Hyperresponsive platelets and a reduced platelet granule release capacity is associated with severity of COVID-19 symptoms and with increased mortality

Background: COVID-19 is often associated with mild thrombocytopenia and increased platelet reactivity. The aim of the current study was to investigate if platelets of COVID-19 patients were primed to hyper-reactive platelets and if the circulating platelets become exhausted during COVID-19 disease. Aim(s): To investigate if platelets of COVID-19 patients were primed to hyper-reactive platelets and if the circulating platelets become exhausted during COVID-19 disease. Method(s): Time dependent platelet activation is studied in whole blood by monitoring the ATP release kinetics from platelets upon stimulation with PAR1 receptor agonist in 41 critical ill COVID-19 patients, 47 COVID-19 patients who were hospitalized but were not critically ill and 30 healthy controls. Result(s): Our study demonstrated that platelets of critical ill COVID-19 patients were hyper-responsive and had a reduced platelet granule release capacity, probably due to exhaustion. The platelet reactivity time of COVID-19 patients admitted to the critical care unit was 2-fold reduced if compared with the response time of healthy controls and 1.6-fold reduced if compared with non-critical COVID-19 patients. Platelet responsiveness was also associated (spearman r;p-value) with D-dimer (0.5;<001), CRP (0.57;<001) and neutrophil-lymphocyte ratio (0.54;<001). Moreover, an increased platelet responsiveness and reduced platelet granule release capacity were associated with an increased mortality (OR;95% CI: 18.8;6.1-57.9 and 4.9;1.5-16.3, respectively). These relationships remained significant after adjustment for age, sex, D-dimer, CRP and neutrophil-lymphocyte ratio. Conclusion(s): Our findings show that platelet hyper-reactivity and reduced platelet granule release capacity were associated with increased critical illness and increased mortality of COVID-19 patients.

Comparison between myocardial function assessed by echocardiography during hospitalization for COVID-19 and at 4 months follow-up.

In patients hospitalized for corona virus infectious disease 19 (COVID-19) it is currently unknown whether myocardial function changes after recovery and whether this is related to elevated cardiac biomarkers. In this single center, prospective cohort study we consecutively enrolled hospitalized COVID-19 patients between 1 April and 12 May 2020. All patients underwent transthoracic echocardiography (TTE) evaluation during hospitalization and at a median of 131 days (IQR; 116-136) follow-up. Of the 51 patients included at baseline, 40 (age: 62 years (IQR; 54-68), 78% male) were available for follow-up TTE. At baseline, 68% of the patients had a normal TTE, regarding left ventricular (LV) and right ventricular (RV) volumes and function, compared to 83% at follow-up (p = 0.07). Median LV ejection fraction (60% vs. 58%, p = 0.54) and tricuspid annular plane systolic excursion (23 vs 22 mm, p = 0.18) were comparable between hospitalization and follow-up, but a significantly lower RV diameter (39 vs. 34 mm, p = 0.002) and trend towards better global longitudinal strain (GLS) (- 18.5% vs - 19.1%, p = 0.07) was found at follow-up. Subgroup analysis showed no relation between patients with and without elevated TroponinT and/or NT-proBNP during hospitalization and myocardial function at follow-up. Although there were no significant differences in individual myocardial function parameters at 4 months follow-up compared to hospitalisation for COVID-19, there was an overall trend towards normalization in myocardial function, predominantly due to a higher rate of normal GLS at follow-up.

Cardiac function in relation to myocardial injury in hospitalised patients with COVID-19.

BACKGROUND: Previous studies have reported on myocardial injury in patients with coronavirus infectious disease 19 (COVID-19) defined as elevated cardiac biomarkers. Whether elevated biomarkers truly represent myocardial dysfunction is not known. The aim of this study was to explore the incidence of ventricular dysfunction and assess its relationship with biomarker analyses. METHODS: This cross-sectional study ran from April 1 to May 12, 2020, and consisted of all consecutively admitted patients to the Radboud university medical centre nursing ward for COVID-19. Laboratory assessment included high-sensitivity Troponin T and N­terminal pro-B-type natriuretic peptide (NT-proBNP). Echocardiographic evaluation focused on left and right ventricular systolic function and global longitudinal strain (GLS). RESULTS: In total, 51 patients were included, with a median age of 63 years (range 51-68 years) of whom 80% was male. Troponin T was elevated (>14 ng/l) in 47%, and a clinically relevant Troponin T elevation (10â€¯× URL) was found in three patients (6%). NT-proBNP was elevated (>300 pg/ml) in 24 patients (47%), and in four (8%) the NT-proBNP concentration was >1,000 pg/ml. Left ventricular dysfunction (ejection fraction <52% and/or GLS >-18%) was observed in 27%, while right ventricular dysfunction (TAPSE <17 mm and/or RV S' < 10 cm/s) was seen in 10%. There was no association between elevated Troponin T or NT-proBNP and left or right ventricular dysfunction. Patients with confirmed pulmonary embolism had normal right ventricular function. CONCLUSIONS: In hospitalised patients, it seems that COVID-19 predominantly affects the respiratory system, while cardiac dysfunction occurs less often. Based on a single echocardiographic evaluation, we found no relation between elevated Troponin T or NT-proBNP, and ventricular dysfunction. Echocardiography has limited value in screening for ventricular dysfunction.