The Association of Baseline Plasma SARS-CoV-2 Nucleocapsid Antigen Level and Outcomes in Patients Hospitalized With COVID-19

Rogers, Angela J.; Wentworth, Deborah; Phillips, Andrew; Shaw-Saliba, Kathryn; Dewar, Robin; Aggarwal, Neil R.; Babiker, Abdel; Chang, Weizhong; Dharan, Nila; Davey, Victoria J.; Higgs, Elizabeth; Gerry, Norman P.; Ginde, Adit A.; Hayanga, JW Awori; Highbarger, Helene; Highbarger, Jeroen; Jain, Mamta K.; Kan, Virginia L.; Kim, Kami; Lallemand, Perrine; Leshnower, Bradley G.; Lutaakome, Joseph; Matthews, Gail; Mourad, Ahmad; Mylonakis, Eleftherios; Natarajan, Ven; Padilla, María L.; Pandit, Lavannya; Paredes, Roger; Pett, Sarah; Ramachandruni, Srikanth; Rehman, Muhammad T; Sherman, Brad T.; Files, D. Clark; Brown, Samuel M.; Matthay, Michael A.; Thompson, B. Taylor; Neaton, James D.; Lane, H. Clifford; Lundgren, Jens D.

doi:10.7326/m22-0924

Cited by 43 publications

(23 citation statements)

References 36 publications

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“…Our study also demonstrates a strong association of SARS-CoV-2 nucleocapsid viral antigen with development of severe disease in COVID-19, consistent with several prior studies of hospitalized patients ( 14 , 19 , 20 , 40 ). Recent data from a large multicenter clinical trial consortium demonstrated that in patients hospitalized with COVID-19, higher SARS-CoV-2 nucleocapsid viral antigen measured within the first 72 hours was associated with worse clinical outcomes at 7 days ( 19 ).…”

Section: Discussionsupporting

confidence: 91%

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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: 91%

“…The soluble receptor for advanced glycation end-products (RAGE) and SARS-CoV-2 nucleocapsid viral antigen are two biomarkers recently shown to have prognostic value in hospitalized patients with COVID-19 ( 12 – 14 ). However, few studies to date have examined these biomarkers in patients presenting to the emergency department.…”

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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“…During the first week of the SARS-CoV-2 infection, detection of N in plasma has a sensitivity of > 90% for the infection with concentration positively correlated to disease severity 8 . Quantification of viremia by N in plasma can therefore be used for risk stratification and/or as a prospective marker for poor outcome in COVID-19 patients 4 , 9 – 12 . However, quantitative assays should have a sensitivity and specificity needed for answering the clinical question raised e.g.…”

Section: Introductionmentioning

confidence: 99%

Sensitivity and performance of three novel quantitative assays of SARS-CoV-2 nucleoprotein in blood

Hillig

Kristensen

Brasen

et al. 2023

Sci Rep

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To assess if SARS-CoV-2 (COVID-19) systemic disease can be determined by available nucleoprotein assays, we compared the performance of three commercial SARS-CoV-2 nucleoprotein (N) assays in plasma. A total of 272 plasma samples collected in the period November–December 2021 were analyzed by the methods Simoa SARS CoV‐2 N Protein Advantage Kit [Quanterix Simoa], Solsten SARS-CoV-2 Antigen enzyme immunosorbent assay (ELISA) [Solsten ELISA], and Elecsys SARS‐CoV‐2 Antigen electrochemiluminescence immunoassay [Elecsys ECLIA]. Additionally, a dilution series of inactivated virus culture was analyzed by the three assays. The SARS CoV-2 PCR-status was not known for the patients. Linear correlation in the pairwise correlation between assays as well as linearity of dilution series of inactivated virus culture was estimated by Spearman score. Sensitivity and specificity were estimated by pairwise comparison. The three assays showed poor agreement on patient samples with regards to concentration. Performance on virus culture was excellent but with different level of detection (LOD). Positive vs negative results show comparable sensitivity and specificity of Quanterix Simoa and Solsten ELISA, with a higher LOD in Elecsys ECLIA and thus lower sensitivity and high specificity. N by all tested assays can be used as a marker for systemic COVID-19 disease.

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“…First of all, this antigen can be directly detected in biological fluids for the purpose of diagnosis in the early stages of infection. The specificity and relatively high sensitivity of this direct analysis has been shown in fluorescence immunochromatographic (FIC) assays [ 15 ] and ELISA tests [ 16 , 17 ]. Moreover, strong positive correlation was observed between elevated plasma N-antigens and odds of pulmonary damage severity, resulting in worsened clinical outcomes [ 17 , 18 ]; therefore, N-level measurement upon hospital admission may improve risk stratification through identification of patients with implicit odd of severe diseases [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

“…The specificity and relatively high sensitivity of this direct analysis has been shown in fluorescence immunochromatographic (FIC) assays [ 15 ] and ELISA tests [ 16 , 17 ]. Moreover, strong positive correlation was observed between elevated plasma N-antigens and odds of pulmonary damage severity, resulting in worsened clinical outcomes [ 17 , 18 ]; therefore, N-level measurement upon hospital admission may improve risk stratification through identification of patients with implicit odd of severe diseases [ 18 ]. An N-antigen-based assay may be performed in a simple self-test format, although its sensitivity and diagnostic accuracy would be lower compared to those of an RT-PCR assay [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Assessment of Immunogenic and Antigenic Properties of Recombinant Nucleocapsid Proteins of Five SARS-CoV-2 Variants in a Mouse Model

Rak

Горбунов

Kostevich

et al. 2023

Viruses

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COVID-19 cases caused by new variants of highly mutable SARS-CoV-2 continue to be identified worldwide. Effective control of the spread of new variants can be achieved through targeting of conserved viral epitopes. In this regard, the SARS-CoV-2 nucleocapsid (N) protein, which is much more conserved than the evolutionarily influenced spike protein (S), is a suitable antigen. The recombinant N protein can be considered not only as a screening antigen but also as a basis for the development of next-generation COVID-19 vaccines, but little is known about induction of antibodies against the N protein via different SARS-CoV-2 variants. In addition, it is important to understand how antibodies produced against the antigen of one variant can react with the N proteins of other variants. Here, we used recombinant N proteins from five SARS-CoV-2 strains to investigate their immunogenicity and antigenicity in a mouse model and to obtain and characterize a panel of hybridoma-derived monoclonal anti-N antibodies. We also analyzed the variable epitopes of the N protein that are potentially involved in differential recognition of antiviral antibodies. These results will further deepen our knowledge of the cross-reactivity of the humoral immune response in COVID-19.

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The Association of Baseline Plasma SARS-CoV-2 Nucleocapsid Antigen Level and Outcomes in Patients Hospitalized With COVID-19

Abstract: In a large cross-sectional study done in 114 centers in 10 countries, the authors assessed whether there was an association of an elevated SARS-CoV-2 plasma antigen level at presentation with a variety of patient characteristics, clinical outcomes, and viral factors.

Cited by 43 publications

References 36 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

Sensitivity and performance of three novel quantitative assays of SARS-CoV-2 nucleoprotein in blood

Assessment of Immunogenic and Antigenic Properties of Recombinant Nucleocapsid Proteins of Five SARS-CoV-2 Variants in a Mouse Model

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