Frontiers in Immunology (Mar 2023)

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

  • Zachary A. Matthay,
  • Alexander T. Fields,
  • Katherine D. Wick,
  • Katherine D. Wick,
  • Chayse Jones,
  • Chayse Jones,
  • H. Clifford Lane,
  • Kimberly Herrera,
  • Brenda Nuñez-Garcia,
  • Efstathios Gennatas,
  • Carolyn M. Hendrickson,
  • Aaron E. Kornblith,
  • Michael A. Matthay,
  • Michael A. Matthay,
  • Lucy Z. Kornblith,
  • the COVID-19 Associated Coagulopathy Inflammation Thrombosis (Co-ACIT) Study Group,
  • Biniam Ambachew,
  • Roland J. Bainton,
  • Sarah Cary,
  • Lauren Chalwell,
  • Christopher Colwell,
  • Clayton Josephy,
  • Philip Kurien,
  • Deanna Lee,
  • Matthieu LeGrand,
  • Juan Carlos Montoy,
  • Viet Nguyen,
  • John J. Park,
  • Arun Prakash,
  • Brittany Robinson,
  • Shelley India

DOI
https://doi.org/10.3389/fimmu.2023.1130821
Journal volume & issue
Vol. 14

Abstract

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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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