Early combination with remdesivir, nirmatrelvir/ritonavir and sotrovimab for the treatment of COVID-19 in immunocompromised hosts

Abstract

Abstract Background: Immunocompromised patients with COVID-19 have higher morbidity and mortality than general population. Some authors have successfully used antiviral combination, but never in the early phase of the infection. Methods: Retrospective cohort study to describe efficacy and safety of the combination of 2 antivirals, with or without a mAb, both in early (within 10 days from symptoms) and in later phase (after 10 days) of SARS-CoV-2 infection in immunocompromised patients admitted to our facility. Results: We treated 11 patients (7 in early phase and 4 in later phase of COVID-19) with 10 days of intravenous remdesivir plus 5 days of oral nirmatelvir/ritonavir, also combined with sotrovimab in 10/11 cases. Notably, 100% of the “early” patients reached virological clearance at day 30 from the end of the therapy and were alive and well at follow-up, whereas corresponding figures in the “late” patients were 50% and 75%. Patients in late group more frequently needed oxygen supplementation (p=0.015) and steroid therapy (p=0.045) during admission and reached higher a COVID-19 severity (p=0.017). Discussion: The combination of antiviral and sotrovimab in early phase of COVID-19 in immunocompromised patients is well tolerated and associated with 100% of virological clearance. Patients treated later have lower response rate and higher disease severity, but a causative role of the therapy in such finding is yet to be demonstrated.