Clinical Impact of Monoclonal Antibodies in the Treatment of High-Risk Patients with SARS-CoV-2 Breakthrough Infections: The ORCHESTRA Prospective Cohort Study
Alessia Savoldi,
Matteo Morra,
Alessandro Castelli,
Massimo Mirandola,
Matilda Berkell,
Mathias Smet,
Angelina Konnova,
Elisa Rossi,
Salvatore Cataudella,
Pasquale De Nardo,
Elisa Gentilotti,
Akshita Gupta,
Daniele Fasan,
Enrico Gibbin,
Filippo Cioli Puviani,
Jan Hasenauer,
Roy Gusinow,
Adriana Tami,
Samir Kumar-Singh,
Surbhi Malhotra-Kumar,
mAb ORCHESTRA Working Group,
Evelina Tacconelli
Affiliations
Alessia Savoldi
Division of Infectious Diseases, Department of Diagnostics and Public Health, University of Verona, P.le L.A. Scuro 10, 37134 Verona, Italy
Matteo Morra
Division of Infectious Diseases, Department of Diagnostics and Public Health, University of Verona, P.le L.A. Scuro 10, 37134 Verona, Italy
Alessandro Castelli
Division of Infectious Diseases, Department of Diagnostics and Public Health, University of Verona, P.le L.A. Scuro 10, 37134 Verona, Italy
Massimo Mirandola
Division of Infectious Diseases, Department of Diagnostics and Public Health, University of Verona, P.le L.A. Scuro 10, 37134 Verona, Italy
Matilda Berkell
Lab of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp, 2610 Antwerp, Belgium
Mathias Smet
Lab of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp, 2610 Antwerp, Belgium
Angelina Konnova
Molecular Pathology Group, Cell Biology & Histology, Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Antwerp, Belgium
Elisa Rossi
CINECA—Interuniversity Consortium, Via Magnanelli 6/3, Casalecchio di Reno, 40033 Bologna, Italy
Salvatore Cataudella
CINECA—Interuniversity Consortium, Via Magnanelli 6/3, Casalecchio di Reno, 40033 Bologna, Italy
Pasquale De Nardo
Division of Infectious Diseases, Department of Diagnostics and Public Health, University of Verona, P.le L.A. Scuro 10, 37134 Verona, Italy
Elisa Gentilotti
Division of Infectious Diseases, Department of Diagnostics and Public Health, University of Verona, P.le L.A. Scuro 10, 37134 Verona, Italy
Akshita Gupta
Molecular Pathology Group, Cell Biology & Histology, Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Antwerp, Belgium
Daniele Fasan
Division of Infectious Diseases, Department of Diagnostics and Public Health, University of Verona, P.le L.A. Scuro 10, 37134 Verona, Italy
Enrico Gibbin
Division of Infectious Diseases, Department of Diagnostics and Public Health, University of Verona, P.le L.A. Scuro 10, 37134 Verona, Italy
Filippo Cioli Puviani
Division of Infectious Diseases, Department of Diagnostics and Public Health, University of Verona, P.le L.A. Scuro 10, 37134 Verona, Italy
Jan Hasenauer
Helmholtz Center Munich—Germany Research Center for Environmental Heath, Institute for Computational Biology, 85764 Neuherberg, Germany
Roy Gusinow
Helmholtz Center Munich—Germany Research Center for Environmental Heath, Institute for Computational Biology, 85764 Neuherberg, Germany
Adriana Tami
Department of Medical Microbiology & Infection Prevention, University Medical Center Groningen, 9713 AV Groningen, The Netherlands
Samir Kumar-Singh
Molecular Pathology Group, Cell Biology & Histology, Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Antwerp, Belgium
Surbhi Malhotra-Kumar
Lab of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp, 2610 Antwerp, Belgium
mAb ORCHESTRA Working Group
Evelina Tacconelli
Division of Infectious Diseases, Department of Diagnostics and Public Health, University of Verona, P.le L.A. Scuro 10, 37134 Verona, Italy
The clinical impact of anti-spike monoclonal antibodies (mAb) in Coronavirus Disease 2019 (COVID-19) breakthrough infections is unclear. We present the results of an observational prospective cohort study assessing and comparing COVID-19 progression in high-risk outpatients receiving mAb according to primary or breakthrough infection. Clinical, serological and virological predictors associated with 28-day COVID-19-related hospitalization were identified using multivariate logistic regression and summarized with odds ratio (aOR) and 95% confidence interval (CI). A total of 847 COVID-19 outpatients were included: 414 with primary and 433 with breakthrough infection. Hospitalization was observed in 42/414 (10.1%) patients with primary and 8/433 (1.8%) patients with breakthrough infection (p p p = 0.003), advanced age (aOR:1.06, 95%CI: 1.03–1.08, p p = 0.037). Among the breakthrough infection group, the median SARS-CoV-2 anti-spike IgGs was lower (p 75 years compared with that in the immunocompetent patients. Our findings suggest that, among mAb patients, those with breakthrough infection have significantly lower hospitalization risk compared with patients with primary infection. Prognostic algorithms combining clinical and immune-virological characteristics are needed to ensure appropriate and up-to-date clinical protocols targeting high-risk categories.
