A Case of Clinical and Viral Rebound Following Completion of a Five-Day Course of Ensitrelvir for COVID-19.

Ensitrelvir inhibits the 3-chymotrypsin-like protease of severe acute respiratory syndrome coronavirus 2 and accelerates viral clearance and symptom improvement through its potent antiviral activity. Reports of rebound after ensitrelvir treatment are scarce. This report presents a case of a healthcare worker in her 50s who had no significant underlying conditions. As a close contact, she underwent nasopharyngeal polymerase chain reaction (PCR) testing after her sister was diagnosed with coronavirus disease. The test result was positive with a cycle threshold (Ct) value of 31.97 by using Cobas® liat. Ensitrelvir treatment was initiated because of a slight sore throat, and rapid improvement was observed starting the following day. Treatment was completed on day five. Examination on day six indicated that the symptoms had resolved. However, the sore throat recurred on day seven, antigen levels increased again, and fever and cough developed on day eight. On day nine, a Ct value of 16.6 was noted, suggesting a strongly positive result and rebound. She received five vaccine doses and had markedly high levels of anti-S immunoglobulin G (IgG) antibodies, but her anti-N IgG antibodies were negative, indicating that she had a normal immune response and had not been infected with COVID-19. Her illness was mild, and symptoms peaked on day 11, without additional treatment. This case strongly suggests viral rebound and symptom relapse after ensitrelvir administration. Therefore, caution is warranted, as rebound may occur after ensitrelvir treatment, similar to that after nirmatrelvir/ritonavir treatment.