). No adverse events, hospitalizations, or mortality were observed.

Discussion: Ensitrelvir demonstrated superior viral clearance compared to symptomatic therapy, facilitating a safer and earlier return to work for HCWs. However, additional precautions, such as mask use, remain essential for HCWs working in high-risk environments, even after ensitrelvir treatment.

Conclusions: Ensitrelvir is a safe and effective option for reducing SARS-CoV-2 viral load in HCWs with mild COVID-19, supporting timely recovery and reducing infectivity.