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

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 observa...

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Autores principales: Di Castelnuovo, Augusto, Costanzo, Simona, Antinori, Andrea, Berselli, Nausicaa, Blandi, Lorenzo, Bonaccio, Marialaura, Bruno, Raffaele, Cauda, Roberto, Gialluisi, Alessandro, Guaraldi, Giovanni, Menicanti, Lorenzo, Mennuni, Marco, My, Ilaria, Parruti, Agostino, Patti, Giuseppe, Perlini, Stefano, Santilli, Francesca, Signorelli, Carlo, Stefanini, Giulio G., Vergori, Alessandra, Ageno, Walter, Aiello, Luca, Agostoni, Piergiuseppe, Al Moghazi, Samir, Arboretti, Rosa, Aucella, Filippo, Barbieri, Greta, Barchitta, Martina, Bartoloni, Alessandro, Bologna, Carolina, Bonfanti, Paolo, Caiano, Lucia, Carrozzi, Laura, Cascio, Antonio, Castiglione, Giacomo, Chiarito, Mauro, Ciccullo, Arturo, Cingolani, Antonella, Cipollone, Francesco, Colomba, Claudia, Colombo, Crizia, Crosta, Francesco, Dalena, Giovanni, Dal Pra, Chiara, Danzi, Gian Battista, D'Ardes, Damiano, de Gaetano Donati, Katleen, Di Gennaro, Francesco, Di Tano, Giuseppe, D'Offizi, Gianpiero, Filippini, Tommaso, Maria Fusco, Francesco, Gaudiosi, Carlo, Gentile, Ivan, Gini, Giancarlo, Grandone, Elvira, Guarnieri, Gabriella, Lamanna, Gennaro L. F., Larizza, Giovanni, Leone, Armando, Lio, Veronica, Losito, Angela Raffaella, Maccagni, Gloria, Maitan, Stefano, Mancarella, Sandro, Manuele, Rosa, Mapelli, Massimo, Maragna, Riccardo, Marra, Lorenzo, Maresca, Giulio, Marotta, Claudia, Mastroianni, Franco, Mazzitelli, Maria, Mengozzi, Alessandro, Menichetti, Francesco, Milic, Jovana, Minutolo, Filippo, Molena, Beatrice, Mussinelli, R., Mussini, Cristina, Musso, Maria, Odone, Anna, Olivieri, Marco, Pasi, Emanuela, Perroni, Annalisa, Petri, Francesco, Pinchera, Biagio, Pivato, Carlo A., Poletti, Venerino, Ravaglia, Claudia, Rossato, Marco, Rossi, Marianna, Sabena, Anna, Salinaro, Francesco, Sangiovanni, Vincenzo, Sanrocco, Carlo, Scorzolini, Laura, Sgariglia, Raffaella, Simeone, Paola Giustina, Spinicci, Michele, Trecarichi, Enrico Maria, Veronesi, Giovanni, Vettor, Roberto, Vianello, Andrea, Vinceti, Marco, Visconti, Elena, Vocciante, Laura, De Caterina, Raffaele, Iacoviello, Licia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221239/
https://www.ncbi.nlm.nih.gov/pubmed/34179035
http://dx.doi.org/10.3389/fmed.2021.639970
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author Di Castelnuovo, Augusto
Costanzo, Simona
Antinori, Andrea
Berselli, Nausicaa
Blandi, Lorenzo
Bonaccio, Marialaura
Bruno, Raffaele
Cauda, Roberto
Gialluisi, Alessandro
Guaraldi, Giovanni
Menicanti, Lorenzo
Mennuni, Marco
My, Ilaria
Parruti, Agostino
Patti, Giuseppe
Perlini, Stefano
Santilli, Francesca
Signorelli, Carlo
Stefanini, Giulio G.
Vergori, Alessandra
Ageno, Walter
Aiello, Luca
Agostoni, Piergiuseppe
Al Moghazi, Samir
Arboretti, Rosa
Aucella, Filippo
Barbieri, Greta
Barchitta, Martina
Bartoloni, Alessandro
Bologna, Carolina
Bonfanti, Paolo
Caiano, Lucia
Carrozzi, Laura
Cascio, Antonio
Castiglione, Giacomo
Chiarito, Mauro
Ciccullo, Arturo
Cingolani, Antonella
Cipollone, Francesco
Colomba, Claudia
Colombo, Crizia
Crosta, Francesco
Dalena, Giovanni
Dal Pra, Chiara
Danzi, Gian Battista
D'Ardes, Damiano
de Gaetano Donati, Katleen
Di Gennaro, Francesco
Di Tano, Giuseppe
D'Offizi, Gianpiero
Filippini, Tommaso
Maria Fusco, Francesco
Gaudiosi, Carlo
Gentile, Ivan
Gini, Giancarlo
Grandone, Elvira
Guarnieri, Gabriella
Lamanna, Gennaro L. F.
Larizza, Giovanni
Leone, Armando
Lio, Veronica
Losito, Angela Raffaella
Maccagni, Gloria
Maitan, Stefano
Mancarella, Sandro
Manuele, Rosa
Mapelli, Massimo
Maragna, Riccardo
Marra, Lorenzo
Maresca, Giulio
Marotta, Claudia
Mastroianni, Franco
Mazzitelli, Maria
Mengozzi, Alessandro
Menichetti, Francesco
Milic, Jovana
Minutolo, Filippo
Molena, Beatrice
Mussinelli, R.
Mussini, Cristina
Musso, Maria
Odone, Anna
Olivieri, Marco
Pasi, Emanuela
Perroni, Annalisa
Petri, Francesco
Pinchera, Biagio
Pivato, Carlo A.
Poletti, Venerino
Ravaglia, Claudia
Rossato, Marco
Rossi, Marianna
Sabena, Anna
Salinaro, Francesco
Sangiovanni, Vincenzo
Sanrocco, Carlo
Scorzolini, Laura
Sgariglia, Raffaella
Simeone, Paola Giustina
Spinicci, Michele
Trecarichi, Enrico Maria
Veronesi, Giovanni
Vettor, Roberto
Vianello, Andrea
Vinceti, Marco
Visconti, Elena
Vocciante, Laura
De Caterina, Raffaele
Iacoviello, Licia
author_facet Di Castelnuovo, Augusto
Costanzo, Simona
Antinori, Andrea
Berselli, Nausicaa
Blandi, Lorenzo
Bonaccio, Marialaura
Bruno, Raffaele
Cauda, Roberto
Gialluisi, Alessandro
Guaraldi, Giovanni
Menicanti, Lorenzo
Mennuni, Marco
My, Ilaria
Parruti, Agostino
Patti, Giuseppe
Perlini, Stefano
Santilli, Francesca
Signorelli, Carlo
Stefanini, Giulio G.
Vergori, Alessandra
Ageno, Walter
Aiello, Luca
Agostoni, Piergiuseppe
Al Moghazi, Samir
Arboretti, Rosa
Aucella, Filippo
Barbieri, Greta
Barchitta, Martina
Bartoloni, Alessandro
Bologna, Carolina
Bonfanti, Paolo
Caiano, Lucia
Carrozzi, Laura
Cascio, Antonio
Castiglione, Giacomo
Chiarito, Mauro
Ciccullo, Arturo
Cingolani, Antonella
Cipollone, Francesco
Colomba, Claudia
Colombo, Crizia
Crosta, Francesco
Dalena, Giovanni
Dal Pra, Chiara
Danzi, Gian Battista
D'Ardes, Damiano
de Gaetano Donati, Katleen
Di Gennaro, Francesco
Di Tano, Giuseppe
D'Offizi, Gianpiero
Filippini, Tommaso
Maria Fusco, Francesco
Gaudiosi, Carlo
Gentile, Ivan
Gini, Giancarlo
Grandone, Elvira
Guarnieri, Gabriella
Lamanna, Gennaro L. F.
Larizza, Giovanni
Leone, Armando
Lio, Veronica
Losito, Angela Raffaella
Maccagni, Gloria
Maitan, Stefano
Mancarella, Sandro
Manuele, Rosa
Mapelli, Massimo
Maragna, Riccardo
Marra, Lorenzo
Maresca, Giulio
Marotta, Claudia
Mastroianni, Franco
Mazzitelli, Maria
Mengozzi, Alessandro
Menichetti, Francesco
Milic, Jovana
Minutolo, Filippo
Molena, Beatrice
Mussinelli, R.
Mussini, Cristina
Musso, Maria
Odone, Anna
Olivieri, Marco
Pasi, Emanuela
Perroni, Annalisa
Petri, Francesco
Pinchera, Biagio
Pivato, Carlo A.
Poletti, Venerino
Ravaglia, Claudia
Rossato, Marco
Rossi, Marianna
Sabena, Anna
Salinaro, Francesco
Sangiovanni, Vincenzo
Sanrocco, Carlo
Scorzolini, Laura
Sgariglia, Raffaella
Simeone, Paola Giustina
Spinicci, Michele
Trecarichi, Enrico Maria
Veronesi, Giovanni
Vettor, Roberto
Vianello, Andrea
Vinceti, Marco
Visconti, Elena
Vocciante, Laura
De Caterina, Raffaele
Iacoviello, Licia
author_sort Di Castelnuovo, Augusto
collection PubMed
description 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.
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spelling pubmed-82212392021-06-24 Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study Di Castelnuovo, Augusto Costanzo, Simona Antinori, Andrea Berselli, Nausicaa Blandi, Lorenzo Bonaccio, Marialaura Bruno, Raffaele Cauda, Roberto Gialluisi, Alessandro Guaraldi, Giovanni Menicanti, Lorenzo Mennuni, Marco My, Ilaria Parruti, Agostino Patti, Giuseppe Perlini, Stefano Santilli, Francesca Signorelli, Carlo Stefanini, Giulio G. Vergori, Alessandra Ageno, Walter Aiello, Luca Agostoni, Piergiuseppe Al Moghazi, Samir Arboretti, Rosa Aucella, Filippo Barbieri, Greta Barchitta, Martina Bartoloni, Alessandro Bologna, Carolina Bonfanti, Paolo Caiano, Lucia Carrozzi, Laura Cascio, Antonio Castiglione, Giacomo Chiarito, Mauro Ciccullo, Arturo Cingolani, Antonella Cipollone, Francesco Colomba, Claudia Colombo, Crizia Crosta, Francesco Dalena, Giovanni Dal Pra, Chiara Danzi, Gian Battista D'Ardes, Damiano de Gaetano Donati, Katleen Di Gennaro, Francesco Di Tano, Giuseppe D'Offizi, Gianpiero Filippini, Tommaso Maria Fusco, Francesco Gaudiosi, Carlo Gentile, Ivan Gini, Giancarlo Grandone, Elvira Guarnieri, Gabriella Lamanna, Gennaro L. F. Larizza, Giovanni Leone, Armando Lio, Veronica Losito, Angela Raffaella Maccagni, Gloria Maitan, Stefano Mancarella, Sandro Manuele, Rosa Mapelli, Massimo Maragna, Riccardo Marra, Lorenzo Maresca, Giulio Marotta, Claudia Mastroianni, Franco Mazzitelli, Maria Mengozzi, Alessandro Menichetti, Francesco Milic, Jovana Minutolo, Filippo Molena, Beatrice Mussinelli, R. Mussini, Cristina Musso, Maria Odone, Anna Olivieri, Marco Pasi, Emanuela Perroni, Annalisa Petri, Francesco Pinchera, Biagio Pivato, Carlo A. Poletti, Venerino Ravaglia, Claudia Rossato, Marco Rossi, Marianna Sabena, Anna Salinaro, Francesco Sangiovanni, Vincenzo Sanrocco, Carlo Scorzolini, Laura Sgariglia, Raffaella Simeone, Paola Giustina Spinicci, Michele Trecarichi, Enrico Maria Veronesi, Giovanni Vettor, Roberto Vianello, Andrea Vinceti, Marco Visconti, Elena Vocciante, Laura De Caterina, Raffaele Iacoviello, Licia Front Med (Lausanne) Medicine 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. Frontiers Media S.A. 2021-06-09 /pmc/articles/PMC8221239/ /pubmed/34179035 http://dx.doi.org/10.3389/fmed.2021.639970 Text en Copyright © 2021 Di Castelnuovo, Costanzo, Antinori, Berselli, Blandi, Bonaccio, Bruno, Cauda, Gialluisi, Guaraldi, Menicanti, Mennuni, My, Parruti, Patti, Perlini, Santilli, Signorelli, Stefanini, Vergori, Ageno, Aiello, Agostoni, Al Moghazi, Arboretti, Aucella, Barbieri, Barchitta, Bartoloni, Bologna, Bonfanti, Caiano, Carrozzi, Cascio, Castiglione, Chiarito, Ciccullo, Cingolani, Cipollone, Colomba, Colombo, Crosta, Dalena, Dal Pra, Danzi, D'Ardes, de Gaetano Donati, Di Gennaro, Di Tano, D'Offizi, Filippini, Maria Fusco, Gaudiosi, Gentile, Gini, Grandone, Guarnieri, Lamanna, Larizza, Leone, Lio, Losito, Maccagni, Maitan, Mancarella, Manuele, Mapelli, Maragna, Marra, Maresca, Marotta, Mastroianni, Mazzitelli, Mengozzi, Menichetti, Milic, Minutolo, Molena, Mussinelli, Mussini, Musso, Odone, Olivieri, Pasi, Perroni, Petri, Pinchera, Pivato, Poletti, Ravaglia, Rossato, Rossi, Sabena, Salinaro, Sangiovanni, Sanrocco, Scorzolini, Sgariglia, Simeone, Spinicci, Trecarichi, Veronesi, Vettor, Vianello, Vinceti, Visconti, Vocciante, De Caterina, Iacoviello and The COVID-19 RISK and Treatments (CORIST) Collaboration. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Medicine
Di Castelnuovo, Augusto
Costanzo, Simona
Antinori, Andrea
Berselli, Nausicaa
Blandi, Lorenzo
Bonaccio, Marialaura
Bruno, Raffaele
Cauda, Roberto
Gialluisi, Alessandro
Guaraldi, Giovanni
Menicanti, Lorenzo
Mennuni, Marco
My, Ilaria
Parruti, Agostino
Patti, Giuseppe
Perlini, Stefano
Santilli, Francesca
Signorelli, Carlo
Stefanini, Giulio G.
Vergori, Alessandra
Ageno, Walter
Aiello, Luca
Agostoni, Piergiuseppe
Al Moghazi, Samir
Arboretti, Rosa
Aucella, Filippo
Barbieri, Greta
Barchitta, Martina
Bartoloni, Alessandro
Bologna, Carolina
Bonfanti, Paolo
Caiano, Lucia
Carrozzi, Laura
Cascio, Antonio
Castiglione, Giacomo
Chiarito, Mauro
Ciccullo, Arturo
Cingolani, Antonella
Cipollone, Francesco
Colomba, Claudia
Colombo, Crizia
Crosta, Francesco
Dalena, Giovanni
Dal Pra, Chiara
Danzi, Gian Battista
D'Ardes, Damiano
de Gaetano Donati, Katleen
Di Gennaro, Francesco
Di Tano, Giuseppe
D'Offizi, Gianpiero
Filippini, Tommaso
Maria Fusco, Francesco
Gaudiosi, Carlo
Gentile, Ivan
Gini, Giancarlo
Grandone, Elvira
Guarnieri, Gabriella
Lamanna, Gennaro L. F.
Larizza, Giovanni
Leone, Armando
Lio, Veronica
Losito, Angela Raffaella
Maccagni, Gloria
Maitan, Stefano
Mancarella, Sandro
Manuele, Rosa
Mapelli, Massimo
Maragna, Riccardo
Marra, Lorenzo
Maresca, Giulio
Marotta, Claudia
Mastroianni, Franco
Mazzitelli, Maria
Mengozzi, Alessandro
Menichetti, Francesco
Milic, Jovana
Minutolo, Filippo
Molena, Beatrice
Mussinelli, R.
Mussini, Cristina
Musso, Maria
Odone, Anna
Olivieri, Marco
Pasi, Emanuela
Perroni, Annalisa
Petri, Francesco
Pinchera, Biagio
Pivato, Carlo A.
Poletti, Venerino
Ravaglia, Claudia
Rossato, Marco
Rossi, Marianna
Sabena, Anna
Salinaro, Francesco
Sangiovanni, Vincenzo
Sanrocco, Carlo
Scorzolini, Laura
Sgariglia, Raffaella
Simeone, Paola Giustina
Spinicci, Michele
Trecarichi, Enrico Maria
Veronesi, Giovanni
Vettor, Roberto
Vianello, Andrea
Vinceti, Marco
Visconti, Elena
Vocciante, Laura
De Caterina, Raffaele
Iacoviello, Licia
Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study
title Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study
title_full Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study
title_fullStr Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study
title_full_unstemmed Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study
title_short Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study
title_sort lopinavir/ritonavir and darunavir/cobicistat in hospitalized covid-19 patients: findings from the multicenter italian corist study
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221239/
https://www.ncbi.nlm.nih.gov/pubmed/34179035
http://dx.doi.org/10.3389/fmed.2021.639970
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