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1.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-322800

ABSTRACT

Background: In severe cases of coronavirus disease (COVID-19), acute respiratory distress syndrome (ARDS) with alveolar tissue injury occurs. However, the time course and specific contributions of alveolar epithelial and endothelial injury to the pathogenesis of COVID-19 ARDS remain unclear. Methods: : We evaluated the levels of a circulating alveolar epithelial injury marker (soluble receptor for advanced glycation end-products: sRAGE) and an endothelial injury marker (angiopoietin-2: ANG-2), along with an alveolar permeability indicator (surfactant protein D: SP-D) in 107 serum samples from nine patients with ARDS and eight without ARDS, all with COVID-19, admitted to Yokohama City University Hospital from January to July 2020. We compared the initial levels of these markers between ARDS and non-ARDS patients, and analysed the temporal changes of these markers in ARDS patients. Results: : All the initial levels of sRAGE (median: 2680 pg/mL, IQR:1522–5076 vs. median 701 pg/mL, IQR:344–1148.0, p=0.0152), ANG-2 (median: 699 pg/mL, IQR: 410-2501 vs. median: 231 pg/mL, IQR: 64-584, p=0.0464), and SP-D (median: 17542 pg/mL, IQR: 7423-22979 vs. 1771 pg/mL, IQR: 458-204, p=0.0274) were significantly higher in the ARDS patients than in the non-ARDS patients. The peak sRAGE level in the ARDS patients was observed at the very early phase of disease progression (median: day 1, IQR: day 1–3.5). However, the peaks of ANG-2 (median: day 4, IQR: day 2.5–6) and SPD (median: day 5, IQR: day 3–7.5) were observed at a later phase. Moreover, the ANG-2 level was significantly correlated with the arterial oxygenation (p=0.030) and the SPD level (p=0.002), but the sRAGE level was not. Conclusion: Evaluation of circulating markers confirms that COVID-19 ARDS is characterised by severe alveolar tissue injury. Our data indicate that the endothelial injury, which continues for a longer period than the epithelial injury, seems to be the main contributor to alveolar barrier disruption. Targeting the endothelial injury may, thus, be a promising approach to overcome ARDS with COVID-19.

3.
Sci Rep ; 11(1): 13431, 2021 06 28.
Article in English | MEDLINE | ID: covidwho-1286474

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.


Subject(s)
COVID-19/pathology , Iron/blood , Adult , Aged , COVID-19/complications , COVID-19/virology , Female , Ferritins/blood , Hospitalization , Humans , Iron/metabolism , Logistic Models , Male , Middle Aged , Respiratory Insufficiency/etiology , SARS-CoV-2/isolation & purification , Severity of Illness Index , Transferrin/analysis
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