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La fibrina impulsa la tromboinflamación y la neuropatología en el COVID-19
Jae Kyu Ryu1,2,3, Zhaoqi Yan1,2, Mauricio Montano4,5
1Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
Nature
|August 28, 2024
Resumen
El fibrinógeno, un componente clave del coágulo, impulsa la inflamación del COVID-19 y los problemas cerebrales al unirse a la proteína del pico. La fibrina dirigida puede tratar los síntomas neurológicos agudos y prolongados de la COVID y la tromboinflamación.
Área de la Ciencia:
- Inmunología
- Neurología
- Hematología
Sus antecedentes:
- El COVID-19 causa coágulos sanguíneos peligrosos y problemas neurológicos, con mecanismos poco claros.
- El fibrinógeno se encuentra en altos niveles en los pulmones y el cerebro de los pacientes con COVID-19, vinculado a la gravedad y los problemas cognitivos.
- Los tratamientos actuales para la coagulopatía y la neuropatología relacionadas con el COVID-19 son insuficientes.
Objetivo del estudio:
- Investigar el papel de la fibrina en la tromboinflamación y la neuropatología inducidas por COVID-19.
- Para explorar la interacción entre la fibrina y la proteína del pico del SARS-CoV-2.
- Para evaluar una posible inmunoterapia dirigida a la fibrina para el COVID-19.
Principales métodos:
- Se ha demostrado la unión de la fibrina a la proteína del pico del SARS-CoV-2.
- Evaluó el papel de la fibrina en el estrés oxidativo, la actividad de los macrófagos y las células asesinas naturales en los pulmones.
- Examinó los efectos de la fibrina en la neuroinflamación, la pérdida neuronal y la activación inmune innata en el cerebro y los pulmones.
- Probó un anticuerpo monoclonal contra el dominio inflamatorio de la fibrina para efectos protectores.
Principales resultados:
- La fibrina se une a la proteína del pico del SARS-CoV-2, creando coágulos inflamatorios que promueven la tromboinflamación y la neuropatología.
- La fibrina impulsa la inflamación pulmonar (estrés oxidativo, activación de los macrófagos) y suprime las células asesinas naturales después de la infección.
- La fibrina induce inflamación cerebral, daño neuronal y activación inmune en los pulmones y el cerebro, independientemente de la infección activa.
- Un anticuerpo dirigido al dominio inflamatorio de la fibrina protegido contra la tromboinflamación pulmonar, la activación microglial y la lesión neuronal.
Conclusiones:
- La fibrina juega un papel crítico en la conducción de la inflamación y la neuropatología en la infección por SARS-CoV-2.
- Dirigir la fibrina con inmunoterapia ofrece una estrategia terapéutica potencial para el COVID agudo y prolongado.
- Este enfoque puede mitigar la tromboinflamación, la neuroinflamación y la lesión neuronal asociadas con el COVID-19.
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