Severe COVID-19 caused by persistent SARS-CoV-2 infection successfully treated with dual direct acting antivirals.

Abstract We report the successful use of combination therapy with two direct acting antivirals for treatment of chronic COVID-19. An immunocompromised 60 year old male with persistent SARS-CoV-2 infection over 4 months had chronic, progressive COVID-19 requiring mechanical ventilation. After failing monotherapy with two antivirals and neutralising monoclonal antibodies, he was treated with a 10 day course of intravenous remdesivir and crushed nirmatrelvir/ritonavir (Paxlovid) administered through a nasogastric tube. Following treatment, SARS-CoV-2 RNA became undetectable, with resolution of supplemental oxygen requirement and acute inflammatory changes on computed tomography. This case demonstrates potential synergy between remdesivir and nirmatrelvir/ritonavir in treating persistent, symptomatic SARS-CoV-2 infection.