Department of Medicine, Division of Infectious Diseases and Immunology
Immunology of Infectious Disease | Immunopathology | Infectious Disease | Virus Diseases
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.
Infectious Diseases, Simoa ultra-sensitive immunoassay, COVID-19, testing, protein assay
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The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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
medRxiv 2020.08.14.20175356; doi: https://doi.org/10.1101/2020.08.14.20175356. Link to preprint on medRxiv service
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
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