The pulmonary endothelium is a metabolically active continuous monolayer of squamous endothelial cells that internally lines blood vessels and mediates key processes involved in lung homoeostasis. Many of these processes are disrupted in acute respiratory distress syndrome (ARDS), which is marked among others by diffuse endothelial injury, intense activation of the coagulation system and increased capillary permeability. Most commonly occurring in the setting of sepsis, ARDS is a devastating illness, associated with increased morbidity and mortality and no effective pharmacological treatment. Endothelial cell damage has an important role in the pathogenesis of ARDS and several biomarkers of endothelial damage have been tested in determining prognosis. By further understanding the endothelial pathobiology, development of endothelial-specific therapeutics might arise. In this review, we will discuss the underlying pathology of endothelial dysfunction leading to ARDS and emerging therapies. Furthermore, we will present a brief overview demonstrating that endotheliopathy is an important feature of hospitalised patients with coronavirus disease-19 (COVID-19).

Endotheliopathy is suggested to be an important feature of COVID-19 in hospitalized patients. To determine whether endotheliopathy is involved in COVID-19-associated mortality, markers of endothelial damage were assessed in critically ill COVID-19 patients upon intensive care unit (ICU) admission. Thirty-eight critically ill COVID-19 patients were included in this observational study, 10 of whom died in the ICU. Endothelial biomarkers, including soluble (s)E-selectin, sP-selectin, angiopoietin 1 and 2 (Ang-1 and Ang-2, respectively), soluble intercellular adhesion molecule 1 (sICAM-1), vascular endothelial growth factor (VEGF), soluble vascular endothelial (VE)-cadherin, and von Willebrand factor (vWf), were measured upon ICU admission. The ICU cohort was subsequently divided into survivors and non-survivors; Kaplan–Meier analysis was used to explore associations between biomarkers and survival, while receiver operating characteristic (ROC) curves were generated to determine their potential prognostic value. sE-selectin, sP-selectin, Ang-2, and sICAM-1 were significantly elevated in ICU non-survivors compared to survivors, and also associated with a higher mortality probability in the Kaplan–Meier analysis. The prognostic values of sE-selectin, Ang-2, and sICAM-1 from the generated ROC curves were greater than 0.85. Hence, we conclude that in our cohort, ICU non-survivors had higher levels of specific endothelial markers compared to survivors. Elevated levels of these markers upon ICU admission could possibly predict mortality in COVID-19.

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Current achievements in medical science and technological advancements in intensive care medicine have allowed better support of critically ill patients in intensive care units (ICUs) and have increased survival probability. Post-intensive care syndrome (PICS) is a relatively new term introduced almost 10 years ago, defined as “new or worsening impairments in physical, cognitive, or mental health status arising after critical illness and persisting beyond acute care hospitalization”. A significant percentage of critically ill patients suffer from PICS for a prolonged period of time, with physical problems being the most common. The exact prevalence of PICS is unknown, and many risk factors have been described well. Coronavirus disease 2019 (COVID-19) survivors seem to be at especially high risk for developing PICS. The families of ICU survivors can also be affected as a response to the stress suffered during the critical illness of their kin. This separate entity is described as PICS family (PICS-F). A multidisciplinary approach is warranted for the treatment of PICS, involving healthcare professionals, clinicians, and scientists from different areas. Improving outcomes is both challenging and imperative for the critical care community. The review of the relevant literature and the study of the physical, cognitive, and mental sequelae could lead to the prevention and timely management of PICS and the subsequent improvement of the quality of life for ICU survivors.

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We aimed to examine whether low intensive care unit (ICU) admission 25-hydroxyvitamin D (25(OH)D) levels are associated with worse outcomes of COVID-19 pneumonia. This was a prospective observational study of SARS-CoV2 positive critically ill patients treated in a multidisciplinary ICU. Thirty (30) Greek patients were included, in whom 25(OH)D was measured on ICU admission. Eighty (80%) percent of patients had vitamin D deficiency, and the remaining insufficiency. Based on 25(OH)D levels, patients were stratified in two groups: higher and lower than the median value of the cohort (15.2 ng/mL). The two groups did not differ in their demographic or clinical characteristics. All patients who died within 28 days belonged to the low vitamin D group. Survival analysis showed that the low vitamin D group had a higher 28-day survival absence probability (log-rank test, p = 0.01). Critically ill COVID-19 patients who died in the ICU within 28 days appeared to have lower ICU admission 25(OH)D levels compared to survivors. When the cohort was divided at the median 25(OH)D value, the low vitamin D group had an increased risk of 28-day mortality. It seems plausible, therefore, that low 25(OH)D levels may predispose COVID-19 patients to an increased 28-day mortality risk.

Endothelial dysfunction, coagulation and inflammation biomarkers are increasingly emerging as prognostic markers of poor outcomes and mortality in severe and critical COVID-19. However, the effect of dexamethasone has not been investigated on these biomarkers. Hence, we studied potential prognostic biomarkers of mortality in critically ill COVID-19 patients who had either received or not dexamethasone. Biomarker serum levels were measured on intensive care unit (ICU) admission (within 24 h) in 37 dexamethasone-free and 29 COVID-19 patients who had received the first dose (6 mg) of dexamethasone. Receiver operating characteristic (ROC) curves were generated to assess their value in ICU mortality prediction, while Kaplan–Meier analysis was used to explore associations between biomarkers and survival. In the dexamethasone-free COVID-19 ICU patients, non-survivors had considerably higher levels of various endothelial, immunothrombotic and inflammatory biomarkers. In the cohort who had received one dexamethasone dose, non-survivors had higher ICU admission levels of only soluble (s) vascular cell adhesion molecule-1 (VCAM-1), soluble urokinase-type plasminogen activator receptor (suPAR) and presepsin. As determined from the generated ROC curves, sVCAM-1, suPAR and presepsin could still be reliable prognostic ICU mortality biomarkers, following dexamethasone administration (0.7 < AUC < 0.9). Moreover, the Kaplan–Meier survival analysis showed that patients with higher than the median values for sVCAM-1 or suPAR exhibited a greater mortality risk than patients with lower values (Log-Rank test, p < 0.01). In our single-center study, sVCAM-1, suPAR and presepsin appear to be valuable prognostic biomarkers in assessing ICU mortality risk in COVID-19 patients, even following dexamethasone administration.

L-Dopa decarboxylase (DDC) has been cloned from several species and was shown to undergo alternative splicing within its 5'-untranslated and coding regions. In this report, we describe a novel splice variant of DDC mRNA in human tissue, lacking exons 10-15 of the full-length transcript but including an alternative exon 10. The isolated alternative human DDC cDNA (alt-DDC) was cloned from human placenta, and was found to be of the neuronal type. Northern blot analysis indicated that the alt-DDC transcript is expressed in high levels in human kidney. Our results demonstrate the detection of a new alternative splicing event within the coding region of the human DDC mRNA, further suggesting that the single copy human DDC gene undergoes complex processing leading to the formation of multiple mRNA isoforms.