Background The role of the renin-angiotensin-aldosterone system in COVID-19 is controversially discussed. SARS-CoV-2 enters host cells by binding to angiotensin-converting enzyme 2 and activity of the renin-angiotensin-aldosterone system may affect susceptibility to SARS-CoV-2 infection and outcome of patients with COVID-19. Methods In this prospective single-center study, we determined the serum levels of ACE-2, angiotensin II and aldosterone in patients with COVID-19 compared to control patients presenting with similar symptoms in the emergency unit. Results We analyzed serum samples from 24 SARS-CoV-2 positive and 61 SARS-CoV-2 negative patients. SARS-CoV-2 positive and control patients did not differ in baseline patients characteristics, symptoms and clinical presentation. Mean serum concentrations of ACE2, angiotensin II, and aldosterone did not differ between the SARS-CoV-2 positive and the control group. In line with this, serum potassium as surrogate parameter for RAAS activity and blood pressure were similar in both groups. Conclusions In summary, we did not find evidence for altered RAAS activity including angiotensin II, aldosterone, or potassium levels, and blood pressure in patients with COVID-19.

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Background Typical lung ultrasound (LUS) findings in patients with a COVID-19 infection were reported early on. During the global SARS-CoV-2 pandemic, LUS was propagated as a useful instrument in triage and monitoring. We evaluated LUS as a rapid diagnostic triage tool for the management of patients with suspected COVID-19 in the emergency department (ED). Methods The study retrospectively enrolled patients with suspected COVID-19, who were admitted from 1st April to 25th of April 2020 to the ED of a tertiary care center in Germany. During clinical work-up, patients underwent LUS and polymerase chain reaction (PCR) testing for SARS-CoV-2. The recorded ultrasound findings were analyzed and judged regarding typical signs of viral pneumonia, blinded for clinical information of the patients. The results were compared with PCR test and chest computed tomography (CT). Results 2236 patients were treated in the ED during the study period. 203 were tested for SARS-CoV-2 using PCR, 135 (66.5%) underwent LUS and 39 (28.9%) of the patients were examined by chest CT scan. 39 (28.9%) of the 135 patients were tested positive for SARS-CoV-2 with PCR. In 52 (38.5%) COVID-19 was suspected from the finding of the LUS, resulting in a sensitivity of 76.9% and a specificity of 77.1% compared with PCR results. The negative predictive value reached 89.2%. The findings of the LUS had - compared to a positive chest CT scan for COVID-19 - a sensitivity of 70.6% and a specificity of 72.7%. Conclusions LUS is a rapid and useful triage tool in the work-up of patients with suspected COVID-19 infection during a pandemic scenario. Still, the results of the LUS depend on the physician’s experience and skills.

ObjectiveThe endothelial protein C-receptor (EPCR) is an endothelial transmembrane protein that binds protein C and activated protein C (APC) with equal affinity, thereby facilitating APC formation. APC has anticoagulant, antiapoptotic and antiinflammatory properties. Soluble EPCR, released by the endothelium, may bind activated neutrophils, thereby modulating cell adhesion. EPCR is therefore considered as a possible link between the anticoagulant properties of protein C and the inflammatory response of neutrophils. In the present study, we aimed to provide proof of concept for a direct binding of EPCR to the β2 –integrin Mac-1 on monocytic cells under static and physiological flow conditions.Measurements and Main ResultsUnder static conditions, human monocytes bind soluble EPCR in a concentration dependent manner, as demonstrated by flow cytometry. Binding can be inhibited by specific antibodies (anti-EPCR and anti-Mac-1). Specific binding was confirmed by a static adhesion assay, where a transfected Mac-1 expressing CHO cell line (Mac-1+ cells) bound significantly more recombinant EPCR compared to Mac-1+ cells blocked by anti-Mac-1-antibody and native CHO cells. Under physiological flow conditions, monocyte binding to the endothelium could be significantly blocked by both, anti-EPCR and anti-Mac-1 antibodies in a dynamic adhesion assay at physiological flow conditions. Pre-treatment of endothelial cells with APC (drotrecogin alfa) diminished monocyte adhesion significantly in a comparable extent to anti-EPCR.ConclusionsIn the present study, we demonstrate a direct binding of Mac-1 on monocytes to the endothelial protein C receptor under static and flow conditions. This binding suggests a link between the protein C anticoagulant pathway and inflammation at the endothelium side, such as in acute vascular inflammation or septicaemia.

The adipocytokine leptin has distinct functions regulating vascular tone, inflammation, and collateral artery growth. Arteriogenesis is an inflammatory process and provides a mechanism to overcome the effects of vascular obstruction. We, therefore, tested the effects of leptin in hypoperfused rat brain (three-vessel occlusion). Systemic leptin administration for 1 week after occlusion surgery increased cerebral hemodynamic reserve similar to granulocyte-macrophage colony-stimulating factor (GM-CSF), as indicated by improved CO(2) reactivity (vehicle 0.53%±0.26% versus leptin 1.05%±0.6% per mm Hg arterial pCO(2), P<0.05). Infusion of microspheres under maximal vasodilation failed to show a positive effect of leptin on cerebral perfusion (vehicle 64.9%±4.5% versus leptin 66.3%±7.0%, occluded/nonoccluded hemisphere). Acute treatment with GM-CSF led to a significant increased CO(2) reactivity and cerebral perfusion (79.2%±8.1% versus 64.9%±4.5%, P<0.05). Vasoconstrictive response of isolated rat carotid artery rings, after phenylephrine was attenuated at 24  hours following preincubation with leptin, was unaffected by removal of endothelium but abrogated by coculture with N-(omega)-nitro-L-arginine methylester, pointing toward an inducible nitric oxide synthase-mediated mechanism. In chronic cerebral hypoperfusion, acute leptin treatment restored the hemodynamic reserve of the cerebral vasculature through its effects on vascular tone, while leaving vascular outward remodeling unaffected. Our results, for the first time, reveal a protective role of leptin on vascular function in hemodynamically compromised brain tissue.