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

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

Impact of chronic liver disease upon admission on COVID-19 in-hospital mortality: Findings from COVOCA study.

BackgroundItaly has been the first Western country to be heavily affected by the spread of SARS-COV-2 infection and among the pioneers of the clinical management of pandemic. To improve the outcome, identification of patients at the highest risk seems mandatory.ObjectivesAim of this study is to identify comorbidities and clinical conditions upon admission associated with in-hospital mortality in several COVID Centers in Campania Region (Italy).MethodsCOVOCA is a multicentre retrospective observational cohort study, which involved 18 COVID Centers throughout Campania Region, Italy. Data were collected from patients who completed their hospitalization between March-June 2020. The endpoint was in-hospital mortality, assessed either from data at discharge or death certificate, whilst all exposure variables were collected at hospital admission.ResultsAmong 618 COVID-19 hospitalized patients included in the study, 143 in-hospital mortality events were recorded, with a cumulative incidence of about 23%. At multivariable logistic analysis, male sex (OR 2.63, 95%CI 1.42-4.90; p = 0.001), Chronic Liver Disease (OR 5.88, 95%CI 2.39-14.46; pConclusionMortality of patients hospitalized for COVID-19 appears strongly affected by both clinical conditions on admission and comorbidities. Originally, we observed a very poor outcome in subjects with a chronic liver disease, alongside with an increase of hepatic damage

Lack of effect on in-hospital mortality of drugs used during COVID-19 pandemic: Findings of the retrospective multicenter COVOCA study

INTRODUCTION: During COVID-19 pandemic, the use of several drugs has represented the worldwide clinical practice. However, though the current increase of knowledge about the disease, there is still no effective treatment for the usage of drugs. Thus, we retrospectively assessed use and effects of therapeutic regimens in hospitalized patients on in-hospital mortality. METHODS: COVOCA is a retrospective observational cohort study on 18 COVID centres throughout Campania Region Hospitals. We included adult patients with confirmed SARS-CoV-2 infection, discharged/dead between March/June 2020. RESULTS: 618 patients were included, with an overall in-hospital cumulative mortality incidence of 23.1%. Most prescribed early treatments were antivirals (72%), antibiotics (65%) and hydroxychloroquine/anticoagulants (≈50%). Tocilizumab, indeed, was largely prescribed late during hospitalization. Multivariable models, with a cut-off at day 2 for early COVID-19 therapy administration, did not disclose any significant association of a single drug administration on the clinical outcome. DISCUSSION: COVOCA represents the first multicenter database in Campania region. None drug class used during the pandemic significantly modified the outcome, regardless of therapy beginning, both overall and net of those already in non-invasive ventilation (NIV)/ orotracheal intubation (OTI) at hospitalization. Our cumulative incidence of mortality seems lower than other described during the same period, particularly in Northern Italy

Heparin in COVID-19 patients is associated with reduced in-hospital mortality: the multicentre Italian CORIST Study

INTRODUCTION: A hypercoagulable condition was described in patients with COVID-19 and proposed as a possible pathogenic mechanism contributing to disease progression and lethality.AIM: We evaluated if in-hospital administration of heparin improved survival in a large cohort of Italian COVID-19 patients.METHODS: In a retrospective observational study, 2,574 unselected patients hospitalised in 30 clinical centres in Italy from February 19, 2020 to May 23, 2020 with laboratory-confirmed SARS-CoV-2 infection, were analysed. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received heparin (low-molecular weight heparin (LMWH) or unfractionated heparin (UFH)) with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores.RESULTS: Out of 2,574 COVID-19 patients, 70.1% received heparin. LMWH was largely the most used formulation (99.5%). Death rates for patients receiving heparin or not were 7.4 and 14.0 per 1,000 person-days, respectively. After adjustment for propensity scores, we found a 40% lower risk of death in patients receiving heparin (HR=0.60; 95%CI: 0.49 to 0.74; E-value=2.04). This association was particularly evident in patients with a higher severity of disease or strong coagulation activation.CONCLUSIONS: In-hospital heparin treatment was associated with lower mortality, particularly in severely ill COVID-19 patients and in those with strong coagulation activation. The results from randomised clinical trials are eagerly awaited to provide clear-cut recommendations

RAAS inhibitors are not associated with mortality in COVID-19 patients: Findings from an observational multicenter study in Italy and a meta-analysis of 19 studies

Objective: The hypothesis that been set forward that use of Renin Angiotensin Aldosterone System (RAAS) inhibitors is associated with COVID-19 severity. We set-up a multicenter Italian collaboration (CORIST Project, ClinicalTrials.gov ID: NCT04318418) to retrospectively investigate the relationship between RAAS inhibitors and COVID-19 in-hospital mortality. We also carried out an updated meta-analysis on the relevant studies.Methods: We analyzed 4069 unselected patients with laboratory-confirmed SARS-CoV-2 infection and hospitalized in 34 clinical centers in Italy from February 19, 2020 to May 23, 2020. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received angiotensin-converting-enzyme inhibitors (ACEeI) or angiotensin-receptor blockers (ARB) with patients who did not. Articles for the meta-analysis were retrieved until July 13th, 2020 by searching in web-based libraries, and data were combined using the general variance-based method.Results: Out of 4069 COVID-19 patients, 13.5% and 13.3% received ACE-I or ARB, respectively. Use of neither ACE-I nor ARB was associated with mortality (multivariable hazard ratio (HR) adjusted also for COVID-19 treatments: 0.96, 95% confidence interval 0.77-1.20 and HR = 0.89, 0.67-1.19 for ACE-I and ARB, respectively). Findings were similar restricting the analysis to hypertensive (N = 2057) patients (HR = 1.00, 0.78-1.26 and HR = 0.88, 0.65-1.20) or when ACE-I or ARB were considered as a single group. Results from the meta-analysis (19 studies, 29,057 COVID-19 adult patients, 9700 with hypertension) confirmed the absence of association.Conclusions: In this observational study and meta-analysis of the literature, ACE-I or ARB use was not associated with severity or in-hospital mortality in COVID-19 patients

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

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

Use of hydroxychloroquine in hospitalised COVID-19 patients is associated with reduced mortality: Findings from the observational multicentre Italian CORIST study

Hydroxychloroquine (HCQ) was proposed as potential treatment for COVID-19