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Clinical Trial
. 2025 Feb 4;231(1):131-136.
doi: 10.1093/infdis/jiae501.

Viral and Symptom Rebound Following Anti-Severe Acute Respiratory Syndrome Coronavirus 2 Monoclonal Antibody Therapy in a Randomized Placebo-Controlled Trial

Kara W Chew  1 , Brooke McGinley  2 , Carlee Moser  3 , Jonathan Z Li  4 , Teresa H Evering  5 , Justin Ritz  3 , Arzhang Cyrus Javan  6 , David Margolis  7 , David A Wohl  8 , Michael D Hughes  3 , Eric S Daar  9 , Judith S Currier  1 , Joseph J Eron  8 , Davey M Smith  10 ; Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)-2/A5401 Study Team, Study Sites, and Investigators
Collaborators, Affiliations
Clinical Trial

Viral and Symptom Rebound Following Anti-Severe Acute Respiratory Syndrome Coronavirus 2 Monoclonal Antibody Therapy in a Randomized Placebo-Controlled Trial

Kara W Chew et al. J Infect Dis. .

Abstract

We explored viral and symptom rebound after coronavirus disease 2019 amubarvimab-romlusevimab monoclonal antibody therapy versus placebo in the randomized ACTIV-2/A5401 trial. Participants underwent nasal severe acute respiratory syndrome coronavirus 2 polymerase chain reaction testing at study days 3, 7, 14, and 28. Viral rebound was defined as RNA ≥3 and ≥0.5 log10 copies/mL increase from day 3 or 7, and symptom rebound as hospitalization or any moderate/severe symptom for ≥2 days after initial symptom improvement. There was no difference in viral rebound (∼5%/arm) (analysis population n = 713) or symptom rebound among participants who initially improved (hazard ratio, 0.95 [95% confidence interval, .52-1.75]; analysis population n = 574); <1% had both viral/symptom rebound.

Keywords: COVID-19; SARS-CoV-2; monoclonal antibodies; nonhospitalized adults; symptom rebound; viral rebound.

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Conflict of interest statement

Potential conflicts of interest. K. W. C. has served as a consultant for Pardes Biosciences. J. Z. L. has received research support to his institution from Merck and consulted for AbbVie. T. H. E. serves as a consultant for Tonix Pharmaceuticals. D. A. W. has received funding to his institution to support research and honoraria for advisory boards and consulting from Gilead Sciences. D. M. is an employee and shareholder of Brii Biosciences. J. J. E. is an ad hoc consultant to GSK/VIR and has consulted for Merck, and is on the data monitoring committee and chair for Adagio (now Invivyd) phase 3 studies. J. S. C. has consulted for Merck and Company. E. S. D. receives consulting fees from Gilead Sciences, Theratechnologies, and GSK/ViiV and research support through his institution from Gilead Sciences and GSK/ViiV. D. M. S. has consulted for the following companies: Fluxergy, Gilead, Linear Therapies, VxBiosciences, Model Medicines, Bayer Pharmaceuticals, Lucira, Pharma Holdings, Hyundai, and Red Queen Therapeutics, and received support for attending meetings and/or travel from A2 Bio. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Percentage of participants with viral rebound by treatment arm and rebound definition. A, Viral rebound definition requiring at least 0.5 log10 increase in nasal viral RNA level and reaching at least 3, 4, or 5 log10 copies/mL. B, Viral rebound definition requiring at least 1 log10 increase in nasal viral RNA level and reaching at least 3, 4, or 5 log10 copies/mL. P values by Fisher exact test for between-arm difference in rebound frequency. Abbreviation: A/R, amubarvimab-romlusevimab.
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References

    1. Charness ME, Gupta K, Stack G, et al. Rebound of SARS-CoV-2 infection after nirmatrelvir-ritonavir treatment. N Engl J Med 2022; 387:1045–7. - PMC - PubMed
    1. Carlin AF, Clark AE, Chaillon A, et al. Virologic and immunologic characterization of coronavirus disease 2019 recrudescence after nirmatrelvir/ritonavir treatment. Clin Infect Dis 2023; 76:e530–2. - PMC - PubMed
    1. Edelstein GE, Boucau J, Uddin R, et al. SARS-CoV-2 virologic rebound with nirmatrelvir-ritonavir therapy: an observational study. Ann Intern Med 2023; 176:1577–85. - PMC - PubMed
    1. Han J, Bae S, Jung J, et al. Clinical characteristics of COVID-19 rebound after nirmatrelvir-ritonavir or molnupiravir therapy: a prospective cohort study. Medicine (Baltimore) 2023; 102:e35094. - PMC - PubMed
    1. Yang Z, Xu Y, Zheng R, et al. COVID-19 rebound after VV116 vs nirmatrelvir-ritonavir treatment: a randomized clinical trial. JAMA Netw Open 2024; 7:e241765. - PMC - PubMed

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