Fig. 3

Directed acylic graphs of causal hypotheses for mediation analysis of hypothesized mediators: DEspR + [NET + Ns] or comparator ANC in COVID-19. A Hypothesis-1: DEspR + [NET + Ns] mediate progression of multi-organ dysfunction causal path between t1 (t1-SOFA score) to multi-organ failure (t-2 SOFA score) or poor clinical outcomes (ICUFD). Alternative mediator tested: ANC, absolute neutrophil counts. B Hypothesis-2: DEspR + [NET + Ns] mediate progression of respiratory distress at t1 (t1-SF ratio) to respiratory failure at t2 (t2-SF) or poor clinical outcomes (ICUFD). SOFA-score, obtained without neurological component; ICUFD, ICU-free days by day 28 with 0 for patients in the ICU > 28 days and competing risk of death [-1]