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      Successful dual antiviral therapy with remdesivir and ensitrelvir in a case of prolonged COVID-19 following B-cell depleting immunotherapy for malignant lymphoma

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          Abstract

          Prolonged COVID-19 following B-cell depleting immunotherapy for malignant lymphoma is characterized by repeated cycles of remission followed by symptom recurrence, persistent detection of SARS-CoV-2, and profound humoral immunodeficiency. To the best of our knowledge, the present report is the first to describe dual antiviral therapy with remdesivir and ensitrelvir for prolonged COVID-19 following B-cell depleting immunotherapy for malignant lymphoma. A 59-year-old, female patient with a history of follicular lymphoma treated with obinutuzumab and bendamustine contracted COVID-19 despite receiving a single course of standard remdesivir therapy. She received dual antiviral therapy with remdesivir following a five-day course of oral ensitrelvir, which improved her clinical symptoms and chest radiology findings and cleared SARS-CoV-2 from respiratory samples. Dual antiviral therapy with remdesivir and ensitrelvir may be sufficient to stop viral replication and promote clinical resolution in prolonged COVID-19 following B-cell depleting immunotherapy for malignant lymphoma.

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          Most cited references20

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          Persistent COVID-19 in an Immunocompromised Patient Temporarily Responsive to Two Courses of Remdesivir Therapy

          Abstract The antiviral drug remdesivir has been shown clinically effective for treatment of COVID-19. We here demonstrate suppressive but not curative effect of remdesivir in an immunocompromised patient. A man in his fifties treated with chemoimmunotherapy for chronic lymphocytic leukemia experienced a 9-week course of COVID-19 with high fever and severe viral pneumonia. During two 10-day courses of remdesivir starting 24 and 45 days after fever onset, pneumonia and spiking fevers remitted, but relapsed after discontinuation. Kinetics of temperature, C-reactive protein, and lymphocyte counts mirrored the remitting/relapsing SARS-CoV-2 infection. Combination therapy or longer treatment duration may be needed in immunocompromised patients.
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            Prolonged in‐hospital stay and higher mortality after Covid‐19 among patients with non‐Hodgkin lymphoma treated with B‐cell depleting immunotherapy

            Prolonged Covid‐19 is an emerging issue for patients with lymphoma or immune deficiency. We aimed to examine prolonged length of in‐hospital stay (LOS) due to Covid‐19 among patients with lymphoma and assess its determinants and outcomes. Adult patients with lymphoma admitted for Covid‐19 to 16 French hospitals in March and April, 2020 were included. Length of in‐hospital stay was analyzed as a competitor vs death. The study included 111 patients. The median age was 65 years (range, 19–92). Ninety‐four patients (85%) had B‐cell non‐Hodgkin lymphoma. Within the 12 months prior to hospitalization for Covid‐19, 79 patients (71%) were treated for their lymphoma. Among them, 63 (57%) received an anti‐CD20 therapy. Fourteen patients (12%) had relapsed/refractory disease. The median LOS was 14 days (range, 1–235). After a median follow‐up of 191 days (3–260), the 6‐month overall survival was 69%. In multivariable analyses, recent administration of anti‐CD20 therapy was associated with prolonged LOS (subdistribution hazard ratio 2.26, 95% confidence interval 1.42–3.6, p  < 0.001) and higher risk of death (hazard ratio 2.17, 95% confidence interval 1.04–4.52, p  = 0.039). An age ≥ 70 years and relapsed/refractory lymphoma were also associated with prolonged LOS and decreased overall survival. In conclusion, an age ≥ 70 years, a relapsed/refractory lymphoma and recent administration of anti‐CD20 therapy are risk factors for prolonged LOS and death for lymphoma patients hospitalized for Covid‐19. These findings may contribute to guide the management of lymphoma during the pandemic, support evaluating specific therapeutic approaches, and raise questions on the efficacy and timing of vaccination of this particular population.
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              Remdesivir failure with SARS-CoV-2 RNA-dependent RNA-polymerase mutation in a B-cell immunodeficient patient with protracted Covid-19

              Abstract SARS-CoV-2 is a new pandemic virus for which Remdesivir is the only antiviral available. We report the occurrence of a mutation in the RdRP (D484Y) following failure of remdesivir in a 76-year-old woman with a post-rituximab B-cell immunodeficiency and persistent SARS-CoV-2 viremia. Cure was reached after supplementation with convalescent plasma.
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                Author and article information

                Contributors
                Journal
                IDCases
                IDCases
                IDCases
                Elsevier
                2214-2509
                30 August 2023
                2023
                30 August 2023
                : 34
                : e01890
                Affiliations
                [a ]Department of Infectious Diseases, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan
                [b ]Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan
                Author notes
                [* ]Corresponding author. seowoongjungpaper@ 123456gmail.com
                Article
                S2214-2509(23)00214-7 e01890
                10.1016/j.idcr.2023.e01890
                10482734
                37693339
                cf340552-a61b-4b86-b638-1f3fa6d0fc43
                © 2023 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 17 August 2023
                : 29 August 2023
                Categories
                Case Report

                prolonged covid-19,b-cell depleting immunotherapy,remdesivir,ensitrelvir,dual antiviral therapy

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