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Title
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Host immunological responses facilitate development of SARS-CoV-2 mutations in patients receiving monoclonal antibody treatments
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Author
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Institution/Organisation
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mAb ORCHESTRA Working Group
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Abstract
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| The role of host immunity in emergence of evasive SARS-CoV-2 Spike mutations under therapeutic monoclonal antibody (mAb) pressure remains to be explored. Here, we show that patients treated with various anti-SARS-CoV-2 mAb regimens develop evasive Spike mutations with remarkable speed and high specificity to the targeted mAb-binding sites. Mutations develop more frequently in immunocompromised patients and strongly correlate not only with neutralizing capacity of the therapeutic mAbs, but also with an anti-inflammatory and healing-promoting host milieu. We further built and deploy machine-learning models on host-derived biomarkers that identify patients at high risk of developing escape mutations against therapeutic mAbs with high accuracy. While our data suggest that host-driven responses are essential for development of mutant SARS-CoV-2, the mechanisms and models described here could also be utilized to reduce risk of treatment failure in high-risk populations receiving anti-SARS-CoV-2 mAb treatments and improve mitigation strategies for possible dissemination of escape SARS-CoV-2 mutants. |
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Language
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English
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Source (journal)
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The journal of clinical investigation. - New York, N.Y., 1924, currens
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Publication
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New York, N.Y.
:
2023
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ISSN
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0021-9738
[print]
1558-8238
[online]
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DOI
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10.1172/JCI166032
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Volume/pages
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133
:6
(2023)
, p. 1-14
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Article Reference
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e166032
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ISI
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000992667400007
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Pubmed ID
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36727404
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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Full text (open access)
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