Dose-dependent impact of tixagevimab–cilgavimab as primary prevention against SARS-CoV-2 in immunocompromised individuals
Daniela Dluzynski, Paddy Ssentongo, Cory M Hale, Shareef K Shaheen, Natella Maglakelidze, Jeffrey M Sivik, Maria Paula Henao, Vernon M Chinchilli, Catharine I Paules
Scientific Reports, doi:10.1038/s41598-025-02240-3
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.
Author contributions D.D., P.S., C.H., S.S., N.M., J.S., M.H., V.C., and C.P. made substantial contributions to the conception and design of this study. D.D., P.S., C.H., S.S., N.M., and C.P. contributed to the data collection. D.D., P.S., and C.P. wrote the main manuscript. P.S. and V.C. processed the data and prepared the figures. All authors reviewed the manuscript.
Competing interests The authors declare no competing interests.
Additional information
Supplementary Information The online version contains supplementary material available at h t t p s : / / d o i . o r g / 1 0 . 1 0 3 8 / s 4 1 5 9 8 -0 2 5 -0 2 2 4 0 -3 . Correspondence and requests for materials should be addressed to C.I.P. Reprints and permissions information is available at www.nature.com/reprints . Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this..
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