Monoclonal antibody therapies against SARS-CoV-2

Focosi, Daniele; McConnell, Scott A.; Casadevall, Arturo; Cappello, Emiliano; Valdiserra, Giulia; Tuccori, Marco

doi:10.1016/s1473-3099(22)00311-5

Cited by 183 publications

(130 citation statements)

References 151 publications

(107 reference statements)

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“…In the top panel, the sites of convergent evolution on the S homotrimer alone are indicated. In the bottom panel, the interfaces with clinically important mAbs from 3 different classes ( Focosi et al, 2022c ) (cilgavimab, bebtelovimab, and sotrovimab; colored blue, dark green and light green, respectively) are displayed to highlight the importance of the positions of convergent evolution in the Omicron S protein. …”

Section: Co-infections and Recombinantsmentioning

confidence: 99%

“…The most concerning implication of Omicron evolution so far has been the progressive escape to vaccine-elicited immunity and anti-Spike monoclonal antibody (mAb) therapies ( Table 1 , Table 2 ), including representatives ( Focosi et al, 2022c ). Models have been developed to predict polyclonal antibody binding to Omicron sublineages remaining after mutating one or more sites in the SARS-CoV-2 RBD, based on deep mutational scanning of RBD targeting antibodies (e.g.…”

Section: Co-infections and Recombinantsmentioning

confidence: 99%

See 1 more Smart Citation

The Omicron variant of concern: Diversification and convergent evolution in spike protein, and escape from anti-Spike monoclonal antibodies

Focosi¹,

McConnell²,

Casadevall³

2022

Drug Resistance Updates

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Section: Co-infections and Recombinantsmentioning

confidence: 99%

Section: Co-infections and Recombinantsmentioning

confidence: 99%

The Omicron variant of concern: Diversification and convergent evolution in spike protein, and escape from anti-Spike monoclonal antibodies

Focosi¹,

McConnell²,

Casadevall³

2022

Drug Resistance Updates

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“…In spite of the marketing of monoclonal antibodies (mAbs) against COVID-19 since February 2021, the high mutation rate of SARS-CoV-2 (approximately a novel variant of concern (VOC) every 6 months) progressively escaped most, if not all, mAbs (10). By contrast, thanks to the prompt availability of CCP against emerging VOCs, CCP maintained its efficacy over time by following the ongoing Spike protein evolution.…”

Section: Introductionmentioning

confidence: 99%

COVID-19 convalescent plasma for the treatment of immunocompromised patients: a systematic review

Senefeld

Franchini

Mengoli

et al. 2022

Preprint

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Immunosuppressed patients have increased risk for morbidity and mortality from COVID-19 because they less frequently mount antibody responses to vaccines and often cannot tolerate small-molecule antivirals. The Omicron variant of concern of SARS-CoV-2 has progressively defeated anti-Spike mAbs authorized so far, paving the way to a return to COVID-19 convalescent plasma (CCP) therapy. In this systematic review we performed a metanalysis of 6 controlled studies (including 2 randomized controlled trials; totaling 368 treated patients and 1119 control), an individual patient data analysis of 125 case reports/series (totaling 265 patients), and a descriptive analysis of 13 uncontrolled large case series without individual patient data available (totaling 358 patients). The metanalysis showed a risk ratio for mortality of 0.61 in treatment with CCP versus standard of care for immunosuppressed COVID-19 patients. On the basis of this evidence, we encourage initiation of high-titer CCP from vaccinees (hybrid plasma) in immunocompromised patients.

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“…Despite growing evidence of treatment-emergent resistance [ 1 , 2 ], the use of mAbs continued even after oral antivirals became available, particularly in frail patients with contraindications to the use of small molecule antivirals. Unfortunately, the advent of the Omicron VOC led to a loss of effectiveness for most of the authorized mAbs [ 3 , 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Prescription of Anti-Spike Monoclonal Antibodies in COVID-19 Patients with Resistant SARS-CoV-2 Variants in Italy

Focosi¹,

Tuccori

2022

Pathogens

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Anti-Spike monoclonal antibodies have been considered a promising approach to COVID-19 therapy. Unfortunately, the advent of resistant lineages jeopardized their effectiveness and prompted limitations in their clinical use. Change in the dominant variant can be fast to such an extent that, in the absence of timely medical education, prescribers can keep using these drugs for relatively long periods even in patients with resistant variants. Therefore, many patients could have been exposed to drugs with unlikely benefits and probable risks. We show here that about 20% of bamlanivimab+etesevimab, 30% of casirivimab+imdevimab, and 30% of sotrovimab courses were administered in Italy during periods in which a fully resistant variant was dominant. Additionally, for monoclonal antibody cocktails, the vast majority of usage occurred against variants for which one of the mAbs within the cocktail was ineffective. Given the high costs of these drugs and their potential side effects, it would be important to consider a frequent review of the appropriateness of these drugs and timely communication when the benefit/risk balance is no longer favorable.

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Monoclonal antibody therapies against SARS-CoV-2

Cited by 183 publications

References 151 publications

The Omicron variant of concern: Diversification and convergent evolution in spike protein, and escape from anti-Spike monoclonal antibodies

The Omicron variant of concern: Diversification and convergent evolution in spike protein, and escape from anti-Spike monoclonal antibodies

COVID-19 convalescent plasma for the treatment of immunocompromised patients: a systematic review

Prescription of Anti-Spike Monoclonal Antibodies in COVID-19 Patients with Resistant SARS-CoV-2 Variants in Italy

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