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 observati...
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Format: | Article |
Language: | English |
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Frontiers Media S.A.
2021-06-01
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Series: | Frontiers in Medicine |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2021.639970/full |
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Augusto Di Castelnuovo Simona Costanzo Andrea Antinori Nausicaa Berselli Lorenzo Blandi Marialaura Bonaccio Raffaele Bruno Raffaele Bruno Roberto Cauda Roberto Cauda Alessandro Gialluisi Giovanni Guaraldi Lorenzo Menicanti Marco Mennuni Ilaria My Agostino Parruti Giuseppe Patti Stefano Perlini Stefano Perlini Francesca Santilli Carlo Signorelli Giulio G. Stefanini Alessandra Vergori Walter Ageno Luca Aiello Piergiuseppe Agostoni Piergiuseppe Agostoni Samir Al Moghazi Rosa Arboretti Filippo Aucella Greta Barbieri Martina Barchitta Alessandro Bartoloni Carolina Bologna Paolo Bonfanti Paolo Bonfanti Lucia Caiano Laura Carrozzi Antonio Cascio Giacomo Castiglione Mauro Chiarito Arturo Ciccullo Antonella Cingolani 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 Massimo Mapelli Riccardo Maragna 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 Marco Vinceti Elena Visconti Laura Vocciante Raffaele De Caterina Licia Iacoviello Licia Iacoviello The COVID-19 RISK and Treatments (CORIST) Collaboration |
spellingShingle |
Augusto Di Castelnuovo Simona Costanzo Andrea Antinori Nausicaa Berselli Lorenzo Blandi Marialaura Bonaccio Raffaele Bruno Raffaele Bruno Roberto Cauda Roberto Cauda Alessandro Gialluisi Giovanni Guaraldi Lorenzo Menicanti Marco Mennuni Ilaria My Agostino Parruti Giuseppe Patti Stefano Perlini Stefano Perlini Francesca Santilli Carlo Signorelli Giulio G. Stefanini Alessandra Vergori Walter Ageno Luca Aiello Piergiuseppe Agostoni Piergiuseppe Agostoni Samir Al Moghazi Rosa Arboretti Filippo Aucella Greta Barbieri Martina Barchitta Alessandro Bartoloni Carolina Bologna Paolo Bonfanti Paolo Bonfanti Lucia Caiano Laura Carrozzi Antonio Cascio Giacomo Castiglione Mauro Chiarito Arturo Ciccullo Antonella Cingolani 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 Massimo Mapelli Riccardo Maragna 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 Marco Vinceti Elena Visconti Laura Vocciante Raffaele De Caterina Licia Iacoviello Licia Iacoviello The COVID-19 RISK and Treatments (CORIST) Collaboration Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study Frontiers in Medicine COVID-19 SARS-CoV-2 darunavir lopinavir in-hospital mortality |
author_facet |
Augusto Di Castelnuovo Simona Costanzo Andrea Antinori Nausicaa Berselli Lorenzo Blandi Marialaura Bonaccio Raffaele Bruno Raffaele Bruno Roberto Cauda Roberto Cauda Alessandro Gialluisi Giovanni Guaraldi Lorenzo Menicanti Marco Mennuni Ilaria My Agostino Parruti Giuseppe Patti Stefano Perlini Stefano Perlini Francesca Santilli Carlo Signorelli Giulio G. Stefanini Alessandra Vergori Walter Ageno Luca Aiello Piergiuseppe Agostoni Piergiuseppe Agostoni Samir Al Moghazi Rosa Arboretti Filippo Aucella Greta Barbieri Martina Barchitta Alessandro Bartoloni Carolina Bologna Paolo Bonfanti Paolo Bonfanti Lucia Caiano Laura Carrozzi Antonio Cascio Giacomo Castiglione Mauro Chiarito Arturo Ciccullo Antonella Cingolani 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 Massimo Mapelli Riccardo Maragna 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 Marco Vinceti Elena Visconti Laura Vocciante Raffaele De Caterina Licia Iacoviello Licia Iacoviello The COVID-19 RISK and Treatments (CORIST) Collaboration |
author_sort |
Augusto Di Castelnuovo |
title |
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_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_sort |
lopinavir/ritonavir and darunavir/cobicistat in hospitalized covid-19 patients: findings from the multicenter italian corist study |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Medicine |
issn |
2296-858X |
publishDate |
2021-06-01 |
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. |
topic |
COVID-19 SARS-CoV-2 darunavir lopinavir in-hospital mortality |
url |
https://www.frontiersin.org/articles/10.3389/fmed.2021.639970/full |
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doaj-f4c84c197fec47feaef5530f66820b4b2021-06-09T15:26:09ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2021-06-01810.3389/fmed.2021.639970639970Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST StudyAugusto Di Castelnuovo0Simona Costanzo1Andrea Antinori2Nausicaa Berselli3Lorenzo Blandi4Marialaura Bonaccio5Raffaele Bruno6Raffaele Bruno7Roberto Cauda8Roberto Cauda9Alessandro Gialluisi10Giovanni Guaraldi11Lorenzo Menicanti12Marco Mennuni13Ilaria My14Agostino Parruti15Giuseppe Patti16Stefano Perlini17Stefano Perlini18Francesca Santilli19Carlo Signorelli20Giulio G. Stefanini21Alessandra Vergori22Walter Ageno23Luca Aiello24Piergiuseppe Agostoni25Piergiuseppe Agostoni26Samir Al Moghazi27Rosa Arboretti28Filippo Aucella29Greta Barbieri30Martina Barchitta31Alessandro Bartoloni32Carolina Bologna33Paolo Bonfanti34Paolo Bonfanti35Lucia Caiano36Laura Carrozzi37Antonio Cascio38Giacomo Castiglione39Mauro Chiarito40Arturo Ciccullo41Antonella Cingolani42Antonella Cingolani43Francesco Cipollone44Claudia Colomba45Crizia Colombo46Francesco Crosta47Giovanni Dalena48Chiara Dal Pra49Gian Battista Danzi50Damiano D'Ardes51Katleen de Gaetano Donati52Francesco Di Gennaro53Giuseppe Di Tano54Gianpiero D'Offizi55Tommaso Filippini56Francesco Maria Fusco57Carlo Gaudiosi58Ivan Gentile59Giancarlo Gini60Elvira Grandone61Gabriella Guarnieri62Gennaro L. F. Lamanna63Giovanni Larizza64Armando Leone65Veronica Lio66Angela Raffaella Losito67Gloria Maccagni68Stefano Maitan69Sandro Mancarella70Rosa Manuele71Massimo Mapelli72Massimo Mapelli73Riccardo Maragna74Riccardo Maragna75Lorenzo Marra76Giulio Maresca77Claudia Marotta78Franco Mastroianni79Maria Mazzitelli80Alessandro Mengozzi81Francesco Menichetti82Jovana Milic83Filippo Minutolo84Beatrice Molena85R. Mussinelli86Cristina Mussini87Maria Musso88Anna Odone89Marco Olivieri90Emanuela Pasi91Annalisa Perroni92Francesco Petri93Biagio Pinchera94Carlo A. Pivato95Venerino Poletti96Claudia Ravaglia97Marco Rossato98Marianna Rossi99Anna Sabena100Francesco Salinaro101Vincenzo Sangiovanni102Carlo Sanrocco103Laura Scorzolini104Raffaella Sgariglia105Paola Giustina Simeone106Michele Spinicci107Enrico Maria Trecarichi108Giovanni Veronesi109Roberto Vettor110Andrea Vianello111Marco Vinceti112Marco Vinceti113Elena Visconti114Laura Vocciante115Raffaele De Caterina116Licia Iacoviello117Licia Iacoviello118The COVID-19 RISK and Treatments (CORIST) CollaborationMediterranea Cardiocentro, Napoli, ItalyDepartment of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, ItalyUOC Immunodeficienze Virali, National Institute for Infectious Diseases L. Spallanzani, IRCCS, Roma, ItalySection of Public Health, Department of Biomedical, Metabolic and Neural Sciences, University of Modena, Modena, ItalyIRCCS Policlinico San Donato, San Donato Milanese, ItalyDepartment of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, ItalyDivision of Infectious Diseases I, Fondazione IRCCS Policlinico San Matteo, Pavia, ItalyDepartment of Clinical, Surgical, Diagnostic, and Paediatric Sciences, University of Pavia, Pavia, ItalyFondazione Policlinico Universitario A. Gemelli IRCCS, Roma, ItalyUniversità Cattolica del Sacro Cuore- Dipartimento di Sicurezza e Bioetica Sede di Roma, Roma, ItalyDepartment of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Italy0Infectious Disease Unit, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, Modena, ItalyIRCCS Policlinico San Donato, San Donato Milanese, Italy1University of Eastern Piedmont, Maggiore della Carità Hospital, Novara, Italy2Humanitas Clinical and Research Hospital IRCCS, Rozzano, Italy3Department of Infectious Disease, Azienda Sanitaria Locale (AUSL) di Pescara, Pescara, Italy1University of Eastern Piedmont, Maggiore della Carità Hospital, Novara, Italy4Emergency Department, IRCCS Policlinico San Matteo Foundation, Pavia, Italy5Department of Internal Medicine, University of Pavia, Pavia, Italy6Department of Medicine and Aging, Clinica Medica, SS. Annunziata Hospital and University of Chieti, Chieti, Italy7School of Medicine, Vita-Salute San Raffaele University, Milano, Italy2Humanitas Clinical and Research Hospital IRCCS, Rozzano, Italy8HIV/AIDS Department, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Roma, Italy9Department of Medicine and Surgery, University of Insubria, Varese, Italy0UOC, Anestesia e Rianimazione, Dipartimento di Chirurgia Generale Ospedale Morgagni-Pierantoni, Forlì, Italy1Centro Cardiologico Monzino IRCCS, Milano, Italy2Cardiovascular Section, Department of Clinical Sciences and Community Health, University of Milano, Milano, Italy3UOC Infezioni Sistemiche dell'Immunodepresso, National Institute for Infectious Diseases L. Spallanzani, IRCCS, Rome, Italy4Department of Civil Environmental and Architectural Engineering, University of Padova, Padova, Italy5Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy6Department of Clinical and Experimental Medicine, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, Pisa, Italy7Department of Medical and Surgical Sciences and Advanced Technologies G.F. Ingrassia, University of Catania, Catania, Italy8Department of Experimental and Clinical Medicine, University of Florence and Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy9Ospedale del Mare, ASL Napoli 1, Napoli, Italy0UOC Malattie Infettive, Ospedale San Gerardo, ASST Monza, Monza, Italy1School of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy9Department of Medicine and Surgery, University of Insubria, Varese, Italy2Cardiovascular and Thoracic Department, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, Pisa, Italy3Infectious and Tropical Diseases Unit- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE) - University of Palermo, Palermo, Italy4Servizio di Anestesia e Rianimazione II UO Rianimazione Ospedale San Marco, AOU Policlinico-Vittorio Emanuele, Catania, Italy2Humanitas Clinical and Research Hospital IRCCS, Rozzano, ItalyFondazione Policlinico Universitario A. Gemelli IRCCS, Roma, ItalyFondazione Policlinico Universitario A. Gemelli IRCCS, Roma, ItalyUniversità Cattolica del Sacro Cuore- Dipartimento di Sicurezza e Bioetica Sede di Roma, Roma, Italy6Department of Medicine and Aging, Clinica Medica, SS. Annunziata Hospital and University of Chieti, Chieti, Italy3Infectious and Tropical Diseases Unit- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE) - University of Palermo, Palermo, Italy1University of Eastern Piedmont, Maggiore della Carità Hospital, Novara, Italy3Department of Infectious Disease, Azienda Sanitaria Locale (AUSL) di Pescara, Pescara, Italy5COVID-19 Unit, EE Ospedale Regionale F. Miulli, Acquaviva delle Fonti, Italy6Clinica Medica 3, Department of Medicine - DIMED, University Hospital of Padova, Padova, Italy7Department of Cardiology, Ospedale di Cremona, Cremona, Italy6Department of Medicine and Aging, Clinica Medica, SS. Annunziata Hospital and University of Chieti, Chieti, ItalyFondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy8Medical Direction, IRCCS Neuromed, Pozzilli, Italy7Department of Cardiology, Ospedale di Cremona, Cremona, Italy9UOC Malattie Infettive-Epatologia, National Institute for Infectious Diseases L. Spallanzani, IRCCS, Roma, ItalySection of Public Health, Department of Biomedical, Metabolic and Neural Sciences, University of Modena, Modena, Italy0UOC Infezioni Sistemiche e dell'Immunodepresso, Azienda Ospedaliera dei Colli, Ospedale Cotugno, Napoli, Italy1Ospedale di Boscotrecase - ASL Napoli 3, Napoli, Italy2Department of Clinical Medicine and Surgery, University of Naples Federico II, Napoli, Italy9Department of Medicine and Surgery, University of Insubria, Varese, Italy5Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy3Respiratory Pathophysiology Division, Department of Cardiologic, Thoracic and Vascular Sciences, University of Padova, Padova, Italy5COVID-19 Unit, EE Ospedale Regionale F. Miulli, Acquaviva delle Fonti, Italy5COVID-19 Unit, EE Ospedale Regionale F. Miulli, Acquaviva delle Fonti, Italy4UOC di Pneumologia, P.O. San Giuseppe Moscati, Taranto, Italy1University of Eastern Piedmont, Maggiore della Carità Hospital, Novara, ItalyFondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy7Department of Cardiology, Ospedale di Cremona, Cremona, Italy0UOC, Anestesia e Rianimazione, Dipartimento di Chirurgia Generale Ospedale Morgagni-Pierantoni, Forlì, Italy5ASST Milano Nord - Ospedale Edoardo Bassini Cinisello Balsamo, Milan, Italy6UOC Malattie Infettive e Tropicali, P.O. San Marco, AOU Policlinico-Vittorio Emanuele, Catania, Italy1Centro Cardiologico Monzino IRCCS, Milano, Italy2Cardiovascular Section, Department of Clinical Sciences and Community Health, University of Milano, Milano, Italy1Centro Cardiologico Monzino IRCCS, Milano, Italy2Cardiovascular Section, Department of Clinical Sciences and Community Health, University of Milano, Milano, Italy4UOC di Pneumologia, P.O. San Giuseppe Moscati, Taranto, Italy7UOC di Medicina - Presidio Ospedaliero S.Maria di Loreto Nuovo, Napoli, Italy8Medical Direction, IRCCS Neuromed, Pozzilli, Italy5COVID-19 Unit, EE Ospedale Regionale F. Miulli, Acquaviva delle Fonti, Italy8Infectious and Tropical Diseases Unit, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy6Department of Clinical and Experimental Medicine, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, Pisa, Italy6Department of Clinical and Experimental Medicine, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, Pisa, Italy0Infectious Disease Unit, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy9Dipartimento di Farmacia, Università di Pisa, Pisa, Italy3Respiratory Pathophysiology Division, Department of Cardiologic, Thoracic and Vascular Sciences, University of Padova, Padova, Italy5Department of Internal Medicine, University of Pavia, Pavia, Italy0Infectious Disease Unit, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy0UOC Malattie Infettive-Apparato Respiratorio, National Institute for Infectious Diseases L. Spallanzani, IRCCS, Roma, Italy7School of Medicine, Vita-Salute San Raffaele University, Milano, Italy1Computer Service, University of Molise, Campobasso, Italy2Medicina Interna. Ospedale di Ravenna, AUSL della Romagna, Ravenna, Italy6Department of Medicine and Aging, Clinica Medica, SS. Annunziata Hospital and University of Chieti, Chieti, Italy0UOC Malattie Infettive, Ospedale San Gerardo, ASST Monza, Monza, Italy2Department of Clinical Medicine and Surgery, University of Naples Federico II, Napoli, Italy2Humanitas Clinical and Research Hospital IRCCS, Rozzano, Italy3UOC Pneumologia, Dipartimento di Malattie Apparato Respiratorio e Torace, Ospedale Morgagni-Pierantoni, Forlì, Italy3UOC Pneumologia, Dipartimento di Malattie Apparato Respiratorio e Torace, Ospedale Morgagni-Pierantoni, Forlì, Italy6Clinica Medica 3, Department of Medicine - DIMED, University Hospital of Padova, Padova, Italy0UOC Malattie Infettive, Ospedale San Gerardo, ASST Monza, Monza, Italy4Emergency Department, IRCCS Policlinico San Matteo Foundation, Pavia, Italy4Emergency Department, IRCCS Policlinico San Matteo Foundation, Pavia, Italy0UOC Infezioni Sistemiche e dell'Immunodepresso, Azienda Ospedaliera dei Colli, Ospedale Cotugno, Napoli, Italy3Department of Infectious Disease, Azienda Sanitaria Locale (AUSL) di Pescara, Pescara, Italy4UOC Malattie Infettive ad Alta Intensità di Cura, National Institute for Infectious Diseases L. Spallanzani, IRCCS, Rome, Italy5ASST Milano Nord - Ospedale Edoardo Bassini Cinisello Balsamo, Milan, Italy3Department of Infectious Disease, Azienda Sanitaria Locale (AUSL) di Pescara, Pescara, Italy8Department of Experimental and Clinical Medicine, University of Florence and Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy8Infectious and Tropical Diseases Unit, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy9Department of Medicine and Surgery, University of Insubria, Varese, Italy6Clinica Medica 3, Department of Medicine - DIMED, University Hospital of Padova, Padova, Italy3Respiratory Pathophysiology Division, Department of Cardiologic, Thoracic and Vascular Sciences, University of Padova, Padova, ItalySection of Public Health, Department of Biomedical, Metabolic and Neural Sciences, University of Modena, Modena, Italy5Department of Epidemiology, Boston University School of Public Health, Boston, MA, United StatesFondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy7UOC di Medicina - Presidio Ospedaliero S.Maria di Loreto Nuovo, Napoli, Italy2Cardiovascular and Thoracic Department, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, Pisa, ItalyDepartment of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Italy9Department of Medicine and Surgery, University of Insubria, Varese, ItalyBackground: 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.https://www.frontiersin.org/articles/10.3389/fmed.2021.639970/fullCOVID-19SARS-CoV-2darunavirlopinavirin-hospital mortality |