AUTHOR=Matthay Zachary A. , Fields Alexander T. , Wick Katherine D. , Jones Chayse , Lane H. Clifford , Herrera Kimberly , Nuñez-Garcia Brenda , Gennatas Efstathios , Hendrickson Carolyn M. , Kornblith Aaron E. , Matthay Michael A. , Kornblith Lucy Z. , the COVID-19 Associated Coagulopathy Inflammation Thrombosis (Co-ACIT) Study Group , Ambachew Biniam , Bainton Roland J. , Cary Sarah , Chalwell Lauren , Colwell Christopher , Josephy Clayton , Kurien Philip , Lee Deanna , LeGrand Matthieu , Montoy Juan Carlos , Nguyen Viet , Park John J. , Prakash Arun , Robinson Brittany , India Shelley TITLE=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 JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1130821 DOI=10.3389/fimmu.2023.1130821 ISSN=1664-3224 ABSTRACT=Introduction

There 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.

Methods

Blood samples were collected on arrival from 77 patients with symptomatic COVID-19, and plasma levels of thromboinflammatory biomarkers were measured.

Results

Differences 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.

Discussion

Elevated 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.