Influence of treatment with neutralizing monoclonal antibodies on the SARS-CoV-2 nasopharyngeal load and quasispecies

Vellas, Camille; Del Bello, Arnaud; Debard, Alexa; Steinmeyer, Zara; Tribaudeau, Laure; Ranger, Noémie; Jeanne, Nicolas; Martin-Blondel, Guillaume; Delobel, Pierre; Kamar, Nassim; Izopet, Jacques

OBJECTIVES: We aimed to evaluate the impact of neutralizing monoclonal antibodies (mAbs) treatment and to determine whether the mAbs selective pressure could facilitate the proliferation of virus variants with spike protein mutations that might attenuate mAb effectiveness. PATIENTS AND METHODS: We therefore evaluated the impact of mAbs on the nasopharyngeal (NP) viral load and virus quasispecies of mAb-treated patients using single molecule real time sequencing (Pacific Biosciences). The mAbs used were: Bamlanivimab alone (4 patients), Bamlanivimab/Etesevimab (23 patients), and Casirivimab/Imdevimab (5 patients). RESULTS: The NP SARS-CoV-2 viral load of mAb-treated patients decreased from 8.2 log(10) copies/ml before administration to 4.3 log(10) copies/ml 7 days after administration. Five immunocompromised patients given Bamlanivimab/Etesevimab were found to have mAbs activity-reducing spike mutations. Two patients harbored SARS-CoV-2 variants with a Q493R spike mutation 7 days after administration, as did a third patient 14 days after administration. The fourth patient harbored a variant with a Q493K spike mutation 7 days post-treatment, and the fifth patient had a variant with a E484K spike mutation on day 21. The emergence of the spike mutation was accompanied by stabilization or rebound of the NP viral load in 3/5 patients. CONCLUSION: Two-mAb therapy can drive the selection of resistant SARS-CoV-2 variants in immunocompromised patients. Patients given mAbs should be closely monitored and measures to limit virus spread reinforced.