Efficacy of Bamlanivimab/Etesevimab and Casirivimab/Imdevimab in Preventing Progression to Severe COVID-19 and Role of Variants of Concern

doi:10.1007/s40121-021-00525-4

. 2021 Dec;10(4):2479-2488.

doi: 10.1007/s40121-021-00525-4. Epub 2021 Aug 25.

Efficacy of Bamlanivimab/Etesevimab and Casirivimab/Imdevimab in Preventing Progression to Severe COVID-19 and Role of Variants of Concern

Affiliations

¹ Infectious Diseases Unit, Department of Clinical and Experimental Medicine, Azienza Ospedaliera Universitaria Pisana, University of Pisa, Via Paradisa 2, 56124, Pisa, Italy. marco.falcone@unipi.it.
² Infectious Diseases Unit, Department of Clinical and Experimental Medicine, Azienza Ospedaliera Universitaria Pisana, University of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
³ Infectious Disease Unit, San Donato Hospital Arezzo, Arezzo, Italy.
⁴ Virology Unit, Pisa University Hospital, Pisa, Italy.
⁵ Retrovirus Center, Department of Translational Research, University of Pisa, Pisa, Italy.

PMID: 34435337
PMCID: PMC8386337
DOI: 10.1007/s40121-021-00525-4

Efficacy of Bamlanivimab/Etesevimab and Casirivimab/Imdevimab in Preventing Progression to Severe COVID-19 and Role of Variants of Concern

Marco Falcone et al. Infect Dis Ther. 2021 Dec.

. 2021 Dec;10(4):2479-2488.

doi: 10.1007/s40121-021-00525-4. Epub 2021 Aug 25.

Affiliations

¹ Infectious Diseases Unit, Department of Clinical and Experimental Medicine, Azienza Ospedaliera Universitaria Pisana, University of Pisa, Via Paradisa 2, 56124, Pisa, Italy. marco.falcone@unipi.it.
² Infectious Diseases Unit, Department of Clinical and Experimental Medicine, Azienza Ospedaliera Universitaria Pisana, University of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
³ Infectious Disease Unit, San Donato Hospital Arezzo, Arezzo, Italy.
⁴ Virology Unit, Pisa University Hospital, Pisa, Italy.
⁵ Retrovirus Center, Department of Translational Research, University of Pisa, Pisa, Italy.

PMID: 34435337
PMCID: PMC8386337
DOI: 10.1007/s40121-021-00525-4

Abstract

Introduction: The aim of this study was to evaluate the risk of hospitalization or death in patients infected by SARS-CoV2 variants of concern (VOCs) receiving combinations of monoclonal antibodies (mAbs), bamlanivimab/etesevimab or casirivimab/imdevimab.

Methods: Observational prospective study conducted in two Italian hospitals (University Hospital of Pisa and San Donato Hospital, Arezzo) including consecutive outpatients with COVID-19 who received bamlanivimab/etesevimab or casirivimab/imdevimab from March 20th to May 10th 2021. All patients were at high risk of COVID-19 progression according to FDA/AIFA recommendations. Patients were divided into two study groups according to the infecting viral strain (VOCs): Alpha and Gamma group. The primary endpoint was a composite of hospitalization or death within 30 days from mAbs infusion. A Cox regression multivariate analysis was performed to identify factors associated with the primary outcome in the overall population.

Results: The study included 165 patients: 105 were infected by the VOC Alpha and 43 by the VOC Gamma. In the Alpha group, no differences in the primary endpoint were observed between patients treated with bamlanivimab/etesevimab or casirivimab/imdevimab. Conversely, in the Gamma group, a higher proportion of patients treated with bamlanivimab/etesevimab met the primary endpoint compared to those receiving casirivimab/imdevimab (55% vs. 17.4%, p = 0.013). On multivariate Cox-regression analysis, the Gamma variant and days from symptoms onset to mAbs infusion were factors independently associated with higher risk of hospitalization or death, while casirivimab/imdevimab was protective (HR 0.33, 95% CI 0.13-0.83, p = 0.019).

Conclusions: In patients infected by the SARS-CoV-2 Gamma variant, bamlanivimab/etesevimab should be used with caution because of the high risk of disease progression.

Keywords: Bamlanivimab/etesevimab; COVID-19; Casirivimab/imdevimab; Monoclonal antibodies; SARS-CoV-2; Variants of concern.

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Figures

**Fig. 1**
Study flow chart. WT wild-type

**Fig. 2**
Survival curves of patients with the Alpha (A) and those with the Gamma (B) VOC according to exposure variable (bamlanivimab/etesevimab or casirivimab/imdevimab). *VOC* variant of concern, *mAbs* monoclonal antibodies, *Bamla/ete* bamlanivimab/etesevimab, *Casi/imd* casirivimab/imdevimab

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References

1. Coppelli A, Giannarelli R, Aragona M, Penno G, Falcone M, Tiseo G, et al. Hyperglycemia at hospital admission is associated with severity of the prognosis in patients hospitalized for COVID-19: the Pisa COVID-19 study. Diabetes Care. 2020;43:2345–2348. doi: 10.2337/dc20-1380. - DOI - PubMed
1. Falcone M, Tiseo G, Barbieri G, Galfo V, Russo A, Virdis A, et al. Role of low-molecular-weight heparin in hospitalized patients with severe acute respiratory syndrome Coronavirus 2 pneumonia: a prospective observational study. Open Forum Infect Dis. 2020;7:ofaa563. doi: 10.1093/ofid/ofaa563. - DOI - PMC - PubMed
1. Falcone M, Tiseo G, Giordano C, Leonildi A, Menichini M, Vecchione A, et al. Predictors of hospital-acquired bacterial and fungal superinfections in COVID-19: a prospective observational study. J Antimicrob Chemother. 2021;76:1078–1084. doi: 10.1093/jac/dkaa530. - DOI - PMC - PubMed
1. Mussini C, Falcone M, Nozza SC, Parrella R, Meschiari M, et al. Therapeutic strategies for severe COVID-19: a position paper from the Italian Society of Infectious and Tropical Diseases (SIMIT) Clin Microbiol Infect. 2021;27:389–395. doi: 10.1016/j.cmi.2020.12.011. - DOI - PMC - PubMed
1. Stebbing J, Sánchez Nievas G, Falcone M, Youhanna S, Richardson P, Ottaviani S, et al. JAK inhibition reduces SARS-CoV-2 liver infectivity and modulates inflammatory responses to reduce morbidity and mortality. Sci Adv. 2021;7:eabe4724. doi: 10.1126/sciadv.abe4724. - DOI - PMC - PubMed

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[1] Coppelli A, Giannarelli R, Aragona M, Penno G, Falcone M, Tiseo G, et al. Hyperglycemia at hospital admission is associated with severity of the prognosis in patients hospitalized for COVID-19: the Pisa COVID-19 study. Diabetes Care. 2020;43:2345–2348. doi: 10.2337/dc20-1380. - DOI - PubMed

[2] Coppelli A, Giannarelli R, Aragona M, Penno G, Falcone M, Tiseo G, et al. Hyperglycemia at hospital admission is associated with severity of the prognosis in patients hospitalized for COVID-19: the Pisa COVID-19 study. Diabetes Care. 2020;43:2345–2348. doi: 10.2337/dc20-1380. - DOI - PubMed

[3] Falcone M, Tiseo G, Barbieri G, Galfo V, Russo A, Virdis A, et al. Role of low-molecular-weight heparin in hospitalized patients with severe acute respiratory syndrome Coronavirus 2 pneumonia: a prospective observational study. Open Forum Infect Dis. 2020;7:ofaa563. doi: 10.1093/ofid/ofaa563. - DOI - PMC - PubMed

[4] Falcone M, Tiseo G, Barbieri G, Galfo V, Russo A, Virdis A, et al. Role of low-molecular-weight heparin in hospitalized patients with severe acute respiratory syndrome Coronavirus 2 pneumonia: a prospective observational study. Open Forum Infect Dis. 2020;7:ofaa563. doi: 10.1093/ofid/ofaa563. - DOI - PMC - PubMed

[5] Falcone M, Tiseo G, Giordano C, Leonildi A, Menichini M, Vecchione A, et al. Predictors of hospital-acquired bacterial and fungal superinfections in COVID-19: a prospective observational study. J Antimicrob Chemother. 2021;76:1078–1084. doi: 10.1093/jac/dkaa530. - DOI - PMC - PubMed

[6] Falcone M, Tiseo G, Giordano C, Leonildi A, Menichini M, Vecchione A, et al. Predictors of hospital-acquired bacterial and fungal superinfections in COVID-19: a prospective observational study. J Antimicrob Chemother. 2021;76:1078–1084. doi: 10.1093/jac/dkaa530. - DOI - PMC - PubMed

[7] Mussini C, Falcone M, Nozza SC, Parrella R, Meschiari M, et al. Therapeutic strategies for severe COVID-19: a position paper from the Italian Society of Infectious and Tropical Diseases (SIMIT) Clin Microbiol Infect. 2021;27:389–395. doi: 10.1016/j.cmi.2020.12.011. - DOI - PMC - PubMed

[8] Mussini C, Falcone M, Nozza SC, Parrella R, Meschiari M, et al. Therapeutic strategies for severe COVID-19: a position paper from the Italian Society of Infectious and Tropical Diseases (SIMIT) Clin Microbiol Infect. 2021;27:389–395. doi: 10.1016/j.cmi.2020.12.011. - DOI - PMC - PubMed

[9] Stebbing J, Sánchez Nievas G, Falcone M, Youhanna S, Richardson P, Ottaviani S, et al. JAK inhibition reduces SARS-CoV-2 liver infectivity and modulates inflammatory responses to reduce morbidity and mortality. Sci Adv. 2021;7:eabe4724. doi: 10.1126/sciadv.abe4724. - DOI - PMC - PubMed

[10] Stebbing J, Sánchez Nievas G, Falcone M, Youhanna S, Richardson P, Ottaviani S, et al. JAK inhibition reduces SARS-CoV-2 liver infectivity and modulates inflammatory responses to reduce morbidity and mortality. Sci Adv. 2021;7:eabe4724. doi: 10.1126/sciadv.abe4724. - DOI - PMC - PubMed

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Efficacy of Bamlanivimab/Etesevimab and Casirivimab/Imdevimab in Preventing Progression to Severe COVID-19 and Role of Variants of Concern

Affiliations

Efficacy of Bamlanivimab/Etesevimab and Casirivimab/Imdevimab in Preventing Progression to Severe COVID-19 and Role of Variants of Concern

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