N-protein presents early in blood, dried blood and saliva during asymptomatic and symptomatic SARS-CoV-2 infection

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

The COVID-19 pandemic continues to have an unprecedented impact on societies and economies worldwide. There remains an ongoing need for high-performance SARS-CoV-2 tests which may be broadly deployed for infection monitoring. Here we report a highly sensitive single molecule array (Simoa) immunoassay in development for detection of SARS-CoV-2 nucleocapsid protein (N-protein) in venous and capillary blood and saliva. In all matrices in the studies conducted to date we observe >98% negative percent agreement and >90% positive percent agreement with molecular testing for days 1–7 in symptomatic, asymptomatic, and pre-symptomatic PCR+ individuals. N-protein load decreases as anti-SARS-CoV-2 spike-IgG increases, and N-protein levels correlate with RT-PCR Ct-values in saliva, and between matched saliva and capillary blood samples. This Simoa SARS-CoV-2 N-protein assay effectively detects SARS-CoV-2 infection via measurement of antigen levels in blood or saliva, using non-invasive, swab-independent collection methods, offering potential for at home and point of care sample collection.