Dose-dependent impact of tixagevimab–cilgavimab as primary prevention against SARS-CoV-2 in immunocompromised individuals

Abstract Tixagevimab–cilgavimab was available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevention from December 2021 to January 2023, with dosing changes to reflect circulating variants. In a retrospective analysis of 597 immunocompromised individuals, incidence of SARS-CoV-2...

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Main Authors: Daniela Dluzynski, Paddy Ssentongo, Cory M. Hale, Shareef K. Shaheen, Natella Maglakelidze, Jeffrey M. Sivik, Maria Paula Henao, Vernon M. Chinchilli, Catharine I. Paules
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-02240-3
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author Daniela Dluzynski
Paddy Ssentongo
Cory M. Hale
Shareef K. Shaheen
Natella Maglakelidze
Jeffrey M. Sivik
Maria Paula Henao
Vernon M. Chinchilli
Catharine I. Paules
author_facet Daniela Dluzynski
Paddy Ssentongo
Cory M. Hale
Shareef K. Shaheen
Natella Maglakelidze
Jeffrey M. Sivik
Maria Paula Henao
Vernon M. Chinchilli
Catharine I. Paules
author_sort Daniela Dluzynski
collection DOAJ
description Abstract Tixagevimab–cilgavimab was available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevention from December 2021 to January 2023, with dosing changes to reflect circulating variants. In a retrospective analysis of 597 immunocompromised individuals, incidence of SARS-CoV-2 infection was compared between those who did and did not receive tixagevimab–cilgavimab. A proportional hazards regression model with a time-dependent regressor for tixagevimab–cilgavimab dose was applied to assess cumulative doses. Secondary analyses were performed in hematopoietic stem cell transplant (HSCT) and chimeric antigen receptor (CAR)-T cell therapy recipients. There was no difference in SARS-CoV-2 infections between tixagevimab–cilgavimab recipients and controls (p = 0.27). There was a trend towards protection with increasing dose from 150 (HR 0.83, CI 0.50–1.38) to 600 mg (HR 0.48, CI 0.06–3.63) when truncating data on November 1st, 2022, which was also seen in HSCT or CAR-T cell therapy recipients, 150 mg (HR 0.71, CI 0.31–1.65) to 600 mg (HR 0.26, CI 0.01–7.47). This was most evident in immunocompromised individuals when variants neutralized by tixagevimab–cilgavimab in vitro were circulating; effectiveness 74%. Supports a proof of concept for monoclonal antibodies in immunocompromised individuals as a prevention strategy against novel viruses.
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spelling doaj-art-3abdd51dffd5496098cc8e67a7bb05b42025-08-20T03:48:15ZengNature PortfolioScientific Reports2045-23222025-05-0115111010.1038/s41598-025-02240-3Dose-dependent impact of tixagevimab–cilgavimab as primary prevention against SARS-CoV-2 in immunocompromised individualsDaniela Dluzynski0Paddy Ssentongo1Cory M. Hale2Shareef K. Shaheen3Natella Maglakelidze4Jeffrey M. Sivik5Maria Paula Henao6Vernon M. Chinchilli7Catharine I. Paules8Penn State College of MedicineDivision of Infectious Diseases, Department of Medicine, Penn State Health Milton S. Hershey Medical CenterDepartment of Pharmacy, Penn State Health Milton S. Hershey Medical CenterPenn State College of MedicinePenn State College of MedicineDepartment of Pharmacy, Penn State Health Milton S. Hershey Medical CenterDivision of Allergy and Immunology, Department of Medicine, Penn State Health Milton S. Hershey Medical CenterDepartment of Public Health Sciences, Penn State College of MedicineDivision of Infectious Diseases, Department of Medicine, Penn State Health Milton S. Hershey Medical CenterAbstract Tixagevimab–cilgavimab was available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevention from December 2021 to January 2023, with dosing changes to reflect circulating variants. In a retrospective analysis of 597 immunocompromised individuals, incidence of SARS-CoV-2 infection was compared between those who did and did not receive tixagevimab–cilgavimab. A proportional hazards regression model with a time-dependent regressor for tixagevimab–cilgavimab dose was applied to assess cumulative doses. Secondary analyses were performed in hematopoietic stem cell transplant (HSCT) and chimeric antigen receptor (CAR)-T cell therapy recipients. There was no difference in SARS-CoV-2 infections between tixagevimab–cilgavimab recipients and controls (p = 0.27). There was a trend towards protection with increasing dose from 150 (HR 0.83, CI 0.50–1.38) to 600 mg (HR 0.48, CI 0.06–3.63) when truncating data on November 1st, 2022, which was also seen in HSCT or CAR-T cell therapy recipients, 150 mg (HR 0.71, CI 0.31–1.65) to 600 mg (HR 0.26, CI 0.01–7.47). This was most evident in immunocompromised individuals when variants neutralized by tixagevimab–cilgavimab in vitro were circulating; effectiveness 74%. Supports a proof of concept for monoclonal antibodies in immunocompromised individuals as a prevention strategy against novel viruses.https://doi.org/10.1038/s41598-025-02240-3COVID-19Tixagevimab–cilgavimabMonoclonal antibodyHematopoietic stem cell transplantChimeric antigen receptor (CAR)-T cell therapy
spellingShingle Daniela Dluzynski
Paddy Ssentongo
Cory M. Hale
Shareef K. Shaheen
Natella Maglakelidze
Jeffrey M. Sivik
Maria Paula Henao
Vernon M. Chinchilli
Catharine I. Paules
Dose-dependent impact of tixagevimab–cilgavimab as primary prevention against SARS-CoV-2 in immunocompromised individuals
Scientific Reports
COVID-19
Tixagevimab–cilgavimab
Monoclonal antibody
Hematopoietic stem cell transplant
Chimeric antigen receptor (CAR)-T cell therapy
title Dose-dependent impact of tixagevimab–cilgavimab as primary prevention against SARS-CoV-2 in immunocompromised individuals
title_full Dose-dependent impact of tixagevimab–cilgavimab as primary prevention against SARS-CoV-2 in immunocompromised individuals
title_fullStr Dose-dependent impact of tixagevimab–cilgavimab as primary prevention against SARS-CoV-2 in immunocompromised individuals
title_full_unstemmed Dose-dependent impact of tixagevimab–cilgavimab as primary prevention against SARS-CoV-2 in immunocompromised individuals
title_short Dose-dependent impact of tixagevimab–cilgavimab as primary prevention against SARS-CoV-2 in immunocompromised individuals
title_sort dose dependent impact of tixagevimab cilgavimab as primary prevention against sars cov 2 in immunocompromised individuals
topic COVID-19
Tixagevimab–cilgavimab
Monoclonal antibody
Hematopoietic stem cell transplant
Chimeric antigen receptor (CAR)-T cell therapy
url https://doi.org/10.1038/s41598-025-02240-3
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