ABSTRACT
Background: Patients suffering from COVID-19 with pre-existing chronic heart failure (CHF) are considered to have a significant risk regarding morbidity and mortality. Similarly, older patients on the intensive care unit (ICU) constitute another vulnerable subgroup. This study investigated the association between pre-existing CHF and clinical practice in critically ill older ICU patients with COVID-19. Method(s): Patients with severe COVID-19 and who were >=70 years old were recruited from this prospective multicenter international study. Patients' treatment, follow-up, and pre-existing heart failure data were collected during ICU stay. Univariate and multivariate logistic regression analyses examined the association between pre-existing heart failure and the primary endpoint of 30-day mortality. Result(s): The study included 3,917 patients, with 407 patients (17%) evidencing pre-existing CHF. These patients were older (77+/-5 versus 76+/-5, p<0.001) and more frail (Clinical Frailty Scale 4+/-2 versus 3+/-2, p<0.0001). The other comorbidities were also significantly more common in CHF patients. Before hospital admission, CHF patients suffered fewer days from symptoms (5 days (3-8) versus 7 days (4-10), p<0.001), but there was no difference in the days in the hospital before ICU admission (2 days (1-5) versus 2 (1-5) days, p=0.21). At ICU admission, disease severity assessed by SOFA scores was significantly higher in CHF patients (7+/-3 versus 5+/-3). During ICU-stay, intubation, mechanical ventilation, and tracheostomy occurred significantly more often in patients without CHF (63% versus 69%, p=0.017;and 13% versus 18%, p=0.002, respectively). In contrast, there was no difference regarding non-invasive ventilation (28% versus 27%, p=0.20), and the need for vasoactive drugs (66% versus 64, p=0.30). Regarding the limitation of life-sustaining therapy, therapy was significantly more often withheld (32% versus 25%, p=0.001) but not withdrawn (18% versus 17%, p=0.21) in CHF patients. Length of ICU stay was significantly shorter in CHF patients (166 (72-336) hours versus 260 hours (120-528), p<0.001). CHF patients had significantly higher ICU-(52% versus 46%, p=0.007), 30-day mortality (60% vs. 48%, p<0.001;OR 1.87, 95% CI 1.5- 2.3) and 3-month mortality (69% vs. 56%, p<0.001). In the univariate regression analysis, having pre-existing CHF was significantly associated with 30-day mortality (OR 1.89, 95% CI 1.5-2.3;p<0.001), but after adjusting for confounders (SOFA, age, gender, frailty), heart failure was not independently associated any more (aOR 1.2, 95% CI 0.5-1.5;p=0.137). Conclusion(s): In critically ill old COVID-19 patients, pre-existing chronic heart failure is associated with significantly increased short-and long-term mortality, but heart failure is not independently associated with increased 30-day mortality when adjusted for confounders.
ABSTRACT
Acute respiratory distress syndrome (ARDS) is a critical illness characterized by a severe hypoxemic respiratory failure, caused by an inflammatory response which results in diffuse lung damage. Despite decades of research, the treatment of ARDS remains supportive. However, in recent years, cell-based therapies have been the subject of intensive ongoing research efforts, showing relevant therapeutic potential in preclinical ARDS models. Among all the different cells that have been identified as suitable candidates for use, mesenchymal stromal cells (MSCs) have been the most attractive candidates and have generated significant interest. MSCs are multipotent adult stem/stromal cells that can modulate the immune response and enhance repair of damaged tissue in multiple in vivo models. Their promising effect seems to be not primarily mediated by MSCs differentiation and engraftment but more by the paracrine release of different soluble mediators and cellular components such as extracellular vesicles (EVs). Preclinical experiments have provided encouraging evidence for the therapeutic potential of MSCs, leading to the launch of several phase I and II clinical trials that have shown safety of MSCs in ARDS, which became very common nowadays due to the Coronavirus disease (COVID-19) pandemic. However, some translational challenges have yet to be solved, such as the reproducibility of cell harvest, storage, reconstitution, and administration of cells/cell-products, before the therapeutic potential of stem cells therapies can be realized. ©2022 The Author(s). Published by MRE Press.
ABSTRACT
Severe viral pneumonia is a significant cause of morbidity and mortality globally, whether due to outbreaks of endemic viruses, periodic viral epidemics, or the rarer but devastating global viral pandemics. While limited anti-viral therapies exist, there is a paucity of direct therapies to directly attenuate viral pneumonia-induced lung injury, and management therefore remains largely supportive. Mesenchymal stromal/stem cells (MSCs) are receiving considerable attention as a cytotherapeutic for viral pneumonia. Several properties of MSCs position them as a promising therapeutic strategy for viral pneumonia-induced lung injury as demonstrated in pre-clinical studies in relevant models. More recently, early phase clinical studies have demonstrated a reassuring safety profile of these cells. These investigations have taken on an added importance and urgency during the COVID-19 pandemic, with multiple trials in progress across the globe. In parallel with clinical translation, strategies are being investigated to enhance the therapeutic potential of these cells in vivo, with different MSC tissue sources, specific cellular products including cell-free options, and strategies to 'licence' or 'pre-activate' these cells, all being explored. This review will assess the therapeutic potential of MSC-based therapies for severe viral pneumonia. It will describe the aetiology and epidemiology of severe viral pneumonia, describe current therapeutic approaches, and examine the data suggesting therapeutic potential of MSCs for severe viral pneumonia in pre-clinical and clinical studies. The challenges and opportunities for MSC-based therapies will then be considered.
ABSTRACT
INTRODUCTION Surrogates for impaired ventilation such as estimated dead-space fractions and the ventilatory ratio are independently associated with an increased risk of mortality in the acute respiratory distress syndrome (ARDS) and small case series of COVID-19 related ARDS. METHODS This study aimed to quantify the dynamics and determine the prognostic value of surrogate markers of impaired ventilation in patients with COVID-19 related ARDS. The present study is a secondary analysis of the PRactice Of VENTilation in COVID-19 patients (PROVENT-COVID) in 22 intensive care unit hospitals in the Netherlands. Surrogates of impaired ventilation such as the estimated dead space fraction (by Harris-Benedict-VD/VT HB and direct method-VD/VT DIR), ventilatory ratio (VR), and end-tidal-to-arterial PCO2 ratio (PETCO2/PaCO2) were used. RESULTS 927 consecutive patients admitted with COVID-19 related ARDS were included in this study. Surrogates of impaired ventilation were significantly higher in non-survivors than survivors at baseline and during the following days of mechanical ventilation (p <0.001). As ARDS severity increased, mortality increased with successive tertiles for VD/VT HB and VD/VT DIR, and VR, and decreased with successive tertiles for PETCO2/PaCO2. Mortality over the first 28 days was higher in patients in the high group of dead space fraction by VD/VT HB (16.4% vs. 12.3%;p = 0.003), but similar in the groups considering the dead space fraction by VD/VT DIR (15.4% vs. 13.3%;p = 0.100), and VR (15.5% vs. 13.2%;p = 0.080) (Figure 2). After adjustment for a base risk model that included chronic comorbidities, ventilation and oxygenation parameters, none of the surrogates of impaired ventilation measured at the start of ventilation or the following days were significantly associated with 28-day mortality. CONCLUSION Surrogate markers for impaired ventilation are abnormal at the start of invasive ventilation in patients with COVID-19 related ARDS and worsen during consequent days. Ventilation impairment seems to be more extensive in non-survivors than in survivors, but they do not yield prognostic information when added to a baseline risk model. In the absence of bedside capnography, surrogates of impaired ventilation may serve as an important tool to assess the severity of COVID-19 related ARDS along with other variables such as oxygenation abnormalities and respiratory mechanics.