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

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.