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

Autor:	Di Castelnuovo A; Mediterranea Cardiocentro, Napoli, Italy., Costanzo S; Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Italy., Antinori A; UOC Immunodeficienze Virali, National Institute for Infectious Diseases L. Spallanzani, IRCCS, Roma, Italy., Berselli N; Section of Public Health, Department of Biomedical, Metabolic and Neural Sciences, University of Modena, Modena, Italy., Blandi L; IRCCS Policlinico San Donato, San Donato Milanese, Italy., Bonaccio M; Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Italy., Bruno R; Division of Infectious Diseases I, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.; Department of Clinical, Surgical, Diagnostic, and Paediatric Sciences, University of Pavia, Pavia, Italy., Cauda R; Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy.; Università Cattolica del Sacro Cuore- Dipartimento di Sicurezza e Bioetica Sede di Roma, Roma, Italy., Gialluisi A; Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Italy., Guaraldi G; Infectious Disease Unit, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy., Menicanti L; IRCCS Policlinico San Donato, San Donato Milanese, Italy., Mennuni M; University of Eastern Piedmont, Maggiore della Carità Hospital, Novara, Italy., My I; Humanitas Clinical and Research Hospital IRCCS, Rozzano, Italy., Parruti A; Department of Infectious Disease, Azienda Sanitaria Locale (AUSL) di Pescara, Pescara, Italy., Patti G; University of Eastern Piedmont, Maggiore della Carità Hospital, Novara, Italy., Perlini S; Emergency Department, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.; Department of Internal Medicine, University of Pavia, Pavia, Italy., Santilli F; Department of Medicine and Aging, Clinica Medica, SS. Annunziata Hospital and University of Chieti, Chieti, Italy., Signorelli C; School of Medicine, Vita-Salute San Raffaele University, Milano, Italy., Stefanini GG; Humanitas Clinical and Research Hospital IRCCS, Rozzano, Italy., Vergori A; HIV/AIDS Department, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Roma, Italy., Ageno W; Department of Medicine and Surgery, University of Insubria, Varese, Italy., Aiello L; UOC, Anestesia e Rianimazione, Dipartimento di Chirurgia Generale Ospedale Morgagni-Pierantoni, Forlì, Italy., Agostoni P; Centro Cardiologico Monzino IRCCS, Milano, Italy.; Cardiovascular Section, Department of Clinical Sciences and Community Health, University of Milano, Milano, Italy., Al Moghazi S; UOC Infezioni Sistemiche dell'Immunodepresso, National Institute for Infectious Diseases L. Spallanzani, IRCCS, Rome, Italy., Arboretti R; Department of Civil Environmental and Architectural Engineering, University of Padova, Padova, Italy., Aucella F; Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy., Barbieri G; Department of Clinical and Experimental Medicine, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, Pisa, Italy., Barchitta M; Department of Medical and Surgical Sciences and Advanced Technologies G.F. Ingrassia, University of Catania, Catania, Italy., Bartoloni A; Department of Experimental and Clinical Medicine, University of Florence and Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy., Bologna C; Ospedale del Mare, ASL Napoli 1, Napoli, Italy., Bonfanti P; UOC Malattie Infettive, Ospedale San Gerardo, ASST Monza, Monza, Italy.; School of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy., Caiano L; Department of Medicine and Surgery, University of Insubria, Varese, Italy., Carrozzi L; Cardiovascular and Thoracic Department, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, Pisa, Italy., Cascio A; Infectious and Tropical Diseases Unit- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE) - University of Palermo, Palermo, Italy., Castiglione G; Servizio di Anestesia e Rianimazione II UO Rianimazione Ospedale San Marco, AOU Policlinico-Vittorio Emanuele, Catania, Italy., Chiarito M; Humanitas Clinical and Research Hospital IRCCS, Rozzano, Italy., Ciccullo A; Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy., Cingolani A; Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy.; Università Cattolica del Sacro Cuore- Dipartimento di Sicurezza e Bioetica Sede di Roma, Roma, Italy., Cipollone F; Department of Medicine and Aging, Clinica Medica, SS. Annunziata Hospital and University of Chieti, Chieti, Italy., Colomba C; Infectious and Tropical Diseases Unit- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE) - University of Palermo, Palermo, Italy., Colombo C; University of Eastern Piedmont, Maggiore della Carità Hospital, Novara, Italy., Crosta F; Department of Infectious Disease, Azienda Sanitaria Locale (AUSL) di Pescara, Pescara, Italy., Dalena G; COVID-19 Unit, EE Ospedale Regionale F. Miulli, Acquaviva delle Fonti, Italy., Dal Pra C; Clinica Medica 3, Department of Medicine - DIMED, University Hospital of Padova, Padova, Italy., Danzi GB; Department of Cardiology, Ospedale di Cremona, Cremona, Italy., D'Ardes D; Department of Medicine and Aging, Clinica Medica, SS. Annunziata Hospital and University of Chieti, Chieti, Italy., de Gaetano Donati K; Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy., Di Gennaro F; Medical Direction, IRCCS Neuromed, Pozzilli, Italy., Di Tano G; Department of Cardiology, Ospedale di Cremona, Cremona, Italy., D'Offizi G; UOC Malattie Infettive-Epatologia, National Institute for Infectious Diseases L. Spallanzani, IRCCS, Roma, Italy., Filippini T; Section of Public Health, Department of Biomedical, Metabolic and Neural Sciences, University of Modena, Modena, Italy., Maria Fusco F; UOC Infezioni Sistemiche e dell'Immunodepresso, Azienda Ospedaliera dei Colli, Ospedale Cotugno, Napoli, Italy., Gaudiosi C; Ospedale di Boscotrecase - ASL Napoli 3, Napoli, Italy., Gentile I; Department of Clinical Medicine and Surgery, University of Naples Federico II, Napoli, Italy., Gini G; Department of Medicine and Surgery, University of Insubria, Varese, Italy., Grandone E; Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy., Guarnieri G; Respiratory Pathophysiology Division, Department of Cardiologic, Thoracic and Vascular Sciences, University of Padova, Padova, Italy., Lamanna GLF; COVID-19 Unit, EE Ospedale Regionale F. Miulli, Acquaviva delle Fonti, Italy., Larizza G; COVID-19 Unit, EE Ospedale Regionale F. Miulli, Acquaviva delle Fonti, Italy., Leone A; UOC di Pneumologia, P.O. San Giuseppe Moscati, Taranto, Italy., Lio V; University of Eastern Piedmont, Maggiore della Carità Hospital, Novara, Italy., Losito AR; Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy., Maccagni G; Department of Cardiology, Ospedale di Cremona, Cremona, Italy., Maitan S; UOC, Anestesia e Rianimazione, Dipartimento di Chirurgia Generale Ospedale Morgagni-Pierantoni, Forlì, Italy., Mancarella S; ASST Milano Nord - Ospedale Edoardo Bassini Cinisello Balsamo, Milan, Italy., Manuele R; UOC Malattie Infettive e Tropicali, P.O. San Marco, AOU Policlinico-Vittorio Emanuele, Catania, Italy., Mapelli M; Centro Cardiologico Monzino IRCCS, Milano, Italy.; Cardiovascular Section, Department of Clinical Sciences and Community Health, University of Milano, Milano, Italy., Maragna R; Centro Cardiologico Monzino IRCCS, Milano, Italy.; Cardiovascular Section, Department of Clinical Sciences and Community Health, University of Milano, Milano, Italy., Marra L; UOC di Pneumologia, P.O. San Giuseppe Moscati, Taranto, Italy., Maresca G; UOC di Medicina - Presidio Ospedaliero S.Maria di Loreto Nuovo, Napoli, Italy., Marotta C; Medical Direction, IRCCS Neuromed, Pozzilli, Italy., Mastroianni F; COVID-19 Unit, EE Ospedale Regionale F. Miulli, Acquaviva delle Fonti, Italy., Mazzitelli M; Infectious and Tropical Diseases Unit, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy., Mengozzi A; Department of Clinical and Experimental Medicine, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, Pisa, Italy., Menichetti F; Department of Clinical and Experimental Medicine, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, Pisa, Italy., Milic J; Infectious Disease Unit, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy., Minutolo F; Dipartimento di Farmacia, Università di Pisa, Pisa, Italy., Molena B; Respiratory Pathophysiology Division, Department of Cardiologic, Thoracic and Vascular Sciences, University of Padova, Padova, Italy., Mussinelli R; Department of Internal Medicine, University of Pavia, Pavia, Italy., Mussini C; Infectious Disease Unit, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy., Musso M; UOC Malattie Infettive-Apparato Respiratorio, National Institute for Infectious Diseases L. Spallanzani, IRCCS, Roma, Italy., Odone A; School of Medicine, Vita-Salute San Raffaele University, Milano, Italy., Olivieri M; Computer Service, University of Molise, Campobasso, Italy., Pasi E; Medicina Interna. Ospedale di Ravenna, AUSL della Romagna, Ravenna, Italy., Perroni A; Department of Medicine and Aging, Clinica Medica, SS. Annunziata Hospital and University of Chieti, Chieti, Italy., Petri F; UOC Malattie Infettive, Ospedale San Gerardo, ASST Monza, Monza, Italy., Pinchera B; Department of Clinical Medicine and Surgery, University of Naples Federico II, Napoli, Italy., Pivato CA; Humanitas Clinical and Research Hospital IRCCS, Rozzano, Italy., Poletti V; UOC Pneumologia, Dipartimento di Malattie Apparato Respiratorio e Torace, Ospedale Morgagni-Pierantoni, Forlì, Italy., Ravaglia C; UOC Pneumologia, Dipartimento di Malattie Apparato Respiratorio e Torace, Ospedale Morgagni-Pierantoni, Forlì, Italy., Rossato M; Clinica Medica 3, Department of Medicine - DIMED, University Hospital of Padova, Padova, Italy., Rossi M; UOC Malattie Infettive, Ospedale San Gerardo, ASST Monza, Monza, Italy., Sabena A; Emergency Department, IRCCS Policlinico San Matteo Foundation, Pavia, Italy., Salinaro F; Emergency Department, IRCCS Policlinico San Matteo Foundation, Pavia, Italy., Sangiovanni V; UOC Infezioni Sistemiche e dell'Immunodepresso, Azienda Ospedaliera dei Colli, Ospedale Cotugno, Napoli, Italy., Sanrocco C; Department of Infectious Disease, Azienda Sanitaria Locale (AUSL) di Pescara, Pescara, Italy., Scorzolini L; UOC Malattie Infettive ad Alta Intensità di Cura, National Institute for Infectious Diseases L. Spallanzani, IRCCS, Rome, Italy., Sgariglia R; ASST Milano Nord - Ospedale Edoardo Bassini Cinisello Balsamo, Milan, Italy., Simeone PG; Department of Infectious Disease, Azienda Sanitaria Locale (AUSL) di Pescara, Pescara, Italy., Spinicci M; Department of Experimental and Clinical Medicine, University of Florence and Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy., Trecarichi EM; Infectious and Tropical Diseases Unit, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy., Veronesi G; Department of Medicine and Surgery, University of Insubria, Varese, Italy., Vettor R; Clinica Medica 3, Department of Medicine - DIMED, University Hospital of Padova, Padova, Italy., Vianello A; Respiratory Pathophysiology Division, Department of Cardiologic, Thoracic and Vascular Sciences, University of Padova, Padova, Italy., Vinceti M; Section of Public Health, Department of Biomedical, Metabolic and Neural Sciences, University of Modena, Modena, Italy.; Department of Epidemiology, Boston University School of Public Health, Boston, MA, United States., Visconti E; Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy., Vocciante L; UOC di Medicina - Presidio Ospedaliero S.Maria di Loreto Nuovo, Napoli, Italy., De Caterina R; Cardiovascular and Thoracic Department, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, Pisa, Italy., Iacoviello L; Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Italy.; Department of Medicine and Surgery, University of Insubria, Varese, Italy.
Jazyk:	angličtina
Zdroj:	Frontiers in medicine [Front Med (Lausanne)] 2021 Jun 09; Vol. 8, pp. 639970. Date of Electronic Publication: 2021 Jun 09 (Print Publication: 2021).
DOI:	10.3389/fmed.2021.639970
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (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.)
Databáze:	MEDLINE
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