ABSTRACT
Acute respiratory distress syndrome (ARDS) with COVID-19 is aggravated by hyperinflammatory responses even after the peak of viral load has passed; however, its underlying mechanisms remain unclear. In the present study, analysis of the alveolar tissue injury markers and epithelial cell death markers in patients with COVID-19 revealed that COVID-19-induced ARDS was characterized by alveolar epithelial necrosis at an early disease stage. Serum levels of HMGB-1, one of DAMPs released from necrotic cells, were also significantly elevated in these patients. Further analysis using mouse model mimicking COVID-19-induced ARDS showed that the alveolar epithelial cell necrosis involved two forms of programmed necrosis, namely necroptosis and pyroptosis. Finally, the neutralization of HMGB-1 attenuated alveolar tissue injury in the mouse model. Collectively, necrosis, including necroptosis and pyroptosis, is the predominant form of alveolar epithelial cell death at an early disease stage and subsequent release of DAMPs is a potential driver of COVID-19-induced ARDS.
ABSTRACT
Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that leads to severe respiratory failure (RF). It is known that host exposure to viral infection triggers an iron-lowering response to mitigate pathogenic load and tissue damage. However, the association between host iron-lowering response and COVID-19 severity is not clear. This two-center observational study of 136 adult hospitalized COVID-19 patients analyzed the association between disease severity and initial serum iron, total iron-binding capacity (TIBC), and transferrin saturation (TSAT) levels. Serum iron levels were significantly lower in patients with mild RF than in the non-RF group; however, there were no significant differences in iron levels between the non-RF and severe RF groups, depicting a U-shaped association between serum iron levels and disease severity. TIBC levels decreased significantly with increasing severity; consequently, TSAT was significantly higher in patients with severe RF than in other patients. Multivariate analysis including only patients with RF adjusted for age and sex demonstrated that higher serum iron and TSAT levels were independently associated with the development of severe RF, indicating that inadequate response to lower serum iron might be an exacerbating factor for COVID-19.
ABSTRACT
The time course and specific contributions of alveolar epithelial and endothelial injury to the pathogenesis of acute respiratory distress syndrome (ARDS) with coronavirus disease (COVID-19) remain unclear. Here, we evaluated the characteristics of circulating markers of alveolar epithelial and endothelial injury in serum samples from eleven ARDS patients and ten non-ARDS patients, all with COVID-19. Our results indicates that the alveolar epithelial injury at the very early disease stage and the endothelial injury which continues to exacerbate during the later disease stage seem to be the hallmarks of ARDS with COVID-19.
ABSTRACT
<b>Purpose</b>: We report two patients receiving high doses of systemic opioids in whom gradual switching of the opioid administration route from systemic to intrathecal provided satisfactory pain relief without excessive sedation or withdrawal symptoms. <b>Case reports</b>: In one of the patients, who was already receiving 500mg morphine intravenously but still suffered from right upper quadrant pain, it was difficult to increase the opioid dosage according to the WHO guidelines because of intolerable side effects. The other patient, in spite of taking a combination of systemic opioids equivalent to 760mg oral morphine, had inadequate pain relief and could not continue receiving home medical care. In both cases we could successfully change from systemic to intrathecal opioid administration in a step-wise manner without deterioration of pain control, adverse effects due to over dosage, or withdrawal symptoms. Intrathecal opioid administration also reduced drowsiness and improved daily activity. <b>Conclusion</b>: Currently, there are no guidelines for change of route of opioid administration from systemic to intrathecal administration and few published reports have concretely documented opioid route switching in Japan. A carefully planned, step-wise switching of opioid administration route from systemic to intrathecal should be considered in patients who are already taking high doses of systemic opioids. Palliat Care Res 2009; 4(1): 317-320
