Spatiotemporal cellular dynamics of germinal center reaction in COVID-19 lung draining lymph node based on imaging-based spatial transcriptomics

Abstract

Although lymph node structures may be compromised in severe SARS-CoV-2 infection, the extent and parameters of recovery in convalescing patients remain unclear. Therefore, this study aimed to elucidate the nuances of lymphoid structural recovery and their implications for immunologic memory in nonhuman primates infected with SARS-CoV-2. To do so, we utilized imaging-based spatial transcriptomics to delineate immune cell composition and tissue architecture formation in the lung-draining lymph nodes during primary infection, convalescence, and reinfection from COVID-19. We noted the establishment of a germinal center with memory B cell differentiation within lymphoid follicles during convalescence accompanied by contrasting transcriptome patterns indicative of the acquisition of follicular helper T cells versus the loss of regulatory T cells. Additionally, repopulation of germinal center-like B cells was observed in the medullary niche with accumulating plasma cells along with enhanced transcriptional expression of B cell-activating factor receptor over the course of reinfection. The spatial transcriptome atlas produced herein enhances our understanding of germinal center formation with immune cell dynamics during COVID-19 convalescence and lymphoid structural recovery with transcriptome dynamics following reinfection. These findings have the potential to inform the optimization of vaccine strategies and the development of precise therapeutic interventions in the spatial context.