A MULTI-HIT MODEL OF LONG COVID PATHOPHYSIOLOGY: THE INTERACTION BETWEEN IMMUNE TRIGGERS AND NERVOUS SYSTEM SIGNALING.
Trans Am Clin Climatol Assoc
; 134: 149-164, 2024.
Article
en En
| MEDLINE
| ID: mdl-39135572
ABSTRACT
Early in the pandemic, clinicians recognized an overlap between Long COVID symptoms and dysautonomia, suggesting autonomic nervous system (ANS) dysfunction. Our clinical experience at Johns Hopkins with primary dysautonomia suggested heritability of sympathetic dysfunction, manifesting primarily as hyperhidrosis and as other dysautonomia symptoms. Whole exome sequencing revealed mutations in genes regulating electrical signaling in the nervous system, thus providing a genetic basis for the sympathetic overdrive observed. We hypothesize that dysautonomia in Long COVID requires two molecular hits a genetic vulnerability to prime the ANS and a SARS-CoV-2 infection, as an immune trigger, to further disrupt ANS function resulting in increased sympathetic activity. Indeed, Long COVID patients show signs of chronic inflammation and autoimmunity. We have translated this two-hit concept to the clinic using ion channel inhibitors to target genetic susceptibility and immunomodulators to treat inflammation. This multi-hit hypothesis shows promise for managing Long COVID and merits further study.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
COVID-19
/
Síndrome Post Agudo de COVID-19
Límite:
Humans
Idioma:
En
Revista:
Trans Am Clin Climatol Assoc
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Estados Unidos