Combination regimen of nirmatrelvir/ritonavir and molnupiravir for the treatment of persistent SARS-CoV-2 infection: A case report and a scoping review of the literature

Immunocompromised patients still experience unpredictable courses of COVID-19, despite that effective vaccines and drugs against SARS-CoV-2 are now available. Antiviral combination regimens may have a role in SARS-CoV-2 infection in immunocompromised hosts, but current knowledge is still limited. We describe the case of a 73-year-old Italian man affected by follicular lymphoma with persistent SARS-CoV-2 infection who was successfully treated with co-administration of oral antivirals (10-day molnupiravir and nirmatrelvir/ritonavir). The therapy was well tolerated both from a clinical and biochemical stand-point, with no signs of toxicity. We also performed a scoping review, to sum up available knowledge on combined antiviral regimens including remdesivir, molnupiravir, or nirmatrelvir/ritonavir. Pending further studies on larger cohorts of patients, our report is consistent with available pre-clinical and clinical data, supporting the possible use of combination therapy in selected difficult-to-treat COVID-19 cases. (c) 2023 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Automated summary

Despite the availability of effective vaccines and drugs against SARS-CoV-2, immunocompromised patients still have unpredictable courses of COVID-19. Combination antiviral regimens may be useful, but current knowledge is limited. This study describes a successful case of using oral antivirals (molnupiravir and nirmatrelvir/ritonavir) to treat a 73-year-old patient with persistent SARS-CoV-2 infection. A scoping review also supports the potential use of combination therapy in difficult-to-treat COVID-19 cases.