University of Massachusetts Medical School Faculty Publications
UMMS Affiliation
Department of Medicine, Division of Infectious Diseases and Immunology
Publication Date
2020-08-28
Document Type
Article Preprint
Disciplines
Immunology of Infectious Disease | Immunopathology | Infectious Disease | Virus Diseases
Abstract
The COVID-19 pandemic continues to have an unprecedented impact on societies and economies worldwide. Despite rapid advances in diagnostic test development and scale-up, there remains an ongoing need for SARS-CoV-2 tests which are highly sensitive, specific, minimally invasive, cost-effective and scalable for broad testing and surveillance. Here we report development of a highly sensitive single molecule array (Simoa) immunoassay on the automated HD-X platform for the detection of SARS-CoV-2 Nucleocapsid protein (N-protein) in venous and capillary blood (fingerstick). In pre-pandemic and clinical sample sets, the assay has 100% specificity and 97.4% sensitivity for serum / plasma samples. The limit of detection (LoD) estimated by titration of inactivated SARS-CoV-2 virus is 0.2 pg/ml, corresponding to 0.05 Median Tissue Culture Infectious Dose (TCID50) per ml, > 2000 times more sensitive than current EUA approved antigen tests. No cross-reactivity to other common respiratory viruses, including hCoV229E, hCoVOC43, hCoVNL63, Influenza A or Influenza B, was observed. We detected elevated N-protein concentrations in symptomatic, asymptomatic, and pre-symptomatic PCR+ individuals using capillary blood from a finger-stick collection device. The Simoa SARS-CoV-2 N-protein assay has the potential to detect COVID-19 infection via antigen in blood with similar or better performance characteristics of molecular tests, while also enabling at home and point of care sample collection.
Keywords
Infectious Diseases, Simoa ultra-sensitive immunoassay, COVID-19, testing, protein assay
Rights and Permissions
The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC 4.0 International license.
DOI of Published Version
10.1101/2020.08.14.20175356
Source
medRxiv 2020.08.14.20175356; doi: https://doi.org/10.1101/2020.08.14.20175356. Link to preprint on medRxiv service
Journal/Book/Conference Title
medRxiv
Repository Citation
Shan D, Latz E, Ball AJ. (2020). SARS-Coronavirus-2 nucleocapsid protein measured in blood using a Simoa ultra-sensitive immunoassay differentiates COVID-19 infection with high clinical sensitivity. [preprint]. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1101/2020.08.14.20175356. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1765
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
Included in
Immunology of Infectious Disease Commons, Immunopathology Commons, Infectious Disease Commons, Virus Diseases Commons
Comments
Full author list omitted for brevity. For the full list of authors, see article.