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

TitleTesting-on-a-probe biosensors reveal association of early SARS-CoV-2 total antibodies and surrogate neutralizing antibodies with mortality in COVID-19 patients.
Publication TypeJournal Article
Year of Publication2021
AuthorsYang HS, Racine-Brzostek SE, Karbaschi M, Yee J, Dillard A, Steel PAD, Lee WT, McDonough KA, Qiu Y, Ketas TJ, Francomano E, Klasse PJ, Hatem L, Westblade L, Wu H, Chen H, Zuk R, Tan H, Girardin RC, Dupuis AP, Payne AF, Moore JP, Cushing MM, Chadburn A, Zhao Z
JournalBiosens Bioelectron
Date Published2021 Apr 15
KeywordsAdult, Aged, Aged, 80 and over, Antibodies, Neutralizing, Antibodies, Viral, Biosensing Techniques, Cohort Studies, COVID-19, COVID-19 Nucleic Acid Testing, COVID-19 Serological Testing, Equipment Design, Female, Humans, Male, Middle Aged, Neutralization Tests, New York City, Pandemics, Proportional Hazards Models, Retrospective Studies, Risk Factors, SARS-CoV-2, Sensitivity and Specificity, Young Adult

The association of mortality with the 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 improve sensitivity and minimize interference. Disposable cartridges containing pre-dispensed reagents require 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 the detection of early SARS-CoV-2 antibodies which associate with mortality.

Alternate JournalBiosens Bioelectron
PubMed ID33515984
PubMed Central IDPMC7816890
Grant ListP01 AI110657 / AI / NIAID NIH HHS / United States
R01 AI036082 / AI / NIAID NIH HHS / United States
Related Faculty: 
Amy Chadburn, M.D. He Sarina Yang, M.D., Ph.D. Lars Westblade, Ph.D. Melissa Cushing, M.D. Sabrina Racine-Brzostek, M.D., Ph.D. Zhen Zhao, Ph.D.


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