Antiviral combination regimens as rescue therapy in immunocompromised hosts with persistent COVID-19

Abstract

The management of severe/prolonged SARS-CoV-2 infections in immunocompromised hosts is still challenging. We describe nine patients with hematologic malignancies with a history of unsuccessful SARS-CoV-2 treatment receiving antiviral combination treatment for persistent infection at a tertiary hospital in central Italy (University Hospital of Careggi, Florence). Combination treatments consisted of nirmatrelvir/ritonavir plus molnupiravir (n = 4), nirmatrelvir/ritonavir plus remdesivir (n = 4) or remdesivir plus molnupiravir (n = 1) for 10 days, in some cases associated with sotrovimab. Combinations were generally well tolerated. One patient obtained viral clearance but died due to the underlying disease. In eight cases, clinical and virological success was confirmed by radiological follow-up. Antivirals combination is likely to become a mainstay in the future management of COVID-19 among immunocompromised patients, but knowledge in this field is still very limited and prospective studies on larger cohorts are urgently warranted.

Keywords:

• SARS-CoV-2
• off-label
• combination
• remdesivir
• nirmatrelvir/ritonavir
• molnupiravir
• relapsing
• rescue
• sotrovimab

Ethical approval

Each off-label treatment was separately approved by the local Ethical Committee and signed informed consent from the patients was obtained. Data collection was approved by the local Ethics Committee (Azienda Ospedaliero Universitaria Careggi, 17104_oss). The study was performed in accordance with the ethical principles of the Declaration of Helsinki and with the International Conference on Harmonization Good Clinical Practice guidelines.

Author contributions

RMA, DM, LZ, AB and MS designed the study. All authors were involved in the clinical management of the patients and ethical approval of the study. RMA, DM, FD, AB, TM and LG collected data. RMA and DM wrote the first draft of the manuscript. LZ, ST, GMR, AB and MS revised and provided significant changes to the manuscript. All authors revised the manuscript and approved it in its final version.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Full dataset is available from the corresponding author upon reasonable request.