Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study

Augusto Di Castelnuovo; Simona Costanzo; Andrea Antinori; Nausicaa Berselli; Lorenzo Blandi; Marialaura Bonaccio; Raffaele Bruno; Roberto Cauda; Alessandro Gialluisi; Giovanni Guaraldi; Lorenzo Menicanti; MARCO GIOVANNI MENNUNI; Ilaria My; Agostino Parruti; Giuseppe Rocco Salvatore Patti; Stefano Perlini; Francesca Santilli; Carlo Signorelli; Giulio G Stefanini; Alessandra Vergori; Walter Ageno; Luca Aiello; Piergiuseppe Agostoni; Samir Al Moghazi; Rosa Arboretti; Filippo Aucella; Greta Barbieri; Martina Barchitta; Alessandro Bartoloni; Carolina Bologna; Paolo Bonfanti; Lucia Caiano; Laura Carrozzi; Antonio Cascio; Giacomo Castiglione; Mauro Chiarito; Arturo Ciccullo; Antonella Cingolani; Francesco Cipollone; Claudia Colomba; Crizia Colombo; Francesco Crosta; Giovanni Dalena; Chiara Dal Pra; Gian Battista Danzi; Damiano D'Ardes; Katleen de Gaetano Donati; Francesco Di Gennaro; Giuseppe Di Tano; Gianpiero D'Offizi; Tommaso Filippini; Francesco Maria Fusco; Carlo Gaudiosi; Ivan Gentile; Giancarlo Gini; Elvira Grandone; Gabriella Guarnieri; Gennaro L F Lamanna; Giovanni Larizza; Armando Leone; Veronica Lio; Angela Raffaella Losito; Gloria Maccagni; Stefano Maitan; Sandro Mancarella; Rosa Manuele; Massimo Mapelli; Riccardo Maragna; Lorenzo Marra; Giulio Maresca; Claudia Marotta; Franco Mastroianni; Maria Mazzitelli; Alessandro Mengozzi; Francesco Menichetti; Jovana Milic; Filippo Minutolo; Beatrice Molena; R Mussinelli; Cristina Mussini; Maria Musso; Anna Odone; Marco Olivieri; Emanuela Pasi; Annalisa Perroni; Francesco Petri; Biagio Pinchera; Carlo A Pivato; Venerino Poletti; Claudia Ravaglia; Marco Rossato; Marianna Rossi; Anna Sabena; Francesco Salinaro; Vincenzo Sangiovanni; Carlo Sanrocco; Laura Scorzolini; Raffaella Sgariglia; Paola Giustina Simeone; Michele Spinicci; Enrico Maria Trecarichi; Giovanni Veronesi; Roberto Vettor; Andrea Vianello; Marco Vinceti; Elena Visconti; Laura Vocciante; Raffaele De Caterina; Licia Iacoviello

doi:10.3389/fmed.2021.639970

Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study

Augusto Di Castelnuovo, Simona Costanzo, Andrea Antinori, Nausicaa Berselli, Lorenzo Blandi, Marialaura Bonaccio, Raffaele Bruno, Roberto Cauda, Alessandro Gialluisi, Giovanni Guaraldi, Lorenzo Menicanti, MARCO GIOVANNI MENNUNI, Ilaria My, Agostino Parruti, Giuseppe Rocco Salvatore Patti, Stefano Perlini, Francesca Santilli, Carlo Signorelli, Giulio G Stefanini, Alessandra VergoriWalter Ageno, Luca Aiello, Piergiuseppe Agostoni, Samir Al Moghazi, Rosa Arboretti, Filippo Aucella, Greta Barbieri, Martina Barchitta, Alessandro Bartoloni, Carolina Bologna, Paolo Bonfanti, Lucia Caiano, Laura Carrozzi, Antonio Cascio, Giacomo Castiglione, Mauro Chiarito, Arturo Ciccullo, Antonella Cingolani, Francesco Cipollone, Claudia Colomba, Crizia Colombo, Francesco Crosta, Giovanni Dalena, Chiara Dal Pra, Gian Battista Danzi, Damiano D'Ardes, Katleen de Gaetano Donati, Francesco Di Gennaro, Giuseppe Di Tano, Gianpiero D'Offizi, Tommaso Filippini, Francesco Maria Fusco, Carlo Gaudiosi, Ivan Gentile, Giancarlo Gini, Elvira Grandone, Gabriella Guarnieri, Gennaro L F Lamanna, Giovanni Larizza, Armando Leone, Veronica Lio, Angela Raffaella Losito, Gloria Maccagni, Stefano Maitan, Sandro Mancarella, Rosa Manuele, Massimo Mapelli, Riccardo Maragna, Lorenzo Marra, Giulio Maresca, Claudia Marotta, Franco Mastroianni, Maria Mazzitelli, Alessandro Mengozzi, Francesco Menichetti, Jovana Milic, Filippo Minutolo, Beatrice Molena, R Mussinelli, Cristina Mussini, Maria Musso, Anna Odone, Marco Olivieri, Emanuela Pasi, Annalisa Perroni, Francesco Petri, Biagio Pinchera, Carlo A Pivato, Venerino Poletti, Claudia Ravaglia, Marco Rossato, Marianna Rossi, Anna Sabena, Francesco Salinaro, Vincenzo Sangiovanni, Carlo Sanrocco, Laura Scorzolini, Raffaella Sgariglia, Paola Giustina Simeone, Michele Spinicci, Enrico Maria Trecarichi, Giovanni Veronesi, Roberto Vettor, Andrea Vianello, Marco Vinceti, Elena Visconti, Laura Vocciante, Raffaele De Caterina, Licia Iacoviello

Dipartimento di Medicina Traslazionale

Risultato della ricerca: Contributo su rivista › Articolo in rivista › peer review

Abstract

Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients. Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients. Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores. Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs. Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients.

Lingua originale	Inglese
pagine (da-a)	639970
Rivista	Frontiers in Medicine
Volume	8
DOI	https://doi.org/10.3389/fmed.2021.639970
Stato di pubblicazione	Pubblicato - 2021

Keywords

COVID-19
SARS-CoV-2
darunavir
in-hospital mortality
lopinavir

Accesso al documento

10.3389/fmed.2021.639970

http://hdl.handle.net/11579/127528

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Di Castelnuovo, A., Costanzo, S., Antinori, A., Berselli, N., Blandi, L., Bonaccio, M., Bruno, R., Cauda, R., Gialluisi, A., Guaraldi, G., Menicanti, L., MENNUNI, MARCO. GIOVANNI., My, I., Parruti, A., Patti, G. R. S., Perlini, S., Santilli, F., Signorelli, C., Stefanini, G. G., ... Iacoviello, L. (2021). Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study. Frontiers in Medicine, 8, 639970. https://doi.org/10.3389/fmed.2021.639970

@article{f12610cbad0543a382a224ee0907690f,

title = "Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study",

abstract = "Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients. Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients. Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores. Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs. Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients.",

keywords = "COVID-19, SARS-CoV-2, darunavir, in-hospital mortality, lopinavir, COVID-19, SARS-CoV-2, darunavir, in-hospital mortality, lopinavir",

author = "{Di Castelnuovo}, Augusto and Simona Costanzo and Andrea Antinori and Nausicaa Berselli and Lorenzo Blandi and Marialaura Bonaccio and Raffaele Bruno and Roberto Cauda and Alessandro Gialluisi and Giovanni Guaraldi and Lorenzo Menicanti and MENNUNI, {MARCO GIOVANNI} and Ilaria My and Agostino Parruti and Patti, {Giuseppe Rocco Salvatore} and Stefano Perlini and Francesca Santilli and Carlo Signorelli and Stefanini, {Giulio G} and Alessandra Vergori and Walter Ageno and Luca Aiello and Piergiuseppe Agostoni and {Al Moghazi}, Samir and Rosa Arboretti and Filippo Aucella and Greta Barbieri and Martina Barchitta and Alessandro Bartoloni and Carolina Bologna and Paolo Bonfanti and Lucia Caiano and Laura Carrozzi and Antonio Cascio and Giacomo Castiglione and Mauro Chiarito and Arturo Ciccullo and Antonella Cingolani and Francesco Cipollone and Claudia Colomba and Crizia Colombo and Francesco Crosta and Giovanni Dalena and {Dal Pra}, Chiara and Danzi, {Gian Battista} and Damiano D'Ardes and {de Gaetano Donati}, Katleen and {Di Gennaro}, Francesco and {Di Tano}, Giuseppe and Gianpiero D'Offizi and Tommaso Filippini and {Maria Fusco}, Francesco and Carlo Gaudiosi and Ivan Gentile and Giancarlo Gini and Elvira Grandone and Gabriella Guarnieri and Lamanna, {Gennaro L F} and Giovanni Larizza and Armando Leone and Veronica Lio and Losito, {Angela Raffaella} and Gloria Maccagni and Stefano Maitan and Sandro Mancarella and Rosa Manuele and Massimo Mapelli and Riccardo Maragna and Lorenzo Marra and Giulio Maresca and Claudia Marotta and Franco Mastroianni and Maria Mazzitelli and Alessandro Mengozzi and Francesco Menichetti and Jovana Milic and Filippo Minutolo and Beatrice Molena and R Mussinelli and Cristina Mussini and Maria Musso and Anna Odone and Marco Olivieri and Emanuela Pasi and Annalisa Perroni and Francesco Petri and Biagio Pinchera and Pivato, {Carlo A} and Venerino Poletti and Claudia Ravaglia and Marco Rossato and Marianna Rossi and Anna Sabena and Francesco Salinaro and Vincenzo Sangiovanni and Carlo Sanrocco and Laura Scorzolini and Raffaella Sgariglia and Simeone, {Paola Giustina} and Michele Spinicci and Trecarichi, {Enrico Maria} and Giovanni Veronesi and Roberto Vettor and Andrea Vianello and Marco Vinceti and Elena Visconti and Laura Vocciante and {De Caterina}, Raffaele and Licia Iacoviello",

year = "2021",

doi = "10.3389/fmed.2021.639970",

language = "English",

volume = "8",

pages = "639970",

journal = "Frontiers in Medicine",

issn = "2296-858X",

publisher = "Frontiers Media S.A.",

}

Di Castelnuovo, A, Costanzo, S, Antinori, A, Berselli, N, Blandi, L, Bonaccio, M, Bruno, R, Cauda, R, Gialluisi, A, Guaraldi, G, Menicanti, L, MENNUNI, MARCOGIOVANNI, My, I, Parruti, A, Patti, GRS, Perlini, S, Santilli, F, Signorelli, C, Stefanini, GG, Vergori, A, Ageno, W, Aiello, L, Agostoni, P, Al Moghazi, S, Arboretti, R, Aucella, F, Barbieri, G, Barchitta, M, Bartoloni, A, Bologna, C, Bonfanti, P, Caiano, L, Carrozzi, L, Cascio, A, Castiglione, G, Chiarito, M, Ciccullo, A, Cingolani, A, Cipollone, F, Colomba, C, Colombo, C, Crosta, F, Dalena, G, Dal Pra, C, Danzi, GB, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Tano, G, D'Offizi, G, Filippini, T, Maria Fusco, F, Gaudiosi, C, Gentile, I, Gini, G, Grandone, E, Guarnieri, G, Lamanna, GLF, Larizza, G, Leone, A, Lio, V, Losito, AR, Maccagni, G, Maitan, S, Mancarella, S, Manuele, R, Mapelli, M, Maragna, R, Marra, L, Maresca, G, Marotta, C, Mastroianni, F, Mazzitelli, M, Mengozzi, A, Menichetti, F, Milic, J, Minutolo, F, Molena, B, Mussinelli, R, Mussini, C, Musso, M, Odone, A, Olivieri, M, Pasi, E, Perroni, A, Petri, F, Pinchera, B, Pivato, CA, Poletti, V, Ravaglia, C, Rossato, M, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Scorzolini, L, Sgariglia, R, Simeone, PG, Spinicci, M, Trecarichi, EM, Veronesi, G, Vettor, R, Vianello, A, Vinceti, M, Visconti, E, Vocciante, L, De Caterina, R & Iacoviello, L 2021, 'Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study', Frontiers in Medicine, vol. 8, pagg. 639970. https://doi.org/10.3389/fmed.2021.639970

TY - JOUR

T1 - Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study

AU - Di Castelnuovo, Augusto

AU - Costanzo, Simona

AU - Antinori, Andrea

AU - Berselli, Nausicaa

AU - Blandi, Lorenzo

AU - Bonaccio, Marialaura

AU - Bruno, Raffaele

AU - Cauda, Roberto

AU - Gialluisi, Alessandro

AU - Guaraldi, Giovanni

AU - Menicanti, Lorenzo

AU - MENNUNI, MARCO GIOVANNI

AU - My, Ilaria

AU - Parruti, Agostino

AU - Patti, Giuseppe Rocco Salvatore

AU - Perlini, Stefano

AU - Santilli, Francesca

AU - Signorelli, Carlo

AU - Stefanini, Giulio G

AU - Vergori, Alessandra

AU - Ageno, Walter

AU - Aiello, Luca

AU - Agostoni, Piergiuseppe

AU - Al Moghazi, Samir

AU - Arboretti, Rosa

AU - Aucella, Filippo

AU - Barbieri, Greta

AU - Barchitta, Martina

AU - Bartoloni, Alessandro

AU - Bologna, Carolina

AU - Bonfanti, Paolo

AU - Caiano, Lucia

AU - Carrozzi, Laura

AU - Cascio, Antonio

AU - Castiglione, Giacomo

AU - Chiarito, Mauro

AU - Ciccullo, Arturo

AU - Cingolani, Antonella

AU - Cipollone, Francesco

AU - Colomba, Claudia

AU - Colombo, Crizia

AU - Crosta, Francesco

AU - Dalena, Giovanni

AU - Dal Pra, Chiara

AU - Danzi, Gian Battista

AU - D'Ardes, Damiano

AU - de Gaetano Donati, Katleen

AU - Di Gennaro, Francesco

AU - Di Tano, Giuseppe

AU - D'Offizi, Gianpiero

AU - Filippini, Tommaso

AU - Maria Fusco, Francesco

AU - Gaudiosi, Carlo

AU - Gentile, Ivan

AU - Gini, Giancarlo

AU - Grandone, Elvira

AU - Guarnieri, Gabriella

AU - Lamanna, Gennaro L F

AU - Larizza, Giovanni

AU - Leone, Armando

AU - Lio, Veronica

AU - Losito, Angela Raffaella

AU - Maccagni, Gloria

AU - Maitan, Stefano

AU - Mancarella, Sandro

AU - Manuele, Rosa

AU - Mapelli, Massimo

AU - Maragna, Riccardo

AU - Marra, Lorenzo

AU - Maresca, Giulio

AU - Marotta, Claudia

AU - Mastroianni, Franco

AU - Mazzitelli, Maria

AU - Mengozzi, Alessandro

AU - Menichetti, Francesco

AU - Milic, Jovana

AU - Minutolo, Filippo

AU - Molena, Beatrice

AU - Mussinelli, R

AU - Mussini, Cristina

AU - Musso, Maria

AU - Odone, Anna

AU - Olivieri, Marco

AU - Pasi, Emanuela

AU - Perroni, Annalisa

AU - Petri, Francesco

AU - Pinchera, Biagio

AU - Pivato, Carlo A

AU - Poletti, Venerino

AU - Ravaglia, Claudia

AU - Rossato, Marco

AU - Rossi, Marianna

AU - Sabena, Anna

AU - Salinaro, Francesco

AU - Sangiovanni, Vincenzo

AU - Sanrocco, Carlo

AU - Scorzolini, Laura

AU - Sgariglia, Raffaella

AU - Simeone, Paola Giustina

AU - Spinicci, Michele

AU - Trecarichi, Enrico Maria

AU - Veronesi, Giovanni

AU - Vettor, Roberto

AU - Vianello, Andrea

AU - Vinceti, Marco

AU - Visconti, Elena

AU - Vocciante, Laura

AU - De Caterina, Raffaele

AU - Iacoviello, Licia

PY - 2021

Y1 - 2021

N2 - Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients. Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients. Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores. Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs. Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients.

AB - Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients. Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients. Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores. Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs. Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients.

KW - COVID-19

KW - SARS-CoV-2

KW - darunavir

KW - in-hospital mortality

KW - lopinavir

KW - COVID-19

KW - SARS-CoV-2

KW - darunavir

KW - in-hospital mortality

KW - lopinavir

UR - https://iris.uniupo.it/handle/11579/127528

U2 - 10.3389/fmed.2021.639970

DO - 10.3389/fmed.2021.639970

M3 - Article

SN - 2296-858X

VL - 8

SP - 639970

JO - Frontiers in Medicine

JF - Frontiers in Medicine

ER -

Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study

Abstract

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