Abstract
Background: Severe coronavirus disease 2019 (COVID-19) is the result of a hyper-inflammatory reaction to the severe acute respiratory syndrome coronavirus 2. The biomarkers of inflammation have been used to risk-stratify patients with COVID-19. Osteopontin (OPN) is an integrin-binding glyco-phosphoprotein involved in the modulation of leukocyte activation; its levels are associated with worse outcomes in patients with sepsis. Whether OPN levels predict outcomes in COVID-19 is unknown. Methods: We measured OPN levels in serum of 341 hospitalized COVID-19 patients collected within 48 h from admission. We characterized the determinants of OPN levels and examined their association with in-hospital outcomes; notably death, need for mechanical ventilation, and need for renal replacement therapy (RRT) and as a composite outcome. The risk discrimination ability of OPN was compared with other inflammatory biomarkers. Results: Patients with COVID-19 (mean age 60, 61.9% male, 27.0% blacks) had significantly higher levels of serum OPN compared to healthy volunteers (96.63 vs. 16.56 ng/mL, p < 0.001). Overall, 104 patients required mechanical ventilation, 35 needed dialysis, and 53 died during their hospitalization. In multivariable analyses, OPN levels ≥140.66 ng/mL (third tertile) were associated with a 3.5 × (95%CI 1.44–8.27) increase in the odds of death, and 4.9 × (95%CI 2.48–9.80) increase in the odds of requiring mechanical ventilation. There was no association between OPN and need for RRT. Finally, OPN levels in the upper tertile turned out as an independent prognostic factor of event-free survival with respect to the composite endpoint. Conclusion: Higher OPN levels are associated with increased odds of death and mechanical ventilation in patients with COVID-19, however, their utility in triage is questionable.
Highlights
COVID-19 represents a hyperinflammatory condition characterized by an excessive immune activation and an overshooting release of cytokines often leading to multi-organ failure [1,2,3]
As many patients with an unfavorable clinical course require mechanical ventilation (MV) or renal replacement therapy (RRT) at some point during treatment, we investigated the predictive function of OPN concentrations upon hospital admission for these clinical endpoints
CRP: C-reactive protein, eGFR: estimated glomerular filtration rate, OPN: The COVID-19 poses an unprecedented challenge to even well-resourced osteopontin
Summary
COVID-19 represents a hyperinflammatory condition characterized by an excessive immune activation and an overshooting release of cytokines often leading to multi-organ failure [1,2,3]. The individual course of COVID-19 is heterogeneous and early identification of patients at risk for a severe course of disease is often not possible. Inflammatory biomarkers such as C-reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin, often used in critically ill patients, have been proposed as risk stratification tools in the context of COVID-19 [3,4,5]. Alveolar macrophages strongly express OPN in patients with non-COVID-19 related acute respiratory distress syndrome (ARDS) (7), and preliminary results from smaller cohorts suggest a predictive role of OPN in the context of COVID-19 [10]. Osteopontin (OPN) is an integrin-binding glyco-phosphoprotein involved in the modulation of leukocyte activation; its levels are associated with worse outcomes in patients with sepsis.
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