Viral clearance and escape during therapy of COVID-19 outpatients: A prospective cohort study
The efficacy of neutralizing SARS-CoV-2 monoclonal antibodies (mAbs) in preventing severe COVID-19 has been hindered by the diversity of viral strains and the complexity of patient populations. In this prospective cohort study, we used regression analyses to identify virological, immunological, and clinical factors associated with viral clearance and emergence of escape mutations. We included 114 mainly immunocompromised high-risk patients with mild-to-moderate COVID-19 who received mAbs or direct antivirals to prevent COVID-19 progression. Nasopharyngeal SARS-CoV-2 RNA level at day 7 was independently associated with viral load at day 0, serum neutralization at day 7, and treatment received. The emergence of mutations within Spike was observed in 21.9% of patients, all being immunocompromised treated by Sotrovimab or Tixagevimab/Cilgavimab after Omicron emergence, and was independently associated with higher viral load and serum neutralization at day 7. Our data show that suboptimal neutralizing antibodies should be avoided in immunocompromised individuals, given the risk of emergence of viral escape mutations.
Authors
- Andréa Cottignies-Calamarte (ORCID: https://orcid.org/0000-0002-1041-4659)
- Raphaëlle Romieu‐Mourez
- Guillaume Martin‐Blondel (ORCID: https://orcid.org/0000-0002-8363-7028)
- X. Boumaza
- Roland Liblau (ORCID: https://orcid.org/0000-0001-5477-5475)
- Céline Dorival
- Youri Yordanov (ORCID: https://orcid.org/0000-0003-0671-6547)
- Françoise Porrot (ORCID: https://orcid.org/0000-0001-8995-3614)
- Timothée Bruel (ORCID: https://orcid.org/0000-0002-3952-4261)
- Anne‐Geneviève Marcelin (ORCID: https://orcid.org/0000-0003-4808-8999)
- Benjamin Gaborit (ORCID: https://orcid.org/0000-0002-6076-9722)
- Olivier Schwartz (ORCID: https://orcid.org/0000-0002-0729-1475)
- Vincent Dubée (ORCID: https://orcid.org/0000-0002-9982-4741)
- Florence Ader (ORCID: https://orcid.org/0000-0002-4778-4338)
- Clovis Lusivika‐Nzinga (ORCID: https://orcid.org/0000-0003-4457-4228)
- François Coustillères (ORCID: https://orcid.org/0000-0002-4034-9341)
- Valentin Leducq (ORCID: https://orcid.org/0000-0002-6817-6227)
- Quentin Richier (ORCID: https://orcid.org/0000-0002-4962-6405)
- Fabrice Carrat (ORCID: https://orcid.org/0000-0002-8672-7918)
- Cathia Soulié (ORCID: https://orcid.org/0009-0008-2032-4148)
- Paul Burgat
- Vincent Cazaentre
- Camille Chaubet
Institutions
- Université Claude Bernard Lyon 1 (FR)
- Université de Tours (FR)
- École Normale Supérieure de Lyon (FR)
- Centre National de la Recherche Scientifique (FR)
- Université Toulouse III - Paul Sabatier (FR)
- Inserm (FR)
- Institut Pasteur (FR)
- Université Fédérale de Toulouse Midi-Pyrénées (FR)
- Université Paris Cité (FR)
- Sorbonne Université (FR)
- Centre Hospitalier Universitaire de Tours (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Toulouse Mathematics Institute (FR)
- Hospices Civils de Lyon (FR)
- Hôpital Saint-Antoine (FR)
- Centre Hospitalier Universitaire d'Angers (FR)
- Institut de Recherche Vaccinale (FR)
- Pitié-Salpêtrière Hospital (FR)
- Hôpital Edouard Herriot (FR)
- Centre d'Investigation Clinique de Nantes (FR)
- Institut Pierre Louis d‘Épidémiologie et de Santé Publique (FR)
- Center for Research in Transplantation and Translational Immunology
- Nantes Université (FR)
Publication Details
- Journal
- iScience
- Published
- 2025-11-26
- DOI
- https://doi.org/10.1016/j.isci.2025.114226
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00