Abstract
Both nirmatrelvir/ritonavir (NMV-r) and ensitrelvir (ESV) are similar protease inhibitors that act against 3C-like protease (3CL protease) which is related the viral replication of SARS-CoV-2, and are recommended as oral treatment for COVID-19 patients in the guidance. However, NMV-r was approved in 2022 for the treatment of patients who are at high risk of progressing to severe COVID-19 based on the clinical trial data during severe original strain period, whereas ESV was approved in 2023 for the treatment of non-risk patients based on the clinical trial data during mild Omicron strain period in Japan. In this study, we investigated the differences in treatment patterns and patient characteristics between COVID-19 patients treated with NMV-r and ESV. NMV-r has usually been used for elderly patients with malignant tumors in the hospital, whereas ESV has been used for younger patients in the outpatient clinic as the common practice. It has been suggested that NMV-r and ESV have been used differently in Japan because there might be gaps in the implementation periods and the evidence from clinical trials. We should use each oral agent appropriately and make different recommendations in the guidance in the near future.