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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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Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study
Author
Augusto Di Castelnuovo 1 ; Costanzo, Simona 2 ; Antinori, Andrea 3 ; Berselli, Nausicaa 4 ; Blandi, Lorenzo 5 ; Bonaccio, Marialaura 2 ; Bruno, Raffaele 6 ; Cauda, Roberto 7 ; Gialluisi, Alessandro 2 ; Guaraldi, Giovanni 8 ; Menicanti, Lorenzo 5 ; Mennuni, Marco 9 ; My, Ilaria 10 ; Parruti, Agostino 11 ; Patti, Giuseppe 9 ; Perlini, Stefano 12 ; Santilli, Francesca 13 ; Signorelli, Carlo 14 ; Stefanini, Giulio G 10 ; Vergori, Alessandra 15 ; Ageno, Walter 16 ; Aiello, Luca 17 ; Agostoni, Piergiuseppe 18 ; Samir Al Moghazi 19 ; Arboretti, Rosa 20 ; Aucella, Filippo 21 ; Barbieri, Greta 22 ; Barchitta, Martina 23 ; Bartoloni, Alessandro 24 ; Bologna, Carolina 25 ; Bonfanti, Paolo 26 ; Caiano, Lucia 16 ; Carrozzi, Laura 27 ; Cascio, Antonio 28 ; Castiglione, Giacomo 29 ; Chiarito, Mauro 10 ; Ciccullo, Arturo 30 ; Cingolani, Antonella 7 ; Cipollone, Francesco 13 ; Colomba, Claudia 28 ; Colombo, Crizia 9 ; Crosta, Francesco 11 ; Dalena, Giovanni 31 ; Chiara Dal Pra 32 ; Danzi, Gian Battista 33 ; D'Ardes, Damiano 13 ; Katleen de Gaetano Donati 30 ; Francesco Di Gennaro 34 ; Giuseppe Di Tano 33 ; D'Offizi, Gianpiero 35 ; Filippini, Tommaso 4 ; Fusco, Francesco Maria 36 ; Gaudiosi, Carlo 37 ; Gentile, Ivan 38 ; Gini, Giancarlo 16 ; Grandone, Elvira 21 ; Guarnieri, Gabriella 39 ; Lamanna, Gennaro L F 31 ; Larizza, Giovanni 31 ; Leone, Armando 40 ; Lio, Veronica 9 ; Losito, Angela Raffaella 30 ; Maccagni, Gloria 33 ; Maitan, Stefano 17 ; Mancarella, Sandro 41 ; Manuele, Rosa 42 ; Mapelli, Massimo 18 ; Maragna, Riccardo 18 ; Marra, Lorenzo 40 ; Maresca, Giulio 43 ; Marotta, Claudia 34 ; Mastroianni, Franco 31 ; Mazzitelli, Maria 44 ; Mengozzi, Alessandro 22 ; Menichetti, Francesco 22 ; Milic, Jovana 8 ; Minutolo, Filippo 45 ; Molena, Beatrice 39 ; Mussinelli, R 46 ; Mussini, Cristina 8 ; Musso, Maria 47 ; Odone, Anna 14 ; Olivieri, Marco 48 ; Pasi, Emanuela 49 ; Perroni, Annalisa 13 ; Petri, Francesco 50 ; Pinchera, Biagio 38 ; Pivato, Carlo A 10 ; Poletti, Venerino 51 ; Ravaglia, Claudia 51 ; Rossato, Marco 32 ; Rossi, Marianna 50 ; Sabena, Anna 52 ; Salinaro, Francesco 52 ; Sangiovanni, Vincenzo 36 ; Sanrocco, Carlo 11 ; Scorzolini, Laura 53 ; Sgariglia, Raffaella 41 ; Simeone, Paola Giustina 11 ; Spinicci, Michele 24 ; Trecarichi, Enrico Maria 44 ; Veronesi, Giovanni 16 ; Vettor, Roberto 32 ; Vianello, Andrea 39 ; Vinceti, Marco 54 ; Visconti, Elena 30 ; Vocciante, Laura 43 ; De Caterina, Raffaele 27 ; Iacoviello, Licia 55
1 Mediterranea Cardiocentro, Napoli, Italy
2 Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Italy
3 UOC Immunodeficienze Virali, National Institute for Infectious Diseases L. Spallanzani, IRCCS, Roma, Italy
4 Section of Public Health, Department of Biomedical, Metabolic and Neural Sciences, University of Modena, Modena, Italy
5 IRCCS Policlinico San Donato, San Donato Milanese, Italy
6 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
7 Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy, Università Cattolica del Sacro Cuore- Dipartimento di Sicurezza e Bioetica Sede di Roma, Roma, Italy
8 Infectious Disease Unit, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy
9 University of Eastern Piedmont, Maggiore della Carità Hospital, Novara, Italy
10 Humanitas Clinical and Research Hospital IRCCS, Rozzano, Italy
11 Department of Infectious Disease, Azienda Sanitaria Locale (AUSL) di Pescara, Pescara, Italy
12 Emergency Department, IRCCS Policlinico San Matteo Foundation, Pavia, Italy, Department of Internal Medicine, University of Pavia, Pavia, Italy
13 Department of Medicine and Aging, Clinica Medica, SS. Annunziata Hospital and University of Chieti, Chieti, Italy
14 School of Medicine, Vita-Salute San Raffaele University, Milano, Italy
15 HIV/AIDS Department, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Roma, Italy
16 Department of Medicine and Surgery, University of Insubria, Varese, Italy
17 UOC, Anestesia e Rianimazione, Dipartimento di Chirurgia Generale Ospedale Morgagni-Pierantoni, Forlì, Italy
18 Centro Cardiologico Monzino IRCCS, Milano, Italy, Cardiovascular Section, Department of Clinical Sciences and Community Health, University of Milano, Milano, Italy
19 UOC Infezioni Sistemiche dell'Immunodepresso, National Institute for Infectious Diseases L. Spallanzani, IRCCS, Rome, Italy
20 Department of Civil Environmental and Architectural Engineering, University of Padova, Padova, Italy
21 Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy
22 Department of Clinical and Experimental Medicine, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, Pisa, Italy
23 Department of Medical and Surgical Sciences and Advanced Technologies G.F. Ingrassia, University of Catania, Catania, Italy
24 Department of Experimental and Clinical Medicine, University of Florence and Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy
25 Ospedale del Mare, ASL Napoli 1, Napoli, Italy
26 UOC Malattie Infettive, Ospedale San Gerardo, ASST Monza, Monza, Italy, School of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy
27 Cardiovascular and Thoracic Department, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, Pisa, Italy
28 Infectious and Tropical Diseases Unit- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE) - University of Palermo, Palermo, Italy
29 Servizio di Anestesia e Rianimazione II UO Rianimazione Ospedale San Marco, AOU Policlinico-Vittorio Emanuele, Catania, Italy
30 Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy
31 COVID-19 Unit, EE Ospedale Regionale F. Miulli, Acquaviva delle Fonti, Italy
32 Clinica Medica 3, Department of Medicine - DIMED, University Hospital of Padova, Padova, Italy
33 Department of Cardiology, Ospedale di Cremona, Cremona, Italy
34 Medical Direction, IRCCS Neuromed, Pozzilli, Italy
35 UOC Malattie Infettive-Epatologia, National Institute for Infectious Diseases L. Spallanzani, IRCCS, Roma, Italy
36 UOC Infezioni Sistemiche e dell'Immunodepresso, Azienda Ospedaliera dei Colli, Ospedale Cotugno, Napoli, Italy
37 Ospedale di Boscotrecase - ASL Napoli 3, Napoli, Italy
38 Department of Clinical Medicine and Surgery, University of Naples Federico II, Napoli, Italy
39 Respiratory Pathophysiology Division, Department of Cardiologic, Thoracic and Vascular Sciences, University of Padova, Padova, Italy
40 UOC di Pneumologia, P.O. San Giuseppe Moscati, Taranto, Italy
41 ASST Milano Nord - Ospedale Edoardo Bassini Cinisello Balsamo, Milan, Italy
42 UOC Malattie Infettive e Tropicali, P.O. San Marco, AOU Policlinico-Vittorio Emanuele, Catania, Italy
43 UOC di Medicina - Presidio Ospedaliero S.Maria di Loreto Nuovo, Napoli, Italy
44 Infectious and Tropical Diseases Unit, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy
45 Dipartimento di Farmacia, Università di Pisa, Pisa, Italy
46 Department of Internal Medicine, University of Pavia, Pavia, Italy
47 UOC Malattie Infettive-Apparato Respiratorio, National Institute for Infectious Diseases L. Spallanzani, IRCCS, Roma, Italy
48 Computer Service, University of Molise, Campobasso, Italy
49 Medicina Interna. Ospedale di Ravenna, AUSL della Romagna, Ravenna, Italy
50 UOC Malattie Infettive, Ospedale San Gerardo, ASST Monza, Monza, Italy
51 UOC Pneumologia, Dipartimento di Malattie Apparato Respiratorio e Torace, Ospedale Morgagni-Pierantoni, Forlì, Italy
52 Emergency Department, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
53 UOC Malattie Infettive ad Alta Intensità di Cura, National Institute for Infectious Diseases L. Spallanzani, IRCCS, Rome, Italy
54 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
55 Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Italy, Department of Medicine and Surgery, University of Insubria, Varese, Italy
1 Mediterranea Cardiocentro, Napoli, Italy
2 Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Italy
3 UOC Immunodeficienze Virali, National Institute for Infectious Diseases L. Spallanzani, IRCCS, Roma, Italy
4 Section of Public Health, Department of Biomedical, Metabolic and Neural Sciences, University of Modena, Modena, Italy
5 IRCCS Policlinico San Donato, San Donato Milanese, Italy
6 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
7 Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy, Università Cattolica del Sacro Cuore- Dipartimento di Sicurezza e Bioetica Sede di Roma, Roma, Italy
8 Infectious Disease Unit, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy
9 University of Eastern Piedmont, Maggiore della Carità Hospital, Novara, Italy
10 Humanitas Clinical and Research Hospital IRCCS, Rozzano, Italy
11 Department of Infectious Disease, Azienda Sanitaria Locale (AUSL) di Pescara, Pescara, Italy
12 Emergency Department, IRCCS Policlinico San Matteo Foundation, Pavia, Italy, Department of Internal Medicine, University of Pavia, Pavia, Italy
13 Department of Medicine and Aging, Clinica Medica, SS. Annunziata Hospital and University of Chieti, Chieti, Italy
14 School of Medicine, Vita-Salute San Raffaele University, Milano, Italy
15 HIV/AIDS Department, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Roma, Italy
16 Department of Medicine and Surgery, University of Insubria, Varese, Italy
17 UOC, Anestesia e Rianimazione, Dipartimento di Chirurgia Generale Ospedale Morgagni-Pierantoni, Forlì, Italy
18 Centro Cardiologico Monzino IRCCS, Milano, Italy, Cardiovascular Section, Department of Clinical Sciences and Community Health, University of Milano, Milano, Italy
19 UOC Infezioni Sistemiche dell'Immunodepresso, National Institute for Infectious Diseases L. Spallanzani, IRCCS, Rome, Italy
20 Department of Civil Environmental and Architectural Engineering, University of Padova, Padova, Italy
21 Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy
22 Department of Clinical and Experimental Medicine, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, Pisa, Italy
23 Department of Medical and Surgical Sciences and Advanced Technologies G.F. Ingrassia, University of Catania, Catania, Italy
24 Department of Experimental and Clinical Medicine, University of Florence and Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy
25 Ospedale del Mare, ASL Napoli 1, Napoli, Italy
26 UOC Malattie Infettive, Ospedale San Gerardo, ASST Monza, Monza, Italy, School of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy
27 Cardiovascular and Thoracic Department, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, Pisa, Italy
28 Infectious and Tropical Diseases Unit- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE) - University of Palermo, Palermo, Italy
29 Servizio di Anestesia e Rianimazione II UO Rianimazione Ospedale San Marco, AOU Policlinico-Vittorio Emanuele, Catania, Italy
30 Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy
31 COVID-19 Unit, EE Ospedale Regionale F. Miulli, Acquaviva delle Fonti, Italy
32 Clinica Medica 3, Department of Medicine - DIMED, University Hospital of Padova, Padova, Italy
33 Department of Cardiology, Ospedale di Cremona, Cremona, Italy
34 Medical Direction, IRCCS Neuromed, Pozzilli, Italy
35 UOC Malattie Infettive-Epatologia, National Institute for Infectious Diseases L. Spallanzani, IRCCS, Roma, Italy
36 UOC Infezioni Sistemiche e dell'Immunodepresso, Azienda Ospedaliera dei Colli, Ospedale Cotugno, Napoli, Italy
37 Ospedale di Boscotrecase - ASL Napoli 3, Napoli, Italy
38 Department of Clinical Medicine and Surgery, University of Naples Federico II, Napoli, Italy
39 Respiratory Pathophysiology Division, Department of Cardiologic, Thoracic and Vascular Sciences, University of Padova, Padova, Italy
40 UOC di Pneumologia, P.O. San Giuseppe Moscati, Taranto, Italy
41 ASST Milano Nord - Ospedale Edoardo Bassini Cinisello Balsamo, Milan, Italy
42 UOC Malattie Infettive e Tropicali, P.O. San Marco, AOU Policlinico-Vittorio Emanuele, Catania, Italy
43 UOC di Medicina - Presidio Ospedaliero S.Maria di Loreto Nuovo, Napoli, Italy
44 Infectious and Tropical Diseases Unit, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy
45 Dipartimento di Farmacia, Università di Pisa, Pisa, Italy
46 Department of Internal Medicine, University of Pavia, Pavia, Italy
47 UOC Malattie Infettive-Apparato Respiratorio, National Institute for Infectious Diseases L. Spallanzani, IRCCS, Roma, Italy
48 Computer Service, University of Molise, Campobasso, Italy
49 Medicina Interna. Ospedale di Ravenna, AUSL della Romagna, Ravenna, Italy
50 UOC Malattie Infettive, Ospedale San Gerardo, ASST Monza, Monza, Italy
51 UOC Pneumologia, Dipartimento di Malattie Apparato Respiratorio e Torace, Ospedale Morgagni-Pierantoni, Forlì, Italy
52 Emergency Department, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
53 UOC Malattie Infettive ad Alta Intensità di Cura, National Institute for Infectious Diseases L. Spallanzani, IRCCS, Rome, Italy
54 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
55 Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Italy, Department of Medicine and Surgery, University of Insubria, Varese, Italy
Frontiers in Medicine; Lausanne
Volume
8
First page
639970
Number of pages
12
Publication year
2021
Publication date
Jun 2021
Place of publication
Lausanne
Country of publication
Switzerland
Publication subject
e-ISSN
2296858X
Source type
Scholarly Journal
Language of publication
English
Document type
Journal Article
Publication history
Online publication date
2021-06-09
Milestone dates
2020-12-10 (Recieved); 2021-05-05 (Accepted)
Publication history
First posting date
09 Jun 2021
ProQuest document ID
3272709870
Document URL
https://www.proquest.com/scholarly-journals/lopinavir-ritonavir-darunavir-cobicistat/docview/3272709870/se-2?accountid=208611
Copyright
© 2021. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
Last updated
2025-11-19
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