SARS-CoV-2-associated T-cell infiltration in the central nervous system. SARS-CoV-2-associated T-cell infiltration in the central nervous system

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). Although an acute SARS-CoV-2 infection mainly presents with respiratory illness, neurologic symptoms and sequelae are increasingly recognized in the long-term treatment of COVID-19 patients. The pathophysiology and the neuropathogenesis behind neurologic complications of COVID-19 remain poorly understood, but mounting evidence points to endothelial dysfunction either directly caused by viral infection or indirectly by inflammatory cytokines, followed by a local immune response that may include virus-specific T cells. However, the type and role of CNS-infiltrating T cells in COVID-19 are complex and not fully understood. Methods: We analyzed distinct anatomical brain regions of patients who had deceased due to COVID-19 and performed T cell receptor Vb repertoire sequencing. Clonotypes were analyzed for SARS-CoV-2 association using public TCR repertoire data. Results: Our descriptive study demonstrates that SARS-CoV-2-associated T-cells are found in almost all brain areas of patients with fatal COVID-19 courses. The olfactory bulb, medulla and cerebellum were brain regions showing the most SARS-CoV-2 specific sequence patterns. Neuropathological workup demonstrated primary CD8+ T cell infiltration with a perivascular infiltration pattern. Conclusion: Future research is needed to better define the relationship between T-cell infiltration and neurological symptoms and its long-term impact on patients' cognitive and mental health.