Combating the SARS-CoV-2 Omicron variant with non-Omicron neutralizing antibodies

Wang, Ying-Dan; Zhang, Xiang; Liu, Jiangyan; Wang, Yanqun; Zhan, Wuqiang; Liu, Mei; Zhang, Meng; Wang, Qimin; Liu, Qianying; Zhu, Tongyu; Wen, Yiping; Chen, Zhenguo; Zhao, Jincun; Wu, Fan; Sun, Lei; Huang, Jinghe

doi:10.1101/2022.01.30.478305

Cited by 4 publications

(1 citation statement)

References 34 publications

(41 reference statements)

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“…As of February 22, 2022, 31 studies met the search criteria (Figure 1). Twelve of the studies were reported in a peer-reviewed publication [10][11][12][13][14][15][16][17][18][19][20][21]; 19 were published as preprints [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]. Two additional studies comprised data available on the NIH National Center for Advancing Translational Sciences (NCATS) SARS-CoV-2 Variants and Therapeutics open data portal [41,42].…”

Section: Search Resultsmentioning

confidence: 99%

Susceptibility of SARS-CoV-2 Omicron Variants to Therapeutic Monoclonal Antibodies: Systematic Review and Meta-Analysis

Tao¹,

Tzou²,

Pond³

et al. 2022

Preprint

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SARS-CoV-2 Omicron variants contain many mutations in its spike receptor binding domain, the target of all authorized monoclonal antibodies (mAbs). Determining the extent to which Omicron variants reduced mAb susceptibility is critical to preventing and treating COVID-19. We systematically reviewed PubMed and three preprint servers, last updated February 22, 2022, of the in vitro activity of authorized mAbs against the Omicron variants. Thirty-three studies were eligible including 33 containing Omicron BA.1 susceptibility data and five that also contained Omicron BA.2 susceptibility data. The first two authorized mAb combinations, bamlanivimab/etesevimab and casirivimab/imdevimab, were inactive against the Omicron BA.1 and BA.2 variants. In 24 studies, sotrovimab (third authorized mAb) displayed a median 4.1-fold (IQR: 2.4-7.6) reduced activity against Omicron BA.1 and, in four studies, a median 26-fold (IQR:16-35) reduced activity against Omicron BA.2. In 18 studies, cilgavimab and tixagevimab independently displayed median reductions in activity of >300-fold against Omicron BA.1, while in ten studies, the cilgavimab/tixagevimab combination (fourth authorized mAb preparation) displayed a median 63-fold (IQR: 26-145) reduced activity against Omicron BA.1. In two studies, cilgavimab was approximately 100-fold more susceptible to BA.2 than to BA.1. In two studies, bebtelovimab, the most recently authorized mAb, was fully active against both the Omicron variants. Disparate results between assays were common as evidenced by a median 42-fold range (IQR: 25-625) in IC50 between assays for the eight authorized individual mAbs and three authorized mAb combinations. Highly disparate results between published assays indicates a need for improved mAb susceptibility test standardization or inter-assay calibration.

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Section: Search Resultsmentioning

confidence: 99%

Susceptibility of SARS-CoV-2 Omicron Variants to Therapeutic Monoclonal Antibodies: Systematic Review and Meta-Analysis

Tao¹,

Tzou²,

Pond³

et al. 2022

Preprint

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Analysis of SARS-CoV-2 mutations associated with resistance to therapeutic monoclonal antibodies that emerge after treatment

Focosi,

McConnell,

Sullivan

et al. 2023

Drug Resistance Updates

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Analysis of SARS-CoV-2 mutations associated with resistance to therapeutic monoclonal antibodies that emerge after treatment

Focosi¹,

McConnell

Sullivan

et al. 2023

Preprint

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The mutation rate of the Omicron sublineage has led to baseline resistance against all previously authorized anti-Spike monoclonal antibodies (mAbs). Nevertheless, in case more antiviral mAbs will be authorized in the future, it is relevant to understand how frequently treatment-emergent resistance has emerged so far, under different combinations and in different patient subgroups. We report the results of a systematic review of the medical literature for case reports and case series for treatment-emergent immune escape, which is defined as emergence of a resistance-driving mutation in at least 20% of sequences in a given host at a given timepoint. We identified 31 publications detailing 201 cases that included different variants of concern (VOC) and found that the incidence of treatment emergent-resistance ranged from 10% to 50%. Most of the treatment-emergent resistance events occurred in immunocompromised patients. Interestingly, resistance also emerged against cocktails of two mAbs, albeit at lower frequencies. The heterogenous therapeutic management of those cases doesn’t allow inferences about the clinical outcome in patients with treatment-emergent resistance. Furthermore, we noted a temporal correlation between the introduction of mAb therapies and a subsequent increase in SARS-CoV-2 sequences across the globe carrying mutations conferring resistance to that mAb, raising concern as to whether these had originated in mAb-treated individuals. Our findings confirm that treatment-emergent immune escape to anti-Spike mAbs represents a frequent and concerning phenomenon and suggests that these are associated with mAb use in immunosuppressed hosts.

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Combating the SARS-CoV-2 Omicron variant with non-Omicron neutralizing antibodies

Cited by 4 publications

References 34 publications

Susceptibility of SARS-CoV-2 Omicron Variants to Therapeutic Monoclonal Antibodies: Systematic Review and Meta-Analysis

Susceptibility of SARS-CoV-2 Omicron Variants to Therapeutic Monoclonal Antibodies: Systematic Review and Meta-Analysis

Analysis of SARS-CoV-2 mutations associated with resistance to therapeutic monoclonal antibodies that emerge after treatment

Analysis of SARS-CoV-2 mutations associated with resistance to therapeutic monoclonal antibodies that emerge after treatment

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