The Effect of Endurance Exercise and its Intensity in Middle- aged Runners; Are they Thrombogenic?

Introduction Despite the well documented benefits of regular exercise, acute exercise induces a transient hypercoagulable state with increasing risk of thrombotic disease with age and intensity. While prior studies have used various conventional coagulation tests in studying the influence of exercise on coagulation, limited attention has been given to clot microstructure and contraction profile in well-trained individuals of middle to older age. Our aim was to identify effects of exercise on these variables using hemorheological biomarkers. Materials and methods Twenty-eight male and female runners aged over 40 years completed a 10 km run at moderate intensity. Of these runners,14 were reinvited to complete a 3 km run to exhaustion. Blood samples were drawn at three time-points, baseline, immediately after exercise and after 1 hour of recovery. Structural biomarker df and measurements of mature clot mechanical properties (Maximum Contractile Force and G’Max) were analysed alongside conventional coagulation markers. Results While df remained stable following long moderate intensity exercise, higher intensity exercise caused an increase in df indicating a hypercoagulable phase. Following an hour of rest, df returned to baseline. These results indicate that the effect of acute exercise on hypercoagulability is intensity dependent and transient. Maximum Contractile Force (CFMax) was reduced by exercise, irrespective of intensity. This effect was lower after an hour of rest, suggesting that some unknown initial compensatory mechanisms are outlasted by a longer period of reduced contractile force. Conclusion df and CFMax detected the hypercoagulable phase that occurred in trained older individuals as a result of exercise. Investigating these effects in more sentient populations could allow risk stratification of exercise rehabilitation programmes and their intensity

High levels of soluble RAGE are associated with a greater risk of mortality in COVID-19 patients treated with dexamethasone

Blood levels of the soluble receptor for advanced glycation end-products (sRAGE) are acutely elevated during the host inflammatory response to infection and predict mortality in COVID-19. However, the prognostic performance of this biomarker in the context of treatments to reduce inflammation is unclear. In this study we investigated the association between sRAGE and mortality in dexamethasone-treated COVID-19 patients. We studied 89 SARS-CoV-2 positive subjects and 22 controls attending the emergency department of a University Teaching Hospital during the second wave of COVID-19 and measured sRAGE at admission. In positive individuals sRAGE increased with disease severity and correlated with the National Early Warning Score 2 (Pearson’s r = 0.56, p  3532 pg/mL) than in those with low sRAGE (p = 0.01). Higher sRAGE levels were associated with an increased risk of death after adjustment for relevant covariates. In contrast, IL-6 did not predict mortality in these patients. These results demonstrate that sRAGE remains an independent predictor of mortality among COVID-19 patients treated with dexamethasone. Determination of sRAGE could be useful for the clinical management of this patient population

Impaired fibrinolysis is implicated in mortality in COVID‑19 infection

Introduction: COVID-19 is a severe respiratory disease associated with a marked inflammatory response. Clinical methods of assessing severity of disease, including National Early Warning Score 2 (NEWS2), have been shown to predict severity in COVID-19 [1]. However, little research has been undertaken comparing NEWS2 to underlying inflammatory processes. In this study, we assessed whether inflammatory markers taken at presentation to the Emergency Department could predict and mortality in COVID-19 patients.Methods: Whole blood samples were taken at admission to the emergency department for procalcitonin, fibrinogen, CRP, von Willebrand Factor (vWF), IL-6 and TNFα. NEWS2 was also recorded on admission. Levels of inflammatory markers were retrospectively compared to NEWS2 scores and mortality outcomes.Results: A total of 95 patients positive for COVID-19 were included. NEWS2 values > 5 were associated with higher CRP (131.5 ± 87.9 vs 86.4 ± 106.5, p = 0.03), IL-6 (71.9 ± 111 vs 43.4 ± 99, p = 0.007), and vWF (334.1 ± 83.3 vs 296.3 ± 93.4, p = 0.04). The trend of increasing inflammatory markers was also shown in patients who died, significantly so for IL-6 (44.4 ± 54.97 vs 18.8 ± 48.36, p = 0.035). NEWS2 was also shown to be significantly higher in patients who died (7.8 ± 2.2 vs 4.3 ± 2.8, p =  < 0.01).Conclusions: NEWS2 predicted the severity of underlying inflammatory response. All inflammatory markers showed a marked increase with severity and mortality, most significant with IL-6. This suggests NEWS2 and inflammatory markers may predict severity and mortality in COVID-19 patients. Further research is required to evaluate these mechanistic changes in inflammatory response.Reference1.Kostakis I et al. Resuscitation. 159:150–157, 2021

Impaired fibrinolysis in severe Covid-19 infection is detectable in early stages of the disease

BACKGROUND: A significant degree of mortality and morbidity in Covid-19 is due to thromboembolic disease. Coagulopathy has been well described in critically unwell patients on ICU. There is less clear evidence regarding these changes at the time of presentation to the Emergency Department and the progression of disease over time. OBJECTIVE: We sought to investigate whether coagulation markers can predict severity and how they change over the disease course. METHODS: Patients presenting to a single University Teaching Hospital were recruited and followed up if PCR was positive. Alongside routine blood testing, Rotational Thromboelastometry (ROTEM) was performed. Outcome data was recorded for all patients, and ROTEM values were compared across outcome groups. RESULTS: Extem and Intem Maximum Lysis were significantly reduced in those who died or required an ICU admission, indicating a reduced ability to break down clot mass in the most critically unwell patients. CONCLUSION: Comparisons between groups demonstrated that one distinguishing feature between those who require ICU admission or die of Covid-19 compared with those who survive a hospital stay to discharge was the extent to which fibrinolysis could occur. Mortality and morbidity in Covid-19 infection appears in part driven by an inability to break down clot mass.</jats:p

High levels of soluble RAGE are associated with a greater risk of mortality in COVID-19 patients treated with dexamethasone

 Blood levels of the soluble receptor for advanced glycation end-products (sRAGE) are acutely elevated during the host inflammatory response to infection and predict mortality in COVID-19. However, the prognostic performance of this biomarker in the context of treatments to reduce inflammation is unclear. In this study we investigated the association between sRAGE and mortality in dexamethasone-treated COVID-19 patients. We studied 89 SARS-CoV-2 positive subjects and 22 controls attending the emergency department of a University Teaching Hospital during the second wave of COVID-19 and measured sRAGE at admission. In positive individuals sRAGE increased with disease severity and correlated with the National Early Warning Score 2 (Pearson’s r = 0.56, p  3532 pg/mL) than in those with low sRAGE (p = 0.01). Higher sRAGE levels were associated with an increased risk of death after adjustment for relevant covariates. In contrast, IL-6 did not predict mortality in these patients. These results demonstrate that sRAGE remains an independent predictor of mortality among COVID-19 patients treated with dexamethasone. Determination of sRAGE could be useful for the clinical management of this patient population. </p

Additional file 1 of High levels of soluble RAGE are associated with a greater risk of mortality in COVID-19 patients treated with dexamethasone

Additional file 1. Supplementary methods

Additional file 2 of High levels of soluble RAGE are associated with a greater risk of mortality in COVID-19 patients treated with dexamethasone

Additional file 2. Table S1. Relationships between sRAGE, NEWS2 and IL-6. Table S2. Univariate analysis for potential predictors of mortality in dexamethasone-treated COVID-19 patients. Table S3. Performance of sRAGE and NEWS2 in their ability to predict mortality in dexamethasone-treated COVID-19 patient