Association of Different Risk Scores and 30-Day Mortality in Kidney Transplant Recipients with COVID-19.

Background and Objectives: Clinical risk scores were poorly examined in kidney transplant recipients (KTR) with COVID-19. Materials and Methods: This observational study compared the association and discrimination of clinical risk scores (MEWS, qCSI, VACO, PSI/PORT, CCI, MuLBSTA, ISTH-DIC, COVID-GRAM and 4C) with 30-day mortality in 65 hospitalized KTRs with COVID-19. Cox regression was used to derive hazard ratios (HR) and 95% confidence intervals (95% CI), and discrimination was assessed by Harrell's C. Results: A significant association with 30-day mortality was demonstrated for MEWS (HR 1.65 95% CI 1.21-2.25, p = 0.002); qCSI (HR 1.32 95% CI 1.15-1.52, p < 0.001); PSI/PORT (HR 1.04 95% CI 1.02-1.07, p = 0.001); CCI (HR 1.79 95% CI 1.13-2.83, p = 0.013); MuLBSTA (HR 1.31 95% CI 1.05-1.64, p = 0.017); COVID-GRAM (HR 1.03 95% CI 1.01-1.06, p = 0.004); and 4C (HR 1.79 95% CI 1.40-2.31, p < 0.001). After multivariable adjustment, significant association persisted for qCSI (HR 1.33 95% CI 1.11-1.59, p = 0.002); PSI/PORT (HR 1.04 95% CI 1.01-1.07, p = 0.012); MuLBSTA (HR 1.36 95% CI 1.01-1.85, p = 0.046); and 4C Mortality Score (HR 1.93 95% CI 1.45-2.57, p < 0.001) risk scores. The best discrimination was observed with the 4C score (Harrell's C = 0.914). Conclusions: Risk scores such as qCSI, PSI/PORT and 4C showed the best association with 30-day mortality amongst KTRs with COVID-19.

Performance of Derived Laboratory Biomarkers with Regard to 30-Day Mortality in Kidney Transplant Recipients with COVID-19.

There are limited data on the performance of laboratory-derived biomarkers in kidney transplant recipients (KTR) with COVID-19. This observational study enrolled 65 KTR with COVID-19 who were treated at the University Hospital of Split up to March 2022. Laboratory-derived biomarkers (neutrophile-to-lymphocyte (NLR) ratio, platelet-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, De Ritis ratio, C-reactive protein (CRP)-to-albumin ratio, lactate dehydrogenase (LDH)-to-hemoglobin ratio, CRP-to-lymphocyte ratio, red cell distribution width-to-albumin ratio, platelet-to-albumin ratio, D-Dimer-to-albumin ratio, D-Dimer-to-NLR ratio, LDH-to-albumin ratio, and LDH-to-white blood cell (WBC) ratio) were calculated, and their performance with regard to 30-day mortality was determined. Mortality events occurred in 12 patients (18.5%), which was significantly associated with increased De Ritis (HR 3.83, 95% CI 1.57-9.35, p = 0.003), CRP-to-albumin (HR 1.36, 95% CI 1.13-1.64, p = 0.001), LDH-to-hemoglobin (HR 1.44, 95% CI 1.07-1.92, p = 0.015), CRP-to-lymphocyte (HR 1.03, 95% CI 1.01-1.07, p = 0.003), D-dimer-to-albumin (HR 4.94, 95% CI 1.38-7.24, p = 0.038), LDH-to-albumin (HR 1.20, 95% CI 1.05-1.36, p = 0.008), and LDH-to-WBC (HR 1.03 95% CI 1.01-1.05, p = 0.024) ratios. Out of these, the best area-under-the-curve (AUC) values were achieved with De Ritis (AUC 0.691), CRP-to-albumin (AUC 0.764), LDH-to-hemoglobin (AUC 0.877), CRP-to-lymphocyte (AUC 0.739), and LDH-to-albumin (AUC 0.827) ratios, while the best discrimination displayed LDH-to-hemoglobin ratio (Harrell's C 0.808 and Somers' D 0.616). The overall calibration was satisfactory for all models. Derived laboratory biomarkers such as the de Ritis, CRP-to-albumin, LDH-to-hemoglobin, CRP-to-lymphocyte, and LDH-to-albumin ratios show significant association and discrimination with all-cause mortality in KTR with COVID-19, suggesting its potential risk stratification role.

Association of the novel CROW-65 risk score and mortality in hospitalized kidney transplant recipients with COVID-19 : A retrospective observational study.

BACKGROUND: Kidney transplant recipients (KTR) are a group of patients with heterogeneous risks for adverse outcomes with COVID-19, but risk stratification tools in this patient group are lacking. METHODS AND PARTICIPANTS: This retrospective observational, hypothesis-generating study included 49 hospitalized adult KTR patients with COVID-19 at the University Hospital of Split (August 2020 to October 2021) and evaluated the performance of novel risk score CROW-65 (age, Charlson Comorbidity Index [CCI] lactate dehydrogenase to white blood cell [LDH:WBC] ratio, and respiratory rate oxygenation [ROX index]). The primary outcome of the study was 30-day postdischarge all-cause mortality. RESULTS: A total of 8 fatal events (16.3%) occurred during the study follow-up. When comparing CROW-65 by survival status, it was significantly increased in patients with fatal event (P < 0.001). Using the Cox proportional hazards regression analysis, the CROW-65 risk score showed statistically significant association with mortality (HR 1.11, 95% CI 1.01-1.23, P = 0.027), while receiving operator characteristics (ROC) showed significant discrimination of all-cause mortality with an AUC of 0.85 (95% CI 0.72-0.94, P < 0.001), and satisfactory calibration (χ2 4.91, P = 0.555 and Harrell's C 0.835). Finally, survival Kaplan-Meier analysis confirmed significantly higher cumulative incidence of mortality with increasing risk score tertiles and curve separation after 13 days (P = 0.009). CONCLUSION: A novel risk score CROW-65 showed significant association with all-cause mortality in KTR yielding important hypothesis-generating findings. Further powered studies should reassess the performance of CROW-65 risk score in this population, including predictability, calibration and discrimination.

Effects of Different Inhalation Therapy on Ventilator-Associated Pneumonia in Ventilated COVID-19 Patients: A Randomized Controlled Trial.

The effect of routine inhalation therapy on ventilator-associated pneumonia (VAP) in mechanically ventilated patients with the coronavirus disease (COVID-19) has not been well-defined. This randomized controlled trial included 175 eligible adult patients with COVID-19 who were treated with mechanical ventilation at the University Hospital of Split between October 2020 and June 2021. Patients were randomized and allocated to a control group (no routine inhalation) or one of the treatment arms (inhalation of N-acetylcysteine; 5% saline solution; or 8.4% sodium bicarbonate). The primary outcome was the incidence of VAP, while secondary outcomes included all-cause mortality. Routine inhalation therapy had no effect on the incidence of bacterial or fungal VAP nor on all-cause mortality (p > 0.05). Secondary analyses revealed a significant reduction of Gram-positive and methicillin-resistant Staphylococcus aureus (MRSA) VAP in the treatment groups. Specifically, the bicarbonate group had a statistically significantly lower incidence of Gram-positive bacterial VAP (4.8%), followed by the N-acetylcysteine group (10.3%), 5% saline group (19.0%), and control group (34.6%; p = 0.001). This difference was driven by a lower incidence of MRSA VAP in the bicarbonate group (2.4%), followed by the N-acetylcysteine group (7.7%), 5% saline group (14.3%), and control group (34.6%; p < 0.001). Longer duration of ventilator therapy was the only significant, independent predictor of any bacterial or fungal VAP in the multivariate analysis (aOR 1.14, 95% CI 1.01-1.29, p = 0.038 and aOR 1.05, 95% CI 1.01-1.10, p = 0.028, respectively). In conclusion, inhalation therapy had no effect on the overall VAP incidence or all-cause mortality. Further studies should explore the secondary findings of this study such as the reduction of Gram-positive or MRSA-caused VAP in treated patients.

In-Hospital Mortality of COVID-19 Patients Treated with High-Flow Nasal Oxygen: Evaluation of Biomarkers and Development of the Novel Risk Score Model CROW-65.

To replace mechanical ventilation (MV), which represents the cornerstone therapy in severe COVID-19 cases, high-flow nasal oxygen (HFNO) therapy has recently emerged as a less-invasive therapeutic possibility for those patients. Respecting the risk of MV delay as a result of HFNO use, we aimed to evaluate which parameters could determine the risk of in-hospital mortality in HFNO-treated COVID-19 patients. This single-center cohort study included 102 COVID-19-positive patients treated with HFNO. Standard therapeutic methods and up-to-date protocols were used. Patients who underwent a fatal event (41.2%) were significantly older, mostly male patients, and had higher comorbidity burdens measured by CCI. In a univariate analysis, older age, shorter HFNO duration, ventilator initiation, higher CCI and lower ROX index all emerged as significant predictors of adverse events (p < 0.05). Variables were dichotomized and included in the multivariate analysis to define their relative weights in the computed risk score model. Based on this, a risk score model for the prediction of in-hospital mortality in COVID-19 patients treated with HFNO consisting of four variables was defined: CCI > 4, ROX index ≤ 4.11, LDH-to-WBC ratio, age > 65 years (CROW-65). The main purpose of CROW-65 is to address whether HFNO should be initiated in the subgroup of patients with a high risk of in-hospital mortality.