While lymph node structures may experience compromise in severe SARS-CoV-2 infections, the extent of recovery in convalescent individuals remains a critical exploration. Our study aims to unravel the nuances of structural recovery, germinal center (GC) dynamics, and their implications for long-term immune memory in non-human primates recovered from SARS-CoV-2. Here, we utilized a Xenium In-situ (10x Genomics) to delineate the immune cell composition and mediastinal lymph node architecture in COVID-19 macaque lungs across primary infection, convalescence, and secondary infection. Noteworthy findings include an increase in follicular helper T cells, GC B cells and plasmablasts within lymphoid follicles during convalescence. In the paracortex, secondary infection results in a decrease in cytotoxic T cells but an increase in follicular helper T cells. In the medulla, a reduction in macrophages is observed, accompanied by increased conventional and plasmacytoid dendritic cells, GC B cells and plasmablasts during secondary infection. This study not only enhances our understanding of GC formation during COVID-19 recovery but also provides insights into immune cell repopulations within draining lymph nodes following secondary infection. These findings have the potential to inform the optimization of vaccine strategies and the design of precise therapeutic interventions.

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