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Abstract
Coronavirus disease 19 (COVID-19) presents with disease severities of varying degree. In its most severe form, infection may lead to respiratory failure and multi-organ dysfunction. Here we study the levels and evolution of the damage associated molecular patterns (DAMPS) cell free DNA (cfDNA), extracellular histone H3 (H3) and neutrophil elastase (NE), and the immune modulators GAS6 and AXL in relation to clinical parameters, ICU scoring systems and mortality in patients (n = 100) with severe COVID-19. cfDNA, H3, NE, GAS6 and AXL were increased in COVID-19 patients compared to controls. These measures associated with occurrence of clinical events and intensive care unit acquired weakness (ICUAW). cfDNA and GAS6 decreased in time in patients surviving to 30 days post ICU admission. A decrease of 27.2 ng/mL cfDNA during ICU stay associated with patient survival, whereas levels of GAS6 decreasing more than 4.0 ng/mL associated with survival. The presence of H3 in plasma was a common feature of COVID-19 patients, detected in 38% of the patients at ICU admission. NETosis markers cfDNA, H3 and NE correlated well with parameters of tissue damage and neutrophil counts. Furthermore, cfDNA correlated with lowest p/f ratio and a lowering in cfDNA was observed in patients with ventilator-free days.
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1 Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Department of Biochemistry, Maastricht, the Netherlands (GRID:grid.5012.6) (ISNI:0000 0001 0481 6099)
2 Uppsala University, Department of Surgical Sciences, Section for Anaesthesia & Intensive Care, Uppsala, Sweden (GRID:grid.8993.b) (ISNI:0000 0004 1936 9457)
3 IIBB-CSIC, IDIBAPS, and BCLC, CIBEREHD, Department of Cell Death and Proliferation, Barcelona, Spain (GRID:grid.10403.36)
4 Uppsala University, Department of Surgical Sciences, Section for Anaesthesia & Intensive Care, Uppsala, Sweden (GRID:grid.8993.b) (ISNI:0000 0004 1936 9457); Uppsala University, Department of Medical Cell Biology, Integrative Physiology, Uppsala, Sweden (GRID:grid.8993.b) (ISNI:0000 0004 1936 9457)
5 Uppsala University, Department of Medical Sciences, Clinical Microbiology, Uppsala, Sweden (GRID:grid.8993.b) (ISNI:0000 0004 1936 9457)
6 Hospital Clinic Barcelona and CIBERCV, Cardiology Department, Barcelona, Spain (GRID:grid.410458.c) (ISNI:0000 0000 9635 9413)
7 Maastricht University Medical Centre MUMC+), Department of Intensive Care Medicine, Maastricht, the Netherlands (GRID:grid.412966.e) (ISNI:0000 0004 0480 1382); Maastricht University Medical Centre, Department of Cardiology, Maastricht, the Netherlands (GRID:grid.412966.e) (ISNI:0000 0004 0480 1382)
8 Uppsala University, Department of Surgical Sciences, Section for Anaesthesia & Intensive Care, Uppsala, Sweden (GRID:grid.8993.b) (ISNI:0000 0004 1936 9457); Uppsala University, Hedenstierna Laboratory, Anaesthesiology and Intensive Care Medicine, Department of Surgical Sciences, Uppsala, Sweden (GRID:grid.8993.b) (ISNI:0000 0004 1936 9457)
9 Maastricht University Medical Centre MUMC+), Department of Intensive Care Medicine, Maastricht, the Netherlands (GRID:grid.412966.e) (ISNI:0000 0004 0480 1382); Maastricht University, Department of Surgery, Maastricht University Medical Centre (MUMC+), School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht, the Netherlands (GRID:grid.5012.6) (ISNI:0000 0001 0481 6099)
10 Uppsala University, Department of Medical Sciences, Clinical Chemistry, Uppsala, Sweden (GRID:grid.8993.b) (ISNI:0000 0004 1936 9457)
11 IIBB-CSIC, IDIBAPS and CIBERCV, Department of Cell Death and Proliferation, Barcelona, Spain (GRID:grid.420258.9) (ISNI:0000 0004 1794 1077)