tetano
Editor, Senior Moderator
Biosens Bioelectron
. 2021 Jan 20;178:113008.
doi: 10.1016/j.bios.2021.113008. Online ahead of print.
Testing-on-a-probe biosensors reveal association of early SARS-CoV-2 total antibodies and surrogate neutralizing antibodies with mortality in COVID-19 patients
He S Yang[SUP] 1 [/SUP], Sabrina E Racine-Brzostek[SUP] 1 [/SUP], Mohsen Karbaschi[SUP] 2 [/SUP], Jim Yee[SUP] 3 [/SUP], Alicia Dillard[SUP] 1 [/SUP], Peter A D Steel[SUP] 4 [/SUP], William T Lee[SUP] 5 [/SUP], Kathleen A McDonough[SUP] 5 [/SUP], Yuqing Qiu[SUP] 6 [/SUP], Thomas J Ketas[SUP] 7 [/SUP], Erik Francomano[SUP] 7 [/SUP], P J Klasse[SUP] 7 [/SUP], Layla Hatem[SUP] 1 [/SUP], Lars Westblade[SUP] 8 [/SUP], Heng Wu[SUP] 2 [/SUP], Haode Chen[SUP] 2 [/SUP], Robert Zuk[SUP] 2 [/SUP], Hong Tan[SUP] 2 [/SUP], Roxanne C Girardin[SUP] 5 [/SUP], Alan P Dupuis 2nd[SUP] 5 [/SUP], Anne F Payne[SUP] 5 [/SUP], John P Moore[SUP] 7 [/SUP], Melissa M Cushing[SUP] 1 [/SUP], Amy Chadburn[SUP] 1 [/SUP], Zhen Zhao[SUP] 9 [/SUP]
Affiliations
Abstract
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.
Keywords: Acute humoral response; Coronavirus Disease-2019 (COVID-19); Mortality; Neutralizing antibody; SARS-CoV-2 antibody; Testing-on-a-probe biosensors.
. 2021 Jan 20;178:113008.
doi: 10.1016/j.bios.2021.113008. Online ahead of print.
Testing-on-a-probe biosensors reveal association of early SARS-CoV-2 total antibodies and surrogate neutralizing antibodies with mortality in COVID-19 patients
He S Yang[SUP] 1 [/SUP], Sabrina E Racine-Brzostek[SUP] 1 [/SUP], Mohsen Karbaschi[SUP] 2 [/SUP], Jim Yee[SUP] 3 [/SUP], Alicia Dillard[SUP] 1 [/SUP], Peter A D Steel[SUP] 4 [/SUP], William T Lee[SUP] 5 [/SUP], Kathleen A McDonough[SUP] 5 [/SUP], Yuqing Qiu[SUP] 6 [/SUP], Thomas J Ketas[SUP] 7 [/SUP], Erik Francomano[SUP] 7 [/SUP], P J Klasse[SUP] 7 [/SUP], Layla Hatem[SUP] 1 [/SUP], Lars Westblade[SUP] 8 [/SUP], Heng Wu[SUP] 2 [/SUP], Haode Chen[SUP] 2 [/SUP], Robert Zuk[SUP] 2 [/SUP], Hong Tan[SUP] 2 [/SUP], Roxanne C Girardin[SUP] 5 [/SUP], Alan P Dupuis 2nd[SUP] 5 [/SUP], Anne F Payne[SUP] 5 [/SUP], John P Moore[SUP] 7 [/SUP], Melissa M Cushing[SUP] 1 [/SUP], Amy Chadburn[SUP] 1 [/SUP], Zhen Zhao[SUP] 9 [/SUP]
Affiliations
- PMID: 33515984
- DOI: 10.1016/j.bios.2021.113008
Abstract
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.
Keywords: Acute humoral response; Coronavirus Disease-2019 (COVID-19); Mortality; Neutralizing antibody; SARS-CoV-2 antibody; Testing-on-a-probe biosensors.