SARS-Coronavirus-2 nucleocapsid protein measured in blood using a Simoa ultra-sensitive immunoassay differentiates COVID-19 infection with high clinical sensitivity

Shan, Dandan; Johnson, Joseph M.; Fernandes, Syrena C.; Mendes, Muriel; Suib, Hannah; Holdridge, Marcella; Burke, Elaine M.; Beauregard, Katie G; Zhang, Ying; Cleary, Megan; Xu, Samantha; Xiao, Yao; Patel, Purvish P.; Plavina, Tatiana; Wilson, David H.; Chang, Lei; Kaiser, Kim M; Natterman, J.; Schmidt, Susanne V.; Latz, Eicke; Hrusovsky, Kevin; Mattoon, Dawn; Ball, Andrew J.

doi:10.1101/2020.08.14.20175356

Cited by 3 publications

(2 citation statements)

References 24 publications

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“…For applications where sample dilution is undesired, whole serum samples can be used requiring a slightly longer (50 min) incubation time to achieve high sensitivity detection. The sensitivity of this immunosensor is within the range of SARS-CoV-2 N protein serum levels in individuals infected with COVID-19 (1 pg to >10,000 pg/ mL 13,14,28 ), suggesting that it will be suitable as a diagnostic tool for the detection of COVID-19 infection.…”

Section: Acs Sensorsmentioning

confidence: 88%

Microfluidic Magneto Immunosensor for Rapid, High Sensitivity Measurements of SARS-CoV-2 Nucleocapsid Protein in Serum

2021

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The COVID-19 pandemic has highlighted the importance and urgent need for rapid and accurate diagnostic tests for COVID-19 detection and screening. The objective of this work was to develop a simple immunosensor for rapid and high sensitivity measurements of SARS-CoV-2 nucleocapsid protein in serum. This assay is based on a unique sensing scheme utilizing duallylabeled magnetic nanobeads for immunomagnetic enrichment and signal amplification. This immunosensor is integrated onto a microfluidic chip, which offers the advantages of minimal sample and reagent consumption, simplified sample handling, and enhanced detection sensitivity. The functionality of this immunosensor was validated by using it to detect SARS-CoV-2 nucleocapsid protein, which could be detected at concentrations as low as 50 pg/mL in whole serum and 10 pg/mL in 5× diluted serum. We also adapted this assay onto a handheld smartphone-based diagnostic device that could detect SARS-CoV-2 nucleocapsid protein at concentrations as low as 230 pg/mL in whole serum and 100 pg/mL in 5× diluted serum. Lastly, we assessed the capability of this immunosensor to diagnose COVID-19 infection by testing clinical serum specimens, which revealed its ability to accurately distinguish PCR-positive COVID-19 patients from healthy, uninfected individuals based on SARS-CoV-2 nucleocapsid protein serum levels. To the best of our knowledge, this work is the first demonstration of rapid (<1 h) SARS-CoV-2 antigen quantification in whole serum samples. The ability to rapidly detect SARS-CoV-2 protein biomarkers with high sensitivity in very small (<50 μL) serum samples makes this platform a promising tool for point-of-care COVID-19 testing.

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Section: Acs Sensorsmentioning

confidence: 88%

Microfluidic Magneto Immunosensor for Rapid, High Sensitivity Measurements of SARS-CoV-2 Nucleocapsid Protein in Serum

2021

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“…In a few recent studies (15)(16)(17)(18), the single molecule array (SIMOA) technology was used to develop an ultrasensitive antigen test to track changes of antigen and antibodies to SARS-CoV-2 in plasma, capillary blood and saliva, with an LOD of 0.2 pg/mL nucleocapsid (N) antigen. Besides the 2 cases in which saliva N protein levels were tracked using the SIMOA assay for about 12 days (18), we are not aware of large-scale studies tracking antigen dynamics in respiratory samples using a highly sensitive antigen test.…”

Section: Introductionmentioning

confidence: 99%

Femtomolar SARS-CoV-2 Antigen Detection Using the Microbubbling Digital Assay with Smartphone Readout Enables Antigen Burden Quantitation and Tracking

et al. 2021

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Background High sensitivity SARS-CoV-2 antigen assays are desirable to mitigate false negative results. Limited data are available to quantify and track SARS-CoV-2 antigen burden in respiratory samples from different populations. Methods We developed the Microbubbling SARS-CoV-2 Antigen Assay (MSAA) with smartphone readout, with a limit of detection (LOD) of 0.5 pg/mL (10.6 fmol/L) nucleocapsid (N) antigen or 4000 copies/mL inactivated SARS-CoV-2 virus in nasopharyngeal (NP) swabs. We developed a computer vision and machine learning-based automatic microbubble image classifier to accurately identify positives and negatives, and quantified and tracked antigen dynamics in ICU COVID inpatients and immunocompromised COVID patients. Results Compared to qualitative RT-PCR methods, the MSAA demonstrated a positive percent agreement (PPA) of 97% (95% confidence interval (CI), 92-99%) and a negative percent agreement (NPA) of 97% (95% CI, 94-100%) in a clinical validation study with 372 residual clinical NP swabs. In immunocompetent individuals, the antigen positivity rate in swabs decreased as days-after-symptom-onset increased, despite persistent nucleic acid positivity. Antigen was detected for longer and variable periods of time in immunocompromised patients with hematologic malignancies. Total microbubble volume, a quantitative marker of antigen burden, correlated inversely with Ct values and days-after-symptom-onset. Viral sequence variations were detected in patients with long duration of high antigen burden. Conclusions The MSAA enables sensitive and specific detection of acute infections, quantification and tracking of antigen burden, and may serve as a screening method in longitudinal studies to identify patients who are likely experiencing active rounds of ongoing replication and warrant close viral sequence monitoring.

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Alzheimer's Disease: A Silent Pandemic - A Systematic Review on the Situation and Patent Landscape of the Diagnosis

Goyzueta-Mamani

Chávez-Fumagalli

Alvarez-Fernandez

et al. 2022

BIOT

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Background: Alzheimer's disease (AD) is characterized by cognitive impairment, tau protein deposits, and amyloid beta plaques. AD impacted 44 million people in 2016, and it is estimated to affect 100 million people by 2050. AD is disregarded as a pandemic compared with other diseases. To date, there is no effective treatment or diagnosis. Objective: We aimed to discuss the current tools used to diagnose COVID-19, to point out their potential to be adapted for AD diagnosis, and to review the landscape of existing patents in the AD field and future perspectives for AD diagnosis. Method: We carried out a scientific screening following a research strategy in PubMed; Web of Science; the Derwent Innovation Index; the KCI-Korean Journal Database; SciELO; the Russian Science Citation index; and the CDerwent, EDerwent, and MDerwent index databases. Results: A total of 326 from 6,446 articles about AD and 376 from 4,595 articles about COVID-19 were analyzed. Of these, AD patents were focused on biomarkers and neuroimaging with no accurate, validated diagnostic methods, and only 7% of kit development patents were found. In comparison, COVID-19 patents were 60% about kit development for diagnosis; they are highly accurate and are now commercialized. Conclusion: AD is still neglected and not recognized as a pandemic that affects the people and economies of all nations. There is a gap in the development of AD diagnostic tools that could be filled if the interest and effort that has been invested to tackle the COVID-19 emergency could also be applied for innovation.

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SARS-Coronavirus-2 nucleocapsid protein measured in blood using a Simoa ultra-sensitive immunoassay differentiates COVID-19 infection with high clinical sensitivity

Cited by 3 publications

References 24 publications

Microfluidic Magneto Immunosensor for Rapid, High Sensitivity Measurements of SARS-CoV-2 Nucleocapsid Protein in Serum

Microfluidic Magneto Immunosensor for Rapid, High Sensitivity Measurements of SARS-CoV-2 Nucleocapsid Protein in Serum

Femtomolar SARS-CoV-2 Antigen Detection Using the Microbubbling Digital Assay with Smartphone Readout Enables Antigen Burden Quantitation and Tracking

Alzheimer's Disease: A Silent Pandemic - A Systematic Review on the Situation and Patent Landscape of the Diagnosis

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