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

Abstract

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.

Multifaceted role of SARS-CoV-2 structural proteins in lung injury

“…Furthermore, Matthay et al. found that high levels of N protein and RAGE at admission were significantly correlated with the development of severe COVID-19 ( 111 ).…”

“…Wick et al demonstrated that N protein levels of plasma samples harvested within 72 h of hospital admission were strongly associated with RAGE and correlated with ICU admission as well as mechanical ventilation at 28 days (110). Furthermore, Matthay et al found that high levels of N protein and RAGE at admission were significantly correlated with the development of severe COVID-19 (111).…”