Biomarkers of thromboinflammation correlate to COVID-19 infection and admission status in emergency department patients

Goswami, Julie; MacArthur, Taleen A.; Sridharan, Meera; Tange, Julie I.; Kirmse, A.; Lundell, Kaitlin; Chen, Dong; Auton, Matthew; Chon, Tony Y.; Hurt, Ryan T.; Salonen, Bradley R.; Ganesh, Ravindra; Erben, Young; Marquez, Christopher P.; Dong, Jing‐fei; Kozar, Rosemary A.; Heller, Stephanie F.; Loomis, Erica A.; Johnstone, Andrea L.; Bailey, Kent R.; Spears, Grant M.; Park, Myung S.

doi:10.1016/j.tru.2021.100090

Cited by 2 publications

(6 citation statements)

References 47 publications

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“…In this study, we examined a panel of biomarkers focusing on RAGE and SARS-CoV-2 nucleocapsid viral antigen in patients presenting to the emergency department with COVID-19. Our findings are consistent with prior literature demonstrating elevations in inflammatory cytokines and chemokines such as IL-6, IL-8, IL-10, IP-10, TNFR-1 and TREM-1 in the development of severe compared to mild COVID-19 (6,(8)(9)(10)(29)(30)(31). We also found increases in some but not all markers of thrombosis in those with severe disease including elevated PAI-1 and vWF activity.…”

Section: Discussionsupporting

confidence: 92%

“…However, most studies have focused on patients who have already been admitted to the hospital or intensive care unit, with a time lag between hospital presentation and sample collection. Data identifying biomarkers on patient presentation in the emergency department predictive of development of severe disease remains limited ( 8 , 9 ). Common laboratory assays such as d-dimer, c-reactive protein, and fibrinogen may be of value, but may lack sensitivity and specificity to accurately predict COVID-19 outcomes ( 3 , 10 , 11 ).…”

Section: Introductionmentioning

confidence: 99%

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Association of SARS-CoV-2 nucleocapsid viral antigen and the receptor for advanced glycation end products with development of severe disease in patients presenting to the emergency department with COVID-19

Matthay

Fields²,

Wick³

et al. 2023

Front. Immunol.

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IntroductionThere remains a need to better identify patients at highest risk for developing severe Coronavirus Disease 2019 (COVID-19) as additional waves of the pandemic continue to impact hospital systems. We sought to characterize the association of receptor for advanced glycation end products (RAGE), SARS-CoV-2 nucleocapsid viral antigen, and a panel of thromboinflammatory biomarkers with development of severe disease in patients presenting to the emergency department with symptomatic COVID-19.MethodsBlood samples were collected on arrival from 77 patients with symptomatic COVID-19, and plasma levels of thromboinflammatory biomarkers were measured.ResultsDifferences in biomarkers between those who did and did not develop severe disease or death 7 days after presentation were analyzed. After adjustment for multiple comparisons, RAGE, SARS-CoV-2 nucleocapsid viral antigen, interleukin (IL)-6, IL-10 and tumor necrosis factor receptor (TNFR)-1 were significantly elevated in the group who developed severe disease (all p<0.05). In a multivariable regression model, RAGE and SARS-CoV-2 nucleocapsid viral antigen remained significant risk factors for development of severe disease (both p<0.05), and each had sensitivity and specificity >80% on cut-point analysis.DiscussionElevated RAGE and SARS-CoV-2 nucleocapsid viral antigen on emergency department presentation are strongly associated with development of severe disease at 7 days. These findings are of clinical relevance for patient prognostication and triage as hospital systems continue to be overwhelmed. Further studies are warranted to determine the feasibility and utility of point-of care measurements of these biomarkers in the emergency department setting to improve patient prognostication and triage.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Association of SARS-CoV-2 nucleocapsid viral antigen and the receptor for advanced glycation end products with development of severe disease in patients presenting to the emergency department with COVID-19

Matthay

Fields²,

Wick³

et al. 2023

Front. Immunol.

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“…84 Indeed, numerous studies have reported elevated levels of vWF in COVID-19 patients. [28][29][30][32][33][34] On the other hand, decreased levels of ADAMTS13 has been detected in these patients, 31,47,48 and ratio of vWF antigen to ADAMTS13 activity is reportedly elevated in them. 6,49 Joly et al highlighted that increased vWF antigen to ADAMTS13 activity ratio is correlated with mortality, 34 while Mancini et al reported that imbalance between vWF antigen and ADAMTS13 activity is associated with disease severity.…”

Section: Von Willebrand Factor and Adamts13 Axismentioning

confidence: 80%

“…A total of 21 studies involving 1837 patients (670 with poor outcome and 1167 with good outcome) were investigated 6,10,28–46 . Meta‐analysis showed an association between higher levels of vWF and poor outcome in COVID‐19 patients (SMD: 0.83 (95% CI: 0.59–1.07), p < 0.00001) (Figure 2, panel A).…”

Section: Resultsmentioning

confidence: 99%

“…A total of 21 studies involving 1837 patients (670 with poor outcome and 1167 with good outcome) were investigated. 6,10,[28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46] Metaanalysis showed an association between higher levels of vWF and poor outcome in COVID-19 patients (SMD: 0.83 (95% CI: 0.59-1.07), p < 0.00001) (Figure 2, panel A). The heterogeneity was high among studies (I 2 = 77%, p < 0.00001).…”

Section: Vwfmentioning

confidence: 99%

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Biomarkers of endothelial dysfunction are associated with poor outcome in COVID‐19 patients: A systematic review and meta‐analysis

Mohebbi

Haybar

Moghaddam

et al. 2023

Reviews in Medical Virology

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Numerous studies have linked coronavirus disease 2019 (COVID‐19) with endothelial dysfunction and reported elevated levels of endothelial biomarkers in this disease. We conducted a systematic review and meta‐analysis of the published evidence in this respect. A systematic literature search of PubMed and Scopus databases was performed to find studies investigating biomarkers of endothelial dysfunction in COVID‐19 patients. Pooled standardized mean differences and their 95% confidence intervals were calculated for each biomarker using random effect model. 74 studies with 7668 patients were included. In comparison to patients with good outcome, those with poor outcome had higher levels of von Willebrand factor (vWF) (SMD: 0.83, 95% CI: 0.59–1.07, p < 0.00001), vWF:ADAMTS13 (1.23, (0.77–1.7), p < 0.00001), angiopoietin‐2 (Ang‐2) (1.06 (0.6–1.51), p < 0.0001), E‐selectin (1.09 (0.55–1.63), p < 0.0001), P‐selectin (0.59 (0.24–0.94), p = 0.001), syndecan‐1 (0.99 (0.6–1.37), p < 0.00001), mid‐regional pro‐adrenomedullin (MR‐proADM) (1.52 (1.35–1.68), p < 0.00001), vascular endothelial growth factor (0.27 (0.02–0.53), p = 0.03), soluble fms‐like tyrosine kinase‐1 (sFLT‐1) (1.93 (0.65–3.21), p = 0.03) and lower levels of ADAMTS13 antigen (−0.69 (−0.9 to −0.47) p < 0.00001) and activity (−0.84 (−1.06 to −0.61) p < 0.0000). Plasminogen activator inhibitor‐1 and tissue plasminogen activator levels were not different between the two groups (p < 0.05). There were elevated levels of endothelial dysfunction biomarkers in COVID‐19 patients with poor outcome, indicating their possible role in disease severity and prognosis. In particular, MR‐proADM, vWF, syndecan‐1 and sFLT‐1 showed a significant association with poor outcome in these patients.

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Biomarkers of thromboinflammation correlate to COVID-19 infection and admission status in emergency department patients

Cited by 2 publications

References 47 publications

Association of SARS-CoV-2 nucleocapsid viral antigen and the receptor for advanced glycation end products with development of severe disease in patients presenting to the emergency department with COVID-19

Association of SARS-CoV-2 nucleocapsid viral antigen and the receptor for advanced glycation end products with development of severe disease in patients presenting to the emergency department with COVID-19

Biomarkers of endothelial dysfunction are associated with poor outcome in COVID‐19 patients: A systematic review and meta‐analysis

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