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

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.