Frontiers in medicine · 2021

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

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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, COVID-19 RISK and Treatments (CORIST) Collaboration

Аннотация

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.

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

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Аннотация