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Sotrovimab lost neutralization efficacy against SARS-CoV-2 subvariants but remained clinically effective: Were monoclonal antibodies against COVID-19 rejected too early?

Bang et al., Journal of Infection and Public Health, doi:10.1016/j.jiph.2024.102512
Aug 2024  
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Sotrovimab for COVID-19
41st treatment shown to reduce risk in May 2023, now with p = 0.002 from 25 studies, recognized in 38 countries. Efficacy is variant dependent.
Lower risk for mortality, ICU admission, and hospitalization.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 109 treatments. c19early.org
Retrospective 14 outpatients treated with sotrovimab showing that while sotrovimab lost in vitro neutralization efficacy against omicron subvariants BA.1 and BA.2, it remained clinically effective in reducing viral load in patients who did not have an endogenous antibody response. The results suggest that monoclonal antibodies should have potentially remained available for certain patient groups despite the strong recommendations against their use issued by health authorities in late 2022 and early 2023, which were largely based on in vitro neutralization results. Authors hypothesize that the immune stimulation induced by monoclonal antibodies, beyond just neutralization, may be beneficial for some patients.
Efficacy is variant dependent. In Vitro studies predict lower efficacy for BA.11-3, BA.4, BA.54, XBB.1.9.3, XBB.1.5.24, XBB.2.9, CH.1.15, and no efficacy for BA.26, XBB, XBB.1.5, ХВВ.1.9.17, XBB.1.16, BQ.1.1.45, and CL.15. US EUA has been revoked.
Bang et al., 12 Aug 2024, Denmark, peer-reviewed, 6 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperSotrovimabAll
Sotrovimab lost neutralization efficacy against SARS-CoV-2 subvariants but remained clinically effective: Were monoclonal antibodies against COVID-19 rejected too early?
Line Lundegaard Bang, Lone Wulff Madsen, Rune Micha Pedersen, Anna Christine Nilsson, Isik Somuncu Johansen, Thomas Emil Andersen
Journal of Infection and Public Health, doi:10.1016/j.jiph.2024.102512
We read with interest the article by Behzad et al. [1
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
References
Behzad, Ali, Niinuma, Butler, Alqahtani, Real world effectiveness of sotrovimab in preventing COVID-19-related hospitalisation or death in patients infected with Omicron BA.2, J Infect Public Health
Cai, Diallo, Rosenthal, Ren, Flores et al., AZD3152 neutralizes SARS-CoV-2 historical and contemporary variants and is protective in hamsters and well tolerated in adults, Sci Transl Med
Driouich, Bernadin, Touret, Lamballerie, Nougairède, Activity of Sotrovimab against BQ.1.1 and XBB.1 Omicron sublineages in a hamster model, Antivir Res
Drysdale, Gibbons, Singh, Rolland, Lavoie et al., Realworld effectiveness of sotrovimab for the treatment of SARS-CoV-2 infection during Omicron BA.2 subvariant predominance: a systematic literature review, Infection
Hérate, Touret, Dereuddre-Bosquet, Donati, Relouzat, Sotrovimab retains activity against SARS-CoV-2 omicron variant BQ.1.1 in a nonhuman primate model, Heliyon
Stadler, Burgess, Schlub, Khan, Chai et al., Monoclonal antibody levels and protection from COVID-19, Nat Commun
Supernova Phase, trial of sipavibart long-acting antibody met primary endpoints in preventing COVID-19 in immunocompromised patient population
Uraki, Kiso, Iida, Imai, Takashita et al., Characterization and antiviral susceptibility of SARS-CoV-2 Omicron BA.2, Nature
Wilhelm, Widera, Grikscheit, Toptan, Schenk et al., Limited neutralisation of the SARS-CoV-2 Omicron subvariants BA.1 and BA.2 by convalescent and vaccine serum and monoclonal antibodies, eBioMedicine
Zhang, Stacey, Agostino, Tugg, Marzok et al., Beyond neutralization: Fc-dependent antibody effector functions in SARS-CoV-2 infection, Nat Rev Immunol
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