High throughput spatial immune mapping reveals an innate immune scar in post-COVID-19 brains

The underlying pathogenesis of neurological sequelae in post-COVID-19 patients remains unclear. Here, we used multidimensional spatial immune phenotyping and machine learning methods on brains from initial COVID-19 survivors to identify the biological correlate associated with previous SARS-CoV-2 challenge. Compared to healthy controls, individuals with post-COVID-19 revealed a high percentage of TMEM119⁺P2RY12⁺CD68⁺Iba1⁺HLA-DR⁺CD11c⁺SCAMP2⁺ microglia assembled in prototypical cellular nodules. In contrast to acute SARS-CoV-2 cases, the frequency of CD8⁺ parenchymal T cells was reduced, suggesting an immune shift toward innate immune activation that may contribute to neurological alterations in post-COVID-19 patients.