Anticoagulation strategies and risk of bleeding events in critically ill COVID-19 patients.

OBJECTIVE: To evaluate the rate of thrombosis, bleeding and mortality comparing anticoagulant doses in critically ill COVID-19 patients. DESIGN: Retrospective observational and analytical cohort study. SETTING: COVID-19 patients admitted to the intensive care unit of a tertiary hospital between March and April 2020. PATIENTS: 201 critically ill COVID-19 patients were included. Patients were categorized into three groups according to the highest anticoagulant dose received during hospitalization: prophylactic, intermediate and therapeutic. INTERVENTIONS: The incidence of venous thromboembolism (VTE), bleeding and mortality was compared between groups. We performed two logistic multivariable regressions to test the association between VTE and bleeding and the anticoagulant regimen. MAIN VARIABLES OF INTEREST: VTE, bleeding and mortality. RESULTS: 78 patients received prophylactic, 94 intermediate and 29 therapeutic doses. No differences in VTE and mortality were found, while bleeding events were more frequent in the therapeutic (31%) and intermediate (15%) dose group than in the prophylactic group (5%) (p<0.001 and p<0.05 respectively). The anticoagulant dose was the strongest determinant for bleeding (odds ratio 2.4, 95% confidence interval 1.26-4.58, p=0.008) but had no impact on VTE. CONCLUSIONS: Intermediate and therapeutic doses appear to have a higher risk of bleeding without a decrease of VTE events and mortality in critically ill COVID-19 patients.

Elevated plasma levels of epithelial and endothelial cell markers in COVID-19 survivors with reduced lung diffusing capacity six months after hospital discharge.

BACKGROUND: Some COVID-19 survivors present lung function abnormalities during follow-up, particularly reduced carbon monoxide lung diffusing capacity (DLCO). To investigate risk factors and underlying pathophysiology, we compared the clinical characteristics and levels of circulating pulmonary epithelial and endothelial markers in COVID-19 survivors with normal or reduced DLCO 6 months after discharge. METHODS: Prospective, observational study. Clinical characteristics during hospitalization, and spirometry, DLCO and plasma levels of epithelial (surfactant protein (SP) A (SP-A), SP-D, Club cell secretory protein-16 (CC16) and secretory leukocyte protease inhibitor (SLPI)), and endothelial (soluble intercellular adhesion molecule 1 (sICAM-1), soluble E-selectin and Angiopoietin-2) 6 months after hospital discharge were determined in 215 COVID-19 survivors. RESULTS: DLCO was < 80% ref. in 125 (58%) of patients, who were older, more frequently smokers, had hypertension, suffered more severe COVID-19 during hospitalization and refer persistent dyspnoea 6 months after discharge. Multivariate regression analysis showed that age ≥ 60 years and severity score of the acute episode ≥ 6 were independent risk factors of reduced DLCO 6 months after discharge. Levels of epithelial (SP-A, SP-D and SLPI) and endothelial (sICAM-1 and angiopoietin-2) markers were higher in patients with reduced DLCO, particularly in those with DLCO ≤ 50% ref. Circulating SP-A levels were associated with the occurrence of acute respiratory distress syndrome (ARDS), organizing pneumonia and pulmonary embolisms during hospitalization. CONCLUSIONS: Reduced DLCO is common in COVID-19 survivors 6 months after hospital discharge, especially in those older than 60 years with very severe acute disease. In these individuals, elevated levels of epithelial and endothelial markers suggest persistent lung damage.

Role of respiratory intermediate care units during the SARS-CoV-2 pandemic.

RATIONALE: The SARS-CoV2 pandemic increased exponentially the need for both Intensive (ICU) and Intermediate Care Units (RICU). The latter are of particular importance because they can play a dual role in critical and post-critical care of COVID-19 patients. Here, we describe the setup of 2 new RICUs in our institution to face the SARS-CoV-2 pandemic and discuss the clinical characteristics and outcomes of the patients attended. METHODS: Retrospective analysis of the characteristics and outcomes of COVID-19 patients admitted to 2 new RICUs built specifically in our institution to face the first wave of the SARS-CoV-2 pandemic, from April 1 until May 30, 2020. RESULTS: During this period, 106 COVID-19 patients were admitted to these 2 RICUs, 65 of them (61%) transferred from an ICU (step-down) and 41 (39%) from the ward or emergency room (step-up). Most of them (72%) were male and mean age was 66 ± 12 years. 31% of them required support with oxygen therapy via high-flow nasal cannula (HFNC) and 14% non-invasive ventilation (NIV). 42 of the 65 patients stepping down (65%) had a previous tracheostomy performed and most of them (74%) were successfully decannulated during their stay in the RICU. Length of stay was 7 [4-11] days. 90-day mortality was 19% being significantly higher in stepping up patients than in those transferred from the ICU (25 vs. 10% respectively; p < 0.001). CONCLUSIONS: RICUs are a valuable hospital resource to respond to the challenges of the SARS-CoV-2 pandemic both to treat deteriorating and recovering COVID-19 patients.

Low birth weight as a potential risk factor for severe COVID-19 in adults.

The identification of factors predisposing to severe COVID-19 in young adults remains partially characterized. Low birth weight (LBW) alters cardiovascular and lung development and predisposes to adult disease. We hypothesized that LBW is a risk factor for severe COVID-19 in non-elderly subjects. We analyzed a prospective cohort of 397 patients (18-70 years) with laboratory-confirmed SARS-CoV-2 infection attended in a tertiary hospital, where 15% required admission to Intensive Care Unit (ICU). Perinatal and current potentially predictive variables were obtained from all patients and LBW was defined as birth weight ≤ 2.500 g. Age (adjusted OR (aOR) 1.04 [1-1.07], P = 0.012), male sex (aOR 3.39 [1.72-6.67], P < 0.001), hypertension (aOR 3.37 [1.69-6.72], P = 0.001), and LBW (aOR 3.61 [1.55-8.43], P = 0.003) independently predicted admission to ICU. The area under the receiver-operating characteristics curve (AUC) of this model was 0.79 [95% CI, 0.74-0.85], with positive and negative predictive values of 29.1% and 97.6% respectively. Results were reproduced in an independent cohort, from a web-based survey in 1822 subjects who self-reported laboratory-positive SARS-CoV-2 infection, where 46 patients (2.5%) needed ICU admission (AUC 0.74 [95% CI 0.68-0.81]). LBW seems to be an independent risk factor for severe COVID-19 in non-elderly adults and might improve the performance of risk stratification algorithms.

Severe acute kidney injury in critically ill COVID-19 patients.

BACKGROUND: Acute kidney injury (AKI) is frequent in Coronavirus Infection Disease 2019 (COVID-19) patients. Factors associated with AKI in COVID-19 intensive care unit (ICU) patients and their outcomes have not been previously explored. METHODS: Prospective observational study of COVID-19 patients admitted to the ICUs of the Hospital Clínic of Barcelona (Spain), from March 25th to April 21st, 2020, who developed AKI stage 2 or higher (AKIN classification). The primary goal was to describe the characteristics of moderate-severe AKI of COVID-19 patients in an ICU context. As a secondary goal, we aimed to find independent predictors of AKI progression, Renal Replacement Therapy (RRT) requirement and mortality among these patients. RESULTS: During the study period, 52 out of 237 ICU patients, developed AKIN stage 2 or higher and were included in the study. A Sequential Organ Failure Assessment (SOFA) score at AKI diagnosis of 8 or higher was associated with RRT, OR 5.2, p 0.032. At the time of AKI diagnosis, patients had a worse liver profile and higher inflammation markers than at admission. Fifty per cent of the patients presented AKI progression from AKIN 2 to 3 and 28.85% required RRT. The use of corticosteroids in 69.2% of patients was associated with a reduced requirement of RRT, OR 0.13 (CI 95% 0.02-0.89), p 0.037. AKI was associated with high mortality (50%) and a longer hospital stay, median 35 vs 18 days (p 0.024). CONCLUSIONS: The prevalence of moderate/severe AKI in COVID-19 patients admitted to the ICU is high and has a strong correlation with mortality and length of hospital stay.