Effectiveness and Tolerability of Dual Antiviral Therapy in Immunosuppressed Patients with Protracted SARS-CoV-2 Infection

Background: Immunosuppressed patients still exhibit a high mortality rate due to SARS-CoV-2 infection, up to 21%. Persistent viral load replication and protracted viral symptoms result in a high risk of developing pneumonia, a potential risk of antiviral resistance, and a subsequent delay of onco-hematological treatments. Methods: Hematological patients and kidney transplant patients with SARS-CoV-2 infection, treated at GOM Niguarda Hospital (Milan) with combined antiviral therapy (remdesivir plus nirmatrelvir/ritonavir at standard doses) between November 2022 and March 2024, were retrospectively reviewed. Results: Thirty-four patients were analyzed. Twenty-four (71%) patients had pneumonia. The median duration of SARS-CoV-2 positivity before antiviral treatment was 40 (10–34) days. The median treatment duration was 11 (10–10) days. All patients went through clinical resolution. Thirteen patients were exposed to a new immune-chemotherapy cycle early after antiviral treatment (median 13, IQR 6–12 days), while five resumed a standard immunosuppressive regimen immediately after viral clearance. No relapse or recurrence of symptoms was reported for up to 226 (106–318) days of follow-up. Antiviral therapy was well tolerated, and no adverse events were observed. The 30-day overall survival was 94%, while the 90-day survival was 88%. No patient died of SARS-CoV-2 infection. Conclusions: The administration of nirmatrelvir/ritonavir and remdesivir lead to the complete resolution of SARS-CoV-2 pneumonia with no side effects in this cohort. The combination of these two antivirals may be a safe option in immunosuppressed population at risk of severe complications and prolonged SARS-CoV-2 infection in order to treat severe clinical presentation and to avoid viral recurrence after chemotherapy.