Platelet Activation and Plasma Levels of Furin Are Associated With Prognosis of Patients With Coronary Artery Disease and COVID-19.

[Figure: see text].

Aη-α and Aη-ß peptides impair LTP ex vivo within the low nanomolar range and impact neuronal activity in vivo.

BACKGROUND: Amyloid precursor protein (APP) processing is central to Alzheimer's disease (AD) etiology. As early cognitive alterations in AD are strongly correlated to abnormal information processing due to increasing synaptic impairment, it is crucial to characterize how peptides generated through APP cleavage modulate synapse function. We previously described a novel APP processing pathway producing η-secretase-derived peptides (Aη) and revealed that Aη-α, the longest form of Aη produced by η-secretase and α-secretase cleavage, impaired hippocampal long-term potentiation (LTP) ex vivo and neuronal activity in vivo. METHODS: With the intention of going beyond this initial observation, we performed a comprehensive analysis to further characterize the effects of both Aη-α and the shorter Aη-ß peptide on hippocampus function using ex vivo field electrophysiology, in vivo multiphoton calcium imaging, and in vivo electrophysiology. RESULTS: We demonstrate that both synthetic peptides acutely impair LTP at low nanomolar concentrations ex vivo and reveal the N-terminus to be a primary site of activity. We further show that Aη-ß, like Aη-α, inhibits neuronal activity in vivo and provide confirmation of LTP impairment by Aη-α in vivo. CONCLUSIONS: These results provide novel insights into the functional role of the recently discovered η-secretase-derived products and suggest that Aη peptides represent important, pathophysiologically relevant, modulators of hippocampal network activity, with profound implications for APP-targeting therapeutic strategies in AD.

Impaired Myocardial Function Is Prognostic for Severe Respiratory Failure in the Course of COVID-19 Infection.

COVID-19 may lead to severe acute respiratory distress syndrome (ARDS) resulting in increased morbidity and mortality. Heart failure and/or pre-existing cardiovascular disease may correlate with poor outcomes and thus require special attention from treating physicians. The present study sought to investigate a possible impact of impaired myocardial function as well as myocardial distress markers on mortality or ARDS with need for mechanical ventilation in 157 consecutive patients with confirmed SARS-CoV-2 infection. All patients were admitted and treated at the University Hospital of Tübingen, Germany, during the first wave of the pandemic. Electrocardiography, echocardiography, and routine blood sampling were performed at hospital admission. Impaired left-ventricular and right-ventricular function, tricuspid regurgitation > grade 1, and elevated RV-pressure as well as thrombotic and myocardial distress markers (D-dimers, NT-pro-BNP, and troponin-I) were associated with mechanical ventilation and/or all-cause mortality. Impaired cardiac function is more frequent amidst ARDS, leading to subsequent need for mechanical ventilation, and thus denotes a poor outcome in COVID-19. Since a causal treatment for SARS-CoV-2 infection is still lacking, guideline-compliant cardiovascular evaluation and treatment remains the best approach to improve outcomes in COVID-19 patients with cardiovascular comorbidities.

Deceleration capacity is associated with acute respiratory distress syndrome in COVID-19.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is considered the main cause of COVID-19 associated morbidity and mortality. Early and reliable risk stratification is of crucial clinical importance in order to identify persons at risk for developing a severe course of disease. Deceleration capacity (DC) of heart rate as a marker of cardiac autonomic function predicts outcome in persons with myocardial infarction and heart failure. We hypothesized that reduced modulation of heart rate may be helpful in identifying persons with COVID-19 at risk for developing ARDS. METHODS: We prospectively enrolled 60 consecutive COVID-19 positive persons presenting at the University Hospital of Tuebingen. Arterial blood gas analysis and 24 h-Holter ECG recordings were performed and analyzed at admission. The primary end point was defined as development of ARDS with regards to the Berlin classification. RESULTS: 61.7% (37 of 60 persons) developed an ARDS. In persons with ARDS DC was significantly reduced when compared to persons with milder course of infection (3.2 ms vs. 6.6 ms, p < 0.001). DC achieved a good discrimination performance (AUC = 0.76) for ARDS in COVID-19 persons. In a multivariate analysis, decreased DC was associated with the development of ARDS. CONCLUSION: Our data suggest a promising role of DC to risk stratification in COVID-19.

Impaired cardiac function is associated with mortality in patients with acute COVID-19 infection.

BACKGROUND: COVID-19 infection may cause severe respiratory distress and is associated with increased morbidity and mortality. Impaired cardiac function and/or pre-existing cardiovascular disease may be associated with poor prognosis. In the present study, we report a comprehensive cardiovascular characterization in the first consecutive collective of patients that was admitted and treated at the University Hospital of Tübingen, Germany. METHODS: 123 consecutive patients with COVID-19 were included. Routine blood sampling, transthoracic echocardiography and electrocardiography were performed at hospital admission. RESULTS: We found that impaired left-ventricular and right-ventricular function as well as tricuspid regurgitation > grade 1 were significantly associated with higher mortality. Furthermore, elevated levels of myocardial distress markers (troponin-I and NT pro-BNP) were associated with poor prognosis in this patient collective. CONCLUSION: Impaired cardiac function is associated with poor prognosis in COVID-19 positive patients. Consequently, treatment of these patients should include careful guideline-conform cardiovascular evaluation and treatment. Thus, formation of a competent Cardio-COVID-19 team may represent a major clinical measure to optimize therapy of cardiovascular patients during this pandemic.