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We present a retrospective study on the treatment outcomes of severely immunocompromised patients with persistent COVID-19. The study analyzed data from 14 patients who received a combination of tixegavimab/cilgavimab and antiviral medications. Response was evaluated based on symptom improvement, PCR cycle-threshold values, and C-reactive protein levels. Eleven patients achieved complete clinical and virological resolution, while three showed partial responses. The study suggests a potential association between non-response and tixegavimab/cilgavimab neutralization. The findings underscore the need for tailored treatment approaches and further research on optimal strategies for managing persistent COVID-19, as well as the development of antivirals and variant-specific monoclonal antibodies.