{"doi":"10.1093/infdis/jiae192","title":"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","abstract":"BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.","journal":"The Journal of Infectious Diseases","year":2024,"id":444622,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9589,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":806067,"name":"Rinki Deo","orcid":null,"position":1,"is_corresponding":false},{"id":571854,"name":"Teresa H. Evering","orcid":null,"position":2,"is_corresponding":false},{"id":315361,"name":"Kara W Chew","orcid":"0000-0003-4865-4348","position":3,"is_corresponding":false},{"id":387866,"name":"Mark J Giganti","orcid":"0000-0003-2255-9756","position":4,"is_corresponding":false},{"id":419481,"name":"Carlee Moser","orcid":"0000-0001-5601-9112","position":5,"is_corresponding":false},{"id":385130,"name":"Justin Ritz","orcid":"0000-0001-6307-4849","position":6,"is_corresponding":false},{"id":218316,"name":"James Regan","orcid":"0000-0003-0449-2295","position":7,"is_corresponding":false},{"id":325436,"name":"James P. Flynn","orcid":"0000-0002-8663-5087","position":8,"is_corresponding":false},{"id":645348,"name":"Charles R. Crain","orcid":null,"position":9,"is_corresponding":false},{"id":340150,"name":"David A. Wohl","orcid":"0000-0002-7764-0212","position":10,"is_corresponding":false},{"id":396976,"name":"Judith S. Currier","orcid":"0000-0003-4279-4737","position":11,"is_corresponding":false},{"id":249713,"name":"Joseph J. Eron","orcid":"0000-0002-4938-0644","position":12,"is_corresponding":false},{"id":105520,"name":"David M. Margolis","orcid":"0000-0001-5714-0002","position":13,"is_corresponding":false},{"id":1042981,"name":"Qing Zhu","orcid":"0000-0001-5148-5157","position":14,"is_corresponding":false},{"id":1260537,"name":"Lijie Zhon","orcid":null,"position":15,"is_corresponding":false},{"id":1260102,"name":"Ya Li","orcid":"0000-0002-7331-2641","position":16,"is_corresponding":false},{"id":108342,"name":"Alexander L. Greninger","orcid":"0000-0002-7443-0527","position":17,"is_corresponding":false},{"id":65752,"name":"Michael D. Hughes","orcid":"0000-0001-8562-2316","position":18,"is_corresponding":false},{"id":36878,"name":"Davey M. Smith","orcid":"0000-0003-3603-1733","position":19,"is_corresponding":false},{"id":351140,"name":"Eric S. Daar","orcid":"0000-0003-1880-7331","position":20,"is_corresponding":false},{"id":108340,"name":"Jonathan Z. Li","orcid":"0000-0001-9914-9662","position":21,"is_corresponding":false},{"id":218333,"name":"Manish C. Choudhary","orcid":"0000-0002-3192-7840","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-19T02:01:37.886033Z","pmid":"38716969","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}