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.

Pharmacokinetics Profile and Genetics of Double Antiviral Therapy with Remdesivir and Nirmatrelvir/Ritonavir for Prolonged COVID-19 in Patients Treated with Rituximab: A Real-Life Study and Literature Review

“…The association of two different antiviral pharmacodynamic mechanisms has been considered useful in order to eradicate SARS-CoV-2 infections in immunocompromised patients [5,11]. In the cases reported by Trottier and Snell [6,11], a 20-day and 10-day course of Remdesivir and Nirmatrelvir/Ritonavir, respectively, resulted in the clinical improvement and negativization of nasopharyngeal swab in patients with prolonged SARS-CoV-2 positivity. Even a prolonged course or retreatment with Remdesivir alone up to 30 days has been shown effective in clinical improvement of symptoms in the works by Rüfenacht et al [5] and Martinez et al [15], despite no proof of virological negativization in the former.…”

“…Patients with hematologic malignancies are more likely to develop severe and prolonged SARS-CoV-2 infection, often showing viral persistence despite the use of authorized antivirals [1,2]. The effectiveness of Remdesivir and Nirmatrelvir/Ritonavir has been demonstrated in vitro and in randomized controlled trials for the treatment of early symptomatic COVID-19 in order to avoid the risk of progression to severe disease [3,4]; however, unfortunately, these therapies are not approved for patients with prolonged and late COVID-19, and the off-label use of direct antivirals and their combination has been reported in few cases as a possible and effective approach in immunocompromised populations [5][6][7][8].…”