Process-Specific Blood Biomarkers and Outcomes in COVID-19 Versus Non-COVID-19 ARDS (APEL–COVID Study): A Prospective, Observational Cohort Study

<b>Background:</b> 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. <b>Results:</b> 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 (<i>p</i> < 0.0001 vs. COVID- patients) and in SARS COVID+ patients (<i>p</i> ≤ 0.02 vs. ARDS), while the IL-6 levels were higher in ARDS COVID- patients (<i>p</i> ≤ 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], <i>p</i> = 0.029) and in SARS patients (FC: 1.65 [95% CI: 1.05-2.6], <i>p</i> = 0.032 vs. non-SARS COVID+ patients, and 1.73 [95% CI: 1.19-2.5], <i>p</i> = 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], <i>p</i> = 0.05, and OR: -0.007 [-0.013-0.0001], <i>p</i> = 0.048). <b>Conclusion:</b> 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).