tetano
Editor, Senior Moderator
Clin Transl Immunology
. 2024 Jan 31;13(2):e1487.
doi: 10.1002/cti2.1487. eCollection 2024. SARS-CoV-2-associated T-cell infiltration in the central nervous system
Malte Mohme[SUP] 1 [/SUP], Christoph Schultheiß[SUP] 2 3 [/SUP], Andras Piffko[SUP] 1 [/SUP], Antonia Fitzek[SUP] 4 [/SUP], Lisa Paschold[SUP] 5 [/SUP], Benjamin Thiele[SUP] 2 3 6 [/SUP], Klaus Püschel[SUP] 4 [/SUP], Markus Glatzel[SUP] 7 [/SUP], Manfred Westphal[SUP] 1 [/SUP], Katrin Lamszus[SUP] 1 [/SUP], Jakob Matschke[SUP] 7 [/SUP], Mascha Binder[SUP] 2 3 [/SUP]
Affiliations
Objectives: 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 recognised 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 central nervous system-infiltrating T cells in COVID-19 are complex and not fully understood.
Methods: We analysed distinct anatomical brain regions of patients who had deceased as a result of COVID-19-associated pneumonia or complications thereof and performed T cell receptor Vβ repertoire sequencing. Clonotypes were analysed 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[SUP]+[/SUP] 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.
Keywords: COVID‐19; COVID‐19‐specific T cell; SARS‐CoV‐2; TCR sequencing; central nervous system; neuroinflammation.
Malte Mohme[SUP] 1 [/SUP], Christoph Schultheiß[SUP] 2 3 [/SUP], Andras Piffko[SUP] 1 [/SUP], Antonia Fitzek[SUP] 4 [/SUP], Lisa Paschold[SUP] 5 [/SUP], Benjamin Thiele[SUP] 2 3 6 [/SUP], Klaus Püschel[SUP] 4 [/SUP], Markus Glatzel[SUP] 7 [/SUP], Manfred Westphal[SUP] 1 [/SUP], Katrin Lamszus[SUP] 1 [/SUP], Jakob Matschke[SUP] 7 [/SUP], Mascha Binder[SUP] 2 3 [/SUP]
Affiliations
Objectives: 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 recognised 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 central nervous system-infiltrating T cells in COVID-19 are complex and not fully understood.
Methods: We analysed distinct anatomical brain regions of patients who had deceased as a result of COVID-19-associated pneumonia or complications thereof and performed T cell receptor Vβ repertoire sequencing. Clonotypes were analysed 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[SUP]+[/SUP] 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.
Keywords: COVID‐19; COVID‐19‐specific T cell; SARS‐CoV‐2; TCR sequencing; central nervous system; neuroinflammation.
. 2024 Jan 31;13(2):e1487.
doi: 10.1002/cti2.1487. eCollection 2024. SARS-CoV-2-associated T-cell infiltration in the central nervous system
Malte Mohme[SUP] 1 [/SUP], Christoph Schultheiß[SUP] 2 3 [/SUP], Andras Piffko[SUP] 1 [/SUP], Antonia Fitzek[SUP] 4 [/SUP], Lisa Paschold[SUP] 5 [/SUP], Benjamin Thiele[SUP] 2 3 6 [/SUP], Klaus Püschel[SUP] 4 [/SUP], Markus Glatzel[SUP] 7 [/SUP], Manfred Westphal[SUP] 1 [/SUP], Katrin Lamszus[SUP] 1 [/SUP], Jakob Matschke[SUP] 7 [/SUP], Mascha Binder[SUP] 2 3 [/SUP]
Affiliations
- PMID: 38304555
- PMCID: PMC10831126
- DOI: 10.1002/cti2.1487
Objectives: 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 recognised 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 central nervous system-infiltrating T cells in COVID-19 are complex and not fully understood.
Methods: We analysed distinct anatomical brain regions of patients who had deceased as a result of COVID-19-associated pneumonia or complications thereof and performed T cell receptor Vβ repertoire sequencing. Clonotypes were analysed 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[SUP]+[/SUP] 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.
Keywords: COVID‐19; COVID‐19‐specific T cell; SARS‐CoV‐2; TCR sequencing; central nervous system; neuroinflammation.
Malte Mohme[SUP] 1 [/SUP], Christoph Schultheiß[SUP] 2 3 [/SUP], Andras Piffko[SUP] 1 [/SUP], Antonia Fitzek[SUP] 4 [/SUP], Lisa Paschold[SUP] 5 [/SUP], Benjamin Thiele[SUP] 2 3 6 [/SUP], Klaus Püschel[SUP] 4 [/SUP], Markus Glatzel[SUP] 7 [/SUP], Manfred Westphal[SUP] 1 [/SUP], Katrin Lamszus[SUP] 1 [/SUP], Jakob Matschke[SUP] 7 [/SUP], Mascha Binder[SUP] 2 3 [/SUP]
Affiliations
- PMID: 38304555
- PMCID: PMC10831126
- DOI: 10.1002/cti2.1487
Objectives: 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 recognised 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 central nervous system-infiltrating T cells in COVID-19 are complex and not fully understood.
Methods: We analysed distinct anatomical brain regions of patients who had deceased as a result of COVID-19-associated pneumonia or complications thereof and performed T cell receptor Vβ repertoire sequencing. Clonotypes were analysed 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[SUP]+[/SUP] 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.
Keywords: COVID‐19; COVID‐19‐specific T cell; SARS‐CoV‐2; TCR sequencing; central nervous system; neuroinflammation.