TY - JOUR
T1 - Clinical Impact of Monoclonal Antibodies in the Treatment of High-Risk Patients with SARS-CoV-2 Breakthrough Infections
T2 - The ORCHESTRA Prospective Cohort Study
AU - mAb ORCHESTRA Working Group
AU - Savoldi, Alessia
AU - Morra, Matteo
AU - Castelli, Alessandro
AU - Mirandola, Massimo
AU - Berkell, Matilda
AU - Smet, Mathias
AU - Konnova, Angelina
AU - Rossi, Elisa
AU - Cataudella, Salvatore
AU - De Nardo, Pasquale
AU - Gentilotti, Elisa
AU - Gupta, Akshita
AU - Fasan, Daniele
AU - Gibbin, Enrico
AU - Puviani, Filippo Cioli
AU - Hasenauer, Jan
AU - Gusinow, Roy
AU - Tami, Adriana
AU - Kumar-Singh, Samir
AU - Malhotra-Kumar, Surbhi
AU - Tacconelli, Evelina
N1 - Funding Information:
The study has been funded by the ORCHESTRA project, which has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 101016167.
Publisher Copyright:
© 2022 by the authors.
PY - 2022/9
Y1 - 2022/9
N2 - 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 < 0.001). aOR for hospitalization was significantly lower for breakthrough infection (aOR 0.12, 95%CI: 0.05–0.27, p < 0.001) and higher for immunocompromised status (aOR:2.35, 95%CI:1.08–5.08, p = 0.003), advanced age (aOR:1.06, 95%CI: 1.03–1.08, p < 0.001), and male gender (aOR:1.97, 95%CI: 1.04–3.73, p = 0.037). Among the breakthrough infection group, the median SARS-CoV-2 anti-spike IgGs was lower (p < 0.001) in immunocompromised and elderly patients >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.
AB - 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 < 0.001). aOR for hospitalization was significantly lower for breakthrough infection (aOR 0.12, 95%CI: 0.05–0.27, p < 0.001) and higher for immunocompromised status (aOR:2.35, 95%CI:1.08–5.08, p = 0.003), advanced age (aOR:1.06, 95%CI: 1.03–1.08, p < 0.001), and male gender (aOR:1.97, 95%CI: 1.04–3.73, p = 0.037). Among the breakthrough infection group, the median SARS-CoV-2 anti-spike IgGs was lower (p < 0.001) in immunocompromised and elderly patients >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.
KW - anti-spike monoclonal antibodies
KW - COVID-19 breakthrough infection
KW - COVID-19 early treatment
U2 - 10.3390/biomedicines10092063
DO - 10.3390/biomedicines10092063
M3 - Article
AN - SCOPUS:85138689702
SN - 2227-9059
VL - 10
JO - Biomedicines
JF - Biomedicines
IS - 9
M1 - 2063
ER -