Recovery of systemic hyperinflammation in patients with severe SARS-CoV-2 infection.

INTRODUCTION: Patients with cardiovascular disease (CVD) and acute SARS-CoV-2 infection might show an altered immune response during COVID-19. MATERIAL AND METHODS: Twenty-three patients with CVD and SARS-CoV-2 infection were prospectively enrolled and received a cardiological assessment at study entry and during follow-up visit. Inclusion criteria of our study were age older than 18 years, presence of CVD, and acute SARS-CoV-2 infection. The median age of the patient cohort was 69 (IQR 55-79) years. 12 (52.2%) patients were men. Peripheral monocytes and chemokine/cytokine profiles were analysed. RESULTS: Numbers of classical and non-classical monocytes were significantly decreased during acute SARS-CoV-2 infection compared to 3-month recovery. While classical monocytes reached the expected level in peripheral blood after 3 months, the number of non-classical monocytes remained significantly reduced. DISCUSSION: All three monocyte subsets exhibited changes of established adhesion and activation markers. Interestingly, they also expressed higher levels of pro-inflammatory cytokines like macrophage migration inhibitory factor (MIF) at the time of recovery, although MIF was only slightly increased during the acute phase. CONCLUSION: Changes of monocyte phenotypes and increased MIF expression after 3-month recovery from acute SARS-CoV-2 infection may indicate persistent, possibly long-lasting, pro-inflammatory monocyte function in CVD patients.

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

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COVID-19 versus seasonal influenza: myocardial injury and prognostic importance.

BACKGROUND: Acute myocardial injury is associated with poor prognosis in respiratory tract infections. We aimed to highlight the differences in prevalence of myocardial injury and its impact on prognosis in patients with COVID-19 compared to those with seasonal influenza. METHODS: This was a single-center prospective cohort study with a historical control group. 300 age-/sex-matched SARS-CoV-2 and seasonal influenza positive patients were enrolled. Myocardial injury was assessed by electrocardiogram (ECG), transthoracic echocardiography and biomarkers including high-sensitivity troponin-I. All patients were followed-up for 30 days after enrollment for all-cause mortalitiy, admission to the intensive care unit (ICU) and mechanical ventilation. RESULTS: Right ventricular distress was more common in COVID-19 whereas pathological ECG findings and impaired left ventricular function were more prevalent among influenza patients. COVID-19 patients suffered from a higher percentage of hypertension and dyslipidaemia. Contrary to COVID-19, pericardial effusion at admission was associated with poor outcome in the influenza group. Severe course of disease and respiratory failure resulted in significantly higher rates of ICU treatment and mechanical ventilation in COVID-19 patients. Although distribution of myocardial injury was similar, significantly fewer cardiac catheterizations were performed in COVID-19 patients. However, number of cardiac catheterizations was low in both groups. Finally, 30-day mortality was significantly higher in COVID-19 compared to influenza patients. CONCLUSIONS: In adults requiring hospitalization due to COVID-19 or seasonal influenza, cardiovascular risk factors and signs of myocardial distress differ significantly. Furthermore, cardiovascular comorbidities may impair prognosis in COVID-19 patients to a higher degree than in their influenza counterparts.

Platelet-Derived PCSK9 Is Associated with LDL Metabolism and Modulates Atherothrombotic Mechanisms in Coronary Artery Disease.

Platelets play a significant role in atherothrombosis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is critically involved in the regulation of LDL metabolism and interacts with platelet function. The effect of PCSK9 in platelet function is poorly understood. The authors of this article sought to characterize platelets as a major source of PCSK9 and PCSK9's role in atherothrombosis. In a large cohort of patients with coronary artery disease (CAD), platelet count, platelet reactivity, and platelet-derived PCSK9 release were analyzed. The role of platelet PCSK9 on platelet and monocyte function was investigated in vitro. Platelet count and hyper-reactivity correlated with plasma LDL in CAD. The circulating platelets express on their surface and release substantial amounts of PCSK9. Release of PCSK9 augmented platelet-dependent thrombosis, monocyte migration, and differentiation into macrophages/foam cells. Platelets and PCSK9 accumulated in tissue derived from atherosclerotic carotid arteries in areas of macrophages. PCSK9 inhibition reduced platelet activation and platelet-dependent thrombo-inflammation. The authors identified platelets as a source of PCSK9 in CAD, which may have an impact on LDL metabolism. Furthermore, platelet-derived PCSK9 contributes to atherothrombosis, and inhibition of PCSK9 attenuates thrombo-inflammation, which may contribute to the reported beneficial clinical effects.

Large-scale lipidomics profiling reveals characteristic lipid signatures associated with an increased cardiovascular risk.

BACKGROUND AND AIMS: Patients with cardiovascular disease (CVD) are at high risk to develop adverse events. The distinct risk of developing adverse cardiovascular (CV) events is not solely explained by traditional risk factors. Platelets are essentially involved in progression of CVD including coronary artery disease (CAD) and platelet hyperreactivity leads to development of adverse CV events. Alterations in the platelet lipidome lead to platelet hyperresponsiveness and thus might alter the individual risk profile. In this study, we investigate the platelet lipidome of CAD patients by untargeted lipidomics and elucidate alterations in the lipid composition of patients with adverse CV events. METHODS: We characterized the platelet lipidome in a large consecutive CAD cohort (n = 1057) by an untargeted lipidomics approach using liquid chromatography coupled to mass spectrometry. RESULTS: The platelet lipidome in this study identified 767 lipids and characteristic changes occurred in patients with adverse CV events. The most prominent upregulated lipids in patients with cardiovascular events primarily belong to the class of phospholipids and fatty acyls. Further, upregulated platelet lipids are associated with an increased cardiovascular or bleeding risk and independently associated with adverse events. In addition, alterations of the platelet lipidome are associated with modulation of in vitro platelet functions. CONCLUSIONS: Our results reveal that the composition of the platelet lipidome is altered in CVD patients with an increased cardiovascular risk and distinct platelet lipids may indicate adverse events. Results of this study may contribute to improved risk discrimination and classification for cardiovascular events in patients with CVD. Main findings of this study and hypothetical impact of altered platelet lipid signatures in patients with adverse cardiovascular events on platelet function and clinical outcome. LPE lysophosphatidylethanolamines, CAR acylcarnitines, FA fatty acids.

Risk assessment in COVID-19: Prognostic importance of cardiovascular parameters.

BACKGROUND: Cardiovascular risk factors and comorbidities are highly prevalent among COVID-19 patients and are associated with worse outcomes. HYPOTHESIS: We therefore investigated if established cardiovascular risk assessment models could efficiently predict adverse outcomes in COVID-19. Furthermore, we aimed to generate novel risk scores including various cardiovascular parameters for prediction of short- and midterm outcomes in COVID-19. METHODS: We included 441 consecutive patients diagnosed with SARS-CoV-2 infection. Patients were followed-up for 30 days after the hospital admission for all-cause mortality (ACM), venous/arterial thromboembolism, and mechanical ventilation. We further followed up the patients for post-COVID-19 syndrome for 6 months and occurrence of myocarditis, heart failure, acute coronary syndrome (ACS), and rhythm events in a 12-month follow-up. Discrimination performance of DAPT, GRACE 2.0, PARIS-CTE, PREDICT-STABLE, CHA2-DS2-VASc, HAS-BLED, PARIS-MB, PRECISE-DAPT scores for selected endpoints was evaluated by ROC-analysis. RESULTS: Out of established risk assessment models, GRACE 2.0 score performed best in predicting combined endpoint and ACM. Risk assessment models including age, cardiovascular risk factors, echocardiographic parameters, and biomarkers, were generated and could successfully predict the combined endpoint, ACM, venous/arterial thromboembolism, need for mechanical ventilation, myocarditis, ACS, heart failure, and rhythm events. Prediction of post-COVID-19 syndrome was poor. CONCLUSION: Risk assessment models including age, laboratory parameters, cardiovascular risk factors, and echocardiographic parameters showed good discrimination performance for adverse short- and midterm outcomes in COVID-19 and outweighed discrimination performance of established cardiovascular risk assessment models.

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.

Numbers and phenotype of non-classical CD14dimCD16+ monocytes are predictors of adverse clinical outcome in patients with coronary artery disease and severe SARS-CoV-2 infection.

AIMS: To elucidate the prognostic role of monocytes in the immune response of patients with coronary artery disease (CAD) at risk for life-threatening heart and lung injury as major complications of SARS-CoV-2 infection. METHODS AND RESULTS: From February to April 2020, we prospectively studied a cohort of 96 participants comprising 47 consecutive patients with CAD and acute SARS-CoV-2 infection (CAD + SARS-CoV-2), 19 CAD patients without infections, and 30 healthy controls. Clinical assessment included blood sampling, echocardiography, and electrocardiography within 12 h of admission. Respiratory failure was stratified by the Horovitz Index (HI) as moderately/severely impaired when HI ≤200 mmHg. The clinical endpoint (EP) was defined as HI ≤200 mmHg with subsequent mechanical ventilation within a follow-up of 30 days. The numbers of CD14dimCD16+ non-classical monocytes in peripheral blood were remarkably low in CAD + SARS-CoV-2 compared with CAD patients without infection and healthy controls (P < 0.0001). Moreover, these CD14dimCD16 monocytes showed decreased expression of established markers of adhesion, migration, and T-cell activation (CD54, CD62L, CX3CR1, CD80, and HLA-DR). Decreased numbers of CD14dimCD16+ monocytes were associated with the occurrence of EP. Kaplan-Meier curves illustrate that CAD + SARS-CoV-2 patients with numbers below the median of CD14dimCD16+ monocytes (median 1443 cells/mL) reached EP significantly more often compared to patients with numbers above the median (log-rank 5.03, P = 0.025). CONCLUSION: Decreased numbers of CD14dimCD16+ monocytes are associated with rapidly progressive respiratory failure in CAD + SARS-CoV-2 patients. Intensified risk assessments comprising monocyte sub- and phenotypes may help to identify patients at risk for respiratory failure.

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.