https://orcid.org/0000-0003-2255-9756
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Manish C Choudhary, Rinki Deo, Teresa H Evering, Kara W Chew, Mark J Giganti, Carlee Moser, Justin Ritz, James Regan, James P Flynn, Charles R Crain, David Alain Wohl, Judith S Currier, Joseph J Eron, David Margolis, Qing Zhu, Lijie Zhon, Li Ya, Alexander L Greninger, Michael D Hughes, Davey Smith, Eric S Daar, Jonathan Z Li, Characterization of Treatment Resistance and Viral Kinetics in the Setting of Single-Active Versus Dual-Active Monoclonal Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2, The Journal of Infectious Diseases, Volume 230, Issue 2, 15 August 2024, Pages 394–402, https://doi.org/10.1093/infdis/jiae192
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Abstract
Monoclonal antibodies (mAbs) represent a crucial antiviral strategy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether combination mAbs offer a benefit over single-active mAb treatment. Amubarvimab and romlusevimab significantly reduced the risk of hospitalizations or death in the ACTIV-2/A5401 trial. Certain SARS-CoV-2 variants are intrinsically resistant against romlusevimab, leading to only single-active mAb therapy with amubarvimab in these variants. We evaluated virologic outcomes in individuals treated with single- versus dual-active mAbs.
Participants were nonhospitalized adults at higher risk of clinical progression randomized to amubarvimab plus romlusevimab or placebo. Quantitative SARS-CoV-2 RNA levels and targeted S-gene next-generation sequencing was performed on anterior nasal samples. We compared viral load kinetics and resistance emergence between individuals treated with effective single- versus dual-active mAbs depending on the infecting variant.
Study participants receiving single- or dual-active mAbs had similar demographics, baseline nasal viral load, symptom score, and symptom duration. Compared with single-active mAb treatment, treatment with dual-active mAbs led to faster viral load decline at study days 3 (P < .001) and 7 (P < .01). Treatment-emergent resistance mutations were more likely to be detected after amubarvimab plus romlusevimab treatment than with placebo (2.6% vs 0%; P < .001) and were more frequently detected in the setting of single-active compared with dual-active mAb treatment (7.3% vs 1.1%; P < .01). Single-active and dual-active mAb treatment resulted in similar decrease in rates of hospitalizations or death.
Compared with single-active mAb therapy, dual-active mAbs led to similar clinical outcomes but significantly faster viral load decline and a lower risk of emergent resistance.
