ABSTRACT
The COVID-19 pandemic raises the need for diverse diagnostic approaches to rapidly detect different stages of viral infection. The flexible and quantitative nature of single-molecule imaging technology renders it optimal for development of new diagnostic tools. Here we present a proof-of-concept for a single-molecule based, enzyme-free assay for detection of SARS-CoV-2. The unified platform we developed allows direct detection of the viral genetic material from patients samples, as well as their immune response consisting of IgG and IgM antibodies. Thus, it establishes a platform for diagnostics of COVID-19, which could also be adjusted to diagnose additional pathogens.
ABSTRACT
Beyond SARS-CoV-2, six more coronaviruses infect humans (hCoVs), four of which cause only mild symptoms (seasonal/common cold hCoVs) 12. Previous exposures to seasonal hCoVs may elicit immunological memory that could benefit the course of SARS-CoV-2 infections 3. While cross-reactive T cells epitopes of SARS-CoV-2 and seasonal hCoVs have been reported in individuals unexposed to SARS-CoV-2 4-6, potential antibody-based cross-reactivity is incompletely understood. Here, we have probed for high resolution antibody binding against all hCoVs represented as 1,539 peptides with a phage-displayed 7 antigen library. We detected broad serum antibody responses against peptides of seasonal hCoVs in up to 75% of individuals. Recovered COVID-19 patients exhibited distinct antibody repertoires targeting variable SARS-CoV-2 epitopes, and could be accurately classified from unexposed individuals (AUC=0.96). Up to 50% of recovered patients also mounted antibody responses against unique epitopes of seasonal hCoV-OC43, that were not detectable in unexposed individuals. These results indicate substantial interindividual variability and antibody cross-reactivity between hCoVs from the direction of SARS-CoV-2 infections towards seasonal hCoVs. Our accurate high throughput assay allows profiling preexisting antibody responses against seasonal hCoVs cost-effectively and could inform on their protective nature against SARS-CoV-2.
