Diagnosis through Sorted Immune Repertoires

Infectious disease laboratory diagnostic testing is still based on targeted test methods (Ag detection,
PCR, ELISA, agglutination, ELISPOT, etc.). However, rapid evolutions in sequencing applications might
soon dramatically change our diagnostic algorithms. For instance, metagenomic sequencing is an
untargeted diagnostic tool for direct (in theory any) infectious pathogen detection without preassumptions
on the causative agent. However, acute infectious pathogens rapidly disappear from the
infected individual (causing diagnostic methods based on direct pathogen detection to fail) leaving
behind its immune imprint (primed B and T cells). We here wish to demonstrate that immune
repertoire sequencing (a cutting-edge sequencing tool that allows high-throughput mapping of B and
T cell receptor variable domains) focused on recently activated immune cells is an indirect untargeted
diagnostic tool for acute infectious pathogen detection. This method could therefore be an alternative
to current indirect targeted assays (serology and T cell assays). To prove this concept, we will exploit
recently collected acute COVID-19 patient samples.