Testing-on-a-probe biosensors reveal association of early SARS-CoV-2 total antibodies and surrogate neutralizing antibodies with mortality in COVID-19 patients
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 (18 min) 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 baseline TAb and SNAb positivity rates and more robust antibody responses were seen in patients who survived COVID-19 than those who died in the hospital. Survival analysis using the Cox Proportional Hazards Model showed that patients who were TAb and SNAb negative 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.
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UpdateIn: Biosens Bioelectron. 2021 Jan 20;178:113008. - PMID 33515984 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2020 |
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| Enthalten in: |
medRxiv : the preprint server for health sciences - (2020) vom: 22. Nov. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yang, He S [VerfasserIn] |
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Date Revised 03.02.2021 published: Electronic UpdateIn: Biosens Bioelectron. 2021 Jan 20;178:113008. - PMID 33515984 Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1101/2020.11.19.20235044 |
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| PPN (Katalog-ID): |
NLM318027224 |
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| 500 | |a UpdateIn: Biosens Bioelectron. 2021 Jan 20;178:113008. - PMID 33515984 | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a 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 (18 min) 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 baseline TAb and SNAb positivity rates and more robust antibody responses were seen in patients who survived COVID-19 than those who died in the hospital. Survival analysis using the Cox Proportional Hazards Model showed that patients who were TAb and SNAb negative 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 | ||
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| 700 | 1 | |a Dillard, Alicia |e verfasserin |4 aut | |
| 700 | 1 | |a Steel, Peter A D |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, William S |e verfasserin |4 aut | |
| 700 | 1 | |a McDonough, Kathleen A |e verfasserin |4 aut | |
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| 700 | 1 | |a Francomano, Eric |e verfasserin |4 aut | |
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| 700 | 1 | |a Tan, Hong |e verfasserin |4 aut | |
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