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Distinct Time Courses and Pathogenic Contributions of Alveolar Epithelial and Endothelial Injury in Acute Respiratory Distress Syndrome With COVID-19: Evidence From Circulating Biomarkers
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, IQR1522–5076 vs. median 701 pg/mL, IQR344–1148.0, 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.

Full text: Available Collection: Preprints Database: EuropePMC Type of study: Evidence synthesis Language: English Year: 2021 Document Type: Preprint

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Full text: Available Collection: Preprints Database: EuropePMC Type of study: Evidence synthesis Language: English Year: 2021 Document Type: Preprint