ABSTRACT
Background: Venovenous extracorporeal membrane oxygenation (ECMO) is a cornerstone in the management of severe acute respiratory distress syndrome (ARDS) and causes hemostatic system activation and inflammation. COVID-19 is known to cause thromboinflammation. Elucidation of the underlying pathomechanisms is of great importance. Aim(s): To evaluate markers of NET formation in COVID-19 and non-COVID- 19 associated ARDS and ECMO and to explore the role of different NET parameters as markers of inflammation and coagulopathy. Method(s): We studied 31 adult COVID-19 patients and 23 adult non-COVID- 19 patients with severe ARDS requiring ECMO and 47 sex-and age-matched healthy controls. Blood was collected at time point A (ECMO day 0-4) and at time point B (ECMO day 7-17). Citrullinated histone H3 (citH3), cell-free DNA (cfDNA), and plasma myeloperoxidase DNA (mpoDNA), as well as d-Dimer, were evaluated. Values are given as median (25th, 75th percentile). Statistical testing was performed using unpaired t-tests of logarithmized parameters. Result(s): COVID-19 and non-COVID- 19 patients exhibited significantly higher levels of citH3, cfDNA, and mpoDNA than healthy controls (Table 1). Levels of citH3 decreased significantly from time point A to B in COVID-19 patients. No comparable effect was identified for cfDNA and mpoDNA (Table 1). In non-COVID- 19 patients, no differences in levels of citH3, cfDNA, and mpoDNA were found between timepoints A and B (Table 1). d-Dimer increased from time point A to timepoint B in both groups (Table 1). Conclusion(s): NET formation is comparably increased in patients on ECMO because of COVID-19 and non-COVID- 19 ARDS. Markers of NET formation could add information on immunothrombosis and the complex interplay of coagulation and inflammation in the context of ECMO.
ABSTRACT
Background : Pulmonary thrombus formation is a hallmark of COVID-19. A dysregulated immune response culminating in thromboinflammation has been described, but the pathomechanisms remain unclear. Aims : To evaluate the role of extracellular vesicles (EV) and citrullinated histone H3 (citH3) as markers of coagulopathy and inflammation. Methods : We studied 41 adult COVID-19 patients with a positive result on a reverse-transcriptase polymerase-chain-reaction assay and 37 sex-and age-matched healthy controls. Number and surface characteristics of EV and citH3 levels were determined in plasma upon admission by flowcytometry and immunoassay, respectively. Values are given as median (25 th , 75 th percentile) and differences by geometric mean ratios (GMR [95% CI]) or mean differences (ΔsMean [95% CI]). Results : 20 patients had severe and 21 mild disease. Patients exhibited significantly higher numbers of total EV, and of EV derived from platelets, endothelial cells, leukocytes, or neutrophils than controls (Table 1). EV from alveolar-macrophages and alveolar-epithelial-cells were detectable in plasma and were significantly higher in patients. ICAM-1 positive EV levels were higher in patients while no difference between TF-positive and ACE-positive EV was seen between the two groups. Levels of EV did not differ between patients with severe and mild COVID-19. citH3 levels were higher in patients than in controls [1.42 (0.6, 3.37) vs 0.31 (0.14, 0.6), GMR 4.44 (2.57, 7.66);P < 0.001], and were significantly lower in patients with mild disease compared to those with severe disease. Conclusions : EV and citH3 are associated with COVID-19. They provide information regarding pathophysiology and could be explored as markers of the disease.
ABSTRACT
We report the case of a female, 77 year old patient with multi-localized skin infarctions following vaccination with mRNA-1273 (Moderna). This phenomenon is to our knowledge otherwise only seen in infection-associated purpura fulminans - which was thoroughly ruled out in our patient. This report demonstrates that we need to be vigilant of a wider array of vascular phenomena related to Covid vaccinations.