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Journal Articles Journal of Infectious Diseases Year : 2023

Spike protein genetic evolution in patients at high-risk of severe COVID-19 treated by monoclonal antibodies

Evolution génétique de la protéine Spike chez des patients à haut risque de COVID-19 sévère traités par anticorps monoclonaux

Emna Ghidaoui
  • Function : Author
Sophie Sayon
  • Function : Author
Céline Dorival
  • Function : Author
Marie-Laure Meledje
  • Function : Author
Clovis Lusivika-Nzinga
  • Function : Author
Youri Yordanov
  • Function : Author
Guillaume Martin-Blondel
  • Function : Author
Fabrice Carrat
  • Function : Author
Anne-Geneviève Marcelin
  • Function : Author
Cathia Soulie
  • Function : Author

Abstract

High-risk patients, often immunocompromised and not responding to vaccine, continue to experience severe COVID-19 and death. Monoclonal antibodies (mAbs) were shown effective to prevent severe COVID-19 for these patients. Nevertheless, concerns about the emergence of resistance mutations were raised. We conducted a multicentric prospective cohort study, including 264 patients with mild-to moderate COVID-19 at high risk for progression to severe COVID-19 and treated early with Casirivimab/Imdevimab, Sotrovimab or Tixagevimab/Cilgavimab. We sequenced the SARS-CoV-2 genome during follow-up and searched for emerging Spike mutations. Immunocompromised patients have a 6-fold increased risk of developing mutations, which are associated with a prolonged duration of viral clearance but no clinical worsening. Emerging P337S/R/L/H, E340D/K/A/Q/V/G and K356T/R substitutions in patients treated with Sotrovimab are associated with higher viral RNA loads for up to 14 days post-treatment initiation. Tixagevimab/Cilgavimab is associated with a 5-fold increased risk of developing mutations. R346K/I/T/S and K444R/N/M substitutions associated with Tixagevimab/Cilgavimab have been identified in multiple SARS-CoV-2 lineages, including BQ.1 and XBB. In conclusion, the probability of emerging mutations arising in response to mAbs is significant, emphasizing the crucial need to investigate these mutations thoroughly and assess their impact on patients and the evolutionary trajectory of the SARS-CoV-2.
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hal-04309349 , version 1 (27-11-2023)

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Valentin Leducq, Karen Zafilaza, Antoine Fauchois, Emna Ghidaoui, Sophie Sayon, et al.. Spike protein genetic evolution in patients at high-risk of severe COVID-19 treated by monoclonal antibodies. Journal of Infectious Diseases, 2023, ⟨10.1093/infdis/jiad523⟩. ⟨hal-04309349⟩
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