Testing-on-a-probe biosensors reveal association of early SARS-CoV-2 total antibodies and surrogate neutralizing antibodies with mortality in COVID-19 patients

Autor: Amy Chadburn, Heng Wu, Kathleen A. McDonough, Eric Francomano, Alicia Dillard, Melissa M. Cushing, Roxanne C. Girardin, Anne F. Payne, John P. Moore, Robert Zuk, Layla Hatem, Jim Yee, Alan P. Dupuis, Lars F. Westblade, Peter A D Steel, Hong Tan, Per Johan Klasse, Yuqing Qiu, Sabrina E Racine-Brzostek, Thomas J. Ketas, He S. Yang, Zhen Zhao, Mohsen Karbaschi, William S Lee, Haode Chen
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
Hospitalized patients
02 engineering and technology
Biosensing Techniques
Antibodies
Viral
01 natural sciences
Cohort Studies
Risk Factors
Electrochemistry
Medicine
Statistics & numerical data
Neutralizing antibody
Aged
80 and over
biology
neutralizing antibody
Equipment Design
General Medicine
Middle Aged
021001 nanoscience & nanotechnology
testing-on-a-probe biosensors
COVID-19 Nucleic Acid Testing
Female
Antibody
0210 nano-technology
Viral load
Biotechnology
Adult
Coronavirus disease 2019 (COVID-19)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Biomedical Engineering
Biophysics
Sensitivity and Specificity
Article
COVID-19 Serological Testing
Young Adult
Neutralization Tests
Humans
Pandemics
SARS-CoV-2 antibody
Survival analysis
Aged
Proportional Hazards Models
Retrospective Studies
business.industry
Proportional hazards model
SARS-CoV-2
010401 analytical chemistry
COVID-19
Acute humoral response
Antibodies
Neutralizing
mortality
0104 chemical sciences
Immunology
biology.protein
Coronavirus Disease-2019 (COVID-19)
New York City
business
Biosensor
Zdroj: Biosensors and Bioelectronics
Biosensors & Bioelectronics
medRxiv
ISSN: 0956-5663
DOI: 10.1016/j.bios.2021.113008
Popis: The association of mortality with early humoral response to SARS-CoV-2 infection within the first few days after onset of symptoms (DAOS) has not been thoroughly investigated partly due to a lack of sufficiently sensitive antibody testing methods. Here we report two sensitive and automated testing-on-a-probe (TOP) biosensor assays for SARS-CoV-2 viral specific total antibodies (TAb) and surrogate neutralizing antibodies (SNAb), which are suitable for clinical use. The TOP assays employ an RBD-coated quartz probe using a Cy5-Streptavidin-polysacharide conjugate to improved sensitivity and minimize interference. Disposable cartridge containing pre-dispensed reagents requires no liquid manipulation or fluidics during testing. The TOP-TAb assay exhibited higher sensitivity in the 0-7 DAOS window than a widely used FDA-EUA assay. The rapid and automated TOP-SNAb correlated well with two well-established SARS-CoV-2 virus neutralization tests. The clinical utility of the TOP assays was demonstrated by evaluating early antibody responses in 120 SARS-CoV-2 RT-PCR positive adult hospitalized patients. Higher TAb and SNAb positivity rates and more robust antibody responses at patient’s initial hospital presentation were seen in inpatients who survived COVID-19 than those who died in the hospital. Survival analysis using the Cox Proportional Hazards Model showed that patients who had negative TAb and/or SNAb at initial hospital presentation were at a higher risk of in-hospital mortality. Furthermore, TAb and SNAb levels at presentation were inversely associated with SARS-CoV-2 viral load based on concurrent RT-PCR testing. Overall, the sensitive and automated TAb and SNAb assays allow detection of early SARS-CoV-2 antibodies which associate with mortality.
Highlights • Novel testing-on-a probe (TOP) biosensors employ Cy5-Streptavidin-polysaccharide with improved conjugation chemistry. • TOP assays allow rapid, sensitive, specific and fully automated detection of SARS-CoV-2 total (TAb) and surrogate neutralizing antibodies (SNAb). • Simple dip-and-read steps on a clinically available platform. • Disposable cartridge containing pre-dispensed reagents requiring no liquid manipulation or fluidics. • TOP-TAb and TOP-SNAb positivity rate and magnitude at initial hospital presentation are associated with in-hospital mortality.
Databáze: OpenAIRE
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