The efficacy of low molecular weight heparin is reduced in Covid-19.

BACKGROUND: A significant degree of mortality and morbidity in Covid-19 is through thromboembolic complications, only partially mitigated by anticoagulant therapy. Reliable markers of infection severity are not fully established. OBJECTIVES: This study investigated whether visco-elastic biomarkers predict disease severity on presentation to the Emergency Department (ED) and how they measure response to anticoagulationMETHODS:Patients testing positive for Covid-19 at a large University Teaching Hospital ED were recruited at presentation. Multiple blood samples were taken throughout hospital admission to monitor disease progression with end outcome recorded. Visco-elastic markers, fractal dimension (df) and Time to Gel Point (TGP) which measure the properties of the incipient clot were compared in patients with and without anticoagulation by Low Molecular Weight Heparin (LMWH). RESULTS: TGP and df did not predict severity of infection with Covid-19. Although LMWH prolonged TGP, there was no change in df indicating LMWH did not change clot microstructure. CONCLUSIONS: Therapeutic efficacy of LMWH appears blunted in Covid-19 infection. This may be due to the inflammatory state creating a resistance to LMWH activity, which may explain why LMWH appears less effective in Covid-19 compared to other disease states. Covid-19 was not predicted by visco-elastic testing at the time of ED presentation.

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.

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 < 0.001). Fourteen out of 72 patients treated with dexamethasone died during 28 days of follow-up. Survival rates were significantly lower in patients with high sRAGE (> 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.