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Process-Specific Blood Biomarkers and Outcomes in COVID-19 Versus Non-COVID-19 ARDS (APEL-COVID Study): A
Olivier Lesur1,2,3, Eric David Segal3, Kevin Rego1,2,3
1Centre de Recherche Clinique du CHU Sherbrooke (CRCHUS), Department of Intensive Care Medicine, Faculty of Medicine and Health Sciences, University of Sherbrooke, 3001 12th Avenue Nord, Sherbrooke, QC J1H 5N4, Canada.
Abstract:
Background: Severe acute respiratory syndrome (SARS) and acute respiratory distress syndrome (ARDS) are often considered separate clinico-radiological entities. Whether these conditions also present a single process-specific systemic biomolecular phenotype and how this relates to patient outcomes remains unknown. A prospective cohort study was conducted, including adult patients admitted to the ICU and general floors for COVID-19-related (COVID+) or non-COVID-19-related (COVID-) acute respiratory failure during the main phase of the pandemic. The primary objective was to study blood biomarkers and outcomes among different groups and severity subsets. Results: A total of 132 patients were included, as follows: 67 COVID+, 54 COVID- (with 11 matched control subjects for biomarker reference), and 58 of these patients allowed for further pre- and post-analysis. The baseline apelin (APL) levels were higher in COVID+ patients (p < 0.0001 vs. COVID- patients) and in SARS COVID+ patients (p ≤ 0.02 vs. ARDS), while the IL-6 levels were higher in ARDS COVID- patients (p ≤ 0.0001 vs. SARS). Multivariable logistic regression analyses with cohort biomarkers and outcome parameters revealed the following: (i) log-transformed neprilysin (NEP) activity was significantly higher in COVID+ patients (1.11 [95% CI: 0.4-1.9] vs. 0.37 [95% CI: 0.1-0.8], fold change (FC): 1.43 [95% CI: 1.04-1.97], p = 0.029) and in SARS patients (FC: 1.65 [95% CI: 1.05-2.6], p = 0.032 vs. non-SARS COVID+ patients, and 1.73 [95% CI: 1.19-2.5], p = 0.005 vs. ARDS COVID- patients) and (ii) higher lysyl oxidase (LOX) activity and APL levels were respectively associated with death and a shorter length of hospital stay in SARS COVID+ patients (Odds Ratios (OR): 1.01 [1.00-1.02], p = 0.05, and OR: -0.007 [-0.013-0.0001], p = 0.048). Conclusion: Process-specific blood biomarkers exhibited distinct profiles between COVID+ and COVID- patients, and across stages of severity. NEP and LOX activities, as well as APL levels, are particularly linked to COVID+ patients and their outcomes (ClinicalTrials.gov Identifier: NCT04632732).
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