Signatures of Functional Immune Responses to Acute and Chronic COVID-19 Infections

Post-acute sequelae of COVID-19 (PASC), characterized by lingering symptoms of disease after infection, affects 31-69% of individuals infected with COVID-19. We currently lack a quantitative description of the differences between individuals with and without PASC. To describe those differences, we focus on the adaptive immune response to COVID-19. The adaptive immune system, with diverse populations of T-cells and B-cells, is complex and ever-evolving, making biophysical models necessary to describe its behavior. We studied T-cell receptor (TCR) repertoires of individuals with and without PASC during and after COVID-19 infection. Using models grounded in statistical physics, we characterized the differential features in the composition of TCR repertoires between patients with and without PASC. We quantified the dynamics of T-cell populations during infection and sharing of T-cells among individuals. By integrating this statistical and dynamical information, our work will shed light on how an individual's T-cell repertoire can predict PASC onset, and how COVID-19 and PASC reorganize an individual's immune repertoire.