Prognostic significance of complement factors in severely ill patients with COVID-19.

Coagulopathy, cytokine release, platelet hyperactivity and endothelial activation are regarded as potential major contributors to COVID-19 morbidity. Complement activation might provide a bridge linking these factors in severe COVID-19 illness. In this study, we investigated the prognostic significance of selected complement factors in hospitalized patients with severe COVID-19 infection. The study included 300 hospitalized adults with severe COVID-19 infection. Complement factors (C3, C3a, C4, sC5b-9) were assessed by commercial ELISA kits. Outcome parameters included mortality, intensive care unit admission and duration of hospital stay. It was found that survivors had significantly higher serum C3 (median (IQR): 128.5 (116.3-141.0) mg/dL vs 98.0 (70.0-112.8) mg/dL, p<0.001) and C4 (median (IQR): 36.0 (30.0-42.0) mg/dL vs 31.0 (26.0-35.0) mg/dL, p<0.001) levels when compared with non-survivors. On the other hand, it was shown that survivors had significantly lower C3a (median (IQR): 203.0 (170.3-244.0) ng/mL vs 385.0 (293.0-424.8) ng/mL, p<0.001) and sC5b-9 (median (IQR): 294.0 (242.0-318.8) ng/mL vs 393.0 (342.0-436.5) ng/mL, p<0.001) levels when compared with non-survivors. Multivariate logistic regression analysis identified C3a (OR: 0.97 (95% CI 0.96 to 0.99), p<0.001) and C4 (OR: 0.92 (95% CI 0.86 to 0.98), p=0.011) levels as significant predictors of mortality. In conclusion, serum levels of complement factors are related to mortality in severely ill patients with COVID-19.

MiR-150 Expression in Chronic Myeloid Leukemia: Relation to Imatinib Response.

OBJECTIVE: To assess the circulating micro-RNA-150 (miR-150) expression in patients with chronic myeloid leukemia (CML) in relation to imatinib response. METHODS: Sixty patients with CML and 20 age- and sex-matched control subjects were enrolled. Circulating miR-150 levels were assessed by quantitative real-time polymerase chain reaction on days 0, 14, and 90 of imatinib therapy for patients and once for control subjects. RESULTS: The baseline miR-150 expression was significantly lower in patients with CML than in control subjects with subsequent elevation at 14 and 90 days after the start of imatinib treatment. Early treatment response (ETR) at 90 days was the main study outcome. The miR-150 expression had a significantly higher level in patients with CML with ETR. On multivariate analysis, miR-150 on day 14 was significantly related to ETR in patients with CML with predictive efficacy (area under the curve = 0.838, 72.9% sensitivity, and 84.2% specificity). CONCLUSION: We found that miR-150 expression on day 14 of imatinib treatment is a useful early predictive candidate for imatinib response in patients with CML.

Circulating miR-146a expression predicts early treatment response to imatinib in adult chronic myeloid leukemia.

This study aimed to investigate the prognostic role of circulating miR-146a in the prediction of early response to imatinib treatment in patients with chronic myeloid leukemia (CML). Sixty patients with CML and 20 healthy controls were recruited in this study. BCR-ABL was assessed by quantitative rt-PCR at days 0 and 90 of imatinib therapy. Circulating miR-146a levels were assessed by quantitative rt-PCR at days 0, 14 and 90 of imatinib therapy for patients and once for controls. At day 90 of treatment, treatment response was achieved in 48 patients (80.0%). Responders had significantly lower baseline Sokal score when compared with non-responders. They also had significantly lower BCR-ABL expression at day 90 of treatment. The circulating miR-146a level was significantly lower in patients with CML than in healthy subjects and showed a significant rise after 14 days of imatinib treatment and an inverse correlation with BCR-ABL expression levels at 90 days. Using multivariate logistic regression analysis, baseline BCR-ABL (%) (OR (95% CI) 1.09 (1.03 to 1.016), p=0.006) and miR-146a at 14 days (OR (95% CI) 0.002 (0.0 to 0.09), p=0.001) were significant predictors of treatment response. Using ROC curve analysis, it was found that miR-146a expression at 14 and 90 days could distinguish responders from non-responders (AUC (95% CI) 0.849 (0.733 to 0.928) and 0.867 (0.755 to 0.941), respectively). This study reported for the first time that measurement of the circulating miR-146a expression at 14 days can predict the early response to imatinib treatment in patients with CML. Thus, this work indicates that miR-146a should be investigated in the setting of treatment response to other tyrosine kinase inhibitors.