SARS-CoV-2 targets endothelial cells through the angiotensin-converting enzyme 2 receptor. The resulting endothelial injury induces widespread thrombosis and microangiopathy. Nevertheless, early specific markers of endothelial dysfunction and vascular redox status in COVID-19 patients are currently missing. Observational study including ICU and non-ICU adult COVID-19 patients admitted in hospital for acute respiratory failure, compared with control subjects matched for cardiovascular risk factors similar to ICU COVID-19 patients, and ICU septic shock patients unrelated to COVID-19. Early SARS-CoV-2 infection was associated with an imbalance between an exacerbated oxidative stress (plasma peroxides levels in ICU patients vs. controls: 1456.0 ± 400.2 vs 436 ± 272.1 mmol/L; P < 0.05) and a reduced nitric oxide bioavailability proportional to disease severity (5-α-nitrosyl-hemoglobin, HbNO in ICU patients vs. controls: 116.1 ± 62.1 vs. 163.3 ± 46.7 nmol/L; P < 0.05). HbNO levels correlated with oxygenation parameters (PaO₂/FiO₂ ratio) in COVID-19 patients (R² = 0.13; P < 0.05). Plasma levels of angiotensin II, aldosterone, renin or serum level of TREM-1 ruled out any hyper-activation of the renin-angiotensin-aldosterone system or leucocyte respiratory burst in ICU COVID-19 patients, contrary to septic patients. Endothelial oxidative stress with ensuing decreased NO bioavailability appears as a likely pathogenic factor of endothelial dysfunction in ICU COVID-19 patients. A correlation between NO bioavailability and oxygenation parameters is observed in hospitalized COVID-19 patients. These results highlight an urgent need for oriented research leading to a better understanding of the specific endothelial oxidative stress that occurs during SARS-CoV-2. Stated in the acknowledgments section.

Pharmacological inhibition of AQP1 prevents H ₂ O ₂ transport and hypertrophy of cardiac myocytes.

Critically ill patients admitted in ICU because of COVID-19 infection display severe hypoxemic respiratory failure. The Surviving Sepsis Campaign recommends oxygenation through high-flow nasal cannula over non-invasive ventilation. The primary outcome of our study was to evaluate the effect of the addition of a surgical mask on a high-flow nasal cannula system on oxygenation parameters in hypoxemic COVID-19 patients admitted in ICU who do not require urgent intubation. The secondary outcomes were relevant changes in PaCO2 associated with clinical modifications and patient’s feelings. We prospectively assessed 21 patients admitted in our mixed Intensive Care Unit of the Cliniques Universitaires Saint Luc. While FiO2 was unchanged, we demonstrate a significant increase of PaO2 (from 59 (± 6), to 79 mmHg (± 16), p < 0.001), PaO2/FiO2 from 83 (± 22), to 111 (± 38), p < 0.001) and SaO2 (from 91% (± 1.5), to 94% (± 1.6), p < 0.001), while the patients were under the surgical mask. The SpO2 returned to pre-treatment values when the surgical mask was removed confirming the effect of the device rather than a spontaneous positive evolution. A surgical mask placed on patient’s face already treated by a High-flow nasal cannula device improves COVID-19 patient’s oxygenation admitted in Intensive Care Unit for severe hypoxemic respiratory failure without any clinically relevant side.

Few studies analyzed gender-related outcome differences of critically ill patients and found inconsistent results. This study aimed to test the independent association of gender and long-term survival of ICU patients. FROG-ICU was a prospective, observational, multi-center cohort designed to investigate the long-term mortality of critically ill adult patients. The primary endpoint of this study was 1-year mortality after ICU admission of women compared to men. The study included 2087 patients, 726 women and 1361 men. Women and men had similar baseline characteristics, clinical presentation, and disease severity. No significant difference in 1-year mortality was found between women and men (34.9% vs. 37.9%, P = 0.18). After multivariable adjustment, no difference in the hazard of death was observed [HR 0.99 (95% CI 0.77–1.28)]. Similar 1-year survival between women and men was found in a propensity score-matched patient cohort of 506 patients [HR 0.79 (95% CI 0.54–1.14)]. Women constituted one-third of the population of critically ill patients and were unexpectedly similar to men regarding demographic characteristics, clinical presentation, and disease severity and had similar risk of death at 1 year after ICU admission. Trial registration ClinicalTrials.gov NCT01367093; registered on June 6, 2011.

Nitric oxide (NO) is implicated in numerous physiological processes, including vascular homeostasis. Reduced NO bioavailability is a hallmark of endothelial dysfunction, a prequel to many cardiovascular diseases. Biomarkers of an early NO-dependent endothelial dysfunction obtained from routine venous blood sampling would be of great interest but are currently lacking. The direct measurement of circulating NO remains a challenge due by its high reactivity and short half-life. The current techniques measure stable products from the NO signaling pathway or metabolic end products of NO that do not accurately represent its bioavailability and, therefore, endothelial function per se. In this review, we will concentrate on an original technique of low temperature electron paramagnetic resonance spectroscopy capable to directly measure the 5-α-coordinated heme nitrosyl-hemoglobin in the T (tense) state (5-α-nitrosyl-hemoglobin or HbNO) obtained from fresh venous human erythrocytes. In humans, HbNO reflects the bioavailability of NO formed in the vasculature from vascular endothelial NOS or exogenous NO donors with minor contribution from erythrocyte NOS. The HbNO signal is directly correlated with the vascular endothelial function and inversely correlated with vascular oxidative stress. Pilot studies support the validity of HbNO measurements both for the detection of endothelial dysfunction in asymptomatic subjects and for the monitoring of such dysfunction in patients with known cardiovascular disease. The impact of therapies or the severity of diseases such as COVID-19 infection involving the endothelium could also be monitored and their incumbent risk of complications better predicted through serial measurements of HbNO.

Introduction: Cytomegalovirus (CMV) DNAemia has been described in critically ill patients, including patients with severe acute respiratory syndrome-coronavirus2 (SARS-CoV-2) infection. Our objective is to evaluate the prevalence and clinical impact of CMV DNAemia among patients undergoing invasive mechanical ventilation (IMV) for severe SARS-CoV-2 infection and to explore the association between CMV DNAemia levels and clinical outcomes. Methods: In this retrospective monocentric study, we included patients admitted in a tertiary ICU for severe COVID-19 and who required IMV. We aimed to compare clinical and demographic variables between patients with and without CMV DNAemia. Univariate and Cox regression analyses were performed to identify factors associated with CMV DNAemia. Results: During the study period, CMV blood DNAemia occurred in 30/135 patients (22%). Patients with CMV blood DNAemia had longer ICU and hospital length of stay, as well as longer duration of IMV, and were more likely to have received dexamethasone. However, there was no significant difference in ICU mortality between patients with and without CMV DNAemia (64.8% vs. 56.7%, p = 0.42). The Cox regression analysis showed that dexamethasone was the only factor independently associated with CMV blood DNAemia (HR 4.23 [1.006–17.792], p = 0.049). Conclusions: In patients with severe SARS-CoV-2 pneumonia requiring IMV, CMV DNAemia is common and associated with prolonged ventilation and increased LOS but not with increased mortality.