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.

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 24h-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.

Objective: Patients with coronary artery disease (CAD) are at increased risk for cardiac death and respiratory failure following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Platelets are crucially involved in pathogenesis of CAD and might also contribute to pathophysiology of SARS-CoV-2 infection. Approach and Results: We enrolled a cohort of 122 participants from February 2020 to July 2020 including 55 patients with preexisting CAD and acute SARS-CoV-2 infection (CAD-SARS-CoV-2 positive ), 28 patients with CAD and without SARS-CoV-2 (CAD-SARS-CoV-2 negative ), and 39 healthy controls. Clinical and cardiac examination of the CAD-SARS-CoV-2 positive group included blood sampling, echocardiography, and electrocardiography within 24 hours after hospital admission. Phenotyping of platelets was performed by flow cytometry; plasma levels of chemokines were analyzed by ELISA. Respiratory failure of patients was stratified by the Horovitz index as moderately/severely impaired when Horovitz index <200 mm Hg. The clinical end point was defined as Horovitz index <200 mm Hg with subsequent mechanical ventilation within a follow-up of 60 days. CAD-SARS-CoV-2 positive patients display a significant enhanced platelet activation and hyper-inflammation early at time of hospital admission. Circulating platelet/leukocyte co-aggregates correlate with plasma levels of cytokines/chemokines like IL (interleukin)-6, CCL2, and CXCL10 as well as activation of platelets is associated with CCL5 and elevation of pulmonary artery pressure. Furthermore, furin is stored and released from activated platelets. High furin plasma levels are associated with poor clinical prognosis in CAD-SARS-CoV-2 positive patients. Conclusions: Patients with CAD and SARS-CoV-2 infection exhibit elevated systemic platelet activation and enhanced plasma levels of the subtilisin-like proprotein convertase furin, which may contribute to an unfavorable clinical prognosis.

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 hours 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 to CAD patients without infection and healthy controls (p &lt; 0.0001). Moreover, these CD14dimCD16 monocytes showed decreased expression of established markers of adhesion, migration, and T cell activation (CD54, CD62L, CX3CR1, CD80, 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. Translational Perspective Patients with coronary artery disease (CAD) are at risk of life-threatening heart and lung injury accelerated by the pro-inflammatory and pro-thrombotic immune response during SARS-CoV-2 infection. We found substantially low numbers of CD14dimCD16+ non-classical monocytes with an altered phenotype suggesting impaired migration behaviour and T cell activation capacity in peripheral blood of SARS-CoV-2 patients with CAD, compared to CAD patients without infection or healthy controls. Decreased numbers of CD14dimCD16+ monocytes predicted rapidly progressive respiratory failure (Horovitz index ≤ 200 mmHg) with subsequent mechanical ventilation. Therefore, early sub- and phenotyping of CD14dimCD16+ monocytes using simple flow cytometry might predict worsening of respiratory failure at an early stage of SARS-CoV-2 infection in high-risk CAD patients, who require an extensive heart failure and anti-thrombotic therapy to improve their clinical outcome.

Objective The relationship between inflammation, obesity and adverse metabolic conditions is associated with adipose tissue macrophages (ATM). We compared the measurements of human ATM using flow cytometry, immunohistochemistry (IHC) and RT-PCR of ATM markers. Methods We evaluated a new software program (AMCounter) to help measure ATM using IHC and compared this to flow cytometry and RT-PCR. Results IHC had good intra-individual reproducibility for total (CD68), pro-inflammatory (CD14) and anti-inflammatory (CD206) ATM. The AMCounter improved inter-reader agreement and was more time efficient. Flow cytometry had acceptable intra-individual reproducibility for the percent of CD68+ cells that were CD14+ or CD206+, but not for ATM/g tissue. ATM/g tissue was much greater using IHC than flow cytometry. The flow cytometry and IHC measures of ATM from the same biopsies were not correlated. There were statistically significant correlations between RT-PCR CD68 and IHC CD68, CD14 and CD206 ATM’s per 100 adipocytes. Of interest, were also statistically significant correlations between RT-PCR CD68 and IHC CD68, CD14 and adipose flow cytometry measures of CD68+, CD68+/CD14+ and CD68+/CD206+ ATM’s per g tissue. Conclusions The AMCounter software helps reproducibly and efficiency measures of IHC ATM’s. Flow cytometry, immunohistochemistry and RT-PCR measures of adipose inflammation provide somewhat different information.