High levels of circulating osteopontin in inflammatory lung disease regardless of Sars‐CoV‐2 infection

Cappellano, Giuseppe; Abreu, Hugo; Raineri, Davide; Scotti, Lorenza; Castello, Luigi Mario; Vaschetto, Rosanna

doi:10.15252/emmm.202114124

Cited by 7 publications

(7 citation statements)

References 12 publications

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“…More specifically, increased OPN-levels were described in patients with interstitial [20] and eosinophilic pneumonias [21]. In another analyses featuring patients hospitalized for respiratory failure, OPN-plasma levels were found to be increased compared to healthy controls, whereas no difference was found between SARS-CoV-2 positive and SARS-CoV-2 negative patients [10]. These findings suggest that OPN cannot be used as a biomarker supporting the diagnosis of SARS-CoV-2 infection but rather as a marker for stratifying patients according to their clinical course.…”

Section: Discussionmentioning

confidence: 94%

“…Elevated levels of circulating OPN have been reported in patients with systemic inflammation such as sepsis [7,8] and are associated with increased mortality rates in these patients [9]. 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].…”

Section: Introductionmentioning

confidence: 99%

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Circulating Osteopontin Levels and Outcomes in Patients Hospitalized for COVID-19

Hayek

Roderburg

Blakely

et al. 2021

JCM

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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.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Circulating Osteopontin Levels and Outcomes in Patients Hospitalized for COVID-19

Hayek

Roderburg

Blakely

et al. 2021

JCM

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“…The fast response is due to OPN's baseline expression and quick upregulation, causing lung vascular leakage and immune cell accumulation within an hour, ultimately resulting in functional impairment with reduced arterial oxygenation. This finding has implications beyond acute kidney injury, as tissue injury due to various causes can raise OPN serum levels in humans, including but not limited to direct lung injury by COVID-19, bacterial pneumonia 49,50 , by sepsis from various causes 32,51,52 , or cardiac injury 47,51 . OPN has also been described as a marker of kidney injury and declining kidney function e.g.…”

Section: Discussionmentioning

confidence: 95%

Circulating osteopontin released by injured kidneys causes pulmonary inflammation and edema

Khamissi¹,

Ning²,

Kefaloyianni³

et al. 2021

Preprint

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Multiorgan failure is devastating, and its mechanisms and mediators are not clear. Tissue injury in one organ appears to trigger disease in remote organs. Kidney and lung are frequently affected, such as when acute kidney injury (AKI) causes acute lung injury (ALI), a frequent clinical condition with high mortality. Here we identify factors secreted from the injured kidney that cause acute lung injury. We developed a murine model mimicking the generation of respiratory failure following acute kidney injury. To identify interorgan crosstalk mediators involved, we performed scRNAseq of mouse kidneys and lungs after AKI. We then applied ligand-receptor (L-R) pairing analysis across cells residing in kidney (ligands) or lung (receptors) to identify kidney-released circulating osteopontin (OPN) as a novel mediator of AKI-induced ALI (AKI-ALI). OPN release very early after AKI largely from tubule cells triggered neutrophil and macrophage infiltration into lungs associated with endothelial leakage, interstitial edema, and functional impairment. Pharmacological or genetic inhibition of OPN prevented AKI-ALI. Transplantation of ischemic wt kidneys into wt mice caused AKI-ALI, while transplantation of ischemic OPN-global-knockout kidneys failed to induce lung endothelial leakage and AKI-ALI, identifying circulating kidney-released OPN as sufficient to cause AKI-ALI in vivo. We show that AKI in humans results in elevations in OPN levels in the serum. Increased serum OPN levels in patients with multiorgan failure have been shown to positively correlate with reduced kidney function, respiratory failure, and mortality. Thus, our results identifying OPN as a mediator of AKI-ALI may have important therapeutic implications in human AKI-ALI and multiorgan failure.

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“…[20][21][22] Although OPN is known to play a role in both physiologic and pathophysiologic processes, the exact mechanisms of action still requires elucidation. [16][17][18][23][24][25][26][27] OPN is known to be involved in a number of normal biological processes including bone remodeling and immune modulation, but it is unclear if these effects are beneficial or detrimental (or both) to health. 20,22 Pathologically, OPN has known roles in cancer, diabetes, kidney stones, lung, and cardiovascular diseases.…”

Section: Impact Statementmentioning

confidence: 99%

“…20,22 Pathologically, OPN has known roles in cancer, diabetes, kidney stones, lung, and cardiovascular diseases. [20][21][22][23] While not a specific marker, levels of OPN have been used to follow disease progression, response to treatment, and guide prognosis in diverse pathologies, including tumor progression, atherosclerosis, and diabetic nephropathy. 20,28,29 Although the pathophysiologic basis for the overexpression of OPN in these diverse pathologies is not yet fully elucidated, OPN is implicated in both inflammation and immune responses.…”

Section: Impact Statementmentioning

confidence: 99%

Osteopontin as a biomarker for COVID-19 severity and multisystem inflammatory syndrome in children: A pilot study

Reisner

Blackwell

Sayeed

et al. 2021

Exp Biol Med (Maywood)

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This study sought to evaluate the candidacy of plasma osteopontin (OPN) as a biomarker of COVID-19 severity and multisystem inflammatory condition in children (MIS-C) in children. A retrospective analysis of 26 children (0–21 years of age) admitted to Children’s Healthcare of Atlanta with a diagnosis of COVID-19 between March 17 and May 26, 2020 was undertaken. The patients were classified into three categories based on COVID-19 severity levels: asymptomatic or minimally symptomatic (control population, admitted for other non-COVID-19 conditions), mild/moderate, and severe COVID-19. A fourth category of children met the Centers for Disease Control and Prevention's case definition for MIS-C. Residual blood samples were analyzed for OPN, a marker of inflammation using commercial ELISA kits (R&D), and results were correlated with clinical data. This study demonstrates that OPN levels are significantly elevated in children hospitalized with moderate and severe COVID-19 and MIS-C compared to OPN levels in mild/asymptomatic children. Further, OPN differentiated among clinical levels of severity in COVID-19, while other inflammatory markers including maximum erythrocyte sedimentation rate, C-reactive protein and ferritin, minimum lymphocyte and platelet counts, soluble interleukin-2R, and interleukin-6 did not. We conclude OPN is a potential biomarker of COVID-19 severity and MIS-C in children that may have future clinical utility. The specificity and positive predictive value of this marker for COVID-19 and MIS-C are areas for future larger prospective research studies.

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High levels of circulating osteopontin in inflammatory lung disease regardless of Sars‐CoV‐2 infection

Cited by 7 publications

References 12 publications

Circulating Osteopontin Levels and Outcomes in Patients Hospitalized for COVID-19

Circulating Osteopontin Levels and Outcomes in Patients Hospitalized for COVID-19

Circulating osteopontin released by injured kidneys causes pulmonary inflammation and edema

Osteopontin as a biomarker for COVID-19 severity and multisystem inflammatory syndrome in children: A pilot study

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