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

Abstract

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.

CT-Based Risk Stratification for Intensive Care Need and Survival in COVID-19 Patients—A Simple Solution

“…The same tendency was shown in patients in need of ICU admission. Castelnuovo et al 2021 have shown that in addition to advanced age, conditions such as hypertension, underlying cardiovascular, pulmonary, or renal disease strongly influence patient outcome [28]. Our data also confirm the findings of a large-scale study in 10,021 hospitalized patients showing that pre-existing chronic pulmonary diseases are more frequent in patients needing invasive ventilation [6].…”

“…The observed improvement in subjective assessment is probably attributable to radiologists' increasing experience with the interpretation of imaging findings in COVID-19 patients and the use of structured reporting. Various studies show that structured reporting can help to install a baseline in reporting and thus enhance diagnostic performance (28). Therefore, it is reasonable to assume that well-trained radiologists, working in a level-1 center with high case numbers of COVID-19 patients, can achieve a performance comparable to that of the SSQ method.…”

“…Furthermore, therapies may also have an impact on outcome in age groups. For example, studies have shown that the combination of darunavir/cobicistat was associated with higher mortality in the elderly [28], whereas heparin may have a productive effect [29]. Older patient age is also considered a risk factor for a severe course of COVID-19 infection [27].…”

HIV and COVID-19: review of clinical course and outcomes

“… 49 , 205–212 A study of darunavir/cobicistat actually showed an increased mortality rate. 213 However, this was an observational study that may have been affected by confounders.…”

The association between first and second wave COVID-19 mortality in Italy

“…In addition, recent assessment of fatality rates between first and second waves in Italy showed that they were comparable [28]. Nonetheless, we cannot rule out that improvement in COVID-19 treatment may have decreased mortality during the pandemic, especially in the second wave, despite the lack of fully effective treatments [29][30][31]. Finally, vaccination had no role in curbing either of the two waves analyzed here, since almost no vaccine doses were administered in Italy in 2020.…”