Fig 2: Patients with COVID-19 present high serum levels of HMGB1, ATP, TF, PGE2, cys-LT, and LTB4 compared to HCs. (a–f) We plotted the highest serum value obtained after analysis of two or three samples received from each patient with COVID-19. Mediators were evaluated as described in Methods section. Data were presented as the median with interquartile range and were analyzed by Mann–Whitney test. Any p < 0.05 was considered statistically significant compared to HCs. COVID-19, coronavirus disease 2019; HCs, healthy controls; TF, tissue factor

Fig 3: HMGB1 serum levels discriminate deceased from discharged patients with COVID-19. (a–f) HMGB1, ATP, TF, PGE2, cys-LT, and LTB4 levels were stratified between discharged and deceased in patients with COVID-19 and compared to HCs. We plotted the highest serum value obtained after analysis of two or three samples received from each patient with COVID-19. The data were presented as the median with interquartile range and were analyzed by Kruskal-Wallis test. Any p < 0.05 was considered statistically significant compared to HCs or discharged groups. COVID-19, coronavirus disease 2019; HCs, healthy controls; ns, not significant; TF, tissue factor

Fig 4: Positive correlations of HMGB1 with cys-LTs, AST, ALT, and D-dimer in patients with COVID-19. (a–d) Spearman's correlation analyses between HMGB1 serum levels peak versus cys-LTs, AST, ALT, and D-dimer levels. We plotted the highest value obtained for HMGB1 after analysis of two or three samples received from each patient with COVID-19. The values for cys-LT, AST, ALT, and D-dimer were paired exactly with the same sample chosen for analysis of HMGB1. (e) ROC curve analysis determines the HMGB1 cutoff value (125.4 ng/ml) that predicts the worst clinical outcome (death). The AUC is 0.8311 ± 0.06 and the 95% CI is 0.7185–0.9437. The diagnostic sensitivity and specificity are 81.6% and 87.5%, respectively. ALT, alanine aminotransferase; AST, aspartate aminotransferase; AUC, area under the curve; CI, confidence interval; COVID-19, coronavirus disease 2019; ROC, receiving operating characteristic

Fig 5: Higher HMGB1 serum levels were observed in the pulmonary phase with hypoxia and hyperinflammatory early phase according to clinical outcome. (a–f) The mediator values were stratified among three temporal phases after hospital admission: pulmonary phase with hypoxia (2–11 days), hyperinflammatory early phase (12–25 days), and hyperinflammatory late phase (26–168 days). Data were presented as mean ± SEM and were analyzed by Kruskal-Wallis test. ns, not significant. Any p < 0.05 was considered statistically significant compared to the indicated phases