Key result
Severe COVID-19 features higher epithelial injury but ~62% lower endothelial dysfunction versus non-COVID critical illness.
Why the study?
Analyses of blood biomarkers involved in the host response to SARS-CoV-2 can reveal distinct biological pathways and inform therapeutic development, motivating evaluation of host endothelial, epithelial, and inflammatory biomarkers in COVID-19.
Do host endothelial, epithelial, and inflammatory biomarker profiles differ between ICU patients with and without COVID-19?
Cohort (n=171)
Yes
Do host endothelial, epithelial, and inflammatory biomarker profiles differ between ICU patients with and without COVID-19?
Effect estimate: adjusted fold change 0.38 (95% CI 0.24-0.62)
p-value: p=<0.001
Severe COVID-19 early after ICU admission is characterized by epithelial cell injury and acute phase protein elaboration rather than endothelial dysfunction, distinguishing it from other causes of critical illness.
Indicates epithelial-dominant injury in early severe COVID-19 ICU illness; hypothesis-generating and should not yet change practice.
BACKGROUND: Analyses of blood biomarkers involved in the host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection can reveal distinct biological pathways and inform development and testing of therapeutics for COVID-19. Our objective was to evaluate host endothelial, epithelial and inflammatory biomarkers in COVID-19. METHODS: We prospectively enrolled 171 ICU patients, including 78 (46%) patients positive and 93 (54%) negative for SARS-CoV-2 infection from April to September, 2020. We compared 22 plasma biomarkers in blood collected within 24 h and 3 days after ICU admission. RESULTS: In critically ill COVID-19 and non-COVID-19 patients, the most common ICU admission diagnoses were respiratory failure or pneumonia, followed by sepsis and other diagnoses. Similar proportions of patients in both groups received invasive mechanical ventilation at the time of study enrollment. COVID-19 and non-COVID-19 patients had similar rates of acute respiratory distress syndrome, severe acute kidney injury, and in-hospital mortality. While concentrations of interleukin 6 and 8 were not different between groups, markers of epithelial cell injury (soluble receptor for advanced glycation end products, sRAGE) and acute phase proteins (serum amyloid A, SAA) were significantly higher in COVID-19 compared to non-COVID-19, adjusting for demographics and APACHE III scores. In contrast, angiopoietin 2:1 (Ang-2:1 ratio) and soluble tumor necrosis factor receptor 1 (sTNFR-1), markers of endothelial dysfunction and inflammation, were significantly lower in COVID-19 (p < 0.002). Ang-2:1 ratio and SAA were associated with mortality only in non-COVID-19 patients. CONCLUSIONS: These studies demonstrate that, unlike other well-studied causes of critical illness, endothelial dysfunction may not be characteristic of severe COVID-19 early after ICU admission. Pathways resulting in elaboration of acute phase proteins and inducing epithelial cell injury may be promising targets for therapeutics in COVID-19.
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Bhatraju et al. (2021) conducted a cohort in Critical illness with suspected COVID-19 (n=171). SARS-CoV-2 infection (COVID-19) vs. ICU patients without COVID-19 was evaluated on Angiopoietin-2:1 (Ang-2:1) ratio (adjusted fold change 0.38, 95% CI 0.24-0.62, p=<0.001). Severe COVID-19 early after ICU admission is characterized by higher markers of epithelial cell injury and acute phase proteins, but significantly lower markers of endothelial dysfunction, compared to non-COVID-19 critical illness.
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