Circulating Endothelial Cells as a Marker of Endothelial Injury in Severe COVID -19.

Beside the commonly described pulmonary expression of the coronavirus disease 2019 (COVID-19), major vascular events have been reported. The objective of this study was to investigate whether increased levels of circulating endothelial cells (CECs) might be associated with severe forms of COVID-19. Ninety-nine patients with COVID-19 were enrolled in this retrospective study. Patients in the intensive care units (ICU) had significantly higher CEC counts than non-ICU patients and the extent of endothelial injury was correlated with putative markers of disease severity and inflammatory cytokines. Together, these data provide in vivo evidence that endothelial injury is a key feature of COVID-19.

Eosinopenia as Predictor of Poor Outcome in Hospitalized COVID-19 Adult Patients from Waves 1 and 2 of 2020 Pandemic.

During SARS-CoV-2 infection, eosinopenia may reflect a hyperactive immune response. In this study of hospitalized COVID-19 patients, we aimed to better understand the prognostic value of severe eosinopenia (absolute eosinophil count = 0 G/L) and decipher its underlying mechanisms. We retrospectively analyzed the records of COVID-19 patients hospitalized from March to June 2020 in three university hospitals in Marseille, France. We assessed the association between severe eosinopenia and a composite poor outcome in these patients, including the need for oxygen supplementation at >6 L/min, ICU admission, and in-hospital death. Among the 551 COVID-19 patients included in this study, severe eosinopenia was found in 228 (51%) of them on admission to hospital and was associated with a composite poor outcome using multivariate analysis (OR = 2.58; CI95 [1.77−3.75]; p < 0.0001). We found a significant association between the presence of severe eosinopenia on admission and the elevation in C-reactive protein, ferritin, IP-10, and suPAR. The histological findings in a series of 37 autopsies from patients who died from severe COVID-19 and presented with severe eosinopenia showed no pulmonary eosinophil trapping. Severe eosinopenia can be a reliable biomarker associated with a composite poor outcome in hospitalized COVID-19 adult patients. It may reflect the magnitude of immune hyperactivation during severe-to-critical COVID-19.

Excess body weight is an independent risk factor for severe forms of COVID-19.

BACKGROUND AND AIMS: Few studies distinguished the independent role of overweight/obesity or their associated-comorbidities in the evolution towards severe forms of COVID-19. Obesity as a unifying risk factor for severe COVID-19 is an emerging hypothesis. The aim of this study was to evaluate whether excessive body weight per se, was a risk factor for developing a severe form of COVID-19. PATIENTS AND METHODS: We included 131 patients hospitalized for COVID-19 pneumonia in a single center of the internal medicine department in Marseille, France. We recorded anthropometric and metabolic parameters such as fasting glycaemia, insulinemia, HOMA-IR, lipids, and all clinical criteria linked to SARS-CoV-2 infection at the admission. Excess body weight was defined by a BMI ≥ 25 kg/m2. The occurrence of a serious event was defined as a high-debit oxygen requirement over 6 L/min, admission into the intensive care unit, or death. RESULTS: Among 113 patients, two thirds (n = 76, 67%) had an excess body weight. The number of serious events was significantly higher in excess body weight patients compared to normal weight patients (respectively 25% vs 8%, p = 0.03) although excess body weight patients were younger (respectively 63.6 vs 70.3 years old, p = 0.01). In multivariate analyses, the excess body weight status was the only predictor for developing a serious event linked to SARS-CoV-2 infection, with an odds ratio at 5.6 (95% CI: 1.30-23.96; p = 0.02), independently of previous obesity associated comorbidities. There was a trend towards a positive association between the BMI (normal weight, overweight and obesity) and the risk of serious events linked to COVID-19, with a marked increase from 8.1% to 20% and 30.6% respectively (p = 0.05). CONCLUSION: Excess body weight was significantly associated with severe forms of the disease, independently of its classical associated comorbidities. Physicians and specialists in Public Health must be sensitized to better protect people with an excess body weight against SARS-CoV-2 infection.

Role of growth hormone in hepatic and intestinal triglyceride-rich lipoprotein metabolism.

BACKGROUND: Elevated plasma concentrations of hepatic- and intestinally-derived triglyceride-rich lipoproteins (TRL) are implicated in the pathogenesis of atherosclerotic cardiovascular disease and all-cause mortality. Excess of TRL is the driving cause of atherogenic dyslipidemia commonly occurring in insulin-resistant individuals such as patients with obesity, type 2 diabetes and metabolic syndrome. Interestingly, growth hormone (GH)-deficient individuals display similar atherogenic dyslipidemia, suggesting an important role of GH and GH deficiency in the regulation of TRL metabolism. OBJECTIVE: We aimed to examine the direct and/or indirect role of GH on TRL metabolism. METHODS: We investigated the effect on fasting and postprandial hepatic-TRL and intestinal-TRL metabolism of short-term (one month) withdrawal of GH in 10 GH-deficient adults. RESULTS: After GH withdrawal, we found a reduction in fasting plasma TRL concentration (significant decrease in TRL-TG, TRL-cholesterol, TRL-apoB-100, TRL-apoC-III and TRL-apoC-II) but not in postprandial TRL response. This reduction was due to fewer fasting TRL particles without a change in TG per particle and was not accompanied by a change in postprandial TRL-apoB-48 response. Individual reductions in TRL correlated strongly with increases in insulin sensitivity and decreases in TRL-apoC-III. CONCLUSION: In this relatively short term 'loss of function' human experimental model, we have shown an unanticipated reduction of hepatic-TRL particles despite increase in total body fat mass and reduction in lean mass. These findings contrast with the atherogenic dyslipidemia previously described in chronic GH deficient states, providing a new perspective for the role of GH in lipoprotein metabolism.

Dissemination of extreme levels of extracellular vesicles: tissue factor activity in patients with severe COVID-19.

Coronavirus disease 2019 (COVID-19) has become one of the biggest public health challenges of this century. Severe forms of the disease are associated with a thrombo-inflammatory state that can turn into thrombosis. Because tissue factor (TF) conveyed by extracellular vesicles (EVs) has been implicated in thrombosis, we quantified the EV-TF activity in a cohort of hospitalized patients with COVID-19 (n = 111) and evaluated its link with inflammation, disease severity, and thrombotic events. Patients with severe disease were compared with those who had moderate disease and with patients who had septic shock not related to COVID-19 (n = 218). The EV-TF activity was notably increased in patients with severe COVID-19 compared with that observed in patients with moderate COVID-19 (median, 231 [25th to 75th percentile, 39-761] vs median, 25 [25th to 75th percentile, 12-59] fM; P < .0001); EV-TF was correlated with leukocytes, D-dimer, and inflammation parameters. High EV-TF values were associated with an increased thrombotic risk in multivariable models. Compared with patients who had septic shock, those with COVID-19 were characterized by a distinct coagulopathy profile with significantly higher EV-TF and EV-fibrinolytic activities that were not counterbalanced by an increase in plasminogen activator inhibitor-1 (PAI-1). Thus, this article is the first to describe the dissemination of extreme levels of EV-TF in patients with severe COVID-19, which supports the international recommendations of systematic preventive anticoagulation in hospitalized patients and potential intensification of anticoagulation in patients with severe disease.

[Clinical management of patients with hemophilia A in nephrology: Diagnostic and therapeutic challenges illustrated by the cases of 2 patients]. / Prise en charge néphrologique des patients hémophiles A : difficultés diagnostiques et thérapeutiques illustrées par le cas de 2 patients.

Hemophilia A is an X-linked genetic hemorrhagic disorder characterized by a factor VIII deficiency. The availability of secured substitution products has led to a dramatic improvement of life expectancy in hemophiliac patients. Nowadays, adult hemophiliac patients may develop Chronic Kidney Disease (CKD) resulting from age-related comorbidities (hypertension, obesity, diabetes). In addition, the high prevalence of viral infections in this population exposes patients to an increased risk of CKD. The risk of hemorrhage in hemophiliac patients is a challenge for their clinical management, both for diagnostic procedures (kidney biopsy in particular) and for renal replacement therapy (dialysis or renal transplantation) when it is needed. This work provides an update of the literature data concerning the management of hemophiliac patients in nephrology, illustrated by the cases of two patients.