Background Monoclonal antibodies (mAbs) targeting the spike of SARS-CoV-2 prevent severe COVID-19. Omicron subvariants BQ.1.1 and XBB.1.5 evade neutralization of therapeutic mAbs, leading to recommendations against their use. Yet, the antiviral activities of mAbs in treated patients remain ill-defined. Methods We investigated neutralization and antibody-dependent cellular cytotoxicity (ADCC) of D614G, BQ.1.1 and XBB.1.5 in 320 sera from 80 immunocompromised patients with mild-to-moderate COVID-19 prospectively treated with mAbs (sotrovimab, n=29; imdevimab/casirivimab, n=34; cilgavimab/tixagevimab, n=4) or anti-protease (nirmatrelvir/ritonavir, n=13). We measured live-virus neutralization titers and quantified ADCC with a reporter assay. Findings Only Sotrovimab elicits serum neutralization and ADCC against BQ.1.1 and XBB.1.5. As compared to D614G, sotrovimab neutralization titers of BQ.1.1 and XBB.1.5 are reduced (71- and 58-fold, respectively), but ADCC levels are only slightly decreased (1.4- and 1-fold, for BQ.1.1 and XBB.1.5, respectively). Interpretation Our results show that sotrovimab is active against BQ.1.1 and XBB.1.5 in treated individuals, suggesting that it may be a valuable therapeutic option.

T.B. and O.S. have a pending patent application for an anti-RBD mAb not used in this study (PCT/FR2021/070522). All other authors declare no conflicts of interest.

NCT04885452

Work in TB and OS lab is funded by Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, Fondation pour la Recherche Medicale (FRM), ANRS-MIE, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), ANR / FRM Flash Covid PROTEO-SARS-CoV-2, ANR Programme Hubert Curien Maimonide, Coronamito, HERA european funding, Sanofi and IDISCOVR. The E.S.-L. laboratory receives funding from Institut Pasteur, the INCEPTION program (Investissements d Avenir grant ANR-16-CONV-0005) and NIH PICREID program (Award Number U01AI151758). The ANRS 0003S CoCoPrev cohort is conducted with the support of ANRS│MIE and funded by French ministries : Ministere des Solidarites et de la Santa and Ministere de l Enseignement Superieur, de la Recherche et de l Innovation.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The protocol was approved by the Comite de protection des personnes (CPP) Sud-Est IV Ethics Committee (Paris, France) and the French Regulatory Authority. Written informed consent was obtained from each patient before enrolment.

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All data produced in the present study are available upon reasonable request to the authors.