Persistence and detection of anti-SARS-CoV-2 antibodies: immunoassay heterogeneity and implications for serosurveillance (preprint)

Serologic studies have been critical in tracking the evolution of the COVID-19 pandemic. The reliability of serologic studies for quantifying the proportion of the population that have been infected depends on the extent of antibody decay as well as on assay performance in detecting both recent and older infections. Data on anti-SARS-CoV-2 antibodies persistence remain sparse, especially from infected individuals with few to no symptoms. In a cohort of mostly mild/asymptomatic SARS-CoV-2-infected individuals tested with three widely-used immunoassays, antibodies persisted for at least 8 months after infection, although detection depended on immunoassay choice, with one of them missing up to 40% of past infections. Simulations reveal that without appropriate adjustment for time-varying assay sensitivity, seroprevalence surveys may underestimate infection rates. As the immune landscape becomes more complex with naturally-infected and vaccinated individuals, assay choice and appropriate assay-performance-adjustment will become even more important for the interpretation of serologic studies.

A high-throughput microfluidic nano-immunoassay for detecting anti-SARS-CoV-2 antibodies in serum or ultra-low volume dried blood samples (preprint)

Novel technologies are needed to facilitate large-scale detection and quantification of SARS-CoV-2 specific antibodies in human blood samples. Such technologies are essential to support seroprevalence studies, vaccine clinical trials, and to monitor quality and duration of immunity. We developed a microfluidic nano-immunnoassay for the detection of anti-SARS-CoV-2 IgG antibodies in 1024 samples per device. The method achieved a specificity of 100% and a sensitivity of 98% based on the analysis of 289 human serum samples. To eliminate the need for venipuncture, we developed low-cost, ultra-low volume whole blood sampling methods based on two commercial devices and repurposed a blood glucose test strip. The glucose test strip permits the collection, shipment, and analysis of 0.6 L whole blood easily obtainable from a simple fingerprick. The nano-immunoassay platform achieves high-throughput, high sensitivity and specificity, negligible reagent consumption, and a decentralized and simple approach to blood sample collection. We expect this technology to be immediately applicable to current and future SARS-CoV-2 related serological studies and to protein biomarker diagnostics in general.