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Case report: Sotrovimab, remdesivir and nirmatrelvir/ritonavir combination as salvage treatment option in two immunocompromised patients hospitalized for COVID-19.

ABSTRACT: COVID-19 in immunocompromised patients is difficult to treat. SARS-CoV-2 interaction with the host immune system and the role of therapy still remains only partly understood. There are no data regarding the use of monoclonal antibodies and the combination of two antivirals in fighting viral replication and disease progression. We report the cases of two patients, both treated with rituximab for non-Hodgkin lymphoma and granulomatosis with polyangiitis, respectively, and both hospitalized for COVID-19 with positive SARS-CoV-2 RNAemia, who were successfully treated with a salvage combination therapy with sotrovimab, remdesivir and nirmatrelvir/ritonavir.

SUBMITTER: Baldi F

PROVIDER: S-EPMC9868302 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Case report: Sotrovimab, remdesivir and nirmatrelvir/ritonavir combination as salvage treatment option in two immunocompromised patients hospitalized for COVID-19.

Baldi Federico F Dentone Chiara C Mikulska Malgorzata M Fenoglio Daniela D Mirabella Michele M Magnè Federica F Portunato Federica F Altosole Tiziana T Sepulcri Chiara C Giacobbe Daniele Roberto DR Uras Chiara C Scavone Graziana G Taramasso Lucia L Orsi Andrea A Cittadini Giuseppe G Filaci Gilberto G Bassetti Matteo M

Frontiers in medicine 20230109

COVID-19 in immunocompromised patients is difficult to treat. SARS-CoV-2 interaction with the host immune system and the role of therapy still remains only partly understood. There are no data regarding the use of monoclonal antibodies and the combination of two antivirals in fighting viral replication and disease progression. We report the cases of two patients, both treated with rituximab for non-Hodgkin lymphoma and granulomatosis with polyangiitis, respectively, and both hospitalized for COV ...[more]

PMID: 36698815

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Project description:BackgroundWhether hospitalized patients benefit from COVID-19 oral antivirals is uncertain.ObjectiveTo examine the real-world effectiveness of molnupiravir and nirmatrelvir-ritonavir in hospitalized patients with COVID-19 during the Omicron outbreak.DesignTarget trial emulation study.SettingElectronic health databases in Hong Kong.ParticipantsThe molnupiravir emulated trial included hospitalized patients with COVID-19 aged 18 years or older between 26 February and 18 July 2022 (n = 16 495). The nirmatrelvir-ritonavir emulated trial included hospitalized patients with COVID-19 aged 18 years or older between 16 March and 18 July 2022 (n = 7119).InterventionInitiation of molnupiravir or nirmatrelvir-ritonavir within 5 days of hospitalization with COVID-19 versus no initiation of molnupiravir or nirmatrelvir-ritonavir.MeasurementsEffectiveness against all-cause mortality, intensive care unit (ICU) admission, or use of ventilatory support within 28 days.ResultsThe use of oral antivirals in hospitalized patients with COVID-19 was associated with a lower risk for all-cause mortality (molnupiravir: hazard ratio [HR], 0.87 [95% CI, 0.81 to 0.93]; nirmatrelvir-ritonavir: HR, 0.77 [CI, 0.66 to 0.90]) but no significant risk reduction in terms of ICU admission (molnupiravir: HR, 1.02 [CI, 0.76 to 1.36]; nirmatrelvir-ritonavir: HR, 1.08 [CI, 0.58 to 2.02]) or the need for ventilatory support (molnupiravir: HR, 1.07 [CI, 0.89 to 1.30]; nirmatrelvir-ritonavir: HR, 1.03 [CI, 0.70 to 1.52]). There was no significant interaction between drug treatment and the number of COVID-19 vaccine doses received, thereby supporting the effectiveness of oral antivirals regardless of vaccination status. No significant interaction between nirmatrelvir-ritonavir treatment and age, sex, or Charlson Comorbidity Index was observed, whereas molnupiravir tended to be more effective in older people.LimitationThe outcome of ICU admission or need for ventilatory support may not capture all severe COVID-19 cases; unmeasured confounders, such as obesity and health behaviors, may exist.ConclusionMolnupiravir and nirmatrelvir-ritonavir reduced all-cause mortality in both vaccinated and unvaccinated hospitalized patients. No significant reduction in ICU admission or the need for ventilatory support was observed.Primary funding sourceHealth and Medical Research Fund Research on COVID-19, Government of the Hong Kong Special Administrative Region; Research Grants Council, Collaborative Research Fund; and Health Bureau, Government of the Hong Kong Special Administrative Region.

Project description:BackgroundNirmatrelvir/ritonavir treatment decreases the hospitalisation rate in immunocompetent patients with COVID-19, but data on efficacy in patients with haematological malignancy are scarce. Here, we describe the outcome of nirmatrelvir/ritonavir treatment in a large cohort of the latter patients.MethodsThis is a retrospective cohort study from the multicentre EPICOVIDEHA registry (NCT04733729) on patients with haematological malignancy, who were diagnosed with COVID-19 between January and September 2022. Patients receiving nirmatrelvir/ritonavir were compared to those who did not. A logistic regression was run to determine factors associated with nirmatrelvir/ritonavir administration in our sample. Mortality between treatment groups was assessed with Kaplan-Meier survival plots after matching all the patients with a propensity score. Additionally, a Cox regression was modelled to detect factors associated with mortality in patients receiving nirmatrelvir/ritonavir.FindingsA total of 1859 patients were analysed, 117 (6%) were treated with nirmatrelvir/ritonavir, 1742 (94%) were treated otherwise. Of 117 patients receiving nirmatrelvir/ritonavir, 80% had received ≥1 anti-SARS-CoV-2 vaccine dose before COVID-19 onset, 13% of which received a 2nd vaccine booster. 5% were admitted to ICU. Nirmatrelvir/ritonavir treatment was associated with the presence of extrapulmonary symptoms at COVID-19 onset, for example anosmia, fever, rhinitis, or sinusitis (aOR 2.509, 95%CI 1.448-4.347) and 2nd vaccine booster (aOR 3.624, 95%CI 1.619-8.109). Chronic pulmonary disease (aOR 0.261, 95%CI 0.093-0.732) and obesity (aOR 0.105, 95%CI 0.014-0.776) were not associated with nirmatrelvir/ritonavir use. After propensity score matching, day-30 mortality rate in patients treated with nirmatrelvir/ritonavir was 2%, significantly lower than in patients with SARS-CoV-2 directed treatment other than nirmatrelvir/ritonavir (11%, p = 0.036). No factor was observed explaining the mortality difference in patients after nirmatrelvir/ritonavir administration.InterpretationHaematological malignancy patients were more likely to receive nirmatrelvir/ritonavir when reporting extrapulmonary symptoms or 2nd vaccine booster at COVID-19 onset, as opposed to chronic pulmonary disease and obesity. The mortality rate in patients treated with nirmatrelvir/ritonavir was lower than in patients with targeted drugs other than nirmatrelvir/ritonavir.FundingEPICOVIDEHA has received funds from Optics COMMIT (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223).

Dataset Information

Case report: Sotrovimab, remdesivir and nirmatrelvir/ritonavir combination as salvage treatment option in two immunocompromised patients hospitalized for COVID-19.

Publications

Case report: Sotrovimab, remdesivir and nirmatrelvir/ritonavir combination as salvage treatment option in two immunocompromised patients hospitalized for COVID-19.

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