Post by Nadica (She/Her) on Aug 2, 2024 2:23:43 GMT
COVID-19 related myocardial injury is associated with immune dysregulation in symptomatic patients with cardiac MRI abnormalities - Published July 29, 2024
Abstract
Aims
While acute cardiovascular complications of COVID-19 are well-described, less is known about longer-term cardiac sequelae. For many individuals with cardiac signs or symptoms arising after COVID-19 infection, the aetiology remains unclear. We examined immune profiles associated with magnetic resonance imaging (MRI) abnormalities in patients with unexplained cardiac injury after COVID-19.
Methods and Results
Twenty-one participants (mean age 47 [SD 13] years, 71% female) with long COVID (n=17), raised troponin (n=2), or unexplained new-onset heart failure (n=2), who did not have pre-existing heart conditions or recent steroid/immunosuppression treatment were enrolled a mean 346 (SD 191) days after COVID-19 infection in a prospective observational study. Cardiac MRI and blood sampling for deep immunophenotyping using mass cytometry by time of flight and measurement of proteomic inflammatory markers was performed. Nine of 21 (43%) participants had MRI abnormalities (MRI(+)), including non-ischaemic patterns of late gadolinium enhancement and/or visually overt myocardial oedema in 8 people. One patient had mildly impaired biventricular function without fibrosis or oedema, and 2 had severe left ventricular impairment. MRI(+) individuals had higher blood CCL3, CCL7, FGF-23 and CD4 Th2 cells, and lower CD8 T effector memory (TEM) cells, than MRI(-). Cluster analysis revealed lower expression of inhibitory receptors PD1 and TIM3 in CD8 TEM cells from MRI(+) patients than MRI(-) patients, and functional studies of CD8 T αβ cells showed higher proportions of cytotoxic granzyme B+ secreting cells upon stimulation. CD8 TEM cells and CCL7 were the strongest predictors of MRI abnormalities in a LASSO regression model (composite AUC 0.96, 95%CI 0.88-1.0). CCL7 was correlated with diffuse myocardial fibrosis/oedema detected by quantitative T1 mapping (r=0.47, p=0.04).
Conclusion
COVID-19 related cardiac injury in symptomatic patients with non-ischaemic myocarditis-like MRI abnormalities is associated with immune dysregulation, including decreased peripheral CD8 TEM cells and increased CCL7, persisting long after the initial infection.
Graphical Abstract
Abstract
Aims
While acute cardiovascular complications of COVID-19 are well-described, less is known about longer-term cardiac sequelae. For many individuals with cardiac signs or symptoms arising after COVID-19 infection, the aetiology remains unclear. We examined immune profiles associated with magnetic resonance imaging (MRI) abnormalities in patients with unexplained cardiac injury after COVID-19.
Methods and Results
Twenty-one participants (mean age 47 [SD 13] years, 71% female) with long COVID (n=17), raised troponin (n=2), or unexplained new-onset heart failure (n=2), who did not have pre-existing heart conditions or recent steroid/immunosuppression treatment were enrolled a mean 346 (SD 191) days after COVID-19 infection in a prospective observational study. Cardiac MRI and blood sampling for deep immunophenotyping using mass cytometry by time of flight and measurement of proteomic inflammatory markers was performed. Nine of 21 (43%) participants had MRI abnormalities (MRI(+)), including non-ischaemic patterns of late gadolinium enhancement and/or visually overt myocardial oedema in 8 people. One patient had mildly impaired biventricular function without fibrosis or oedema, and 2 had severe left ventricular impairment. MRI(+) individuals had higher blood CCL3, CCL7, FGF-23 and CD4 Th2 cells, and lower CD8 T effector memory (TEM) cells, than MRI(-). Cluster analysis revealed lower expression of inhibitory receptors PD1 and TIM3 in CD8 TEM cells from MRI(+) patients than MRI(-) patients, and functional studies of CD8 T αβ cells showed higher proportions of cytotoxic granzyme B+ secreting cells upon stimulation. CD8 TEM cells and CCL7 were the strongest predictors of MRI abnormalities in a LASSO regression model (composite AUC 0.96, 95%CI 0.88-1.0). CCL7 was correlated with diffuse myocardial fibrosis/oedema detected by quantitative T1 mapping (r=0.47, p=0.04).
Conclusion
COVID-19 related cardiac injury in symptomatic patients with non-ischaemic myocarditis-like MRI abnormalities is associated with immune dysregulation, including decreased peripheral CD8 TEM cells and increased CCL7, persisting long after the initial infection.
Graphical Abstract